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Il Ruolo dell’Ecoendoscopia nelle Lesioni Pancreatiche Alberto Larghi MD, PhD Digestive Endoscopy Unit European Endoscopy Training Centre Catholic University, Rome
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Il Ruolo dellrsquoEcoendoscopia nelle Lesioni Pancreatiche
Alberto Larghi MD PhDDigestive Endoscopy Unit
European Endoscopy Training Centre Catholic University Rome
1980 First studies published in the literatureHisanaga K AJR 1980 Di Magno EP Lancet 1980 Strohm WD Endoscopy1980
1984-88 Diagnostic EUS Staging of luminal GI and pancreatic cancersCaletti GC Scand J Gastroenterol 1984 Tanada Y Scand J Gastroenterol 1984Yasuda K Gastrointest Endosc 1988
1992 EUS-FNA Vilman P Gastrointest Endosc 1992 Wegener M Ultraschall Med 1992
1970 Development of the technique
Endoscopic UltrasoundEndoscopic UltrasoundHistorical BackgroundHistorical Background
1996 Interventional EUS Wiersema MJ Gastrointestinal Endoscopy 1996 Gress F Gastrointestinal Endoscopy 1996 Giovannini M Endoscopy 2001
2013 Therapeutic EUS
Radial EUS
Ultrasound beam
Radial Echoendoscope
Linear EUS
Ultrasound beam
Mass
Linear Echoendoscope
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
High-Risks IndividualsRisk Group Gene Life Time Risk
Hereditary Pancreatitis PRSS1 40
Peutz-Jeghers Syndrome STK 11LKB1 36
Familial Atypical Multiple Mole Melanoma (FAMMM)
CDKN2a 17
Familial Breast-Ovarian Cancer (FBOC) with one affected FDR
BRCA2 10-15
Familial Pancreatic Cancer unknown
PC in ge 3 blood relatives (at
least 1 FDR)
40
PC in ge 2 FDR 8-12
PC in ge 2 blood relatives (at
least 1 FDR)
6
gt5 lifetime risk or fivefold increased RR Canto MI GUT 201362339-47
High-Risks Individuals
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
High-Risks IndividualsResults of Screening
Canto MI GUT 201362339-47
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
1980 First studies published in the literatureHisanaga K AJR 1980 Di Magno EP Lancet 1980 Strohm WD Endoscopy1980
1984-88 Diagnostic EUS Staging of luminal GI and pancreatic cancersCaletti GC Scand J Gastroenterol 1984 Tanada Y Scand J Gastroenterol 1984Yasuda K Gastrointest Endosc 1988
1992 EUS-FNA Vilman P Gastrointest Endosc 1992 Wegener M Ultraschall Med 1992
1970 Development of the technique
Endoscopic UltrasoundEndoscopic UltrasoundHistorical BackgroundHistorical Background
1996 Interventional EUS Wiersema MJ Gastrointestinal Endoscopy 1996 Gress F Gastrointestinal Endoscopy 1996 Giovannini M Endoscopy 2001
2013 Therapeutic EUS
Radial EUS
Ultrasound beam
Radial Echoendoscope
Linear EUS
Ultrasound beam
Mass
Linear Echoendoscope
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
High-Risks IndividualsRisk Group Gene Life Time Risk
Hereditary Pancreatitis PRSS1 40
Peutz-Jeghers Syndrome STK 11LKB1 36
Familial Atypical Multiple Mole Melanoma (FAMMM)
CDKN2a 17
Familial Breast-Ovarian Cancer (FBOC) with one affected FDR
BRCA2 10-15
Familial Pancreatic Cancer unknown
PC in ge 3 blood relatives (at
least 1 FDR)
40
PC in ge 2 FDR 8-12
PC in ge 2 blood relatives (at
least 1 FDR)
6
gt5 lifetime risk or fivefold increased RR Canto MI GUT 201362339-47
High-Risks Individuals
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
High-Risks IndividualsResults of Screening
Canto MI GUT 201362339-47
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Radial EUS
Ultrasound beam
Radial Echoendoscope
Linear EUS
Ultrasound beam
Mass
Linear Echoendoscope
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
High-Risks IndividualsRisk Group Gene Life Time Risk
Hereditary Pancreatitis PRSS1 40
Peutz-Jeghers Syndrome STK 11LKB1 36
Familial Atypical Multiple Mole Melanoma (FAMMM)
CDKN2a 17
Familial Breast-Ovarian Cancer (FBOC) with one affected FDR
BRCA2 10-15
Familial Pancreatic Cancer unknown
PC in ge 3 blood relatives (at
least 1 FDR)
40
PC in ge 2 FDR 8-12
PC in ge 2 blood relatives (at
least 1 FDR)
6
gt5 lifetime risk or fivefold increased RR Canto MI GUT 201362339-47
High-Risks Individuals
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
High-Risks IndividualsResults of Screening
Canto MI GUT 201362339-47
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Linear EUS
Ultrasound beam
Mass
Linear Echoendoscope
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
High-Risks IndividualsRisk Group Gene Life Time Risk
Hereditary Pancreatitis PRSS1 40
Peutz-Jeghers Syndrome STK 11LKB1 36
Familial Atypical Multiple Mole Melanoma (FAMMM)
CDKN2a 17
Familial Breast-Ovarian Cancer (FBOC) with one affected FDR
BRCA2 10-15
Familial Pancreatic Cancer unknown
PC in ge 3 blood relatives (at
least 1 FDR)
40
PC in ge 2 FDR 8-12
PC in ge 2 blood relatives (at
least 1 FDR)
6
gt5 lifetime risk or fivefold increased RR Canto MI GUT 201362339-47
High-Risks Individuals
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
High-Risks IndividualsResults of Screening
Canto MI GUT 201362339-47
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
High-Risks IndividualsRisk Group Gene Life Time Risk
Hereditary Pancreatitis PRSS1 40
Peutz-Jeghers Syndrome STK 11LKB1 36
Familial Atypical Multiple Mole Melanoma (FAMMM)
CDKN2a 17
Familial Breast-Ovarian Cancer (FBOC) with one affected FDR
BRCA2 10-15
Familial Pancreatic Cancer unknown
PC in ge 3 blood relatives (at
least 1 FDR)
40
PC in ge 2 FDR 8-12
PC in ge 2 blood relatives (at
least 1 FDR)
6
gt5 lifetime risk or fivefold increased RR Canto MI GUT 201362339-47
High-Risks Individuals
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
High-Risks IndividualsResults of Screening
Canto MI GUT 201362339-47
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
High-Risks IndividualsRisk Group Gene Life Time Risk
Hereditary Pancreatitis PRSS1 40
Peutz-Jeghers Syndrome STK 11LKB1 36
Familial Atypical Multiple Mole Melanoma (FAMMM)
CDKN2a 17
Familial Breast-Ovarian Cancer (FBOC) with one affected FDR
BRCA2 10-15
Familial Pancreatic Cancer unknown
PC in ge 3 blood relatives (at
least 1 FDR)
40
PC in ge 2 FDR 8-12
PC in ge 2 blood relatives (at
least 1 FDR)
6
gt5 lifetime risk or fivefold increased RR Canto MI GUT 201362339-47
High-Risks Individuals
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
High-Risks IndividualsResults of Screening
Canto MI GUT 201362339-47
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
High-Risks Individuals
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
How to ScreenMRCPEUS
When to Start40 yrs for HP 50 yrs for others
How frequently to SurveilYearly
High-Risks IndividualsResults of Screening
Canto MI GUT 201362339-47
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
High-Risks IndividualsResults of Screening
Canto MI GUT 201362339-47
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Detection of Pancreatic CancerEUS vs CT
Author yrNo Of
PatientsRate of
malignancy
Ho 2006 50 8
Singh 2008 107 21
Horwhat 2009 69 9
Reddymasu 2011 320 9
Non specific CT changes (enlarged prominent pancreas)
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
104 patients with suspected pancreatic cancer 80 with confirmed PC Sensitivity 98 vs 86 P=0012
for masses le25mm 89 vs 53 P=007
Non specific CT changes (enlarged prominent pancreas)
DeWitt J Ann Intern Med 2004141753-63
EUS MDHCT
All Lesionsdeg 93 74
Insulinoma^ 84 32
Khashab MA Gastrointest Endosc 201173691-6
64-slice CT degP=006 ^P=000164-slice CT degP=006 ^P=0001
Detection of Pancreatic CancerEUS vs CT
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
HIGH NEGATIVE PREDICTIVE VALUE
Author
Pts negative
EUS
Negative Predictive
ValueMean fu
(mos)
Catanzaro lsquo03 58 100 24
Klapman lsquo05 155 100 25
Detection of Pancreatic CancerEUS Performance
Catanzaro Al Gastrointest Endosc 200358836-40
Klapman JB Am J Gastroenterol 20051002658-61
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
EUS-FNA Unresectable Tumors
EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Unresectable Tumors EUS-FNA vs CTUS-FNA
Restrospective study on 1050 pancreatic FNAs
EUS (843) USCT (207) For lesions le 3cm EUS accuracy significantly better than CTUS (p=0015)
Prospective randomized study on 84 pancreatic FNAs
EUS (41) USCT (43) EUS vs USCT sensitivity 84 vs 62 p=ns
accuracy 89 vs 72 p=0074
Volmar KE Gastrointest Endosc 200561854-61
Horwhat JD Gastrointest Endosc 200663966-75
Eloubedi M Gastrointest Endosc 200663622-9
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
American Joint Committee on CancerEUS-FNA preferred sampling technique for
pancreatic cancer
Incidence of peritoneal carcinomatosis
EUS-FNA 22 Percutaneous FNA 163
P lt 0025
SeedingEUS-FNA vs USCT-FNA
Micames C Gastrointest Endosc 200358690-5
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
EUS-FNA for Pancreatic MassesPerformance
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Meta-analysis and systematic review (41 studies 4766 patients)
Pooled sensitivity 868 (95 CI 855-879)
Pooled specificity 958 (95 CI 946-967)
Positive likelihood ratio 152 (95 CI 85-273)
Negative likelihood ratio 017 (95 CI 013-021)
Puli SR Pancreas 20134220-6
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Resectable TumorsShould FNA be performed
Patient demands definitive diagnosis
To exclude other diagnoses
Preoperative neoadjuvant
Volmar KE et al Gastrointest Endosc 200561854-61Barugola G et al Ann Surg Oncol 200916331622
Probability of cancer-related deaths (lt12 mos) after surgical resection
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
EUS for Pancreatic MassesTissue is the issue
19G19G22G22G
25G25G
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Prospective study in 61 consecutive patients with pancreatic solid masses
One needle pass performed Core biopsy samples in 5561 (901)
Sensitivity 875 Specificity 100 PPV 100 NPV 417 Diagnostic accuracy 885
Larghi A Surg Endosc 2013 273733-8
EUS for Pancreatic MassesTissue is the issue
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
42 patients with ADK with pro-op EUS-NB and surgical specimen
4 pathologists (Rome Marseille Santiago di Compostela) independently reviewed biopsy slides
Overall agreement among the four pathologists was only fair (k=027 95 CI 014-038)
Agreement well-moderately differentiated versus poorly differentiated was only fair (k=027 95 CI 021-049)
EUS-guided Needle BiopsyInterobserver Agreement for Grading
Larghi A Am J Gastroenterol 2014submitted
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
3 2 2 3 1 2 2 1
3 1 2 2 2 1 3 2
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Nopts 30
Mean Age 557plusmn149
Lesion size 169plusmn61mm
Location
Uncinate
Head
Isthmus
BodyTail
3
5
4
18
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
EUS-FNTA successful in all patients without complications
Adequate samples for histological examination were retrieved in 2830 patients (929) and in all of them a diagnosis of PNENs was made
Ki-67 determination could be carried out in 2628 patients (866 of the initial entire cohort and in 929 of the patients with successful EUS-FNTA)
Larghi A et al Gastrointest Endosc 201276570-7
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Surgery le2 2-20 gt20
le 2 7 1
2-20 1 2
gt20 1
EUS-FNTA
EUS-FNTA and surgical pathology agreement in 12 pts
Histological Grading concordance in 1012
Surgery le5 5-20 gt20
le 5 8
5-20 3
gt20 1
Histological Grading concordance in 1212
EUS-FNTAPancreatic Neuroendocrine Neoplasms
Larghi A et al Gastrointest Endosc 201276570-7
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies
Chemo-sensitivity and Pancreatic Cancer can the EUS FNA replace surgical biopsy on chemo sensitivity assessment
Tissue is the Issue
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Pancreatic Cancer Stem Cells Isolation and Culture
48 hours from isolation
Magnification 10X
12 days from isolation
Magnification 10X
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Pancreatic CancerT stage
T stagingT1 Tumor limited to pancreas
Size le 2cm in greatest dimensionT2 Tumor limited to pancreas
Size gt 2cm in greatest dimensionT3 Tumor infiltration of bile duct
papilla duodenumT4 Tumor infiltration of stomach spleen
colon major arteries and PV SMV
and PV SMV
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
Diagnostic accuracy of EUS for vascular invasion a meta-analysis (29 studies)
Sensitivity 73 Specificity 90 Positive likelihood ratio 91 (measure of how
well the test identifies the disease) Negative likelihood ratio 03 (how well the test performs in excluding the disease)EUS is a better test to identify vascular invasion rather then excluding it
EUS StagingVascular Invasion
Puri SR Gastrointest Endosc 200765788-97
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Pancreatic CancerVascular Invasion
Sensitivity 50-90
Specificity 90-100
PVconfluence EUS superiorSMV Equivalent (~CT)Celiac trunk Equivalent (~CT)HA SMA CT superior
SMV
Mass
Confluence with PV
Stomach
Liver
Encasement of SMV
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
EUS-FNA in Pancreatic Cancer Staging
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Pancreatic Cancer Clinical Impact of EUS-FNA
Lack of data besides tissue diagnosis 99 patients elegible for surgery
In 12 patients (12) EUS FNA revealed Metastatic distant lymph nodes (6) Liver mets (4) Malignant ascites (1) Retroperitoneal infiltration (1)
Mortensen MB Endoscopy 200133478-83
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Pancreatic LesionsRole of EUS
Screening Equivocal results of previous
imaging modalities Differential diagnosis and risk
assessment Staging TherapyInterventional EUS
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Biliary Access and Drainage
Candidates Patients with benign and malignant biliary
diseases after ERCP failure
Approach Transgastric or transduodenal
Procedure Rendez-vous Direct stent placement
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
EUS-Guided Biliary Drainage
Intrahepatic ExtrahepaticIntrahepatic Extrahepatic
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Author yr
No of Patients
Technical success
Clinical Success
Complications
Maranki 2009 49 84 80 18
Park do 2011 57 96 89 47
Shah 2012 68 85 85 9
Iwashita 2012 40 73 73 12
Dhir 2012 58 98 98 3
Vila 2012 106 70 70 23
Horaguchi 2012 21 100 100 10
Park do 2013 45 91 87 11
Dhir 2013 35 97 97 23
Khashab 2013 35 94 91 14
Dhir 2013 68 97 97 21
Kawakubo 2013 64 95 95 42
Gupta 2014 240 99 87 35
EUS-Guided Biliary Drainage
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Lumen-Apposing DevicesAxios stent
Lumen-Apposing DevicesHot Axios stent
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma
EUS-guided fine needle injection(EUS-FNI)
EUS-guided Implantation Therapy
EUS-guided Tumor Ablation
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Cytoimplant (allogenic mixed lymphocyte culture) for pancreatic cancer
ONYX-015 for pancreatic cancer in association with RT + Gemcitabine
TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX GM-CSF carried by Oncolytic herpes
Virus
EUS-guided Fine Needle Injection
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Fine Needle InjectionTNFerade
TNFerade in pancreatic adenocarcinoma
IONIZING RADIATION TNF alpha
Enhanced Radiosensitivity
Enhanced Tumor Necrosis
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
50 pts locally advanced panc adenocarcinoma 5 wks treatment of weekly TNFerade (4x109
4x1010 4x1011 particles unit in 2ml) IV 5-FU (200mgm2d x 5dwk)+Radiation (504 Gy) Toxicity mild well tolerated Higher dose vs Lower doses
Greater locoregional control Longer progression free survival Improved median survival
45 pts tumor resected with negative margins and 3 survived more than 24 mos
Hecht JR Gastrointest Endosc 201275332-8
EUS-guided FNI of Pancreatic ADKTNFerade Injection
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
304 pts locally advanced panc adenocarcinoma Randomly assigned 21 to standard of care plus
TNFerade (SOC 1113088 TNFerade) versus SOC alone SOC IV 5-FU (200mgm2d x 5dwk)+Radiation
(504 Gy) followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy
TNFerade 4x1011 PU weekly for 5 wks Median progression-free survival (PFS) 68 mos for
SOC + TNFerade vs 70 mos for SOC (P = 51) Multivariate analysis EUS-TNFerade injection was
a risk factor for inferior PFS Herman JM J Clin Oncol 201331886-94
EUS-guided FNI of Pancreatic ADKTNFerade Injection
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Implantation Therapy
Fiducial markers placement for IGRT and Cyberknife
Brachytherapy
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Implantation TherapyFiducial Placement
Antibiotic prophylaxis Sterilized gold fiducials
3mm in length 08mm in diameter with 19G needle 10mm in length 035mm in diameter with 22G needle
Preloaded into the needle Needle tip sealed with wax Deployed by advancing the stylet or hydrostatic
pressure with sterile water 4-6 fiducials should be deployed
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Implantation TherapyFiducial Placement
Author (yr) No pts
Fiducial
needle
Site Success Complications
Pishvaian 2006
13 5x08mm
19G
Mediastinal and abdominal malignancies
1113 (85)
1 Infection within 1 month
Yang 2009 16 5x08mm
19G
Prostate 1616 (100)
None
Park 2010 57 25x08mm19G
Pancreas 5053 (94)
1 Minor bleeding
Varadarajulu 2010
9 3x08mm 19G
Pancreas 99 (100)
None
Sanders 2010
51 3x08mm 19G
Pancreas 4550 (90)
1 Pancreatitis
3 Spontaneous migration
DiMaio 2010 30 10x035mm 22G
Mediastinal and abdominal malignancies
2930 (97)
1 Fever
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Implantation TherapyBrachytherapy
Author (yr)
No pts
Success Results Complications
Suns 2006
151515
(100)
Partial remission in 27 minimal 20 stable 33 Pain relief in 30 but not limited in time
AP in 3 pts with pseudocyst formation in 2
Jin 2008
222222
(100)
Partial remission in 136 stable in 455 Pain relief of 1 month duration
Fever in 545
EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
EUS-guided directed Therapy
Gastrointest Endosc 20045995-9
Animal Studies Photodynamic therapy (Chan HH
Gastrointest Endosc 20045995-9 Yusuf TE Gastrointest Endosc 200867957-61)
NdYAG laser (Di Matteo Gastrointest Endosc 201072358-63 Di Matteo Gastrointest Endosc 201378750-5)
High-Intensity Focused Ultrasound (Hwang J Gastrointest Endosc 201173AB155)
Radiofrequency Ablation
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
EUS-guided treatment of Pancreatic ADKCryoThermal Ablation
22 pts locally advanced panc adenocarcinoma Flexible bipolar device that combines bipolar
radiofrequency with cryogenic cooling Radiofrequency heating 18 W pressure for cooling
650 psi (Pounds per Square Inch) application time depending on tumor size
Successfully applied in 16 patients (73) Cystic fluid collection formation in one patient In 6 patients clear definition of the tumor margins
after ablation was possible and decreased tumor size was observed (p=07)
Arcidiacono PG Gastrointest Endosc 2012 761142-51
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
Therapeutic EUS and PNENsAlcohol Ablation
78 yo F with insulinoma unfit for surgery
13mm lesion in the body
8ml of 95 ethanol injected
Mild transient pancreatitis
Symptoms disappearance after injection
F with insulinoma refused surgery
11 and 7mm lesions in the body
2ml of 45 ethanol injected 2 sessions
After second section pancreatic necrosis requiring surgery
