DETERMINING RESECTABILITYIN PANCREATIC CANCER

Moderator :

Dr. B. Srihari rao M.SDr. C. Srikanth Reddy M.SDr. K. Keerthinmayee M.S

Presenter: Dr. Harish Y S

Discussed by

INTRODUCTION CLASSIFICATION OF TUMORS STAGING OF TUMORS ANATOMY OF PANCREAS National Comprehensive Cancer Network (NCCN)

GUIDELINES INCREASING RESECTABILITY RATES VENOUS RESECTION ARTERIAL RESECTION. MANAGEMENT

INTRODUCTION It is the 13th most common cancer worldwide. 5th MC cause of cancer-related mortality.

Incidence rate is 9.7 per 100,000. Its peak incidence between the 7 & 8 decades

and It is rare < 40yrs. Male to female ratio is 1:1

Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The globalpicture. Eur J Cancer. 2001;37 Suppl 8:S4-66

INTRODUCTION It has an overall survival of 0.4% to 4%. These patients presents late,

At the time of diagnosis < 20% of patients are surgically resectable disease

Of the inoperable ones, 1/3 rd. with distant metastases and Remaining 1/3 rd. with locally advanced disease.

Defining resectability is therefore one of the most important and crucial aspects in the management of pancreatic cancer.

WHO Classification of pancreatic exocrine tumors

Benign tumors:

Serous cystadenoma

Mucinous cystadenoma Intraductal papillary-mucinous adenoma Mature teratoma Borderline (uncertain malignant potential) Solid-pseudopapillary neoplasm

Most common

WHO Classification of pancreatic exocrine tumorsMalignant tumors: Ductal adenocarcinoma

Mucinous noncystic carcinoma Signet ring cell carcinoma Adenosquamous carcinoma Undifferentiated (anaplastic) carcinoma

Serous cystadenocarcinoma Mucinous cystadenocarcinoma intraductal papillary-mucinous carcinoma Acinar cell carcinoma Pancreatoblastoma Solid-pseudopapillary carcinoma

TNM STAGING:

The American joint committee on cancer stage

Arterial supply of pancreas

Venous drainage of pancreas

Lymphatic drainage of pancreas

Historically pancreatic tumours have been classified as either resectable or unresectable.

It is primarily the relationship of the pancreatic cancer to the vessels that defines resectability.

Over the last two decades the terms “locally advanced” and “borderline resectable” pancreatic cancer have come in to use.

LOCALLY ADVANCED PANCREATIC CANCER Locally advanced pancreatic cancer is described as

Tumor invaded locally adjacent structures such as major blood vessels, lymph nodes, bowel or the bile duct, without evidence of distant metastatic disease.

Involvement of para-aortic LN considered as metastasis and sugically contrindicated.

Locally advanced pancreatic cancer may or may not be resectable and would include T3 and T4, whereas T1 and T2 are considered resectable tumours.

BORDERLINE RESECTABLE PANCREATIC CANCER It is defined by two groups

MD Anderson Cancer Center (MDACC) American HepatoPancreatoBiliary Association (AHPBA)/

Society of Surgical Oncology (SSO)/Society for Surgery of the Alimentary Tract (SSAT)

MDACC group describes any venous involvement as resectable disease and only occlusion of the SMV or PV (with the possibility of reconstruction) as borderline.

Cooper AB, Tzeng CW, Katz MH. Treatment of borderline resectable pancreaticcancer. Current treatment options in oncology. 2013;14(3):293-310.

National Comprehensive Cancer Network (NCCN) Guidelines for pancreatic cancer treatment. Pancreatic cancers classified in to

Resectable Borderline resectable and Unresectable.

Resectable Arterial: Clear fat planes around the coeliac axis (CA), SMA

and HA. Venous: The SMV or PV abutment but no distortion of the

vessels.

Borderline ResectableArterial :Pancreatic head /uncinate process: Solid tumor contact with CHA without extension to

celiac axis or hepatic artery bifurcation. Solid tumor contact with the SMA of ≤180° Presence of variant arterial anatomy (ex:

accessory right hepatic artery, replaced right hepatic artery, replaced CHA) and the presence and degree of tumor contact should be noted if present as it may affect surgical planning.

Borderline ResectablePancreatic body/tail: Solid tumor contact with the CA of ≤180° Solid tumor contact with the CA of ˃180°

without involvement of the aorta and with intact and uninvolved gastroduodenal artery.

Venous: Venous involvement of the SMV or PV with distortion or narrowing of the vein or occlusion of the vein with suitable vessel proximal and distal, allowing for safe resection and replacement.

Unresectable:

Arterial (Head of Pancreas): Greater than 180° encasement of the circumference of the SMA or any CA abutment.

Arterial (Body/Tail of Pancreas): SMA or CA encasement >180°.

Arterial (Any Part of the Pancreas): Aortic invasion or encasement.

Venous: Unreconstructable SMV and/or PV.

Nodal Status: Metastases to lymph nodes beyond the field of resection should be considered unresectable.

Grading system proposed by Lu et al. for predicting vascular invasion by tumor based on the degree of tumor contiguity with a vessel

GRADE DESCRIPTION COMMENTGrade 0 No contiguity of tumor with a

vesselVascular invasion in 0% of cases

Grade 1 Tumor is encasing <25% of the circumference of a vessel

0%

Grade 2 25–50% of the circumference of a vessel

57%

Grade 3 50–75% of the circumference of a vessel

88%

Grade 4 >75% of the circumference of a vessel or any vessel constriction

All cases

A fat plane is seen between thetumor and the superior mesenteric artery (SMA) and superior mesentericvein. No evidence of vascular invasion is seen.

The tumor is contiguous with < 90° of the superior mesenteric vein (Lu grade 1). There is no narrowing or wall irregularity of the SMV

MDCT OF PANCREATIC CARCINOMA

The tumor is contiguous with 90°- 180 of the superior mesenteric vein (Lu grade 2). There is no narrowing or wall irregularity of the SMV.

The tumor (T) in the head ofthe pancreas eroding the wall of the superior mesenteric vein (SMV) and penetrating it to form a tumor thrombus

Grading system proposed by Loyer et al. for predicting vascular invasion by tumorGRADE DESCRIPTION COMMENTType A Fat plane separates the tumor

and the normal pancreatic parenchyma from adjacent vessels

Overall resection rate: 100%.

Type B Normal parenchyma separates the tumorfrom adjacent vessels

Overall resection rate: 100%.

Type C Tumor is inseparable from adjacent vessels, and the points of contact form a convexity against the vessels

Overall resection rate: 89%.

Type D The points of contact form a concavityagainst the vessels or partially encircle the vessels

Overall resection rate: 47%.

Type E Tumor encircles adjacent vessels, and nofat plane is identified between the tumor and the vessels

Overall resection rate: 0%.

Type F Tumor occludes the vessels Overall resection rate: 0%.

APPROCH TO A PATIENT

Clinical suspicion of pancreatic cancer or evidence of dilated pancreatic duct.

MDCT angiography

Mass in pancreas

No mass in pancreas

No metastasis

Multidisciplanary review• LFT• EUS• Chest

imaging

Metastasis

Biopsy confirmation

No metastasis

• LFT• EUS/FNA• Chest

imaging• MRCP/ERCP

Metastasis

Biopsy confirmation

EUS

APPROCH TO A PATIENT

No metastatic disease on physical examination and imaging

No jaundice jaundice

Symptoms of cholangitis or fever

Short or self expanding metal stents and antibiotic coverage

No symptoms of cholangitis

Per operative CA-19-9

RESECTABLEBORDERLINE RESECTABLE

LOCALLY ADVANCED , UNRESECTABLE

RESECTABLE TUMORConsider staging laparoscopy in high risk patients

LAPAROTOMY

Surgical resection

Adjuvent treatment and surveillance

Unresectable tumor

Biopsy confirmation, if not performed previously

No jaundice

Gastrojujunostomy + celiac plexus

neurolysis (if pain)

Jaundice

Self expanding metal stents or biliary

bypass +Gastrojujunostomy

+ celiac plexus neurolysis (if pain)

The goals of surgical extirpation of pancreatic carcinoma focus on the achievement of an R0 resection

a margin positive specimen is associated with poor long-term survival

Achievement of a margin negative dissection must focus on meticulous perivascular dissection of the lesion in resectional procedures, recognition of the need for vascular resection and/or reconstruction

Surgical Procedures

Tumors of the Body and Tail Distal

Pancreatectomy

Removal of body & tail of pancreas

spleen

Surgical Procedures

Head of the pancreas: Whipple Procedure Removal of:

Distal stomach Duodenum and

proximal jejunem Head of pancreas Gallbladder and

common bile duct

Total pancreatectomy Indicated in tumor with multilocular or large

tumors.

It is combination of pancreaticoduodenectomy and distal pancreatectomy with local lymphadenectomy.

Complications are post operative exocrine and endocrine insufficiency and associated with high mortality rates.

If the tumor is found to be unresectable during surgery

biopsy confirmation of adenocarcinoma can be done.

If a patient with jaundice is found to be unresectable at surgery stenting or biliary bypass can be done

BORDERLINE RESECTABLE, NO METASTASISPlanned neoadjuvent therapy

Biopsy/ EUS+FNA / staging laparoscopy

Biopsy confirmed

Imaging: abdomen , chest and pelvis

Consider staging laparoscopy

Surgical resection Unresectable

Cancer not confirmed

Repeat biopsy

Biopsy confirmed

Biopsy not confirmed

Planned resection

INCREASING RESECTABILITY RATES Survival for pancreatic cancer has not changed in

the last 40 years. However, with advancement in surgical technique and improvement in perioperative care.

In Specialised centres, postoperative mortality rates of 2–3% have been reported.

The increased resectability and improve in long-term survival for patients with pancreatic cancer, extensive surgical procedures have been developed, mainly involving vascular reconstruction techniques.

INCREASING RESECTABILITY RATES Birkmeyer et al. first reported aggressive surgery

for borderline resectable pancreatic cancer with the first SMV resection and reconstruction in 1951.

In 1973, Fortner first described the regional pancreatectomy. This involved a total pancreatectomy, radical lymph node clearance, combined PV resection (type 1) and/or combined arterial resection and reconstruction (type 2).

Venous Resection Venous involvement is not considered a contraindication

to surgical resection.

Pancreatic resection requiring venous reconstruction is technically challenging and may be associated with a higher morbidity.

Ravikumar et al. published multicentre retrospective cohort study comparing, PD with venous resection (PDVR) and surgical bypass for T3 adenocarcinoma of the head of the pancreas.

1.Morbidity was similar between the PDVR and PD groups,

2.Patients requiring blood transfusion being greater in the PDVR group.Ravikumar R, Sabin C, Abu Hilal M, et al. Portal vein resection in borderline

resectable pancreatic cancer: a United Kingdom multicenter study. J Am Coll Surg. 2014;218(3):401-11.

Venous Resection

In 2006, Siriwardana reported a large systematic review of 1646 patientswho had undergone portal-SMV resection during pancreatectomy forcancer.

concluded that, with the high rate of nodal metastases and thelow five-year survival rates, once the PV is involved cure is unlikely evenwith radical surgery.

Several studies have shown that PV resection in patients with pancreatic cancer has comparable survival compared to standard pancreatectomy and

It is a safe procedure when performed in specialist HPB Units

Siriwardana HP, Siriwardena AK. Systematic review of outcome of synchronous portal-superior mesenteric vein resection during pancreatectomy for cancer. Br J Surg. 2006;93(6):662-73

Venous Resection

Lygidakis et al. compared en bloc splenopancreatic and venous resection versus palliative gastrobiliary bypass and reported two-year survival rates of 81.8% and 0%, respectively.Randomised controlled trial by Doi et al. in 2008 was closed early when interim analysis showed a clear survival benefit for PDVR with chemoradiotherapy compared with chemoradiotherapy with or without a surgical bypass

Lygidakis NJ, Singh G, Bardaxoglou E, et al. Mono-bloc total spleno-pancreaticoduodenectomyfor pancreatic head carcinoma with portal-mesenteric venous invasion. A prospective randomized study. Hepatogastroenterology. 2004;51(56):427-33. Doi R, Imamura M, Hosotani R, et al. Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial. Surg Today. 2008;38(11):1021-8.

Arterial Resection In 2007, Hirano et al. reported their long-term

follow-up for patients undergoing distal pancreatectomy with en bloc CA resection (DP-CAR)

They reported 1yr and 5yr survival rates of 71% and 42%, respectively, and

concluded that DP-CAR offers a high resectability rate and may potentially achieve complete local control in selected patients.

Hirano S, Kondo S, Hara T, et al. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg. 2007;246(1):46-51.

Arterial Resection Bachellier et al., in 2011, matched a group of patients

undergoing pancreatectomy with arterial resection to conventional pancreatectomy and demonstrated similar three-year survival rates.

Bockhorn et al. reported one of the largest series on pancreatectomy with simultaneous arterial resection (n = 29) and

concluded that there was no overall difference in disease-specific survival for patients who underwent arterial reconstruction versus those patients who underwent pancreatectomy alone

Bachellier P, Rosso E, Lucescu I, et al. Is the need for an arterial resection a contraindication to pancreatic resection for locally advanced pancreatic adenocarcinoma? A case-matched controlled study. J Surg Oncol. 2011;103(1):75-84.

Bockhorn M, Burdelski C, Bogoevski D, et al. Arterial en bloc resection for pancreatic carcinoma. Br J Surg. 2011;98(1):86-92.

Arterial Resection Mollberg et al. in 2011, systematic review and meta-

analysis. This report included 26 studies, a total of 2609 patients,

366, out of the 2609 patients underwent an arterial resection and reconstruction in conjunction with a pancreatectomy.

Results: Significantly increased perioperative morbidity and a mortality

rate compared with standard pancreatectomy . Significantly poorer survival outcomes at

one year (49.1%), three years (8.3%) and five years (0%) were demonstrated in this study

LOCALLY ADVANCED UNRESECTABLE TUMOR

Biopsy ,if not previously performed

Adenocarcinoma confirmed

If jaundice, placement of

self expanding

metal stents.

CHEMOTHERAPY

Cancer not confirmed

Repeat biopsy

Others cancers

Treat as appropriate

LOCALLY ADVANCED UNRESECTABLE TUMOR

FOLFIRINOX or

Gemcitabine or

Gemcitabine + albumine bound paclitaxel. or

Capecitabine + continuous IV

5-FU or

Fluropyrimidine + oxaliplatine or

Clinical trial preferred.

Fluropyrimidine based therapy if previously treated with Gemcitabine based therapy

Gemcitabine based therapy if previously treated with Fluropyrimidine based therapy

PALLIATIVE AND BEST SUPPORTIVE CARE

METASTATIC DISEASE

If jaundice, placement of self expanding metal stents.

Good performance

CHEMOTHERAPY

Poor performance

Palliative and supportive care.

SURVIVAL 5-year survival rate of

R0 resection - 24.2% R1 and R2 resection - 4.3%

Median survival in R0 resected patients, the was 28 months with pancreaticoduodenectomy and 26 months with PPPD.

R1 resected patients - 15 months R2 resected patients - 9.8 months Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg 2004;91:58694

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