Cancer Gastrico- Peru 2013

8/12/2019 Cancer Gastrico- Peru 2013

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CANCER GASTRICO: ESTADO ACTUALCarlos A. Garberoglio, MD, FACS

Professor of Surgery

Chief of Surgical OncologyChairman, Department of Surgery

Chief Surgical Services for LLU

XIII Congreso Internacional de CirugaGeneral y IX Congreso del Capitulo

Peruano del ACS


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Epidemiology

Incidence of gastric cancer declining

Most common cause of cancer death among menand third among women in the US in 1930

Currently no longer in the top 10 causes ofcancer death in the US

Incidence of EGJ cancer increasing

Dempsey, DT. (2010).Schwartz's principles of surgery(pp. 889- 948).Siegel, R et al (2012). CA Cancer J Clin 62, 10-29

LYMPHADENECTOMY IN GASTRIC ADENOCARCINOMA


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Siewert type 1

Siewert type 2

Siewert type 3

Anatomic Cardias

Esophago-Gastric Junction Cancer

Siewert Classification

5cm

1cm

2cm

5cm


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National Comprehensive Cancer

Network Guidelines 2011

ESOPHAGEAL & EGJCANCERS:

Removal of at least 15 lymphnodes for adequate staging forthosewithout neoadjuvanttherapy.

For thosewith neoadjuvanttherapy no optimum numberof nodes have been establishedalthough 15 lymph nodes isrecommended

GASTRIC CANCER:

Gastric resection should

include the regionallymphatics:

Perigastric lymph nodes (D1)

Those along the namedvessels of the celiac axis (D2)

A goal of examining at least 15or greater lymph nodes


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Role of the Surgeon

Staging

Resectable Tumors

Unresectable tumors

D1 vs D2

Palliative procedures

Intraperitoneal hyperthermic chemotherapy(IPEC)

Hereditary Diffuse Gastric Cancer (HDGC)


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Role of the Surgeon

Staging:

Extent of disease, CT, EUS, PET

Laparoscopy (peritoneal washing)

Cytology

Sarela AI ef al AM J Surg. 2006;191(1):134-138

Mezhir JJ ef al Ann Surg Oncol. 2010 Jun 29.


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CT C/A/P

PET Scan

EUS

HER2-neu


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Role of the Surgeon

Resectable Tumors:

Tis or T1 (T1a) EMRT1b- T2- T3

Distal Gastrectomy

Subtotal Gastrectomy

Total GastrectomyT4

D1 vs D2 or LNs > 15

Splenectomy


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Principles of Gastric Surgery

Gastrectomy

Location of tumor Margins

Lymph nodes

Splenectomy

Jejunostomy Reconstruction


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Distal

Location of Tumor

Roux-en-y


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A. Total

B. Subtotal

Location of Tumor


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Principles of Gastric Surgery Margins >or= 4cm

Ito, H. et al. J Am Coll Surg, Vol. 199, No. 6, Dec 2004


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Gastrectomy

Lymph Nodes

The # of positive nodes best defines the prognosticinfluence of metastatic LNs in gastric cancer

Survival estimates were significantly influenced byexamining 15 or more nodes

Karpeh M ef al, Ann of Surg, Vol 232,3,362,2006


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Lymph node stations according to the Japanese ResearchSociety for Gastric Cancer (JRSGC)


Tamura S. et al. Int J Surg Oncol. 2011;2011:748745


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Japanese surgeons reported goodsurvival data with D2 dissections asearly as the 1970's; D2

lymphadenectomy became well-established in Japan and otherEastern nations

Surgeons in the West, however, weremore reluctant to adopt the moreinvasive techniques due to concernover the potential for complications

Standards of Care and Retrospective Studies


Bonenkamp et al. The Lancet, 1995; 345, 745-8.


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Randomized controlled trials comparing D1 withD2/D3


Tamura S. et al. Int J Surg Oncol. 2011;2011:748745


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D2 vs. D3 Meta-analysis

4 randomized controlled

trials 4 non-randomized

controlled trials

No difference in survival

Show D3 can be done assafely as D2 dissection

Wang Z et al. World J Gastroenterol 2010; 16(9), 1138-49.


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Sentinel Lymph Nodes A retrospective analysis

of lymph nodepathology following D2lymphadenectomy

Describes patterns inlymph node metastases

Adjacent, transverse,and skip metastases

Validity of JRSGClymph node stations?

Liu CG, et al. World J Gastroenterol. 2007; 13(35), 4776-80.


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Rational

Lymphadenectomy

Specific recommendations byauthors: Upper stomach, lesser curvature,

treat 7 and 8 as N1

Middle stomach, lesser curvature,treat 7 as N1 Middle stomach, greater

curvature, inspect 10 carefully,and if suspicious, performsplenectomy (40 of 41 injectionsof Prussian Blue into the greatercurvature flowed directly tostation 10 [Chen, et al.])

Lower stomach, lesser curvature,inspect 1, 7, and 8 carefully

Liu CG, et al. World J Gastroenterol. 2007; 13(35), 4776-80.


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Accuracy of Sentinel Node Mapping 80 patients with intraoperative dye injection

Lower T stage, higher chance of SLN discovery

T1 90.9%, T2 88.2%, T3 68.8%

Overall positive correlation fairly high

In 90.2%, SLN status matched nSLN status (35 SLN+ werenSLN+; 20 SLN- were nSLN-)

However, 6 of 26 patients with SLN- were nSLN+

Rabin I, et al. Gastric Cancer. 2010; 13, 30-35.


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Number of Nodes Important?

Retrospective cohort taken from Surveillance,Epidemiology, and End Results database Selected for patients who had gastrectomy for

nonmetastatic gastric cancer, including 1 lymph nodedissected and analyzed, and whose tumors fell underT1-3 N0-1 stages (1973-2000, n = 3814)

Found linear relationship between number of lymphnodes dissected and analyzed, and overall survival Cannot dismiss effect of understaging

Smith DD, et al. J Clin Oncol. 2005; 23(28), 7114-24.


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Principles of Gastric Surgery, Contd

Gastrectomy with and without Splenectomy

Yu W, et al. British Journal of Surgery 2006, 93: 559-563


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Robotic Gastrectomy and

Lymphadenectomy


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da VinciGastrectomy

Excellent retraction and exposureenabling meticulous dissection12,13,14,15

Ability to offer a minimallyinvasive approach for complete D2lymph node dissection13,14,15

Enhanced capability for intra-corporeal anastomosis14

Improved vascular identification andaccess for precise dissection andtransection15,16


Lymphadenectomy


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Lymphadenectomy


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The celiac trunk (CT) and its branches are completely exposed after node dissection.CHA, common hepatic artery; LGA, left gastric artery; SA, splenic artery


Lymphadenectomy


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The terminal esophagus fully mobilized. Diaphragmatic crura are exposedand freed from the surrounding adipose and lymphatic tissue


Lymphadenectomy


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Lymphadenectomy

The anvil head is introduced into the esophageal stump and secured with thepurse-string suture


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Lymphadenectomy (Initial Experience)

Anderson C, Pigazzi A et al. Surg Endosc 2007 21: 1662-66


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Conclusions

Arguments for D2 vs. D1 lymphadenectomy Long-term survival benefit

Recurrence-free survival

Gastric cancer specific survival Overall survival benefit possible?

Improved accuracy of staging

New directions and new research

Studies using pancreas- and spleen-sparingapproaches Sentinel lymph node dissection D2 lymphadenectomy and esophageal anastomoses

made easier technically by robotic technology


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Unresectable Tumors

Palliative gastric resection?

LN dissection?

Gastric bypass vs stenting?

Venting gastrostomy x or jejunostomy


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Role of the SurgeonUnresectable tumors:

Locoregionally advance

Level 3 or 4 LNs (+)

Invasion or encasement of vessels

Distant mets Peritoneal etc


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Criteria of Unresectability for Cure Locoregionally advanced

Level 3 or 4 LNs

Invasion or encasement of vessels

Ascitis

Distant Metastasis


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Role of the SurgeonPalliative procedures

Gastric resection

LND Not required

Gastric bypass vs stenting

Venting gastrostomy and/or jejunostomy


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Role of the SurgeonIntraperitoneal hyperthermic chemotherapy(IPEC)

Peritonectomy

T4 M0


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Hyperthermic Intra Peritoneal

Chemotherapy (HIPEC)

Table 2

Stewart J.H., et al Exp. Rev. Autica Ther. 8(11), 2008


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Table 3. Results of intraperitoneal hyperthermic chemotherapy for gastric and

colorectal peritoneal carcinomatosis

Author Patients

(n)

Drug Median

survival

(months)

1-year

survival

(%)

3-year

survival

(%)

5-year

survival

(%)

Morbidity

(%)

Mortality

(%)

Ref

Colorectal cancer

Cavalier et al.

(2006)

120 Cisplatin

MMC

25.8 22.5 3.3 [42]

Zanon et al.

(2006)

25 MMC 30.3 64 24 4 [43]

Glehen et al.

(2004)

506 Various 19 72 39 19 23 4 [44]

Glehen et al.

(2004)

53 MMC 13 55 11 23 4 [4]

Shen et al.

(2003)

40 MMC 14 60 25 36 8 [32]

Gastric Cancer

Yonemura et al. 107 MMCEtoposide

Cisplatin

11.5 6.7 22 3 [48]

Glehen et al.

(2004)

49 MMC 10 48 20 16 27 4 [49]

Levin et al.

(2004)

34 MMC 8 27 23 6 35 0 [50]

MMC: Mitomycin-C


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Intra Peritoneal Hyperthermic

Chemoterapy (IPHC)

Meta-analysis 10 studies

IPHC and resection of advance gastric cancer isassociated with improved overall survival

Yan, Tristan D., et al. Ann. SurgOnc 14 (10) 2007


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Chemoterapy (IPHC)

Current Indications

Gastric CA with R0/1 resection

T4M0

Survival

R0/1: 11.2 months

R2: 4.6 months


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Role of the SurgeonHereditary Diffuse Gastric Cancer (HDGC)

Prophylactic T. gastrectomy


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Loma Linda University Robotic and Advanced Laparoscopy Surgical Center


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Staging

Criteria of Unresectability for Cure Resectable Tumors

Unresectable Tumor (Palliative)


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Resectable Tumors TIS or T1 (T1a) EMR

T1b T3

Gastrectomy

T4

En bloc resection

Soetikno R. J Clin Oncol. 2005;23(20):4490-4498


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Dutch Gastric Cancer Trial

Study design: Randomized 1078 patients enrolled 711 curative resection

380 to D1 arm 331 to D2 arm

285 received palliativetreatment

82 were excluded 35 due to lack of supervising

surgeon Remainder due to

misdiagnosis or unfit physicalcondition

Japanese proctor andcentralized quality control

Bonenkamp et al. The Lancet, 1995; 345, 745-8.

Leyden University Medical Center


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Dutch Gastric Cancer Trial Showed significantly higher post-operativemorbidity and mortality in D2 patients than D1

Failed to show survival benefit for D2 dissection

5-year survival 45% in D1 vs. 47% in D2 Concluded D2 dissection should not be usedtherapeutically or routinely

Bonenkamp et al. The Lancet. 1995; 345, 745-8.

Bonenkamp et al. N Engl J Med.1999; 340(12), 908-14.


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UK Medical Research Council Study design

737 patients underwent staging laparotomy

400 patients were eligible and were randomized 200 to D1 200 to D2

Complete follow-up to death or 3 years in 96%

Median follow-up duration 6.5 years Intention-to-treat analysis

Cuschieri, A, et al. The Lancet. 1996; 347, 995-9.

Cuschieri, A, et al. Br J Cancer. 1998; 79, 1522-30.


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UK Medical Research Council

This study also showed increased morbidity andmortality in the D2 arm, which subset analysis attributedto pancreatico-splenectomy

Showed no overall survival benefit at 5 years (35 vs.

33%), even with postoperative deaths censored Showed no difference in recurrence rates

Ninewells Hospital and Medical SchoolDundee, United Kingdom


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MRC Analysis of Pancreatico-splenectomy

The authors of the UK MRC published ananalysis of the morbidity and mortality

associated with pancreatic-splenectomy When controlled for pancreatic-splenectomy, D2dissection showed survival benefit

Tumor location was possible confounder, as thosepatients who had D2 therapy withoutpancreaticosplenectomy had tumors locatedoverwhelmingly in the gastric antrum

Cuschieri, A, et al. Br J Cancer. 1999; 79, 1522-30


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Italian Gastric Cancer Study Group (IGCSG) Single arm, prospective trial

191 patients enrolled All underwent D2 resection

Pancreas preserved

39 nodes average (range 22-93) Compared favorably

Morbidity 20.9% (43% DGCT)Anastamotic leak 7.1%

Lower mortality, as well

3.1% overall (10% DGCT), 7.49% aftertotal gastrectomy 17 day average hospital stay (25

DGCT, D2 arm)City of Turin, Italy

Degiuli, M, et al. J Clin Oncol. 1998; 16(4), 1490-3.


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15-year Follow-up to DGCT

After 15 years, authors of DGCT show gastric cancer-specific survival benefit and lower locoregionalrecurrence for D2 dissection

They speculate that pancreas- and spleen-sparing

techniques may have shown overall survival benefit

Songun I et al. Lancet Onc. 2010; 11, 439-49.


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Italian Gastric Cancer Study Group

Enrolled 267, randomised to treatment arms 133 in D1 arm, 134 in D2 arm Enrollment stopped early, lowering power

Could not show noninferiority with ITT analysis Upper limit of C.I. (13) > established limit (12) Significant contamination and non-compliance

Degiuli M, et al. Br J Surg. 2010; 97, 643-9.


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Chemoterapy (IPHC)

Table 3

Stewart J.H., et al Exp. Rev. Autica Ther. 8(11), 2008

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Cancer Gastrico- Peru 2013

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