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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Principles of Gastric Surgery
Distal
Location of Tumor
Roux-en-y
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Principles of Gastric Surgery
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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Principles of Gastric Surgery
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)
LYMPHADENECTOMY IN GASTRIC ADENOCARCINOMA
Tamura S. et al. Int J Surg Oncol. 2011;2011:748745
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LYMPHADENECTOMY IN GASTRIC ADENOCARCINOMA
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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
LYMPHADENECTOMY IN GASTRIC ADENOCARCINOMA
Bonenkamp et al. The Lancet, 1995; 345, 745-8.
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Randomized controlled trials comparing D1 withD2/D3
LYMPHADENECTOMY IN GASTRIC ADENOCARCINOMA
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
Robotic Gastrectomy and
Lymphadenectomy
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Robotic Gastrectomy and
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
Robotic Gastrectomy and
Lymphadenectomy
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The terminal esophagus fully mobilized. Diaphragmatic crura are exposedand freed from the surrounding adipose and lymphatic tissue
Robotic Gastrectomy and
Lymphadenectomy
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Robotic Gastrectomy and
Lymphadenectomy
The anvil head is introduced into the esophageal stump and secured with thepurse-string suture
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Robotic Gastrectomy and
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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Principles of Gastric Surgery
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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Principles of Gastric Surgery
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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Intra Peritoneal Hyperthermic
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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Principles of Gastric Surgery
Staging
Criteria of Unresectability for Cure Resectable Tumors
Unresectable Tumor (Palliative)
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Principles of Gastric Surgery
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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Intra Peritoneal Hyperthermic
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Intra Peritoneal Hyperthermic
Chemoterapy (IPHC)
Table 3
Stewart J.H., et al Exp. Rev. Autica Ther. 8(11), 2008
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