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GASTRIC CANCER
Joyce Au SUNY Downstate Grand Rounds July 11, 2013
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xxM with gastric adenocarcinoma on biopsy of antral lesion on EGD at outside hospital
PMH: residual schizophrenia, HTN PSH: exploratory laparotomy and omental patch
repair for perforated gastric ulcer in 2012 Soc hx: 30 pack years; assisted living facility
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Thin NAD AAO RRR Clear BS b/l Abd soft, ND, NT, well healed midline scar Ext – no edema No CVA tenderness
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CBC: 10.3 / 14.3 / 44.7 / 280 BMP: 137 / 4.4 / 100 / 26 / 11 / 0.71 / 95 Coags: 10.1 / 0.9 / 25.2 EKG – normal sinus rhythm Chest CT – normal, no metastasis Abd CT – irregular mass at antrum causing partial
gastric outlet obstruction, no metastasis
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OR EGD - ulcerated mass in the antrum Findings: antral mass, no liver or peritoneal lesions Procedure: subtotal gastrectomy with D2
lymphadenectomy and Billroth II reconstruction EBL: 50ml JP by duodenal stump
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Patient pulled out NG on POD#4 Started on clear liquid diet on POD#5 which was
tolerated and advanced JP was removed Discharged back to assisted living on POD#7
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Pathology 3 cm moderately differentiated adenocarcinoma Intestinal type Invasion into muscularis propria Negative margins 0/23 LN
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GASTRIC CANCER Introduction Workup Surgery Chemoradiation
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INTRODUCTION
World’s 4th leading cause of cancer-related death >10,000 deaths from gastric cancer annually in the
U.S.
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Risk factors Ethnicity
Japanese, Koreans, Native Americans, Hawaiians > Chinese, African Americans, Latinos > Caucasians, Filipinos
Male > female Obesity (proximal CA) Prior radiation, EBV (proximal, diffuse type) History of gastric resection
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Diet salt, smoked, cured, nitrates, nitrites, nitrosamines… carcinogenic N-
nitroso compounds Tobacco Pernicious anemia (synchronous lesions) Villous adenomas in gastric polyps H. pylori
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Genetic Hereditary diffuse gastric cancer
Autosomal dominant CDH1 mutation for E-cadherin Prophylactic gastrectomy
Li-Fraumeni syndrome - p53 mutation BRCA2 HNPCC FAP Peutz-Jeghers syndrome
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Pathology Arise from mucous-producing cells in 95% Lauren classification
WHO classification tubular, mucinous, papillary, signet cell
INTESTINAL TYPE DIFFUSE TYPE
Well to moderately differentiated Poorly differentiated
Intestinal metaplasia, chronic gastritis Signet cells, mucin
Older, male, lower socioeconomic Younger, obese
Proximal tumors Distal tumor
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Distal vs. proximal (cardia) cancer Most lesions are in the antrum Recently, have decreasing distal lesions and increasing cardia
lesions 9% involve entire stomach – linitus plastica Lesser curvature > greater curvature
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Presentation Most common sx: weight loss, epigastric pain, vomiting,
anorexia 10% with signs of metastatic disease
Virchow node, Sister Mary Joseph node Blummer shelf Ascites, jaundice, liver mass
Asymptomatic from EGD screening in Japan and Korea
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WORKUP
H&P EGD – 4-6 bx for dx; surgical planning; palliative
interventions (ablation, stents, etc.) EUS - 75% accuracy in staging; FNA Chest/abd/pelvis CT – 66-77% accuracy in staging Laparoscopy – <5 mm lesions seen in about 30%
patients Peritoneal cytology – 3-9 month median survival; M1
MD Anderson Surgical Oncology Handbook, 5th ed.
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7th edition AJCC Staging, 2010 Tumors in the GEJ, or arising <5 cm from GEJ and
crosses the GEJ are staged as esophageal carcinomas Tumors in the lamina propria are now T1a Fewer nodes for higher nodal status (ex. N1=1-2 LN) + peritoneal cytology is M1
Washington et al. Ann Surg Oncol 2010;17:3077-3079
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(tnm)
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Washington et al. Ann Surg Oncol 2010;17:3077-3079
1
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SURGERY
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History 400 B.C. Aesculapius cut out a stomach ulcer Pean in 1879 and Rydigier in 1880 resected
the pylorus, but their patients died Billroth in 1881 performed the 1st successful
gastrectomy with gastroduodenostomy Wolfler in 1882 performed a palliative loop
gastrojejunostomy Billroth in 1885 reconstructed with
gastrojejunostomy
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A.) Gastrectomy B.) Splenectomy C.) Lymphadenectomy D.) Reconstruction
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A.) What kind of gastrectomy? • Unresectable if encasing major vascular structures, N3
or N4, or peritoneal or distant metastasis
• Endoscopic mucosal resection in Japan • Limited to mucosa (Tis or T1a), <1 cm with depressed types, <2
cm with elevated types, well-differentiated • No randomized controlled trials on it
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Participants - 648 patients, 31 centers Intervention – subtotal gastrectomy; vs. total
gastrectomy; both with D2 Similar 5-year survival
Bozzetti et al. Ann Surg 1999;230:170-178
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Subtotal gastrectomy 25-30% remnant supplied by short gastrics 5-6 cm proximal margin Frozen section to confirm negative margin
With negative margin as a requirement, subtotal gastrectomy is preferred for better nutritional status and quality of life
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B.) What about splenectomy? Splenectomy did not improve survival, even with
metastatic LN by splenic hilum or artery
Yu et al. Br J Surg 2006;93:559-563
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Splenectomy with greater septic complications Up to two-fold risk of postoperative morbidity and
mortality with splenectomy and distal pancreatectomy
Unless there is malignant invasion into the spleen, splenectomy should be avoided
Fang et al. Hepatogastroenterology 2012;59:1150-1154 Csendes et al. Surgery 2002;131:401-407 Bozzetti et al. Ann Surg 1997;226:613-620
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C.) Lymphadenectomy – D1 or D2? Goal to examine at least 16 LN D1 = perigastric LN; within 3 cm D2 = perigastric LN + LN of the celiac and its main branches
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D1 D2 www.downstatesurgery.org
D2 is a standard in Asia Studies in the West question D1 vs. D2
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MRC ST01 Participants: 400 patients Intervention: D2, with pancreatectomy & splenectomy; vs.
D1 Similar 5-year survival (33% vs. 35%) Similar gastric-cancer related survival and recurrence-
free survival
Cuschieri et al. Br J Cancer 1999;79:1522-1530
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Participants: 711 patients, 80 hospitals Intervention: D2, with pancreatectomy & splenectomy; vs.
D1 Outcomes:
Higher postoperative mortality (10% vs. 4%) Higher postoperative morbidity (43% vs. 25%) Higher reoperation (18% vs. 8%) Similar 5-year relapse rate (37% vs. 43%) Similar 5-year survival (47% vs. 45%)
Bonenkamp et al. NEJM 1999;340:908-914
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Outcome at 11 years Similar survival at 11 years (35% vs. 30%) Among patients with N2 disease, trend for greater survival with
D2 dissection (21% vs. 0%, p=0.078) Greater morbidity and mortality with D2, pancreatectomy,
splenectomy, age >70 years
Hartgrink et al. J Clin Onc 2004;22:2069-2077
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Outcome at 15 years D2 with less gastric-cancer
related deaths (37% vs. 48%) Less local recurrence
(12% vs. 22%) Less regional recurrence (13%
vs. 19%) Less metastasis
(11% vs. 17%)
Songun et al. Lancet Oncol 2010;11:439-449
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Addition of para-aortic LN dissection did not improve survival but did increase blood loss and operative time compared to D2 dissection
Modified D2 lymphadenectomy without pancreatectomy or splenectomy by experienced surgeons can be recommended; otherwise, D1 lymphadenectomy is recommended
Sasako et al. NEJM 2008;359:453-462
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D.) Reconstruction Many options Subtotal gastrectomy - Billroth II Total gastrectomy - Roux-en-y
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CHEMORADIATION Macdonald et al – postop 5FU, leucovorin + radiation Cunningham et al – MAGIC trial: pre and postop
epirubicin, cisplatin, 5FU (“ECF”) Sakuramoto et al – postop S-1 (prodrug fluorouracil) Boige et al – preop 5FU, cisplatin
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If tumor is T2 or higher, +LN perioperative chemotherapy preoperative chemoradiation
If patient did not receive preoperative treatment, and is T3 or higher, or T1-2,+LN, or T2N0 with high risk features postoperative chemoradiation
If patient had D2 resection and is T3 or higher, or T1-2,+LN postoperative chemotherapy
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TAKE-HOME POINTS
LN status has become more powerful in staging as a prognostic indicator for gastric cancer
Unless mandated by extent of invasion, total gastrectomy and splenectomy are not necessary and to be avoided
Modified D2 lymphadenectomy in experienced centers may offer long-term survival benefit
Chemotherapy and radiation improve survival
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QUESTIONS
1.) Which of the following on gastric cancer is NOT true?
a. Highest incidence is in Japan b. Predominance among males or females varies
geographically c. Incidence and death rates in the U.S. have
decreased d. Higher incidence in patients who have undergone
gastric resection for duodenal ulcer
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2.) 65M has a biopsy proven gastric carcinoma on the lesser curvature, 5 cm distal to the esophagogastric junction. CT showed enlarged LN, which are confirmed by laparoscopy. The most appropriate surgical therapy would be:
a. esophagogastrectomy with colonic interposition b. subtotal gastrectomy with a Billroth II anastomosis c. total gastrectomy d. total gastrectomy and splenectomy e. esophagogastrectomy with jejunal interposition
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3.) A 65M has a total gastrectomy for a T2N1M0 gastric adenocarcinoma. The margins of resection are negative. This patient should also receive:
a. external beam radiation b. fluorouracil-based chemotherapy c. a and b d. cisplatinum and external beam radiation e. no additional therapy
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Thank you
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