GASTRIC CANCER Joyce Au SUNY Downstate Grand Rounds July 11, 2013
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
Thin NAD AAO RRR Clear BS b/l Abd soft, ND, NT, well healed midline scar Ext no edema No CVA tenderness
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
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
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
Pathology 3 cm moderately differentiated adenocarcinoma Intestinal type Invasion into muscularis propria Negative margins 0/23 LN
GASTRIC CANCER Introduction Workup Surgery Chemoradiation
INTRODUCTION World s 4 th leading cause of cancer-related death >10,000 deaths from gastric cancer annually in the U.S.
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
Diet salt, smoked, cured, nitrates, nitrites, nitrosamines carcinogenic N- nitroso compounds Tobacco Pernicious anemia (synchronous lesions) Villous adenomas in gastric polyps H. pylori www.downstatesurgery.org
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
Pathology Arise from mucous-producing cells in 95% Lauren classification INTESTINAL TYPE Well to moderately differentiated Intestinal metaplasia, chronic gastritis Older, male, lower socioeconomic Proximal tumors DIFFUSE TYPE Poorly differentiated Signet cells, mucin Younger, obese Distal tumor WHO classification tubular, mucinous, papillary, signet cell
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
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
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, 5 th ed.
7 th 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
(tnm) www.downstatesurgery.org
1 Washington et al. Ann Surg Oncol 2010;17:3077-3079
SURGERY www.downstatesurgery.org
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 1 st successful gastrectomy with gastroduodenostomy Wolfler in 1882 performed a palliative loop gastrojejunostomy Billroth in 1885 reconstructed with gastrojejunostomy
A.) Gastrectomy B.) Splenectomy C.) Lymphadenectomy D.) Reconstruction
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
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
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
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
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
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
D1 D2
D2 is a standard in Asia Studies in the West question D1 vs. D2
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 recurrencefree survival Cuschieri et al. Br J Cancer 1999;79:1522-1530
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
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
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
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
D.) Reconstruction www.downstatesurgery.org Many options Subtotal gastrectomy - Billroth II Total gastrectomy - Roux-en-y
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
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
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
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
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
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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