1 Gastric Cancer 2 S.M. 70 yo AA man Antrectomy/Vagotomy/BII 1960s for peptic ulcer disease Right 99 then left 01 lobectomy for primary lung ca Followed for 4 years by endoscopy for benign hyperplastic polyp distal stomach (proximal to gastrojejunostomy) (l ast EGD 2 years before current presentation) Seve ral months wt loss vague upper abdominal pain Repeat upper endoscopy reveals ulceration of previous polyp site biopsy now positive for adenocarcinoma CT and PET/CT reveal primary gastric tumor and hot nodule in lung but no clear mets or nodes EUS primary tumor confined to mucosa 3 Almost total gastrectomy (rim of stomach left intact at EG junction) and Roux-en-Y gastrojej Pathology T2b N0 M0 Tumor invades muscularis propria not serosa 0/11 LN negative for tumor No additional therapy for gastric cancer Scheduled for VATS /- lobectomy 4 R.G. 74 yo C woman Substernal/epigastric pain Progressed to dysphagia to solids then liquids 10-15 pound wt loss EGD- ulcerated lesion gastric cardia biopsy positive adenoca with signet ring cell characteristics CT (chest/abd/pel) diffusely thickened proximal stomach no mets/involved nodes 5 Exploratory laparotomy reveals leather bottle stomach extending from the EG junction distally involving grossly 80 of the stomach. 2mm implant in L paracolic gutter positive for poorly diff adenoca Underwent palliative radical esophagogastrectomy Pathology T3N2M1 (peritoneal implant) 8/35 LN positive Proximal (continuous) and distal (noncontinuous) margins positive Adjuvant chemotherapy 6 L.H. 47 yo AA woman Previous R breast lumpectomy ALND XRT then completion mastectomy and chemo Reflux sx progressive solid food dysphagia 20 wt loss EGD 2-3cm ulcerated lesion gastric cardia Bx positive adenoca w/ signet ring cell features CT chest/abd/pelvis and PET negative mets- primary tumor contiguous with tail of pancreas 7 Exploratory laparotomy revealed large mass cardia extending posteriorly and laterally to involve tail of pancreas and left crus EG junction grossly uninvolved Underwent resection with total gastrectomy distal pancreatectomy splenectomy with Roux-en-Y esophagojejunostomy Esophageal margin positive on frozen section R1 resection Final pathology 8 Gastric Cancer Incidence/Epidemiology
21900 new cases 12200 deaths in United States in 2003
Peak incidence 40-70 years old
21 MaleFemale ratio
Proximal adenocarcinoma becoming more common than distal cancers
Low socioeconomic status
Fruit/Vegetable poor diet
Salt/Smoke food preservation
Type A blood
Chronic atrophic gastritis
partial gastrectomy for benign disease
Gastric adenomatous polyps
10 Classification of Gastric Cancer
90 of gastric cancer
Subdivided into 2 types (Lauren Histological Classification)
More common in areas with high incidence
Develop in distal third of stomach
Strongly associated with environmental factors
Abnormalities of epidermal growth factor receptors (erbB2 erbB3)
Areas of lower risk/incidence
Proximal stomach/GE junction (reflux and Barretts related)
Abnormalities of fibroblast growth factors (K-sam oncogene)
11 Cancer Staging American Joint Committee on Cancer System T0- no primary tumor. Tis- Carcinoma in situ. No invasion of lamina propria. T1-Invasion of lamina propria or submucosa T2- Invasion of muscularis propria or subserosa. T3-Penetration of serosa. T4- Invasion of adjacent structures. 12 Cancer Staging American Joint Committee on Cancer System Number of involved lymph nodes critical to staging. Must sample at least 15 regional nodes. Location is not important. N1 1-6 regional nodes N2 7-15 regional nodes N3 gt 15 regional nodes M1 Distant metastases or involvement of non regional nodes. 13 5-YEAR SURVIVAL RATES AFTER GASTRECTOMY WITH COMPLETE (R0) RESECTION (Cancer 2000 88921-32) AJCC stage U.S. Japan Japanese-Americans I A 78 95 95 IB 58 86 75 II 34 71 46 IIIA 20 59 48 IIIB 8 35 18 IV 7 17 5 Overall 28 NR 42 gt 15 lymph nodes resected 14 (No Transcript) 15 Surgical Management Gastrectomy and Lymphadenectomy
Need 6 cm margin.
10 incidence of tumor margin if only 4-6 cm gross margin is taken.
30 incidence of margin if 2 cm gross margin is taken.
16 Classification Staging of Lymph Node Groups
Japanese Gastric Cancer Assoc. (JGC)
N1 1 right paracardial 2 left paracardial 3 lesser curvature 4 greater curvature 5 suprapyloric 6 infrapyloric.
N2 7 left gastric artery 8 common hepatic artery 9 celiac artery 10 splenic hilus 11 splenic artery.
Dissection of Stations 1-6 (D1) 1-11(D2) 1-14 (D3) and 1-16 (D4)
17 DOES EXTENDED LYMPHADENECTOMY IMPROVE SURVIVAL Study Year Pts 5-yr survival (D1 v. D2) Kodama/ 1981 850 19 v. 38 Japan Wanebo/ 1 996 18346 30 v. 26 USA Bonenkamp/ 1999 711 45 v. 46 Netherlands Cuschieri/ 1999 400 35 v. 33 UK Siewert/ 1998 1654 45 v. 47 Germany Jatzko/ 1995 345 25 v. 42 Austria 18 Why are the Results Different
Different patient populations and disease biology East v. West.
Differences in staging/earlier detection may bias japanese results
19 Dutch Gastric Cancer Group Trial
Long term follow-up of largest randomized study of D1 D2 dissection
1078 eligible patients 711 well-matched patients were randomized to D1 or D2 resection median follow-up 11 years
In-hospital mortality was 4 D1 group and 10 (p0.004) for D2 group
Univariate analysis of subgroups on selected prognostic variables (age pathologic stage lymph node stage total vs partial gastrectomry) demonstrated no difference in survival rates between D1 D2 resections
20 Survival Probability (A) and Relapse Risk (B) of patients (711) treated with curative intent
Survival rates at 11 years were 30 for D1 and 35 for D2 (p0.53)
Risk of relapse was 70 for D1 and 65 for D2 (p0.43)
Hartgrink et al J Clin Oncol 222069-2077 21 Survival of patients treated with curative intent according to N stage. (A) N0 (B) N1 (C) N2 (D) N3
D2 dissection did tend to benefit patients with N2 disease offering the only possible cure
N2 disease can at the moment only be determined postoperatively after histologic examination
Hartgrink et al J Clin Oncol 222069-2077 22 DCG Conclusions
No long-term overall survival benefit from an extended lymph node dissection in Western patients w/ gastric cancer
Associatied higher postoperative mortality may offset any long-term effect in survival
Extended lymph node dissection may offer cure to patients with N2 disease but difficult to identify
Focus should instead be placed on performing a complete D1 lymphadenectomy researching new adjuvant and neoadjuvant protocols and increasing efficacy of radiation therapy
23 Adjuvant Therapy for Gastric Cancer
Gastric cancer is often resistant
palliation only no survival benefit
Adjuvant RT does not increase survival after curative resection
5-FU provides 20 response rate
Other drugs with reported activity mitomycin cisplatin doxorubicin methotrexate CPT-11 paclitaxel taxotere
Meta-analyses of chemotherapy after curative resection vs resection alone find only modest survival benefit (see figure)
24 (No Transcript) 25 Adjuvant Chemoradiotherapy SWOG9008/INT0116 study of adjuvant chemoradiaiton 556 pts randomized to surgery alone or surgery adj CRT Gastric resection with D2 lymphadenectomy recommended 5 days 5-FU plus leucovorin then 4500 cGy XRT at 180 cGy per day (5 days/week for 5 weeks) in conjunction with dose- reduced 2nd and 3rd cycles of chemo Critics argue 54 of pts underwent less than D1 lymphadenectomy High local (29) and regional (72) relapse rates in surgery alone 26 Neoadjuvant Chemotherapy Theorectical Advantages better tolerated down-sizing improves resectability early treatment of systemic disease Preliminary results of UK Medical Research Council MAGIC trial 503 pts stage II and III gastric cancer randomized to surgery alone or 3 cycles preop epirubicine cisplatin and fluorouracil (ECF) followed by surgery then 3 additional post-op ECF cycles Higher proportion of smaller or T1/T2 tumors resulting in higher perceived resectability (79 vs 69) based on surgeons description NOT pathologic R0 vs R1 designation. 2-year survival 48 neoadjuvant group vs 40 surgery alone (p0.063). Definitive answers await pathologic data and 5-year survival results
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