Gastric Cancer

Gastric Cancer Ahmet Kilic October 12, 2005 UMMS Surgical Resident Conference Gastric Neoplasia  Benign   Gastric polyps Ectopic pancreas Gastric Adenocarcinoma Gastric Lymphoma Gastric Sarcoma  Malignant    Gastric Cancer          Epidemiology Risk Factors Pathology Clinical Presentation Preoperative Evaluation Staging Treatment Outcomes Surveillance Epidemiology    1980’s – most common CA worldwide Geography (Japan / S. America) United States   10th most common; dec. incidence in past 70 years Male : Female = 2:1 Pathology       Gastric Adenocarcinoma (~ 95%) Squamous Cell Carcinoma Adenoacanthoma Carcinoid Gastrointestinal stromal tumors (GISTs) Lymphoma Borrmann System Lauren System  Intestinal   Environmental  Diffuse   Gastric atrophy, intestinal metaplasia Increasing inc. w/ age Blood type A Women > men   Men > women  Younger age group        Gland formation Hematogenous Spread Microsatellite instability APC gene mutations p53, p16 inactivation APC, adenomatous polyposis coli    Poorly differentiated, signet ring cells Transmural / lymphatic spread Decreased E-cadhedrin p53, p16 inactivation WHO Classification  5 main categories  Adenocarcinoma, Adenosquamous cell carcinoma, squamous cell carcinoma, undifferentiated carcinoma and unclassified carcinoma Papillary, tubular, mucinous, signet ring  Adenocarcinoma – subdivided   Further subdivided based on differentiation PRIMARY TUMOR (T) TX T0 Tis T1 T2 Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria Tumor invades lamina propria or submucosa Tumor invades muscularis propria or subserosa T2a T2b T3 T4 Tumor invades muscularis propria Tumor invades subserosa Tumor penetrates serosa (visceral peritoneum) without invasion of adjacent structures Tumor invades adjacent structures REGIONAL LYMPH NODES (N) NX N0 N1 N2 N3 Regional lymph node(s) cannot be assessed No regional lymph node metastasis Metastasis in 1 to 6 regional lymph nodes Metastasis in 7 to 15 regional lymph nodes Metastasis in more than 15 regional lymph nodes DISTANT METASTASIS (M) MX M0 M1 Distant metastasis cannot be assessed No distant metastasis Distant metastasis STAGE GROUPING Stage 0 Stage 1A Stage IB Stage II Tis T1 T1 N0 N0 N1 M0 M0 M0 T2a/b T1 T2a/b T3 Stage IIIA T2a/b T3 T4 Stage IIIB Stage IV T3 T4 T1–3 Any T N0 N2 N1 N0 N2 N1 N0 N2 N1–3 N3 Any N M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1 From AJCC Cancer Staging Manual, 6th ed. New York, Springer-Verlag, 2001. Clinical Presentation   Asymptomatic Early    More advanced disease     Vague epigastric discomfort / indigestion Pain is constant, nonradiating, unrelieved by food digestion Weight loss Anorexia Fatigue Emesis Proximal Distal Diffuse  Symptoms dependent on location     GI bleeding, obstruction Clinical Presentation  Physical signs – late        Assoc. w/ locally advanced or mets Palpable abdominal mass Palpable supraclavicular (Virchow’s) LN Palpable periumbilical (Sister May Joseph’s) LN Peritoneal mets palpable by rectal exam (Blumer’s shelf) Palpable ovarian mass (Krukenberg’s tumor) S/Sx of hepatomegaly Pre-operative Evaluation  Once gastric cancer is suspected  Flex. Upper endoscopy modality of choice  Double contrast barium upper gi cost effective w/ 90% accuracy – however can not distinguish benign from malignant gastric ulcers.  Flex. Upper Endo w/ multiple biopsies (>7) around ulcer crater for histo Biopsy of ulcer crater → necrotic debris  Accuracy (98%) → inc. w/ direct-brush cytology  Pre-operative Evaluation  Esophagogastroduodenoscopy – palliation    Laser ablation Dilation Tumor stenting Aid in staging gastric wall tumor invasion  LN status   EUS  Diagnosis: Gastric Cancer      CBC, CMP, Coags CXR, CT scan of abdomen Women  CT chest for proximal gastric cancer Limitations   Pelvic CT / US   Laparoscopy  < 5 mm mets on liver/peritoneum Staging for LN mets 25 – 86 % Cytology of peritoneal fluid / peritoneal lavage  23 – 37 % mets + finding → poor prognosis Staging  TNM system  1997  Nodal status  Location → number of positive nodes   Cardia vs distal - ? Survival R status    R0 – microscopically negative margin R1 – micro +, gross – R2 – gross residual disease Staging Surgical Treatment   Absence of distant mets Resection margin w/ neg. microscopic margins   Gastric tumors char. by extensive intramural spread Line of resection at least 6 cm from the tumor mass to decrease recurrence at anastomosis  App surgery based on location / pattern of spread Surgical Treatment   Cardia / proximal ~ 35-50% of gastric adenocarcinomas Proximal    More advanced at presentation Curative resection is rare Total gastrectomy or proximal gastric resection Proximal / Cardia  Proximal Gastrectomy– increased morbidity / mortality  Buhl, et al.  Dumping, heartburn, reduced appetite  Norwegian Stomach Ca Trial Prox. gastrectomy morbid / mortal 52% 16%  Total gastrectomy morbid / mortal 38% 8%   Total gastrectomy considered procedure of choice for proximal gastric lesions Distal Tumors  Account for ~ 35 % of all gastric cancers    No 5-year survival difference b/n subtotal vs total gastrectomy Subtotal appropriate if negative margins Recurrence vs nonrecurrence depends on margin of 3.5 cm vs 6.5 cm Extended Lymphadenectomy  Controversial  Japanese system D1 – group 1 LN  D2 – groups 1 & 2  D3 – D2 plus para-aortic LN  To remove station 10 & 11 LN – splenectomy  D2 resection – partial pancreatectomy  Extended Lymphadenectomy  No longer routine    Dutch   Used for tumor extension Removal of station 10 LN D1 vs D2 resection   Japan  Increased intra-hosp mortality West  D2 improved survival over D1 No improvement Palliation      20 – 30% of gastric cancer presents w/ stage IV disease Relief of symptoms w/ minimal morbidity Surgical palliation Percutaneous, endoscopic, radiotherapuetic techniques Nonoperative tx  Laser recanalization, endoscopic dilatation (+/- stent) Adjuvant Therapy  1999  ~ 29% of gastrectomy pts underwent some type of adjuvant tx (71% sx alone) 5-FU, Leucovorin w/ chemorad for R0 Sx – 27 mos 3 yr survival 41%  Chem/Rad – 36 mos 3 yr survival 50%   Southwest Cancer Oncology Group trial  Outcomes Recurrence  After gastrectomy quite high    40 – 80 % Most occur w/in first 3 years Locoregional failure 38 – 45%  Anastomosis, gastric bed and regional nodes  Peritoneal dissemination – 54% Surveillance  Recurrence high first 3 years  Complete H&P every 4 mos for 1 year Then every 6 mos for 2 years  Annually after     CBC, LFT – as clinically indicated CXR, CT abd/pel - ? Routinely Annual endoscopy for subtotal gastrectomy Gastric Lymphomas      Epidemiology Pathology Evaluation Staging Treatment Epidemiology   Stomach most common site for lymphomas in GI system Primary gastric lymphoma – uncommon  ~ 15 % of gastric CA, ~ 2 % of lymphomas Epigastric pain, early satiety and fatigue Bleeding uncommon   Vague symptoms   50% have anemia on presentation   6th and 7th decade (M:F is 2:1) Most commonly in antrum Pathology  Multiple classification systems      Most common diffuse large B-cell ~ 55% Extranodal marginal cell lymphoma (MALT) Burkitt’s lymphoma ~3% Mantel cell ~1% Follicular lymphoma ~1% ~ 40% Pathology  Diffuse large B-cell    Usually primary May occur from progression of less aggressive lymphomas (chronic lymphocytic leukemia / small lymphocytic lymphoma, follicular lymphoma or MALT) Risk factors  Immunodeficiencies, H. pylori “extranodal marginal zone lymphomas of MALT type”  Gastric MALT  Commonly preceded by H. pylori associated gastritis t(1;14) (p22;q32) and t(11;18)(q21;q21)   Impaired response to apoptotic singaling Increased NF-κB Predicts responsiveness to tx by H. pylori eradication  t(11;18)(q21;q21)  Burkitt’s Lymphoma     EBV virus Highly aggressive Younger population Cardia / body of stomach (rather than antrum) Staging   Controversial TNM like gastric adenocarcinoma Treatment  Multimodality – early stage   Resection – controversial Chemo/rads alone Perforation w/ chemo ~5%  CHOP – cyclophosphamide, hydroxy- daunomycin, oncovin, predinose)   5 year survival Sx/Chemo/Rad 82 %  Chemo/Rad 84.4 %  Treatment  Radiation  Limited in large tumors Local control 100% < 3 cm  60 – 70 % if > 6 cm   Risk of complications 30% at 10 years Treatment  Late-stage  Not amenable to sx; chemo  MALT/very limited diffuse large B-cell  H. pylori eradication alone 75%  Repeat endo in 2 mos. ; biannual endo for 3 years   Failure of above increased if  Transmural, node +, transformation Bcl-10 Gastric Sarcoma      Epidemiology Pathology Staging Clinical Manifestation / Evaluation Treatment Epidemiology    Arise from mesenchymal components of gastric wall ~3% of all gastric CA GIST most common  Stomach (60-70%)   After 4th decade Mean age 60 GIST - Pathology    Initially thought to arise from smooth muscle cells – previously classified as leiomyoma / leiomyosarcoma Histo  GIST    Muscularis propria – likely from cells of Cajal Cellular Spindle cell Pleomorphic mesenchymal tumors  Kit protein, CD34+ Staging   No current system Prognosis  Mitotic frequency  Low – benign; High – malignant Size > 5 cm; cellular atypia, necrosis or local invasion, c-kit,  Other signs of malignancy  Clinical  Most common presentation  GI bleeding, pain dyspepsia w/ biopsy ~50%  Endoscopy – first diagnostic test    CT best – since neoplasm grows intramurally Double-contrast UGI – smooth edged filling defect Treatment  Surgery       Most recurrences in first 2 years  Negative margin (en-bloc if adjacent organs) Avoid rupture of tumor to prevent peritoneal seeding LN mets rare (<10%) – no added benefit Local disease w/ assoc. liver mets 5 year survival 48% (19 – 56%) Adjuvant tx    Radiation – no proven benefit 5% respond to doxorubicin Glivic/Gleevec – 54% partial response  Approved fro CD117+ unresectbale, mets Questions A patient has an 8 mm lesion on the lesser curvature of the stomach near the gastroesophageal junction. CT of the abdomen is negative. Gastric biopsy is returned as mucosal associated lymphoid tumor (MALToma). The most appropriate initial treatment would be: A. Radical gastrectomy, roux-en-Y esophagojejunostomy B. Proximal gastrectomy, esophagogastrostomy C. Metastatic work-up; treatment for H. pylori; chemotherapy; radiotherapy D. Treatment for H. pylori E. Wedge resection Questions A patient has an 8 mm lesion on the lesser curvature of the stomach near the gastroesophageal junction. CT of the abdomen is negative. Gastric biopsy is returned as mucosal associated lymphoid tumor (MALToma). The most appropriate initial treatment would be: A. Radical gastrectomy, roux-en-Y esophagojejunostomy B. Proximal gastrectomy, esophagogastrostomy C. Metastatic work-up; treatment for H. pylori; chemotherapy; radiotherapy D. Treatment for H. pylori E. Wedge resection Questions Regarding gastric anatomy, physiology, and pathology, which of the following statements is correct? A. Helicobacter pylori, a gram-negative bacteria that produces urease, has B. C. D. E. been implicated in the genesis of gastric carcinoma The right and left gastroepiploic arteries – branches of the gastroduodenal and left gastric arteries, respectively – are responsible for the blood supply of the greater curvature of the stomach Truncal vagotomy accelerates emptying of solids and delays emptying of liquids In patients with Zollinger-Ellison syndrome, the treatment of choice for multiple ulcers is total gastrectomy Gastric cancers are the most common tumors in the GI tract to present with sub-mucosal spreading, needing at least 5 cm of resection margins Questions Regarding gastric anatomy, physiology, and pathology, which of the following statements is correct? A. Helicobacter pylori, a gram-negative bacteria that produces urease, has B. C. D. E. been implicated in the genesis of gastric carcinoma The right and left gastroepiploic arteries – branches of the gastroduodenal and left gastric arteries, respectively – are responsible for the blood supply of the greater curvature of the stomach Truncal vagotomy accelerates emptying of solids and delays emptying of liquids In patients with Zollinger-Ellison syndrome, the treatment of choice for multiple ulcers is total gastrectomy Gastric cancers are the most common tumors in the GI tract to present with sub-mucosal spreading, needing at least 5 cm of resection margins Questions Which of the following statements about the clinical evaluation of gastric lymphoma is MOST accurate? A. Best diagnosed by abdominal computed tomographic (CT) scan with oral contrast B. Accounts for approximately 20% of gastric malignancies C. Usually detected by upper gastrointestinal endoscopy and biopsy D. Abdominal pain is an infrequent presenting complaint E. Usually presents urgently with hemorrhage, perforation, or obstruction Questions Which of the following statements about the clinical evaluation of gastric lymphoma is MOST accurate? A. Best diagnosed by abdominal computed tomographic (CT) scan with oral contrast B. Accounts for approximately 20% of gastric malignancies C. Usually detected by upper gastrointestinal endoscopy and biopsy D. Abdominal pain is an infrequent presenting complaint E. Usually presents urgently with hemorrhage, perforation, or obstruction Questions A 42 year old physician has three month history of dark stools, vague abdominal pain, and early satiety. PE demonstrates heme positive stool. The patient is anemic. Upper endoscopy shows a 4.9 cm polypoid mass located in the distal antrum. Endoscopic biopsies of this lesion are inconclusive. At exploration, a gastric lymphoma confined to the stomach and regional nodes is confirmed. The most appropriate management is: A. B. C. D. E. Chemotherapy Radiation therapy Chemotherapy and radiation Curative resection Resection plus adjuvant chemoradiation Questions A 42 year old physician has three month history of dark stools, vague abdominal pain, and early satiety. PE demonstrates heme positive stool. The patient is anemic. Upper endoscopy shows a 4.9 cm polypoid mass located in the distal antrum. Endoscopic biopsies of this lesion are inconclusive. At exploration, a gastric lymphoma confined to the stomach and regional nodes is confirmed. The most appropriate management is: A. B. C. D. E. Chemotherapy Radiation therapy Chemotherapy and radiation Curative resection Resection plus adjuvant chemoradiation Questions The most common symptoms present at initial diagnosis of gastric carcinoma are A. Weight loss and vague abdominal pain B. Ulcer-type pain and early satiety C. Anorexia and vomiting D. Melena and lower abdominal pain E. Nausea and dysphagia Questions The most common symptoms present at initial diagnosis of gastric carcinoma are A. Weight loss and vague abdominal pain B. Ulcer-type pain and early satiety C. Anorexia and vomiting D. Melena and lower abdominal pain E. Nausea and dysphagia