Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 39-10 Gastric Adenocarcinoma + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Dyspeptic symptoms with weight loss in patients age > 40 Iron deficiency anemia; occult blood in stools Abnormality on upper gastrointestinal series or endoscopy +++ General Considerations ++ There are two main histologic variants of gastric cancer Intestinal-type Diffuse Intestinal-type gastric cancer resembles intestinal cancers in forming glandular structures Accounts for 70–80% of cases Occurs twice as often in men as women Primarily affects older people (mean age 68 years) More strongly associated with environmental factors Diffuse gastric cancer is poorly differentiated, has signet-ring cells, and lacks formation of glandular structures Accounts for 20–30% of cases Affects men and women equally Occurs more commonly in young people Not as strongly related to Helicobacter pylori infection Has a worse prognosis than the intestinal type with early metastasis Most diffuse gastric cancers are attributable to acquired or hereditary mutations in the genes regulating the E-cadherin cell adhesion protein In addition to the hereditary diffuse gastric cancer, there are other hereditary cancer predisposition syndromes that account for 3–5% of gastric cancers Lynch syndrome Juvenile polyposis syndrome Peutz-Jeghers syndrome Familial adenomatous polyposis Most gastric cancers arise in the body and antrum Chronic H pylori gastritis is the major risk factor Other risk factors for intestinal-type gastric cancer Pernicious anemia Partial gastric resection > 15 years previously Smoking Diets that are high in nitrates or salt and low in vitamin C +++ Demographics ++ Gastric adenocarcinoma is the third most common cancer worldwide Incidence in the United States has declined rapidly over last 70 years In 2019 in the United States, there were an estimated 27,510 new cases and 11,140 deaths Incidence is higher in Asian Americans, Hispanics, African Americans and American Indian/Alaska Natives + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Generally asymptomatic or nonspecific symptoms until advanced disease Dyspepsia, vague epigastric pain, anorexia, early satiety, and weight loss Acute upper gastrointestinal bleeding with hematemesis or melena Postprandial vomiting suggests pyloric obstruction Progressive dysphagia suggests lower esophageal obstruction Physical examination rarely helpful Gastric mass is palpated in < 20% Signs of metastatic spread include Left supraclavicular lymph node (Virchow node) Umbilical nodule (Sister Mary Joseph nodule) Rigid rectal shelf (Blumer shelf) Ovarian metastases (Krukenberg tumors) +++ Differential Diagnosis ++ Benign gastric ulcers Lymphoma Ménétrier disease + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Iron deficiency anemia or anemia of chronic disease Liver biochemical test abnormalities, particularly elevation of alkaline phosphatase, if there is metastasis to liver Tumor markers Do not have established clinical validity in screening, diagnosis, or management of gastric cancer However, can assist in monitoring treatment response when checked serially +++ Imaging Studies ++ Upper gastrointestinal series may not detect small or superficial lesions and cannot reliably distinguish benign from malignant ulcerations Preoperative evaluation with contrast CT of chest, abdomen, and pelvis and endoscopic ultrasonography Endoscopic ultrasonography Superior to CT in determining the depth of tumor penetration Useful for evaluating early gastric cancers that may be removed by endoscopic mucosal resection Positron emission tomography (PET) or combined PET-CT imaging is recommended for detection of distant metastasis +++ Diagnostic Procedures ++ Staging by TNM system T1 tumors invade the lamina propria (T1a) or submucosa (T1b) T2 invade the muscularis propria T3 penetrate the serosa T4 invade adjacent structures Lymph nodes are graded as N0 if there is no involvement, and N1, N2, or N3 if there are is involvement of 1–2, 3–6, or more than 7 regional nodes M1 signifies the presence of metastatic disease Testing for microsatellite instability (MSI), deficiency in mismatch repair proteins (dMMR) and programmed death ligand-1 (PD-L1) is recommended in advanced disease to identify tumors that may respond to immunotherapy + Treatment Download Section PDF Listen +++ +++ Medications ++ Systemic therapy may be considered in patients with metastatic disease who still have good functional status and expected survival of at least several months Two-drug combination regimens are preferred for first-line therapy, with most common regimens including a fluoropyrimidine (eg, 5-fluorouracil or capecitabine) or a taxane agent (eg, docetaxel or paclitaxel) plus a platinum agent (eg, cisplatin or oxaliplatin) A three-drug combination of epirubicin or docetaxel plus cisplatin and 5-fluorouracil may be appropriate for first-line treatment in medically fit patients Trastuzumab Prolongs survival in ~15% of patients with advanced gastric adenocarcinomas harboring amplification of EGFR-2 (HER2) when added to standard chemotherapy Not recommended for combination with anthracyclines, such as epirubicin, due to risk of cardiotoxicity After progression on first-line chemotherapy, further chemotherapy treatments are associated with better overall survival than supportive care alone Second-line treatments include Ramucirumab, a monoclonal antibody Targets the VEGF receptor-2 Can be used both as monotherapy and in combination with paclitaxel Irinotecan Taxol Of note, adding lapatinib to chemotherapy does not result in improvement in overall survival Pembrolizumab, a drug that targets lymphocyte PD-L1, is approved by the FDA for second-line or subsequent therapy for MSI-H or dMMR cancers and for third-line or beyond therapy for PD-L1-positive adenocarcinomas In Japan, nivolumab is approved for advanced gastric cancers after progression on standard therapies +++ Surgery ++ For patients with clinically localized disease (stages I–III), surgical exploration Patients with confirmed localized disease should undergo radical surgical resection Approximately 25% will be found to have locally unresectable tumors or peritoneal, hepatic, or distant lymph node metastases, and "curative" surgical resection is not warranted For patients with unresectable disease, gastrojejunostomy can prevent obstruction +++ Therapeutic Procedures ++ For adenocarcinoma localized to the distal two-thirds of the stomach, a subtotal gastrectomy should be performed D2 lymphadenectomy Has been shown to improve disease-specific survival However, it is associated with increased postoperative mortality For proximal gastric cancer or diffusely infiltrating disease, total gastrectomy is necessary + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ After surgical therapy, further follow-up is determined by clinical course Routine follow-up not recommended Vitamin B12 supplementation is required after gastrectomy +++ Complications ++ Acute or chronic gastrointestinal blood loss Pyloric obstruction +++ Prognosis ++ Survival related to tumor stage, location, and histologic features 5-year survival is about 30% Stage I and stage II tumors resected for cure have a > 60% long-term survival Patients with stage III tumors have a < 20% long-term survival Tumors of the diffuse and signet ring type have a worse prognosis than those of the intestinal type Tumors of the proximal stomach (fundus and cardia) have 5-year survival of < 15%, a far worse prognosis than distal lesions +++ Prevention ++ Prophylactic gastrectomy should be considered in patients known to carry specific mutations in the genes regulating the E-cadherin cell adhesion protein +++ When to Refer ++ Patients with dysphagia, weight loss, protracted vomiting, iron-deficiency anemia, or new-onset of dyspepsia (especially if age 55 years or older or associated with other alarm symptoms) in whom gastric cancer is suspected should be referred for endoscopy Patients should be referred to a surgeon for attempt at curative resection in stage I, II, or III cancer, including staging laparoscopy if indicated Prior to surgery, patients should be referred to an oncologist to determine the role for neoadjuvant chemotherapy or adjuvant chemoradiation or chemotherapy Patients who have undergone gastrectomy require consultation with a nutritionist due to propensity for malnutrition and postoperative complications such as dumping syndrome and vitamin B12 deficiency Patients with unresectable or metastatic disease should be referred to an oncologist for consideration of palliative chemotherapy or chemoradiation +++ When to Admit ++ Patients with protracted vomiting, inability to maintain hydration or nutrition, or acute bleeding + References Download Section PDF Listen +++ + +Anandappa G et al. Emerging novel therapeutic agents in the treatment of patients with gastroesophageal and gastric adenocarcinoma. Hematol Oncol Clin North Am. 2017 Jun;31(3):529–44. [PubMed: 28501092] + +Cats A et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616. [PubMed: 29650363] + +Choi IJ et al. Helicobacter pylori treatment for the prevention of metachronous gastric cancer. N Engl J Med. 2018 May 22;378(12):1085–95. [PubMed: 29562147] + +Jang S et al. Superiority of gastrojejunostomy over endoscopic stenting for palliation of malignant gastric outlet obstruction. Clin Gastroenterol Hepatol. 2019 Jun;17(7):1295–302. [PubMed: 30391433] + +Makris EA et al. Surgical considerations in the management of gastric adenocarcinoma. Surg Clin North Am. 2017 Apr; 97(2):295–316. [PubMed: 28325188] + +National Cancer Institute. SEER Cancer Statistics Factsheets: Stomach Cancer, 2018. https://seer.cancer.gov/statfacts/html/stomach.html + +National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Gastric Cancer. Version 2.2018. 2018 May 22. https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf + +Ngamruengphong S et al. Endoscopic management of early gastric adenocarcinoma and preinvasive gastric lesions. Surg Clin North Am. 2017 Apr;97(2):371–85. [PubMed: 28325192] + +Rugge M et al. Gastric cancer as preventable disease. Clin Gastroenterol Hepatol. 2017 Dec;15(12):1833–43. [PubMed: 28532700] + +Sitarz R et al. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 2018 Feb 7;10:239–48. [PubMed: 29445300] + +Wagner AD et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2017 Aug 29;8:CD004064. [PubMed: 28850174]