Highest incidence in Japan, China, Chile, Ireland; incidence decreasing worldwide, eightfold in the United States over past 60 years; in 2019, 27,510 new cases and 11,140 deaths. Male:female = 2:1; peak incidence sixth and seventh decades; overall 5-year survival <15%.

Decreasing incidence in the United States over past 80 years. Increased incidence in lower socioeconomic groups; environmental component is suggested by studies of migrants and their offspring. Several dietary factors correlated with increased incidence: nitrates, smoked foods, heavily salted foods; genetic component suggested by increased incidence in first-degree relatives of affected pts; other risk factors: atrophic gastritis, Helicobacter pylori infection, Billroth II gastrectomy, gastrojejunostomy, adenomatous gastric polyps, pernicious anemia, hyperplastic gastric polyps (latter two associated with atrophic gastritis), Ménétrier’s disease, slight increased risk with blood group A.

Adenocarcinoma in 85%; usually focal (polypoid, ulcerative), two-thirds arising in antrum or lesser curvature, frequently ulcerative (“intestinal type”); less commonly diffuse infiltrative (linitis plastica) or superficial spreading (diffuse lesions more prevalent in younger pts; exhibit less geographic variation; have extremely poor prognosis); spreads primarily to local nodes, liver, peritoneum; systemic spread uncommon; lymphoma accounts for 15% (most frequent extranodal site in immunocompetent pts), either low-grade tumor of mucosa-associated lymphoid tissue (MALT) or aggressive diffuse large B cell lymphoma; leiomyosarcoma or gastrointestinal stromal tumor (GIST) is rare.

Most commonly presents with progressive upper abdominal discomfort, frequently with weight loss, anorexia, nausea; acute or chronic GI bleeding (mucosal ulceration) common; dysphagia (location in cardia); vomiting (pyloric and widespread disease); early satiety; examination often unrevealing early in course; later, abdominal tenderness, pallor, and cachexia most common signs; palpable mass uncommon; metastatic spread may be manifest by hepatomegaly, ascites, left supraclavicular or scalene adenopathy, periumbilical, ovarian, or prerectal mass (Blumer’s shelf), low-grade fever, skin abnormalities (nodules, dermatomyositis, acanthosis nigricans, or multiple seborrheic keratoses). Laboratory findings: iron-deficiency anemia in two-thirds of pts; fecal occult blood in 80%; rarely associated with pancytopenia and microangiopathic hemolytic anemia (from marrow infiltration), leukemoid reaction, migratory thrombophlebitis, or acanthosis nigricans.

Double-contrast barium swallow useful but has been supplanted by the more sensitive and specific esophagogastroscopy and CT for staging and assessing resectability; pathologic confirmation by biopsy and cytologic examination of mucosal brushings; superficial biopsies less sensitive for lymphomas (frequently submucosal); important to differentiate benign from malignant gastric ulcers with multiple biopsies and follow-up examinations to demonstrate ulcer healing.

Adenocarcinoma: Gastrectomy offers only chance of cure (only possible in less than one-third); the rare tumors limited to mucosa are resectable for cure in 80%; deeper invasion, nodal metastases decrease 5-year survival to 20% of pts with resectable tumors in absence of obvious metastatic spread (Table 72-1). Subtotal gastrectomy has similar efficacy to total gastrectomy for distal stomach lesions, but with less morbidity; no clear benefit for resection of spleen and a portion of the pancreas, or for radical lymph node removal. Adjuvant chemotherapy (5FU/leucovorin) plus radiation therapy following primary surgery leads to a 7-month increase in median survival. Neoadjuvant chemotherapy with epirubicin or docetaxel with cisplatin, and 5FU or capecitabine may downstage tumors and increase the efficacy of surgery. Use of chemotherapy before and after surgery may be more effective. Immune checkpoint inhibitors appear to have activity in some pts. Palliative therapy for pain, obstruction, and bleeding includes surgery, endoscopic dilatation, radiation therapy, chemotherapy, and ramucirumab, an antiangiogenic antibody.

Lymphoma: Low-grade MALT lymphoma is caused by H. pylori infection, and eradication of the infection causes complete remissions in 50% of pts; rest are responsive to combination chemotherapy including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) plus rituximab. Diffuse large B cell lymphoma may be treated with either CHOP plus rituximab or subtotal gastrectomy followed by chemotherapy; 50–60% 5-year survival.

Leiomyosarcoma: Surgical resection curative in most pts. Tumors expressing the c-kit tyrosine kinase (CD117)—GIST—respond to imatinib mesylate in a substantial fraction of cases.