Gastric & Small Bowel Neoplasms, Including Neuroendocrine Tumors
Which tumor gets antibiotics, which gets imatinib, which gets gastrectomy, and why carcinoid needs the liver
Gastric adenocarcinoma: risk and pathology
Risk factors. Nearly all gastric cancers are adenocarcinomas. H. pylori is the dominant risk factor; others are diets rich in smoked, salted, or pickled foods (nitrosamines), smoking, chronic atrophic gastritis and pernicious anemia, prior partial gastrectomy (cancer in the remnant usually appears more than 15 years later, promoted by bile reflux), EBV, male sex, and East Asian ancestry.
| Feature | Intestinal type | Diffuse type |
|---|---|---|
| Histology | Gland-forming adenocarcinoma | Signet ring cells infiltrating singly, no glands |
| Pathway | H. pylori cascade: chronic gastritis → atrophy → intestinal metaplasia → dysplasia → cancer | E-cadherin (CDH1) loss, sporadic or germline |
| Patients | Older men; most common type | Younger patients; worse prognosis |
| Gross | Mass or ulcer, often antral | Linitis plastica: thick, rigid "leather-bottle" stomach |
Hereditary diffuse gastric cancer. Autosomal dominant germline CDH1 variants confer a high lifetime risk of diffuse gastric cancer and, in women, lobular breast cancer. Because signet ring foci spread beneath intact mucosa and escape endoscopic surveillance, carriers are offered prophylactic total gastrectomy in early adulthood; those who decline get annual high-quality endoscopic surveillance with multiple random biopsies.
Gastric adenocarcinoma: presentation, diagnosis and treatment
Presentation. Disease is usually advanced at diagnosis. Weight loss, early satiety, epigastric pain, and iron-deficiency anemia from occult bleeding are typical; cardia tumors cause dysphagia and antral tumors cause gastric outlet obstruction with vomiting.
Signs of spread and paraneoplastic clues.
- Virchow node: left supraclavicular node, reached through thoracic duct drainage
- Irish node: left axillary node
- Sister Mary Joseph nodule: periumbilical metastasis from peritoneal spread
- Krukenberg tumor: ovarian metastases of signet ring cells, often bilateral
- Blumer shelf: drop metastasis in the rectovesical or rectouterine pouch, felt as a shelf on rectal exam
- Leser-Trélat sign (sudden eruption of many seborrheic keratoses) and malignant acanthosis nigricans
- DiagnoseEGD with multiple biopsies. Biopsy every gastric ulcer and repeat EGD to document healing, because an ulcerated cancer can look benign.
- StageCT of the chest, abdomen, and pelvis; EUS for depth (T) and nodes (N); PET-CT in selected patients; staging laparoscopy for occult peritoneal disease.
- Profile advanced tumorsHER2, PD-L1, and mismatch repair status.
- Treat by stageEarly mucosal (T1a) cancer: endoscopic resection. Locally advanced (≥T2 or node-positive): perioperative chemotherapy (FLOT: fluorouracil, leucovorin, oxaliplatin, docetaxel) before and after gastrectomy with D2 lymphadenectomy. Metastatic: systemic chemotherapy, plus trastuzumab for HER2-positive tumors and immunotherapy when indicated.
After total gastrectomy, replace vitamin B12 for life (no intrinsic factor) and watch for dumping syndrome and iron deficiency.
Other gastric tumors and polyps
Gastric MALT lymphoma. Extranodal marginal zone lymphoma arises from lymphoid tissue induced by chronic H. pylori infection. Localized, low-grade, H. pylori-positive disease often regresses completely after eradication therapy alone. Tumors with t(11;18) (API2-MALT1) grow independently of H. pylori and rarely respond; persistent or H. pylori-negative disease is treated with radiation, and transformation to diffuse large B-cell lymphoma requires R-CHOP.
Gastrointestinal stromal tumor (GIST). GISTs arise from the interstitial cells of Cajal, the gut pacemaker cells, through activating KIT or PDGFRA mutations, and stain for CD117 (c-KIT) and DOG1. The stomach is the most common site, followed by the small bowel; they present as submucosal masses that may ulcerate and bleed, and are sampled by EUS-guided biopsy. Treatment is complete resection with negative margins; lymphadenectomy is unnecessary because nodal spread is rare, and metastases go to the liver and peritoneum. Imatinib, a KIT tyrosine kinase inhibitor, is given as adjuvant therapy for high-risk tumors and first-line for unresectable or metastatic disease. GISTs also occur with NF1.
| Polyp | Association | Malignant potential | Management |
|---|---|---|---|
| Fundic gland | Most common; long-term PPI use; FAP | Negligible if sporadic; may be dysplastic in FAP | Leave small sporadic polyps; many in a young patient without PPI use → evaluate for FAP |
| Hyperplastic | H. pylori or atrophic gastritis | Low; rises with size | Remove if >1 cm; treat H. pylori |
| Adenomatous | Atrophic gastritis, intestinal metaplasia | True neoplasm; cancer precursor | Always resect; look for synchronous cancer |
Small bowel neuroendocrine tumors
Epidemiology and behavior. Neuroendocrine (carcinoid) tumors are the most common small bowel malignancy. They cluster in the distal ileum, are often multifocal, and grow slowly. The primary is usually tiny; the typical CT finding is a calcified, spiculated mesenteric mass (nodal metastasis with desmoplastic reaction) that can kink the bowel or its vessels, causing obstruction or ischemia. Many are found late with nodal or liver metastases.
Carcinoid syndrome. Midgut tumors secrete serotonin into the portal circulation, where hepatic monoamine oxidase inactivates it, so the syndrome appears only after liver metastasis. Features are flushing, secretory diarrhea, wheezing, and fibrous plaques on the right-sided valves (tricuspid regurgitation, pulmonic stenosis). The left-sided valves are spared because the lungs also inactivate serotonin. Diverting tryptophan into serotonin can cause niacin deficiency (pellagra: dermatitis, diarrhea, dementia). Bronchial and ovarian NETs drain directly into the systemic veins and can cause the syndrome without liver metastases.
Diagnosis. A 24-hour urine 5-HIAA (the serotonin metabolite) confirms serotonin excess; bananas, pineapple, kiwi, walnuts, avocado, and tomatoes can raise it falsely. Ga-68 DOTATATE PET-CT localizes tumors by imaging somatostatin receptors, and chromogranin A is a supportive marker.
Treatment. Resect the primary and mesenteric nodes when feasible. Somatostatin analogs (octreotide, lanreotide) control flushing and diarrhea and slow tumor growth.
Anesthesia, surgery, and tumor manipulation can trigger carcinoid crisis (flushing, hypotension, bronchospasm). Give octreotide before and during such procedures.
Small bowel adenocarcinoma and lymphoma
Adenocarcinoma. Most common in the duodenum, often periampullary. Predisposing conditions include Crohn disease (in the inflamed ileum), celiac disease, familial adenomatous polyposis, Lynch syndrome, and Peutz-Jeghers syndrome (STK11; hamartomatous polyps with lip and buccal pigmentation). It presents with obstruction, bleeding, or obstructive jaundice.
Enteropathy-associated T-cell lymphoma (EATL). A T-cell lymphoma that complicates long-standing, often refractory celiac disease, usually in the jejunum. Suspect it when diarrhea, weight loss, abdominal pain, bleeding, or perforation return despite a strict gluten-free diet. Strict gluten avoidance lowers the risk, and prognosis is poor.