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NET of Stomach & Small Intestine [ Bailey]

Neuroendocrine Tumours (NETs) of the Stomach and Small Intestine

Embryology and Physiology:

  • APUD cells: Present throughout the GI tract, developed from foregut, midgut, and hindgut.
  • Neuroendocrine cells: Secrete neuroendocrine markers like Chromogranin A, Synaptophysin, and Neurone-specific enolase.
  • Gastrin: Secreted by enterochromaffin-like (ECL) cells in the stomach, critical in regulating gastric acid secretion.
  • Serotonin (5-HT): Main neurotransmitter, involved in intestinal motility and secretion.
  • Main functional test: Measurement of 5-HIAA in urine for jejunal and ileal NETs.

Pathogenesis:

  • Tumors arise from neuroendocrine cells and secrete serotonin (5-HT) in excess.
  • In the presence of liver metastases, serotonin bypasses liver metabolism, leading to carcinoid syndrome.
    • Symptoms include flushing, sweating, bronchospasm, and right-sided valvular heart disease (Hedinger syndrome).
  • NETs can be either benign or malignant.
  • Incidence: 2.5-5.0 per 100,000/year with prevalence up to 35 per 100,000.

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Stomach NETs:

  • Incidence: Rare, about 0.2 per 100,000/year.
  • Pathology:
    • Type I (70-80%): Linked to atrophic gastritis and high gastrin levels.
    • Type II (5%): Polyps / Small tumors [ <1 cm]; Associated with Zollinger-Ellison Syndrome (ZES), small gastrinomas.
    • Type III (15-25%): Larger tumors [>1-2 cm] with low gastrin levels, more aggressive, and often malignant.
  • Clinical Presentation:
    • Type I: Found incidentally during gastroscopy for vague dyspeptic symptoms.
    • Type II: Multiple and complicated peptic ulcers, typically in ZES patients.
    • Type III: Present with bleeding or discomfort.
  • Diagnosis:
    • Upper endoscopy with biopsy for localized tumors.
    • EUS: To assess tumor depth and local involvement.
    • Staging: CT, SRS, or 68Ga-DOTATOC PET for metastasis.
  • Treatment:
    • Medical: Type I - B12 replacement, Type II - PPI therapy, regular endoscopic surveillance.
    • Surgical:
      • Absolute Indications:
        • Local excision for Type I polyps >1 cm.
        • Gastrinoma resection for Type II.
        • Type III requires aggressive resection as they tend to metastasize to the liver.

Duodenal NETs:

  • Incidence: Exceptionally rare (1-3% of GI-NETs).
  • Pathology:
    • Usually small, <20 mm.
    • Can be functional (e.g., gastrinomas, somatostatinomas) or non-functional.
    • Gastrinomas often associated with MEN 1.
  • Clinical Presentation:
    • Gastrinoma: Presents like Type II gastric NET or part of MEN 1.
    • Somatostatinoma: Often associated with NF-1, causes gallstones.
  • Diagnosis:
    • Elevated gastrin in gastrinomas.
    • Chromogranin A is often elevated.
    • EUS, CT, SRS for staging.
  • Treatment:
    • PPI therapy for gastrinomas.
    • Resection for localized duodenal tumors.

Small Intestine NETs:

  • Incidence: Midgut carcinoids are the most common NETs, peak diagnosis at 60-70 years.
  • Pathology:
    • Arise from enterochromaffin cells.
    • Secrete serotonin and substance P.
    • Typically small (5-20 mm) and can be solitary or multiple.
    • Frequently present at an advanced stage with regional lymph node and liver metastases.
  • Clinical Presentation:
    • Chronic abdominal pain is the most common symptom.
    • Carcinoid syndrome in 20-30% of patients with liver metastases.
    • Small bowel ischemia due to constriction of mesenteric vessels by lymph node metastases.
  • Diagnosis:
    • Chromogranin A: Elevated, but non-specific.
    • 24-hour urinary 5-HIAA: Specific for NETs.
    • CT/MRI: Identify mesenteric lymph node involvement and liver metastases.
    • Biopsy: For diagnosis, Ki-67 grading is crucial for prognosis.

  • Treatment:

    • Surgical:

      • Stages I-III are cadidates for curative resection
      • Curative resection (R0) for localized disease.
      • The limiting factor is often lymph node involvement around the superior mesenteric artery, especially in the presence of severe desmoplastic reaction.
      • Palliative resection for obstructive symptoms in metastatic disease.
      • Concomitant cholecystectomy should be considered owing to the risk of gallstone formation secondary to SSAs.

    • Medical:

      • Somatostatin analogs (SSAs) for syndrome control and antiproliferative purposes.
      • Peptide Receptor Radionuclide Therapy (PRRT) as second-line for SSA failure.
      • Cisplatin-based chemotherapy for grade III tumors (NEC).

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Appendiceal NETs:

  • Incidence: Most common neoplasm of the appendix.
  • Pathology: Classified by tumor size and involvement of subserosa or mesoappendix.
  • Treatment:
    • Appendectomy curative for tumors <10 mm.
    • Right hemicolectomy for tumors >20 mm or deep mesoappendiceal invasion.

Prognosis:

  • Type I: Excellent, with surveillance for recurrence.
  • Type II: Good, though slightly higher risk of metastasis.
  • Type III: Poorer prognosis, with 25-30% 5-year survival due to higher rates of metastasis.