What is the recommended management for a patient with well-differentiated neuroendocrine tumors (G1) in the stomach, with clear margins and no lymph node involvement, following resection?

Management of Resected Well-Differentiated Gastric Neuroendocrine Tumors (G1)

Primary Recommendation

For this patient with multifocal well-differentiated G1 gastric NETs (1.2 cm and <1 cm), both completely resected with clear margins, pT2 stage, and no lymph node assessment, the recommended management is endoscopic surveillance every 6-12 months for the first 3 years, then annually for up to 10 years, with consideration of chromogranin A monitoring. 1

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Rationale for Surveillance Over Additional Surgery

Tumor Characteristics Favor Conservative Management

• Both tumors are G1 (well-differentiated) with <2 mitoses per 2 mm², indicating indolent biological behavior 1
• The larger tumor (1.2 cm) invades only the submucosa (pT2), which is associated with excellent prognosis in G1 gastric NETs 2
• Complete resection with clear margins (0.3 cm closest margin) has been achieved, eliminating the primary disease burden 1
• No lymphovascular invasion was identified, which is a critical favorable prognostic factor 2

Type Classification Determines Management Strategy

• These tumors require gastrin level assessment to determine type (Type 1 vs Type 3), as this fundamentally changes surveillance approach 1
• If hypergastrinemic (Type 1): These are associated with chronic atrophic gastritis and have extremely low malignant potential—surveillance with endoscopy every 6-12 months for 3 years, then annually is appropriate 1
• If normal gastrin (Type 3): More aggressive behavior is possible, but recent evidence shows G1 tumors ≤1.5 cm without lymphovascular invasion have favorable outcomes with local resection alone 2

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Surveillance Protocol

Endoscopic Surveillance Schedule

• Perform follow-up endoscopy at 6 and 12 months after resection, then every 6-12 months for up to 10 years 1
• For Type 1 gastric NETs specifically: endoscopy every 6-12 months for the first 3 years, then annually thereafter 1
• Endoscopy should include biopsy of the resection site and adjacent mucosa to assess for recurrence and evaluate for intestinal metaplasia 1

Biochemical Monitoring

• Chromogranin A levels may be monitored (Category 3 evidence), though elevations can occur with proton pump inhibitor use, renal insufficiency, or hepatic insufficiency 1
• Chromogranin A levels elevated twice the normal limit or higher are associated with shorter survival in metastatic disease (HR 2.8), but rising levels in asymptomatic patients with stable imaging do not necessarily mandate treatment initiation 1
• 24-hour urine 5-HIAA is generally not indicated for gastric NETs unless carcinoid syndrome is suspected 1

Cross-Sectional Imaging

• Multiphasic CT or MRI of the abdomen/pelvis should be performed at 3-12 months post-resection, then every 6-12 months as clinically indicated 1
• Somatostatin receptor scintigraphy (Octreoscan) is not routinely recommended for surveillance after definitive resection 1

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When Additional Surgery Would Be Indicated

Indications for Radical Resection

• If these were Type 3 gastric NETs (normal gastrin) AND either tumor was >2 cm, partial or total gastrectomy with lymph node dissection would have been indicated initially 1
• If lymph node metastases are discovered on subsequent imaging, surgical resection should be considered 1
• If recurrence occurs with unfavorable histology (G2 or higher) or invasion beyond submucosa, surgical intervention may be warranted 2

Why Lymphadenectomy Is Not Routinely Needed Now

• For G1 gastric NETs ≤2 cm with clear margins and no lymphovascular invasion, local excision is adequate—neither wide margins nor routine lymph node dissection are necessary 1
• The absence of lymph nodes in the submitted specimen (pNX) is acceptable for these small, low-grade tumors 2
• Lymph node metastasis risk is extremely low in G1 gastric NETs <1.5 cm without lymphovascular invasion 2

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Special Considerations for Multifocal Disease

Management of Multiple Tumors

• Multifocal gastric NETs are common, particularly in Type 1 disease associated with hypergastrinemia and atrophic gastritis 1
• Having ≤5 lesions is associated with significantly lower progression risk (HR 0.14) compared to >5 lesions 3
• This patient has only 2 tumors, which places them in a favorable prognostic category 3

Antrectomy Consideration for Type 1 Disease

• If Type 1 gastric NETs are confirmed (hypergastrinemia with atrophic gastritis), antrectomy to remove the source of gastrin production can be considered if new lesions or increasing tumor burden is observed during surveillance 1
• This is not indicated at initial presentation with complete resection, but remains an option for progressive disease 1

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Prognosis and Expected Outcomes

Excellent Long-Term Survival

• Type 1 gastric NETs ≤10 mm have a 5-year progression-free survival rate of 97.8%, with only 4% progression rate over median 72-month follow-up 3
• G1 gastric NETs ≤1.5 cm without lymphovascular invasion treated with wedge or endoscopic resection show no recurrence in most cases 2
• In one series of 22 patients with G1 NETs treated with local resection, only one patient with a tumor >1.5 cm developed lymph node recurrence after median 59-month follow-up 2

Mortality Considerations

• In patients with small Type 1 gastric NETs under surveillance, no tumor-related deaths occurred, though 8.8% died from other causes 3
• Low-grade Type 3 gastric NETs have non-aggressive features and favorable prognosis when completely resected 2

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Common Pitfalls to Avoid

Do Not Over-Treat Low-Grade Disease

• Radical gastrectomy with lymphadenectomy is not indicated for completely resected G1 gastric NETs ≤2 cm without adverse features 1, 2
• The historical approach of aggressive surgery for all gastric NETs has been replaced by risk-stratified management based on size, grade, and type 4

Do Not Under-Surveil

• Despite excellent prognosis, surveillance for up to 10 years is recommended because recurrence can occur after many years 1
• Failure to assess gastrin levels prevents proper type classification and may lead to inappropriate management 1

Recognize Limitations of Chromogranin A

• Chromogranin A is elevated in many concurrent conditions and with proton pump inhibitor use—do not initiate new therapy based solely on rising chromogranin A in asymptomatic patients with stable imaging 1
• Gastrin levels remain persistently high in Type 1 gastric NETs with atrophic gastritis, making them uninformative for surveillance 1

Ensure Proper Histologic Classification

• Confirm well-differentiated histology and G1 grade (mitotic rate <2 per 2 mm² and Ki-67 <3%)—G2 or G3 tumors require different management 1
• Verify absence of lymphovascular invasion, as its presence significantly increases metastatic risk even in small tumors 2