Overview
Definition:
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms arising from neuroendocrine cells throughout the body
Surgical management aims for complete tumor removal
Enucleation involves surgically isolating and removing a tumor from surrounding tissue, preserving the bulk of the organ, typically used for small, benign or low-grade NETs
Resection involves removing the tumor along with a margin of surrounding healthy tissue, often including part or all of an organ, indicated for larger, malignant, or potentially invasive NETs.
Epidemiology:
NETs are rare, with an incidence of approximately 5-7 per 100,000 population annually
They can occur anywhere in the body, but are most common in the gastrointestinal tract and pancreas
Pancreatic NETs account for about 20-30% of all NETs
Incidence is increasing, partly due to improved diagnostic modalities
They occur in both sexes, with a slight female predilection for certain subtypes.
Clinical Significance:
The surgical approach for NETs is critical for achieving curative intent and preventing recurrence
Differentiating between enucleation and resection requires careful consideration of tumor size, grade, location, presence of invasion, and patient-specific factors
Incorrect surgical management can lead to incomplete tumor removal, recurrence, or unnecessary organ loss
Understanding these nuances is vital for surgical residents preparing for DNB and NEET SS examinations and for optimal patient outcomes.
Diagnostic Approach
History Taking:
Detailed patient history focusing on symptoms related to hormonal hypersecretion (e.g., flushing, diarrhea, peptic ulcers, hypoglycemia), constitutional symptoms (e.g., weight loss, fatigue), and prior medical history of malignancy or endocrine disorders
Inquire about family history of MEN syndromes.
Physical Examination:
Systematic physical examination looking for palpable masses, signs of hormonal excess (e.g., carci nod syndrome, hypoglycemia-induced neurological deficits), hepatomegaly due to metastases, lymphadenopathy, and stigmata of chronic disease
Assess for any abdominal distension or tenderness.
Investigations:
Laboratory investigations include serum chromogranin A (CgA) as a general tumor marker, specific hormone assays (e.g., insulin, gastrin, glucagon, VIP, serotonin) based on suspected functionality
Imaging modalities: CT scan of abdomen and pelvis with contrast for tumor localization and staging, MRI for better soft tissue delineation and pancreatic NETs, endoscopic ultrasound (EUS) for small pancreatic NETs and biopsy, somatostatin receptor scintigraphy (e.g., Octreoscan) for receptor status and metastatic evaluation
Biopsy for histological confirmation and grading (Ki-67 index).
Differential Diagnosis:
Differential diagnosis includes benign cysts, other pancreatic neoplasms (e.g., adenocarcinoma, IPMN), metastatic disease from other primary sites, and functional endocrine disorders of non-neoplastic origin
Distinguishing benign from malignant NETs, and localized disease from metastatic disease is paramount.
Surgical Management
Indications:
Surgical resection is indicated for all localized, symptomatic, or potentially malignant NETs
Indications for enucleation are typically reserved for small (<2 cm), benign-appearing, well-circumscribed, non-functional or hormonally inactive NETs of the pancreas or duodenum where vital structures can be preserved
Resection is indicated for larger tumors (>2 cm), malignant-appearing tumors, those with evidence of local invasion or nodal involvement, functional tumors causing significant symptoms, or when enucleation risks compromising organ function.
Preoperative Preparation:
Multidisciplinary team discussion involving surgeons, endocrinologists, oncologists, and radiologists
For functional NETs, preoperative medical management to control hormone secretion (e.g., somatostatin analogs, proton pump inhibitors, alpha/beta-blockers)
Nutritional assessment and optimization
Standard preoperative blood work, ECG, and anesthesia assessment
Careful imaging review to delineate tumor location and vascular involvement.
Procedure Steps:
Enucleation: Careful dissection to mobilize the tumor from surrounding pancreatic parenchyma or duodenal wall, taking care to identify and preserve critical structures like pancreatic ducts, bile ducts, and major vessels
Hemostasis is meticulous
Resection: Based on tumor location, procedures include pancreaticoduodenectomy (Whipple procedure) for head of pancreas NETs, distal pancreatectomy for body/tail NETs, pylorus-preserving pancreatectomy, spleen-preserving distal pancreatectomy, or segmental bowel resections for intestinal NETs
Lymphadenectomy is often performed with resection
Intraoperative ultrasound is crucial for precise localization.
Postoperative Care:
Close monitoring for hormonal crisis, bleeding, pancreatic fistula, bile leak, and ileus
Pain management
Gradual reintroduction of oral diet
Monitoring of blood glucose levels, especially after pancreatic surgery
Management of any specific hormonal symptoms
Mobilization and physiotherapy
Wound care.
Complications
Early Complications:
Pancreatic fistula (most common after pancreatic enucleation/resection), intra-abdominal abscess, hemorrhage, bile leak, delayed gastric emptying, pancreatitis, surgical site infection, prolonged ileus, wound dehiscence
Hormone withdrawal symptoms in functional tumors can also occur.
Late Complications:
Recurrence of NET (local or metastatic), development of new primary NETs, exocrine pancreatic insufficiency, endocrine pancreatic insufficiency (diabetes mellitus), bile duct stricture, adhesions leading to bowel obstruction, carcinoid crisis (rare but serious).
Prevention Strategies:
Meticulous surgical technique, careful identification and preservation of vital structures, appropriate use of drains and stents, prophylactic somatostatin analogs in high-risk cases, appropriate antibiotic prophylaxis, early mobilization, and vigilant postoperative monitoring
Adherence to oncological principles for resection margins.
Prognosis
Factors Affecting Prognosis:
Tumor grade (Ki-67 index), stage at diagnosis, presence of metastasis, completeness of surgical resection (R0 vs R1/R2), tumor location, tumor functionality, and patient's overall health status
Well-differentiated, low-grade, localized NETs have a good prognosis, with 5-year survival rates exceeding 80%
Poorly differentiated, high-grade, or metastatic NETs have a poorer prognosis.
Outcomes:
For localized NETs amenable to complete resection, the goal is cure
Survival rates are significantly better for NETs treated with R0 resection
For unresectable or metastatic disease, palliative surgery and medical management aim to control symptoms and prolong survival
Enucleation, when appropriate, can offer excellent outcomes with preservation of organ function.
Follow Up:
Regular lifelong follow-up is essential, typically including clinical assessment, serum chromogranin A levels, and cross-sectional imaging (CT/MRI) every 6-12 months for the first few years, then annually
Frequency and modality depend on tumor stage, grade, and resection status
Surveillance aims to detect recurrence or new primary tumors early.
Key Points
Exam Focus:
Differentiate indications for enucleation vs
resection in pancreatic and duodenal NETs
Understand the role of Ki-67 and CgA
Recognize common complications like pancreatic fistula and carcinoid syndrome
Know the principles of staging and surgical margins for NETs
MEN syndromes association.
Clinical Pearls:
Always consider NET in patients with unexplained hormonal syndromes or gastrointestinal symptoms
Intraoperative ultrasound is invaluable for precise localization of small NETs, especially for enucleation
Sentinel lymph node biopsy may be considered in select cases of small NETs
For functional NETs, preoperative medical control is key to prevent perioperative complications.
Common Mistakes:
Incorrectly selecting enucleation for malignant/invasive tumors, leading to incomplete resection
Aggressive resection when enucleation is sufficient, leading to unnecessary morbidity
Inadequate lymphadenectomy in resectable NETs
Failure to adequately control hormonal hypersecretion preoperatively
Over-reliance on single imaging modality, missing small lesions or metastatic disease.