Neuroendocrine tumors (NETs) are rare malignancies arising from the diffuse neuroendocrine system, often in the gastroenteropancreatic (GEP) tract. GEP-NETs, primarily involving the intestines (50%) and pancreas (30%), may occasionally secrete hormones, causing syndromes. Diagnosis relies on markers like chromogranin A, synaptophysin, and Ki-67, along with imaging modalities. Rising NETs incidence is attributed to advancements in diagnostic modalities, particularly endoscopic ultrasonography (EUS). EUS demonstrates high accuracy in detecting small lesions, assessing tumor depth, and identifying locoregional lymph nodes. Despite its proven diagnostic utility, there is limited data on EUS's role in evaluating GEP-NETs in resource-constrained settings like Pakistan.

To evaluate the diagnostic role of EUS in characterizing GEP-NETs based on clinical, histopathological, tumor grading, and site-specific differences.

This single-center retrospective descriptive study was conducted at Aga Khan University Hospital, Karachi, a tertiary care hospital, from January 2021 to December 2023. Fourteen adult patients (≥ 18 years) with suspected NETs who underwent EUS and were diagnosed via histopathology were included. Data on demographics, clinical features, radiological findings, and histopathological characteristics were collected. Descriptive analysis was performed using SPSS version 23, with descriptive statistics expressed as means ± SD for continuous variables and frequencies/percentages for categorical data.

A total of 14 adult GEP-NETs patients who underwent EUS were included, with a mean age of 52 ± 14 years and the majority being male (71.4%). Common clinical presentations included weight loss (85.7%) and abdominal pain (78.6%). Computed tomography scans were performed in 92.9% of cases, with pancreatic masses detected in 42.9% of patients. EUS-guided fine needle biopsy (FNB) had a 100% diagnostic yield. The pancreas was the most common tumor site (57.1%). Histopathology revealed 78.6% of cases as well-differentiated NETs with 42.9% being grade II. Metastases were seen in 57.1% of patients, with the liver being the most common site. Surgical interventions were performed in 28.6% of patients, and all patients were alive at the time of study analysis.

EUS, with accurate imaging and effective EUS-FNB, is the gold standard for GEP-NET diagnosis, aiding tumor assessment and prognosis. Larger studies are needed to validate its impact on management outcomes.

• Neuroendocrine tumors
• Gastro-enteropancreatic neuroendocrine tumors
• Diagnostic imaging
• Endosonography
• Neoplasm grading
• Biopsy
• Fine-needle
• Endoscopic ultrasound-guided fine needle aspiration
• Immunohistochemistry
• Developing countries

Gastric neuroendocrine tumors (G-NETs) are rare tumors originating from enterochromaffin-like cells, with an incidence of 0.4 per 100000 annually. There are three main types: (1) Type I, linked to chronic atrophic gastritis and hypergastrinemia, makes up 75%–80% of G-NETs; (2) Type II, associated with Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia, comprises 5%; and (3) Type III, sporadic tumors with a higher metastatic potential, accounting for 15%–25%. Diagnosis involves endoscopy, biopsy, and histological examination. Additional methods include serum gastrin testing, immunohistochemistry, and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis. Type I treatment usually involves endoscopic resection (ER), with surgical resection for recurrence. Somatostatin analogs (SSAs) can reduce tumor size, and the prognosis is generally excellent. Type II treatment centers on surgical removal of the gastrinoma, with ER for smaller lesions and SSAs for symptom management. Type III requires surgical resection (partial or total gastrectomy) with lymph node dissection, and possibly chemotherapy. This type has a worse prognosis due to its aggressive nature. Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases, and ongoing research into immunotherapies is expanding future treatment options. Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types. Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment, particularly for those associated with less favorable cases.

To improve diagnostic precision and treatment, particularly for those associated with less favorable cases.

A systematic search was conducted in PubMed, Scopus, and Web of Science until September 2024. Two independent reviewers screened titles, abstracts, and full texts for eligibility based on G-NET treatment in adults. Eligible studies included cohort studies, clinical trials, case series, and case reports, while in vitro, pediatric, and non-English studies were excluded. Relevant data were extracted independently, and disagreements were resolved through discussion. Study quality was assessed using appropriate tools.

G-NETs are rare, classified into three types: (1) Type I; (2) Type II; and (3) Type III. Type I G-NETs, often associated with chronic atrophic gastritis, are typically slow-growing and low-grade, with favorable outcomes following surgical resection. Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES, showing moderate malignancy risk. Type III G-NETs, the most aggressive and least common, present with distant metastases and poor prognosis. Diagnosis relies on endoscopy, imaging, and biomarkers like chromogranin A. Treatment varies by type, ranging from ER to aggressive surgery and chemotherapy for advanced cases. Regular follow-up is essential to monitor recurrence, particularly for type III G-NETs.

G-NETs require tailored diagnosis and treatment based on type and stage. Types I and II generally have better prognosis, while types III and IV are linked to poorer outcomes due to invasion and metastasis. Treatment strategies vary from ER for type I to extensive surgery for type III. Emerging therapies, like somatostatin analogs and peptide-receptor radionuclide therapies, show promise in advanced cases. Further research is essential to improve early diagnosis and treatment, particularly for high-risk lesions.

• Stomach
• Neuroendocrine tumors
• Neuroendocrine
• Tumor
• Neoplasm
• Carcinoma
• Treatment
• Peptide receptor radionuclide therapy
• Endoscopic resection

• Neuroendocrine neoplasms
• Peptide receptor radionuclide therapy
• Positron emission tomography
• Somatostatin receptors
• Theranostics

• Neuroendocrine Tumors/therapy
• Neuroendocrine Tumors/epidemiology
• Neuroendocrine Tumors/diagnosis
• Neuroendocrine Tumors/pathology
• Humans
• Prognosis
• Incidence
• Neoplasm Staging
• Symptom Assessment
• Clinical Relevance

• MiNEN
• multimodality treatment
• neuroendocrine carcinoma
• neuroendocrine neoplasms
• neuroendocrine tumor

• Humans
• Female
• Male
• Middle Aged
• Gallbladder Neoplasms/pathology
• Gallbladder Neoplasms/therapy
• Gallbladder Neoplasms/mortality
• Aged
• Retrospective Studies
• Adult
• Neuroendocrine Tumors/pathology
• Neuroendocrine Tumors/therapy
• Neuroendocrine Tumors/mortality
• Aged, 80 and over
• Prognosis
• Survival Rate
• Follow-Up Studies
• Combined Modality Therapy

• Classification
• Neuroendocrine tumor
• Stomach
• Survival
• World Health Organization

• Humans
• Middle Aged
• Retrospective Studies
• Neuroendocrine Tumors/surgery
• Neuroendocrine Tumors/pathology
• Stomach Neoplasms/pathology
• Prognosis
• World Health Organization
• Neoplasm Grading

• duodenal neuroendocrine tumours
• gastric carcinoids
• guidelines
• management
• prognosis

• Humans
• Neuroendocrine Tumors/diagnosis
• Neuroendocrine Tumors/therapy
• Neuroendocrine Tumors/pathology
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/pathology
• Societies
• Carcinoma, Neuroendocrine

• adenocarcinoma
• gallbladder
• neuroendocrine neoplasm
• prognosis
• surgery

• Humans
• Male
• Female
• Aged
• Gallbladder/surgery
• Gallbladder/pathology
• Retrospective Studies
• Neuroendocrine Tumors
• Prognosis
• Gastrointestinal Neoplasms
• Neoplasm Staging
• Gallbladder Neoplasms/surgery
• Gallbladder Neoplasms/pathology

• Carcinoid syndrome
• Endoscopy
• Functional neuroendocrine tumor
• Gastroenteropancreatic neuroendocrine tumor

Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered, often incidentally, throughout the gastrointestinal tract with varying degrees of activity and malignant potential. Confusing nomenclature has added to the complexity of managing these lesions. The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm, which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms. A comprehensive multidisciplinary approach is important for clinicians to diagnose, stage and manage these lesions. While histological diagnosis is the gold standard, recent advancements in endoscopy, conventional imaging, functional imaging, and serum biomarkers complement histology for tailoring specific treatment options. In light of developing technology, our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors, including innovations in radiolabeled peptide imaging, circulating biomarkers, and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.

• Gastroenteropancreatic neuroendocrine neoplasms
• Neuroendocrine tumors
• Neuroendocrine carcinoma
• Gastrointestinal
• Pancreas
• Small intestine

• Diagnosis
• Gastroenteropancreatic neuroendocrine neoplasms
• Neuroendocrine carcinoma
• Neuroendocrine tumours
• Treatment
• World Health Organization classification

• Gastrointestinal Neoplasms/diagnosis
• Gastrointestinal Neoplasms/genetics
• Gastrointestinal Neoplasms/therapy
• Humans
• Neuroendocrine Tumors/diagnosis
• Neuroendocrine Tumors/pathology
• Neuroendocrine Tumors/therapy
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/therapy
• Prognosis

• Future perspectives
• Gastroenteropancreatic neuroendocrine neoplasms
• Medical treatments
• Overview
• Radical surgery
• Therapeutic strategies

Neuroendocrine neoplasms (NENs) of the gallbladder (GB) are extremely rare. We aimed to compare the clinical features of GB-NENs with those of adenocarcinomas (ADCs) of the GB. Among 21 patients with GB-NENs, 20 were diagnosed with poorly differentiated small-cell neuroendocrine carcinoma (NEC), and 1 patient had large-cell NEC. At initial presentation, all patients had advanced stages of cancer, with extensive local extension and/or distant metastasis. Nine patients with GB-NEC who underwent surgical resection had a significantly better progression-free survival (PFS) than those who did not undergo surgery. After a propensity score matching with a 1:1 ratio using the American Joint Committee on Cancer (AJCC) stage, age, sex, and operation status, there was no difference in the overall survival or PFS between AJCC stage-matched patients with GB-NEC or GB-ADC. In conclusion, GB-NEC is difficult to diagnose early and has a prognosis similar to that of GB-ADC.

Neuroendocrine neoplasms (NENs) of the gallbladder (GB) are extremely rare. We aimed to compare the clinical features, disease progression, management, and prognosis of patients with GB-NENs with those of patients with GB-adenocarcinomas (ADCs). A total of 21 patients with GB-NENs and 206 patients with GB-ADCs, treated at three tertiary medical centers between January 2010 and December 2020, were enrolled. Of the 21 patients with GB-NENs, 20 were diagnosed with poorly differentiated small-cell neuroendocrine carcinomas (NECs), and 1 patient had large-cell NEC. All patients presented with advanced stages of cancer with extensive local extension and/or distant metastasis and non-specific symptoms. Tumor-node-metastasis stage IIIB and IV (A/B) tumors were found in 6 and 15 (1/14) patients, respectively. Nine patients with GB-NEC who underwent surgical resection had a significantly better progression-free survival (PFS) than those who did not undergo surgery. After a propensity score matching with a 1:1 ratio using the American Joint Committee on Cancer stage, age, sex, and operation status, 19 pairs of patients were included. Compared with stage-matched patients with GB-ADC, patients with GB-NEC had similar overall survival and PFS. However, as GB-NEC is rarely diagnosed early, further studies investigating methods for the early diagnosis and improvement in the survival of patients with GB-NEC are needed.

• adenocarcinoma
• gallbladder
• neuroendocrine carcinoma
• neuroendocrine neoplasm
• propensity score matching

• Endoscopy
• Gastrointestinal tract
• Neuroendocrine tumors

• gastroenterology
• gastrointestinal surgery
• general surgery
• pernicious anemia
• surgery

• Carcinoid Tumor/surgery
• Endoscopy
• Gastritis, Atrophic
• Humans
• Stomach Neoplasms/surgery
• Zollinger-Ellison Syndrome

• duodenum
• endoscopic resection
• lymph node metastasis
• neuroendocrine neoplasm
• upper gastrointestinal tract

• Aged
• Endoscopic Mucosal Resection
• Female
• Humans
• Lymphatic Metastasis/diagnosis
• Male
• Middle Aged
• Neuroendocrine Tumors/mortality
• Neuroendocrine Tumors/pathology
• Neuroendocrine Tumors/surgery
• Retrospective Studies
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery

• HER2
• PD-L1
• gastric cancer
• oesophageal cancer
• targeted therapy

• Adenocarcinoma/drug therapy
• Adenocarcinoma/pathology
• Antibodies, Monoclonal, Humanized/therapeutic use
• Antineoplastic Agents, Immunological/therapeutic use
• Esophageal Neoplasms/drug therapy
• Esophageal Neoplasms/pathology
• Humans
• Molecular Targeted Therapy
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/pathology
• Trastuzumab/therapeutic use
• Ramucirumab

• Endoscopic surveillance
• Gastric carcinoids
• Gastric neuroendocrine tumour
• Type 1 gastric neuroendocrine neoplasms

• cytoreductive surgery
• endoscopic resection
• enterectomy with lymph node dissection
• gastrointestinal neuroendocrine tumors

• Carcinoid syndrome
• Colonic neuroendocrine tumors
• Gastric neuroendocrine tumors
• Gastrointestinal neuroendocrine tumors
• Rectal neuroendocrine tumors
• Small intestinal neuroendocrine tumors

Neuroendocrine neoplasms (NENs) are derived from neuroendocrine cell system and can have benign or malignant characteristics. They are rare tumors, but have been increasing in incidence over the past 40 years. Patients with NENs may develop symptoms due to primary tumor invasion, metastasis, or from secretion of hormonally active tumor substances. Multiple imaging modalities are used for diagnosis and staging, including specialty scans such as ¹¹¹In pentetreotide (Octreoscan) and ⁶⁸Gallium-DOTATATE, along with endoscopy, endoscopic ultrasound, and biochemical marker testing. Treatment involves both surgical approach, for both primary and metastatic lesions, as well as medical management for symptom management and disease progression. This article will review the current clinical knowledge regarding the diagnosis, treatment, and prognosis of these fascinating neoplasms and the associated hormonal syndromes.

• Neuroendocrine tumor
• carcinoid syndrome
• malignant carcinoid
• neuroendocrine carcinoma

• classification
• control follow-up
• diagnosis
• duodenal neuroendocrine tumors
• endoscopic treatment
• surgery

• Duodenum
• Neuroendocrine tumour
• Pancreaticoduodenectomy