Liver metastases of neuroendocrine tumors: Conventional transarterial chemoembolization and thermal ablation.

PURPOSE: To identify prognostic factors for patients with neuroendocrine liver metastases (NELM) undergoing conventional transarterial chemoembolization (c-TACE), microwave ablation (MWA), or laser interstitial thermotherapy (LITT) and to determine the most effective therapy regarding volume reduction of NELM and survival. MATERIALS AND METHODS: Between 1996 and 2020, 130 patients (82 men, 48 women) were treated with c-TACE, and 40 patients were additionally treated with thermal ablation. Survival was retrospectively analyzed using the Kaplan-Meier-method. Additional analyses were performed depending on the therapeutic intention (curative, palliative, symptomatic). Prognostic factors were derived using Cox regression. To find predictive factors for volume reduction in response to c-TACE, a mixed-effects model was used. RESULTS: With c-TACE, an overall median volume reduction of 23.5 % was achieved. An average decrease in tumor volume was shown until the 6th c-TACE treatment, then the effect stopped. C-TACE interventions were most effective at the beginning of c-TACE therapy, and treatment breaks longer than 90 days negatively influenced the outcome. Significant prognostic factors for survival were number of liver lesions (p = 0.0001) and type of therapeutic intention (p < 0.0001). Minor complications and one major complication occurred in 20.3 % of LITT and only in 8.6 % of MWA interventions. Complete ablation was observed in 95.7 % (LITT) and 93.1 % (MWA) of interventions. CONCLUSION: New prognostic factors were found for survival and volume reduction. Efficacy of c-TACE decreases after the 6th intervention and treatment breaks longer than 90 days should be avoided. With thermal ablation, a high rate of complete ablation was achieved, and survival improved. KEY POINTS: · Number of liver lesions and therapeutic intention are prognostic factors for survival.. · Regarding volume reduction, C-TACE is most effective at the beginning of treatment and longer treatment breaks should be avoided.. · With MWA and LITT, a high rate of complete ablation was achieved. MWA trends toward fewer complications than LITT in the treatment of NELM (p = 0.07)..

Management of type 1 gastric neuroendocrine tumors: an 11-year retrospective single-center study.

BACKGROUND: Type 1 gastric neuroendocrine tumors (NETs) are relatively rare to the extent that some physicians have little experience in diagnosing and treating them. The purpose of this study was to increase the understanding of the disease by analyzing and summarizing the management and prognoses of patients with type 1 gastric NETs at our center. METHODS: The data of 229 patients (59.4% female) with type 1 gastric NETs who were treated at our center during 2011-2022 were retrospectively analyzed. RESULTS: The average patient age was 50.5 ± 10.8 years. Multiple tumors affected 72.5% of the patients; 66.4% of the tumors were < 1 cm, 69.4% were NET G1, and 2.2% were stage III-IV. A total of 76.9% of the patients had received endoscopic management, 60.7% had received traditional Chinese medicine treatment, 10.5% received somatostatin analogues treatment, and 6.6% underwent surgical resection. Seventy patients (41.2%) experienced the first recurrence after a median follow-up of 31 months (range: 2-122 months), and the median recurrence-free time was 43 months. The 1-, 2-, and 3-year cumulative recurrence-free survival rates were 71.8%, 56.8%, and 50.3%, respectively. During a median follow-up of 39 months (range: 2-132 months), one patient had bilateral pulmonary metastasis, and no disease-related deaths were observed. CONCLUSION: Type 1 gastric NETs have a high recurrence rate and a long disease course, underscoring the importance of long-term and comprehensive management.

[Treatment options for peritoneal metastases from hepato-pancreato-biliary tumors and neuroendocrine tumors]. / Therapeutische Optionen bei peritonealer Metastasierung hepatopankreatikobiliärer Tumoren und neuroendokriner Tumoren.

Peritoneal metastasis (PM) in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and hepato-pancreato-biliary (HPB) tumors has a low incidence and has rarely been studied as a stand-alone condition. The clinical relevance of PM in HPB tumors and GEP-NET arises from the fact that PM significantly worsens the prognosis of the underlying tumors. In GEP-NET, the particular situation is that PM has a negative prognostic impact compared to patients without metastases, which is not evident compared to patients with metastases in other locations. Complete surgical cytoreduction (CRS) is a curative treatment option for patients with PM in GEP-NET. Complete surgical resection should always be strived for, although patients may benefit from incomplete resection (70-90%) or resection of the primary tumor alone. Additional hyperthermic chemoperfusion (HIPEC) is currently not recommended. For nonresectable GEP-NET, systemic treatment is available that is oriented to the studies for generally metastasized GEP-NET. For PM in carcinomas of the bile duct and pancreatic carcinomas, there are no valid data or indications for CRS and HIPEC. In contrast, case series for PM in hepatocellular carcinoma (HCC) after CRS or CRS/HIPEC show good survival outcomes that justify a surgical approach under the condition of a complete resection. Patients with PM in GEP-NET and HCC should therefore be referred to a center for peritoneal tumor surgery to evaluate the option of complete CRS and use it as a curative option.

Surgical, Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Clinical Practice Guideline.

INTRODUCTION: The aim of this guideline was to provide recommendations for the most effective therapy for patients with thymic epithelial tumors, including thymoma, thymic carcinoma, and thymic neuroendocrine tumors (NETs). This guideline is intended to be used by all health care professionals managing patients with thymic epithelial tumors. METHODS: The guideline was developed by Ontario Health (Cancer Care Ontario)'s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of the evidence, expert consensus, and formal internal and external reviews. RESULTS: Evidence-based recommendations were developed to improve the management of patients with thymic epithelial tumors. The guideline includes recommendations for surgical, radiation, and systemic treatments for patients with thymoma, thymic carcinoma, and thymic NETs separated by stage of disease using the TNM staging system. Recommendations for patients with thymic NETs were endorsed from the 2021 National Comprehensive Cancer Network Neuroendocrine and Adrenal Tumors Guideline. CONCLUSIONS: This guideline reflects the new staging system for patients with thymoma and thymic carcinoma and includes supporting evidence from the best available studies.

[Interpretation of updated international guidelines for diagnosis and treatment of gastroenter-opancreatic neuroendocrine neoplasms].

The incidence of neuroendocrine neoplasms (NEN) is continuously increasing with gastrointestinal tract and pancreas being the most common primary sites. Currently, the guidelines proposed by European Neuroendocrine Tumor Society (ENETS), National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) and North American Neuroendocrine Tumor Society (NANETS) are being widely applied. Among these, ENETS and NANETS guidelines were proposed in 2017 while ESMO and NCCN recently updated their guidelines for gastroenteropancreatic NEN in 2020 and 2021, respectively. This article interprets the diagnosis and treatment of gastroenteropancreatic NEN based on the newly updated ESMO and NCCN guidelines. The diagnosis of gastroenteropancreatic NEN depends on histological assessment including morphological evaluation, grading and immunohistochemistry results. Combination of different imaging methods can help determine tumor staging and risk assessment. Decision-making of treatment and follow-up strategies is based on primary tumor site, tumor classification, tumor grade, tumor type, functional status etc.

Insurance-based Disparities in Gastro-Entero-Pancreatic Neuroendocrine Tumor Patients.

In the United States, uninsurance remains a major barrier in accessing health care for many citizens and residents. Studies have shown that uninsured patients with many cancers and chronic diseases have worse survival than insured patients. A recent study similarly showed that uninsured patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) have significantly shortened survival. While GEP-NETs are indolent tumors with generally favorable prognosis, comprehensive care involves years of surveillance, imaging, and treatment following resection, all of which carry a large financial burden. In this commentary, we expand on these findings as they relate to insurance-based disparities as well as management and policy implications.

Comparison of Nausea and Vomiting Associated With Amino Acid Formulations Coinfused With Peptide Receptor Radionuclide Therapy: Commercial Parenteral Nutrition Formulas Versus Compounded Arginine/Lysine.

OBJECTIVES: Positively charged amino acids (AA) such as arginine/lysine are coinfused with radiolabeled somatostatin analogs to reduce rates of nephrotoxicity. In the phase 3 NETTER-1 trial, commercial AA formulations were used in association with 177Lu-DOTA-0-Tyr3-Octreotate (DOTATATE). These formulations were also used in an early-access program (EAP) before regulatory approval of 177Lu-DOTATATE. Our program transitioned to compounded l-arginine 2.5%/l-lysine 2.5% in 0.9% NaCl after commercial approval of 177Lu-DOTATATE. We sought to compare rates of nausea/vomiting with arginine/lysine versus commercial parenteral AA formulations. METHODS: Rates of nausea/vomiting of all 20 EAP patients who received commercial AAs (15% Clinisol) were compared with the first 29 patients to receive 177Lu-DOTATATE after commercial approval and coinfused with arginine/lysine. Other parameters reviewed included infusion rates, need for PRN nausea medications, and other toxicities. RESULTS: Seventeen percent of patients who received compounded arginine/lysine experienced nausea, compared with 100% of patients in the EAP group (P < 0.0001). Infusion-related reactions occurred in 3% of the arginine/lysine cohort versus 35% in the EAP group. Infusion durations were substantially shorter in the arginine/lysine cohort (reduced by 61%). CONCLUSIONS: Coinfusions of arginine/lysine with radiolabeled somatostatin analogs result in substantially lower rates of nausea/vomiting compared with commercial AA formulations designed for parenteral nutrition.

Hereditary Neuroendocrine Tumors: Providing Comprehensive Care for Individuals Who Have a Germline Pathogenic Variant Associated With Paragangliomas and Pheochromocytomas.

Both paragangliomas and pheochromocytomas can be associated with germline pathogenic variants. Although these neuroendocrine tumors are relatively rare, the identification of patients and families with germline risk enables the implementation of surveillance programs to decrease the morbidity and mortality associated with these tumors. Individuals with germline risk require lifelong screening, which is implemented as early as age 5 years. In addition to ensuring that surveillance protocols are implemented, nurses provide education about symptoms that require prompt evaluation.

Interpretation of updated international guidelines for diagnosis and treatment of gastroenter-opancreatic neuroendocrine neoplasms / 中华胃肠外科杂志

The incidence of neuroendocrine neoplasms (NEN) is continuously increasing with gastrointestinal tract and pancreas being the most common primary sites. Currently, the guidelines proposed by European Neuroendocrine Tumor Society (ENETS), National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) and North American Neuroendocrine Tumor Society (NANETS) are being widely applied. Among these, ENETS and NANETS guidelines were proposed in 2017 while ESMO and NCCN recently updated their guidelines for gastroenteropancreatic NEN in 2020 and 2021, respectively. This article interprets the diagnosis and treatment of gastroenteropancreatic NEN based on the newly updated ESMO and NCCN guidelines. The diagnosis of gastroenteropancreatic NEN depends on histological assessment including morphological evaluation, grading and immunohistochemistry results. Combination of different imaging methods can help determine tumor staging and risk assessment. Decision-making of treatment and follow-up strategies is based on primary tumor site, tumor classification, tumor grade, tumor type, functional status etc.

The patient-level effect of the cost of Cancer care - financial burden in German Cancer patients.

BACKGROUND: Financial toxicity of cancer has so far been discussed primarily in the US health care system and is associated with higher morbidity and mortality. In European health care systems, the socio-economic impact of cancer is poorly understood. This study investigates the financial burden and patient-reported outcomes of neuroendocrine (NET) or colorectal (CRC) cancer patients at a German Comprehensive Cancer Center. METHODS: This prospective cross-sectional study surveyed 247 advanced stage patients (n = 122 NET/n = 125 CRC) at the National Center for Tumor Diseases, in Germany about cancer-related out-of-pocket costs, income loss, distress, and quality of life. Multiple linear regression analysis was performed to demonstrate the effects of economic deterioration on patients' quality of life and distress. RESULTS: 81% (n = 199) of the patients reported out-of-pocket costs, and 37% (n = 92) income loss as a consequence of their disease. While monthly out-of-pocket costs did not exceed 200€ in 77% of affected patients, 24% of those with income losses reported losing more than 1.200€ per month. High financial loss relative to income was significantly associated with patients' reporting a worse quality of life (p < .05) and more distress (p < .05). CONCLUSIONS: Financial toxicity in third-party payer health care systems like Germany is caused rather by income loss than by co-payments. Distress and reduced quality of life due to financial problems seem to amplify the burden that already results from a cancer diagnosis and treatment. If confirmed at a broader scale, there is a need for targeted support measures at the individual and system level.

The Neuroendocrine Neoplasms of the Digestive Tract: Diagnosis, Treatment and Nutrition.

Nuroendocrine neoplasms (NENs) are a group of rare neoplasms originating from dispersed neuroendocrine cells, mainly of the digestive and respiratory tract, showing characteristic histology and immunoprofile contributing to classification of NENs. Some NENs have the ability to produce biogenic amines and peptide hormones, which may be associated with clinical syndromes like, e.g., the carcinoid syndrome caused by unmetabolized overproduced serotonin, hypoglycemic syndrome in case of insulinoma, or Zollinger-Ellison syndrome accompanying gastrinoma. Diagnostics for these include ultrasound with endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography/computed tomography (PET/CT). Different nuclear medicine procedures can also be used, like somatostatin analogues scintigraphy (SRS) and 68Ga-Dota-Peptide PET/CT, as well as biochemical methods to determine the level of general neuroendocrine markers, such as chromogranin A (CgA), 5-hydroxyindolacetic acid (5-HIAA), synaptopfysin and cell type-specific peptide hormones, and neurotransmitters like gastrin, insulin, serotonin, and histamine. NENs influence the whole organism by modulating metabolism. The treatment options for neuroendocrine neoplasms include surgery, somatostatin analogue therapy, radionuclide therapy, chemotherapy, molecular targeted therapies, alpha-interferon therapy, and inhibitors of serotonin production. In the case of hypersensitivity to biogenic amines, a diet that limits the main sources of amines should be used. The symptoms are usually connected with histamine, tyramine and putrescine. Exogenic sources of histamine are products that take a long time to mature and ferment. Patients with a genetic insufficiency of the diamine oxidase enzyme (DAO), and those that take medicine belonging to the group of monoamine oxidases (MAO), are particularly susceptible to the negative effects of amines. Diet plays an important role in the initiation, promotion, and progression of cancers. As a result of the illness, the consumption of some nutrients can be reduced, leading to nutritional deficiencies and resulting in malnutrition. Changes in metabolism may lead to cachexia in some patients suffering from NENs. The aim of this narrative review was to advance the knowledge in this area, and to determine possibilities related to dietary support. The authors also paid attention to role of biogenic amines in the treatment of patients with NENs. We can use this information to better understand nutritional issues faced by patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), and to help inform the development of screening tools and clinical practice guidelines.

Treatment sequence in patients with neuroendocrine tumours: a nationwide multicentre, observational analysis of the Swiss neuroendocrine tumour registry.

BACKGROUND: In recent years, several treatment modalities have proved to be effective in the treatment of neuroendocrine tumours (NETs). However, there is currently no consensus on the sequence in which these options are best used. METHODS: In this observational study, we analysed the treatment modalities and sequences of all patients included in the Swiss NeuroEndocrine Tumour registry (SwissNET). SwissNET is a national registry, which has prospectively included patients with a NET from all regions of Switzerland since 2008. RESULTS: The registry includes 1366 patients; 1063 had documented therapies after the main diagnosis and were included in the analysis. The median follow-up time was 1.86 years. The most common primary site was the small intestine (291 patients, 27%) followed by pancreas (254 patients, 24%), lung (172 patients, 16%) and appendix (163 patients, 15%). A total of 167 different therapy sequences were observed. In 708 (67%) patients, surgery was the only treatment. The sequence of surgery followed by chemotherapy was most frequently documented in poorly (G3) differentiated (24 patients, 60%) and pancreatic (15 patients, 34%) NETs. Tumours treated with surgery followed by biotherapy or followed by peptide receptor radionuclide therapy (PRRT) were predominantly well-differentiated G1 NETs of the small intestine. In patients who were treated with either PRRT or systemic therapy (chemotherapy or molecular therapy) or both, PRRT was used more frequently than systemic therapy in patients with a small intestinal NET (35 patients, 62% vs 30, 54%), whereas the opposite held true in pancreatic (44 patients, 59% vs 56, 70%) and lung NETs (6 patients, 14% vs 40, 97%). If both chemotherapy and molecular therapy were used, chemotherapy was applied prior to molecular therapy in 13 of 19 (68%) patients with a pancreatic NET. CONCLUSION: Surgery represents the treatment of choice in most patients with a NET irrespective of tumour stage. In patients receiving additional treatment, an impressive variety of treatment sequences were documented. In small intestinal NETs, patients received PRRT more often than chemotherapy, whereas the opposite holds true for patients with pancreatic and lung NETs.

Complementary and alternative medicine use during chemotherapy for neuroendocrine tumours.

Exploring the patient experience of complementary and alternative medicine (CAM) can provide insight into the needs, preferences and values of patients with an neuroendocrine tumour (NET). Use and interest in CAM after a NET diagnosis has not been investigated until now. The authors aimed to identify the types of CAM being used by patients undergoing chemotherapy and what types of CAM patients considered most beneficial. Patients were identified for clinical audit from one hospital's NET nurse chemotherapy database. A questionnaire was given to 79 patients who had completed intravenous chemotherapy during the previous 3 years. CAM use by NET patients was found to be popular and included practices to support both physical and emotional health. Massage and taking vitamin and mineral supplements were most widely used. The antioxidant effects of some high-dose supplements may impact on chemotherapy outcomes. Massage, despite its irregular use, was perceived by patients to be the most useful CAM.

68Gallium-DOTATATE positron emission tomography-computed tomography (PET CT) changes management in a majority of patients with neuroendocrine tumors.

BACKGROUND: 68Gallium-DOTATATE positron emission tomography-computed tomography (PET CT) has shown superior accuracy in detecting grade 1 and 2 neuroendocrine tumors over previous imaging modalities and was recently included in National Comprehensive Cancer Network guidelines. It remains unclear which patients benefit most from this imaging modality. We therefore reviewed our initial experience with 68Gallium-DOTATATE PET CT to evaluate its usefulness in diagnosing, staging, and surveilling neuroendocrine tumors. METHODS: Records of patients who underwent 68Gallium-DOTATATE PET CT from March to December 2017 were prospectively evaluated. The primary endpoint was whether 68Gallium-DOTATATE PET CT changes treatment in patients with neuroendocrine tumors. Descriptive statistics, Fisher exact tests, and nested logistic regressions were conducted. RESULTS: A total of 50 consecutive patients were included. Of these, 41 patients (82%) had a biopsy-proven neuroendocrine tumor at the time of imaging. The remaining 9 patients (18%) had symptoms or biochemistry suggestive of a neuroendocrine tumor with negative cross-sectional imaging. 68Gallium-DOTATATE PET CT changed management in 33 patients (66%). There were 24 patients with intermodality changes in management and 9 patients with intramodality changes in management. Patients with scans performed for staging had a higher likelihood of a change in management (P = .006). CONCLUSION: Performing 68Gallium-DOTATATE PET CT should be considered for staging and surveillance of neuroendocrine tumors because it is frequently associated with changes in management.

Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial.

BACKGROUND: Neuroendocrine tumors (NETs) are the second most common gastrointestinal malignancy after colon cancer. Up to 90% of patients with NETs develop liver metastases, which are a major determinant of symptoms and survival. Current guidelines recommend embolotherapy for progressive or symptomatic NET liver metastases, but the optimal technique among bland embolization, lipiodol chemoembolization, and drug-eluting bead chemoembolization remains unknown and controversial. METHODS/DESIGN: A prospective, open-label, multicenter randomized controlled trial will be conducted in patients with progressive or symptomatic unresectable NET liver metastases. Patients will be randomized to treatment with bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization, with 60 enrollees per arm. The primary endpoint will be hepatic progression-free survival (HPFS) following initial embolotherapy by RECIST criteria. The sample size is powered to detect an HR of 1.78 for HPFS following chemoembolization compared with bland embolization, which was estimated on the basis of existing retrospective studies. Secondary endpoints include overall progression-free survival, duration of symptom control, quality of life, rate of adverse events, and interval between embolotherapy cycles. Interim safety analyses will be performed at 10 and 30 patients per arm. DISCUSSION: The RETNET trial is a prospective, multicenter randomized controlled trial designed to determine the optimal embolotherapy technique for NET liver metastases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02724540 . Registered on March 31, 2016.

NCCN Guidelines Insights: Neuroendocrine and Adrenal Tumors, Version 2.2018.

The NCCN Guidelines for Neuroendocrine and Adrenal Tumors provide recommendations for the management of adult patients with neuroendocrine tumors (NETs), adrenal gland tumors, pheochromocytomas, and paragangliomas. Management of NETs relies heavily on the site of the primary NET. These NCCN Guidelines Insights summarize the management options and the 2018 updates to the guidelines for locoregional advanced disease, and/or distant metastasis originating from gastrointestinal tract, bronchopulmonary, and thymus primary NETs.

Current and emerging therapies for PNETs in patients with or without MEN1.

Pancreatic neuroendocrine tumours (PNETs) might occur as a non-familial isolated endocrinopathy or as part of a complex hereditary syndrome, such as multiple endocrine neoplasia type 1 (MEN1). MEN1 is an autosomal dominant disorder characterized by the combined occurrence of PNETs with tumours of the parathyroids and anterior pituitary. Treatments for primary PNETs include surgery. Treatments for non-resectable PNETs and metastases include biotherapy (for example, somatostatin analogues, inhibitors of receptors and monoclonal antibodies), chemotherapy and radiological therapy. All these treatments are effective for PNETs in patients without MEN1; however, there is a scarcity of clinical trials reporting the efficacy of the same treatments of PNETs in patients with MEN1. Treatment of PNETs in patients with MEN1 is challenging owing to the concomitant development of other tumours, which might have metastasized. In recent years, preclinical studies have identified potential new therapeutic targets for treating MEN1-associated neuroendocrine tumours (including PNETs), and these include epigenetic modification, the ß-catenin-wingless (WNT) pathway, Hedgehog signalling, somatostatin receptors and MEN1 gene replacement therapy. This Review discusses these advances.

Management of Well-differentiated Gastroenteropancreatic Neuroendocrine Tumors (GEPNETs): A Review.

PURPOSE: Neuroendocrine tumors (NETs) are heterogeneous tumors that arise from the neuroendocrine cells of the digestive tract and other organs, such as the lung, ovary, and thyroid glands. They can be well differentiated or poorly differentiated, and management of these tumors differs for each histologic subtype. We have performed a review of NETs and focused on management of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEPNETs) and carcinoid syndrome. METHODS: A PubMed search was performed to obtain articles on the management of well-differentiated NETs. Using the key words neuroendocrine tumors, carcinoid, pNET, octreotide, somatostatin analogues, and radiolabeled therapy, we reviewed Phase II and III trials that were published over the past 30 years. We also reviewed guidelines from the European Neuroendocrine Tumor Society, North America Neuroendocrine Tumor Society, and National Comprehensive Cancer Network in our search. FINDINGS: NETs are usually slow-growing tumors that remain asymptomatic for a long duration and can be either nonfunctioning or functioning. Surgical resection is recommended for locoregional disease, impending obstruction, symptom control, and advanced disease. Nonsurgical treatment options include somatostatin analogues (SSAs), multikinase inhibitors, targeted therapy, chemotherapy, and radiolabeled SSAs. Carcinoid syndrome is mainly treated with SSAs. IMPLICATIONS: Although GEPNETs are slow-growing tumors, most patients are diagnosed with metastatic disease, and therefore it is important that the management of each patient be discussed in a multidisciplinary setting to optimize the treatment strategy. Patients should be considered for clinical trials and refractory cases referred to a specialty center.

[Consensus and controversy of endoscopic diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors].

Neuroendocrine neoplasms(NENs) are relatively rare tumors originating from the diffuse neuroendocrine system, and gastrointestinal tract is one of the most common location of the tumors. Currently, the European Neuroendocrine Neoplasm Society (ENETS) and the National Comprehensive Cancer Network (NCCN) have released the international guidelines for NENs management. And also, experts from Chinese Society of Clinical Oncology (CSCO) have proposed "The Consensus on Gastroenteropancreatic Neuroendocrine Neoplasm in China" in 2016, which is also one of the most important reference standard for the diagnosis and treatment of gastroenteropancreatic(GEP) NENs in China. Here we will interpret these three guidelines or consensus. There are few controversies about endoscopic management principle for GEP-NEN of different locations and sizes among these three guidelines or consensus, but for small NENs without involving intrinsic muscularis, endoscopic resection is recommended and considered. We hope that this interpretation may help clinicians for clinical decision making.