Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Clinical features and prognosis of malignant small bowel tumors: Experience from a university hospital in Chile / Características clínicas y pronóstico de los tumores malignos de intestino delgado: experiencia en un hospital universitario de Chile

Background Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America.AimTo describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs.MethodsRetrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile.ResultsA total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1–99.2), 82.2% (95%CI: 57.6–93.3), 40.0% (95%CI: 16.5–82.8) and 25.9% (95%CI: 4.5–55.7%), respectively. NET (HR 6.1; 95%CI: 2.1–17.2) and GIST (HR 24.4; 95%CI: 3.0–19.8) were independently associated with higher survival compared to AC, adjusted for age and sex.ConclusionsMalignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes. (AU)

Introducción Los tumores del intestino delgado (TID) son infrecuentes y la información sobre ellos es escasa en Latinoamérica.ObjetivoDescribir la epidemiología, características clínicas, métodos diagnósticos y supervivencia de los TID malignos.MétodosEstudio observacional retrospectivo de pacientes adultos con diagnóstico histopatológico de TID entre 2007-2021 en un hospital universitario de Chile.ResultadosSe observaron 104 pacientes (51,9% hombres; edad media 57 años) con TID. El tipo histológico fue tumor neuroendocrino (TNE) (43,7%, n=38), tumor estromal gastrointestinal (GIST) (21,8%, n=19), linfoma (17,2%, n=15) y adenocarcinoma (AC) (11,5%, n=10). Los GIST fueron más frecuentes en el duodeno (50%; n=12) y los TNE en el íleon (65,8%; n=25). Hubo 17 casos de metástasis, más comúnmente de colon y melanoma. Las náuseas y los vómitos se observaron con mayor frecuencia en AC (p=0,035), así como el sangrado gastrointestinal en GIST (p=0,007). Las herramientas de valoración más comunes fueron TC y enteroclisis por TC con un rendimiento diagnóstico alto (86% y 94%, respectivamente). La supervivencia a cinco años de los GIST, TNE, linfoma y AC fue 94,7% (intervalo de confianza [IC] 95%: 68,1-99,2), 82,2% (IC 95%: 57,6-93,3), 40,0% (IC 95%: 16,5-82,8) y 25,9% (IC 95%: 4,5-55,7), respectivamente. Los TNE (hazard ratio [HR] 6,1; IC 95%: 2,1-17,2) y GIST (HR 24,4; IC 95%: 3,0-19,8) se asociaron de forma independiente con una mayor supervivencia en comparación con AC, ajustado por edad y sexo.ConclusionesLos TID malignos son enfermedades poco frecuentes y los TNE son el subtipo histológico más común. La presentación clínica en el momento del diagnóstico, localización o complicaciones pueden sugerir un dictamen más probable. Los GIST y TNE se asocian a una mejor supervivencia en comparación con otros subtipos malignos. (AU)

Prevalence of metastases outside the liver and abdominal lymph nodes on 68Ga-DOTATOC-PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours.

Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (68Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on 68Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by 68Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified. The most recent 68Ga-DOTATOC-PET/CT report for each patient was reviewed, and the location and number of metastases of interest were recorded. Lesions outside the liver and abdominal nodes were found in 26% of patients (n = 310/1177), of whom 21.5% (255/1177) were diagnosed with Si-NET and 4.5% (55/1177) Pan-NET. Bone metastases were found in 18.4% (215/1177), metastases to Virchow's lymph node in 7.1% (83/1177), and lung/pleura in 4.8% (56/1177). In the subset of 255 Si-NET patients, 5.4% (41/255) manifested lesions in the pancreas, 1.5% in the breast (18/255), 1.3% in the heart (15/255) and 1% in the orbita (12/255). In Si-NET patients, the Ki-67 proliferation index was higher in those with ≥2 metastatic sites of interest, than with 1 metastatic site, (p <0.001). Overall, extra-abdominal or pancreatic metastases were more often found in patients with Si-NET (34%) than in those with Pan-NET (13%) (p <0.001). Bone metastases were 2.6 times more frequent in patients with Si-NET compared to Pan-NET patients (p <0.001). Lesions to the breast and orbita were encountered in almost only Si-NET patients. In conclusion, lesions outside the liver and abdominal nodes were detected in as many as 26% of the patients, with different prevalence and metastatic patterns in patients with Si-NET compared to Pan-NET. The impact of such metastases on overall survival and clinical decision-making needs further evaluation.

Clinical features and prognosis of malignant small bowel tumors: Experience from a university hospital in Chile.

BACKGROUND: Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America. AIM: To describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs. METHODS: Retrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile. RESULTS: A total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1-99.2), 82.2% (95%CI: 57.6-93.3), 40.0% (95%CI: 16.5-82.8) and 25.9% (95%CI: 4.5-55.7%), respectively. NET (HR 6.1; 95%CI: 2.1-17.2) and GIST (HR 24.4; 95%CI: 3.0-19.8) were independently associated with higher survival compared to AC, adjusted for age and sex. CONCLUSIONS: Malignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes.

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database.

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083).

Gastroenteropancreatic neuroendocrine carcinoma in children and adolescents: a population-based study.

PURPOSE: Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC) in children is an exceptionally rare and aggressive form of cancer. We aimed to conduct a population-based cohort study to predict overall survival (OS) in pediatric patients with GEP-NEC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was employed to identify all pediatric patients with GEP-NEC diagnosed between 2000 and 2019. To create survival curves based on various criteria, Kaplane-Meier estimations were utilized. The log-rank test was used to compare survival curves. The variables associated with OS were determined using Cox proportional-hazards regression. Furthermore, we developed a nomogram to predict overall survival in pediatric GEP-NEC patients. RESULTS: A total of 103 pediatric GEP-NEC patients were identified. The tumors primarily affected females (62.2%). The majority of GEP-NEC was found in the appendix (63.1%), followed by the pancreas (23.3%) and the intestinal tract (13.6%). The highest rates of localized stage (76.9%) and surgery (98.5%) were found in the NEC of appendix origin. However, pancreatic origins had the largest proportion of distant disease (66.7%) but the lowest percentage of surgery (37.5%). Overall 1-year, 3-year, and 5-year survival rates for all patients were 94.4%, 85.4%, and 85.4%, respectively. Tumors of pancreatic origin had the worst survival compared with those of the appendix and intestinal tract. The Cox proportional hazard regression revealed that only site was an important independent predictor of survival. CONCLUSIONS: Our study revealed that only the primary site was found to be the most important predictor of the OS in pediatric GEP-NEC. It's important to work closely with a multidisciplinary team, including oncologists, surgeons, and other specialists, to determine the most appropriate treatment plan for pediatric GEP-NEC.

Surveillance of the small-bowel by capsule endoscopy in Lynch syndrome - A systematic review with meta-analysis.

BACKGROUND & AIMS: The role of small-bowel (SB) cancer surveillance by capsule endoscopy (CE) in Lynch syndrome (LS) patients has been investigated in recent years, with contradicting results. This meta-analysis evaluates the diagnostic yield (DY) of CE as a screening tool in asymptomatic LS patients. METHODS: A systematic literature search was performed for all studies reporting the results of SB cancer screening in patients with LS. The primary outcome was the evaluation of the DY of CE in this setting for consecutive screening rounds. RESULTS: Five studies comprising 428 patients and CE 677 procedures were included for data extraction and statistical analysis. The estimated pooled DY for CE-identified pathological findings was 8% in the first screening round and 6% in the second. Limiting the analysis to histologically-confirmed pathological findings, the pooled DY of second-round screening dropped to 0%. The included studies showed a significantly different prevalence of pathogenic variants in mismatch repair (path_MMR) genes, which underlie different cumulative incidences of extracolonic cancers. CONCLUSIONS: SB surveillance by CE with a 2-year interval in asymptomatic LS individuals does not appear to be an effective screening strategy. Confirmatory prospective studies in this context are needed, considering the different cumulative incidence of SB tumors according to underlying path_MMR defects.

Site-specific trends in gastroenteropancreatic neuroendocrine neoplasms in Bavaria, Germany.

INTRODUCTION: Neuroendocrine neoplasms (NEN) are rare and heterogeneous epithelial tumors, occurring throughout the body. For gastroenteropancreatic (GEP)-NEN, rising incidence rates were reported for the last decades, with underlying causes remaining largely unexplained. We evaluated NEN trends stratifying by their histologic subtypes. METHODS: Incident cases of GEP-NEN diagnosed between 2005 and 2019 were retrieved from the prospective, population-based Bavarian Cancer Registry. GEP-NEN were divided in their histologic subtypes, that is, neuroendocrine tumors (NET) G1, NET G2/G3, other NET versus small-cell neuroendocrine carcinoma (NEC), large-cell NEC, and other NEC. We calculated annual age-standardized incidence rates (ASIRs) per 100,000 persons for the total of GEP-NEN, NEN histologic subtypes, and tumor sites. We used an annual percentage change (APC) approach including a joinpoint analysis to investigate NEN incidence trends. RESULTS: ASIR of GEP-NEN rose from 2.2 in 2005 to 4.8 in 2019, characterized by a significant increase until 2012 (APC 2005-2012: 10.1%), followed by modest rise (APC 2012-2019: 1.5%). In the last decade, this increase was mainly driven by the rise of NET G1 and G2/G3, while incidence for NEC declined. Over the study period, ASIR increased significantly for all GEP-sites except the colon. APCs were largest for the stomach, the appendix, the pancreas, and the rectum. CONCLUSIONS: This study found a significant increase in the incidence of GEP-NET. Though this development may partially be attributable to the increased use of advanced detection techniques and changes in NEN classification, further research should also focus on the identification of NEN risk factors.

Symptoms Contributing to the Diagnosis of Small Bowel Tumors.

INTRODUCTION: Small bowel tumors (SBTs) are difficult to diagnose because of limited opportunities and technical difficulties in evaluating the small bowel. Asymptomatic conditions or nonspecific symptoms make SBT diagnosis more challenging. In Asia, SBTs are reported to be more frequently malignant lymphoma (ML), adenocarcinoma, and gastrointestinal stromal tumor (GIST). In this study, we examined 66 patients diagnosed with SBTs and determined their clinical characteristics. METHODS: This retrospective study was conducted from January 2013 to July 2020 at Kurume University Hospital. The modalities used to detect SBTs were computed tomography (CT), positron emission tomography, magnetic resonance imaging, and ultrasonography. Endoscopy was also performed in some cases to confirm SBT diagnosis. The study included 66 patients. The medical data collected included presenting symptoms, tumor location, underlying condition, diagnostic modalities, pathologic diagnosis, and treatment. RESULTS: ML and adenocarcinoma were the most common tumors (22.7%), followed by GIST (21.2%) and metastatic SBT (18.2%). Symptoms that led to SBT detection were abdominal pain (44.5%), asymptomatic conditions (28.8%), hematochezia (12.1%), and anemia (10.6%). CT was the most used modality to detect SBTs. Nineteen patients were asymptomatic, and SBTs were incidentally detected in them. GISTs and benign tumors were more often asymptomatic than other malignant tumors. CONCLUSION: Abdominal pain was the main symptom for SBTs in particular adenocarcinoma, ML, and metastatic SBT. In addition, GIST, which was highly prevalent in Asia, had fewer symptoms. An understanding of these characteristics may be helpful in the clinical practice of SBTs.

Incidence, Risk Factors, and Temporal Trends of Small Intestinal Cancer: A Global Analysis of Cancer Registries.

BACKGROUND & AIMS: Small intestinal cancer is a rare cancer, with limited studies exploring its epidemiology. To our knowledge, this study is the first effort to comprehensively analyze the incidence, risk factors, and trends for small intestinal cancer by sex, age, and country. METHODS: Global Cancer Observatory, Cancer Incidence in Five Continents Plus, and Global Burden of Disease were accessed to estimate the age-standardized rates of small intestinal cancer incidence (International Classification of Diseases, 10th Revision, Clinical Modification: C17) and prevalence of lifestyle risk factors, metabolic risk factors, and inflammatory bowel disease (IBD). Risk factor associations were assessed by linear and logistic regressions. Average annual percent change was calculated using joinpoint regression. RESULTS: A total of 64,477 small intestinal cancer cases (age-standardized rate, 0.60 per 100,000) were estimated globally in 2020, with a higher disease burden found in North America (1.4). Higher small intestinal cancer incidence was associated with higher human development index; gross domestic product; and prevalence of smoking, alcohol drinking, physical inactivity, obesity, diabetes, lipid disorder, and IBD (ß = 0.008-0.198; odds ratios, 1.07-10.01). There was an overall increasing trend of small intestinal cancer incidence (average annual percent change, 2.20-21.67), and the increasing trend was comparable among the 2 sexes but more evident in the older population aged 50-74 years than in the younger population aged 15-49 years. CONCLUSION: There was a substantial geographic disparity in the burden of small intestinal cancer, with higher incidence observed in countries with higher human development index; gross domestic product; and prevalence of unhealthy lifestyle habits, metabolic disorders, and IBD. There was an overall increasing trend in small intestinal cancer incidence, calling for the development of preventive strategies.

Characteristics and treatment results of patients with gastroenteropancreatic neuroendocrine tumors in a tertiary care centre.

BACKGROUND: Gastroenteropancreatic Neuroendocrine tumors (GEP-NET) are rare neoplasms with limited reported data from the Middle East. Our study aims to report the clinicopathological feature, treatment patterns, and survival outcomes of patients with GEP-NET from our part of the world. METHODS: Medical records of patients diagnosed with GEP-NET between January 2011 and December 2016 at a single center in Saudi Arabia were reviewed retrospectively, and complete clinicopathological and treatment data were collected. Patients' survival was estimated by the Kaplan-Meier method. RESULTS: A total of 72 patients were identified with a median age of 51 years (range 27-82) and male-to-female ratio of (1.1). The most common tumor location was the pancreas (29.1%), followed by small bowel (25%), stomach (12.5%), rectum (8.3%), colon (8.3%), and appendix (6.9%). Forty-one patients (57%) had well-differentiated grade (G)1, 21 (29%) had G2, and 4 (6%) had G3. In five patients, the pathology was neuroendocrine carcinoma and in one it could not be classified. 54.2% of the patients were metastatic at diagnosis. Forty-two patients underwent surgical resection as primary management while 26 underwent systemic therapy, three patients were put on active surveillance, and one was treated endoscopically with polypectomy. The 5-year overall survival and progression-free survivals were 77.2% and 49%, respectively, for the whole group. Patients with G1 and 2 disease, lower Ki-67 index, and surgically treated as primary management had significantly better survival outcomes. CONCLUSION: Our study suggests that the most common tumor locations are similar to western reported data. However, there seems to be a higher incidence of metastatic disease at presentation than in the rest of the world.

Lifestyle Factors and Development and Natural Course of Gastroenteropancreatic Neuroendocrine Tumors: A Review of the Literature.

INTRODUCTION: The rarity of neuroendocrine tumors (NETs) and their heterogeneous presentation complicate the identification of risk factors for their development and natural course. Several tumor-specific prognostic factors have been identified, but less attention has been given to lifestyle factors as risk and prognostic factors. This review aimed to identify studies on smoking, alcohol use, physical activity, diet, body mass index (BMI), and diabetes and their association with the development and course of gastroenteropancreatic (GEP-) NETs. METHODS: The literature was systematically searched for articles on lifestyle factors and NETs available via PubMed and Embase. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS: A total of 25 eligible studies out of 3,021 screened articles were included. Most studies reported on smoking and alcohol, reporting conflicting results. Diet seems to have an influence on NET development, but few studies were published. Articles reporting on BMI were not unanimous on the effect on GEP-NETs. Diabetes was reported as a risk factor for NETs, while a protective effect was observed with metformin use. CONCLUSION: Different tissues, i.e., the pancreas and small intestine, may respond differently to exposure to alcohol and smoking. Evidence for diet so far is too limited to draw conclusions. Diabetes seems to be an important risk factor for the development of pancreatic NETs with a protective role in disease progression, while BMI is not unequivocally associated with the development and prognosis of NETs. Hence, our findings suggest that lifestyle factors play an important role in NET development as a disease course. Future research should consider lifestyle as an influence on disease progression and treatment response.

Characteristics and outcome of patients with small bowel adenocarcinoma (SBA).

BACKGROUND: Small bowel adenocarcinoma (SBA) remains a rare malignancy accounting for less than 5% of all the gastrointestinal tract cancers. However, only limited data and expert guidelines are available for this entity. As a result, treatment concepts are predominantly derived from colorectal cancer. METHODS: To substantiate data on the course of disease, diagnosis and treatment of SBA, we performed a population-based analysis from a Bavarian population of 2.2 million people. RESULTS: We identified 223 patients with SBA. Mean age at diagnosis was 67.8 years and patients were diagnosed rather late (34.5% UICC stage IV). Largest proportion of these patients were diagnosed with adenocarcinoma of the duodenum (132 patients, 59.2%) and most patients were diagnosed with late stage cancer, stage IV (70 patients, 31.4%). With respect to treatment, most patients underwent primary surgery (187 patients, 84.6%). Systemic therapy seemed to have an impact in UICC stage IV patients but not in UICC stage IIB or III. The 5-year survival rate was 29.0%. This was significantly less compared to colon cancer in the same cohort, which was 50.0%. Furthermore, median survival of patients with small bowel cancer was only 2.0 years (95% CI 1.4-2.5) compared to 4.9 years (95% CI 4.8-5.1) of patients with colon cancer. CONCLUSION: SBA showed a distinct epidemiology compared to colon cancer. Thus, data acquisition particularly on systemic treatment are paramount, with the objective to complement the available guidelines.

[Chinese expert consensus on gastroenteropancreatic neuroendocrine neoplasms (2022 edition)].

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are highly heterogeneous tumors. According to the 2019 World Health Organization classification and grading criteria for neuroendocrine neoplasms of the gastrointestinal tract and hepatopancreatobiliary organs, GEP-NENs include well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). GEP-NETs may present as hormonally functioning or nonfunctioning tumors and may have distinct clinical features based on their sites of origin. The Expert Committee of Neuroendocrine Tumors, Chinese Society of Clinical Oncology revised and updated the 2016 version of Chinese expert consensus on GEP-NENs. The update the consensus includes the epidemiology, clinical manifestations, biochemical and imaging examinations, pathological features, and treatment and follow-up of GEP-NENs.

A Real-World, Population-Based Study for the Incidence and Outcomes of Neuroendocrine Neoplasms of Nondigestive, Nonpulmonary Primary.

OBJECTIVES: The aim of this study was to assess incidence and outcomes of neuroendocrine neoplasms (NENs) arising from primary sites other than digestive organs, lung, or thymic gland. METHODS: Surveillance, Epidemiology, and End Results database (1975-2016) was accessed, and cases of NENs arising from primary sites other than digestive organs, lung, or thymic gland were reviewed. Overall and cancer-specific survival outcomes for NENs arising from different organs compared with small intestinal NENs were evaluated. RESULTS: A total of 4405 patients were included in the study. Compared with small intestinal NENs, some NENs arising from uncommon sites in the current study have worse cancer-specific survival (hazard ratio [HR] for genitourinary vs small intestinal NENs, 1.80; 95% confidence interval [CI], 1.44-2.25; HR for gynecological vs small intestinal NENs, 1.88; 95% CI, 1.52-2.33). When the analysis was limited for patients with distant stage only, small intestinal NENs have better outcomes compared with genitourinary and gynecological NENs (HR for genitourinary NENs with distant stage vs small intestinal NENs with distant stage, 1.38; 95% CI, 1.01-1.88; HR for gynecological NENs with distant stage vs small intestinal NENs with distant stage, 2.02; 95% CI, 1.54-2.66). CONCLUSIONS: Compared with small intestinal NENs, NENs arising from uncommon sites (such as genitourinary, gynecological) have worse survival outcomes.

Gastroenteropancreatic Neuroendocrine Tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of these tumors. This article reviews the presentation, diagnosis, and management of both localized and advanced GEP-NETs, with increased emphasis on the role of endoscopy, to enable gastroenterologists and other practitioners to have the necessary tools for the care of patients with these tumors.

Survival of patients with small bowel neuroendocrine neoplasms in Auckland, Aotearoa New Zealand.

BACKGROUND: Small intestinal Neuroendocrine Neoplasms (SI-NENs) are the most common primary malignancy of the small bowel. The aim of this study is to define the survival of patients with an SI-NEN in Auckland, Aotearoa New Zealand (AoNZ). METHODS: A retrospective study of all patients diagnosed with a jejunal or ileal SI-NEN in the Auckland region between 2000 and 2012 was performed. The New Zealand NETwork! Registry was searched to identify the study cohort. Retrospective data collection was performed to collect stage, survival and follow up data. RESULTS: One hundred and seven patients were included in the study. The mean age of patients was 62.8 years (SD 11.9). The 5 and 10-year disease-specific survival for all patients was 66.1% (95% CI 56.5-75.7%) and 61.8% (95% CI 51.8-71.8%), respectively. Ten-year disease-specific survival was 100% for stage I and II, 74% (95%CI 61.7-84.4%) for stage III and 33.9% (95%CI 16.9-35.6%) for stage IV SI-NEN. Eleven of 40 (27.5%) patients with stage III disease had recurrence and 3 of 7 (42.8%) patients with stage IV disease had recurrence. In patients with stage IV disease, neither primary resection (HR 2.25, 95% CI 0.92-5.5) nor distant resection (HR 1.72, 95% CI 0.63-4.7) were significantly associated with a disease-specific or overall survival benefit. CONCLUSION: This study demonstrates that stage at SI-NEN diagnosis is associated with survival, but resection of the primary or distant metastases in patients with stage IV disease is not. There was no recurrence in patients with stage I or II disease after complete resection.

Incidence and prognosis of patients with small intestinal neuroendocrine tumors in a population based nationwide study.

BACKGROUND & AIMS: Small intestinal neuroendocrine tumours (SI-NETs) are the most frequent malignant tumours of the small intestine. Population based studies on SI-NETs are scarce. We aimed to examine the incidence, presentation of disease and prognosis of SI-NET and to determine patient prognosis in those undergoing emergency or elective surgery. METHODS: This was a retrospective population-based study. Information on all patients diagnosed with neuroendocrine tumours of the small intestine (excluding duodenum) from the beginning of the Icelandic Cancer Registry and the pathology departments in the country (1966-2017). Detailed phenotypic information was obtained from medical records on symptoms at diagnosis, treatment, recurrence and survival. RESULTS: A total of 113 patients with SI-NETs were identified, 3 patients were excluded due to lack of data and/or diagnostic error, leaving 110 patients for final analysis. The incidence of SI-NET was 0.78/100,000 and did not increase during the study period. A total of 42 % (n = 46) of patients were diagnosed incidentally. Long-term prognosis, after a landmark of 12 months, was better in patients who were diagnosed incidentally (HR 0.52; p = 0.03). Overall 89 % (n = 98) of cases underwent surgical resection of the primary tumor, 31 % (n = 30) patients acute or semi-acute surgery and 69 % (n = 68) elective surgery. Emergency surgery was associated with a 6-fold risk of death in the first 12 months after surgery (HR: 5.99; p = 0.01) and associated with more severe surgical complications. However, there was no difference in the long-term risk of death after the first 12 months (HR: 1.39; p = 0.27). CONCLUSIONS: The incidence of SI-NETs has not changed significantly in the last decades. Incidentally diagnosed SI-NET was associated with a favorable long-term prognosis. Emergency surgery in patients with SI-NET was associated with a significantly worse short-term risk of mortality compared to those who underwent elective surgery.

An update on the diagnosis of gastroenteropancreatic neuroendocrine neoplasms.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) arise from neuroendocrine cells found throughout the gastrointestinal tract and islet cells of the pancreas. The incidence and prevalence of GEP-NENs have been increasing each year due to higher awareness, improved diagnostic modalities, and increased incidental detection on cross-sectional imaging and endoscopy for cancer screening and other conditions and symptoms. GEP-NENs are a heterogeneous group of tumors and have a wide range in clinical presentation, histopathologic features, and molecular biology. Clinical presentation most commonly depends on whether the GEP-NEN secretes an active hormone. The World Health Organization recently updated the classification of GEP-NENs to introduce a distinction between high-grade neuroendocrine tumors and neuroendocrine carcinomas, which can be identified using histology and molecular studies and are more aggressive with a worse prognosis compared to high-grade neuroendocrine tumors. As our understanding of the biology of GEP-NENs has grown, new and improved diagnostic modalities can be developed and optimized. Here, we discuss clinical features and updates in diagnosis, including histopathological analysis, biomarkers, molecular techniques, and radiology of GEP-NENs. We review established diagnostic tests and discuss promising novel diagnostic tests that are currently in development or require further investigation and validation prior to broad utilization in patient care.

Second primary malignancies after ovarian cancer: A SEER-based analysis (1975-2016).

OBJECTIVE: To investigate the risk of occurrence of second primary malignancies (SPMs) in survivors of ovarian cancer (OC) using large data from the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Multiple primaries standardized incidence ratios (MP-SIRs) to calculate the risk of developing second primary malignancies after a diagnosis of ovarian cancer. RESULTS: Of our included 59,880 women with OC, 3972 cases (6.6%) developed 4495 s primary malignancies over an average follow-up period of 114.39 (±102.66) months. Overall, the risk of occurrence of second primary malignancies after a diagnosis of OC was greater than what would be expected for a reference US population (SIR = 1.05, 95%CI = 1.02-1.08, p-value < 0.05). The occurrence of second myeloid malignancies and second thyroid cancer were most notable across our latency periods. Among the most significant second primary malignancies by latency were malignancies of the appendix (SIR = 14.04, 95%CI = 5.65-28.93, p-value <0.05) at 2-11 months, the small intestine (SIR = 3.15, 95%CI = 1.76-5.2, p-value <0.05) at 12-59 months, and the urinary bladder (SIR = 1.63, 95%CI = 1.3-2.02, p-value <0.05) after 10 years of an OC diagnosis. CONCLUSION: Women with OC are at significant risk for the development of second primary malignancies across all sites, as compared to a reference US population, and may benefit from second primary malignancies site-specific screening post-diagnosis.