Small Bowel Neuroendocrine Tumors Research Articles

Small Bowel Neuroendocrine Tumors-10-Year Experience of the Ottawa Hospital (TOH).

(1) Aim: The prevalence and incidence of small bowel NETs have increased significantly over the past two decades. This study aims to report the 10-year experience of SB-NET management at a regional cancer center in Canada. (2) Materials and methods: We conducted a retrospective study of the clinical and pathological data of patients diagnosed with biopsy-proven SB-NET at The Ottawa Hospital (TOH), Ottawa, Canada between 2011 and 2021. We report the clinicopathological characteristics of these patients, as well as their outcomes data, including survival rates. (3) Results: Between 2011 and 2021, a total of 177 SB-NET cases were identified with 51% (n = 91) of cases being males. The most common sites of the tumors were the ileum 53% (n = 94), followed by the duodenum 9% (n = 16) and jejunum 7% (n = 12). Approximately 24% (n = 42) of the patients had symptoms for over six months prior to diagnosis and 18% (n = 32) had functioning SB-NET during the course of the disease. The majority of patients had locally advanced or metastatic disease at the time of presentation with stage III, and stage IV representing 42% (n = 75), and 41% (n = 73) respectively. The majority of patients 84% (n = 148) had well-differentiated histology. One hundred twenty patients underwent surgical resection of the primary tumor including 28 patients (16%) with limited metastatic disease. A total of 21 patients (18%) had recurrence after curative surgery. A total of 62 patients (35%) received first-line somatostatin analog (SSA) therapy for unresectable disease and seven patients had PRRT after progression on SSA. Five years OS was 100%, 91%, 97%, and 73% for stages I, II, III, and IV respectively. In univariate analysis, carcinoid symptoms, T stage, and differentiation were significant predictors for worse overall survival, but not RFS. (4) Conclusions: Compared to published historical controls, our study suggests improvement in the 5-year survival rate of SB-NETs over the last 10 years.

Accuracy of DOTATATE PET imaging in the preoperative planning of small bowel neuroendocrine tumor resection.

We assessed the accuracy of preoperative gallium-68 DOTA-Tyr3-octreotate (DOTATATE) positron emission tomography (PET) imaging in estimating multifocality and nodal metastases of small bowel neuroendocrine tumors (sbNETs). A multicenter analysis was performed on patients with sbNETs who underwent preoperative DOTATATE PET imaging and surgical resection, with manual palpation of the entire length of the small bowel, between January 2016 and August 2022. Preoperative imaging reports and blinded secondary imaging reviews were compared to the final postoperative pathology reports. Descriptive statistics were applied. One-hundred and four patients met inclusion criteria. Pathology showed 53 (51%) patients had multifocal sbNETs and 96 (92%) had nodal metastases. The original preoperative DOTATATE PET imaging identified multifocal sbNET in 28 (27%) patients and lymph node(LN) metastases in 80 (77%) patients. Based on original radiology reports, sensitivity for multifocal sbNET identification was 45%, specificity was 92%, positive predictive value (PPV) was 86%, and negative predictive value (NPV) was 62%. For the identification of LN metastases, sensitivity was 82%, specificity was 88%, PPV was 99%, and NPV was 29%. Although DOTATATE PET imaging is specific and relatively accurate, sensitivity and NPV are insufficient to guide surgical planning. Preoperative use should not replace open palpation to identify additional synchronous lesions or to omit regional lymphadenectomy.

Metastatic small-bowel neuroendocrine tumours: medical management of the primary.

Metastatic small-bowel neuroendocrine tumours: medical management of the primary.

Prognostic differences in grading and metastatic lymph node pattern in patients with small bowel neuroendocrine tumors

PurposeNeuroendocrine tumors of the smallintestine (si-NET) describe a heterogenous group of neoplasms. Based on the Ki67 proliferation index si-NET are divided into G1 (Ki67 < 2%), G2 (Ki67 3–20%) and rarely G3 (Ki67 > 20%) tumors. However, few studies evaluate the impact of tumor grading on prognosis in si-NET. Moreover, si-NET can form distinct lymphatic spread patterns to the mesenteric root, aortocaval lymph nodes, and distant organs. This study aims to identify prognostic factors within the lymphatic spread patterns and grading.MethodsDemographic, pathological, and surgical data of 208 (90 male, 118 female) individuals with si-NETs treated at Charité University Medicine Berlin between 2010 and 2020 were analyzed retrospectively.ResultsA total of 113 (54.5%) specimens were defined as G1 and 93 (44.7%) as G2 tumors. Interestingly, splitting the G2 group in two subgroups: G2 low (Ki67 3–9%) and G2 high (Ki67 10–20%), displayed significant differences in overall survival (OS) (p = 0.008) and progression free survival (PFS) (p = 0.004) between these subgroups. Remission after surgery was less often achieved in patients with higher Ki67 index (> 10%). Lymph node metastases (N +) were present in 174 (83.6%) patients. Patients with isolated locoregional disease showed better PFS and OS in comparison to patients with additional aortocaval and distant lymph node metastases.ConclusionLymphatic spread pattern influences patient outcome. In G2 tumors, low and high grading shows heterogenous outcome in OS and PFS. Differentiation within this group might impact follow-up, adjuvant treatment, and surgical strategy.

Mortality in small bowel cancers and adenomas – A nationwide, population-based matched cohort study

BackgroundSmall bowel adenocarcinoma (SBA), neuroendocrine tumors (NET) and gastrointestinal stromal tumors (GIST) are neoplastic lesions of the small bowel while small bowel adenomas are precursors of SBA. AimTo examine mortality in patients diagnosed with SBA, small bowel adenomas, NET and GIST. MethodsWe performed a population-based matched cohort study encompassing all individuals with SBA (n = 2289), adenomas (n = 3700), NET (n = 1884) and GIST (n = 509) in the small bowel diagnosed at any of Sweden’s 28 pathology departments between 2000 and 2016 (the “ESPRESSO study”). Each case was matched by sex, age, calendar year and county of residence to up to 5 comparators from the general population. Through Cox regression we estimated hazard ratios (HRs) and 95% confidence intervals (95%CIs) for death and cause-specific death adjusting for education. ResultsDuring follow-up until December 31, 2017, 1836 (80%) deaths occurred in SBA patients, 1615 (44%) in adenoma, 866 (46%) in NET and 162 (32%) in GIST patients. This corresponded to incidence rates of 295, 74, 80 and 62/1000 person-years respectively and adjusted HRs of 7.60 (95%CI=6.95–8.31), 2.21 (2.07–2.36), 2.74 (2.50–3.01) and 2.33 (1.90–2.87). Adjustment for education had a substantial impact on the HR for death in SBA but not for other neoplasias. The predominant cause of excess death was cancer in all groups. ConclusionThis study confirms earlier findings of increased death rates in patients with SBA and NET in a modern study population. We also demonstrate a more than 2-fold increased risk of death in both GIST and the SBA precursor adenoma.

Correlation of cancer testis antigen and interleukin expression with survival in small bowel neuroendocrine tumors.

e16247 Background: Patients with small bowel neuroendocrine tumors (SBNETs) frequently present with metastatic disease, and unfortunately, the range and efficacy of available therapies is limited. Immunotherapeutic checkpoint inhibitors have demonstrated benefit in other malignancies and may also play a role in SBNETs, although relatively little is known about the immune infiltrate in these tumors. Toward a goal of developing novel immunomodulatory strategies, we sought to evaluate the tumor immune microenvironment of SBNETs utilizing Nanostring transcriptional profiling. Methods: Patients with SBNETs who underwent surgical resection at MD Anderson Cancer Center from 2003 to 2016 were retrospectively analyzed. Clinicopathologic data was collected, and patients were stratified by survival. Overall survival (OS) from date of resection was assessed using the Kaplan-Meier method, and p-values were calculated using the log-rank test. Multivariate (MV) analysis was performed using the Cox proportional hazards model. Transcription expression from bulk RNA was analyzed using the Nanostring PanCancer Immune Profiling Panel. Results: Resected SBNETs from 45 patients were selected for transcriptional analysis. Unsupervised clustering of RNA expression data revealed separation into high and low expression groups in two distinct transcription panels: cancer testis antigens (CTA) and interleukins (IL). All patients in the IL-high group also were in the CTA-high group. CTA-high patients (n=13) had significantly improved overall survival compared to CTA-low patients (n=32; median OS not reached vs 1975 days, p=0.0032). MV analysis controlling for age, gender, metastatic disease and history of carcinoid syndrome confirmed CTA-high status as an independent predictor of improved OS (hazard ratio 6.6, 95% confidence interval 1.7-26.4, p=0.008). CTA-high patients had significantly elevated expression of CTAs (such as PRAME and GAGE1) and cytokines (such as IL2 and CXCR1). High normalized expression levels of these single genes were independent predictors of improved OS in MV analysis (PRAME p=0.008, GAGE1 p=0.006, IL2 p=0.008, CXCR1 p&lt;0.0001). Conclusions: High expression of CTA and IL signatures in resected SBNETs identified patients with improved survival agnostic of stage. While CTA expression across multiple tumor subtypes have been implicated in their immunogenicity and potential for therapeutic targeting, this is the first work to identify a clinically relevant signal in SBNET. The concurrent increase of key cytokines (which are known to mediate anti-tumor activity) among CTA-high patients suggests an immune-mediated component to their improved survival. Further work is underway to elucidate the epigenetic mechanisms of CTA expression and silencing, with the goal of validating key CTAs such as PRAME and GAGE1 as predictive and therapeutic targets for immunologic intervention.

Clinical and radiological criteria for candidate patients with small bowel neuroendocrine neoplasms (SB-NEN) for minimally invasive surgery: A single-centre experience.

e16246 Background: Although open resection represents the standard of care of localized small bowel neuroendocrine neoplasms (SB-NEN), minimally invasive surgery (MIS) has proven to be a viable alternative in patients with low disease burden. This study aims to assess the reliability of preoperative clinical and radiological criteria used at European Institute of Oncology (IEO) to candidate patients with SI-NEN to MIS. Methods: Patients diagnosed with SB-NEN and eligible for MIS at IEO were retrospectively evaluated between 2013 and 2022. Preoperative physical examination, CT enterography (CTE) and Ga68-DOTATOC-PET-CT were used for clinical staging. At IEO NEN multidisciplinary tumor board, the following eligibility criteria were adopted to candidate patients to MIS (curative or palliative): number and localization of primary tumor, grade of superior mesentery artery and vein encasement by lymph-node metastases of 0-2 according IEO criteria (based on Lardiere-Degalte classification). Information on morphology and carcinoid syndrome were collected. The primary endpoint was laparotomy conversion rate. Results: Twelve patients were selected. Patients’ characteristics are available. Median age at surgery was 55 years (range: 33–73). Among these patients, based on pathological findings, 8 (67%) had confirmed nodal involvement, 3 (25%) metastatic disease and 4 (33%) multifocal primary tumor. Vascular involvement (based on IEO criteria) was found in 9 patients (75%). Of note, only 3 (25%) patients had a functioning tumor as a preoperative finding and all tumors resulted well-differentiated. Among 12 patients which underwent laparoscopic surgery, none has been converted to laparotomy surgery. After a median follow-up of 25.3 months (range: 2.5-71.3), the 1-year disease free survival for non-metastatic patients was of 100%. Conclusions: the assessment of tumor burden with 68Ga-PET-CT and CTE according to IEO criteria could be a reliable method to candidate patients affected by SB-NEN to MIS, according to a multidisciplinary approach.[Table: see text]

Gut inflammation and tumorigenesis: every site has a different tale to tell.

Gut inflammation has been correlated with cancerogenesis by disrupting gastrointestinal homeostasis. Numerous chronic inflammatory disorders of the tubular gastrointestinal tract (e.g., gastroesophageal reflux disease, Helicobacter pylori-induced and autoimmune chronic gastritis, celiac disease, and inflammatory bowel diseases) have been variably associated with an increased neoplastic risk. Gastrointestinal inflammation-induced neoplasms include epithelial tumors (esophageal squamous cell carcinoma and adenocarcinoma, gastric adenocarcinoma and neuroendocrine tumors, small bowel adenocarcinoma and neuroendocrine tumors, and colorectal cancer) and lymphomas (such as gastric marginal zone lymphomas and enteropathy-associated T cell lymphoma). In the last decades, numerous studies have investigated the pathogenetic mechanisms and the microenvironmental/microbiome changes that trigger genetic and/or epigenetic alterations eventually leading to tumorigenesis, often through a histologically recognizable inflammation-dysplasia-carcinoma cancerogenic sequence. In the present review, an overview of the current knowledge on the links between inflammatory diseases and neoplasms of the tubular GI tract, applying a site-by-site approach, is provided.

O143 Management strategies and outcomes for small bowel neuroendocrine tumours with involvement of the superior mesenteric vascular root: a systematic review

Abstract Introduction Small intestine neuroendocrine tumours (SI-NETs) are the most common small bowel tumours. A particularly challenging subset of these tumours are those that involve the superior mesenteric artery (SMA) or vein (SMV) for which the role and feasibility of surgery is often questioned. This review aimed to identify and evaluate the management strategies used for these complex SI-NETs. Methods Primary studies concerning SI-NETs with SMA and/or SMV involvement were identified from PubMed and Embase review and data abstraction was performed. Results Initial literature search identified 155 potentially eligible studies, from which nine non-randomised primary retrospective studies met inclusion criteria. Treatments identified include stenting the SMV, debulking and resection, auto-transplantation, and endovascular occlusion and tumour excision (EVOTE) procedures. The level of involvement of the SMA and SMV was associated with resectability such that more proximal involvement yielded a lower likelihood of successful resection. Auto-transplantation strategies may show promise in more proximal mesenteric root involvement. To date, one study reported a case of a patient with SMV encasement who was successfully treated with auto-transplantation of ileocolic and ileojejunal segments after resection of the affected structures. Conclusion The present study highlights a role for aggressive surgical and multimodal management in cases of SI-NETs with vascular involvement of the mesenteric root. The use of classification systems to stratify mesenteric masses by level of vascular involvement can help identify patients who could benefit from resection. Large scale prospective studies are needed to better elucidate the effectiveness of surgical management strategies in these challenging SI-NETs.

Small bowel neuroendocrine tumors: An analysis of clinical presentation, diagnostic workup and surgical approach-A single center retrospective study.

Neurocrine neoplasms (NEN) of the small bowel (SBNEN) are a rare entity and mostly asymptomatic. The aim of this study was to explore trends in the clinical presentation, diagnostic workup, surgical approach and oncological outcome in patients with SBNEN at our surgical department. All patients who underwent surgical resection for SBNEN from 2004 to 2020 at our department were enrolled in this single center retrospective study. A total of 32 patients were included in this study. In most cases, the diagnosis was based on incidental findings during endoscopy or radiographic imaging (n = 23; 72%). Twenty cases had a G1 tumor and 12 cases a G2 tumor. The 1-, 3- and 5-year overall survival (OS) were 96%, 86% and 81%, respectively. Patients with a tumor more than 30 mm had a significantly lower OS (p = 0.01). For G1 tumors, the estimated disease-free survival (DFS) was 109 months. Again, the DFS was significantly lower when the tumor had more than 30 mm in diameter (p = 0.013). Due to the mostly asymptomatic presentation, the diagnostic workup can be difficult. An aggressive approach and a strict follow-up seem to be important for the oncological outcome.

Small bowel neuroendocrine tumours - casting the net wide.

Our aim is to provide an overview of small bowel neuroendocrine tumours (NETs), clinical presentation, diagnosis algorithm and management options. We also highlight the latest evidence on management and suggest areas for future research. Dodecanetetraacetic acid (DOTATATE) scan can detect NETs with an improved sensitivity than when compared with an Octreotide scan. It is complimentary to small bowel endoscopy that provides mucosal views and allows the delineation of small lesions undetectable on imaging. Surgical resection is the best management modality even in metastatic disease. Prognosis can be improved with the administration of somatostatin analogues and Evarolimus as second-line therapies. NETs are heterogenous tumours affecting most commonly the distal small bowel as single or multiple lesions. Their secretary behaviour can lead to symptoms, most commonly diarrhoea and weight loss. Metastases to the liver are associated with carcinoid syndrome.

Carcinoid Heart Disease in Patients Diagnosed with Small Bowel and Lung Neuroendocrine Tumors

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Prevalence of Sarcopenia and Impact on Survival in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumours.

Sarcopenia in patients with cancer is associated with adverse outcomes such as shorter survival. However, there exists little evidence regarding the prevalence of sarcopenia in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Patients with a histologically confirmed newly diagnosed metastatic GEP-NET between 2006 and 2018, CT scan, and anthropometric data at diagnosis were included in this study. CT scans were analysed for the presence of sarcopenia and correlated with overall survival (OS). In total, 183 patients, 87 male (48%), with a median age of 62 years (IQR 52-68 years), were included. In 44 patients (24%), there was a pancreas NET, and in 136 patients, there was a small bowel NET (74%). Sarcopenia was present in 128 patients (69%) and unrelated to BMI (median 25.1). There were significant survival differences between patients with pancreatic and small bowel NETs at 86 vs. 141 months, respectively (p = 0.04). For patients with pancreatic NETs, the presence of sarcopenia was independently associated with shorter OS (HR 3.79 95% CI 1.1-13.03, p-value 0.035). A high prevalence of sarcopenia at the time of diagnosis of a metastatic GEP-NET was seen and associated with worse OS in patients with pancreatic NETs. Further research should focus on how to reverse sarcopenia and its impact on OS and/or quality of life.

Practice patterns for reporting digestive system neuroendocrine neoplasms: results from a large, comprehensive international survey.

Criteria for the interpretation of digestive system neuroendocrine neoplasms (NENs) continue to evolve. Although there are some literature recommendations regarding workup and diagnosis of these lesions, different practice patterns exist among pathologists when signing out these specimens. The aim of this study was to assess practice trends among pathologists worldwide when reporting these neoplasms. We created an online survey with multiple questions pertaining to digestive NENs. The results were analysed based on type of practice setting, years of sign-out experience, and practice location. Respondents included 384 practicing pathologists: 70% academic, 30% private practice; 63% gastrointestinal (GI) pathology-subspecialised, 37% not; 39% North American, 42% European, 19% others; 45% with ≤10 years in practice; 55% with >10 years. Some question responses were chosen by the majority (e.g. 85% use both mitotic count and Ki67 index for grading NENs, 82% complete a synoptic, and Ki67 stain even for small incidental appendiceal neuroendocrine tumours [NETs], and 96% utilize the diagnosis of grade 3 NET). However, some questions showed varying responses, including counting mitotic figures, Ki67 stain interpretation, and pancreatic grade 3 NEN workup. Pathologists also had some variability in interpreting regional metastatic foci of small bowel NETs and in choosing blocks for Ki67 staining in multifocal lesions. There existed scenarios wherein practice patterns varied despite recommendations in the literature, and there were also scenarios lacking clear guidelines wherein pathologists used varying judgement. This survey highlights current key grey areas in digestive system NEN evaluation, leading to variation in practice patterns.

Association between surveillance imaging and survival outcomes in small bowel neuroendocrine tumors

Surveillance guidelines following the resection of small bowel neuroendocrine tumors (SB-NETs) are inconsistent. We evaluated the impact of surveillance imaging on SB-NET recurrence and overall survival (OS). Patients with completely resected SB-NETs referred to a provincial cancer center (2004-2015) were reviewed. Associations between imaging frequency, recurrence, post-recurrence treatment, and OS were determined using univariate and Cox-regression analyses. Among 195 completely resected SB-NET patients, 31% were ≥70 years, 43% were female, and 80% had grade 1 disease. Imaging frequency was predictive of recurrence (hazard ratio 2.52, 95% confidence interval 1.84-3.46, p < 0.001). 72% underwent interventions for recurrent disease. Patients who were treated for the recurrent disease had comparable OS to those who did not recur (median 152 vs. 164 months; p = 0.25). Imaging frequency was not associated with OS in those with treated recurrent disease (p = 0.65). Patients who recurred underwent more computerized tomography(CT) scans than those who did not recur (CT: 1.47 ± 0.89 vs. 1.02 ± 0.81 scans/year, p < 0.001). Detection of disease recurrence was 5%-7% per year during the first 6 years of surveillance and peaked at 17% in Year 9. Less frequent imaging over a longer duration should be emphasized to capture clinically relevant recurrences that can be treated to improve OS.

Evaluation of quality of clinical management of neuroendocrine tumors.

Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms predominantly found in the gastrointestinal and bronchopulmonary tractus. Despite a rising incidence, implementation of evidence-based standardized care for this heterogenous group remains challenging. The European Neuroendocrine Tumor Society regularly reviews guidelines regarding diagnostic and treatment strategies for NETs. The aim of this study is to shed light on the care of patients with a NET in Belgian Limburg, to provide data as a basis for future studies and to check whether data and results are according to consensus guidelines and outcomes described in literature. Our study concerned a detailed observational data collection of two large Belgian hospitals (Jessa Hospital Hasselt and Hospital Oost-Limburg Genk) with special interest in patient profile, quality of pathology reports, use of diagnostic imaging, and overall survival. Data on 188 patients were assembled between January 2010 and December 2014 with follow-up until June 2016 (median follow-up: 33.6 months). Fifty percent of patients were male. NETs were located mainly in the digestive tract (63.8%) and lung (20.2%). Appendiceal NETs were diagnosed at a significantly younger age than other tumors (41.3vs. 64.0years). Overall, a mean pathology report quality score of 3.0/5 was observed with the highest scores for small bowel NETs. Diagnostic and nuclear imaging was performed in 74.5% and 29.8% of cases, respectively. Seventy-four percentof the population survived until the end of the observation period with highest survival rates for appendiceal and small bowel NETs. Overall, epidemiological results were comparable with findings in the literature. Gastrointestinal NETs met most of the requirements of qualitative pathology reporting and diagnostic imaging as listed in the European Neuroendocrine Tumor Societyconsensus guidelines. However, consensus with regard to bronchopulmonary NETs is still scarce and remains an objective for future research. Moreover, discussing treatment strategies in specialized multidisciplinary tumor boards would facilitate regional care.

The role of laparoscopic surgery in the management of appendiceal and small bowel Neuroendocrine tumours

The role of laparoscopic surgery in the management of appendiceal and small bowel Neuroendocrine tumours

Does Synchronous Liver Intervention Increase Risk of Venous Thromboembolism in Patients with Metastatic Small-Bowel and Pancreatic Neuroendocrine Tumors?

INTRODUCTION: Previous literature suggests a higher incidence of venous thromboembolism (VTE) in patients with pancreatic neuroendocrine tumor (PNET) but no other gastrointestinal NET. In this study, we analyze the incidence of VTE in patients with metastatic small-bowel neuroendocrine tumors (SBNETs) and PNET undergoing synchronous liver procedures to determine whether these patients require extended VTE prophylaxis. METHODS: The American College of Surgeons NSQIP database was queried from 2008 to 2019 for patients undergoing operation for SBNET, PNET, benign small bowel, and pancreatic pathology. Patients with SBNET and PNET were stratified by additional operative procedures for liver metastasis (LM). The rate of 30-day postoperative VTE (pulmonary embolism [PE] and/or deep vein thrombosis [DVT]) was compared. Pearson’s chi-square and ANOVA tests were used for analysis. RESULTS: A total of 89,054 patients met inclusion criteria (63,396 benign small bowel, 3,073 SBNET, including 918 with LM, 18,724 benign pancreas, 3,861 PNET including 949 with LM). There was no statistically significant difference in the rate of VTE in patients with small-bowel disease with or without LM. Patients in the PNET with LM group had a significantly higher rate of PE but not DVT than those undergoing pancreatic operation for benign pathology (2.4% vs 1.1%; p < 0.001). Total operation time (odds ratio [OR] 1.002; p = 0.002), length of hospital stay (OR 1.027; p < 0.001), and preoperative dialysis (OR 3.779; p = 0.004) were independently associated with VTE. However, synchronous liver intervention was not an independent factor associated with VTE or PE in patients with PNET (Table 1). Table 1. - Rates of DVT and PE in Patients with PNETs and SBNETs Undergoing Synchronous Liver Procedures Group Total Rate of DVT Rate of PE Benign small-bowel procedures 63,396 987 (1.6%) 398 (0.6%) Procedures for SBNETs 2,155 26 (1.2%) 11 (0.5%) SBNETs with synchronous liver procedures 918 12 (1.3%) 9 (1.0%) Benign pancreas procedures 18,724 400 (2.1%) 203 (1.1%) Procedures for PNETs 2,912 59 (2.0%) 44 (1.5%) PNETs with synchronous liver procedures 949 18 (1.9%) 23 (2.4%) CONCLUSION: Synchronous liver intervention does not increase the risk of VTE in patients with metastatic SBNET or PNET.

Incidence of psychiatric illness in patients with neuroendocrine tumors: a comparative population-based analysis.

Diversion of tryptophan to tumoral hormonal production has been suggested to result in psychiatric illnesses in neuroendocrine tumors (NET). We measured the occurrence of psychiatric illness after NET diagnosis and compare it to colon cancer (CC). We conducted a population-based retrospective cohort study. Adults with NET were matched 1:1 to CC (2000-2019). Psychiatric illness was defined by mental health diagnoses and mental health care use after a cancer diagnosis, categorized as severe, other, and none. Cumulative incidence functions accounted for death as a competing risk. A total of 11,223 NETs were matched to CC controls. Five-year cumulative incidences of severe psychiatric illness for NETs vs. CC was 7.7% (95%CI 7.2-8.2%) vs 7.6% (95%CI 7.2-8.2%) (p = 0.50), and that of other psychiatric illness was 32.9% (95%CI 32.0-33.9%) vs 31.6% (95%CI 30.8-32.6%) (p = 0.005). In small bowel and lung NETs, 5-year cumulative incidences of severe (8.1% [95%CI 7.3-8.9%] vs. 7.0% [95%CI 6.3-7.8%]; p = 0.01) and other psychiatric illness (34.7% [95%CI 33.3-36.1%] vs. 31.1% [95%CI 29.7-32.5%]; p < 0.01) were higher than for matched CC. The same was observed for serotonin-producing NETs for both severe (7.9% [95%CI 6.5-9.4%] vs. 6.8% [95%CI 5.5-8.2%]; p = 0.02) and other psychiatric illness (35.4% [95%CI 32.8-38.1%] vs. 31.9% [95%CI 29.3-34.4%]; p = 0.02). In all NETs, there was no difference observed in the incidence of psychiatric illness compared to CC. For sub-groups of small bowel and lung NETs and of serotonin-producing NETs, the incidence of psychiatric illness was higher than for CC. These data suggest a signal towards a relationship between those sub-groups of NETs and psychiatric illness.

Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update

The prevalence of gastrointestinal neuroendocrine tumors (GI-NETs) is increasing, and despite recent advances in their therapy, it remains inadequate in patients with advanced well-differentiated neuroendocrine tumors. These tumors present many challenges concerning the molecular basis and genomic profile, pathophysiology, clinicopathological features, histopathologic classification, diagnosis and treatment. There has been an ongoing debate on diagnostic criteria and clinical behavior, and various changes have been made over the last few years. Neuroendocrine carcinoma of the gastrointestinal system is a rare but highly malignant neoplasm that is genetically distinct from gastrointestinal system neuroendocrine tumors (NETs). The diagnosis and management have changed over the past decade. Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools. Progress in positron emission tomography-computerized tomography and scintigraphy with new radioactive agents (64Cu-DOTATATE or 68Ga-DOTATATE) replacing enough octreoscan, has improved further the current diagnostic imaging. Promising results provide targeted therapies with biological agents, new drugs, chemotherapy and immunotherapy. However, the role of surgery is important, since it is the cornerstone of management. Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge. Endoscopy offers novel options not only for diagnosis but also for interventional management. The therapeutic option should be individualized based on current multidisciplinary information.