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Pancreatic neuroendocrine tumours can have varied and complex presentations. Whilst hormone hypersecretion often induces characteristic clinical syndromes, non-specific symptoms may arise due to localized tumour effects. Malignant invasion of local vasculature is an increasingly recognized complication of these neoplasms and can be associated with significant morbidity. Herein, we present the case of a 47-year-old male with a recurrence of a pancreatic neuroendocrine tumour who presented with unusual upper gastrointestinal bleeding. The tumour had recurred within the superior mesenteric vein, replacing the vessel and invading its branches. This resulted in porto-mesenteric hypertension and the formation of bleeding mesenteric varices. The patient subsequently developed progressive metabolic disturbances and was diagnosed with ectopic Cushing’s syndrome, despite his primary tumour having been non-functional. This case demonstrates not only a rare pattern of tumour recurrence but also the potential for pancreatic neuroendocrine tumours to de-differentiate and change from non-functional to hormone secreting, a phenomenon which may complicate diagnosis and management.

Background/aims: Long-term outcomes are understudied in patients with well-differentiated appendiceal neuroendocrine neoplasms (WD-ANENs). We aimed to evaluate the validity of currently applied criteria for completion prophylactic right hemicolectomy (pRHC) and determine its association with patient outcomes, including health-related quality of life (HRQoL). Methods: Eligible patients from five European referral centers were divided between those who underwent appendectomy alone and those who underwent completion pRHC. HRQoL EORTC-QLC-C30 questionnaires and cross-sectional imaging data were prospectively collected. Age- and sex-matched healthy controls were recruited for HRQoL analysis’ validation. Results: We included 166 patients (119 women [71.2%]: mean age at baseline: 31 ± 16 years). Mean follow-up was 50.9 ± 54 months. Most patients (152 [92%]) had tumors ≤20 mm in size. Fifty-eight patients (34.9%) underwent pRHC that in final analysis was regarded as an overtreatment in 38/58 (65.5%). In multivariable analysis, tumor size >20 mm was the only independent predictor for lymph node (LN) involvement (p= 0.002). No mortality was reported, whereas 2-, 5- and 10-year recurrence-free survival in patients subjected to postoperative cross-sectional imaging (n= 136) was 98.5%, 97.8%, and 97.8%, respectively. Global HRQoL was not significantly impaired in patients with WD-ANEN compared with age- and sex-matched healthy individuals (median scores 0.83[0.08−1] vs 0.83[0.4−1], respectively; p= 0.929). Among patients with WD-ANEN impaired social functioning (p= 0.016), diarrhea (p= 0.003) and financial difficulties (0.024) were more frequently reported in the pRHC group. Conclusions: WD-ANEN is a low-malignant neoplasm with unconfirmed associated mortality, low recurrence rate, and overall preserved HRQoL. pRHC comes at a price of excessive surgery, functional HRQoL issues, and diarrhea. The value per se of a prophylactic surgical approach to patients with WD-ANENs <20 mm is challenged.

Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.

To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs). Seventy-four patients were recruited from four NEN centers in this observational multicenter study. Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4–395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589–14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14–463) months. Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.

Neuroendocrine tumors are heterogeneous cancers that can present with advanced disease. Treatment stratification is often based on limited characterization of tumor behavior from histological grade and imaging assessments. Personalized medicine strategies focus on tailoring therapy through characterization of cancer pathways and the development of biomarkers. This review article explores the current personalized medicine landscape in gastroenteropancreatic neuroendocrine tumors, from tissue and circulating biomarkers development through to tumor heterogeneity and reimbursement issues.

AbstractNeuroendocrine tumors are heterogeneous cancers that can present with advanced disease. Treatment stratification is often based on limited characterization of tumor behavior from histological grade and imaging assessments. Personalized medicine strategies focus on tailoring therapy through characterization of cancer pathways and the development of biomarkers. This review article explores the current personalized medicine landscape in gastroenteropancreatic neuroendocrine tumors, from tissue and circulating biomarkers development through to tumor heterogeneity and reimbursement issues.

Neuroendocrine tumors (NETs) can arise from a variety of organs. They can vary widely in clinical behavior; consequently, optimizing their treatment plan can be problematic. NETs display diverse tumor biology; however, most secrete peptides such as chromogranin A into the circulation, consistent with their neuroendocrine origin. In this study, we sought to identify other potential markers for NETs by analyzing the secreted proteomes of three neuroendocrine cell lines. BON-1, NCI-H727, and SHP-77 cells were grown in serum-free media, and the secreted proteins were separated by SDS-PAGE and identified by LC-MS/MS. We identified 205 proteins of which 61 were secreted by two or more of the cell lines and 19 were secreted by all three lines. Mac-2-binding protein (Mac-2BP) was found to be secreted by all three cell lines, and this was confirmed by Western blotting. Immunohistochemical analysis found 29 of 33 NET cases from different primary sites to be positive for Mac-2BP. Serum Mac-2BP was significantly elevated in NET patients compared with healthy controls (p < 0.001). This study demonstrated that analysis of the secreted proteomes of neuroendocrine cell lines can identify potential biomarkers for NET. Initial assessment showed that serum Mac-2BP is significantly elevated in patients with NET and is expressed by the majority of NET tissues.

Neuroendocrine tumors (NETs) can arise from a variety of organs. They can vary widely in clinical behavior; consequently, optimizing their treatment plan can be problematic. NETs display diverse tumor biology; however, most secrete peptides such as chromogranin A into the circulation, consistent with their neuroendocrine origin. In this study, we sought to identify other potential markers for NETs by analyzing the secreted proteomes of three neuroendocrine cell lines. BON-1, NCI-H727, and SHP-77 cells were grown in serum-free media, and the secreted proteins were separated by SDS-PAGE and identified by LC-MS/MS. We identified 205 proteins of which 61 were secreted by two or more of the cell lines and 19 were secreted by all three lines. Mac-2-binding protein (Mac-2BP) was found to be secreted by all three cell lines, and this was confirmed by Western blotting. Immunohistochemical analysis found 29 of 33 NET cases from different primary sites to be positive for Mac-2BP. Serum Mac-2BP was significantly elevated in NET patients compared with healthy controls (p< 0.001). This study demonstrated that analysis of the secreted proteomes of neuroendocrine cell lines can identify potential biomarkers for NET. Initial assessment showed that serum Mac-2BP is significantly elevated in patients with NET and is expressed by the majority of NET tissues.

111In-pentetreotide scan (OctreoScan) is a widely available agent with high sensitivity for imaging neuroendocrine tumours. Negative 111In-pentetreotide poses diagnostic as well as therapeutic problems in terms of staging and consideration of targeted radionuclide therapy.

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.