Genetic diagnosis in acromegaly and gigantism: From research to clinical practice.

It is usually considered that only 5% of all pituitary neuroendocrine tumours are due to inheritable causes. Since this estimate was reported, however, multiple genetic defects driving syndromic and nonsyndromic somatotrophinomas have been unveiled. This heterogeneous genetic background results in overlapping phenotypes of GH excess. Genetic tests should be part of the approach to patients with acromegaly and gigantism because they can refine the clinical diagnoses, opening the possibility to tailor the clinical conduct to each patient. Even more, genetic testing and clinical screening of at-risk individuals have a positive impact on disease outcomes, by allowing for the timely detection and treatment of somatotrophinomas at early stages. Future research should focus on determining the actual frequency of novel genetic drivers of somatotrophinomas in the general population, developing up-to-date disease-specific multi-gene panels for clinical use, and finding strategies to improve access to modern genetic testing worldwide.

Li-Fraumeni-associated pancreatic neuroendocrine tumour and XAF1 p.Glu134Ter risk modifier variant.

Studies have demonstrated that up to 17% of patients with pancreatic neuroendocrine tumours (pNETs) present pathogenic germline variants (PGVs) in several different genes, irrespective of family cancer history. Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome related to PGVs in the TP53 gene. A previous case of a pNET associated with LFS (c.1009C > T, p.R337C) has been reported. Here we report the first case of a patient with pNET and TP53 p.R337H and XAF1 p.E134* germline variants, expanding the knowledge of LFS and germline mutations in neuroendocrine tumours.

Use of healthcare REsources and associated COsts in controlled versus uncontrolled carcinoid SYndrome in patients with neuroendocrine tumours: the RECOSY study.

PURPOSE: To report healthcare resource use and associated costs in controlled versus uncontrolled carcinoid syndrome (CS) in patients with neuroendocrine tumours. METHODS: A cross-sectional, non-interventional multicentre study was conducted with retrospective data analysis. Resource use was compared between two patient groups: those with controlled CS (> 12 months with no uncontrolled CS episodes) and uncontrolled CS (< 12 months since last uncontrolled episode). Patients were matched for age, sex, and origin and grade of tumour. When no matching patients were available, data from deceased patients were used. Information on healthcare resource use came from review of medical records, patient history and physician reports. Working capacity was assessed using the Work Productivity and Activity Impairment General Health questionnaire. RESULTS: Twenty-six university hospitals in Spain participated, between July 2017 and April 2018. 137 patients were enrolled; 104 were analysed (2 groups of 52). Patients with uncontrolled CS had 10 times more emergency department (ED) visits (mean 1.0 vs 0.10 visits; P = 0.0167), were more likely to have a hospital admission (40.4% vs 19.2%; P = 0.0116) and had longer hospital stays (mean 7.87 vs 2.10 days; P = 0.0178) than those with controlled CS. This corresponded to higher annual hospitalisation costs (mean €5511.59 vs €1457.22; P = 0.028) and ED costs (€161.25 vs €14.85; P = 0.0236). The mean annual total healthcare costs were 60.0% higher in patients with uncontrolled than controlled CS (P = NS). CONCLUSION: This study quantifies higher health resource use, and higher hospitalisation and ED costs in patients with uncontrolled CS. Better control of CS may result 3in lower medical costs.

[Tumor neuroendocrino ano-rectal: desde un pólipo con buen pronóstico hasta un carcinoma letal]. / Ano-rectal neuroendocrine tumour: from a polyp with a good prognosis to a lethal carcinoma.

INTRODUCCIÓN: Aunque los tumores neuroendocrinos rectales son neoplasias poco frecuentes, su incidencia está aumentando en las tres últimas décadas. El objetivo de este trabajo es el estudio del comportamiento de dichos tumores basándonos en sus variables clínicas, diagnósticas, terapéuticas y anatomopatológicas en un hospital terciario. MÉTODO: Estudio retrospectivo de los tumores neuroendocrinos rectales desde el año 2000 hasta el año 2017 en nuestro hospital. Se realizó una búsqueda informatizada en el programa SNOMED del servicio de anatomía patológica, empleando los criterios «tumor neuroendocrino¼ y «tumor carcinoide¼. RESULTADOS: Se hallaron 16 pacientes con tumor neuroendocrino ano-rectal. El 75% eran varones. La mediana de edad fue de 53 años (rango: 34-83). El diagnóstico fue incidental en el 62,5%. El tratamiento fue endoscópico en 13 (81%) pacientes y quirúrgico en 3 (19%). El 75% de las lesiones fueron T1. El 68,7% de los tumores presentaban un grado de agresividad G1. La media de seguimiento fue de 29 meses; no hubo recidivas. Durante el seguimiento fallecieron 3 (18,5%) pacientes, todos ellos con tumor G3 metastásico, y la supervivencia media fue de 8 meses. CONCLUSIONES: Los tumores neuroendocrinos rectales son cada vez más frecuentes y presentan unos patrones variables, cuyo pronóstico dependerá de su agresividad histológica. El aumento de su incidencia puede deberse a una mayor concienciación de la existencia de estos tumores, a las campañas de cribado del cáncer colorrectal, al aumento del número de colonoscopias realizadas y a la generalización de los estudios histológicos con marcadores neuroendocrinos. BACKGROUND: Although rectal neuroendocrine tumours are rare neoplasms, their incidence is increasing in the last three decades. The objective of this work is to study the behaviour of these tumours based on their clinical, diagnostic, therapeutic, and pathological variables in a tertiary hospital. METHOD: Retrospective study of rectal neuroendocrine tumours from 2000 to 2017 in our hospital. A computerized search was performed in the SNOMED program of the pathological anatomy service, using the criteria "neuroendocrine tumour" and "carcinoid tumour". RESULTS: We found 16 patients with ano-rectal neuroendocrine tumour; 75% were male. The median age was 53 years (range: 34-83). The diagnosis was incidental in 62.5%, with endoscopic treatment in 13 patients (81%) and surgical treatment in 3 (19%). 75% of the lesions were T1. 68.7% of the tumours showed a degree of G1 aggression. The mean follow-up was 29 months; no recurrences. During follow-up, three patients died (18.5%), all of them with metastatic G3 tumour and the mean survival was 8 months. CONCLUSIONS: The rectal neuroendocrine tumours are increasingly frequent and present variable patterns, whose prognosis will depend on their histological aggressiveness. The increase incidence may be due to a greater awareness of the existence of these tumours, to colorectal cancer screening, to the increase in the number of colonoscopies performed and to the generalization of histological studies with neuroendocrine markers.

Cushing Syndrome Caused by a Pancreatic Neuroendocrine Tumour and Its Pelvic Metastases.

Cushing's syndrome caused by an ectopic tumour secreting adrenocorticotropic hormone (ACTH) is not common. Furthermore, an ACTH-secreting panreatic neoplasm is extremely rare. We present a 27-year old female patient suffering from a pancreatic neuroendocrine tumour (p-NET) with extensive pelvic metastases, which could secrete ACTH and cause Cushing's syndrome. The postoperative pathologic examinations of this patient prompted pancreatic poorly differentiated neuroendocrine tumour with extensive metastases of bilateral ovarian, uterus and pelvic peritoneum. The immunohistochemical staining of her tumour tissues was positive for Chromogranin A, Synaptophysin and ACTH. The main aim of this article is to share the experience of her diagnosis and treatment and to review the relevant literature, with an emphasis on discussing the possible transfer modes. Moreover, we strongly suggest that a careful examination of pelvic cavity during the follow-up of patients diagnosed as ACTH-secreting p-NET should also be carried out.