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Background and Objective: Patient-reported outcome measures can provide clinicians with valuable information to improve doctor-patient communication and inform clinical decision-making. The aim of this study was to evaluate the physician-perceived utility of the QLQ-GINET21 in routine clinical practice in patients with gastrointestinal neuroendocrine tumours (GI-NETs). Secondary aims were to explore the patient, clinician, and/or centre-related variables potentially associated with perceived clinical utility., Methods: Non-interventional, cross-sectional, multicentre study conducted at 34 hospitals in Spain and Portugal (NCT02853422). Patients diagnosed with GI-NETs completed two health-related quality of life (HRQoL) questionnaires (QLQ-C30, QLQ-GINET21) during a single routine visit. Physicians completed a 14-item ad hoc survey to rate the clinical utility of QLQ-GINET21 on three dimensions: 1)therapeutic and clinical decision-making, 2)doctor-patient communication, 3)questionnaire characteristics., Results: A total of 199 patients at 34 centres were enrolled by 36 participating clinicians. The highest rated dimension on the QLQ-GINET21 was questionnaire characteristics (86.9% of responses indicating "high utility"), followed by doctor-patient communication (74.4%), and therapeutic and clinical decision-making (65.8%). One physician-related variable (GI-NET patient volume > 30 patients/year) was associated with high clinical utility and two variables (older age/less experience treating GI-NETs) with low clinical utility., Conclusions: Clinician-perceived clinical utility of QLQ-GINET21 is high. Clinicians valued the instruments' capacity to provide a better understanding of patient perspectives and to identify the factors that had the largest influence on patient HRQoL.

Objective: To detect doubts and training needs in an urban health and family doctor training centre during the usual practice., Material and Methods: A cross-sectional descriptive study was conducted for one month in an urban health centre in Madrid. Family doctors were interviewed after their daily clinics about the doubts they had identified, choosing two of them. Unresolved questions were grouped by subject and according to the current taxonomies. A teaching program was then developed to tackle them., Results: Out of a total 21 physicians of the centre, 19 attended 10,678 patients during the period. The doubt detection rate was 0.44 doubts for every 10 patients attended. Of the 384 questions chosen, 83.34% were clinical and 16.66% were non-clinical. Just over half (51.2%) of these were still unresolved 15days later the consultation event. The main methods for their resolution were using the scientific bases on the internet (mainly PubMed, UpToDate and Clinical Practice Guidelines; 38%), followed by consultation with other colleagues (34.9%)., Conclusions: Most of the doubts generated during clinics were clinical, although there is a significant burden of bureaucratic questions. More than half of the doubts are not resolved during the consultation or within the following 15days. The scientific databases on the internet are the main sources of information, although consulting other colleagues was often used as well. Additional time for dealing with patients and enhanced access to solve complex questions should be available to improve the success rate., (Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki-67 cutoff values in GEP-NENs., Subjects, Materials, and Methods: A total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 <2%), G2 (Ki-67 3%-20%), or G3 (Ki-67 >20%). Patients were stratified into five cohorts: NET-G1, NET-G2, NET-G3, NEC-G2, and NEC-G3., Results: Five-year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67 3%-5%], 72% [Ki-67 6%-10%], 52% [Ki-67 11%-20%]) and G3 NENs (5-year survival: 35% [Ki-67 21%-50%], 22% [Ki-67 51%-100%]). Five-year survival was significantly greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3 (43.7% vs. 25.4%)., Conclusion: Substantial clinical heterogeneity is observed within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index., Implications for Practice: Gastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real-world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Purpose: An association between neuroendocrine tumors (NETs) and second primary malignancies (SPMs) has been reported. We have examined the incidence and etiology of SPMs in patients with NETs included in the Neuroendocrine Tumor Association of Andalusia (ATNEA) Registry., Methods: Data on 111 patients were collected. Sex, age, NET site, chromogranin A levels, neuropeptide secretion and disease stage were compared between NETs with and without SPMs., Results: SPMs were present in 21 patients (18.9 %): five colorectal tumors, four non-small-cell lung cancers, three gastric cancers, two tumors in the small intestine, one hepatocarcinoma, two ovarian tumors, one breast adenocarcinoma, one hypernephroma, one bladder cancer, and one neuroblastoma. SPMs were present in 18 % of patients with a gastrointestinal NET and 22 % of those with a non-gastrointestinal NET. SPMs were found in 23 % of patients with elevated levels of serum chromogranin A, compared to 17 % of patients with normal levels, and in 22 % of patients with functional tumors, compared to 11 % of those with non-functional tumors. Finally, SPMs were observed in 24 % of patients with a local or locoregional tumor but in only 13 % of those with a metastatic tumor. No other differences between patients with and without SPMs were observed., Conclusions: The percentage of patients with SPMs in the ATNEA Registry is similar to those reported in other series. In our registry, patients with functional NETs and local/locoregional tumors have higher probability of SPMs. The low number of patients, selection bias and other etiologic factors of SPMs may have influenced our results.

Introduction: Pancreatic neuroendocrine neoplasms (PNENs) are uncommon neoplasms with a wide spectrum of clinical behavior. The objective of this study was to assess in a large cohort of patients the relative impact of prognostic factors on survival., Methods: From June 2001 through October 2010, 1,271 patients were prospectively registered online (www.getne.org) at the Spanish National Cancer Registry for Gastroenteropancreatic Neuroendocrine Tumors (RGETNE) by participating centers. Clinical and histopathological features were assessed as potential prognostic factors by uni- and multivariate analyses., Results: Of 483 PNENs, 171 (35%) were functional (F) and 312 (65%) non-functional (NF). NF-PNENs were associated with a higher incidence of histological features denoting more aggressive disease, such as poor tumor differentiation, Ki-67 >20%, or vascular invasion (NF- vs. F-PNENs, respectively, p < 0.05). Nevertheless, functionality was not a significant predictor of survival (p = 0.19). Stage at diagnosis, Ki-67 index, tumor differentiation and surgical resection of the primary tumor were all significant prognostic factors in univariate analysis. However, Ki-67 (>20 vs. ≤2%) (hazard ratio (HR) 2.21, p = 0.01) and surgical resection (yes vs. no) (HR 0.92, p = 0.001) were the only independent predictors of survival in multivariate analysis. Among patients who underwent surgery, high Ki-67 index (HR 10.37, p = 0.02) and poor differentiation (HR 8.16, p = 0.03) were the only independent predictors of clinical outcome., Conclusion: Ki-67 index and tumor differentiation are key prognostic factors influencing survival of patients with PNENs and, in contrast to what it is observed for other solid malignancies, they seem to have a greater impact on survival than the extent of disease. This should be borne in mind by physicians in order to appropriately tailor therapeutic strategies and surveillance of these patients., (Copyright © 2013 S. Karger AG, Basel.)

Colorectal cancer is the third most common malignant neoplasm and the second cause of death by cancer in western countries. In this manuscript, the clinical guidelines of the Spanish Society of Medical Oncology (SEOM) for diagnosis and adjuvant treatment of colon cancer and rectal cancer are reported.

Background: Neuroendocrine tumors (NETs) are an unusual family of neoplasms with a wide and complex spectrum of clinical behavior. Here, we present the first report of a National Cancer Registry of gastroenteropancreatic neuroendocrine tumors from a Southern European country., Patients and Methods: Data was provided online at www.retegep.net by participating centers and assessed for internal consistency by external independent reviewers., Results: The study cohort comprised 907 tumors. The most common tumor types were carcinoids (55%), pancreatic nonfunctional tumors (20%), metastatic NETs of unknown primary (9%), insulinomas (8%) and gastrinomas (4%). Forty-four percent presented with distant disease at diagnosis, most often those from small intestine (65%), colon (48%), rectum (40%) and pancreas (38%), being most unusual in appendix primaries (1.3%). Stage at diagnosis varied significantly according to sex, localization of primary tumor, tumor type and grade. Overall 5-year survival was 75.4% (95% confidence interval 71.3% to 79.5%) and was significantly greater in women, younger patients and patients with hormonal syndrome and early stage or lower grade tumors. Prognosis also differed according to tumor type and primary tumor site. However, stage and Ki-67 index were the only independent predictors for survival., Conclusion: This national database reveals relevant information regarding epidemiology, current clinical practices and prognosis of NETs in Spain, providing valuable insights that may contribute to understand regional disparities in the incidence, patterns of care and survival of this heterogeneous disease across different continents and countries.

The Eurasian wild boar (Sus scrofa) is increasingly relevant as a host for several pathogenic mycobacteria. We aimed to characterize the first experimental Mycobacterium avium subsp. avium (MAA) infection in wild boar in order to describe the lesions and the immune response as compared to uninfected controls. Twelve 1-4-month-old wild boar piglets were housed in class III bio-containment facilities. Four concentrations of MAA suspension were used: 10, 10(2) and 10(4) mycobacteria (2 animals each, oropharyngeal route) and 2.5 x 10(6) mycobacteria (2 animals each by the oropharyngeal and nasal routes). No clinical signs were observed and pathology evidenced a low pathogenicity of this MAA strain for this particular host. Bacteriological and pathological evidence of successful infection after experimental inoculation was found for the group challenged with 2.5 x 10(6) mycobacteria. These four wild boar showed a positive IFN-gamma response to the avian PPD and the real-time RT-PCR data revealed that three genes, complement component C3, IFN-gamma and RANTES, were significantly down regulated in infected animals. These results were similar to those found in naturally and experimentally M. bovis-infected wild boar and may constitute biomarkers of mycobacterial infection in this species., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Background: Similarities between human inflammatory bowel disease (IBD) and ruminant paratuberculosis have fueled a heated discussion on the role of Mycobacterium avium subsp. paratuberculosis (MAP) in the etiology of IBD., Methods: In order to determine microbiological and immunological evidence of an association between MAP and IBD, blood from 222 inflammatory bowel disease patients and 80 healthy donors from the Basque Country (Spain) were subjected to nested PCR for MAP-specific insertion sequence IS900, interferon-gamma (IFN-gamma) release test with PPA-3 MAP antigen (IFNMAP) or phosphate-buffered saline (IFNPBS), and antibody ELISA with PPA-3 MAP antigen (ABMAP)., Results: Highly significant differences in the proportion of PCR-positive IBD patients (17%) and healthy controls (43%) as well as lower IFNMAP and higher ABMAP and IFNPBS responses were observed. Treatment was associated with decreases in IFNMAP and PCR-positive frequency., Conclusions: These results indicate the existence of immune responses and treatment interactions with MAP that strongly support an etiological role of this agent in IBD.