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      The Novel WHO 2010 Classification for Gastrointestinal Neuroendocrine Tumours Correlates Well with the Metastatic Potential of Rectal Neuroendocrine Tumours

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          Abstract

          Background: Approximately 10–15% of gastroenteropancreatic neuroendocrine tumours (NETs, carcinoids) occur in the rectum, some of which are potentially able to metastasize. The new WHO 2010 classification of NETs applies to all gastroenteropancreatic NETs, but no reports have studied its correlation with the prognosis of rectal NETs. Patients and Methods: We retrospectively classified 73 rectal NETs according to the novel WHO 2010 and the previous WHO 2000 classifications. The aim was to assess the validity of the classifications in distinguishing indolent rectal NETs from metastasising tumours. Results: Using the WHO 2010 criteria, we identified 61 G1 tumours, none of which had metastasised during follow-up. Of 11 G2 tumours, 9 had shown distant metastases. The only G3 neuroendocrine carcinoma that occurred had been disseminated at initial presentation. Conclusion: Our results show that rectal NETs classified as G1 according to the WHO 2010 classification have an indolent clinical course, whereas G2 NETs often metastasise. The WHO 2010 classification of NETs predicts the metastatic potential of rectal NETs better than the WHO 2000 classification.

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          Most cited references23

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          Updated population-based review of carcinoid tumors.

          To determine the population-based incidence, anatomic distribution, and survival rates of gastrointestinal carcinoid tumors. Carcinoid tumors arise from neuroendocrine cells and may develop in almost any organ. Many textbooks and articles represent single institution studies and report varying incidence rates, anatomic distribution of tumors, and patient survival rates. Population-based statistics remain largely unknown. Data was obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results program (1973 to 1997). Incidence rates, distribution, and 5-year survival rates were analyzed. Multivariate Cox regression was used to identify predictors of survival using age, race/ethnicity, gender, and tumor characteristics (size, lymph node status, and stage). Of the 11,427 cases analyzed, the average age was 60.9 years, and 54.2% were female. The overall incidence rates for carcinoid tumors have increased significantly over the past 25 years, although rates for some sites have decreased (eg, appendix). The gastrointestinal tract accounted for 54.5% of the tumors. Within the gastrointestinal tract, the small intestine was the most common site (44.7%), followed by the rectum (19.6%), appendix (16.7%), colon (10.6%), and stomach (7.2%). The 5-year survival rates for the most common gastrointestinal sites were stomach (75.1%), small intestine (76.1%), appendix (76.3%), and rectum (87.5%). Using national, population-based cancer registry data, this study demonstrates that (1) incidence rates for carcinoid tumors have changed, (2) the most common gastrointestinal site is not the appendix (as is often quoted), but the small intestine, followed in frequency by the rectum, and (3) survival rates differ between individual anatomic sites.
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            Small-cell carcinomas of the gastrointestinal tract: a review.

            To improve our understanding of the entity of small-cell carcinoma (SmCC) of the gastrointestinal (GI) tract. A MEDLINE search was done, using the terms "small cell carcinoma" or "oat cell carcinoma" combined with "gastrointestinal" or with any of the GI sites, for the period 1970 to 2003. The 138 eligible reports identified in this way were reviewed for clinical data. To date, approximately 544 cases of GI SmCC have been reported. The disease represents 0.1% to 1% of all GI malignancies, with the esophagus being the most common primary site. A majority of patients present with overt distant metastases. Systemic symptoms are common; ectopic hormonal secretion may occur. By light microscopy, GI SmCCs are essentially indistinguishable from primary pulmonary SmCC. The presence of non-SmCC components is common. Data from molecular analysis of the disease has identified some similarities to pulmonary SmCC. Chemotherapy represents the main treatment option, with modest impact on survival. In locoregional disease, the literature suggests that treatment be initiated using chemoradiotherapy and then, if metastatic disease is still excluded, surgical resection be considered. The disease is highly aggressive, and survival is in the range of several weeks for untreated patients and of 6 to 12 months for those receiving therapy. SmCC of the GI tract is a rare and lethal disease. Although there are many similarities to pulmonary SmCC, some differences between the two entities are suggested. While chemotherapy can achieve significant palliation, surgery may have a potential impact on long-term survival of patients with locoregional disease.
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              Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years.

              Colorectal carcinoids are often described as low-grade malignant. However, no study has compared the survival between patients with colorectal carcinoids and those with carcinomas, in a large series. In addition, no global consensus has been established on the crucial determinants of metastasis in colorectal carcinoids. To determine the predictive factors for metastasis in colorectal carcinoids and clarify their prognosis compared with adenocarcinomas. Data of all patients diagnosed as having colorectal carcinoids were extracted from a large nationwide database of colorectal tumours, the Multi-Institutional Registry of Large-Bowel Cancer in Japan, for the period from 1984 to 1998. Risk factors for lymph node (LN) metastases and distant metastases were analysed among those who were undergoing surgery, by univariate and multivariate analysis. Cancer-specific survival was also compared between patients with colorectal carcinoids and those with adenocarcinomas registered in the same period. Among the 90 057 cases of colorectal tumours that were diagnosed, a total of 345 cases of carcinoids were identified, including 247 colorectal carcinoids of those undergoing surgery. Risk factors for LN metastasis were tumour size >/=11 mm and lymphatic invasion, whereas those for distant metastasis were tumour size >/=21 mm and venous invasion. Colorectal carcinoids without these risk factors exhibited no LN metastasis or distant metastasis. Cancer-specific survival of patients with colorectal carcinoids without metastasis was better than that of those with adenocarcinomas. However, the survival was similar between carcinoids and adenocarcinomas if the tumours had LN metastasis or distant metastasis. The presence of metastasis in colorectal carcinoids could lead to survival that is as poor as in adenocarcinomas. Tumours
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2012
                June 2012
                07 February 2012
                : 95
                : 4
                : 317-324
                Affiliations
                aDepartment of Pathology, Haartman Institute and HUSLAB, bDivision of Endocrinology, Department of Medicine, and cDepartment of Surgery, Helsinki University Central Hospital, Helsinki, Finland
                Author notes
                *Juha Jernman, Department of Pathology, Haartman Institute, University of Helsinki, Haarmaninkatu 3, PO Box 21, FI–00014 Helsinki (Finland), Tel. +358 331 175 755, E-Mail juha.jernman@pshp.fi
                Article
                333035 Neuroendocrinology 2012;95:317–324
                10.1159/000333035
                22327359
                173b5647-79ac-414b-94ed-e8a8021bb9a4
                © 2011 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 09 June 2011
                : 07 September 2011
                Page count
                Figures: 3, Tables: 3, Pages: 8
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Carcinoid,Neuroendocrine tumour,Metastasis,Rectum,Classification

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