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Desandes E, Clavel J, Molinié F, Delafosse P, Trétarre B, Systchenko T, Velten M, Coureau G, Hammas K, Cowppli-Bony A, Woronoff AS, Démaret V, Ganry O, Vigneron N, Bara S, Daubisse-Marliac L, Huré-Papaïconomou F, Monnereau A, Troussard X, Baldi I, Launoy G, Lacour B, Marec-Berard P. Trends in the Incidence of Cancer Among Adolescents and Young Adults Between 2000 and 2020: A Study Based on French Population-Based Registry Data. J Adolesc Young Adult Oncol 2025:0. [PMID: 40094816 DOI: 10.1089/jayao.2024.0136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025] Open
Abstract
Purpose: The recent rise in the incidence of cancer in younger adults has been described in high-income countries. This study aimed to identify cancer incidence trends in France among adolescent and young adult (AYA) population. Methods: All cases of cancer diagnosed in 15-39 years, recorded by all French population-based registries (24% of the population), over the 2000-2020 period, were included. World age-standardized incidence rates (ASR) and annual percentage change (APC) of incidence over time were calculated. Results: We analyzed 54,735 cancer diagnoses in AYAs. The ASR over the 2000-2020 period in 15-39 years was 58.1 per 100,000 (95% confidence interval [CI] 57.0-59.2). ASR was lower in males (47.2 [45.7-48.6]) than in females (68.9 [67.2-70.6]). Incidence per 100,000 differed with age group from the lowest, 20.5 (19.8-21.2) in 15-19 years, to the highest, 130.3 (128.6-132.0) in 35-39 years. Increases in incidence were observed for essential thrombocythemia (APC: 3.33% [1.52-5.16]), Hodgkin lymphoma (HL) (APC: 1.86% [1.21-2.52]), liposarcoma (APC: 3.68% [0.83-6.61]), carcinomas of urinary tract (APC: 3.95% [2.85-5.06]), gastrointestinal tract (APC: 2.62% [1.96-3.28]), and breast (APC: 1.61% [1.22-2.01]) from 2000 to 2020, glioblastoma (APC: 6.11% [3.06-9.26]), and other astrocytomas (APC: 7.41% [5.13-9.75]) from 2005 to 2020. Decreases in incidence were observed for oligodendroglioma (APC: -8.78% during 2005-2020), and other invasive carcinomas (APC: -3.34% during 2000-2020). Conclusion: Increases in the incidence of some AYA cancer types are observed HL, liposarcoma, carcinomas of colorectum, breast, and kidney. Results for central nervous system tumors are still to be confirmed in the years to come. Extensive efforts are needed to identify underlying risk factors responsible for these trends to inform prevention strategies.
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Affiliation(s)
- Emmanuel Desandes
- Registre National des cancers de l'Enfant / Registre National des Tumeurs Solides de l'Enfant, CHRU Nancy, Vandœuvre lès Nancy, France
- Centre de Recherche en Epidémiologie et en Statistique Sorbonne-Paris Cité (CRESS), UMR 1153, INSERM, Université Paris-Descartes, Paris, France
| | - Jacqueline Clavel
- Centre de Recherche en Epidémiologie et en Statistique Sorbonne-Paris Cité (CRESS), UMR 1153, INSERM, Université Paris-Descartes, Paris, France
- Registre National des cancers de l'Enfant / Registre National des Hémopathies de l'Enfant, Hôpital Paul Brousse,Groupe Hospitalier Universitaire Paris Sud,APHP, Villejuif, France
| | - Florence Molinié
- Registre des cancers de Loire-Atlantique/Vendée, CHU Nantes, Nantes, France
| | | | | | | | - Michel Velten
- Registre des cancers du Bas-Rhin, Laboratoire d'épidémiologie et de santé publique, Université de Strasbourg, Inserm UMR-S1113/Centre Paul Strauss, Service de santé publique, Strasbourg, France
| | - Gaelle Coureau
- Registre général des cancers de la Gironde, Université Bordeaux, Epicène, Equipe EPICENE, centre Inserm U1219, CHU de Bordeaux, service d'information médicale, Bordeaux, France
| | - Karima Hammas
- Registre des cancers du Haut-Rhin, ARER68, Groupe hospitalier de la région de Mulhouse et Sud-Alsace (GHRMSA), Mulhouse, France
| | - Anne Cowppli-Bony
- Registre des cancers de Loire-Atlantique/Vendée, CHU Nantes, Nantes, France
| | | | - Vincent Démaret
- Registre général des cancers de Lille et de sa région, Lille, France
| | - Olivier Ganry
- Registre Général du Cancer de la Somme, CHU Amiens, France
| | - Nicolas Vigneron
- Registre Général des Tumeurs du Calvados, Centre François Baclesse, Caen, France
| | - Simona Bara
- Registre des Cancers de la Manche, Cherbourg-Octeville, France
| | - Laetitia Daubisse-Marliac
- Registre des cancers du Tarn, Oncopole Claudius Regaud, IUCT-O, CHU Toulouse/CERPOP Inserm U1295, Université Paul Sabatier, Toulouse, France
| | | | - Alain Monnereau
- Institut Bergonié, registre des hémopathies malignes de la Gironde/Université de Bordeaux, Inserm U1219, équipe EPICENE, ISPED, Bordeaux, France
| | - Xavier Troussard
- Registre des Hémopathies Malignes de Basse Normandie, Caen, France
| | - Isabelle Baldi
- Equipe EPICENE, INSERM U1219, Université de Bordeaux/Service Santé Travail Environnement, CHU Bordeaux, France
| | - Guy Launoy
- Registre des Tumeurs Digestives du Calvados, Caen, France
| | - Brigitte Lacour
- Registre National des cancers de l'Enfant / Registre National des Tumeurs Solides de l'Enfant, CHRU Nancy, Vandœuvre lès Nancy, France
- Centre de Recherche en Epidémiologie et en Statistique Sorbonne-Paris Cité (CRESS), UMR 1153, INSERM, Université Paris-Descartes, Paris, France
| | - Perrine Marec-Berard
- IHOPe (Institut d'hématologie et d'oncologie pédiatrique), Centre Léon Bérard, Lyon, France
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Hayashi Y, Ogino H, Minoda Y, Tanaka Y, Hata Y, Kubokawa M, Sakisaka S, Haraguchi K, Fukuda SI, Itaba S, Yoshimura D, Takahashi S, Tanaka M, Kubo H, Somada S, Ihara E, Ogawa Y. Endoscopic resection of rectal neuroendocrine tumors: zero disease-related deaths during a 10-year follow-up period. BMC Gastroenterol 2025; 25:155. [PMID: 40069652 PMCID: PMC11900432 DOI: 10.1186/s12876-025-03736-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Gastrointestinal neuroendocrine tumors (GI-NETs) are slow-growing tumors with the potential for malignancy that originate from neuroendocrine cells. Therefore, early diagnosis and treatment of GI-NETs are necessary to prevent metastasis. The widespread use of colonoscopy, which allows early detection of rectal neuroendocrine tumors (rNETs) that are small enough to be treated endoscopically, has resulted in an increasing rate of endoscopic resection of rNETs. However, whether the long-term prognosis of endoscopically resected rNETs is favorable has not yet been determined. This study aimed to assess whether endoscopically resected rNETs affect the long-term prognosis of patients. METHODS We retrospectively reviewed the medical records of 163 consecutive patients with rNETs who underwent endoscopic resection at 11 hospitals in Japan between 1999 and 2012. The primary analysis focused on 47 patients with 51 rNETs who underwent ≥ 10 years of follow-up. The secondary analysis focused on patients who underwent less than 10 years of follow-up. RESULTS The median follow-up period of patients included in the primary analysis was 12.3 years (range, 10-19.1 years). The median lesion size was 5 mm (range, 2-12). Three lesions were treated using conventional endoscopic mucosal resection (EMR). Twenty-nine lesions were treated using modified EMR. Nineteen lesions were treated using endoscopic submucosal dissection. The R1 resection rate and lymphovascular invasion rate were 15.7% and 25.5%, respectively. The curative resection (CR) rate and non-CR rate were 66.7% and 33.3%, respectively. Two patients with lesions treated with non-CR underwent radical surgery. None of the 47 patients experienced lesion recurrence during the 10-year follow-up period. Two patients whose lesions were treated with CR died of other diseases. CONCLUSIONS Death attributable to rNETs did not occur among patients who underwent at least 10 years of follow-up after endoscopic resection.
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Affiliation(s)
- Yasuyo Hayashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka, Japan
| | - Haruei Ogino
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka, Japan.
| | - Yosuke Minoda
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka, Japan
| | - Yoshimasa Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka, Japan
| | - Yoshitaka Hata
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka, Japan
| | - Masaru Kubokawa
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka, Japan
| | - Seiichiro Sakisaka
- Department of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan
| | - Kazuhiro Haraguchi
- Department of Gastroenterology, Harasanshin Hospital, Hakata-Ku, Fukuoka, Japan
| | - Shin-Ichiro Fukuda
- Department of Gastroenterology, Kitakyushu Municipal Medical Center, Kokurakita-Ku, Kitakyushu, Japan
| | - Soichi Itaba
- Department of Gastroenterology, Kyushu Rosai Hospital, Kitakyushu, Fukuoka, Japan
| | - Daisuke Yoshimura
- Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Chuo-Ku, Fukuoka, Japan
| | - Shunsuke Takahashi
- Department of Gastroenterology, Fukuoka City Hospital, Hakata-Ku, Fukuoka, Japan
| | - Munehiro Tanaka
- Department of Gastroenterology and Hepatology, NHO Fukuokahigashi Medical Center, Koga, Japan
| | | | - Shinichi Somada
- Department of Gastroenterology, National Hospital Organization Beppu Medical Center, Beppu, Oita, Japan
| | - Eikichi Ihara
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka, Japan
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3
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McMurry HS, Rivero JD, Chen EY, Kardosh A, Lopez CD, Pegna GJ. Gastroenteropancreatic neuroendocrine tumors: Epigenetic landscape and clinical implications. Curr Probl Cancer 2024; 52:101131. [PMID: 39173542 DOI: 10.1016/j.currproblcancer.2024.101131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 05/22/2024] [Indexed: 08/24/2024]
Abstract
Neuroendocrine tumors (NETs) are a rare, heterogenous group of neoplasms arising from cells of the neuroendocrine system. Amongst solid tumor malignancies, NETs are notable for overall genetic stability and recent data supports the notion that epigenetic changes may drive NET pathogenesis. In this review, major epigenetic mechanisms of NET pathogenesis are reviewed, including changes in DNA methylation, histone modification, chromatin remodeling, and microRNA. Prognostic implications of the above are discussed, as well as the expanding diagnostic utility of epigenetic markers in NETs. Lastly, preclinical and clinical evaluations of epigenetically targeted therapies in NETs and are reviewed, with a focus on future directions in therapeutic advancement.
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Affiliation(s)
- Hannah S McMurry
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States
| | - Jaydira Del Rivero
- Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Emerson Y Chen
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States
| | - Adel Kardosh
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States
| | - Charles D Lopez
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States
| | - Guillaume J Pegna
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States.
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4
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Rimondi A, Despott EJ, Chacchi R, Lazaridis N, Costa D, Bucalau AM, Mandair D, Pioche M, Rivory J, Santos-Antunes J, Marques M, Ramos-Zabala F, Barbaro F, Pimentel-Nunes P, Dinis-Ribeiro M, Albeniz E, Tantau M, Spada C, Lemmers A, Caplin M, Toumpanakis C, Murino A. Endoscopic submucosal dissection for rectal neuroendocrine tumours: A multicentric retrospective study. Dig Liver Dis 2024; 56:1752-1757. [PMID: 38763794 DOI: 10.1016/j.dld.2024.04.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 04/16/2024] [Accepted: 04/29/2024] [Indexed: 05/21/2024]
Abstract
INTRODUCTION Endoscopic Submucosal Dissection (ESD) has been reported as a feasible and effective treatment for Rectal Neuroendocrine Tumours (R-NETs). However, most of the experience on the topic comes from retrospective tertiary centre from Eastern Asia. Data on ESD for R-NETs in Western centres are lacking. MATERIALS AND METHODS This is a retrospective study, including patients who underwent endoscopic resection of R-NETS by ESD between 2015 and 2020 in Western Centres. Important clinical variables such as demographic, size of R-NETs, histological type, presence of lymphovascular invasion or distant metastasis, completeness of the endoscopic resection, recurrence, and procedure related complications were recorded. RESULTS 40 ESD procedure on R-NETs from 39 patients from 8 centres were included. Mean R-NETs size was 10.3 mm (SD 4.01). Endoscopic en-bloc resection was achieved in 39/40 ESD (97.5 %), R0 margin resection was obtained in 87.5 % (35/40) of the procedures, one patient was referred to surgery for lymphovascular invasion, two procedures (5 %) reported significant episodes of bleeding, whereas a perforation occurred in one case (1/40, 2.5 %) managed endoscopically. Recurrence occurred in 1 patient (2.5 %). CONCLUSION ESD is an effective and safe treatment for R-NETs in western centres.
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Affiliation(s)
- Alessandro Rimondi
- Royal Free Unit for Endoscopy, The Royal Free Hospital, University College London Institute for Liver and Digestive Health, Hampstead, London, United Kingdom
| | - Edward J Despott
- Royal Free Unit for Endoscopy, The Royal Free Hospital, University College London Institute for Liver and Digestive Health, Hampstead, London, United Kingdom
| | - Rocio Chacchi
- Royal Free Unit for Endoscopy, The Royal Free Hospital, University College London Institute for Liver and Digestive Health, Hampstead, London, United Kingdom
| | - Nikolaos Lazaridis
- Royal Free Unit for Endoscopy, The Royal Free Hospital, University College London Institute for Liver and Digestive Health, Hampstead, London, United Kingdom
| | - Deborah Costa
- Royal Free Unit for Endoscopy, The Royal Free Hospital, University College London Institute for Liver and Digestive Health, Hampstead, London, United Kingdom
| | - Ana-Maria Bucalau
- Erasme Hospital, Gastroenterology, Hepatopancreatology and Digestive Oncology Department, HUB (Hôpital Universitaire de Bruxelles), ULB (Université Libre de Bruxelles), Brussels, Belgium
| | - Dalvinder Mandair
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, ENETS Centre of Excellence, Royal Free London NHS. Foundation Trust, London, United Kingdom
| | - Mathieu Pioche
- Edouard Herriot Hospital, Endoscopy Unit, Digestive Disease Department, Lyon, Rhône-Alpes, France
| | - Jérome Rivory
- Edouard Herriot Hospital, Endoscopy Unit, Digestive Disease Department, Lyon, Rhône-Alpes, France
| | - Joao Santos-Antunes
- Centro Hospitalar São João, Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Margarida Marques
- Centro Hospitalar São João, Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Felipe Ramos-Zabala
- Servicio de Gastroenterología, Departamento de Ciencias Médicas Clínicas, Hospital Universitario HM Montepríncipe. HM Hospitales, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain
| | - Federico Barbaro
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Pedro Pimentel-Nunes
- Department of Surgery and Physiology, Porto Faculty of Medicine, Portugal, CINTESIS/ Biostatistics and Medical Informatics, Porto Faculty of Medicine, Portugal; RISE@CI-IPO (Health Research Network), Portuguese Oncology Institute, Porto, Portugal
| | - Mario Dinis-Ribeiro
- Department of Surgery and Physiology, Porto Faculty of Medicine, Portugal, CINTESIS/ Biostatistics and Medical Informatics, Porto Faculty of Medicine, Portugal
| | - Eduardo Albeniz
- Gastroenterology Department, Endoscopy Unit, Navarrabiomed-UPNA-IdiSNA, Pamplona, Spain
| | - Marcel Tantau
- University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - Cristiano Spada
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Arnaud Lemmers
- Erasme Hospital, Gastroenterology, Hepatopancreatology and Digestive Oncology Department, HUB (Hôpital Universitaire de Bruxelles), ULB (Université Libre de Bruxelles), Brussels, Belgium
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, ENETS Centre of Excellence, Royal Free London NHS. Foundation Trust, London, United Kingdom
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, ENETS Centre of Excellence, Royal Free London NHS. Foundation Trust, London, United Kingdom
| | - Alberto Murino
- Royal Free Unit for Endoscopy, The Royal Free Hospital, University College London Institute for Liver and Digestive Health, Hampstead, London, United Kingdom.
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La Rosa S. Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future. Endocr Pathol 2023; 34:79-97. [PMID: 36797453 PMCID: PMC10011307 DOI: 10.1007/s12022-023-09755-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/31/2023] [Indexed: 02/18/2023]
Abstract
The introduction of Ki67 immunohistochemistry in the work-up of neuroendocrine neoplasms (NENs) has opened a new approach for their diagnosis and prognostic evaluation. Since the first demonstration of the prognostic role of Ki67 proliferative index in pancreatic NENs in 1996, several studies have been performed to explore its prognostic, diagnostic, and predictive role in other neuroendocrine and endocrine neoplasms. A large amount of information is now available and published results globally indicate that Ki67 proliferative index is useful to this scope, although some differences exist in relation to tumor site and type. In gut and pancreatic NENs, the Ki67 proliferative index has a well-documented and accepted diagnostic and prognostic role and its evaluation is mandatory in their diagnostic work-up. In the lung, the Ki67 index is recommended for the diagnosis of NENs on biopsy specimens, but its diagnostic role in surgical specimens still remains to be officially accepted, although its prognostic role is now well documented. In other organs, such as the pituitary, parathyroid, thyroid (follicular cell-derived neoplasms), and adrenal medulla, the Ki67 index does not play a diagnostic role and its prognostic value still remains a controversial issue. In medullary thyroid carcinoma, the Ki67 labelling index is used to define the tumor grade together with other morphological parameters, while in the adrenal cortical carcinoma, it is useful to select patients to treated with mitotane therapy. In the present review, the most important information on the diagnostic, prognostic, and predictive role of Ki67 proliferative index is presented discussing the current knowledge. In addition, technical issues related to the evaluation of Ki67 proliferative index and the future perspectives of the application of Ki67 immunostaining in endocrine and neuroendocrine neoplasms is discussed.
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Affiliation(s)
- Stefano La Rosa
- Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Via O. Rossi 9, Varese, 21100, Italy.
- Unit of Pathology, Department of Oncology, ASST Sette Laghi, Varese, Italy.
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Wang Q, Yin R, Tang W, Li C, Zheng H, Zhang X, Jin X, Ying M, Fu J. Resection of primary lesion with chemotherapy improves the survival of patients with metastatic colorectal neuroendocrine carcinoma. Zhejiang Da Xue Xue Bao Yi Xue Ban 2022; 51:594-602. [PMID: 36581574 PMCID: PMC10264974 DOI: 10.3724/zdxbyxb-2021-0387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 09/25/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To evaluate the effect of resection of primary lesion and chemotherapy on survival of patients with metastatic colorectal neuroendocrine carcinoma (CRNEC). METHODS Clinical data of 393 patients with metastatic CRNECs between January 2010 and December 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, including 171 patients who received resection of primary lesion and 221 patients who did not undergo surgery. With the propensity score matching method 172 non-operated patients were selected as controls. Kaplan-Meier method and Log-rank test were used to evaluate the survival differences, while the prognostic factors were analyzed by Cox proportional-hazards model. Metastatic CRNEC patients from January 2001 to December 2021 in Affiliated Jinhua Hospital, Zhejiang University School of Medicine were selected for validation. RESULTS Compared with non-operated patients, patients who received resection had longer cause-specific survival ( P<0.05). Patients with resected positive lymph nodes>8 had a poorer prognosis compared to those with resected positive lymph nodes≤8 ( P<0.05). Multivariate analysis showed that gender, location of primary lesion and treatments were independent risk factors for cause-specific survival in patients with metastatic CRNEC (all P<0.05). For metastatic CRNEC patients with resection of primary lesion, rectal neuroendocrine carcinoma, positive resected lymph nodes≤8 and resection of primary lesion combined with chemotherapy were associated with better cause-specific survival (all P<0.05). CONCLUSIONS Patients with metastatic CRNEC may benefit from resection of primary lesion, and resection of primary lesion combined with chemotherapy might be the better strategy for metastatic CRNECs. The number of positive lymph nodes resected is correlated with the prognosis of patients.
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Affiliation(s)
- Qinghua Wang
- 1. Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Ruihua Yin
- 1. Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Wanfen Tang
- 1. Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Chenghui Li
- 1. Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Hongjuan Zheng
- 1. Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Xia Zhang
- 1. Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Xiayun Jin
- 1. Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Mingliang Ying
- 2. Department of Medical Imaging, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Jianfei Fu
- 1. Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
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7
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Iorio J, Antonuzzo L, Scarpi E, D’Amico M, Duranti C, Messerini L, Sparano C, Caputo D, Lavacchi D, Borzomati D, Antonelli A, Nibid L, Perrone G, Coppola A, Coppola R, di Costanzo F, Lastraioli E, Arcangeli A. Prognostic role of hERG1 Potassium Channels in Neuroendocrine Tumours of the Ileum and Pancreas. Int J Mol Sci 2022; 23:10623. [PMID: 36142530 PMCID: PMC9504580 DOI: 10.3390/ijms231810623] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/08/2022] [Accepted: 09/10/2022] [Indexed: 11/16/2022] Open
Abstract
hERG1 potassium channels are widely expressed in human cancers of different origins, where they affect several key aspects of cellular behaviour. The present study was designed to evaluate the expression and clinical relevance of hERG1 protein in cancer tissues from patients suffering from neuroendocrine tumours (NETs) of ileal (iNETs) and pancreatic (pNETs) origin, with available clinicopathological history and follow-up. The study was carried out by immunohistochemistry with an anti-hERG1 monoclonal antibody. In a subset of samples, a different antibody directed against the hERG1/β1 integrin complex was also used. The analysis showed for the first time that hERG1 is expressed in human NETs originating from either the ileum or the pancreas. hERG1 turned out to have a prognostic value in NETs, showing (i) a statistically significant positive impact on OS of patients affected by ileal NETs, regardless the TNM stage; (ii) a statistically significant positive impact on OS of patients affected by aggressive (TNM stage IV) disease, either ileal or pancreatic; (iii) a trend to a negative impact on OS of patients affected by less aggressive (TNM stage I-III) disease, either ileal or pancreatic. Moreover, in order to evaluate whether ERG1 was functionally expressed in a cellular model of pNET, the INS1E rat insulinoma cell line was used, and it emerged that blocking ERG1 with a specific inhibitor of the channel (E4031) turned out in a significant reduction in cell proliferation.
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Affiliation(s)
- Jessica Iorio
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Lorenzo Antonuzzo
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
- Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy
| | - Emanuela Scarpi
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | | | - Claudia Duranti
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Luca Messerini
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Clotilde Sparano
- Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy
| | - Damiano Caputo
- General Surgery, Campus Bio-Medico University, 00128 Rome, Italy
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Daniele Lavacchi
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
- Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy
| | - Domenico Borzomati
- General Surgery, Campus Bio-Medico University, 00128 Rome, Italy
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Alice Antonelli
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
- Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy
| | - Lorenzo Nibid
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
- Pathology Unit, Campus Bio-Medico University, 00128 Rome, Italy
| | - Giuseppe Perrone
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
- Pathology Unit, Campus Bio-Medico University, 00128 Rome, Italy
| | - Alessandro Coppola
- General Surgery, Campus Bio-Medico University, 00128 Rome, Italy
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Roberto Coppola
- General Surgery, Campus Bio-Medico University, 00128 Rome, Italy
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | | | - Elena Lastraioli
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
- Complex Dynamics Study Centre (CSDC), University of Florence, 50100 Florence, Italy
| | - Annarosa Arcangeli
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
- Complex Dynamics Study Centre (CSDC), University of Florence, 50100 Florence, Italy
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8
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Chang D, González APG, Migaly J. Management of neuroendocrine tumors of the rectum. SEMINARS IN COLON AND RECTAL SURGERY 2022. [DOI: 10.1016/j.scrs.2022.100901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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9
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Khanna V, Reddy T, Nagar T, Tegeltija V. Metastatic Large Cell Neuroendocrine Carcinoma of the Colon: A Case Report. Cureus 2022; 14:e26075. [PMID: 35747103 PMCID: PMC9209407 DOI: 10.7759/cureus.26075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2022] [Indexed: 11/05/2022] Open
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10
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Fujikawa K, Noura S, Suzuki Y, Takeyama H. Lymph Node Diameter as a Predictor of Lymph Node Metastasis in Patients with Colorectal Neuroendocrine Neoplasms. J Anus Rectum Colon 2022; 6:129-133. [PMID: 35572486 PMCID: PMC9045853 DOI: 10.23922/jarc.2021-061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 12/02/2021] [Indexed: 11/30/2022] Open
Abstract
Objectives: The ideal cut-off value for the diameter of metastasis-positive lymph nodes (LNs) in patients with colorectal neuroendocrine neoplasms (NENs) is unclear. Thus, in this study, we investigated the correlation between the LN diameter and LN metastasis. Methods: A total of 148 LNs of 42 patients with colorectal NEN who underwent surgical dissection or local resection from April 2010 to March 2016 were included in the present study. The LN diameters were measured on computed tomography, and LN metastases were either pathologically proven or evaluated during the follow-up period. Results: Overall, 18 (12.2%) LNs were positive for LN metastasis, and 130 (87.8%) were negative. The short diameter in metastatic-positive LNs was longer than that in negative LNs (4.9 [3.0-6.3] vs. 2.0 [1.0-2.0] mm; P = 0.01). An LN of >3 mm predicted LN metastasis with 88.8% sensitivity and 78.5% specificity with an area under the curve of 0.852. Conclusions: Surgical resection with lymphadenectomy should be considered for patients with LNs of >3 mm in diameter.
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Affiliation(s)
| | - Shingo Noura
- Department of Surgery, Toyonaka Municipal Hospital
| | - Yozo Suzuki
- Department of Surgery, Toyonaka Municipal Hospital
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11
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Jimenez-Fonseca P, Carmona-Bayonas A, Lamarca A, Barriuso J, Castaño A, Benavent M, Alonso V, Riesco MDC, Alonso-Gordoa T, Custodio A, Sanchez Canovas M, Hernando J, López C, La Casta A, Fernandez Montes A, Marazuela M, Crespo G, Diaz JA, Feliciangeli E, Gallego J, Llanos M, Segura A, Vilardell F, Percovich JC, Grande E, Capdevila J, Valle J, Garcia-Carbonero R. External Validity of Somatostatin Analogs Trials in Advanced Neuroendocrine Neoplasms: The GETNE-TRASGU Study. Neuroendocrinology 2022; 112:88-100. [PMID: 33508849 DOI: 10.1159/000514808] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 01/27/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Somatostatin analogs (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NENs. METHODS We identified patients with well-differentiated (Ki-67% ≤20%), metastatic GEP-NENs treated in first line with SSA monotherapy from the Spanish R-GETNE registry. The therapeutic effect was evaluated using a Bayesian Cox model. The objective was to compare survival-based outcomes from real-world clinical practice versus RCTs. RESULTS The dataset contained 535 patients with a median age of 62 years (range: 26-89). The median Ki-67% was 4 (range: 0-20). The most common primary tumor sites were as follows: midgut, 46%; pancreas, 34%; unknown primary, 10%; and colorectal, 10%. Half of the patients received octreotide LAR (n = 266) and half, lanreotide autogel (n = 269). The median PFS was 28.0 months (95% CI: 22.1-32.0) for octreotide versus 30.1 months (95% CI: 23.1-38.0) for lanreotide. The overall hazard ratio for lanreotide versus octreotide was 0.90 (95% credible interval: 0.71-1.12). The probability of effect sizes >30% with lanreotide versus octreotide was 2 and 6% for midgut and foregut NENs, respectively. CONCLUSION Our study evaluated the external validity of RCTs examining SSAs in the real world, as well as the main effect-modifying factors (progression status, symptoms, tumor site, specific metastases, and analytical data). Our results indicate that both octreotide LAR and lanreotide autogel had a similar effect on PFS. Consequently, both represent valid alternatives in patients with well-differentiated, metastatic GEP-NENs.
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Affiliation(s)
- Paula Jimenez-Fonseca
- Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain
| | - Alberto Carmona-Bayonas
- Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, UMU, IMIB, Murcia, Spain
| | - Angela Lamarca
- Medical Oncology Department, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
- Division of Cancer Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Jorge Barriuso
- Medical Oncology Department, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
- Division of Cancer Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Angel Castaño
- Pathology Department, Hospital Universitario de Fuenlabrada, Madrid, Spain
| | - Marta Benavent
- Medical Oncology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain
| | - Vicente Alonso
- Medical Oncology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Maria Del Carmen Riesco
- Medical Oncology Department, Hospital Universitario Doce de Octubre, IIS imas12, UCM, CNIO, CIBERONC, Madrid, Spain
| | - Teresa Alonso-Gordoa
- Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Ana Custodio
- Medical Oncology Department, Hospital Universitario La Paz, CIBERONC CB16/12/00398, Madrid, Spain
| | - Manuel Sanchez Canovas
- Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, UMU, IMIB, Murcia, Spain
| | - Jorge Hernando
- Medical Oncology Department, Hospital Universitario Vall d'Hebron, Vall Hebron Institute of Oncology (VHIO), Autonomous University of Barcelona, Barcelona, Spain
| | - Carlos López
- Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Adelaida La Casta
- Medical Oncology Department, Hospital Universitario Donostia, San Sebastián, Spain
| | - Ana Fernandez Montes
- Medical Oncology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain
| | - Mónica Marazuela
- Endocrinology Department, Hospital Universitario de la Princesa, Madrid, Spain
| | - Guillermo Crespo
- Medical Oncology Department, Complejo Asistencial Universitario de Burgos, Burgos, Spain
| | - Jose Angel Diaz
- Endocrinology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Eduardo Feliciangeli
- Medical Oncology Department, Hospital Universitario Santa Lucia, Cartagena, Spain
| | - Javier Gallego
- Medical Oncology Department, Hospital General Universitario de Elche, Elche, Spain
| | - Marta Llanos
- Medical Oncology Department, Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Spain
| | - Angel Segura
- Medical Oncology Department, Hospital Universitario La Fe, Valencia, Spain
| | - Felip Vilardell
- Pathology Department, Hospital Universitari Arnau de Vilanova, Lleida, Spain
| | | | - Enrique Grande
- Medical Oncology Department, MD Anderson Cancer Center Madrid, Madrid, Spain
| | - Jaume Capdevila
- Medical Oncology Department, Hospital Universitario Vall d'Hebron, Vall Hebron Institute of Oncology (VHIO), Autonomous University of Barcelona, Barcelona, Spain
| | - Juan Valle
- Medical Oncology Department, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
- Division of Cancer Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Rocio Garcia-Carbonero
- Medical Oncology Department, Hospital Universitario Doce de Octubre, IIS imas12, UCM, CNIO, CIBERONC, Madrid, Spain
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Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplastic proliferations showing different morphological features, immunophenotype, molecular background, clinical presentation, and outcome. They can virtually originate in every organ of the human body and their classification is not uniform among different sites. Indeed, as they have historically been classified according to the organ in which they primarily arise, the different nomenclature that has resulted have created some confusion among pathologists and clinicians. Although a uniform terminology to classify neuroendocrine neoplasms arising in different systems has recently been proposed by WHO/IARC, some issues remain unsolved or need to be clarified. In this review, we discuss the lights and shadows of the current WHO classifications used to define and characterize NENs of the pituitary gland, lung, breast and those of the head and neck region, and digestive and urogenital systems.
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Affiliation(s)
- Stefano La Rosa
- Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland.
- Institut Universitaire de Pathologie, CHUV, 25 rue du Bugnon, CH-1011, Lausanne, Switzerland.
| | - Silvia Uccella
- Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy
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13
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Comparison of endoscopic therapies for rectal neuroendocrine tumors: endoscopic submucosal dissection with myectomy versus endoscopic submucosal dissection. Surg Endosc 2021; 35:6374-6378. [PMID: 34231072 DOI: 10.1007/s00464-021-08622-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 06/14/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Endoscopic submucosal dissection (ESD) has been a valuable treatment of choice for rectal neuroendocrine tumors (NETs). However, the vertical margin may remain positive after ESD because the neuroendocrine tumors develop in a submucosal tumor (SMT)-like way. Endoscopic submucosal dissection with myectomy (ESD-ME), a new method for rectal NETs, may overcome this problem. METHODS From August 2013 to August 2020, the medical records of 69 patients (72 rectal neuroendocrine tumors) who received endoscopic submucosal dissection (ESD) or endoscopic submucosal dissection with myectomy (ESD-ME) for rectal NETs were investigated retrospectively. The characteristics of the patients and tumors, the rate of complete resection, and the rate of complications were analyzed retrospectively. RESULTS The ESD-ME group contained 27 patients (12 males, 15 females; age range 29-72 years) and the ESD group contained 42 patients (21 males, 21 females; age range 29-71 years). Both groups had similar mean rectal neuroendocrine tumor diameters (ESD-ME 6.1 ± 1.8 mm, ESD 6.7 ± 2.6 mm; P = 0.219). The procedure time was not different significantly between groups (ESD-ME 21.1 ± 6.3, ESD 19.3 ± 3.1; P = 0.115). The endoscopic complete resection rate did not differ significantly between the ESD-ME and ESD groups (100% for each). The histological complete resection rate was 100% (27 of 27) in the ESD-ME group and 81.0% (34 of 42) in the ESD group (P = 0.043). Delayed bleeding occurred in 1 ESD-ME patient (3.7%) and in 2 ESD patients (4.8%) (P = 1.000). Perforation occurred in 1 ESD-ME patient (3.7%) and the patient was successfully managed by conservative measure, and there was no perforation after ESD (P = 0.391). CONCLUSIONS When compared with ESD, ESD-ME resulted in a higher histological complete resection rate, had a similar complication rate, and took similar time to perform. ESD-ME can be considered an effective and safe resection method for rectal NETs < 16 mm in diameter without metastasis.
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14
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Li YW, He YP, Liu FQ, Peng JJ, Cai SJ, Xu Y, Wang MH. Grade G2 Rectal Neuroendocrine Tumor Is Much More Invasive Compared With G1 Tumor. Front Oncol 2021; 11:646536. [PMID: 33777809 PMCID: PMC7991726 DOI: 10.3389/fonc.2021.646536] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 01/28/2021] [Indexed: 11/29/2022] Open
Abstract
Background To compare clinicopathologic feature of rectal neuroendocrine tumor (NET) grade G1 with G2 NET. Methods Six hundred-one cases of rectal G1 and G2 NETs diagnosed in our center were analyzed. Results Of 601 cases of rectal NET, 515 cases were with grade G1 and 86 cases were with grade G2. Median tumor size was 0.7 cm. Compared with G1 NET, G2 tumors were with significantly larger tumor size (0.8 vs 2.2 cm, p < 0.001), less percentages of patients with tumors confined to submucosa (92.6 vs 42.8%, p < 0.001), more frequent presence of microvascular invasion (MVI) (3.6 vs 16.9%, p < 0.001) or peri-neural invasion (PNI) (2.0 vs 24.1%, p < 0.001). Incidence of lymph node and distant metastasis was 5.2 and 2.1% in G1 NET compared with 44.2 and 31.4% in G2 tumor, respectively (p < 0.001). For tumors sized 1–2 cm and confined to submucosa, incidence of lymph node metastasis was 6.1% for G1 NET compared with 21.1% for G2 NET. Status of MVI/PNI was predictive of lymph node metastasis for G2 tumor rather than G1 NET in this subgroup. Conclusions Rectal G2 NET was much more invasive with significantly elevated prevalence of lymph node metastasis compared with G1 tumor.
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Affiliation(s)
- Yi-Wei Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi-Ping He
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Endoscopy, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Fang-Qi Liu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jun-Jie Peng
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - San-Jun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ye Xu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ming-He Wang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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15
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Ali AS, Langer SW, Federspiel B, Hjortland GO, Grønbæk H, Ladekarl M, Welin S, Weber Vestermark L, Arola J, Osterlund P, Knigge U, Sørbye H, Micke P, Grimelius L, Grönberg M, Tiensuu Janson E. PD-L1 expression in gastroenteropancreatic neuroendocrine neoplasms grade 3. PLoS One 2020; 15:e0243900. [PMID: 33315908 PMCID: PMC7735636 DOI: 10.1371/journal.pone.0243900] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 11/30/2020] [Indexed: 02/07/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms grade 3 (GEP-NENs G3) are rare tumors. These highly aggressive neoplasms are traditionally treated with platinum-based chemotherapy in combination with etoposide. Immune checkpoint proteins such as programmed cell death ligand (PD-L1) may have a role in different cancers allowing them escape the immune system and hence, progress. We aimed to investigate the immunohistochemical expression of PD-L1 in GEP-NEN G3 and evaluate its correlation to clinical parameters. In a cohort of 136 patients, 14 (10%) expressed PD-L1 immunoreactivity; four (3%) patients in the tumor cells and 10 (7%) had immunoreactive immune cells. PD-L1 expression did not correlate to clinical parameters, progression-free survival or overall survival. We conclude that PD-L1 expression is present only in a subset of GEP-NEN G3 patients. Further studies are needed to fully understand the role of PD-L1 in patients with GEP-NEN G3, including the future possibility for treatment with immune checkpoint inhibitors.
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Affiliation(s)
- Abir Salwa Ali
- Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | - Seppo W. Langer
- Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Birgitte Federspiel
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | | | - Henning Grønbæk
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Morten Ladekarl
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
- Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
| | - Staffan Welin
- Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | | | - Johanna Arola
- Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Pia Osterlund
- Department of Oncology, Helsinki University Hospital and Helsinki University, Helsinki Finland
- Department of Oncology, Tampere University Hospital and Tampere University, Tampere, Finland
| | - Ulrich Knigge
- Department of Surgery C and Endocrinology PE, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Halfdan Sørbye
- Department of Oncology, Haukeland University Hospital and Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Patrick Micke
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Lars Grimelius
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Malin Grönberg
- Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
- * E-mail:
| | - Eva Tiensuu Janson
- Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
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Bai Y, Wu H, Han B, Xu K, Liu Y, Liu Y, Miao S, Zhang Y, Zhou L. Long intergenic non-protein coding RNA-467 targets microRNA-451a in human colorectal cancer. Oncol Lett 2020; 20:124. [PMID: 32934693 PMCID: PMC7471755 DOI: 10.3892/ol.2020.11987] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 07/13/2020] [Indexed: 02/05/2023] Open
Abstract
Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are frequently overexpressed in colorectal cancer (CRC). However, few related lncRNA signatures have been established for predicting CRC metastasis. The purpose of the present study was to identify lncRNAs that serve key roles in the metastasis of human CRC, and their potential downstream targets. A total of 31 human CRC biopsy samples were collected, and the expression of long intergenic non-protein coding RNA-467 (linc00467) and its association with clinical characteristics were evaluated. Consequently, linc00467 was revealed to be overexpressed in human CRC tissues, and its expression was significantly associated with metastasis and Tumor-Node-Metastasis stage. In HT29 and HCT116 cells, linc00467-knockout was revealed to decrease cellular proliferation and increase apoptosis (P<0.05). Finally, the downstream target of linc00467 in CRC promotion was predicted using bioinformatics analysis. The results demonstrated that linc00467 targets and regulates the expression of microRNA (miR)-451a, promoting carcinogenesis and metastasis in CRC. In conclusion, the results of the present study indicate that increased linc00467 expression promotes metastasis by targeting miR-451a, which ultimately increases cellular proliferation and inhibits apoptosis in human CRC cells.
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Affiliation(s)
- Yang Bai
- Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Haiyan Wu
- Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Bin Han
- Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Ke Xu
- Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Yuanqi Liu
- Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Yin Liu
- Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Shikun Miao
- Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Yuanyuan Zhang
- Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Liming Zhou
- Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
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Flórez NF, Pérez Cadavid JC, Turizo Agámez Á, Cuesta Castro DP. Caracterización de pacientes con tumores neuroendocrinos en un hospital de referencia de alta complejidad. REVISTA COLOMBIANA DE CIRUGÍA 2020. [DOI: 10.30944/20117582.786] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Introducción. Los tumores neuroendocrinos comprenden una amplia familia tumoral, siendo de mayor frecuencia aquellos localizados en el tracto gastrointestinal, los pulmones, el timo y el páncreas. Ocurren con poca frecuencia y cursan con un comportamiento biológico variable. El objetivo del presente estudio fue describir las características demográficas y clínicas de los pacientes con esta entidad en un hospital de alta complejidad.
Métodos. Estudio descriptivo con revisión de historias clínicas correspondientes a pacientes con tumor neuroendocrino, cuya muestra histológica fue analizada en el Departamento de Patología del Hospital Pablo Tobón Uribe, Medellín, Colombia, entre 2010 y 2015. Se describen frecuencias de localización, grado de diferenciación y perfil de inmuno-histoquímica.
Resultados. Se revisaron 111 historias, de las que el 51,5 % correspondió a pacientes masculinos, con una mediana de edad al momento del diagnóstico de 48 años. Las comorbilidades más frecuentes fueron: hipertensión arterial (38,6 %), hipotiroidismo (15,8 %) y diabetes mellitus (11,9 %). El antecedente de neoplasia estuvo presente en el 13,9 % de los casos. Un 59,4 % de las muestras correspondieron a tumores primarios, el 34,8 % estaban localizados en el páncreas. El hígado fue el órgano más comprometido por metástasis (73,3 %).
De los tumores neuroendocrinos, el 27 % correspondió a tumores grado 1 del tracto gastrointestinal o del páncreas, el 36 % a grado 2 y el 27,9 % a grado 3. El 3,6 % correspondió a tumores pulmonares de grado bajo o intermedio y el 5,4 % a tumores pulmonares de alto grado. Los marcadores tumorales con mayor positividad fueron sinaptofisina (97,2 %), citoqueratinas AE1/AE3 (95 %), CD56 (91,3%) y cromogranina (87,8%).
Discusión. Los tumores neuroendocrinos tienen características clínicas e histopatológicas diversas. Conocer las características de los pacientes afectados permite una aproximación de la epidemiología local aplicable a futuras investigaciones.
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Chida K, Watanabe J, Hirasawa K, Inayama Y, Misumi T, Kunisaki C, Endo I. A novel risk-scoring system for predicting lymph node metastasis of rectal neuroendocrine tumors. Ann Gastroenterol Surg 2020; 4:562-570. [PMID: 33005851 PMCID: PMC7511567 DOI: 10.1002/ags3.12355] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 05/11/2020] [Accepted: 05/14/2020] [Indexed: 01/02/2023] Open
Abstract
AIM Although rectal neuroendocrine tumors (NETs) are considered to be rare low-grade malignancies when lymph node metastasis (LNM) is present, their degree of malignancy is comparable to that of colorectal cancer (CRC). However, it remains unclear as to which patients require radical lymph node dissection. The aim of this study was to elucidate the risk factors for LNM and develop a risk-scoring system for LNM to help determine appropriate therapeutic approaches. METHODS In this study, we examined 103 patients with rectal NETs who underwent local resection (n = 55) or radical resection with LN dissection (n = 48). We evaluated each pathological feature, including the depth of submucosal invasion (SM depth) and tumor budding grade. RESULTS According to our univariate analyses and previous reports, the significant five risk factors for LNM were weighted with point values: 2 points for tumor size ≥ 15 mm and muscularis invasion, and 1 point each for SM depth ≥ 2000 µm, positive lymphovascular invasion, budding grade 3, and vertical margin. The area under the receiver operating curve for the scoring system was 0.899 (95% CI: 0.843-0.955). When a score of 2 was used as the cut-off value, the sensitivity and specificity for the prediction of LNM were 100% and 72.1%, respectively. CONCLUSIONS The risk-scoring system for LNM of rectal NETs showed high diagnostic performance. Using this risk-scoring system, it is possible to predict the risk of LNM and thereby potentially avoid unnecessary surgery. Further prospective external validation studies should be performed. The study was registered in the Japanese Clinical Trials Registry as UMIN000036658.
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Affiliation(s)
- Keigo Chida
- Department of Gastroenterological SurgeryYokohama City University Graduate School of MedicineYokohamaJapan
| | - Jun Watanabe
- Department of SurgeryGastroenterological CenterYokohama City University Medical CenterYokohamaJapan
| | - Kingo Hirasawa
- Division of EndoscopyYokohama City University Medical CenterYokohamaJapan
| | - Yoshiaki Inayama
- Department of PathologyYokohama City University Medical CenterYokohamaJapan
| | - Toshihiro Misumi
- Department of BiostatisticsYokohama City University School of MedicineYokohamaJapan
| | - Chikara Kunisaki
- Department of SurgeryGastroenterological CenterYokohama City University Medical CenterYokohamaJapan
| | - Itaru Endo
- Department of Gastroenterological SurgeryYokohama City University Graduate School of MedicineYokohamaJapan
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Maeda K, Koide Y, Katsuno H, Matsuoka H. Malignant potential of multiple rectal carcinoid tumors measuring ≤10 mm. Asian J Surg 2020; 43:1033-1034. [PMID: 32631622 DOI: 10.1016/j.asjsur.2020.06.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 06/23/2020] [Indexed: 11/15/2022] Open
Affiliation(s)
- Kotaro Maeda
- International Medical Center, Fujita Health University Hospital, Japan.
| | - Yoshikazu Koide
- Department of Surgery, Fujita Health University School of Medicine, Japan.
| | - Hidetoshi Katsuno
- Department of Surgery, Fujita Health University Okazaki Medical Center, Japan.
| | - Hiroshi Matsuoka
- Department of Surgery, Fujita Health University School of Medicine, Japan.
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20
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Pobłocki J, Jasińska A, Syrenicz A, Andrysiak-Mamos E, Szczuko M. The Neuroendocrine Neoplasms of the Digestive Tract: Diagnosis, Treatment and Nutrition. Nutrients 2020; 12:E1437. [PMID: 32429294 PMCID: PMC7284837 DOI: 10.3390/nu12051437] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/04/2020] [Accepted: 05/13/2020] [Indexed: 12/18/2022] Open
Abstract
Nuroendocrine neoplasms (NENs) are a group of rare neoplasms originating from dispersed neuroendocrine cells, mainly of the digestive and respiratory tract, showing characteristic histology and immunoprofile contributing to classification of NENs. Some NENs have the ability to produce biogenic amines and peptide hormones, which may be associated with clinical syndromes like, e.g., the carcinoid syndrome caused by unmetabolized overproduced serotonin, hypoglycemic syndrome in case of insulinoma, or Zollinger-Ellison syndrome accompanying gastrinoma. Diagnostics for these include ultrasound with endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography/computed tomography (PET/CT). Different nuclear medicine procedures can also be used, like somatostatin analogues scintigraphy (SRS) and 68Ga-Dota-Peptide PET/CT, as well as biochemical methods to determine the level of general neuroendocrine markers, such as chromogranin A (CgA), 5-hydroxyindolacetic acid (5-HIAA), synaptopfysin and cell type-specific peptide hormones, and neurotransmitters like gastrin, insulin, serotonin, and histamine. NENs influence the whole organism by modulating metabolism. The treatment options for neuroendocrine neoplasms include surgery, somatostatin analogue therapy, radionuclide therapy, chemotherapy, molecular targeted therapies, alpha-interferon therapy, and inhibitors of serotonin production. In the case of hypersensitivity to biogenic amines, a diet that limits the main sources of amines should be used. The symptoms are usually connected with histamine, tyramine and putrescine. Exogenic sources of histamine are products that take a long time to mature and ferment. Patients with a genetic insufficiency of the diamine oxidase enzyme (DAO), and those that take medicine belonging to the group of monoamine oxidases (MAO), are particularly susceptible to the negative effects of amines. Diet plays an important role in the initiation, promotion, and progression of cancers. As a result of the illness, the consumption of some nutrients can be reduced, leading to nutritional deficiencies and resulting in malnutrition. Changes in metabolism may lead to cachexia in some patients suffering from NENs. The aim of this narrative review was to advance the knowledge in this area, and to determine possibilities related to dietary support. The authors also paid attention to role of biogenic amines in the treatment of patients with NENs. We can use this information to better understand nutritional issues faced by patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), and to help inform the development of screening tools and clinical practice guidelines.
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Affiliation(s)
- Jakub Pobłocki
- Department of Endocrinology, Metabolic Diseases and Internal Diseases, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1str, 70-252 Szczecin, Poland; (J.P.); (A.S.); (E.A.-M.)
| | - Anna Jasińska
- Department of Human Nutrition and Metabolomic, Pomeranian Medical University in Szczecin, Broniewskiego 24 str, 71-460 Szczecin, Poland;
| | - Anhelli Syrenicz
- Department of Endocrinology, Metabolic Diseases and Internal Diseases, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1str, 70-252 Szczecin, Poland; (J.P.); (A.S.); (E.A.-M.)
| | - Elżbieta Andrysiak-Mamos
- Department of Endocrinology, Metabolic Diseases and Internal Diseases, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1str, 70-252 Szczecin, Poland; (J.P.); (A.S.); (E.A.-M.)
| | - Małgorzata Szczuko
- Department of Human Nutrition and Metabolomic, Pomeranian Medical University in Szczecin, Broniewskiego 24 str, 71-460 Szczecin, Poland;
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21
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Cai W, Ge W, Hu H, Mao J. Rectal NETs and rectosigmoid junction NETs may need to be treated differently. Cancer Med 2019; 9:971-979. [PMID: 31840409 PMCID: PMC6997099 DOI: 10.1002/cam4.2779] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 11/03/2019] [Accepted: 12/02/2019] [Indexed: 12/21/2022] Open
Abstract
Neuroendocrine tumors (NETs) are heterogeneous, and the incidence of NETs is rapidly increasing. We observed different survival in patients with rectal NETs and rectosigmoid junction NETs, which are treated similarly. We included patients with rectal and rectosigmoid junction NETs from the SEER database. The 5‐year survival was set as the end‐point. 6675 patients with rectal NETs and 329 patients with rectosigmoid junction NETs, were eligible for the analysis. Initially, the survival analyses suggested that the 5‐year survival significantly differed between the patients with rectal and rectosigmoid junction NETs (HR = 0.82, 95% CI 0.70‐0.95; P = .01). Tumor differentiation, an invasion deeper than T2, and lymph node and distant metastases were still important risk factors affecting survival for both location. While, the males showed better survival (HR = 0.69, 95% CI 0.55‐0.88; P < .01) and primary tumor surgery had no benefits (P = .56) for patients with rectosigmoid junction NETs. The factors that predict regional lymph node metastases varied by location. In rectal NETs, invasion deeper than T1 and a tumor larger than 1 cm could significantly increase the risk of regional lymph node metastases (all OR > 5, P < .01). In rectosigmoid junction NETs, the risk of regional lymph node metastases was considered significantly higher with invasion deeper than T1 (all OR > 5, P < .01) and a tumor larger than 2 cm (OR = 31.32, 95% CI 2.53‐387.57; P < .01). We advocate a clear and consistent definition of the rectosigmoid junction for future studies, and more studies are needed to determine the reason underlying differences between rectum and rectosigmoid junction.
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Affiliation(s)
- Wen Cai
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Weiting Ge
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Hanguang Hu
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Department of Medical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jianshan Mao
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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22
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Bruera G, Giuliani A, Romano L, Chiominto A, Di Sibio A, Mastropietro S, Cosenza P, Ricevuto E, Schietroma M, Carlei F. Poorly differentiated neuroendocrine rectal carcinoma with uncommon immune-histochemical features and clinical presentation with a subcutaneous metastasis, treated with first line intensive triplet chemotherapy plus bevacizumab FIr-B/FOx regimen: an experience of multidisciplinary management in clinical practice. BMC Cancer 2019; 19:960. [PMID: 31619203 PMCID: PMC6796336 DOI: 10.1186/s12885-019-6214-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 09/29/2019] [Indexed: 12/15/2022] Open
Abstract
Background Neuroendocrine tumors (NETs) are heterogeneous, widely distributed tumors arising from neuroendocrine cells. Gastrointestinal (GI)-NETs are the most common and NETs of the rectum represent 15, 2% of gastrointestinal malignancies. Poorly differentiated neuroendocrine carcinomas of the GI tract are uncommon. We report a rare case of poorly differentiated locally advanced rectal neuroendocrine carcinoma with nodal and a subcutaneous metastasis, with a cytoplasmic staining positive for Synaptophysin and Thyroid Transcription Factor-1. Case presentation A 72-year-old male presented to hospital, due to lumbar, abdominal, perineal pain, and severe constipation. A whole-body computed tomography scan showed a mass of the right lateral wall of the rectum, determining significant reduction of lumen caliber. It also showed a subcutaneous metastasis of the posterior abdominal wall. Patient underwent a multidisciplinary evaluation, diagnostic and therapeutic plan was shared and defined. The pathological examination of rectal biopsy and subcutaneous nodule revealed features consistent with small-cell poorly differentiated neuroendocrine carcinoma. First line medical treatment with triplet chemotherapy and bevacizumab, according to FIr-B/FOx intensive regimen, administered for the first time in this young elderly patient affected by metastatic rectal NEC was highly active and tolerable, as previously reported in metastatic colo-rectal carcinoma (MCRC). A consistent rapid improvement in clinical conditions were observed during treatment. After 6 cycles of treatment, CT scan and endoscopic evaluation showed clinical complete response of rectal mass and lymph nodes; patient underwent curative surgery confirming the pathologic complete response at PFS 9 months. Discussion and conclusions This case report of a locally advanced rectal NEC with an unusual subcutaneous metastasis deserves further investigation of triplet chemotherapy-based intensive regimens in metastatic GEP NEC.
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Affiliation(s)
- Gemma Bruera
- Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy.,Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Antonio Giuliani
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.,UOC Chirurgia Generale Universitaria, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy
| | - Lucia Romano
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. .,UOC Chirurgia Generale Universitaria, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy.
| | - Alessandro Chiominto
- UOC Anatomia Patologica, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L'Aquila, Italy
| | - Alessandra Di Sibio
- Department of Radiology, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L'Aquila, Italy
| | - Stefania Mastropietro
- Short Hospitalization Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L'Aquila, Italy
| | - Pierluigi Cosenza
- Short Hospitalization Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L'Aquila, Italy
| | - Enrico Ricevuto
- Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy.,Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Mario Schietroma
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.,UOC Chirurgia Generale Universitaria, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy
| | - Francesco Carlei
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.,UOC Chirurgia Generale Universitaria, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy
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23
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Peptides derived from the extracellular domain of the somatostatin receptor splicing variant SST5TMD4 increase malignancy in multiple cancer cell types. Transl Res 2019; 211:147-160. [PMID: 30904441 DOI: 10.1016/j.trsl.2019.02.013] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 02/06/2019] [Accepted: 02/26/2019] [Indexed: 12/19/2022]
Abstract
Extracellular fragments derived from plasma membrane receptors can play relevant roles in the development/progression of tumor pathologies, thereby offering novel diagnostic or therapeutic opportunities. The truncated variant of somatostatin receptor subtype-5, SST5TMD4, is an aberrantly spliced receptor with 4 transmembrane domains, highly overexpressed in several tumor types, whose C-terminal tail is exposed towards the extracellular matrix, and could therefore be the substrate for proteolytic enzymes. In silico analysis implemented herein predicted 2 possible cleavage sites for metalloproteases MMP2, 9, 14, and 16 in its sequence, which could generate 3 releasable peptides. Of note, expression of those MMPs was directly correlated with SST5TMD4 in several cancer-derived cell lines (ie neuroendocrine tumors and prostate, breast, and liver cancers). Moreover, incubation with SST5TMD4-derived peptides enhanced malignancy features in all cancer cell types tested (ie proliferation, migration, etc.) and blunted the antiproliferative response to somatostatin in QGP-1 cells, acting probably through PI3K/AKT and/or MEK/ERK signaling pathways and the modulation of key cancer-associated genes (eg MMPs, MKI67, ACTR2/3, CD24/44). These results suggest that SST5TMD4-derived peptides could contribute to the strong oncogenic role of SST5TMD4 observed in multiple tumor pathologies, and, therefore, represent potential candidates to identify novel diagnostic, prognostic, or therapeutic targets in cancer.
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24
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Carmona-Bayonas A, Jiménez-Fonseca P, Lamarca Á, Barriuso J, Castaño Á, Benavent M, Alonso V, Riesco-Martínez MDC, Alonso-Gordoa T, Custodio A, Sánchez Cánovas M, Hernando Cubero J, López C, Lacasta A, Fernández Montes A, Marazuela M, Crespo G, Escudero P, Diaz JÁ, Feliciangeli E, Gallego J, Llanos M, Segura Á, Vilardell F, Percovich JC, Grande E, Capdevila J, Valle JW, García-Carbonero R. Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study. J Clin Oncol 2019; 37:2571-2580. [PMID: 31390276 PMCID: PMC6768612 DOI: 10.1200/jco.19.00980] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
PURPOSE Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.
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Affiliation(s)
- Alberto Carmona-Bayonas
- Hospital Universitario Morales Meseguer, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain
| | | | - Ángela Lamarca
- The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Jorge Barriuso
- The Christie NHS Foundation Trust, Manchester, United Kingdom.,University of Manchester, Manchester, United Kingdom
| | - Ángel Castaño
- Hospital Universitario de Fuenlabrada, Madrid, Spain
| | - Marta Benavent
- Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Sevilla, Spain
| | | | | | | | - Ana Custodio
- Hospital Universitario La Paz, Centro de Investigación Biomédica en Red Cáncer, CB16/12/00398, Madrid, Spain
| | - Manuel Sánchez Cánovas
- Hospital Universitario Morales Meseguer, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain
| | - Jorge Hernando Cubero
- Hospital Universitario Vall d'Hebron, Vall Hebron Institute of Oncology, Autonomous University of Barcelona, Barcelona, Spain
| | - Carlos López
- Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | | | | | | | | | - Pilar Escudero
- Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | | | | | | | - Marta Llanos
- Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Spain
| | | | | | | | | | - Jaume Capdevila
- Hospital Universitario Vall d'Hebron, Vall Hebron Institute of Oncology, Autonomous University of Barcelona, Barcelona, Spain
| | - Juan W Valle
- The Christie NHS Foundation Trust, Manchester, United Kingdom.,University of Manchester, Manchester, United Kingdom
| | - Rocío García-Carbonero
- Hospital Universitario Doce de Octubre, Universidad Complutense de Madrid, Centro Nacional de Investigaciones Oncológicas, Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain
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25
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Xu K, Han B, Bai Y, Ma XY, Ji ZN, Xiong Y, Miao SK, Zhang YY, Zhou LM. MiR-451a suppressing BAP31 can inhibit proliferation and increase apoptosis through inducing ER stress in colorectal cancer. Cell Death Dis 2019; 10:152. [PMID: 30770794 PMCID: PMC6377610 DOI: 10.1038/s41419-019-1403-x] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 12/23/2018] [Accepted: 01/18/2019] [Indexed: 02/05/2023]
Abstract
The global morbidity and mortality of colorectal cancer (CRC) are ranked the third among gastrointestinal tumors in the world. MiR-451a is associated with several types of cancer, including CRC. However, the roles and mechanisms of miR-451a in CRC have not been elucidated. BAP31 is a predicted target gene of miR-451a in our suppression subtractive hybridization library. Its relationship with miR-451a and function in CRC are unclear. We hypothesized that miR-451a could induce apoptosis through suppressing BAP31 in CRC. Immunohistochemistry and real-time PCR were used to measure BAP31 expressions in CRC tissues and pericarcinous tissues from 57 CRC patients and CRC cell lines. Dual-luciferase reporter assay was used to detect the binding of miR-451a to BAP31. The expression of BAP31 protein in CRC tissues was significantly higher than that in pericarcinous tissues, which was correlated with distant metastasis and advanced clinical stages of CRC patients. The expression of BAP31 was higher in HCT116, HT29, SW620, and DLD cells than that in the normal colonic epithelial cell line NCM460. The expression of BAP31 was absolutely down-regulated when over-expressing miR-451a in HCT116 and SW620 cells compared with control cells. Mir-451a inhibited the expression of BAP31 by binding to its 5'-UTR. Over-expressing miR-451a or silencing BAP31 suppressed the proliferation and apoptosis of CRC cells by increasing the expressions of endoplasmic reticulum stress (ERS)-associated proteins, including GRP78/BIP, BAX, and PERK/elF2α/ATF4/CHOP, which resulted in increased ERS, cytoplasmic calcium ion flowing, and apoptosis of CRC cells. These changes resulting from over-expressing miR-451a were reversed by over-expressing BAP31 with mutated miR-451a-binding sites. Over-expressing miR-451a or silencing BAP31 inhibited tumor growth by inducing ERS. The present study demonstrated that miR-451a can inhibit proliferation and increase apoptosis through inducing ERS by binding to the 5'-UTR of BAP31 in CRC.
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Affiliation(s)
- Ke Xu
- Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China
- 985 Science and Technology Platform for Innovative Drugs, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Bin Han
- Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China
- 985 Science and Technology Platform for Innovative Drugs, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yang Bai
- Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China
- 985 Science and Technology Platform for Innovative Drugs, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Xiu-Ying Ma
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, China
| | - Zhen-Ni Ji
- Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China
- 985 Science and Technology Platform for Innovative Drugs, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yao Xiong
- Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China
- 985 Science and Technology Platform for Innovative Drugs, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Shi-Kun Miao
- Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China
- 985 Science and Technology Platform for Innovative Drugs, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yuan-Yuan Zhang
- Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China.
- 985 Science and Technology Platform for Innovative Drugs, Sichuan University, Chengdu, Sichuan, 610041, China.
| | - Li-Ming Zhou
- Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China.
- 985 Science and Technology Platform for Innovative Drugs, Sichuan University, Chengdu, Sichuan, 610041, China.
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26
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Dholaria SG, Lakhera KK, Patni S. Rare Case Report of Neuroendocrine Tumor in Axilla-Metastasis from Unknown Primary or De Novo? Indian J Surg Oncol 2018; 9:340-342. [PMID: 30287994 DOI: 10.1007/s13193-017-0716-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 10/30/2017] [Indexed: 11/24/2022] Open
Abstract
Neuroendocrine tumors (NET) are the neoplasm arising from neuroendocrine cells which are present throughout the body. It can be benign, being more common or malignant. Gut is the most common site, but they can be seen in any part of the body. We had a case of grade III NET in axilla presented with a fungating lesion with unknown primary. Clinical behavior of such tumor is predicted by tumor grade or differentiation. We treated this patient by surgery and adjuvant chemotherapy.
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Affiliation(s)
- Shreyas G Dholaria
- 1Department Surgical oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, 'A'-Block, 103, JLN Marg, Opp MNIT, Jaipur, Rajasthan 302017 India
| | - Kamal Kishor Lakhera
- 2MCh Surgical Oncology, Bhagwan Mahaveer Cancer Hospital & Research Centre, Jaipur, India
| | - Sanjeev Patni
- 3HOD Surgical Oncology Department, Bhagwan Mahaveer Cancer Hospital & Research Centre, Jaipur, India
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27
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Watson GA, Ahmed Y, Picardo S, Chew S, Cobbe S, Mahony C, Crotty J, Wallis F, Shelly MJ, Kiely P, Ipadeola OB, Healy V, Osman N, Gupta RK. Unusual Sites of High-Grade Neuroendocrine Carcinomas: A Case Series and Review of the Literature. AMERICAN JOURNAL OF CASE REPORTS 2018; 19:710-723. [PMID: 29915166 PMCID: PMC6044230 DOI: 10.12659/ajcr.908953] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Case series Patient: Female, 29 • Female, 69 • Female, 52 • Female, 71 • Male, 62 • Female, 67 Final Diagnosis: Neuroendocrine carcinoma Symptoms: Abdominal pain Medication: — Clinical Procedure: — Specialty: Oncology
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Affiliation(s)
- Geoffrey A Watson
- Department of Medical Oncology, University Hospital Limerick, Limerick, Ireland
| | - Yasar Ahmed
- Department of Medical Oncology, University Hospital Limerick, Limerick, Ireland
| | - Sarah Picardo
- Department of Medical Oncology, University Hospital Limerick, Limerick, Ireland
| | - Sonya Chew
- Department of Medical Oncology, University Hospital Limerick, Limerick, Ireland
| | - Shona Cobbe
- Graduate Entry Medical School, University Hospital Limerick, Limerick, Ireland
| | - Cillian Mahony
- Graduate Entry Medical School, University Hospital Limerick, Limerick, Ireland
| | - James Crotty
- Department of Radiology, University Hospital Limerick, Limerick, Ireland
| | - Fintan Wallis
- Department of Radiology, University Hospital Limerick, Limerick, Ireland
| | - Martin J Shelly
- Department of Radiology, University Hospital Limerick, Limerick, Ireland
| | - Patrick Kiely
- Department of Radiology, University Hospital Limerick, Limerick, Ireland
| | - Olu Bunmi Ipadeola
- Department of Histopathology, University Hospital Limerick, Limerick, Ireland
| | - Vourneen Healy
- Department of Histopathology, University Hospital Limerick, Limerick, Ireland
| | - Nemer Osman
- Department of Medical Oncology, University Hospital Limerick, Limerick, Ireland
| | - Rajnish K Gupta
- Department of Medical Oncology, University Hospital Limerick, Limerick, Ireland.,Graduate Entry Medical School, University Hospital Limerick, Limerick, Ireland
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Tanaka T, Nozawa H, Kawai K, Hata K, Kiyomatsu T, Nishikawa T, Otani K, Sasaki K, Murono K, Watanabe T. Lymph Node Size on Computed Tomography Images Is a Predictive Indicator for Lymph Node Metastasis in Patients with Colorectal Neuroendocrine Tumors. ACTA ACUST UNITED AC 2018; 31:1011-1017. [PMID: 28882974 DOI: 10.21873/invivo.11162] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 07/15/2017] [Accepted: 07/17/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Colorectal neuroendocrine tumors (NET) are a rare manifestation of colorectal neoplasia, requiring for radical dissection of the regional lymph nodes along with colorectal resection similar to that required for colorectal cancer. However, thus far, no reports have described the ability of computed tomography (CT) to predict lymph node involvement. In this study, we revealed the prediction rate of lymph node metastasis using contrast-enhanced CT. PATIENTS AND METHODS A total of 21 patients with colorectal NET undergoing colorectal resection were recruited from January 2010 to June 2016. We compared the CT findings between samples with or without pathologically proven lymph node metastasis, in each field (pericolic/perirectal and intermediate nodes). RESULTS Within the pericolic/perirectal field, any lymph node larger than 5 mm in the CT images was a predictive indicator of lymph node metastasis with a sensitivity, specificity, and area under ROC curve (AUC) of 66.7%, 87.5%, and 0.844, respectively. Within the intermediate field, any visible lymph node on the CT was a predictive indicator of lymph node metastasis with a sensitivity, specificity, and AUC of 100%, 76.4%, and 0.890, respectively. In addition, when we observed lymph nodes larger than 3 mm on the CT images, the sensitivity and specificity were 100% and 82.4%, respectively, with an AUC of 0.8971. CONCLUSION CT images provide predictive information for lymph node metastasis with a high rate of accuracy.
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Affiliation(s)
- Toshiaki Tanaka
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomomichi Kiyomatsu
- Division of Colorectal Surgery, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Takeshi Nishikawa
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kensuke Otani
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhito Sasaki
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Koji Murono
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Takeda K, Kudo SE, Misawa M, Mori Y, Yamano M, Inoue H. Endocytoscopic findings of colorectal neuroendocrine tumors (with video). Endosc Int Open 2018; 6:E589-E593. [PMID: 29756017 PMCID: PMC5943698 DOI: 10.1055/a-0591-9279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Accepted: 02/20/2018] [Indexed: 02/08/2023] Open
Abstract
Background and study aims Gastrointestinal neuroendocrine tumors (NET) are generally submucosal in location. Because these tumors are covered with normal mucosa, biopsy is necessary to confirm histological diagnosis before treatment. We explored the diagnostic capabilities of the endocytoscope, which can perform ultra-high magnification in vivo, for staining and diagnosing submucosal tumors in situ.
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Affiliation(s)
- Kenichi Takeda
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Shin-ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan,Corresponding author Shin-ei Kudo Digestive Disease Center, Showa University Northern Yokohama HospitalKanagawa 35-1, Chigasaki-chuo Tsuzuki-ku, Yokohama-city, Kanagawa 224-8503Japan+81-45-949-7535
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Yuichi Mori
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Miki Yamano
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Haruhiro Inoue
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo, Japan
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30
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Klöppel G, La Rosa S. Ki67 labeling index: assessment and prognostic role in gastroenteropancreatic neuroendocrine neoplasms. Virchows Arch 2017; 472:341-349. [PMID: 29134440 DOI: 10.1007/s00428-017-2258-0] [Citation(s) in RCA: 114] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 10/10/2017] [Accepted: 10/23/2017] [Indexed: 02/07/2023]
Abstract
In 1983, a monoclonal antibody, Ki67, was generated, that labeled the nuclei of proliferating non-neoplastic and neoplastic cells. The name Ki67 derived from the city of Kiel (Ki) where the antibody was produced in the university department of pathology and refers to the number of the original clone (67). Systematic assessment of the proliferative activity of tumors using Ki67 started in the 1990s, when Ki67, which only worked on frozen tissue, was complemented by the antibody MIB-1 that also worked in formalin-fixed tissues. Pancreatic neuroendocrine neoplasms (PanNENs) were the first endocrine tumors whose proliferative activity was assessed with Ki67. This approach was so successful that Ki67 was included as prognostic marker in the 2000 and 2004 WHO classifications of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In 2010, the WHO classification of GEP-NENs introduced a three-tiered grading, originally proposed by ENETS in 2006 that was mainly based on the Ki67 index. As it has subsequently been shown that the Ki67 index is the most reliable factor in the prognostic evaluation of GEP-NENs, especially of PanNENs, the 2017 WHO classification of PanNENs requires its use and strongly recommends exact assessment of the proportion Ki67-labeled cells as basis for the calculation of the Ki67 index. Problems in assessing the Ki67 index include intertumoral and intratumoral staining heterogeneity and counting methods. Despite such problems, the Ki67 index has emerged as indispensable for the prognostic and therapeutic stratification of the majority of GEP-NENs and can barely be replaced by counting mitoses. In future, however, it can be anticipated that the Ki67 cut-offs experience refinement in relation to the type of tumor, its location, and its response to therapy. It is also possible that the prognostic risk of an individual tumor is calculated for each Ki67 unit and not for an "a priori" fixed Ki67 class.
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Affiliation(s)
- Günter Klöppel
- Institute of Pathology, Consultation Center for Pancreatic and Endocrine Tumors, Technical University of Munich, Trogerstr. 18, 81675, Munich, Germany.
| | - Stefano La Rosa
- Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland
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31
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Yang JJ, Huang H, Xiao MB, Jiang F, Ni WK, Ji YF, Lu CH, Ni RZ. Sex comb on midleg like-2 is a novel specific marker for the diagnosis of gastroenteropancreatic neuroendocrine tumors. Exp Ther Med 2017; 14:1749-1755. [PMID: 28810646 DOI: 10.3892/etm.2017.4677] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 04/21/2017] [Indexed: 12/14/2022] Open
Abstract
Sex comb on midleg like-2 (SCML2) is a polycomb-group protein that encodes transcriptional repressors essential for appropriate development in the fly and in mammals. On the basis of previous findings, the present study aimed to explore the possibility of developing SCML2 into a new diagnostic marker for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A total of 64 paired GEP-NET tissues and adjacent non-tumorous tissues were obtained from patients who had undergone surgical resection between January 2009 and January 2014, and the expression of SCML2 and two neuroendocrine markers, namely synaptophysin (Syn) and chromogranin A (CgA), in the tissues was assessed by immunohistochemistry. Strong SCML2 staining was observed predominantly in the cell nuclei of GEP-NET tissues, and the overall expression rate and staining intensity of SCML2 were higher than those of Syn or CgA, respectively. Spearman rank correlation analysis demonstrated that SCML2 was not correlated with either Syn or CgA, while the combined detection of SCML2 with Syn or with CgA increased the diagnostic sensitivity to 100%. SCML2 expression in GEP-NETs was associated with several clinicopathological parameters, such as histological type, tumor grade, depth of invasion and clinical stage. Kaplan-Meier survival curves revealed that patients with higher SCML2 expression had lower survival rates than those with lower expression levels, while Cox proportional hazards regression analysis revealed that SCML2 was not an independent prognostic factor for GEP-NET patients. Therefore, SCML2 may have potential as a specific marker for joint use with other markers to improve the diagnostic efficiency of GEP-NETs.
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Affiliation(s)
- Jiao-Jiao Yang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Hua Huang
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Ming-Bing Xiao
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Feng Jiang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Wen-Kai Ni
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Yi-Fei Ji
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Cui-Hua Lu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Run-Zhou Ni
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
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32
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Stoner P, Ghaffaripour T, Cohen D. Aggressive large-cell neuroendocrine carcinoma of the sigmoid colon in a patient with ulcerative colitis. BMJ Case Rep 2017; 2017:bcr-2017-220093. [PMID: 28790093 DOI: 10.1136/bcr-2017-220093] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Colonic inflammation seen in inflammatory bowel disease (IBD) predisposes to the development of colorectal adenocarcinoma. In contrast, colorectal neuroendocrine carcinomas (NECs) have rarely been reported in the setting of IBD, and no definitive relationship between these tumours and IBD has been established. Dysplasia from chronic inflammation leading to neuroendocrine cell differentiation may be responsible for NEC development, though this finding has not been seen consistently. We present a case of large-cell neuroendocrine carcinoma of the sigmoid colon in a 65-year-old woman with long-standing ulcerative colitis. Although she underwent regular endoscopic follow-ups and was receiving the tumour necrosis factor alpha inhibitor infliximab, her tumour was large and aggressive, with metastases to the liver discovered at time of diagnosis. This case highlights the aggressive nature and poor prognosis of NECs and stresses the need to identify patients at high risk of developing NECs and develop improved surveillance guidelines for detecting them.
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Affiliation(s)
- Patrick Stoner
- Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Taban Ghaffaripour
- Department of Pathology, Mount Sinai Medical Center, Miami Beach, Florida, USA
| | - David Cohen
- Department of Medicine, Division of Gastroenterology, Mount Sinai Medical Center, Miami Beach, Florida, USA
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33
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Sagar VM, Cooper SC, Johnson J, Shetty S, Shah T. Gastrointestinal manifestations of neuroendocrine tumours: their investigation and management. Postgrad Med J 2017; 93:494-497. [PMID: 28600342 DOI: 10.1136/postgradmedj-2017-134847] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 04/11/2017] [Accepted: 04/23/2017] [Indexed: 12/16/2022]
Abstract
The incidence of neuroendocrine tumours (NETs) is on the rise in the UK. Patients with NETs need to be managed by a team of clinical specialties. There are a number of challenging gastrointestinal (GI) manifestations related to NETs that can occur in these patients, but a limited literature base exists to guide clinicians.Whilst life expectancy can be several years for patients with NETs, the GI symptoms can have a significant impact on their quality of life. It is therefore imperative to be familiar with the common GI manifestations associated with NETs, so symptoms can be appropriately managed with an overall aim of restoring the patient's quality of life.
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Affiliation(s)
- Vandana M Sagar
- Department of Liver Medicine, University Hospitals Birmingham, Edgbaston, Birmingham, UK
| | - Sheldon C Cooper
- Department of Gastroenterology, University Hospitals Birmingham, Edgbaston, Birmingham, UK
| | - Jill Johnson
- Department of Dietetics, Therapy Services, University Hospitals Birmingham, Edgbaston, Birmingham, UK
| | - Shishir Shetty
- Department of Liver Medicine, University Hospitals Birmingham, Edgbaston, Birmingham, UK
| | - Tahir Shah
- Department of Liver Medicine, University Hospitals Birmingham, Edgbaston, Birmingham, UK
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34
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Iwata R, Maruyama M, Ito T, Nakano Y, Kanemura Y, Koike T, Oe S, Yoshimura K, Nonaka M, Nomura S, Sugimoto T, Yamada H, Asai A. Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine tumor. Med Mol Morphol 2017; 50:211-219. [PMID: 28516286 DOI: 10.1007/s00795-017-0160-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 05/09/2017] [Indexed: 02/07/2023]
Abstract
Neuroendocrine tumors are rare, and little is known about the existence of cancer stem cells in this disease. Identification of the tumorigenic population will contribute to the development of effective therapies targeting neuroendocrine tumors. Surgically resected brain metastases from a primary neuroendocrine tumor of unknown origin were dissociated and cultured in serum-free neurosphere medium. Stem cell properties, including self-renewal, differentiation potential, and stem cell marker expression, were examined. Tumor formation was evaluated using intracranial xenograft models. The effect of temozolomide was measured in vitro by cell viability assays. We established the neuroendocrine tumor sphere cell line ANI-27S, which displayed stable exponential growth, virtually unlimited expansion in vitro, and expression of stem-cell markers such as CD133, nestin, Sox2, and aldehyde dehydrogenase. FBS-induced differentiation decreased Sox2 and nestin expression. On the basis of real-time PCR, ANI-27S cells expressed the neuroendocrine markers synaptophysin and chromogranin A. Intracranial xenotransplanted brain tumors recapitulated the original patient tumor and temozolomide exhibited cytotoxic effects on tumor sphere cells. For the first time, we demonstrated the presence of a sphere-forming, stem cell-like population in brain metastases from a primary neuroendocrine tumor. We also demonstrated the potential therapeutic effects of temozolomide for this disease.
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Affiliation(s)
- Ryoichi Iwata
- Department of Neurosurgery, Kansai Medical University, Hirakata, Japan
| | - Masato Maruyama
- Department of Anatomy and Brain Science, Kansai Medical University, Hirakata, Japan
| | - Tomoki Ito
- First Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Yosuke Nakano
- Department of Anatomy and Brain Science, Kansai Medical University, Hirakata, Japan
| | - Yonehiro Kanemura
- Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan
| | - Taro Koike
- Department of Anatomy and Cell Science, Kansai Medical University, Hirakata, Japan
| | - Souichi Oe
- Department of Anatomy and Cell Science, Kansai Medical University, Hirakata, Japan
| | | | - Masahiro Nonaka
- Department of Neurosurgery, Kansai Medical University, Hirakata, Japan
| | - Shosaku Nomura
- First Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Tetsuo Sugimoto
- Department of Anatomy and Brain Science, Kansai Medical University, Hirakata, Japan
| | - Hisao Yamada
- Department of Anatomy and Cell Science, Kansai Medical University, Hirakata, Japan
| | - Akio Asai
- Department of Neurosurgery, Kansai Medical University, Hirakata, Japan.
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35
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Xu K, Zhang YY, Han B, Bai Y, Xiong Y, Song Y, Zhou LM. Suppression subtractive hybridization identified differentially expressed genes in colorectal cancer: microRNA-451a as a novel colorectal cancer–related gene. Tumour Biol 2017; 39:1010428317705504. [PMID: 28468585 DOI: 10.1177/1010428317705504] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
To investigate differentially expressed genes regulated by microRNA-451a in colorectal cancer. We detected expression of microRNA-451a in colorectal cancer samples and normal pericarcinous tissues from 68 colorectal cancer patients and the correlation between microRNA-451a and clinical features of these patients. Then, the expression of microRNA-451a in HCT116, SW620, HT29, SW480, and DLD cells was also measured. The suppression subtractive hybridization method was used with two HCT116 cell lines with overexpressing or underexpressing microRNA-451a, respectively. The most highly increased genes were screened. Their functions were predicted by gene ontology analysis. The expression ratio of microRNA-451a in colorectal cancer to pericarcinous tissues was 0.37. Expression of microRNA-451a was decreased in HCT116, SW620, HT29, SW480, and DLD cells. In our suppression subtractive hybridization library, expression of seven genes was the most highly increased when underexpressing microRNA-451a. They were BCAP31, EEF1A1, CDC20, WDR6, TUFM, RPL13, and RPL7A. Expression of DKK1, PSME1, NDUFA3, and GNB2 was most highly increased when overexpressing microRNA-451a. Gene ontology analysis showed that the main functions of these genes were associated with translational elongation, protein localization to the endoplasmic reticulum, translation, poly(A) RNA binding, negative regulations of Wnt signaling pathway, and so on. MicroRNA-451a was demonstrated to be downregulated in colorectal cancer patient tissues whose target genes were analyzed and functions were predicted by suppression subtractive hybridization.
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Affiliation(s)
- Ke Xu
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P.R. China
| | - Yuan-Yuan Zhang
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P.R. China
| | - Bin Han
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P.R. China
| | - Yang Bai
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P.R. China
| | - Yao Xiong
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P.R. China
| | - Yi Song
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Li-Ming Zhou
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P.R. China
- 985 Science and Technology Platform for Innovative Drugs, Sichuan University, Chengdu, P.R. China
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36
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Gordillo Hernández A, Nogales Muñoz Á, Oliva Mompeán F. Unusual presentation of obstructive jaundice. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 109:238-239. [PMID: 28190362 DOI: 10.17235/reed.2017.4501/2016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Carcinoid tumors of the ampulla of Vater grow slowly and have an excellent prognosis after complete resection of local disease. Histopathological diagnosis is definitive, and the Whipple's procedure is performed as a standard at the present time, although more novel minimally-invasive techniques may be highly useful for selected patients. While tumor size is not a reliable marker of tumor aggression, it is nonetheless related to lymphatic invasion, hence an accurate diagnosis is important if the patient is to be offered the best option available for the treatment of their disease. Endoscopic ultrasound (EUS) is the technique of choice for presurgical assessment and endocopic excision, as it may rule out vascular and nodal involvement, and establish whether submucosal invasion is present, which precludes endoscopic resection. Local resection has been shown to obtain similar results as compared to CDP in terms of overall survival in patients with small periampullary NETs, with the advantage of significantly lower morbidity in selected cases.
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37
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Shigematsu Y, Kanda H, Konishi T, Takazawa Y, Inoue Y, Muto T, Ishikawa Y, Takahashi S. Recurrence 30 Years after Surgical Resection of a Localized Rectal Neuroendocrine Tumor. Intern Med 2017; 56. [PMID: 28626177 PMCID: PMC5505907 DOI: 10.2169/internalmedicine.56.7547] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Localized small rectal neuroendocrine tumors (NETs) without any vascular involvement rarely metastasize, and their resection alone is considered curative. We herein report a case of localized rectal NET (10×8 mm) without vascular involvement. Although resected initially, it recurred as liver metastasis 30 years later. For rectal NETs smaller than 10 to 20 mm, surveillance for 12 months is considered sufficient. However, this case suggests that such tumors can recur even 30 years after curative resection. The interval of recurrence is the longest among reported cases.
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Affiliation(s)
- Yasuyuki Shigematsu
- Division of General Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Japan
- Department of Pathology, The Cancer Institute of JFCR, Japan
| | - Hiroaki Kanda
- Department of Pathology, The Cancer Institute of JFCR, Japan
| | - Tsuyoshi Konishi
- Division of Gastroenterology Center, The Cancer Institute Hospital, JFCR, Japan
| | - Yutaka Takazawa
- Department of Pathology, The Cancer Institute of JFCR, Japan
| | - Yosuke Inoue
- Division of Gastroenterology Center, The Cancer Institute Hospital, JFCR, Japan
| | - Tetsuichiro Muto
- Division of Gastroenterology Center, The Cancer Institute Hospital, JFCR, Japan
| | - Yuichi Ishikawa
- Department of Pathology, The Cancer Institute of JFCR, Japan
| | - Shunji Takahashi
- Division of General Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Japan
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38
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Honjo K, Kure K, Ichikawa R, Ro H, Takahashi R, Niwa K, Ishiyama S, Sugimoto K, Kamiyama H, Takahashi M, Kojima Y, Goto M, Tomiki Y, Sakamoto K, Fukumura Y, Yao T. Two Cases of Rectal Neuroendocrine Tumor Resection Combined with Dissection of the Circular Muscle Layer Using the Endoscopic Submucosal Dissection Technique. Case Rep Gastroenterol 2016; 10:693-700. [PMID: 27990103 PMCID: PMC5156890 DOI: 10.1159/000452758] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 10/17/2016] [Indexed: 12/27/2022] Open
Abstract
Generally, lesions of rectal neuroendocrine tumors (NETs) 10 mm or smaller are less malignant and are indicated for endoscopic therapy. However, the vertical margin may remain positive after conventional endoscopic mucosal resection (EMR) because NETs develop in a way similar to submucosal tumors (SMTs). The usefulness of EMR with a ligation device, which is modified EMR, and endoscopic submucosal dissection (ESD) was reported, but no standard treatment has been established. We encountered 2 patients in whom rectal NETs were completely resected by combined dissection and resection of the circular muscle layer using the ESD technique. Case 1 was an 8-mm NET of the lower rectum. Case 2 was NET of the lower rectum treated with additional resection for a positive vertical margin after EMR. In both cases, the circular muscle layer was dissected applying the conventional ESD technique, followed by en bloc resection while conserving the longitudinal muscle layer. No problems occurred in the postoperative course in either case. Rectal NETs are observed in the lower rectum in many cases, and it is less likely that intestinal perforation by endoscopic therapy causes peritonitis. The method employed in these cases, namely combined dissection and resection of the circular muscle layer using the ESD technique, can be performed relatively safely, and it is possible to ensure negativity of the vertical margin. In addition, it may also be useful for additional treatment of cases with a positive vertical margin after EMR.
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Affiliation(s)
- Kumpei Honjo
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kazumasa Kure
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Ryosuke Ichikawa
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Hisashi Ro
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Rina Takahashi
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Koichiro Niwa
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Shun Ishiyama
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kiichi Sugimoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Hirohiko Kamiyama
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Makoto Takahashi
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yutaka Kojima
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Michitoshi Goto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yuichi Tomiki
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, Japan
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39
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Pyo JH, Hong SN, Min BH, Lee JH, Chang DK, Rhee PL, Kim JJ, Choi SK, Jung SH, Son HJ, Kim YH. Evaluation of the risk factors associated with rectal neuroendocrine tumors: a big data analytic study from a health screening center. J Gastroenterol 2016; 51:1112-1121. [PMID: 27025841 DOI: 10.1007/s00535-016-1198-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 03/14/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Rectal neuroendocrine tumor (NET) is the most common NET in Asia. The risk factors associated with rectal NETs are unclear because of the overall low incidence rate of these tumors and the associated difficulty in conducting large epidemiological studies on rare cases. The aim of this study was to exploit the benefits of big data analytics to assess the risk factors associated with rectal NET. METHODS A retrospective case-control study was conducted, including 102 patients with histologically confirmed rectal NETs and 52,583 healthy controls who underwent screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea between January 2002 and December 2012. Information on different risk factors was collected and logistic regression analysis applied to identify predictive factors. RESULTS Four factors were significantly associated with rectal NET: higher levels of cholesterol [odds ratio (OR) = 1.007, 95 % confidence interval (CI), 1.001-1.013, p = 0.016] and ferritin (OR = 1.502, 95 % CI, 1.167-1.935, p = 0.002), presence of metabolic syndrome (OR = 1.768, 95 % CI, 1.071-2.918, p = 0.026), and family history of cancer among first-degree relatives (OR = 1.664, 95 % CI, 1.019-2.718, p = 0.042). CONCLUSION The findings of our study demonstrate the benefits of using big data analytics for research and clinical risk factor studies. Specifically, in this study, this analytical method was applied to identify higher levels of serum cholesterol and ferritin, metabolic syndrome, and family history of cancer as factors that may explain the increasing incidence and prevalence of rectal NET.
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Affiliation(s)
- Jeung Hui Pyo
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Byung-Hoon Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Poong-Lyul Rhee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Jae Jun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Sun Kyu Choi
- Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sin-Ho Jung
- Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Jung Son
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
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Marchevsky AM, Wick MR. Diagnostic difficulties with the diagnosis of small cell carcinoma of the lung. Semin Diagn Pathol 2015; 32:480-8. [DOI: 10.1053/j.semdp.2015.11.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Neuroendocrine Rectal Tumors: Main Features and Management. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2015; 22:213-220. [PMID: 28868410 PMCID: PMC5579972 DOI: 10.1016/j.jpge.2015.04.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Accepted: 04/29/2015] [Indexed: 12/16/2022]
Abstract
The incidence of neuroendocrine tumors of the rectum has been increasing in the last decades, partly due to improved investigation. They are mostly well-differentiated small tumors with a rather good overall prognosis. In the last few years, some aspects of neuroendocrine tumors have been evolving. In 2010, the World Health Organization proposed a new classification, indicating that these tumors, as a category, should be considered malignant. Afterwards the European Neuroendocrine Tumor Society published their guidelines for the management of colorectal neoplasms. Treatment algorithm is mainly based on tumor size and grading and, in general, well-differentiated rectal tumors <2 cm can be endoscopically resected. Endorectal ultrasound plays a particularly important role by accurately assessing tumor size and depth of invasion prior to resection. There are no specific recommendations on the optimal endoscopic resection method, but data from recent studies suggests that modified endoscopic mucosal resection techniques and endoscopic submucosal dissection have superior complete resection rates.
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PROX1 is involved in progression of rectal neuroendocrine tumors, NETs. Virchows Arch 2015; 467:279-84. [PMID: 26063416 DOI: 10.1007/s00428-015-1795-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 05/13/2015] [Accepted: 05/28/2015] [Indexed: 10/23/2022]
Abstract
PROX1 is a homeobox transcription factor involved in the development of the lens, liver and heart and found upregulated in colorectal cancers. We studied PROX1 expression by immunohistochemistry in rectal neuroendocrine tumors (NETs). Approximately 10 to 15 % of gastroenteropancreatic NETs occur in the rectum, and some may metastasize. Yet little is known about the molecular pathogenesis of rectal NETs or their metastasis propensity. The objectives were to find out whether PROX1 plays a role in progression of rectal NETs and whether it has value as prognostic marker. In grading of rectal NETs, we applied the WHO 2010 classification. We carried out immunohistochemical staining of PROX1 on 72 primary tumors and six metastases and evaluated nuclear positivity in each tumor. Correlation between PROX1 expression, metastasis and patient survival was then assessed. Annexin A1, a downstream target of PROX1, was immunohistochemically assessed in 18 tumors. PROX1 protein was detected in about half of the tumors, with stronger expression in metastasized cases. PROX1 expression correlated with tumor metastasis and patient prognosis. Annexin A1 was negative in most of the high-grade tumors correlating strongly with grade and metastatic potential. Our results indicate that immunohistochemical detection of PROX1 correlates with a more malignant phenotype in rectal NETs. High PROX1 expression was associated with increased metastatic potential and poor patient survival but not as strongly as grade by the WHO 2010 classification. PROX1 may be involved in progression of rectal NETs as a part of the Wnt pathway.
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Celotti A, Pulcini G, Schieppati M, Ministrini S, Berruti A, Ronconi M. An unusual case of a well-differentiated neuroendocrine tumour of the ileum with peritoneal carcinomatosis: a case report. World J Surg Oncol 2015; 13:169. [PMID: 25933800 PMCID: PMC4419448 DOI: 10.1186/s12957-015-0585-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 04/14/2015] [Indexed: 01/25/2023] Open
Abstract
Neuroendocrine tumours (NETs) are a family of neoplasms that come from neuroendocrine cells and express neural markers, such as synaptophysin or chromogranin A. The current classifications of these tumours are presented by the WHO 2000 classification, based on histological parameters, and the WHO 2010 classification, based on the proliferative index, that divides the NETs into a neuroendocrine tumour of a low grade, neuroendocrine tumour of a intermediate grade and neuroendocrine carcinoma (NEC) of a high grade. We are reporting a very rare case of a G1 low-grade neuroendocrine tumour (NET) of the ileum with a peritoneal carcinomatosis. This case is challenging because the tumour expresses low proliferative index as G1 tumours, but it has an aggressive clinical behaviour such as node metastasis and peritoneal carcinomatosis. The peritoneal carcinomatosis is not actually considered by the current classifications of NETs, so it is difficult to predict the prognosis of this patient.
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Affiliation(s)
- Andrea Celotti
- Surgical Clinic of Brescia, Piazzale Spedali Civili, 1, Brescia, Italy.
| | - Giuseppe Pulcini
- Surgical Unit, Hospital of Gardone Val Trompia, Gardone Val Trompia, Italy.
| | - Mattia Schieppati
- Surgical Unit, Hospital of Gardone Val Trompia, Gardone Val Trompia, Italy.
| | - Silvia Ministrini
- Surgical Clinic of Brescia, Piazzale Spedali Civili, 1, Brescia, Italy.
| | | | - Maurizio Ronconi
- Surgical Unit, Hospital of Gardone Val Trompia, Gardone Val Trompia, Italy.
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Kim SH, Yang DH, Lee JS, Park S, Lee HS, Lee H, Park SH, Kim KJ, Ye BD, Byeon JS, Myung SJ, Yang SK, Kim JH, Kim CW, Kim J. Natural course of an untreated metastatic perirectal lymph node after the endoscopic resection of a rectal neuroendocrine tumor. Intest Res 2015; 13:175-9. [PMID: 25932004 PMCID: PMC4414761 DOI: 10.5217/ir.2015.13.2.175] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Revised: 08/20/2014] [Accepted: 09/01/2014] [Indexed: 12/13/2022] Open
Abstract
Lymph node metastasis is rare in small (i.e., <10 mm) rectal neuroendocrine tumors (NETs). In addition to tumor size, pathological features such as the mitotic or Ki-67 proliferation index are associated with lymph node metastasis in rectal NETs. We recently treated a patient who underwent endoscopic treatment of a small, grade 1 rectal NET that recurred in the form of perirectal lymph node metastasis 7 years later. A 7-mm-sized perirectal lymph node was noted at the time of the initial endoscopic treatment. The same lymph node was found to be slightly enlarged on follow-up and finally confirmed as a metastatic NET. Therefore, the perirectal lymph node metastasis might have been present at the time of the initial diagnosis. However, the growth rate of the lymph node was extremely low, and it took 7 years to increase in size from 7 to 10 mm. NETs with low Ki-67 proliferation index and without mitotic activity may grow extremely slowly even if they are metastatic.
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Affiliation(s)
- Sang Hyung Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jung Su Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Soyoung Park
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ho-Su Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyojeong Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung-Jo Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin-Ho Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chan Wook Kim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jihun Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Sohn JH, Cho MY, Park Y, Kim H, Kim WH, Kim JM, Jung ES, Kim KM, Lee JH, Chan HK, Park DY, Joo M, Kim S, Moon WS, Kang MS, Jin SY, Kang YK, Yoon SO, Han H, Choi E. Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters. Cancer Res Treat 2015; 47:813-22. [PMID: 25715764 PMCID: PMC4614207 DOI: 10.4143/crt.2014.238] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Accepted: 11/04/2014] [Indexed: 02/08/2023] Open
Abstract
Purpose In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. Materials and Methods A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped. Results In univariate survival analysis, tumor grade (p < 0.0001), extent (p < 0.0001), size (p < 0.0001), lymph node metastasis (p=0.0063), and L-cell phenotype (p < 0.0001) showed significant correlation with the prognosis of rectal NENs; however, none of these markers achieved independent significance in multivariate analysis. The 10-year OS of tumors of NET grade 1, < 10 mm, the mucosa/submucosa was 97.58%, 99.47%, and 99.03%, respectively. L-Cell marker, glucagon II (GLP-1&2), with a cut off score of > 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. Conclusion From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.
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Affiliation(s)
| | - Jin Hee Sohn
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mee-Yon Cho
- Department of Pathology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Yangsoon Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyunki Kim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Woo Ho Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Joon Mee Kim
- Department of Pathology, Department of Pathology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Eun Sun Jung
- Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyoung-Mee Kim
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Hyuk Lee
- Department of Pathology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Hee Kyung Chan
- Department of Pathology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
| | - Do Youn Park
- Department of Pathology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Mee Joo
- Department of Pathology, Inje University Ilsan Paik Hospital, Inje Univeristy College of Medicine, Goyang, Korea
| | - Sujin Kim
- Department of Pathology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea
| | - Woo Sung Moon
- Department of Pathology, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - Mi Seon Kang
- Department of Pathology, Inje University Busan Paik Hospital,Inje University College of Medicine, Busan, Korea
| | - So-Young Jin
- Department of Pathology, Soon Chun Hyang University Hospital, Soon Chun Hyang University College of Medicine, Seoul, Korea
| | - Yun Kyung Kang
- Department of Pathology, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Sun Och Yoon
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - HyeSeung Han
- Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - EunHee Choi
- Division of Statistics in Institute of ifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
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A case of rectal neuroendocrine tumor presenting as polyp. Int J Surg Case Rep 2015; 8C:59-61. [PMID: 25625492 PMCID: PMC4353928 DOI: 10.1016/j.ijscr.2015.01.031] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Revised: 01/14/2015] [Accepted: 01/18/2015] [Indexed: 12/20/2022] Open
Abstract
Pointing out the rarely seen rectal neuroendocrine tumors (NETs). Rectal neuroendocrine tumors (NETs) can be presented as polypes. Emphasizing the importance of classification. Classifying the variety of treatments. Neuroendocrine tumor (NET) is detected in the examination of polypectomy material, presenting as rectal polyp. Since this is a rare case, we aimed to summarize the approach to rectal NET’s.
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Chi Y, Du F, Zhao H, Wang JW, Cai JQ. Characteristics and long-term prognosis of patients with rectal neuroendocrine tumors. World J Gastroenterol 2014; 20:16252-16257. [PMID: 25473180 PMCID: PMC4239514 DOI: 10.3748/wjg.v20.i43.16252] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 06/09/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze the clinicopathologic characteristics and prognostic factors of rectal neuroendocrine tumors.
METHODS: The records of 48 patients with rectal neuroendocrine tumors who were treated at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, from March 2004 to September 2009 were retrospectively reviewed. The clinicopathological data were extracted and analyzed, and patients were followed-up by telephone or follow-up letter to determine their survival status. Follow-up data were available for all 48 patients. Uni- and multivariate Cox regression analyses were performed to determine the prognostic factors significantly associated with overall survival.
RESULTS: The tumors occurred mostly in the middle and lower rectum, and the most prominent symptoms experienced by patients were hematochezia and diarrhea. The median distance between the tumors and the anal edges was 5.0 ± 2.257 cm, and the median diameter of the tumors was 0.8 ± 1.413 cm. The major pathological type was a typical carcinoid tumor, which accounted for 93.8% (45/48) of patients. Tumor-node-metastasis (TNM) stages I, II, III and IV tumors accounted for 78.8%, 3.9%, 9.6% and 7.7% of patients, respectively. The main treatment method, in 72.9% (35/48) of patients, was transanal extended excision. The 1-, 3- and 5-year survival rates of the whole group of patients were 100%, 93.7%, and 91.3%, respectively. Univariate analysis showed that age (P = 0.032), tumor diameter (P < 0.001), histological type (P < 0.001), TNM stage (P < 0.001), and surgical approach (P = 0.002) were all prognostic factors. On multivariate analysis, only the pathological type was shown to be an independent prognostic factor (HR = 2.797, 95%CI: 1.676-4.668, P = 0.004).
CONCLUSION: In patients with rectal neuroendocrine tumors, TNM stage I is the most common stage found, and lymph node or distant metastases are rarely seen. The pathological type of the tumor is an independent prognostic factor.
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Large cell neuroendocrine carcinoma of the rectum presenting with extensive metastatic disease. Case Rep Oncol Med 2014; 2014:386379. [PMID: 25225617 PMCID: PMC4124645 DOI: 10.1155/2014/386379] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2014] [Accepted: 07/04/2014] [Indexed: 11/18/2022] Open
Abstract
Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC) is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT) scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.
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Jernman J, Välimäki MJ, Hagström J, Louhimo J, Haapasalo H, Arola J, Haglund C. Cyclin A predicts metastatic potential of rectal neuroendocrine tumors. Hum Pathol 2014; 45:1605-9. [PMID: 24824027 DOI: 10.1016/j.humpath.2014.03.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2014] [Revised: 03/09/2014] [Accepted: 03/20/2014] [Indexed: 11/24/2022]
Abstract
Rectal neuroendocrine tumors (NETs) are rare tumors representing 10% to 15% of gastroenteropancreatic NETs. The grade of these tumors, according to the World Health Organization (WHO) 2010 classification and based on Ki-67 index and mitotic count, correlates with their metastatic potential. We studied the expression of a cell cycle regulatory protein, cyclin A, in rectal NETs. Our tumor series of rectal NETs comprised 73 tumors, of which 71 cases were available for immunohistochemistry. We assessed how well expression of cyclin A predicts the occurrence of metastatic lesions. Expression of cyclin A correlated well with metastatic potential because all tumors with high expression (≥5%) were metastatic. Cyclin A expression and WHO 2010 grade were independent prognostic factors. Cyclin A failed to recognize 3 metastatic tumors classified as grade 2 tumors. On the other hand, 2 grade 2 tumors with low expression of cyclin A remained local. The WHO 2010 classification showed excellent prognostic accuracy for rectal NETs. Additional reliable prognostic tools would nevertheless be valuable. This study showed cyclin A expression to correlate well with metastatic potential. Both cyclin A and WHO 2010 grade were very specific in identifying patients at risk for metastasis (100% versus 96%). Grade was more sensitive (100% versus 60%). Tumors with strong expression of both cyclin A and Ki-67 were all metastatic, and these patients will require careful monitoring and may benefit from adjuvant therapy.
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Affiliation(s)
- Juha Jernman
- Department of Pathology, University of Helsinki and Huslab, 00014 Helsinki, Finland; Department of Pathology, Fimlab Laboratories, 33101 Tampere, Finland.
| | - Matti J Välimäki
- Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, 00014 Helsinki, Finland
| | - Jaana Hagström
- Department of Pathology, University of Helsinki and Huslab, 00014 Helsinki, Finland
| | - Johanna Louhimo
- Department of Surgery, Helsinki University Central Hospital, 00014 Helsinki, Finland
| | - Hannu Haapasalo
- Department of Pathology, Fimlab Laboratories, 33101 Tampere, Finland
| | - Johanna Arola
- Department of Pathology, University of Helsinki and Huslab, 00014 Helsinki, Finland
| | - Caj Haglund
- Department of Pathology, University of Helsinki and Huslab, 00014 Helsinki, Finland; Department of Surgery, Helsinki University Central Hospital, 00014 Helsinki, Finland; Research Programs Unit, Translational Cancer Biology, University of Helsinki, 00014 Helsinki, Finland
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Singh RK, Parthasarathy G. Small rectal carcinoids: not always benign. J Gastroenterol Hepatol 2012; 27:1765-6. [PMID: 23167521 DOI: 10.1111/jgh.12000] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/12/2012] [Indexed: 12/09/2022]
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