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      A case of long-survival insulinoma with multiple neuroendocline tumour type 1 controlled by multimodal therapy

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          Abstract

          Insulinomas with multiple neuroendocrine tumour type 1 (MEN1) sometimes have metachronous or recurrent tumours. However, the treatment for these tumours is controversial, and published reports regarding multimodal therapy for insulinomas are limited. We report a 73-year-old woman with recurrent insulinoma with MEN1 successfully controlled by multimodal therapy. She had several complications, and poor performance status. Her hypoglycaemia did not improve after 6-month octreotide LAR; as such, she underwent enucleation of the pancreatic tumour. Within 7 years after the first operation, she underwent four succeeding surgeries for recurrent tumours. Her medications during follow-up were octreotide-LAR and Everolimus. Insulinoma can be managed through various treatment options. Medical treatment includes octreotide-LAR and Everolimus, while surgical approach includes enucleation and pancreaticoduodenectomy. Some tumours, particularly those that are MEN1, can recur repeatedly. Thus, several treatments are needed to control them. We highlight the importance of multimodal therapy, including repeated surgery, for the control of the disease.

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          Clinical studies of multiple endocrine neoplasia type 1 (MEN1)

          Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. To facilitate a screening programme for MEN1, we investigated 709 people (364 males and 345 females, age range 1-84 years) from 62 MEN1 families, and 36 non-familial MEN1 patients. Of those investigated, 220 (95 males and 125 females, age range 8-79 years) suffered from MEN1. Parathyroid, pancreatic and pituitary tumours occurred in 95%, 41% and 30% of the patients, respectively. Parathyroid tumours were the first manifestation of MEN1 in 87% of patients, and amongst the pituitary and pancreatic tumours, somatotrophinomas and gastrinomas were more common in patients above the age of 40 years, whilst insulinomas occurred more frequently in patients below the age of 40 years. Biochemical screening indicated that the penetrance of MEN1 by the ages of 20, 35 and 50 years was 43%, 85% and 94%, respectively, and that the development of MEN1 was confined to first-degree relatives in 91% of patients and to second-degree relatives in 9% of patients. These findings have helped to define a proposed screening programme for MEN1.
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            Surgical management of insulinomas: short- and long-term outcomes after enucleations and pancreatic resections.

            To analyze the characteristics and outcomes following enucleation and pancreatic resections of insulinomas. Retrospective cohort study; prospective database. Academic, tertiary, and referral centers. Consecutive patients with insulinomas (symptoms of hyperinsulinism and positive fasting glucose test) who underwent surgical treatment between January 1990 and December 2009. Operative morbidity, tumor recurrence, and survival after treatment. A total of 198 patients (58.5% women; median age, 48 years) were identified. There were 175 (88%) neuroendocrine tumors grade G1 and 23 (12%) neuroendocrine tumors grade G2. Malignant insulinomas defined by lymph node/liver metastases were found in 7 patients (3.5%). Multiple insulinomas were found in 8% of patients, and 5.5% of patients had multiple endocrine neoplasia type 1. Surgical procedures included 106 enucleations (54%) and 92 pancreatic resections (46%). Mortality was nil. Rate of clinically significant pancreatic fistula was 18%. Enucleations had a higher reoperation rate compared with pancreatic resections (8.5% vs 1%; P = .02). Multiple endocrine neoplasia type 1 was significantly associated with younger age at onset (P < .005) and higher rates of malignancies and multiple lesions. Median follow-up was 65 months. Six patients (3%; 5 patients had neuroendocrine tumors grade G2) developed tumor recurrence. Four patients (2%) died of disease. New exocrine (1.5%) and endocrine (4%) insufficiencies were associated only with pancreatic resections. Outcomes following surgical resection of insulinomas are satisfactory, with no mortality and good functional results. Recurrence is uncommon (3%), and it is more likely associated with neuroendocrine tumors grade G2. Insulinomas in multiple endocrine neoplasia type 1 are at higher risk for being malignant and multifocal, requiring pancreatic resections.
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              Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study.

              Preclinical and clinical studies suggest synergistic activity between somatostatin analogues and mammalian target of rapamycin inhibitors. The activity and safety of everolimus was assessed in combination with octreotide long-acting repeatable (LAR) in patients with neuroendocrine tumors (NETs) of gastroenteropancreatic and lung origin.
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                Author and article information

                Journal
                J Surg Case Rep
                J Surg Case Rep
                jscr
                Journal of Surgical Case Reports
                Oxford University Press
                2042-8812
                December 2017
                11 December 2017
                11 December 2017
                : 2017
                : 12
                : rjx244
                Affiliations
                Department of Surgery, Institute of Gastroenterology, Tokyo Woman’s Medical University, Tokyo, Japan
                Department of Pathology, and International Research and Educational Institute for Integrated Medical Sciences, Tokyo Woman’s Medical University , 8-1 Kawada-cho Shinjuku-ku, Tokyo 162-8666, Japan
                Author notes
                Correspondence address. Masahiro Shiihara, Department of Surgery, Institute of Gastroenterology, Tokyo Woman’s Medical University, 8-1 Kawada-cho Shinjuku-ku, Tokyo 162-8666, Japan. Tel: +81-3-3353-8111; E-mail: shiihara.ige@ 123456twmu.ac.jp
                Article
                rjx244
                10.1093/jscr/rjx244
                5724024
                b8fe119b-10bb-41bb-83e0-88f613e5db0c
                Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2017.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 31 August 2017
                : 16 November 2017
                Page count
                Pages: 4
                Categories
                Case Report

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