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      Risk of desmoid formation after laparoscopic versus open colectomy and ileorectal anastomosis for familial adenomatous polyposis

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          Abstract

          Background

          Laparoscopy is used increasingly in prophylactic surgery for patients with familial adenomatous polyposis (FAP) undergoing colectomy with ileorectal anastomosis (IRA). Little is known about the impact of laparoscopy on subsequent desmoid risk. This study documented the risk of desmoid in patients undergoing laparoscopic and open IRA.

          Methods

          This was an observational study of patients with FAP and known germline APC mutation, undergoing IRA at a tertiary referral centre between 1996 and 2016. Patients were retrieved from a prospectively maintained polyposis registry. Data included genotype, family history of desmoid, sex, surgical approach at IRA and postoperative complications. The main outcome was development of either a clinically or radiologically significant desmoid.

          Results

          Some 112 patients (61 female) underwent colectomy and IRA. A laparoscopic approach was used in 69 patients (61·6 per cent). Baseline characteristics did not differ between patients having an open or laparoscopic approach. Median follow‐up was 5·8 (i.q.r. 2·4–11·2) years. Patients who underwent laparoscopic IRA had a reduced risk of desmoid formation (3 of 69 (4 per cent) versus 7 of 43 (16 per cent) in the open group; P = 0·043).

          Discussion

          Laparoscopic IRA may reduce risk of subsequent desmoid formation in patients with FAP.

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          Most cited references8

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          Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate.

          The nationwide Danish polyposis register includes all known Danish cases of familial adenomatous polyposis (FAP) and their relatives. By identifying all FAP patients born between 1920 and 1949, we found the frequency of the disease to be 1 in 13,528. By comparing the number of affected and nonaffected offspring born to affected parents during the same period we found the penetrance of the disease for inherited cases to be close to 100% at the age of 40 years. The mutation rate found by the direct method was 9 mutations per million gametes per generation and the proportion of new mutants was estimated to 25%. Fitness for patients between 15 and 29 years was found close to one, while for patients older than 30 the fitness was reduced, but increasing during the three decades (from 0.44 to 0.71) probably because treatment became more widespread and efficient. As we have used the overall fitness in the period, 0.87, to estimate the mutation rate by the indirect method, we found a lower value than by the direct method, namely 5 mutations per million gametes per generation.
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            Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis.

            Desmoids represent the most important cause of death, after colorectal cancer, in patients affected with familial adenomatous polyposis (FAP), an inherited disease due to mutations in the APC gene. The aims of our study were to estimate the risk of developing desmoids in FAP patients and to evaluate the association between desmoids and different risk factors. The occurrence of desmoids, colorectal cancer and other extra-colonic manifestations were assessed in 897 FAP patients, 653 of whom were also investigated for APC mutations. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using an unconditional multiple logistic regression model. Desmoids developed in 107 patients (11.9%), with a cumulative risk of 20.6%. Females had a significantly higher risk than males (OR = 2.1; 95% CI 1.4-3.1). Family history of desmoids (OR = 8.75; 95% CI 5.66-13.51), osteomas (OR = 2.9; 95% CI 1.8-4.8) and epidermoid cysts (OR = 1.8; 95% CI 1.1-3.2) was also significantly associated with the occurrence of disease. Subjects with APC mutations beyond codon 1444 had a 12-fold increased risk, compared with patients with mutations located upstream. Mutations beyond codon 1309 conferred a 17-fold higher risk, compared with mutations upstream codon 452. Multivariate analysis identified as independent predictors mutation beyond codon 1444 (OR = 6.2; 95% CI 2.5-15.8), family history of desmoids (OR = 5.8; 95% CI 3.1-10.6), female gender (OR = 2.1; 95% CI 1.1-3.8) and the presence of osteomas (OR = 1.9; 95% CI 1.1-3.4). Our results indicate that integrating genetic and clinical data is helpful in defining subgroups of patients at higher risk for desmoids, who may benefit from specific prevention programs. Copyright 2001 Wiley-Liss, Inc.
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              Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis.

              Desmoid tumours (DT) are myofibroblastic proliferations occurring in 15% of patients with familial adenomatous polyposis (FAP). Several small series have analysed the incidence of DT and predisposing risk factors. Using meta-analytical techniques, this study aimed to identify risk factors for DT development in patients with FAP. Studies of sporadic DT were excluded. The study end-points were the incidence of DT in FAP and DT development by gender, adenomatous polyposis coli (APC) mutation, family history of DT and previous abdominal surgery. A random effect Mantel-Haenszel model was used to calculate odds ratios for each risk factor and age group. Ten studies of 4625 patients with FAP fulfilled our inclusion criteria. A total of 559 (12%) patients developed DT. Cumulative analysis demonstrated that 80% of DT developed by age 40, the peak incidence rate being in the second and third decades. A positive family history of DT was the most significant risk factor (OR 7.02, 95% CI 4.15-11.9, P < 0.001). An APC mutation 3' to codon 1399 (OR 4.37, 95% CI 2.14-8.91, P < 0.001) and previous abdominal surgery (OR 3.35, 95% CI 1.33-8.41, P = 0.01) were also implicated. Women were more likely to develop DT (OR 1.57, 95% CI 1.13-2.18, P = 0.007). There is consistency amongst polyposis registries in documenting the incidence and risk factors for DT development. Having a positive family history for DT is of greater significance than a 3' mutation, suggesting the existence of modifier genes, independent of the APC genotype-phenotype correlation. Few of these risk factors are modifiable. Delaying prophylactic surgery could be appropriate in female patients with a 3' APC mutation and attenuated polyposis. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.
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                Author and article information

                Contributors
                ashishsinha@nhs.net
                Journal
                BJS Open
                BJS Open
                10.1002/(ISSN)2474-9842
                BJS5
                BJS Open
                John Wiley & Sons, Ltd (Chichester, UK )
                2474-9842
                08 August 2018
                December 2018
                : 2
                : 6 ( doiID: 10.1002/bjs5.2018.2.issue-6 )
                : 452-455
                Affiliations
                [ 1 ] The Polyposis Registry, Level 5 St Mark's Hospital Northwick Park, Watford Road, Harrow HA1 3UJ UK
                Author notes
                [*] [* ] Correspondence to: Mr A. Sinha (e‐mail: ashishsinha@ 123456nhs.net )
                Author information
                https://orcid.org/0000-0002-5828-3475
                https://orcid.org/0000-0002-0070-6332
                Article
                BJS590
                10.1002/bjs5.90
                6253786
                30511045
                f8ccfde6-1cd7-4eeb-a3ed-14435624065b
                © 2018 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of BJS Society Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 October 2017
                : 30 May 2018
                Page count
                Figures: 1, Tables: 3, Pages: 4, Words: 2048
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                bjs590
                December 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.3 mode:remove_FC converted:26.11.2018

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