Y. Parc

Guidelines for the clinical management of familial adenomatous polyposis (FAP)

Background: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. A systematic literature search using Pubmed and reference lists of retrieved articles, and manual searches of relevant articles, was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may be helpful in the appropriate management of FAP families. In order to improve the care of these families further, prospective controlled studies should be undertaken.

Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer)

Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.

Peutz–Jeghers syndrome: a systematic review and recommendations for management

Peutz–Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype–phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.

Recommendations to improve identification of hereditary and familial colorectal cancer in Europe

Familial colorectal cancer (CRC) accounts for 10–15% of all CRCs. In about 5% of all cases, CRC is associated with a highly penetrant dominant inherited syndrome. The most common inherited form of non-polyposis CRC is the Lynch syndrome which is responsible for about 2–4% of all cases. Surveillance of individuals at high risk for CRC prevents the development of advanced CRC. About 1xa0million individuals in Western Europe are at risk for Lynch syndrome. We performed a survey to evaluate the strategies currently used to identify individuals at high risk for CRC in 14 Western European countries. Questionnaires were distributed amongst members of a European collaborative group of experts that aims to improve the prognosis of families with hereditary CRC. The survey showed that in all countries obtaining a family history followed by referral to clinical genetics centres of suspected cases was the main strategy to identify familial and hereditary CRC. In five out of seven countries with a (regional or national) CRC population screening program, attention was paid in the program to the detection of familial CRC. In only one country were special campaigns organized to increase the awareness of familial CRC among the general population. In almost all countries, the family history is assessed when a patient visits a general practitioner or hospital. However, the quality of family history taking was felt to be rather poor. Microsatellite instability testing (MSI) or immunohistochemical analysis (IHC) of CRC are usually recommended as tools to select high-risk patients for genetic testing and are performed in most countries in patients suspected of Lynch syndrome. In one country, IHC was recommended in all new cases of CRC. In most countries there are no specific programs on cancer genetics in the teaching curriculum for medical doctors. In conclusion, the outcome of this survey and the discussions within an European expert group may be used to improve the strategies to identify individuals at high risk of CRC. More attention should be given to increasing the awareness of the general population of hereditary CRC. Immunohistochemical analysis or MSI-analysis of all CRCs may be an effective tool for identifying all Lynch syndrome families. The cost-effectiveness of this approach should be further evaluated. All countries with a CRC population screening program should obtain a full family history as part of patient assessment.

Prognostic significance of microsatellite instability determined by immunohistochemical staining of MSH2 and MLH1 in sporadic T3N0M0 colon cancer

Background: Microsatellite instability (MSI) has been identified as a factor with good prognosis and chemosensitivity in stage III C colon cancer. The purpose of this study was to evaluate the routine use of immunohistochemical analysis (immunohistochemical staining of MSH2 and MLH1) to identify T3N0M0 (stage II) colon cancer with MSI and assess the prognostic value of this analysis. The study was conducted in a large cohort of patients in a single institution who had a curatively resected T3N0M0 colon cancer and were not receiving adjuvant therapy. Methods: Between June 1995 and December 2001, 142 patients (77 females) with a mean age of 68 years, suffering from T3N0M0 colon cancer curatively resected and not receiving adjuvant therapy, were checked in terms of their follow up status. The results of colonoscopy, hepatic ultrasonography, chest x ray, and blood carcinoembryological antigen were noted. All tumours were immunohistochemically stained for MSH2 and MLH1. Perineural invasion, lymphovascular invasion, and the presence of vascular neoplastic emboli were assessed. Results: Twenty four patients (17%) had MSI tumours. Patients with MSI and microsatellite stable (MSS) tumours did not differ in terms of age, perineural or lymphovascular invasion, or the presence of vascular neoplastic emboli. Patients with MSI tumours were more frequently female (18/24 v 60/118; pu200a=u200a0.001) and more frequently suffered from right sided cancer (19/24 v 58/118; p<0.001). Patients with MSI tumours exhibited significantly better recurrence free survival than those with MSS tumours (pu200a=u200a0.02). Cox analysis identified age and MSI determined by immunohistochemistry as independent predictive factors of good prognosis (pu200a=u200a0.009, odds ratio 1.04 (1.01–1.08); pu200a=u200a0.04, odds ratio 7.9 (1.05–59.6)). Conclusions: MSI determined by immunohistochemistry is an independent predictive factor of good prognosis in T3N0M0 colon cancer. The prognosis for MSI T3N0M0 colon cancer is excellent and chemotherapy should not be proposed in these patients as immunohistochemical analysis produces rapid results.

Family history, surgery, and APC mutation are risk factors for desmoid tumors in familial adenomatous polyposis: an international cohort study.

BACKGROUND: Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice. OBJECTIVES: Our aim was to assess several risk factors for desmoid tumor development in an international cohort of patients with familial adenomatous polyposis and to evaluate the clinical relevance of risk factors. DESIGN: This was a retrospective cohort study. SETTING AND PATIENTS: Polyposis registries in The Netherlands, France, Denmark, Finland, and Italy provided information on familial adenomatous polyposis patients with desmoid tumors. MAIN OUTCOME MEASURES: We used univariate and multivariable analyses of data from registries in The Netherlands, France, Denmark, and Finland to test whether gender, APC mutation site, previous colorectal surgery, colorectal cancer, and family history for desmoid tumors contribute to risk of developing desmoid tumors at any location, or specifically at an intra-abdominal location. The effect of family history was tested with a generalized linear mixed model. RESULTS: Of 2260 patients with familial adenomatous polyposis from 912 families in The Netherlands, France, Denmark, and Finland, 220 patients (10%) had desmoid tumors (101 men). In 387 patients with desmoid tumors (including 167 patients from the Italian registry), the median age at diagnosis of the first desmoid tumor was 31 years (range, 4 months–74 years). Desmoid locations were intra-abdominal (53%), abdominal wall (24%), extremities (9%), and unknown sites or combinations of sites (14%). Multivariable analysis of risk factors for desmoids at any location showed surgery (OR, 2.58; P = .0004), an APC mutation 3′ of codon 1444 (OR, 3.0; P < .0001), and a positive family history (P < .0001) to be independently associated with desmoid development. When only intra-abdominal location was analyzed, APC mutation site was not associated with desmoid development. LIMITATIONS: Selection bias may have occurred. CONCLUSIONS: A positive family history for desmoid tumors, abdominal surgery, and APC mutation site are significant risk factors for development of desmoid tumors. The results may have implications for determining the optimal management of FAP patients and guide future studies.

Surgical resection of retrorectal tumours in adults: long‐term results in 47 patients

Retrorectal tumours (RT) are uncommon, and diagnosis and management remain difficult. The aim of this study was to evaluate the results of the surgical management of RT in our institution.

Practice patterns in complex ventral hernia repair and place of biological grafts: A national survey among French digestive academic surgeons

BACKGROUNDnDespite the prevalence of complex ventral hernias, there is little agreement on the most appropriate technique or prosthetic to repair these defects, especially in contaminated fields. Our objective was to determine French surgical practice patterns among academic surgeons in complex ventral hernia repair (CVHR) with regard to indications, most appropriate techniques, choice of prosthesis, and experience with complications.nnnMETHODSnA survey consisting of 21 questions and 6 case-scenarios was e-mailed to French practicing academic surgeons performing CVHR, representing all French University Hospitals.nnnRESULTSnForty over 54 surgeons (74%) responded to the survey, representing 29 French University Hospitals. Regarding the techniques used for CVHR, primary closure without reinforcement was provided in 31.6% of cases, primary closure using the component separation technique without mesh use in 43.7% of cases, mesh positioned as a bridge in 16.5% of cases, size reduction of the defect by using aponeurotomy incisions without mesh use in 8.2% of cases. Among the 40 respondents, 36 had experience with biologic mesh. There was a strong consensus among surveyed surgeons for not using synthetic mesh in contaminated or dirty fields (100%), but for using it in clean settings (100%). There was also a strong consensus between respondents for using biologic mesh in contaminated (82.5%) or infected (77.5%) fields and for not using it in clean setting (95%). In clean-contaminated surgery, there was no consensus for defining the optimal therapeutic strategy in CVHR. Infection was the most common complication reported after biologic mesh used (58%). The most commonly reported influences for the use of biologic grafts included literature, conferences and discussion with colleagues (85.0%), personal experience (45.0%) and cost (40.0%).nnnCONCLUSIONSnDespite a lack of level I evidence, biologic meshes are being used by 90% of surveyed surgeons for CVHR. Importantly, there was a strong consensus for using them in contaminated or infected fields and for not using them in clean setting. To better guide surgeons, prospective, randomized trials should be undertaken to evaluate the short- and long-term outcomes associated with these materials in various surgical wound classifications.

Antegrade colonic enema for faecal incontinence in adults: long-term results of 75 patients

Aimu2002 Faecal incontinence is a significant source of distress, and a permanent stoma is frequently offered to these patients. The antegrade colonic enema (ACE) procedure is an alternative approach to treat faecal incontinence. The long‐term outcome remains unknown in adults with faecal incontinence. The aim of this study was to evaluate the long‐term results of the ACE procedure for incontinence in adults and its impact upon quality of life.

Radiofrequency ablation for recurrent pelvic cancer

Objectiveu2002 Local recurrence of pelvic cancer is a therapeutic challenge. The purpose of the study was to evaluate radiofrequency ablation (RFA, intra‐operative or CT‐guided) for the treatment of pelvic recurrence in patients not eligible for curative surgical resection.