Familial colorectal cancer risk assessment needs improvement for more effective cancer prevention in relatives.

AIM: Twelve to thirty % of colorectal cancer (CRC) patients and relatives with an increased familial risk of CRC are referred for preventive measures. New guidelines recommend genetic counselling for high-risk families and surveillance colonoscopy for moderate-risk families. Assessment of familial risk of CRC and referral rates for these preventive measures were determined 1 year after the introduction of new guidelines. METHOD: Assessment of familial risk of CRC and referral for preventive measures were measured in clinical practice among 358 patients with CRC in 18 hospitals using medical records and questionnaires. Additionally, a knowledge survey was performed among 312 clinicians. RESULTS: Sixty-seven % of patients with an increased familial risk (n = 65/97) were referred for preventive measures, as were 23% (61/261) of low-risk patients. The uptake of genetic counselling in high-risk families was 33% (12/36). The uptake of surveillance colonoscopy in moderate-risk families was 34% (21/61). In the knowledge survey clinicians correctly determined familial risk in 55% and preventive measures in 65% of cases. CONCLUSION: Currently 67% of individuals with an increased familial risk of CRC were referred for preventive measures. Only one-third were referred in accordance with guidelines.

Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist's initiative.

According to the Dutch Guideline on Hereditary Colorectal Cancer published in 2008, patients with recently diagnosed colorectal cancer (CRC) should undergo microsatellite instability (MSI) testing by a pathologist immediately after tumour resection if they are younger than 50 years, or if a second CRC has been diagnosed before the age of 70 years, owing to the high risk of Lynch syndrome (MIPA). The aim of the present MIPAPS study was to investigate general distress and cancer-specific distress following MSI testing. From March 2007 to September 2009, 400 patients who had been tested for MSI after newly diagnosed CRC were recruited from 30 Dutch hospitals. Levels of general distress (SCL-90) and cancer-specific distress (IES) were assessed immediately after MSI result disclosure (T1) and 6 months later (T2). Response rates were 23/77 (30%) in the MSI-positive patients and 58/323 (18%) in the MSI-negative patients. Levels of general distress and cancer-specific distress were moderate. In the MSI-positive group, 27% of the patients had high general distress at T1 versus 18% at T2 (p = 0.5), whereas in the MSI-negative group, these percentage were 14 and 18% (p = 0.6), respectively. At T1 and T2, cancer-specific distress rates in the MSI-positive group and MSI-negative group were 39 versus 27% (p = 0.3) and 38 versus 36% (p = 1.0), respectively. High levels of general distress were correlated with female gender, low social support and high perceived cancer risk. Moderate levels of distress were observed after MSI testing, similar to those found in other patients diagnosed with CRC. Immediately after result disclosure, high cancer-specific distress was observed in 40% of the MSI-positive patients.

High detection rate of adenomas in familial colorectal cancer.

BACKGROUND AND AIMS: Subjects with one first-degree relative (FDR) with colorectal cancer (CRC) <50 years old or two FDRs with CRC have an increased risk for CRC (RR 4-6). Current guidelines recommend colonoscopic surveillance of such families. However, information about the yield of surveillance is limited. The aim of the present study was to evaluate the outcome of surveillance and to identify risk factors for the development of adenomas. PATIENTS AND METHODS: Subjects were included if they fulfilled the following criteria: asymptomatic subjects aged between 45 and 65 years, with one FDR with CRC <50 years old (group A) or two FDRs with CRC diagnosed at any age (group B). Subjects with a personal history of inflammatory bowel disease or colorectal surgery were excluded. RESULTS: A total of 551 subjects (242 male) met the selection criteria. Ninety-five subjects with a previous colonoscopy were excluded. Two of 456 remaining subjects (0.4%) were found to have a colorectal tumour (one CRC and one carcinoid). Adenomas were detected in 85 (18.6%) and adenomas with advanced pathology in 37 subjects (8.1%). 30 subjects (6.6%) had multiple (>1) adenomas. Men were more often found to have an adenoma than women (24% vs 14.3%; p=0.01). Adenomas were more frequent in group B compared with group A (22.0% vs 15.6%; p=0.09). CONCLUSION: The yield of colonoscopic surveillance in familial CRC is substantially higher than the yield of screening reported for the general population.

Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients.

BACKGROUND: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients. METHODS: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids. RESULTS: Median follow-up was 8 years. For intra-abdominal desmoids (n=62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P=0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy. CONCLUSION: For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extra-abdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin.

Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome.

INTRODUCTION: Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable evidence concerning the magnitude of a possible excess risk is necessary to determine whether preventive measures, like screening colonoscopies, in FDRs are justified. AIMS AND METHODS: We analysed the incidence rate of CRC in FDRs and compared this with the general population through person-year analysis after adjustment for demographic characteristics. Population-based incidence data from the Eindhoven Cancer Registry during the period 1970-2006 were used to compare observed numbers of CRC cases in FDRs with expected numbers based on the incidence in the general population. RESULTS: A total of 347 FDRs (41% male) from 57 pedigrees were included, contributing 11 053 person-years of follow-up. During the study period, a total of 27 CRC cases occurred among FDRs compared to five expected CRC cases (p<0.001). The RR of CRC in FDRs compared to the general population was 5.4 (95% CI 3.7 to 7.8). Four FDRs satisfied the criteria for HPS. Based on the estimated HPS prevalence of 1:3000 in the general population the projected RR of HPS in FDRs was 39 (95% CI 13 to 121). CONCLUSIONS: FDRs of HPS patients have an increased risk for both CRC and HPS compared to the general population. Hence, as long as no genetic substrate has been identified, screening colonoscopies for FDRs seem justified but this needs to be prospectively evaluated.

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.

Electronic reminders for pathologists promote recognition of patients at risk for Lynch syndrome: cluster-randomised controlled trial.

We investigated success factors for the introduction of a guideline on recognition of Lynch syndrome in patients recently diagnosed with colorectal cancer (CRC) below age 50 or a second CRC below age 70. Pathologists were asked to start microsatellite instability (MSI) testing and report to surgeons with the advice to consider genetic counselling when MSI test or family history was positive. A multicentre cluster-randomised controlled trial (ClinicalTrials.gov, number NCT00141466) was performed in 12 pathology laboratories (clusters), serving 29 community hospitals. All received an introduction to the new guideline. In the intervention group, surgeons received education and tumour test result reminders; pathologists were provided with inclusion criteria cards, an electronic patient inclusion reminder system and feedback on inclusion. Two hundred sixty-six CRC patients were eligible for recognition as at risk for Lynch syndrome. The actual recognition was 18% more successful in the intervention as compared to the control arm (77% (120 of 156) compared to 59% (65 of 110)), with an adjusted odds ratio (OR) = 2.8 (95% confidence interval (CI) 1.1-7.0). The electronic reminder system for pathologists was most strongly associated with recognition of high-risk patients, OR = 4.2 (95% CI 1.7-10.1). An electronic reminder system for pathologists appeared effective for adherence to a new complex guideline and will enhance the recognition of Lynch syndrome.

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 1 million 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.

Genetic polymorphism in UDP-glucuronosyltransferase 2B7 and colorectal cancer risk.

Colorectal cancer (CRC) is one of the most common malignancies in the Western world. CRC is strongly associated with lifestyle factors. Susceptibility to CRC may be partly due to deficient detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes result in variations in detoxification activities, which might influence the levels of carcinogens in the gastrointestinal tract, influencing the risk for CRC. To determine whether a genetic polymorphism in the detoxification enzyme UDP-glucuronosyltransferase 2B7 (UGT2B7) predisposes to CRC, 411 Caucasian patients with sporadic CRC and 600 Caucasian controls recruited from the same geographic area were genotyped for the functional UGT2B7 H268Y polymorphism. DNA was isolated and tested by a dual-color real-time polymerase chain reaction assay. Overall, no differences in genotype distributions between patients with CRC and controls were observed. When analyzed with respect to tumor location, a shift from the UGT2B7*I *2 into the UGT2B7*2*2 genotype was seen in patients with proximal CRC (OR 1.80, 95% CI 1.11-2.89). In the male patient subpopulation an even stronger association was observed (*1*1 + *1*2 vs. *2*2: OR 2.17, 95% CI 1.11-4.04; *1*2 vs. *2*2: OR 2.19, 95% CI 1.10-4.37). No associations with respect to tumor stage were seen. In conclusion, the frequency of the UGT2B7*2*2 genotype is higher in CRC patients with proximal location of the tumor, especially in males, which suggests that this genotype is associated with an increased risk for proximal CRC.

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.

Detoxification enzyme polymorphisms are not involved in duodenal adenomatosis in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) are at high risk of developing duodenal adenomas and carcinomas. Besides germline mutations in the adenomatous polyposis coli (APC) gene, additional factors may influence the age of onset and number of duodenal adenomas. This study compared the genotype distributions of duodenal detoxification enzyme isoforms in patients with FAP and controls. METHODS: The study included 85 patients with FAP and 218 healthy age- and sex-matched controls. Genotyping of all participants using polymerase chain reaction was performed to detect polymorphisms in isoforms of uridine 5'-diphosphate glucuronosyltransferases (UGTs) and glutathione S-transferases (GSTs): UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A10, UGT2B4, UGT2B7, UGT2B15, GSTA1, GSTP1, GSTM1 and GSTT1. RESULTS: The variant genotypes of UGT1A3 were less common in patients with FAP than in controls (odds ratio 0.39 (95 per cent confidence interval 0.22 to 0.67)). There were no associations between FAP and the other polymorphic genes. The polymorphisms investigated had no predictive value for the severity of duodenal adenomatosis in patients with FAP. CONCLUSION: Although the variant genotypes of UGT1A3 were less common in patients with FAP than in those without, this did not modulate the severity of duodenal adenomatosis.

Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis.

To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices, respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance.

Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis.

A small fraction of families with familial adenomatous polyposis (FAP) display an attenuated form of FAP (AFAP). We aimed to assess the presence of germline mutations in the MUTYH and adenomatous polyposis coli (APC) genes in AFAP families and to compare the clinical features between the two causative genes. Families with clinical AFAP were selected from the Dutch Polyposis Registry according to the following criteria: (a) at least two patients with 10-99 adenomas diagnosed at age >30 years or (b) one patient with 10-99 adenomas at age >30 years and a first-degree relative with colorectal cancer (CRC) with a few adenomas, and, applying for both criteria, no family members with more than 100 polyps before the age of 30 years. All probands were screened for germline mutations in the APC and MUTYH genes. Twenty-five of 315 Dutch families with FAP (8%) met our criteria for AFAP. These families included 146 patients with adenomas and/or CRC. Germline APC mutations were identified in nine families and biallelic MUTYH mutations in another nine families. CRC was identified at a mean age of 54 years (range 24-83 years) in families with APC and at 50 years (range 39-70 years) in families with MUTYH (p = 0.29). APC and biallelic MUTYH mutations are responsible for the majority of AFAP families. Based on our results and those reported in the literature, we recommend colonoscopy once every 2 years in AFAP families, starting surveillance from the late teens in APC mutation carriers and from age 20-25 years in biallelic MUTYH mutation carriers.

Is surveillance of the small bowel indicated for Lynch syndrome families?

BACKGROUND: Small bowel cancer (SBC) is one of the tumours associated with Lynch syndrome (LS). To advise on screening for this tumour it is paramount to be informed about the lifetime risk. The aim of this study was to calculate the lifetime risk of SBC in LS and to identify possible risk factors. METHODS: Clinical and pathological data were collected on 1496 proven or putative carriers of a mismatch repair gene mutation from 189 families. Kaplan-Meier survival analysis was used to calculate the lifetime risk and to assess potential risk factors. RESULTS: 28 (1.9%) of the 1496 (putative) mutation carriers were identified with SBC. The median age at diagnosis was 52 years (range 23-69 years). The lifetime risk of developing SBC was 4.2%. There was no difference in risk between males and females (log rank: p = 0.2470), or between MLH1 and MSH2 mutation carriers (log rank: p = 0.2754). SBC was not observed in MSH6 mutation carriers (n = 203). The previous occurrence of colorectal cancer and a family history of SBC did not increase the risk significantly. CONCLUSIONS: Approximately, one out of 25 mutation carriers will develop SBC during life. No specific risk factors were identified. The risk appeared to be too low to advise screening by means of an invasive burdensome procedure like double balloon enteroscopy. However, screening by a non-invasive procedure (videocapsule endoscopy) might be considered if future studies will show its cost effectiveness. In patients with unexplained abdominal complaints and/or unexplained iron deficiency anaemia SBC should be considered.

[Tracing colorectal carcinoma in patients with inflammatory bowel disease]. / Opsporing van colorectaal carcinoom bij patiënten met inflammatoir darmlijden.

In patients with ulcerative colitis the risk of colorectal cancer is increased. Based on a number of studies, British and American guidelines support endoscopic surveillance in these patients. As the cancer risk in ulcerative colitis increases with disease duration, it is recommended that surveillance is started 8-20 years after diagnosis depending on the extent of disease. Although previous studies have shown that the observed cancer risk in colonic Crohn's disease is unrelated to duration of disease, similar surveillance of these patients is suggested. A substantial number of cases of carcinoma in patients with inflammatory bowel disease present before scheduled onset of surveillance. Therefore, the optimal time of onset of surveillance is disputable. However, taking into account the relatively low risk of colorectal cancer in the early stages of inflammatory bowel disease, it will be hard to achieve an acceptable risk-benefit ratio of extending surveillance by starting surveillance colonoscopies at a younger age.

[Preventive resection of hereditary diffuse gastric cancer]. / Preventieve resectie van erfelijk, diffuus maagcarcinoom.

Hereditary diffuse gastric cancers are rare, accounting for at most 1-3% of gastric cancers. It can be caused by a mutation in the tumour-suppressor gene CDH1. A healthy person carrying a CDH1 mutation has a cumulative risk of developing gastric cancer of 70-80%. In most cases, gastric cancer is detected before the age of 40 years. The effectiveness of screening for hereditary diffuse gastric cancer or early detection with twice-yearly upper GI endoscopy with blind biopsies is highly questionable. Given the poor prognosis of patients with hereditary diffuse gastric cancer, prophylactic gastrectomy can be considered an option for patients with a CDH1 mutation. It is recommended that the supervision, screening and possible preventative gastrectomy for hereditary diffuse gastric cancers are handled by a multidisciplinary team in a specialised centre.

[Thalidomide for the treatment of recurrent gastrointestinal blood loss due to intestinal angiodysplasias]. / Thalidomide als behandeling bij recidiverend gastro-intestinaal bloedverlies op basis van intestinale angiodysplasieën.

Two female patients, 86 and 80 years of age, had been treated with blood transfusions for several years and several months, respectively, due to iron-deficiency anaemia caused by gastrointestinal blood loss. Angiodysplasias were detected and subsequently coagulated in the course of repeated gastroscopies and colonoscopies. Due to the failure of this treatment, treatment with thalidomide was started. Thereafter, the gastrointestinal bleeding stopped and there was no longer any need for blood transfusions. Treatment with thalidomide seems an effective therapy for patients with frequently recurring gastrointestinal blood loss due to angiodysplasias who no longer tolerate conventional and invasive procedures due to their physical condition.

What is the appropriate screening protocol in Lynch syndrome?

INTRODUCTION: Lynch syndrome families have a substantial risk of developing colorectal cancer (CRC). The recommended surveillance protocol includes colonoscopy every 2 years from age 20-25 years. It is yet unknown whether annual screening of patients aged 40-60 years is more effective than bi-annual screening, whether patients who had an adenoma removed should be re-examined after a year and whether surveillance of second-degree relatives is indicated. The aim of this study was to address these issues. METHODS: All carriers of a mismatch repair gene mutation who participated in the surveillance program were selected from the Dutch Lynch syndrome registry. The results of colonoscopy were prospectively collected. RESULTS: A total of 666 mutation carriers were identified in 110 families. Fourty-one CRCs were detected during endoscopic follow-up, of which 34 (83%) were diagnosed between age 40 and 60 years. In five of 34 patients, CRC was diagnosed within 1 year after colonoscopy, eight cancers were diagnosed between 1 and 2 years and the remaining tumors more than 2 years after colonoscopy. All eight CRCs detected between 1 and 2 years were at local stage. At least one adenoma was diagnosed at 141 examinations. The risk of developing CRC during follow-up in carriers with an adenoma was similar as in carriers without an adenoma at the previous colonoscopy. 280 parent-child couples with at least one Lynch syndrome-related carcinoma were identified in 110 families. In only 19 (6.8%) of these couples, CRC developed earlier in the child than an Lynch syndrome-associated cancer in the parent. CONCLUSION: The current surveillance protocol, i.e., bi-annual colonoscopy in first-degree relatives independent of age and endoscopic findings, appears to be appropriate.

Decreased levels of mucosal detoxification enzymes in the pouch of patients with familial adenomatous polyposis.

BACKGROUND: Adenomas can develop in the pouch after colectomy with ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP). Glutathione S-transferases (GSTs) have a protective role in carcinogenesis. GST activity is much higher in the ileum than in the colon. The present study examined the hypothesis that the protective capacity of GSTs may be lowered as a result of colonic metaplasia of the ileal pouch. METHODS: Levels of GSTs, glutathione and cysteine, and the degree of inflammation and colonic metaplasia were quantified in biopsies from the pouch and afferent loop of 26 patients with FAP. RESULTS: GST enzyme activity, and levels of GST alpha, glutathione and cysteine in the pouch were significantly lower than those in the afferent loop (308 versus 398 nmol per min per mg protein (P<0.001), 4604 versus 5286 ng per mg protein (P=0.010), 27.1 versus 34.8 nmol per mg protein (P=0.023) and 0 versus 4.8 nmol per mg protein (P=0.009) respectively). No correlation was found between inflammation or colonic metaplasia of the pouch and GST enzyme activity in the pouch. CONCLUSION: After IPAA, GST detoxification activity in the pouch is significantly lower than that in the afferent ileal loop, which may promote tumorigenesis.