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.

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.

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.

[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.

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.

[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.

[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.

Optimizing the detection of hereditary non-polyposis colorectal cancer: an update.

Hereditary non-polyposis colorectal cancer (HNPCC) is a dominant inherited disease and accounts for up to 5% of all colorectal cancer (CRC) patients. Despite the optimization of selection criteria and enhancements in molecular techniques for identifying more families with HNPCC, most cases are not recognized. Poor patient recollection of family history and inadequate family history-taking are main causative factors. We propose a new strategy for detecting HNPCC, one in which the pathologist selects patients for microsatellite instability (MSI) testing. Criteria for MSI analysis are: (1) CRC before the age of 50 years, (2) second CRC before 70 years, (3) CRC and HNPCC-associated cancer before 70 years, or (4) adenoma before 40 years. Additionally, patients with a positive MSI test and patients with a positive family history are offered referral for genetic counselling. With this strategy, at least twice the number of HNPCC patients will be identified among a population of CRC patients, and in a cost-effective, efficient and feasible way. The identification of patients with HNPCC is important because intensive surveillance can prevent death from CRC.

MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families.

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and MSH6. The aims of the present study were to compare the risk of developing colorectal, endometrial, and other cancers between families with the various MMR-gene mutations. PATIENTS AND METHODS: Clinical and pathologic data were collected from 138 families with HNPCC. Mutation analyses were performed for all families. Survival analysis was used to calculate the cumulative risk of developing cancer in the various subsets of relatives. RESULTS: Mutations were identified in 79 families: 34 in MLH1, 40 in MSH2, and five in MSH6. The lifetime risk of developing cancer at any site was significantly higher for MSH2 mutation carriers than for MLH1 mutation carriers (P < .01). The risk of developing colorectal or endometrial cancer was higher in MSH2 mutation carriers than in MLH1 mutation carriers, but the difference was not significant (P = .13 and P = .057, respectively). MSH2 mutation carriers were found to have a significantly higher risk of developing cancer of the urinary tract (P < .05). The risk of developing cancer of the ovaries, stomach, and brain was also higher in the MSH2 mutation carriers than in the MLH1 mutation carriers, but the difference was not statistically significant. CONCLUSION: Pending large prospective studies, the extension of the current surveillance program in MSH2 mutation carriers with the inclusion of the urinary tract should be considered.

[Liver abscesses as a complication of Crohn's disease]. / Leverabcessen als complicatie bij de ziekte van Crohn.

Liver abscesses were found in two women aged 23 and 34 years who suffered from Crohn's disease. The first patient was seen because of fever and thoracic pain and had been treated with infliximab. The second patient, who was pregnant, presented with abdominal pain that was thought to be due to an exacerbation of her inflammatory bowel disease. Ultrasonography and CT revealed that both patients had large liver abscesses. Both received antibiotic treatment, the first patient underwent drainage of the abscess, and the second underwent puncture twice, resulting in clinical improvements in both patients. In contrast to intra-abdominal abscesses, liver abscesses are rarely seen in patients with Crohn's disease. The clinical presentation can be mistaken for an exacerbation of Crohn's disease, but the diagnosis can be made easily using ultrasonography or CT. Treatment consists of (ultrasound-guided) percutaneous drainage and administration of antibiotics.

[More hereditary intestinal cancer can be detected if patients with colorectal carcinoma that are selected by the pathologist are examined for microsatellite instability]. / Meer opsporing van erfelijke darmkanker met onderzoek op microsatellietinstabiliteit bij door de patholoog geselecteerde patiënten met een colon-rectumcarcinoom.

OBJECTIVE: To determine whether an investigation of microsatellite instability (MSI) in patients with colorectal carcinoma that have been selected by the pathologist could increase the number of detected families with hereditary non-polyposis colorectal carcinoma (HNPCC). DESIGN: Prospective inventory. METHOD: Pathologists selected patients with a newly diagnosed colorectal carcinoma for MSI analysis of their tumour tissue if they met one of the following four criteria: (a) colorectal carcinoma diagnosed below 50 years of age; (b) a second colorectal carcinoma; (c) a combination of colorectal carcinoma and another HNPCC-related cancer; (d) colorectal adenoma with high-grade dysplasia diagnosed below 40 years of age. Patients with a positive MSI-test were referred to a clinical geneticist. The new strategy was introduced and explored in 5 hospitals for a period of to months. RESULTS: The new strategy was adopted and implemented successfully by pathologists and surgeons and accepted with satisfaction by the patients. Of the 55 patients included, 10 had a positive MSI-test. In 8/10 patients, DNA-mutation analysis was started by the clinical geneticist and 3 germline mutations in the MSH2-gene were detected. In 2 of 3 families with a pathogenic mutation, the family history alone did not fulfil the clinical criteria for HNPCC. CONCLUSION: Selection by the pathologist for MSI investigation was feasible in daily practice and identified more HNPCC patients than selection based on family history alone.

Effect of resistant starch on breath-hydrogen and methane excretion in healthy volunteers.

Colonic fermentation of dietary carbohydrates and fiber might produce a protective effect against the development of large bowel cancer. Resistant starch, ie, starch that escapes small bowel digestion, is a candidate fermentable substrate that has been hitherto little studied. We supplemented 19 healthy volunteers with 15 g native amylomaize (Hylon-VII) three times a day, containing 28 g type II resistant starch, or with dextrins as a placebo for 7 d in a crossover design. Pre-experimentally, 11 subjects regularly produced breath methane and 8 did not. Resistant starch increased 24-h integrated excretion of breath hydrogen. The mean rise relative to placebo was 35% (P = 0.03) for all subjects and 60% for eight subjects not producing methane (P = 0.02). The 11 methane producers showed a 93% increase in breath-methane excretion on resistant starch (P = 0.03). Continued consumption of 28 g type II resistant starch/d is well tolerated and increases colonic fermentation in healthy volunteers.

Bacterial fermentation of fructooligosaccharides and resistant starch in patients with an ileal pouch-anal anastomosis.

Patients with large bowel disease may undergo ileal pouch-anal anastomosis, in which the colon is removed and part of the distal ileum is used to construct a pelvic reservoir. Competence of the ileal pouch to ferment carbohydrates is associated with the absence of pouchitis. However, the extent to which bacterial fermentation takes place and whether it is affected by diet are unclear. We investigated fermentation of two nondigestible carbohydrates, fructooligosaccharides and resistant starch, in 15 healthy patients with an ileal pouch by using a placebo-controlled crossover design (with glucose as the placebo). Apparent fermentability of fructooligosaccharides was 83%; that of resistant starch was 46%. Resistant starch increased fecal excretion of butyrate by 69% whereas fructooligosaccharides reduced excretion of amino acid-derived isobutyrate by 94% and of isovalerate by 77%. Fructooligosaccharides also significantly increased fecal weight (651 compared with 541 g/d) and breath-hydrogen excretion (286 compared with 85 ppm x h). Bacterial fermentation of nondigestible carbohydrates in pouches takes place to an appreciable extent and in a substrate-specific manner. The relation between such fermentation and inflammation of the pouch (pouchitis) deserves study.

Effect of transgalactooligosaccharides on the composition of the human intestinal microflora and on putative risk markers for colon cancer.

BACKGROUND: Nondigestible oligosaccharides have been claimed to benefit the health of the colon by selectively stimulating the growth of bifidobacteria and by decreasing the toxicity of the colon contents. OBJECTIVE: We compared the effect of 2 doses of transgalactooligosaccharides and a placebo on the composition and activity of the intestinal microflora in 18 women and 22 men. DESIGN: Strictly controlled experimental diets were supplied to 3 intervention groups in a parallel design. The study was divided into 2 consecutive 3-wk periods during which each participant consumed a run-in diet followed by an intervention diet that differed only in the amount of transgalactooligosaccharides: 0 (placebo), 7.5, and 15 g/d. Breath samples and fecal samples were collected at the end of both the run-in and intervention periods. RESULTS: Apparent fermentability of transgalactooligosaccharides was 100%. The highest dose of transgalactooligosaccharides significantly increased the concentration of breath hydrogen by 130% (P < 0.01) and the nitrogen density of the feces by 8.5% (P < 0.05). The number of bifidobacteria increased after both placebo and transgalactooligosaccharides ingestion, but the differences between these increases were not significantly different. Transgalactooligosaccharides did not significantly affect bowel habits; stool composition; the concentration of short-chain fatty acids or bile acids in fecal water; the concentration of ammonia, indoles, or skatoles in feces; fecal pH; or the composition of the intestinal microflora. CONCLUSION: We conclude that transgalactooligosaccharides are completely fermented in the human colon, but do not beneficially change the composition of the intestinal microflora, the amount of protein fermentation products in feces, or the profile of bile acids in fecal water.