Beneficial effects of probiotic bifidobacterium and galacto-oligosaccharide in patients with ulcerative colitis: a randomized controlled study.

BACKGROUND/AIM: In previous studies, we described the beneficial effects of bifidobacteria-fermented milk in patients with ulcerative colitis (UC). Here, we examined the effects of a live Bifidobacterium breve strain Yakult, a probiotic contained in bifidobacteria-fermented milk, and galacto-oligosaccharide (GOS) as synbiotics in UC patients. METHODS: Forty-one patients with mild to moderate UC were assigned to two groups; one group was treated with the synbiotics and the other was not (control). The treatment group ingested 1 g of the probiotic powder (10(9) CFU/g) three times a day, and 5.5 g of GOS once a day for one year. At the start and the end of this study, colonoscopic index and the amount of myeloperoxidase in a lavage solution were used as disease activity indices. Bacterial counts in the feces at the start and the end of this study were also examined. RESULTS: After a one-year treatment with the synbiotics, the clinical status of the UC patients as assessed by colonoscopy, significantly improved. Furthermore, the amount of myeloperoxidase in the lavage also decreased in these patients after the synbiotic treatment. The synbiotics significantly reduced the fecal counts of Bacteroidaceae and fecal pH. CONCLUSION: Administration of live B. breve strain Yakult and GOS can improve the clinical condition of patients with UC. These results encouraged us to perform a large-scale randomized, placebo-controlled trial.

Excessive fat restriction might promote the recurrence of colorectal tumors.

The incidence of colorectal cancer is rapidly increasing in Japan. This trend has been suggested to be caused by an increasing fat intake as a result of the Westernized diet among Japanese. We investigated whether dietary instruction optimizing the fat energy ratio suppresses the recurrence of colorectal tumors. The subjects, 373 men and women, were the participants in a randomized clinical trial of colorectal cancer prophylaxis. At entry, each participant completed a 3-consecutive-day food record on which dietary instruction was given to restrict fat energy ratio to 18-22%. Data obtained before and after the intervention were examined by cohort analysis. The primary endpoint was the presence or absence of colorectal tumor(s) at colonoscopy after 4 yr. Unexpectedly, the recurrence of tumor increased as the subjects reduced their fat intake. The lowest tumor recurrence among the men was observed in the group with 23.8-26.4% fat energy ratio after the intervention. Furthermore, in men, the risk of tumors decreased significantly as the intake of linoleic acids per body weight increased. For women, similar trends were observed. These results suggest that extreme fat restriction is highly likely to promote the recurrence of colorectal tumors, which may be partly attributable to linoleic acid deficiency.

Significance of fecal deoxycholic acid concentration for colorectal tumor enlargement.

Deoxycholic acid (DCA) has been shown to promote proliferation of colonic carcinoma cells in many fundamental studies. However, no large-scale prospective clinical study providing direct evidence for an association of DCA with progress of colorectal tumor development in humans has been reported to date. To address this question, we conducted a two-step epidemiological study applying enzyme-linked immunosorbent assays to measure fecal cholic acid (CA) and DCA concentrations. Firstly, we compared bile acid concentrations of fecal samples from 366 patients who had multiple colorectal tumors removed endoscopically (tumor group) with those from 24 controls without abnormality in their large intestine (control group). Secondly, the tumor group was followed-up to evaluate the association between fecal bile acid concentrations and recurrence of colorectal tumors four years later. Fecal DCA level in the tumor group were significantly higher than that in the controls, whereas there was no difference in CA levels between the two groups. In the tumor group, a subgroup with high DCA level had higher recurrence risk of large adenomas (> 3 mm) four years later than the low DCA subgroup (odds ratio:1.85, 95% confidence interval: 1.12-3.05). This trend was observed more strongly in the left side colon. In conclusion, a high fecal DCA concentration may be a promoter of colorectal tumor enlargement.

Effect of Lactobacillus casei on Streptococcus bovis in faecal flora.

Bacteraemia caused by Streptococcus bovis is often associated with colorectal tumours. Also, experimental studies have been proposed that S bovis acts as a promoter of tumours. We report the case of a man with colon adenoma who had a high proportion of S bovis in his faecal flora. He was treated with a Lactobacillus casei preparation (BLP) and the effect on the faecal flora was examined. L casei reduced the proportion of S bovis (from 43% down to 9%), and the effect continued after the administration of BLP was stopped. Our data indicate that BLP can repress the excessive colonisation of S bovis.

[Investigation of the Giardia lamblia infection rate using whole gut lavage fluid].

BACKGROUND: Approximately 100 cases of giardiasis incidence are reported each year in Japan. The actual infection rate, however, is suspected to be higher since giardiasis is often overlooked due to the mildness of its symptoms. We investigated the presence of trophozoites of Giardia lamblia microscopically in sediment of whole gut lavage fluid obtained from patients undergoing colonoscopy. METHODS: Whole gut lavage fluid was collected from all 3035 cases (2355 persons) undergoing colonoscopy at Osaka Medical Center for Cancer and Cardiovascular Diseases from 1993 to 1997. After Papanicolaou staining, sediment specimens of the lavage fluid were microscopically observed. RESULTS: Giardia lamblia were identified in 15 cases (12 persons: 0.51%). Among them, four patients had diarrhea and/or abdominal pain. Subsequently, three of them were treated with metronidazole. CONCLUSION: Giardiasis is not a rare infectious disease among the Japanese; therefore it should be taken into consideration in evaluating enteritis.

Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer.

Aged garlic extract (AGE) has manifold biological activities including immunomodulative and antioxidative effects. It is used as a major component of nonprescription tonics and cold-prevention medicines or dietary supplements. Advanced-cancer patients decline in immune functions and quality of life (QOL). The study's subjects were patients with inoperable colorectal, liver, or pancreatic cancer. In a randomized double-blind trial, AGE was administered to one group and a placebo was administered to another for 6 mo. The primary endpoint was a QOL questionnaire based on the Functional Assessment of Cancer Therapy (FACT). The subendpoints were changes in the natural-killer (NK) cell activity the salivary cortisol level from before and after administering AGE. Out of 55 patients invited to participate in the trial, 50 (91%) consented to enroll. They consisted of 42 patients with liver cancer (84%), 7 patients with pancreatic cancer (14%), and 1 patient with colon cancer (2%). Drug compliance was relatively good in both the AGE and placebo groups. Although no difference was observed in QOL, both the number of NK cells and the NK cell activity increased significantly in the AGE group. No adverse effect was observed in either group. The study showed that administering AGE to patients with advanced cancer of the digestive system improved NK cell activity, but caused no improvement in QOL.

Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of colorectal tumors.

The epidemiologic evidence that dietary fiber protects against colorectal cancer is equivocal. No large-scale clinical study of the administration of Lactobacillus casei has been reported. We examined whether dietary fiber and L. casei prevented the occurrence of colorectal tumors. Subjects were 398 men and women presently free from tumor who had had at least 2 colorectal tumors removed. Subjects were randomly assigned to 4 groups administered wheat bran, L. casei, both or neither. The primary end point was the presence or absence of new colorectal tumor(s) diagnosed by colonoscopy after 2 and 4 years. Among 380 subjects who completed the study, 95, 96, 96 and 93 were assigned to the wheat bran, L. casei, both and no treatment groups, respectively. Multivariate adjusted ORs for occurrence of tumors were 1.31 (95% CI 0.87-1.98) in the wheat bran group and 0.76 (0.50-1.15) in the L. casei group compared to the control group. There was a significantly higher number of large tumors after 4 years in the wheat bran group. The occurrence rate of tumors with a grade of moderate atypia or higher was significantly lower in the group administered L. casei. No significant difference in the development of new colorectal tumors was observed with administration of either wheat bran or L. casei. However, our results suggest that L. casei prevented atypia of colorectal tumors.

Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis.

BACKGROUND: Alterations of intestinal flora, such as reduction in the concentration of bifidobacteria and increase in that of Bacteroides species, are apparently associated with the severity of ulcerative colitis. OBJECTIVE: We conducted a randomised clinical trial of the use of a bifidobacteria-fermented milk (BFM) supplement as a dietary adjunct in the treatment of ulcerative colitis. METHODS: The subjects were randomly divided into two groups: a group with BFM supplementation (BFM group, 11 subjects) and a control group (control group, 10 subjects). The BFM group was given 100 mL/day of BFM for one year. Colonoscopies, general blood markers and examinations of intestinal flora including the analysis of fecal organic acids were performed at the commencement of the study and after one year. RESULTS: Exacerbation of symptoms was seen in 3 out of 11 subjects in the BFM group and in 9 out of 10 in the control group. Log rank statistic analysis of the cumulative exacerbation rates showed a significant reduction in exacerbations for the BFM group (p = 0.0184). The analysis of microflora and the organic acids in the feces showed a significant reduction in the relative proportion of B. vulgatus in Bacteroidaceae and butyrate concentration, respectively, after supplementation with BFM, in comparison with before. CONCLUSION: Supplementation with the BFM product was successful in maintaining remission and had possible preventive effects on the relapse of ulcerative colitis.

Phase II study of paclitaxel with 3-h infusion in patients with advanced gastric cancer.

BACKGROUND: To increase the options for agents for gastric cancer chemotherapy, we performed a phase II clinical trial on the use of a 3-h infusion of paclitaxel to confirm its efficacy and the feasibility of its use in patients with advanced gastric cancer. METHODS: Thirty-two (32) patients with measurable metastatic gastric cancer were enrolled in this study. Seventeen patients (53%) had received prior chemotherapy for metastatic disease, 4 patients (13%) had adjuvant chemotherapy alone, and 11 patients (34%) were chemotherapy-naive. Paclitaxel was intravenously infused for 3 h, at a dose of 210 mg/m(2), once every 3 weeks. To prevent hypersensitivity reactions, standard premedication was administered to all patients. RESULTS: Nine (28%; 9/32 ) objective partial responses (PRs) were observed (95% confidence interval [CI], 14%-47%), and the remaining 23 patients showed stable (12 patients; 37.5%) and progressive disease (11 patients; 34.4%). The median time to response was 20 days (range, 14-38 days). The median response duration was 87 days (range, 50-103 days). The median survival of all patients was 234 days (range, 13-646+ days). The major adverse reactions were myelosuppression (grade 3/4 leukopenia and neutropenia were observed in 59% and 88% of the patients, respectively), alopecia, and peripheral neuropathy. Peripheral neuropathy was observed in 19 patients, however, most of the patients recovered after the completion of treatment. CONCLUSION: A 3-h infusion of paclitaxel is an effective therapy for advanced gastric cancer and is clinically well tolerated by the patients.

Study of Prevention of Colorectal Cancer through Lifestyle Modification: an Introduction to the Protocol.

Previous epidemiological studies have suggested that lack of exercise and a high fat diet increase the risk of colorectal cancer. We planned a clinical trial to test these propositions, using subjects with multiple colorectal adenomas and/or carcinomas. Enrolment in this study was conducted in two stages. First, patients were invited to participate in the dietary modification part of the study. Those agreeing to participate were given dietary advice, and 3 months later all subjects to whom the exercise exclusion criteria do not apply were invited to participate in the exercise part of the study. The subjects were randomized to two groups. A total of two hundred and eleven patients meeting the entry criteria have been invited to join the trial, of whom 165 (78%) consented to participate in the dietary modification part of the study. After excluding those unsuitable according to the exclusion criteria for the exercise regimen, the remaining 124 subjects were further invited to participate in the exercise regimen part of the study. One hundred and three (83%) subjects have given their consent. Obtaining informed consent in two stages and the free provision of lifestyle modification measures were factors that contributed to this favorable participation rate.

Prevention of infectious complications subsequent to endoscopic treatment of the colon and rectum.

We investigated the effect of antibiotics for the prevention of infectious complications subsequent to endscopic treatment of the colon and rectum. Thirty-three patients who underwent endoscopic polypectomies and/or hot-biopsies were divided into two groups: (A, n = 17) with and (B, n = 16) without prophylactic administration of antibiotics. The oral lavage solution method with isotonic magnesium citrate was used for bowel preparation. For group A, 250 mg of kanamycin was administered orally four times, at 30-min intervals, after the oral lavage solution of isotonic magnesium citrate was administered, and 3.2 g of clavulanic acid-ticarcillin was administered by drip infusion after the endoscopic treatment. Latent inflammatory reactions were assessed based on blood cell analysis, erythrocyte sedimentation rate, serum C-reactive protein, and serum phospholipase A2 activity before and the day after the endoscopic treatment. Postoperative platelet, white blood cell, and neutrophil counts were significantly increased in group B, while increases in these parameters were all suppressed in group A. These results suggested that bacterial infections developed subsequent to endoscopic surgery on the colon and rectum. Although we do not need to administer antibiotics to all patients, in patients at high risk of infection, such as those with leukemia or diabetes mellitus, endoscopic polypectomy or hot-biopsy of the colon and rectum should be performed with the administration of antibiotics.