Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis

AIM: To evaluate the effect of pyrrolidine dithio- carbamate (PDTC; an NF-κB inhibitor) administered at low (50 mg/kg) and high (100 mg/kg) doses in suppressing colitis in mice with dextran sodium sulfate (DSS)-induced colitis. METHODS: Mice were divided into a DSS-untreated group (normal group), DSS-treated control group, DSS+PDTC-treated groupⅠ(low-dose group), and DSS+PDTC-treated groupⅡ (high-dose group). In each group, the disease activity index score (DAI score), intestinal length, histological score, and the levels of activated NF-κB and inflammatory cytokines (IL-1β and TNF-α) in tissue were measured. RESULTS: The DSS+PDTC-treated groupⅡ exhibited suppression of shortening of intestinal length and reduction of DAI score. Activated NF-κB level and IL-1β and TNF-α levels were significantly lower in DSS+PDTC- treated groupⅡ. CONCLUSION: These findings suggest that PDTC is useful for the treatment of ulcerative colitis.

Effects of oral tacrolimus as a rapid induction therapy in ulcerative colitis

AIM:To determine the efficacy and safety of rapid induction therapy with oral tacrolimus without a meal in steroid-refractory ulcerative colitis(UC)patients.METHODS:This was a prospective,multicenter,observational study.Between May 2010 and August 2012,49 steroid-refractory UC patients(55 flare-ups)were consecutively enrolled.All patients were treated with oral tacrolimus without a meal at an initial dose of 0.1mg/kg per day.The dose was adjusted to maintain trough whole-blood levels of 10-15 ng/m L for the first 2 wk.Induction of remission at 2 and 4 wk after tacrolimus treatment initiation was evaluated using Lichtiger’s clinical activity index(CAI).RESULTS:The mean CAI was 12.6±3.6 at onset.Within the first 7 d,93.5%of patients maintained high trough levels(10-15 ng/m L).The CAI significantly decreased beginning 2 d after treatment initiation.At 2wk,73.1%of patients experienced clinical responses.After tacrolimus initiation,31.4%and 75.6%of patients achieved clinical remission at 2 and 4 wk,respectively.Treatment was well tolerated.CONCLUSION:Rapid induction therapy with oral tacrolimus shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation.Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC.

Usefulness of fecal lactoferrin and hemoglobin in diagnosis of colorectal diseases

AIM:To evaluate prospectively usefulness of fecal lactoferrin(Lf)and fecal hemoglobin(Hb)in the diagnosis of colorectal diseases.METHODS:Fecal Lf and Hb were measured using ELISA in 872 patients before they underwent colorectal endoscopy.RESULTS:Lf was positive in 18(50%)of 36 patients with colorectal cancer,25(15.9%)of 157 with colorectal polyps,29(46.8%)of 62 with ulcerative colitis,and 25(62.5%)of 40(62.5%)with Crohn's disease.The Hb-positive rates were 50%,12.1%,41.9% and 32.5%,respectively.Of the 318 patients free of abnormalities by colorectal endoscopy,Lf was positive in 29(9.1%)and Hb was positive in 15(4.7%).Among patients with Crohn's disease,the Lf-positive rate was significantly higher than the Hb-positive rate.If either high Lf or Hb levels were considered positive,the positive rates rose to 61.1%,51.6%,and 67.5% in the colorectal cancer group,ulcerative colitis group,and Crohn's disease group,respectively.If both high Lf and Hb levels were rated positive,the positive predictive values(PPV)were 21% for colorectal cancer,33% for ulcerative colitis,and 17% for Crohn's disease,and PPV of high Hb level alone was 18%,25% and 13%,respectively.CONCLUSION:Fecal Lf and Hb were found useful in the detection of colorectal diseases,and the combination of the two measurements appears to increase the sensitivity and efficacy of diagnosis.

BRIEF ARTICLE New reduced volume preparation regimen in colon capsule endoscopy

AIM:To evaluate the effectiveness of our proposed bowel preparation method for colon capsule endoscopy.METHODS:A pilot,multicenter,randomized controlled trial compared our proposed "reduced volume method"(group A) with the "conventional volume method"(group B) preparation regimens.Group A did not drink polyethylene glycol electrolyte lavage solution(PEGELS) the day before the capsule procedure,while group B drank 2 L.During the procedure day,groups A and B drank 2 L and 1 L of PEG-ELS,respectively,and swallowed the colon capsule(PillCam COLON capsule).Two hours later the first booster of 100 g magnesium citrate mixed with 900 mL water was administered to both groups,and the second booster was administered six hours post capsule ingestion as long as the capsule had not been excreted by that time.Capsule videos were reviewed for grading of cleansing level,RESULTS:Sixty-four subjects were enrolled,with results from 60 analyzed.Groups A and B included 31 and 29 subjects,respectively.Twenty-nine(94%) subjects in group A and 25(86%) subjects in group B had adequate bowel preparation(ns).Twenty-two(71%) of the 31 subjects in group A excreted the capsule within its battery life compared to 16(55%) of the 29 subjects in group B(ns).Of the remaining 22 subjects whose capsules were not excreted within the battery life,all of the capsules reached the left side colon before they stopped functioning.A single adverse event was reported in one subject who had mild symptoms of nausea and vomiting one hour after starting to drink PEG-ELS,due to ingesting the PEG-ELS faster than recommended.CONCLUSION:Our proposed reduced volume bowel preparation method for colon capsule without PEG-ELS during the days before the procedure was as effective as the conventional volume method.

Refractory ulcerative colitis accompanied with cytomegalovirus colitis and multiple liver abscesses: A case report

Various hepato-biliary complications are an increased incidence in patients with inflammatory bowel disease,and portal bacteremia is well documented in patients with ulcerative colitis (UC). However, few reports mention UC in association with liver abscesses. Recently, there are several reports describing cytomegalovirus (CMV) infection in association with disease exacerbation and steroid refractoriness in patients with UC. Here we present a case of refractory UC accompanied with multiple liver abscesses and CMV colitis. The patient, a 72-year-old male, with a five-year history of repeated admissions to our hospital for UC, presented with an exacerbation of his UC.Sigmoidoscopy performed on admission suggested that his UC was exacerbated, then he was given prednisolone and mesalazine orally, and betamethasone enemas.However, he had exacerbated symptoms. Repeat sigmoidoscopy revealed multiple longitudinal ulcers and pseudopolyps in the rectosigmoid colon. Although immunohistochemical staining of biopsy specimens and the serum testing for antigenemia were negative on admission and after the repeat sigmoidoscopy, they became histologically positive for CMV. Nonetheless, the patient developed spiking fevers, soon after ganciclovir was administered. Laboratory studies revealed an increased white cell count with left shift, and Enterococcus fecalis grew in blood cultures. An abdominal computed tomography (CT) scan was obtained and the diagnosis of liver abscesses associated with UC was made, based on CT results. The hepatic abscesses were successfully treated with intravenous meropenem for 6 wk, without further percutaneous drainage. To our knowledge, this is the first reported case of multiple liver abscesses that develop during UC exacerbation complicated by CMV colitis.

Histopathological and genetic differences between polypoid and non-polypoid submucosal colorectal carcinoma

AIM： To investigate the histopathological and geneticdifferences between polypoid growth （PG） and nonpolypoid growth （NPG） submucosal invasive colorectal carcinoma （CRC）.METHODS： A total of 96 cases of submucosal CRC were divided into two groups according to their growth type;60 cases of PG and 36 cases of NPG. The size, histological degree of dysplasia, depth of submucosal invasion and lymph node metastasis were compared between the two groups. Furthermore, expression of p53 was detected by immunohistochemical staining, and K-ras gene mutation was examined by polymerase chain reaction based single-strand conformation polymorphism （SSCP）.RESULTS： The average size of the lesions in the NPG group was significantly smaller than those in the PG group （7.5 mm vs 13.8 mm, P 〈 0.001）. The histological degree of dysplasia tended to be more severe in NPG group, while the incidence of submucosal massive invasion and the lymph node metastasis were both significantly higher in the NPG type than in the PG group （64.3% vs 43.3%, P = 0.004; 43% vs 7%, P =0.008, respectively）. In addition, K-ras gene mutations were detected in 67% of lesions in the PG group, but none in the NPG group, while no difference in p53immunohistochemical expression was found between the two groups.CONCLUSION： Compared with PG submucosal CRC,NPG type demonstrates more frequent submucosal massive invasion, more lymph node metastasis and a higher degree dysplasia. Genetically, NPG type shows much less frequent K-ras mutation.

Clinical effects of adalimumab treatment with concomitant azathioprine in Japanese Crohn's disease patients

AIM:To assess adalimumab's efficacy with concomitant azathioprine (AZA) for induction and maintenance of clinical remission in Japanese Crohn's disease (CD) patients. METHODS:This retrospective, observational, singlecenter study enrolled 28 consecutive CD patients treated with adalimumab (ADA). Mean age and mean disease duration were 38.1 ± 11.8 years and 11.8 ± 10.1 years, respectively. The baseline mean Crohn's disease activity index (CDAI) and C-reactive protein were 177.8 ± 82.0 and 0.70 ± 0.83 mg/dL, respectively. Twelve of these patients also received a concomitant stable dose of AZA. ADA was subcutaneously administered:160 mg at week 0, 80 mg at week 2, followed by 40 mg every other week. Clinical response and remission rates were assessed via CDAI and C-reactive protein for 24 wk. RESULTS:The mean CDAI at weeks 2, 4, 8, and 24 was 124.4, 120.2, 123.6, and 135.1, respectively. The CDAI was significantly decreased at weeks 2 and 4 with ADA and was significantly suppressed at 24 wk with ADA/AZA. Overall clinical remission rates at weeks 4 and 24 were 66.7% and 63.2%, respectively. Although no statistically significant difference in C-reactive protein was demonstrated, ADA with AZA resulted in a greater statistically significant improvement in CDAI at 24 wk, compared to ADA alone. CONCLUSION:Scheduled ADA with concomitant AZA may be more effective for clinical remission achievement at 24 wk in Japanese Crohn's disease patients.