Considerable Risk of Restenosis After Endoscopic Treatment for Hepaticojejunostomy Stricture After Living-Donor Liver Transplantation.

BACKGROUND: There are few reports on the short- and long-term follow-up of endoscopic retrograde cholangiography (ERC) in adult patients with hepaticojejunostomy (HJS) stricture after living-donor liver transplantation (LDLT). METHODS: Nine LDLT recipients underwent ERC with the use of double-balloon endoscopy (DBE) for HJS stricture at Nagoya University Hospital. We assessed the rate of reaching biliary anastomosis, procedure success rate, procedure duration, complications, improvement in liver function test results, and biliary anastomosis patency. RESULTS: In total, 19 ERC procedures with the use of DBE were performed for 9 adult LDLT recipients with HJS stricture from June 2006 to September 2014. Balloon dilation with the use of DBE was successfully performed in 5 of the 9 patients during the 1st procedure. Of the 4 patients in whom DBE-ERC failed to be completed, 3 patients underwent 2nd procedures successfully. Liver function test results were significantly improved in the successful cases. Four patients underwent 2nd DBE-ERC for stricture recurrence at a mean time of 2.3 years after the 1st successful procedure. Of those, 2 patients required 3rd procedures for stricture recurrence after the 2nd procedure. CONCLUSIONS: DBE-ERC is promising as a treatment for HJS stricture in adult LDLT recipients in the short term. However, the DBE-ERC procedure may have a considerable risk of restenosis.

Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease.

BACKGROUND: The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised. AIM: To determine the risk factors of symptomatic NSAID-induced small intestinal injuries, including diaphragm disease. METHODS: Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double-balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5'-nuclease assays. RESULTS: Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID-induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID-induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05-8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04-24.40, P = 0.002, respectively). The combination of aspirin and non-aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34-1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55-108.36, P = 0.018, respectively). CONCLUSION: The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.

Endoscopic diagnosis of follicular lymphoma with small-bowel involvement using video capsule endoscopy and double-balloon endoscopy: a case series.

The aims of this study were to compare the detection rates of gastrointestinal follicular lymphoma lesions by video capsule endoscopy (VCE) and double-balloon endoscopy (DBE), and to determine the pathologic diagnostic yields of DBE-directed biopsies. A total of 27 consecutive patients were enrolled. No significant difference in detection rates was observed in 12 patients who underwent total enteroscopy at both VCE and DBE. Pathologic diagnostic yields stratified by location were 91 % in the proximal duodenum at esophagogastroduodenoscopy, 88 % in the jejunum at antegrade DBE, 52 % in the ileum at retrograde DBE, and 57 % in the terminal ileum at colonoscopy. VCE and DBE were helpful in determining treatment in 44 % of patients.

Role of endoscopic ultrasonography in predicting the response to cyclosporin A in ulcerative colitis refractory to steroids.

BACKGROUND AND AIMS: Although cyclosporin A has been reported to be effective in the treatment of severe ulcerative colitis, factors predicting its therapeutic efficacy remain unclear. Technical progress in endoscopic ultrasonography has improved visualisation of the structure of the colon wall. Here, to assess the value of endoscopic ultrasonography in predicting the response to cyclosporin A treatment, we evaluated the therapeutic effect of cyclosporin A by determining the pre- and post-cyclosporin A thickness of the mucosal layer in the rectum using endoscopic ultrasonography with an ultrasonic catheter probe. PATIENTS AND METHODS: Fifteen ulcerative colitis patients who did not respond to high-doses of corticosteroids were treated with cyclosporin A by continuous intravenous infusion at 4mg/kg/day for 20 days. Before and 20 days after cyclosporin A therapy, clinical disease activity was assessed using clinical activity index scores. Colonoscopy and endoscopic ultrasonography were undertaken before and 20 days after cyclosporin A therapy. RESULTS: Following treatment with cyclosporin A, nine patients showed a decrease in clinical activity index score by six points or more and were defined as responders, while the other six were defined as non-responders. Endoscopic ultrasonography measurement using an ultrasonic catheter probe showed that thickness of the rectal mucosal layer before cyclosporin A was significantly greater in responders than in non-responders (p<0.05). Further, thickness after cyclosporin A was statistically decreased (p<0.01) in the responders but not in the non-responders. CONCLUSIONS: The ultrasonic catheter probe may represent a useful means of predicting and evaluating the efficacy of cyclosporin A treatment in severely ill ulcerative colitis patients.

Abnormalities in the upper gastrointestinal tract in inflammatory bowel disease.

The predominant histopathologic feature of inflammatory bowel disease is the infiltration of acute and chronic inflammatory cells, including polymorphonuclear neutrophils, macrophages and lymphocytes, in the affected intestine. Helicobacter pylori is recognized as the most common cause of upper gastrointestinal lesions, and Helicobacter pylori-associated gastritis is characterized by increased numbers of acute and chronic inflammatory cells. The pathogenesis of inflammatory bowel disease or Helicobacter pylori-associated gastritis involves immunological abnormalities, including the deficient or excessive expression of cytokines. The chronic inflammatory process in patients with Crohn's disease may affect any part of the gastrointestinal tract, whereas ulcerative colitis affects mainly the colon and rectum. Here, we discuss abnormalities in the upper gastrointestinal tract in inflammatory bowel disease. Although the prevalence rate of Helicobacter pylori infection is low in Crohn's disease, these patients often have abnormalities in the upper gastrointestinal tract.

The interaction of host genetic factors and Helicobacter pylori infection.

Helicobacter pylori plays an important role in the development of atrophic gastritis that represents the most recognized pathway in multistep gastric carcinogenesis. Recent studies suggest that a combination of host genetic factors, bacterial virulence factors, and environmental and lifestyle factors determine the severity of gastric damage and the eventual clinical outcome of Helicobacter pylori infection. As to bacterial virulence factors, a high proportion of Japanese strains are cagA(+)vacAs1. The CagA protein is injected from attached Helicobacter pylori into gastric epithelial cells and the CagA-SHP-2 interactions elicit cellular changes that increase the risk of carcinogenesis. Host cytokine gene polymorphisms and a frequent single nucleotide polymorphism in the PTPN11 gene that encodes SHP-2 may associate with gastric atrophy among Helicobacter pylori-infected subjects. Prevention of gastric cancer requires the development of better screening strategies for determining eradication candidates and further improvement of treatments of Helicobacter pylori infection.

Usefulness of an elemental diet in Crohn's disease.

Crohn's disease is a chronic relapsing disease for which no complete cure is available. Although drug therapy with agents such as corticosteroids and azathiopurine is useful, the long-term side effects of these drugs are problematic. The advent of infliximab has recently brought a change in treatment, but the long-term side effects of this agent remain uncertain. In contrast, nutritional therapy produces no drug-induced side effects and is effective in inducing and maintaining remission. However, sufficient efficacy cannot be expected in patients in whom compliance with nutritional regimens gradually decreases owing to unpalatability. In these cases, combination therapy with agents such as immunosuppressors and infliximab may be useful.

DNA hypermethylation in colorectal neoplasms and inflammatory bowel disease: a mini review.

DNA hypermethylation is one of major epigenetic changes. Hypermethylation of many genes has been reported to be related with carcinogenesis and tumor progression of colorectal cancer. Some genes including estrogen receptor is associated with ageing, and changes related with ageing may be accelerated in inflammatory bowel disease. Furthermore, fecal DNA methylation will be able to be used as a marker of colorectal cancer and inflammatory bowel disease. Evaluation of hypermethylation potentially contributes diagnosis of colorectal diseases.

Confocal endomicroscopy for the diagnosis of gastric cancer in vivo.

BACKGROUND AND STUDY AIMS: Advances in endoscopy have led to imaging of the details of the gastric mucosa, but the histological diagnosis usually has to be confirmed by endoscopic biopsy. A method of confocal endomicroscopy that has recently been developed allows the observation of living cells in vivo. Several investigators have reported that the technique is of value, but there have as yet been no studies describing its application in gastric cancer. PATIENTS AND METHODS: Twenty-seven patients with early gastric cancer underwent confocal endomicroscopy (Pentax EG-3870CIK; Pentax, Tokyo, Japan). After intravenous administration of fluorescein sodium, confocal images obtained from the normal mucosa and from cancerous lesions were interpreted by two pathologists independently and compared with the histological findings, including CD34 immunostaining of biopsy specimens or resected specimens from the same sites. RESULTS: Fluorescein yielded high-quality confocal images of the gastric mucosa; if cancer could be targeted (59%) images were mostly graded good. The images corresponded to the hematoxylin-eosin staining of transverse sections of specimens from the same sites. In the results for the interpretation by the two pathologists, the accuracy for the diagnosis of gastric cancer was 94.2% (pathologist A), and 96.2% (pathologist B), respectively. The accuracy decreased substantially when poor images and inaccessible lesions were included. CONCLUSIONS: Confocal endomicroscopy is useful in the diagnosis of gastric cancer but good quality images cannot always be obtained. In the future, it may allow virtual biopsy and help reduce unnecessary biopsies.

Pit patterns in rectal mucosa assessed by magnifying colonoscope are predictive of relapse in patients with quiescent ulcerative colitis.

BACKGROUND: Relapse of ulcerative colitis is difficult to predict by routine colonoscopy. A high-resolution video-magnifying colonoscope with chromoscopy enables the observation of colorectal mucosal pit patterns. AIMS: To investigate the association of pit patterns as assessed by magnifying colonoscopy (MCS) with histological inflammation and mucosal chemokine activity in patients with quiescent ulcerative colitis, and to prospectively analyse the prognostic factors that may predict exacerbations. METHODS: MCS was performed in 113 patients with ulcerative colitis in remission. Pit patterns in the rectal mucosa were classified into four MCS grades on the basis of size, shape and arrangement. Mucosal interleukin (IL) 8 activity was measured in biopsy specimens of rectal mucosa and the specimens were assessed for histological disease activity. The patients were then followed until relapse or for a maximum of 12 months. Multivariate survival analysis was carried out to determine the independent predictors of clinical relapse. RESULTS: A positive correlation was identified between MCS grade, histological grade (p = 0.001) and mucosal IL8 activity (p<0.001). Multivariate proportional hazard model analysis showed that MCS grade was a significant predictor of relapse (relative risk 2.06, p = 0.001). Kaplan-Meier estimate of relapse during 12 months of follow-up was found to increase with increasing MCS grade, with values of 0% for grade 1, 21% for grade 2, 43% for grade 3 and 60% for grade 4. CONCLUSION: MCS grading is associated with the degree of histological inflammation and mucosal IL8 activity in patients with quiescent ulcerative colitis, and may predict the probability of subsequent disease relapse in patients with ulcerative colitis in remission.

Preliminary comparison of capsule endoscopy and double-balloon enteroscopy in patients with suspected small-bowel bleeding.

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) have been introduced as modalities for examining the entire small bowel. The aim of the present study was to assess the clinical effects of CE and DBE to consider the roles of CE and DBE and the indications for the procedures in patients with suspected small-bowel bleeding. PATIENTS AND METHODS: Between June 2004 and January 2005, 32 patients in whom a site of bleeding in the gastrointestinal tract had not been identified were enrolled in the study. Twenty-eight patients were examined with both methods. Bleeding sources were categorized as either A1 lesions (immediate hemostatic procedures required) or A2 lesions (close observation required). CE and DBE were evaluated with regard to whether or not they were capable of accessing the entire small bowel and provided a diagnosis, and the access and diagnostic rates were calculated. RESULTS: On CE, 13 patients were diagnosed with A1 lesions and six with A2 lesions; on DBE, 11 had A1 lesions and one had an A2 lesion. The access rate for the entire small intestine on CE was 90.6 % (29 of 32), significantly higher than with DBE at 62.5 % (10 of 16; P < 0.05). The diagnostic rate on CE was 59.4 % (19 of 32), higher than with DBE at 42.9 % (12 of 28; P = 0.30), but not significantly different. Among patients with A1 lesions who were diagnosed with DBE, histological diagnoses were obtained in six of the 11, and three patients were treated. CONCLUSIONS: In many suspected small-bowel bleeding cases, CE should be selected for the initial diagnosis and DBE for treatment or histopathological diagnosis after detection of the bleeding site on CE.

Quantitative analysis of the microvascular architecture observed on magnification endoscopy in cancerous and benign gastric lesions.

BACKGROUND AND STUDY AIMS: Gastric cancer remains a common malignant tumor in Japan. The aim of this study was to attempt a quantitative evaluation of the microvascular architecture observed by magnification endoscopy using image analysis, and to investigate whether this method is able to distinguish between gastric cancers and benign lesions. PATIENTS AND METHODS: A total of 132 patients were studied using magnification endoscopy, and image analysis was performed in 71 patients (32 patients with early gastric cancer, 39 patients with benign lesions). Analysis was not possible in the other 61 patients because the quality of the image was not good enough. A square region of interest was selected from the magnified images of the gastric mucosa. From this we extracted the vascular images corresponding to microvessels and calculated the mean caliber of vessels in the region of interest. RESULTS: Image analysis provided good-quality images of microvessels and enabled evaluation of the microvascular architecture. The mean caliber of vessels was 4.454 pixels in 17 differentiated adenocarcinomas, 4.319 pixels in 15 undifferentiated adenocarcinomas, and 4.034 pixels in the 39 benign lesions. This represented a significant difference between gastric cancers and benign lesions (P<0.0001). Histopathological investigation of surgically resected tumors demonstrated the mean caliber of microvessels in cancerous lesions to be greater than that of microvessels in the surrounding mucosa. CONCLUSIONS: Image analysis was useful for evaluating the microvascular architecture of the gastric mucosa, and calculation of the mean caliber of the vessels may prove helpful in the differential diagnosis of gastric cancers. However, analysis was not possible in 61 of the 132 patients studied because of inadequate image quality, and this represents a significant limitation of this diagnostic method.

The use of endoscopic ultrasound-guided fine-needle aspiration for investigation of submucosal and extrinsic masses of the colon and rectum.

BACKGROUND AND STUDY AIM: Ensdoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been reported as a useful technique for histological diagnosis of submucosal or extrinsic gastrointestinal and pancreatic lesions. The aim of this study was to evaluate the use of EUS-FNA for the diagnosis of lesions either within or adjacent to the wall of the colon and rectum. PATIENTS AND METHODS: A total of 22 patients with a lesion within the wall of, or adjacent to, the colon or rectum underwent EUS-FNA. They were divided into two groups: patients who had previously had a malignancy (the "previous +ve" group, n = 11), and patients who had not previously had a malignancy (the "previous -ve" group, n = 11). In the four patients who had lesions located proximal to the sigmoid colon, EUS-FNA was performed using a guide wire and overtube. The success rates for adequate tissue sampling and for detecting malignant and benign masses by EUS-FNA were evaluated and the success rate for detection was compared with the success rate of EUS and computed tomography. RESULTS: Sufficient tissue for evaluation was obtained from 21 of the 22 patients (95.5 %). The overall rate of detection of malignant and benign masses was 95.5 % (21/22) for EUS-FNA and 81.8 % (18/22) for pre-EUS-FNA imaging investigations. Of the 11 patients in the previous +ve group, ten were diagnosed with recurrences of primary malignancies; of the 11 patients in the previous -ve group, four were diagnosed with primary malignancies and seven were diagnosed with benign lesions. There were no complications related to the EUS-FNA procedure. CONCLUSIONS: EUS-FNA is a safe technique which is useful in the planning of treatment for patients who have a mass within the wall or adjacent to the wall of the entire length of the colon or rectum.

Usefulness of magnifying endoscopy in the diagnosis of early gastric cancer.

BACKGROUND AND STUDY AIMS: We investigated the characteristic findings of early gastric cancer revealed by magnifying endoscopy, and clarified their relationship with histopathological features. PATIENTS AND METHODS: A total of 74 patients with early gastric cancer underwent magnifying endoscopy ( x 80) between March 2000 and December 2001. The endoscopic findings demonstrated 11 elevated-type carcinomas and 63 depressed-type, and histological examination showed 56 differentiated carcinomas and 18 undifferentiated carcinomas. The histopathological results were compared with findings from magnifying endoscopy regarding minute surface structure and microvessels. RESULTS: We were able to roughly classify the minute surface structure of early gastric cancer as shown by magnifying endoscopy into three patterns, as follows: (i). a small regular pattern of sulci and ridges; (ii). an irregular pattern of sulci and ridges; and (iii). a lack of visible structure. Abnormal microvessels observed in cancerous lesions were classified according to two patterns: irregular minute vessels and variation of vessel caliber. The small regular pattern of sulci and ridges was significantly more frequently observed in differentiated carcinoma (30/56, 53.6 %) than in undifferentiated carcinoma (2/18, 11.1 %). Lack of visible structure and irregular minute vessels were significantly more frequently observed in undifferentiated carcinoma (44.4 % and 77.7 %) than in differentiated carcinomas (5.4 % and 51.8 %). CONCLUSION: The minute surface structure and microvessels observed by magnifying endoscopy were related to histopathological findings. Magnifying endoscopy is valuable for predicting the histological nature in the diagnosis of early gastric cancer.

Simultaneous multiple early cancers of esophagus and stomach treated by endoscopic mucosal resection.

Endoscopic mucosal resection (EMR) has been accepted as a completely curative treatment of gastrointestinal mucosal cancers. With advances in diagnostic techniques, the tendency to detect simultaneous multiple primary cancers is increasing. Patients with another cancer coexisting with esophageal cancer have had a poor prognosis, but if both cancers are detected in the early stage, complete treatment consisting only of endoscopic surgery, with a good prognosis, is expected. We describe two cases of simultaneous multiple early cancers of the stomach and esophagus, treated by EMR.

Exacerbatory mechanism responsible for water immersion stress-induced gastric lesions in aged rats compared with young rats.

1. The present study was designed to investigate whether or not ageing affects the development of water immersion stress-induced gastric lesions in rats. Effects of cetraxate, an anti-ulcer drug, were also examined. 2. Gastric lesions were induced by 6 h water immersion stress in rats. Gastric mucosal blood flow was determined by the hydrogen gas clearance technique and nitric oxide synthase (NOS) activity was measured enzymatically. 3. Early development of gastric lesions was observed in aged rats and exacerbation of gastric lesions was also found. Lowering of gastric mucosal blood flow and reduced NOS activity were observed in aged rats. 4. Cetraxate mitigated the development of gastric lesions in young rats and also increased gastric mucosal blood flow and NOS activity. However, these favourable effects were diminished in aged rats. 5. Decreased NOS activity may be an important exacerbatory factor to the development of gastric lesions in aged rats. 6. Effects of cetraxate differed between young rats and aged rats. 7. These results may explain the refractoriness and drug resistance in gastric ulcers encountered by elderly individuals.

Germline and somatic mutations in hMSH6 and hMSH3 in gastrointestinal cancers of the microsatellite mutator phenotype.

Hereditary and sporadic gastrointestinal cancer of the microsatellite mutator phenotype (MMP) is characterized by a remarkable genomic instability at simple repeated sequences. The genomic instability is often caused by germline and somatic mutations in DNA mismatch repair (MMR) genes hMSH2 and hMLH1. The MMP can be also caused by epigenetic inactivation of hMLH1. The MMP generates many somatic frameshift mutations in genes containing mononucleotide repeats. We previously reported that in MMP tumors the hMSH6 and hMSH3 MMR genes often carry frameshift mutations in their (C)(8) and (A)(8) tracks, respectively. We proposed that these 'secondary mutator mutations' contribute to a gradual manifestation of the MMP. Here we report the detection of other frameshift, nonsense, and missense mutations in these genes in colon and gastric cancers of the MMP. A germline frameshift mutation was found in hMSH6 in a colon tumor harboring another somatic frameshift mutation. Several germline sequence variants and somatic missense mutations at conserved residues were detected in hMSH6 and only one was detected in hMSH3. Of the three hMSH6 germline variants in conserved residues, one coexisted with a somatic mutation at the (C)(8) track and another had a somatic missense mutation. We suggest that some of these germline and somatic missense variants are pathogenic. While biallelic hMSH6 and hMSH3 frameshift mutations were found in some tumors, many tumors seemed to contain only monoallelic mutations. In some tumors, these somatic monoallelic frameshift mutations at the (C)(8) and (A)(8) tracks were found to coexist with other somatic mutations in the other allele, supporting their functionality during tumorigenesis. However, the low incidence of these additional somatic mutations in hMSH6 and hMSH3 leaves many tumors with only monoallelic mutations. The impact of the frameshift mutations in gene expression was studied by comparative analysis of RNA and protein expression in different tumor cell clones with different genotypes. The results show that the hMSH6 (C)(8) frameshift mutation abolishes protein expression, ruling out a dominant negative effect by a truncated protein. We suggest the functionality of these secondary monoallelic mutator mutations in the context of an accumulative haploinsufficiency model.

Asymptomatic inflammatory bowel disease with special reference to ulcerative colitis in apparently healthy persons.

OBJECTIVE: We examined cases of asymptomatic inflammatory bowel diseases, particularly asymptomatic ulcerative colitis, which were found in apparently healthy Japanese persons who underwent general health screening. METHODS: Patients with positive immunological fecal occult blood test (IFOBT) among approximately 236,000 persons participating in the health screening program at the Aichi Prefectural Center for Health Care for the past 9 yr underwent total colonoscopy. In patients with ulcerative colitis, we investigated the sex and age distributions, extent of lesion, endoscopic activity, incidence rate, and clinical course. RESULTS: In all, 35 cases of inflammatory bowel disease were detected, and 274 cases of colorectal cancer (not discussed here) were detected in the same population. The 35 cases of inflammatory bowel disease consisted of 19 cases of ulcerative colitis (12 of asymptomatic and minimally symptomatic ulcerative colitis, and seven of symptomatic or with past history of ulcerative colitis); five of intestinal tuberculosis; two of Crohn's disease; two of amebic colitis; and seven of endoscopic colitis. The 12 patients with asymptomatic and minimally symptomatic ulcerative colitis consisted of 11 men and one woman aged 36-63 yr (mean 46.2 yr). We classified these cases into three grades of severity according to endoscopic findings: four cases were mild, eight moderate, and none severe. Of these 12 cases, three were found endoscopically because of positive IFOBT, although barium enema was normal. Anatomic types of colitis cases included three of total colitis, three left-sided colitis, two proctitis, and four right-sided or segmental colitis. In one case, the disease extended proximally during the course of observation. CONCLUSIONS: We found 35 cases of inflammatory bowel disease because of positive IFOBT performed as part of a general health screening. Of these, 19 cases were ulcerative colitis. These included many asymptomatic and minimally symptomatic cases, which could be very important in helping to elucidate the natural history of ulcerative colitis; thus, long-term follow up is necessary.

Clinical results and development of variable-stiffness video colonoscopes.

BACKGROUND AND STUDY AIMS: This study was designed to assess the usefulness of variable-stiffness video colonoscopes, compared with conventional videoscopes. PATIENTS AND METHODS: The first prototype XCF-QAY1 and the latter prototype XCF-Q240A1 used in this study can be varied to 4 levels of stiffness of tube insertion during examination. In 352 consecutive colonoscopic examinations performed using these and two conventional scopes, the following data were recorded: time for intubation to the cecum, frequency of changes in the patients' posture, frequency of abdominal pressure attempts, and pain score. The degree of stiffness of the insertion tube and the examiners' impressions score were recorded only in procedures where the variable-stiffness scopes were used. RESULTS: There was no significant difference between colonoscopes in the pain score. Total colonoscopy rate was 97.4%. The frequency of usage of the varying stiffness control in the colon according to site was as follows: descending colon, 57.3%; transverse colon, 32.8%, sigmoid colon, 7.6%; and ascending colon, 2.3%. A significant difference in the mean time for intubation to the cecum between the XCF-Q240A1 and conventional scopes was observed. Moreover, there were significant differences in the frequency of abdominal pressure attempts and changes in the patient's posture between conventional scopes and the new scopes. CONCLUSIONS: These results suggest that only one scope, the XCF-Q240A1, is needed for any colonic examination by any examiner.

Role of nitric oxide synthase inhibitor in experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid in rats.

1. The present study was designed to investigate the role of nitric oxide (NO) in modulating 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. 2. Damage scores and NO synthase (NOS) activity were measured. 3. The damage scores and NOS activity reached a peak on the 4th day after administration of TNBS solution (day 0), thereafter gradually decreasing, and were significantly higher than in the group treated with saline throughout the experimental period. 4. Subsequently, we divided the stage of colitis into two groups, one from day 0 to day 3 after induction of colitis, and the other from day 4 onwards. We evaluated the effects of the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA), on TNBS-hapten-induced colitis and colonic mucosal blood flow. Two different methods of L-NMMA administration, from day 0 to day 3, and from day 4 onwards, were undertaken. 5. The damage score in the early L-NMMA treatment group was significantly higher than in the group without L-NMMA on day 14. In contrast, the damage score in the late L-NMMA treatment group was not significantly different from the group without L-NMMA. Colonic mucosal blood flow in the early L-NMMA treatment group was not significantly different from that in the late L-NMMA treatment group. 6. These data suggest that NO is important for inhibiting inflammation during the early stages.