Search

To clarify the protective role of transforming growth factor (TGF)-beta for the intestinal epithelial injury in vivo, the effect of antibodies against TGF-beta on epithelial destruction and apoptosis was assessed in dextran sulfate sodium (DSS)-induced colitis by histological analysis of colonic sections, account of apoptotic epithelial cells. To evaluate the pathways of epithelial apoptosis, we analyzed the activities of caspases, the level of Fas and cellular FLICE-inhibitory protein (cFLIP) expression in epithelial cells. Apoptotic epithelial cells were increased prior to the onset of ulceration in DSS-induced colitis, and the neutralization of TGF-beta exacerbated epithelial apoptosis and histological damage score. The up-regulation of caspase-8 activity and Fas expression and reduced cFLIP expression were observed in intestinal epithelial cells from anti-TGF-beta antibody-treated mice. The present study revealed that suppression of TGF-beta deteriorated epithelial apoptosis, and the increase of apoptotic epithelial cells may amplify the inflammation in gut mucosa.

The mutations of the SCN5A gene have been implicated to play a pathogenetic role in Brugada syndrome, which causes ventricular fibrillation. To determine the Brugada-associated mutations in Japanese patients, facilitate pre-symptomatic diagnosis, and allow genotype-phenotype studies, we screened unrelated patients with Brugada syndrome for mutations. DNAs from 6 Japanese patients were obtained and the sequence in the translated region of SCN5A was determined. We could not find the mutations reported previously, but found 17 sites of nucleotide change, consisting of 7 synonymous and 10 non-synonymous nucleotide changes in our patients. Among them, two non-synonymous nucleotide changes (G1663A and G5227A) are specific to our patients and these changes were not found in 53 healthy controls. In 4 patients out of 6, no specific nucleotide change for Brugada syndrome could be detected. Our findings demonstrating no patient-specific change in the translated region of the SCN5A gene among two thirds of the small number of patients examined here imply that another gene other than the SCN5A may be associated with this disease, supporting previous investigations in Japan and other countries.

It was reported that in only 19 (11%) of 173 patients was the common channel at the junction of the pancreatic and bile ducts found to be 6 mm or longer. Pancreaticobiliary maljunction (PBM) is defined as an anomaly with a markedly long common channel with the junction located outside the duodenal wall, so the action of the sphincter of Oddi does not functionally affect the junction. We defined high confluence of pancreaticobiliary ducts (HCPBD) as a length of the common channelor = 6 mm, in which the communication between the pancreatic and bile ducts was occluded when the sphincter was contracted. This study aims at investigating the clinical significance of HCPBD.2,980 consecutive cases with an adequate endoscopic retrograde cholangiopancreatography were reviewed. PBM and HCPBD were diagnosed according to the above definitions. PBM was divided into two groups: with or without biliary dilatation.PBM and HCPBD were detected in 63 (2.1%) and 50 (1.7%) cases, respectively. Biliary dilatation was detected in 30 cases having PBM. The incidences of gallbladder carcinoma associated with PBM with or without biliary dilatation and HCPBD were 13, 67, and 12%, being significantly higher than in controls (p0.05, p0.01, and p0.05). Pancreatic ductal reflux was detected in 11 (85%) of 13 patients with HCPBD in whom postoperative T tube cholangiograms were performed, and acute pancreatitis occurred in 14 (24%) of the 50 patients with HCPBD.HCPBD may be an intermediate variant of PBM. It is necessary to pay attention to an associated gallbladder carcinoma in patients with HCPBD as well as in those with PBM.

Gut lavage fluid, collected by the oral administration of an electrolyte lavage solution, was found to be an excellent and easily collectible source of abundant mucin. Furthermore, the biochemical features of mucin from patients with ulcerative colitis (UC) and Crohn's disease (CD) were investigated. The mucin was separated into four fractions by Sepharose CL-4B, Sepharose CL-2B, and DEAE Sephacel chromatography. Compared to healthy subjects, the total yields of mucin from ulcerative colitis patients were low due to a deficiency of neutral mucin, whereas those from Crohn's disease patients were high, mainly due to high-molecular-weight mucin. Fucose and sulfate content was low in ulcerative colitis, but only the former was low in Crohn's disease. The different biochemical features of mucin obtained from gut lavage fluid appear to reflect the mucosal pathological changes associated with inflammatory bowel disease.

Mucus glycoproteins (mucins) are high molecular weight O-linked glycoproteins produced by the gastrointestinal epithelial cells. They have important biological functions, however, the elongation patterns of the O-glycan chains and their biosynthesis mechanisms are not fully understood. In this study, GalNAc-PNP was used as a primer and added to the medium of a cultured human colon adenocarcinoma cell line, DLD-1. After incubation, GalNAc-PNP-induced oligosaccharides were derived from the medium and analyzed. Because DLD-1 produced galactosyl(Gal)-GalNAc-PNP but not N-acetylglucosaminyl (GlcNAc)-GalNAc-PNP, and produced considerably more branched Gal-(GlcNAc-) GalNAc-PNP than unbranched GlcNAc-Gal-GalNAc-PNP, it was considered that N-acetylglucosamine binds to N-acetylgalactosamine after the initial binding of galactose to N-acetylgalactosamine. It is also likely that further elongation of O-glycan chains is inhibited by the binding of sialic acid to N-acetylgalactosamine. In summary, sugar-chain elongation analysis of GalNAc-PNP in cultured DLD-1 cells is a potentially useful method for elucidating the biosynthetic mechanisms underlying the production of O-linked glycoproteins.

Background: Topical pharyngeal anesthesia is generally used as a pretreatment for upper endoscopy. However its efficacy has not been established. Methods: A randomized double—blind placebo-controlled study was undertaken. Subjects were 201 patients who underwent upper endoscopy and gave informed consent. Relative risks (RR) of patient discomfort were calculated for pharyngeal anesthesia, anxiety, and other potential confounding factors by using logistic regression analyses. Results: The RR of patient discomfort on intubation was 0.56 for the anesthesia versus the placebo group (95% CI, 0.31-1.01). RR was higher in patients aged 39 or younger than in those 40 or over (RR = 2.22, 95% CI, 1.04-4.74). With subgroup analysis in those examinees less than 40 years old, the RR of patient discomfort was 0.21 for the topical anesthesia (95% CI, 0.04-0.99) versus the placebo group and 4.93 for patients undergoing upper endoscopy for the first time (95% CI, 1.13-21.60). In the first-time patients, the RR was lower in the topical anesthesia than in the placebo group (RR = 0.20; 95% CI, 0.04-0.93); it was higher in patients with a trait-anxiety score higher by 10 points than in those with a lower score (RR = 3.35, 95% CI, 1.01-11.15). With the Bonferroni correction for multiple testing of data, statistical significance is indicated by a CI of 97.5% in the subgroup analyses. Conclusions: Topical pharyngeal anesthesia appears to be effective in patients less than 40 years old and in those undergoing the procedure for the first time. A high trait-anxiety score could be a predictor of discomfort in first-time examinees. (Gastrointest Endosc 2001;53:14-8.)

Cap polyposis (CP) is a rare disease that was first described by Williams et al.1 in 1985. It is characterized by multiple polyps with a mucoid and fibrinopurulent cap. Although the pathogenesis is unknown, the characteristic histological appearance is similar to that of mucosal prolapse syndrome (MPS). Endoscopically, it is difficult to distinguish the polyps of CP from inflammatory polyps and neoplasms. True neoplasms can be differentiated from non-neoplastic lesions by magnifying colonoscopy, but the changes in the mucosal surface of CP have not been investigated in detail. A case of CP that was treated successfully with conservative therapy, is described, as well as the findings obtained by magnifying colonoscopy.

Background: The non-lifting sign is considered a contraindication to endoscopic resection. Our objective was to investigate whether lifting or nonlifting of a lesion is determined by the volume of normal submucosal tissue. Methods: We measured the thickness of the submucosa and examined the relation between submucosal invasion and lesion elevation induced by submucosal injection in 60 patients with colorectal cancer with evidence of submucosal invasion. Extent of tumor elevation was classified into two groups: A, lifting; B, non-lifting. Submucosal invasion was classified as sm1, sm2, or sm3. The distance between the carcinoma and the line of resection and that between the carcinoma and the muscularis propria were measured. Results: Of 31 sm1 lesions, 29 (93.5%) were group A. All 6 sm3 lesions were group B. All lesions in group A had a value for the distance between carcinoma and muscularis propria of more than 1000 μm. Group B lesions with sm3 invasion had distances of only 105 to 750 μm. Conclusion: Lesions classified as sm3 do not elevate in response to submucosal injection, and lesions that become elevated on injection can be resected endoscopically because they are sm1 or sm2 and have a thickness of normal submucosa of more than 1000 μm. (Gastrointest Endosc 1999;50:329-33.)

72 congenital or acquired bleeding disorder patients who all showed prolonged BT (more than 15 minutes).

phangiomas before surgery. EUS revealed the characteristics of the intracystic space, such as the epithelial papillary-like growth features that were not detected with CT. A sagittal section of the resected specimen showed features consistent with the preoperative EUS findings. These findings suggest that EUS is a useful method for diagnosis of appendiceal mucocele. In conclusion, we diagnosed a case of vermiform appendiceal mucocele at colonoscopy with the use of an EUS probe. The endoscopic and EUS images were highly suggestive of an appendiceal mucocele. If findings at routine colonoscopy suggest the presence of an appendiceal mucocele, EUS with a miniprobe should be performed for accurate preoperative diagnosis. Although the lesion in the present case was benign, we believe that EUS would also reveal the irregular thickness or the disruption of the cyst wall that are likely to occur with invasion into the stroma. Therefore, in the future, EUS may be able to distinguish the more benign lesions from the more malignant types. REFERENCES

We evaluated the preventive effects of wheat bran (40%, weight percent of diet) on the development of large bowel carcinoma induced by weekly intraperitoneal administration of 25 mg/kg (body weight) of 1,2-dimethylhydrazine over 19 weeks in the rat. Feces number and volume per pellet in wheat bran diet group were significantly greater than those in basal diet group, and the induction rates of tumor in the wheat bran diet group was found to be significantly lower than that in the basal diet group. These results suggested that wheat bran was effective in inhibiting large bowel carcinogenesis, and that the increased fecal weight and volume from wheat bran may be involved in such an inhibitory effect.

In this report, we attempt to propose a recommended level of dietary fiber (DF) for the Japanese from several epidemiological reports. The authors previously investigated the daily DF intake in 50 patients with colon polyp, 33 patients with colon diverticulosis, 45 patients with colorectal cancer, and two groups 84 and 45 control subjects; the values obtained were 18.2, 17.4, 14.9, and 21.1 and 19.9 g, respectively. In another study, of the 5 regions in Japan, in only one, Aomori, where the rate of the colon diverticulosis detection was the lowest, did the DF intake exceed 20 g. Furthermore, in Japan the incidence of colorectal cancer showed a marked increase after 1955. It was assumed that the period between the diagnosis of colorectal cancer and death was 15 years, and that the DF intakes at this time (before 1940) to had contributed to the development of the disease. However unfortunately daily DF intake before 1940 in Japan were unknown, and we have only data 25.0 g in 1946. Thus, it is proposed that the recommended level for daily DF intake in Japanese be set at about 20–25 g, i.e. 10 g per 1,000 kcal.

Epidemiological and experimental studies have shown that dietary fiber may prevent colon cancer. Resistant starch, like dietary fiber, is not subject to digestion in the small intestine. However, it is unknown whether resistant starch inhibits colonic carcinogenesis. In vitro studies have shown that butyrate slows the growth of cultured colon cancer cells. The effect of resistant starch diet on 1,2-dimethylhydrazine-induced colonic carcinogenesis in rats was evaluated, and the colonic butyrate concentration was measured.Sprague-Dawley rats were randomly divided into five groups that were fed diets containing no fiber, 3% cellulose, 10% cellulose, 3% resistant starch, or 10% resistant starch. Colonic carcinogenesis and butyrate concentration of colonic contents and feces in each diet group were compared.Total cancer volume per rat in the 10% cellulose group was significantly lower than that in the basal group (109 +/- 54 mm3 and 247 +/- 83 mm3; P0.05), but the other groups showed no significant differences. The butyrate concentration in colonic content and in feces were higher in the resistant starch groups than in the cellulose groups.The resistant starch diet increased butyrate concentration but did not inhibit colonic carcinogenesis. It remains doubtful whether butyrate inhibits the proliferation of colon cancer cells.

From the First Department of Internal Medicine, the First Department of Surgery, and Central Pathology, Hirosaki University School of Medicine, Hirosaki, Japan. Reprint requests: Shinsaku Fukuda, MD, First Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 0368562 Aomori, Japan. Copyright © 2001 by the American Society for Gastrointestinal Endoscopy 0016-5107/2001/$35.00 + 0 37/4/112368 doi:10.1067/mge.2001.112368 A case of early-stage primary malignant melanoma of the esophagus

Although leiomyomas of the stomach or small intestine are relatively common, those of the colon or rectum are rare.1-4 Several cases of endoscopic resection of colorectal leiomyomas have been described.5-7 However, conventional polypectomy of leiomyomas can result in perforation.8 To reduce the risk of perforation, submucosal injection can be performed before removal. We report a case of rectal leiomyoma in which complete enucleation was performed endoscopically using this method.

Postpolypectomy hemorrhage, the most common complication of polypectomy, can be classified as immediate or delayed bleeding. Immediate bleeding can be controlled with various endoscopic methods (regrasping the stalk, epinephrine injection, coagulation with hot biopsy forceps or heater probe, rubber band ligation).1 Delayed bleeding seems to be more common.2,3 Most delayed hemorrhaging stops spontaneously and can be managed with conservative therapy. However, delayed arterial bleeding may necessitate transfusion, angiography, or surgical intervention. Injection of the stalk with epinephrine or sclerosants before transection is recommended to diminish risk for postpolypectomy hemorrhage. Epinephrine injection, however, may prevent only immediate bleeding, and use of sclerosants may increase risk for perforation.4 A detachable snare5-7 has been developed for the prevention of postpolypectomy hemorrhage. We performed endoscopic placement of a detachable snare to ligate a site of postpolypectomy arterial bleeding in the sigmoid colon.

Background : Endoscopic injection has recently been reported as effective for several treatments. Because the common channel (suction and biopsy) is usually contaminated with aspirated gastrointestinal juice containing bacteria, often the tip of the injector needle is also. We report a new catheter needle with a covered tip designed to prevent bacteremia from endoscopic injection. Methods : The new covered needle catheter (Clisco needle) has a 23-gauge retractable needle with a 3 mm extrusion in one lumen. Its distal tip is covered with rubber, blocking infiltration of contaminated gut juice. Ten of these catheters and 10 other disposable needles were inserted through the colonoscope's biopsy channel for 10 patients. Needle tips were cut off after extrusion, and bacteria cultured were counted by standard plate count method. Results : All cultures from ordinary needles grew Escherichia coli , whereas only 3 new needles grew E. coli . Average counts of bacteria cultured from these 3 catheters and 10 disposable needles were 1–250 and 90–6.1 × 10 6 , respectively. The difference was highly significant ( p Conclusions : This new covered needle catheter reduces contaminating bacteria in patients who require endoscopic injection and may prevent bacteremia without antibiotic prophylaxis.

The technique of saline-assisted polypectomy (SAP) is being increasingly used for resection of sessile polyps, z Previous reports indicate that the method is easy to master and appears to be safe. We present a case of Escherichia coli bacteremia occurring after SAP in which no colonic perforation was found. The infection cleared with intravenous antibiotics. The bacteremia may have resulted from contamination of the injection needle catheter as it was passed through the suction channel of the colonoscope. The case suggests the need for inventing a new type of injection needle that is protected from such bacterial contamination. In recent years, the submucosal injection of saline has been increasingly used before resecting sessile polyps during colonoscopy (SAP). Rosenberg 2 first developed this technique for use during polypectomy performed through a rigid proctoscope in 1955. Rosenberg's technique used submucosal saline injection through a long, hard needle passed through a rigid scope. ~ In principle, that technique is identical to SAP n ow widely performed by passing a long, flexible needle through the biopsy channel of a flexible endoscope. SAP appears to be helpful in the removal of large sessile polyps, although late bleeding may be more frequent than during traditional polypectomy. 4 Injection o f fluid into the submucosa beneath the polyp increases the distance between the base of the polyp and t he deeper tissues of the

BACKGROUND: Chronic gastritis induced by Helicobacter pylori (H. pylon) is charactsrisnd by considerable neutrophil infiltration into the gastric mucosa. Neutropbils are considered to play an important role in oxidative injury of gastric mucosa. The aim of this study was to examine the effects of H. pyloriwater extracts on oxidative burst and chemokine production of human neutrophils. METHODS: H. pylori cells were extracted by harvesting into distilled water and centr'itugation. Filtered water extracts were added to 5x10' neotrophils separated from volunteers without H. pylori infection. Neutrophil oxidative burst was measured using luminol-dependent chemiluminescence (LmCL) at 37 °C for 1 hour. Further incubation was performed at 37 °C for 12 hours and the production of IL-8 (CXC chemoldne) and MIP-la,(CC chemokine) was measured by ELISA. Neutrophils were also pre-incubated with H. pylor/water extracts (f.c. 0-2.0 %) for 30 min. After the pre-incubation, neutrophils were stimulated by H. pyloricells to examine the neutrophil-priming effects of H. pylor/water extracts. RESULTS: H. pyloriwater extracts induced neutrophil oxidative burst but the LmCL response was weak (

Background: Colonic surface color on endoscopy is largely determined by hemoglobin content in the colonic tissue, which has been calculated from spectral reflectance of the colonic surface as an index of hemoglobin (IHB). Histological colonic layers, influencing the surface reflectance has, however, still remained undetermined. Aims: The aim of this study was to determine the colonic layers, which influence the surface reflectance and the relative IHB against the total IHB in each colonic layer. Methods: Colonic tissue specimen with a gradation of thickness was constructed by using normal parts of resected colon from 5 patients with colorectal cancer. By using a spectrophotometer, spectral reflectance (410 to 690 nm) was measured at sampling points along a line of interest on the specimen at every 1mm intervals for IHB, which is give by 32Log (r650/r569). r650 and r569 designate reflectance at a wavelength of 650 and 569 nm, respectively. After photometry, the specimen was fixed in 10% formalin and sliced along the line of interest for a thickness of histological layers (micro-meter) in each sampling site. Results: IHB linearly increased to reach plateau as a thickness of the submucosa increased (Table). When a thickness of the submucosa exceeded 400 micro-meter, IHB remained constant, regardless of the presence or absence of deeper layers (propria muscle, subserosa and serosa). A thickness of the mucosa was found to have only least influence on IHB. The relative IHB against the total IHB was less than 45% for the mucosa and the remaining more than 55% for the submucosa. Conclusions: On colonoscopy, surface color was determined exclusively by the mucosa (45%) and submucosa (55%). In spectroscopy, it should be cautious to interpret IHB exclusively as mucosal hemoglobin especially in normal colon.

Background: We have previously demonstrated that the degree of endoscopic surface redness was significantly larger in colonic carcinoma than in normal mucosa. Aim: The aim of this study was to correlate endoscopic redness with histological variables, concerning microvasculature in the tissue of colonic carcinoma and normal mucosa. Methods: Five patients with colorectal carcinoma were studied. They underwent colonoscopy for pictures of the growth and normal appearing parts more than 5 cm apart from the growth. Endoscopic pictures were processed for an index of hemoglobin (IHB) as the degree of surface redness in each region of interest by an image processor. The surgical specimens, sliced were stained with CD34 for vascular counts (/mm 2 ) and the total cross sectional area of vasculature per the unit area of region of interest (%VA). In this study, the spatial direction of longitudinal axis of each vascular canal (θ) was reconstructed from a shape of vascular cross section. When the direction is vertical to the mucosal surface (θ=0 degree), the vessel is recognized as a point on endoscopy. While, when it is parallel to the mucosal surface (θ=90 degree), the vessel is recognized as a line. Results: IHB was significantly larger in colonic carcinoma (37.0± 8.1) than in normal mucosa (29.7±5.8, p=0.049). Vascular counts was large in colonic carcinoma (274±183) compared with that in normal mucosa (203±58), but it did not reach the significant level (p =0.176). %VA also was larger in carcinoma (3.8±2.0) than in normal mucosa (3.1±1.5), although it was not statistically significant (p=0.253). While, θ was significantly larger in carcinoma (52.1±6.7) than in normal mucosa (44.0±5.8, p=0.021). Conclusions: Colonic carcinoma was significantly more red than normal mucosa. A novel histological variable, the spatial arrangement of microvasculature can reasonably account for this difference along with vascular counts and vascular bed area.