Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine.

BACKGROUND: The 5-HT(3) receptor antagonists are known to be effective for the treatment of diarrhea-predominant irritable bowel syndrome (IBS), but not widely used yet. The aim of this study was to compare the efficacy and safety of ramosetron, a 5-HT(3) receptor antagonist, and mebeverine in male patients with IBS with diarrhea (IBS-D). METHODS: This study was performed in a multicenter, randomized, open-label design. Data of 343 male patients with IBS-D who were randomized to either a 4-week treatment of ramosetron 5µg once daily or a 4-week treatment of mebeverine 135 mg three times daily were analyzed by the intent-to-treat analysis. The primary efficacy parameter was the proportion of patients with adequate relief of IBS symptoms at the last week of treatment. The secondary endpoints were changes in each symptom score and the safety profiles. KEY RESULTS: The responder rates for global IBS symptoms, abdominal pain/discomfort and abnormal bowel habits in the ramosetron and mebeverine groups significantly increased during the treatment period. The severity scores of abdominal pain/discomfort and urgency, the stool form score, and the stool frequency in both treatment arms were significantly reduced, compared with the baselines. There were no significant differences in the responder rates (37%vs 38% on ITT analysis) and adverse event profiles between the ramosetron and mebeverine groups. Neither severe constipation nor ischemic colitis was reported by ramosetron-treated patients. CONCLUSIONS & INFERENCES: Ramosetron 5µg once daily is as effective as mebeverine three times daily in male patients with IBS-D.

Differences in the prevalence of colorectal polyps in patients undergoing endoscopic removal of gastric adenoma or early gastric cancer and in healthy individuals.

BACKGROUND AND AIMS: We compared the prevalence of adenomatous and cancerous colon polyps in patients who underwent endoscopic removal of gastric neoplasms and in healthy controls. MATERIALS AND METHODS: This retrospective study reviewed the medical records of 186 patients with gastric neoplasms and 186 healthy subjects from January 2002 to October 2008. The gastric neoplasm group was comprised of patients undergoing endoscopic removal of gastric adenomas or early gastric cancers and serial fiberoptic colonoscopy (FCS) for checkups. The control group was comprised of subjects undergoing fiberoptic esophagogastroduodenoscopy (FEGD) and FCS for general checkup and was matched for age and sex with the gastric neoplasm group. Advanced colonic neoplasm was defined by any of the following: (1) the presence of three or more polyps; (2) polyp size at least 1.0 cm; (3) high-grade dysplasia or adenocarcinoma confirmed by histopathologic examination. RESULTS: Of the 372 persons, colorectal polyps were detected in 124 (33.3 %), advanced colonic neoplasms in 44 (11.8 %), and adenocarcinomas in 10 (2.7 %). The overall prevalence of adenomatous or cancerous polyps ("all polyps") and the prevalence of advanced colonic neoplasms were significantly higher in the gastric neoplasm group than in the control group (all polyps: 40.9 % in the gastric neoplasm group vs. 25.8 % in the control group, P = 0.002; advanced colonic neoplasms: 15.6 % vs. 8.1 %, P = 0.025). The risk factors for all polyps were age, male sex, diabetes mellitus, and being assigned to the gastric neoplasm group, and those for advanced colonic neoplasms were age and being assigned to the gastric neoplasm group. Confining the analysis to the gastric neoplasm group, the risk factors for all polyps were identical with those for the total group; however, those for advanced colonic neoplasm were different (age vs. diabetes and hypertriglyceridemia). CONCLUSION: Endoscopists should consider performing routine FCS in patients undergoing endoscopic removal of gastric neoplasms.

Spinal cord injury subsequent to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

Transcatheter arterial chemoembolization is one of the most common treatment modalities for hepatocellular carcinoma. Transcatheter arterial chemoembolization is considered to be a relatively safe procedure, but transcatheter arterial chemoembolization is associated with a number of disastrous complications. Among the ischaemic complications caused by transcatheter arterial chemoembolization, spinal cord injury is very rare, but can occur via the intercostal or lumbar arteries. We report two cases of extremely rare spinal cord injuries after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. The patients had sensory loss below the T9 or T10 dermatomes and paraparesis or paraplegia within 6-8h after transcatheter arterial chemoembolization. One patient sustained paraplegia until death 2 months after transcatheter arterial chemoembolization and the other patient recovered almost completely 2 months after transcatheter arterial chemoembolization.

Clinical significance of duodenal lymphangiectasia incidentally found during routine upper gastrointestinal endoscopy.

BACKGROUND AND STUDY AIM: Although duodenal lymphangiectasia in individuals without clinical evidence of malabsorption has been reported, the prevalence and clinical significance in this situation are not yet known. The aim of this study was to evaluate the prevalence and clinical significance of incidentally found duodenal lymphangiectasia. PATIENTS AND METHODS: A retrospective review of medical records was undertaken for consecutive patients who had undergone diagnostic upper endoscopy between January 2005 and June 2006. A prospective study was then performed in consecutive individuals undergoing routine upper endoscopy for health examination between July 2006 to October 2006. Endoscopic features of duodenal lymphangiectasia were classified into three types: (1) multiple scattered pinpoint white spots; (2) diffuse prominent villi with whitish-discolored tips; and (3) focal small whitish macule or nodule. The histologic grade of duodenal lymphangiectasia was classified according to the depth and severity of lymphatic duct dilatations. Prevalence and clinical data of incidentally found duodenal lymphangiectasia were evaluated in the retrospective and prospective studies. RESULTS: Among 1866 retrospective cases, duodenal lymphangiectasia was endoscopically suspected in 59 cases (3.2%), and histologically confirmed in 35 cases (1.9%). No clinical evidence of malabsorption was noted in the duodenal lymphangiectasia cases. The "scattered pinpoint white spots" type was the most frequently found endoscopic feature (40.0%). Duodenal lymphangiectasia was persistent in seven of 10 individuals who underwent repeat endoscopy after a median of 12 months. Among 134 prospective cases, duodenal lymphangiectasia was histologically confirmed in 12 cases (8.9%). There was no significant clinical difference between groups with and without duodenal lymphangiectasia. Lymphatic duct dilatation was histologically more severe in the "focal small whitish macule or nodule" type than in the other types. CONCLUSION: Duodenal lymphangiectasia without clinical evidence of malabsorption is not extremely rare among cases undergoing routine upper gastrointestinal endoscopy.

Esophageal dysmotility and acid sensitivity in patients with mitral valve prolapse and chest pain.

Mitral valve prolapse (MVP) patients often experience non-cardiac chest pain. The aims of this study were to determine, in patients with non-cardiac chest pain: (i) whether esophageal dysmotility is more common in patients with MVP than in patients without MVP; and (ii) if acid sensitivity is an important cause of the chest pain in MVP patients. Esophageal manometry and acid perfusion testing were performed in 277 consecutive patients with non-cardiac chest pain. Patients with MVP (13 female, one male; mean age 49 years) were more likely (P = 0.01) to have esophageal dysmotility, while acid perfusion was less likely (P < 0.05) to provoke their chest pain, than in patients without MVP. The most common esophageal motor abnormalities detected in patients with and without MVP were diffuse esophageal spasm (prevalence, 57%) and non-specific motor disorder (prevalence, 9%), respectively. This study, the first large prospective series examining possible esophageal sensorimotor correlates of chest pain in MVP patients, demonstrates that in the absence of a cardiac cause for chest pain, a specific esophageal motility disorder should be excluded, rather than assuming the chest pain is likely to be due to acid sensitivity.

An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome.

BACKGROUND: Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western populations. However, little information is available regarding the use of tegaserod in the Asia-Pacific population. AIMS: To evaluate the efficacy, safety, and tolerability of tegaserod versus placebo in patients with IBS from the Asia-Pacific region. PATIENTS: A total of 520 patients from the Asia-Pacific region with IBS, excluding those with diarrhoea predominant IBS. METHODS: Patients were randomised to receive either tegaserod 6 mg twice daily (n=259) or placebo (n=261) for a 12 week treatment period. The primary efficacy variable (over weeks 1-4) was the response to the question: "Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?" Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and individual symptoms of IBS. RESULTS: The mean proportion of patients with overall satisfactory relief was greater in the tegaserod group than in the placebo group over weeks 1-4 (56% v 35%, respectively; p<0.0001) and weeks 1-12 (62% v 44%, respectively; p<0.0001). A clinically relevant effect was observed as early as week 1 and was maintained throughout the treatment period. Reductions in the number of days with at least moderate abdominal pain/discomfort, bloating, no bowel movements, and hard/lumpy stools were greater in the tegaserod group compared with the placebo group. Headache was the most commonly reported adverse event (12.0% tegaserod v 11.1% placebo). Diarrhoea led to discontinuation in 2.3% of tegaserod patients. Serious adverse events were infrequent (1.5% tegaserod v 3.4% placebo). CONCLUSIONS: Tegaserod 6 mg twice daily is an effective, safe, and well tolerated treatment for patients in the Asia-Pacific region suffering from IBS and whose main bowel symptom is not diarrhoea.

Molecular epidemiology of hepatitis A virus in Korea.

BACKGROUND: The prevalence of antibodies for hepatitis A virus (anti-HAV) in adolescents and young adults has decreased remarkably following the economic growth in Korea. As a result, this age group has a high risk for HAV infection paradoxically, and over 1500 cases of clinically overt hepatitis A occurred in 1998. Human isolates of hepatitis A virus (HAV) are categorized within four genotypes (I, II, III, and VII). In some geographic regions, closely related isolates cluster, suggesting endemic spread of the virus, while in other regions multiple genotypes circulate. Virtually no data are available with regard to the genetic relatedness of Korean strains of HAV. METHODS AND RESULTS: A 168 base pair segment encompassing the putative VP1/2A junction of the HAV genome was amplified by RT-PCR and sequenced in sera of 18 Korean patients with a sporadic form of acute hepatitis A. Pairwise comparisons of the nucleic acid and amino acid sequences of 18 Korean isolates with one another revealed that the Korean isolates showed > 94.6% and > 96.4% identity, respectively. All of the 18 Korean isolates clustered within genotype IA, irrespective of the geographic locations and the time that hepatitis occurred. Unique amino acid sequence changes that had never been reported in genotype IA were found in nine of the 18 isolates. These changes were Gln-->Ser and Lys-->Arg in 2A-19 and 2A-10 amino acid positions. CONCLUSION: The presence of single genotype and unique mutations may be related with the circulation of endemic HAV over a long period of time in Korea.

Detection of hepatitis A viral RNA in sera of patients with acute hepatitis A.

BACKGROUND AND AIMS: The Detection of hepatitis A virus (HAV) is important for diagnosis and epidemiological studies of hepatitis A. The polymerase chain reaction (PCR) technique is a sensitive test to detect HAV-RNA in specimens. The aims of the present study were to clarify the detection rate of serum HAV-RNA by PCR and the natural history of HAV viraemia, and to determine the correlation between viraemia and the clinical characteristics in patients with acute hepatitis A. METHODS: Hepatitis A virus RNA was tested in 74 serum samples which were serially collected from 27 patients with acute hepatitis A. A nested reverse transcription (RT)-PCR for HAV-RNA was performed with primer sets located at the VP1 region of the HAV genome and the PCR products were electrophoresed on a 1.5% agarose gel. RESULTS: Hepatitis A virus RNA was found in 18 of 27 (67%) patients with hepatitis A. There were no significant differences between groups positive and negative for HAV-RNA in clinical and laboratory data, except the time interval between clinical onset and initial serum sampling for RT-PCR (10 +/- 6 vs 19 +/- 14 days) and the alanine aminotransferase (ALT) level at initial serum sampling for RT-PCR (1436 +/- 1416 vs 518 +/- 432 IU/L). The mean duration of HAV viraemia was 30 +/- 19 days (range, 5-59 days). The duration of HAV viraemia and duration of abnormal ALT levels from clinical onset were positively correlated (r = 0.685, P = 0.007). CONCLUSION: In conclusion, HAV-RNA RT-PCR is a useful tool to detect HAV viraemia and to study the molecular epidemiology of HAV infection.

Protein-losing enteropathy with an endoscopic feature of 'the watermelon colon'.

A watermelon lesion involving the gastrointestinal tract other than the stomach has not been reported previously except for two cases with rectal involvement and another case with caecal involvement. This report describes a case of protein-losing enteropathy with endoscopic features of 'the watermelon lesion' involving nearly the entire colon. A 57-year-old man presented with a six-month history of generalized oedema and diarrhoea. Laboratory findings included elevated erythrocyte sedimentation rate and decreased serum total protein and albumin. Serum fluorescent anti-nuclear antibody, anti-dsDNA antibody and anti-La antibody were positive. Upper gastrointestinal endoscopy was unremarkable. Colonoscopy showed seven or eight longitudinal reddish stripes along the entire length of the colon and rectum sparing the caecum. Biopsies from the duodenum and colon revealed mildly ectatic lymphatics in the submucosa. Colonic biopsy also exhibited some haemosiderin-laden macrophages in the muscularis mucosae and submucosa. 99mTc-human serum albumin scintigraphy demonstrated a leak into the intestinal lumen. Oral prednisolone therapy was started and his symptoms and signs gradually improved over months. Steroid could be withdrawn after 7 months of therapy, and the patient has remained free of symptoms for 1 year of follow-up after withdrawal of the steroid.

Fructose-sorbitol malabsorption and symptom provocation in irritable bowel syndrome: relationship to enteric hypersensitivity and dysmotility.

BACKGROUND: Fructose-sorbitol (F-S) mixtures can provoke symptoms in irritable bowel syndrome (IBS) patients, and a proportion of IBS patients also have enteric hypersensitivity to distension. We hypothesized, therefore, that sugar malabsorption and fermentation to produce hydrogen gas may provoke symptoms to a greater extent in IBS patients hypersensitive to distension than in those patients without such hypersensitivity. Our aims were therefore to compare, in IBS patients, symptoms and breath hydrogen responses after F-S, on the basis of jejunal sensitivity and jejunal motor function. METHODS: Fifteen female IBS patients (44 +/- 15 years) underwent, on separate occasions, 3-h breath hydrogen analyses after ingesting 10 g lactulose and 25 g fructose with 5 g sorbitol. Jejunal sensitivity and motor function were determined by balloon distension and 24-h manometry studies, respectively. Cumulative symptom scores and breath hydrogen production were analysed on the basis of the presence or absence of jejunal hypersensitivity and dysmotility. RESULTS: Four and seven patients had jejunal hypersensitivity for initial perception and pain, respectively. Eleven, nine, and nine patients had jejunal dysmotility for fasting phase 3, phase 2, and fed motor activity, respectively. Of the patients with symptom provocation after F-S (n = 8 within 3 h, n = 12 within 12 h) or with F-S malabsorption (n = 10), the relative proportion did not differ on the basis of the presence or absence of jejunal hypersensitivity or of motor dysfunction. Symptom scores and hydrogen production also were not different in these subgroups. CONCLUSIONS: Although carbohydrate malabsorption can provoke symptoms in some IBS patients, there is no consistent association between such a phenomenon and the presence of either jejunal hypersensitivity or dysmotility.

Validity of the specialized columnar epithelium as a diagnostic criterion of the short segment Barrett's esophagus.

OBJECTIVE: In the areas where intestinal metaplasia of the stomach is highly prevalent, diagnosing Barrett's esophagus solely by the presence of specialized columnar epithelium in the distal esophagus may lead to many false positive diagnoses. The aim of this study was to test validity of the specialized columnar epithelium as a diagnostic criterion of the short segment Barrett's esophagus in Korea. METHODS: During routine gastroscopy, the length of columnar-lined esophagus was measured and biopsy samples were taken from the mucosa immediately distal to the squamocolumnar junction. Under light microscopy, alcian blue-positive cells were identified. RESULTS: Prevalence of the specialized columnar epithelium in cases without the columnar-lined esophagus and with the short segment columnar-lined esophagus were 57.1% and 31.2%, respectively (P = 0.0281). The specialized columnar epithelium is frequently seen around the cardia in Koreans with or without the columnar-lined esophagus. CONCLUSION: Simple presence of the specialized columnar epithelium is not a valid criterion for a diagnosis of Barrett's esophagus. We propose that both the short segment Barrett's esophagus and the goblet cell metaplasia of the cardia might be grouped together under a title of "the specialized columnar epithelium around the gastroesophageal junction" as a potential preceding condition of adenocarcinoma around the cardia.

Massive bleeding from left colonic arteriovenous malformation in a young patient with ventricular septal defect.

Arteriovenous malformation of the gut is well known to have been an important bleeding focus in past ages. We report a young Korean male patient, who had been known to have ventricular septal defect, presenting massive lower gastrointestinal bleeding from an arteriovenous malformation involving a long segment of the left colon. Angiographic, gross and histologic findings are presented and the literature is reviewed.

Endoscopic treatment in a case with extensive spontaneous intramural dissection of the oesophagus.

Spontaneous intramural dissection of the oesophagus has been recognized as a separate clinical entity between a transmural oesophageal rupture (Boerhaave syndrome) and an oesophageal mucosal tear (Mallory-Weiss syndrome). It is important to differentiate this condition from myocardiac infarction, dissecting aneurysm and other acute surgical conditions. Conservative management is usually thought to be adequate. We report a case of spontaneous intramural oesophageal dissection, in which the symptom of dysphagia did not improve with the conservative management and an endoscopic incision of the septum between true and false lumens using a needle-type diathermy knife was done safely and effectively.

Gastroparesis and small bowel dysmotility in irritable bowel syndrome.

Alterations in both gastric emptying (GE) and small bowel motility have been reported in irritable bowel syndrome (IBS); the relationship, however, between these different measures of upper gut motor function in IBS has not been assessed. The aims of this study were therefore: (1) to compare the prevalence and characteristics of altered small bowel motility in IBS patients with and without delayed GE; and (2) to assess the interrelationships between fasting and postprandial small bowel motility in IBS, accounting for delayed GE. Forty-four IBS patients and 25 healthy controls underwent 24 hr ambulant recording of interdigestive and digestive small bowel motility. On a separate occasion the IBS patients had GE of both solids and liquids measured by a dual-isotope scintigraphic technique. Thirty-nine percent of IBS patients had delayed GE. Patients with normal GE had no interdigestive small bowel abnormalities. However, in patients with delayed GE fasting phase II burst frequency was higher than in controls [median 0.21/hr (IQR 0.15-0.34) vs 0.06/hr (0-0,16), P = 0.004]. Postprandially, abnormal phase III-like activity was higher in diarrhea-predominant IBS patients (0-0.08/hr vs 0/hr, P = 0.01), than in patients with normal GE or controls. Furthermore, IBS patients with delayed GE did not have the normal correlation between fasting and postprandial motor parameters (percentage occurrence of clustered contractions, postprandial pattern duration vs preceding MMC cycle length). In conclusion, small bowel motor dysfunction occurs more frequently in IBS patients with concomitant gastroparesis than in patients with normal GE. These findings provide further evidence that a neuropathic process may contribute to the pathogenesis of IBS in a subgroup of IBS patients.

Effects of oral cisapride on small bowel motility in irritable bowel syndrome.

BACKGROUND: Cisapride has been reported to improve symptoms in patients with constipation-predominant irritable bowel syndrome. AIM: To compare the effects of a 24-h oral dose regimen of cisapride on interdigestive and post-prandial small bowel motor activity in irritable bowel syndrome patients with predominant constipation, irritable bowel syndrome patients with predominant diarrhoea and healthy subjects. METHODS: In 12 irritable bowel syndrome patients (11 females, aged 44 +/- 12 years)--constipation-predominant (irritable bowel syndrome-C, n = 5) and diarrhoea-predominant (irritable bowel syndrome-D, n = 7)--and six healthy subjects, small bowel motor activity was continuously recorded using an ambulatory technique over a 48-h period. Subjects received, in single-blind fashion, placebo tablets q.d.s. in the first 24 h then cisapride 10 mg q.d.s. in the second 24 h. Additional control groups were 13 healthy subjects (eight females, aged 39 +/- 13 years) and 10 irritable bowel syndrome patients (10 females, aged 49 +/- 14 years) who were studied in identical fashion but who did not receive cisapride. RESULTS: Cisapride increased migrating motor complex phase 2 motility index in both irritable bowel syndrome-D (P < 0.01) and irritable bowel syndrome-C (P < 0.05) patients, as well as in healthy subjects (P < 0.01). An increase in fasting discrete clustered contractions occurred in irritable bowel syndrome-D patients (P < 0.001) and in healthy subjects (P < 0.01), but not in irritable bowel syndrome-C patients; the proportion of discrete clustered contractions that were propagated, however, increased only in irritable bowel syndrome-D patients (P < 0.001). In addition, cisapride resulted in an increase in post-prandial motility index in irritable bowel syndrome patients (P < 0.05). Such motor alterations were not observed during the 48-h recording period in the healthy or irritable bowel syndrome patient control groups who did not receive cisapride. CONCLUSIONS: Oral cisapride influences interdigestive and post-prandial small bowel motor activity in both irritable bowel syndrome patients and healthy subjects; the effects of cisapride may be more marked in patients with predominant diarrhoea than in patients with predominant constipation.

Small bowel dysmotility in patients with postcholecystectomy sphincter of Oddi dysfunction.

Postcholecystectomy patients (N = 27) with severe recurrent biliary-like pain who had no evidence of organic disease were subdivided into those with and those without objective evidence of sphincter of Oddi dysfunction (SOD) based on two separate criteria: (1) clinical criteria-elevated liver function tests and/or amylase with pain, and/or a dilated bile duct, and/or delayed drainage at ERCP (N = 14, SOD classes I and II); and (2) abnormal biliary manometry (N = 19). Prolonged (24-48 hr) ambulant recording of duodenojejunal motor activity was performed in all patients and interdigestive small bowel motor activity compared between patient subgroups and a healthy control group. Phase II motor abnormality was more frequent in patients with, compared to those without, objective clinical criteria of SOD (7/14 vs 0/13, P = 0.003). Phase III abnormality also tended to be more frequent in these patients (7/14 vs 2/13, P = 0.06). In addition, both phase III (P = 0.03) and phase II (P = 0.03) motility index (MI) was higher in patients with sphincter dyskinesia compared to controls; phase II MI was also higher in patients with sphincter stenosis (P = 0.005). Disturbances of small bowel interdigestive motor activity are more prevalent in postcholecystectomy patients with, compared to those without, objective evidence of SOD, and especially in patients with SO dyskinesia. Postcholecystectomy SOD in some patients may thus represent a component of a more generalized intestinal motor disorder.