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Background Previous studies showed that 5 μg of ramosetron, a serotonin (5-hydroxytryptamine: 5- HT)-3 receptor antagonist, is only effective in male patients with irritable bowel syndrome ( IBS) with diarrhea ( IBS-D). We hypothesized that either dose 1.25, 2.5, or 5 μg of ramosetron would be effective in female patients with IBS-D. Methods This randomized, double-blind, placebo-controlled, phase II dose-finding exploratory trial included 409 female outpatients with IBS-D treated in Japan. They were administered oral placebo ( n=102), or 1.25 μg ( n=104), 2.5 μg ( n=104), or 5 μg ( n=99) of ramosetron once daily for 12 weeks after a 1-week baseline period. The primary endpoint was monthly responder rates of global improvement of IBS symptoms in the first month. Secondary endpoints included global improvement in the other months, abdominal pain/discomfort, weekly mean changes in the Bristol Stool Form Scale ( BSFS), and IBS- QOL. Key Results Middle dose (2.5 μg) of ramosetron significantly improved abdominal pain/discomfort at second month (62.5%, P=.002), third month (60.6%, P=.005), and the last evaluation point (63.5%, P=.002) and weekly BSFS ( P<.05) except at Week 8, 11, and 12 than placebo. IBS- QOL did not change. Ramosetron induced more constipation than placebo. Conclusions & Inferences The trial suggested that 2.5 μg of ramosetron is the most effective and least harmful option for treating female patients with IBS-D (Clinicaltrials.gov ID: NCT01274000). [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease-related diseases, such as Barrett's esophagus and adenocarcinoma of the esophagogastric junction (AEGJ), are believed to occur less frequently in Asia than in Western countries. However, the number of reported cases is increasing, yet little is known regarding the epidemiology of AEGJ in Japan. The primary study aim is to investigate the clinicoepidemiological characteristics of AEGJ. The secondary aim is to identify factors associated with it. In the 6.5 years between January 2008 and June 2014, we reviewed 88,199 esophagogastroduodenoscopy (EGD) reports and associated medical records (Study 1). We conducted a case-control study to identify factors associated with AEGJ (Study 2). Control subjects were randomly selected and age and sex matched from among subjects who underwent EGD during medical evaluations. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using an unconditional logistic regression method. During the study period, 83 patients with AEGJ (72 men and 11 women; mean age 68 years) were diagnosed. Six cases were Siewert type I and 77 were type II. The incidence rate of AEGJ was 0.6-1.7/100,000 person-years. Compared with the 101 control subjects, obesity (body mass index - 25 kg/m2; [OR = 2.82; 95% CI: 1.13-7.01]) was associated with AEGJ. The incidence rate of AEGJ is lower in Japan than inWestern countries, but associated factors similar to those in Western patients were detected, including obesity, a hiatal hernia, smoking, and the male sex. [ABSTRACT FROM AUTHOR]

Background Splenic vein ligation may result in sinistral (left-sided) portal hypertension and gastrointestinal haemorrhage. The aim of this study was to analyse the pathogenesis of sinistral portal hypertension following splenic vein ligation in pancreaticoduodenectomy. Methods Patients who underwent pancreaticoduodenectomy for pancreatic cancer between January 2005 and December 2012 were included in this retrospective study. The venous flow pattern from the spleen and splenic hypertrophy were examined after surgery. Results Of 103 patients who underwent pancreaticoduodenectomy with portal vein resection, 43 had splenic vein ligation. There were two predominant venous flow patterns from the spleen. In the varicose route (27 patients), flow from the spleen passed to colonic varices and/or other varicose veins. In the non-varicose route, flow from the spleen passed through a splenocolonic collateral (14 patients) or a spontaneous splenorenal shunt (2 patients). The varicose route was associated with significantly greater splenic hypertrophy than the non-varicose route (median splenic hypertrophy ratio 1·52 versus 0·94; P < 0·001). All patients with the varicose route had colonic varices, and none had a right colic marginal vein at the hepatic flexure. Conclusion Pancreaticoduodenectomy with splenic vein ligation may lead to sinistral portal hypertension. To avoid the development of varices, it is important to preserve the right colic marginal vein. Reconstruction of the splenic vein should be considered if the right colic marginal vein is divided. [ABSTRACT FROM AUTHOR]

Background: This long-term 48-week study of acotiamide was carried out to investigate the efficacy, safety and administration pattern in patients with functional dyspepsia (FD). Methods: This was a multicenter, open-label, single-arm, long-term phase III study in which patients with FD were given acotiamide, 100 mg t.i.d., for 48 weeks. The two major efficacy endpoints were global overall treatment efficacy (OTE) and the elimination rate of three cardinal symptoms (i.e. postprandial fullness, early satiation and upper abdominal bloating), which were evaluated weekly and daily by the patients, respectively. The long-term administration patterns were investigated by following the patients based on cessation and readministration criteria. Results: Efficacy was analyzed in 405 patients. The OTE improvement rate was 26.1% at week 1 and increased with time. It was 60.6% at week 8 and subsequently maintained. Similarly, the symptom elimination rate increased up to week 8. Many patients who met the cessation criterion achieved remission of FD symptoms after experiencing dose interruption and readministration. The incidence rate of adverse drug reactions was 11.5% and most of the adverse drug reactions were mild in severity except increased ALT in 1 patient. Conclusion: FD symptoms were controlled by intermittent administration of acotiamide even in patients with relapsing FD. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Peritoneal venous shunts (PVSs) are widely used for palliating symptoms of refractory malignant ascites and are recognized as one of the practical methods. However, reliable clinical data are insufficient because most previous reports have been small studies from single centers. We conducted a retrospective, multicenter study to evaluate the safety and efficacy of radiologically placed PVSs in patients with malignant refractory ascites. Methods: A total of 133 patients with malignant ascites refractory to medical therapies were evaluated for patient characteristics, technical success, efficacy, survival times, adverse events, and changes in laboratory data. Results: PVSs were successfully placed in all patients and were effective (i.e., improvement of ascites symptoms lasting 7 days or more) in 110 (82.7%). The median duration of symptom palliation was 26 days and median survival time was 41 days. The most frequent adverse event was PVS dysfunction, which occurred in 60 (45.1%) patients, among whom function was recovered with an additional minimally invasive procedure in 9. Abnormalities in coagulation (subclinical disseminated intravascular coagulation) occurred in 37 (27.8%) patients, although only 7 (5.3%) developed clinical disseminated intravascular coagulation. Other major adverse events were gastrointestinal bleeding (9.8%), sepsis (3.8%), and acute heart failure (3.0%). PVS was least effective in patients with elevated serum creatinine, bloody ascites, or gynecologic tumor. Conclusions: Radiological PVS is a technically feasible and effective method for palliating the symptoms from refractory malignant ascites, but preoperative evaluation and monitoring the postprocedural complications are mandatory to preclude severe adverse events after PVS. [ABSTRACT FROM AUTHOR]

The purpose of the current study was to evaluate the incidence and course of upper-extremity deep vein thrombosis (UEDVT) related to an implanted central venous port (CV-port) system in cancer patients. From July 2007 to July 2008, 92 consecutive patients who underwent implantation of a CV-port for chemotherapy for colorectal cancer were prospectively enrolled in the study. All patients were examined at prescribed intervals by ultrasonography (US) to estimate the incidence of catheter-related venous thrombosis. We categorised ultrasound diagnosis into three types: Type 0, no thrombus; Type I, thrombi around catheter without obstruction of venous flow; Type II: thrombi with obstruction of venous flow. Upon initial ultrasound examination, 25 cases (27%) were categorised as Type 0, 64 (70%) as Type I and III (3%) as Type II. Of the 64 Type-I cases, 4 cases worsened to Type II within a month, and 3 others (including 1 patient who developed pulmonary embolism) became Type II after 1 month. Of the other Type-I cases, 12 cases improved to Type 0 and 45 cases remained Type I. All 10 patients categorised as Type II underwent anticoagulant therapy and resumed their chemotherapy without exacerbations of thrombosis. In cancer patients undergoing long-term chemotherapy, there is an unexpectedly high prevalence of catheter-related UEDVT, which can be detected by ultrasound at an early stage after implantation of a CV-port. Given that cancer patients with UEDVT may have worse outcomes than those without, clinicians should consider careful monitoring for UEDVT and introducing anticoagulant therapy. [ABSTRACT FROM AUTHOR]

Objective Preoperative use of emission tomography with18F-fluorodeoxyglucose (FDG-PET) in patients with primary colorectal cancer remains controversial. This study evaluated the additional value of FDG-PET in comparison with routine multidetector row computed tomography (MDCT) in patients with primary colorectal cancer. Method Retrospective analysis was performed in 65 patients with colorectal cancer who underwent whole-body FDG-PET. Results of FDG-PET were compared with routine preoperative evaluation by MDCT regarding detection of primary tumour, lymph node involvement and distant metastases. All images were evaluated before surgery. Results Tumour detection rate was 100% (63/63) for MDCT and 98% (62/63) for FDG-PET. Lymph node involvement was pathologically confirmed in 35 patients. MDCT and FDG-PET displayed sensitivities of 89% (31/35; 95% CI: 73–97%) and 43% (15/35; 95% CI: 26–61%) and specificities of 52% (11/21; 95% CI: 30–74%) and 95% (20/21; 95% CI: 76–100%), respectively. Liver metastases were present in 22 patients. MDCT and FDG-PET showed accuracies of 98% (64/65; 95% CI: 92–100%) and 97% (63/65; 95% CI: 89–100%), respectively. FDG-PET detected additional extrahepatic metastatic lesions and affected treatment plan compared with MDCT in 10 patients. Conclusion Preoperative FDG-PET is not superior to MDCT for detection of primary tumour, lymph node involvement or liver metastases, but may have potential clinical value in patients with advanced colorectal cancer by detecting extrahepatic distant metastases. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Serotonin type 3 (5-HT3) receptor antagonist alosetron hydrochloride is indicated for women with chronic, severe diarrhea-predominant IBS who have not responded adequately to conventional therapy. However, whether or not the therapeutic efficacy of 5-HT3 receptor antagonists has gender difference is uncertain. Methods: A double-blind, placebo-controlled, parallel-group, comparative study was conducted to evaluate the effect of novel 5-HT3 receptor antagonist, ramosetron hydrochloride, in male and female patients with diarrhea-predominant IBS. 418 subjects were randomized (109 subjects: placebo, 105 subjects: 1 μg, 103 subjects: 5 μg, and 101 subjects: 10 μg) and administered the study drug once daily. Results: The monthly responder rates of ‘Patient-reported global assessment of relief of irritable bowel syndrome symptoms’ in the 5- and 10-μg ramosetron hydrochloride-administered groups were higher than the placebo group (26.92, 42.57, and 43.01% for placebo, 5 and 10 μg). Moreover, the difference of the responder rate in comparison with the placebo group was similar in males and females. As for safety, there was tolerability at doses up to 10 μg. Conclusion: Ramosetron is an effective and well-tolerated treatment not only for female IBS patients but also for male patients. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We recently reported an improved method to induce colitis by 2,4,6-trinitrobenzene sulfonic acid. This method enabled us to induce colitis at appropriate regions. This study aimed to investigate the regional differences on the healing process of colitis in rats. Colitis was induced at the proximal, middle or distal colon. On Day 10, the size of colitis was large in the order of the middle, distal and proximal colon. Colitis of the proximal colon healed more rapidly than that of the middle colon. Prostaglandin E2 generation in the normal colonic mucosa was measured. Prostaglandin E2 generation correlated with sizes of colitis among three regions. It was found that there was the regional difference on the healing process of the colitis and prostaglandin E2 generation may show the different protective integrity of the colonic mucosa from the fact that higher prostaglandin E2 generation showed larger colitis size. [ABSTRACT FROM AUTHOR]

After the screening of microorganism culture, the culture of Propionibacterium freudenreichii ET-3 in the milk whey (milk whey culture) was found to stimulate the growth of our own Bifidobacteria in the colon but not the growth of other microorganisms. One of the active substances was identified as 1,4-dihydroxy-2-naphthoic acid (DHNA). In healthy volunteers, the ingestion containing milk whey culture significantly increased the population of Bifidobacteria to total fecal bacterium. In the TNBS-induced colitis model of rats, milk whey culture significantly accelerated the healing of the colitis in a dose-dependent manner. It has been reported that DHNA inhibited the lymphocyte infiltration through reduction of MAdCAM-1 in DSS colitis model of mice and that the ingestion of milk whey culture was effective in the treatment of ulcerative colitis in human pilot study. These findings suggest that milk whey culture is a useful prebiotic for the therapy of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

We describe a rare case of hepatoid carcinoma of the pancreas with production of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP). The patient was a 49-year-old woman admitted because of high serum levels of PIVKA-II (1.63 AU/ml) and AFP (623 ng/ml) and abnormal ultrasonographic findings of the pancreas, found incidentally at medical checkup. Both ultrasonography and computed tomography showed swelling of the pancreas with small areas of low density, but no hepatic lesions. The serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were not increased. A PIVKA-II and AFP-producing pancreatic cancer was strongly suspected, and total pancreatectomy was performed. Pathological examination showed that the tumor cells were arranged in trabecular and solid patterns with bile production, and were immunohistochemically positive for PIVKA-II and AFP, resembling hepatocellular carcinoma cells. The tumor was diagnosed as hepatoid carcinoma of the pancreas, and the patient has survived 48 months after initial diagnosis. It is important that hepatoid carcinoma be considered as a possible malignant tumor of the pancreas, and simultaneous measurement of the serum levels of AFP and PIVKA-II will enable earlier diagnosis. This is the first report describing hepatoid carcinoma of the pancreas producing PIVKA-II. [ABSTRACT FROM AUTHOR]

Background: To define radiographically simple prolapse or intussusception in cases of distal migration of duodenal tumors.Methods: In one pyloric and four duodenal tumors showing distal migration, the findings of gastrointestinal contrast examinations were retrospectively evaluated in relation to CT and operative findings.Results: All lesions were intraluminal growing and well demarcated, and they included two carcinoids, a papillary adenoma, a Brunner's gland adenoma, and a hyperplastic polyp. All lesions were accompanied by long mucosal stalks, and, in three, folding deformity of the proximal jejunum was observed. CT showed no target signs except for one with gastroduodenal intussusception. Intussusception was not verified surgically in any cases.Conclusion: Distal migration of duodenal tumors can occur as the result of mucosal elongation and slipping. Duodenojejunal intussusception is not necessarily associated with that phenomenon. [ABSTRACT FROM AUTHOR]

Background: To investigate nontumorous focal enhancement (FE) with computed tomographic hepatic arteriography (CTHA) and perfusion defect (PD) with computed tomographic arterial portography (CTAP) in pericystic liver tissue.Methods: Incidence, shape, and size of nontumorous FE on CTHA and PD on CTAP were examined in 100 consecutive noncirrhotic and 100 consecutive cirrhotic patients.Results: FE was observed on CTHA in 77 noncirrhotic and 61 cirrhotic patients, whereas PD was observed on CTAP in 50 noncirrhotic and 51 cirrhotic patients. When both findings were visualized in both CT studies, the shape of the FE on CTHA was similar to the overlapping PD on CTAP in 81% of patients but was larger in 92% of patients.Conclusions: FE on CTHA and PD on CTAP are frequently noted in pericystic liver tissue. The size of FE on CTHA is often larger than PD on CTAP, although the shapes are generally the same. Size discrepancy suggests the presence of both portal supply and splanchnic venous drainage. [ABSTRACT FROM AUTHOR]

We describe an extremely rare case of granulocytic sarcoma of the porta hepatis causing obstructive jaundice. The patient was an 84-year-old man admitted because of obstructive jaundice. Ultrasonography (US) and computed tomography (CT) scanning of the abdomen disclosed a mass about 2.5 cm in diameter near the neck of the gallbladder, and thickening of the gallbladder wall. Based on these findings, gallbladder carcinoma was suspected. After endoscopic retrograde biliary drainage (ERBD) was performed, the jaundice resolved. However, blast cells were detected in the peripheral blood 51 days after admission, and laboratory studies disclosed acute myelocytic leukemia (AML: French-American-British [FAB] type M0). We treated him conservatively, with antibiotics and ERBD but he died of disseminated intravascular coagulation. Autopsy showed that the suspected gallbladder carcinoma was actually a granulocytic sarcoma arising in association with AML and causing obstructive jaundice. The largest tumor involved the porta hepatis. It should be kept in mind that granuloctyic sarcoma is a possible cause of obstructive jaundice, even in patients with no evidence of AML. [ABSTRACT FROM AUTHOR]

We examined the correlation between the incidence of Crohn disease and dietary change in a relatively homogeneous Japanese population. The incidence and daily intake of each dietary component were compared annually from 1966 to 1985. The univariate analysis showed that the increased incidence of Crohn disease was strongly (P < 0.001) correlated with increased dietary intake of total fat (r = 0.919), animal fat (r = 0.880), n-6 polyunsaturated fatty acids (r = 0.883), animal protein (r = 0.908), milk protein (r = 0.924), and the ratio of n-6 to n-3 fatty acid intake (r = 0.792). It was less correlated with intake of total protein (r = 0.482, P < 0.05), was not correlated with intake of fish protein (r = 0.055, P > 0.1), and was inversely correlated with intake of vegetable protein (r = -0.941, P < 0.001). The multivariate analysis showed that increased intake of animal protein was the strongest independent factor with a weaker second factor, an increased ratio of n-6 to n-3 polyunsaturated fatty acids. The present study in association with reported clinical studies suggests that increased dietary intake of animal protein and n-6 polyunsaturated fatty acids with less n-3 polyunsaturated fatty acids may contribute to the development of Crohn disease. (c) 1996 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

During attempted oesophageal stent placement in a patient with cervical oesophageal cancer in whom swallowing of even saliva was impossible, transoral access to the cervical oesophagus was unsuccessful. Under ultrasound and fluoroscopy guidance, percutaneous gastric puncture was performed, and using an angiographic catheter and guidewire, access to the oesophagus by a retrograde transgastric route was successfully achieved. The obstructed segment of the oesophagus was traversed. It was then possible to pull the guidewire through the mouth and place an oesophageal stent via an antegrade approach. [ABSTRACT FROM AUTHOR]

A 51-year-old man with posthepatitis cirrhosis underwent a transjugular intrahepatic portosystemic shunt (TIPS) for bleeding of recurrent esophageal varices. The patient had a coexisting, spontaneous, splenorenal shunt. He subsequently developed hepatic encephalopathy, presumably due to excessive portosystemic shunting. Since medical management resulted in no significant improvement, the splenorenal shunt was embolized from the jugular vein approach via renal vein access during temporary balloon occlusion. Within a few days, the patient's hepatic encephalopathy resolved. Twelve months later the patient showed no recurrence of encephalopathy and had maintained a patent TIPS. [ABSTRACT FROM AUTHOR]

Background Acotiamide is a selective acetylcholinesterase inhibitor and enhances the actions of cholinergic neurons localized in the stomach. Methods The present two studies were conducted to examine the optimal dosage of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia (FD) in Japan. Key Results The improvement rate of ‘subjects global assessment of overall treatment efficacy (OTE)’ at the final evaluation was approximately 10% higher in the acotiamide 100 mg group than that in the placebo group with good reproducibility though there was no significant differences at primary endpoint. The elimination rate of postprandial fullness in the acotiamide 100 mg group was significantly higher compared to placebo group. In addition, the post hoc analysis showed that in patients whose main complaints are meal-related symptoms such as postprandial fullness, upper abdominal bloating and/or early satiety, the improvement rate of ‘OTE’ at final evaluation in acotiamide 100 mg group was significantly superior to that in the placebo group. Conclusions & Inferences These results suggest that acotiamide possesses efficacy on FD and more specifically its meal-related symptoms of FD. [ABSTRACT FROM AUTHOR]