Clinical characteristics and associated factors of Japanese patients with adenocarcinoma of the esophagogastric junction: a multicenter clinicoepidemiological study.

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 in Western countries, but associated factors similar to those in Western patients were detected, including obesity, a hiatal hernia, smoking, and the male sex.

Optimal dose of ramosetron in female patients with irritable bowel syndrome with diarrhea: A randomized, placebo-controlled phase II study.

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).

Sinistral portal hypertension after pancreaticoduodenectomy with splenic vein ligation.

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.

A long-term study of acotiamide in patients with functional dyspepsia: results from an open-label phase III trial in Japan on efficacy, safety and pattern of administration.

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.

Upper-extremity deep vein thrombosis related to central venous port systems implanted in cancer patients.

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.

Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia - 100 mg t.i.d. is an optimal dosage.

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.

Comparison of preoperative whole-body positron emission tomography with MDCT in patients with primary colorectal cancer.

OBJECTIVE: Preoperative use of emission tomography with(18)F-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.

A phase II trial of the novel serotonin type 3 receptor antagonist ramosetron in Japanese male and female patients with diarrhea-predominant irritable bowel syndrome.

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 microg, 103 subjects: 5 microg, and 101 subjects: 10 microg) 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-microg ramosetron hydrochloride-administered groups were higher than the placebo group (26.92, 42.57, and 43.01% for placebo, 5 and 10 microg). 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 microg. CONCLUSION: Ramosetron is an effective and well-tolerated treatment not only for female IBS patients but also for male patients.

Regional difference in the healing process of colitis induced by 2,4,6-trinitrobenzene sulfonic acid in rats.

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 E(2) generation in the normal colonic mucosa was measured. Prostaglandin E(2) 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 E(2) generation may show the different protective integrity of the colonic mucosa from the fact that higher prostaglandin E(2) generation showed larger colitis size.

Characteristic of milk whey culture with Propionibacterium freudenreichii ET-3 and its application to the inflammatory bowel disease therapy.

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.

Cervical oesophageal stent placement via a retrograde transgastric route.

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.

Mediastinal abscess successfully treated by percutaneous drainage using a unified CT and fluoroscopy system.

We report two patients with mediastinal abscess developing after surgery for oesophageal cancer who were treated by percutaneous drainage using a unified CT and angiography system, which allows both CT and fluoroscopy to be conducted with the patient on the same bed. Fine needle puncture is performed under CT guidance and this needle is used as a tandem for insertion of the drainage needle under fluoroscopic guidance, making safe puncture possible whilst confirming the position of the needle tip. Moreover, contrast medium can be injected from the drainage tube, allowing the extent of the abscess cavity to be determined by fluoroscopy and CT, thereby making accurate drainage possible.

Severe obstruction of the superior vena cava caused by tumor invasion. Recanalization using a PTFE-covered Z stent.

Bare stents are commonly used for the treatment of malignant vena cava stenoses. However, the therapeutic effect of treatment using bare stents for cases with intraluminal tumor invasion is not satisfactory. We report a case with severe obstruction of the superior vena cava caused by tumor invasion of mediastinal lymph node metastases from colon cancer, which was successfully treated by the recanalization of superior vena cava using a polytetrafluoroethylene-covered Z stent. The covered stent could not be fully expanded at first, and re-obstruction developed at the stented site due to thrombus formation soon after stenting. So, the additional balloon dilatation made the stent expend fully on another day of stenting. After the balloon dilatation blood flow improved immediately and the clinical symptoms associated with the superior vena cava obstruction resolved. Thereafter no symptomatic recurrence has been observed in 12 months of follow-up period.

Distal migration of duodenal tumors: simple prolapse or intussusception?

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.

Right gastric artery embolization to prevent acute gastric mucosal lesions in patients undergoing repeat hepatic arterial infusion chemotherapy.

PURPOSE: The purpose of the study was to investigate the technical outcome and clinical effect of right gastric artery (RGA) embolization to prevent acute gastric mucosal lesions caused by influx of anticancer agents into the RGA in patients undergoing repeat hepatic arterial infusion chemotherapy (HAIC). MATERIALS AND METHODS: In 217 patients with malignant hepatic tumors, we attempted RGA embolization with use of metallic coils and/or a mixture of n-butyl cyanoacrylate (n-BCA) and iodized oil, along with the embolization of the gastroduodenal artery. After this procedure, an infusion catheter was placed radiologically and HAIC was performed. We then evaluated the technical outcome and clinical effect of RGA embolization. RESULTS: RGA embolization was technically successful in 201 of 217 patients (93%). Major complications--nausea, epigastric pain, and fever--were noted in 12%, 4%, and 2% of successful cases, respectively, and were treated conservatively. Recanalization occurred in 4% (nine of 201) of the patients. Eventually, sufficient RGA embolization was achieved in 192 patients. The incidence of acute gastric mucosal lesions confirmed endoscopically was only 3% (five of 192) in patients with sufficient RGA embolization, whereas it was 36% (nine of 25) in patients without sufficient RGA embolization, with a significant difference (P <.01). CONCLUSION: RGA embolization is a highly feasible procedure that can reduce the incidence of acute gastric mucosal lesions associated with HAIC.

Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor necrosis factor-alpha for Crohn's disease in Japan: evaluation by rapid turnover proteins, and radiologic and endoscopic findings.

BACKGROUND: Several studies have reported that the chimeric monoclonal antibody to tumor necrosis factor (TNF)-alpha (Infliximab) is extremely valuable in the treatment of Crohn's disease. The aim of this study was to clarify the efficacy of this treatment in Japanese patients with Crohn's disease. METHODS: A 12-week multicenter, open trial of Infliximab was carried out and involved 25 patients with moderate to severe Crohn's disease who were resistant to conventional treatment. Patients received a single 2-h intravenous infusion of Infliximab at a dose of 1, 3, 5 or 10 mg/kg bodyweight. Clinical evaluation of this treatment response was defined as a reduction in the index of the inflammatory bowel disease (IOIBD) and of the Crohn's disease activity index scores (CDAI), and in serum levels of C-reactive protein (CRP) at 2, 4, 8 and 12 weeks, and as an increase in serum levels of rapid turnover proteins as well as improvement of radiologic and endoscopic findings at 4 weeks. RESULTS: The IOIBD score was reduced after 4 weeks in 66.7% of the group receiving 1 mg/kg Infliximab, 71.4% in the group receiving 3 mg/kg, 80.0% in the group receiving 5 mg/kg, and 85.7% in the group receiving 10 mg/kg. Improvement was better maintained over 12 weeks in the 5 and 10 mg/kg groups compared with the 1 and 3 mg/kg groups. Similar results were obtained for the CDAI scores. Serum levels of rapid turnover proteins significantly increased to within the normal ranges after infusion in all groups. Seven of the 11 (63.6%) patients evaluated showed improvement of radiologic and endoscopic findings. CONCLUSIONS: A single infusion of Infliximab was effective for the treatment of Japanese patients with Crohn's disease. Serum rapid turnover proteins reflected the clinical response to antibody for TNF-alpha well.