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Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p

Carbon 11-choline positron emission tomography/computed tomography (11C-choline PET/CT) and subsequent local therapy for oligometastatic prostate cancer have been reported to be effective, but their effectiveness in castration-resistant prostate cancer (CRPC) remains unclear. Here, we evaluated the findings of 11C-choline PET/CT in CRPC patients and the efficacy of local treatments in correspondence of the pathologic choline uptake. We collected 12 cases of CRPC patients who underwent 11C-choline PET/CT between 2014 and 2016. The outcomes assessed included age, the prostate-specific antigen (PSA) value, the findings of 11C-choline PET/CT, the subsequent treatments, the PSA response following the treatments, and the progression-free survival (PFS). Seven of 12 cases (median PSA, 3.29 ng/mL) had local prostate cancer and/or one or two metastatic lesions detected by the choline PET/CT. These localized lesions were treated with radiotherapy or lymphadenectomy. PSA decreased in all the seven cases and median PSA response was 86% (range, 23–100%). Median PFS was 8.5 months (range, 2.8–25.3 months). The other five cases (median PSA, 7.41 ng/mL) had multiple metastases and systemic therapies were continued in those cases. 11C-choline PET/CT and the correspondent local treatments may play an important role in the treatment sequence of CRPC in selected patients.

Bladder tumors can be broadly divided into those of epithelial or mesodermal origin. Furthermore, 90% of bladder tumors arise from the epithelium of the bladder, and most cases of bladder cancer are histologically urothelial carcinomas. Mesodermal tumors are exceptionally rare and often benign. Of the mesenchymal tumors of the bladder, leiomyomas are the most common, and their prognosis depends on their histology. The present report describes a case of submucosal urothelial cancer in a patient with no past history of bladder cancer. To the best of our knowledge, there are no previous reports of urothelial cancer occurring in the submucosa. The present report was the first to document a case of submucosal urothelial cancer, whose diagnosis was made possible only by transurethral resection of bladder tumor. Although the precise pathomechanism of the present case was unclear, two hypotheses were considered. First, the urothelial cancer developed within a diverticulum, then the entrance of the diverticulum closed, sealing in the cancer. Second, the bladder cancer stemmed from aberrant urothelium in the submucosal tissue. If submucosal urothelial bladder carcinoma develops within the diverticular environment, its prognosis can be as poor as that of invasive bladder cancer due to the features of the diverticular environment. Even in a patient with a submucosal bladder tumor but no previous history of bladder cancer, bladder cancer should be considered in the differential diagnosis.

The present study aimed to examine the safety of a gemcitabine and cisplatin (GC) combination chemotherapy regimen with short hydration for the treatment of urothelial cancer administered on the same day (same day regimen). Patients with locally advanced or metastatic urothelial cancer received the same-day GC regimen with short hydration every 4 weeks, and their serum creatinine (Cr) level was measured to assess renal function using linear mixed model analysis. A total of 20 patients receiving the same-day regimen exhibited no significant change in their serum Cr level; nor was there any significant change in the serum Cr level between patients who received the same day regimen and those who received the drugs on different days. The present study demonstrated that the same-day regimen was safe for patients with urothelial cancer.

Central nervous system (CNS) metastasis of urothelial carcinoma (UC) is rare. Immune checkpoint inhibitors, which were developed for the treatment of patients with advanced cancer, have limited efficacy against CNS metastases due to the unique immune microenvironment of the brain. The brain is an immune-privileged organ and is protected by the blood-brain barrier. However, the management of CNS metastases of UC is crucial to improving the prognosis. The present report describes two cases of cerebral metastasis occurring in the context of systemic disease control using immunotherapy. To the best of our knowledge, the present report is the first to describe a CNS metastasis during remission induced by immunotherapy.

Collecting duct carcinoma (CDC) is a rare, extremely aggressive form of renal cancer. Recently, immune checkpoint inhibitors (ICI), anti-programmed death-1 (PD-1) antibody, and anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody were approved for use against metastatic renal cell carcinoma. We herein described two cases of metastatic renal collecting duct carcinoma treated with a combination immunotherapy consisting of nivolumab and ipilimumab. In the first case, which included a bone metastasis, the best response achieved was stable disease (SD) for one year. In the second case, which was accompanied by a lung metastasis, the best response achieved was a partial response. The outcome of these cases suggested that the combination of nivolumab and ipilimumab is effective against renal collecting duct carcinoma.

Three cases with a long-term follow-up of myopic macular neovascularization (MNV) and MNV-related macular atrophy are shown. The progression of other lesions of myopic maculopathy is also demonstrated.

Background and study aims We developed a new reporting system based on structured data entry, which selectively extracts only endoscopic findings from endoscopists’ oral statements and automatically inputs them into appropriate columns in real time during endoscopic procedures. Methods We compared the time for endoscopic procedures and report preparation (ER time) by using an esophagogastroduodenoscopy simulator in three groups: one preparing reports using a mouse after endoscopic procedures (CE group); a second group preparing reports by using voice alone during endoscopic procedures (SR group); and the final group preparing reports by operating the system with a foot switch and inputting findings using voice during endoscopic procedures (SR + FS group). For the SR and SR + FS groups, we identified the recognition rates of the speech recognition system. Results Mean ER times for cases with three findings each were 162, 130 and 119 seconds in the CE, SR and SR + FS groups, respectively. The mean ER times for cases with six findings each were 220, 144 and 128 seconds, respectively. The times in the SR and SR + FS groups were significantly shorter than that in the CE group (P Conclusion Our reporting system was demonstrated to allow an endoscopist to efficiently complete the report in real time during endoscopic procedures.

Discovery of a high-risk group for pancreatic cancer is important for prevention of pancreatic cancer. The present study was conducted as a nested case-control study including 170 pancreatic cancer cases and 340 matched controls of our population-based cohort study involving 30 239 subjects who answered a baseline questionnaire and supplied blood samples. Twelve targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were calculated using conditional logistic regression models. Statistically significant P-value was defined as P < .05. Increasing 1,5-anhydro-d-glucitol (1,5-AG) levels were associated with a decreasing trend in pancreatic cancer risk (OR of quartile 4 [Q4], 0.50; 95% CI, 0.27-0.93; P = .02). Increasing methionine levels were also associated with an increasing trend of pancreatic cancer risk (OR of Q4, 1.79; 95% CI, 0.94-3.40: P = .03). Additional adjustment for potential confounders attenuated the observed associations of 1,5-AG and methionine (P for trend = .06 and .07, respectively). Comparing subjects diagnosed in the first 0-6 years, higher levels of 1,5-AG, asparagine, tyrosine and uric acid showed a decreasing trend for pancreatic cancer risk (P for trend = .04, .04, .04 and .02, respectively), even after adjustment for potential confounders. We found that the 12 target metabolites were not associated with pancreatic cancer risk. However, metabolic changes in the subjects diagnosed in the first 0-6 years showed a similar tendency to our previous reports. These results might suggest that these metabolites are useful for early detection but not for prediction of pancreatic cancer.

Background The feasibility and safety of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms extending to the cervical esophagus currently remain unknown because of the limited number of cases. We aimed to clarify the clinical outcomes of these cases. Methods This was a case series study conducted at a single institution that enrolled 26 consecutive patients with superficial esophageal neoplasms extending to the cervical esophagus who underwent ESD between July 2003 and December 2015. Results En bloc and complete resection rates were both 100 % and no major intraprocedural complications occurred. Thirteen patients were treated with prophylactic steroid therapy. The incidence of postoperative stricture in patients with a circumferential mucosal defect of more than three-quarters was 72.7 %. Four patients required entire circumferential resection, with perforation occurring after endoscopic balloon dilation (EBD) in two and EBD being required for more than 1 year in the other two. Conclusions ESD including the cervical esophagus is technically feasible. Circumferential resection may cause refractory postoperative stricture or post-EBD perforation, so needs to be avoided where possible.

Background and study aims Endoscopic submucosal dissection (ESD) for duodenal tumors results in a high delayed perforation rate due to the thinness of the duodenal wall. In most cases with perforation after duodenal ESD, additional surgery is needed due to severe peritonitis. A newly developed procedure, laparoscopic endoscopic cooperative surgery for duodenal tumors (D-LECS), may help to avoid perforation after ESD. In our institution, patients with superficial non-ampullary duodenal epithelial tumors (SNADET) smaller than 50 mm which could not have en-bloc resection by endoscopic mucosal resection were treated with D-LECS. After a laparoscopic exposure of anterior duodenal wall of second portion, ESD was performed. Laparoscopic suturing from the serosal side of ESD site was performed for reinforcement. There were neither postoperative leakage nor other complications. Therefore, D-LECS can be performed safely and prevent perforation after ESD for SNADET. D-LECS could be selected as a treatment for SNADET which can be cured by ESD.

AIM To investigated the hemostatic ability of the S and F1-10 methods in clinical and ex vivo studies. METHODS The hemostatic abilities of the two methods were analyzed retrospectively in all six gastric endoscopic submucosal dissection cases. The treated vessel diameter, compressed vessel frequency, and bleeding frequency after cutting the vessels were noted by the recorded videos. The coagulation mechanism of the two power settings was evaluated using the data recording program and histological examination on macro- and microscopic levels in the ex vivo experiments using porcine tissues. RESULTS F1-10 method showed a significantly better hemostatic ability for vessels ≥ 2 mm in diameter and a trend of overall better coagulation effect, evaluated by the bleeding rate after cutting the vessels. F1-10 method could sustain electrical current longer and effectively coagulate the tissue wider and deeper than the S method in the porcine model. CONCLUSION F1-10 method is suggested to achieve a stronger hemostatic effect than the S method in clinical procedures and ex vivo models.

Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (P

Background and study aims Peroral endoscopic myotomy (POEM) is an evolving new treatment strategy for achalasia. Although several kinds of electrosurgical knives have been used in performing POEM, the best device has yet to be determined. The FlushKnife BT is a waterjet-emitting short needle-knife with a small ball tip (BT) that offers the potential to perform all aspects of POEM with a single device. In this study, we evaluated the safety and efficiency of the FlushKnife BT for POEM. Patients and methods A total of 54 consecutive patients with achalasia and other spastic esophageal motility disorders, such as jackhammer esophagus or distal esophageal spasm, who underwent POEM between January 2016 and August 2016, were included in this retrospective study. Results The median operation time was 73.0 minutes (range 39 – 184 minutes). All procedures were completed using only the FlushKnife BT without changing to any other electrosurgical instrument. The median number of additional submucosal injections with an injection needle was 0 (range 0 – 1). Endoscopic vessel sealing was performed a mean of 3 times (range 0 – 7). The median number of bleeding episodes requiring treatment with hemostatic forceps was 0 (range 0 – 5). There were no significant adverse events. Seven of 52 patients (13.5 %) reported symptoms of gastroesophageal reflux disease such as heartburn or acid reflux at 3 month follow-up. Conclusions The FlushKnife BT enabled POEM to be performed with very few device exchanges, either for re-injection or to control intraoperative bleeding. In this uncontrolled case series, the ability of the FlushKnife BT to perform nearly all aspects of the POEM procedure seems to make it particularly well suited to this procedure.

A 66-year-old man was diagnosed with a gastric submucosal tumor. Endoscopic ultrasound (EUS) revealed an iso/hypoechoic mass in the third layer. No malignant cells were detected in a histological examination. Yearly follow-up endoscopy and EUS showed the slow growth of the tumor. Endoscopic submucosal dissection (ESD) was performed and a glistening tumor was resected. The lesion showed a multinodular plexiform growth pattern consisting of spindle cells with an abundant fibromyxoid stroma that was rich in small vessels. The tumor was diagnosed as plexiform fibromyxoma (PF) by immunohistochemistry. Although difficulties are associated with reaching a diagnosis preoperatively, chronological changes on EUS may contribute to the diagnosis of PF. ESD may also be useful in the diagnosis and treatment of PF.

Background and Aim Currently, endoscopic submucosal dissection (ESD) is a widely accepted standard treatment for early gastric cancer, but one challenging aspect of ESD is hemostasis. We developed a new hemostatic forceps (FD-Y0007) with the aim of achieving more effective hemostasis and investigated the hemostatic ability of the FD-Y0007 during gastric ESD in humans. Methods This study was a prospective randomized controlled trial, which was conducted at a cancer referral center. Sixty-six patients who were scheduled to undergo ESD were enrolled and randomly assigned to either the Coagrasper or the FD-Y0007, which was used for hemostasis throughout the case. The primary end point was the time required to obtain hemostasis, which was measured for the first episode of bleeding during each case. Results Hemostasis time for the first bleeding episode during ESD was 73.0 s for the Coagrasper and 21.5 s for the FD-Y0007 (P

// Shin Nishiumi 1, * , Takashi Kobayashi 1, * , Shuichi Kawana 2 , Yumi Unno 2 , Takero Sakai 2 , Koji Okamoto 3 , Yasuhide Yamada 4 , Kazuki Sudo 4 , Taiki Yamaji 5 , Yutaka Saito 6 , Yukihide Kanemitsu 7 , Natsuko Tsuda Okita 4 , Hiroshi Saito 8 , Shoichiro Tsugane 9 , Takeshi Azuma 1 , Noriyuki Ojima 2 , Masaru Yoshida 1, 10, 11 1 Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan 2 Analytical and Measuring Instruments Division, Shimadzu Corporation, Nakagyo-ku, Kyoto 604-8511, Japan 3 Division of Cancer Differentiation, National Cancer Center Research Institute, Tokyo 104-0045, Japan 4 Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan 5 Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan 6 Endoscopy Division, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan 7 Department of Colorectal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan 8 Division of Screening Assessment and Management, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan 9 Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan 10 Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan 11 AMED-CREST, AMED, Chuo-ku, Kobe, Hyogo 650-0017, Japan * These authors have contributed equally to this work Correspondence to: Masaru Yoshida, email: myoshida@med.kobe-u.ac.jp Keywords: metabolomics, colorectal cancer, biomarker, gas chromatography/triple-quadrupole mass spectrometry, metabolite Received: November 14, 2016 Accepted: January 09, 2017 Published: February 04, 2017 ABSTRACT In developed countries, the number of patients with colorectal cancer has been increasing, and colorectal cancer is one of the most common causes of cancer death. To improve the quality of life of colorectal cancer patients, it is necessary to establish novel screening methods that would allow early detection of colorectal cancer. We performed metabolome analysis of a plasma sample set from 282 stage 0/I/II colorectal cancer patients and 291 healthy volunteers using gas chromatography/triple-quadrupole mass spectrometry in an attempt to identify metabolite biomarkers of stage 0/I/II colorectal cancer. The colorectal cancer patients included patients with stage 0 (N=79), I (N=80), and II (N=123) in whom invasion and metastasis were absent. Our analytical system detected 64 metabolites in the plasma samples, and the levels of 29 metabolites differed significantly (Bonferroni-corrected p=0.000781) between the patients and healthy volunteers. Based on these results, a multiple logistic regression analysis of various metabolite biomarkers was carried out, and a stage 0/I/II colorectal cancer prediction model was established. The area under the curve, sensitivity, and specificity values of this model for detecting stage 0/I/II colorectal cancer were 0.996, 99.3%, and 93.8%, respectively. The model’s sensitivity and specificity values for each disease stage were >90%, and surprisingly, its sensitivity for stage 0, specificity for stage 0, and sensitivity for stage II disease were all 100%. Our predictive model can aid early detection of colorectal cancer and has potential as a novel screening test for cases of colorectal cancer that do not involve lymph node or distant metastasis.

AIM To investigated the usefulness of a novel slim type balltipped FlushKnife (FlushKnife-BTS) over ball-tipped FlushKnife (FlushKnife-BT) in functional experiments and clinical practice. METHODS In order to evaluate the functionality of FlushKnife-BTS, water aspiration speed, resistance to knife insertion through the scope, and waterjet flushing speed were compared between FlushKnife-BTS and BT. In clinical practice, esophageal endoscopic submucosal dissection (ESD) performed using FlushKnife-BTS or BT by an experienced endoscopist between October 2015 and January 2016 were retrospectively reviewed. The treatment speed and frequency of removing and reinserting the knife to aspirate fluid and air during ESD sessions were analyzed. RESULTS Functional experiments revealed that water aspiration speed by the endoscope equipped with a 2.8-mm working channel with FlushKnife-BTS was 7.7-fold faster than that with conventional FlushKnife-BT. Resistance to knife insertion inside the scope with a 2.8-mm working channel was reduced by 40% with FlushKnife-BTS. The waterjet flushing speed was faster with the use of FlushKnife-BT. In clinical practice, a comparison of 6 and 7 ESD using FlushKnife-BT and BTS, respectively, revealed that the median treatment speed was 25.5 mm(2)/min (range 19.6-30.3) in the BT group and 44.2 mm(2)/min (range 15.5-55.4) in the BTS group (P = 0.0633). However, the median treatment speed was significantly faster with FlushKnife-BTS when the resection size was larger than 1000 m(2) (n = 4, median 24.2 mm(2)/min, range 19.6-27.7 vs n = 4, median 47.4 mm(2)/min, range 44.2-55.4, P = 0.0209). The frequency of knife replacement was less in the BTS group (median 1.76 times in one hour, range 0-5.45) than in the BT group (7.02 times in one hour, range 4.23-15) (P = 0.0065). CONCLUSION Our results indicate that FlushKnife-BTS enhances the performance of ESD, particularly for large lesions, by improving air and fluid aspiration and knife insertion during ESD and reducing the frequency of knife removal and reinsertion.

Background and study aims A 54-year-old man was diagnosed with a rectal tumor extending through the submucosal layer. The patient refused surgery and therefore endoscopic submucosal dissection (ESD) was pursued. The lesion exhibited the muscle retraction sign. After dissecting circumferentially around the fibrotic area by double tunneling method, a myotomy was performed through the internal circular muscle layer, creating a plane of dissection between the internal circular muscle layer and the external longitudinal muscle layer, and a myectomy was completed.The pathologic specimen verified T1b grade 1 sprouting adenocarcinoma with 4350 µm invasion into the submucosa with negative resection margins.

Background and aims Shielding methods for post-endoscopic submucosal dissection (ESD) ulcers have delivery-related problems. We developed an enveloped device for this purpose and evaluated its usefulness. Materials and methods Polyglycolic acid (PGA) sheets were delivered to six 3.0-cm ulcers in two resected porcine stomachs and six 5.0-cm ulcers in another three stomachs. In the regular method group, small PGA sheets were delivered via forceps. In the novel method group, a large PGA sheet was delivered via the new device. The methods were compared in terms of time, and macroscopic and histological findings of the ulcer floor. Results The median time required to cover a 3.0-cm ulcer was 0.39 min/cm 2 in the novel method group and 1.03 min/cm 2 in the regular method group ( P = 0.03), and to cover a 5.0-cm ulcer was 0.38 min/cm 2 and 0.85 min/cm 2 , respectively ( P = 0.03). In the novel method group, the PGA sheets were in close contact, fully covering the ulcer floor. In the regular method group, the sheets were partly elevated from the ulcer floor. Conclusions This novel technique seems promising in this preliminary study.

Background and aim Lymph node metastasis predicts poorer prognoses in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Factors associated with lymph node metastasis of invasive IPMN remain unclear. Therefore, this study aimed to define factors associated with lymph node metastasis of invasive IPMN. Methods Between June 2000 to August 2015, 156 consecutive patients with IPMN underwent surgical resection at Kobe University Hospital, and were enrolled in this study. The relationship between lymph node metastasis and clinical characteristics, including imaging studies and serum tumor markers, was evaluated. A multivariate logistic regression analysis was performed to assess the relationship between serum tumor markers and the presence of lymph node metastasis of IPMN, adjusted for clinical characteristics. Results Lymph node metastasis was observed in 7.7% (12/156) of IPMNs via a pathological examination. The multivariate logistic regression analysis revealed that serum SPan-1 was associated with the presence of lymph node metastasis of IPMN (odds ratio [OR] = 7.32; 95% confidence interval [CI] = 1.10 to 56.0; P = 0.04). In addition, survival was poorer among serum SPan-1-positive patients than SPan-1 negative patients (Log-rank test; P = 0.0002). Lymph node enlargement was detected preoperatively on computed tomography scans in only 16.7% (2/12) of cases that were positive for lymph node metastasis. Conclusions Elevated serum SPan-1 was associated with lymph node metastasis in this cohort of patients who underwent resection for invasive IPMN.

Background: Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood. Methods: A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring. The severity of colitis was evaluated by measuring body weight, histological scoring, and endoscopic scoring. The expression of inflammatory cytokines in ear and colon tissue was evaluated using real-time PCR. 16S rRNA DNA sequencing of feces from OXA-induced colitis mice was performed before and after IND treatment. The effects of IND on OXA-induced colitis were also evaluated after depleting the gut flora with antibiotics to test whether alteration of the gut flora by IND influenced the course of intestinal inflammation in this model. Results: IND treatment ameliorated OXA dermatitis with a reduction in IL-4 and eosinophil recruitment. However, OXA colitis was significantly aggravated in spite of a reduction in intestinal IL-13, a pivotal cytokine in the induction of the colitis. It was found that IND dramatically altered the gut flora and IND no longer exacerbated colitis when colitis was induced after gut flora depletion. Conclusions: Our data suggest that IND could modify the inflammatory immune response in multiple ways, either directly (i.e., modification of the allergic immune cell activity) or indirectly (i.e., alteration of commensal compositions).

Introduction Methotrexate has been reported to increase the risk of lymphoproliferative disorders. We report a rare case who was clinically diagnosed with methotrexate-associated lymphoproliferative disorders of the kidney. Case presentation A 77-year-old patient with rheumatoid arthritis had taken low-dose methotrexate for 13 years. The patient developed left renal mass 3 cm in size and multiple pulmonary nodules. Initially, renal malignant tumor with lung metastases was considered and the renal biopsy was planned. However, under possible diagnosis of methotrexate-related lymphoproliferative disorder, we withdrew methotrexate treatment at first and then observed spontaneous regression of the tumorous lesions of the kidney and lungs. Conclusion Although methotrexate-related lymphoproliferative disorder in kidneys is very rare, our case advocates the importance of a relevant differential diagnosis of methotrexate-related lymphoproliferative disorder under the setting of long-term treatment of methotrexate for rheumatoid arthritis.

Background Helicobacter pylori infection has become increasingly resistant to traditional first-line treatment regimens because of emerging antibiotic resistance coupled with poor patient compliance with completing the treatment course. There is limited data regarding the incidence of H. pylori treatment resistance in the Philippines. This study aims to guide physicians in deciding the choice of the treatment regimen for both treatment-naive and treatment-resistant organisms. Methods This is a prospective, cohort study in St. Luke’s Medical Center. We currently enrolled 73 patients positive for H. pylori infection based on rapid urease test, and gastroscopy, biopsy of the antrum, incisura and corpus and subsequent H. pylori culture and sensitivity against amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin were done. Results Thirty-eight percent (38%) or 28 out of 73 patients enrolled are H. pylori culture positive and we were able to isolate and do sensitivity analysis in 42 samples. The incidence rate of Helicobacter treatment-resistant infection is high at 66.7% or 28 out of 42 isolates. Among the medications used, no resistance was noted for amoxicillin and tetracycline, while the resistance rates are as follows for other antibiotics: clarithromycin 28.6% (12/42), metronidazole 40.5% (17/42) and levofloxacin 61.9% (26/42). Conclusions The rates of resistance to clarithromycin, metronidazole and levofloxacin are high in Filipino H. pylori strains. This is in contrast to the earlier antibiotic susceptibility study by Destura et. al in 2004 in which all isolated strains were sensitive to tested antibiotics. This new pattern of resistance indicates the decreased usefulness of the first line therapy in the Philippines and the need for other treatment regimens is emerging.

Sequential therapy using tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors is the mainstay of treatment for metastatic renal cell carcinoma. Recently, anti-programmed death-1 (PD-1) antibody, a type of immune checkpoint inhibitor, was approved for use against metastatic renal cell carcinoma. In the present report, two cases of TKI-refractory metastatic renal cell carcinoma which regained sensitivity to TKI after immunotherapy with nivolumab were described. In one case, a third challenge with axitinib after nivolumab treatment resulted in tumor shrinkage, although the second challenge with axitinib immediately before nivolumab treatment had no effect. In another case, a second challenge with pazopanib after nivolumab slightly reduced lung metastasis, which was refractory to pazopanib before nivolumab treatment. These cases suggest that nivolumab can influence the response to subsequent TKI treatment.

Background B7-H3 is a member of the B7 family of immune-regulatory ligands and is a costimulatory molecule promoting the T cell response in vitro. We herein investigated the clinical utility of serum soluble B7-H3 (sB7-H3) in patients with non-muscle invasive bladder cancer (NMIBC). Methods We analyzed 555 patients in whom NMIBC was diagnosed at Tokyo Metropolitan Tama Medical Center between 2008 and 2013. We measured the serum sB7-H3 (sB7-H3) level using the enzyme-linked immunosorbent assay (ELISA) and evaluated the utility of sB7-H3 as a prognostic biomarker for NMIBC. We used the Cox proportional hazards regression model to assess recurrence-free survival (RFS) and progression-free survival (PFS) with the sB7-H3 level. Results We detected high levels of sB7-H3 in the sera of 47% of patients with NMIBC versus only 8% in healthy donors. The increase of sB7-H3 was significantly associated with poor RFS and PFS. Multivariate analysis showed that elevated sB7-H3 was an independent prognostic factor of RFS and PFS. According to the European Organization for Research and Treatment of Cancer (EORTC), in intermediate-low and intermediate-high risk groups, the presence of sB7-H3 significantly determined the rate of recurrence and progression. Conclusions Our data suggested that evaluating serum sB7-H3 expression is a useful tool for predicting the prognosis of patients with NMIBC.

Postoperative abdominal adhesions are one of the most common post-laparotomy complications observed. Several types of adhesion preventative agents are available and their effectiveness and adverse impact have been clinically evaluated in previous studies. However, few basic studies have tested whether those agents do not trigger any unwanted xenobiotic reaction, which makes some surgeons hesitant to use them. To clarify this point, we investigated whether the adhesion preventative agent Seprafilm® (KAKEN PHARMACEUTICAL CO., LTD., Tokyo, Japan), one of the most widely used hyaluronate-based bioresorbable membrane (HBBM), can trigger an inflammatory response in normal abdominal tissue and delay the healing process. The rat underwent laparotomy and a HBBM was placed directly below the incision. Tissue samples at the incision and away from the incision (normal tissue) were harvested and inflammatory response and fibrosis were evaluated using quantitative PCR and histological scoring. We found that HBBM did not induce inflammatory cytokine expression at mRNA level in the peritoneal wall tissue or modify the fibrosis process in the abdominal cavity. These findings confirm the safety of using HBBM for the prevention of adhesion development post-laparotomy.

Aim: To examine a novel screening method for pancreatic cancer involving gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry-based metabolomics analysis. Materials & methods: Sera from pancreatic cancer patients (n = 59) and healthy volunteers (n = 59) were allocated to the training set or validation set. Serum metabolome analysis was carried out using our multiplatform metabolomics system. A diagnostic model was constructed using a two-phase screening method that was newly advocated. Results: When the training set was used, the constructed diagnostic model exhibited high sensitivity (100%) and specificity (80%) for pancreatic cancer. When the validation set was used, the model displayed high sensitivity (84.1%) and specificity (84.1%). Conclusion: We successfully developed a diagnostic model for pancreatic cancer using a multiplatform serum metabolomics system.

Endoscopic submucosal dissection (ESD) has been applied to treat early colorectal cancers. The aim of this study was to clarify the clinical course of ESD for lesions involving the ileocecal valve (ICV) by evaluating the successful resection rates, and the risk and frequency of adverse events.The outcome of ESD on 38 ICV lesions was compared with the outcome of 132 cecal lesions that did not involve the ICV or appendiceal orifice during the same study period. The factors related to longer procedure time, postoperative stricture development, and tumor recurrence were investigated for ESD of ICV lesions.There was no significant difference between the ICV and non-ICV groups in the en block resection rates. The median procedure time was significantly longer in the ICV group than in the non-ICV group, with a point estimate of the difference of 37 minutes (95 % confidence interval [CI] 20.00 to 56.00; P 0.01). None of the patients developed symptomatic post-ESD stricture or tumor recurrence. ESD procedure duration was ≥ 120 minutes in 16 lesions and 120 minutes in 22 lesions of the ICV group. A specimen diameter of ≥ 40 mm and tumor extension into terminal ileum were factors related to a longer procedure time (odds ratio [OR] 8.40, 95 %CI 1.53 to 46.10, P = 0.01; OR 10.60, 95 %CI 2.17 to 51.40, P 0.01, respectively).ICV lesions can be resected by ESD without major adverse events or causing symptomatic stricture development. However, ESD for ICV lesions should be performed only by expert endoscopists, as the procedure requires accomplished endoscopic skill and experience.

We report a 59-year-old male patient with metastatic small cell carcinoma of the bladder treated with systemic chemotherapy including an amrubicin. The patient was referred to our hospital complaining of macrohematuria. A cytoscopy revealed a non-papillary, broad-based tumor extending from the right to the posterior wall of the bladder. A computed tomography showed bilateral hydronephrosis caused by the bladder tumor and multiple metastases to the para-aortic and common iliac lymph nodes. The histopathological findings following a transurethral resection of the bladder tumor revealed a T2N3M1, LYM, stage IV small cell carcinoma. We administered two courses of systemic chemotherapy consisting of cisplatin (CDDP) plus an etoposide (VP-16), a first-line treatment usually administered to patients with small cell carcinoma of the lung. We then administered second-line chemotherapy consisting of CDDP plus an irinotecan. When the first and second-line therapies failed to halt progression of the disease, we decided to use amrubicin as the third-line therapy concomitant with radiotherapy for local control. Although the NSE (neuron-specific enolase) value decreased, the patient died 11 months after the initial examination. To our knowledge, this is the first case in which small cell carcinoma of the bladder was treated with amrubicin.

Recent studies have suggested that a peculiar tumor mimicking intraductal tubulopapillary neoplasms (ITPN) of the pancreas can develop in the bile duct. Here, we present a similar case and review the published work on the newly proposed biliary neoplasm. A 68-year-old woman was referred to us for further evaluation of a liver mass. On imaging, the tumor was 40 mm in size and intraductal in location, and was enhanced slightly on the contrast-enhanced computed tomography. No mucin overproduction was found. She underwent right hepatectomy for suspected intraductal papillary neoplasm of the bile duct. The tumor histologically consisted of the biliary-type epithelium arranged in a tubular architecture within the dilated bile duct. Tumor cells had features of high-grade dysplasia but no stroma invasion. No expressions of MUC2 and MUC5AC were noted. On molecular studies, KRAS and GNAS appeared to be wild-type genotypes. These features were in keeping with ITPN. In the published work review, "biliary ITPN" described in four manuscripts were characterized by predominantly intrahepatic/hilar in location, histological tubular architecture, negative expressions of MUC2 and MUC5AC, and uncommon alterations of KRAS, GNAS and BRAF. Although invasive malignancy was present in 71%, the outcome was favorable with the 5-year survival expected to be approximately 90%. Biliary ITPN are supposedly uncommon, but a greater awareness of this condition may give more chance to diagnose the underrecognized neoplasm.

Aim: To identify the serum metabolomics signature that is correlated with the chemoradiosensitivity of esophageal squamous cell carcinoma (ESCC). Materials & methods: Untargeted and targeted metabolomics analysis of serum samples from 26 ESCC patients, which were collected before the neoadjuvant chemoradiotherapy, was performed. Results: On receiving the results of untargeted metabolomics analysis, we performed the targeted metabolomics analysis of the six metabolites (arabitol, betaine, glycine, L-serine, L-arginine and L-aspartate). The serum levels of the four metabolites (arabitol, glycine, L-serine and L-arginine) were significantly lower in the patients who achieved pathological complete response with neoadjuvant chemoradiotherapy compared with the patients who did not achieve pathological complete response (p = 0.0086, 0.0345, 0.0106 and 0.0373, respectively). Conclusion: The serum levels of metabolites might be useful for predicting the chemoradiosensitivity of ESCC patients.

Background/Objectives: The recent guideline for intraductal papillary mucinous neoplasms (IPMNs) focuses on morphological features of the lesion as signs of malignant transformation, but ignores the background pancreatic parenchyma, including features of chronic pancreatitis (CP), which is a risk factor for pancreatic malignancies. Endoscopic ultrasonography frequently reveals evidence of CP (EUS-CP findings) in the background pancreatic parenchyma of patients with IPMNs. Therefore, we investigated whether background EUS-CP findings were associated with malignant IPMN. Methods: The clinical data of 69 consecutive patients with IPMNs who underwent preoperative EUS and surgical resection between April 2010 and October 2014 were collected prospectively. The association of EUS-CP findings (total number of EUS-CP findings; 0 vs. ≥1) with invasive IPMN was examined. The association of EUS-CP findings with pathological changes of the background pancreatic parenchyma (atrophy/inflammation/fibrosis) was also examined. Results: Among patients with EUS-CP findings, invasive intraductal papillary mucinous carcinoma (IPMC) was significantly more frequent than among patients without EUS-CP findings (42.5% [17/40] vs. 3.4% [1/29], p = 0.0002). In addition, patients with EUS-CP findings had higher grades of pancreatic atrophy and inflammation than patients without EUS-CP findings (atrophy: 72.5% [29/40] vs. 34.5% [10/29], p = 0.003; inflammation: 45.0% [18/40] vs. 20.7% [6/29], p = 0.04). Conclusions: In IPMN patients, detection of EUS-CP findings in the background pancreatic parenchyma was associated with a higher prevalence of invasive IPMC. Accordingly, EUS examination should not only assess the morphological features of the lesion itself, but also EUS-CP findings in the background parenchyma.

It has previously been demonstrated that the intratumoral generation of the potent androgen dihydrotestosterone (DHT), contributes critically to the progression of prostate cancer and its castration-resistant form, castration-resistant prostate cancer (CRPC). Circulating testosterone is converted into DHT by 5α-reductase (SRD5A). Dutasteride is a dual inhibitor of type I and II SRD5A. The present study assessed the effectiveness of dutasteride in the treatment of CRPC. Between 2010 and 2013, CRPC was diagnosed in 41 patients at the Tokyo Metropolitan Tama Medical Center. Following diagnosis, the patients received 0.5 mg dutasteride daily. The patients' median age was 77.3 years (range, 63-90). Bone metastases were recognized in 12 patients. All the patients received dexamethasone. Twenty-four (59%) patients had previously undergone chemotherapy, while 11 (27%) received docetaxel, and 24 (59%) estramustine. The prostatic-specific antigen (PSA) level declined in 17 (41%) patients from the baseline value, following dutasteride treatment. The median value for the PSA decrease was 23% (range, 4.3-89.8%), and the median duration of the response was 4 months (range, 1-10). The PSA response rate (defined as >50% decline in PSA from the baseline value) was recognized in 7 (17%) patients. The median duration of the response was 3 months (range, 2-10). Dutasteride was efficacious against CRPC in certain patients and may be a promising option in CRPC treatment. A prospective randomized trial is necessary to verify the efficacy of dutasteride.

Objectives The present study was conducted in order to elucidate the relationship between the number of cyst-existing regions and incidence of pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN), which currently remains unclear. Methods Subjects comprised 141 patients undergoing resection for IPMN (Non-invasive IPMN (IPMN with low-to high-grade dysplasia): N = 94, invasive IPMN: N = 31, and PDAC concomitant with IPMN: N = 16) between November 2000 and February 2017. A logistic regression analysis was performed to assess the relationship between the number of cyst-existing regions (one region/two or more regions) and incidence of PDAC concomitant with IPMN, adjusted by clinical characteristics. Cyst-existing regions were defined by the number of anatomical parts of the pancreas: the head/body/tail of the pancreas. Results Multiple cyst-existing regions (two or more regions) correlated with the incidence of PDAC concomitant with IPMN (PDAC concomitant with IPMN in one region vs. two or more regions: 3/66 vs. 13/75, multivariable odds ratio [OR] = 4.11, 95% confidence interval [CI] = 1.22 to 18.8, P = 0.02). In contrast, multiple cyst-existing regions did not correlate with the incidence of IPMN (invasive IPMN in one region vs. two or more regions: 13/66 vs. 18/75, OR = 1.19, 95% CI = 0.52 to 2.76, P = 0.67). Conclusions Multifocal cysts correlated with the incidence of PDAC concomitant with IPMN, and may be a high-risk factor for PDAC concomitant with IPMN.

Aim The neuropsychiatric test (NP test) is a clinically available modality to confirm minimal hepatic encephalopathy (MHE), but it takes at least 30 min for outpatients to complete. An easier primary screening tool of the NP test would be helpful to predict MHE in routine testing on the public. Methods We performed a prospective cohort study on 59 cirrhotic outpatients at Kobe University Hospital. Laboratory measurements, the NP test and the Chronic Liver Disease Questionnaire (CLDQ) were performed. As an indicator of MHE, cases with and without two abnormal subsets or more in the NP test were compared, and the independent risk factors were statistically examined. Predictive scoring systems of the risk of MHE were established using multivariate logistic regression. Results CLDQ worry (WO) was the best predictive factor of MHE diagnosed by the NP test (P = 0.006). The predictive model using CLDQ WO discriminated well between patients with and without MHE (area under the curve, 0.714; 95% confidence interval, 0.582–0.824). The predictive scores of MHE enable the patient-specific probability to be easily looked up. Conclusion CLDQ WO was shown to be an independent factor associated with the NP test to diagnose MHE in cirrhotic patients. The easy predictive scoring system of the risk of MHE using CLDQ WO could become a primary screening tool before performing the NP test in a social setting.

Background and study aims: During colorectal endoscopic submucosal dissection (ESD), the feature of a muscle layer being pulled toward a neoplastic tumor is sometimes detected. We call this feature the muscle-retracting sign (MR sign). The aim of this study was to evaluate whether the MR sign is associated with particular types of neoplastic lesions and whether it has any clinical significance for ESD sessions. Patients and methods: A total of 329 patients underwent ESD for 357 colorectal neoplasms. The frequency of positivity for the MR sign was evaluated in different morphologic and histopathologic types of neoplasm. The success rate of complete resection and the incidence of complications were also evaluated according to whether lesions were positive or negative for the MR sign. Results: The rates of positivity for the MR sign in the various lesion types were as follows: laterally spreading tumor – granular nodular mixed type (LST-G-M), 9.6 %; laterally spreading tumor – granular homogeneous type (LST-G-H) and laterally spreading tumor – nongranular type (LST-NG), 0 %; sessile type, 41.2 %. The resection rate was 100 % (329 /329) in lesions negative for the MR sign; however, it was 64.3 % (18 /28) in lesions positive for the MR sign, which was significantly lower (P

Recently, endoscopic submucosal dissection (ESD) has been applied for superficial colorectal neoplasms and the number of publications about it has been increasing, but little is known about the outcomes of colorectal ESD for the lesions50 mm. In this study, we evaluated the feasibility and safety of colorectal ESD for the lesions50 mm compared with the lesions50 mm.A total of 674 superficial colorectal neoplasms in 629 patients treated by ESD at Kobe University Hospital from July 2008 to July 2013 were included in the analysis.The median operation time (range) in the large lesion group (≥ 5 cm) was 109 (37 to 596) minutes, and it was 55 (6 to 248) minutes in the small lesion group (5 cm). Median procedure speed (range) in the large lesion group was 0.28 (0.06 to 0.83) cm2/min, and it was 0.19 (0.04 to 0.83) cm2/min in the small lesion group. The en bloc resection rate and the curative resection rate in the small lesion group was 98.7% and 96.0%, and those were 95.7% and 91.4% in the large lesion group, respectively. In terms of adverse events, perforation, muscle damage, and postoperative bleeding occurred at similar frequency in both groups.ESD on colorectal lesions50 mm takes longer operation time; however, it is resected time effectively without increasing the risk of adverse events compared with smaller lesions by ESD.

Afferent loop obstruction caused by cancer recurrence after pancreaticoduodenectomy (PD) can be managed by either surgical or nonsurgical treatment. The general condition of patients with recurrent pancreaticobiliary cancer is often not good enough for them to undergo surgery, so less invasive nonsurgical treatment is desirable. We report a case of a 66-year-old male who had undergone PD for pancreatic head adenocarcinoma 10 months previously and who presented at our hospital with fever and jaundice due to afferent loop obstruction caused by pancreatic cancer recurrence. An endoscopic self-expandable metal stent (SEMS) was placed for afferent loop obstruction without any complications. He quickly recovered after SEMS placement. He retained a good quality of life by receiving chemotherapy until his death due to cancer progression. Our case indicates that this method could be an easy, effective, safe, and less invasive treatment, which may confer a better quality of life for patients with afferent loop obstruction due to cancer recurrence after PD.

Objective To characterize nocturia in men based on frequency volume chart data and symptom profiles assessed using the Core Lower Urinary Tract Symptom Score and Athens Insomnia Scale questionnaires. Methods The Core Lower Urinary Tract Symptom Score and Athens Insomnia Scale questionnaires were administered to 299 consecutive treatment naive men with nocturia (≥one time per night). Frequency volume chart data were recorded for 2 days. Correlations between nocturia and clinical characteristics including symptom scores, clinical diagnosis, Charlson Comorbidity Index, estimated glomerular filtration rate, uroflowmetry and prostate volume were analyzed. Results Patients were divided into five groups: one time (n = 36), two times (n = 65), three times (n = 85), four times (n = 78) and five times (n = 34) of nocturia. Age, prevalence or severity of chronic kidney disease, hyperlipidemia, low bladder capacity, nocturnal polyuria, urgency, bladder pain and sleep disorders were significantly correlated with the severity of nocturia. The Spearman correlation analysis identified eight possible independent factors for nocturia: age, estimated glomerular filtration rate, urgency, bladder pain, sleep quality, sleepiness during the day, average voided volume and nocturnal volume divided by body weight. Logistic regression analysis showed that nocturnal volume divided by body weight was the strongest factor of nocturia, and ≥7, 9 and 9.7 mL/kg were practical cut-off values of three, four and five times per night of nocturia, respectively. Conclusions Nocturia in men is a chaotic condition dominated by nocturnal polyuria, and related to multiple factors including age, renal function, urgency, bladder pain, insomnia and bladder volume.

Objective Superficial colorectal tumors can be treated effectively by endoscopic submucosal dissection (ESD). Few data are available on using ESD for residual or recurrent tumors after the first endoscopic resection. This study aimed to evaluate the efficacy of ESD for these lesions. Methods In all, 28 patients with residual or recurrent superficial colorectal tumors were referred to the Kobe University Hospital for ESD. The therapeutic outcomes and the possible factors predictive of procedure difficulties for ESD were analyzed. Results In total, 27 (96.4%) patients were successfully treated using ESD. There was no related immediate complication. One patient had a delayed perforation which was then treated surgically. En bloc R0 resection was possible in all the patients and curative resection in 26 patients (92.9%). One invasive cancer was treated surgically. More than one previous endoscopic resection was the only significant predictive factor for the difficulty in performing ESD. None of the patients experienced recurrence during a follow-up of 22 months (range 3–41 months). Conclusions The use of ESD allowed a high rate of en bloc resection for residual or locally recurrent colorectal tumors. Furthermore, these lesions should be treated by ESD as a first-line treatment.

Aim: Transcatheter arterial chemoembolization (TACE) is thought to be a safe and effective treatment for hepatocellular carcinoma (HCC). However, in some HCC patients, it potentially shortens survival due to liver damage. We aimed to identify independent factors to predict overall survival of HCC after TACE. Methods: We included a total of 96 consecutive HCC patients who underwent TACE at Kobe University Hospital. Areas of skeletal muscle and fat tissue were measured by computed tomography (CT) scan before TACE. We divided the patients into two groups in terms of the presence or absence of 1-year mortality after TACE. Factors associated with 1-year mortality after TACE were assessed by multivariate analyses, and the optimal cut-off values were evaluated using a propensity score. Results: Multivariate analyses showed that visceral fat accumulation on CT was an independent factor associated with 1-year mortality after TACE (p = 0.033). There were no differences in skeletal muscle area and subcutaneous and intermuscular fat area between the two groups. Cut-off values for visceral fat area associated with 1-year mortality after TACE were defined as 33.3 cm 2 /m 2 for males and 24.4 cm 2 /m 2 for females. Conclusions: High visceral fat area was a prognostic factor associated with increased mortality rate in HCC patients undergoing TACE. Using this value, 1-year mortality risk after TACE would be better estimated before the day TACE was performed. * Corresponding author.

OBJECTIVE The standard treatment for submucosal esophageal cancer is esophagectomy or chemoradiotherapy (CRT). However, these treatment modalities could deteriorate the general condition and quality of life of the patients who are intolerant to invasive therapy. It is therefore important and beneficial to develop less invasive treatment protocols for these patients. METHODS The study included 43 patients who were clinically suspected of mucosa or submucosal esophageal cancer but underwent endoscopic submucosal dissection (ESD) as a primary treatment, due to the patients' poor performance statuses and/or preferences for less invasive therapy. According to the pathological findings and patient's general condition, whether the patient underwent additional treatments or remained hospitalized without additional treatments was thereafter decided for each patient. We retrospectively analyzed the outcomes of these patients. RESULTS Fifteen patients underwent additional surgery, 11 patients underwent CRT/radiation therapy (RT) and 17 patients were followed without additional treatments. During the 3-year follow-up period, the relapse-free survival rates in the patients who received or did not receive additional treatments were 88% and 64%, respectively (95% confidence interval, 0.45-0.76, p=0.04). The relapse-free and overall survival rates in the patients with additional treatments were equivalent or superior to those described in previous reports of the standard treatments. Preceding ESD contributed to reduce the local relapse significantly to approximately 3.5% and additional CRT-related toxicities. CONCLUSION Preceding ESD is very effective for the local control of cancer, and useful for histologically confirming the high-risk factors of relapse, such as ≥submucosal layer 2 (SM2) invasion and lymphovascular involvements. ESD with additional therapy may be a promising strategy for optimizing the selection of therapy depending on the patient's general condition.

New strategies for the care of irritable bowel syndrome (IBS) are developing and several novel treatments have been globally produced. New methods of care should be customized geographically because each country has a specific medical system, life style, eating habit, gut microbiota, genes and so on. Several clinical guidelines for IBS have been proposed and the Japanese Society of Gastroenterology (JSGE) subsequently developed evidence-based clinical practice guidelines for IBS. Sixty-two clinical questions (CQs) comprising 1 definition, 6 epidemiology, 6 pathophysiology, 10 diagnosis, 30 treatment, 4 prognosis, and 5 complications were proposed and statements were made to answer to CQs. A diagnosis algorithm and a three-step treatment was provided for patients with chronic abdominal pain or abdominal discomfort and/or abnormal bowel movement. If more than one alarm symptom/sign, risk factor and/or routine examination is positive, colonoscopy is indicated. If all of them, or the subsequent colonoscopy, are/is negative, Rome III or compatible criteria is applied. After IBS diagnosis, step 1 therapy consisting of diet therapy, behavioral modification and gut-targeted pharmacotherapy is indicated for four weeks. Non-responders to step 1 therapy proceed to the second step that includes psychopharmacological agents and simple psychotherapy for four weeks. In the third step, for patients non-responsive to step 2 therapy, a combination of gut-targeted pharmacotherapy, psychopharmacological treatments and/or specific psychotherapy is/are indicated. Clinical guidelines and consensus for IBS treatment in Japan are well suited for Japanese IBS patients; as such, they may provide useful insight for IBS treatment in other countries around the world.

Background and Aim Proton-pump inhibitors are known to be effective in the treatment and prevention of ulcers related to low-dose aspirin (LDA), but few reports address H2-receptor antagonists (H2RAs) and gastroprotective agents (GPs). This study was intended to compare the therapeutic effects of an H2RA and a GP against gastroduodenal mucosal injuries in patients taking LDA. Methods The subjects consisted of patients requiring continuous LDA treatment, in whom no peptic ulcer was found on endoscopy at enrollment. The patients were randomized to either famotidine 20 mg/day (group F) or teprenone 150 mg/day (group T). The study medication was administered for 12 weeks. The patients underwent endoscopy after administration of the study medication in order to obtain a Lanza score. Results A total of 66 patients (38 in group F, 28 in group T) were included in the efficacy analysis population. The Lanza score changed as follows: in group F, it improved significantly, from 0.89 ± 1.03 (mean ± standard deviation) before medication to 0.39 ± 0.75 after medication (P = 0.006); in group T, no significant difference was observed: 0.75 ± 0.93 before medication and 0.68 ± 0.82 after medication. Conclusion Famotidine is better than teprenone in terms of reducing the number of the erosions under use of LDA.