Search

BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide (TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis. AIM To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan. METHODS Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography (CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria. RESULTS A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis (sensitivity, 73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis (specificity, 62.5%). The area under the curve (AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade. CONCLUSION We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID‐19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID‐19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID‐19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID‐19; (ii) practical protective equipment for medical personnel depending on the risk for COVID‐19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow‐up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID‐19.

Background and Objective Tolvaptan, an oral vasopressin V2 receptor antagonist, has been widely used for the treatment of patients with cirrhosis and ascites. However, its efficacy in patients with renal dysfunction remains unknown. The objective of this study was to investigate the efficacy and safety of tolvaptan in patients with decompensated cirrhosis and severe chronic kidney disease (s-CKD). Methods We studied 43 patients with liver cirrhosis who received tolvaptan (7.5 mg/day) for refractory ascites. s-CKD was defined as an estimated glomerular filtration rate (eGFR)

This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy. A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks. Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg)

Accessory spleens (ASs), ectopic splenic tissue at intrapancreatic and extrapancreatic sites, rarely contain epidermoid cysts. Our aim was to analyze the incidence of epidermoid cysts in ASs and perform an immunohistochemical analysis of its epithelial lining. We included in the study 148 ASs from 135 patients, for which pathological data were available. Eleven were intrapancreatic ASs (IPASs) and 137 were extrapancreatic ASs (EPASs). Six of the eleven (55%) IPASs contained epidermoid cysts, but they were not detected in EPASs. Immunohistochemical analysis showed that both the superficial/luminal and basal layer of the epithelial lining of epidermoid cysts in IPASs are negative for MUC2, MUC5AC, MUC6, WT-1, calretinin, thrombomodulin, uroplakin-II, and uroplakin-III. The superficial/luminal layer was positive for MUC4, CK7, and CA19-9 in all cases (100%), for CEA and HBME-1 in three cases (50%), and for MUC1, CK5/6, and CK20 in two cases (33%). The superficial/luminal layer was negative for p63 and D2-40 in all cases. The basal layer was positive for MUC1, CK5/6, p63, and HBME-1 in all six cases (100%), for CK7 and D2-40 in two cases (33%), and for CEA in one case (17%). The basal layer was negative for MUC4, CK20, and CA19-9 in all cases. Epidermoid cysts are a characteristic feature of IPASs but not of EPASs. Immunohistochemical analysis showed that the epithelial lining of epidermoid cysts in IPASs has a mixed character of glandular, squamous, mesothelial, and urothelial epithelium.

AimsThe loss, or decreased expression, of nectin-like molecule 4 (Necl-4; an immunoglobulin-like cell adhesion molecule) is reported to be associated with the development and progression of certain types of cancer. We investigated the clinicopathological significance of Necl-4 expression in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsImmunohistochemical analyses of Necl-4 (n=258) and E-cadherin (n=256) expression were performed using tissue microarray blocks of PDAC samples. Necl-4 expression of 38 pancreatic intraepithelial neoplasia (PanIN) lesions included in tissue microarray cores was also evaluated. Necl-4 and E-cadherin expression was considered positive if >30% of cells were stained, and negative if ≤30% of cells were stained.ResultsNecl-4 expression was positive in 45.7% (n=118) and negative in 54.3% (n=140) of PDAC cases. Necl-4 staining was positive in 96.7% (n=29) and negative in 3.3% (n=1) of low-grade PanIN cases, and positive in 62.5% (n=5) and negative in 37.5% (n=3) of high-grade PanIN cases. The number of cases with positive Necl-4 expression decreased in the order low-grade PanIN>high-grade PanIN>PDAC (p30 mm, perineural invasion, lymphatic involvement, lymph node metastasis (pN1), an advanced TNM (tumour, node, metastases) stage (stage IIB–IV), an advanced histological grade (G2/3), and shorter overall survival. E-cadherin staining was positive in 46.1% (n=118) and negative in 53.9% (n=138) of PDAC cases. Necl-4 expression correlated positively with E-cadherin expression (r=0.405, pConclusionsThe results suggest that Necl-4 is associated with carcinogenesis and aggressiveness of PDAC.

Background /Objectives: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP. Methods Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models. Results The 1,097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology. Conclusions No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions.

We aimed to characterize the mucosal immune microenvironment and immune checkpoint of Ulcerative colitis (UC) by immunohistochemistry with correlation to prognosis: requirement of second-line steroid-therapy within the 2-years after diagnosis (SR). A series of 72 cases included 56 UC, 43 non-SR (with first-line treatment 5-ASA) and 13 SR, 11 infectious colitis and 5 normal colonic biopsies. Normal mucosa was characterized by low infiltrates but high BTLA and TNFRSF14. Compared to normal, UC had increased pan-immune-markers of CD3, CD8, FOXP3, PD-1, CD68, CD16, CD163, PTX3 and CD11C but had decreased BTLA (P < 0.05); by GSEA analysis comparable results were found in an independent UC gene-expression-data set (GSE38713). Compared to infectious, UC had higher CD4, CD8, PTX3 and CD11C but lower BTLA (P < 0.05). Compared to non-SR, SR had lower FOXP3 + Tregs (Odds-Ratio = 0.114, P = 0.002), PD-1 (OR = 0.176, P = 0.002) and CD163/CD68 M2-ratio (OR, 0.019, P = 0.019) but higher CD68 + pan-macrophages (OR = 6.034, P = 0.002). Higher Baron endoscopic and Geboes histologic disease activity scores also correlated with SR. In summary, UC was characterized by increased pan-immune-markers, normal TNFRSF14 and low BTLA. SR had increased CD68 + pan-macrophages but lower immune inhibitors of FOXP3 + Tregs, PD-1 and CD163/CD68 M2-macrophage ratio. In conclusion, alterations of the immune homeostasis mechanisms are relevant in the UC pathogenesis and steroid-requiring situation.

Dyskeratosis congenita (DC) is a rare inherited disease in which the telomere complex cannot be maintained. Shortened telomeres can cause a number of clinical conditions. We herein report a case of unrelated bone marrow transplantation due to aplastic anemia associated with DC. The patient died of uncontrollable refractory intestinal bleeding. Three cases of DC with life-threatening hemorrhaging after transplantation have been reported; however, the bleeding origin could not be determined. Our case is the only patient in which a gastrointestinal bleeding point, jejunal multiple angioectasia, was determined.

Intestinal fibrotic stricture is a major complication of inflammatory bowel disease. Despite its clinical importance, anti-fibrotic therapy has not been implemented. Transforming growth factor-β (TGF-β) is considered to be a major factor contributing to tissue fibrosis. We have previously shown that the administration of a small compound, HSc025, which promotes the nuclear translocation of YB-1 as a downstream effector of IFN-γ and antagonizes TGF-β/Smad signaling, improves fibrosis in several murine tissues. In this study, we evaluated the anti-fibrotic effect of HSc025 on colorectal fibrosis in TNBS-induced murine chronic colitis. Daily oral administration of HSc025 (3, 15 and 75 mg/kg) suppressed collagen production and decreased the severity of colorectal fibrosis in a dose-dependent manner. In addition, the local production of TGF-β was decreased after HSc025 treatment, whereas that of IL-13 and TNF-α was not affected. HSc025 administration maintained the level of IFN-γ production, even at a late stage when IFN-γ production was lost without the drug treatment. These results demonstrate that HSc025 could be a therapeutic candidate for intestinal fibrosis in inflammatory bowel disease that acts by altering the local production of cytokines, as well as by directly suppressing collagen production.

The role of surgery in pancreatic neuroendocrine neoplasm grade 3 (pNEN-G3) treatment remains unclear. We aimed to clarify the role of surgery for pNEN-G3, which has recently been reclassified as pancreatic neuroendocrine tumor-G3 (pNET-G3) and pancreatic neuroendocrine carcinoma-G3 (pNEC-G3), with and without metastases, respectively. We analyzed a subgroup of patients from the Japanese pancreatic NEC study, a Japanese multicenter case-series study of pNEN-G3. Pathologists subclassified 67 patients as having pNET-G3 or pNEC-G3 based on morphological features. We compared the overall survival (OS) rates among patients who were grouped according to whether they had undergone tumor-targeted surgery for tumors without (SwoM) or with (SwM) metastases, or non-surgical procedures (NS). Data from 21 patients with pNET-G3 (SwoM, n = 6; SwM, n = 5; NS, n = 10) and 46 patients with pNEC-G3 (SwoM, n = 8; SwM, n = 5; NS, n = 33) were analyzed. OS of patients with pNET-G3 was significantly longer after SwoM and SwM than with NS (p = 0.018 and p = 0.022). In contrast, OS did not significantly differ between either SwoM or SwM and NS (p = 0.093 and p = 0.489) among patients with pNEC-G3. The role of surgery should be considered separately for pNET-G3 and pNEC-G3. Although SwoM and SwM can be considered for pNET-G3, caution is advised before considering SwM and SwoM for pNEC-G3.

Treatment of recurrent chronic obstructive pancreatitis is pancreatic duct decompression with endoscopic drainage (endoscopic pancreatic stenting [EPS] with extracorporeal shockwave lithotripsy [ESWL]) or surgical drainage. Despite the recent popularization of endoscopic drainage, treatment or stent removal is difficult in many patients. We compared the efficacy, safety, and medical cost of endoscopic and surgical treatments.We retrospectively compared the treatment course and medical cost of hospitalization between 41 patients who had undergone pancreatic stenting between 2006 and 2010 (EPS group) and 10 patients who had undergone surgery for poor control of pancreatitis between 2001 and 2005 (surgical drainage group).No intergroup differences were observed in causes, symptoms, disease duration, smoking history, or endocrine and exocrine functions. The technical success rate was 100% in both groups, and pain had improved in all of the patients in both groups. The incidences of complications did not differ significantly, and the mortality rate was 0% in both groups. The rehospitalization rate was significantly higher in the EPS group (78%) than that in the surgical drainage group (20%; P0.01). This was considered attributable to rehospitalization for stent replacement. The effects to improve endocrine and exocrine functions were not different between the two groups before and after treatment, and the current condition was maintained in 80% or more of the patients. For the entire EPS group, the mean hospitalization period was 18 days and the mean medical cost of hospitalization was 2,133,330 yen. For the entire surgical drainage group, the mean hospitalization period was 23 days and the mean medical cost of hospitalization was 2,246,548 yen, thus indicating no significant differences between the two groups.Although both endoscopic and surgical treatments achieved high symptom control and safety rates, re-hospitalization is required for stent replacement, which leads to poor cost-effectiveness, particularly in patients in whom stent removal is difficult. Endoscopic treatment for severe pancreatic duct stenosis will need to be advanced and evaluated in the future.

Ischemic colitis (IC) is a relatively common acute inflammation disorder of the intestine. It was considered to be a disorder of elderly people with risk factors for arteriosclerosis; however, a considerable number of young people with IC have been reported recently. We performed a case-control study to determine the risk factors for IC and compare the risk factors between elderly and non-elderly people.The study included 209 consecutive patients diagnosed with IC between December 2004 and March 2017 at Tokai University Hospital. The study also included 209 randomly selected controls in the same calendar year so as to match age and sex. Possible risk factors for IC were identified and compared between age groups.The mean age of IC group was 64.9 with 60 males and 115 elderly patients aged 65 or more in each group. On multivariable conditional logistic regression analysis, drinking, abdominal surgery, hypertension, and malignant diseases were risk factors for IC in all ages. In non-elderly patients, only hypertension and laxative/enema use were significant factors, while in elderly, abdominal surgery, hypertension, COPD, malignant disease and antiplatelet drugs were significant.The risk factors in elderly people might be quite different from younger ones, while hypertension seemed to be a common risk in all ages.

Sequences of long-interspersed elements (LINE-1, L1) make up ∼17% of the human genome. De novo insertions of retrotransposition-active L1s can result in genetic diseases. It has been recently shown that the homozygous inactivation of two adjacent genes SLCO1B1 and SLCO1B3 encoding organic anion transporting polypeptides OATP1B1 and OATP1B3 causes a benign recessive disease presenting with conjugated hyperbilirubinemia, Rotor syndrome. Here, we examined SLCO1B1 and SLCO1B3 genes in six Japanese diagnosed with Rotor syndrome on the basis of laboratory data and laparoscopy. All six Japanese patients were homozygous for the c.1738C>T nonsense mutation in SLCO1B1 and homozygous for the insertion of a ∼6.1-kbp L1 retrotransposon in intron 5 of SLCO1B3, which altogether make up a Japanese-specific haplotype. RNA analysis revealed that the L1 insertion induced deleterious splicing resulting in SLCO1B3 transcripts lacking exon 5 or exons 5-7 and containing premature stop codons. The expression of OATP1B1 and OATP1B3 proteins was not detected in liver tissues. This is the first documented case of a population-specific polymorphic intronic L1 transposon insertion contributing to molecular etiology of recessive genetic disease. Since L1 activity in human genomes is currently seen as a major source of individual genetic variation, further investigations are warranted to determine whether this phenomenon results in other autosomal-recessive diseases.

We describe our initial clinical experience regarding the use of a 3D roadmap during balloon-occluded retrograde transvenous obliteration (BRTO) in three patients.Between June 2016 and July 2016, three BRTO procedures were performed in three patients with gastric varices. Preprocedural intravenous dynamic CT was performed, and portal venous phase CT images were postprocessed to obtain volume rendering (VR) images. A 3D roadmap was developed by overlaying the VR images onto the real-time X-ray fluoroscopy images. This 3D roadmap was used for interventional guidance during the BRTO procedure.Using a 3D roadmap, the catheterization of the gastrorenal shunt was successfully accomplished. In addition, in all three patients, the sclerosant could reach the gastric varices without the administration of iodinated contrast medium. Fluoroscopy time and the iodinated contrast dose administered in the present cohort were also substantially lower than in our previous cohorts that did not use a 3D roadmap.Using a 3D roadmap during BRTO enables easier and faster catheter manipulation, thereby helping to reduce both radiation exposure and the need to administer iodinated contrast medium.

Nectin-1 is a cell adhesion molecule that regulates the formation of adherens junctions and tight junctions. We measured the expression of nectin-1 in cancer-associated fibroblasts (CAFs) in patients with pancreatic ductal adenocarcinoma (PDAC). Nectin-1 expression was measured via immunohistochemistry using tissue microarray blocks constructed from resected PDAC tissue from 258 patients. We screened for associations between nectin-1 expression and clinicopathological parameters. According to the percentage of CAFs stained, expression was classified as negative at ≤ 30% and positive at > 30%. Nectin-1 expression was confirmed in CAFs from 64 patients (24.8%), and was associated with lymph node metastasis (p = 0.016), advanced Union for International Cancer Control stage (p = 0.016), perineural invasion (p = 0.022), pancreatic head tumors (p = 0.023), and shorter overall survival (p = 0.003). Multivariate analysis revealed that nectin-1 expression in CAFs was an independent prognostic factor (p = 0.038). Diffuse nectin-1 expression in the CAFs of PDAC patients is associated with invasion, metastasis, and shorter survival.

Although there is evidence about the beneficial effects of probiotics, their effects on aspirin-induced small bowel injuries have not been well examined. We evaluated the effects of the probiotic Lactobacillus gasseri OLL2716 (LG) on aspirin-induced small intestinal lesions, such as ulcers, erosions, reddened lesions, and bleeding.This study enrolled 64 patients who received aspirin for more than 1 month and provided written informed consent to be part of the study. The patients received 112 ml of yogurt containing LG or placebo twice daily for 6 weeks. Small bowel injuries were evaluated by capsule endoscopy before and after consuming the yogurt. The effect of LG on patient symptoms was also assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires before and after 6 weeks of treatment. There was no significant difference in any baseline characteristics and the number of small bowel mucosal breaks between the 2 groups. In contrast with the placebo group, the LG group had significantly fewer small bowel mucosal breaks and reddened lesions after 6 weeks (p0.01). The FSSG and GSRS scores were also significantly improved in the LG group but not in the placebo group. Key Messages: This double-blind, placebo-controlled study found that LG may be useful in reducing aspirin-induced small bowel injuries and in mitigating gastrointestinal symptoms.

Background In Japan, the eradication rate of first-line therapy for Helicobacter pylori (H. pylori) with a proton pump inhibitor (PPI), amoxicillin (AMPC) and clarithromycin (CAM) has been decreasing because of a high prevalence of CAM resistance. A possible decrease of the eradication rate for second-line therapy with a PPI, AMPC and metronidazole (MNZ) is of concern. The aim of this study is to assess the trends in second-line eradication therapy for H. pylori in Japan. Materials and Methods We accumulated data retrospectively on patients administered second-line eradication therapy for Helicobacter pylori with a PPI, AMPC, and MNZ for 1 week after failure of first-line eradication therapy with a PPI, AMPC and CAM at 15 facilities in the Tokyo metropolitan area in Japan from 2007 to 2011. Trends for second-line eradication rates in modified intention-to-treat (ITT) analyses were investigated. Second-line eradication rates were categorized by three PPIs (rabeprazole (RPZ), lansoprazole (LPZ) or omeprazole (OMZ)) and evaluated. Results We accumulated data on 1373 patients. The overall second-line eradication rate was 92.4%. Second-line eradication rates in 2007, 2008, 2009, 2010 and 2011 were 97.7, 90.6, 94.5, 91.8 and 91.8%, respectively, with no significant trends revealed. Second-line eradication rates categorized by three PPIs for the entire 5-year period were 91.6, 93.4 and 92.4% (RPZ, LPZ and OPZ, respectively) with no significant differences among the three PPIs. Conclusions From 2007 to 2011, there were no significant trends in the second-line eradication rates and the rates remained consistently high. From the viewpoint of high prevalence of CAM resistance in Japan, triple therapy with PPI, AMPC and MNZ may be a better strategy for first-line therapy compared to triple therapy with PPI, AMPC and CAM.

A 74-year-old woman undergoing outpatient follow-up for reflux esophagitis and atrophic gastritis tested positive for Helicobacter pylori and underwent primary eradication therapy with lansoprazole (LPZ) 30 mg, amoxicillin (AMPC) 750 mg, and clarithromycin (CAM) 200 mg twice daily for 1 week in August 2012. A urea breath test (UBT) after this treatment revealed that eradication had failed. Secondary eradication therapy was carried out with esomeprazole (EPZ) 20 mg, AMPC 750 mg, and metronidazole (MNZ) 250 mg twice daily for 1 week, but this also failed. The third attempt at eradication consisted of EPZ 20 mg, AMPC 750 mg, and sitafloxacin (STFX) 100 mg twice daily for 1 week, but this also ended in failure. A fourth attempt using rabeprazole (RPZ) 20 mg (4 times daily) with MNZ 250 mg and STFX 100 mg twice daily for 2 weeks also failed, as did a fifth attempt in April 2015 using vonoprazan (VPZ) 20 mg, AMPC 750 mg, and MNZ 250 mg twice daily for 1 week. Eradication was finally successful after the sixth attempt, in which the patient was treated with vonoprazan 20 mg, MNZ 250 mg, and STFX 100 mg twice daily for 2 weeks.

Background and study aims: Studies have estimated that failure of cecal intubation occurs with conventional colonoscopy in up to 10 % of cases. Double-balloon endoscopy (DBE) systems, magnetic endoscope imaging (MEI), and transparent cap have been shown to improve success rates for colonoscopy. This study evaluated the utility of DBE for complete examination of the colon compared with MEI plus cap (MEI-Cap) after incomplete or technically difficult colonoscopy in a randomized comparative manner. Patients and methods: A total of 94 patients with incomplete or technically difficult colonoscopy were randomly assigned to receive either DBE (n = 47) or colonoscopy with MEI–Cap (n = 47). The primary end point was cecal intubation rate within 30 minutes. Secondary end points included intubation time, pain score using a visual analog scale, abdominal pressure attempts, doses of sedative medication, and changes in patient position during colonoscopy. Results: Patient characteristics were comparable in both groups. Cecal intubation rate within 30 minutes was significantly higher for DBE (45 /47, 95.7 %) than for MEI–Cap (34 /47, 72.3 %) ( P = 0.0049). Mean time to reach the cecum was significantly lower in the DBE group (13.0 ± 5.3 minutes) than in the MEI–Cap group (16.4 ± 4.8 minutes; P = 0.0003). No complications were encountered in either group. Conclusion: DBE is more useful for complete examination of the colon than MEI–Cap in patients with incomplete or technically difficult colonoscopy.

This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer. Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25–60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses. Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7–37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes. The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.

Background and Goals: The prevalence of irritable bowel syndrome (IBS) among Japanese patients who visit hospitals departments of internal medicine is thought to be high. However, no clear statistical evidence has been provided to support such a claim. We tested the hypotheses that the prevalence of IBS in medical outpatients clinics in Japan is high, and that IBS patients feel more psychosocial stress than patients without IBS. Study: The subjects in this study were 633 patients who visited participating physicians. Patients were asked to fill in the Japanese version of the Rome II Modular Questionnaire (RIIMQ) for IBS diagnosis, the Self-reported Irritable Bowel Syndrome Questionnaire (SIBSQ) for severity of the disease and the demographic questionnaire for perceived stress and life style. Results: Rome II-defined IBS was diagnosed in 196 patients (31%). Analysis of variance revealed significant difference in the IBS scores of SIBSQ among IBS subjects (39.0 ± 11.1, mean ± SD), functional bowel disorder subjects (27.1 ± 10.2), and normal subjects (24.0 ± 10.0, P < 0.01). The prevalence of IBS depending on age formed 2 peaks, one among adolescents and the other among the elderly. IBS patients had significantly more perceived stress (P < 0.0001), irregular sleep habit (P < 0.0001), and irregular meal habit (P < 0.0001) than those without IBS. Conclusions: The prevalence of IBS among medical outpatients in Japan is high (31%). IBS subjects among medically ill patients are thought to have more perceived stress and less regular life styles.

Background: Idiopathic thrombocytopenic purpura (ITP) is associated with the cytokine response and dysregulation of the cytokine network. Gene polymorphisms of proinflammatory cytokines are associated with several diseases including ITP. Recently, the successful eradication of Helicobacter pylori has been reported to improve the platelet counts in some patients with ITP. The aim of this study was to elucidate the relationship between cytokine gene polymorphisms and platelet recovery in ITP patients after the eradication of H. pylori. Materials and Methods: Gastric H. pylori infection was confirmed using a culture method or specific IgG antibodies against H. pylori in the serum. Thirty-six adult H. pylori-positive ITP patients received antibiotic therapy for H. pylori. The response to treatment was defined as complete response (CR) if the platelet count was above 150 × 103/µl and partial response (PR) if the platelet count increased by more than 50 × 103/µl above the pretreatment count. Genomic DNA was extracted from peripheral blood and polymorphisms in IL-1B (–31, –511), IL-1RN (long or short), TNFA (–308) and TNFB (+252) were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Of the 36 ITP patients, twenty patients (responders) exhibited a platelet response after successful H. pylori eradication therapy, but the other patients (nonresponders) did not. There were no statistical differences in the frequencies of polymorphisms in IL-1B, IL-1RN and TNFA genes between responders and nonresponders. In contrast, the frequency of responders in ITP patients with the TNFB G/G or G/A genotype was significantly higher (69.6%) than that with the TNFB A/A genotype (30.8%). Conclusion: The TNFB (+252) G/G or G/A genotype may therefore be a good predictor of platelet recovery in ITP patients after the eradication of H. pylori.

Until the development of wireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE), it was extremely difficult to examine the entire small intestine. To assess the usefulness of DBE for diagnosing suspected small intestinal bleeding, we retrospectively compared the diagnoses and treatments of cases before and after its introduction at one hospital. Between September 2003 and December 2005, 21 consecutive patients with suspected small intestinal bleeding underwent DBE at Tokai University Hospital (group A), and subsequently 2 were excluded from the study after being diagnosed with bleeding from a diverticulum and an angiodysplasia in the ascending colon, respectively. For comparison, inpatients who were negative for gastrointestinal bleeding on colonoscopy and gastroscopy between May 1998 and August 2003 were reviewed and 27 consecutive patients who had not undergone DBE were selected as the control group (group B). All patients had been diagnosed negative for a source of bleeding on more than one colonoscopy and gastroscopy. There were no significant differences between the two groups in terms of age, gender, history of blood transfusion, blood hemoglobin value on admission, or symptoms. The diagnostic yield of DBE in identifying the source of bleeding was 78.9%: six cases of small intestinal ulcers, five cases of angiodysplasia, two cases of hard submucosal tumor (SMT), one case of small pulsating SMT, and one case of small intestinal cancer. DBE was also used to successfully treat three cases of angiodysplasia with argon plasma coagulation. In the control group, conventional investigations, including enteroclysis, angiography, Meckel scan, scintigraphy with technetium-labeled red blood cells, and/or push enteroscopy, were performed in 88.9%, 29.6%, 29.6%, 55.6%, and 25.9%, respectively. The overall diagnostic yield of the conventional approaches was only 11.1% (P < 0.01), comprising a Meckel's diverticulum, a polyp, and an angiodysplasia. We conclude that DBE can be used to diagnose suspected small intestinal bleeding and to treat some cases, such as angiodysplasia.

Background and Aim: Controversy remains regarding the treatment of choice for chronic gastritis patients with dyspeptic symptoms when Helicobacter pylori eradication is not indicated or fails for their gastric lesions. A multicenter, randomized, double-blind trial was performed to compare the effectiveness of geranylgeranylacetone (GGA), a mucoprotective drug, against cimetidine (CIT), an H2-receptor antagonist, on the treatment of erosions and petechial hemorrhage in H. pylori-infected patients with dyspeptic symptoms. Methods: 128 H. pylori-positive gastritis patients with mucosal erosions and/or petechial hemorrhage were randomized to receive 150 mg GGA t.i.d. or 400 mg CIT b.i.d. for 2 weeks. Improvement and cure rates on endoscopic findings, symptom disappearance rates, and changes in mucosal neutrophil infiltration were compared. Results: Endoscopic improvement rates were significantly higher in the GGA group (n = 50) than in the CIT group (n = 54; 86.0 vs. 64.8%, p = 0.014). Endoscopic cure rates were also significantly higher for GGA than for CIT (80.0 vs. 55.6%, p = 0.012). Symptom disappearance rates were 52.0% for GGA and 42.6% for CIT, but the difference was not significant. There was also no significant difference in mucosal neutrophil infiltration between the groups. Conclusion: GGA treatment appears to be more effective than CIT for chronic gastritis-associated erosion and petechial hemorrhage.

A survey of 21,493 patients who visited our Health Check-up Center during the 6-year period from 2005 to 2010 was conducted for the endpoints of drinking situation and various lifestyle-related diseases. Males accounted for 57.2% (mean age: 53.2 ± 11.4) and females accounted for 42.8% (mean age: 52.5 ± 11.4) of patients surveyed. Patients with no drinking habit accounted for 24.8% and 62.9% of males and females, respectively, and a large gender difference was seen in drinking frequency. When examined by age group, drinking frequency was found to increase with age in males, but gradually decreased with age in females. An examination of alcohol consumption in males revealed that 23.5% had an ethanol conversion rate of 10 g/day, 19.1% had a rate of20 g/day, and 18.2% had a rate of40 g/day. Meanwhile, in females, 22.7% had a rate of ≤ 10 g/day, 7.6% had a rate of ≤ 20 g/day and 4.6% had a rate of ≤ 40 g/day. The association between lifestyle-related disease endpoints and alcohol consumption was next examined by multivariate logistic analysis. The association between drinking and body mass index (BMI) revealed an odds ratio of around 0.8 in patients who consumed ≤ 40 g/day and a significantly reduced frequency of obesity. The odds ratio of hypertension increased in a dose-dependent manner from 1.3 to 1.6 in patients who consumed ≥ 40 g/day. The frequency of high low-density lipoprotein cholesterol (LDL-C) was reduced in light drinkers and the odds ratio decreased from 0.77 to about 0.6 as alcohol consumption increased: The frequency of low high-density lipoprotein cholesterol (HDL-C) was similarly reduced in light drinkers, and the odds ratio decreased remarkably in a dose-dependent manner from 0.73 to 0.22 as alcohol consumption increased. The risk of triglycerides was reduced in light drinkers and was conversely significantly enhanced in heavy drinkers. In patients who consumed ≥ 20 g/day, the risk of impaired glucose tolerance increased significantly in a dose-dependent manner. Increased risk of hyperuricemia was seen even in light drinkers. and the odds ratio increased from 1.2 to 1.8 as alcohol consumption increased. The results of this cross-sectional study suggested that light drinking has a positive effect on BMI, LDL-C, HDL-C and triglycerides. On the other hand, heavy drinking was found to have a positive effect on LDL-C and HDL-C, but a negative effect on systolic blood pressure, triglycerides, fasting blood glucose and uric acid.

The purpose of this study was to evaluate the clinical results of the management of gastric varices by balloon-occluded retrograde transvenous obliteration with polidocanol foam versus ethanolamine oleate.Twenty patients treated with ethanolamine oleate and 21 patients treated with polidocanol foam were enrolled in this study. Early therapeutic effects were assessed mainly by dynamic contrast-enhanced CT. Subjective symptoms, objective findings associated with the procedures, and changes in laboratory data during the obliteration process were evaluated. Rebleeding from gastric varices was assessed after the procedures.Complete obliteration was confirmed in all but one case of early recanalization after treatment with polidocanol foam. One patient died of acute respiratory distress syndrome after treatment with ethanolamine oleate. The total sclerosant volume was significantly lower for 3% polidocanol foam (13.5 ± 6.8 mL) than for 5% ethanolamine oleate (30.6 ± 15.6 mL) (p0.01). Polidocanol foam caused fewer severe reactions, including pain, during and after injection. High body temperature, hemoglobinuria, and reactive pleural effusion were not observed with polidocanol foam. The variance in laboratory data values associated with hemolysis was significantly greater with ethanolamine oleate. No postprocedural rebleeding from the gastric varices was observed during a median follow-up time of 39.5 months after procedures with ethanolamine oleate and 34 months after procedures with polidocanol foam.Polidocanol foam can achieve obliteration of gastric varices comparable to that of ethanolamine oleate but with a significantly lower sclerosant dose and reduced risk of hemolysis-induced complications and harmful reactions, including pain and fever.

Pancreatic neuroendocrine microadenomas (pNEMAs) are neuroendocrine tumors measuring5 mm in diameter. They are considered the precursor of pancreatic neuroendocrine tumors (pNETs). The aim of this study was to investigate the immunohistochemical differences between pNEMA, pNET, and hyperplasia of pancreatic islet cells (HPIL) in patients with non-familial syndromes.We evaluated 21 pNEMAs, 19 HPILs, and 21 non-functional pNETs (10 G1 and 11 G2 cases) in patients with non-familial syndromes. Immunohistochemistry for tumor-associated markers death domain-associated protein (DAXX), alpha thalassemia/mental retardation X-linked (ATRX), cytokeratin 19 (CK19), bcl-2, and CD99 was performed.DAXX was expressed in 95%, 71%, and 71% of HPIL, pNEMA, and pNET samples, respectively; the differences were not significant. ATRX expression in pNEMA and pNET was significantly lower than that in HPIL, whereas there was no significant difference between pNEMA and pNET (HPIL: 95%, pNEMA: 43%, and pNET: 52%). All HPIL and pNEMA cases were negative for bcl-2 and positive for CD99, whereas 29% of pNETs were positive for bcl-2 and 24% were negative for CD99. CK19 expression in HPIL was significantly lower than in pNEMA and pNET, although no significant difference was observed between pNEMA and pNET (HPIL: 5%, pNEMA: 57%, and pNET: 43%). Among G1 and G2 pNETs, CD99 was expressed in 50% of G1 pNETs but not in any G2 pNET cases.Non-familial HPIL, pNEMA, and pNET patients exhibit distinct ATRX, CD99, CK19, and bcl-2 molecular profiles.

A 29-year-old female with ulcerative colitis was found to have advanced sigmoid colon cancer on colonoscopy. Computed tomography (CT) was performed after colonoscopy for the evaluation of metastasis. CT colonography (CTC) could be understood adding carbon dioxide because of soon after colonoscopic examination. Images of CTC were evaluated by two- and three-dimensional images including virtual endoscopic, virtual colon dissection and air images, and then compared with conventional endoscopic images. Virtual endoscopic images of flat elevated cancer with shallow ulcer were similar to those findings by conventional endoscopy. This lesion could be depicted by computer-aided detection.

European studies have revealed that the ABCB11 c.1331T>C (V444A) polymorphism (rs2287622) C-allele frequency is higher among patients with drug-induced cholestasis. Given the low incidence of this disease, however, this association has not been sufficiently elucidated. We aimed to investigate the significance of this polymorphism in Japanese patients. We determined ABCB11 V444A polymorphism frequencies and HLA genotypes in two independent drug-induced cholestasis cohorts. Expression and taurocholate transport activity of proteins from 444A variants were analyzed using Madin-Darby canine kidney II cells. In cohort 1 (n = 40), the V444A polymorphism C-allele frequency (66%) was lower than that in controls (n = 190, 78%), but this difference was not significant (P = 0.09). In cohort 2 (n = 119), comprising patients with cholestatic (n = 19), hepatocellular (n = 74), and mixed (n = 26) liver injuries, the C-allele frequency was lower among patients with cholestatic liver injury (68%) than among those with hepatocellular (75%) or mixed liver injury (83%), although this difference was not significant. In cohort 1, HLA-A*0201 was observed more frequently in patients (22%) than in controls [11%; P = 0.003; odds ratio, 2.4 (95% confidence interval, 1.4-4.0)]. Taurocholate transport activity of 444A-encoded protein was significantly lower than that of 444V-encoded protein (81% of 444V, P < 0.05) because of the reduced protein stability. In conclusion, ABCB11 444A had slightly reduced transport activity, but it did not contribute to the occurrence of drug-induced cholestasis in Japanese patients. Therefore, genetic susceptibility to acquired cholestasis may differ considerably by ethnicity.

Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm. Solid pseudopapillary neoplasm is rare in men, and most SPN cases are in young women. This study aimed to investigate sex differences in SPN clinical histopathology including capillary density and expression of immunochemical markers, including glypican 3. A total of 22 resected tumors from pancreatic SPN patients, including 16 women (73%) and 6 men (27%), were analyzed histopathologically and immunohistochemically for synaptophysin, β-catenin, estrogen receptor, progesterone receptor, Ki-67, CD10, CD31, and glypican 3. The median age was 52.5 years in men and 24 years in women (P = .046). The median tumor size was 22.5 mm in men and 40 mm in women (P = .337). In 11 of the 16 women (69%), but in none of the men, tumors showed complete or incomplete fibrous cap`sules (P = .006). Cholesterol clefts were observed in tumors from 10 women (63%) but in none from the men (P = .012). No significant sex differences were noted in tumor characteristics, including size, macroscopic cystic degeneration, necrosis, lymphovascular involvement, and perineural invasion. The SPNs were weakly positive for glypican 3, although there was no significant difference between sexes. Capillary density tended to be lower in tumors from men than in those from women, but not significantly. Thus, except for the fibrous capsule and cholesterol clefts often found in tumors and the younger age of the women, there were no significant sex differences in histopathologic or immunohistochemical features of SPN, despite its markedly higher occurrence in women.

Background: With the increase in the frequency of clarithromydn-resistant Helicobacter pylori (H. pylori), there is rising concern about the decline of the eradication rate of this infection following treatment. The Tokyo Hp Study Group examined the eradication rate in response to a second-line regimen consisting of proton pump inhibitor (PPI), amoxicillin, and metronidazole by conducting a multicenter study in the Tokyo Metropolitan Area. Materials and Methods: Two hundred and twenty-eight patients with H. pylori infection, in whom the first-line therapy with a PPI, amoxicillin, and clarithromycin administered for 1 week had failed to eradicate the infection, were enrolled in this study. These cases were randomly assigned to one of the two second-line regimens containing metronidazole (API/AM 500 or API/AM 750 ) administered for 1 week. 13 C-urea breath test was performed as a diagnostic method test for H. pylori infection not earlier than 8 weeks after the second-line therapy. Results: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed an eradication rate of 87.6 and 90.6%, respectively, following API/AM 500 treatment, and 86.9 and 88.6%, respectively, following API/AM 750 treatment. Neither analysis revealed any significant difference in the eradication rate between API/AM 500 and API/AM 750 (p = .876 and .621, respectively). According to ITT and PP analyses, the eradication rates following treatment with API/AM 500 were 85.2 and 88.5% with the use of lansoprazole, 62.5 and 62.5% with the use of omeprazole, and 93.2 and 96.5% with the use of rabeprazole, respectively. There was a significant difference in the eradication rates between PPI (omeprazole)/AM 500 and PPI (rabeprazole)/AM 500 . In the case of API/AM 750 , the corresponding eradication rates were 84.8 and 87.0% with the use of lansoprazole, 92.9 and 92.9% with the use of omeprazole, and 92.9 and 92.9% with the use of rabeprazole, respectively. There were no significant differences in the eradication rates obtained with the use of the three PPIs. Conclusions: Both API/AM 500 and API/AM 750 administered for 1 week appeared to be highly effective second-line regimens for the treatment of H. pylori infection in Japanese patients. From the viewpoint of adverse events, API/AM 500 appeared to be safe compared with API/AM 750 .

Background: A proton pump inhibitor (PPI)-based triple therapy with clarithromycin (CAM) and amoxicillin (AMPC) is now a standard regimen for Helicobacter pylori (HP) eradication in Japan. However, the CAM-resistant rate has increased recently and alternative therapies are sorely needed. Therefore the aim of the present study was to evaluate the effectiveness and safety of the PPI–tetracycline (TC)–metronidazole (MNZ) regimen (the PTM regimen) as an alternative therapy in comparison with the PPI–AMPC–MNZ (PAM) regimen. Methods: Sixty-four HP-positive patients visiting the HP-eradication clinic in Tokai University Hospital from July 1998 to March 2003 were treated with either PTM or PAM as alternative therapies. The HP eradication was assessed by urea breath test (UBT), HP stool antigen test, or HP culture method more than 2 months after completion of the treatments. The drug resistances against CAM, AMPC, TC, and MNZ were assessed by the agar dilution method. Results: Fifty-six patients (26 PTM and 30 PAM) completed medication and evaluation of the eradication. The eradication rates of PTM were 82.8% (24/29) and 92.3% (24/26), while those of PAM were 74.3% (26/35) and 89.7% (26/29) by intention-to-treat and per-protocol analysis, respectively. The differences between the regimens were not statistically significant. There were no severe adverse effects observed in either of the regimens. The drug-resistance analyses showed 15 CAM- and one MNZ-resistant cases but no TC or AMPC resistance in the available 25 samples. Conclusion: The PTM and PAM regimens were equally effective and safe as alternative HP eradication therapies. And PTM would be particularly useful in penicillin allergy cases.

Helicobacter pylori (H. pylori) infection is a strong risk factor for the development of gastric cancer. In 2013, the Japanese government approved H. pylori eradication therapy in patients with chronic gastritis as well as peptic ulcer. However, the continuing decline in eradication rates for first-line H. pylori eradication therapies is an urgent problem. In this study, we investigated changes in the first-line eradication rate from 2001 to 2010.Eradication rates for 7-day triple therapy [proton pump inhibitor (rabeprazole 20 mg, lansoprazole 60 mg, or omeprazole 40 mg)+amoxicillin 1500 mg + clarithromycin (CAM) 400 or 800 mg, daily] were collated from 14 hospitals in the Tokyo metropolitan area. The urea breath test was used for the evaluation of eradication. The cut-off value was less than 2.5%.The yearly eradication rates (intention to treat/per protocol) were 78.5/79.5% (2001, n=242), 71.2%/72.9% (2002, n=208), 67.8%/70.5% (2003, n=183), 75.6%/84.6% (2004, n=131), 56.4%/70.5% (2005, n=114), 70.5%/75.8% (2006, n=271), 67.4%/82.0% (2007, n=135), 64.0%/76.3% (2008, n=261), 60.5%/74.3% (2009, n=329), and 66.5%/78.8% (2010, n=370), respectively. Examination of eradication rates according to CAM dosage revealed an eradication rate of 65.6% (383/584) for CAM 400 mg daily, and 68.5% (1124/1642) for CAM 800 mg daily, with no significant difference seen between dosages.In recent years, eradication rates for first-line triple therapy have obviously decreased, but no noticeable decrease has occurred after 2001.

Background. Multiple regimens for the eradication of Helicobacter pylori have been tested, but the best therapy has not been determined yet. To determine the efficacy of a new triple agent regimen using a combination of lansoprazole, amoxicillin, and clarithromycin against Helicobacter pylori (H. pylori), and to examine H. pylori resistance to this therapy in ineffective cases. Methods. We studied a total of 71 patients infected with H. pylori who had gastric ulcer (n~=~37) or duodenal ulcer (n~=~34) as confirmed by endoscopy. Patients received 1500~mg amoxicillin, 400~mg clarithromycin and 30~mg lansoprazole for 2~weeks followed by 30~mg lansoprazole for 6~weeks in patients with gastric ulcer or for 4~weeks in those with duodenal ulcer. Endoscopic examination was performed before treatment and at 1~month, 2~months, and 5~months after initiating treatment to check the status of ulceration and H. pylori infection. Results. The eradication rate of H. pylori was 92% (CI, 83–100%) in the gastric ulcer group and 94% (CI, 86–100%) in the duodenal ulcer group at 5~months, as determined by per-protocol analysis. Resistance to clarithromycin was present in 1 of 71 (1%) patients before treatment and in 2 of 5 (40%) patients after treatment. No resistance to amoxicillin and lansoprazole was found in patients before or after treatment. The resistance to clarithromycin changed during the observation period. Conclusions. The new triple agent regimen was effective against H. pylori. Resistance to clarithromycin may not be permanent and it might be one of the risk factors which affect the efficacy of a clarithromycin-based therapy.

Pancreatitis is the most common and serious complication of endoscopic retrograde cholangiopancreatography (ERCP). Several studies have compared contrast media (CM) with different osmolalities, but the results are conflicting. We conducted this study to clarify the difference between 2 CM used in ERCP.Five hundred and seventy-six patients were examined by using ERCP in our hospital during 2010. Out of these, 56 patients were enrolled in this study. We investigated the incidence of post ERCP pancreatitis (PEP) and hyperamylasemia. Serum amylase levels were compared in the 2 groups.Twenty-seven patients were treated with iodixanol and 29 with diatrizoate meglumine Na. The rate of PEP in the diatrizoate meglumine Na group and iodixanol group was 0% (0/29) and 7.4% (2/27), respectively (P = 0.228). The rate of hyperamylasemia was 10.3% (3/29) and 14.8% (4/27), respectively (P = 0.70). There were no significant differences between two groups for amylase levels pre-procedure (P = 0.082), 3 h post procedure (P = 0.744), or next morning (P = 0.265).There were no significant differences in the rates of PEP or hyperamylasemia between CMs in ERCP. We believe it is unnecessary to use the more expensive low osmolality CM in ERCP to prevent PEP.

In the present study, the effects of short-term treatment with lansoprazole on healing and recurrence of peptic ulcer were investigated. Complete healing (change to the S2 stage) after 3 or 4 weeks of treatment with lansoprazole was observed in 9.9% of gastric ulcers and 38.3% of duodenal ulcers. Complete healing was observed after 3 or 4 weeks of treatment with lansoprazole in gastric ulcers and was significantly related to the serum titer of IgG anti-Helicobacter pylori antibodies. This was not the case in duodenal ulcers. Complete healing after 6 or 8 weeks of treatment with lansoprazole was not dependent on serum levels of IgG anti-H. pylori antibodies. Short-term treatment by lansoprazole did not affect serum levels of IgG anti-H. pylori antibodies immediately after the end of lansoprazole treatment, but significantly reduced serum levels of IgG anti-H. pylori antibodies were found 9 months after treatment.

To evaluate the use of diffusion-weighted imaging (DWI) for estimating infarcted splenic volume during partial splenic embolisation (PSE) using n-butyl cyanoacrylate (NBCA). Twenty consecutive patients (57.2 ± 11.7 years) with hypersplenism underwent PSE. Intrasplenic branches were embolised using NBCA via a 2.1-French microcatheter aiming at infarction of 50 to 80 % of total splenic volume. Immediately after PSE, signal intensities (SI) of embolised and non-embolised splenic parenchyma were measured on DWI. Semi-automated volumetry (SAV) on DWI was compared with conventional manual volumetry (MV) on contrast-enhanced CT 1 week after PSE. Platelet counts were recorded before and after PSE. The SI on DWI in the embolised parenchyma decreased significantly (P

Aims: Our aim was to investigate plasma amino acid levels in chronic pancreatitis (CP) patients and examine their relationship with exocrine insufficiency. Methods: Thirty-nine patients with alcoholic CP and 20 healthy controls were examined. CP patients were divided into an exocrine normal group (n = 28) and an exocrine insufficiency group (n = 11). Selected clinical and laboratory values were compared among the three groups, and the effect of an elemental diet was observed in 6 patients of the exocrine insufficiency group. Results: Total amino acid concentration was significantly higher in the control group than in the exocrine normal group and exocrine insufficiency group (p = 0.032, p = 0.020). In the exocrine insufficiency group, significant reductions in the concentrations of serum histidine and methionine were found compared with the control group and exocrine normal group (histidine: p = 0.032, p = 0.045; methionine: p = 0.043, p = 0.049). In the exocrine normal group and exocrine insufficiency group, significant elevation in the concentration of serum glutamate was found compared with the control group (p = 0.036, p = 0.029). Elemental diet improved these amino acid concentrations. Conclusion: Patients with CP exhibit alterations in the levels of several amino acids, such as histidine, methionine, and glutamate. These amino acid deficiencies seem to correlate with exocrine insufficiency and be improved by an elemental diet.

Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD.Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health-related quality of life (HR-QOL) by the SF-36 Japanese version, and patients' compliance to medication was evaluated.Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two-week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR-QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication.Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy.

We recently detected an annular ulcer thought to have been caused by non-steroidal anti-inflammatory drugs (NSAIDs) when we performed small bowel capsule endoscopy on a patient with suspected small-bowel bleeding and a history of frequent use of oral NSAIDs. The patient was a 64-year-old woman who complained of bloody stools and abdominal pain. The annular ulcer showed concentric stenosis, which caused retention of the capsule endoscope. NSAIDs are some of the most frequently used anti-inflammatory analgesics, and even more frequent use can be expected with the aging of society. No reports to date appear to have described retention of a capsule endoscope due to annular ulceration caused by NSAIDs. We report herein our experience with a patient showing small-bowel ulcer caused by NSAIDs.

The usefulness of endoscopic ultrasound (EUS) in the diagnosis of small pancreatic cancer is widely accepted. We experienced a small, 8 mm, pancreatic cancer with intra-pancreatic metastasis of 2 mm revealed by EUS. The patient was a 71-year-old female with a small low echoic tumor observed by abdominal ultrasonography. She was referred to our hospital for further investigation. She complained of mild abdominal pain. She had a past history of myoma uteri. Ultrasonography showed a 10 mm low echoic mass in the body of the pancreas, but it was difficult to make a distinction between a solid mass and a cystic lesion. No tumor was shown by CT or MRI. EUS was performed, and showed a solid low echoic tumor of 8 mm and a low echoic mass of 2 mm in a diameter near the tumor. An ERCP study was performed, but the cytology of the normal main pancreatic duct was shown to be benign. We diagnosed the patient with pancreatic cancer, and surgery was performed. A pathological examination revealed a 10 mm invasive ductal carcinoma and intra-pancreatic metastasis.

A 64-year-old woman presented with advanced gastric cancer (signet ring cell carcinoma) and underwent total gastrectomy in 1996. Postoperative recovery was good, and she was monitored regularly on an outpatient basis. Abdominal computed tomography in 1999 revealed a soft tissue shadow ventral to the origin of the celiac artery. Careful monitoring was continued on an outpatient basis. The patient began to experience gluteal swelling and pain in April 2008. Symptoms rapidly exacerbated and the patient was hospitalized for further examination. Gluteal muscle biopsy revealed signet ring cell carcinoma and bilateral hydronephrosis. Gluteal recurrence of the original gastric cancer was suggested, and systemic chemotherapy consisting of S-1 at 100 mg/day (3 weeks on, 1 week off) and CDDP (day 8) was started. Following the 6th cycle of chemotherapy, gluteal symptoms disappeared and the patient was judged to have achieved clinical complete response (CR). No adverse events or image findings suggesting new recurrence have since been identified. The patient received a total CDDP dose of 585 mg and clinical CR has been maintained as of 14 years after total gastrectomy and 18 months after recurrence.

BACKGROUND: Radiofrequency ablation (RFA) is becoming a well-known local therapy for hepatocellular carcinoma (HCC). Transcatheter arterial chemoembolization (TACE) is expected to enhance the effects of subsequent RFA by reducing arterial blood flow. However, the long-term efficacy of this combined therapy has not been elucidated. In this study, the survival rates of patients who received TACE combined with RFA (TACE + RFA) were compared with those of patients treated surgically. METHODS: The study included consecutive patients who received TACE + RFA or surgical resection as the initial curative treatment for HCC between 2000 and 2005 at Tokai University Hospital. Inclusion criteria were a single HCC ≤50 mm or up to 3 HCCs ≤30 mm, presence of cirrhosis classified as Child-Pugh class A, no vascular invasion, and no extrahepatic metastasis. RESULTS: Sixty-two patients (23 women, 39 men; aged 67.5 ± 8.4 years [mean ± standard deviation]) received TACE + RFA, and 55 patients (15 women, 40 men; aged 66.1 ± 8.4 years) underwent surgical resection. Median follow-up periods were similar (50 months in the TACE + RFA group vs 49 months in the resection group). The probabilities of overall survival at 1, 3, and 5 years in the TACE + RFA group (100%, 94.8%, and 64.6%, respectively) were similar (P = .788) to those in the resection group (92.5%, 82.7%, and 76.9%, respectively). Two major RFA-related complications were observed (1.5%). CONCLUSIONS: RFA combined with TACE is an efficient and safe treatment that provides overall survival rates similar to those achieved with surgical resection. Cancer 2010. © 2010 American Cancer Society.

Lamivudine is a potent oral anti-viral medicine for the treatment of hepatitis B virus (HBV) infection. However, one of the major problems is the breakthrough (BT) followed by flare-up of hepatitis. We examined the influences of clinical background, progression of liver fibrosis, presence or absence of HBeAg and previous interferon (IFN) therapy on the occurrence of breakthrough.This study comprised 51 patients with HBV related chronic hepatitis (CH) or cirrhosis (LC) who were treated with lamivudine for the mean period of 33.8 ± 13.1 months (range 3-63 months). Thirty-six patients were CH, 25 were HBeAg- positive, and 25 had a previous history of IFN therapy. Patients were divided into two groups according to the occurrence of BT, either BT(+) or BT(-). Age, gender, alanine aminotransferase (ALT) and HBV titer before treatment, normalization of ALT (≤ 40 IU/L) and flare-up of hepatitis (ALT80 IU/L) rates, degree of hepatic fibrosis (CH/LC), presence or absence of HBeAg (HBeAg(+)/(-), and previous IFN therapy (IFN(+)/(-) were analyzed using Cox's proportional hazards analysis.Twenty-five patients showed BT. Background data were not different between the patients with and without BT. Flare-up of hepatitis occurred more frequently in BT. Rates of BT were markedly higher in LC (P = 0.025) and IFN(+) (P = 0.036), but HBeAg was not associated with BT. In multivariate analysis, progression of liver fibrosis (P = 0.006) and previous IFN therapy were independent risk factors for BT (P = 0.023).BT significantly occurred in patients with LC and the history of previous IFN therapy. Multivariate analysis showed that progression of hepatic fibrosis and previous interferon therapy are independent risk factors for BT.

Submucosal hematoma of the esophagus is a rare disorder. We encountered a 70-year-old woman with an extremely large submucosal hematoma of the esophagus that extended from the cervical esophagus to the gastric angle. It was likely that her hematoma was caused by accidental ingestion of a fish bone, and her condition improved with conservative treatment alone. In this article, we summarize the reported cases of submucosal hematoma of the esophagus in Japan, and discuss the case with a review of the literature.

The authors describe here the use of foam sclerotherapy under C-arm computed tomography (CT) guidance for the treatment of gastric varices via balloon-occluded retrograde transvenous obliteration in seven patients and percutaneous transhepatic obliteration in one patient. All gastric varices were occluded successfully after replacement of blood by foam, which was trapped in the gastric varices as shown by C-arm CT. It also helped reduce the amount of sclerosant, an issue that is associated with severe complications, such as hemolysis, allergy, acute respiratory distress syndrome, and others. Foam sclerotherapy under C-arm CT guidance is a promising tool in the therapeutic armamentarium against gastric varices.

Endoscopy is usually effective in treating duodenal ulcer bleeding, but depending on the lesion site and overall patient condition, hemostasis may be difficult to achieve with endoscopy alone. We described two patients with duodenal ulcer bleeding in whom endoscopic hemostasis was difficult. Immediately after transcatheter arterial embolization, endoscopic examination was used to confirm hemostasis and completing of the angiographic procedures.

The association between gastroesophageal reflux disease (GERD) and chronic renal failure (CRF) remains unclear. The aim of the present study is to assess the gastroendoscopic findings and the prevalence of GERD in CRF patients by endoscopic examination.This study consisted of 156 CRF patients (97 men and 59 women, mean age: 64.2 years) whose creatinine level was more than 2 mg/dl and who underwent endoscopic examination. We checked their renal function, gastrointestinal symptoms and gastroendoscopical findings, and examined the relationship between renal function and gastroendoscopic findings, and the prevalence of GERD.In the gastroendoscopic findings of the 156 CRF patients who underwent endoscopic examination, the prevalence of GERD was 34.0%. Especially, in symptomatic cases, the prevalence of GERD was 44.0%. In hemodialysis patients, the prevalence of GERD was 50.0%. The prevalence of GERD tended to increase as renal function become worse. There were statistically significant differences between the patients on hemodialysis and pre-dialysis in the prevalence of GERD (P0.01). The severity of GERD tended to be mild.Compared to the reported prevalence of GERD in 6010 Japanese adults (16.3%), the prevalence of GERD in CRF patients, especially who underwent hemodialysis (50.0%), was increased.