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BACKGROUND Metastasis occurs as a late event in the natural history of hepatocellular carcinoma (HCC), and most patients die of liver failure attributed to the tumor supplanting the liver. Conversely, the brain is a less common metastatic site. CASE SUMMARY We describe a rare case of hepatitis C virus-related multiple HCC metastasizing to the cavernous sinus, Meckel’s cave, and the petrous bone involving multiple cranial nerves in an 82-year-old woman. At admission imaging studies including Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (MRI) revealed multiple HCC nodules in both right and left lobes. Ultrasound guided biopsy of the left lobe revealed moderately differentiated HCC. Molecular targeted therapy with Lenvatinib (8 mg/d for 94 d, per os) and Ramucirumab (340 mg/d and 320 mg/d, two times by intravenous injection) were administered for 4 mo, resulting in progression of the disease. Three months after the start of molecular target therapy, the patient presented with symptoms of hyperalgesia of the right face and limited abduction of the right eye, indicating disturbances in the right trigeminal and abducens nerves. Brain MRI disclosed a mass involving the cavernous sinus, Meckel’s cave and the petrous bone. Contrast-enhanced MRI with gadolinium-chelated contrast medium revealed a well-defined mass with abnormal enhancement around the right cavernous sinus and the right Meckel’s cave. CONCLUSION The diagnosis of metastatic HCC to the cavernous sinus, Meckel’s cave, and the petrous bone was made based on neurological findings and imaging studies including MRI, but not on histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

AIM To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. METHODS The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. RESULTS The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients’ GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P < 0.005). In erosive esophagitis patients, the FSSG scores of the CYP2C19 rapid metabolizers (RMs) were significantly higher than the scores of the poor metabolizers and intermediate metabolizers (total scores: 16.7 ± 8.6 vs 7.8 ± 5.4, P < 0.05; acid reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P < 0.005). In contrast, the FSSG scores of the CYP2C19 RMs in the non-erosive reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). CONCLUSION Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P<0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.

Novel and effective drugs against acute pancreatitis are required. Therefore, we examined the changes in the metabolite levels in the serum and pancreatic tissue of mice with cerulein- and arginine-induced pancreatitis using gas-chromatography/mass-spectrometry (GC/MS) and investigated whether these alterations affected the severity of acute pancreatitis. In the cerulein-induced pancreatitis model, 93 and 129 metabolites were detected in the serum and pancreatic tissue, respectively. In the L-arginine-induced acute pancreatitis model, 120 and 133 metabolites were detected in the serum and pancreatic tissue, respectively. Among the metabolites, the concentrations of tricarboxylic acid (TCA) cycle intermediates and amino acids were altered in pancreatitis, and in pancreatic tissue, the levels of the intermediates involved in the initial part of the TCA cycle were increased and those of the intermediates involved in the latter part of the TCA cycle were decreased. Some metabolites exhibited similar changes in both pancreatitis mouse models, e.g., the levels of glutamic acid and O-phosphoethanolamine were significantly decreased in the pancreatic tissue. Supplementation with glutamic acid and O-phosphoethanolamine attenuated the severity of cerulein-induced acute pancreatitis. Our results suggest that GC/MS-based metabolomics is capable of accurately representing the status of acute pancreatitis, leading to the discovery of therapeutic agents for pancreatitis.

Patients using low-dose aspirin (LDA) have an increased risk of gastroduodenal mucosal lesions and upper gastrointestinal symptoms. We aimed to clarify the efficacy of rabeprazole for preventing peptic ulcer, esophagitis, and gastrointestinal symptoms associated with LDA.Patients with a history of peptic ulcers who were receiving LDA for cardiovascular or cerebrovascular disease were randomly assigned to receive rabeprazole at 10 mg daily, rabeprazole at 20 mg daily, or gefarnate (a cytoprotective anti-ulcer agent) at 50 mg twice daily. The primary endpoint was the development of gastric and/or duodenal ulcer at 12 weeks. The modified Lanza score (MLS) and gastrointestinal symptoms were evaluated at baseline and at 12 weeks.The full analysis set comprised 261 patients (rabeprazole 10 mg: n = 87, rabeprazole 20 mg: n = 89, gefarnate 100 mg: n = 85). The cumulative incidences of gastroduodenal ulcers at 12 weeks in the 10 mg rabeprazole group, 20 mg rabeprazole group, and gefarnate group were 7.4, 3.7, and 26.7 %, respectively (rabeprazole group 5.5 % vs. gefarnate group 26.7 %, hazard ratio [HR] 0.179; 95 % confidence interval [CI] 0.082-0.394; p0.0001). The proportions of patients with an MLS of ≥1 and erosive esophagitis were significantly lower in the rabeprazole group than in the gefarnate group at 12 weeks (gastric lesions 33.5 vs. 62.4 %, p0.0001; duodenal lesions 5.7 vs. 24.7 %, p0.0001; erosive esophagitis 5.8 vs. 19.4 %, p0.0001). Rabeprazole was significantly more effective than gefarnate for the resolution and prevention of gastrointestinal symptoms (resolution 53.6 vs. 25.0 %, p = 0.017; occurrence 9.2 vs. 28.3 %, p = 0.0026).Rabeprazole is more effective than gefarnate for reducing the risk of recurrence of peptic ulcer, esophagitis, and gastrointestinal symptoms in LDA users.

Sphincter of Oddi disorder (SOD) is a functional disorder of the sphincter of Oddi (SO) and is pathophysiologically equivalent to functional gastrointestinal disorder (FGID) of the digestive tract. SOD is important as a cause of biliary pain of unknown origin and idiopathic acute recurrent pancreatitis; however, the concept of SOD has not generally spread in the same way as FGID. SOD is diagnosed using ROME III criteria which were revised in 2006 to reduce the number of unnecessary and potentially risky procedures. Many cases of SOD still need SO manometry (SOM) which is performed during endoscopic retrograde cholangiopancreatography (ERCP). It is problematic that SOD patients, who already have a high risk of post-ERCP pancreatitis, require SOM for a definitive diagnosis. SOM is an invasive examination that is accompanied by a high risk of post-procedure pancreatitis and can be performed only at a limited number of institutions because of technical difficulties. In the treatment of SOD, the effectiveness of the drugs is uncertain, and the role of drug therapy in the management of SOD has not yet been established. In recent years, endoscopic sphincterotomy (EST) has been recognized as standard treatment for SOD; however, the effect of EST is not yet clear. The development of less invasive diagnostic techniques is desirable in the future. Furthermore, patient eligibility criteria for EST and the long-term prognosis after EST should be clarified.

症例は63歳の日本人男性．インドネシア在任中にA型急性肝炎に罹患し，入院した．経過観察にて一定の改善を認めたものの，トランスアミナーゼ値は正常化せず，肝障害の遷延を認めた．A型肝炎が沈静化している一方でIgGの上昇，抗LKM-1抗体の上昇を確認したため，肝生検を施行した．この時点で国際診断基準ではII型自己免疫性肝炎疑診例に相当し，肝障害遷延の原因になっていると考えられた．ステロイド内服治療を開始したところ著効し，トランスアミナーゼ値の正常化を認めた．A型肝炎により誘導された自己免疫性肝炎の報告例は非常に少ないが，さらに本症例は病型がII型であった，きわめて稀な1例と考えられたため報告した．

We report a stricture occurring during chemotherapy for malignant lymphoma that was successfully treated by endoscopic balloon dilation. The patient was diagnosed with stage IV malignant lymphoma by esophagogastroduodenoscopy and computed tomography scans. She complained of nausea and vomiting after undergoing the second cycle of chemotherapy. A small intestinal series through an ileus tube showed severe stricture of the ileum. Endoscopic balloon dilation was successfully performed with single-balloon endoscopy. After the procedure, her symptoms subsided and did not recur even 8 months after endoscopic dilation therapy.

Objective: Seven-day administration of omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day is currently approved in Japan for the eradication of Helicobacter pylori infection. We investigated the efficacy and safety of an omeprazole-based triple therapy regimen in combination with amoxicillin and low-dose clarithromycin in Japanese patients. Methods: Patients were randomly assigned to either the low-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 400 mg/day) or the high-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day). A total of 288 patients were allocated to the low-dose (143) and high-dose (145) groups and were treated twice daily for 1 week. Results: For the full-analysis set, H. pylori eradication rates were 81.1% (116/143 patients, 90% confidence interval [CI] 74.9, 86.3) in the low-dose group and 80.0% (116/145 patients, 90% CI 73.7, 85.3) in the high-dose group. Per-protocol eradication rates were 81.7% (103/126 patients, 90% CI 75.1, 87.2) and 84.1% (90/107 patients, 90% CI 77.1, 89.6), respectively. When patients with non-susceptibility to clarithromycin were excluded, eradication rates were ⋙80% for both gastric and duodenal ulcers in the two groups. The results suggested that eradication rates were affected more by susceptibility to clarithromycin than to amoxicillin. Both regimens were well tolerated. Conclusion: This study demonstrated that an omeprazole-based triple-therapy regimen with clarithromycin 400 mg/day was as effective as that with clarithromycin 800 mg/day for H. pylori eradication.

It is well recognized that long-term administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA) can induce liver fibrosis via a steatohepatitis-like inflammatory process. Several non-invasive tests have been investigated as alternatives to liver biopsy, which is, however, still recognized as a final diagnostic modality to detect the MTX-induced liver damage. To clarify whether there is a significant discrepancy between clinical estimations and pathologic findings of this hepatic condition, we performed a following comparative study. Four RA patients (4 women, age 67-80 yr) with MTX-induced liver damage were reviewed. The severity of hepatic damage estimated clinically was compared with histopathologic findings. Consequently, the liver biopsies showed the relatively earlier stages of and milder degrees of hepatic damages than the clinical estimations. The histopathologic findings were more reliable and useful than any other clinical examinations, to plan and modify the treatment strategies, especially in cases of liver damages with multiple etiologies besides MTX. These findings suggest that liver biopsy is an unavoidable examination to assess precisely MTX-induced liver damage. Non-invasive tests may be useful to monitor the hepatic condition of RA patients receiving MTX but do not constitute an acceptable alternative to liver biopsy.

Background: A new plastic stent was designed for endoscopic biliary stenting to achieve a long and effective drainage period. Method: The Double layer stent is composed of Teflon as the inner layer and nylon as the outer layer divided with metallic mesh. This structure gives the stent several side-flaps without side-holes. Double layer stents were applied in 24 patients with inoperable malignant biliary obstruction. Results: The Double layer stents were successfully placed in all cases, and the effective drainage rate of these stents was 96%. The mean patency period evaluated by the Kaplan–Meier method without ineffective cases was 207 days, which was longer than the ordinary plastic stent of the same diameter. Concerning the complications related to inserting, we experienced dislocation was experienced in three patients. Conclusions: The authors regard this new device as an useful stent, which users can expect long patency period, easy exchange management, and reduced cost for the patients with inoperable obstruction in the biliary tract.

Background: It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19–9, carcinoembryonic antigen (CEA) and K-ras mutations. Methods: One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19–9, CEA, K-ras mutations and CTSE. Results: The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; χ2 = 34.76; P < 0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19–9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct. Conclusions: Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.

患者は68歳女性で, 右季肋下で5横指, 心窩部で4横指にわたる肝腫大を認めた. 血液検査成績では, 血清アルブミンの著しい低下と胆道系酵素の上昇を認めた. 腹部造影CT検査にて肝右葉と左葉の一部に造影効果の乏しい部分を認め, dynamic MRIでも同様の部位に著しい造影効果の低下を示した. また, 99mTc-PYP (ピロ燐酸) シンチグラムにて肝に取込みを認め, 肝アミロイドーシスを疑った. 超音波下肝生検像では, アミロイドの沈着および肝細胞の圧迫と萎縮を認めた. 免疫組織学的検討では, 沈着物質はκ型AL蛋白であり, 原発性アミロイドーシスと診断し, 腎生検でも同様の所見が得られた. アミロイドーシスの確定診断は組織学的手段によるが, 近年の画像診断の進歩はめざましく, 各種の画像診断法を駆使することで肝生検に迫る診断が可能であると考える.

Telaprevir, a non-structural (NS)3/4A protease inhibitor, is a direct-acting antiviral drug that inhibits viral replication. Triple therapy with telaprevir, pegylated interferon, and ribavirin is a standard therapeutic regimen for patients with genotype 1b chronic hepatitis C virus (HCV) infection and a high viral load. Several factors, including mutations in the NS5A gene, are important predictors of the efficacy of interferon therapy. In this study, we examined the mutational diversity of NS5A and its impact on the efficacy of triple therapy. We enrolled patients with genotype 1b chronic HCV infection and a high viral load (31 males/17 females; mean age, 57.6 years), who were treated with triple therapy. This study was conducted at Kobe University Hospital and at three affiliated hospitals in Hyogo prefecture, Japan, between November 2011 and June 2013. A sustained viral response after 12 weeks (SVR12) was achieved in 37/48 patients (77%). Based on intent-to-treat analysis, SVR12 was significantly greater in patients with the major allele than in those with the minor allele for the IL28B single nucleotide polymorphism (SNP; 88 vs. 56%; P

Background Conducting randomized controlled trial (RCT) for each of the risk factors associated with prophylactic pancreatic duct stent (PPDS) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is difficult owing to the volume of cases and ethical considerations. In this study, we tried to reveal the degree of preventive effects of PPDS for each individual risk factor within the high-risk group of PEP using the propensity score analysis. Methods The clinical data of 1131 ERCP practices performed at Kobe University Hospital from April 2006 to February 2009 were collected prospectively. We investigated their clinical characteristics including the risk factors of PEP, the use of PPDS and complications of ERCP. We conducted the stratification analysis using the propensity score matching analysis. Results In 210 propensity score-matched ERCPs, PPDS proved to be effective in preventing PEP in patients with a history of pancreatitis (odds ratio 0.11, 95% CI 0.01–0.76, P = 0.01) and cases of difficult cannulation (requiring more than 30 min) (odds ratio 0.13, 95% CI 0.01–1.14, P = 0.08). Conclusions Patients with a history of pancreatitis and cases of difficult cannulation are strongly recommended for PPDS placement. The propensity score analysis can be adapted to the ERCP-related analysis with many procedure-related factors with using retrospective data, and may be adapted to investigate the matters that are unsuitable for RCT by volume and ethical issue.

We describe a 69-year-old man with a history of multiple gastroduodenal ulcers, presenting with the onset of obstructive jaundice. Abdominal CT, MRI and EUS demonstrated a sheet-like mass in the pancreaticoduodenal groove. EUS-FNA did not reveal malignancy. Conservative treatment did not improve his clinical condition and repeated acute pancreatitis occurred during his treatment. Thus, pancreaticoduodenectomy was performed. Histopathological findings showed a duodenal ulcer penetrating the pancreas and infiltration of inflammatory cells and fibrosis in the pancreaticoduodenal groove. The spread of inflammation associated with the duodenal ulcer may have been one of the causes of groove pancreatitis.

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells. Cathepsin E (CTSE) is a non-secretory, intracellular, but non-lysosomal proteinase found in the highest concentration in the superficial epithelial cells of the stomach. The aims of our study were to examine the expression of CTSE in the pancreas, to establish an assay system of CTSE and to evaluate the diagnostic usefulness of CTSE in the pancreatic juice. Eleven patients with pancreatic ductal adenocarcinoma, 10 with mucin-producing adenoma, 3 with intraductal papillary hyperplasia and 43 with chronic pancreatitis were examined. Surgically resected pancreatic tissues were subjected to immunohistochemistry for CTSE. Pancreatic juice was collected from the patients and subjected to sandwich ELISA and Western analysis for detecting CTSE. Positive staining for CTSE was observed in pancreatic ductal adenocarcinoma by immunohistochemistry. CTSE was also expressed in mucin-producing adenoma, intraductal papillary hyperplasia and mucinous hyperplasia. CTSE in the pancreatic juice was present in 8 of 11 patients with pancreatic ductal adenocarcinoma, 5 of 10 patients with mucin-producing tumor, 1 of 3 patients with intraductal papillary hyperplasia and 4 of 43 patients with chronic pancreatitis. The detection frequency of CTSE in the pancreatic juice was significantly higher in the patients with pancreatic ductal adenocarcinoma than in the patients with chronic pancreatitis. Our findings suggest that the expression of CTSE is associated with the pathogenesis of pancreatic ductal adenocarcinoma, that CTSE in the pancreatic juice seems to be a useful marker for a definitive diagnosis and that CTSE may be expressed at a relatively early stage of multistep carcinogenesis in pancreatic lesions.

Sphincter of Oddi manometry (SOM) is recognized as the standard diagnostic modality for sphincter of Oddi dysfunction (SOD). However, SOM is not commonly performed because of its technical difficulty and the high incidence of post-procedural pancreatitis. To diminish post-procedural pancreatitis, we tried to develop a new method of SOM. This study examined the feasibility of SOM with a guide-wire-type manometer, which is commonly used to measure the arterial pressure for coronary angiography, for the assessment of SO motility.A total of 35 procedures were performed in 8 patients with biliary type III SOD and 14 patients with other disease. We performed SOM using the guide-wire-type manometer on SOD cases and other cases [amplitude, duration, frequency and the area under the curve (AUC) of SO contractions].The mean time required for the measurement was 7.5 ± 4.1 min. The amplitude, frequency and AUC of SO contractions were significantly larger in the SOD cases than in other diseases (147.2 vs. 92.8 mmHg, p = 0.042; 10 vs. 5/min, p = 0.007; 2,837 vs. 1,122 mmHg s, p = 0.003, respectively). In 6 patients who underwent endoscopic sphincterotomy (EST), the SO amplitude decreased dramatically after EST. In this study, mild pancreatitis was observed in only one patient.SOM using a guide-wire-type manometer is safe, reliable and easy to apply for the clinical assessment of SO motility. The guide-wire-type manometer may become a new method to measure SO function for the diagnosis of SOD.

Lymphoepithelial cyst (LEC) of the pancreas is a rare benign lesion, which is difficult to diagnose preoperatively. We describe a case of a 60-year-old male, incidentally diagnosed as having LEC of the pancreas, which was managed by laparoscopic distal pancreatectomy. Most of the reported cases of LEC were asymptomatic and diagnosed incidentally. A high index of suspicion under EUS may help in making a diagnosis and avoiding unnecessary surgery in asymptomatic patients. In particular, the unique “cheerios-like” appearance of the lesion in EUS, which was also found in this case, might be helpful in the differential diagnosis of pancreatic cystic lesions.

We report the case of a 56-year-old female with lipomatous hypertrophy of the pancreas. Abdominal CT and MRI showed fatty replacement over the entire pancreas. The pancreatic parenchyma was completely absent. ERCP showed no abnormal findings in the main pancreatic duct. EUS-FNA was performed to achieve a definitive diagnosis. Histological features of the FNA specimens revealed that adipose tissue generally replaced the pancreatic parenchyma, and pancreatic acini were identified with a scattered distribution. To consider the differential diagnosis of lipomatous pseudohypertrophy of the pancreas, it is necessary to distinguish it from obesity, diabetes, and age-related pancreatic fat infiltration and liposarcoma. By performing EUS-FNA, it was possible to obtain a definitive diagnosis in this patient. In conclusion, EUS-FNA may be helpful to make a definitive diagnosis in patients with lipomatous hypertrophy of the pancreas.

We aimed to clarify the lifestyle factors associated with erosive esophagitis and non-erosive reflux disease (NERD) in a Japanese population. Among 886 subjects who underwent health screening, we selected, according to their scores on the FSSG (frequency scale for symptoms of gastroesophageal reflux disease; GERD) questionnaire and the findings of upper gastrointestinal endoscopy, 138 subjects with erosive esophagitis (EE), 148 subjects with NERD (absence of esophagitis, FSSG score ≥8, and acid reflux-related symptoms score ≥4), and 565 control subjects (absence of esophagitis and FSSG score ≤7). We compared clinical characteristics and various lifestyle factors in these three groups. The lifestyle factors significantly associated with NERD compared with findings in the control group were intake of egg (odds ratio [OR] 1.89, 95 % confidence interval [CI] 1.01–3.50), sleep shortage (OR 2.44, 95 % CI 1.54–3.88), and strong psychological stress (OR 1.77, 95 % CI 1.18–2.62). In male subjects, current smoking (OR 2.06, 95 % CI 1.13–3.74; OR 1.87, 95 % CI 1.09–3.20) was a significant risk factor for both NERD and EE. Moreover, alcohol >200 kcal/day (OR 3.99, 95 % CI 1.03–15.55) and intake of a large quantity of food at supper (OR 7.85, 95 % CI 1.66–37.05) were significant risk factors for EE in subjects with hiatal hernia. Intake of a large quantity of food at supper (OR 2.09, 95 % CI 1.06–4.13) was more common in the NERD group than in the EE group. There were differences in the associated lifestyle factors between patients with NERD and those with EE, and there was also a gender-related difference between these groups.

Endoscopic submucosal dissection (ESD) has come to be widely performed for reduced invasiveness; however, its safety in patients with co-morbidities is not fully examined. We aimed to evaluate the safety and efficacy of gastric ESD with co-morbidities categorized according to ASA Physical Status Classification. Two hundred and forty patients of ASA 1 (no co-morbidities), 268 of ASA 2 (mild), and 19 of ASA 3 (severe) were treated by ESD for gastric neoplasms. We retrospectively compared clinicopathological features and treatment results of these three groups. Cases (by percent) treated with anticoagulant/platelet agents were more common in the higher ASA grades (ASA 1, 5.8%; ASA 2, 29.1%; ASA 3, 31.6%; P

BACKGROUND: Early stage colorectal tumors can be removed by endoscopic mucosal resection but larger such tumors (>20mm) may require piecemeal resection. Endoscopic submucosal dissection (ESD) using newly developed endoknives has enabled en-block resection of lesions regardless of size and shape. However ESD for colorectal tumor is technically difficult. Therefore, we performed EMR with small incision (EMR with SI) for more reliable EMR, ESD with snaring (simplified ESD) and ESD using thestandard Flush knife and the novel ball tipped Flush knife (Flush knife BT) for easier and safer colorectal ESD. AIMS: The aims of our study were 1) to compare the treatment results of the following 3 methods (EMR with SI/simplified ESD/ ESD) for early stage colorectal tumors, and 2) to assess the performance of Flush knife BT in colorectal ESD. METHODS: We treated 24/44/468 colorectal tumors and examined the clinicopathological features and treatment results such as tumor size, resected specimen size, procedure time, en-bloc resection rate, complication rate. We also treated 58 colorectal tumors (LST-NG:20, LST-G:36, other:2) using standard Flush knife and 80 colorectal tumors (LST-NG:32, LSTG: 44, other:2) using Flush knife BT, and examined the clinicopathological features and treatment results mentioned above and also the procedure speed. RESULT: The median tumor size (mm) (EMR with SI/ simplified EMR/ESD) was 20/17/30 (EMR with SI vs. simplified ESD:p=n.s, simplified ESD vs. ESD:p< 0.0001). The median resected specimen size (mm) was 22.5/26 /41 (EMR with SI vs. simplified ESD: p=0.0018, simplified ESD vs. ESD: p

Gastroesophageal reflux disease (GERD) is a common condition, and acid-suppressing agents are the mainstays of treatment. For the acute medical management of GERD, two different strategies can be proposed: either the most effective therapy, i.e., proton-pump inhibitors (PPIs), can be given first, or histamine H2-receptor antagonists (H2RAs) can be attempted first (the “step-up” approach). A clinical decision analysis comparing the PPI-first strategy and the H2RA-first “step-up” strategy for the acute treatment of reflux esophagitis in Japan was performed, using a Markov chain approach. The PPI-first strategy was consistently superior to the step-up strategy with regard to clinical outcomes for the patient and with regard to cost-effectiveness (direct cost per patient to achieve clinical success). This superiority was robust within the plausible range of probabilities according to the sensitivity analyses. The PPI-first strategy is superior to the H2RA-first “step-up” strategy with regard to both efficacy and cost-effectiveness and therefore, the PPI-first strategy is the preferred therapeutic approach for the acute medical treatment of reflux esophagitis.

GERD is a common condition and acid-suppressing agents are the mainstay of treatment. A cost-effectiveness analysis comparing a PPI, lansoprazole (LPZ) and a H2RA, famotidine (FAM) for the maintenance treatment of reflux esophagitis in Japan was performed using a Markov chain approach. The time period studied was 6 months and payer perspective was chosen. Transition probabilities were estimated from meta-analyses. Expected days without esophagitis (healthy days) were 166 for LPZ 30 mg/day, 161 for LPZ 15 mg/day and 143 for FAM 40 mg/day. Direct costs were 55,624 yen for LPZ 30 mg/day, 42,078 yen for LPZ 15 mg/day and 67,969 yen for FAM 40 mg/day. Cost-effectiveness ratio (direct costs/healthy days) was 335 yen for LPZ 30 mg/day, 262 yen for LPZ 15 mg/day and 477 yen for FAM 40 mg/day. Lansoprazole was superior to famotidine with regard to both efficacy and cost-effectiveness and therefore is the preferred therapeutic agent for the maintenance treatment of GERD.

It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19-9, carcinoembryonic antigen (CEA) and K-ras mutations.One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19-9, CEA, K-ras mutations and CTSE.The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; chi2 = 34.76; P0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19-9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct.Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.

The c-K-ras 2 gene mutations were examined in colorectal tumours from patients with synchronous or metachronous tumours in order to investigate tumorigenesis. Sixty-seven colorectal carcinomas from patients with a single lesion, 50 from patients with synchronous lesions, and 12 from patients with metachronous lesions were analysed for the presence of point mutations in codons 12 and 13 of c-K-ras proto-oncogene. In the patients with metachronous or synchronous lesions, the finding of the mutation in one tumour was not associated with a greater frequency of the mutation in other carcinomas from the same patient. In the patients with tumours that each contained the mutation, the mutations were not always the same. In tumours from the patients with original and synchronous lesions, the mutation frequency was significantly lower in advanced carcinomas invading through the entire muscularis propria (10.5%) than in early carcinomas confined to the mucosa (47.8%), and the mutation frequency in carcinomas invading through the entire muscularis propria was significantly lower in patients with synchronous lesions (10.5%) than in patients with a single lesion (37.7%). These results suggest that the tumorigenesis of colorectal carcinomas from patients with synchronous lesions is different from that in patients with a single lesion.

Recently, endoscopic methods for diagnosing biliary malignancy were developed. In this study, diagnostic ability of endoscopic methods in detecting the tumor mass and the staging for carcinoma of the extrahepatic bile duct were studied. [Patients]From 1984 to 1998, we studied 73 patients with carcinoma of the extrahepatic bile duct. Twenty-five of these patients underwent surgery. [Methods]The diagnostic methods that we investigated were endoscopic retrograde cholangiopancreatography(ERCP), peroral cholangioscopy(PCS) , biopsy study under PCS or through the ampulla of Vater under fluoroscopy, endoscopic ultrasonography(EUS), and intraductal ultrasonography(IDUS) through the ampulla of Vater. We performed PCS, using TJF-200,20, TJF-M200,20(Olympus) for mother duodenoscope, and CHF-BP30, CHF-B200, 20(Olympus) for baby cholangioscope.We used GF-UM200, 20(Olympus, 7.5MHz) for EUS, and UM-3R(Olympus, 20MHz) for IDUS. The way of evaluation was the detection rate of tumor in ERCP, EUS and IDUS, the successful visualization rate of tumor in PCS, the positive rate of biopsy study, the accuracy of staging(TNM staging system) in EUS and IDUS. [Results]The detection rate of tumor was 100% in ERCP(79/79), EUS(48/48), and IDUS(20/20). In patients with T1 lesion, the detection rate of tumor was also 100% in EUS(7/7), and IDUS(3/3). The ability of detecting tumor was excellent in these methods, and in EUS and IDUS the rate of detecting small lesion was also high. The successful visualization rate of tumor in PCS was 97%(29/30). The positive rate of biopsy study under PCS, which was 60%(6/10), was higher than that of biopsy study under fluoroscopy, which was 20%(1/5). PCS and biopsy study under PCS were useful to diagnose biliary malignancies. However, in cases with insufficient preoperative diagnosis for extension to hilar side of bile duct by PCS, or ineffective biopsy study under PCS, percutaneous transhepatic cholangioscopy(PTCS) and biopsy study under PTCS are necessary. In patients with surgery, the accuracy of T staging was 84%(21/25) in EUS, 89%(8/9) in IDUS, and the accuracy of N staging was 68%(17/25) in EUS, 78%(7/9) in IDUS. For N staging, combination of audinary ultrasound study(US) was helpful. [Conclusion]1.In diagnosing carcinoma of the extrahepatic bile duct, ERCP, EUS and IDUS are valuable for detecting the tumor. 2.EUS and IDUS are useful for the preoperative staging, especially in T staging. 3.PCS is useful for the direct visualization and biopsy.

[Aim] Gastroesophageal reflux diseases(GERD) is a clinical entity in which refluxing gastric contents produce symptoms, and impairs the quality of life. Patients with GERD tend to be have impaired feeling of well-being and functional status, yet the impact of GERD on quality of life including emotional functioning has not carefully studied. We examined whether GERD and its severity were related to anxiety and depression as assessed by the hospital anxiety and depression (HAD) scale. [Methods] We studied 97 patients who visited our department with reflux symptom. Inclusion criteria was primary symptom of heartburn without other organic diseases. A control group compromised 106 patients referred to our department without symptom. All patients completed self report HAD questionnaires and GERD symptom questionnaires including the grading of GERD symptom. GERD patients were asked whether their daily activities were interrupted because of GERD symptom, and were asked to rate their overall health related quality of life as excellent, good, or poor. [Results] The GERD patients gave higher HAD scores than the normal group(anxiety score: mean 5.44 vs. 3.59, depression score: mean 5.30 vs. 3.69, p < 0.01). The severer the GERD symptom was, the higher HAD score tended to be(mean anxiety score: excellent 3.59, good 6.97, poor 6.22, mean depression score: excellent 4.23, good 5.71, poor 7.66). There was a significant correlation between HAD score and GERD severity(anxiety: r=0.328, p < 0.01, depression: r=0.320, p < 0.01). [Conclusion] This study confirms that anxiety and depression scores are higher in patients with GERD symptom than in controls. The severity of GERD symptom has close relationship to the mental health. This research was made possible by grant from Astra Japan.