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Background and Aim The aim of the present study was to evaluate the efficacy and safety of sedation with a combination of propofol (PF) and dexmedetomidine (DEX) compared with sedation with benzodiazepines in esophageal endoscopic submucosal dissection (ESD). Methods We retrospectively reviewed clinical data for 40 consecutive patients who had undergone esophageal ESD at the Yokohama City University Hospital between July 2012 and August 2014. Of these patients, 20 were sedated with benzodiazepines (conventional group) and another 20 patients were sedated with a combination of PF and DEX (combination group). Parameters for efficacy and safety of sedation were evaluated by comparisons between the two groups. Results Median procedural times in the combination group were shorter than those in the conventional group (61 min vs 89 min, P = 0.03), and the percentage of patients who showed restlessness in the combination group was significantly lower than that in the conventional group (25% vs 65%, P = 0.025). Incidences of hypotension and bradycardia in the combination group were higher than those in the conventional group (60% vs 15%, P = 0.008, and 60% vs 15%, P = 0.008, respectively). Conclusion This retrospective study suggests that a combination of PF and DEX may provide stable deep sedation with less body movement than benzodiazepines during esophageal ESD. [ABSTRACT FROM AUTHOR]

Aim To identify the predictive factors for the presence of small bowel lesions in patients with obscure gastrointestinal bleeding ( OGIB). Methods A total of 242 patients with OGIB (overt 149: occult 93) were retrospectively included in the present study. Capsule endoscopy ( CE) was carried out to investigate the small bowel, and detected lesions were classified according to the P0- P2 system. Only P2 lesions were defined as significant lesions. Univariate and multivariate logistic regression analyses were carried out to define the predictive factors for the presence of small bowel lesions. Results In patients with overt OGIB, chronic kidney disease ( CKD) ≥stage 4 (odds ratio [ OR] 4.03; 95% confidence interval [ CI] 1.45-11.1, P = 0.007) was identified as an independent predictor of the presence of vascular lesions, and a history of non-steroidalanti-inflammatory drug ( NSAID) use as that of erosive/ulcerated lesions ( OR 4.73; 95% CI 1.47-15.2, P = 0.009). However, in patients with occult OGIB, no significant predictors of the presence of vascular lesions were identified, whereas a history of low-dose aspirin ( LDA) ( OR 3.57; 95% CI 1.21-10.5, P = 0.02) and proton pump inhibitor ( PPI) use ( OR 3.18; 95% CI 1.02-9.92, P = 0.05) were identified as independent predictors of the presence of erosive/ulcerated lesions. Conclusions Our results indicated that bleeding pattern and clinical characteristics could contribute to predicting the origin of OGIB. [ABSTRACT FROM AUTHOR]

The major limitation of capsule endoscopy (CE) has been the lack of a standardized and validated severity scale for mucosal injury. The aim of the present study was to verify the usefulness of quantifying small bowel mucosal changes associated with giving low-dose aspirin (LDA) using a CE scoring index. The CE score for small bowel mucosal injury was investigated to evaluate the severity of mucosal injury. Healthy volunteers and patients suspected of having small bowel disease were recruited for this study. The short-term LDA group (V + S-LDA group) consisted of volunteers who took low-dose aspirin for 14 days; this group was then compared with healthy volunteers who did not receive LDA treatment (V-Control group). The long-term LDA group (L-LDA group) consisted of patients with at least a 3-month history of daily LDA use; this group was compared with non-users of LDA (P-Control group). The CE score was significantly higher in the V + S-LDA group than in the V-Control group. In the V-Control group, almost all the subjects were categorized as exhibiting a 'normal' change. 'Mild' changes were observed significantly more frequently in the V + S-LDA group than in the V-Control group. The CE score was significantly higher in the L-LDA group than in the P-Control group. 'Mild' or 'moderate or severe' changes were observed significantly more frequently in the L-LDA group than in the P-Control group. The CE scoring system was useful for evaluating LDA-associated small bowel mucosal disease activity and for objectively scoring the small bowel inflammatory disease state. [ABSTRACT FROM AUTHOR]

Aim: Genetic factors as well as environmental factors play an important role in the development of non-alcoholic fatty liver disease (NAFLD). Recently, inducible nitric oxide synthase (iNOS) was significantly higher in the severest form of non-alcoholic steatohepatitis (NASH), and nitric oxide (NO) has been determined to play an important role in the process of fibrosis in NASH. In this study, we investigated iNOS gene polymorphisms for associations with NAFLD. Methods: A total of 115 NAFLD patients, consisting of 65 patients with NASH and 50 patients with simple steatosis, in whom a positive diagnosis had been made by liver biopsy, and 435 healthy control subjects, were recruited into this study. Results: We investigated 10 single nucleotide polymorphisms (SNP) of the iNOS gene, one of which, rs1060822, had the lowest P-value in the allele frequency model ( P = 0.00078) with an odds ratio (95% confidence interval) of 0.49 (0.32–0.75). Four SNP, rs2297510, rs2297511, rs2797512 and rs1060822, were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs1060822 and three other SNP, rs2297510, rs2297511 and rs2797512, were in the same block. We also investigated associations between rs1060822 genotypes and the fibrosis index, and the results of the analysis revealed an additive increase in the fibrosis index and intrahepatic iNOS mRNA expression in the patients with the T allele of rs1060822. Conclusion: This is the first study to identify genetic variations in iNOS that may influence the risk of NAFLD and liver fibrosis in NAFLD. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver injury in many countries. Genetic factors are important for the development of NAFLD, as well as environmental factors. Recently an angiotensin II type 1 receptor (AGTR1) has been recognized as important in the aetiology of fibrosis in the liver. Objective: In this study we investigated the association between angiotensin II type 1 receptor gene polymorphism ( ATGR1) and NAFLD. Methods: One hundred and sixty-seven NAFLD patients [106 with nonalcoholic steatohepatitis (NASH) and 61 with simple steatosis] with a positive diagnosis by liver biopsy and 435 healthy control subjects were recruited in this study. Results: We investigated 12 single nucleotide polymorphisms (SNPs) of the ATGR1 gene, among which rs3772622 showed the lowest P-value of allele frequency model ( P=0.0000012) with an odds ratio (95% confidence interval) of 1.95 (1.49–2.55). Five SNPs (rs3772622, rs3772633, rs2276736, rs3772630 and rs3772627) were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs3772622 and another four SNPs (rs3772633, rs2276736, rs3772630 and rs3772627) were in the same block. We investigated the association between rs3772622 genotypes and the fibrosis index. The results of the analysis revealed an additive increase of the fibrosis index in the patients with the A allele of rs3772622. Conclusions: This is the first report to demonstrate the genetic variations in ATGR1 that may influence the risk of NAFLD and liver fibrosis in NAFLD. [ABSTRACT FROM AUTHOR]

The association between obesity and the risk of colorectal cancer (CRC) cannot be easily evaluated because CRC itself is associated with a gradual loss of bodyweight. Aberrant crypt foci (ACF) can be classified as dysplastic ACF or non-dysplastic ACF by magnifying colonoscopy, and dysplastic ACF are thought to be a biomarker of CRC. Ninety-four participants who underwent colonoscopy at Yokohama City University Hospital, Japan, were enrolled in the current study. We detected 557 ACF, including 67 dysplastic ACF (12.0%). Univariate regression analysis was conducted to determine correlations between the number of dysplastic ACF and various potential risk factors, including patient age, waist circumference, body mass index, visceral fat area (VFA), and plasma adiponectin level. The results of multiple regression analysis revealed that the number of dysplastic ACF correlated with age (correlation coefficient r = 0.212, P = 0.0383) and plasma adiponectin level ( r = –0.201, P = 0.0371), even after adjustments for sex, waist circumference, body mass index, and VFA. Our univariate correlation analysis data showed a significant correlation with the number of dysplastic ACF with VFA ( r = 0.238, P = 0.0209), no correlation with subcutaneous fat area, and an inverse correlation with the plasma level of adiponectin ( r = –0.258, P = 0.0118). Thus, our results suggest that aging and visceral fat accumulation could correlate moderately with colorectal carcinogenesis. The novelty of our study lies in the finding that visceral fat accumulation and a low plasma adiponectin level may promote colorectal carcinogenesis; therefore, these obesity-related parameters may serve as novel targets for CRC prevention. ( Cancer Sci 2009; 100: 29–32) [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor that has been implicated in the carcinogenesis and progression of various solid tumors, including pancreatic carcinomas. We aimed to clarify the role of this receptor in pancreatic cell motility in vitro and in metastasis in vivo. Cell motility was examined by assaying transwell migration and wound filling in Capan-1 and Panc-1 pancreatic cancer cells, with or without the PPARγ-specific inhibitor T0070907. A severe combined immunodeficiency xenograft metastasis model was used to examine the in vivo effect of PPARγ inhibition on pancreatic cancer metastasis. In both transwell-migration and wound-filling assays, inhibition of PPARγ activity suppressed pancreatic cell motility without affecting in vitro cell proliferation. Inhibition of PPARγ also suppressed liver metastasis in vivo in metastatic mice. In PPARγ-inhibited cells, p120 catenin accumulation was induced predominantly in cell membranes, and the Ras-homologous GTPases Rac1 and Cdc42 were inactive. Inhibition of PPARγ in pancreatic cancer cells decreased cell motility by altering p120ctn localization and by suppressing the activity of the Ras-homologous GTPases Rac1 and Cdc42. Based on these findings, PPARγ could function as a novel target for the therapeutic control of cancer cell invasion or metastasis. ( Cancer Sci 2008; 99: 1892–1900) [ABSTRACT FROM AUTHOR]

Recently we have identified a novel gene mina53 ( mina), which is a direct transcriptional target of oncoprotein Myc. Mina53 protein was shown to be highly expressed in tumour cells and to play a role in cell proliferation. Here we report the expression of Mina53 in mouse testis, which contains proliferating cells and expresses many cancer-related genes. Immunohistochemical studies by using newly produced monoclonal antibody to Mina53 showed that Mina53 was expressed in the nuclei of spermatogonia. Mina53 was also expressed in meiotic prophase cells such as preleptotene, leptotene and zygotene, and weakly in early pachytene spermatocytes, but was absent in late pachytene spermatocytes, spermatids and mature sperm. The expression pattern of Mina53 was quite similar to that of proliferation cell nuclear antigen (PCNA). Using experimental cryptorchid testis, it was found that Mina53 was highly expressed in undifferentiated spermatogonia, which were PCNA-positive. These results suggest that Mina53 is prominently expressed in proliferating, undifferentiated spermatogonia, and plays a role in cell proliferation from the spermatogonial stage to the meiotic prophase in spermatogenesis, but not in meiotic divisions per se. [ABSTRACT FROM AUTHOR]

Abstract: This study evaluated the operative outcome of dialysis patients undergoing coronary artery bypass (CAB). In the past 6 years, 38 dialysis patients with a mean age of 57.5 years underwent CAB. Thirty-one operations were elective, and 7 were nonelective operations. Thirty-two operations were performed under cardiac arrest, 3 operations were performed under fibrillatory arrest, and 3 operations were performed without cardiopulmonary bypass. The average number of bypass grafts was 2.8. In all patients, the internal thoracic artery was used. Hospital mortality was 5.3%. Actuarial survival rates at 1, 3, and 5 years including all causes of death were 88%, 80%, and 72%, respectively. With improvements in perioperative management, coronary artery bypass can be performed with acceptable mortality and morbidity in dialysis patients. Complete revascularization without cardiopulmonary bypass is the ideal method and will increase in usage. However, the conventional CAB also provides acceptable results. [ABSTRACT FROM AUTHOR]

Paraganglioma, a sporadically occurring rare tumor should be included in the differential diagnosis of retroperitoneal tumors, such as malignant lymphomas, gastrointestinal stromal tumors, sarcoma and carcinoma of unknown primary site. A 58-year-old Japanese woman presented with a large retroperitoneal tumor detected by ultrasonography (US). She had no medical history of hypertension. Computed tomography showed a mass, 7 cm in diameter, located between the pancreas and the inferior vena cava. It was unclear whether the mass originated from the duodenum or the mesentery. Endoscopic ultrasonography (EUS) demonstrated a large solid paraduodenal mass. Doppler US revealed sparse vascularity in the tumor. With the differential diagnosis of retroperitoneal tumor, we carried out EUS-FNA. At the time of the third needle puncture, transient severe hypertension was noted, with a blood pressure measurement of 269/130 mmHg. Data obtained from urine and blood examinations after EUS-fine-needle aspiration indicated a diagnosis of paraganglioma. [ABSTRACT FROM AUTHOR]