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Aim: This study was aimed to clarify the effectiveness of conservative treatment without performing early colonoscopy and the indications for early colonoscopy in patients with colonic diverticular hemorrhage., Methods: This retrospective study included 142 participants who were urgently hospitalized due to bloody stools and were diagnosed with colonic diverticular hemorrhage between April 2012 and December 2016. At the time of hospital visit, only when both shock based on vital signs and intestinal extravasation on abdominal contrast-enhanced computed tomography were observed, early colonoscopy was performed within 24 hours after hospitalization. However, in other cases, patients were conservatively treated without undergoing early colonoscopy. In cases of initial treatment failure in patients with shock, interventional radiology (IVR) was performed without undergoing early colonoscopy., Results: Conservative treatment was performed in 137 (96.5%) patients, and spontaneous hemostasis was achieved in all patients. By contrast, urgent hemostasis was performed in five (3.5%) patients; three and two attained successful hemostasis via early colonoscopy and IVR, respectively. There were no significant differences between two groups in terms of early rebleeding (7.3% vs. 0%, P =0.690) and recurrent bleeding (22.7% vs. 20.0%, P =0.685). The factors associated with the cumulative recurrent bleeding rates were a previous history of colonic diverticular hemorrhage (hazard ratio 5.63, 95% confidence interval 2.68-12.0, P < 0.0001) and oral administration of thienopyridine derivative (hazard ratio 3.05, 95% confidence interval 1.23-7.53, P =0.016)., Conclusions: In this series, conservative treatment without early colonoscopy was successful in patients with colonic diverticular hemorrhage., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Hirosato Doi et al.)

Background: Recently, early detection and early treatment of the colorectal cancer have been enabled by the improvement of endoscopic diagnosis and introduction of new techniques. In Japan, although Japan Polyp Study is running, there is no standard strategy concerning the post-polypectomy colonoscopic surveillance yet. Post-polypectomy colonoscopic surveillance is so far entrusted to each institute or each gastroenterologist at present., Material and Method: To analyze the present states of the surveillance after polypectomy in Japan, we performed questionary survey and compared them with the results in U.S. and U.S. Multisociety Task Force on colorectal Cancer. A simple random sample of 132 doctors who engaged in a digestive organ disease in plural institutes was obtained., Result: Many doctors recommend surveillance every around 1 year regardless of the kind of the polyp. Doctors in Japan tend to recommend postpolypectomy colonoscopic surveillance more frequently than that recommended U.S. Multisociety Task Force on colorectal Cancer. Furthermore in all types of polyps except for 12 mm tubular adenoma with high grade dysplasia, the majority of doctors in Japan recommend post-polypectomy colonoscopic surveillance more frequently than American doctors. Significant difference was found in surveillance of hyperplastic polyp among doctors with 1 to 5 years experience and those with more than 6 years., Conclusion: It has been shown that surveillance intervals varies substantially in each doctor. The agreement of the surveillance program in Japan is necessary to standardize the strategy for the post-polypectomy surveillance of the colon.

Objectives: The discovery of novel and effective treatment methods would be of great help to patients with acute pancreatitis. The aims of this study were to determine the inhibitory effects of vitamin K3 (VK3) against cerulein-induced acute pancreatitis in mice and to examine the mechanisms behind these effects., Methods: Acute pancreatitis in mice was induced by intraperitoneal injection of cerulein 6 times at hourly intervals. Vitamin K3 was administered once before the first injection of cerulein or twice before and after the first injection of cerulein. The degrees of inflammation and autophagy in the pancreatic tissue were estimated by histological examination, measurement of enzyme activity, confocal microscopy, and Western blotting. The inhibitory effects of VK3 against rapamycin-induced autophagy were also examined using HeLa cells stably expressing green fluorescent protein LC3., Results: Cerulein-induced acute pancreatitis was markedly attenuated by the administration of VK3. In addition, VK3 led to the inhibition of cerulein-evoked autophagic changes and colocalization of autophagosomes and lysosomes in the pancreatic tissue. Vitamin K3 also reduced rapamycin-induced autophagy in HeLa/green fluorescent protein LC3 cells., Conclusions: Our data suggest that the administration of VK3 reduces pancreatic inflammation in acute pancreatitis through inhibition of the autophagic pathway. Vitamin K3 may be an effective therapeutic strategy against acute pancreatitis.

Background and Aims: Recently, several new endoscopic instruments have been developed. However, even with the full use of current modalities, the safety of endoscopic surgery is not guaranteed. Information regarding factors such as fibrosis and the blood vessels under the mucosa is very important for avoiding procedure-related complications. The aim of this study was to define the detailed anatomy of the gastric wall structure in vivo using original endoluminal radiofrequency coils for safer endoscopic therapy., Methods: Swine were used as the subjects and controlled with general anesthesia. Anatomical images were obtained with T1-weighted fast spin echo (T1FSE) and T2-weighted fast spin echo (T2FSE). Dynamic magnetic resonance (MR) angiography was also obtained with three-dimensional T1-weighted fast spoiled gradient recalled acquisition in the steady state (3D-DMRA) following the injection of hyaluronic acid sodium into the submucosal layer., Results: Porcine gastric wall structure was visualized, and four layers were discriminated in the T1FSE and T2FSE images. The vascular structure was clearly recognized in the submucosa on 3D-DMRA., Conclusion: Endoluminal MR imaging was able to visualize the porcine stomach with similar quality to endoscopic ultrasonography imaging. Additionally, it was possible to visualize the vascular structures in the submucosal layer. This is the first report to show that blood vessels under the gastric mucosa can be depicted in vivo.

Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the colon utilizing attaching and effacing lesions to adhere specifically to the surfaces of intestinal epithelial cells and cause mucosal inflammation. CD4+ T cells, B cells, and immunoglobulin G (IgG), but not secretory IgA or IgM, play a critical role in eradicating this pathogen. Consistent with the importance of IgG in C. rodentium eradication, IgG transport by the neonatal Fc receptor for IgG within the intestinal epithelium also has a critical role in the regulation of C. rodentium infection. It remains to be determined, however, whether Fcgamma receptors (FcgammaRs), the receptors for the Fc portion of IgG, regulate this bacterial infection within mucosal tissues. Therefore, we investigated the roles of FcgammaRs during C. rodentium infection. Fc receptor common gamma chain (FcRgamma)-deficient mice were more susceptible to C. rodentium-induced colitis. This occurred through decreased efficiency of FcR-mediated endocytosis and maturation of dendritic cells and consequently T-cell activation of antigen-specific T cells. Moreover, in the absence of FcgammaRs, phagocytosis by macrophages was significantly diminished. Therefore, activating FcgammaRs play an important role in defending against C. rodentium infection, indicating that the critical role played by IgG in this infection is not mediated by IgG alone but is dependent upon this class of receptors.

Objective: Recently guidelines for the treatment and prevention of ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs) have been established. The aim of the present study was to examine factors influencing orthopedists in Japan in the use of cytoprotective drugs to prevent NSAID-associated gastrointestinal adverse events., Methods: We sent a questionnaire to 402 orthopedists in Hyogo Prefecture. A standardized 10-item questionnaire was used to collect information on NSAID prescriptions (drug name, pharmaceutical form, doses, and duration of use) and associated drugs, especially gastroprotective drugs., Results: Two hundred eight (51.7%) orthopedists returned the questionnaire. The most frequently used NSAIDs, in descending order, were loxoprofen sodium, diclofenac sodium, and etodolac. Most doctors (80%) reported patients with abdominal symptoms associated with NSAIDs. Of these doctors, 59% treated the symptoms by themselves, and prescribed gastroprotective agents (32.2%), histamine H2-receptor antagonists (H2RAs) (26.4%), prostaglandin analogues (PAs) (17.0%), or proton pump inhibitors (PPIs) (16.2%). Sixty-seven percent of doctors reported that those drugs reduced the symptoms. Most orthopedists (96%) prescribed some type of drug to prevent NSAID-associated gastrointestinal events, including gastroprotective drugs (44.6%), H2RAs (19.5%), PAs (17.4%), and PPIs (10.8%). The doctors reported that they prescribed medicines for NSAID-associated gastrointestinal events on the basis of their experience (23%), by considering medical insurance restrictions (17%), and by referring to information provided by pharmaceutical company representatives (16%)., Conclusion: Most orthopedists prescribe some type of drug to prevent NSAID-induced ulcers but do not refer to the guidelines. We therefore strongly recommend that the guidelines be made more widely known to gastroenterologists and to physicians in every field of clinical practice, including orthopedics.

With the development of regeneration medicine, many researchers have attempted hepatic differentiation from nonhepatic-origin cell sources. The differentiation of embryonic stem (ES) cells into hepatocyte-like cells has been reported in several papers. Mouse ES cells have shown a potential to develop into hepatocyte-like cells in vitro on the basis of hepatic gene expression after adding several growth factors. We transplanted cultured embryoid body (EB) cells (male) into female mice. A liver specimen of the recipient was examined by immunohistochemical staining for albumin and fluorescence in situ hybridization for the Y chromosome after transplantation. Both Y chromosome- and albumin-positive cells were recognized in the recipient female liver, and were considered to be hepatocyte-like cells derived from ES cells containing the Y chromosome. Many groups, including ourselves, have studied hepatocyte-like cell differentiation from umbilical cord blood cells (UBCs). We cultured nucleated cells isolated from UBCs. Using immunostaining, ALB-positive and CK-19-positive cells were recognized in the culture. Dual staining of ALB and CK-19 demonstrated that ALB was coexpressed with CK-19, suggesting the existence of hepatic progenitors. In this review, we consider recent studies of the differentiation of hepatocytes from nonhepatic origins, especially ES cells and umbilical cord blood.

We determined the sequence of the hepatitis delta virus (HDV) genome in 40 Japanese patients, most of whom were from the Miyako Islands, Okinawa, Japan. Consensus sequences from 33 HDV full genomes out of a total of 40 patients were determined by directly sequencing four partially overlapping PCR products. Phylogenetic tree analysis classified these 33 complete HDV genomes as HDV genotype I (two patients), genotype IIa (one patient) and genotype IIb (30 patients). Among the 30 genotype IIb patients, there were two clusters of genetic variants. One group consisted of six isolates showing significant homology with genotype IIb, previously reported from Taiwan. The other group consisted of 24 isolates, whose sequences formed a new genetic subgroup (genotype IIb-Miyako; IIb-M). When the genetic structures were compared in detail between IIb and IIb-M, characteristic variations were found in the C-terminal sequence of the large delta antigen-conferring packaging signal as well as the RNA editing site. Determination of subclasses of genotype IIb in a total of 37 patients, including seven HDV patients whose partial HDV sequence was determined, revealed eight patients with IIb and 29 patients with IIb-M. Although there was no significant difference in the clinical background or virological state of hepatitis B virus between these two groups, patients with genotype IIb-M showed greater progression of chronic hepatitis and cirrhosis than those with genotype IIb (P=0.0009). These data indicate the existence of a genetic subgroup of HDV genotype IIb, which is associated with different clinical characteristics and which could be related to genetic variations in functionally important parts of the HDV genome.

Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation because of the immaturity of newborn cells compared with adult cells. In contrast to their hematopoietic and mesenchymal potential, it remains unclear whether UCB cells have endodermal competence. Here, with a view to utilize UCB cells for cell transplantation into injured liver, we investigated the hepatic potential of UCB cells both in vitro and in vivo. We determined the most efficient conditions leading UCB cells to produce albumin (ALB). In a novel primary culture system supplemented with a combination of growth/differentiation factors, about 50% of UCB cells in 21-day cultures expressed ALB, and the ALB(+) cells coexpressed hepatocyte lineage markers. The ALB-expressing cells were able to proliferate in the culture system. Moreover, in the cell-transplantation model into liver-injured severe combined immunodeficient mice, inoculated UCB cells developed into functional hepatocytes in the liver, which released human ALB into the sera of the recipient mice. In conclusion, this study demonstrates that human UCB is a source of transplantable hepatic progenitor cells. Our findings may have relevance to clinical application of UCB-derived cell transplantation as a novel therapeutic option for liver failure.

Embryonic stem (ES) cells have a potential to differentiate into various progenitor cells. Here we investigated the differentiation capacity of mouse ES cells into hepatocytes both in vitro and in vivo. During the culture of embryoid bodies (EBs) derived from ES cells, albumin (ALB) messenger RNA (mRNA) was expressed within 12 days after removal of leukemia inhibitory factor, and alpha-fetoprotein (AFP) mRNA was observed within 9 days without additional exogenous growth factors. In ES cells and early EBs, by contrast, neither ALB mRNA nor AFP mRNA was observed. ALB protein was first detected at day 15 and the level increased with the culture period. The differentiation of EBs facilitated the synthesis of urea with the culture period, whereas early EBs and ES cells produced no urea. These results suggest that cultured EBs contain hepatocytes capable of producing ALB and urea. ES cells and the isolated cells from EBs were transplanted through portal vein to the liver after 30% partial hepatectomy of female mice pretreated with 2-acetylaminofluorene. Four weeks after transplantation with isolated cells from day-9 EBs, ES-derived cells containing Y-chromosome in the liver were positive for ALB (0.2% of total liver cells), whereas teratoma was found in mice transplanted with ES cells or EBs up to day 6. The incidence of teratoma was decreased with the culture duration and no teratoma was observed in the liver transplanted with isolated cells from day-9 EBs. In conclusion, our in vitro and in vivo experiments revealed that cultured EBs contain functional hepatocytes or hepatocyte-like cells.

Background and Aim: It has been a conflicting issue whether TT virus (TTV), a newly isolated DNA virus from a patient with liver injury of unknown cause, is a causative agent of acute and/or chronic hepatitis. TT Virus DNA titers were shown to be 10-100-fold greater in liver tissue than in serum, whereas the majority of TTV-positive cases had no biochemical or histological evidence of significant liver damage. We therefore attempted in situ hybridization to investigate whether TTV is hepatotropic., Methods: Because of the marked divergence in TTV genome types, a template for TTV-DNA (coding region for N22 clone) was amplified and labeled with digoxigenin-dUTP by using hemi-nested PCR from the serum, then DNA probes were applied to the liver sections of the same case. After hybridization, the probes were visualized immunohistochemically. Besides TTV-DNA-negative cases, competitive inhibition experiments with unlabeled probes were performed to confirm the specificity., Results: There were no positive signals in the negative controls, and the intensity of positive signals was markedly diminished in the competitive inhibition experiments. No cross-hybridization with different genotype probes also confirms the specificity. Under the optimal conditions, the positive signals were located in the cytoplasm of the hepatocytes in eight of nine TTV-DNA-positive cases. The signals were not seen in non-parenchymal cells of the liver., Conclusion: TT Virus is proved to be hepatotropic by in situ hybridization.