逆流性食道炎の現状と予防

Gastroesophageal reflux disease（GERD）, classified into reflux esophagitis（RE） and nonerosive reflux disease, is one of the most common upper gastrointestinal disorders worldwide and may decrease quality of life. Recently, the prevalence of GERD, including RE, has been increasing and was approximately 8-30% in the world, and there may be approximately 10-15 million patients with RE in Japan. RE is a major risk factor for Barrett’s esophagus, which is the precursor to esophageal adenocarcinoma. Therefore, prevention of RE is important for the prevention of esophageal adenocarcinoma. Additionally, the effective countermeasure of RE is essential for the prevention of RE because there are many high-risk patients for RE, such as those with obesity, metabolic syndrome, metabolic dysfunction, and unfavorable lifestyle habits. We herein introduced our several research about the extraction of high-risk patients for the development RE. From our research, in addition to conventional reported risk factors related with RE, distinction of individuals based on the severity of metabolic syndrome, qualitative assessment of visceral fat, and several metabolites related with RE maybe important for the prevention of RE. As regards alcohol intake, although the influence of alcohol consumption on RE was different between men and women, age and drinking status such as quantity and frequency should be assessed when considering the prevention of RE. We want to contribute to a decrease of patients with esophageal adenocarcinoma by continuing study for RE

Erosive Esophagitis in Women With Metabolic Syndrome

Obesity and metabolic syndrome (MS) are strongly associated with erosive esophagitis (EE). The prevalence of MS and EE, and the distribution of adipose tissue have been known to differ markedly between men and women. Although the prevalence of EE in men with MS is known to be higher in visceral fat type MS (V-type MS) than in subcutaneous fat type MS (S-type MS), the association between EE and the types of MS in women with MS is unclear. This study was a cross-sectional study elucidating the association between EE and the types of MS in women with MS. Subjects were 454 women with MS who underwent a regular health check-up. A distinction was made between V-type MS and S-type MS and the prevalence of EE and the association between EE and other data were elucidated. Although there were some significant different factors in characteristics between V-type MS and S-type MS, there was no significant difference in the prevalence of EE between V-type MS and S-type MS. The presence of Helicobacter pylori (H. pylori) was significantly lower than in subjects with EE (13.7%) than in subjects without EE (41.9%). The frequency of hiatal hernia was significantly higher in subjects with EE (60.8%) than in subjects without EE (24.6%). Logistic regression analysis showed hiatal hernia (odds ratio: 4.673; 95% confidence interval: 2.448–8.920; P < 0.001), hemoglobin A1c (HbA1c) (2.325; 1.110–4.870; P < 0.05), and the presence of H. pylori (0.239; 0.101–0.567; P < 0.005) were significant predictors of the prevalence of EE. V-type MS may not be such an important factor for the prevalence of EE in women with MS as in men with MS. The absence of H. pylori, hiatal hernia, and HbA1c may be more important for the prevalence of EE than the types of MS in women with MS

Acceptability in subjects undergoing EGD

Esophagogastroduodenoscopy (EGD) has become an indispensable examination to discover upper gastrointestinal diseases, including cancer, and perform endoscopic treatment. However, many individuals who undergo the procedure have feelings of anxiety and fear regarding EGD. Although the use of medication for sedation during EGD is useful for reducing anxiety and the stability of hemodynamics, sedation may increase the likelihood of complications. Several noninvasive distractions have been introduced to decrease pain and anxiety during endoscopic examinations ; however, most assessments of these distractions evaluated subjective items such as impression. We herein add the results of our studies using objective items and review the effectiveness of distractions for EGD

Current and future status of the cell-free and concentrated ascites reinfusion therapy (CART)

Cell-free and concentrated ascites reinfusion therapy (CART) is an effective and safe therapy for patients with refractory ascites or pleural effusion. CART was mainly performed conventionally for patients with liver cirrhosis. In addition to the improvement of the device and procedure, CART has been performed widely for patients with advanced cancer by progress of the intraperitoneal chemotherapy. Furthermore, cancer therapy that applies cancer cells obtained by filtration process is considered, and CART attracts attention as one of the important therapies to support future cancer therapy. However, the therapeutic method of CART has not been standardized yet, and the accumulated evidence about its effectiveness and safety is insufficient. Therefore, aiming at the development of guidelines to perform CART safely and effectively, standardization of the CART procedure and evaluation of its efficacy and safety, establishment of an educational system, and environmental improvement, including the development of equipment, are necessary

Contrast medium-removing effect of hemofiltration and hemodiafiltration

The contrast medium-removing effect of hemofiltration (HF) and hemodiafiltration (HDF) was experimentally investigated using a bovine blood tank model. HF and HDF were performed at a blood flow rate of 100ml/min with a polysulfone hemofilter (PS filter-CF ; membrane area : 0.7 m2). Two hundred milliliters of iomeprol (300 mgI/ml) was administered by a single injection into 4 liters of bovine blood. The blood half-lives of iomeprol were 1.0 hr for the high flow rate HDF group [replacement fluid flow rate (QF) : 10 ml/min and dialysate flow rate (QD) : 40 ml/min], 1.8 hr for the HDF group (QF : 10 ml/min and QD : 10 ml/min), and 3.8 hr for the HF group (QF : 10 ml/min). The mean clearance rates were 39.7 ml/min for the high flow rate HDF group, 21.4 ml/min for the HDF group, and 12.0 ml/min for the HF group. Iomeprol was mostly excreted in the waste fluid. It is concluded that HDF can remove contrast media more effectively than HF

Busulfan for lymphoma with CNS involvement

The prognosis of relapsed or refractory lymphoma with central nervous system (CNS) involvement remains poor because of the lack of anticancer drugs with sufficient CNS penetration. [Case 1] A 65-year-old man was diagnosed with Stage IV mantle cell lymphoma. After two courses of chemotherapy and autologous hematopoietic stem cell (HSC) collection, urinary retention with fever developed. Cerebrospinal fluid analysis revealed leptomeningeal involvement, which was refractory to high-dose methotrexate therapy. Autologous peripheral blood stem cell transplantation (ASCT) was performed, followed by intravenous busulfan (ivBU), cyclophosphamide, and etoposide ; thereafter, no relapse has been detected for over six years. [Case 2] A 40-year-old woman with right lower hemiplegia was diagnosed with primary CNS lymphoma. Although four courses of high-dose methotrexate therapy were administered, the cerebral tumor increased in size. HSCs were collected after methotrexate therapy, and ASCT was performed in addition to conditioning using ivBU, cyclophosphamide, and etoposide, followed by whole-brain and local boost irradiation. She achieved complete remission, but relapsed two years after ASCT. High-dose ivBU-containing conditioning regimens with ASCT may be useful for refractory B-cell lymphoma with CNS involvement

Gastroduodenal Mucosal Injury and Antiplatelet Drug Users

Antiplatelet drugs are widely used for the prevention of cardiovascular disease and cerebral vascular disorders. Although there have been several studies on gastroduodenal mucosal injury with gastrointestinal (GI) symptoms such as GI bleeding, in antiplatelet drug users (including low-dose aspirin (LDA)), there have been few reports on the association between antiplatelet drug use and gastroduodenal mucosal injury in asymptomatic antiplatelet drug users. This study was a cross-sectional study elucidating the association between antiplatelet drug use and gastroduodenal mucosal injury in asymptomatic antiplatelet drug users. Subjects were 186 asymptomatic Japanese antiplatelet drug users who underwent a regular health checkup. Subjects were divided into those with and without gastroduodenal mucosal injury endoscopically, and the association between gastroduodenal mucosal injury and other data in asymptomatic antiplatelet drug users was investigated. The prevalence of males and drinkers were significantly higher in subjects with gastroduodenal mucosal injury than in those without. In addition, the prevalence of proton pump inhibitor (PPI) users was significantly lower in subjects with gastroduodenal mucosal injury than in subjects without gastroduodenal mucosal injury. Logistic regression analysis showed PPI (odds ratios: 0.116; 95% confidence intervals: 0.021–0.638; P < 0.05) was a significant predictor of a decreased prevalence of gastroduodenal mucosal injury and closed-type (C-type) atrophy (3.172; 1.322–7.609; P < 0.01) was a significant predictor of an increased prevalence of severe gastroduodenal mucosal injury in asymptomatic antiplatelet drug users. Gender and lifestyle, such as drinking, may have an impact on risk of gastroduodenal mucosal injury in asymptomatic subjects taking antiplatelet drugs. Although PPI is a significant predictor of a decreased prevalence of gastroduodenal mucosal injury, including in asymptomatic antiplatelet drug users, status of gastric atrophy should also be considered against severe gastroduodenal mucosal injury

Sorafenib as a secondary treatment

Background and Aim: Currently, there is no molecular‐targeted agent that has demonstrated evidence of efficacy in patients with unresectable hepatocellular carcinoma (u‐HCC) who have developed resistance to treatment with lenvatinib (LEN). In this real‐world study, we aimed to investigate the therapeutic effect and safety of sorafenib (SOR) in patients with u‐HCC after progression on treatment with LEN. Methods (Patients) and Results: A total of 13 patients with u‐HCC (12 males and 1 female), who were treated with SOR after progression on LEN, were enrolled in this retrospective study. Therapeutic efficacy was evaluated via contrast‐enhanced computerized tomography at 8 weeks after the initiation of SOR therapy according to modified response evaluation criteria in solid tumors (mRECIST) and RECIST. According to mRECIST, the objective response rate (ORR) and disease control rate (DCR) were 15.3% (2/13) and 69.2% (9/13), respectively. According to RECIST, the ORR and DCR were 0% (0/13) and 69.2% (9/13), respectively. The median progression‐free survival was 4.1 months. The median albumin‐bilirubin scores did not deteriorate significantly at 4, 6, and 8 weeks after initiation of SOR, compared with the scores at the baseline. The most frequent grade 1 or 2 adverse events (AEs) were palmar–plantar erythrodysesthesia, fatigue, diarrhea, and hypertension. There was no incidence of grade 3 AEs. Conclusion: Treatment with SOR may be effective for u‐HCC after failure on LEN and may not worsen the liver reserve

Novel antimyeloma therapeutic option with inhibition of the HDAC1-IRF4 axis and PIM kinase

Multiple myeloma (MM) preferentially expands and acquires drug resistance in the bone marrow (BM). We herein examined the role of histone deacetylase 1 (HDAC1) in the constitutive activation of the master transcription factor IRF4 and the prosurvival mediator PIM2 kinase in MM cells. The knockdown or inhibition of HDAC1 by the class I HDAC inhibitor MS-275 reduced the basal expression of IRF4 and PIM2 in MM cells. Mechanistically, the inhibition of HDAC1 decreased IRF4 transcription through histone hyperacetylation and inhibiting the recruitment of RNA polymerase II at the IRF4 locus, thereby reducing IRF4-targeting genes, including PIM2. In addition to the transcriptional regulation of PIM2 by the HDAC1-IRF4 axis, PIM2 was markedly upregulated by external stimuli from BM stromal cells and interleukin-6 (IL-6). Upregulated PIM2 contributed to the attenuation of the cytotoxic effects of MS-275. Class I HDAC and PIM kinase inhibitors cooperatively suppressed MM cell growth in the presence of IL-6 and in vivo. Therefore, the present results demonstrate the potential of the simultaneous targeting of the intrinsic HDAC1-IRF4 axis plus externally activated PIM2 as an efficient therapeutic option for MM fostered in the BM