関節リウマチ(RA)患者のNSAIDs長期投与における胃粘膜障害発生因子ならびにファモチジンの治療効果に関する検討

The objective of this study was to investigate the prevalence of gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). Upper gastrointestinal endoscopy was performed on 100 RA patients treated with NSAIDs. Patient factors potentially contributing to the development of NSAID-induced gastric mucosal injury were identified by logistic regression analysis; gastric mucosal injury and ulcers were used as objective variables. Gastric mucosal injury was detected in 62 of 100 patients, and eight of these patients had ulcers. Previous history of ulcers, lifestyle, NSAID dosage, and body mass index were associated with the development of gastric mucosal injury, and the use of diclofenac and steroid dose were associated with the development of ulcers. Disease-modifying antirheumatic drugs (DMARDs) did not appear to influence the risk of NSAID-induced gastric mucosal injury. RA patients treated for long periods with NSAIDs for RA symptoms should be controlled with DMARDs, without consideration of increased doses of steroids, in terms of risk for NSAID-induced gastric mucosal injury. Simultaneously, concomitant use of histamine-2 receptor antagonists (H2RA) such as famotidine should be considered.博士（医学）・乙第1354号・平成27年3月16日© Japan College of Rheumatology 2009© Springer International Publishing AG, Part of Springer Science+Business Medi

Up-to-date information on gastric mucosal lesions from long-term NSAID therapy in orthopedic outpatients: a study using logistic regression analysis

AbstractBackgroundAn increase in gastric mucosal lesions due to nonsteroidal antiinflammatory drugs (NSAIDs) has been reported along with the aging of society; even orthopedic surgeons can no longer remain unconcerned about this disease. However, no study has accurately examined the incidence of gastric mucosal lesions; therefore, adequate evidence has not been established. In this study, endoscopic examinations were performed to determine the status of gastric mucosal lesions in patients receiving long-term NSAID therapy.MethodsIn 261 patients receiving NSAIDs other than aspirin for more than 28 days, excluding external application, upper gastrointestinal endoscopy was performed regardless of any subjective symptoms after obtaining the patient’s medical history. The severity of the gastric mucosal lesions was evaluated using the modified Lanza score. Patient factors involved in the development of lesions were examined using a logistic regression analysis with criterion variables of gastric mucosal lesions and ulcers and the factors of sex, age, Helicobacter pylori infection, and type of NSAID as candidates for the explanatory variable.ResultsGastric mucosal lesions were observed in 164 patients (62.8%); 27 (10.3%) had ulcers. The use of diclofenac, subjective symptoms, irregular lifestyle, and increased body mass index (BMI) were four factors associated with the development of gastric mucosal lesions; the odds ratios were 2.99, 1.92, 1.80, and 1.09, respectively. Also, the use of diclofenac, presence of H. pylori, irregular lifestyle, alcohol consumption, and aging were five factors associated with the development of ulcers; the odds ratios were 6.40, 6.07, 2.62, 2.06, and 1.05, respectively.ConclusionsDiclofenac can cause gastric mucosal lesions, including ulcers, more easily than other NSAIDs. H. pylori infection is a high-risk factor for ulcers in patients receiving long-term NSAIDs therapy. In NSAID-treated patients, subjective symptoms are not grounds for a diagnosis of gastric mucosal lesions, especially ulcers

内視鏡的硬化療法の手技と治療成績における透明フードの有用性

Objective: Although the effectiveness of a transparent hood has been reported in various endoscopic procedures, there are only a few reports regarding the benefit of a transparent hood in endoscopic injection sclerotherapy(EIS). In the current study, we conducted a retrospective evaluation of the efficacy and long-term benefit of an oblique transparent hood on EIS. Methods: The transparent hood, manufactured by Olympus (MAJ295 or MAJ296), consisted of a reusable wide oblique distal attachment with rim. This hood was attached when the varix was fine (F0 or F1). In this retrospective study, a total of 201 patients were recruited, and 99 patients (designated as the "Hood Group") received this hood while 102 patients (designated as the "Conventional Group") did not. We compared the rate of intravariceal injection, enhanced supply vessels, variceal eradication, and recurrence between these two groups. Results: This transparent hood provided a better visual field, and there was no serious complication in any of the patients. Intravariceal injection rates in the Hood Group and Conventional Group were 73.9% (190/257) and 57.7% (146/253) respectively (p<0.01). The rates of enhanced supply vessels in the Hood Group and Conventional Group were 89.8% (89/99) and 72.5% (74/102) respectively (p<0.01). The rates of variceal eradication did not differ significantly. We also assessed the cumulative non-recurrence probability for up to 3000 days between the two groups. The Hood Group was statistically superior to the Conventional Group (p<0.01) Conclusion: The application of an oblique transparent hood method is safe and effective for intravariceal EIS. This hood contributes especially to reduction of the long-term recurrence probability.博士（医学）・乙第1365号・平成27年11月27

EFFICACY OF INTERFERON THERAPY FOR CHRONIC HEPATITIS C ： A COOPERATIVE STUDY IN ELEVEN HOSPITALS

We investigated the influences of liver histology，serum levels of hepatitis C virus (HCV) and HCV genotypes on responsiveness to interferon (IFN) therapy in 342 patients with chronic hepatitis C. Either 9 million units (MU) of lymphoblastoid alpha IFN or 3 MU of recombinant IFN-alpha was administered daily for 2 weeks and then three times a week for 22 weeks. IFN responses were divided into three groups on the basis of the results of polymerase chain reaction (PCR) assay detecting HCV-RNA in serum. Complete response (CR) was defined as sustained elimination of HCV for at least 6 months after treatment，partial response (PR) as HCV elimination for a limited period，non-response (NR) as continuously positive for HCV-RNA in serum. Quantitation of pre-treament HCV-RNA amount in serum was determined by competitive PCR assay in 47 patients. HCV genotyping was performed in 114 patients by PCR with genotype-specific primers. CR was obtained in 97 patients (28.4%)，PR in 104 (30.4%) and NR in 141 (41.2%). IFN responses，represented by CR/PR/NR，were 15/18/11 in 44 patients with chronic persistent hepatitis (CPH)，72/65/73 in 210 patients with chronic aggressive hepatitis (CAH) 2a，and 10/21/57 in 88 patients with CAH2b. CR rate was lower in patients with CAH2b (11.4%) compared to those with CPH (34.1%) or CAH2a (34.3%). Averages of pre-treatment serum HCV-RNA amount (copies/50μl) were 10³·⁵⁵ in 13 CRs，10⁴·⁵⁶ in 17 PRs，and 10⁵·⁹⁵ in 17 NRs. There was a positive correlation between pre-treatment HCV-RNA levels and IFN unresponsiveness. HCV genotyping in 114 patients revealed that HCV type Ⅰ infection was observed in one，type Ⅱ in 94，type Ⅲ in 11，type Ⅳ in 6 and mixed (types Ⅱ and Ⅳ) in 2 patients，and their IFN responses (CR/PR/NR) were 0/0/1，28/26/40，3/5/3，1/3/2 and 0/1/1，respectively

スルフォラファンの肝癌発育抑制効果および血管新生抑制効果に関する基礎的検討

Sulforaphane (SFN) exhibits inhibitory effects in different types of cancers. However, its inhibitory effect on liver cancer remains unknown. This study aimed to determine the therapeutic potential of SFN for the treatment of liver cancer and explore the functional mechanisms underlying the inhibitory effects of SFN. Water-Soluble Tetrazolium salt (WST-1) assay was performed to assess the in vitro effect of SFN on cell proliferation in the human liver cancer cell lines, HepG2 and Huh-7. The mRNA levels of Nrf2 target genes and cell cycle-related genes were determined using quantitative RT-PCR. For assessing the inhibitory effect of SFN in vivo, we injected immortalized liver cancer cells into BALB/c nude mice as a xenograft model. SFN was orally administrated daily after tumor inoculation and continued for thirty-five days until their sacrifices. Nrf2 activation, induced by SFN, was confirmed by mRNA upregulation of HO-1, MRP2, and NQO1 in both the cell lines. Significant inhibition of liver cancer cell proliferation by SFN was shown in vitro in a dose-dependent manner by the downregulation of CCND1, CCNB1, CDK1 and CDK2. In in vivo studies, the administration of SFN significantly reduced the subcutaneous tumor burdens at the end of experiments by suppressing tumor cell proliferation, confirmed by Ki67 immunohistochemical analysis. The mRNA levels of CCND1, CCNB1, CDK1 and CDK2 were also decreased in these SFNtreated xenograft tumors. Moreover, CD34 immunostaining elucidated that the intratumoral neovascularization was markedly attenuated in the SFN-treated xenograft tumors. SFN exerts inhibitory effect on human liver cancer cells with antiangiogenic activity. The earlier version of this study was presented at the meeting of AASLD Liver Learning on Oct 2017.博士（医学）・甲第707号・平成31年3月15日© The Author(s) 2018 Under License of Creative Commons Attribution 3.0 License https://creativecommons.org/licenses/by/3.0

Salvage living donor liver transplantation after percutaneous transluminal angioplasty for recurrent Budd-Chiari syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Budd-Chiari syndrome is a very rare pathological entity that ultimately leads to liver failure. Several therapeutic modalities, including percutaneous transluminal angioplasty, have been attempted to save the life of patients with Budd-Chiari syndrome. Few reports have described a salvage living donor liver transplantation performed after percutaneous transluminal angioplasty in a patient with acute Budd-Chiari syndrome.</p> <p>Case presentation</p> <p>A 26-year-old Japanese man developed severe progressive manifestations, such as massive ascites and hematemesis due to rupture of esophageal varices. After making several investigations, we diagnosed the case as Budd-Chiari syndrome. We first performed percutaneous transluminal angioplasty to dilate a short-segment stenosis of his inferior vena cava. The first percutaneous transluminal angioplasty greatly improved the clinical manifestations. However, after a year, re-stenosis was detected, and a second percutaneous transluminal angioplasty failed to open the severe stricture of his inferior vena cava. Since our patient had manifestations of acute liver failure, we decided to perform salvage living donor liver transplantation from his brother. The transplantation was successfully performed and all clinical manifestations were remarkably alleviated.</p> <p>Conclusion</p> <p>In cases of recurrent Budd-Chiari syndrome, the blocked hepatic venous outflow is not always relieved, even with invasive therapies. We have to take into account the possibility of adopting alternative salvage therapies if the first therapeutic modalities fail. When invasive therapy such as percutaneous transluminal angioplasty fails, liver transplantation should be considered as an alternative option.</p

Symptomatic periesophageal vagal nerve injury by different energy sources during atrial fibrillation ablation

BackgroundSymptomatic gastric hypomotility (SGH) is a rare but major complication of atrial fibrillation (AF) ablation, but data on this are scarce.ObjectiveWe compared the clinical course of SGH occurring with different energy sources.MethodsThis multicenter study retrospectively collected the characteristics and clinical outcomes of patients with SGH after AF ablation.ResultsThe data of 93 patients (67.0 ± 11.2 years, 68 men, 52 paroxysmal AF) with SGH after AF ablation were collected from 23 cardiovascular centers. Left atrial (LA) ablation sets included pulmonary vein isolation (PVI) alone, a PVI plus a roof-line, and an LA posterior wall isolation in 42 (45.2%), 11 (11.8%), and 40 (43.0%) patients, respectively. LA ablation was performed by radiofrequency ablation, cryoballoon ablation, or both in 38 (40.8%), 38 (40.8%), and 17 (18.3%) patients, respectively. SGH diagnoses were confirmed at 2 (1–4) days post-procedure, and 28 (30.1%) patients required re-hospitalizations. Fasting was required in 81 (92.0%) patients for 4 (2.5–5) days; the total hospitalization duration was 11 [7–19.8] days. After conservative treatment, symptoms disappeared in 22.3% of patients at 1 month, 48.9% at 2 months, 57.6% at 3 months, 84.6% at 6 months, and 89.7% at 12 months, however, one patient required surgery after radiofrequency ablation. Symptoms persisted for &gt;1-year post-procedure in 7 patients. The outcomes were similar regardless of the energy source and LA lesion set.ConclusionsThe clinical course of SGH was similar regardless of the energy source. The diagnosis was often delayed, and most recovered within 6 months, yet could persist for over 1 year in 10%