Language：Japanese   Publisher：(一社)日本肝臓学会  

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AIM: This study aimed to analyze the current trends of drug-induced liver-related adverse events in the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases. METHODS: The characteristics of implicated drugs were investigated by analyzing big data on drug-induced liver-related adverse events over the past 20 years in FAERS, comparing drug rankings between the JADER and FAERS databases, and calculating rankings of drugs inducing liver-related adverse events using the Medical Dictionary for Regulatory Activities Terminology. RESULTS: In the 452,272 cases registered in FAERS from 1997 to 2019, warfarin, paracetamol, and adalimumab were the drugs most related to DILI. In the 38,919 cases registered in the JADER from 2004 to 2019, sorafenib, nivolumab, and herbal extracts were the drugs most related to DILI. No associations were found between the top 30 drugs in either of the two databases. Notably, the number of drug-induced liver-related adverse event reports and total adverse events has sharply increased in recent years. CONCLUSIONS: Although liver-related adverse events are largely caused by host immunity and other constitutional factors, differences in primary diseases, countries, and historical backgrounds lead to differences in the number of reports. Securing an appropriate database and a mechanism to collect real-time information on the frequency of adverse drug reactions is warranted. This article is protected by copyright. All rights reserved.

DOI： 10.1111/hepr.13883

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AIM: Acute-on-chronic liver failure (ACLF), a disease with poor prognosis, is reportedly caused by cellular senescence due to mitochondrial dysfunction. In this study, we described and analyzed the underlying mechanism of a novel approach for ACLF using ABT263/navitoclax (Navi) that selectively eliminates senescent cells. METHODS: Irradiation-induced senescent hepatocytes were used for in vitro evaluation of the effects of Navi on ACLF (n = 6 for each group). Lipopolysaccharide- and carbon tetrachloride-induced ACLF mouse model was used for in vivo evaluation of the effects of Navi administration compared with the control using one-way or two-way analysis of variance, followed by Student's t-test or Kruskal-Wallis test. The effects on the senescence-associated secretory phenotype (n = 8 for each group) and mitochondrial functions, including adenosine triphosphate concentration and membrane potential (n = 8 for each group), were investigated using real-time polymerase chain reaction, immunohistochemistry, and enzyme analysis. RESULTS: Navi eliminated irradiation-induced senescent hepatocytes in vitro, leading to non-senescent hepatocyte proliferation. Navi eliminated senescent cells in the liver in vivo, resulting in downregulation of mRNA expression of senescence-associated secretory phenotype factors, a decrease of liver enzymes, and upregulated proliferation of non-senescent cells in the liver. Regarding mitochondrial functional assessment in the liver, adenosine triphosphate concentration and membrane potential were upregulated after Navi administration in vitro and in vivo. CONCLUSIONS: Navi may ameliorate ACLF damage by eliminating senescent cells in the liver, downregulating senescence-associated secretory phenotype factors, and upregulating mitochondrial functions. We believe that this novel approach using Navi will pave the way for ACLF treatment.

DOI： 10.1111/hepr.13879

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Language：English   Publisher：日本消化器病学会-甲信越支部  

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Acute pancreatitis is an uncommon occurrence in acute liver failure. Furthermore, such cases are rarely complicated by parenchymal hemorrhages. Herein, we report the case of a 69-year-old male patient with multiple pancreatic parenchymal hemorrhages concomitant with acute liver failure. The patient underwent conservative treatment for acute liver failure caused by hepatitis B virus infection. Plain computed tomography on the 30th day revealed two high-density mass lesions in the pancreatic body and tail, which were suspected to be multiple pancreatic parenchymal hemorrhages. Despite restarting gabexate mesylate, the patient died of multiple organ failure on the 49th day. The clinical information of the present case and our literature review of 61 similar cases in 43 case reports identified via a systematic keyword search of the PubMed database, which described acute pancreatitis concomitant with acute hepatitis and acute liver failure, will aid physicians in the diagnosis and treatment of this rare condition.

DOI： 10.1007/s12328-022-01738-x

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Background and Aim: Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods: This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan-Meier analysis with propensity score matching and logistic progression analysis. Results: The cumulative risk of developing a new symptom after 10 and 20 years of follow-up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033-1.165; P = 0.002), the serum D-Bil level (HR, 6.262; 95% CI, 2.522-15.553, P < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183-1.036; P = 0.037) were significant independent predictors of a new symptom. Kaplan-Meier analysis showed that the overall survival and liver-related death were not significant between patients with and without a new symptom. Conclusion: The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D-Bil level, and Paris II criteria.

DOI： 10.1002/jgh3.12789

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

大量の肝性腹水が腹腔内圧の上昇をもたらし、腹部コンパートメント症候群を発症している状況を腹水前後の膀胱内圧測定、腎静脈流速測定を中心に検討した。対象症例は穿刺前後の膀胱内圧測定、腎静脈の流速測定等が可能であった腹水合併肝硬変8例。穿刺前後の膀胱内圧、尿潜血反応、腎機能、腎静脈流速等を経時的に観察した。末期肝硬変患者が肝腎症候群へ移行する過程で腹水による腹腔内圧の上昇が腎うっ血を併発させ、レニン-アンギオテンシン-アルドステロン系の亢進に関係する可能性が示唆された。(著者抄録)

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

大量の肝性腹水が腹腔内圧の上昇をもたらし、腹部コンパートメント症候群を発症している状況を腹水前後の膀胱内圧測定、腎静脈流速測定を中心に検討した。対象症例は穿刺前後の膀胱内圧測定、腎静脈の流速測定等が可能であった腹水合併肝硬変8例。穿刺前後の膀胱内圧、尿潜血反応、腎機能、腎静脈流速等を経時的に観察した。末期肝硬変患者が肝腎症候群へ移行する過程で腹水による腹腔内圧の上昇が腎うっ血を併発させ、レニン-アンギオテンシン-アルドステロン系の亢進に関係する可能性が示唆された。(著者抄録)

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Language：English   Publisher：日本消化器病学会-甲信越支部  

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Language：English   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Objectives: Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota. Methods: Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double-ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method. Results: All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2-3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α-diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT. Conclusions: This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.

DOI： 10.1002/deo2.63

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Language：Japanese   Publisher：(一社)日本再生医療学会  

肝硬変症に対する治療として、2003年実施した臨床研究:自己骨髄細胞投与療法により、肝線維化改善とそれに引き続く肝再生の誘導、それに伴う肝機能の改善効果を確認してきた。その後、2017年より、肝硬変症に対する他家脂肪組織由来間葉系幹細胞投与療法の企業治験、現在軽症の肝硬変に対する他家脂肪組織由来間葉系幹細胞の医師主導治験を2021年より実施している。さらに2020年よりHMGB1ペプチドを用いた医師主導治験を実施しており、より効率のいい再生療法の開発を行っている。さらに次のステップとして間葉系幹細胞由来エクソソームを用いた治療の準備を行っている。本稿では、現時点における我々の肝硬変症に対するアプローチを紹介する。(著者抄録)

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Due to the developments in the treatment for hepatitis, it is possible to prevent the progression of liver fibrosis and improve patients' prognosis even if it has already led to liver cirrhosis (LC). Consequently, a two-step study was conducted. To begin with, a retrospective study was conducted to identify the potential predictors of non-malignancy-related mortality from LC. Then, we prospectively analyzed the validity of these parameters as well as their association with patients' quality of life. In the retrospective study, 89 cases were included, and the multivariate Cox regression analysis indicated that age (P = 0.012), model for end-stage liver disease (MELD) score (P = 0.012), and annual rate of change of the albumin-bilirubin (ALBI) score (P < 0.001) were significantly associated with LC prognosis. In the prospective study, 70 patients were included, and the patients were divided into cirrhosis progression and non-progression groups. The univariate logistic regression analysis indicated the serum procollagen type III N-terminal peptide level (P = 0.040) and MELD score (P = 0.010) were significantly associated with the annual rate of change of the ALBI score. Furthermore, the mean Chronic Liver Disease Questionnaire score worsened from 5.3 to 4.9 in the cirrhosis progression group (P = 0.034). In conclusion, a longitudinal increase in the ALBI score is closely associated with non-malignancy-related mortality and quality of life.

DOI： 10.1371/journal.pone.0263464

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Language：English   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：English   Publisher：日本消化器病学会-甲信越支部  

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BACKGROUND: Biochemical response to treatment in patients with primary biliary cholangitis (PBC) reflects prognosis. However, the best predictive criteria to detect biochemical response remain undetermined. In addition, because these criteria need > 6 months until definition, parameters that can estimate its results before initiating treatment are needed. METHODS: We conducted a single-center retrospective study on 196 patients with PBC, followed up for at least 12 months after initiating treatment. RESULTS: Kaplan-Meier analysis showed that Paris II (p = 0.002) and Rotterdam criteria (p = 0.001) could estimate the overall survival of PBC patients, whereas Paris II (p = 0.001), Rotterdam (p = 0.001), and Rochester criteria (p= 0.025) could estimate liver-related deaths. Cox hazard analysis revealed Paris II and Rotterdam criteria as significantly independent predictors of overall survival (hazard ratio (HR) 3.948, 95% CI 1.293-12.054, p = 0.016 and HR 6.040, 95% CI 1.969-18.527, p = 0.002, respectively) and liver-related deaths (HR 10.461, 95% CI 1.231-88.936, p = 0.032 and HR 10.824, 95% CI 1.252-93.572, p = 0.032, respectively). The results of Paris II criteria could be estimated by serum prothrombin time (Odds ratio (OR) 1.052, 95% CI 1.008-1.098, p = 0.021) and alanine transaminase level (OR 0.954, 95% CI 0.919-0.991, p = 0.014) whereas, those of Rotterdam criteria could be estimated by serum albumin level (OR 3.649, 95% CI 1.098-12.128, p = 0.035) at the time of diagnosis. CONCLUSIONS: This study highlights the best prediction criteria and pre-treatment parameters that facilitate the prognosis of PBC patients.

DOI： 10.1007/s12072-021-10163-0

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AIM: Disease characteristics of primary biliary cholangitis have changed recently. However, detailed studies on the subject have been limited. Therefore, we aimed to clarify disease characteristics of patients with recent primary biliary cholangitis using the cohort from Niigata University and 21 affiliated hospitals. METHODS: Overall, 508 patients were enrolled in this study from 1982 to 2016, divided into three cohorts according to their year of diagnosis: ≤1999, 2000-2009 and ≥2010. We compared differences in clinical characteristics, response to ursodeoxycholic acid and prognosis. RESULTS: The male-to-female ratio increased incrementally from 1:16.4 (≤1999) to 1:3.8 (≥2010) (P < 0.001). In women, the median age at diagnosis increased incrementally from 54.0 years (≤1999) to 60.5 years (≥2010) (P < 0.001) and serum albumin decreased gradually (P = 0.001), which might have affected the increase in the Fibrosis-4 Index and albumin-bilirubin score. The ursodeoxycholic acid response rate according to the Barcelona criteria increased incrementally from 26.7% (≤1999) to 78.4% (≥2010) (P < 0.010), and those according to other criteria (Paris-I, Rotterdam and Toronto) were approximately ≥80% in all cohorts. Ten-year survival rate in the ≤1999 and 2000-2009 cohorts were 98.6% and 95.6%, respectively. These earlier cohorts were also characterized by a higher rate of asymptomatic state and mild histology (83.5% [≤1999] and 84.7% [2000-2009], and 93.6% [≤1999] and 91.1% [2000-2009]). CONCLUSIONS: Patients with primary biliary cholangitis were characterized by older age at diagnosis and an increase in male to female ratio as well as higher response rates of ursodeoxycholic acid and longer survival, resulting from the early recognition of primary biliary cholangitis.

DOI： 10.1111/hepr.13586

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Focal nodular hyperplasia (FNH) is the second most frequent benign liver tumor, and it is a fiber-rich stiff lesion. Typically, FNH can be diagnosed by imaging without biopsy. However, liver biopsy and diagnostic resection may be required to differentiate atypical FNH from other liver tumors, such as hepatocellular adenoma (HCA). Therefore, improved noninvasive diagnostic methods are needed. We experienced 2 cases where combination of magnetic resonance elastography (MRE) and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) helped diagnose FNH. A 36-year-old woman and 17-year-old boy with liver tumors measuring 40 mm in diameter each showed hypointense nodule centers, indicating a central scar, surrounded by hyperintense signals during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. To rule out HCA, we performed MRE and liver biopsy. On MRE, the mean stiffness of the mass was 11.6 kPa (mean stiffness of the background liver was 1.7 kPa) and 11.1 kPa (mean stiffness of the background liver was 2.4 kPa) in the first and second patients, respectively. Histological examination of both specimens showed CK7-positive bile-ductular proliferations, abundant fibrous tissue, and few Ki-67-positive cells. Based on these results, we diagnosed these tumors as FNH. Combination of Gd-EOB-DTPA-enhanced MRI and MRE can evaluate the character and stiffness of lesion and help in the diagnosis of FNH.

DOI： 10.1159/000516552

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Background and Aim: Considering the increasing prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH), the development of an effective screening and follow-up system that enables the recognition of etiological changes by primary physicians in clinics and specialists in hospitals is required. Methods: Chronic hepatitis B (HBV) and C (HCV), NASH, and alcoholic steatohepatitis (ASH) patients who were assayed for Mac-2-binding protein glycosylation isomer (M2BPGi) (n = 272) and underwent magnetic resonance elastography (MRE) (n = 119) were enrolled. Patients who underwent MRE were also tested by ultrasound elastography (USE) (n = 80) and for M2BPGi (n = 97), autotaxin (ATX) (n = 62), and platelet count (n = 119), and their fibrosis-4 (FIB-4) index was calculated (n = 119). Results: FIB-4 index >2, excluding HBV-infected patients, M2BPGi >0.5, ATX >0.5, and platelet count <20 × 104/μL were the benchmark indices, and we took into consideration other risk factors, such as diabetes mellitus and age, to recommend further examinations, such as USE, based on the local situation to avoid overlooking hepatocellular carcinoma (HCC) in the clinic. During specialty care in the hospital, MRE exhibited high diagnostic ability for fibrosis stages >F3 or F4; it could efficiently predict collateral circulation with high sensitivity, which can replace USE. We also identified etiological features and found that collateral circulation in NASH/ASH patients tended to exceed high-risk levels; moreover, these patients exhibited more variation in HCC-associated liver stiffness than the HBV and HCV patients. Conclusions: Using appropriate markers and tools, we can establish a stepwise, practical, noninvasive, and etiology-based screening and follow-up system in primary and specialty care.

DOI： 10.1002/jgh3.12406

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Pancreatic pseudocyst-portal vein (PP-PV) fistula, mostly occurring after pseudocyst formation following acute/chronic pancreatitis, is a rare but life-threatening condition. The majority of treatments are based on conservative or surgical interventions. We report the case of a 70-year-old man with a PP-PV fistula and PV thrombosis. We adopted conservative treatment at first due to his mild symptoms. However, after resuming food intake, the patient had severe abdominal pain. Following endoscopic retrograde cholangiopancreatography, we found that the pseudocyst was connected with the PV through the fistula. Subsequently, an endoscopic nasopancreatic drainage (ENPD) catheter was inserted into the main pancreatic duct to establish pancreatic drainage, which resulted in a decrease in the abdominal pain. After the ENPD tube had been exchanged for endoscopic pancreatic stenting, his abdominal pain did not recur. Therefore, this case demonstrated endoscopic treatment as an effective treatment option for PP-PV fistula.

DOI： 10.1159/000510331

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BACKGROUND: The relationship between the amount of adipose tissue and advanced-stage liver cirrhosis with esophageal varices (EV) is unknown. We aimed to reveal the prognostic significance of adipose tissues in patients with liver cirrhosis. METHODS: We enrolled 87 patients with EV who received initial endoscopic treatment and underwent scheduled treatments in our hospital. Computed tomography (CT) images were obtained of a 5-mm slice at the umbilical level. We evaluated the effect of mortality based on the visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral subcutaneous adipose tissue ratio (VSR). RESULTS: Cox hazard multivariate analysis showed that the presence of hepatocellular carcinoma (HCC; hazard ratio [HR]: 4.650, 95% confidence interval [CI]: 1.750-12.353, P = 0.002), γ-GTP (HR: 1.003, 95% CI: 1.001-1.006, P = 0.026) and VATI (HR: 1.057, 95% CI: 1.030-1.085, P < 0.001) significantly affected mortality. Cox hazard multivariate analysis for liver-related death was also significantly affected by HCC (HR: 1.057, 95% CI: 1.030-1.085, P < 0.001) and VATI (HR: 1.052, 95% CI: 1.019-1.086, P = 0.002). The difference between the Child-Pugh scores 12 months post-treatment and that during initial treatment were significantly positively correlated with VATI (r = 0.326, P = 0.027). Patients with high VSR had a significantly higher frequency of HCC after EV treatment by Kaplan-Meier analysis (P = 0.024). CONCLUSION: Our findings suggest that VATI measured by CT could significantly predict mortality in cirrhosis patients through decreasing liver function and increasing HCC frequency and appropriately controlling VATI could improve their prognosis.

DOI： 10.1159/000508867

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A 75-year-old woman with liver cirrhosis was admitted for treatment of portal vein thrombosis (PVT). Computed tomography (CT) showed PVT, massive ascites, and multiple abdominal organ embolism. Blood tests revealed a decreased liver function (Child-Pugh grade C). Language impairment followed by progressive left hemi-paralysis was subsequently detected. Magnetic resonance imaging revealed multiple small acute cerebral infarctions and, on CT, a 30-mm bladder tumour; a biopsy specimen examination showed squamous cell carcinoma. Her general condition worsened rapidly, and the best supportive care was chosen. Our findings suggest that, in patients with PVT, Trousseau syndrome should be considered, even in cases of liver cirrhosis.

DOI： 10.2169/internalmedicine.4112-19

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Ulcerative colitis, a chronic and recurrent inflammatory disease, is localized to the colonic mucosa but can affect other organs and lead to various complications. Gastroduodenitis associated with ulcerative colitis has been reported. However, little is known about esophageal ulcers. We herein report two rare cases of esophageal ulcers associated with ulcerative colitis. Furthermore, the clinical and histological characteristics of 18 previously reported cases are summarized. This case series and literature review will encourage the accurate diagnosis and treatment of esophageal ulcers associated with ulcerative colitis.

DOI： 10.2169/internalmedicine.4437-20

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The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the ensuing worldwide pandemic. The spread of the virus has had global effects such as activity restriction, economic stagnation, and collapse of healthcare infrastructure. Severe SARS-CoV-2 infection induces a cytokine storm, leading to acute respiratory distress syndrome (ARDS) and multiple organ failure, which are very serious health conditions and must be mitigated or resolved as soon as possible. Mesenchymal stem cells (MSCs) and their exosomes can affect immune cells by inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and can inactivate T cells. Hence, they are potential candidate agents for treatment of severe cases of COVID-19. In this review, we report the background of severe cases of COVID-19, basic aspects and mechanisms of action of MSCs and their exosomes, and discuss basic and clinical studies based on MSCs and exosomes for influenza-induced ARDS. Finally, we report the potential of MSC and exosome therapy in severe cases of COVID-19 in recently initiated or planned clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov.

DOI： 10.1186/s41232-020-00121-y

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© 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd. This report highlights the easy peeling of the esophageal epithelium with Nikolsky phenomenon after swallowing the foreign body and the healing status of the esophagus only 3 days later in a patient of pemphigus vulgaris.

DOI： 10.1002/ccr3.2846

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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AIM: A significant concern for autoimmune hepatitis (AIH) patients is diagnostic specificity. Delayed treatment due to delayed diagnosis leads to poor survival. We recently reported that chemokine C-C receptor 7 (CCR7)- /programmed cell death-1 (PD-1)+ follicular helper T (Tfh) cells could be involved in AIH pathogenesis. We hypothesized that Tfh cell frequencies might contribute to AIH diagnosis. METHODS: Peripheral blood was collected from 12 patients with AIH from April 2013 to March 2016, as well as 24 patients with hepatitis B virus (HBV) infection and 44 healthy controls (HC). Mononuclear cells were separated using a Ficoll gradient, and surface markers were investigated using flow cytometry. RESULTS: The frequency of CCR7- PD-1+ Tfh cells was significantly higher in AIH patients (39.1 ± 8.6) compared to that in HC (25.1 ± 7.9%, P < 0.01) and HBV patients (22.7 ± 7.8, P < 0.01). The area under the receiver operating characteristic curve for the frequency of the CCR7- PD-1+ Tfh cell subset for AIH and HC and AIH and HBV was 0.905 and 0.927, respectively. The frequency of the CCR7- PD-1+ Tfh cell subset was not correlated with International Autoimmune Hepatitis Group (IAIHG) scoring, Simplified AIH scoring, or Japanese diagnostic guidelines (R = 0.10, 0.947; R = 0.0008, 0.180; and R = 0.348, 0.558, respectively). Therefore, these frequencies could diagnose AIH patients who were not diagnosed with the IAIHG or simplified AIH scores. CONCLUSIONS: The frequency of the peripheral CCR7- PD-1+ Tfh cell subset could be useful for diagnosing AIH even in patients who were not diagnosed with IAIHG or simplified AIH scores.

DOI： 10.1111/hepr.13356

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BACKGROUND: Achalasia is a well-known esophageal motility disorder, but epidemiological studies in Japan are lacking. We investigated the incidence and period prevalence of achalasia in Japan, including the rate of coexistence of esophageal carcinoma, and evaluated treatment trends. METHODS: To estimate the nationwide number of patients with achalasia, a large-scale insurance claims database from 2005 to 2017 were used for our analyses. Patients with achalasia and coexistence of esophageal carcinoma were identified based on the diagnosis code registered. Interventional treatment was also evaluated. RESULTS: Of the total 5,493,650 populations, 385 were diagnosed with primary achalasia. The incidence was calculated as 0.81-1.37 per 100,000 person-years (male-to-female ratio was almost 1; mean age at diagnosis was 43.3 ± 14.4 years). The period prevalence was 7.0 per 100,000 persons. There were statistically significant trends of increase in the incidence and period prevalence over age groups (all p values < 0.0001). Four men with achalasia developed esophageal carcinoma, and the incidence of esophageal carcinoma with achalasia was estimated as 0.25 per 100 person-years. With regard to intervention, esophageal dilation was performed as a first treatment in 64.7% of patients, with repeat intervention required in 56.9% of these. The proportion of patients treated using peroral endoscopic myotomy (POEM) increased annually to 41.1% in 2017. CONCLUSIONS: In Japan, the incidence and period prevalence of achalasia is comparable to that in other countries. The absolute risk of esophageal carcinoma is rather low. Esophageal dilation has been the mainstay of achalasia treatment, and the role of POEM has increased annually.

DOI： 10.1007/s00535-018-01544-8

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Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease involving the intestine, and Guillain-Barré Syndrome (GBS) is rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. UC and GBS can be caused by immune system abnormalities and can co-exist. To date, there are 7 reported cases of GBS in patients with UC. However, only one patient developed UC after GBS treatment. We report a rare case of UC that appeared after intravenous immunoglobulin therapy for GBS. This case report and literature review will allow accurate and prompt diagnosis of co-existent GBS and UC.

DOI： 10.1007/s12328-019-00939-1

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DOI： 10.1111/den.13383

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Hepatocellular carcinomas (HCCs), which often arise from chronic liver damage, have poor conditional 5-year survival and are recognized as heterogeneous tumors. Considering the heterogeneity of HCCs, diverse perspectives need to be addressed for treating such tumors, besides the findings of conventional imaging modalities and tumor markers. Data from the latest technologies, such as liquid biopsy, and the detection of the presence of cancer cells with stem/progenitor cell markers, gene mutations and diverse pathways, crosstalk with immune cells and cancer-associated fibroblasts, and mechanisms of epithelial-mesenchymal transition provide diverse lines of information. Integration of these data with clinical data might be necessary to develop effective therapies for precision medicine. Here, we review several aspects of dealing with the complexity of heterogeneous HCCs.

DOI： 10.1016/j.heliyon.2019.e01325

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Hepatic progenitor cell (HPC) marker-positive hepatocellular carcinomas (HCCs) have recently been extensively analyzed, and their prognosis has been reported as poor compared to HPC marker-negative HCCs. However, previous studies have analyzed the existence of HPC marker-positive cancer cells only in primary lesions, as well as the recurrence rate and prognosis of such tumors. Here, we are the first to report the behavior of HPC marker-positive cancer cells during vascular invasion and metastasis of an HCC. We concurrently analyzed EpCAM- and/or NCAM-expressing cancer cells in the primary, vascular invasion, and metastatic lesions of an HCC. An HCC which includes EpCAM- and/or NCAM-expressing cancer cells has not been previously reported. EpCAM- and/or NCAM-positive cancer cells invaded the vessels and formed heterogeneous populations of these HPC marker-positive cancer cells with HPC marker-negative cancer cells. The frequency of HPC marker-positive cancer colonies and cells in vessels was higher than that in the primary HCC. In the metastatic lesions, EpCAM-positive cancer cells were more frequently detected than NCAM-positive cancer cells, indicating that EpCAM may be more important than NCAM for cancer cell settlement in the metastatic lesions. Furthermore, bigger metastatic tumors tended to include HPC marker-positive cancer cells, suggesting that HPC marker-positive cancer cells have a growth advantage in the metastatic lesions. These results showed that HPC marker-positive cancer cells would be important for vascular invasion and metastasis and suggested that HPC marker-positive cancer cells are an important target in HCC treatment. (C) 2019 The Author(s) Published by S. Karger AG, Basel.

DOI： 10.1159/000498913

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Introduction: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are involved in anti-bacterial immunity. MAIT cells are found in the intestines, but their role and distribution within the large intestine have not been fully elucidated. Therefore, we investigated the distribution of MAIT cells within the cecum and colon. Material and methods: Surgically resected tissues of the cecum and colon were obtained from 4 patients with cecal appendix cancer and 8 patients with colorectal cancer, respectively. Lymphocytes were isolated from the intestinal epithelium (intraepithelial lymphocytes - IELs) and the underlying lamina propria (lamina propria lymphocytes - LPLs), and then, MAIT cells were analyzed by flow cytometry. Results: Compared with the colon, the cecum showed a significantly increased frequency of MAIT cells among IELs (p < 0.01). CD69 expression on MAIT cells was significantly increased in the cecum and colon compared with that in the blood, and the frequency of natural killer group 2, member A+ cells among MAIT cells was significantly increased in the cecum. Conclusions: These results suggest that the distribution of MAIT cells was different between the cecum and colon and that MAIT cells were more likely to be activated, especially in the intestinal epithelium of the cecum than in the colon and blood.

DOI： 10.5114/ceji.2019.84020

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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Our case highlights the need for caution during vascular endothelial growth factor pathway inhibitor (VPI) therapy and for the occurrence of aortic dissection. If Stanford classification type A aortic dissection occurs during VPI therapy, surgical intervention should be considered to prevent cardiac tamponade if the patient's clinical condition permits it.

DOI： 10.1002/ccr3.1674

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We report a case of inferior vena cava (IVC) thrombosis caused by compression by a giant liver cyst. A 68-year-old man with a 1-day history of abdominal pain was referred to another hospital. Ultrasonography (US) and enhanced computed tomography (CT) showed a multilobular cyst on the right liver lobe that had increased to 300 mm in diameter from 90 mm 18 months earlier. Thrombosis was detected in the IVC, which was compressed by the cyst. Percutaneous transhepatic cyst drainage achieved no significant change in size. Cytological analysis from the percutaneous drainage tube fluid showed no evidence of malignancy. He was referred to our hospital for further assessment and treatment. Enhanced US using perfluorobutane, CT, and magnetic resonance imaging showed no tumorous lesions in the cyst. Thus, we diagnosed it as a multilobular cyst with no evidence of malignancy. A 3-week course of heparin resulted in the successful resolution of the thrombosis. Cystectomy was subsequently performed and pathological examination showed a multifocal cyst consisting of central suppurative inflammatory exudation and hemorrhagic material, with no malignancy. This case demonstrates that giant, expanding, non-tumorous cysts can cause IVC thrombosis. Careful treatment using heparin successfully resolved the thrombosis and allowed successful cystectomy.

DOI： 10.1007/s12328-018-0885-x

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The liver plays a key role in the metabolism of proteins. Liver dysfunction affects many organs because it communicates with the spleen and all digestive organs through the portal vein. Additionally, the kidney is an organ that is closely related to the liver and is involved in liver diseases. Glomerulonephritis is an important extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. Nucleos(t)ide analog (NA) therapy effectively suppresses HBV replication by inhibiting HBV polymerase, thus decreasing the levels of serum HBV-DNA and delaying the progression of cirrhosis. Although NA therapy is recommended for all patients with chronic HBV infection, regardless of the level of renal dysfunction, there is limited information on NA use in patients with chronic kidney disease. In addition, in patients with end-stage liver cirrhosis, hepatorenal syndrome can be fatal. Hence, we should take into account the stage of impaired renal function in patients with cirrhosis. The aims of this article are to review the epidemiology, clinical presentation, treatment, and prevention of HBV-associated nephropathy.

DOI： 10.3390/diseases6020052

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BACKGROUND AND AIM: Mucosal-associated invariant T (MAIT) cells constitute a novel subset of innate-like T lymphocytes characterized by a semi-invariant T-cell receptor repertoire capable of recognizing bacterial products. Considering the abundance of MAIT cells in the liver and the possible association between bacterial infections and primary biliary cholangitis (PBC), we aimed to analyze the involvement of MAIT cells in the immunopathogenesis of PBC. METHODS: Peripheral blood and liver biopsy specimens were collected from 25 patients with PBC and 19 patients with chronic viral hepatitis. Surgically removed liver tissues distant from tumors in patients with metastatic liver tumors were used as controls. Mononuclear cells were separated using Ficoll gradient, and the expression of various markers was investigated by flow cytometry. Cytokine production was investigated using blood MAIT cells after stimulation by anti-CD3/CD28-coupled beads with/without interleukin-7 (IL-7). RESULTS: Mucosal-associated invariant T cells were significantly reduced in both the blood and liver of PBC patients compared with those in controls. MAIT cells in the blood of PBC patients expressed significantly lower levels of activation markers and IL-7 receptor. Moreover, MAIT cells in the blood of PBC patients showed impaired production of cytokines, especially tumor necrosis factor alpha, after in vitro stimulation with IL-7. Interestingly, even after biochemical responses were achieved by ursodeoxycholic acid treatment, the frequencies of MAIT cells did not fully recover to normal levels. CONCLUSIONS: These findings suggested that MAIT cells were activated, exhausted, and persistently depleted in PBC patients even after ursodeoxycholic acid treatment, possibly as a consequence of persistent liver inflammation.

DOI： 10.1111/jgh.14076

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DOI： 10.1159/000491384

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

Background and Aim: Recent studies have demonstrated that B cells and follicular helper T (Tfh) cells, which are central regulators of humoral immune response, contribute to the development and progression of autoimmune diseases. Because Tfh cells can be divided into several subsets with distinct functional properties, this study aimed to examine the roles of different subsets of circulating Tfh cells in the immune pathogenesis of autoimmune hepatitis (AIH). Methods: Thirty-five patients with AIH, 28 patients with primary biliary cholangitis, 22 patients with chronic hepatitis B (CHB), and 44 health controls (HC) were enrolled. The frequencies of different Tfh subsets in the blood and liver were examined by flow cytometry and immunohistochemical staining. The function of circulating Tfh subsets was examined after in vitro stimulation. Results: In newly diagnosed AIH patients, the frequency of circulating chemokine C-C receptor 7−programmed cell death-1+ Tfh subset was significantly increased compared with that in CHB patients and HC, significantly correlated with clinical parameters, including serum IgG, prothrombin time and albumin levels, and significantly decreased after corticosteroid treatment. In the liver of AIH patients, the frequencies of activated Tfh subsets were significantly increased and positively correlated with those in the blood. Moreover, the ability to produce interleukin-21 and interleukin-17 from circulating Tfh cells was significantly increased in AIH patients compared with HC. Conclusions: These results significantly extend our understanding of Tfh subsets in AIH and suggest a potential role of dysregulated chemokine C-C receptor 7−programmed cell death-1+ Tfh subset in the pathogenesis and disease progression of AIH.

DOI： 10.1111/jgh.13844

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Cell motility plays an important role in intrahepatic metastasis of hepatocellular carcinoma (HCC), and predicts poor prognosis in patients. The present study investigated the role of a disintegrin and metalloproteinases (ADAMs) in HCC, since these proteins are known to be associated with cell motility. We confirmed the expression of 12 ADAMs with putative metalloproteinase activity in HCC cells, and established a KYN-2 HCC cell line stably expressing short interfering RNA against ADAM21 to investigate the effect of ADAM21 deficiency on HCC cell motility and metastasis in vitro and in vivo. We also examined ADAM21 expression in a cohort of 119 HCC patients by immunohistochemistry. ADAM21 was overexpressed in KYN-2 cells, and its knockdown reduced invasion, migration, proliferation, and metastasis relative to controls. In clinical specimens, ADAM21 positivity was associated with vascular invasion, large tumor size, high histological grade, and lower overall and recurrence-free survival as compared to cases that were negative for ADAM21 expression. A multivariate analysis revealed that ADAM21 positivity was an independent risk factor for overall (P = 0.003) and recurrence-free (P = 0.001) survival. These results suggest that ADAM21 plays a role in HCC metastasis and can serve as a prognostic marker for disease progression.

DOI： 10.1038/s41598-017-15800-z

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Language：English   Publisher：WILEY  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMEDICAL RESEARCH PRESS LTD  

munity. Recent studies have demonstrated that MAIT cells might be implicated in inflammatory bowel diseases (IBDs), but their precise function in IBD remains to be elucidated. We investigated the possible involvement of MAIT cells in the immunopathogenesis of IBDs. Heparinized peripheral blood and biopsy specimens of the colon were collected from 25 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), and 19 heathy individuals. Lymphocytes were isolated from the blood and colon, and then MAIT cells were analyzed by flow cytometry. The frequency of MAIT cells was significantly lower in the blood of IBD patients compared to healthy donors and significantly higher in the inflamed colons compared to healthy colons (P = 0.001). Among the IBD patients, the frequency of MAIT cells in the blood and colon was correlated with disease activities. In vitro activated MAIT cells from IBD patients secreted significantly more tumor necrosis factor-alpha and interleukin-17 than those from healthy donors. These findings indicate that MAIT cells are activated in IBD patients, and their accumulation in the inflamed mucosa is correlated with disease activities.

DOI： 10.2220/biomedres.38.111

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Language：English   Publisher：WILEY  

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Language：English   Publisher：WILEY-BLACKWELL  

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AimHepatocellular carcinoma (HCC) is frequently complicated with cirrhosis, and it is not unusual for treatment options to be limited as a result of pancytopenia due to hypersplenism. Partial splenic embolization (PSE) has been performed for thrombocytopenia resulting from hypersplenism. We studied the efficacy in terms of hepatic functional reserve and safety in patients who underwent concurrent transcatheter arterial chemoembolization (TACE) with PSE for HCC.
MethodsThe study population consisted of 101 HCC patients with thrombocytopenia. Fifty-three patients were treated with concurrent TACE/PSE (PSE group), and the remaining 48 TACE patients without PSE (non-PSE group) were investigated hepatic functional reserve.
ResultsPlatelet counts were significantly higher in the PSE group after 2 weeks, 2 months and 6 months after TACE than the non-PSE group. Child-Pugh score significantly deteriorated from 7.131.16 to 7.60 +/- 1.20 at 2 weeks, to 7.71 +/- 1.25 at 2 months, and 7.71 +/- 1.35 at 6 weeks after TACE in the non-PSE group. Hence, it worsened from 7.04 +/- 1.05 to 7.21 +/- 0.99 at 2 weeks temporally, but improved to 7.00 +/- 1.17 after 2 months and 6.70 +/- 1.16 at 6 weeks after TACE in the PSE group.
ConclusionThrombocytopenia has been improved and treatment continued using concurrent PSE. In addition, hepatic functional reserve could be maintained even after treatment for HCC. Concurrent TACE and PSE for HCC with thrombocytopenia can be expected to help maintain hepatic reserve, and may contribute to improving the prognosis of HCC.

DOI： 10.1111/hepr.12222

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Language：English   Publisher：WILEY-BLACKWELL  

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Background/Aims: The Child-Pugh classification system is the most widely used system for assessing hepatic functional reserve in HCC treatment. In the Child-Pugh classification system, serum albumin levels are used to accurately assess the status of protein metabolism and nutrition. To date, a lack of attention has been given to amino acid metabolism. In the present study, we investigated whether the branched-chain amino acids to tyrosine ratio (BTR) as an indicator of amino acid metabolism can serve as both a prognostic factor for early HCC and a predictive factor for recurrence. Methodology: We conducted a cohort study of 50 patients with stage I/II HCC enrolled between May 2002 and December 2010. It was investigated whether BTR can serve as both a prognostic factor and a predictive factor for HCC recurrence. Results: Overall survival rates were significantly higher in patients with high baseline BTR than in those with low BTR. Multivariate analysis showed that both BTR and serum albumin were prognostic factors, and that BTR was the best predictive factor for recurrence. Conclusions: BTR was a prognostic factor for early HCC and the most predictive factor for intrahepatic distant recurrence and contributing factors for survival. © H.G.E. Update Medical Publishing S.A.

DOI： 10.5754/hge13488

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DOI： 10.1111/hepr.12074

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BAISHIDENG PUBL GRP CO LTD  

AIM: To determine whether fluid injection during radiofrequency ablation (RFA) can increase the coagulation area.
METHODS: Bovine liver (1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base, and the liver was punctured by an expandable electrode. During RFA, 5% glucose; 50% glucose; or saline fluid was infused continuously at a rate of 1.0 mL/min through the infusion line connected to the infusion port. The area and volume of the thermocoagulated region of bovine liver were determined after RFA. The Joule heat generated was determined from the temporal change in output during the RFA experiment.
RESULTS: No liquid infusion was 17.3 +/- 1.6 mL, similar to the volume of a 3-cm diameter sphere (14.1 mL). Mean thermocoagulated volume was significantly larger with continuous infusion of saline (29.3 +/- 3.3 mL) than with 5% glucose (21.4 +/- 2.2 mL), 50% glucose (16.5 +/- 0.9 mL) or no liquid infusion (17.3 +/- 1.6 mL). The ablated volume for RFA with saline was approximately 1.7-times greater than for RFA with no liquid infusion, representing a significant difference between these two conditions. Total Joule heat generated during RFA was highest with saline, and lowest with 50% glucose.
CONCLUSION: RFA with continuous saline infusion achieves a large ablation zone, and may help inhibit local recurrence by obtaining sufficient ablation margins. RFA during continuous saline infusion can extend ablation margins, and may be prevent local recurrence. (C) 2013 Baishideng. All rights reserved.

DOI： 10.3748/wjg.v19.i8.1278

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Objective Postsplenectomy sepsis (PSS) and overwhelming postsplenectomy infection (OPSI) following splenectomy or the development of hyposplenism are associated with a high mortality rate. The presence of Howell-Jolly bodies (HJBs) in peripheral erythrocytes is attracting attention as a parameter of hyposplenism. To date, whether HJBs appear following partial splenic embolization (PSE) has not been investigated. Therefore, we examined the prevalence of HJBs in patients who have undergone PSE.
Methods Whether HJBs were present in 95 patients who underwent PSE between November 2007 and August 2012 was assessed.
Results No serious complications occurred due to PSE; however, 17 of the 95 patients (17.89%) exhibited HJBs during the follow-up. The residual spleen volume and splenic infarction rate did not differ significantly compared to those observed in the HJB-negative group.
Conclusion With the recent increase in the use of autoanalyzers, the opportunities to perform microscopic examinations have been decreasing. Therefore, the presence of HJBs, which can only be confirmed visually, may be overlooked, and the clinical significance of these bodies tends to be disregarded. However, the presence of HJBs is associated with a risk of PSS and OPSI due to hyposplenism. Because HJBs are common in the peripheral erythrocytes of patients who have undergone PSE, irrespective of the residual spleen volume or splenic infarction rate, the presence or absence of HJBs should be assessed visually. In HJB-positive patients, preventing serious infections, for example, by administering the pneumococcal vaccine, is important.

DOI： 10.2169/internalmedicine.52.0407

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Introduction Rice cake is a traditional but very popular food in Asia including Japan and has never been known as a cause of ileus. Rice cake is now becoming widespread in the United States and European countries along with other Japanese foods. We may encounter rice cake ileus all over the world. This study was aimed at characterizing the rice cake ileus.
Methods We consecutively encountered 14 patients with rice cake ileus from April 2003 to October 2010 in our hospital. All of the characteristics of the cases were reviewed and analyzed.
Results All patients had ingested rice cake by swallowing without chewing. It has most frequently occurred in January (57.1%). The main symptoms were abdominal colicky pain (100%) and nausea (85.7%) and physical findings included abdominal tenderness (100%) and muscular defense (28.6%). All patients improved by conservative therapy including fluid supply (100%), naso-gastric tube (28.6%) and long tube (28.6%) insertion. No patient needed emergency open surgery.
Conclusion Rice cake ileus which is caused by swallowing the rice cake without chewing, frequently occurs in January, has previous history of abdominal surgery and shows high density intestinal contents on CT and only needs conservative therapy. Globalism in food culture may provide a new disease entity. Therefore, we should be aware of this type of ileus and be prepared to manage it appropriately.

DOI： 10.2169/internalmedicine.50.6152

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(株)アークメディア  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：Japan Society of Hepatology  

We reported a case of neuroendocrine tumor of the liver. A 57-years-old female was pointed out to have a liver tumor. At first, she was initially diagnosed as hemangioma of liver by CT and MRI. The serum was negative for hepatitis B surface antigen, core antigen, and for hepatitis C virus antibody. Tumor makers such as a- fetoprotein (AFP), protein induced by vitamin K absence or antagonist (PIVKA-II) were negative. The tumor size was enlarged by follow-up abdominal ultrasonography (US) findings after six months. US demonstrated irregular high echoic nodule. Plain CT showed a low density. In dynamic examination, the tumor showed marginal enhancement. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI showed low intensity area on hepatobiliary phase. Single-level dynamic CTA showed ring enhancement. Esophagogastro- duodenoscopy, colonoscopy and positron emission tomography (PET) CT did not reveal other malignancies. Tumor biopsy was performed for definitive diagnosis. The tumor was diagnosed pathologically as a neuroendocrine tumor. After diagnosis, partial hepatic resection was performed. She has been followed in the clinic without evidence of recurrence. Primary hepatic neuroendocrine tumor is rare, and so we report this case which appears to be of primary hepatic neuroendocrine tumor.

DOI： 10.2957/kanzo.55.690

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Language：Japanese   Publisher：新潟医学会  

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Language：Japanese   Publisher：The Japan Society of Hepatology  

Here, we report a case of radiofrequency ablation therapy (RFA) for liver metastases from colon cancer in a patient with deep-brain stimulation for Parkinson's disease. A 73 -year-old man was admitted to our hospital for the metastases in the liver from rectal cancer. He was inserted into the anterior chest
(DBS Deep Brain Stimulators) deep brain stimulation device for Parkinson's disease in 2006. He underwent low anterior resection for rectal cancer in our hospital. Eighteen months later, he was pointed out metastatic lesions at segment 4-8 in liver by abdominal computed tomography. We performed RFA under stopping deep-brain stimulation. During RFA, he had are no tremor of Parkinson disease. Electromagnetic interference was not observed during and after RFA. With careful management, RFA is potentially useful treatment strategy for patients with deep-brain stimulation for Parkinson's disease. © 2013 The Japan Society of Hepatology.

DOI： 10.2957/kanzo.54.486

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Language：Japanese   Publisher：The Japan Society for Portal Hypertension  

血小板減少を伴う肝細胞癌に対し，部分的脾動脈塞栓術（Partial splenic arterial embolization: PSE）と肝動脈化学塞栓療法（transcatheter arterial chemoembolization: TACE）を同時施行した症例の検討を行った．対象は血小板減少を伴う肝細胞癌症例に対し，TACEと同時にPSEを施行した術前血小板数5万/&amp;mu;l以下の23症例である．平均脾梗塞率は55.19％であり，術前平均血小板値は4.41万/&amp;mu;lで，術後平均血小板値は7.58万/&amp;mu;lに上昇した．血小板の上昇により，RFAを含めた穿刺治療は可能となった．血小板減少のためにTACE，RFAが困難な進行肝細胞癌症例に対し，PSEを同時併用することで，血小板を増加させ，治療を継続することができ，集学的治療の一環としてのPSEの有用性が示唆された．

DOI： 10.11423/jsph.19.179

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We report herein on two cases of ischemic heart disease induced by acute gastrointestinal hemorrhage during antiplatelet therapy. CASE 1: A 64-year-old male was referred to our emergency room (ER) with hematemesis and melena while taking clopidogrel after a cerebral infarction. His epigastric discomfort continued even after endoscopic hemostasis for a bleeding gastric ulcer. Finally, he was diagnosed as having acute myocardial infarction following additional examinations. Cardiac computed tomography and coronary angiography showed severe stenosis of the left anterior descending branch and right coronary artery. Percutaneous coronary intervention was carried out, and thereafter no relapse has been encountered under administration of clopidogrel and a proton pump inhibitor. CASE 2: An 80-year-old male who was given low-dose aspirin for the secondary prevention of cerebral infarction, came to the ER with bloody stools. He was severely anemic and simultaneously complained of angina. Myocardial scintigraphy indicated myocardial ischemia in the antero-septal wall. Angina rapidly disappeared after the improvement in his anemia by blood transfusion. He currently remains well under the good control of only his blood pressure. Antiplatelet therapy is being widely used for atherosclerotic diseases. Thus, gastrointestinal hemorrhage has become the most important adverse event during antiplatelet therapy. Preventive antacid therapy or eradication of Helicobacter pylori before administration is thus recommended. In addition, rapidly advancing anemia is a risk-factor for provoking ischemic heart disease. In conclusion, whenever we see a patient with gastrointestinal hemorrhage under antiplatelet therapy, cardiovascular risk has also to be taken into consideration.

DOI： 10.11231/jaem.32.657

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