A Case of Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Refractory to Epirubicin That Showed Marked Decrease in Tumor Markers after Transcatheter Arterial Infusion with Miriplatin

Miriplatin, a cisplatin derivative with a high affinity for iodized ethyl esters of fatty acids from poppy seed oil, is a novel chemotherapeutic agent designed for use in the transarterial treatment of hepatocellular carcinoma (HCC). Here, we describe transcatheter arterial infusion (TAI) using miriplatin to treat a case of advanced HCC with portal vein tumor thrombus (PVTT) refractory to TAI with epirubicin. A 66-year-old man with advanced hepatitis C virus-related HCC with PVTT in the right lobe of the liver was treated with TAI with epirubicin suspended in iodized oil; however, tumor marker levels (alpha-fetoprotein and des-gamma-carboxy protein) did not decrease. Next, he was treated twice with TAI with miriplatin suspended in iodized oil. The tumor marker levels markedly decreased to a nearly normal range and the size of the main tumor was markedly reduced according to dynamic computed tomography. No serious adverse events occurred during the course of treatment with TAI and miriplatin. Therefore, we suggest that TAI with miriplatin is a safe and effective treatment option for advanced HCCs refractory to TAI with epirubicin

The effect of pegylated interferon-alpha2b and ribavirin combination therapy for chronic hepatitis C infection in elderly patients

<p>Abstract</p> <p>Background</p> <p>The clearance of hepatitis C virus infection by interferon therapy significantly reduces the incidence of hepatocellular carcinoma and death in elderly chronic hepatitis patients. However, there are few reports concerning the efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients. The aims of the present study were to examine the effect and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in 427 patients with chronic hepatitis C infection. We compared the rates of sustained virological response--defined as the absence of detectable hepatitis C virus in serum 24 weeks after the treatment ended--and the treatment discontinuation rate between 319 younger patients aged < 65 years and 108 elderly patients aged ≥ 65 years. We also examined the factors contributing to a sustained virological response.</p> <p>Results</p> <p>There was no significant difference in the sustained virological response rate between younger patients and elderly patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7% (35/86) for genotype 1; <it>P </it>= 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype 2; <it>P </it>= 0.703, respectively). There was also no significant difference in the treatment discontinuation rate between the two age groups (10.3% (33/319) and 13.9% (15/108), respectively; <it>P </it>= 0.378). There were no serious adverse events requiring hospitalization. The factors contributing significantly to a sustained virological response in elderly patients were gender, hepatitis C virus genotype, platelet count, and the presence of a rapid or early virological response (undetectable hepatitis C virus in serum at weeks 4 or 12 of treatment, respectively). However, upon multivariate analysis, the presence of an early virological response was the only significant factor (odds ratio: 0.115, 95% confidence interval: 0.040- 0.330, <it>P </it>< 0.001).</p> <p>Conclusions</p> <p>The efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients are not always inferior to those in younger patients. Obtaining an early virological response may be essential to achieve a sustained virological response in elderly patients with chronic hepatitis C infection.</p

Investigation of Patients with Oral Trauma Treated at University Hospital Department of Pedodontics－Comparison with Examination and Treatment Conditions 17 years Prior

我々は，2007年4月から2010年3月までの3年間に本院小児歯科へ口腔外傷を主訴として受診した0歳から15歳の233人（男154人，女79人）を対象として調査を行い，17年前に行った同様の調査報告と比較検討を行った。1．受傷時年齢は幼児期後期が最も高いが，17年前の45．5％から38．2％と減少傾向を示した。学童期後期についても17年前の15．6％から10．7％へと減少傾向を示した。一方，幼児期前期は17年前の13.8％から25.3％と増加傾向が認められた。2．受傷原因は，17年前は打撲による受傷が35.9％と最も多く，次いで転倒25.7％，親の目が届かない原因不明の受傷が24.6％の順で多かったが，今回は転倒による受傷が55.4％と最も多く，次いで衝突18.9％の順であった。3．受傷の既往歴があった小児はほぼ変わらなかったが，受傷の既往が不明である割合は17年前の22.8％からO.4％へと減少傾向を示した。4. 受傷部位については17年前とほぼ同様で，上顎前歯部の受傷が約7割を占めた。5. 受傷様式では，17年前と比べ軟組織の裂傷を合併するものが多い傾向を示した。6. 来院までに何らかの処置を受けた者は，17年前も現在も約15％とほぼ同じ割合であった。初診時の処置は経過観察が多いが，今回は整復固定といった機能維持や修復による審美回復の処置が増加傾向を示した

Comparison of percutaneous radiofrequency thermal ablation and surgical resection for small hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>The purpose of this investigation was to compare the outcome of percutaneous radiofrequency thermal ablation therapy (PRFA) with surgical resection (SR) in the treatment of single and small hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>We conducted a retrospective cohort study on 231 treatment naive patients with a single HCC ≤ 3 cm who had received either curative PRFA (162 patients) or curative SR (69 patients). All patients were regularly followed up after treatment at our department with blood and radiologic tests.</p> <p>Results</p> <p>The 1-, 3- and 5-year overall survival rates after PRFA and SR were 95.4%, 79.6% and 63.1%, respectively in the PRFA group and 100%, 81.4% and 74.6%, respectively in the SR group. The corresponding recurrence free survival rates at 1, 3 and 5 years after PRFA and SR were 82.0%, 38.3% and 18.0%, respectively in the PRFA group and 86.0%, 47.2% and 26.0%, respectively in the SR group. In terms of overall survival and recurrence free survival, there were no significant differences between these two groups. In comparison of PRFA group patients with liver cirrhosis (LC) (n = 127) and SR group patients with LC (n = 50) and in comparison of PRFA group patients without LC (n = 35) and SR group patients without LC (n = 19), there were also no significant differences between two groups in terms of overall survival and recurrence free survival. In the multivariate analysis of the risk factors contributing to overall survival, serum albumin level was the sole significant factor. In the multivariate analysis of the risk factors contributing to recurrence free survival, presence of LC was the sole significant factor. The rate of serious adverse events in the SR group was significantly higher than that in the PRFA group (P = 0.023). Hospitalization length in the SR group was significantly longer than in the PRFA group (P = 0.013).</p> <p>Conclusions</p> <p>PRFA is as effective as SR in the treatment of single and small HCC, and is less invasive than SR. Therefore, PRFA could be a first choice for the treatment of single and small HCC.</p

B型肝炎ウイルス潜伏感染者からのウイルス再活性化病態は野生株またはG1896A変異株の均質な感染に特徴づけられる

京都大学0048新制・課程博士博士(医学)甲第19593号医博第4100号新制||医||1014(附属図書館)32629京都大学大学院医学研究科医学専攻(主査)教授 松岡 雅雄, 教授 朝長 啓造, 教授 西渕 光昭学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Expansion of viral variants associated with immune escape and impaired virion secretion in patients with HBV reactivation after resolved infection

HBV reactivation could be induced under immunosuppressive conditions in patients with resolved infection. This study aimed to clarify the viral factors associated with the pathogenesis of HBV reactivation in association with the immunosuppressive status. Whole HBV genome sequences were determined from the sera of 24 patients with HBV reactivation, including 8 cases under strong immunosuppression mediated by hematopoietic stem cell transplantation (HSCT) and 16 cases without HSCT. Ultra-deep sequencing revealed that the prevalence of genotype B and the ratio of non-synonymous to synonymous evolutionary changes in the surface (S) gene were significantly higher in non-HSCT cases than in patients with HSCT. Those non-synonymous variants included immune escape (6/16 cases) and MHC class II-restricted T-cell epitope variants (6/16 cases). Furthermore, reactivated HBV in 11 of 16 (69%) non-HSCT cases possessed substitutions associated with impaired virion secretion, including E2G, L77R, L98V, T118K, and Q129H in the S region, and M1I/V in the PreS2 region. In conclusion, virologic features of reactivated HBV clones differed depending on the intensity of the immunosuppressive condition. HBV reactivation triggered by immunosuppressive conditions, especially those without HSCT, was characterized by the expansion of variants associated with immune escape, MHC class II-restricted T-cell epitope alterations, and/or impaired virion secretion

Leptin receptor somatic mutations are frequent in HCV-infected cirrhotic liver and associated with hepatocellular carcinoma.

[Background & Aims]Hepatocellular carcinoma develops in patients with chronic hepatitis or cirrhosis via a stepwise accumulation of various genetic alterations. To explore the genetic basis of development of hepatocellular carcinoma in hepatitis C virus (HCV)-associated chronic liver disease, we evaluated genetic variants that accumulate in nontumor cirrhotic liver. [Methods]We determined the whole exome sequences of 7 tumors and background cirrhotic liver tissues from 4 patients with HCV infection. We then performed additional sequencing of selected exomes of mutated genes, identified by whole exome sequencing, and of representative tumor-related genes on samples from 22 cirrhotic livers with HCV infection. We performed in vitro and in vivo functional studies for one of the mutated genes. [Results]Whole exome sequencing showed that somatic mutations accumulated in various genes in HCV-infected cirrhotic liver tissues. Among the identified genes, the leptin receptor gene (LEPR) was one of the most frequently mutated in tumor and nontumor cirrhotic liver tissue. Selected exome sequencing analyses detected LEPR mutations in 12 of 22 (54.5%) nontumorous cirrhotic livers. In vitro, 4 of 7 (57.1%) LEPRmutations found in cirrhotic livers reduced phosphorylation of STAT3 to inactivate LEPR-mediated signaling. Moreover, 40% of Lepr-deficient (C57BL/KsJ-db/db) mice developed liver tumors after administration of thioacetamide compared with none of the control mice. [Conclusions]Based on analysis of liver tissue samples from patients, somatic mutations accumulate in LEPR in cirrhotic liver with chronic HCV infection. These mutations could disrupt LEPR signaling and increase susceptibility to hepatocarcinogenesis