Feasibility and mid- to long-term results of endovascular treatment for portal vein thrombosis after living-donor liver transplantation

PURPOSEWe aimed to evaluate mid- to long-term results of endovascular treatment for portal vein thrombosis (PVT) after living-donor liver transplantation (LDLT).METHODSThirty cases (14 males, 16 females; age range, 0.67–65 years) who underwent endovascular treatment including thrombolysis, angioplasty, stent placement, and/or collateral embolization for PVT after LDLT from 2001 to 2017 were retrospectively reviewed. Clinical and procedural data were collected and analyzed regarding the patency of the PVT site at the last follow-up date (PVT-free persistency) using Log-rank test. Results were considered statistically significant at P < 0.05.RESULTSMedian follow-up was 120 months. The technical success rate was 80% (n=24). Patency rates at 1 week and 1, 3, 6, 12, 36, and 60 months were 73%, 59%, 55%, 51%, 51%, 51%, and 51% for primary patency and 80%, 70%, 66%, 66%, 66%, 61%, and 61% for assisted patency after secondary endovascular treatment. PVT-free persistency rates regarding the subgroups were as follows: children under 12 years vs. adults, 50% vs. 68% (P = 0.42); acute vs. nonacute, 76% vs. 46% (P = 0.10); localized vs. extensive, 90% vs. 50% (P = 0.035); transileocolic approach vs. percutaneous-transhepatic approach, 71% vs. 54% (P = 0.39); and thrombolysis-based treatment vs. non-thrombolysis-based treatment, 71% vs. 44% (P = 0.12), respectively. Among technically successful cases, PVT-free persistency rate was 94% for those with hepatopetal flow in the peripheral portal vein vs. 17% for those without hepatopetal flow (P < 0.001). The only major complication occurring was pleural hemorrhage (n=1). Minor complications (i.e., fever) occurred in 18 patients (60%).CONCLUSIONIn conclusion, mid- to long-term portal patency following endovascular treatment was approximately 50%–60% in PVT patients after LDLT. PVT site patency over three months after the first endovascular treatment, localized PVT, and hepatopetal flow in the peripheral portal vein were identified as key prognostic factors for mid- to long-term portal patency

Imaging findings of granulocyte colony-stimulating factor-producing tumors: a case series and review of the literature

Granulocyte colony-stimulating factor (G-CSF)-producing tumors have an aggressive clinical course. Here, we report five cases of G-CSF-producing tumors and review the literature, focusing on imaging findings related to tumor-produced G-CSF. In addition to our cases, we identified 30 previous reports of G-CSF-producing tumors on which 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT, bone scintigraphy, or evaluation of bone marrow MR findings was performed. White blood cell count, serum C-reactive protein, and serum interleukin-6 were elevated in all cases for which these parameters were measured. G-CSF-producing tumors presented large necrotic masses (mean diameter 83.2 mm, range 17–195 mm) with marked FDG uptake (mean maximum standardized uptake value: 20.09). Diffuse FDG uptake into the bone marrow was shown in 28 of the 31 cases in which FDG-PET/CT was performed. The signal intensity of bone marrow suggested marrow reconversion in all seven MRI-assessable cases. Bone scintigraphy demonstrated no significant uptake, except in two cases with bone metastases. Splenic FDG uptake was increased in 8 of 10 cases in which it was evaluated. These imaging findings may reflect the effects of tumor-produced G-CSF. The presence of G-CSF-producing tumors should be considered in patients with cancer who show these imaging findings and marked inflammatory features of unknown origin

Concentration distributions of dissolved Sb(III) and Sb(V) species in size-classified inhalable airborne particulate matter † ‡

In order to obtain more accurate assessments of global contamination by potentially toxic antimony (Sb) and the toxicological effects of Sb on ecosystems, speciation analysis of inorganic Sb species in size-classified airborne particulate matter (APM) was performed. Thirteen fractions of size-classified APM (with aerodynamic diameters: Dp &lt;0. 06, 0.06-0.12, 0.12-0.20, 0.20-0.30, 0.30-0.50, 0.50-0.70, 0.70-1.2, 1.2-2.1, 2.1-3.6, 3.6-5.2, 5.2-7.9, 7.9-11, and &gt;11 mm) were collected on a filter by using a multistage cascade impactor sampler. Speciation analysis of inorganic Sb(III) and Sb(V) was performed by using HPLC-ICP-MS. Portions of sample-loaded filters were sonicated with 30 mmol l À1 citric acid under purified N 2 in order to avoid the oxidation of Sb(III) to Sb(V) during the extraction process. Sb(III) and Sb(V) were separated on a PRP-X100 anion exchange column using a mixture of 10 mmol l À1 EDTA and 1 mmol l À1 phthalic acid (pH 4.5) as a mobile phase, and they were subsequently detected by ICP-MS. The size distributions of the total Sb concentration exhibit a bimodal profile in which peaks corresponded to fine (0.50-0.70 mm) and coarse (3.6-5.2 mm) fractions. The speciation analysis demonstrated for the first time that Sb(III), which is the more toxic form, is dominated by coarse fractions whereas Sb(V) is distributed in both the fine and coarse fractions. The presented high-resolution size distributions of inorganic Sb species will provide helpful information in discussing both health risks by inhalation exposure to Sb and the extent of the effects of emission sources by atmospheric circulation

Correlation between HIV disease and lipid metabolism in antiretroviral-naïve HIV-infected patients in Japan

Antiretroviral therapy alters lipid metabolism in HIV-infected patients. However, interpreting the impact of HIV infection on lipid metabolism is difficult because of various associated factors, including antiretroviral drugs and demographic characteristics. A few studies have associated HIV infection with lipid metabolism in antiretroviral-naïve HIV-infected patients. Because there were no data in this regard from Japan, the present study examined the impact of HIV infection, as well as demographic and clinical features, on lipid metabolism in antiretroviral-naïve HIV-infected patients in Japan. We performed a cross-sectional study to examine the impact of HIV disease, demographic and clinical characteristics on lipid metabolism among 168 HIV-infected Japanese men who were antiretroviral naïve and who did not have hemophilia, including patients who took medication for dyslipidemia. The mean age of the patients was 45.7 years; 0.6% of the patients took medication to dyslipidemia. The mean CD4 lymphocyte count was 289/μL, the mean baseline log10 HIV viral load was 4.2 HIV-1 RNA copies/mL, and 22% of the patients had a history of AIDS-defining events. A higher HDL-C concentration was associated with a higher CD4 lymphocyte count (p = 0.043). Also, a higher LDL-C concentration was associated with a higher CD4 lymphocyte count (p = 0.003). Infection with HIV was associated with dyslipidemia in antiretroviral-naïve patients. More advanced HIV disease was associated with less favorable lipid homeostatic profiles. These results are similar to findings from other countries

Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations

Background & Aims Biliary tract cancers (BTCs) are clinically and pathologically heterogeneous and respond poorly to treatment. Genomic profiling can offer a clearer understanding of their carcinogenesis, classification and treatment strategy. We performed large-scale genome sequencing analyses on BTCs to investigate their somatic and germline driver events and characterize their genomic landscape. Methods We analyzed 412 BTC samples from Japanese and Italian populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing (WGS), and a further 266 samples by targeted sequencing. The subtypes were 136 intrahepatic cholangiocarcinomas (ICCs), 101 distal cholangiocarcinomas (DCCs), 109 peri-hilar type cholangiocarcinomas (PHCs), and 66 gallbladder or cystic duct cancers (GBCs/CDCs). We identified somatic alterations and searched for driver genes in BTCs, finding pathogenic germline variants of cancer-predisposing genes. We predicted cell-of-origin for BTCs by combining somatic mutation patterns and epigenetic features. Results We identified 32 significantly and commonly mutated genes including TP53 , KRAS , SMAD4 , NF1 , ARID1A , PBRM1 , and ATR , some of which negatively affected patient prognosis. A novel deletion of MUC17 at 7q22.1 affected patient prognosis. Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes such as BRCA1 , BRCA2 , RAD51D , MLH1 , or MSH2 were detected in 11% (16/146) of BTC patients. Conclusions BTCs have distinct genetic features including somatic events and germline predisposition. These findings could be useful to establish treatment and diagnostic strategies for BTCs based on genetic information. Lay summary We here analyzed genomic features of 412 BTC samples from Japanese and Italian populations. A total of 32 significantly and commonly mutated genes were identified, some of which negatively affected patient prognosis, including a novel deletion of MUC17 at 7q22.1 . Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes were detected in 11% of patients with BTC. BTCs have distinct genetic features including somatic events and germline predisposition

トクシマケン イシカイ トウニョウビョウ タイサクハン ダイ1ジ ダイ2ジ カツドウ ノ セイカ

Objective : The effectiveness of diabetes prevention programs for the general population in Tokushima Prefecture was investigated. The programs were designed by Tokushima Medical Association’ s（TMA’s）Steering Committee for Diabetes Prevention. Research design and methods : The committee promoted diabetes prevention by disseminating educational messages on diabetes to the general public and medical care providers, and establishing a referral system among public health centers and medical institutes throughout Tokushima Prefecture during the period from ２００４ to ２００９. The outcome of these activities were evaluated by analyzing data from the Prefectural Health and Nutrition Survey in Tokushima conducted in１９９７（n＝ ９９８）,２００３ （n＝１００８） and ２０１０ （n＝１１３０）, and then comparing these results with those of the national survey at the corresponding times. Results : The percentage of subjects with glucose intolerance at the time of initiation of the prevention program in Tokushima tended to increase from １９９７ to ２００３, but was slightly decreased in ２０１０, although the differences were not statistically significant. However, the percentage of subjects with glucose intolerance was significantly increased throughout Japan during the same period. Obesity parameters, physical activity evaluated by the number of steps and the average total energy intake changed favorably in parallel with changes in the prevalence of diabetes during the study period in Tokushima. Conclusion : The diabetes prevention programs initiated by the TMA’s committee may be useful in ameliorating the situation of diabetes in Tokushima Prefecture

Immunohistochemical Profile for Unknown Primary Adenocarcinoma

BACKGROUND: Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed. METHODOLOGY/PRINCIPAL FINDINGS: We developed an algorithm based on primary known adenocarcinoma for testing sensitivity and specificity. Formalin-fixed paraffin-embedded tissue samples from 71 patients of unfavorable subsets of unknown primary adenocarcinoma were obtained. We examined 15 molecular markers using the algorithm incorporating these IPs and classified the tumours into 9 subsets based on the primary tumour site. The sensitivity and specificity of this algorithm were 80.3% and 97.6%, respectively. Apparent primary sites were lung in 17 patients, digestive organs in 13, gynecological organs in 9, prostate in 7, liver or kidney in 6, breast in 4, urothelial organ in 2, biliary tract and pancreatic profile in none, and unclassified in 13. The response rate to chemotherapy was highest for the gynecological IPs. Patients with gynecological or lung cancer IPs had longer median progression-free survival than those with others: 11.2 months for gynecological IPs (p<0.001) and 6.8 months for lung IPs (p = 0.05). Lung, digestive, prostate, and gynecological profiles were associated with significantly longer median survival time than the other profiles. Multivariate analysis confirmed that the IPs were independent prognostic factors for survival. CONCLUSIONS/SIGNIFICANCE: The IPs identified in this study can be used to further stratify patient prognosis for unfavorable subsets of unknown primary adenocarcinoma

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

小肝転移の検出に対する単極性拡散強調画像と双極性拡散強調画像の比較

京都大学0048新制・論文博士博士(医学)乙第12889号論医博第2089号新制||医||1007(附属図書館)31643(主査)教授 福山 秀直, 教授 千葉 勉, 教授 平岡 眞寛学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDFA

Biliary peritonitis after radiofrequency ablation diagnosed by gadoxetic acid-enhanced MR imaging.

This study describes the first case of biliary peritonitis after radiofrequency ablation diagnosed by magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), a hepatocyte-specific MR imaging contrast agent. The image acquired 300 minutes after the administration of Gd-EOB-DTPA was useful to make a definite diagnosis and to identify the pathway of bile leakage. It is important to decide on the acquisition timing with consideration of the predicted location of bile duct injury