蛍光イメージングを用いた肝静脈閉塞領域の肝機能評価と肝切除・肝移植への応用

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 渡邉 聡明, 東京大学教授 大友 邦, 東京大学講師 山下 裕玄, 東京大学講師 石原 聡一郎, 東京大学教授 小池 和彦University of Tokyo(東京大学

Targeted Exome-Based Predictors of Patterns of Progression of Colorectal Liver Metastasis After Percutaneous Thermal Ablation

BACKGROUND: Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood. METHODS: In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM. RESULTS: A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFβ pathway were associated with increased risk of development of new intrahepatic tumours (hazard ratio [HR], 2.75, 95% confidence interval [95% CI] 1.39-5.45, P = 0.004); and alterations in the Wnt pathway were associated with increased probability of receiving salvage LRT for any intrahepatic progression (HR, 5.8, 95% CI 1.94-19.5, P = 0.003). CONCLUSIONS: Our findings indicate that genomic alterations in cancer-related signalling pathways can predict different progression patterns and the likelihood of receiving salvage LRT following percutaneous thermal ablation of CLM

Living donor liver transplantation using sensitized lymphocytotoxic crossmatch positive graft

We describe a successful living donor liver transplantation (LDLT) using a lymphocytotoxic crossmatch highly positive graft. A 41-year-old woman with alcoholic liver cirrhosis was referred as a potential candidate for LDLT, and her husband was willing to donate his partial liver. As the T-lymphocytotoxic crossmatch titer was over 10,000×, the patient was first infused with rituximab for preoperative desensitization, and then five rounds of plasmapheresis were performed. After the third plasmapheresis, the lymphocytotoxic crossmatch test was negative. A left liver graft including the caudate lobe was implanted, and anti-CD25 antibody (basiliximab) was administered on postoperative days 1 and 4. The postoperative course was uneventful except for an episode of mild acute cellular rejection on postoperative day 27. Although the impact of a lymphocytotoxic crossmatch-positive liver graft on acute cellular rejection and graft survival in LDLT remains controversial, perioperative desensitization may provide benefits when using a highly sensitized liver graft

Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals

Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci (P<5 × 10–8) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci—TMEM18, TM4SF4, MXD3-LMAN2, PSORS1C1-PSORS1C2, and HNF4A—are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578, is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout

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