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

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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Pure abdominal laparoscopic approach versus thoraco-abdominal laparoscopic approach: What is the best technique for liver resection in segment 7 and segment 8? An answer from the Institut Mutualiste Montsouris experience with short- and long-term outcome evaluation

Background: Lesions in segments 7 and 8 are a challenge during standard laparoscopic liver resection. The addition of transthoracic trocars could be useful in the standard abdominal approach for laparoscopic liver resection. We report our experience with a thoraco-abdominal laparoscopic combined approach for liver resection with the aim of comparing short- and long-term outcomes. Methods: We reviewed 1,003 laparoscopic liver resections in a prospectively maintained, single-institution database. We compared patient outcomes intraoperatively and postoperatively. We analyzed the long-term outcomes of the colorectal liver metastasis subgroup. Propensity score matching 1:1 was performed based on the following variables: age, American Society of Anesthesiologists, body mass index, previous abdominal surgery, multiple or single liver resection, lesion &gt;50 mm or &lt;50 mm, presence of solitary or multiple lesions, T stage, and N stage. Results: The standard abdominal approach was used in 110 laparoscopic liver resections, and the thoraco-abdominal laparoscopic combined approach was used in 62 laparoscopic liver resections. The thoraco-abdominal laparoscopic combined approach was associated with better intraoperative results (less blood loss and no need for conversion to open surgery). The R1s rate for segmentectomy 7 and 8 was lower in the thoraco-abdominal laparoscopic combined approach in the entire group and in the colorectal liver metastasis subgroup. In the colorectal liver metastasis subgroup, the 3- and 5-year overall survival was 90% and 80% in the thoraco-abdominal laparoscopic combined approach group and 76% and 52% in the standard abdominal approach group, respectively (P&nbsp;= .02). In univariate and multivariate analysis, the thoraco-abdominal laparoscopic combined approach was a significant factor that positively affected disease-free survival and overall survival. Conclusion: The thoraco-abdominal laparoscopic combined approach in laparoscopic liver resection in segments 7 and 8 is safe and feasible, and it has demonstrated better oncologic outcomes than the pure abdominal approach, especially in segmentectomy