C型肝炎SVR後の肝病変改善度の経時的解析

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 國土 典宏, 東京大学准教授 池田 均, 東京大学准教授 高橋 聡, 東京大学講師 渡辺 昌文, 東京大学准教授 桐生 茂University of Tokyo(東京大学

Temporal subtraction CT with nonrigid image registration improves detection of bone metastases by radiologists: results of a large-scale observer study

To determine whether temporal subtraction (TS) CT obtained with non-rigid image registration improves detection of various bone metastases during serial clinical follow-up examinations by numerous radiologists. Six board-certified radiologists retrospectively scrutinized CT images for patients with history of malignancy sequentially. These radiologists selected 50 positive and 50 negative subjects with and without bone metastases, respectively. Furthermore, for each subject, they selected a pair of previous and current CT images satisfying predefined criteria by consensus. Previous images were non-rigidly transformed to match current images and subtracted from current images to automatically generate TS images. Subsequently, 18 radiologists independently interpreted the 100 CT image pairs to identify bone metastases, both without and with TS images, with each interpretation separated from the other by an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Compared with interpretation without TS images, interpretation with TS images was associated with a significantly higher mean figure of merit (0.710 vs. 0.658; JAFROC analysis, P = 0.0027). Mean sensitivity at lesion-based was significantly higher for interpretation with TS compared with that without TS (46.1% vs. 33.9%; P = 0.003). Mean false positive count per subject was also significantly higher for interpretation with TS than for that without TS (0.28 vs. 0.15; P < 0.001). At the subject-based, mean sensitivity was significantly higher for interpretation with TS images than that without TS images (73.2% vs. 65.4%; P = 0.003). There was no significant difference in mean specificity (0.93 vs. 0.95; P = 0.083). TS significantly improved overall performance in the detection of various bone metastases

Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma

Background & AimsObesity defined by body mass index (BMI) significantly increases the risk of hepatocellular carcinoma (HCC). In contrast, not only obesity but also underweight is associated with poor prognosis in patients with HCC. Differences in body composition rather than BMI were suggested to be true determinants of prognosis. However, this hypothesis has not been demonstrated conclusively.MethodsWe measured skeletal muscle index (SMI), mean muscle attenuation (MA), visceral adipose tissue index, subcutaneous adipose tissue index, and visceral to subcutaneous adipose tissue area ratios (VSR) via computed tomography in a large-scale retrospective cohort of 1257 patients with different stages of HCC, and comprehensively analyzed the impact of body composition on the prognoses.ResultsAmong five body composition components, low SMI (called sarcopenia), low MA (called intramuscular fat [IMF] deposition), and high VSR (called visceral adiposity) were significantly associated with mortality, independently of cancer stage or Child-Pugh class. A multivariate analysis revealed that sarcopenia (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.18–1.96; p=0.001), IMF deposition (HR, 1.34; 95% CI, 1.05–1.71; p=0.020), and visceral adiposity (HR, 1.35; 95% CI, 1.09–1.66; p=0.005) but not BMI were significant predictors of survival. The prevalence of poor prognostic body composition components was significantly higher in underweight and obese patients than in normal weight patients.ConclusionsSarcopenia, IMF deposition, and visceral adiposity independently predict mortality in patients with HCC. Body composition rather than BMI is a major determinant of prognosis in patients with HCC

Identification of hydroxychavicol and its dimers, the lipase inhibitors contained in the Indonesian spice, Eugenia polyantha

Inhibition of pancreatic lipase is effective for a prevention of obesity. Eugenia polyantha is a tropical tree whose leaves are known as a spice and also as an ingredient for Jamu, the traditional medicine of Indonesia. We found inhibitory activity against pancreatic lipase in the extract of E. polyantha leaves. Purification of the active principals resulted in isolation of hydroxychavicol, and two structurally new dimers. All of the isolated compounds showed inhibitory activity against the porcine pancreatic lipase and high content of hydroxychavicol (1.83 wt%) indicated this compound to be responsible for the majority of inhibitory activity of E. polyantha extract. Furthermore, hydroxychavicol is reported to possess anti-carcinogenic, anti-oxidant, anti-microbial and anti-inflammatory activity which is related to traditional usage of this plant. These results offer this plant as an attractive material for treating various health problems including obesity

Substrate-like water soluble lipase inhibitors from Filipendula kamtschatica

Filipendula kamtschatica is a plant utilized as a traditional medicine by Ainu people in Japan, but its chemical constituents are not much studied. Pancreatic lipase inhibitors are a promising tool for the treatment of obesity. We searched for natural lipase inhibitors from F. kamtschatica and two new compounds were isolated along with the known flavonoid glycoside. The structure elucidation of new compounds revealed these two to be 2-O-caffeoyl-4-O-galloyl-L-threonic acid and 3-O-caffeoyl-4-O-galloyl-L-threonic acid, which can be recognized as a pancreatic lipase's substrate-like structure. The isolated compounds all showed an inhibitory activity against porcine pancreatic lipase and one of the isomer, 3-O-caffeoyl-4-O-galloyl-L-threonic acid, possessed the most potent activity with IC50 value showing an order lower value compared to others. The substrate-like structure of the new compounds seemed to be important for their activity