大腸癌予後・ 診断バイオマーカーとしての組織中RAD54Bおよび血漿遊離DNA LINE-1の役割

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 瀬戸 泰之, 東京大学講師 保科 克行, 東京大学准教授 平田 康隆, 東京大学准教授 池田 均, 東京大学准教授 藤城 光弘University of Tokyo(東京大学

Catalyst deactivation of a silica-supported bismuth-molybdenum complex oxide and the related complex oxides for the oxidative dehydrogenation of 1-butene to 1,3-butadiene

This study was an examination of the catalyst deactivation of a silica-supported bismuth-molybdenum complex oxide, and that of catalysts used in the absence of bismuth, for the oxidative dehydrogenation of 1-butene. Due to the detection of deactivation, the molar ratio of 1-butene against oxygen in the reactant gas was adjusted to a ratio similar to that used in industrial processes where reaction temperatures average 100 K higher. Regardless of the presence or absence of bismuth in the catalysts, the conversion of 1-butene was decreased by 6 h on-stream. Both the progress of the coking from the inlet to the outlet of the catalyst and the reduction of molybdenum in the catalysts directly contributed to the deactivation. X-ray photoelectron spectrometry revealed that a greater reduction of molybdenum in the near-surface region and a smaller partial pressure of oxygen (P(O2)) in the reactant gas, although the molybdenum on the surface was not reduced at all. This indicated that the lattice oxygen was pumped from the near-surface region to the surface during the reaction and the oxygen-poor conditions of the near-surface region both in the gas and catalyst phases were formed at a smaller P(O2), which resulted in the enhancements of both the reduction of molybdenum and that of coking. Based on the thermogravimetric analysis, the silica-supported bismuth-molybdenum complex oxide used at P(O2) = 4.1 kPa (color of the catalyst = black) was increased in weight while that used at P(O2) = 16.4 kPa (color of the catalyst = gray) showed a weight decrease, which indicated that the weight decrease caused by the reduction in molybdenum in the near-surface region used at 4.1 kPa was greater than the weight increase from the coking. It was concluded that the reduction in molybdenum followed by the coking on the catalyst surface were the main factors in the catalyst deactivation

Multiple Hepatolithiasis Following Hepaticojejunostomy Successfully Treated with Left Hemihepatectomy and Double Hepaticojejunostomy Reconstruction

Surgical intervention for hepatolithiasis following hepaticojejunostomy (HJ) has rarely been reported. Herein, we present a case of post-HJ multiple hepatolithiasis treated with left hemihepatectomy with double HJ reconstruction. A 72-year-old woman who had undergone HJ for iatrogenic bile duct injury developed repeated cholangitis due to complicated hepatolithiasis accompanied by an atrophied left hepatic lobe and HJ stricture. Since endoscopic intervention was unsuccessful, the patient underwent left hemihepatectomy with HJ re-anastomoses of the common hepatic duct and left hepatic duct (double HJ technique). The double HJ technique with hepatectomy can be a useful option for treating complicated hepatolithiasis following HJ

Liquid Water Cloud Measurements Using the Raman Lidar Technique: Current Understanding and Future Research Needs

This paper describes recent work in the Raman lidar liquid water cloud measurement technique. The range-resolved spectral measurements at the National Aeronautics and Space Administration Goddard Space Flight Center indicate that the Raman backscattering spectra measured in and below low clouds agree well with theoretical spectra for vapor and liquid water. The calibration coefficients of the liquid water measurement for the Raman lidar at the Atmospheric Radiation Measurement Program Southern Great Plains site of the U.S. Department of Energy were determined by comparison with the liquid water path (LWP) obtained with Atmospheric Emitted Radiance Interferometer (AERI) and the liquid water content (LWC) obtained with the millimeter wavelength cloud radar and water vapor radiometer (MMCR-WVR) together. These comparisons were used to estimate the Raman liquid water cross-sectional value. The results indicate a bias consistent with an effective liquid water Raman cross-sectional value that is 28%-46% lower than published, which may be explained by the fact that the difference in the detectors' sensitivity has not been accounted for. The LWP of a thin altostratus cloud showed good qualitative agreement between lidar retrievals and AERI. However, the overall ensemble of comparisons of LWP showed considerable scatter, possibly because of the different fields of view of the instruments, the 350-m distance between the instruments, and the horizontal inhomogeneity of the clouds. The LWC profiles for a thick stratus cloud showed agreement between lidar retrievals andMMCR-WVR between the cloud base and 150m above that where the optical depth was less than 3. Areas requiring further research in this technique are discussed

Left Hemihepatectomy for Hepatocellular Carcinoma Following Esophagectomy with Retrosternal Gastric Tube Reconstruction for Esophageal Cancer

Approximately 4% of patients with esophageal cancer develop a second primary malignancy in the upper gastrointestinal trunk. However, hepatectomy following esophagectomy for esophageal cancer has rarely been reported. We report the case of a 70-year-old man who underwent an esophagectomy for esophageal cancer with retrosternal gastric tube reconstruction. Nine years later, he developed hepatocellular carcinoma with tumor thrombus involving the left portal vein, and was successfully treated with left hemihepatectomy. Special attention should be paid to avoiding incidental injury of the gastric tube as well as the right gastroepiploic artery during the hepatectomy

LINE-1 hypomethylation status of circulating cell-free DNA in plasma as a biomarker for colorectal cancer.

Colorectal cancer (CRC) is a serious public health problem and non-invasive biomarkers improving diagnosis or therapy are strongly required. Circulating cell-free DNA (cfDNA) has been a promising target for this purpose. In this study, we evaluated the potential of long interspersed nuclear element-1 (LINE-1) hypomethylation as a blood biomarker for CRC. LINE-1 hypomethylation level in plasma cfDNA in 114 CRC patients was retrospectively examined by absolute quantitative analysis of methylated alleles real-time PCR, and was expressed using LINE-1 hypomethylation index (LHI) [unmethylated copy number/ (methylated copy number + unmethylated copy number)]. Greater LHI values indicated enhanced hypomethylation. In our clinicopathological analysis, CRC patients with large tumors (≥6.0 cm), advanced N stage (≥2), and distant metastasis (M1) had statistically significantly higher cfDNA LHI than other CRC patients, suggesting cfDNA LHI as a disease progression biomarker for CRC. Furthermore, early stage I/II (n = 57) as well as advanced stage III/IV (n =57) CRC patients had significantly higher cfDNA LHI than healthy donors (n=53) [stage I/II: median 0.369 (95% confidence interval, 0.360-0.380) vs. 0.332 (0.325-0.339), P \u3c 0.0001; stage III/IV: 0.372 (0.365-0.388) vs. 0.332 (0.325-0.339), P \u3c 0.0001]. The receiver operating characteristic analysis showed that cfDNA LHI had the detection capacity of CRC with area under the curve(AUC) of 0.79 and 0.83 in stage I/II and stage III/IV CRC patients, respectively. The present study demonstrated for the first time the potential of plasma cfDNA LHI as a novel biomarker for CRC, particularly for early stage detection

Essential anatomy for lateral lymph node dissection

In Western countries, the gold-standard therapeutic strategy for rectal cancer is preoperative chemoradiotherapy (CRT) following total mesorectal excision (TME), without lateral lymph node dissection (LLND). However, preoperative CRT has recently been reported to be insufficient to control lateral lymph node recurrence in cases of enlarged lateral lymph nodes before CRT, and LLND is considered necessary in such cases. We performed a literature review on aspects of pelvic anatomy associated with rectal surgery and LLND, and then combined this information with our experience and knowledge of pelvic anatomy. In this review, drawing upon research using a 3-dimensional anatomical model and actual operative views, we aimed to clarify the essential anatomy for LLND. The LLND procedure was developed in Asian countries and can now be safely performed in terms of functional preservation. Nonetheless, the longer operative time, hemorrhage, and higher complication rates with TME accompanied by LLND than with TME alone indicate that LLND is still a challenging procedure. Laparoscopic or robotic LLND has been shown to be useful and is widely performed; however, without a sufficient understanding of anatomical landmarks, misrecognition of vessels and nerves often occurs. To perform safe and accurate LLND, understanding the landmarks of LLND is essential

Catalyst Deactivation of a Silica-Supported Bismuth–Molybdenum Complex Oxide and the Related Complex Oxides for the Oxidative Dehydrogenation of 1-Butene to 1,3-Butadiene

This study was an examination of the catalyst deactivation of a silica-supported bismuth-molybdenum complex oxide, and that of catalysts used in the absence of bismuth, for the oxidative dehydrogenation of 1-butene. Due to the detection of deactivation, the molar ratio of 1-butene against oxygen in the reactant gas was adjusted to a ratio similar to that used in industrial processes where reaction temperatures average 100 K higher. Regardless of the presence or absence of bismuth in the catalysts, the conversion of 1-butene was decreased by 6 h on-stream. Both the progress of the coking from the inlet to the outlet of the catalyst and the reduction of molybdenum in the catalysts directly contributed to the deactivation. X-ray photoelectron spectrometry revealed that a greater reduction of molybdenum in the near-surface region and a smaller partial pressure of oxygen (P(O2)) in the reactant gas, although the molybdenum on the surface was not reduced at all. This indicated that the lattice oxygen was pumped from the near-surface region to the surface during the reaction and the oxygen-poor conditions of the near-surface region both in the gas and catalyst phases were formed at a smaller P(O2), which resulted in the enhancements of both the reduction of molybdenum and that of coking. Based on the thermogravimetric analysis, the silica-supported bismuth-molybdenum complex oxide used at P(O2) = 4.1 kPa (color of the catalyst = black) was increased in weight while that used at P(O2) = 16.4 kPa (color of the catalyst = gray) showed a weight decrease, which indicated that the weight decrease caused by the reduction in molybdenum in the near-surface region used at 4.1 kPa was greater than the weight increase from the coking. It was concluded that the reduction in molybdenum followed by the coking on the catalyst surface were the main factors in the catalyst deactivation

Safety and Efficacy of Intensity-Modulated Stereotactic Body Radiotherapy Using Helical Tomotherapy for Lung Cancer and Lung Metastasis

Stereotactic body radiotherapy (SBRT) proved to be an effective treatment with acceptable toxicity for lung tumors. However, the use of helical intensity-modulated (IM) SBRT is controversial. We investigated the outcome of lung tumor patients treated by IMSBRT using helical tomotherapy with a Japanese standard fractionation schedule of 48 Gy in 4 fractions (n=37) or modified protocols of 50–60 Gy in 5–8 fractions (n=35). Median patient’s age was 76 years and median follow-up period for living patients was 20 months (range, 6–46). The median PTV was 6.9 cc in the 4-fraction group and 14 cc in the 5- to 8-fraction group (P=0.001). Grade 2 radiation pneumonitis was seen in 2 of 37 patients in the 4-fraction group and in 2 of 35 patients in the 5- to 8-fraction group (log-rank P=0.92). Other major complications were not observed. The LC rates at 2 years were 87% in the 4-fraction group and 83% in the 5- to 8-fraction group. Helical IMSBRT for lung tumors is safe and effective. Patients with a high risk of developing severe complications may also be safely treated using 5–8 fractions. The results of the current study warrant further studies of helical IMSBRT

Treatment of Single or Multiple Brain Metastases by Hypofractionated Stereotactic Radiotherapy Using Helical Tomotherapy

This study investigated the clinical outcomes of a 4-fraction stereotactic radiotherapy (SRT) study using helical tomotherapy for brain metastases. Between August 2009 and June 2013, 54 patients with a total of 128 brain metastases underwent SRT using tomotherapy. A total dose of 28 or 28.8 Gy at 80% isodose was administered in 4 fractions for all tumors. The mean gross tumor volume (GTV) was 1.9 cc. Local control (LC) rates at 6, 12, and 18 months were 96%, 91%, and 88%, respectively. The 12-month LC rates for tumors with GTV ≤0.25, >0.25 and ≤1, and >1 cc were 98%, 82%, and 93%, respectively; the rates were 92% for tumors >3 cc and 100% for >10 cc. The 6-month rates for freedom from distant brain failure were 57%, 71%, and 55% for patients with 1, 2, and >3 brain metastases, respectively. No differences were significant. No major complications were observed. The 4-fraction SRT protocol provided excellent tumor control with minimal toxicity. Distant brain failure was not so frequent, even in patients with multiple tumors. The results of the current study warrant a prospective randomized study comparing single-fraction stereotactic radiosurgery (SRS) with SRT in this patient population