Precise navigation surgery of tumours in the lung in mouse models enabled by in situ fluorescence labelling with a killer-reporter adenovirus.

BackgroundCurrent methods of image-guided surgery of tumours of the lung mostly rely on CT. A sensitive procedure of selective tumour fluorescence labelling would allow simple and high-resolution visualisation of the tumour for precise surgical navigation.MethodsHuman lung cancer cell lines H460 and A549 were genetically transformed to express red fluorescent protein (RFP). Tumours were grown subcutaneously for each cell line and harvested and minced for surgical orthotopic implantation on the left lung of nude mice. Tumour growth was measured by fluorescence imaging. After the tumours reached 5 mm in diameter, they were injected under fluorescence guidance with the telomerase-dependent green fluorescent protein (GFP)-containing adenovirus, OBP-401. Viral labelling of the lung tumours with GFP precisely colocalised with tumour RFP expression. Three days after administration of OBP-401, fluorescence-guided surgery (FGS) was performed.ResultsFGS of tumours in the lung was enabled by labelling with a telomerase-dependent adenovirus containing the GFP gene. Tumours in the lung were selectively and brightly labelled. FGS enabled complete lung tumour resection with no residual fluorescent tumour.ConclusionsFGS of tumours in the lung is feasible and more effective than bright-light surgery

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence.

We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model

Improved Resection and Outcome of Colon-Cancer Liver Metastasis with Fluorescence-Guided Surgery Using In Situ GFP Labeling with a Telomerase-Dependent Adenovirus in an Orthotopic Mouse Model.

Fluorescence-guided surgery (FGS) of cancer is an area of intense development. In the present report, we demonstrate that the telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 could label colon-cancer liver metastasis in situ in an orthotopic mouse model enabling successful FGS. OBP-401-GFP-labeled liver metastasis resulted in complete resection with FGS, in contrast, conventional bright-light surgery (BLS) did not result in complete resection of the metastasis. OBP-401-FGS reduced the recurrence rate and prolonged over-all survival compared with BLS. In conclusion, adenovirus OBP-401 is a powerful tool to label liver metastasis in situ with GFP which enables its complete resection, not possible with conventional BLS

人工膝関節置換術後の関節周囲感染が疑われる症例の発生頻度は、術中麻酔維持使用薬剤の選択と関連するか（プロポフォールによる全静脈麻酔と、セボフルランでの麻酔維持での比較）：後ろ向きコホート研究

PURPOSE: Periprosthetic joint infection is a serious complication of total knee arthroplasty. Though there are many factors that might increase its risk, the use of propofol for maintaining general anesthesia could theoretically increase the incidence of infection because of its lipid component that supports bacterial growth. Nevertheless, the relationship between anesthetic maintenance agents and the occurrence of periprosthetic joint infection remains uncertain. The purpose of this study was to compare the incidence of suspected early-onset periprosthetic joint infection between patients undergoing total knee arthroplasty under propofol vs sevoflurane anesthesia. METHODS: We conducted a retrospective cohort study of patients in the national inpatient Diagnosis Procedure Combination database in Japan who underwent total knee arthroplasty. Suspected periprosthetic joint infection was surrogately defined as the need for arthrocentesis or debridement within 30 days of surgery. Propensity score matching was performed between patients who received either propofol or sevoflurane for anesthetic maintenance to determine the proportion of those with infection. RESULTS: Eligible patients (n = 21,899) were categorized into either the propofol (n = 7,439) or sevoflurane (n = 14,460) groups. In the 5,140 propensity-matched patient pairs, there was no significant difference in the proportion of arthrocentesis or debridement [1.3% propofol vs 1.7% sevoflurane; respectively (relative risk, 0.76; 95% CI, 0.55 to 1.04; P = 0.10)] between the groups. The mean (SD) length of stay in the propofol group was significantly longer than in the sevoflurane group [32.5 (18.4) days vs 31.4 (14.4) days, respectively; mean difference, 1.1; 95% CI, 0.5 to 1.8; P < 0.001]. CONCLUSION: Propensity score analysis suggested no significant association between the choice of anesthetic maintenance agent and the occurrence of suspected early-onset periprosthetic joint infection in patients undergoing total knee arthroplasty.博士（医学）・甲第700号・平成31年3月15日© Canadian Anesthesiologists' Society 2018This is a post-peer-review, pre-copyedit version of an article published in Canadian journal of anaesthesia. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12630-018-1139-6

心室中隔欠損症に対する小児心臓カテーテル検査における麻酔方法と重症合併症の関連

Pediatric cardiac catheterization requires unconsciousness and immobilization through general anesthesia or sedation. This study aimed to compare the occurrence of severe complications in pediatric diagnostic cardiac catheterization for ventricular septal defect between general anesthesia and sedation performed under similar institutional environments. Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified pediatric patients (aged <2 years) who underwent diagnostic cardiac catheterization for ventricular septal defect between July 2010 and March 2019. The composite outcome was the occurrence of severe complications, including catecholamine use and intensive care unit admission, within seven days after catheterization. Overlap weighting based on propensity scores was used to adjust for patient- and hospital-level confounding factors. We identified 3159 patients from 87 hospitals, including 930 under general anesthesia and 2229 under sedation. The patient- and hospital-level baseline characteristics differed between the groups. After adjustment, the proportion of patients with severe complications was significantly higher in the general anesthesia group than in the sedation group (2.4% vs. 0.6%; risk difference, 1.8% [95% confidence interval, 0.93–2.6%]). Severe complications occurred more frequently in the general anesthesia group than in the sedation group. Further research on anesthetic methods is necessary to assess the safety and accuracy of pediatric diagnostic cardiac catheterization.博士（医学）・甲第867号・令和5年3月15

経動脈的化学塞栓術における予防的抗菌薬と肝膿瘍発症の関連 : 後方視的コホート研究

Objectives: Clinical evidence on prophylactic antibiotics for transarterial chemoembolization (TACE) to prevent liver abscess is limited because liver abscess is a rare event. This study aimed to analyse the association between prophylactic antibiotic use for TACE and the occurrence of liver abscess after TACE. Methods: Using the nationwide Diagnosis Procedure Combination database in Japan, we retrospectively identified patients who underwent TACE for hepatic cancer between July 2010 and March 2017. The primary outcome was liver abscess requiring procedural intervention within 30 days of TACE. Secondary outcomes included 30-day in-hospital mortality and length of stay. Propensity score matching was performed to adjust for potential confounding factors and compare outcomes between patients with and without prophylactic antibiotics. Results: Among 167 544 eligible patients, 134 712 received antibiotics and 32 832 did not. In the matched cohort of 29 211 pairs, the proportion of patients with liver abscess requiring procedural intervention was significantly lower in the antibiotics group than in the no-antibiotics group (0.08% vs. 0.22%, p 0.001; relative risk (95% confidence interval), 0.35 (0.22-0.57); absolute risk reduction, 0.0014 (0.0008-0.0021); and number needed to treat, 696 (476-1223)). There was no significant difference in 30-day in-hospital mortality between the groups. The length of stay was longer in the antibiotics group than in the no-antibiotics group (median, 10 vs. 9 days, p < 0.001). Conclusions: Prophylactic antibiotic use in patients undergoing TACE was associated with a reduced occurrence of liver abscess requiring procedural intervention.博士（医学）・甲第794号・令和3年6月25日Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved

Gamma-Ray Spectroscopy in Lambda Hypernuclei

The present status of hypernuclear gamma-ray spectroscopy with Hyperball is summarized. We observed two gamma transitions of 16-Lambda-O(1- -> 1-,0-) and obtained the strength of the Lambda-N tensor force. In 10B(K-,pi- gamma) data, we did not observe the spin-flip M1 transition of 10-Lambda-B(2- -> 1-), but gamma rays from hyperfragments such as 7-Lambda-Li(7/2+ -> 5/2+) and 9-Lambda-Be(3/2+ ->1/2+) were observed. In 11B(pi+,K+ gamma) data, we observed six gamma transitions of 11_Lambda-B. We also attempted an inclusive gamma-ray measurement with stopped K- beam.Comment: 10 pages, 9 figures, 8th International Conference on Hypernuclear and Strange Particle Physics (HYP2003), Newport News, Virginia, 14-18 Oct 2003, to appear in Nuclear Physics