脱髄型シャルコー・マリトゥス病患者における超音波検査による正中神経、尺骨神経、頸神経根の神経肥厚の検出 : 慢性炎症性脱髄性多発ニューロパチー患者との鑑別

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(医学)Philosophy in Medical Sciencedoctora

Mid-term Outcomes and Predictors of Transarterial Embolization for Type II Endoleak After Endovascular Abdominal Aortic Aneurysm Repair

Purpose To evaluate the mid-term outcomes of transarterial embolization (TAE) for type II endoleak after endovascular abdominal aortic aneurysm repair (EVAR) and investigate the predictors of sac enlargement after embolization. Materials and Methods We conducted a retrospective analysis of 55 patients [48 men and 7 women, median age 79.0 (interquartile ranges 74-82) years] who underwent TAE for type II endoleak from 2010 to 2018. The aneurysmal sac enlargement, endoleaks, aneurysm-related adverse event rate, and reintervention rate were evaluated. Patients' characteristics and clinical factors were evaluated for their association with sac enlargement. Results Fifty-five patients underwent TAE with technical success and were subsequently followed for a median of 636 (interquartile ranges 446-1292) days. The freedom from sac enlargement rates at 1, 3, and 5 years was 73.2%, 32.0%, and 26.7%, respectively. After initial TAE, the recurrent type II, delayed type I, and occult type III endoleak were identified in 39 (71%), 5 (9%), and 3 (5%) patients, respectively. Although a patient had aorto-duodenal fistula, there was no aneurysm-related death. The freedom from reintervention rates was 84.6%, 35.7%, and 17.0%, respectively. In the multivariate analysis, sac diameter > 55 mm at initial TAE (hazard ratios, 3.23; 95% confidence intervals, 1.22-8.58; P 55 mm at initial TAE was a significant predictor of sac enlargement

Hepatic Artery Embolization Induces the Local Overexpression of Transforming Growth Factor β1 in a Rat Hepatoma Model

Introduction: The underlying mechanism involved in the recurrence of hepatoma after hepatic arterial embolization (HAE) is not adequately examined. An immunosuppressive cytokine, transforming growth factor β1 (TGF-β1), can lead to tumor progression and is affected by hypoxia in various cancers. The study aimed to assess the effect of HAE on the expression of TGF-β1 in a rat hepatoma model. Methods: Sprague-Dawley rats bearing N1S1 hepatoma cells underwent HAE (HAE group, n = 5) or sham treatment (sham group, n = 4). The animals were euthanized at 48 h, and liver tissues were harvested. Immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR) were performed to compare the expression of TGF-β1 and hypoxia-inducible factor 1α (HIF-1α) between the HAE and sham groups. In vitro experiments with the N1S1 cell line were also performed under normoxic (21% O2) or hypoxic (1% O2) conditions for 48 h, and the expression of TGF-β1 and HIF-1α was assessed with western blotting and enzyme-linked immunosorbent assay. Statistical data comparisons were performed by Student t test. Results: IHC showed that both the TGF-β1-positive and HIF-1α-positive tumor peripheral areas were larger in the HAE group (6.59 ± 2.49 and 10.26 ± 4.14%; p < 0.001, respectively) than in the sham group (0.34 ± 0.41 and 0.40 ± 0.84% respectively). Similarly, qPCR showed that the mRNA expression levels of TGF-β1 and HIF-1α were higher (1.95 ± 0.38-fold and 1.62 ± 0.37-fold; p < 0.001 and p = 0.002, respectively) in the HAE group than those in the sham group. TGF-β1 expression was suppressed when HIF-1α inhibitors were added (p = 0.001), and HIF-1α expression was upregulated when exogenous TGF-β1 was added (p = 0.033) in N1S1 cells. Conclusion: HAE enhanced local TGF-β1 expression in a rat hepatoma model. In vitro experiments suggest that HAE-induced hypoxic stress may trigger the interdependent expression of TGF-β1 and HIF-1α

In vivo evaluation of percutaneous carbon dioxide treatment for improving intratumoral hypoxia using 18F-fluoromisonidazole PET-CT

Carbon dioxide (CO2) treatment is reported to have an antitumor effect owing to the improvement in intratumoral hypoxia. Previous studies were based on histological analysis alone. In the present study, the improvement in intratumoral hypoxia by percutaneous CO2 treatment in vivo was determined using 18F-fluoromisonidazole positron emission tomography-computed tomography (18F-FMISO PET-CT) images. Twelve Japanese nude mice underwent implantation of LM8 tumor cells in the dorsal subcutaneous area 2 weeks before percutaneous CO2 treatment and 18F-FMISO PET-CT scans. Immediately after intravenous injection of 18F-FMISO, CO2 and room air were administered transcutaneously in the CO2-treated group (n=6) and a control group (n=6), respectively; each treatment was performed for 10 minutes. PET-CT was performed 2 h after administration of 18F-FMISO. 18F-FMISO tumor uptake was quantitatively evaluated using the maximum standardized uptake value (SUVmax), tumor-to-liver ratio (TLR), tumor-to-muscle ratio (TMR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Mean ± standard error of the mean (SEM) of the tumor volume was not significantly different between the two groups (CO2-treated group, 1.178±0.450 cm3; control group, 1.368±0.295 cm3; P=0.485). Mean ± SEM of SUVmax, TLR, MTV (cm3) and TLG were significantly lower in the CO2-treated group compared with the control group (0.880±0.095 vs. 1.253±0.071, P=0.015; 1.063±0.147361 vs. 1.455±0.078, P=0.041; 0.353±0.139 vs. 1.569±0.438, P=0.015; 0.182±0.070 vs. 1.028±0.338, P=0.015), respectively. TMR was not significantly different between the two groups (4.520±0.503 vs. 5.504±0.310; P=0.240). In conclusion, 18F-FMISO PET revealed that percutaneous CO2 treatment improved intratumoral hypoxia in vivo. This technique enables assessment of the therapeutic effect in CO2 treatment by imaging, and may contribute to its clinical application