A surveillance study of patterns of reirradiation practice using external beam radiotherapy in Japan

The aim of this study was to survey the present status and patterns of reirradiation (Re-RT) practice using external beam radiotherapy in Japan. We distributed an e-mail questionnaire to the Japanese Society for Radiation Oncology partner institutions, which consisted of part 1 (number of Re-RT cases in 2008–2012 and 2013–2018) and part 2 (indications and treatment planning for Re-RT and eight case scenarios). Of the 85 institutions that replied to part 1, 75 (88%) performed Re-RTs. However, 59 of these 75 institutions (79%) reported difficulty in obtaining Re-RT case information from their databases. The responses from 37 institutions included the number of Re-RT cases, which totaled 508 in the period from 2009 to 2013 (institution median 3; 0–235), and an increase to 762 cases in the period from 2014 to 2018 (12.5; 0–295). A total of 47 physicians responded to part 2 of the survey. Important indications for Re-RT that were considered were age, performance status, life expectancy, absence of distant metastases and time interval since previous radiotherapy. In addition to clinical decision-making factors, previous total radiation dose, volume of irradiated tissue and the biologically equivalent dose were considered during Re-RT planning. From the eight site-specific scenarios presented to the respondents, >60% of radiation oncologists agreed to perform Re-RT. Re-RT cases have increased in number, and interest in Re-RT among radiation oncologists has increased recently due to advances in technology. However, several problems exist that emphasize the need for consensus building and the establishment of guidelines for practice and prospective evaluation.     

I型内皮素受体反义寡聚核苷酸抑制VSMC增殖及内膜增生

目的　观察 型内皮素受体 (ETA)反义寡核苷酸(ODN)对血管平滑肌细胞 (VSMC)增殖和内膜增生的抑制作用 .方法　 1细胞培养 :取家兔主动脉中膜消化后培养传代 ,经抗 α- actin鉴定后使用第 4～ 6代传代细胞 ;2人工合成ODN:经 Genbank检索筛选 ,合成含 18bp ETA- ODN片段 ,再对 5 端硫代修饰以增加稳定性 ,同时行地高辛标记以检测反义片段的细胞膜穿透性 ;3 MTT分光光度法检测 ETA-ODN对 VSMC增殖的抑制作用 ;4运用放射受体结合分析法 (1 2 5I- ET- 1)了解 ODN对 ETA蛋白表达的抑制作用 ,以探讨其反义作用 ;5兔颈动脉空气干燥模型在体研究 ODN对血管内膜增生的抑制作用 :应用 F- 12 7凝胶载体携带 ETA-ODN(3.0μmol· L- 1 )导入血管周围 ,术后不同时间观察增生内膜相对厚度 .结果　 ODN于培养后 12 h进入细胞内 ,并逐渐增加 ;15 μmol· L- 1 ETA- ODN对 VSMC增殖具有抑制作用 ,2 4h后即有显著作用 ;ETA- ODN对 ETA表达亦有明显的抑制作用 ,表现为 CPM于 2 4h逐渐减少 ;ETA- ODN导入后 ,血管增生内膜相对厚度减少 .结论　 ETA- ODN以浓度和时间依赖方式抑制 ETA蛋白表达以及 VSMC的增殖 ;反义寡核苷酸是通过反义机制实现对 ETA蛋白和 VSMC增殖的抑制作用     

前列腺癌肿瘤血管生成的研究

目的：探讨肿瘤微血管与前列腺癌生长,转移的关系。方法：应用免疫组化技术结合放射免疫测定检测第Ⅷ因子相关抗原和前列腺特异性抗原（PSA）在19例前列腺癌和40例前列腺增生中的表达和平均值及其相关关系。结果：前列腺癌组织中微血管密度（MVD）和PSA值明显高于前列腺增生,转移性前列腺癌MVD和PSA值高于非转移性前列腺癌,前列腺癌MVD与PSA呈正相关,结论：血管形成与前列腺癌的发生,发展和转移密切相关,肿瘤的增长和转移有赖于肿瘤血管的生成。     

职业性慢性放射病临床诊断及预后

目的：探讨慢性放射病（以下简称慢放病）的诊断、治疗及预后。方法：以受照剂量,临床症状,造血功能,Ｔ淋巴细胞百分率,染色体畸变率对３０例慢性放射损伤患者进行综合分析判断,对其中１１例慢放病用胸腺肽治疗并追踪观察１０年。结果：慢放病患者受照剂量超过２Ｓｖ,白细胞下降伴有几髓造血功能障碍,Ｔ淋巴细胞百分率下降,染色体畸变率显著上升。胸腺肽能改善临床症状,显著提高细胞免疫功能。慢放病各项指标恢复依时间顺序为：Ｔ淋巴细胞百分率（２年）,临床症状（３．５年）,造血功能（５～８年）,染色体畸变率（１０年）。结论：受照剂量是误断慢放病的重要依据;白细胞总数、骨髓造血功能改变是诊断的关键;Ｔ淋巴细胞百分率、染色体畸变率可作为鉴别诊断指标。慢放病是一种可以恢复的职业性疾病,胸腺肽治疗有助于慢放病的恢复。     

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

An experimental study of radiation-induced cognitive dysfunction in an adult rat model

The objectives of this study were to establish an adult rat model for the late onset of radiation-induced cognitive dysfunction and to compare behavioural dysfunction with histopathological changes. While under anaesthesia, 30 rats (experimental group) were irradiated with a total dose of 40 Gy, given as eight fractions in 24 days. Another 30 rats (control group) underwent sham irradiation. The cognitive functions of all rats were evaluated at 6, 9 and 12 months after irradiation using the Morris water maze and passive avoidance tasks. Histopathological examination of these rats was carried out after the evaluation of cognitive functions was complete. At 6 and 9 months after irradiation there were no significant differences between the control and irradiated groups in passive avoidance and water maze tests. At 12 months after irradiation, the passive avoidance task revealed a deterioration of cognitive function in the experimental group. Histopathological observations revealed no abnormal findings in the irradiated brains at the light microscope level. Late onset cognitive dysfunction following cranial irradiation was observed in an adult rat model. Pathological investigations showed no abnormalities in the irradiated brains. These findings indicate that radiation-induced cognitive dysfunction can precede morphological changes in the brain or that they arise without them. The present model seems useful for elucidating the pathogenesis of radiation-induced cognitive dysfunction and for developing methods for therapy and prophylaxis.     

Propofol decreases diaphragmatic contractility in dogs

Volatile anesthetics depress diaphragmatic muscle function; however, no data are available regarding the effect of propofol on diaphragmatic contractility. We therefore studied this effect in dogs. Pentobarbital-anesthetized animals were divided into three groups of 10 each. Group I received only maintenance fluid; Group II was infused with a subhypnotic dose of propofol (0.1-mg/kg initial dose plus 1.5-mg x kg(-1) x h(-1) maintenance dose); Group III was infused with an anesthetic dose of propofol (0.1-mg/kg initial dose plus 6.0-mg x kg(-1) x h(-1) maintenance dose). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). With an infusion of propofol in Groups II and III, Pdi at low-frequency (20-Hz) stimulation decreased from the baseline values (P < 0.05), whereas Pdi at high-frequency (100-Hz) stimulation did not change. Compared with Group I, Pdi at 20-Hz stimulation decreased during propofol administration in Groups II and III (P < 0.05). The decrease in Pdi was more in Group III than in Group II (P < 0.05). We conclude that propofol is associated with a dose-related inhibitory effect on diaphragmatic contractility in dogs. IMPLICATIONS: Propofol is an effective IV anesthetic for the induction and maintenance of anesthesia. Subhypnotic and anesthetic doses of propofol decrease diaphragmatic contractility in dogs.     

Two cases of bladder tumor producing granulocyte colony stimulating factor

Two cases of bladder tumor producing granulocyte colony-stimulating factor (G-CSF) are reported. The first case was in a 79-year-old female patient. A large bladder tumor was diagnosed as right-sided hydronephrosis. The tumor consisted mostly of squamous cell carcinoma with a few transitional cells. Total cystectomy could not be performed because of direct invasion by the tumor into the pelvis. The patient died without aggressive treatment about 7 months after admission. Her leukocyte count consistently increased up to 76,200/mm3. The serum G-CSF levels were not analyzed. However, immunohistochemical examination revealed a high concentration of G-CSF in the tumor specimen. The other case was in an 80-year-old male patient. The patient, who had refused total cystectomy for bladder tumor (transitional cell carcinoma, grade 2, T2N0M0) 2 years earlier, underwent ureterocutaneostomy for obstructive renal insufficiency. Total cystectomy was not performed at this admission because of tumor invasion into the rectum and his advanced age. Radiotherapy was administered. However, he developed ileus caused by direct tumor invasion into the ileum. He died about 10 months after the urinary diversion. Leukocytosis, which improved transiently following radiotherapy, became more severe. The maximum leukocyte count was 49,500/mm3 just before death. The serum G-CSF levels during and after radiotherapy were 54 pg/ml and < 30 pg/ml, respectively. Immunohistochemical examination revealed the presence of G-CSF in the tumor. These findings suggest the production of G-CSF by the bladder tumor.