Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Effect of deuteration on the single dose pharmacokinetic properties and postoperative analgesic activity of methadone

Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d₉-methadone.The pharmacokinetic profiles of d₉-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d₉-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD₅₀ value for a single intravenous dose of d₉-methadone was 2.1-fold higher than that for methadone. Moreover, d₉-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy.     

肺癌脑转移放射治疗方式及进展

肺癌是发病率和死亡率最高的恶性肿瘤，其脑转移发生率高且预后差。近年来随着靶向以及免疫治疗药物相继研制成功，肺癌原发灶局部控制率得以提升，因此对其脑转移的治疗更加关注。放射治疗是肺癌脑转移治疗的重要手段之一，现将肺癌脑转移放射治疗方式及进展进行综述。     

单孔加一孔联合ERAS在高位直肠及乙状结肠癌中的应用

目的 探讨单孔加一孔腹腔镜手术联合 ERAS 治疗高位直肠及乙状结肠癌的近期疗效。方法 回顾性分析 2017 年 11 月至2018 年 10 月在福建省肿瘤医院胃肠肿瘤外科进行加速康复外科干预的 92 例高位直肠及乙状结肠癌患者资料，根 据手术方式的不同，分为单孔加一孔手术联合快速康复外科组39 例及常规腹腔镜手术联合ERAS 组 53 例，对比两组围术 期情况。结果 两组患者基线资料无明显统计学差异（P ＞ 0.05），且在手术时间、出血量、上下切缘、清扫淋巴结数量及 并发症方面无明显统计学差异（P ＞ 0.05）。但单孔加一孔手术联合ERAS 组较常规手术联合ERAS 组，总切口长度更短 [（6.7±1.1）cm 比（8.5±1.3）cm，P=0.000]，术后首次下床时间更早 [（22.2±5.2）h 比（27.1±7.9）h，P=0.001]，首次排便 时间更早[（70.2±19.8）h比（83.1±20.4）h，P=0.005]，术后第一天C反应蛋白值更低[（43.5±28.6）mg/L比（57.2±33.2） mg/L，P=0.038]，术后住院时间更短 [（7.0±1.7）d 比（8.1±2.1）d，P=0.010]，且术后 2~4 天疼痛评分更低（P ＜ 0.05）。 结论 经验丰富的腔镜医师采用单孔加一孔手术治疗高位直肠及乙状结肠癌并联合 ERAS 干预是安全可行的，且单孔加一孔 手术可减低操作难度，具有疼痛轻、术后恢复快等优势，值得临床推广。     

接受选择性淋巴结照射的食管鳞癌患者预后和失败模式的分析

目的探讨接受选择性淋巴结照射(ENI)的食管鳞癌患者预后和失败模式。方法回顾性分析2005年1月至2012年12月河北医科大学第四医院收治的179例符合入组条件的食管鳞癌患者,分析肿瘤局部相关因素预测患者预后的价值,分析影响患者近期疗效、预后的影响因素,并对影响患者总生存率(OS)、无进展生存率(PFS)和复发的指标分别进行单因素和多因素分析。结果全组患者1、3、5年OS和PFS分别为77.1%、40.1%、26.0%和62.6%、30.6%、20.3%。多因素分析结果显示声音嘶哑、cN分期、cTNM分期、GTV-横径(GTV-D)和GTV-体积/长度(GTV-V/L)为影响患者OS的独立性影响因素(P<0.05);声音嘶哑、cTNM分期和近期疗效为影响患者PFS的独立性影响因素(P<0.05)。全组有75例(41.9%)患者出现复发,61例(34.1%)远处转移,其中19例(10.6%)为合并复发和远处转移。75例复发患者中64例(85.3%)患者为单纯食管复发,4例(5.3%)为单纯淋巴结复发,另7例(9.3%)患者为食管合并淋巴结复发。治疗后达完全缓解(CR)的63例患者中有18例患者出现复发,其中仅有2例患者出现淋巴结复发;logistic多因素分析结果显示患者周边组织/器官受侵、GTV-D和近期疗效为影响患者复发的独立性影响因素(P<0.05)。结论食管鳞癌患者接受ENI确实可行,其失败主要模式仍为食管复发;治疗前声音嘶哑、GTV-D和GTV-V/L较大、临床分期较晚和近期疗效不佳为患者预后较差的指标;肿瘤周边组织受侵、GTV-D和近期疗效是影响患者失败的独立性因素。     

Pre- or postoperative radiotherapy for soft tissue sarcomas

Sarcomas are rare tumours arising from mesenchymal tissue. A multimodal management in an expert centre combining surgery and radiotherapy is the current standard of care for localized soft-tissue sarcomas of the extremities, to enable limb-sparing strategies. The delivery of pre- radiotherapy or postoperative radiotherapy offers similar local control and survival rates but the toxicity profile is quite different: preoperative radiotherapy increases the risk of wound complications and postoperative radiotherapy affects long-term functional outcomes. While postoperative radiotherapy has long been the rule, especially in Europe, technical improvements with image-guided- and intensity-modulated radiotherapy associated with a better management of postoperative wounds has tended to change practices with more frequent preoperative radiotherapy. More recently the possibilities of a hypofractionated regimen or potentiation by nanoparticles to increase the therapeutic index plead in favour of a preoperative delivery of radiotherapy. The aim of this paper is to report pros and cons of pre- and post-operative radiotherapy for soft-tissue sarcomas.     

坐骨重叠征与发育性髋关节脱位手术后再脱位的相关性分析

目的提出坐骨重叠征(ischium overlap sign,IOS)的概念,并分析其与发育性髋关节脱位(developmental dysplasia of the hip,DDH)手术后再脱位的关系。方法回顾性分析2013年9月至2017年5月山东大学附属省立医院治疗的88例(105髋)DDH患儿病例资料,其中男童16例、女童72例;平均年龄12(5~24)个月,平均随访时间34(15~59)个月;双侧17例,左侧63髋,右侧42髋;1髋为髋臼发育不良,11髋半脱位,93髋全脱位。术中行髋关节造影检查,按照Bowen标准选择闭合或切开复位石膏固定术。IOS是指在人类位髋关节造影平片上股骨头软骨内缘与坐骨外缘的重叠关系,二者重叠为Ⅰ度,相接为Ⅱ度,分离为Ⅲ度。将93髋全脱位按照IOS分度进行分组,比较组间再脱位发生率。结果 1髋髋臼发育不良和11髋半脱位者IOS均为Ⅰ度。93髋全脱位中IOSⅠ度14髋,Ⅱ度39髋,此两组均行闭合复位石膏固定,无再脱位病例;Ⅲ度40髋中,闭合复位石膏固定17髋,6髋再脱位;切开复位石膏固定23髋,1髋再脱位。本研究发现Ⅲ度组的再脱位发生率(7/40,17.5%)高于其他两组(P=0.006)。IOS为Ⅲ度的40髋中,闭合复位的再脱位发生率(6/17,35.3%)高于切开复位(1/23,4.4%),差异有统计学意义(X^2=4.518,P=0.034)。结论 IOS与DDH术后再脱位有一定的关系,IOS为Ⅲ度的髋关节如行闭合复位,再脱位的风险较高。