Hypofractionated radiation therapy for invasive breast cancer: From moderate to extreme protocols

Adjuvant irradiation is the standard treatment after breast conservative surgery. Normofractionated regimen with an overall treatment time of 5 to 6 weeks is often considered as a limiting factor for irradiation compliance. In order to answer this issue, moderate and more recently extreme hypofractionated protocols appeared. We report here oncological outcomes and toxicity of hypofractionated breast irradiation. After defining the frame of moderate and extreme hypofractionated breast irradiations based on overall treatment time, patient selection criteria were listed. According to their levels of proof, the results of moderate and extreme hypofractionated breast irradiation were analysed. Overall treatment time for moderate hypofractionated breast irradiation ranged from 3 to 4 weeks, while for extreme hypofractionated breast irradiation, it was less than 1 week. For moderate hypofractionated breast irradiation, whole breast irradiation was currently performed with or without lymph node irradiation. Moderate hypofractionated breast irradiation has proven to be as safe and as efficient as normofractionated breast irradiation with level IA evidence. For extreme hypofractionated breast irradiation, phase III randomized trials confirmed that accelerated partial breast irradiation was non-inferior in terms of local control compared to normofractionated whole breast irradiation (with external beam radiation therapy and multicatheter brachytherapy), with similar acute and late toxicity. While the use of intraoperative breast irradiation remains under debate, new very accelerated partial breast irradiation (overall treatment time not exceeding 2 days) protocols emerged with encouraging results. Accelerated partial breast irradiation is warranted for extreme hypofractionated breast irradiation and is indicated for low-risk breast cancers. Moderate and extreme hypofractionated breast irradiation regimens are validated and can be routinely proposed according to patient selection criteria.     

Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology

Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.

Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.

Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors.     

2013-2017年我国四种恶性肿瘤住院费用水平及结构变动度分析

背景　恶性肿瘤给家庭、社会带来了沉重的医疗、经济负担，极易导致部分家庭“因病致贫”或放弃治疗，目前相关研究多集中于单一病种、分散地域的研究，仍缺乏对于全国范围与多病种恶性肿瘤住院费用变化及结构构成的考量。目的　分析2013-2017年我国4种恶性肿瘤住院费用水平以及影响住院费用的主要项目和结构变动情况，为控制医疗费用上涨、深化新医改提供参考依据。方法　本研究数据来源于《2014中国卫生和计划生育统计年鉴》《2015中国卫生和计划生育统计年鉴》《2016中国卫生和计划生育统计年鉴》《2017中国卫生和计划生育统计年鉴》以及《2018中国卫生健康统计年鉴》，样本跨度为2013-2017年。统计“30种疾病人均住院费用”中的胃恶性肿瘤、肺恶性肿瘤、食管恶性肿瘤以及膀胱恶性肿瘤的数据，4种恶性肿瘤的人均住院费用包括药费、检查费、治疗费、手术费和手术材料费。2019年4-8月，采用结构变动度法分析我国2013-2017年4种恶性肿瘤的住院费用的结构变动情况〔结构变动值（VSV）、结构变动度（DSV）、结构变动贡献率〕。结果　2013-2017年，4种恶性肿瘤的人均住院费用逐年上升，其中胃恶性肿瘤的人均住院费用始终最高，且肺恶性肿瘤的人均住院费用上升幅度最大。2013-2017年，在4种恶性肿瘤住院各项费用的占比中，药费占比最高且总体逐年下降。从4种恶性肿瘤住院各项费用的实际变化来看，药费在2013-2014年有所上升，2014-2017年逐年下降；检查费在2013-2014年下降，2014-2017年缓慢上升；手术费与手术材料费在2013-2017年逐年上升。2013-2017年，在4种恶性肿瘤住院各项费用中均是药费的VSV最大；4种恶性肿瘤药费、检查费的VSV均呈负向变化，手术费和手术材料费的VSV均呈正向变化，治疗费的VSV增减均不明显。2013-2017年，4种恶性肿瘤住院费用的DSV从大到小依次为肺恶性肿瘤、胃恶性肿瘤、食管恶性肿瘤、膀胱恶性肿瘤。2013-2017年，4种恶性肿瘤住院各项费用中均是药费的结构变动贡献率最大，治疗费的结构变动贡献率最小；除药费外，胃恶性肿瘤、肺恶性肿瘤住院各项费用中均是手术材料费和手术费的结构变动贡献率次之，食管恶性肿瘤住院各项费用中手术费、检查费的结构变动贡献率次之，膀胱恶性肿瘤住院各项费用中检查费、手术材料费的结构变动贡献率次之。结论　2013-2017年我国4种恶性肿瘤手术费的结构变动贡献率虽然较为理想，但药费、治疗费仍是住院费用结构的重点调整对象；同时为有效降低恶性肿瘤的人均住院费用，应当加强控制手术材料费与检查费；而胃恶性肿瘤与肺恶性肿瘤患者的疾病经济负担严重，若要缓解应加强疾病的早期预防与住院费用管控。     

益气养精法对老年肺癌患者肿瘤标志物、生存期影响研究

目的探究益气养精法对老年肺癌患者肿瘤标志物、生存期影响。方法研究纳入60例老年肺癌患者,均由本院2016年1月-2017年1月收治,采取随机数字表法将患者分为两组,对照组患者(30例)常规化疗治疗,观察组患者(30例)在化疗基础上联合益气养精法治疗,比较两组患者治疗效果、治疗前后癌胚抗原(carcino-embryonic antigen,CEA)及血清癌抗原125(serum oncoantigen 125,CA 125)肿瘤标志物水平、不良反应情况及患者2年生存率。结果观察组患治疗有效率高于对照组,P<0.05;治疗前,两组患者CEA及CA 125水平相当,P>0.05,治疗后均改善,观察组优于对照组,P<0.05;观察组患者不良反应与对照组相当,均较低,P>0.05;观察组患者2年生存率高于对照组,P<0.05。结论益气养精法治疗老年肺癌患者效果患者,患者症状改善,不良反应少,安全可靠,且患者2年生存率较高。     

The appearance of breast cancer metastases on dry bone: Implications for forensic anthropology

Breast carcinoma is a major cause of morbidity and mortality in women. The study of bone pathologies presents considerable potential in anthropology, paleopathology, forensic science and medicine. In this paper, we present and discuss metastatic lesions found in the skeletons of known individuals from the CAL Milano Cemetery Skeletal Collection, clinically diagnosed with breast cancer during life. Fourteen skeletons from a contemporary and identified collection were macroscopically studied and metastases were identified by comparison with clinical literature. As a result, bone metastases were observed in 43% of the study sample. They were located most commonly on the ribs (28.1%), pelvic girdle (19.8%), vertebrae (15.6%), skull (15.6%), scapulae (10.2%) as well as proximal segment of the femora (8.4%) and humeri (2.4%) respectively, favoring sites of high vascularization. The majority of the lesions were osteolytic, although osteoblastic and mixed metastases did occur. Osteolytic metastases appear as coalescent porosity or round to oval perforating lesions on bones with denticulated margins and pitted surrounding bone, whereas osteoblastic metastases thickened the existing trabecula (spongiosclerosis). Mixed metastases were perforating lytic lesions exposing the osteoblastic activity in the underlying trabecular bone. These results, consistent with the data from the literature, strengthen the diagnostic criteria for metastases and illustrate the aspect of bone metastases in breast carcinoma.     

Direct insertion of an ultra‐slim upper endoscope for cholangioscopy in patients undergoing choledochoduodenostomy

Direct peroral cholangioscopy (POC) using an ultra‐slim upper endoscope is one modality of POC for intraductal endoscopic evaluation and treatment of the bile duct. Choledochoduodenostomy (CDS) is one modality of biliary bypass surgery that provides a new route to the bile duct. We carried out direct POC using an ultra‐slim upper endoscope without the use of accessories in 10 patients (four sump syndromes, three bile duct strictures and three intrahepatic duct stones) previously undergoing surgical CDS. Direct POC was successful in all patients. The use of an intraductal balloon catheter was required in one patient for advancement of the endoscope into the bile duct. Distal bile ducts with sump syndromes were cleared using baskets and water irrigation under direct POC. Cholangiocarcinoma was diagnosed in one patient with hilar bile duct stricture after cholangioscopic evaluation and a targeting forceps biopsy under direct POC. Intrahepatic duct stones were successfully extracted after intraductal fragmentation under direct POC. Oozing bleeding occurred during intraductal lithotripsy but stopped spontaneously. Direct POC using an ultra‐slim upper endoscope without the assistance of accessories can easily be carried out in patients undergoing CDS.