硼中子俘获治疗外阴黑色素瘤和生殖器乳腺外Paget病的疗效

背景与目的尽管目前对生殖器区的黑色素瘤和乳腺外Paget病(extramammary Paget’s disease,EMPD)最常推荐的治疗方法是广泛性手术切除病变,但该方法侵害性极高并可导致功能性和性方面的问题。当扩大局部切除术不可行的情况下,替代疗法已被用于进行局部控制。本研究描述了4例接受硼中子俘获治疗(boron neutron capture therapy,BNCT)的生殖器恶性肿瘤患者。方法 4例患者中包括1例外阴黑色素瘤(vulvar melanoma,VM)和3例生殖器EMPD患者。他们于2005至2014年间在Kyoto大学研究堆接受了对二羟基硼酰苯丙氨酸作为硼携带剂的BNCT治疗。他们接受了介于治愈性肿瘤剂量和可耐受的皮肤/黏膜剂量之间的超热中子束照射。结果所有患者在BNCT治疗后均表现出相似的肿瘤和正常组织反应,并在6个月内达到完全缓解。最严重的正常组织反应前2个月内出现,随后逐渐减弱的中度皮肤糜烂,排尿困难或接触性疼痛持续2个月,完全解决需4个月。结论 BNCT治疗VM和EMPD后局部肿瘤得到完全控制。根据我们的临床经验,我们认为BNCT是治疗生殖器区原发性VM和EMPD的一种有前景的方法。

硼中子俘获治疗作为癌症治疗方式的现实评估

硼中子俘获治疗(boron neutron capture therapy,BNCT)是一种基于核俘获和裂变反应的二元治疗方式,裂变反应发生于稳定的同位素硼-10被中子辐射时产生高能α粒子和反冲锂-7核。本评论聚焦了2017年9月在北京国家会议中心举办的名为"硼中子俘获治疗癌症回顾与展望研讨会"上报告的一些文章。来自日本、芬兰、美国、中国大陆和中国台湾地区的临床医生报告了他们的研究结果,他们一直从事BNCT临床应用所需的多学科工作。主要的研究焦点为恶性脑肿瘤、复发性头颈部肿瘤和皮肤黑色素瘤患者的治疗。他们对这些患者的治疗结果进行了详细报道,虽然多数脑肿瘤和头颈癌的患者未被治愈,但获得的证据支持了该疗法具有一定的临床疗效。虽然仍有很多问题须被解决,但评价BNCT疗效的进一步临床研究是可以开展的。首先,尽管过去40年大量研究人员进行了相当大的努力,但临床使用的含硼药物仍只有两种:二羟基苯丙氨酸硼(l-boronophenylalanine,BPA)和巯基硼烷(sodium borocaptate,BSH)。因此,在新的更有效的硼携带剂研发出来之前,改善BPA和BSH的剂量和给药应是努力的方向。第二,由于多种原因,基于核反应堆的BNCT已经在除中国大陆和台湾地区之外的地区停止使用。因此,BNCT的未来取决于日本正在进行的II期临床试验以及芬兰即将启动的试验结果。如果这些临床试验的结果有足够前景,那么BNCT将有一条通往未来的清晰路径,特别是对治疗上具有挑战的恶性肿瘤患者,这些恶性肿瘤类型过去应用反应堆基BNCT进行过治疗。

What did Sun Yat-sen really die of?A re-assessment of his illness and the cause of his death

This year is the 150 th anniversary of the birth of Sun Yat-sen(November 12, 1866) and the 91 st year following his death(March 12, 1925). It generally has been believed that the cause of his death was "liver cancer." However, as indicated in the oicial autopsy report, dated March 13, 1925, of the Peking Union Medical College Hospital(PUMCH) in Beijing, the cause of his death in reality was an adenocarcinoma of the gallbladder with direct extension to the liver and diaphragm as well as widespread metastases to the peritoneal cavity. This important piece of information seems to have never been reported in the English language literature, and it was only in 2013 that the true cause of his death was stated in a one-line sentence in a non-medical Chinese online source. It had been mistakenly believed that the cause of Dr. Sun's death was liver cancer, based on the observations made following an exploratory laparotomy, which had been performed at PUMCH on January 26, 1925. The purpose of this short report is to provide more details relating to his terminal illness and to correct the historical record for a medical audience as to the cause of the death of Sun Yat-sen, a very important igure in the history of 20 th century China.

用于中子俘获治疗的硼携带剂

硼中子俘获治疗(boron neutron capture therapy,BNCT)是一种基于稳定同位素硼-10被中子照射产生高能α粒子时发生的核俘获和裂变反应的二元放射疗法。本综述关注了这个二元系统的一个重要组分,即具有肿瘤靶向性的硼携带剂。目前临床上正在使用的两种低分子量含硼药物是硼苯丙氨酸(boronophenylalanine,BPA)和硼卡钠(sodium borocaptate,BSH)。尽管还远未达到理想水平,但它们的治疗效果已经在高级别神经胶质瘤、头颈部复发性肿瘤以及小部分皮肤和皮肤外黑色素瘤患者中得到了证实。由于它们存在局限性,在过去的40年中,研究者们一直在为临床应用努力研发具有更高生物分布和摄取性的新型硼携带剂。这些物质包括含硼的卟啉、氨基酸、多胺、核苷、多肽、单克隆抗体、脂质体和各种类型的纳米颗粒,以及硼簇合物和共聚物。然而到目前为止,还没有一种化合物获得过有说服力的数据,能使之进入临床生物分布研究。因此,目前进一步提高BNCT临床疗效的最佳途径是优化BPA和BSH单独使用或联合使用的给药模式和递送方式,并希望未来的研究能发现更新更好的硼携带剂供临床使用。

Boron delivery agents for neutron capture therapy of cancer

Boron neutron capture therapy(BNCT)is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope,boron-10,is irradiated with neutrons to produce high energy alpha particles.This review will focus on tumor-targeting boron delivery agents that are an essential component of this binary system.Two low molecular weight boron-containing drugs currently are being used clinically,boronopheny-lalanine(BPA)and sodium borocaptate(BSH).Although they are far from being ideal,their therapeutic efficacy has been demonstrated in patients with high grade gliomas,recurrent tumors of the head and neck region,and a much smaller number with cutaneous and extra-cutaneous melanomas.Because of their limitations,great effort has been expended over the past 40 years to develop new boron delivery agents that have more favorable biodistribution and uptake for clinical use.These include boron-containing porphyrins,amino acids,polyamines,nucleosides,peptides,monoclonal antibodies,liposomes,nanoparticles of various types,boron cluster compounds and co-polymers.Cur-rently,however,none of these have reached the stage where there is enough convincing data to warrant clinical biodistribution studies.Therefore,at present the best way to further improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH,either alone or in combination,with the hope that future research will identify new and better boron delivery agents for clinical use.

Boron neutron capture therapy for vulvar melanoma and genital extramammary Paget’s disease with curative responses

Background:Although the most commonly recommended treatment for melanoma and extramammary Paget’s disease(EMPD)of the genital region is wide surgical excision of the lesion,the procedure is highly invasive and can lead to functional and sexual problems.Alternative treatments have been used for local control when wide local exci-sion was not feasible.Here,we describe four patients with genital malignancies who were treated with boron neutron capture therapy(BNCT).Methods:The four patients included one patient with vulvar melanoma(VM)and three with genital EMPD.They underwent BNCT at the Kyoto University Research Reactor between 2005 and 2014 using para-boronophenylalanine as the boron delivery agent.They were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin/mucosal doses.Results:All patients showed similar tumor and normal tissue responses following BNCT and achieved complete responses within 6 months.The most severe normal tissue response was moderate skin erosion during the first 2 months,which diminished gradually thereafter.Dysuria or contact pain persisted for 2 months and resolved com-pletely by 4 months.Conclusions:Treating VM and EMPD with BNCT resulted in complete local tumor control.Based on our clinical expe-rience,we conclude that BNCT is a promising treatment for primary VM and EMPD of the genital region.

有关孙中山先生死因释疑——由Cash博士的尸检报告谈起

2016年正值孙中山先生诞辰150周年暨逝世91周年之际，孙中山先生逝世时中外媒体均报道其死因为肝癌，这一信息主要依据北京协和医院基本外科主任Adrian Taylor于先生生前（1925年1月26日）行剖腹探查手术的术中所见而推测出。Taylor医师发现先生的肝脏被一个恶性肿瘤大面积浸润，累及腹腔脏器及肺组织，据此判断先生罹患肝癌，时日无多。