Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age‐adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.     

Mutations of the TP53 gene in adenocarcinoma and squamous cell carcinoma of the cervix: A systematic review

ObjectiveMutations of the tumor suppressor gene TP53 are the most significant events in several human cancers. Few studies have analyzed the frequency of TP53 alterations in squamous cell carcinoma and adenocarcinoma of the cervix with controversial results. This study provides a detailed analysis of TP53 mutation spectra in cervical squamous cell carcinoma and adenocarcinoma from different geographical regions.MethodsThe analysis of TP53 mutational profiles was performed in 1353 cervical cancers retrieved from the IARC p53 mutation database (R15, 2010) and the COSMIC data along with the literature review of related studies identified by PubMed searching.ResultsThis analysis showed a significant higher mutation frequency of TP53 gene in cervical adenocarcinoma (32 of 241; 13.3%) compared to squamous cell carcinoma (39 of 657; 5.9%; P = 0.0003, χ² test). The proportion of adenocarcinoma with mutated TP53 varied from 4% in North America to 19% in Asia. Among the six hot-spot codons of TP53 gene, three codons (175, 248 and 273) were the most commonly mutated in both types of cervical cancer, one codon (249) mainly in squamous cell carcinoma and one codon (282) only in adenocarcinoma. The G to A and C to T transitions were the prevalent type of mutations in both squamous cell carcinoma and adenocarcinoma (48.7% and 53.5% of all mutations, respectively). The frequency of C to A transversion was relatively high only in adenocarcinoma (25%), while the mirror mutation G to T was comparatively frequent in squamous cell carcinoma (14.6%).ConclusionsDifferent patterns of TP53 mutations occur in squamous cell carcinoma and adenocarcinoma of the cervix in different regions of the world. The highest frequency of mutated TP53 has been observed in cervical adenocarcinoma from Asia. Further studies are needed to better define the role of TP53 alterations in cervical cancer and possibly to understand the impact of mutations on cancer prognosis and outcomes.     

冠脉造影联合动态心电图监测在老年冠心病患者诊断中的应用分析

目的分析冠脉造影联合动态心电图监测在老年冠心病患者患者诊断中的应用价值。方法本次研究选取我院2013年3月至2014年3月治疗的82例冠心病老年患者为例,患者均使用冠脉造影联合12导联动态心电图监测进行诊断。结果 82例患者中,共有63例患者为阳性冠结果,19例患者为阴性结果 ;59例患者12导联动态心电图结果为阳性,23例患者12导联动态心电图结果为阴性。患者冠状动脉病变程度与12导联动态心电图ST低压阳性率差异并不明显,不存在统计学意义(P0.05)。结论只使用12导联动态心电图监测诊断老年冠心病的应用效果较差,可以使用冠脉造影配合诊断,提高老年冠心病的诊断准确率,适合进行临床推广。     

Revisiting colorectal cancer animal model – An improved metastatic model for distal rectosigmoid colon carcinoma

Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model.We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1?×?10⁷ cells/animal) in RNU rats (n?=?55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, β-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (^99mTc-MIBI).Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake.With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.     

mTOR通路激活后上调SNCG表达水平抑制 乳腺癌细胞辐射 敏感性的研究

目的：探讨乳腺癌T47D细胞通过激活mTOR通路调控SNCG表达水平，从而抑制乳腺癌细胞辐射敏感性的分子机制。方法：检测不同剂量γ射线照射后的T47D乳腺癌细胞中mTOR蛋白表达水平。在细胞培养液中加入不用浓度磷脂酸（PA，mTOR通路激活剂）进行培养，以常规培养细胞为对照组，采用Western blot法检测对照组和激活剂组细胞SNCG蛋白的表达。对照组和激活组细胞采用4 Gy γ射线照射24 h，检测照射后SNCG mRNA和蛋白的表达情况，并采用平板细胞克隆形成实验检测克隆形成率。同时，将转染SNCG siRNA的乳腺癌T47D细胞株分成激活组和对照组，验证SNCG在乳腺癌细胞辐射敏感性抵抗中的生物学功能。结果：不同剂量射线照射后，mTOR蛋白表达水平显著升高。mTOR激活剂PA处理后的细胞对乳腺癌细胞放射敏感性具有明显的抑制作用，同时Western blot显示γ射线照射处理后的乳腺癌细胞中SNCG蛋白的表达水平异常。Western blot和qPCR方法检测发现，T47D对照组和干扰SNCG基因的T47D细胞实验组中，激活mTOR或γ射线照射均能引起SNCG蛋白和mRNA表达增加。克隆形成实验进一步证明，降低SNCG的表达可显著抑制T47D细胞克隆形成能力。结论：在乳腺癌细胞中，mTOR介导的SNCG表达调控对乳腺癌细胞抗辐射起着重要作用，降低SNCG的表达可提高辐射敏感性，提示在临床治疗中有可能通过使用SNCG抑制剂或mTOR抑制剂提高乳腺癌细胞在放化疗中的敏感性。     

实施医疗责任保险的思考

概述医疗事故技术鉴定的现状,从分散执业风险,减轻赔偿压力;保护合法权益,理赔更加便捷;缓解社会矛盾,稳定医疗秩序;增强风险意识,提升防范水平方面分析医疗责任保险的社会意义,提出改革医疗事故责任鉴定,制定完善法律法规体系,健全医患纠纷解决机制等医疗责任保险的发展建议。