恶性骨肿瘤的保肢治疗

目的 探讨肢体恶性骨肿瘤保肢手术结合辅助化疗的临床疗效。方法 我科于2000年1月至2002年10月间，对平均年龄为18．5岁的29例四肢恶性骨肿瘤患进行保肢治疗，其中25例进行了辅助性化疗。29例中，骨肉瘤21例，尤氏瘤4例，软骨肉瘤4例。按Enneking分期，ⅡA期1例，ⅡB期28例。除软骨肉瘤外，均作术前化疗，3例骨肉瘤未作术后化疗。施行人工关节置换术14例，瘤骨灭活再植10例，异体骨关节移植3例，腓骨肿瘤切除2例。广泛切除15例，边缘性切除14例。结果 发生并发症8例，其中局部复发、皮肤坏死、骨不愈合各2例，皮下积液、切口感染各1例。随访4～31个月，平均14个月，局部复发2例，肺转移2例，按Enneking肢体肌肉骨骼系统肿瘤外科治疗重建术后功能评定标准，优良率为80％。结论 保肢手术结合辅助化疗是治疗肢体恶性骨肿瘤的比较理想的方法，有效的术前化疗是保肢成功的关键，坚持术后化疗是预防肺转移的有效措施。     

体外循环热药灌注术治疗下肢肌骨系统恶性肿瘤的效果

目的探讨体外循环热药灌注治疗肌骨系统恶性肿瘤。方法对20例下肢恶性肿瘤行股动、静脉插管，体外循环，顺铂加热灌注化疗lh。软组织肉瘤灌注术前行新辅助化疗，术后行广泛切除术，再行放疗；骨恶性肿瘤灌注术前行新辅助化疗，术后行问室外切除术，而后继续术后化疗。结果ll例随访2～8年，无复发及转移，肢体功能良好。5例干术后3个月～1年死亡。l例1年、2．5年复发2次，进一步治疗后5年无复发及转移。2例l～3年内局部复发，再次行广泛切除术，术后放化疗，术后无瘤生存。l例行广泛切除术后伤口皮瓣坏死、发生病理性骨折而行截肢，截肢后未行放化疗，术后5年无瘤生存。结论体外循环热药灌注术是保肢治疗肢体恶性肿瘤的方法之一。     

肩部恶性骨肿瘤的保肢治疗

目的 探讨肩部恶性骨肿瘤保肢治疗的方法选择。方法 自1992年，我们对19例肩部恶性骨肿瘤实施了保肢术。男12例，女7例；年龄14～60岁，平均29.8岁。肱骨上端13例，肩胛骨6例。软骨肉瘤7例，骨肉瘤4例，转移癌3例，骨巨细胞瘤3例，尤文肉瘤2例。瘤段切除灭活再植术5例，全肩胛骨切除、肱骨头吊悬术4例，瘤段切除同侧锁骨移植术4例，瘤段切除人工关节置换术2例，肩胛骨部分切除术2例，瘤段切除自体腓骨移植术和瘤段切除骨水泥充填术各1例。术后应用化疗骨肉4例瘤、软骨肉瘤3例和尤文肉瘤2例。结果 19例患者中3例失访，16例随访平均2年2个月(3个月～7年)。1例复发；4例发生肺转移；6例死亡。根据Enneking肢体功能评价标准：优4例，良5例，可5例，差2例。结论 对于肩部恶性骨肿瘤应根据肿瘤的不同部位选择不同的手术方法，不仅可以达到彻底切除肿瘤的目的，而且还可以保存一定的肩部功能。     

髋臼周围肿瘤切除术后重建

目的探讨对髋臼周围肿瘤手术切除及重建骨盆稳定性的方法，最大限度保留肢体功能，减少复发。方法2002～2005年15例髋臼周围肿瘤患者，其中软骨肉瘤8例，恶性纤维组织细胞瘤3例，Ewing肉瘤2例，转移瘤2例；6例配合化疗，4例行瘤段灭活再植，1例行瘤段灭活再植＋人工全髋置换，10例行人工假体置换（包括全髋）。结果1例术后死亡，1例感染，清创后股骨头旷置；14例术后随访9～33个月，4例软骨肉瘤复发，其他病例均能保留患肢部分功能和骨盆稳定性。结论恶性纤维组织细胞瘤、Ewing肉瘤化疗有效者保肢率高，局部复发率低；软骨肉瘤复发率高；瘤段灭活再植因骨愈合时间长，影响功能；股骨头旷置肢体短缩，跛行明显；人工假体置换可最大限度地保留肢体功能；单纯转移瘤为提高生存质量，减轻痛苦，可考虑手术治疗，但年龄大，全身脏器应急能力差者，手术应慎重。     

四肢软组织低度恶性肿瘤的保肢治疗

目的:探讨四肢软组织低度恶性肿瘤的临床特点及保肢治疗的可行性。方法:2008年-2014年我院共34例四肢软组织恶性肿瘤患者:滑膜肉瘤11例,横纹肌肉瘤7例,脂肪肉瘤6例,腱鞘巨细胞瘤3例,平滑肌肉瘤3例,恶性纤维组织细胞瘤2例,软骨肉瘤1例,恶性肉芽肿1例。其中18例行肿瘤扩大切除术,6例行根除性切除术,5例行微波灭活瘤体切除术,3例行瘤段切除、离体灭活再植术,2例行局部切除术。根据患者具体情况术中给予皮瓣修复术。根据肿瘤性质和全身情况在术后给予放疗或化疗治疗。结果:全部34例患者均获得随访,随访时间（23.5±14.6）个月,其中3例患者复发,2例患者死亡。患肢功能良好。结论:对于四肢的软组织低度恶性肿瘤,及时给予扩大切除,微波灭活等合适的保肢治疗,可以取得良好的临床治疗效果和肢体功能恢复。     

带血管腓骨复合灭活瘤骨修复节段性骨缺损

目的探讨用带血管腓骨复合自体灭活瘤骨用于四肢长骨恶性肿瘤切除后节段性缺损重建临床结果。方法 2013～2018年间对8例(股骨远端4例,胫骨近端4例)长骨恶性骨肿瘤进行保肢手术,术时患者平均年龄(14±3.6)(10～21)岁。对肿瘤切除后肢体的节段性骨缺损用带血管自体腓骨复合自体灭活瘤骨进行重建。通过骨扫描评估移植腓骨的成活情况,通过X线片评估骨结合部的愈合情况。对患者随访进行肿瘤学和影像学结果的评估。国际保肢骨与软组织肿瘤学会93评分标准用于保肢后功能评估。结果术后平均随访42 (15～51)个月。4例采用游离腓骨瓣与自体灭活瘤骨复合,4例胫骨缺损采用同侧带蒂腓骨瓣局部转移与自体灭活瘤骨复合。肿瘤切除后平均骨缺损长度为(16.25±4.1) cm,移植腓骨平均长度为(18.8±3.8) cm。骨扫描结果证实所有移植腓骨均成活,自体灭活瘤骨和宿主骨之间的平均愈合时间分别为:股骨:(7.6±0.4)个月,胫骨:(8.4±1.5)个月。最终随访时的MSTS平均得分为95.5%。无感染和骨不连病例。4年以上随访患者肿瘤学结果:6例CDF (confinuous disease free),2例DOD (died of disease)。结论带血管的自体腓骨复合自体灭活瘤骨可用于长骨恶性肿瘤切除后节段性骨缺损的重建,带血管腓骨促进了自体灭活瘤骨与宿主骨之间的愈合,是复合生物重建获得良好功能结果的基础。     

瘤段骨灭活回植术在骨干部恶性骨肿瘤保肢治疗中的应用

目的探讨瘤段骨灭活回植术治疗骨干部恶性骨肿瘤的实用性和疗效。方法自2007年9月至2010年11月,采用瘤段骨灭活回植的方法共治疗骨干部恶性骨肿瘤12例,男8例,女4例。年龄16-57岁,平均27．3岁。部位：肱骨2例,尺骨1例,桡骨1例,股骨4例,胫骨4例。病理类型：骨肉瘤3例,恶性纤维组织细胞瘤5例,软骨肉瘤2例,骨纤维肉瘤2例。所有患者术前经临床、影像学检查及病理活检明确诊断,并接收2个周期的规范化化疗。手术距骨肿瘤边缘上下5cm处截骨,将瘤段骨完整切除,剔除瘤段骨上的肿瘤组织及软组织并打通髓腔,然后用95％乙醇灭活30min,植骨或骨水泥填塞瘤段骨的骨缺损区,原位回植后用内固定物予以固定。术后2周开始进行4个周期的化疗。术后采用ISOLS系统对患者肢体功能进行评价。按时进行影像学检查观察骨愈合情况及有无肿瘤局部复发。结果本组12例患者均获得随访,随访时间15-53个月,平均32．6个月。其中1例恶性纤维组织细胞瘤患者于术后31个月因肺转移死亡,其余11例ISOLS评分为25～29分,平均26．5分。所有患者均获得骨性愈合,愈合时间6—11个月,平均愈合时间7．8个月。至末次随访时所有病例均无局部复发。结论瘤段骨灭活回植术具有费用低廉、操作易掌握等特点,结合新辅助化疗治疗骨干部恶性骨肿瘤疗效满意,目前仍然具有实用价值。     

软组织肉瘤动脉灌注新辅助化疗后的保肢治疗

目的探讨术前动脉内灌注化疗对软组织肉瘤的疗效及在保肢治疗中的意义。方法28例肢体软组织肉瘤,其中恶性纤维组织细胞瘤18例,滑膜肉瘤3例,脂肪肉瘤6例,原始神经外胚层肿瘤（PNET）1例。术前均给予选择性肿瘤供血动脉灌注化疗2-3周期,化疗药物为阿霉素／顺铂和异环磷酰胺。化疗后均行保肢手术治疗。结果28例术前化疗后均有疼痛缓解、皮温降低、肿胀减轻、瘤体不同程度缩小、边缘变清楚及关节活动度增加。化疗后均行肿瘤广泛切除术,术中获得良好的外科切除界限。随访6-46个月,平均25个月。2例死亡,1例局部复发行截肢术。术后12个月后采用MSTS93评分系统评分为24-29分,平均为27分。28例3年生存率为92.9％,初次保肢率100％,最终保肢率89.3％。结论肢体软组织肉瘤术前动脉灌注新辅助化疗是一种有效的保肢治疗方法。     

负瘤骨截除后煮沸灭活再植治疗亚性骨肿瘤的临床研究（附16例报告）

用煮沸灭活的方法治疗恶性骨肿瘤１６例，即将截除的瘤段煮沸灭活，然后再植回原位达到保肢的目的。随访１年至４年４个月，健在８例。煮沸灭活之骨都已成活并和主骨愈合。局部感染２例，骨折３例，复发３例，保留后的肢体功能较好。同其它保肢方法如假体、异体骨置换，酒精灭活等比较，此方法具有经济、安全、简单易行等优点，值得推广。     

胫骨成骨肉瘤的保肢治疗

目的 探讨胫骨成骨肉瘤的保肢治疗。方法 对1992年～2001年收治的胫骨成骨肉瘤75例，采用插入式微波天线阵列诱导高温原位灭活，辅以手术前、后化疗及术后免疫治疗，并按Enneking标准评价肢体关节功能。结果 平均随访4．5年，术后6个月～2．2年内因肿瘤转移而死亡者17例，存活58例，存活率77．3％。存活者中，3例因局部复发而截肢，1例复发者行瘤段截除大段异体骨植骨融合。对58例肢体关节功能评价：优39例；良15例；因复发行瘤段截除大段异体骨融合者可；3例截肢者配带假肢功能差。结论插入式微波天线阵列诱导高温原位灭活胫骨成骨肉瘤，并辅以化疗、免疫治疗，安全、有效，可望普及推广。     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.     

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 or elmex gelee. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In nonirradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 or elmex gelee led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected by remineralization than the dentine.     

Consultation multidisciplinaire pour les patients atteints d’une pathologie tumorale (carcinome infiltrant ou lésion précancéreuse) liée à HPV : la consultation multidisciplinaire papillomavirus

Given the recent increase in the number of human papillomavirus (HPV)-induced cancers in other locations than gynaecological, the number of patients with two cancers at distinct sites, and because of the lack of exhaustive data, we decided to create a multidisciplinary network around an HPV consultation at the Georges-Pompidou European Hospital (HEGP). This network aims to set up the best tools for detecting HPV-associated “multisite” precancerous lesions in order to determine the possible impact of dedicated care for this at-risk population. This monthly consultation was created at the HEGP in June 2014. It is currently organized around five consultations: gynaecological, ENT, urological, digestive and immunological. Every patient who has been diagnosed with HPV-related cancer and whose care is provided at the HEGP is offered this particular follow-up: systematically, once the initial lesion has been treated, the patient is convened annually for a day during which it benefits from the consultations mentioned above. A consultation with a psychologist is systematically proposed. Local samples are taken at each site: a cytological examination, the analysis of known predictive and prognostic virological markers are carried out. This study fits more broadly in a theme of clinical and fundamental research around cancers related to HPV.     

Differentiation state and invasiveness of human breast cancer cell lines

Summary Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and ₁ and ₄ integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47D_CO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis.