中晚期喉癌患者颈部淋巴结转移状况及相关影响因素分析

目的：探讨中晚期喉癌患者颈部淋巴结转移情况及相关影响因素。方法回顾性分析68例中晚期喉癌患者颈部淋巴结转移与肿瘤原发部位、T分期、N分期、病理分级、临床分期、淋巴结受累侧数的关系,应用Logistic回归分析喉癌淋巴结转移相关因素和喉癌患者死亡的危险因素。结果68例患者中有16例发生淋巴结转移,转移率为23．53％。 Logistic回归分析的因素包括年龄、性别、病变部位、病理分级、T分期、N分期、临床分期、淋巴结受累侧数,结果显示,病理分级（P＝0．001）、T分期（P＝0．021）、临床分期（P＝0．007）是喉癌淋巴结转移的相关因素。淋巴结转移（P＝0．001）与T分期（P＝0．003）是喉癌患者死亡的危险因素,而N分期和病理分级对于喉癌患者死亡的影响差异无统计学意义。结论中晚期喉癌患者颈部淋巴结转移情况与病理分级、T分期、临床分期有关,喉癌患者的死亡因素与淋巴结转移和T分期相关。     

cN0声门上型喉癌的颈部复发相关因素分析

背景与目的:声门上型喉癌的隐性淋巴结转移率高,是此类喉癌诊治的重点之一。本研究旨在探讨声门上型喉癌的隐性淋巴结转移的相关因素、预后及治疗情况。方法:回顾分析1992～1999年我科收治的cN0声门上型喉癌104例,对其隐性淋巴结转移率、转移淋巴结的分布、影响隐性淋巴结转移的因素及颈部处理等进行研究。结果:本组cN0声门上型喉癌隐性淋巴结转移率为23.1%(24/104),其中T2期23.9%(11/46),T3期30.8%(8/26),T4期18.5%(5/17)。隐性转移淋巴结主要位于病变侧Ⅱ、Ⅲ区(22/24)。出现隐性转移组预后差(log-rank=10.66,P=0.001)。切缘阳性影响隐性淋巴结转移率(χ2=10.015,P=0.002)。病理分化程度(χ2=3.349,P=0.175)、T分期(χ2=2.701,P=0.440)、原发灶处理方式(χ2=1.093,P=0.296)等对隐性淋巴结转移率影响差异无统计学意义。颈部选择性清扫能降低cN0声门上型喉癌隐性淋巴结转移率(χ2=4.070,P=0.044)。结论:cN0声门上型喉癌的隐性淋巴结转移主要位于病变侧Ⅱ、Ⅲ区;出现隐性淋巴结转移影响预后;切缘阳性影响隐性淋巴结转移率;对T1N0期喉癌颈部可观察,T2-4N0期喉癌行侧颈清扫(Ⅱ～Ⅳ区)是合理有效的。     

65例喉癌患者预后影响因素分析

背景与目的：既往研究表明T分期和N分期是喉癌预后的独立影响因素。本研究回顾分析本院治疗的65例喉癌患者，进一步探讨喉癌的生存情况及预后影响因素。方法：收集2000年8月-2007年12月65例喉鳞状细胞癌患者的临床和预后资料，选择9个临床因素，通过单因素分析和Cox模型多因素分析，确定喉癌患者的预后影响因素。结果：经过中位随访期28个月，死于局部复发5例，颈淋巴结转移3例，远处转移2例，非本病死亡2例，原因不明2例。65例患者的3年生存率为74．9％，5年生存率为70．5％。单因素分析结果显示，临床总分期（P=0．021）、N分期（P=0．001）、临床分型（P=0．003）、有无复发（P=0．000）对预后的影响有统计学意义（P〈0．05），而年龄、T分期、病理分级、治疗方法与患者的预后无关。Cox多因素分析结果显示，T分期（P=0．006）、淋巴结转移（P=0．025）、复发（P=0．002）和临床分型（P=0．018）是喉癌预后的独立影响因素。结论：喉癌患者预后的独立影响因素是T分期、淋巴结转移、复发、临床分型。坚持治疗后随访、及早发现肿瘤复发、及时行挽救性治疗是提高喉癌患者生存率的关键。     

声门上喉癌临床 N0期病例隐性颈淋巴结转移的预测

目的：探讨声门上喉癌临床N0期病例隐性颈淋巴结转移的相关因素。材料和方法：回顾1982年至1991年于中山医科大学肿瘤医院住院治疗的81例声门上喉癌病例资料，其中48例为临床N0期病例。应用单因素Kaplan-Meier与多因素Cox模型分析影响声门上喉癌临床N0期病例隐性颈淋巴结转移的因素。结果：本组81例声门上喉癌中33例（40．7％）出现颈淋巴结转移。48例临床N0期的病例中隐性颈淋巴结转移率为23％（11／48）。出现和未出现隐性颈淋巴结转移的5年生存率分别为0％和86．5％，存在显著性差异（Log Rank=24.55，P＝0．0000）。20例T1＋T2及28例T3＋T4病例的隐性颈淋巴结转移率分别为28．2％和35．6％，无显著性差异（LogRank=0.02,P=0.9000)。鳞癌高、中、低分化的隐性颈淋巴结转移率分别为12．2％，45．3％和50％，存在显著性差异（Log Rank=6.97,P=0.0307)。多因素Cox模型分析亦显示仅鳞癌病理分化级别显著隐性颈淋巴结转移（P＝0．0337）。结论：鳞癌病理分化级别是声门上喉癌临床N0期病例隐性颈淋巴结转移的相关因素，低分化鳞癌易出现隐性颈淋巴结转移。     

T3-T4期声门型喉癌颈淋巴结转移情况及其与预后的关系

背景与目的:声门型喉癌颈淋巴结转移率低,有关报道不多,本研究旨在探讨T3-T4期声门型喉癌颈淋巴结转移的相关因素及其对预后的影响。方法:回顾性分析我院1992～2000年收治T3-T4期声门型喉癌83例的临床资料,对颈淋巴结转移率、转移淋巴结的分布、影响cN0颈部复发的因素(颈部预防性放疗、病理分级及T分期)、淋巴结转移与预后的关系。结果:T3-T4期声门型喉癌,总的颈淋巴结转移率为20.5%,cN0颈部复发率为14.3%。绝大多数转移淋巴结位于同侧Ⅱ、Ⅲ、Ⅳ区,仅1例位于对侧Ⅱ区。cN0者中,颈部预防性放疗与颈部观察在颈部复发率上无差异(P=0.772);病理分级影响cN0颈部复发率(P=0.028);不同T分期颈部复发率无差异(P=0.217)。cN 患者预后明显差于cN0患者(P<0.001);cN0颈部复发不影响预后(P=0.460)。对T3-T4期声门型喉癌cN 患者采用治疗性颈清扫;对cN0患者颈部可密切观察,待出现淋巴结复发再积极治疗。结论:T3-T4期声门型喉癌主要转移至同侧Ⅱ、Ⅲ、Ⅳ区;病理组织分化级别越差,cN0颈部复发的风险越大;cN0颈部复发与预后无关;对cN0患者颈部可进行密切观察;对出现淋巴结复发者应积极治疗。     

喉癌中央区淋巴结转移：11年喉癌手术病例回顾性分析

背景与目的：对于喉癌患者是否常规行颈部中央区淋巴结清扫,目前尚存在争议。本研究探讨喉癌患者中央区和侧颈区淋巴结转移、颈部复发以及疾病预后生存情况。方法：回顾性分析1999—2009年复旦大学附属肿瘤医院收治的118例确诊为喉癌患者的临床病理资料。其中34例患者行颈部中央区淋巴结清扫。回顾分析肿瘤原发灶分级,中央区和侧颈区淋巴结转移临床资料,以及患者总生存率(overall survival, OS),无病生存率(diseas-free survival, DFS)和局控率(local control rate, LCR)。结果：在118例喉癌患者中,颈部中央区淋巴结转移率为11.9%(14/118),包括在34例中央区淋巴结清扫患者中证实10例,未作淋巴结清扫,在随访中发现中央区淋巴结转移4例。肿瘤声门下或者梨状窝侵犯是中央区转移以及中央区复发的危险因素(P=0.002)。中央区淋巴结转移与颈部IV区转移相关(P<0.001),侧颈区淋巴结包膜外侵犯(P=0.001)和血管侵犯(P=0.015)是中央区淋巴结转移、中央区复发和颈侧区复发的危险因素。中央区淋巴结转移阳性喉癌患者较阴性患者局控率低(P=0.035)。侧颈区淋巴结转移阳性患者较阴性患者无病生存率(P=0.014)和局控率(P=0.025)低。声门上喉癌更容易发生颈部Ⅱ区淋巴结转移(P=0.044)。结论：喉癌患者应注意中央区淋巴结清扫。声门上喉癌患者应注意颈部Ⅱ区淋巴结清扫。中央区淋巴结转移阳性患者应注意颈部Ⅳ区淋巴结清扫。     

局部晚期喉癌颈部淋巴结转移规律及相关因素分析

目的 分析局部晚期(T3、T4期)喉癌颈部淋巴结转移(LNM)规律,为喉癌放疗颈部靶区勾画提供参考。方法 回顾分析2000-2017年中国医学科学院肿瘤医院初治局部晚期喉癌患者,所有患者至少行双颈Ⅱ-Ⅳ区淋巴结清扫,计算颈部各区LNM率。采用Logistic回归分析LNM相关因素。结果 共272例患者纳入研究,全组患者LNM率为57.1%(156/272)。根据原发病变部位分3个组:A组(72例),原发灶局限于一侧;B组(86例),原发灶主体偏于一侧但侵犯过中线;C组(114例),原发灶为巨大或中央型病变。各组不同颈部分区LNM率:A组同侧颈部Ⅱ区36.3%、Ⅲ区26.4%、Ⅳ区6.9%,对侧分别为13.9%、8.3%、1.4%;B组:同侧颈部Ⅱ区41.9%、Ⅲ区29.1%、Ⅳ区11.6%,对侧分别为18.6%、14.0%、1.2%;C组:左侧Ⅱ区24.6%、Ⅲ区 23.7%、Ⅳ区2.6%,右侧分别为21.9%、26.3%、6.1%。局限单侧(A组)与中线受侵(B、C组)双侧LNM率相近(15.3%、25.0%,P=0.093)。同侧Ⅲ区是否转移和临床淋巴结分期与对侧颈是否LNM相关(OR=2.929,95%CI为1.041~8.245,P=0.042)和OR=0.082,95%CI为0.018~0.373,P=0.001)。同侧Ⅱ区、Ⅲ区转移是同侧Ⅳ区转移的危险因素(P=0.043、0.009)。结论 双侧颈部Ⅱ、Ⅲ区是高危LNM区,Ⅳ、Ⅴ区转移较少见;同侧Ⅱ、Ⅲ区转移是同侧Ⅳ区及对侧颈LNM的相关因素,cN0期患者少见对侧颈LNM。     

局部晚期喉癌颈部淋巴结转移规律及相关因素分析

目的 分析局部晚期(T3、T4期)喉癌颈部淋巴结转移(LNM)规律,为喉癌放疗颈部靶区勾画提供参考。方法 回顾分析2000-2017年中国医学科学院肿瘤医院初治局部晚期喉癌患者,所有患者至少行双颈Ⅱ-Ⅳ区淋巴结清扫,计算颈部各区LNM率。采用Logistic回归分析LNM相关因素。结果 共272例患者纳入研究,全组患者LNM率为57.1%(156/272)。根据原发病变部位分3个组:A组(72例),原发灶局限于一侧;B组(86例),原发灶主体偏于一侧但侵犯过中线;C组(114例),原发灶为巨大或中央型病变。各组不同颈部分区LNM率:A组同侧颈部Ⅱ区36.3%、Ⅲ区26.4%、Ⅳ区6.9%,对侧分别为13.9%、8.3%、1.4%;B组:同侧颈部Ⅱ区41.9%、Ⅲ区29.1%、Ⅳ区11.6%,对侧分别为18.6%、14.0%、1.2%;C组:左侧Ⅱ区24.6%、Ⅲ区 23.7%、Ⅳ区2.6%,右侧分别为21.9%、26.3%、6.1%。局限单侧(A组)与中线受侵(B、C组)双侧LNM率相近(15.3%、25.0%,P=0.093)。同侧Ⅲ区是否转移和临床淋巴结分期与对侧颈是否LNM相关(OR=2.929,95%CI为1.041~8.245,P=0.042)和OR=0.082,95%CI为0.018~0.373,P=0.001)。同侧Ⅱ区、Ⅲ区转移是同侧Ⅳ区转移的危险因素(P=0.043、0.009)。结论 双侧颈部Ⅱ、Ⅲ区是高危LNM区,Ⅳ、Ⅴ区转移较少见;同侧Ⅱ、Ⅲ区转移是同侧Ⅳ区及对侧颈LNM的相关因素,cN0期患者少见对侧颈LNM。     

淋巴结转移率在T3期胃癌预后中的临床意义（附347例）

目的:探讨T3期胃癌患者淋巴结转移率的影响因素及淋巴结转移率对于预后生存的临床意义。方法:回顾性分析2007年1月至2010年12月期间哈尔滨医科大学肿瘤医院347例接受手术治疗的T3期胃癌患者的临床病理资料,通过χ2检验分析淋巴结转移率与相关临床病理因素之间的关系;Logistic回归分析淋巴结转移率的影响因素;利用Kaplan-Meier法绘制生存曲线图以及Log-rank检验比较不同组间患者生存率的差异;采用Cox比例风险回归模型对患者预后进行分析。结果:与淋巴结转移率≤28.66%组相比,淋巴结转移率>28.66%组患者肿瘤病理分型较差［93.3%(127/136) vs 76.8%(162/211),P=0.000］,肿瘤位于全胃的比例较高［12.5%(17/136) vs 3.8%(8/211),P=0.002］,肿瘤直径较大［49.3%(67/136) vs 27.5%(58/211),P=0.000］,血清CEA浓度较高［33.1%(45/136) vs 22.7%(48/211),P=0.034］,远处器官发生转移的几率较大［11.0%(15/136) vs 2.4%(5/211),P=0.001］。Logistic回归分析表明:肿瘤位置(全胃)、肿瘤直径(>6.1 cm)、病理分化类型(分化较差)、血清CEA水平(>5 ng/ml)、血清白蛋白浓度(≤40 g/L)是导致淋巴结转移率较高的危险因素(均P<0.05)。随访期间内有233例(67.1%)患者因肿瘤进展死亡;术后5年生存率为33.1%。单因素分析表明:年龄≤60岁、根治性手术、肿瘤单发、淋巴结转移率≤28.66%、M0、肿瘤直径≤6.1 cm、血清CA19-9≤37 U/ml的T3期胃癌患者预后较好(均P<0.05),而淋巴结的清扫数目并不影响患者的预后生存(P=0.089);多因素分析显示:年龄［HR(95%CI):1.487(1.139~1.941),P=0.004］、手术［HR(95%CI):1.741(1.205~2.515),P=0.003］、淋巴结转移率［HR(95%CI):3.053(2.293~4.065),P=0.000］、是否发生远处转移［HR(95%CI):1.766(1.043~2.991),P=0.034］是T3期胃癌患者的预后独立危险因素。结论:淋巴结转移率是影响T3期胃癌患者预后的独立危险因素,而肿瘤位置、病理分化类型、肿瘤直径、血清CEA浓度、远处器官发生转移是淋巴结转移率的影响因素。因此,对于T3期的胃癌患者,术前可以通过相关血液、影像检查,对患者的淋巴结转移率及预后进行准确而有效的评估。     

333例声门型喉癌颈淋巴结转移与预后的关系

背景与目的:声门型喉癌颈淋巴结转移率不高,颈部处理尚无统一认识.本研究探讨声门型喉癌颈淋巴结转移的预后及其影响因素.方法:收集1992年1月1日至2000年12月31日中山大学肿瘤防治中心收治的333例声门型喉癌患者的临床资料,对颈淋巴结转移情况、预后及颈部处理进行回顾性分析.结果:全组患者总的颈淋巴结转移率9.61%(32/333),隐性淋巴结转移率6.23%(20/321).绝大多数转移淋巴结位于同侧Ⅱ、Ⅲ、Ⅳ区(28/32).病理分化级别与总的淋巴结转移率(P=0.092)及隐性淋巴结转移率(P=0.067)无明显相关性.总的淋巴结转移率(P=0.002)及隐性淋巴结转移率(P=0.015)随T分期升高而增高.cN0患者颈选择性放疗对隐性淋巴结转移率的影响无显著性(P=0.363).初治cN 组(3、5年生存率分别为56.25%、46;67%)预后差于初治cN0组(3、5年生存率分别为88.70%、85.37%)(P＜0.001);初治cN0组中出现隐性淋巴结转移的预后(3、5年生存率分别为68.18%、63.31%)差于未出现隐性淋巴结转移(3、5年生存率分别为89.00%、85.55%):初治cN 组有淋巴结转移的预后(3、5年生存率分别为41.67%、16.67%)差于初治cNO组中出现隐性淋巴结转移组(3、5年生存率分别为68.18%、63.31%)(P=0.004).结论:声门型喉癌绝大多数转移淋巴结位于同侧Ⅱ、Ⅲ、Ⅳ区,最多位于同侧Ⅱ区;声门型喉癌颈淋巴结转移影响预后.     

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.