MRI在鼻咽癌分期中的作用

背景与目的:随着磁共振成像(magnetic resonance imaging,MRI)的广泛应用,MRI对于鼻咽癌的诊断价值已被证实明显优于CT.本研究旨在分析MRI与CT检查对鼻咽癌'92分期及6th UICC/AJCC分期的影响.方法:收集2003年1月至2004年6月收治的、经病理证实的初诊鼻咽癌250例,所有病例同时具有治疗前鼻咽和颈部的增强CT及MRI资料.结合临床资料如颅神经受损及颈淋巴结大小,分别采用CT和MRI检查进行'92分期及6th UICC/AJCC分期,评价两者之间的差异.结果:MRI在诊断鼻咽癌软组织超腔侵犯(口咽、鼻腔、咽旁间隙)、咽后淋巴结转移以及颅底骨质、副鼻窦、海绵窦/颅内、颞下窝及颈椎侵犯等方面均明显优于CT,而对于颈部巴结转移的检出两者无显著性差异.对于'92分期,MRI使32.0%的T分期发生改变(26.0%升级,6.0%降级);11.6%的N分期发生改变(6.4%升级,5.2%降级);30.4%的临床分期发生改变(24.0%升级,6.4%降级).对于6th UICC/AJCC分期,MRI使39.6%的T分期发生改变(36.0%升级,3.6%降级);9.2%的N分期发生改变(5.6%升级,3.6%降级);37.6%的临床分期发生改变(33.6%升级,4.0%降级).结论:MRI检测鼻咽癌局部病灶的侵犯范围要明显优于CT,而在颈部淋巴结转移的检出方面与CT结果相似.建立新的、以MRI为主要手段的鼻咽癌临床分期系统的研究具有临床必要性及可行性.     

鼻咽癌2008分期和第7版UICC分期的比较研究

目的:通过对鼻咽癌2008分期和第7版UICC分期的比较,探讨其合理性,为2008分期的修订完善提供参考.方法:收集广西医科大学第一附属医院放疗科收治的经病理证实、无远处转移的初诊鼻咽癌患者100例,按各个分期标准中提及的所有解剖结构进行MRI阅片,结合患者就诊时的临床体检资料(如脑神经麻痹、淋巴结大小等),按鼻咽癌两种临床分期标准进行分期.结果:解剖结构定义不同的鼻腔受侵16例(第7版UICC 27例)、口咽受侵犯3例(第7版UICC 11例),两种分期中T1、T2例数完全相同.T3、T4例数有一定差别,这与第7版UICC分期中将鼻窦受侵归为T3有关.N0例数完全相同,N1例数相差最大,未出现淋巴结最大径>6cm的病例,临床总分期基本一致.Ⅲ+Ⅳ期病例分别为97例和95例,晚期病例占绝大多数.结论:两种分期鼻咽和口咽、鼻腔的分界不同,口咽和鼻腔受侵的T分期归属不同,但第7版UICC分期中鼻腔和口咽受侵均全部合并更高期别的T因素,所以未造成两种分期T1、T2例数的差别.2008分期中,翼内肌受侵(37%),100%合并同期别和更高期别T因素,故翼内肌的合理性有待研究.2008分期中副鼻窦受侵归为T4、咽后淋巴结归转移为N1a、N分期采用3cm的标准是合理的.可对RTOG(2006年版)颈部淋巴结影像学分区做适当调整,制定出锁骨上区的影像学边界,以便与UICC分期接轨.两种分期的脑神经受累的MRI诊断标准需要完善.     

鼻咽癌2008分期应用的研究

背景与目的：鼻咽癌2008分期自推出应用于临床至今已有半年,其分期标准以及对某些解剖结构的定义有别于鼻咽癌’92分期和UICC2002分期。本文旨在从MRI影像学的角度,探讨鼻咽癌2008分期标准的合理性,提出2008分期中没有涉及或明确定义的分期因素,分析2008分期是否使病例期别分布产生变化。方法：收集177例初治鼻咽癌患者的MRI资料,按各个分期标准中提及的所有解剖部位,分别标记受侵犯与否,按2008分期标准,鼻腔和鼻咽的分界为双侧上颌窦后壁的连线。结果：口咽、鼻腔、软腭、椎前肌、茎突后间隙、颅内、眼眶和第1、2颈椎100％,翼内肌、翼外肌及以外的咀嚼肌间隙95％以上合并同期别或更高期别T因素。本组76．3％有颈部淋巴结转移,其中Ⅱb区占91．9％;64．4％病例有咽后淋巴结转移,其中90．4％合并颈部淋巴结转移,咽后淋巴结〉3cm的有3例,按2008分期分别为T4N3M0、T2N1aM0、T4N1bM0。全组淋巴结包膜外侵犯63例,双侧颈淋巴结转移77例,这两项在相同最大横径和最长纵径中的比例差异没有统计学意义（P〈0．05）。11例腮腺淋巴结转移中（6．2％）1例为N0,1例为N1a,其余9例合并N1b以上的淋巴结转移。2008分期、UICC和’92分期的晚期病例分别为81．4％、78．5％和75．7％。结论：2008分期对鼻咽和鼻腔的分界定义偏前,以及将翼内肌列为T3,有其合理性;翼内肌和翼外肌之间的间隙受侵,应该给予明确定义;咽后淋巴结〉3cm,不论大小、侧数一律归为N1a．是合理可行的：淋巴结最大横径或最长纵径可能跟预后无关：淋巴结转移跨区时应该明确定义;腮腺淋巴结转移和耳前（咬肌前）淋巴结转移需要明确N分期归属;使用2008分期,对病例的分期分布影响不大。     

鼻咽癌临床分期因素意义的探讨

目的 通过对大宗鼻咽癌病例的临床分期因素分析,探讨随着影像学、放疗技术的进展及综合治疗策略的改进,鼻咽癌分期因素预测预后变化情况的意义。方法 回顾性分析无远处转移初治鼻咽癌患者749例,根据’92分期标准,以疾病相关死亡、局部复发及远处转移等作为观察指标,对性别、年龄、T、N分期等因素作单因素和多因素分析。结果 Ⅰ、Ⅱ、Ⅲ、Ⅳ期的病例数分别占4．0％、29．8％、33．6％和32．6％,各临床分期疾病相关生存曲线能较好地分开。单因素分析显示,所有与T和N分期有关的因素均有统计学意义;多因索分析显示,疾病相关死亡的独立预后因素有性别、年龄、口咽侵犯、副鼻窦侵犯、咽旁间隙受侵、颅神经受损、颅内侵犯及颈部淋巴结转移的部位、侧数等。局部复发的独立预后因素包括副鼻窦受侵、颅底骨质破坏、咽旁问隙受侵和颅内侵犯等。远处转移的独立预后因素包括咽旁间隙受侵、颅内侵犯、颈部淋巴结转移的部位、侧数等。结论 ’92分期标准基本能区分不同预后的患者,各临床分期的病例数分布较为合理,鼻咽癌分期因素的预后分析结果可为各种临床研究设计提供依据。T分期中可将各种颅神经受损情况归为同一期,使分期简单化。N分期中则应考虑颈部转移淋巴结单双侧的信息。     

咽后淋巴结转移在鼻咽癌分期中的意义

背景与目的：鼻咽癌咽后淋巴结转移的发生率高,＇92分期系统未明确其在临床分期中的意义,本研究旨在分析咽后淋巴结转移对鼻咽癌预后的影响及评价它在鼻咽癌分期中的意义。方法：收集1999年1月至1999年12月间中山大学肿瘤防治中心放疗科收治的经病理证实、治疗前进行鼻咽和颈部增强CT扫描的初诊鼻咽癌749例。多因素分析采用Cox风险比例模型、根据临床分期的原则,采用风险一致性、风险差异性、预后预测及分布及分布均衡性等指标进行评价。结果：咽后淋巴结转移的发生率为51.5%。T分期、N分期及临床分析晚的患者咽后淋巴结转移发生率分别为57.8%、60.3%和57.9%,高于早期患者的发生率（45.2%、47.6%和38.9%）,其差异均有统计学意义（P值分别为0.001、0.001、〈0.001）.咽后淋巴结转移患者和无咽后淋巴结转移患者5年总生存率分别为58.7%和72.2%,5年无远处转移生存率分别为74.5%和84.9%,其差异有统计学意义（P均〈0.001）多因素分析,咽后淋巴结转移并不是影响鼻咽癌总生存率的独立预后因素,对无远处转移生存率的影响有临界意义（P=0.053）。N0合并咽后淋巴结转移的死亡及远处转移的风险比分别为0.540及0.411,与N1组（0.601及0.555）相似。将其归为N1或T2比较,前者N分期预后的风险一致性较好,但N分期分布极不均衡,N1患者比例达50.2%。后者N分期及临床分期预后的风险差异性明显,且T、N分期及临床分期分布均衡性较好。结论：咽后淋巴结转移对鼻咽癌无远处转移生存率可以有影响,在目前92分期系统及现行的鼻咽癌原发灶放射治疗模式的情况下,将咽后淋巴结转移归为T2分期内容更符合分期的原则。     

鼻咽癌临床分期因素意义的探讨

目的通过对大宗鼻咽癌病例的临床分期因素分析,探讨随着影像学、放疗技术的进展及综合治疗策略的改进,鼻咽癌分期因素预测预后变化情况的意义。方法回顾性分析无远处转移初治鼻咽癌患者749例,根据’92分期标准,以疾病相关死亡、局部复发及远处转移等作为观察指标,对性别、年龄、T、N分期等因素作单因素和多因素分析。结果Ⅰ、Ⅱ、Ⅲ、Ⅳ期的病例数分别占4．0％、29．8％、33．6％和32．6％,各临床分期疾病相关生存曲线能较好地分开。单因素分析显示,所有与T和N分期有关的因素均有统计学意义;多因素分析显示,疾病相关死亡的独立预后因素有性别、年龄、口咽侵犯、副鼻窦侵犯、咽旁间隙受侵、颅神经受损、颅内侵犯及颈部淋巴结转移的部位、侧数等。局部复发的独立预后因素包括副鼻窦受侵、颅底骨质破坏、咽旁间隙受侵和颅内侵犯等。远处转移的独立预后因素包括咽旁间隙受侵、颅内侵犯、颈部淋巴结转移的部位、侧数等。结论’92分期标准基本能区分不同预后的患者,各临床分期的病例数分布较为合理,鼻咽癌分期因素的预后分析结果可为各种临床研究设计提供依据。T分期中可将各种颅神经受损情况归为同一期,使分期简单化。N分期中则应考虑颈部转移淋巴结单双侧的信息。     

应用磁共振成像技术探讨鼻咽癌咽后淋巴结转移的规律

目的采用磁共振成像(MRI)技术,探讨鼻咽癌咽后淋巴结转移的发生率、分布和转移规律。方法回顾性分析294例经病理证实的初治鼻咽癌患者的磁共振(MR)资料,分析咽后淋巴结转移与鼻咽癌原发灶侵犯部位、颈部淋巴结转移和鼻咽癌分期的关系。结果有165例(56.1%)患者发现有咽后淋巴结转移。从C1到C3水平,外侧组咽后淋巴结转移率呈递减趋势。口咽、鼻腔、茎突前后间隙侵犯和颈部淋巴结转移患者的咽后淋巴结转移率较高。294例患者中,有219例(74.5%)出现咽后淋巴结和颈部淋巴结转移,其中31例(10.5%)仅出现咽后淋巴结转移,54例(18.4%)仅出现颈部淋巴结转移,134例(45.6%)同时出现咽后和颈部淋巴结转移。T1、N0及Ⅰ期的患者咽后淋巴结转移率较低。结论咽后淋巴结转移与鼻咽癌早期局部侵犯及上颈链、颈后三角的淋巴结转移密切相关。咽后淋巴结和Ⅱ区颈部淋巴结均为是鼻咽癌淋巴结转移的首站。     

肿瘤体积在鼻咽癌不同分期系统中的意义比较

目的根据鼻咽癌（nasopharyngeal carcinoma,NPC）原发灶肿瘤、颈部转移淋巴结体积大小分别在鼻咽癌中国2008分期与美国癌症研究联合会（American Joint Committee on Cancer,AJCC）分期中的关系进行比较,验证两种分期系统中T分期、N分期的合理性。方法将100例鼻咽癌患者治疗前行磁共振增强扫描后,应用美国CMS适形调强4.0治疗计划系统进行NPC原发肿瘤靶区鼻咽部大体肿瘤体积（nasopharynx gross tumor volume,GTVnx）及颈部阳性淋巴结大体肿瘤体积（lymph node gross tumor volume,GTVnd）勾画和体积计算。结果在鼻咽癌T分期中,中国2008分期原发病灶肿瘤体积大小在不同T分期之间差异具有统计学意义（P=0.000）,两两比较中T2、T3分期差别不大,差异无统计学意义（P=0.225）;第7版AJCC分期中,原发病灶肿瘤体积大小在不同T分期之间差异具有统计学意义（P=0.000）,且两两比较,各组之间差异均有统计学意义（均P〈0.05）。在鼻咽癌N分期中,两种分期系统颈部转移淋巴结体积大小在不同N分期之间差异具有统计学意义（P=0.0008）,两两比较相邻N分期之间差异无统计学意义（均P〉0.05）。结论鼻咽癌原发灶肿瘤、颈部转移淋巴结体积与两种分期均具有相关性,建议将体积因素作为预后判断指标,鼻咽癌第7版AJCC系统在T2、T3分期较中国2008分期合理,建议中国2008分期进一步细化。     

鼻咽癌的CT与MRI对比研究

目的:比较CT与MRI对鼻咽癌侵犯部位检出率的差别;评价MRI相对于CT对92分期产生的影响.方法:收集2003年1月至2004年6月收治、经病理证实的初诊鼻咽癌250例,所有病例同时具有治疗前鼻咽和颈部的CT及MRI资料.在CT和MRI上分别评价各个解剖部位的受侵犯情况.结合临床资料分别采用CT和MRI进行92分期.结果:MRI对于鼻咽超腔、茎突前间隙、口咽、咽后淋巴结、颅底骨质、海绵窦、鼻窦、颈椎和颞下窝等侵犯的检出率明显高于CT,有统计学意义.CT与MRI对于鼻腔、茎突后间隙侵犯及颈部淋巴结的检出差别无统计学意义.MRI使32.0%的T分期发生改变;11.6%的N分期发生改变;30.0%的临床分期发生改变.结论:MRI对于诊断鼻咽癌的超腔侵犯、颅底骨质、鼻窦、海绵窦受侵,以及咽后淋巴结转移要明显优于CT;而在颈部淋巴结转移的检出方面与CT结果一致.MRI主要影响鼻咽癌92分期的T分期;对N分期影响不大,临床分期的改变将有利于指引治疗方案的调整.     

PET/CT与MRI在鼻咽癌淋巴结转移诊断和N分期中的比较研究

目的 比较PET／CT与MRI在鼻咽癌淋巴结转移诊断和N分期中的作用。方法116例鼻咽癌患者于治疗前行PET／CT和MRI检查。依据随访结果比较PET／CT和MRI在淋巴结转移诊断和N分期中的作用。结果116例患者的614个淋巴结的随访结果显示,阳性340个,阴性274个。PET／CT诊断转移淋巴结的敏感性、特异性及准确性分别为93．2％、98．2％和95．4％,而MRI分别为88．8％、91．2％和89．9％,两者各指标比较,差异有统计学意义（P〈0．05）。按1992年福州分期,109例（94．0％）的PET／CT分期正确,103例（88．8％）的MRI分期正确;按UICC分期,108例（93．1％）的PET／CT分期正确,100例（86．2％）的MRI分期正确。结论PET／CT判断鼻咽癌淋巴结转移和N分期较MRI准确,但对炎性增生、大面积坏死淋巴结,或直径小于PET空间分辨率的转移淋巴结应警惕其假阳性和假阴性判断。     

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.