572例放疗前CT扫描的鼻咽癌患者的生存分析:探讨提高生存率的关键因素

连续抽取中山医科大学肿瘤医院CT室1984年4月至1987年7月所有经病理证实,放射治疗前CT扫描的鼻咽癌572例,以CT显示肿瘤原发灶的准确范围为基础,采用多因素Cox模型,分析各受侵部位对预后的意义,探讨提高鼻咽癌生存率的关键因素。结果表明,正确的T分期是影响生存的最主要因素,其次是N分期。通过对原发病灶15个因素的筛选,按比例危险度的大小列出了主要影响生存的受侵部位。强调加强对颈动脉鞘区的完全控制是提高鼻咽癌生存率的关键因素之一。     

Computed tomographic findings of nasopharyngeal carcinoma with skull base and intracranial involvement

Twenty-nine patients with nasopharyngeal carcinoma (NPC) with skull base or intracranial involvement were analyzed by high-resolution computed tomography (CT). We divided the path of the primary tumor spread into six directions from the nasopharynx. The most common direction of spread was the anterior region, and the second most common was the posterolateral region. Recently, high resolution CT has been used for the diagnosis of the nasopharynx. T-staging of NPC was made according to the International Union Against Cancer (UICC) TNM classification system, depending on clinical findings and conventional radiograph examinations (not including CT). CT images were valuable for detection of the primary tumor involvement of the skull base region in NPC. Furthermore, bone target CT images were better for searching for subtle bony changes. Therefore, we recommend that CT should be used in T-staging of NPC systematically. When CT is used as one of the staging criteria, some patients with NPC with subtle bony changes will be upstaged.     

Ku70蛋白在鼻咽癌组织中的表达及临床意义

目的:探讨接受根治性放疗鼻咽癌(nasopharyngeal carcinoma,NPC)患者Ku70蛋白的表达与患者预后的关系。方法:符合入组条件的73例鼻咽癌放疗前活检标本,应用免疫组织化学技术检测Ku70的表达,并分析Ku70表达与NPC的分期,复发,转移,生存率之间的关系。结果:NPC原发灶中Ku70阳性表达率为98.7%。χ2分析Ku70蛋白高表达与T分期密切相关(P<0.01),与N分期和TNM分期无关。Cox分析显示Ku70蛋白与鼻咽癌的局控率、无进展生存率、总体生存率有关系,与无远处转移生存率无关。Ku70不或低表达者的局控率、无进展生存率、总体生存率均较高,反之则较低,各曲线之间差异具有统计学意义(P<0.05)。结论:Ku70的高表达能预测肿瘤复发,对判断鼻咽癌预后有重要的参考价值。     

Conversion of T-stages of nasopharyngeal carcinoma by computed tomography

Thirty-six patients with nasopharyngeal carcinoma (NPC) were examined with computed tomography (CT) before definitive radiation therapy. CT clearly delineated the extent of the primary tumors. CT frequently showed subtle destruction of the paranasal sinuses and pterygoid plate, which was not usually detected by conventional X ray examinations. T-staging was made according to the UICC TNM classification system (1978) or another system, depending on clinical findings and the conventional X ray examinations (non-CT T-stage). Then, the non-CT T-stage of each patient was compared with T-stage diagnosed with CT findings alone (CT T-stage). CT upstaged non-CT T-stage in 14 of the 36 patients according to either system. Only one patient was downstaged by CT; this patient had cranial nerve palsy but no detectable bone destruction as shown by CI. We conclude that CT is the single, most reliable imaging method for primary tumors of NPC patients. Since CT detects subtle bone destruction, however, a large number of patients will be classified as having advanced tumors. Further modification of the TNM system may be needed for NPC patients in this era of CT.     

Magnetic Resonance for T-staging of nasopharyngeal carcinoma--the most informative pair of sequences

OBJECTIVE: To evaluate the most informative pair of sequences in magnetic resonance (MR) for T-staging of nasopharyngeal carcinoma (NPC). METHODS: The MR images of 134 patients with newly diagnosed NPC, from 1996 to 2002, were retrospectively reviewed. All the patients were scanned using 1.5 Tesla MR systems. The images of the nasopharynx were reviewed by two qualified radiologists to determine the positive findings and the T-stage by UICC (6th edition) System, using each sequence separately. The T-stage derived from a single MR sequence was then compared with the T-stage based on the five selected sequences to assess the number and percentage of patients who were being understaged. Therefore, the overall percentage accuracy of each single sequence could be determined. A pair of sequences providing information to achieve almost 100% diagnostic accuracy was then derived. RESULTS: The overall percentage accuracy of five individual sequences of the nasopharynx is as follows: contrast-enhanced (CE) fat suppression (FS) axial T1 (94.8%), CE FS coronal T1 (88.1%), FS axial T2 (85.8%), non-contrast enhanced (NE) axial T1 (78.4%) and non-contrast enhanced (NE) coronal T1 (77.6%). CE FS axial T1 has the best accuracy. All the structures that are missed in CE FS axial T1, which lead to apparent understaging, are appreciated in NE axial T1-weighted images. CONCLUSION: Individual sequences supplement each other in the NPC staging. CE FS axial T1 is the most informative individual sequence. Combination of CE FS axial T1 and NE axial T1 of the nasopharynx provides sufficient information to achieve almost 100% diagnostic accuracy in T-staging; therefore, both should be included in the MR-staging protocol.     

Serglycin is a theranostic target in nasopharyngeal carcinoma that promotes metastasis

Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial-mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients.     

鼻咽癌多药耐药相关蛋白表达与原发灶放疗敏感性关系的研究

目的:探讨多药耐药相关蛋白(multidrug resistance-associated protein,MRP)在鼻咽癌中的表达以及与原发灶放疗敏感性的关系。方法:回顾性分析我科1999年1月~2000年12月治疗的鼻咽癌共51例。采用免疫组化S-P法,检测鼻咽癌中MRP的表达,并评价其表达与鼻咽癌原发灶放疗敏感性的关系。结果:鼻咽癌中MRP的阳性表达率为68·63%(35/51),其表达在低T分期(T1-2)和高T分期(T3-4)间差异有显著性意义(P<0·05),MRP表达与原发灶放疗敏感性无关,差异无显著性意义(χ2=0·000,P>0·05)。结论:鼻咽癌中MRP呈高表达,其表达与原发灶放疗敏感性无关,不能作为鼻咽癌原发灶放疗敏感性的预测指标。     

鼻咽癌分期的研究—评’92福州分期标准

研究鼻咽癌分期。材料与方法首次放疗前经ＣＴ扫描检查的鼻咽癌２０４例，１９７９年长沙分期法和１９９２年福州分期法进行评价。结果本组随访率为９４．６％，５年生存率为５２．２％。按’９２福州分期法本组各项分布是：Ⅰ期２．５％，Ⅱ期２２．１％，Ⅲ期４８．５％，Ⅳ期２４．０％，Ⅳｂ期２．９％：各期５年生存率分别是８０％，７６．２％，５２．７％，４３．７％和０％。结论作者建议：（１）将原发肿瘤局限在鼻咽腔者列为Ｔ１。（２）将Ⅳ期分为Ⅳ。期（Ｔ４或Ｎ３）和Ⅳｂ期（任何Ｔ，任何Ｎ，Ｍ１）。     

环氧化酶-2对鼻咽癌血管生成及预后的影响

Objective： The purpose of this study was to evaluate cyclooxygenase-2 （COX-2） expression in nasopharyngeal carcinoma （NPC） and its correlation with clinicopathologic features, angiogenesis, and prognosis. Methods： The expressions of COX-2 and vascular endothelial growth factor （VEGF） and microvascular density （MVD） were determined with immunohistochemical methods in eighty-six NPC patients followed up over 5 years. Results： Sixty-three tumors （73.3%） were classified as COX-2 positive. COX-2 expression was positively related to VEGF expression （r=0.438, P〈0.01） and correlated with the tumor pathological grade, extent of primary lesion, lymph node metastasis, distant metastasis and shorter survival. Conclusion： Our results suggest that COX-2, being highly expressed and strongly correlated with angiogenesis in nasopharyngeal carcinoma, is apt to be used as a predictor of prognosis, including local recurrence and distant metastasis.     

335例鼻咽癌根治性放疗后晚期反应分析

目的 分析我院鼻咽癌患者根治性常规放疗后长期生存情况和晚期反应.方法 我院335例经病理证实为鼻咽癌的初治患者均接受根治性常规放疗,57.0％的患者接受顺铂+氟尿嘧啶为主的化疗.观察并记录患者的长期生存情况和晚期反应.结果 随访率92.2％,中位随访时间55(1～104)个月.全组5年总生存率、无进展生存率、无复发生存...     

FDG PET-CT相关参数对鼻咽癌预后影响研究

目的 鼻咽癌是一种具有特殊地域性分布和生物学行为的头颈部肿瘤,研究显示FDG PET-CT相关参数在高发区鼻咽癌预后中具有一定价值。本研究探讨FDG PET-CT相关参数对低发区鼻咽癌的预后价值。方法 回顾分析2003—2013年在Albert Einstein医学院Beth Israel医疗中心诊治的 83例鼻咽癌患者资料,采用梯度法并依据PET-CT图像指导靶区勾画,获取FDG PET-CT参数 SUV_max、MTV、TLG。结果 3年样本数 37例,3年FFS率为74%,3年LRFS率为88%,3年DMFS率为85%。单因素分析结果显示 SUV_max、TLG是 3年LRFS和FFS的影响因素(P=0.004、0.014和 P=0.024、0.033),多因素分析结果显示 SUV_max是 3年FFS的影响因素。结论 治疗前原发肿瘤 SUV_max是影响鼻咽癌患者FFS的因素。     

Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma

BACKGROUND: Interleukin-10 (IL-10) has been implicated as an important modulator of lymphoid cells, and its sequence is homologous to an open reading frame in the Epstein-Barr virus (EBV) genome. Nasopharyngeal carcinoma (NPC) is a representative tumor related to EBV infection. METHODS: The authors investigated the expression of IL-10 in 21 primary NPCs by using an immunohistochemical approach to examine its prognostic significance. RESULTS: IL-10 staining was positive in 12 of 21 primary NPCs (57%). There was no association between IL-10 expression and gender, tumor size, the occurrence of lymph node metastases, clinical stage, or recurrence. However, there was a significant difference in overall survival between the negative expression and positive expression of IL-10 (P = 0.0348). Although 87.5% of the IL-10 negative group survived for 5 years, only 15.6% of IL-10 positive patients survived for that length of time by the Kaplan-Meier method. IL-10 expression was significant as an independent prognostic indicator of overall survival by multivariate analysis using the Cox proportional hazards model (odds ratio, 26.64; P = 0.0019). CONCLUSIONS: The results imply that expression of IL-10 is a prognostic factor in patients with NPC and may prove valuable in selecting patients with NPC who are candidates for aggressive therapy.     

调强放疗时代诱导化疗在Ⅱ~Ⅳa期鼻咽癌中的研究进展

调强放射治疗的应用使得鼻咽癌的生存得到显著改善,但Ⅱ~Ⅳa期鼻咽癌治疗失败的主要原因仍为远处转移。诱导化疗由于具有减轻肿瘤负荷、消除微转移等优势在临床得到广泛关注,但诱导化疗在Ⅱ期鼻咽癌中的应用价值以及在局部晚期鼻咽癌中的最佳治疗模式尚不明确,全文回顾分析近年来诱导化疗联合调强放疗的相关研究,就调强放疗时代诱导化疗在Ⅱ~Ⅳa期鼻咽癌中相关进展作一综述。     

As an independent unfavorable prognostic factor, IL-8 promotes metastasis of nasopharyngeal carcinoma through induction of epithelial-mesenchymal transition and activation of AKT signaling

Nasopharyngeal carcinoma (NPC) has the highest metastatic potential among head and neck cancers. Distant metastasis is the major cause of treatment failure. The role of interleukin-8 (IL-8) in NPC progression remains unknown. Our multivariate survival analyses of 255 patients with NPC revealed that higher IL-8 expression in primary NPC tissue was an independent prognostic factor for overall survival, disease-free survival, and distant metastasis-free survival of the patients. In vitro study revealed that IL-8 was highly expressed in the established high-metastasis NPC clone S18 relative to the low-metastasis cells. Suppression of IL-8 by short-hairpin RNA reduced the expression of IL-8 in S18 cells and subsequently inhibited migration, invasion, and hepatic metastasis of the cells without influencing cellular growth. Overexpression of IL-8 in S26 cells resulted in increased migration, invasion, and metastasis capabilities of the cells without affecting cellular growth. Exogenous IL-8 enhanced the migration and invasion of low-metastasis CNE-2 cells in a dose-dependent manner. An epithelial-mesenchymal transition (EMT) could be induced by IL-8 in various NPC cell lines. The high level of phosphorylated AKT in S18 cells could be suppressed by knocking down IL-8 expression. Further, IL-8-promoted migration and invasion could be abolished by either the application of the phosphoinositide-3-kinase inhibitor LY294002 or the knock down of AKT expression by using small-interfering RNA. In summary, IL-8 serves as an independent prognostic indicator of overall survival, disease-free survival, and metastasis-free survival for patients with NPC. IL-8 promotes NPC metastasis via autocrine and paracrine means, involving activation of AKT signaling and inducing EMT in NPC cells.     

鼻咽癌调强放疗后长期生存结果及失败模式分析

目的 回顾分析IMRT治疗鼻咽癌的10年生存结果及失败模式,为鼻咽癌的优化治疗提供参考。方法 收集2001-2008年间865例采用IMRT的鼻咽癌患者的临床资料。生存分析采用Kaplan-Meier法,Logrank检验和单因素分析,Cox模型多因素预后分析。结果 中位随访时间为132.0个月,全组患者10年无局部复发生存(LRFS)、无远处转移生存(DMFS)、无进展生存(PFS)、肿瘤特异生存(DSS)分别为92.0%、83.4%、75.7%、78.6%。共210例死亡,其中124例(124/210,59.0%)死于远处转移, 47例(41/210,22.3%)死于局部区域复发。DSS的独立不良预后因素包括年龄>50岁(P=0.00)、LDH≥245 IU/L (P=0.00)、Hb<120 g/L (P=0.01)、T2-T4期(P=0.00)、N1-N3期(P=0.00)和GTV-nx>20 cm³(P=0.00)。Ⅱ期鼻咽癌患者单纯放疗组与联合化疗组10年LRFS、DMFS、DSS均相近(P=0.83、0.22、0.23),Ⅲ期鼻咽癌患者联合化疗组10年LRFS、DSS均优于单纯放疗组(P=0.01、0.01)但10年DMFS相近(P=0.14),Ⅳ a+Ⅳ b期患者总体预后较差。结论 IMRT改善了鼻咽癌患者的远期生存,远处转移成为最主要的失败模式;而Ⅰ-Ⅱ期患者采用单纯IMRT可取得满意生存结果,联合化疗可进一步提高Ⅲ期患者LRFS及DSS,而Ⅳ a+Ⅳ b期患者治疗模式仍需更多探讨。     

鼻咽癌复发的影响因素及再程放疗的效果——附214例分析

我院1985年1422例首程放疗的鼻咽癌患者五年内复发214例。原发灶与颈淋巴结五年复发率分别为11.18和7.17％,头三年内复发占85.05％。本文资料显示原发灶复发与首程放疗靶区遗漏有密切关系,颈淋巴结复发与首程放疗前的大小及活动度有密切关系。提示减少复发的关键在于首程放疗,要做到准确确定靶区范围和合理设计照射野。再程放疗由于仍是简单重复首程放疗方法,故疗效不佳,与未再程放疗比较,仅显示SR_1有差别(P<0.05),放疗组中,颈淋巴结复发的SR_3较原发灶、原发灶加颈淋巴结同时复发组有明显差别(P<0、01)、再程放疗的后遗症发生相当高,提示需个别化地选用最佳方案行再程放疗及需要寻找优于单纯放疗的综合治疗方案,才能提高再程放疗的效果及改善生存质量。     

鼻咽癌放疗后第二原发舌鳞癌35例

 目的　探讨鼻咽癌放疗后第二原发舌鳞癌的临床特点、有效的治疗手段、生存情况和影响预后的因素。方法　回顾性分析35例鼻咽癌放疗后第二原发舌鳞癌患者的临床和随访资料,应用Kaplan-Meier法及Log-Rank检验、COX回归模型等对本组病例资料进行统计分析。结果　35例患者总的3、5年生存率分别为55 %、47 %,淋巴结转移率为5.71 %;单因素分析提示性别（χ2＝8.89,P＝0.00）、T分级（χ2＝5.58,P＝0.02）、临床分期（χ2＝8.51,P＝0.04）、治疗方法（χ2＝29.37,P＝0.00）是影响预后的重要因素;多因素分析显示治疗方法（P＝0.00）、T分级（P＝0.03）是与预后有关的重要独立因素;手术治疗组较非手术治疗组预后好,差异有统计学意义（P <0.05）;男性患者发生第二原发舌鳞癌的风险较女性患者高;第二原发舌鳞癌随鼻咽癌放疗后时间的延长发病率升高。结论　鼻咽癌放疗后第二原发舌鳞癌淋巴转移率较低;治疗方法和T分期是影响预后的独立因素;鼻咽癌放疗后需长期随访,早期诊断第二原发舌鳞癌,并给予手术或包含手术的综合治疗,以取得好的疗效。     

Patterns of failure in nasopharyngeal cancer treated with megavoltage irradiation

From 1976 to 1982, 78 patients with nasopharyngeal cancer (NPC) were treated with definitive megavoltage irradiation in accordance with a uniform protocol. The results of treatment were analyzed and prognostic factors reviewed. The incidence of primary failures was directly related to the extent of nasopharyngeal disease, since the relapse rate was 11% in T1T2 patients compared with 37.5% in T3T4 patients. Similarly, failure in the neck correlated with the N stage, being negligible for N0 and N1, while 35.7% for N3. The presence of bulky cervical nodes was associated with a higher risk for metastases: hematogenous dissemination occurred in 50% of N3B patients. The histology pattern seemed to significantly affect the ultimate outcome of patients with NPC, since disease-free survival was 65.5% in patients with a diagnosis of undifferentiated carcinoma (UC) and 23.8% in patients with squamous cell carcinoma (SC). The major cause of poor survival in this latter patient group was not only a higher recurrence rate of both primary and nodal disease but a greater incidence of distant metastases as well.     

Association of Epstein-Barr virus with tumor cell proliferation: clinical implication in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is characterized by its association with Epstein-Barr virus (EBV) infection. Unlike other upper aerodigestive tract squamous cell carcinomas, clinical and pathologic features are unable to predict outcome in NPC. EBV has been demonstrated to have transforming potential in B-cell systems so that its infection can rapidly and efficiently induce sustained lymphocyte proliferation in vitro. However, the relationship between cell proliferation and EBV infection in NPC has not been previously reported. This study was designed to determine the association of EBV infection and NPC tumor cell proliferation. Cell proliferation index, as measured by two markers, PCNA and Ki-67, were moderately correlated (r=0.534, p=0.033). Quantitative analysis of EBV positivity was highly correlated with both cell proliferation indices (r=0.802, p=0.0039 and r=0.720, p=0.0174 for PCNA and Ki-67, respectively). TNM staging did not demonstrate prognostic significance. NPC patients whose tumors were EBV positive demonstrated increased survival compared with patients whose tumors were EBV negative (p=0.043). These results indicate that EBV infection may regulate cell proliferation in NPC and the presence of EBV can be used as a positive prognostic factor.