喉癌外科疗效的系统评价及TopoⅡ-α表达与喉癌临床特征的相关研究

发布时间：2018-06-07 17:28

本文选题：喉肿瘤 + 放射疗法　；参考：《山西医科大学》2011年博士论文

【摘要】：目的:通过采用系统评价的方法,评估单纯手术及手术与放疗相结合治疗喉癌的疗效,为临床喉癌的合理治疗提供循证学依据。方法:按照Cochrane系统评估的方法,系统检索Cochrane图书馆、Medline、Embase、中国生物医学数据库(CBM)、相关期刊论文(CNKI)等国内外权威数据库中有关喉癌外科治疗的所有文献,将喉癌治疗方式中开放性喉切除术、单纯CO2激光手术、单纯放疗、术前放疗加手术及手术加术后放疗治疗后患者生存率、生存质量和嗓音质量分别进行两两比较。使用Revman5.0.17对符合纳入标准的文献进行Meta分析,对定量资料中二分类变量采用RR和95%CI表示效应量,对定性资料采用描述性分析。检索时间截至为2011年3月31日。结果:按照检索策略进行文献检索,符合纳入标准的文献共63篇,其中随机对照试验7篇,前瞻性非随机对照试验1篇,其余均为回顾性研究。研究分为9个比较组。结果显示: (1)对不同术式的开放性喉部分切除术疗效进行比较的文献共8篇,未描述各组患者的分期分型。A:3年生存率:3年总生存率为85.88%(949/1105)。喉裂开声带切除术优于声门上水平喉部分切除术、水平垂直喉部分切除术及近全喉切除术RR分别为0.28、0.14、0.23,95%CI分别为(0.10,0.78)、(0.04,0.50)、(0.08,0.66)。B:5年生存率:5年总生存率为73.19%(685/899)。喉裂开声带切除术优于侧位垂直喉部分切除术、声门上水平喉部分切除术、水平垂直喉部分切除术及近全喉切除术,RR为0.37、0.27、0.25、0.23,95%CI为(0.18,0.75)、(0.14,0.51)、(0.12,0.50)、(0.08,0.72)。垂直半喉切除术、水平半喉切除及喉次全切除均优于喉全切除术,RR为0.26、0.22、0.45,95%CI为(0.13,0.51)、(0.07,0.68)、(0.23,0.87)。C:10年生存率:10年总生存率为54.29%(177/326)。喉裂开声带切除术优于前位喉部分切除术、声门上水平喉部分切除术、水平垂直喉部分切除术、扩大喉部分切除术及近喉全切除术,RR为0.34、0.34、0.38、0.28、0.34,95%CI为(0.14,0.87)、(0.15,0.81)、(0.16,0.94)、(0.12,0.65)、(0.17,0.66)。垂直半喉切除术和水平半喉切除术优于喉全切除术,RR为0.45、0.49,95%CI为(0.28,0.73)、(0.26,0.93)。侧位垂直喉部分切除术优于扩大喉次全切除术RR为0.62,95%CI为(0.42,0.93)。垂直半喉切除术优于喉次全切除术,RR为0.44,95%CI为(0.28,0.70)。喉部分切除患者生存质量优于喉全切除患者。喉声门上水平部分切除术后嗓音质量优于喉垂直部分切除术和3/4喉部分切除术。纳入研究均未比较不同术式患者的局部控制率。 (2)单纯开放性喉切除术组与单纯CO2激光手术组患者局部控制率、总生存率和嗓音质量差异无统计学意义,纳入研究均未比较患者的生存质量。 (3)单纯开放性喉切除术组与单纯放疗组比较,低剂量放疗组患者3年局部控制率较单纯开放性喉切除术组差,差异有统计学意义,RR为0.37,95%CI为(0.22,0.61)。患者的总生存率、生存质量及嗓音质量差异均无统计学意义。 (4)单纯CO2激光手术组与单纯放疗组患者局部控制率、总生存率、嗓音质量差异均无统计学意义,研究未比较术后患者生存质量。 (5)单纯开放性喉切除术组生存质量优于手术加术后放疗组。单纯开放性喉切除术组与手术加术后放疗组患者治疗局部控制率、总生存率、嗓音质量差异均无统计学意义。 (6)单纯开放性喉切除术组与术前放疗加手术组患者治疗后总生存率差异均无统计学意义,未比较局部控制率、生存质量及嗓音质量。 (7)术前放疗加手术组与单纯放疗组总生存率差异均无统计学意义,未比较局部控制率、生存质量及嗓音质量。 (8)术前放疗加手术组与手术加术后放疗组总生存率差异均无统计学意义,未比较局部控制率、生存质量及嗓音质量。 (9)手术加术后放疗组与单纯放疗组局部控制率、总生存率差异均无统计学意义,未比较生存质量和嗓音质量。结论:现有研究显示(1)系统评价结果显示:低剂量放疗后患者生存率较单纯手术差;喉部分切除患者生存质量较喉全切除患者优;放疗对患者术后生存质量有一定的影响;早期声门型喉癌采用单纯CO2激光手术和单纯放疗均可取得较好的疗效,治疗后患者生存率及嗓音质量相似。(2)目前临床上喉癌外科治疗的术式较多,针对不同分期分型的喉癌采用不同的术式,喉癌治疗的疗效参差不齐,文献设计类型以回顾性研究为主,随机对照试验数量有限。(3)目前尚缺少高质量的随机对照试验,临床上应加强大样本高质量的对不同分期分型喉癌治疗的随机对照试验,为喉癌的治疗提供更加可靠合理的循证依据。目的:在蛋白水平和基因水平检测TopoⅡ-α在喉癌中的表达,了解TopoⅡ-α表达与喉癌临床特征的相关性,探讨TopoⅡ-α在喉癌发生、发展及预后中的作用,为喉癌生物学治疗提供理论依据。方法:提取病例资料齐全的77例喉鳞癌患者的组织蜡块进行研究。其中22例包含喉癌组织及癌旁正常组织,55例未包含癌旁组织。采用免疫组化和免疫荧光法对22例喉癌及癌旁正常组织中的TopoⅡ-α蛋白进行定性、定量测定,分析其在癌旁不同距离组织中的表达变化。采用组织芯片技术将55例未包含癌旁组织的蜡块制作成组织芯片,运用荧光原位杂交方法检测组织芯片中TopoⅡ-α基因扩增及17号染色体倍体性的情况。采用SPSS15.0软件进行统计学分析,χ2检验或Fisher确切概率法比较TopoⅡ-α蛋白在喉癌不同临床分型、不同T、N分期及不同分化程度之间的表达差异,并比较TopoⅡ-α蛋白表达阴性与阳性组中基因扩增及17号染色体倍体性的情况。TopoⅡ-α蛋白阳性率与基因扩增及17号染色体倍体性之间的关联分析采用Spearman法,以P0.05为差异有统计学意义。结果:(1)在组织芯片蜡块中,由于未取到鳞癌组织或者所取鳞癌组织很少,5例组织无法进行有效分析,有2例组织处理掉片,共48例组织可以进行有效分析。(2)TopoⅡ-α蛋白在喉癌组织中阳性率为71.43%(50/70),明显高于喉黏膜正常组织中阳性率10%。(3)中分化+低分化组TopoⅡ-α蛋白阳性率明显高于高分化组,差异有统计学意义(χ2=23.58,P0.05)。(4)T3+T4组TopoⅡ-α蛋白阳性率明显高于T1+T2组,差异有统计学意义(χ2=3.92,P0.05)。(5)分别比较声门上型、声门型、声门下型三组中TopoⅡ-α蛋白阳性率,差异均无统计学意义(χ2=1.16,P0.05)。(6)颈淋巴结转移组与淋巴结未转移组中TopoⅡ-α蛋白阳性率比较,差异无统计学意义(χ2=2.13,P0.05)。(7)从癌组织到逐渐远离癌组织的癌旁组织中,TopoⅡ-α蛋白表达逐渐减少,在喉癌旁组织0.3-0.5cm的范围内,TopoⅡ-α蛋白表达显著变化。(8)喉癌中TopoⅡ-α蛋白表达量与与基因扩增状态之间无相关性(r=0.15,P0.05);TopoⅡ-α蛋白表达量与17号染色体的倍体异常率正相关(r=0.44,P0.05),随着17号染色体的倍体异常率的增高,TopoⅡ-α蛋白表达量也相应增加。结论:TopoⅡ-α蛋白表达水平与肿瘤临床分期及分化程度等临床特征有关,可作为判断预后的指标之一。TopoⅡ-α在喉癌发生、发展中起着重要作用,通过对TopoⅡ-α蛋白及基因的检测可以对喉癌预后的评估和为生物治疗肿瘤提供一定的科学依据。
[Abstract]:Objective: To evaluate the efficacy of simple surgery, surgery and radiotherapy in the treatment of larynx cancer by means of systematic evaluation, and provide evidence-based evidence for rational treatment of laryngeal carcinoma.
Methods: according to the method of Cochrane system evaluation, we systematically retrieved Cochrane library, Medline, Embase, Chinese biomedical database (CBM), Chinese journal full text database (CNKI) and other domestic and foreign authoritative databases on laryngectomy for laryngectomy, open laryngectomy, simple CO2 laser surgery, pure CO2 laser surgery, and pure CO2 laser surgery. The survival rate, the quality of life and the voice quality were compared between radiotherapy, preoperative radiotherapy plus surgery and postoperative radiotherapy. Revman5.0.17 was used to perform Meta analysis on the documents which were in conformity with the inclusion criteria. The two classification variables in the quantitative data were measured by RR and 95%CI, and the qualitative data were analyzed by descriptive analysis. The time ended in March 31, 2011.
Results: according to the retrieval strategy, 63 articles were included, including 7 randomized controlled trials, 1 prospective non randomized controlled trials, and the rest were retrospective study. The study was divided into 9 comparative groups. The results showed that:
(1) a total of 8 articles were compared for different surgical procedures of open laryngectomy. The survival rate of.A:3 years was not described in each group: the total survival rate of 3 years was 85.88% (949/1105). The laryngeal fissure vocal cord resection was superior to the supra glottal partial laryngectomy, and the vertical partial laryngectomy and the near total laryngectomy RR were 0, respectively. .28,0.14,0.23,95%CI (0.10,0.78), (0.04,0.50), (0.08,0.66).B:5 year survival rate: 5 year total survival rate was 73.19% (685/899). Laryngeal fissure vocal cord resection was superior to lateral vertical partial laryngectomy, supra glottal partial laryngectomy, horizontal vertical laryngectomy and near total laryngectomy, and RR for 0.37,0.27,0.25,0.23,95%CI (0.1). 8,0.75), (0.14,0.51), (0.12,0.50), (0.08,0.72). Vertical hemiclaryngectomy, horizontal half laryngectomy and laryngeal subtotal excision were superior to total laryngectomy, RR was 0.26,0.22,0.45,95%CI (0.13,0.51), (0.07,0.68), (0.23,0.87).C:10 year survival rate: 10 years total survival rate was 54.29% (177/326). Laryngeal fissure vocal cord resection was superior to anterior laryngectomy, Partial partial laryngectomy, horizontal vertical laryngectomy, extended partial laryngectomy and total laryngectomy, RR 0.34,0.34,0.38,0.28,0.34,95%CI (0.14,0.87), (0.15,0.81), (0.16,0.94), (0.12,0.65), (0.17,0.66). Vertical hemiclaryngectomy and horizontal hemiclaryngectomy are superior to total laryngectomy, RR is 0.45,0.49,95%CI (0.28,0.73), (0.26,0.93). Lateral vertical partial laryngectomy is superior to extended laryngectomy with RR 0.62,95%CI (0.42,0.93). Vertical semi laryngectomy is superior to subtotal laryngectomy, and RR is 0.44,95%CI (0.28,0.70).
The quality of life of the patients with partial laryngectomy is better than that of total laryngectomy. The quality of voice after partial laryngectomy is better than that of vertical partial laryngectomy and 3/4 partial laryngectomy.
(2) there was no significant difference in the local control rate, the total survival rate and the voice quality difference between the simple open laryngectomy group and the simple CO2 laser operation group, and the quality of life of the patients was not compared.
(3) compared with the simple radiotherapy group, the 3 year local control rate of the patients in the low dose radiotherapy group was less than that of the simple open laryngectomy group. The difference was statistically significant, the RR was 0.37,95%CI (0.22,0.61). The total survival rate, the quality of life and the difference of voice quality were not statistically significant.
(4) there was no significant difference in local control rate, total survival rate and voice quality difference between the simple CO2 laser operation group and the simple radiotherapy group. The study did not compare the quality of life of the patients after the operation.
(5) the quality of life in the simple open laryngectomy group was better than that of the operation plus postoperative radiotherapy group. There was no significant difference in the local control rate, the total survival rate and the voice quality difference between the simple open laryngectomy group and the operation plus postoperative radiotherapy group.
(6) there was no significant difference in the total survival rate between the simple open laryngectomy group and the preoperative radiotherapy plus surgery group, and there was no local control rate, quality of life and voice quality.
(7) there was no significant difference in the overall survival rate between preoperative radiotherapy plus surgery group and radiotherapy alone group. There was no significant difference in local control rate, quality of life and voice quality.
(8) there was no significant difference in overall survival rate between preoperative radiotherapy plus operation group and postoperative radiotherapy group. There was no significant difference in local control rate, quality of life and voice quality.
(9) there was no significant difference in the local control rate and the overall survival rate between the surgery plus radiotherapy group and the radiotherapy alone group, with no significant difference in quality of life and voice quality.
Conclusion: the present study showed that (1) the results of systematic evaluation showed that the survival rate of the patients after low dose radiotherapy was worse than that of the simple operation; the survival quality of the patients with laryngectomy was better than that of the total laryngectomy, and the radiotherapy had a certain influence on the quality of life after the operation, and the early glottic laryngectomy with simple CO2 laser surgery and simple radiotherapy could be better. The survival rate and voice quality were similar after treatment. (2) there were many surgical treatments for larynx cancer at present. Different surgical procedures were used for laryngocarcinoma in different stages. The curative effect of larynx cancer treatment was uneven. The literature design type was based on retrospective study, and the number of controlled trials was limited. (3) there is still lack of high quality at present. Randomized controlled trials should strengthen randomized controlled trials of large sample and high quality treatment for different stages of larynx cancer, and provide more reliable evidence for the treatment of larynx cancer.
Objective: to detect the expression of Topo II - alpha in laryngeal carcinoma at the protein level and gene level, to understand the correlation between the expression of Topo II - alpha and the clinical characteristics of laryngeal carcinoma, and to explore the role of Topo II - alpha in the occurrence, development and prognosis of laryngeal carcinoma, and provide a theoretical basis for the biological treatment of larynx cancer.
Methods: 77 cases of laryngeal squamous cell carcinoma were extracted from 77 cases of laryngeal squamous cell carcinoma. 22 of them included laryngeal carcinoma tissue and normal tissue adjacent to cancer, 55 cases were not included in para cancerous tissue. Immunohistochemistry and immunofluorescence were used to determine the quality of Topo II - alpha egg white in 22 cases of larynx cancer and normal tissues adjacent to cancer. Expression changes in different distance tissues. Tissue chip technology was used to make 55 paraffin blocks without paracancerous tissues into tissue chips. The fluorescence in situ hybridization was used to detect Topo - II - alpha gene amplification and chromosome 17 ploidy in tissue chips. SPSS15.0 software was used for statistical analysis, chi chi 2 test, or Fisher exact probability Ratio method was used to compare the expression differences of Topo II - alpha protein in different clinical types of laryngeal carcinoma, different T, N staging and differentiation, and compared the correlation of the positive rate of.Topo II - alpha protein with gene amplification and chromosome 17 ploidy in the negative and positive group of Topo II - alpha protein and the chromosome ploidy of 17 Analysis using Spearman method, P0.05 as the difference was statistically significant.
Results: (1) in the tissue chip wax block, 5 tissues could not be effectively analyzed because of the lack of squamous carcinoma tissue or the squamous cell carcinoma tissue. There were 2 cases of tissue processing and 48 tissues could be effectively analyzed. (2) the positive rate of Topo II - alpha protein in the larynx tissues was 71.43% (50/70), which was significantly higher than that in the normal tissues of the larynx. The positive rate of Topo II - alpha protein in 10%. (3) and low differentiation group was significantly higher than that in the high differentiation group (x 2=23.58, P0.05). (4) the positive rate of Topo II - alpha protein in T3+T4 group was significantly higher than that in the T1+T2 group, and the difference was statistically significant (5) compared to the supra glottic, glottic and subglottic three groups of Topo II - alpha protein, respectively. The positive rate was not statistically significant (x 2=1.16, P0.05). (6) there was no significant difference in the positive rate of Topo II - alpha protein in the cervical lymph node metastasis group and the non metastatic lymph node group (x 2=2.13, P0.05). (7) the expression of Topo - a protein in the paracancerous tissue from the cancer tissue to the gradually far away from the cancer tissue, the expression of Topo - a protein was gradually reduced, and the 0.3-0.5cm was organized near the larynx cancer. The expression of Topo II - alpha protein was significantly changed. (8) there was no correlation between Topo - II - alpha protein expression and gene amplification state (r=0.15, P0.05) in larynx cancer. The expression of Topo - II - alpha protein was positively correlated with the ploidy abnormal rate of chromosome 17 (r=0.44, P0.05), and the expression of Topo - A - alpha protein with the increase of chromosome ploidy rate of chromosome 17 It also increases accordingly.
Conclusion: the level of Topo - II - alpha protein expression is related to clinical features of tumor clinical stage and differentiation, which can be used as one of the indicators to judge the prognosis..Topo II - alpha plays an important role in the development of larynx cancer. The detection of Topo - II - alpha protein and gene can provide a certain family for the assessment of larynx cancer and the biological treatment of tumor. Learn the basis.
【学位授予单位】：山西医科大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R739.65

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