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学科主题: 肿瘤学
题名:
淋巴结阴性胃癌的预后因素分析及改良Lauren分型系统在可切除胃癌中的预后价值
作者: 刘新志
答辩日期: 2016-05-25
导师: 季加孚
专业: 肿瘤学
授予单位: 北京大学
授予地点: 北京大学临床肿瘤学院
学位: 博士
关键词: 淋巴结阴性 ; 胃癌 ; Lauren分型 ; 肿瘤部位 ; MLC ; 预后分析
其他题名: The prognosis analysis of patients with node-negative gastric cancer and The prognostic value of modified Lauren classification in resectable gastric cancer
分类号: R735.2
摘要:

第一部分

背景:胃癌在全球范围的发病率及死亡率一直居于恶性肿瘤前列,在东亚地区特别是中国,造成了严重的经济及社会负担。随着近些年胃癌诊疗理念及技术的进步,胃癌的生存率已经有了一定程度的提高,但是5年生存率仍然只有20-30%。多种临床病理因素对胃癌的预后有影响。其中UICC/AJCC的TNM分期是判断胃癌预后及指导进一步治疗的主要指标。TNM分期中的N分期是非常重要的预后指标。多项研究证实,淋巴结阴性胃癌的预后明显优于淋巴结阳性胃癌。但淋巴结阴性胃癌仍有复发及死亡的风险。而目前临床上对于淋巴结阴性胃癌术后是否需要治疗仍有争议,第7版胃癌NCCN指南推荐T1N0M0患者术后定期复查,T2N0M0合并高危因素(低分化、脉管癌栓阳性、神经侵犯或者年龄<50岁)的胃癌患者术后辅助化疗,T3-4N0M0的胃癌患者术后需行辅助治疗。但是,第3版日本胃癌治疗指南指出,对于T1N0M0及淋巴结阴性的进展期胃癌(≤T3),不推荐术后辅助治疗。目的:探讨T1-3N0M0胃癌患者不良预后因素,指导该分期患者术后进一步治疗。方法:回顾性分析1995年1月至2007年12月就诊于北京肿瘤医院胃肠肿瘤中心并且行根治性手术治疗的pT1-3/pN0胃腺癌患者,收集相关临床病理资料及生存资料。首先通过单因素及多因素生存分析,探讨淋巴结阴性胃癌不良预后因素。然后比较LVI(+)组及LVI(-)组胃癌患者临床病理特征的差异,最后应用Kaplan-Meier法分析LVI对不同T分期淋巴结阴性胃癌的预后影响。结果: 共纳入261例pT1-3/pN0胃癌患者,5年OS为81.1%,单因素生存分析中有统计学意义的因素包括胃切除类型(P<0.0001),肿瘤长径(P=0.004),肿瘤部位(P=0.002),LVI(P<0.0001),肿瘤浸润深度(P<0.0001),术后化疗(P=0.001)。多因素生存分析结果显示T3(HR,3.7;95%CI,2.162~6.332;P<0.0001)及LVI(HR,2.173;95%CI,1.229~3.841;P=0.008)为独立不良预后因素。进一步对LVI分组,LVI(-)胃癌患者220例,LVI(+)胃癌患者41例。两组在肿瘤长径及T分期方面,差异均有统计学意义(P均<0.05)。LVI(-)组5年OS(Overall survival,总生存)明显优于LVI(+)组,分别为84.7%和61.3%(P<0.05)。LVI对T1-2N0M0胃癌患者5年OS无影响,但是LVI对T3N0M0胃癌患者5年OS有影响。结论:LVI及T3(浆膜下侵犯)是T1-3N0M0胃癌的不良预后因素。T3N0M0胃癌患者术后需辅助化疗及密切随访,T2N0/LVI(+)术后可能需要辅助化疗。

第二部分

目的:最近基于Lauren 分型及肿瘤解剖部位,出现了一种新的胃癌分型系统。研究证实,三种分型在基因表达方面完全不同。本研究探讨改良Lauren分型系统在可切除胃癌中的预后价值及提供术后治疗参考。

 

方法:回顾性分析1995年1月至2007年12月就诊北京肿瘤医院胃肠肿瘤中心并且行根治性手术治疗的920例胃癌患者,所有患者分为三型:PND、DND及D。比较各型胃癌患者临床病理资料,通过单因素及多因素分析,研究MLC对胃癌的预后作用。

 

结果:PND型352例,D型85例,DND型483例。各分型患者5年总生存率分别为38.7%,13.7%及64.1%。DND型患者较另外两型总生存时间更长(P均小于0.05),PND型总生存优于D型(P<0.05)。多因素分析显示:脉管癌栓、TNM分期及MLC是胃癌独立的生存预后因素(P均〈0.05)。

 

结论:MLC是胃癌可靠并且独立的预后指标,将来的胃癌治疗中应该充分考虑MLC

 

 

 

英文摘要:

the first part

 

Background: The morbidity and mortality of gastric cancer has laid in the front rank of malignancy worldwide, in east Asia, especially in China, resulting serious economic and social burden. As the concept and technology progress of gastric cancer diagnosis and treatment in recent years, the survival rate of gastric cancer has been improved to a certain extent. But the 5-year survival rate remains only 20-30%. The UICC/AJCC TNM staging system is the major predictor of gastric cancer prognosis and guiding further treatment. Especially, the N staging bears the important prognostic value. Although compared to patients with node-positive gastric cancer ,the patients with node-negative gastric cancer have been confirmed a favorable prognosis. The patients with node-negative gastric cancer are also at the risk of recurrence and death. In present clinical practice, it is still controversial that whether or not to administer adjuvant treatment in patients with node-negative gastric cancer. According to the seventh edition of NCCN gastric cancer guideline, adjuvant treatment is recommended for the patients staged T2N0M0 with high risk (poor differentiation, lymphovascular invasion, perinerve invasion or age < 50 years). But adjuvant treatment is not recommended for node-negative advanced gastric cancer (AGC) ≤T3 (subserosa invasion) according to recent Japanese gastric cancer treatment guideline, because of lack of evidence.

Objective: To investigate the adverse prognostic factors in patients with staged T1-3N0M0 gastric cancer and guide the further postoperative treatment in this group patients.

 

Methods: A total of 261 patients with staged T1-3N0M0 gastric adenocarcinoma cases who underwent radical gastrectomy were collected from 1995 to 2007 at Peking University Cancer Hospital and Institute. These patients were then divided into 2 groups: LVI negative group and LVI positive group. The clinicopathological acteristics of each group was analyzed retrospectively. The prognostic value of LVI was investigated by univariate and multivariate analyses.

 

Results: This study included 261 patients staged T1-3N0M0 with gastric cancer. The 5-year overall survival in these patients was 81.1%. The factors significantly associated with overall survival on univariate analysis included gastrectomy type (P<0.0001), tumor size (P=0.004), tumor location (P=0.002), LVI(P<0.0001),depth of invasion (P<0.0001) and postoperative chemotherapy (P=0.001).Multivariate analysis indicates that subserosa invasion(HR,3.7;95%CI,2.162~6.332;P<0.0001) and LVI(HR,2.173;95%CI,1.229~3.841;P=0.008) were independent adverse prognostic factors. The number of LVI (-) and LVI (+) group were 220 and 41 respectively. The tumors in patients with LVI (+) had more aggressive clinicopathological features than those in patients with LVI (-). LVI had no impact on 5-year survival in patients staged T1-2N0M0. In contrast, LVI exerted prognostic effect in patients staged T3N0M0.

 

Conclusions: LVI and T-stage 3 are independent adverse prognostic factors in patients with node-negative gastric cancer. Patients staged T3N0M0 may benefit from adjuvant therapy and close follow-up scheduling. Patients staged T2N0M0 with LVI may benefit from postoperative chemotherapy.

 

the second part

Objective: Recently ,based on Lauren’s classification and anatomic tumor location, a new classification for gastric cancer was proposed. The resulting three types were confirmed distinguished from each other at gene expression level. The focus of the study was to clarify the prognostic value of modified Lauren classification in resectable gastric cancer, and provide references of postoperative treatment.

Methods: A total of 920 patients with gastric adenocarcinoma who underwent radical gastrectomy were collected from 1995 to 2007 at Peking University Cancer Hospital and Institute. According to the MLC system, all of the patients were divided into three type: proximal non-diffuse(PND), diffuse(D), and distal non-diffuse (DND) type. The three groups were compared regarding clinicopathological acteristics and overall survival. The prognostic value of MLC system was investigated by univariate and multivariate analyses.

Results: A total of 920 gastric cancer patients were included: 352 belonged to PND ,85 to D and 483 belonged to DND. Their  5-year  overall survival rates were 38.7%, 13.7% and 64.1%. Compared to PND and D ,DND presented a longer overall survival (both P<0.05) . PND was associated with better overall survival than D (P<0.05).Multivariate analysis revealed that lymphovascular invasion, TNM stage and MLC were independent prognostic factors for overall survival.

Conclusions: MLC is a reliable and independent prognostic indicator in gastric cancer patients .The MLC system should be taken into consideration when determining the best treatment for the gastric cancer individuals.

Keywords: Gastric cancer;Lauren classification;Tumor location; Modified Lauren classification;Prognosis

 

语种: 中文
相关网址: 查看原文
内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/125695
Appears in Collections:北京大学临床肿瘤学院_学位论文

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作者单位: 北京大学临床肿瘤学院

Recommended Citation:
刘新志. 淋巴结阴性胃癌的预后因素分析及改良Lauren分型系统在可切除胃癌中的预后价值[D]. 北京大学临床肿瘤学院. 北京大学. 2016.
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