直肠癌神经周围浸润的临床研究

Objective To investigate the clinical significance of perineural invasion (PNI) in rectal cancer. Methods Clinical data of 204 patients undergoing resection of low rectal cancer from January 2003 to January 2005 at the First People's Hospital of Chenzhou were analyzed retrospectively.Paraffin sections of surgical specimens from all the patients who underwent resection of low rectal cancer were stained with HE. PNI-positive was defined as infiltration of carcinoma cell into the perineurium or neural fascia. The association of PNI with clinicopathologic features and prognosis of rectal cancer was analyzed. Results PNI was positive in 31.9% (65/204) of the patients. The tumor size, depth of invasion, lymph node metastasis, TNM stage, tumor growth pattern, histologic grade, tumor resection were significantly associated with PNI. The overall survival time of the PNI-positive patients was shorter than that of the PNI-negative patients [(43.8±1.5) months vs.(57.2±1.5) months, P＜0.01].Furthermore, the overall survival time of the PNI-positive stage Ⅱ patients was shorter than that of the stageⅢ patients [(46.5±3.2) months vs. (55.7±1.2) months, P＜0.05]. Conclusion PNI can be used as one of the indicators to predict the prognosis of patients with rectal cancer.     

中低位直肠癌系膜浸润程度的临床研究

目的探讨中低位直肠癌直肠系膜浸润程度与临床病理特征及预后的关系。方法采用大组织切片技术,测量行全直肠系膜切除术的49例中低位直肠癌标本的肿瘤浸润深度及直肠系膜厚度,计算直肠系膜浸润程度;并分析其临床病理特征和随访结果。结果本组中低位直肠癌术后局部复发率为12．2％（6／49）,远处转移率为26．5％（13／49）。直肠癌直肠系膜浸润程度Ⅰ度20例（40．8％）,Ⅱ度13例（26．5％）,Ⅲ度16例（32．7％）,Ⅰ、Ⅱ、Ⅲ度者术后局部复发率分别为0、7．7％和31．3％（X^2=7．357,P=0．015）;远处转移率分别为10％、23．1％和50％（X^2=7．405,P=0．025）;5年生存率则分别为90．9％、69．2％和28．6％（p=0．013）。直肠系膜浸润程度与肿瘤直径（X^2=6．849,P=0．033）、T分期（X^2=34．845,P=0．000）、N分期（X^2=17．266,P=0．002）有关。结论直肠系膜浸润程度是影响直肠癌预后的重要因素。     

肿瘤浸润淋巴细胞在结直肠癌中的研究进展

随着肿瘤免疫学的研究进展,人们发现人体免疫系统抗肿瘤的作用更能决定患者的预后。结直肠癌问质中肿瘤浸润淋巴细胞（TIL）与结直肠癌的关系成为目前研究的热点之一。本文总结了近年来关于不同亚型肿瘤浸润T淋巴细胞与结直肠癌的临床病理因素、预后及微卫星不稳定性（MSI）的关系。     

肿瘤浸润肥大细胞对结直肠癌患者生存预测的价值

目的 探讨肿瘤浸润肥大细胞(TIM)在结直肠癌患者中的预后价值.方法 收集2002年1月至2005年12月中山大学附属第一医院收治的282例行首次根治性切除的结直肠癌患者的肿瘤石蜡标本,通过免疫组织化学染色计算TIM的密度,根据TIM的平均密度[(8.4±6.5)／高倍视野],将患者分为TIM少量浸润组(TIM平均密度＜8.4/高倍视野)和TIM大量浸润组(TIM平均密度≥8.4／高倍视野),比较两组患者的临床病理因素及其预后情况.计量资料采用t检验,计数资料采用x2检验.采用KaplanMeier法绘制生存曲线,Log-rank检验分析患者生存情况.影响结直肠癌患者生存时间的单因素及多因素分析采用COX比例风险模型.结果 TIM在结直肠癌患者中均有不同程度的浸润.TIM少量浸润组和TIM大量浸润组患者在结直肠癌的N分期和TNM分期方面比较,差异有统计学意义(x2=6.025,7.410,P＜0.05).随访截至2010年9月,TIM少量浸润组、TIM大量浸润组患者的5年总生存率和无瘤生存率分别为82.9％、79.0％和63.1％、59.3％,两组比较,差异均有统计学意义(P＜0.05).COX比例风险模型单因素分析结果显示,肥大细胞在肿瘤组织中的浸润是影响结直肠癌患者总生存时间和无瘤生存时间的不良因素(RR=2.119,95％可信区间1.326～3.386;RR =2.084,95％可信区间1.357～3.199,P ＜0.05).多因素分析结果显示TIM是结直肠癌患者总生存时间和无瘤生存时间的独立影响因素(RR=1.651,95％可信区间1.009～2.702;RR=1.680,95％可信区间1.047～2.629,P＜0.05).结论 TIM与结直肠癌的N分期和TNM分期相关,并且TIM是结直肠癌患者预后不良的独立影响因素.     

人胆管癌细胞神经周围浸润模型的构建与初步观察

目的构建人胆管癌细胞神经周围浸润模型，观察培养神经细胞的生长、人胆管癌细胞的增殖与神经周围浸润的过程的形态学变化。方法应用小鼠背根神经节（Dorsal Root Ganglia，DRG）置于Matrigel基质中体外培养，同时在其表面接种人胆管癌细胞QBC939，观察神经纤维的生长、QBC939细胞粘附、浸润神经纤维的过程及其形态学变化。结果小鼠DRG置于Matrigel基质中体外培养时，神经纤维生长迅速，人胆管癌细胞QBC939能够穿过人工基质粘附并浸润神经纤维，形成包绕神经纤维的细胞团。结论DRG／神经细胞-肿瘤细胞共培养模型较好的模拟了肿瘤细胞穿过细胞基质，浸润神经纤维的过程，人胆管癌细胞QBC939细胞对神经纤维具有亲嗜性。     

胃癌神经旁浸润的临床特征与预后分析

目的 探讨胃癌神经旁浸润（PNI）的临床意义.方法 对2004年1月至2008年5月期间178例行胃癌根治术后的胃癌组织石蜡标本行苏木精-伊红染色,以肿瘤细胞浸润神经束或神经束膜判定为PNI阳性.分析PNI与胃癌临床病理特征及预后的关系.结果 PNI阳性78例（43.8%）.PNI与肿瘤浸润深度（P＜0.01）、淋巴结转移（P＜0.01）和TNM分期（P＜0.01）有关,但与患者的年龄、性别、肿瘤位置和分化程度无关.单因素分析显示,胃癌患者总体生存率与PNI、胃癌浸润深度、淋巴结转移和TNM分期有关（均P＜0.01）;PNI阳性患者平均生存期（28.6个月）明显短于PNI阴性患者（44.3个月）（P＜0.01）.多因素分析显示,PNI是影响患者总体生存率的独立因素（相对危险度为2.257,95%CI为1.268～4.019,P=0.006）.结论 PNI与肿瘤的进展有关,胃癌术后检测PNI可以作为判断患者预后指标之一.     

人胆管癌细胞神经周围浸润模型的构建与初步观察

目的构建人胆管癌细胞神经周围浸润模型,观察培养神经细胞的生长、人胆管癌细胞的增殖与神经周围浸润的过程的形态学变化。方法应用小鼠背根神经节(DorsalRootGanglia,DRG)置于Matrigel基质中体外培养,同时在其表面接种人胆管癌细胞QBC939,观察神经纤维的生长、QBC939细胞粘附、浸润神经纤维的过程及其形态学变化。结果小鼠DRG置于Matrigel基质中体外培养时,神经纤维生长迅速,人胆管癌细胞QBC939能够穿过人工基质粘附并浸润神经纤维,形成包绕神经纤维的细胞团。结论DRG/神经细胞-肿瘤细胞共培养模型较好的模拟了肿瘤细胞穿过细胞基质,浸润神经纤维的过程,人胆管癌细胞QBC939细胞对神经纤维具有亲嗜性。     

直肠癌周围神经浸润的研究现状

直肠癌是常见的消化道恶性肿瘤，占消化道恶性肿瘤发病率的第2位，且有逐渐增高的趋势。随着医学的发展，直肠癌外科治疗有了更为丰富的内容，总体疗效也有了一定的提高。但是直肠癌术后局部复发率仍然较高，预后也不尽人意。影响直肠癌局部复发、转移和预后的因素有多种。研究发现，在某些上皮来源的恶性肿瘤如前列腺癌、乳腺癌、肺癌和胰腺癌等组织中，常见癌对神经组织的浸润，是引起癌肿局部复发和预后不良的重要因素。在直肠癌中的神经浸润亦具有重要意义。     

胃癌神经旁浸润的临床特征与预后分析

Objective To investigate the association between perineural invasion (PNI) and clinicopathological factors and the effect of PNI on overall survival in patients with gastric carcinoma.Methods A total of 178 patients with gastric carcinoma from January 2004 to May 2008 were analyzed retrospectively. Paraffin sections of surgical specimens from all the patients who underwent gastric resection were stained with laminin. PNl-positive was defined as infiltration of carcinoma cells into the perineurium or neural fascicles. The association of PNI with clinicopathologic features and prognosis of gastric carcinoma was studied. Results PNI was positive in 78 of 178 patients (43.8%). The proportions of T stage, lymph node metastasis and TNM stage were significantly higher in PNI-positive group than those in PNl-negative group (all P＜0.01 ). The PNI positive rate was correlated with the depth of gastric mural invasion and clinical stage. The overall survival in PNI-positive group was significantly lower than that in PNI-negative group by univariate analysis (P＜0.01). The mean survival of PNI-positive patients (28.6 months) was significantly shorter than that of PNI-negative patients (44.3 months,P＜0.01), which was also influenced by pN stage, pT stage, and clinical stage(P＜0.0l ). By multivariable Cox proportional hazards model of overall survival, the positivity of PNI appeared to be an independent prognostic factor (hazards ratio=2.257,95% CI: 1.268-4.019, P=0.006).Conclusions PNI is associated with the degree of malignancy in gastric cancer. PNI can be a candidate of new prognostic factor.     

Prognostic significance of lymphovascular or perineural invasion in patients with locally advanced colorectal cancer

Background

This study was designed to evaluate the prognostic significance of the positivity of lymphovascular (LVI) and perineural invasion (PNI) in patients with locally advanced colorectal cancer.

Methods

From January 1999 to December 2009, 1,437 consecutive patients who underwent curative surgery for stage II or III colorectal cancer were analyzed. Patients were then categorized into 4 groups: LVI−/PNI− (n = 850), LVI+ only (n = 178), PNI+ only (n = 271), and LVI+/PNI+ (n = 138).

Results

With a median follow-up period of 56 months, the 5-year overall survival rates of patients with LVI−/PNI−, LVI+ only, PNI+ only, and LVI+/PNI+ were 82%, 73%, 71%, and 56%, respectively (P < .001), and the 5-year disease-free survival rates of patients with LVI−/PNI−, LVI+ only, PNI+ only, and LVI+/PNI+ were 80%, 70%, 65%, and 46%, respectively (P < .001). In multivariate analysis, LVI+/PNI+ was an independent prognostic factor for both overall survival (P < .001) and disease-free survival (P < .001).

Conclusions

Positivity of both LVI and PNI is a strong predictor of overall and disease-free survival in patients with stages II and III colorectal cancer.     

神经旁浸润阳性胃癌患者的临床特征与预后分析

背景与目的 神经旁浸润（PNI）是胃癌局部外侵转移的生物学特性之一,其临床价值尚未得到重视。本研究旨在探讨胃癌伴发PNI的临床病理特征以及PNI对胃癌患者预后的影响。方法 回顾性分析2011年6月—2016年12月期间施行开腹根治性胃切除手术的543例胃癌患者的临床病理资料。根据癌组织PNI结果,胃癌患者分为PNI阳性组和PNI阴性组,比较两组在临床病理指标上的差异。应用倾向评分匹配法均衡两组与预后相关的基本资料变量,采用Kaplan-Meier法进行生存分析,采用Cox风险回归模型分析与PNI阳性胃癌患者术后生存相关的危险因素。结果 全组胃癌患者中PNI阳性率21.18%（115/543）。匹配前两组的肿瘤大小、肿瘤部位、细胞分化程度、肿瘤TNM分期、脉管侵犯、手术切除范围及术后辅助化疗等方面差异有统计学意义（均P<0.05）;匹配后,PNI阳性组56例,PNI阴性组98例,两组患者基线资料均衡（均P>0.05）。PNI阳性组的总生存时间（OS）明显短于PNI阴性组（中位OS：19个月vs. 49个月,P=0.002）;亚组分析显示,TNM I~II患者中,PNI阳性对OS无明显影响（P=0.432）,但明显缩短III期患者的OS（中位OS：18个月vs. 2个月,P<0.001）。在PNI阳性患者中,术后辅助化疗对I~II期患者的OS无明显影响（P=0.975）,但能明显延长III患者的OS（中位OS：18个月vs. 2个月,P<0.001）。单因素分析结果提示年龄（P=0.008）、TNM分期（P=0.034）和术后辅助化疗（P=0.006）与PNI阳性胃癌患者术后预后紧密相关;多因素分析发现TNM分期处于III期（HR=2.591,95% CI=1.291~5.198,P=0.007）、未进行术后辅助化疗（HR=0.345,95% CI=0.184~0.649,P=0.001）是影响PNI阳性胃癌患者预后的独立危险因素。结论 PNI阳性胃癌患者的预后明显差于PNI阴性胃癌患者,其对预后的影响在TNM III期患者中尤为明显。积极的术后辅助化疗有助于改善该类胃癌患者的预后。     

新辅助治疗在直肠癌脉管癌栓中的临床意义

目的 研究新辅助治疗后直肠癌脉管癌栓在中低位直肠癌组织中的分布规律,探讨脉管癌栓对直肠癌预后评价的意义.方法 按照入选标准收集2002年8月至2005年8月北京大学临床肿瘤学院连续收治的接受根治性切除的中低位直肠癌患者297例,根据是否接受术前辅助治疗将患者分成新辅助治疗组和对照组,观察两组患者术后病理标本中的脉管癌栓并根据术后随访资料研究脉管癌栓与预后的关系.采用x2检验分析其相关性,Kaplan-Meier生存法分析无病生存率和总生存率.结果 脉管癌栓总体阳性率为23.9%(71/297),新辅助治疗组阳性率为21.5%(31/144),对照组阳性率为26.1%(40/153),两组比较,差异无统计学意义(x2=0.872,P＞0.05).新辅助治疗组和对照组的脉管癌栓均与病理T、N分期及组织学分化程度有关(x2=13.490,27.401,7.323;16.188,21.623,16.534,P<0.05).新辅助治疗组脉管癌栓与局部复发无关(x2=0.000,P＞0.05),对照组的脉管癌栓与局部复发有关(x2=4.010,P<0.05).两组的脉管癌栓均与远处转移有关(x2=4.950,14.332,P<0.05).脉管癌栓阳性者比阴性者的无病生存率和总体生率低,分别为46.4%(26/56)和75.1%(148/197)、56.7%(34/60)和79.4%(166/209),两者比较,差异有统计学意义(x2=16.720,12.660,P<0.05).结论 新辅助治疗并未使脉管癌栓减少,但脉管癌栓在生物学行为上已经发生了变化,且脉管癌栓阳性的患者有可能从新辅助治疗中获益.     

Risk factors associated with perineural invasion in prostate cancer

ObjectivesThe prognostic importance of perineural invasion (PNI) in prostate cancer (PC) has been postulated by some authors. Few studies have investigated the risk factors associated with PNI. The aim of this study was to identify factors associated with PNI in PC.Patients and methodsThe study group of 113 patients diagnosed with PC during the period 2005–2010 consisted of 66 who underwent radical prostatectomy (RP) and 66 who did not. Each group was further divided into those with and without PNI. The association between clinicopathological parameters and PNI in prostate biopsy (Pbx) and RP specimens was investigated using t-test and logistic regression analysis. Discordance in PNI prevalence and PNI up-migration between Pbx and RP specimens were also studied.ResultsIn patients who did not undergo RP, Pbx Gleason score (GS) ≥ 7 was a significant predictor for the presence of PNI. In patients who underwent RP, Pbx GS > 7 increased the risk of PNI in Pbx and RP samples, while a high RP GS predicted PNI in the RP specimen. The discordance rate for PNI in Pbx and RP specimens was 27.3%. Up-migration to a PNI positive cancer between Pbx and RP specimens was seen in 45.5% of cases and RP GS was the only factor associated with PNI up-migration.ConclusionThe association of PNI with a high GS and the high rate of discordance between Pbx and RP specimens indicate that in patients with a high GS on Pbx, the pathologist should look more carefully for PNI, and the surgeon should be aware of sampling errors and the unreliability of Pbx specimens in detecting PNI.     

细胞周期蛋白E对直肠癌预后判断的价值及与血管侵袭的相关性

目的研究细胞周期蛋白（cyclin）E表达与直肠癌预后的相关性及其对血管侵袭（BVI）的影响。方法蛋白质印迹法检测130例Ⅰ～Ⅲ期直肠癌组织eyelinE的表达：抗CD34单克隆抗体免疫组化反映BVI。结果全组直肠癌组织中eye[inE高表达率为23．1％（30／130）。除病理大体类型、BVI外。eyelinE表达与其他临床病理因素无明显相关性。eyelinE高表达的患者发生BVI的危险性为低表达者的3．145倍（P=0．001）；eyelinE高表达者生存率低。其5年生存率29．2％。与低表达者的70．5％相比。P=0．001。COX回归多因素分析显示。eyelinE是影响全组直肠癌术后预后的独立因素[RR值（95％CI）3．544（1．528～8．215）。P〈0．05]；分层分析显示。eyelinE是Ⅰ～Ⅱ期直肠癌预后的主要影响因素之一[RR值（95％CI）4．066（1．217～13．39）。P〈0．01]。联合检测时．eyelinE高表达及BVI阳性的患者死亡危险度是eyelinE低表达及BVI阴性患者的6．693倍（95％CI2．539～17．646）。结论CyclinE是影响直肠癌预后的重要分子生物学指标。CyclinE高表达者易发生BVI。eyelinE与BVI联合检测有助于提高对直肠癌预后判断的准确性。     

直肠癌壁外血管侵犯影像学评价的研究进展

直肠癌壁外血管侵犯是影响直肠癌病人预后的重要因素,术前准确诊断壁外血管侵犯,可指导治疗方案的制订,从而改善病人预后和远期生存。MRI检查和CT检查是术前评估直肠癌的主要检查手段。笔者将对影像学检查在直肠癌壁外血管侵犯评价的作用进行综述。     

Prognostic significance of lymphovascular invasion in surgically cured rectal carcinoma

BACKGROUND: Surgery is considered curative in Dukes' B rectal cancer; however, many patients present with early relapse. To identify additional staging information, venous and lymphatic invasion were evaluated as potential prognostic factors. METHODS: Patients with Dukes' B or C rectal disease treated between 1976 and 2001 at a single institution were compared. Patient and treatment characteristics and vascular invasion were documented. The impact of vessel invasion was determined using Cox proportional hazards model. RESULTS: There were 256 Dukes' B patients and 74 Dukes' C cases without vascular invasion. Five-year survival was 76.5% for Dukes' B and 57.1% for Dukes' C patients. Vessel involvement increased the risk of recurrence (hazard ratio [HR] = 3.27, P = .0003) and death (HR = 3.11, P = .002) in B2 patients. The magnitude of these associations were comparable to that of C1 patients for recurrence (HR = 2.81, P = .004) and death (HR = 3.05, P = .005), as well as C2 patients for recurrence (HR = 3.45, P = .0008) and death (HR = 3.87, P = .0005). CONCLUSION: Vascular invasion may be useful in characterizing patients with aggressive Dukes' B disease, who might benefit the most from adjuvant systemic therapy.