肝肠钙黏蛋白在胃癌中的表达及其与患者预后的关系

目的 探讨肝肠钙黏蛋白(CDH17)在胃癌中的表达及其与预后的关系.方法 应用组织芯片和免疫组织化学方法检测264例胃癌、正常黏膜及104例转移淋巴结中CDH17的表达.结果 CDH17在胃癌中的表达率高于正常黏膜(63.26%比9.85%,P＜0.001),与临床分期(P＜0.01)、浸润深度(P＜0.01)、淋巴结转移(P＜0.01)和远处转移(P＜0.05)相关.转移淋巴结的CDH17表达率(81.73%)高于原发癌和正常黏膜(P＜0.001).CDH17表达与术后总体生存率和无瘤生存率负相关,CDH17是影响总体生存[风险比(HR)3.97;95%可信区间(CI)1.39～10.28;P＜0.05]和无瘤生存(HR 2.32;95%CI 1.17～4.52;P＜0.05)的独立预后因素.结论 CDH17在胃癌进展中起重要作用,可作为预测术后转移复发的标记物.

Abstract：

Objective To explore the expressiom of liver-intestine (CDH17) in gastric cancer and its correlation with prognosis. Methods CDH17 protein expression was detected by immunohistochemistry on tissue microarray, which containing 264 samples of primary gastric cancer and the corresponding paracancerous tissue,and 104 paired lymph node metastases (LNM). Results CDH17 was up-regulated in gastric cancer compared with paired nomal gastric mucosa and correlated with clinical stage,invasion depth,LNM,distant metastasis. Immnoreactivity of CDH17 was significantly higher in LNM than in primary gastric cancer and normal mucosa. There was a negative correlation between the high expression of CDH17 and overall survival (OS) or disease free survival (DFS) of gastric cancer patients. CDH17 was an independent prognostic factor for OS [hazard ratio ( HR) 3. 97 ; 95% confidence interval ( CI) 1. 39-10. 28; P ＜ 0. 05] and DFS (HR 2. 32 ;95% CI 1.17-4. 52; P ＜ 0. 05). Conclusion CDH17 may play an important role in gastric cancer progression and could serve as a biomarker to identify patients at risk of metastasis or recurrence after gastrectomy.     

胞吐作用调节蛋白SCRN1在结肠癌中的表达及意义

目的:探讨胞吐作用调节蛋白SCRN1在结肠癌发生发展中的意义。方法:应用激光捕获显微切割(LCM)-基因芯片技术及长标签基因表达系列(longSAGE)分析建立纯化的结肠癌实质细胞转录组数据库,筛选结肠癌肿瘤相关基因SCRN1,应用定量聚合酶链反应(PCR)技术检测15例结肠癌中SCRNl mRNA表达,应用组织芯片和免疫组织化学技术检测173例正常结肠黏膜、结肠癌和54例转移淋巴结中SCRNl蛋白表达。结果:SCRNl mRNA在80%(12/15)的结肠癌组织中表达上调2倍以上。SCRN1在结肠癌及转移淋巴结中的表达高于正常黏膜,与AJCC分期(P<0.01)、淋巴转移(P<0.01)显著相关。SCRN1表达高低与患者术后5年无瘤生存率(P>0.05)和总体生存率(P>0.05)无明显相关性,SCRN1不是影响无瘤生存和总体生存的独立预后因素。结论:SCRN1表达增高可能是结肠癌发生发展过程中的重要分子事件。     

胃肠道富集Krüppel样因子表达与胃癌患者预后的关系

目的 探讨KLF4在胃癌组织中的表达及其与胃癌患者预后的关系.方法 收集上海交通大学附属第一人民医院2004-2009年胃癌根治性手术标本264例,应用实时定量PCR和免疫组织化学染色方法检测KLF4在胃癌及癌旁组织中的表达.结果 KLF4蛋白在胃癌和癌旁组织中的阳性表达率分别为43.2％(114/264)和79.2％(209/264),差异有统计学意义(P＜0.01).KLF4表达与浸润深度(P＜0.05)、淋巴结转移(P＜0.01)、远处转移(P＜0.05)及临床分期(P＜0.05)有关.KLF4阳性与阴性表达患者5年总体生存率分别为65.2％和41.2％,5年无瘤生存率分别为50.4％和36.2％,差异均有统计学意义(P＜0.05).KLF4表达是胃癌患者总体生存(HR=2.89,95％CI:1.18～9.23)和无瘤生存(HR=2.14,95％CI:1.03～4.37)的独立预后因素.结论 KLF4在胃癌组织中的表达显著下调;KLF4有可能成为预测胃癌患者预后的生物学标志物.     

TGF-β1和VEGF在结肠癌组织中的表达和临床意义

目的:研究转化生长因子β 1 (TGF-β1)与血管内皮生长因子(VEGF)在结肠癌组织中的表达、相互关系及临床意义.方法:采用免疫组织化学SP法检测65例结肠癌组织标本中 TGF-β 1、VEGF蛋白表达,RT-PCR检测其mRNA表达,并选择39例正常人结肠黏膜组织作为正常对照.结果:免疫组化法检测TGF-β 1、VEGF蛋白在结肠癌组织中的阳性率较正常对照组明显增高(P＜0.05),RT-PCR检测TGF-β1、VEGF mRNA表达量癌组织高于正常组织.免疫组化检测的TGF-β1和VEGF表达阳性率在T3～T4高于T1～T2;有淋巴结转移组高于无淋巴结转移组DukesC～D期表达阳性率高于DukesA～B期,差异均有统计学意义(P＜ 0.05);VEGF和TGF-β1之间存在较明显的相关性(P＜0.05).结论:TGF-β 1、VEGF在结肠癌组织中呈高表达,与浸漓深度、淋巴结转移、Dukes分期密切相关,两者也存在相关性,与肿瘤进展及预后相关,可作为结肠癌判断预后的参考指标.     

外周血中生存素的表达与结肠癌预后的相关研究

目的 探讨检测外周血生存素(survivin)的表达与结肠癌复发、转移的关系.方法 采用反转录-聚合酶链反应-酶联免疫吸附试验(RT-PCR-ELISA)方法检测结肠癌患者外周血中survivinmRNA的表达,分析其与临床病理因素之间的关系.对其中51例患者进行36个月随访,比较复发及转移时间与外周血中survivin mRNA表达之间的关系.结果 95例结肠癌患者中35例survivin mRNA表达阳性(36.8％).肿瘤高中分化及低未分化患者survivin mRNA表达率分别为31.0％和45.0％(P＜0.05),浸润深度达浆膜层者表达率为44.0％,高于侵及黏膜下层及肌层者(20.0％)(P＜0.05),淋巴结有转移者表达率为47.5％,高于无淋巴结转移者(19.4％)(P＜0.05).随访发现外周血survivin表达阳性患者的复发及转移率(47.3％)明显高于阴性患者(16.6％).提示survivin mRNA在外周血的表达与肿瘤分化、浸润深度、淋巴结转移和临床分期有关,但与肿瘤部位无明显关系.结论 外周血survivin阳性患者易于复发或转移;外周血survivin的表达可作为评价结肠癌生物学行为及预后的参考指标.     

结肠癌组织标本Rho解离抑制因子2的表达及其与临床病理的关系

目的 探讨结肠癌Rho解离抑制因子2(RhoGDI2)基因的表达及其与临床病理的关系.方法 运用组织芯片技术、免疫组织化学法检测75例结肠癌患者原发癌灶和癌旁正常结肠组织的RhoGDI2的表达及其与相应结肠癌临床病理参数之间的关系.运用Western blot和实时定量聚合酶链反应(Real-time PCR)检测18例配对结肠腺癌原发灶组织和癌旁5 cm正常结肠组织的RhoGDI2的表达.结果 RhoGDI2阳性率在结肠癌原发癌灶和癌旁正常组织分别为73.33％和33.33％ (P＜0.05);RhoGDI2阳性率与临床TNM分期相关(P＜0.01),与原发灶T分期范围相关(P＜0.05),与淋巴结N分期、远处转移M无明显相关(P＞0.05).18例结肠癌RhoGDI2 Western blot灰度值高于正常组织的4.8倍(P＜0.05).Real-time PCR结果显示癌灶组RhoGDI2相对表达量高于癌旁对照组(P ＜0.05);RhoGDI2表达阳性率与临床TNM分期明显相关(P＜0.01),与原发灶T分期明显相关(P＜0.05).结论 RhoGDI2在结肠癌中表达上调,与临床TNM分期明显相关.     

食管鳞癌组织中趋化因子受体CXCR4与淋巴结转移的关系

目的 研究食管鳞癌组织中趋化因子受体(2XCR4与淋巴结转移的关系.方法 应用免疫组织化学方法检测68例正常食管黏膜组织、68例食管鳞癌组织、37例食管鳞癌淋巴结转移组织CXCR4表达情况,生存率计算用寿命表法.结果 正常食管黏膜组织、食管鳞癌组织、食管鳞癌淋巴结转移组织CXCR4阳性率分别为12%(8/68)、54%(37/68)、84%(31/37);食管鳞癌组织cx(2R4阳性率与临床分期、淋巴结转移、淋巴管浸润有关(X2=5.40,8.26,6.61,P＜0.05).食管鳞癌CXCR4阳性表达者3年生存率为32%(12/37),明显低于阴性表达者58%(18/31)(X2=4.50,P＜0.05).结论 CXCR4阳性表达与食管鳞癌的淋巴结转移有关,有助于判断预后.     

B细胞特异的莫洛尼白血病病毒插入位点1基因蛋白在结肠癌中的表达及其意义

目的 探讨B细胞特异的莫洛尼白血病病毒插入位点1基因(Bmi-1)的表达对结肠癌临床诊断及预后的意义.方法 逆转录-聚合酶链反应(RT-PCR)检测Bmi-1 mRNA在癌组织及癌旁黏膜中的表达差异.免疫组织化学研究203例结肠癌癌组织、203例癌旁正常黏膜和66例癌转移淋巴结中Bmi-1的表达,分析Bmi-1与临床病理特征和预后的相关性.结果 RT-PCR显示结肠癌中Bmi-1 mRNA表达显著高于癌旁正常黏膜.免疫组织化学结果显示癌旁正常黏膜、癌组织和癌转移淋巴结中的表达率分别为7.9%、66.6%、86.4%.Bmi-1过表达与临床分期、浸润深度、淋巴结转移和远处转移相关.Kaplan-Meier分析显示Bmi-1阳性组的无病生存时间和总生存时间较阴性组显著减低.COX回归多因素分析显示Bmi-1是影响结肠癌预后的独立因素之一(P<0.05).结论 Bmi-1过度表达可能参与结肠癌的发生发展过程.     

探讨结肠区域淋巴结转移率在Ⅲ期结肠癌预后中的相关研究

目的 探讨区域淋巴结转移率和Ⅲ期结肠癌预后的相关性.方法 对125例Ⅲ期结肠癌患者进行5年随访,分析性别,年龄,肿瘤部位,分化程度,浸润深度,淋巴结转移率,转移淋巴结个数和结肠癌预后的关系以及对5年生存率的影响.并且根据淋巴结转移率(LNR≥0.2和＜0.2)和淋巴结转移个数(转移淋巴结≥3枚和＜3枚)各分成两组,比较组间的预后差异.筛选出影响Ⅲ期结肠癌5年预后相关的独立危险因素.结果 统计发现不同性别、年龄、部位、浸润深度(T分期),进行分组分析,组间检验,差异无统计学意义(P＞0.05).以年龄,肿瘤分化,淋巴结转移率和淋巴结转移个数分组,组间有明显差别(P＜0.05).对影响5年生存率的相关因素进行Cox比例风险模分析,LNR(B=-1.270,Sig=0.00)和肿瘤的T分期(B=0.845,Sig =0.16)是影响5年生存的独立危险因素.结论 为了准确的对Ⅲ期结肠癌的患者进行预后分析,一定要强调术后病理严格按照TNM分期的原则报道,报告中补充LNR的值,有利于临床医师对患者预后的总体判断.     

KIF14在胃癌中的表达及其意义

目的：探讨KIF14在胃癌中的表达及其意义。方法：应用实时定量聚合酶链反应技术检测30例胃癌中KIF14 mRNA的表达,应用免疫组织化学方法检测89例胃癌、正常黏膜及35例转移淋巴结中KIF14蛋白的表达。结果：KIF14 mRNA在66.7%的胃癌组织中高表达;KIF14蛋白在胃癌组织中的表达率为62.9%,高于正常黏膜（6.74%,P〈0.05）,且与TNM分期（P〈0.01）、浸润深度（P〈0.05）、淋巴结转移（P〈0.05）、远处转移（P〈0.05）及Ki67相关。转移淋巴结中KIF14蛋白表达率（82.9%）高于原发癌和正常黏膜（P〈0.01）。KIF14蛋白阳性患者总体生存率和无病生存率均显著降低,KIF14是影响总体生存（P〈0.001）和无病生存（P〈0.001）的独立预后因素。结论：KIF14在胃癌发生发展中起重要作用,可能是新的预后指标。     

Is hepatic resection justified for non-colorectal non-neuroendocrine liver metastases? A systematic review and meta-analysis

BackgroundHepatic resection (HR) is effective for colorectal or neuroendocrine liver metastases. However, the role of HR for non-colorectal non-neuroendocrine liver metastases (NCNNLM) is unknown. This study aims to perform a systematic review and meta-analysis on long-term clinical outcomes after HR for NCNNLM.Methodselectronic search was performed to identify relevant publications using PRISMA and MOOSE guidelines. Primary outcomes were 3- and 5-year overall survival (OS) and disease-free survival (DFS). Secondary outcomes were post-operative morbidity and 30-day mortality.ResultsThere were 40 selected studies involving 5696 patients with NCNNLM undergone HR. Pooled data analyses showed that the 3- and 5-year OS were 40% (95% CI 0.35–0.46) and 32% (95% CI 0.29–0.36), whereas the 3- and 5-year DFS were 28% (95% CI 0.21–0.36) and 24% (95% CI 0.20–0.30), respectively. The postoperative morbidity rate was 28%, while the 30-day mortality was 2%. Subgroup analysis on HR for gastric cancer liver metastasis revealed the 3-year and 5-year OS of 39% and 25%, respectively.ConclusionsHR for NCNNLM may achieve satisfactory survival outcome in selected patients with low morbidities and mortalities. However, more concrete evidence from prospective study is warrant in future.     

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??PredictIve value of EMVI detected by MDCT combined with CA19-9 for prognosis of stage III colon caner patients ZHOU Jing*,Yao Xun,ZHANG Hui, et al.*Department of Gastroenterological Surgery,Peking University People’s Hospital, Beijing 100044??China
Corresponding author: WANG Shan, E-mail??wangshan@pkuph.edu.cn
Abstract Objecetive To investigate the ability of extramural vascular invasion??EMVI?? in predicting 3-years disease-free survival ??3yr DFS?? of patients with colon cancer. Methods Between February 2009 and December 2013?? patients who had histologically proven primary colon cancer and underwent curative resection were included in this retrospective study. EMVI was defined as tumor tissue in adjacent vessels beyond colon wall on MDCT. DFS was defined as the time from the date of curative resection to the date of local recurrence?? and/or distant disease?? or tumor-related death. Univariate and multivariate analysis were conducted to identify prognostic factors associated with 3yr DFS. Kaplan-Meier analyses were used to compare 3yr DFS. Cox’s proportional hazards models were used to measure the impact of confounding variables on survival rates. Chi-square test was used to analyze the difference of recurrent/metastatic rate. Results In final?? 90 patients were included in this study that were identified as stage ?? patients by pathology based on American Joint Committee on Cancer ??AJCC??. Multivariate analysis showed that elevated serum CA19-9??HR=2.229??95%CI 1.040-4.776??P=0.039??and EMVI positive ??HR=3.266??95%CI 1.648-7.173??P=0.003?? were identified as independent predictors of 3yr DFS in stage ?? colon cancer. Cumulative 3-year DFS were 52.8% and 81.5%??95%CI 1.648-7.173?? for EMVI positive and negative patients?? and 55.6% and 76.6%??95%CI 1.040-4.776?? for elevated serum CA19-9 and normal serum CA19-9?? significances were seen ??P??0.05??. Compared with ctEMVI positive combined with elevated serum CA19-9?? 3yr recurrent/metastatic rate of ctEMVI negative combined with normal serum CA19-9 was lowerer significantly ??10.5% vs. 54.5%?? P??0.05?? .Conclusion EMVI detected with ceMDCT?? and elevated serum CA19-9 level could be used as independent predictors of 3yr DFS in patients with stage ?? colon cancer.     

Prognostic Significance of Post-Operative Morbidity Severity Score After Potentially Curative D2 Gastrectomy for Carcinoma

Background

Survival and relapse after gastric cancer surgery are largely attributed to tumor biology and surgical radicality; yet, other prognostic factors have been reported, including respiratory sepsis and anastomotic leakage, but not global morbidity severity score (MSS). The hypothesis tested was that MSS would be associated with both disease-free (DFS) and overall survival (OS).

Methods

Consecutive 373 patients undergoing potentially curative surgery for gastric adenocarcinoma between 2004 and 2016 in a UK cancer network were studied. Complications were defined prospectively as any deviation from a pre-determined post-operative course within 30 days of surgery and classified according to the Clavien-Dindo severity classification (CDSC). Primary outcome measures were DFS and OS.

Results

Post-operative complications were identified in 127 (34.0%) patients, which was associated with 9 (2.4%) post-operative deaths. Five-year DFS and OS were 35.9 and 38.5% for patients with a post-operative complication compared with 59.5 and 61.5% in controls (p?<?0.001, p?=?0.001, respectively). On multivariable DFS analysis, post-operative morbidity [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.06–2.50, p?=?0.026] was independently associated with poor survival. On multivariable OS analysis, post-operative morbidity HR 2.25 (95% CI 1.04–4.85, p?=?0.039) and CDSC HR 1.76 (95% CI 1.35–2.29, p?<?0.001) were independently associated with poor survival. These associations were also observed in patients with TNM stage I and II disease with morbidity HR 7.06 (95% CI 1.89–26.38, p?=?0.004) and CDSC HR 2.93 (95% CI 1.89–4.55, p?<?0.001) offering independent prognostic value.

Conclusion

Post-operative CDSC was an important independent prognostic factor after potentially curative gastrectomy for carcinoma associated with both DFS and OS. Prehabilitation strategies to minimize complications are warranted.

     

Prognostic value of FOXA1 in breast cancer: A systematic review and meta-analysis

BackgroundDespite some published papers analyzing the prognostic role of forkhead-box A1 (FOXA1) in breast cancer, it has not yet been considered as an established prognostic factor in clinical practice. The present meta-analysis evaluated the prognostic value of FOXA1 in breast cancer.MethodsPubMed, Web of Science and Embase databases were searched for relevant published literature that evaluated the correlation between FOXA1 and breast cancer. Either a fixed or random effect model was applied to estimate the pooled hazard ratio (HR) for FOXA1 prognosis in breast cancer.ResultA total of nine articles comprising 6386 breast cancer patients met the inclusion criteria. Among these nine studies, five studies and four studies investigated the prognostic association with disease-free survival (DFS), and overall survival (OS), respectively. Meta-analysis results suggested that high FOXA1 expression was positively associated with DFS (pooled HR: 0.43, 95% CI: 0.23–0.81; P < 0.05) and OS (pooled HR: 0.39, 95% CI: 0.26–0.60; P < 0.05) in breast cancer patients. No publication bias was discovered by Begg's test in this meta-analysis.ConclusionThe results from this meta-analysis indicated that elevated FOXA1 expression level was associated with better outcome in breast cancer.     

Internal mammary node irradiation in node-positive breast cancer treated with mastectomy and taxane-based chemotherapy

BackgroundIt is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy.MethodsWe analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups.ResultsAfter a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018).ConclusionsIMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.     

New onset vasomotor symptoms but not musculoskeletal symptoms associate with clinical outcomes on extended adjuvant letrozole – Analyses from NCIC CTG MA.17

PurposeNew onset symptoms on adjuvant aromatase inhibitors for hormone receptor positive early breast cancer may associate with clinical outcomes. We performed this exploratory analysis of the association of new onset musculoskeletal (MSK) and vasomotor (VM) symptoms with clinical outcomes in the NCIC CTG MA.17 trial 5 years of extended adjuvant endocrine therapy with letrozole after tamoxifen.MethodsSymptoms were collected at baseline, 1, 6, and every 12 months on study. Multivariate Cox Models adjusting for age, nodal status, duration of tamoxifen and prior chemotherapy were used to compare disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) based on data collected before, and after, the unblinding between women with VM or MSK symptoms and those without.ResultsData post-unblinding showed new VM symptoms on extended letrozole significantly improved DFS and DDFS when occurring 1 month (DFS HR 0.52, 95% CI, 0.28–0.96; p = 0.04; DDFS HR 0.49, 95% CI, 0.24–0.99; p = 0.046) and 6 months (DFS HR 0.43, 95% CI, 0.24–0.78; p = 0.006; DDFS HR 0.44, 95% CI, 0.22–0.85; p = 0.02) after treatment initiation. Those with new VM symptoms at 12 months also had a significantly better DFS (HR 0.47, 95% CI 0.26, 0.84; P = 0.01) and a trend in improved DDFS. Only a trend to improved OS was found for those with VM symptoms 6 month after treatment. No significant improvement was found for those with new MSK symptoms at any time point or for any endpoint.ConclusionsNew onset VM symptoms with extended letrozole may be useful in predicting treatment benefit.