结直肠癌患者体质量指数及临床特征与远期预后的相关性

目的研究结直肠癌患者的体质量指数、血清脂肪因子及一般临床特征,探索体质量指数对结直肠患者远期预后的影响。方法 110例结直肠癌患者依据入院BMI值,分为体质量正常组(对照组,n=62)和超重肥胖组(观察组,n=48),比较两组患者血清脂联素、瘦素、TNF-α与VEGF水平;比较结直肠癌患者不同BMI组基线特征;对术后五年生存情况进行回归分析。结果超重肥胖组患者血清瘦素、TNF-α与VEGF水平均较对照组显著降低,脂联素水平显著高于对照组,差异均具有统计学意义(P <0.05);相关性分析结果表明:BMI与脂联素呈负相关(P <0.05),与瘦素、TNF-α及VEGF呈显著正相关(P <0.05);对两组患者男性比例、年龄、肿瘤大小、肿瘤位置、肿瘤分化程度、淋巴结转移以及TNM分期等资料比较,差异无统计学意义(P> 0.05);生存曲线结果表明:两组患者的生存时间分布差异具有统计学意义(χ^(2)=4.976,P=0.026)。Logistic回归分析结果表明,肿瘤分化程度、淋巴结转移以及TNM分期是五年生存率的危险因素(P <0.05),BMI不是五年生存率的危险因素(P> 0.05)。结论超重肥胖的结直肠癌患者血清脂联素、瘦素、TNF-α与VEGF水平异常表达,其指标水平与BMI有相关性;影响患者远期预后的主要因素是肿瘤分化程度、淋巴结转移以及TNM分期;体质量指数对五年生存率有一定的影响。

结直肠癌Ang-2和CD147的水平及其对预后的预测价值

探讨结直肠癌患者促血管生成素Ⅱ(angiopoietin-2,Ang-2)和簇分笔者医化抗原147 (cluster of differentiation 147,CD147)的水平及其对预后的预测价值。方法:回顾性分析2012年6月~2016年5月笔者医院诊治的260例结直肠癌患者,根据随访结果分为生存组( n =215)和死亡组( n =45),并选择50例结直肠息肉作为对照组,均应用组织芯片技术进行免疫组化结果分析,比较Ang-2和CD147不同表达水平间临床和病理表现的差异及对预后的预测价值。结果:结直肠癌组与对照组患者的年龄、性别、BMI和既往史之间比较差异无统计学意义( P >0.05)。结直肠癌组患者Ang-2及CD147表达水平明显高于对照组( P =0.000)。生存组与死亡组患者的年龄、性别、BMI和既往史之间比较差异无统计学意义( P >0.05)。生存组与死亡组患者的肿瘤部位、病理类型、分化程度、临床分期及治疗方式等资料间比较差异无统计学意义( P >0.05);生存组Ang-2及CD147表达分值明显低于死亡组( P =0.000),淋巴结转移情况明显低于死亡组( P =0.000)。ROC曲线显示,应用Ang-2及CD147表达水平对预测结直肠癌患者预后具有较高的诊断效能,其AUC分别为0.821和0.788,差异无统计学意义(P >0.05);Youden 指数提示Ang-2及CD147表达水平预测结直肠癌患者预后的最佳截点分别为≥4分和≥3分。Ang-2及CD147表达水平预测结直肠癌患者预后的诊断准确率(81.88%,83.33%)、敏感度(81.30%,82.00%)、特异性(83.33%,87.69%)和阳性预测值(87.23%,89.23%)比较,差异无统计学意义( P >0.05)。结论:结直肠癌患者Ang-2和CD147表达水平较高,Ang-2和CD147在预测结直肠癌患者预后中有较高价值,Ang-2≥4分和CD147≥3分可作为提示不良预后的参考指标。

运用组织芯片技术检测COX-2在结直肠癌中的表达及其临床意义

目的探讨结直肠癌组织中COX-2的表达及其与各临床病理因素的关系,评价COX-2在结直肠癌预后判断中的价值。方法应用组织芯片技术结合免疫组织化学SABC法,检测126例早中期结直肠癌组织中COX-2的表达情况,回顾性分析COX-2与各临床病理因素及预后之间的关系。结果根据免疫组化染色强度,所有病例被分为COX-2高表达组和低表达组,其中高表达组有32例(25.4%),低表达组有94例(74.6%)。COX-2在结直肠癌中表达情况与年龄、性别、肿瘤大小、肿瘤部位、组织学类型、浸润深度、淋巴是否转移、Dukes分期均无相关。然而,高表达的COX-2与肿瘤复发、特别是血行转移显著相关(P<0.05)。两组之间生存率具有显著差异(P=0.0067),COX-2高表达组术后五年生存率显著低于低表达组。多因素回归模型分析结果显示,在潜在的预后因素中(年龄、性别、肿瘤大小、肿瘤部位、组织学类型、淋巴是否转移、Dukes分期、COX-2表达),COX-2表达和Dukes分期可作为是结直肠癌根治术后独立预后因素,COX-2的检测可作为结直肠癌患者预后判断的一个有价值的指标。结论高表达的COX-2与肿瘤复发、特别是血行转移显著相关,COX-2的检测可作为结直肠癌患者预后判断的一个有价值的指标。应用组织芯片高效检测临床组织样本具有快速、方便、经济、准确的优点。

Levels of v5 and v6 CD44 splice variants in serum of patients with colorectal cancer are not correlated with pT stage,histopathological grade of malignancy and clinical features

AIM:This study was designed to compare the levels of v5 and v6 splice variants of CD44 evaluated using EITSA test in the serum of patients with colorectal cancer in different stages of progression of the disease estimated in pT stage according to WHO score,histopathological grade of malignancy and some clinicopathological features. METHODS:The serum obtained from 114 persons with colorectal adenocarcinomas was examined using ELISA method,pT stage and grade of malignancy of the tumour were examined in formalin fixed and paraffin embedded materials obtained during operation. RESULTS:Only the level of CD44 v5 in the serum of patients before operation with G2 pT4 tumour was lower than that in other probes and the difference was statistically significant. We did not find any other correlations between the level of v5 and v6 CD44 variants and other evaluated parameters. CONCLUSION:The level of CD44 v5 and v6 estimated by ELISA test in the serum can not be used as a prognostic factor in colorectal cancer.

Role of von Willebrand factor levels in the prognosis of stage Ⅳ colorectal cancer: Do we have enough evidence?

Cancer patients usually present a prothrombotic condition. Several clotting-related proteins, such as von Willebrand factor （vWF）, presenting higher plasma concentrations in these patients, may play a key role in this process. Moreover, some of those proteins are currently being characterized as response rate and overall survival markers in metastatic colorectal cancer （MCRC）. In this comment article,

Neural cell adhesion molecule-180 expression as a prognostic criterion in colorectal carcinoma:Feasible or not?

AIM： To evaluate the frequency of neural cell adhesion molecule （NCAM）-180 expression in fresh tumor tissue samples and to discuss the prognostic value of NCAM-180 in routine clinical practice.METHODS： Twenty-six patients （16 men, 10 women） with colorectal cancer were included in the study. Fresh tumor tissue samples and macroscopically healthy proximal margins of each specimen were subjected to flow-cytometric analysis for NCAM-180 expression.RESULTS： Flow-cytometric analysis determined NCAM-180 expression in whole tissue samples of macroscopically healthy colorectal tissues. However, NCAM-180 expression was positive in only one case （3.84%） with well-differentiated Stage Ⅱ disease who experienced no active disease at 30 months follow-up. CONCLUSION： As a consequence of the limited number of cases in our series, it might not be possible to make a generalisation, nevertheless the routine use of NCAM-180 expression as a prognostic marker for colorectal carcinoma seems to be unfeasible and not cost-effective in clinical practice due to its very low incidence.

Loss of heterozygosity: An independent prognostic factor of colorectal cancer

AIM: Colorectal cancers result from the accumulation of several distinct genetic alterations. This study was to investigate the frequency and prognostic value of loss of heterozygosity (LOH) and microsatellite instability (MSI) at 14 genetic loci located near or within regions containing important genes implicated in colorectal tumorigenesis. METHODS: We studied colorectal cancers with corresponding normal mucosae in 207 patients (139 males and 68 females, mean age at the time of tumor resection 66.2±12.4 years, range 22-88 years). There were 37 right-sided colonic tumors, 85 left-sided colonic tumors and 85 rectal tumors. The distribution of tumor staging was stage Ⅰ in 25, stage Ⅱ in 73, stage Ⅲ in 68, and stage Ⅳ in 41. We analyzed the LOH and MSI of HPC1, hMSH2, hMLH1, APC, MET, P53, NH23-H1, DCC, BAT25, BAT26, D17S250, MYCL1 and D8S254 with fluorescent polymerase chain reaction and denatured gel electrophoresis. High-frequency LOH was determined to be greater than three, or more than 50% of the informative marker with LOH. High-frequency MSI (MSI-H) was determined as more than four markers with instability (>30%). Correlations of LOH and MSI with clinical outcomes and pathological features were analyzed and compared. RESULTS: The occurrence of MSI-H was 7.25%, located predominantly in the right colons (7/15) and had a higher frequency of poor differentiation (6/15) and mucin production (7/15). LOH in at least one genetic locus occurred in 78.7% of the tumors and was significantly associated with disease progression. Of the 166 potentially cured patients, 45 developed tumor recurrence within 36 mo of follow-up. Clinicopathological factors affecting 3-year disease-free survival (DFS) were TNM staging, grade of differentiation, preoperative CEA level, and high LOH status. Patients with high LOH tumors had a significantly lower DFS (50%) compared with patients with low LOH tumors (84%). Of the patients developing subsequent tumor recurrence, the number and percentage of LOH were 2.97 and 46.8% respectively, similar to the stage IV disease patients. TNM staging had the most significant impact on DFS, followed by high LOH status. CONCLUSION: Clinical manifestations of LOH and MSI are different in colorectal cancer patients. High-frequency LOH is associated with high metastatic potential of colorectal cancers.

Analysis of Prognosis of 122 Colorectal Cancer Patients with Concurrent Liver Metastasis

OBJECTIVE To explore prognostic factors and treatmentchoices for colorectal cancer (CRC) patients with concurrent livermetastases (CLM).METHODS The data of the 122 CRC patients with CLM, whowere treated in our hospital from January 2000 to December 2005,were collected. Overall survival rate of the patients in our groupwas analyzed using Kaplan-Meier method, and the univariateand multivariate analyses of the 18 factors affecting the survivalrate, including clinicopathologic factors and treatment methods,were conducted using Log-rank test and Cox regression model(SPSS13.0).RESULTS The median survival time of the 122 patients withCRC was 13 months. The 1, 2, 3 and 5-year survival rate was52.46%, 24.59%, 12.30% and 3.28%, respectively. Univariateanalysis combined with Kaplan-Meier curve revealed that thefactors of prognosis included the size of the primary tumor, thelevels of differentiation, lymphatic status, cancerous ileus (CI),the number, size and distribution of liver metastases, extrahepaticinvolvement, the serum CEA level at diagnosis, treatmentmodality, the extent of primary resection, chemotherapeuticmodality and regimen. Multivariate analysis showed that CI,differentiation levels, serum CEA value at diagnosis and treatmentmodality were the independent prognostic factors of CRC patientswith CLM.CONCLUSION For the CRC patients with CLM, poordifferentiation of the tumor and CI, as well as a high CEAlevel indicate an unfavorable prognosis. Treatment choice is ofspecial significance in treating the CRC patients with CLM, soactive radical excision of the primary tumor and liver metastasisis strongly recommended in the CRC patients with hepaticmetastasis alone. Interventional chemotherapy has advantagescompared with the whole-body chemotherapy via peripheral vein,and the regimen of systemic chemotherapy containing oxaliplatinis preferred.

Influence of the Number of Lymph Nodes Examined on the Prognosis of Patients with Dukes' B and C Colorectal Carcinoma

OBJECTIVE To analyze the influence of the number of lymph nodes examined on the prognosis of Dukes' B and C colorectal cancer patients.METHODS The relationship between the clinicopathologic features of 373 patients with Dukes' B and C colorectal cancer and number of the lymph nodes examined was retrospectively analyzed.The effect of the different number of nodes examined on the prognosis of the patients was appraised RESULTS The overall mean number of retrieved lymph nodes of the 373 patients with Dukes' B and C colorectal cancer was 13.71±9.38.The site and size of the tumor as well as the depth of tumor infiltration were the major reasons which influenced the number of lymph nodes retrieved.The mean number of lymph nodes examined in the colon-cancer patients was 17.51± 12.79,which was significantly more than the 11.09±6.17(P = 0.000)exam-ined in the rectal-cancer patients.The 5-year survival rate of the patients with Dukes' B large intestinal carcinoma,with fewer lymph nodes retrieved(0 to 10),was only 60.4%,while those with more lymph node retrieved(≥10)had a 5-year survival of 77.5%.So there was a significant difference between the two groups.However the number of lymph nodes examined had no effect on prognosis of the patients with Dukes' C large intestinal carcinoma.Separate analysis of the colon and rectal cancers indicated that to improve the 5-year survival rate,the number of retrieved nodes in cases with rectal cancer should be at least 9,and with colon cancer cases at least 13.CONCLUSION In order to guarantee an accuracy of tumor staging for developing a possible postoperative treatment,at least 9 lymph nodes in rec-tal cancer patients or 13 in colon cancer patients should be harvested.

Molecular subtypes of colorectal cancer:Evaluation of outcomes and treatment

Colorectal cancer(CRC) is a biologically heterogeneous disease with diverse clinical outcomes and responses to treatment. In the past two to three decades, a major effort has focused on classifying colorectal cancer subtypes based on causation, etiology, gene expression profiles, different pathways, and translational data from clinical trials. The goal is to uncover prognostic and predictive factors for outcomes in patients with colorectal cancer and to guide therapeutic approaches and management for the improvement of overall survival. Significant advances have been achieved in this area. However, tremendous work is still needed to accomplish the goal of better understanding intratumoral heterogeneity and the influence of the colonic environment, among other facets of colorectal cancer.

Recurrence and survival rates of inflammatory bowel disease-associated colorectal cancer following postoperative chemotherapy:a comparative study

Background and Aim:Inflammatory bowel disease(IBD)is associated with an increased risk of colorectal cancer(CRC).Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC,suggesting differences in tumor behavior and response to treatment.We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD.Methods:Search of the Cleveland Clinic’s CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010.Twenty-one patients were excluded due to incomplete clinical data.Propensity score-matching based on age,surgery intent,CRC site,tumor grade,American Joint Committee on Cancer(AJCC)stage and T stage was used to match IBD and non-IBD patients(1:4).Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival,respectively.Results:Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC.Among IBD patients,29(66%)had ulcerative colitis,14(32%)had Crohn’s disease,and one(2%)had indeterminate colitis.Mean IBD diagnosis age was 28.1±14.5 years,and mean IBD duration at time of CRC treatment was 21.5±12.6 years.Ten(23%)IBD patients had tumor recurrence compared with 34(19%)non-IBD patients(P=.074).There was no significant difference in disease-free survival(hazard ratio[HR]=0.60;95%CI:0.35–1.05;P=0.074)or overall survival(HR=0.87;95%CI:0.54–1.4;P=0.58)between IBD and non-IBD patients.Conclusion:Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD.Prospective studies are needed to confirm these findings and guide therapeutic decisions.

Global changes of 5-hydroxymethylcytosine and 5-methylcytosine from normal to tumor tissues are associated with carcinogenesis and prognosis in colorectal cancer

Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal cancer(CRC) and their association with the prognosis. The levels of genomic 5-hydroxymethylcytosine(5hmC) and 5-methylcytosine(5mC) in cancerous tissues were significantly lower than those in corresponding adjacent normal tissues. The genomic levels of 5mC were significantly positively correlated with 5hmC in normal and cancerous tissues(all P<0.05). The ratio of 5mC in cancerous tissues to matched normal tissues(C/N-5mC) was also significantly positively correlated with the ratio of 5hmC in cancerous tissues to matched normal tissues(C/N-5hmC)(P=0.01). The 5mC levels and C/N-5mC ratios decreased with age(all P<0.05). Higher 5mC and 5hmC levels were found in rectal than in colon tissues(all P<0.05). High levels of 5mC in cancerous tissues and high C/N-5hmC ratios were each associated with lymph node metastasis(all P<0.05). Survival analysis indicated that the C/N-5mC ratio(P=0.04) is an independent protective factor for overall survival. The data showed that patients with a combination of high C/N-5hmC and low C/N-5mC ratios tended to have a worse prognosis(P<0.01). Our findings showed that the C/N-5mC ratio may be an independent prognostic factor for CRC outcome. Patients with both a high C/N-5hmC ratio and a low C/N-5mC ratio exhibited the worst survival, suggesting that 5mC and 5hmC can be used as critical markers in tumorigenesis and prognosis estimation.