Impact of Serum Apolipoprotein A-I on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer: a Propensity Score-Matched Analysis

PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I) as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low– and high–ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P < .001) and PFS (P < .001) than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P < .001) and PFS (P = .001). PFS (P < .001) in either the high– or low–ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P = .049). CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.     

贝伐单抗二线治疗转移性结直肠癌的临床观察

目的:观察贝伐单抗二线治疗转移性结直肠癌患者的临床疗效和毒副反应。方法:回顾性分析2008年8月至2011年10月我院经组织病理学证实的转移性结直肠癌患者21例,一线治疗进展后,二线治疗方案中加用贝伐单抗,用法为5mg/kg,每2-3周1次,与化疗方案同步。化疗方案以奥沙利铂及伊立替康为基础,完成2-3周期治疗后评定疗效,观察毒副反应。结果:21例患者中PR1例,SD11例,PD9例,客观缓解率为4.8%,疾病控制率为57.1%,中位TTP为3.7个月。患者出现的不良反应有骨髓抑制、皮疹、恶心呕吐、腹泻、肝功能损害、神经毒性等,贝伐单抗所致高血压的发生率为14.3%(3/21),鼻衄发生率为4%(2/21)。结论:二线治疗中使用贝伐单抗,对一线治疗进展后的转移性结直肠癌疗效有限,毒副反应可耐受。     

贝伐珠单抗联合化疗治疗晚期结直肠癌的临床疗效

目的:探讨晚期结直肠癌采用贝伐珠单抗联合化疗的临床疗效,为临床治疗提供参考。方法:按照随机数字表法将2010年2月~2013年2月我院收治的50例晚期结直肠癌患者分为两组,观察组采用贝伐珠单抗联合奥沙利铂,卡培他滨化疗,对照组单用奥沙利铂,卡培他滨进行化疗,比较两组的临床疗效、血清肿瘤标志物浓度变化及不良反应。结果:化疗4个周期后观察组有效率为56.00%高于对照组的24.00%,差异有统计学意义(P0.01),观察组疾病控制率为84.00%高于对照组的60.00%,差异有统计学意义(P0.05);观察组治疗后的CEA、CA242、CA19-9浓度均低于对照组,差异有统计学意义(P0.01);化疗后两组不良反应主要有恶心、呕吐、食欲减低等胃肠道反应,乏力,肝功能损害,骨髓抑制,脱发,贫血以及中性粒细胞下降等,其中观察组乏力,肝功能损害发生率低于对照组,差异有统计学意义(P0.05),其余不良反应两组差异无统计学意义(P0.05)。结论:结直肠癌采用贝伐珠单抗联合化疗治疗具有近期疗效好,安全性高等特点,临床有重要参考价值。     

Clinical Efficacy of Chemotherapy Combined with Verapamil in Metastatic Colorectal Patients

In order to determine the clinical efficacy and adverse reactions of chemotherapy and verapamil infusion through a target artery to treat colorectal cancer patients with metastasis after failure with previous conventional treatments. Patients with metastatic colon cancer (n = 36) received an infusion of verapamil, interleukin-2, oxaliplatin (or hydroxy camptothecin or irinotecan hydrochloride), fluorouracil and calcium folinate through target artery using the Seldinger puncture technique. From the second day of infusion, the patients were treated with fluorouracil and calcium folinate via systematic intravenous injection for 2–3 days. Efficacy was evaluated after at least two treatment courses. The objective response including complete or partial response was 58.3% in the 36 patients; clinical benefit rate, evaluated by Karnofsky Performance Status score was 91.7%; by weight was 83.3%; by the amount of painkiller consumed was 80.6%. No patient experienced side effects associated with heart function. Post-treatment, the P–R period, Q–T period, QRS, and heart rate were not significantly different than before treatment. Liver function was significantly improved. Side effects of chemotherapy were minor in comparison to those observed with intravenous chemotherapy. Infusion of verapamil and chemotherapy directly into pelvic tumor tissue can increase treatment efficacy and has been shown to be a relatively safe technique.     

Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab

Purpose

We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC).

Experimental Design

Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV): screening (n = 212) and validation (n = 121) cohorts, or CAPEOX alone: control cohort (n = 127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR) arrays and expression levels were related to time to disease progression (TTP) and overall survival (OS). Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH) was done for selected miRNAs.

Results

In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts.

Conclusions

We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials.     

EMAST Is Associated with a Poor Prognosis in Microsatellite Instable Metastatic Colorectal Cancer

Purpose

To determine the frequency and prognostic value of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in metastatic colorectal cancer (mCRC) patients in relation to microsatellite instability (MSI) status and MSH3 protein expression.

Material and Methods

The frequency of EMAST was evaluated in mCRC patients with MSI tumors and microsatellite stable (MSS) tumors. A literature overview was performed to compare the frequency of EMAST in our study with existing data. Immunohistochemistry for MSH3 was compared with EMAST status. Outcome was studied in terms of overall survival (OS) of mCRC patients with MSI and MSS tumors.

Results

EMAST was evaluated in 89 patients with MSI tumors (including 39 patients with Lynch syndrome) and 94 patients with MSS tumors. EMAST was observed in 45.9% (84 out of 183) of patients, with an increased frequency in MSI tumors (79.8% versus 13.8%, p < 0.001). We found no correlation between EMAST and MSH3 protein expression. There was no effect of EMAST on prognosis in patients with MSS tumors, but patients with MSI / non-EMAST tumors had a significantly better prognosis than patients with MSI / EMAST tumors (OS: HR 3.22, 95% CI 1.25-8.30).

Conclusion

Frequency of EMAST was increased in mCRC patients with MSI tumors, compared to MSS tumors. Our data suggest that the presence of EMAST correlates with worse OS in these patients. There was no effect of EMAST on the prognosis of patients with MSS tumors. A limitation of our study is the small number of patients in our subgroup analysis.     

Prospective Validation of Candidate SNPs of VEGF/VEGFR Pathway in Metastatic Colorectal Cancer Patients Treated with First-Line FOLFIRI Plus Bevacizumab

Purpose

The potential impact of different SNPs of VEGF/VEGFR pathway on the clinical outcome of mCRC patients receiving bev-containing regimens has been investigated in retrospective experiences with contrasting results. We previously reported the association of VEGFA rs833061 C/T variants with PFS in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab. The primary objective of this work was to prospectively validate that retrospective finding. A confirmatory analysis of other SNPs of VEGF/VEGFR pathway genes was included.

Experimental design

To detect a HR for PFS of 1.7 for VEGFA rs833061 T/T compared to C- variants in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab, setting two-sided α = 0.05 and β = 0.20, 199 events were required. VEGFA rs699946 A/G, rs699947 A/C, VEGFR1 rs9582036 A/C and rs7993418 A/G, VEGFR2 rs11133360 C/T, rs12505758 C/T and rs2305948 C/T and EPAS1 rs4145836 A/G were also tested. Germ-line DNA was extracted from peripheral blood. SNPs were analyzed by PCR and sequencing.

Results

Four-hundred-twenty-four pts were included. At the univariate analysis, no differences according to VEGFA rs833061 C/T variants were observed in PFS (p = 0.38) or OS (p = 0.95). Among analyzed SNPs, only VEGFR2 rs12505758 C- variants, compared to T/T, were associated to shorter PFS (HR: 1.36 [1.05–1.75], p = 0.015, dominant genetic model) and OS, with a trend toward significance (HR: 1.34 [0.95–1.88], p = 0.088). In the multivariate model, this association retained significance (HR: 1.405 [1.082–1.825], p = 0.012) in PFS, that was lost by applying multiple testing correction (p = 0.14).

Conclusion

This prospective experience failed to validate the hypothesized predictive impact of VEGFA rs833061 variants. Retrospective findings on different candidate SNPs were not confirmed. Only VEGFR2 rs12505758 variants, whose prognostic and not predictive impact was previously reported, correlated with PFS. Given the complexity of angiogenesis, it is rather unlike that a single germ-line SNP might be a good predictor of benefit from bevacizumab.     

Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

Background

In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates.

Methodology/Principal Findings

KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12–1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23–1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18–2.64).

Conclusions/Significance

This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.     

贝伐单抗新辅助化疗对直肠癌患者微血管密度的影响

目的：对直肠癌患者进行联合贝伐单抗新辅助化疗的临床病理进行评估,研究贝伐单抗对肿瘤组织微血管的影响。方法：回 顾性分析在我院普外科治疗的47 例直肠癌患者进行联合或不联合贝伐单抗（Bev）的新辅助化疗（NAC）治疗,用最大肿瘤直径评 估肿瘤客观反应,用肿瘤消退分级评估肿瘤病理反应。结果：有31 例（66%）患者进行联合贝伐单抗（Bev）的新辅助化疗治疗（联合 Bev组）和其他16 例患者进行不联合Bev的新辅助化疗治疗（不联合Bev 组）。联合Bev组的肿瘤客观反应率明显高于不联合 Bev组（64.5 vs. 25.0 %,P=0.015）。联合Bev组(41.9 %)的病理反应率高于不联合Bev 组（41.9%vs. 12.5 %,p=0.052）,但并没有明 显差异。联合Bev 组的微血管密度（MVD）低于不联合Bev 组。结论：联合Bev的新辅助化疗治疗患者的靶向和病理反应好于不 联合Bev 新辅助化疗的患者。联合Bev治疗患者的肿瘤组织的(MVD)受到抑制。     

Correlation of Hypertension and Proteinuria with Outcome in Elderly Bevacizumab-Treated Patients with Metastatic Colorectal Cancer

Background

Studies suggest a relationship between hypertension and outcome in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We performed a retrospective analysis of two phase II studies (BECA and BECOX) to determine if hypertension and proteinuria predict outcome in elderly patients with mCRC treated with bevacizumab.

Patients and Methods

Patients ≥70 years of age received either capecitabine 1250 mg/m² bid days 1–14 + bevacizumab 7.5 mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m² bid days 1–14 with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m² day 1 (BECOX study). The primary objective was to correlate hypertension and proteinuria with overall response rate (ORR), time to progression (TTP) and overall survival (OS). Secondary objectives included identification of risk factors associated with the development of hypertension and proteinuria and determining whether development of hypertension or proteinuria in the first 2 cycles was related to ORR, disease-control rate (DCR), TTP or OS.

Results

In total, 127 patients (median age 75.5 years) were included in the study. Hypertension correlated with DCR and OS; proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors for hypertension were female gender (odds ratio [OR] 0.241; P = 0.011) and more bevacizumab cycles (OR 1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P = 0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis identified as having prognostic value: baseline lactate dehydrogenase, haemoglobin, number of metastatic lesions and DCR.

Conclusion

This analysis of two phase II studies suggests that hypertension is significantly correlated with OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not with OS and TTP. Both hypertension and proteinuria are associated with the duration of bevacizumab treatment and do not represent an independent prognostic factor.     

不同原发肿瘤位置对于西妥昔单抗联合化疗治疗K-ras 基因 野生型的转移性结直肠癌患者的预后比较

目的:探讨不同原发肿瘤位置对于西妥昔单抗治疗K-ras基因野生型的转移性结直肠癌患者的预后影响。方法:回顾性分析2008年1月1日至2013年12月31日187例我院行西妥昔单抗联合FOLFOX或FOLFIRI治疗的转移性结直肠癌患者,根据原发肿瘤位置,以结肠左曲为分界点分为右半结肠癌和左半结肠癌两组,按照严格的配对标准进行1:2配对,最终获得右半结肠癌组16例,左半结肠癌组32例,进行分析,比较两组患者的近期疗效和无进展生存期。结果:右半结肠癌组ORR为56.3%,左半结肠癌组ORR为62.5%,2组比较差异无统计学意义(X2=0.174,P=0.676)。右半结肠癌组DCR为87.5%,左半结肠癌组DCR为93.7%。2组比较差异无统计学意义(X2=0.545,P=0.460)。右半结肠癌组的中位无进展生存时间(m PFS)为5.0个月,左半结肠癌组mPFS为7.7个月,两组差别有统计学意义(P0.05)。结论:K-Ras基因野生型的左半结肠癌患者应用西妥昔单抗治疗,预后好于右半结肠癌。     

术中局部化疗对大肠癌患者预后影响的临床观察

目的:观察术中局部化疗对大肠癌患者的预后影响,探讨提高大肠癌患者临床疗效的辅助治疗方法。方法:选择DuckB期和DuckC期患者76例,根据自愿的原则均分为常规手术组和术中化疗组,常规手术组采取常规手术治疗,术中化疗组在常规手术过程中给予局部化疗治疗,比较两组患者术后第7d血常规、肝肾功能及两组患者术后并发症,并随访两组患者术后12个月和24个月局部复发情况。结果:两组患者在术后血常规、肝肾功能及术后并发症方面比较,差异无统计学意义(P>0.05);术后12个月和24个月局部复发病例比较,差异具有统计学意义(P<0.05),术中化疗组显著少于常规手术组。结论:在DuckB期和DuckC期大肠癌患者外科手术治疗过程中,应积极采取术中化疗的治疗措施。     

术中局部化疗对大肠癌患者预后影响的临床观察

目的：观察术中局部化疗对大肠癌患者的预后影响,探讨提高大肠癌患者临床疗效的辅助治疗方法。方法：选择DuckB期和DuckC期患者76例,根据自愿的原则均分为常规手术组和术中化疗组,常规手术组采取常规手术治疗,术中化疗组在常规手术过程中给予局部化疗治疗,比较两组患者术后第7d血常规、肝肾功能及两组患者术后并发症,并随访两组患者术后12个月和24个月局部复发情况。结果：两组患者在术后血常规、肝肾功能及术后并发症方面比较,差异无统计学意义（P〉0．05）;术后12个月和24个月局部复发病例比较,差异具有统计学意义①〈0．05）,术中化疗组显著少于常规手术组。结论：在DuckB期和DuckC期大肠癌患者外科手术治疗过程中．应积极采取术中化疗的治疗措施。     

Association between GWAS-Identified Genetic Variations and Disease Prognosis for Patients with Colorectal Cancer

Genome-wide association studies (GWASs) have already identified at least 22 common susceptibility loci associated with an increased risk of colorectal cancer (CRC). This study examined the relationship between these single nucleotide polymorphisms (SNPs) and the clinical outcomes of patients with colorectal cancer. Seven hundred seventy-six patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. Twenty-two of the GWAS-identified SNPs were genotyped using a Sequenom MassARRAY. Among the 22 SNPs, two (rs1321311G>T in CDKN1A and rs10411210C>T in RHPN2) were significantly associated with the survival outcomes of CRC in a multivariate survival analysis. In a recessive model, the rs1321311 TT genotype (vs. GG + GT) and rs10411210 TT genotype (vs. CC + CT) were associated with a worse prognosis for disease-free survival (adjusted HR = 1.90; 95% confidence interval = 1.00-3.60; P = 0.050, adjusted HR = 1.94; 95% confidence interval = 1.05-3.57; P = 0.034, respectively) and overall survival (adjusted HR = 2.05; 95% confidence interval = 1.00-4.20; P = 0.049, adjusted HR = 2.06; 95% confidence interval = 1.05-4.05; P = 0.036, respectively). None of the other SNPs was significantly associated with any clinicopathologic features or survival. The present results suggest that the genetic variants of the CDKN1A (rs1321311) and RHPN2 (rs10411210) genes can be used as prognostic biomarkers for patients with surgically resected colorectal cancer.     

Cryptochrome 1 Overexpression Correlates with Tumor Progression and Poor Prognosis in Patients with Colorectal Cancer

Background

Clock genes drive about 5–15% of genome-wide mRNA expression, and disruption of the circadian clock may deregulate the cell''s normal biological functions. Cryptochrome 1 is a key regulator of the circadian feedback loop and plays an important role in organisms. The present study was conducted to investigate the expression of Cry1 and its prognostic significance in colorectal cancer (CRC). In addition, the function of Cry1 in human CRC was investigated in cell culture models.

Methods

Real-time quantitative PCR, Western blot analysis and immunohistochemistry were used to explore Cry1 expression in CRC cell lines and primary CRC clinical specimens. MTT and colony formation assays were used to determine effects on cellular proliferation ability. The animal model was used to explore the Cry1 impact on the tumor cellular proliferation ability in vivo. Transwell assays were performed to detect the migration ability of the cell lines. Statistical analyzes were applied to evaluate the diagnostic value and the associations of Cry1 expression with clinical parameters.

Results

Cry1 expression was up regulated in the majority of the CRC cell lines and 168 primary CRC clinical specimens at the protein level. Clinical pathological analysis showed that Cry1 expression was significantly correlated with lymph node metastasis (p = 0.004) and the TNM stage (p = 0.003). High Cry1 expression was associated with poor overall survival in CRC patients (p = 0.010). Experimentally, we found that up-regulation of Cry1 promoted the proliferation and migration of HCT116 cells, while down-regulation of Cry1 inhibited the colony formation and migration of SW480 cells.

Conclusions

These results suggest that Cry1 likely plays important roles in CRC development and progression andCry1 may be a prognostic biomarker and a promising therapeutic target for CRC.     

Clinical Implication of UGT1A1 Promoter Polymorphism for Irinotecan Dose Escalation in Metastatic Colorectal Cancer Patients Treated with Bevacizumab Combined with FOLFIRI in the First-line Setting

PURPOSE: This study aimed to identify the efficacy and toxicity of the FOLFIRI regimen (fluorouracil, leucovorin, and irinotecan) with irinotecan dose escalation plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer (mCRC) via UGT1A1 genotyping. METHODS: We administered bevacizumab plus FOLFIRI with irinotecan dose escalation to treat 70 mCRC patients. The UGT1A1 *1/*1 and *1/*28 genotypes started with a 180-mg/m² dose of irinotecan, and UGT1A1 *28/*28 genotype started with a dose of 120 mg/m². The dose of irinotecan was escalated at increasing intervals of 20 to 30 mg/m² until grade 3/4 adverse events (AEs) occurred. The clinical response rate, toxicity, and survival were analyzed. RESULTS: The clinical response and disease control rates of mCRC patients treated with FOLFIRI plus bevacizumab were significantly better in patients with UGT1A1 *1/*1 and *1/*28 genotypes than in patients with UGT1A1 *28/*28 (P = .006 and P < .001, respectively). Grade 3/4 AEs were significantly more common in mCRC patients with the UGT1A1 *28/*28 genotype (P < .001). Progression-free survival was significantly higher in UGT1A1 *1/*1 and *1/*28 patients (P = .002). mCRC patients who underwent metastasectomy achieved better overall survival than those who did not undergo metastasectomy (P = .015). CONCLUSIONS: Our study showed that mCRC patients with UGT1A1 *1/*1 and *1/*28 genotypes could receive escalated doses of irinotecan to obtain a more favorable clinical outcome without significant AEs.     

不同体质量指数对腹腔镜结直肠癌切除术患者临床疗效和远期预后的影响

摘要 目的：研究不同体质量指数（BMI）对腹腔镜结直肠癌切除术患者临床疗效和远期预后的影响。方法：将从2014年1月～2016年1月于我院接受腹腔镜结直肠癌切除术治疗的110例患者纳入研究。将所有受试者根据BMI的差异分作正常组（18.6 kg/m²≦BMI<23.0 kg/m²）35例、超重组（23.0 kg/m²≦BMI<25.0 kg/m²）53例、肥胖组（BMI≧25.0 kg/m²）22例。分析三组患者各项基线资料,临床疗效,术后并发症发生情况,远期预后等方面的差异。结果：三组患者各项基线资料比较差异均不明显（均P＞0.05）。肥胖组手术时长为（268.01±36.14）min,均明显高于正常组、超重组的（211.73±30.56）min、（224.12±34.87）min（均P＜0.05）;三组术中失血量、肛门排气时间以及住院康复时间对比均不明显（均P＞0.05）。三组患者术后肺部感染、下肢静脉血栓、切口感染以及吻合口出血发生率对比均不明显（均P＞0.05）。正常组5年生存率为45.71%（16/35）,超重组5年生存率为47.17%（25/53）,肥胖组5年生存率为45.45%（10/22）,三组比较差异无统计学意义（均P＞0.05）。结论：不同BMI对腹腔镜结直肠癌切除术患者的手术时长具有一定影响,但和远期预后无关,值得临床重点关注。     

Correlation between the Lactate Dehydrogenase Levels with Laboratory Variables in the Clinical Severity of Sickle Cell Anemia in Congolese Patients

BackgroundSickle cell anemia is an inflammatory disease and is characterized by chronic hemolysis. We sought to evaluate the association of lactate dehydrogenase levels with specific clinical phenotypes and laboratory variables in patients with sickle cell anemia.MethodsThe present cross-sectional study was conducted in Sickle Cell Centre of Yolo in Kinshasa, the Democratic Republic of Congo. Two hundred and eleven patients with Sickle Cell Anemia in steady state were recruited. Seventy-four participants with normal Hb (Hb-AA) were selected as a control group.ResultsThe average rates of hemoglobin, hematocrit, and red blood cells tended to be significantly lower in subjects with Hb-SS (p<0.001). The average rates of white blood cells, platelets, reticulocytes and serum LDH were significantly higher in subjects with Hb-SS (p<0.001). The average rates of Hb, HbF, hematocrit and red blood cells of Hb-SS patients with asymptomatic clinical phenotype were significantly higher than those of the two other phenotypes. However, the average rates of white blood cells, platelets, reticulocytes, and LDH of Hb-SS patients with the severe clinical phenotype are higher than those of two other clinical phenotypes. Significant correlations were observed between Hb and white blood cell in severe clinical phenotype (r3 = -0.37 *) between Hb and red blood cells in the three phenotypes (r1 = 0.69 * r2 * = 0.69, r3 = 0.83 *), and finally between Hb and reticulocytes in the asymptomatic clinical phenotype and severe clinical phenotype (r1 = -0.50 * r3 = 0.45 *). A significant increase in LDH was observed in patients with leg ulcer, cholelithiasis and aseptic necrosis of the femoral head.ConclusionThe increase in serum LDH is accompanied by changes in hematological parameters. In our midst, serum LDH may be considered as an indicator of the severity of the disease.     

Gene Expression Profiles Accurately Predict Outcome Following Liver Resection in Patients with Metastatic Colorectal Cancer

Purpose

The aim of this study was to build a molecular prognostic model based on gene signatures for patients with completely resected hepatic metastases from colorectal cancer (MCRC).

Methods

Using the Illumina HumanHT-12 gene chip, RNA samples from the liver metastases of 96 patients who underwent R0 liver resection were analyzed. Patients were randomly assigned to a training (n = 60) and test (n = 36) set. The genes associated with disease-specific survival (DSS) and liver-recurrence-free survival (LRFS) were identified by Cox-regression and selected to construct a molecular risk score (MRS) using the supervised principle component method on the training set. The MRS was then evaluated in the independent test set.

Results

Nineteen and 115 genes were selected to construct the MRS for DSS and LRFS, respectively. Each MRS was validated in the test set; 3-year DSS/LRFS rates were 42/32% and 79/80% for patients with high and low MRS, respectively (p = 0.007 for DSS and p = 0.046 for LRFS). In a multivariate model controlling for a previously validated clinical risk score (CRS), the MRS remained a significant predictor of DSS (p = 0.001) and LRFS (p = 0.03). When CRS and MRS were combined, the patients were discriminated better with 3-year DSS/LRFS rates of 90/89% in the low risk group (both risk scores low) vs 42/26% in the high risk group (both risk scores high), respectively (p = 0.002/0.004 for DSS/LRFS).

Conclusion

MRS based on gene expression profiling has high prognostic value and is independent of CRS. This finding provides a potential strategy for better risk-stratification of patients with liver MCRC.