淋巴结转移阴性的胃癌患者临床病理特征及生存探讨

目的:探讨淋巴结转移阴性胃癌患者的临床病理特征以及预后影响因素。方法:收集2000年1月至2009年1月我院收治的胃癌患者325例,其中经病理检查显示淋巴结转移阴性的105例患者作为阴性组(LN-组),另229例阳性患者作为阳性组(LN+组),比较两组的临床病理特征及临床预后。结果:LN-组的肿瘤直径、浸润深度及术后化疗与LN+组比较差异显著(P0.05);LN-组的5年生存率为76.2%,显著高于LN+组的43.2%(P0.05)。未透浆膜的LN-患者3年、5年生存率显著高于浸透浆膜者,术后化疗的LN-患者5年生存率显著高于未化疗者(P0.05),肿瘤直径5 cm的LN-患者3、5年生存率显著高于≥5 cm者(P0.05)。单因素分析显示浸润深度、肿瘤大小及术后化疗与LN-胃癌患者的预后具有密切关系(P0.05)。COX多因素分析显示浸润深度是影响LN-胃癌患者临床预后的独立因素(P0.05)。结论:淋巴结转移阴性胃癌患者的病灶多位于中下部,男性多于女性,发病年龄多在60岁以内,肿瘤直径多不超过5 cm,浸润深度多未浸透浆膜,临床预后优于淋巴结转移阳性胃癌患者,浸润深度是影响淋巴结转移阴性胃癌患者临床预后的独立因素。     

Multimodality Imaging to Predict Response to Systemic Treatment in Patients with Advanced Colorectal Cancer

Aim

Aim of this study was to investigate the potential of ¹⁸F-FDG PET, diffusion weighted imaging (DWI) and susceptibility-weighted (T2*) MRI to predict response to systemic treatment in patients with colorectal liver metastases. The predictive values of pretreatment measurements and of early changes one week after start of therapy, were evaluated.

Methods

Imaging was performed prior to and one week after start of first line chemotherapy in 39 patients with colorectal liver metastases. ¹⁸F-FDG PET scans were performed on a PET/CT scanner and DWI and T2* were performed on a 1.5T MR scanner. The maximum standardized uptake values (SUV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC) and T2* value were assessed in the same lesions. Up to 5 liver metastases per patient were analyzed. Outcome measures were progression free survival (PFS), overall survival (OS) and size response.

Results

Pretreatment, high SUV_max, high TLG, low ADC and high T2* were associated with a shorter OS. Low pretreatment ADC value was associated with shorter PFS. After 1 week a significant drop in SUV_max and rise in ADC were observed. The drop in SUV was correlated with the rise in ADC (r=-0.58, p=0.002). Neither change in ADC nor in SUV was predictive of PFS or OS. T2* did not significantly change after start of treatment.

Conclusion

Pretreatment SUV_max, TLG, ADC, and T2* values in colorectal liver metastases are predictive of patient outcome. Despite sensitivity of DWI and ¹⁸F-FDG PET for early treatment effects, change in these parameters was not predictive of long term outcome.     

Clinicopathological and Prognostic Significance of CD24 Overexpression in Patients with Gastric Cancer: A Meta-Analysis

Objective

The prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer.

Methods

A comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed.

Results

A total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR = 0.45, 95% confidence interval [CI]  = 0.32–0.63; P<0.00001), status of lymph nodes (OR = 0.40, 95% CI = 0.25–0.64; P = 0.0001) and tumor node metastasis (TNM) stage (OR = 0.56, 95% CI = 0.41–0.77; P = 0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR = 1.99, 95% CI = 1.29–3.07, P = 0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications.

Conclusion

CD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors.     

Prognostic Influence of Pre-Operative C-Reactive Protein in Node-Negative Breast Cancer Patients

The importance of inflammation is increasingly noticed in cancer. The aim of this study was to analyze the prognostic influence of pre-operative serum C-reactive protein (CRP) in a cohort of 148 lymph node-negative breast cancer patients. The prognostic significance of CRP level for disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) was evaluated using univariate and multivariate Cox regression, also including information on age at diagnosis, tumor size, tumor grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, proliferation index (Ki67) and molecular subtype, as well as an assessment of the presence of necrosis and inflammation in the tumor tissue. Univariate analysis showed that CRP, as a continuous variable, was significantly associated with DFS (P = 0.002, hazard ratio [HR]  = 1.04, 95% confidence interval [CI]  = 1.02–1.07) and OS (P = 0.036, HR  = 1.03, 95% CI  = 1.00–1.06), whereas a trend was observed for MFS (P = 0.111). In the multivariate analysis, CRP retained its significance for DFS (P = 0.033, HR  = 1.01, 95% CI  = 1.00–1.07) as well as OS (P = 0.023, HR  = 1.03, 95% CI  = 1.00–1.06), independent of established prognostic factors. Furthermore, large-scale gene expression analysis by Affymetrix HG-U133A arrays was performed for 72 (48.6%) patients. The correlations between serum CRP and gene expression levels in the corresponding carcinoma of the breast were assessed using Spearman''s rank correlation, controlled for false-discovery rate. No significant correlation was observed between CRP level and gene expression indicative of an ongoing local inflammatory process. In summary, pre-operatively elevated CRP levels at the time of diagnosis were associated with shorter DFS and OS independent of established prognostic factors in node-negative breast cancer, supporting a possible link between inflammation and prognosis in breast cancer.     

A Prognostic Model to Predict Recovery of COVID-19 Patients Based on Longitudinal Laboratory Findings

Virologica Sinica - The temporal change patterns of laboratory data may provide insightful clues into the whole course of COVID-19. This study aimed to evaluate longitudinal change patterns of key...     

The Relationships between Body Composition and the Systemic Inflammatory Response in Patients with Primary Operable Colorectal Cancer

Background

Weight loss is recognised as a marker of poor prognosis in patients with cancer but the aetiology of cancer cachexia remains unclear. The aim of the present study was to examine the relationships between CT measured parameters of body composition and the systemic inflammatory response in patients with primary operable colorectal cancer.

Patient and Methods

174 patients with primary operable colorectal cancer who underwent resection with curative intent (2003–2010). Image analysis of CT scans was used to measure total fat index (cm²/m²), subcutaneous fat index (cm²/m²), visceral fat index (cm²/m²) and skeletal muscle index (cm²/m²). Systemic inflammatory response was measured by serum white cell count (WCC), neutrophil:lymphocyte ratio (NLR) and the Glasgow Prognostic Score (mGPS).

Results

There were no relationships between any parameter of body composition and serum WCC or NLR. There was a significant relationship between low skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p = 0.001). This was confirmed by linear relationships between skeletal muscle index and both C-reactive protein (r = −0.21, p = 0.005) and albumin (r = 0.31, p<0.001). There was no association between skeletal muscle index and tumour stage.

Conclusions

The present study highlights a direct relationship between low levels of skeletal muscle and the presence of a systemic inflammatory response in patients with primary operable colorectal cancer.     

Surgical Outcomes and Prognostic Factors of T4 Gastric Cancer Patients without Distant Metastasis

Objective

To evaluate surgical outcomes and prognostic factors for T4 gastric cancer treated with curative resection.

Methods

Between January 1994 and December 2008, 94 patients diagnosed with histological T4 gastric carcinoma and treated with curative resection were recruited. Patient characteristics, surgical complications, survival, and prognostic factors were analyzed.

Results

Postoperative morbidity and mortality were 18.1% and 2.1%, respectively. Multivariate analysis indicated lymph node metastasis (hazard ratio, 2.496; 95% confidence interval, 1.218–5.115; p = 0.012) was independent prognostic factor.

Conclusions

For patients with T4 gastric cancer, lymph node metastasis was associated with poorer survival. Neoadjuvant chemotherapy or aggressive adjuvant chemotherapy after radical resection was strongly recommended for these patients.     

HER2、VEGF和MVD与胃癌患者临床病理特征的关系

目的：探讨HER2、VEGF的表达和MVD水平及这三者与胃癌的临床病理和生物学特性的关系。方法：胃癌患者26例,其中14例患者接受了全胃切除术,12例患者行胃癌活检,在癌组织中心获得有效标本设为胃癌组,以距离癌组织中心5cm的正常癌组织为正常组。RT-PCR法检测两组胃组织中HER2mRNA的表达;免疫组织化学检测胃组织中VEGF的表达;计算各组微血管密度。结果：与正常组相比,胃癌组HER2mRNA表达明显增加;正常组胃组织VEGF平均灰度值为21．51±4．64,而胃癌组胃组织VEGF平均灰度值为167．23±18．85,两组相比有明显差异;正常组胃组织MVD为13．44±5．34个,与正常组相比,胃癌组胃组织MVD水平（65．74±9．87个）明显增高;HER2与患者TNM分期成正相关,VEGF与患者性别及TNM分期均成正相关,而MVD与患者临床病理特征无相关性。结论：血管内皮生长因子的表达及与胃癌患者临床病理特征的相关性表明,HER2、VEGF两个分子生物标志物在肿瘤的发生发展中具有重要作用,其能够被用来作为预测的侵袭性胃癌预后的重要参数。     

Prognostic Value Analysis of Mutational and Clinicopathological Factors in Non-Small Cell Lung Cancer

Introduction

Targeting activating oncogenic driver mutations in lung adenocarcinoma has led to prolonged survival in patients harboring these specific genetic alterations. The prognostic value of these mutations has not yet been elucidated. The prevalence of recently uncovered non-coding somatic mutation in promoter region of TERT gene is also to be validated in lung cancer. The purpose of this study is to show the prevalence, association with clinicalpathological features and prognostic value of these factors.

Methods

In a cohort of patients with non-small cell lung cancer (NSCLC) (n = 174, including 107 lung adenocarcinoma and 67 lung squamous cell carcinoma), EGFR, KRAS, HER2 and BRAF were directly sequenced in lung adeoncarcinoma, ALK fusions were screened using FISH (Fluorescence in situ Hybridization).TERT promoter region was sequenced in all of the 174 NSCLC samples. Associations of these somatic mutations and clinicopathological features, as well as prognostic factors were evaluated.

Results

EGFR, KRAS, HER2, BRAF mutation and ALK fusion were mutated in 25.2%, 6.5%, 1.9%, 0.9% and 3.7% of lung adenocarcinomas. No TERT promoter mutation was validated by reverse-sided sequencing. Lung adenocarcinoma with EGFR and KRAS mutations showed no significant difference in Disease-free Survival (DFS) and Overall Survival (OS). Cox Multi-variate analysis revealed that only N stage and HER2 mutation were independent predictors of worse overall survival (HR = 1.653, 95% CI 1.219–2.241, P = 0.001; HR = 12.344, 95% CI 2.615–58.275, P = 0.002).

Conclusions

We have further confirmed that TERT promoter mutation may only exist in a very small fraction of NSCLCs. These results indicate that dividing lung adenocarcinoma into molecular subtypes according to oncogenic driver mutations doesn''t predict survival difference of the disease.     

Stage-Stratified Analysis of Prognostic Significance of Tumor Size in Patients with Gastric Cancer

Background

The prognostic significance of tumor size in gastric cancer is not well defined. The objective of this study was to identify the prognostic value of tumor size in patients with gastric cancer.

Methods

We retrospectively reviewed a total of 1800 patients with gastric cancer admitted to our hospital between 1997 and 2007. These patients were divided into two groups according to tumor size: small size group (SSG, tumor ≤5 cm) and large size group (LSG, tumor >5 cm). We compared clinico-pathologic features of the two groups and investigated the prognostic factors by performing univariate, multivariate, and stage- stratified analyses according to tumor size.

Results

LSG had more aggressive clinico-pathologic features than SSG. Tumor size was an independent prognostic indicator in patients with gastric cancer. In a stratified-pT, pN, and pTNM analysis, survival of patients with LSG was significantly worse than that of patients with SSG and advanced stage. Tumor size was not a significant predictor of survival in patients with early stage tumors. Large tumor size was associated with shorter survival in patients with stages N0, N1, N2, and N3, and stages I, II, III, and IV.

Conclusions

Tumor size is a simple and practical prognostic factor in patients with gastric cancer. Tumor size could supplement clinical staging in the future.     

全身炎性反应综合征-急性肺损伤大鼠模型的研究

目的　研究大鼠经“一次打击”和“二次打击”后导致全身炎性反应综合征 肺损伤 (systemicinflammato ryresponsesyndrome acutelunginjury ,SIRS ALI)的动物模型 ,并探讨其意义。方法　用梯级剂量的大肠埃希菌脂多糖(lipopolysaccharide ,LPS)致伤大鼠 ,复制“一次打击”模型 ;用小剂量油酸致伤大鼠后 ,再予小剂量LPS ,复制“二次打击”模型。结合动脉血气分析、外周血白细胞计数、肺湿重 干重比值 (W D)及肺组织病理观察 ,评估两种SIRS ALI动物模型。结果　在“一次打击”模型中 ,当LPS≥ 8mg kg时 ,动物出现顽固的低氧血症和明显的病理组织学改变 ,类似SIRS失控 ;小剂量油酸加LPS两次打击 ,亦可导致SIRS失控。结论　较大剂量LPS一次性致伤 ,类似临床严重感染导致单相速发型SIRS ALI的发生过程 ;而油酸加LPS两次致伤 ,可模拟创伤后继发感染导致双相迟发型SIRS ALI的发生过程     

胃癌患者术后并发症的危险因素分析

目的:探讨胃癌术后并发症的危险因素及其防治措施.方法:调查117例胃癌患者手术治疗前后的临床资料,并对术后发生并发症可能的危险因素进行评估、分析.结果:胃癌术后并发症包括切口感染、肺部感染或胸腔积液、腹腔感染、肠梗阻、吻合口瘘,发生率为35.04％(41/117),手术方式、手术时间、胃管留置时间、术后生活习惯与手术后并发症相关(P＜0.05).结论:胃癌术后并发症由多种原因综合引起,除患者素质和病变因素外,6个危险因素依次为:行全胃切除、D2清扫、手术时间＞4h、术中出血量≥800mL、胃管留置时间＞3d、长期吸烟,应重视其围手术期处理.     

Prognostic Significance of Systemic Inflammation-Based Lymphocyte- Monocyte Ratio in Patients with Lung Cancer: Based on a Large Cohort Study

Increasing evidence indicates cancer-related inflammatory biomarkers show great promise for predicting the outcome of cancer patients. The lymphocyte- monocyte ratio (LMR) was demonstrated to be independent prognostic factor mainly in hematologic tumor. The aim of the present study was to investigate the prognostic value of LMR in operable lung cancer. We retrospectively enrolled a large cohort of patients with primary lung cancer who underwent complete resection at our institution from 2006 to 2011. Inflammatory biomarkers including lymphocyte count and monocyte count were collected from routinely performed preoperative blood tests and the LMR was calculated. Survival analyses were calculated for overall survival (OS) and disease-free survival (DFS). A total of 1453 patients were enrolled in the study. The LMR was significantly associated with OS and DFS in multivariate analyses of the whole cohort (HR = 1.522, 95% CI: 1.275–1.816 for OS, and HR = 1.338, 95% CI: 1.152–1.556 for DFS). Univariate subgroup analyses disclosed that the prognostic value was limited to patients with non-small-cell lung cancer (NSCLC) (HR: 1.824, 95% CI: 1.520–2.190), in contrast to patients with small cell lung cancer (HR: 1.718, 95% CI: 0.946–3.122). Multivariate analyses demonstrated that LMR was still an independent prognostic factor in NSCLC. LMR can be considered as a useful independent prognostic marker in patients with NSCLC after complete resection. This will provide a reliable and convenient biomarker to stratify high risk of death in patients with operable NSCLC.     

PRR11 Is a Prognostic Marker and Potential Oncogene in Patients with Gastric Cancer

PRR11 is a potential candidate oncogene that has been implicated in the pathogenesis of lung cancer, however the role of PRR11 in gastric cancer is currently unclear. In the present study, we investigated the role of PRR11 in gastric cancer by evaluating its expression status in samples from a cohort of 216 patients with gastric cancer. PRR11 was found to be overexpressed in 107 (49.5%) patients by immunohistochemistry of tissue microarrays generated using the patient samples. Furthermore, PRR11 overexpression was found to correlate significantly with clinicopathologic features such as tumor invasion, tumor differentiation, and disease stage. Survival analysis of the cohort revealed that PRR11 is an independent prognostic factor for gastric cancer patients. PRR11 was stably silenced in a gastric carcinoma cell line using an shRNA-based approach, and treated cells showed decreased cellular proliferation and colony formation in vitro and cell growth in vivo, companied by decreased expression of CTHRC1 and increased expression of LXN, proteins involved in tumor progression. Evaluation of human gastric cancer samples demonstrated that PRR11 expression was also associated with increased CTHRC1 and decreased LXN expression. These data indicate that PRR11 may be widely activated in human gastric cancer and are consistent with the hypothesis that PRR11 functions as an oncogene in the development and progression of gastric cancer.     

Study of Regulatory T-Cells in Patients with Gastric Malt Lymphoma: Influence on Treatment Response and Outcome

Purpose

FOXP3+ regulatory T cells (Treg) play an essential role in modulating host responses to tumors and infections. The role of these cells in the pathogenesis of MALT lymphomas remains unknown. The aims of the study were to quantify the number of infiltrating FOXP3+ and CD3+ cells in patients with gastric MALT lymphoma at diagnosis and to study kinetics of these cells and CD20+ tumor cells after treatment and during long-term follow-up.

Methods

FOXP3+, CD3+ and CD20+ cells were analyzed by immunohistochemistry and the number of cells was quantified using a micrometric ocular. Samples of 35 patients with gastric MALT lymphoma at diagnosis and after treatment were included. Diagnostic samples were compared to 19 cases of chronic gastritis and diffuse large B-cell lymphoma (DLBCL) of the stomach.

Results

The median number of FOXP3+ infiltrating cells was higher (27 cells/cm²) in gastric MALT patients than in DLBCL (10 cells; p = 0.162) but similar to chronic gastritis (20 cells; p = 0.605). No characteristic or specific distribution pattern of infiltrating FOXP3+ cells was found. Gastric MALT lymphoma patients responding to bacterial eradication therapy had higher number of FOXP3+ cells at study entry. Kinetics of both infiltrating FOXP3+ cells and tumor CD20+ cells were strongly dependent on the treatment administered.

Discussion

Gastric MALT lymphomas have a number of Treg cells more similar to chronic gastritis than to DLBCL. Patients with higher number of tumor infiltrating FOXP3+ cells at study entry seem to have better response to antibiotics. Kinetics of Treg and tumor cells are influenced by type of treatment.     

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.     

Prognostic Value of Survivin in Patients with Gastric Cancer: A Systematic Review with Meta-Analysis

Objective

The prognostic significance of survivin for the survival of patients with gastric cancer remains controversial. Thus, the objective of this study was to conduct a systematic review of the literature evaluating survivin expression in gastric cancer as a prognostic indicator.

Methods

Relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases. A meta-analysis of the association between survivin expression and overall survival in patients with gastric cancer was performed. Studies were pooled and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted.

Results

Final analysis of 1365 patients from 16 eligible studies was performed. Combined HR suggested that survivin expression had an unfavorable impact on survival of gastric cancer patients (HR=1.39, 95% CI: 1.16-1.68). The unfavorable impact also appeared significant when stratified according to the studies categorized by patients’ ethnicity, detection methods, type of sample, and HR estimate. The combined HR in the English literature showed an inverse effect on survival (HR=1.40, 95% CI: 1.13-1.75), while HR in the non-English literature did not (HR=1.38, 95% CI: 0.93-2.05). When stratified according to the location of survivin expression, combined HR showed that expression in cytoplasm was significantly associated with poor prognosis of gastric cancer patients (HR=1.46, 95% CI: 1.12-1.90). While expression in nucleus was not significantly associated with poor prognosis (HR=1.29, 95% CI: 0.72-2.31), the heterogeneity was highly significant (chi-squared=11.5, I²=74%, p=0.009).

Conclusions

This study showed that survivin expression was associated with a poor prognosis in patients with gastric cancer. Cytoplasmic expression of survivin may be regarded as a prognostic factor for gastric cancer patients. In contrast, survivin expression in nucleus did not have a significant impact on patients’ overall survival.     

Prognostic Significance of Neutrophil Lymphocyte Ratio in Patients with Gastric Cancer: A Meta-Analysis

Background

Several studies have shown that neutrophil lymphocyte ratio (NLR) may be associated with the prognosis of gastric cancer (GC), but the results are controversial.

Methods

This study was performed to evaluate the prognostic implications of neutrophil lymphocyte ratio of GC in all available studies. We surveyed 2 medical databases, PubMed and EMBASE, to identifyall relevant studies. Data were collected from studies comparing overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) in patients with GC.

Results

Ten studies (n = 2,952) evaluated the role of NLR as a predictor of outcome were involved for this meta-analysis (10 for OS, 3 for DFS, and 2 for PFS). Overall and disease-free survival were significantly better in patients with low NLR value and the pooled HRs was significant at 1.83 ([95% CI], 1.62–2.07) and 1.58 ([95% CI], 1.12–2.21), respectively. For progression-free survival, the pooled hazard ratio of NLR was significant at 1.54 ([95% CI], 1.22–1.95). No evidence of significant heterogeneity or publication bias for OS and DFS was seen in any of the included studies.

Conclusion

This meta-analysis indicated that elevated NLR may be associated with a worse prognosis for patients with GC.     

舒芬太尼复合地佐辛麻醉对腹腔镜胃癌切除患者血清炎性因子和早期认知功能的影响

目的:研究舒芬太尼复合地佐辛对腹腔镜胃癌切除患者术后炎性因子、早期认知功能的影响。方法:选取2015年4月至2016年3月本院收治的84例胃癌患者,根据入院顺序分为观察组和对照组,每组42例。对照组采取单纯舒芬太尼术后镇痛,观察组使用舒芬太尼符合地佐辛术后镇痛。比较两组患者术前、术后的视觉模拟评分(VAS)、炎性因子水平和认知功能评分变化。结果:两组患者术后6、12、24、48小时VAS均较术前呈下降趋势,观察组在术后6、12、24、48 h VAS均显著低于对照组(P0.05)。术后7天,观察组患者血清IL-6、TNF-α水平显著低于对照组,IL-10水平显著高于对照组,差异均有统计学意义(P0.05)。观察组患者的认知功能评分(80.43±1.32)显著高于对照组(66.54±1.56)(P0.05)。观察组和对照组的不良反应发生率比较无统计学差异[14.29%(6/42)比19.05%(8/42)](P0.05)。结论:腹腔镜胃癌切除患者应用舒芬太尼复合地佐辛术后镇痛可有效缓解患者术后疼痛感,调节术后炎性因子水平,改善早期认知功能障碍,且安全性较高。     

Aberrant DNA Damage Response Pathways May Predict the Outcome of Platinum Chemotherapy in Ovarian Cancer

Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR) pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/C30) to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs) from OC patients, sensitive (n = 7) or resistant (n = 4) to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9) were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05). Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t_1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t_1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03). Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05). We conclude that perturbations of DNA repair pathways as measured in PBMCs from OC patients correlate with the drug sensitivity of these cells and reflect the individualized response to platinum-based chemotherapy.