Kongjia Luo

The impact of body mass index on complication and survival in resected oesophageal cancer: a clinical-based cohort and meta-analysis

Background:Body mass index (BMI) has been associated with the risk of oesophageal cancer. But the influence of BMI on postoperative complication and prognosis has always been controversial.Methods:In total, 2031 consecutive patients who underwent oesophagectomy between 1998 and 2008 were classified according to Asian-specific BMI (kg m−2) cutoff values. The impact of BMI on overall survival (OS) was estimated using the Kaplan–Meier method and Cox proportional hazard models. We performed a meta-analysis to examine the association of BMI with OS and postoperative complication.Results:Patients with higher BMI had more postoperative complication (P=0.002), such as anastomotic leakage (P=0.016) and cardiovascular diseases (P<0.001), but less incidence of chylous leakage (P=0.010). Logistic regression analysis showed that BMI (P=0.005) was a confounding factor associated with postoperative complication. Multivariate analysis showed that overweight and obese patients had a more favourable survival than normal weight patients (HR (hazard ratio) = 0.80, 95% CI (confidence interval): 0.70–0.92, P=0.001). Subgroup analysis showed that the association with higher BMI and increased OS was observed in patients with oesophageal squamous cell carcinoma (ESCC) (P<0.001), oesophageal adenocarcinoma (EA) (P=0.034), never-smoking (P=0.035), ever-smoking (P=0.035), never alcohol consumption (P=0.005), weight loss (P=0.003) and advanced pathological stage (P<0.001). The meta-analysis further corroborated that higher BMI was associated with increased complication of anastomotic leakage (RR (risk ratio)=1.04, 95% CI: 1.02–1.06, P=0.001), wound infection (RR=1.03, 95% CI: 1.00–1.05, P=0.031) and cardiovascular diseases (RR=1.02, 95% CI: 1.00–1.05, P=0.039), but decreased incidence of chylous leakage (RR=0.98, 95% CI: 0.96–0.99, P<0.001). In addition, high BMI could significantly improved OS (HR=0.78, 95% CI: 0.71–0.85, P<0.001).Conclusion:Preoperative BMI was an independent prognostic factor for survival, and strongly associated with postoperative complications in oesophageal cancer.

Overexpression of cyclooxygenase-2 is associated with chemoradiotherapy resistance and prognosis in esophageal squamous cell carcinoma patients

Our objective was to investigate whether cyclooxygenase-2 (COX-2) expression can predict the patients response to chemoradiotherapy (CRT) and ensuing prognosis in esophageal squamous cell carcinoma (ESCC). The clinicopathological and follow-up data of 112 patients with ESCC who underwent CRT from January 2001 to June 2006 were analyzed retrospectively. The immunohistochemical expression level of COX-2 was examined for all biopsy specimens of primary tumors, and the correlation of COX-2 expression with the patients response to CRT and prognosis was examined. COX-2 positive immunostaining was detected in 111 (99.1%) of the patients, including overexpression in 54 (48.2%) patients and low expression in 58 (51.8%) of the patients. The response of tumors with a low level expression of COX-2 (70.7%, 41/58) was significantly higher than that of tumors with COX-2 overexpression (42.6%, 23/54; P = 0.003). Patients with a low level of COX-2 expression had a higher downstaged rate than those with a high level of COX-2 expression (9/13 vs 2/8), but the difference was not statistically significant (P = 0.08). In the definitive CRT group (91 cases), COX-2 overexpression was significantly associated with poor 3-year overall survival (P = 0.028). Multivariate analysis showed that only metastatic stage (nonregional node metastasis) was an independent prognosis factor. The assessment of COX-2 status may provide additional information to identify ESCC patients with poor chances of response to CRT and potential candidates for more individualized treatment.

Adjuvant chemotherapy versus surgery alone for esophageal squamous cell carcinoma: a meta-analysis of randomized controlled trials and nonrandomized studies

The effect of adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas is still controversial, and the subgroup of patients who will most likely benefit from the adjuvant chemotherapy on long-term survival has not yet been identified clearly. Studies published from 1995 to May 2012 were searched in Medline, Embase, PubMed, Cancerlit, the Cochrane Library, CNKI and major scientific meetings. Randomized controlled trials and nonrandomized studies comparing surgery plus adjuvant chemotherapy with surgery alone in patients with resectable thoracic esophageal squamous cell carcinomas were included. Eleven studies with a total of 2047 patients were identified, consisting of the adjuvant chemotherapy arm (n = 887) and surgery-alone arm (n = 1160). There was not statistically significant benefit on 3-year overall survival for adjuvant chemotherapy (risk ratio [RR] = 0.89, 95% confidence interval [CI], 0.72 to 1.09; P = 0.25). Adjuvant chemotherapy could significantly prolong the 1-year disease-free survival (DFS) (RR = 0.68, 95%CI, 0.51 to 0.89; P = 0.006), but not 3-year DFS (RR = 0.97, 95%CI, 0.73 to 1.29; P = 0.84). Further analysis showed that patients with stage III-IV diseases could benefit from adjuvant chemotherapy on 3-year overall survival (RR = 0.43, 95%CI, 0.31 to 0.61; P = 0.00001), but not in the case of patients with stageI-IIdiseases (RR = 1.12, 95%CI, 0.65 to 1.93; P = 0.68). Additionally, patients with positive lymph node could benefit on 5-year DFS from adjuvant chemotherapy (RR = 0.79, 95%CI, 0.64 to 0.99; P = 0.04). The modality treatment with adjuvant chemotherapy for patients with squamous cell carcinoma of thoracic esophagus might be determined according to pathological stage or the status of lymph node metastasis.

Prognostic value of preoperative platelet–lymphocyte and neutrophil–lymphocyte ratio in patients undergoing surgery for esophageal squamous cell cancer

Increasing evidence has suggested that the host inflammatory status is associated with prognosis of several solid tumors. Preoperative platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), both acquired from routine blood tests, can reflect the status of systematic inflammation. However, whether they are correlated with clinical outcomes of esophageal carcinoma is still unknown. The purpose of this study was to determine the prognostic value of preoperative PLR and NLR in patients with resected esophageal squamous cell carcinoma (ESCC). Preoperative PLR and NLR were evaluated in 317 eligible ESCC patients from September 2008 to December 2010. Receiver operating characteristic curves were applied to establish optimal cutoff points. The prognostic values of PLR and NLR were determined by both univariate and multivariate analyses. The optimal cutoff value of preoperative PLR and NLR were 103.0 and 2.1, respectively. One hundred and ninety-seven (62.1%) patients showed high level of preoperative PLR, while 148 (46.7%) patients showed high level of preoperative NLR. Both elevated PLR (P < 0.001) and NLR (P = 0.009) were correlated with poor disease-specific survival in univariate analysis. However, only preoperative PLR (P = 0.003) had a significant correlation with prognosis in multivariate analysis. In subgroup analyses, the predictive value of PLR was significant for stage I (P = 0.008) and stage II (P = 0.044) patients, but not for stage III patients (P = 0.100). Preoperative PLR is easily obtained from a routine blood test and may provide additional prognostic information for ESCC patients, especially in the early stage.

Identification of EGFR and KRAS mutations in Chinese patients with esophageal squamous cell carcinoma

The prognosis of esophageal squamous cell carcinoma (ESCC) is poor. It is urgent to improve this situation. Epidermal growth factor receptor (EGFR)-targeted therapy possesses a promising clinical efficacy. Mutations of EGFR and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) have been identified in esophageal carcinoma, but corresponding Chinese data are limited. So we investigated the mutation status of EGFR and KRAS in Chinese patients with ESCC, and explored their correlations with clinicopathological features. Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 50 randomly selected Chinese patients with ESCC. EGFR mutations in exons 18-21 were detected by Scorpions amplification refractory mutation system technology. KRAS mutations in codons 12, 13 were detected by direct sequencing of polymerase chain reaction products. The correlations between clinicopathological features and the mutation status of EGFR and KRAS were analyzed using the Statistical Package for the Social Sciences. In the present study, EGFR mutations were found in 7 (14%) out of 50 patients, including G719X missense mutation (n= 1), in-frame deletion (n= 2), and L858R missense mutation (n= 5). Six (12%) out of 50 patients had KRAS mutations in codon 12. Concurrent EGFR and KRAS mutations were detected in one sample. The presences of EGFR and KRAS mutations were not associated with gender, age, smoking history, cell differentiation, or cancer stage. In conclusion, the incidence of EGFR mutations in Chinese patients with ESCC was higher than that of previous reports, and the incidence of KRAS mutations was not low. EGFR and KRAS mutations were mainly located in exons 19 and 21 and codon 12, respectively. Unlike in NSCLC, concurrent EGFR and KRAS mutations existed.

A novel blood tool of cancer prognosis in esophageal squamous cell carcinoma: The Fibrinogen/Albumin ratio

Background: Coagulation and nutrition play important roles in cancer progression. We aim to investigate the impact of the fibrinogen/albumin ratio(FAR) in esophageal squamous cell carcinoma (ESCC) patients. Methods: We retrospectively analyzed 1135 patients with radical esophagectomy for ESCC from January 2008 to December 2010 in our center. X-tile software was used to determine the optimal cutoff levels for these biomarkers. Results: The optimal cutoff value was 0.08 for the FAR by the X-tile software. The FAR was statistically significantly associated with age(p=0.003), sex(p=0.030), tumor length (p=0.043), pT status(p<0.001) and pN status(p<0.001). Pearsons correlation indicated that the FAR were positively associated with the serum C-reactive protein (CRP) ( r=0.583, p<0.001), and the NLR ( r=0.316, p<0.001). Multivariate analysis indicated that age, tumor grade, pT status, pN status and preoperative FAR were independent prognostic factors in patients with ESCC. Conclusions: Preoperative FAR was an independent prognostic factor in ESCC patients. Lower FAR may improve OS of ESCC patients.

Identification and Validation of Lymphovascular Invasion as a Prognostic and Staging Factor in Node-Negative Esophageal Squamous Cell Carcinoma

Introduction: Lymphovascular invasion (LVI) is a histopathological feature that is associated with an increased risk for micrometastasis. The aim of this study was to determine the prognostic and staging value of LVI among patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy. Methods: A prospective database of patients with ESCC was used to retrospectively analyze 666 cases to identify the relationship between LVI and survival, and to evaluate predictive accuracy of prognosis after combining LVI and the tumor, node, and metastasis (TNM) system. Pathological slides were reassessed by gastrointestinal pathologists according to the strict criteria; 1000‐bootstrap resampling was used for internal validation, and 222 cases from an independent multicenter database were used for external validation. Results: LVI was present in 33.8% of patients, and the proportion increased with advancing T and N classification. LVI was an independent predictor of unfavorable disease‐specific survival (DSS) (hazard ratio = 1.59, 95% confidence interval: 1.30–1.94) and disease‐free survival (DFS) (hazard ratio = 1.62, 95% confidence interval: 1.32–1.98) after T classification. Among node‐negative patients, LVI and T classification were two independent predictors of DSS and DFS (p < 0.001). The risk score model combing LVI and T classification improved the predictive accuracy of the TNM system for DSS and DFS by 3.5% and 4.8%, respectively (p < 0.001). The external validation showed congruent results. The DSS of TxN0MO disease with LVI was similar to the DSS of TxN1M0 (both p > 0.05). In contrast, LVI was not associated with DSS or DFS among node‐positive patients. Conclusions: The independent prognostic significance of LVI existed only in node‐negative patients with ESCC, and the combination of LVI and the TNM system enhanced the predictive accuracy of prognosis. After confirmation, node‐negative patients with LVI might be considered for upstaging in pathological staging.

MiRNA Expression Analysis of Pretreatment Biopsies Predicts the Pathological Response of Esophageal Squamous Cell Carcinomas to Neoadjuvant Chemoradiotherapy.

Objective:To identify miRNA markers useful for esophageal squamous cell carcinoma (ESCC) neoadjuvant chemoradiotherapy (neo-CRT) response prediction. Summary:Neo-CRT followed by surgery improves ESCC patients’ survival compared with surgery alone. However, CRT outcomes are heterogeneous, and no current methods can predict CRT responses. Methods:Differentially expressed miRNAs between ESCC pathological responders and nonresponders after neo-CRT were identified by miRNA profiling and verified by real-time quantitative polymerase chain reaction (qPCR) of 27 ESCCs in the training set. Several class prediction algorithms were used to build the response-classifying models with the qPCR data. Predictive powers of the models were further assessed with a second set of 79 ESCCs. Results:Ten miRNAs with greater than a 1.5-fold change between pathological responders and nonresponders were identified and verified, respectively. A support vector machine (SVM) prediction model, composed of 4 miRNAs (miR-145-5p, miR-152, miR-193b-3p, and miR-376a-3p), were developed. It provided overall accuracies of 100% and 87.3% for discriminating pathological responders and nonresponders in the training and external validation sets, respectively. In multivariate analysis, the subgroup determined by the SVM model was the only independent factor significantly associated with neo-CRT response in the external validation sets. Conclusions:Combined qPCR of the 4 miRNAs provides the possibility of ESCC neo-CRT response prediction, which may facilitate individualized ESCC treatment. Further prospective validation in larger independent cohorts is necessary to fully assess its predictive power.

Localization of peripheral pulmonary lesions to aid surgical resection: a novel approach for electromagnetic navigation bronchoscopic dye marking

OBJECTIVES Video‐assisted thoracoscopic sublobar resection of ultra‐small, non‐visible and non‐palpable pulmonary lesions is challenging. The purpose of this study was to explore an alternative and efficient method for the localization of pulmonary lesions using electromagnetic navigation bronchoscopy (ENB). METHODS Between May 2015 and April 2016, 24 consecutive patients with 30 pulmonary peripheral lesions underwent video‐assisted thoracoscopic surgery for sublobar resection in our hospital. ENB was performed before surgery to guide a catheter adjacent to the target lesion, and fibrin sealant mixed with methylene blue was injected. RESULTS All patients underwent ENB with pleural dye marking followed immediately by surgery. No surgical complications occurred. The median size of the nodules was 11.0 mm (range, 6‐19 mm). The median navigation time was 18.0 min (range, 13 to 120 min), and the average interval between dye marking and thoracic surgery was 22.1 min (range, 15‐40 min). In all cases, the target pulmonary parenchyma was stained and had tactile sense with few complications. All lesions were fully excised, and pathological examination confirmed the accuracy of the dye staining. CONCLUSIONS Fibrin sealant mixed with methylene blue injection with ENB guidance is a new effective approach to localize even ultra‐small and non‐palpable pulmonary lesions. The visible staining and tactile sensation of this method may allow more rapid intraoperative identification of lesions.

Smoking affects treatment outcome in patients with resected esophageal squamous cell carcinoma who received chemotherapy.

Background Cigarette smoking is reported to decrease survival and induce chemotherapy resistance in patients with various cancers. However, the impact of cigarette smoking on patients with esophageal squamous cell carcinoma (ESCC) remains unknown. Methods A total of 1,084 ESCC patients were retrospectively enrolled from a southern Chinese institution. Patients were divided into two groups according to their treatment modalities: the SC group (surgery with chemotherapy) (n = 306) and the S group (surgery without chemotherapy) (n = 778). Smoking status was quantified as smoking history (non-smoker, ex-smoker, and current smoker) and cumulative smoking (0, between 0 and 20, and greater than 20 pack-years). The association between cigarette smoking and overall survival (OS) was evaluated using the Kaplan-Meier method and univariate/multivariate regression analysis. Results Among 1,084 patients, 702 (64.8%) reported a cigarette smoking history, and the 5-year OS for non-smokers and smokers was 45.8% and 37.3%, respectively. In the SC group, compared with non-smoker, the adjusted HRs of ex-smoker and current smoker were 1.540 (95% CI, 1.1–2.2) and 2.110 (95% CI, 1.4–3.1), respectively; there is a correlative trend of decreased OS with increased cigarette smoking (P trend = 0.001). These associations were insignificant in the S group. In subgroup analysis of the SC group, the lower OS conferred by smoking was not significantly modified by age, gender, body mass index, alcohol drinking, or chemotherapy method (chemotherapy and chemoradiotherapy). Conclusion Our results suggest that smoking may affect treatment outcome in patients with resected ESCC who received chemotherapy.