Qianwen Liu

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.

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.

Preoperative level of serum amyloid A is superior to C-reactive protein in the prognosis of esophageal squamous cell carcinoma.

Preoperative elevations in the levels of serum amyloid A (SAA) or C-reactive protein (CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma (ESCC). In total, 252 patients with ESCC who had undergone surgery with curative-intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic (ROC) curve (AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Coxs proportional hazards model. The 1-, 3-, and 5-year overall survival (OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant (r(2) = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels (AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III (P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor (P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis.

Impact of the number of resected lymph nodes on postoperative survival of patients with node-negative oesophageal squamous cell carcinoma

OBJECTIVES Research on the number of resected lymph nodes (LNs) in the cases of node-negative oesophageal squamous cell carcinoma (ESCC) is inadequate. This study was designed to analyse the prognostic impact of the number of resected LNs on node-negative ESCC. METHODS Node-negative ESCC patients (n = 666) who underwent oesophagectomy between January 1990 and December 2005 were classified into three groups according to the number of LNs resected during surgery (≤8, 9-15 and ≥16). Kaplan-Meier curves and stratified analyses according to the American Joint Committee on Cancer staging were used to compare oesophageal cancer-specific survival (CSS). Cox regression and stratified analyses were used to identify the independent prognostic factors related to postoperative survival. RESULTS CSS rates increased with the number of negative resected LNs (P < 0.01). Three- and 5-year survival rates were 67.8 and 59.8%, respectively, for patients with ≥16 resected LNs, 64.8 and 53.8%, respectively, for patients with 9-15 resected LNs and 55.3 and 43.6%, respectively, for patients with ≤8 resected LNs. Multivariate analysis showed that the number of resected nodes [P < 0.01, relative risk (RR) = 1.0, 95% confidence interval (CI) 1.0-1.0] was an independent factor for CSS among node-negative ESCC patients. Further stratified analysis revealed that the number of resected LNs was an independent factor for survival in Stage IIA ESCC patients (P < 0.01, RR = 0.9, 95% CI 0.9-1.0). CONCLUSIONS The number of resected LNs is an independent prognostic factor for the survival of node-negative ESCC patients. The minimum resection number recommended for accurate staging is 16.

Elevated pretreatment serum lactate dehydrogenase level predicts inferior overall survival and disease-free survival after resection of thymic carcinoma

Background The prognostic significance of serum lactate dehydrogenase (LDH) level in thymic carcinoma (TC) remains unclear. Therefore, we evaluated the role of pretreatment serum LDH level in the prognosis for TC in this study. Methods Sixty consecutive surgical patients were analyzed in this study with pathologic confirmed TC in Sun Yat-sen University Cancer Center from June 1996 to June 2014. Results The cut-off value of LDH was 210.50 IU/L. In both univariate analysis and multivariable analysis, only pretreatment serum LDH level (P=0.027) and pathological Masaoka stage (P=0.041) were associated with overall survival (OS). In univariate analysis, pretreatment serum LDH level, tumor size, postoperative radiotherapy (PORT) and pathological Masaoka stage were associated with disease-free survival (DFS) (all P<0.050). Multivariable analysis showed that LDH level (P=0.001), PORT (P=0.001) and pathological Masaoka stage (P=0.038) were independently prognostic factors of DFS. This study also revealed that male patients and larger tumor size had a significantly higher rate of elevated pretreatment serum LDH level than in the other groups. Conclusions In conclusion, pretreatment serum LDH level was an independent prognosis factor of OS and DFS for patients with TC.

Lymph node station ratio: Revised nodal category for resected esophageal squamous cell carcinoma patients

The objective of this study was to evaluate a revised nodal category based on the value of the lymph node (LN) station ratio (SR, metastatic LN stations/examined LN stations) in esophageal squamous cell carcinoma (ESCC) patients.

Association between positive murine double minute 2 expression and clinicopathological characteristics of esophageal squamous cell carcinoma: a meta-analysis

The correlations of murine double minute 2 (MDM2) T309G and esophageal cancer were elucidated because the association between MDM2 expression states and clinicopathological parameters of esophageal squamous cell carcinoma (ESCC) is controversial. We conducted a meta-analysis on studies screened from PubMed, Web of Science, Embase, the Cochrane Library, and the Chinese Biomedical Literature Databases that were published before October 2014. All studies describing the association between MDM2 and ESCC were traced. Meta-analysis was performed using the STATA software (Stata Corp., College Station, TX, USA). A total of 9 studies with 707 cases and 324 controls were included. MDM2 expression was higher in ESCC than in normal esophageal epithelium (odds ratio [OR] 10.38, 95% confidence interval [CI] 6.42-16.78, P < 0.001). High MDM2 expression was associated with early primary tumor stage (T1/T2 vs. T3/T4, OR 0.59, 95% CI 0.38-0.92, P = 0.018) and increased risk of regional lymph node metastasis (N0 vs. N1, OR 1.66, 95% CI 1.03-2.67, P = 0.039). However, no relationship was observed between MDM2 expression and the risk of distant metastasis (OR = 2.09, 95% CI 1.00-4.36, P = 0.050), and MDM2 was not significantly correlated with TP53 expression (OR 1.22, 95% CI 0.53-2.77, P = 0.643). Our analysis suggests that MDM2 acts as a potent marker of early primary tumor stage but higher risk of regional lymph node metastasis in ESCC. However, because of the limited number of studies included, the result should be further clarified by well-designed prospective studies.

Clinical predictors of pathologically response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma: long term outcomes of a phase II study

Background A pathologically complete response (pCR) or near pCR to neoadjuvant chemoradiotherapy (NCRT) might imply a better prognosis in patients with esophageal cancer. The aim of the study is to identify clinical factors associated with a pCR or near pCR. Methods We retrospectively analyzed 40 patients with radical esophagectomy after NCRT for esophageal squamous cell carcinoma (ESCC) from January 2001 to December 2006 in Sun Yat-sen University Cancer Center. Clinical factors included age, gender, weight loss, dysphagia, drinking status, smoking status, tumor location, tumor length, tumor grade, cT status, cN status, the regimen of chemotherapy and the interval between NCRT and surgery as potential predictors for a pCR or near pCR. Logistic regression was used to estimate the independent factors for a pCR or near pCR. Results After surgical resection, 22.5% of the patients obtained the pCR. Patients with pCR had a better prognosis than those with non-pCR. However, there was no statistically significantly difference between the two groups (P=0.124). We separated the patients into pCR or near pCR (good responders, GRs) and poor responders (PR) based on the histology. GR showed better overall survival (OS) than PR (P=0.014). Univariate analysis indicated that short tumor length, good tumor grade and never drinking were associated with GR to NCRT. Using logistic regression analysis, good tumor grade was the only independent factor for the GR to NCRT (P=0.021). Cox regression revealed that weight loss, drinking status and GR were independent factors in ESCC patients with radical esophagectomy after NCRT. Conclusions Our study indicated that good tumor grade were an independent significant factor for the GR to NCRT. Weight loss, drinking status and GR were independent factors in patients with radical esophagectomy after NCRT. GR may improve OS of ESCC patients receiving NCRT.

miR-424 coordinates multilayered regulation of cell cycle progression to promote esophageal squamous cell carcinoma cell proliferation

Background Dysregulation of the cell cycle has been implicated in esophageal squamous cell carcinoma (ESCC) progression. This study aimed to evaluate the role of miR-424 in cell cycle regulation and ESCC proliferation. Methods The role of miR-424 in cell proliferation was evaluated in vitro and in vivo. Transcriptional activation of miR-424 was determined using chromatin immunoprecipitation, and binding of miR-424 to targets was verified using miRNA ribonucleoprotein complex immunoprecipitation. Findings miR-424 was upregulated and correlated with poor survival in ESCC patients. Repression or overexpression of miR-424 respectively decreased or increased ESCC cell proliferation in vitro and in vivo. miR-424 expression is transcriptionally regulated by E2F1 and increased during G1/S transition. Knockdown or overexpression of miR-424 respectively inhibited or promoted both G1/S and G2/M cell cycle transitions in ESCC cells, and these effects were mediated by two newly identified miR-424 targets, PRKCD and WEE1, respectively. Consequently, elevation of PRKCD by miR-424 knockdown led to enhanced stability of the p21Cip1 protein via increased activation of PRKCD and downstream p38 MAPK and JNK signaling to block CDK2 activation and G1/S transition, while elevated WEE1 maintained CDC2 in an inactive state to block G2/M transition. However, circLARP4 could sponge the binding of miR-424 to PRKCD, thus compromising the regulation of G1/S progression by miR-424. Interpretation miR-424 coordinates a previously unknown, multilayered regulation of ESCC cell cycle progression to promote ESCC proliferation, and may be used as a novel prognostic marker and an effective therapeutic target for ESCCs. Fund National Natural Science Foundation of China.

Comparison of right- and left-approach esophagectomy for elderly patients with operable thoracic esophageal squamous cell carcinoma: a propensity matched study

BACKGROUND the right- and left-approach open esophagectomies remain the general procedures among patients with operable thoracic esophageal squamous cell carcinoma (ESCC). The choice between the two approaches for elderly patients is controversial. METHODS we performed a 1:1 propensity score matching (PSM) analysis to compare the impact of right- and left-approach esophagectomies on survival and perioperative complications of elderly ESCC patients. Patients aged over 70 receiving esophagectomy to treat the thoracic ESCC were retrospectively retrieved. RESULTS a total of 276 patients were included in the study. Among them, 75 (27.2%) patients received right-approach esophagectomy. After match, 114 patients (57 pairs) undertook right or left-approach esophagectomy displayed no difference among clinicopathological characteristics. Both the overall survival (54.6% vs. 32.6%, P=0.036) and disease-free survival (52.7% vs. 20.2%, P=0.021) were significant better in right-approach group, along with better lymph node resection, and lower incidence of recurrence. However, increased incidences of postoperative pneumonia (P=0.040), respiratory failure (P=0.028), and sub-clinical anastomotic leak (P=0.032) were found in right-approach group as well, although the perioperative mortality was similar between groups. CONCLUSIONS Right-approach esophagectomy should be accepted as a preferential surgical approach for elderly patients with ESCC.