The Effect Of Systemic Inflammation And Clinical Pathological Factors On The Prognosis Of Esophageal Squamous Cell Carcinoma

PartⅠ The impact of Perineural invasion on Prognosis in the resected esophageal squamous cell carcinomaBackground: Postoperative survival of esophageal squamous cell carcinoma(ESCC) remains dismal.Purpose: This study aimed to examine the association between PNI and the survival in ESCC patients.Method: We retrospectively reviewed 347 consecutive ESCC patients resected at our institution. Tumors sections were re-evaluated for PNI. O verall and disease- free survivals were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox regression model were used to evaluate the differences.Results: Overall, 324 patients were enrolled into this study. PNI was identified in 20%(65/324) of pathologic sections. The 5-year disease- free survival was favorable for patients with PNI-negative versus those with PNI-positive(40.7% vs. 22.7%, respectively; P=0.001). The 5-year overall survival was 44.9% for patients with PNI- negative versus 22.5% for PNI-positive(P<0.001). On multivariate analysis, PNI was an independent prognostic factor for both overall and disease- free survival. In a subset analysis in early-stage patients, PNI was evaluated as a prognostic predictor as well(P<0.05). And no significant difference was observed in disease-free and overall survival between early-stage patients with PNI-positive and locally advanced patients with PNI-negative(P>0.05). In patients received PORT, PNI was evaluated as a prognostic predictor as well(P<0.05). In contrast to patients without PORT, PORT couldn’t improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive(P >0.05).Conclusion: PNI is grossly underreported in ESCC and could serve as an independent prognostic factor in ESCC patients. PNI status should be considered to make a treatment decision in resected ESCC patients.PartⅡ Proposed Modification of Nodal Staging as an Alternative to the Seventh Edition of the American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Improves the Prognostic Prediction in the Resected Esophageal Squamous-Cell CarcinomaBackground: The 7th AJCC-TNM staging system for esophageal cancer defined N-classification based on the number of metastatic lymph nodes(LNs). However, this classification might neglect the extent of LNs metastasis.Purpose: This study aimed to revise N-classification based on the extent of LNs metastasis and propose a modification to the current AJCC staging system for better representing the prognostic characteristics of Chinese esophageal squamous cell carcinoma(ESCC).Methods: We retrospectively reviewed 1993 ESCC patients underwent curative resection. The proposed N categories based on the number of LNs metastasis stations was compared with the current staging system by univariate and multivariate Cox regression analyses. Homogeneity, discriminatory ability, and monotonicity of gradients of two staging systems were compared using likelihood ratio χ2 statistics and Akaike information criterion(AIC) calculations.Results: The survival differences were not significant for N2 versus N3 category(P=0.231) and stages IIIB versus IIIC(P=0.713) based on the 7th AJCC staging system. When the modified staging system was adopted, the survival difference for N2 versus N3 and IIIB versus IIIC could be well discriminated. Statistical analysis showed that the modified staging system had higher likelihood ratio χ2 scores and smaller AIC values than the 7th AJCC staging system, which represented the optimum prognostic stratification.Conclusions: The modified staging system with the revised N categories based on the number of LNs metastasis stations better predicts the survival of Chinese ESCC population than the 7th AJCC staging system. Further studies are required to confirm this result.PartⅢ Effect of the number of lymph nodes resected on postoperative survival in patients with lymph node-negative esophageal squamous cell carcinomaBackground: No consensus was achieved regarding the optimal extent of LNs dissection for node-negative ESCC patients. This study aimed to determine the optimal extent of LNs dissection for node-negative ESCC patients.Methods: We retrospectively reviewed 515 ESCC patients with pathologic node-negative and no preoperative therapy. Optimal cut-off values of resected negative LNs count were determined by x-tile software. Overall survival(OS) was determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic role of the number of lymph nodes resected on the prognosis in ESCC patients with node-negative.Results: 481 patients were included into this study. The 5- year OS was 51.7% and 64.7% for patients with 1-5 and ≥ 6 negative LNs resected, respectively(P<0.001). However, there was no significant survival difference between patients with 6-12 resected negative LNs and patients with over 12 resected negative LNs(P=0.205). Multivariate analysis indicated the negative LNs count was independently associated with better survival. In subgroup analysis, no optimum lymphadenectomy was defined for T1; the minimum number of LNs needed to be resected was 6 nodes for T2 and 7 for T3. No survival benefit was observed when extensive lymphadenectomy, more than 12 negative LNs resected was performed.Conclusions: Our study suggest that ESCC patients with LN-negative should have at least 6 LNs examined for T2 and 7 LNs for T3, but extensive lymphadenectomy was not recommended.PartⅣ The effect of preoperative nutritional markers on the survival in resected esophageal squamous cell carcinomaBackground: Prognostic significance of prealbumin and albumin in esophageal cancer prognosis remain unclear.Purpose: The study aimed to explore the prognostic role of preoperative nutritional markers in the resected esophageal squamous cell carcinoma(ESCC).Methods: 1374 resected ESCC patients were retrospectively reviewed. Serum for prealbumin and albumin analyses was taken within 1–3 days before operation. O verall survival(OS) was determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic role of prealbumin and albumin. A receiver operating characteristic(ROC) curves were plotted and the area under the curve(AUC) was calculated to compare the prediction accuracy of prealbumin and albumin for OS.Results: 532 patients were included in this study. The 5-year OS was favorable for high prealbumin group versus median and low prealbumin group(58.1% vs. 44.6% and 31.1%, respectively; P < 0.001). The 5-year OS was favorable for high albumin group versus low albumin group(53.7% vs. 30.5%, P<0.001). Univariate and multivariate analysis identified serum prealbumin, T stage, N stage, differentiation and albumin as independent prognostic factors for OS. ROC curves indicated prealbumin may be superior to albumin as a prognostic predictor in ESCC patients, but the difference between two AUCs was not statistically significant(P=0.068).Conclusions: Serum prealbumin and albumin are independent prognostic factor and prognosticate postoperative outcomes in ESCC patients. Future prospective study is warranted to confirm our results. Part Ⅴ Prognostic Nomogram Integrated Systemic Inflammation Score for Patients with Esophageal Squamouscell Carcinoma Undergoing Radical EsophagectomyBackground: Increasing evidence indicates that nomogram combined with the biomarkers of systemic inflammation response could provide more accurate prediction than conventional staging systems in tumors.Purpose: This study aimed to establish an effective prognostic nomogram for resectable thoracic esophageal squamouscell carcinoma(ESCC) based on the clinicopathological parameters and inflammation-based prognostic scores.Methods: We retrospectively investigated 916 ESCC patients who underwent radical esophagectomy. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index(C- index) and calibration curve, and compared with the 6th and 7th AJCC TNM classifications. The neutrophil lymphocyte ratio(N LR), C-reactive protein albumin(C RP/Alb) ratio, histological grade, T stage and modified N stage were integrated in the nomogram.Results: The C-index of the nomogram for predicting the survival was 0.72, which showed better predictive ability of OS than the 6t h or 7th TNM stages in the primary cohort(P<0.001). The calibration curve showed high consistency between the nomogram and actual observation. The decision curve analysis showed more potential of clinical application of the prediction models compared with TNM staging system. Moreover, our findings were supported by the validation cohort.Conclusions: The proposed nomogram which was based on the clinicopathological parameters and inflammation-based prognostic scores showed more accurate prognostic prediction for patients with ESCC after radical esophagectomy.