Zihui Tan

Can Lymph Node Ratio Replace pN Categories in the Tumor-Node-Metastasis Classification System for Esophageal Cancer?

Background: We evaluated the prognostic value of lymph node ratio (LNR) in esophageal squamous cell carcinoma (ESCC) patients after tri-incisional esophagectomy by making comparisons with pN categories in the UICC/AJCC (International Union Against Cancer/American Joint Committee on Cancer) classification system (seventh edition). Methods: Seven hundred ESCC patients underwent tri-incisional esophagectomy at our center (1988–2008) without neoadjuvant therapy. The adjusted X-tile cutoff values for LNR of 0 and 0.25 were compared with those in UICC/AJCC pN categories. Results: Univariate and multivariate analyses identified LNR as a significant prognostic factor regardless of the number of retrieved LNs. Spearman’s correlation analysis showed close linear correlations between the number of examined and metastatic LNs (r = 0.205, p < 0.001), but not between the number of examined LNs and LNR (r = 0.058, p = 0.123). Significant prognostic differences were seen among LNR categories in all pT categories (p < 0.05), but not in pN categories stratified by tumor status (except T3: p < 0.001). Significant prognostic difference was seen among LNR categories in all pN categories (p < 0.05), but not between pN categories in all LNR categories (p > 0.05). Significant differences in 5-year cancer-specific survival rates were found among retrieved-node groups in the same pN category (except N2+3: p = 0.733), but not within the same LNR category (except N0: p < 0.001). Conclusions: LNR is an independent prognostic factor after tri-incisional esophagectomy, regardless of the number of retrieved LNs. In ESCC, LNR might reduce stage migration, have more potential for predicting patient outcomes, and compensate for deficiencies in UICC/AJCC pN categories.

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.

Surgical treatment for limited-stage primary small cell cancer of the esophagus.

BACKGROUND Primary small cell cancer of the esophagus (PSCCE) is a rare, aggressive, and highly metastatic disease. Surgical intervention, radiotherapy, and chemotherapy have been used alone or in combination to improve survival. This retrospective study tried to evaluate the significance of surgical procedures for the treatment of limited-stage PSCCE. METHODS We retrospectively evaluated 44 patients with limited-stage PSCCE who received esophagectomy with lymphadenectomy in our center between 1994 and 2011. The clinical and pathologic characteristics, median survival time (MST), overall survival (OS), and relevant prognostic factors were analyzed. RESULTS The MST in our cohort was 18.0 months (95% confidence interval [CI], 9.6-26.4 months), and the 6-, 12-, 24-, 36-, and 60-month OS rates were 73%, 58%, 39%, 30%, and 18%, respectively. The MST of patients with positive lymph nodes was significantly shorter than that of those with negative lymph nodes (14 months versus 47 months; p = 0.031). Survival analysis confirmed that regional lymph node involvement (relative risk [RR], 5.287; 95% CI, 1.036-26.978; p = 0.045) was an independent prognostic factor. CONCLUSIONS Although the standard treatment protocol for PSCCE has not been established, the results of our study indicated that radical esophagectomy with extended lymphadenectomy should be considered as the primary treatment for patients with limited-stage PSCCE, particularly for those without regional lymph node involvement.

Prognostic significance of the pN classification supplemented by body mass index for esophageal squamous cell carcinoma.

Body mass index (BMI) has been associated with the risk of esophageal cancer. But the influence of BMI on postoperative complications and prognosis has always been controversial.

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.

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.

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.

PS01.41: A Novel Blood Marker of Tumor Prognosis in a Large Cohort of Esophageal Squamous Cell Carcinoma Patients: The Fibrinogen/Albumin Ratio: Topic: Surgery

Methods: We analyzed data of 672 consecutive LCP (age1⁄457.5±8.3 years; tumor size1⁄44.4±2.4 cm) radically operated and monitored in 1985-2016 (m1⁄4581, f1⁄491; lobectomies1⁄4430, pneumonectomies1⁄4242, combined procedures with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus1⁄4184; only surgery1⁄4530, adjuvant chemoimmunoradiotherapyAT1⁄4142: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T11⁄4239, T21⁄4249, T31⁄4129, T41⁄455; N01⁄4425, N11⁄4130, N21⁄4117, M01⁄4672; G11⁄4168, G21⁄4201, G31⁄4303; squamous1⁄4380, adenocarcinoma1⁄4247, large cell1⁄445; early LC1⁄4134, invasive LC1⁄4538. Multivariate Cox modeling, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence. Results: Overall life span (LS) was 2104.2±1685.2 days and cumulative 5-year survival (5YS) reached 69.7%, 10 years e 61.9%, 20 years e 42.5%. 417 LCP lived more than 5 years (LS1⁄43044.7±1472.2 days), 109 LCP e more than 10 years (LS1⁄45048±1471.6 days). 194 LCP died because of LC (LS1⁄4560.7±372.9 days). AT significantly improved 5YS (65.3% vs. 34.3%) (P1⁄40.00001 by log-rank test) only for LCP with N1-2. Cox modeling displayed (Chi21⁄4292.44, df1⁄413, P1⁄40.000) that 5YS of LCP significantly depended on: phase transition (PT)“early-invasive LC” in terms of synergetics, PT N0-N12, histology, G, blood cell subpopulations, cell ratio factors (ratio between blood cells subpopulations and cancer cellsCC), prothrombin index, heparin tolerance, recalcification time, glucose, AT (P1⁄40.000-0.033). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT“early-invasive LC” (rank1⁄41), PT N0-N12 (rank1⁄42), AT (3), segmented neutrophils (4), lymphocytes (5), prothrombin index (6),healthy cells/CC (7), T1-4 (8), tumor size (9), thrombocytes/ CC (10), erythrocytes/CC (11),lymphocytes/CC (12). Correct prediction of 5YS was 100% by neural networks computing (error1⁄40.000; area under ROC curve1⁄41.0). Conclusion: Optimal management for LCP are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.