Node-negative Esophageal Squamous Cell Carcinoma Research Articles

Insulin-like growth factor-2 mRNA-binding protein 3 promotes cell migration, invasion, and epithelial-mesenchymal transition of esophageal squamous cell carcinoma cells by targeting zinc finger E-box-binding homeobox 1 mRNA.

The role and mechanism of insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) in the metastasis of esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, IGF2BP3 mRNA and protein expression levels were evaluated in ESCC tissues. Small interfering RNAs (siRNAs), plasmid overexpression, and stable lentivirus transfection were used to manipulate intracellular IGF2BP3 expression levels. The role of IGF2BP3 in ESCC tumorigenesis was investigated in vitro and in vivo. IGF2BP3target transcripts were detected, and the acetylation effect ratios of the IGF2BP3 promoter region by H3K27ac were determined. IGF2BP3 mRNA expression levels were significantly higher in ESCC tissues than in normal esophageal tissues. Increased IGF2BP3 expression levels were detected in node-negative ESCC tissues and correlated with greater lesion depth in ESCC. Overexpression of IGF2BP3 promoted ESCC development in vitro and in vivo, and IGF2BP3 knockdown caused an opposite effect. IGF2BP3 was found to directly bind to the zinc finger E-box-binding homeobox 1 (Zeb1) mRNA, and the downregulation of IGF2BP3 reduced the stability of Zeb1 mRNA. IGF2BP3 induced epithelial-mesenchymal transition in ESCC cells in a Zeb1-dependent manner. IGF2BP3 was transcriptionally activated in ESCC cell lines via H3K27 acetylation. Our results demonstrate that IGF2BP3 plays a vital role in ESCC cell proliferation, invasion, and metastasis and is a potential therapeutic target for treating ESCC.

A Recurrence Predictive Model for Node-negative Esophageal Squamous Cell Carcinoma After Upfront Esophagectomy

The prognosis for pathologically node-negative (pN0) esophageal squamous cell carcinoma (ESCC) with surgery alone remains poor. We aimed to develop a model for a more precise prediction of recurrence, which will allow personalized management for pN0 ESCC after upfront complete resection. Clinical and pathological records of patients with completely resected pT1-3N0M0 ESCC were retrospectively analyzed between January 2014 and December 2019. A nomogram for the prediction of recurrence was established based on the Cox regression analysis and evaluated by C-index, AUC, and calibration curves. The model was further validated using bootstrap resampling and k-fold cross-validation and compared with the 8th edition of the AJCC TNM staging system using Td-ROC, NRI, IDI, and DCA. Two-hundred-and seventy cases were included in this study. The median follow-up was 45 months. Distant and/or loco-regional recurrences were noted in 89 (33.0%) patients. The predictive model revealed pT-category, differentiation, perineural invasion, examined lymph nodes (ELN), and prognostic nutritional index (PNI) as independent risk factors for recurrence, with a c-index of 0.725 in the bootstrapping cohort. Td-ROC, NRI, and IDI showed a better predictive ability than the AJCC 8th TNM staging system. Based on this model, patients in the low-risk group had a significantly lower recurrence incidence than those in the high-risk group (p < .001). The predictive model developed in this study may facilitate the precise prediction of recurrences for pN0 ESCC after upfront surgery. Stratifying management of those patients might bring significantly better survival benefits.

Lymphatic invasion is a prognostic factor of pathological N0 esophageal squamous cell carcinoma.

Adjuvant treatment after upfront esophagectomy for esophageal squamous cell carcinoma (ESCC) is indicated only for patients with lymph node metastasis in Japan. However, the recurrence rate after curative resection is high even for node-negative patients; thus, understanding the prognostic factors for patients with node-negative ESCC, which still remains unidentified, is important. Here, we aimed to reveal the prognostic factors for the long-term outcomes of patients with node-negative ESCC. Moreover, we compared the long-term outcomes among high-risk node-negative and node-positive patients. This single-institution retrospective study included 103 patients with pT1b-3N0 ESCC who underwent upfront surgery to identify the population at a high risk of recurrence. To compare overall survival (OS) and recurrence-free survival (RFS) between high-risk node-negative and node-positive patients, 51 node-positive ESCC patients with pStage IIIA or less who had undergone upfront surgery were also included. Univariable and multivariable analyses were performed using the Cox proportional hazard regression model. OS and RFS were compared using the log-rank test. Only lymphatic invasion (Ly+) was associated with worse 3-year OS (hazard ratio, 8.63; 95% confidence interval, 2.09-35.69; P = 0.0029) and RFS (hazard ratio, 4.87; 95% confidence interval, 1.69-14.02; P = 0.0034). The node-negative and Ly+ patients showed significantly worse OS (P = 0.0242) and RFS (P = 0.0114) than the node-positive patients who underwent chemotherapy. Ly+ is the only independent prognostic factor in patients with node-negative ESCC. Patients with node-negative and Ly+ ESCC may benefit from adjuvant treatment.

Prognostic impact of lymph node harvest for patients with node-negative esophageal squamous cell carcinoma: a large-scale multicenter study.

We examined the association between the number of resected lymph nodes and survival to determine the optimal lymphadenectomy for thoracic esophageal squamous cell carcinoma (ESCC) patients with negative lymph node. We included 1,836 patients from Chinese three high-volumed hospitals with corresponding clinicopathological characters such as gender, age, tumor location, tumor grade and TNM stage of patients. The median follow-up of included patients was 45.7 months (range, 1.03-117.3 months). X-Tile plot was used to identify the lowest number of lymphadenectomy. The multivariate model's construction was in use of parameters with clinical significance for survival and a nomogram based on clinical variable with P<0.05 in Cox regression analysis. Both two models were validated using a cohort extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database between 1975 and 2016 (n=951). More lymphadenectomy numbers were significantly associated with better survival in patients both in training cohort [hazard ratio (HR) =0.980; 95% confidence interval (CI): 0.971-0.988; P<0.001] and validation cohort (HR =0.980; 95% CI: 0.968-0.991; P=0.001). Cut-off point analysis determined the lowest number of 9 for thoracic ESCC patients in N0 stage through training cohort (C-index: 0.623; sensitivity: 80.7%; 1 - specificity: 72.5%) when compared with 10 in validation cohort (C-index: 0.643; sensitivity: 78.2%; 1 - specificity: 63.0%). The cut-off points of 9 were examined in training cohort and validated in the divided cohort from validation cohort (all P<0.05). Meanwhile, nomograms for both cohorts were constructed and the calibration curves for both cohorts agreed well with the actual observations in terms of predicting 3- and 5-year survival, respectively. Larger number for lymphadenectomy was associated with better survival in thoracic ESCC patients in N0 stage. Nine was what we got as the lowest number for lymphadenectomy in pN0 ESCC patients through this study, and our result should be confirmed further.

The impact of adjuvant therapy on survival for node-negative esophageal squamous cell carcinoma: a propensity score-matched analysis.

BackgroundAt present, the primary treatment of esophageal cancer is surgery-based comprehensive treatment, including adjuvant therapy such as chemotherapy and/or radiotherapy. However, the role of adjuvant therapy for esophageal squamous cell carcinoma (ESCC) with pathologically node-negative (pN0) disease is controversial. This study aimed to evaluate the impact of postoperative adjuvant therapy on survival in patients with pN0 ESCC.MethodsPatients with ESCC who underwent R0 esophagectomy in the Department of Thoracic Surgery of Sichuan Cancer Hospital from January 2008 to December 2013 were enrolled. Patients were divided into two groups: a surgery alone (Group S) group or a surgery + adjuvant therapy (Group S + A) group. The primary outcomes were overall survival (OS) and disease-free survival (DFS), and every consecutive case was followed up until death or the last follow-up.ResultsA total of 387 patients with ESCC patients who had pN0 were enrolled in the study. After propensity score matching (PSM), each group consisted of 150 patients. In the overall cohort, the 5-year OS (75.6% vs. 69.7%; P=0.004) and 5-year DFS (64.9% vs. 48.2%; P=0.003) rates were higher in Group S + A than in Group S. In the matched samples, the same outcomes were observed (5-year OS: 75.6% vs. 69.7%, P=0.026; 5-year DFS: 67.6% vs. 69.6%, P=0.036). Multivariate regression analysis indicated that postoperative chemotherapy was associated with longer OS [hazard ratio (HR): 0.622, 95% confidence interval (CI): 0.416–0.928; P=0.02] and DFS (HR: 0.571, 95% CI: 0.390–0.836; P=0.004); in contrast, T3 stage tumors (HR: 1.953, 95% CI: 1.238–3.082; P=0.004) and <15 lymph node dissections (HR: 1.81; 95% CI: 1.238–2.648; P = 0.002) were found to be independent risk factors for pN0 ESCC.ConclusionsAdjuvant therapy, especially chemotherapy, prolonged OS and DFS for patients with ESCC who had pN0 disease. Fewer lymph node dissections and T3 stage tumors were independent risk factors for OS and DFS.

Lymphovascular invasion predicts disease-specific survival in node-negative esophageal squamous cell carcinoma patients after minimally invasive esophagectomy.

IntroductionLymphovascular invasion (LVI) is reported to be a potential prognostic predictor in esophageal squamous cell carcinoma (ESCC) patients.AimTo investigate the prognostic value of LVI in ESCC node-negative patients after minimally invasive esophagectomy (MIE).Material and methods1406 consecutive ESCC patients who underwent MIE were reviewed retrospectively. After exclusion, 880 patients were enrolled, and 298 node-negative patients were used for the further analysis. The Kaplan-Meier method was used to examine the survival difference. Univariate and multivariate analyses were performed to identify prognostic predictors.ResultsLVI was observed in 29.4% of all patients. Totally, the proportion of LVI was increased with advanced T (p < 0.01) and N (p < 0.01) stage and poor tumor differentiation (p < 0.01). In the node-negative patients, a similar result was obtained in T stage (p = 0.0252) and tumor differentiation (p = 0.0080). In survival analysis, the disease-specific survival (DSS) (p = 0.0146) rate was significantly lower in node-negative patients with LVI than in those without. The difference was absent when calculating disease-free survival (DFS) (p = 0.0796). Additionally, the presence of LVI was associated with lower DSS (p = 0.0187) but not DFS (p = 0.0785) in univariate analysis in node-negative patients. Moreover, in multivariate Cox regression analysis, the presence of LVI was identified as an independent prognostic factor only in DSS (p = 0.0496) but not in DFS (p = 0.5670) in node-negative patients.ConclusionsLVI is associated with shorter DSS and an independent prognostic factor in ESCC node-negative patients after MIE.

Lymphovascular Invasion as the Major Prognostic Factor in Node-Negative Esophageal Cancer After Primary Esophagectomy

BackgroundStudies addressing both lymphovascular invasion (LVI) and perineural invasion (PNI) in patients with esophageal squamous cell carcinoma (ESCC) treated with or without neoadjuvant therapy are limited. We aimed to analyze the incidence and prognostic significance of LVI and PNI in patients with thoracic ESCC. MethodsThis retrospective study included 520 patients with ESCC: 174 patients after neoadjuvant treatment followed by surgery and 346 after primary esophagectomy, from two medical centers. The relationships between LVI, PNI, and other histological factors were evaluated. The Cox regression model was used for survival analysis. ResultsPositive LVI and PNI were noted in 35.6% and 22.4% of patients with residual primary tumor after neoadjuvant treatment and in 39.6% and 24.0% of patients who underwent primary esophagectomy, respectively. In patients with neoadjuvant treatments, the 5-year overall survival rates were 12.7% and 28.3% in patients with positive LVI and negative LVI, respectively (p = 0.001). The 5-year overall survival rates were 6.4% and 29.9% in patients with positive PNI and negative PNI, respectively (p < 0.001). In patients who did not receive neoadjuvant treatment, the 5-year overall survival rates were 28.2% and 61.1% in patients with positive LVI and negative LVI, respectively (p < 0.001). The 5-year overall survival rates were 30.2% and 52.5% in patients with positive PNI and negative PNI (p < 0.001). In subgroup analysis, the presence of PNI was an independent prognostic factor in patients with neoadjuvant treatments, whereas the presence of LVI had more significant prognostic impact in patients with node-negative ESCC after primary esophagectomy. ConclusionsBoth LVI and PNI statuses are significant prognostic factors for patients with ESCC. However, the prognostic impact of LVI was majorly in the subgroup of node-negative patients who received primary esophagectomy.

Pattern of recurrence and prognostic factors in patients with pT1-3\u2009N0 esophageal squamous cell carcinoma after surgery: analysis of a single center experience

BackgroundThe aims of this study were to determine the recurrence rate and the prognostic factors for recurrence-free survival (RFS) in esophageal squamous cell carcinoma (ESCC) patients without lymph node metastasis (LNM).MethodsBetween January 2011 and June 2017, 101 patients with ESCC were treated and pathologically confirmed to be lymph node negative. The clinicopathological parameters were evaluated to identify the prognostic factors for RFS using Cox proportional hazards models.ResultsNineteen out of 101 patients (18.8%) developed recurrence, and the median RFS was 41 months. The most common pattern of relapse was local recurrence (n = 11; 57.9%), followed by distant recurrence (n = 7; 36.8%); one patient developed local and distant recurrence simultaneously. The results of multivariate analysis showed that the independent prognostic factors for decreased RFS in node-negative patients were a tumor located in the upper chest (odds ratio [OR], 0.767; 95% confidence intervals (CI), 1.523–14.916, P = 0.007), the presence of lymphovascular invasion (OR, 3.534; 95% CI, 1.077–11.596, P = 0.037), and a preoperative serum carcinoembryonic antigen level ≥ 5 μg/ml (OR = 5.466; 95% CI, 1.590–18.787, P = 0.007).ConclusionsThe aforementioned parameters were the prognostic factors in node-negative ESCC patients, and they associated with a higher probability of recurrence after surgery. These patients should be followed closely, and adjuvant therapy should be considered.

Prognostic value of EGFR family expression in lymph node-negative esophageal squamous cell carcinoma patients

The human epidermal growth factor receptor (EGFR) family has been widely studied in cancer, however, the prognostic role of EGFR family expression in lymph node-negative esophageal squamous cell carcinoma (ESCC) patients have not been invalidated. This study was designed to determine the prognostic value of EGFR family expression in a population of lymph node-negative ESCC patients treated with curative resection. EGFR family protein expression was examined by immunohistochemical analysis of tissue microarrays of 94 patients with lymph node-negative ESCC after radical esophagectomy with three-field lymphadenectomy. Survival differences were compared using Kaplan–Meier analysis. Cox regression analyses were performed to determine the prognostic factors for overall survival and disease-free survival (DFS). ErbB4 expression was found to be an independent prognostic factor for DFS in patients without lymph node metastasis; increased ErbB4 expression was associated with decreased DFS. Additionally, patients with high ErbB4 expression tended to have worse overall survival. EGFR, ErbB2 and ErbB3 expression were not significantly associated with survival in lymph node-negative ESCC patients. Increased ErbB4 immunohistochemical expression was associated with poor prognosis in lymph node-negative ESCC patients.

Outcome of postoperative adjuvant chemotherapy and surgery alone for patients with stage pT1b-3N0M0 squamous cell carcinoma of the thoracic esophagus

Objective: To compare the outcome of postoperative adjuvant chemotherapy and surgery alone for stage pT1b-3N0M0 squamous cell carcinoma (SCC) of the thoracic esophagus. Methods: Two hundred and thirty-eight patients who underwent esophagectomy for stage pT1b-3N0M0 SCC of the thoracic esophagus in Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University between January 2008 and February 2011 were analyzed retrospectively. These included postoperative adjuvant chemotherapy for 118 patients and surgery alone for 120 patients. In postoperative adjuvant chemotherapy arm, 3 or 4 cycles of taxol+ cisplatin (TP, n=33) or fluorouracil+ cisplatin (FP, n=85) regimens were given commencing from 4 to 6 weeks after surgery. Survival analysis was performed using Kaplan-Meier method. Univariate analysis for prognostic factors was performed by Log-rank test and multivariate by Cox regression model. Results: The 3- and 5-year disease-free survival (DFS) rates were 57.9% and 53.8%, respectively for postoperative adjuvant chemotherapy patients, compared to 40.4% and 32.5% for patients who underwent surgery alone (χ2=11.973, P=0.001). The 3- and 5-year overall survival (OS) rates were 64.4% and 55.9% in postoperative adjuvant chemotherapy patients, and 46.7% and 33.5% in surgery alone patients (χ2=13.110, P=0.000). Stratification analysis showed that there was significant difference in stage T3 patients (χ2=7.895, P=0.006), but not in stage T1b (χ2=0.762, P=0.383) and T2 (χ2=1.259, P=0.262) patients between adjuvant chemotherapy and surgery alone. Both DFS rate (χ2=1.748, P=0.186) and OS rate (χ2=2.200, P=0.138) of TP group were similar with FP group. Conclusion: In lymph node negative esophageal SCC patients, postoperative adjuvant chemotherapy shows survival benefits in stage T3 patients.

Development and validation of nomogram based on lncRNA ZFAS1 for predicting survival in lymph node-negative esophageal squamous cell carcinoma patients.

BackgroundThere is increasing evidence of a relationship between long non-coding RNA (lncRNA) and cancer. This study aimed to examine the prognostic value of the lncRNA ZFAS1 in esophageal squamous cell carcinoma (ESCC).ResultsThe results showed that ZFAS1 expression was significantly higher in ESCC tissues compared with the corresponding adjacent normal tissues (P < 0.001). ESCC patients with high ZFAS1 expression had a poor overall survival (OS). Histological grade, T stage and ZFAS1 expression were integrated to develop the nomogram. The nomogram showed a significantly better prediction of OS for patients with lymph node-negative ESCC. The ROC curve also showed higher specificity and sensitivity for predicting 3- and 5-year ESCC patient survival compared with the AJCC staging system. The decision curve analysis also indicated a greater potential for the nomogram in clinical application compared with the AJCC staging system. Importantly, our findings were supported by a validation cohort.Materials and MethodsWe retrospectively investigated 398 lymph node-negative ESCC patients. Data from the primary cohort (n = 246) were used to develop a multivariate nomogram. The nomogram was internally validated for discrimination and calibration with bootstrap samples and was externally validated with an independent patient cohort (n = 152).ConclusionsOur proposed nomogram, which integrates clinicopathological factors and ZFAS1 expression, can accurately predict the prognosis of lymph node-negative ESCC patients without preoperative chemoradiotherapy.

Alcohol and survival in ESCC: prediagnosis alcohol consumption and postoperative survival in lymph node-negative esophageal carcinoma patients.

BackgroundThe association between esophageal cancer and prediagnosis alcohol consumption is well established. However, evidence that prediagnosis alcohol consumption affects postoperative survival in patients with lymph node-negative esophageal squamous cell carcinoma (ESCC) is lacking. We conducted a retrospective study on the effect of prediagnosis alcohol consumption on the postoperative survival of patients with lymph node-negative ESCC in China.MethodsWe enrolled 643 ESCC patients with negative lymphatic metastasis who had undergone esophagectomy between 1990 and 2005 at the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China, and reviewed their demographic, pathologic, preoperative, and cancer outcome data obtained from medical records. These data were analyzed using life table and Kaplan–Meier analyses and multivariate Cox regression.ResultsThere was a significant reduction in 3- and 5-year survival in drinkers with lymph node-negative ESCC. For drinkers, 3- and 5-year survival rates were 43% and 36% respectively, whereas, for nondrinkers, the corresponding values were 63% and 58%, respectively (p < 0.05). Multivariate Cox regression showed that drinking (p = 0.001, relative risk =1.583) was an independent factor for survival in patients with lymph node-negative ESCC. Striated analysis revealed that drinking was an independent factor for survival in patients with stage II A (p = 0.008, relative risk =1.679), stage IB (p = 0.044, relative risk=1.517), and well (p=0.011, relative risk =1.783) and moderately (p = 0.002, relative risk = 1.915) differentiated ESCC.ConclusionsPrediagnosis alcohol consumption is an independent prognostic factor for postoperative survival in patients with lymph node-negative ESCC.

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

IntroductionLymphovascular 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. MethodsA 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. ResultsLVI 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. ConclusionsThe 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.

Right versus left transthoracic approach for lymph node-negative esophageal squamous cell carcinoma.

BackgroundTo compare the right and left transthoracic approach on the post-operative survival of patients with lymph node-negative esophageal squamous cell carcinoma.MethodsSix hundred and ninety-five ESCC patients who underwent esophagectomy between 1990 and 2005 were retrospectively enrolled in the present study and were confirmed by histology to be of no lymph node metastasis. Those who had received neoadjuvant chemotherapy or radiotherapy were excluded from the study. Patients were divided into two groups, the left (n = 545) and right (n = 150) transthoracic groups. The follow-up duration ranged from 1 to 20 years with a mean of 7 years. Kaplan–Meier and univariate and multivariate Cox proportional hazards were used for analysis.Results3- and 5-year CSS rates were 62.0 % and 44.0 % in the left group, while the corresponding figures in the right group were 56.0 % and 40.0 %(P < 0.05). The overall survival for the two groups was significantly different (P = 0.045). Survival analyses were stratified by stages, which found that the favorable survival advantage was not present. When the survival curves were stratified by tumor locations, a significant difference was not revealed. Surgical approaches were regarded as one of the prognostic factors in the univariate analysis (P = 0.019). However, this significance could not be confirmed in multivariate Cox regression analysis (P = 0.193).ConclusionsThe left transthoracic approach is superior in some aspects to the right transthoracic approach regarding surgical and oncological outcomes in the treatment of lymph node negative ESCC.

A novel multivariate scoring system for determining the prognosis of lymph node-negative esophageal squamous cell carcinoma following surgical therapy: An observational study

BackgroundIdentifying patients with esophageal squamous cell carcinoma (ESCC) with negative prognostic factors, which have an extremely low survival rate, has been problematic. MethodsWe retrospectively collected clinical data for 648 patients with lymph node-negative ESCC who were treated at the Sun Yat-Sen University Cancer Center from 1990 to 2005. Survival difference was compared using Kaplan–Meier analysis and multivariate Cox regression analysis. ResultsWe identified advancing age, smoking history, alcohol consumption history, decreased forced expiratory volume in 1 s (FEV1), surgical procedure, tumor location, number of resected lymph nodes, poor tumor differentiation, and surgical stage as independent prognostic risk factors. Furthermore, based on the results of multivariate analysis, we constructed a novel scoring system that included the factors of age, smoking history, alcohol consumption history, number of resected lymph nodes, tumor differentiation, and surgical stage. Risk score (RS) was computed with the scoring system, and patients were divided into Class A (RS: 0–5) and Class B (RS: 6–10). P < 0.001 indicated statistical significance. A significant difference (p < 0.001) demonstrated that Class B was strongly related to a low survival rate and poor prognosis. ConclusionWe developed a new simple flexible scoring system of high prognostic significance, which has the potential to guide postoperative therapeutic strategies and follow-up frequency and to provide better prognostic information for patients and their families.

Analysis of the tumor length and other prognosis factors in pT1-2 node-negative esophageal squamous cell carcinoma in a Chinese population.

BackgroundTumor length is an important prognostic factor for many carcinomas, but its role in esophageal cancer remained undetermined. The aim of this study was to investigate the effect of tumor length on survival for patients with confined tumors (grade pT1-2) without lymph-node metastases in esophageal squamous cell carcinoma.MethodsWe enrolled 201 patients with esophageal squamous cell carcinoma (SCC) who had undergone surgical resection and been confirmed as pT1-2N0M0. The relationship of tumor length with overall survival was assessed and compared with other factors detailed in the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system published in 2009.ResultsThe overall survival (OS) rates at 1, 3, and 5 years were 93.0%, 83.7%, and 69.2%, respectively. The tumor length adversely affected OS, with the 5-year rate being 93.5%, 82.0%, 68.6%, 67.9%, 55.3% and 41.1%, respectively for tumor lengths of less than 10 mm, 10 to 20 mm, 20 to 30 mm, 30 to 40 mm, 40 to 50 mm, and greater than 50 mm (P< 0.001). Multivariate analyses showed that the pathologic T classification and grade of tumor was significantly associated with OS. Tumor length of 30 mm or more remained an independent prognostic factor (P = 0.04), as did the other current TNM factors.ConclusionTumor length appears to affect the OS of patients with early-stage esophageal squamous cell carcinoma. It may provide additional prognostic information for the current TNM staging system.

Prediagnostic smoking and postoperative survival in lymph node-negative esophagus squamous cell carcinoma patients.

Smoking is well known as a risk factor for esophageal cancer, but controversial as a prognostic factor. Moreover, evidence is scarce that a dose-response relationship exists. We conducted a retrospective study on the effect and dose-response relationship of prediagnostic smoking on the postoperative disease-specific survival of patients with lymph node-negative esophageal squamous cell carcinoma (ESCC). We enrolled 643 patients with lymph node-negative ESCC who had undergone esophagectomy between 1990 and 2005 at the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. The patients' demographic, pathological, preoperative and cancer outcome data were obtained from medical records. These data were reviewed and analyzed using life table, Kaplan-Meier analysis and multivariate Cox regression. A significant reduction in 3- and 5-year survival rates was observed in smokers with lymph node-negative ESCC compared with those in non-smokers. The 3- and 5-year survival rates were 54% and 46% for smokers, and 67% and 64% for non-drinkers, respectively (P<0.05). Multivariate Cox analysis revealed that smoking was an independent prognostic factor (P=0.008, hazard ratio=1.404). Both log-rank test (P=0.065) and multivariate analysis (P=0.091) showed no significant difference between the survival rates of light and heavy smokers. Prediagnostic smoking is an independent prognostic factor for patients with lymph node-negative ESCC, but the dose-response relationship needs further investigation.

Lymphatic vessel invasion detected by the D2‐40 monoclonal antibody is an independent prognostic factor in node‐negative esophageal squamous cell carcinoma

D2-40 staining has been reported to be useful for both identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) in various cancers. The aim of this study was to clarify the prognostic significance of D2-40 staining in patients with esophageal squamous cell carcinoma (ESCC). A total of 159 consecutive patients with ESCC who underwent an esophagectomy with lymph node dissection were eligible. LVI was diagnosed by both hematoxylin-eosin (LVI-HE) and D2-40 staining (LVI-D2-40) in the largest central sections of the entire tumors, while both the intratumoral and peritumoral LVD were counted by D2-40 staining. The correlation between the prognosis and clinicopathological factors was investigated. An univariate analysis revealed that tumor invasion beyond the muscularis propria, lymph node metastasis (LNM), LVI-HE, LVI-D2-40, high intratumoral LVD, and blood vessel invasion correlated with worse patients' prognosis (P < 0.05). A multivariate analysis revealed LNM to be the only independent prognostic factor in all cases (P = 0.0083). On the other hand, when the prognostic factors of 83 patients without LNM were investigated, LVI-D2-40 was revealed to be the only independent prognostic factor (P = 0.048). LVI detected by D2-40 staining was an independent prognostic factor in patients with node-negative ESCC.