Project description:BackgroundThe incidence and mortality of esophageal cancer are high. Therefore, the authors aimed to investigate how the number of dissected lymph nodes (LNs) during esophagectomy for esophageal squamous cell carcinoma impacts overall survival (OS), particularly that of patients with positive LNs.Materials and methodsData from 2010 to 2017 were obtained from the Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database. Participants were divided into two groups: patients with negative lymph nodes (N0) and patients with positive lymph nodes (N+). The median number of resected LNs during surgery was 24; therefore, patients with 15-23 and those with 24 or more resected LNs were assigned to subgroups A and B, respectively.ResultsAfter a median follow-up of 60.33 months, 1624 patients who underwent esophagectomy were evaluated; 60.53 and 39.47% had a pathological diagnosis of N+ or N0, respectively. The median OS was 33.9 months for the N+ group; however, the N0 group did not achieve the median OS. The mean OS was 84.9 months. In the N+ group, the median OS times of subgroups A and B were 31.2 and 37.1 months, respectively. The OS rates at 1, 3, and 5 years were 82, 43, and 34%, respectively, for subgroup A of the N+ group; they were 86, 51, and 38%, respectively, for subgroup B of the N+ group. Subgroups A and B of the N0 group exhibited no statistically significant differences.ConclusionIncreasing the number of LNs harvested during surgery to 24 or more could improve the OS of patients with positive LNs but not that of patients with negative LNs.
Project description:BackgroundNeoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT.MethodsThe hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used.ResultsIn total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84-0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84-0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups.ConclusionThis cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.
Project description:We aimed to report patients' survival after surgical resection of eSCC and to ascertain the clinical, imaging, and pathological factors related to patient prognosis. This retrospective study included 435 patients with eSCC of <stage T2 (median follow-up period, 49.3 months). A total of 103 (23.7%) patients died, and 89 (20.5%) experienced recurrence during follow-up. The maximum standardized uptake value (SUVmax) on positron emission tomography (PET)/computed tomography (CT) of the primary tumor was significantly correlated with tumor length, nodal metastasis, and pathologic T stage in a positive linear fashion. In the multivariate analysis, higher SUVmax on PET/CT was a negative prognostic factor for both disease-free survival (DFS) and overall survival (OS). Contrarily, the presence of nodal metastasis was a prognostic factor only for DFS, and pathologic T stage only for OS. By applying SUVmax cut-off, both DFS and OS were significantly different among three groups when divided by cut-off values (A: SUVmax ≤ 3.05, B: SUVmax 3.06 - 5.64, C: SUVmax ≥ 5.65). In patients with a surgically resectable eSCC, measuring the SUVmax of the primary tumor during PET/CT can help predict patient survival. Additionally, PET/CT renders triage criterion for endoscopic submucosal dissection (ESD; T1a cancer and SUVmax, ≤3.05).
Project description:Esophageal squamous cell carcinoma (ESCC) is more prevalent than esophageal adenocarcinoma in Asia, especially in China, where more than half of ESCC cases occur worldwide. Many studies have reported that the automatic detection of lymph node metastasis using semantic segmentation shows good performance in breast cancer and other adenocarcinomas. However, the detection of squamous cell carcinoma metastasis in hematoxylin-eosin (H&E)-stained slides has never been reported. We collected a training set of 110 esophageal lymph node slides with metastasis and 132 lymph node slides without metastasis. An iPad-based annotation system was used to draw the contours of the cancer metastasis region. A DeepLab v3 model was trained to achieve the best fit with the training data. The learned model could estimate the probability of metastasis. To evaluate the effectiveness of the detection model of learned metastasis, we used another large cohort of clinical H&E-stained esophageal lymph node slides containing 795 esophageal lymph nodes from 154 esophageal cancer patients. The basic authenticity label for each slide was confirmed by experienced pathologists. After filtering isolated noise in the prediction, we obtained an accuracy of 94%. Furthermore, we applied the learned model to throat and lung lymph node squamous cell carcinoma metastases and achieved the following promising results: an accuracy of 96.7% in throat cancer and an accuracy of 90% in lung cancer. In this work, we organized an annotated dataset of H&E-stained esophageal lymph node and trained a deep neural network to detect lymph node metastasis in H&E-stained slides of squamous cell carcinoma automatically. Moreover, it is possible to use this model to detect lymph nodes metastasis in squamous cell carcinoma from other organs. This study directly demonstrates the potential for determining the localization of squamous cell carcinoma metastases in lymph node and assisting in pathological diagnosis.
Project description:BackgroundAccording to the National Comprehensive Cancer Network (NCCN) guidelines, surveillance or adjuvant chemoradiation is recommended for patients with completely resected pT2-4aN0M0 esophageal carcinoma (EC). Due to this population's variant prognosis, we developed novel nomograms to define the high-risk patients who may need closer follow-up or even post-operative therapy.MethodsCases with resected pT2-4aN0M0 EC from the Surveillance, Epidemiology, and End Results (SEER) database and the Sun Yat-sen University Cancer Center (SYSUCC) were enrolled in the study. The SEER database cases were randomly assigned into the training cohort (SEER-T) and the internal validation cohort (SEER-V). Cases from the SYSUCC served as the external validation cohort (SYSUCC-V). Overall survival (OS) and cancer specific survival (CSS) were compared between groups. Multivariate analyses were applied to identify the prognostic factors. Nomograms and risk-classifying systems were developed. The nomograms' performances were evaluated by concordance index (C-index), calibration plots and decision curve analysis (DCA).ResultsA total of 2,441 eligible EC cases (SEER-T, n=839; SEER-V, n=279; SYSUCC-V, n=1,323) were included. Age, sex, chemotherapy, lymph node harvested (LNH) and T stage were identified as the independent predictors for CSS. Regarding OS, it also included the prognostic factor of histology. Nomograms were formulated. For CSS, the C-index was 0.68 [95% confidence interval (CI): 0.66-0.71], 0.67 (95% CI: 0.63-0.71) and 0.61 (95% CI: 0.59-0.63) for the SEER-T, SEER-V, and SYSUCC-V, respectively. For OS, the C-index was 0.69 (95% CI: 0.66-0.72), 0.64 (95% CI: 0.59-0.69) and 0.62 (95% CI: 0.61-0.63) for the SEER-T, SEER-V, and SYSUCC-V, respectively. The calibration curves and DCA showed good performances of the nomograms. In further analyses, risk-classification systems stratified pT2-4aN0M0 EC into low-risk and high-risk subgroup. The OS and CSS curves of these 2 subgroups, in the full analysis set or stratified by TNM stage, histology, T stage and LNH categories, showed significant distinctions.ConclusionsThe novel prognostic nomograms and risk-stratifying systems which separated resected pT2-4aN0M0 esophageal carcinoma patients into the low-risk and high-risk prognostic groups were developed. It may help clinicians estimate individual survival and develop individualized treatment strategies.
Project description:Tumor-resident memory T (TRM ) cells in primary tumors are reportedly associated with a favorable prognosis in several malignancies. However, the behaviors and functions of TRM cells in regional lymph nodes (LNs) of esophageal cancer remain poorly understood. The aim of this study was to elucidate the effects of TRM cells in regional LNs of esophageal cancer on clinicopathological findings and prognosis. Specimens of esophageal cancer and primary metastatic LNs (recurrent nerve LNs) were obtained from 84 patients who underwent radical esophagectomy between 2011 and 2017. We performed immunohistochemistry to enumerate and analyze TRM cells, and used flow cytometry to investigate the function of TRM cells. TRM cells were observed in both metastatic LNs and primary tumors. TRM cell-rich specimens exhibited reduced lymphatic invasion and LN metastasis and prolonged survival compared with TRM cell-poor specimens. TRM cells in metastatic LNs were more significantly associated with enhanced survival than TRM cells in primary tumors. TRM cells expressed high levels of granzyme B as a cytotoxicity marker. Our results suggested that high TRM cell infiltration in metastatic LNs improves survival even though LN metastasis is commonly associated with poor prognosis. TRM cells possibly contribute to antitumor immunity in regional LNs.
Project description:BackgroundGlutathione S-transferase mu 3 (GSTM3) plays a crucial role in tumor progression in various cancers. However, the relationship between GSTM3 expression and the clinical prognosis of esophageal squamous cell carcinoma (ESCC) has not been studied to date. We aimed to characterize the role of GSTM3 in predicting postoperative prognosis of ESCC patients.MethodsIn the retrospective study, GSTM3 mRNA levels in 184 ESCC tissues and matched 43 adjacent nontumorous tissues were measured by quantitative real-time PCR. GSTM3 protein levels in 247 ESCC tissues were measured by immunohistochemistry.ResultsDownregulation of GSTM3 occurred in 62.8 % of primary ESCC tissues compared with their nontumor counterparts. Patients with low GSTM3 expression tended to exhibit an increased rate of poor differentiation in both the mRNA cohort (p = 0.024) and protein cohort (p = 0.004). In the mRNA cohort, low GSTM3 expression was associated with unfavorable 3-year disease-free survival (DFS) (39.2 % vs. 57.4 %) and 5-year DFS (26.8 % vs. 45.1 %) (p = 0.023). The result was confirmed in the protein cohort. Patients with low GSTM3 expression had unfavorable 3-year disease-free survival (DFS) (18.7 % vs. 33.5 %) and 5-year DFS (5.3 % vs. 30.5 %) (p = 0.006). Cox multivariate analysis revealed that GSTM3 expression was an independent prognostic factor.ConclusionsThe findings of the present study provide evidence that GSTM3 may function as a tumor suppressor in ESCC and represents a potential novel prognostic biomarker for disease-free survival for resected ESCC patients.
Project description:Epithelial-mesenchymal transition (EMT) plays a key role in tumor metastasis, but the significance of EMT phenotype to the prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. We used immunohistochemistry to examine the expression of the EMT-related proteins E-cadherin, N-cadherin and vimentin in samples of T3N1-3M0 ESCC from 155 primary tumors (PTs) with paired metastatic lymph nodes (MLNs) and 58 PTs without paired MLNs. Based on the expression pattern of the EMT markers, PTs and MLNs were classified as EMT wild, hybrid, null or complete type. The hybrid (42.7%) and complete (39.4%) types predominated among PTs, whereas the wild (34.2%) and hybrid (52.9%) types predominated among MLNs, and EMT phenotypes differed between the paired PTs and MLNs (P < 0.001). Univariate analysis revealed that, for PTs, the EMT phenotype was associated with N-stage (P = 0.039) but not patient survival, and that patients with complete or hybrid type MLNs had better overall survival (OS, P = 0.001) and disease-free survival (DFS, P = 0.005) than patients with null and wild type MLNs, especially those with N1-stage disease (P = 0.017 for OS, and P = 0.017 for DFS, respectively). Multivariate analysis revealed that wild and null type MLNs as well as older age and N2-3 stage were independent predictors of OS and DFS (P < 0.05). Thus MLNs exhibit EMT phenotypes that are distinct from those of their PT and may serve as a novel independent prognostic indicator in ESCC.
Project description:BackgroundThe counts of examined lymph nodes (ELNs) in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) is a controversial issue. We conducted a retrospective study to develop an ELNs-based model to individualize ESCC prognosis.MethodsPatients with ESCC from the SEER database and our center were strictly screened. The optimal threshold value was determine by the X-tile software. A prognostic model for ESCC patients was developed and validated with R. The model's efficacy was evaluated by C-index, ROC curve, and decision curve analysis (DCA).Results3,629 cases and 286 cases were screened from the SEER database and our center, respectively. The optimal cut-off value of ELNs was 10. Based on this, we constructed a model with a favorable C-index (training group: 0.708; external group 1: 0.687; external group 2: 0.652). The model performance evaluated with ROC curve is still reliable among the groups. 1-year AUC for nomogram in three groups (i.e., 0.753, 0.761, and 0.686) were superior to that of the TNM stage (P < 0.05). Similarly, the 3-year AUC and the 5-year AUC results for the model were also higher than that of the 8th TNM stage. By contrast, DCA showed the benefit of this model was better in the same follow-up period.ConclusionMore than 10 ELNs are helpful to evaluate the survival of ESCC patients. Based on this, an improved model for predicting the prognosis of ESCC patients was proposed.
Project description:Tertiary lymphoid structures (TLSs) are considered to have a good prognosis in multiple solid tumors. However, the prognostic value of TLS in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we retrospectively enrolled 185 ESCC patients who underwent surgical resection. Hematoxylin and eosin staining was performed to investigate the presence, the abundance, the maturation, and the location of TLSs. We explored the cellular composition of TLSs using traditional immunohistochemistry in serial sections. The prognostic value of TLSs was investigated by univariate and multivariate analyses. A nomogram was constructed to predict the prognosis. TLS-positive tumors were infiltrated with more CD45+ leukocytes, CD20+ B cells, CD4+ and CD8+ T cells, and CD11c+ dendritic cells(DCs) compared with negative tumors. Kaplan-Meier curves showed that the presence and the abundance of TLSs were associated with longer disease-free survival (DFS) (p = 0.0130) and overall survival (OS) (p = 0.0164). In addition, patients with tumors containing more CD20+ B cell infiltration had longer DFS (p = 0.0105) and OS (p = 0.0341). Multivariate analyses demonstrated that the presence of TLSs was an independent prognostic factor for DFS (hazard ratio [HR] = 0.384, p < 0.001) and OS (HR = 0.293, p < 0.001). The nomogram that integrated the tumor stage, histologic grade, and TLS presence had higher prognostic accuracy. Our study suggests that ESCC-related TLSs can be used as a new biomarker for the prognosis of ESCC patients, and further understanding of their formation and mechanism of induction can provide a possible direction and target for immunotherapy of ESCC.