Great progress has been made in immunotherapy for esophageal squamous cell carcinoma in recent years. However, for thoracic surgeons, immunotherapy is still a new thing and they lack enough experience. Therefore, this paper attempts to discuss some hot issues of immunotherapy, including the indications, side effects, clinical efficacy and evaluation of efficacy. The author hopes that this article will help and attract the attention of thoracic surgeons.
Objective To investigate the prognostic value of preoperative inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and fibrinogen-to-prealbumin ratio (FPR), for postoperative survival in patients with resectable esophageal squamous cell carcinoma (ESCC). Additionally, to construct and validate a prognostic model for ESCC based on these inflammatory markers combined with TNM staging. Methods We retrospectively analyzed the clinical data of patients with histologically confirmed ESCC who underwent surgical resection at the First Affiliated Hospital of the University of Science and Technology of China during 2017. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values for preoperative NLR, PLR, SII, and FPR. Clinicopathological characteristics were compared between patient groups with different levels of these markers. Survival analysis was performed using the Kaplan-Meier method, and univariate and multivariate regression analyses were conducted using the Cox proportional hazards model to identify prognostic factors. Nomograms for predicting overall survival (OS) and disease-free survival (DFS) were constructed using R software. The model's discrimination was assessed with ROC curves, its calibration was evaluated with calibration curves, and its clinical utility was determined by decision curve analysis (DCA). Results A total of 224 patients who underwent surgery for ESCC were included, comprising 180 males and 44 females. The optimal preoperative cut-off values of NLR, PLR, SII, and FPR for predicting postoperative OS were 2.70, 140.34, 360.73, and 0.015, respectively. The 5-year OS and DFS rates in the high-NLR group were lower than in the low-NLR group (both P<0.001). Similarly, patients in the high-PLR group (P=0.005 and P=0.009, respectively), high-SII group (P=0.008 and P=0.018, respectively), and high-FPR group (both P<0.001) had lower 5-year OS and DFS rates compared to their low-level counterparts. Multivariate Cox regression analysis revealed that patient age, T stage, N stage, tumor differentiation, and NLR>2.70 et al were independent prognostic factors for both OS and DFS. Based on these factors, nomograms for OS and DFS were constructed. The area under the ROC curve (AUC) for 3- and 5-year OS were 0.966 and 0.907, respectively, and for 3- and 5-year DFS were 0.960 and 0.919, respectively. The calibration curves showed good agreement between predicted and actual outcomes. DCA demonstrated that the models provided a positive net benefit for all patients under intervention. Conclusion Preoperative levels of NLR, PLR, SII, and FPR are associated with the prognosis of patients with ESCC, with NLR being an independent prognostic predictor. The nomogram models, constructed based on patient age, tumor differentiation, T stage, N stage, and preoperative NLR level, can accurately predict the prognosis of patients with ESCC. These models may help guide preoperative clinical decision-making and tailor treatment and follow-up strategies.
ObjectiveTo investigate the expression of MicroRNA 155 (miR-155) in esophageal squamous cell carcinoma (ESCC) and analyze its correlation with clinicopathological features of ESCC.
MethodsThis study included 54 patients with primary ESCC who underwent radical esophagectomy in Department of Thoracic Surgery, Henan Cancer Hospital of Zhengzhou University between January 2010 and November 2012. There were 47 males and 7 females with median age of 61 years (range, 45 to 82 years). Forty patients were in stage Ⅰ or Ⅱ and 14 patients in stage Ⅲ a+b. Expression of miR-155 was determined by SYBR Green qRT-PCR in ESCC tissue and corresponding adjacent normal mucosa in surgical samples from the 54 patients, and its correlation with clinicopathological features was analyzed.
ResultsExpression of miR-155 was significantly lower in ESCC tissue than that in adjacent normal mucosa (Z=-4.258, P=0.000).Expression level of miR-155 was significantly correlated with lymph node metastasis (P=0.040), but not significantly correlated with smoking (P=0.430), drinking (P=0.429), age (P=0.769), gender (P=0.671), depth of invasion (P=0.230), differentiation degree (P=0.896) or pTNM (P=0.407) of ESCC.
ConclusionUnder-regulation of miR- 155 expression in ESCC tissue may lead to disorders of inflammation response, immune response and relevant tumor suppressor, and may play a significant role in carcinogenesis and progression of ESCC.
ObjectiveTo evaluate the safety and necessity of recurrent laryngeal lymph node resection by comparing the complications and prognosis of patients with recurrent laryngeal nerve injury receiving different recurrent laryngeal lymph node resections.MethodsWe reviewed the clinical data of 153 patients with stage T1N0M0 esophageal squamous cell carcinoma who underwent radical esophageal cancer surgery at the Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2014 to May 2016. Among them, 125 were male and 28 were female, at an average age of 62 years. All patients underwent bilateral recurrent laryngeal nodes sampling. They were divided into 3 groups according to the dissection situation: patients with only one recurrent laryngeal lymph node resection on both sides during the operation were treated as a sampling group (n=49); patients with only one recurrent laryngeal lymph node resection on one side and more than one recurrent laryngeal lymph nodes resection on the other side were treated as a unilateral dissection group (n=49); patients with more than one recurrent laryngeal lymph nodes resection on both sides were treated as a bilateral dissection group (n=55). Follow-up was performed to compare the prognostic differences among the three groups. Seven days after the operation, the vocal cords of the patients were examined with an electronic laryngoscope and classified using the Clavien-Dindo system. The differences in complications related to recurrent laryngeal nerve injury among the three groups were compared.ResultsThe 5-year overall survival (OS) rate of the patients in the sampling group, unilateral dissection group and bilateral dissection group was 66.8%, 88.5%, 93.8%, respectively. There was statistical difference between the sampling group and the unilateral dissection group or the bilateral dissection group (P<0.05), and no statistical difference between the unilateral dissection group and the bilateral dissection group (P>0.05). The incidence of complications among the three groups was not statistically different (P>0.05).ConclusionFor patients with esophageal squamous cell carcinoma of stage T1N0M0, the lymph nodes of the bilateral recurrent laryngeal nerves should be removed during the operation as many as possible, which will help improve the 5-year survival rate of the patients.
Increasing evidence suggests that many types of cancers contain a population of cells that display stem cell properties. These cells are called cancer stem cells （CSCs），which are closely related to tumor initiation，growth，metastasis and chemoresistance. CSCs are also found in esophageal squamous cell carcinoma （ESCC）. These cells are characterized by potential of self-renewal and differentiation，tumor formation in nude mice and chemotherapy resistance，and thus may play an important role in targeted cancer therapies. Current methods for culturing and sorting CSCs in ESCC mainly include fluorescence activated cell sorting （FACS），magnetic activated cell sorting （MACS），suspension culture，and side population （SP） cell sorting. In this review，we focus on current research methods for CSCs in ESCC，their biological characteristics and areas for improvement. We believe that a combination of multiple cell-surface makers is needed for research of CSCs in ESCC.
Resection is one of the most important treatments for esophageal squamous cell carcinoma, and routine postoperative follow-up is an effective method for early detection and treatment of recurrent metastases, which can improve patients' quality of life and prognosis. This consensus aims to provide a reference for colleagues responsible for postoperative follow-up of esophageal squamous cell carcinoma patients in China, and further improve the standardization of the diagnosis and treatment of esophageal squamous cell carcinoma.
ObjectiveTo investigate the expression of Cyclin D1 in stage T2-3N0M0 esophageal squamous cell carcinoma (ESCC) and its relationship with patient prognosis.
MethodsExpression of Cyclin D1 in 227 ESCC specimens at stage T2-3N0M0 was detected by immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve analysis was performed to select the cut-off score for high or low IHC reactivity. Correlations between Cyclin D1 expression and clinicopathological features as well as prognosis of ESCC patients were determined.
ResultsAmong the 227 patients, 90 (39.6%) patients had low expression of Cyclin D1, and 137 (60.4%) patients had high expression of Cyclin D1.No significant correlation was observed between Cyclin D1 expression and patient gender (P=0.298), age(P=0.525), tumor location (P=0.570), tumor length (P=0.056), tumor grade (P=0.713), and depth of invasion (P=0.557). There was significant difference in prognosis between low-expression Cyclin D1 group and high-expression Cyclin D1 group (3-year survival rate:51.1% vs. 43.8%, 5-year survival rate:43.3% vs. 30.7%, P=0.047). Cox proportional-hazards regression model analysis showed that Cyclin D1 was not an independent prognostic factor for ESCC patients at stage T2-3N0M0 (relative risk=1.378, 95% CI:0.990-1.919, P=0.057).
ConclusionOver expression of Cyclin D1 may be an adverse prognostic factor of ESCC patients at stage T2-3N0M0.
ObjectiveTo explore the effects and molecular mechanisms of histone methylase G9a inhibitor BIX-01294 on apoptosis in esophageal squamous cell carcinoma (ESCC).MethodsMTT assay and Colony-forming Units were adopted to determine the effects of BIX-01294 on the growth and proliferation of ESCC cell lines EC109 and KYSE150. Flow cytometry was used to analyze the apoptosis status of ESCC cells after the treatment of BIX-01294. The effects of BIX-01294 treatment on the expressions of G9a catalytic product H3K9me2, DNA double-strand break (DSB) markers, and apoptosis-related proteins were detected by Western blotting.ResultsBIX-01294 inhibited the growth of EC109 and KYSE150 cells in a dose-dependent manner (P<0.05), and BIX-01294 with the inhibitory concentration 50% (IC50) significantly inhibited the formation of colony (P<0.05). After 24 hours treatment of BIX-01294 (IC50), the apoptosis rate of EC109 cells increased from 11.5%±2.1% to 42.5%±5.4%, and KYSE150 cells from 7.5%±0.9% to 49.2%±5.2% (P<0.05). The expression level of the G9a catalytic product, H3K9me2, significantly decreased (P<0.05); while the expression of the DSB marker γH2AX was dramatically enhanced (P<0.05). We also found that the mitochondrial apoptosis pathway was activated and the expression levels of cleaved caspase3 and cleaved PARP were significantly elevated (P<0.05).ConclusionBIX-01294, the inhibitor of methyltransferase G9a, prompted apoptosis in ESCC cells by inducing DSB damage and activating mitochondrial apoptosis pathway.
ObjectiveTo investigate the short-term therapeutic effect of neoadjuvant immunotherapy combined with chemotherapy in the locally advanced esophageal squamous cell carcinoma. MethodsThe clinical data of patients with esophageal squamous cell carcinoma treated with neoadjuvant treatment in Gaozhou People's Hospital from August 2019 to October 2020 were retrospectively analyzed. According to the different treatments, the patients were divided into two groups: a neoadjuvant immunotherapy combined with chemotherapy group (NIC group) and a neoadjuvant chemoradiotherapy group (NC group). The baseline data, incidence of adverse events during treatment, perioperative indicators, postoperative pathological remission rate and incidence of postoperative complications were compared between the two groups. ResultsTotally 33 patients were enrolled, including 15 males and 18 females, with an average age of 62.37±7.99 years. There were 17 patients in the NIC group and 16 patients in the NC group. In the NIC group, the carcinoma was mainly located in the middle and lower esophagus, with 5 paitents in stage Ⅱ, 9 patients in stage Ⅲ, and 3 patients in stage Ⅳa. In the NC group, the carcinoma was mainly located in the upper-middle esophagus, with 1 patient in stage Ⅱ and 15 patients in stage Ⅲ. During the neoadjuvant treatment, there was no significant difference in the occurrence of bone marrow suppression or gastrointestinal reactions between the two groups (P>0.05). There were 4 immune-related rashes in the NIC group and 1 esophageal perforation in the NC group. Fourteen (82.35%) patients in the NIC group and 12 (75.00%) patients in the NC group completed the operation on schedule. The postoperative ICU stay time and chest tube indwelling time in the NIC group were shorter than those in the NC group (P<0.05). There were 5 patients of complete remission in the NIC group, and 6 patients in the NC group. There was no significant difference in the pathological regression grade or residual tumor cells between the two groups (P>0.05). There was no significant difference in the incidence of anastomotic fistula, thoracic gastric fistula, bronchial mediastinal fistula, abdominal distension, pulmonary infection, stroke, or hoarseness during the perioperative period between the two groups of patients who completed the operation (P>0.05). In the NC group, 2 patients died during the perioperative period because of thoracic gastric fistula complicated by severe infection. ConclusionNeoadjuvant immunotherapy combined with chemotherapy dose not significantly increase the occurrence of adverse events and shows a good rate of pathological remission, which indicates that the neoadjuvant immunotherapy combined with chemotherapy is a safe, feasible and potential new treatment model.
Esophageal cancer is a serious threat to the health of Chinese people. The key to solve this problem is early diagnosis and early treatment, and the most important method is endoscopic screening. The rapid development of artificial intelligence (AI) technology makes its application and research in the field of digestive endoscopy growing, and it is expected to become the "right-hand man" for endoscopists in the early diagnosis of esophageal cancer. Currently, the application of multimodal and multifunctional AI systems has achieved good performance in the diagnosis of superficial esophageal squamous cell carcinoma and precancerous lesions. This study summarized and reviewed the research progress of AI in the diagnosis of superficial esophageal squamous cell carcinoma and precancerous lesions, and also explored its development direction in the future.
