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.
Esophageal squamous cell carcinoma is the main histological type of esophageal cancer in China, which seriously threatens the health of people. The application of immunotherapy, mainly immune checkpoint inhibitors, has greatly improved the prognosis of patients with esophageal squamous cell carcinoma, but the efficacy of treatment is still limited. Tertiary lymphoid structure (TLS) is an ectopic organized lymphoid structure that accumulates in non-lymphoid organs. Previous studies have found that TLS in esophageal squamous cell carcinoma is associated with better patient outcomes and enhanced immunotherapy efficacy. Based on current researches about TLS in esophageal squamous cell carcinoma, this paper reviews the relationship between TLS and the prognosis and immunotherapy of patients. We hope to provide reference for the precise immunotherapy of esophageal squamous cell carcinoma.
Objective To evaluate the security and outcomes of thoracolaparoscopic esophagectomy (TLE) versus open approach (OA) for thoracic esophageal squamous cell carcinoma. Methods From June 2014 to June 2015, 125 patients with thoracic esophageal squamous cell carcinoma underwent esophagectomy through McKeown approach, including TLE (a TLE group, 107 patients, 77 males and 30 females) and OA (an OA group, 18 patients, 13 males and 5 females). The data of operation and postoperative complications of the two groups were analyzed retrospectively. Results There was no statistical difference in the duration of operation and ICU stay and resected lymph nodes around laryngeal recurrent nerve between the TLE group and the OA group (333.58±72.84 min vs. 369.17±91.24 min, P=0.067; 2.84±1.44 d vs. 6.44±13.46 d, P=0.272; 4.71±3.87 vs. 3.89±3.97, P=0.408) . There was a statistical difference in blood loss, total resected lymph nodes and resected lymph nodes groups between TLE group and OA group (222.62±139.77 ml vs. 427.78±276.65, P=0.006; 19.62±9.61 vs. 14.61±8.07, P=0.038; 3.70±0.99 vs. 3.11±1.13, P=0.024). The rate of postoperative complications was 32.7% in the TLE group and 38.9% in the OA group (P=0.608). There was a statistical difference (P=0.011) in incidence of pulmonary infection (2.8% in the TLE group and 16.7% in the OA group). Incidences of complications, such as anastomotic leakage, cardiac complications, left-side hydrothorax, right-side pneumothorax, voice hoarse and incision infection, showed no statistical difference between two groups. Conclusion For patients with thoracic esophageal squamous cell carcinoma, TLE possesses advantages of more harvested lymph nodes, less blood loss and less pulmonary infection comparing with open approach, and is complied with the principles of security and oncological radicality of surgery.
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.
Objective To explore the expression of CD105 protein in esophageal squamous cell carcinoma and it＇s relationship with P53 protein. Methods Using streptavidin biotinperoxidase （SP） method, the expression of CD105 protein and P53 protein in esophageal squamous cell carcinoma were examined in normal esophageal tissues （n=10） and esophageal squamous cell carcinoma tissues（n=86）. Results The expression positive rate of CD105 protein was 74. 4%（64/86） in esophageal squamous cell carcinoma , 0% in normal esophageal epithelium. Expression positive rate of CD105 protein was 66. 1%（37/56） in early stage （stage Ⅰ-Ⅱ ）, 90.0% （27/30） in later stages （stage Ⅲ-Ⅳ ）. The expression of CD105 protein were bly associated with P53 protein（P〈0. 05）. Conclusion CD105 protein may participate in the onset and progression of esophageal squamous cell carcinoma. CD105 protein could he a new diagnostic /therapeutic target in esophageal squamous cell carcinoma.
ObjectiveTo evaluate the expression level of histone deacetylase 9 (HDAC9) in lung squamous cell carcinoma (LUSC) tissues, to analyze its correlations with clinicopathological characteristics and prognosis of LUSC patients, and to explore the effect it exerts on the proliferation of LUSC cells.MethodsThe expression level of HDAC9 was detected by immunohistochemistry staining (IHC), and its correlations with clinicopathological characteristics were analyzed by χ2 test. Survival analysis was performed using Kaplan-Meier method. Univariate and multivariate Cox proportional hazards model were employed to analyze independent predictors for overall survival (OS) of LUSC patients. CRISPR/dCas9 activation system was used to activate the transcription of HDAC9 gene in LUSC cell line EBC-1. CCK8 cell proliferation assay and colony formation test were performed to investigate the effect that transcriptional activation of HDAC9 exerts on the proliferation of LUSC cells.ResultsOf the 129 LUSC patients, 39 (30.2%) were in the HDAC9 low expression group and 90 (69.8%) were in the HDAC9 high expression group. The OS of the patients with HDAC9 high expression was shorter than that of patients with HDAC9 low expression (P=0.032). The expression level of HDAC9 was associated with tumor grade (P=0.035), primary tumor size (P=0.041), and lymph node metastasis (P=0.013). The expression level of HDAC9 (P=0.023), tumor grade (P=0.003), primary tumor size (P=0.003), and lymph node metastasis (P=0.002) were independent predictors for OS of LUSC patients. Transcriptional activation of HDAC9 promoted colony formation of LUSC cells and cell proliferating curves showed that LUSC cells with HDAC9 transcriptional activation proliferated faster than non-targeting cells (F=52.7, P=0.002).ConclusionLUSC patients with HDAC9 high expression have poorer prognosis than HDAC9 low expression ones. The expression level of HDAC9 is associated with tumor grade, primary tumor size, and lymph node metastasis, and is identified as an independent predictor for prognosis of LUSC. Transcriptional activation of HDAC9 promotes cell proliferation in LUSC. These results suggest that HDAC9 may serve as a promising biomarker for prognosis in LUSC.
Objective To investigate the expression and clinical significance of CXCR4 in esophageal squamous cell carcinoma (ESCC). Methods Databases including PubMed, EMbase, Web of Science, CBM, VIP, CNKI and WanFang Data were searched from inception to April 2012, and the relevant references were also retrieved to collect relevant case-control studies. Two reviewers independently screened literature according to the inclusion and exclusion criteria, and evaluated the quality of the included studies. Then the meta-analysis was conducted using RevMan 5.1 software. Results A total of 5 case-control studies involving 493 ESCC tissues and 136 normal esophageal tissues were included. The results of the meta-analyses showed that, as for the positive rate of CXCR4 expression, it was higher in ESCC tissues rather than normal esophageal tissues (OR=12.03, 95%CI 6.76 to 21.44, Plt;0.000 01), in ESCC tissues with lymph node metastasis rather than those without lymph node metastasis (OR=4.35, 95%CI 2.48 to 7.62, Plt;0.000 01), as well as in moderate and low differentiated ESCC tissues rather than high differentiated ESCC tissues (OR=0.51, 95%CI 0.32 to 0.81, P=0.004); but no significant difference was found between the clinical stage I-II and clinical stage III-IV ESCC tissues. Conclusion The presently limited evidence shows CXCR4 expression is associated with ESCC, lymph node metastasis and degree of cell differentiation, indicating that CXCR4 may take a role in the whole course of carcinogenesis of ESCC. But the relationship between CXCR4 expression and clinical stage of ESCC is still unclear, which needs to be further proved by more large-scale, well-designed and high quality case-control studies.
ObjectiveTo explore the mechanism of DDX46 regulation of esophageal squamous cell carcinoma.MethodsPicture signals of fluorescence in gene array were scanned and differential expression of gene in two groups (a DDX46-shRNA-LV group and a control-LV group) were compared by GCOSvL.4 software. These differential expressed genes were analyzed by bioinformatics methods finally, and validated by quantitative real time polymerase chain reaction (qRT-PCR) analysis.ResultsAccording to the screening criteria of fold change ≥2 and P<0.05, 1 006 genes were differentially expressed after DDX46 knockdown, including 362 up-regulated and 644 down-regulated genes. Bioinformatics analysis and gene co-expression network building identified that these differentially expressed genes were mainly involved in cell cycle, proliferation, apoptosis, adhesion, energy metabolism, immune response, etc. Phosphatidylinositol 3-kinase (PI3K) was the key molecule in the network. The results of RT-qPCR were completely consistent with the results of gene microarra.ConclusionBioinformatics can effectively exploit the microarray data of esophageal squamous cell carcinoma after DDX46 knockdown, which provides a valuable clue for further exploration of DDX46 tumorigenesis mechanism and helps to find potential drug therapy.
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 misdiagnosis of primary squamous cell carcinoma of liver (PSCCL) as cholangiocarcinoma before operation and its clinical manifestations, imaging manifestations, etiology, histological origin, pathological characteristics, diagnosis and differential diagnosis, selection of treatment methods, and prognosis, so as to improve understanding and reasonable diagnosis and treatment of disease.MethodThe clinicopathologic data of a case of PSCCL misdiagnosed as cholangiocarcinoma in the West China Hospital of Sichuan University were analyzed retrospectively.ResultsThe patient was admitted to the West China Hospital of Sichuan University with the right hepatic space occupying. The preoperative imaging examination showed that the patient had the imaging characteristics of hepatic cholangiocarcinoma, then the right hemihepatectomy was performed. The postoperative pathological diagnosis was the PSCCL.ConclusionsPreoperative diagnosis of PSCCL is extremely difficult and it is difficult to differentiate it from primary liver cancer, and it is easy to overlook liver metastasis’s occurrence in other parts of the squamous cell carcinoma, which leads to liver metastasis. It is usually diagnosed by pathological diagnosis after operation, and then original lesions in other parts are excluded by various examinations. PSCCL is treated in a variety of ways, but it’s prognosis is not good. At present, there is no unified treatment principle, most of which are surgery, followed by postoperative radiotherapy and chemotherapy. In most cases, because PSCCL’s etiology is unknown and mechanism is not clear, clinicians can only implement individualized treatment according to patient’s condition.