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.
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.
ObjectiveTo improve the knowledge of double primary lung cancer. MethodsA case of synchronous double primary lung cancers, who was diagnosed by bronchoscopic examination and immunohistochemical staining in our department in 2012, was analyzed retrospectively. The literatures were review with "double primary, lung cancer, squamous cell carcinoma, small cell lung carcinoma" as the research terms in Wanfang, CNKI and PubMed database. ResultsA 76-year-old male patient complained of intermittent cough, chest pain and wheezing over half a month. Chest computer tomography showed masslike lesion with high density in hilum of right lung. The patient received bronchoscopic examination, the pathological and immunohistochemical findings was squamous cell carcinoma and small cell lung carcinoma. The imaging manifestations and bronchoscopy findings were consistent with pathologic diagnosis. A total of 7 pieces of literature were retrived in above-mentioned databases. Seven patients had long smoke history and 6 were male. Four patients complained about couph and sputum, and 1 patient had chest pain. CT showed masses in the lung or hilus with or without stenosis and obliteration of the bronchus. Five patients were proven by bronchoscopy and biopsy. ConclusionDouble primary lung cancer has characteristics in radiologic features and bronchoscopy performance, so can be early diagnosed by bronchoscopy and histopathology.
Objective To observe the growth of orthotopic transplanted tumor in nude mice after stomatin-like protein 2 (SLP-2) expression decreased, and to further study the role of SLP-2 in the development and progression of esophageal squamous cell carcinoma. Methods Using RNA interference technique, esophageal squamous cell carcinoma cell lines with specific expression of SLP-2 and stable expression of luciferase were established. The healthy female nude mice with weight ranging from 19 to 22 g were randomly divided into 3 groups (n=12), 6 mice were used to establish subcutaneous xenografts, and the other 6 mice were used to establish the orthotopic transplanted tumor model (Group 1: cell infected with SLP-2-1 plasmid; group 2: cell infected with SLP-2-2 plasmid; group 3: cell infected with SHGFP plasmid). Index of the experiment end was weight loss and poor general situation in any mouse. Before the nude mice were sacrificed, the luciferase value of the tumor was detected by using in vivo imaging technique. After the nude mice were sacrificed, the primary tumor was removed for pathology examination. Results There was no significant difference in region of interest (ROI) value between the group 1 and group 2 (P=0.943). The ROI value for both groups 1 and 2 was significantly lower than that in the group 3 (P=0.002, P=0.000). The primary tumor infiltrated into the muscularis propria of esophageal was observed in all groups. Conclusion SLP-2 is involved in the development and progression of esophageal squamous cell carcinoma, and the decrease of SLP-2 expression can inhibit the growth of esophageal squamous cell carcinoma.
Objective To investigate whether postoperative therapy can bring survival benefits to patients with locally advanced esophageal squamous cell carcinoma who have received neoadjuvant chemotherapy with TP regimen. Methods We retrospectively reviewed clinical data of 115 patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy with TP regimen and underwent esophagectomy in our hospital from January 2007 through December 2016. Patients were divided into two groups including a non-receiving treatment group (54 patients with 47 males and 7 females) and a receiving treatment group (61 patients with 52 males and 9 females). There were 31 patients with postoperative chemotherapy, 14 with postoperative radiotherapy, and 16 with postoperative chemotherapy and radiotherapy in the receiving treatment group. Results In the non-receiving treatment group, the 5-year median disease free survival (DFS) rate was 54.7%, and the 5-year overall survival (OS) rate was 55.3%. In the receiving treatment group, the median DFS was 46.0 months (95% CI 22.9–69.1), the 5-year DFS rate was 42.3%; and the median OS was 68.0 months (95% CI 33.0–103.0), the 5-year OS rate was 51.3%. Furthermore, there was no statistical difference between the two groups with regards to DFS (P=0.641) or OS (P=0.757) using Kaplan-Meier method. Besides, in each subgroup, the results of Cox proportional hazard model analysis showed postoperative treatment did not improve survival (P>0.05, respectively). Conclusion Postoperative treatment does not bring survival benefits to patients with esophageal squamous cell carcinoma who have received neoadjuvant chemotherapy with TP regimen.
ObjectiveTo explore whether surgery combined with adjuvant chemotherapy can bring survival benefits to patients with cervical and upper thoracic esophageal squamous cell carcinoma (ESCC).MethodsThe clinical data of patients with cervical and upper thoracic ESCC who underwent R0 resection and neck anastomosis in our department from 2006 to 2010 were retrospectively analyzed. Patients received neoadjuvant therapy or adjuvant radiotherapy were excluded. The adjuvant chemotherapy group was given a combination of taxanes and platinum based chemotherapy after surgery; the surgery alone group did not receive adjuvant chemotherapy. The Kaplan-Meier method was used to analyze the survival difference between the adjuvant chemotherapy group and the surgery alone group. ResultsA total of 181 patients were enrolled, including 141 (77.9%) males and 40 (22.1%) females, with an average age of 61.0±8.2 years (80 patients aged≤61 years, 101 patients aged>61 years). There were 70 (38.7%) patients of cervical ESCC, and 111 (61.3%) patients of upper thoracic ESCC. Eighty-seven (48.1%) patients underwent postoperative adjuvant chemotherapy, and 94 (51.9%) patients underwent surgery alone, and the basic clinical characteristics were well balanced between the two groups (P>0.05). The median survival time of patients in the adjuvant chemotherapy group and the surgery alone group was 31.93 months and 26.07 months, and the 5-year survival rate was 35.0% and 32.0%, respectively (P=0.227). There was no statistical difference in median survival time between the cervical ESCC and upper thoracic ESCC group (31.83 months vs. 29.76 months, P=0.763). For cervical ESCC patients, the median survival time was 45.07 months in the adjuvant chemotherapy group and 14.70 months in the surgery alone group (P=0.074). Further analysis showed that the median survival time of lymph node negative group was 32.53 months, and the lymph node positive group was 24.57 months (P=0.356). The median survival time was 30.43 months in the lymph-node positive group with adjuvant chemotherapy and 17.77 months in the lymph-node positive group with surgery alone. The survival curve showed a trend of difference, but the difference was not statistically significant (P=0.557).ConclusionThere is no statistical difference in the long-term survival of cervical and upper thoracic ESCC patients after R0 resection. Postoperative adjuvant chemotherapy may have survival benefits for patients with cervical ESCC and upper ESCC with postoperative positive lymph nodes, but the differences are not statistically significant in this setting.
Objective To investigate the operative procedure and the effectiveness of cranial bone reconstruction after one-stage resection of scalp squamous carcinoma invading the skull. Methods Between January 2005 and December 2008,14 patients with scalp squamous carcinoma invading the skull were treated. There were 6 males and 8 females with a median age of 53 years (range, 29-76 years). The disease duration ranged from 3 to 8 years (mean, 6 years). The tumor locations were right temporal area in 2 cases, left temporal area in 2 cases, right frontal area in 3 cases, left frontal area in 1 case, right occi pital area in 1 case, left occi pital area in 2 cases, frontal area in 2 cases, and the top of the head in 1 case. Scalp lesions showed exogenous growth, and lesion diameter ranged from 5 to 12 cm (mean, 8 cm). TNM classification showed T4N0M0 tumor in all cases. MRI showed that tumors invaded the skull, 12 cases had smooth intradural side and 2 cases had brain involvement without lymph node metastasis or detected distant metastasis. Under general anesthesia, all the lesions of the scalp, skull, dura, and brain tissue were removed completely. The size defect of the scalp, skull, and dura ranged from 8 cm × 7 cm to 15 cm × 14 cm, from 5 cm × 4 cm to 12 cm × 12 cm, and from 4 cm × 4 cm to 9 cm × 8 cm, respectively, which were repaired with artificial patch, titanium metal, mesh, and local flaps, respectively. The donor site was repaired by spl it-thickness skin graft. Results The skin flaps and grafts survived and incision healed by first intention without cerebrospinal fluid leakage, intracranial and subdural hemorrhage, andother compl ications. All patients were followed up 2 to 5 years (mean, 4 years), and no recurrence was found. The compatibil ity of titanium mesh and local tissue was good. The patients had good hair growth without exposure of titanium mesh, seizures, partial paralysis, and other neurological damage performance. Conclusion After one-stage resection of scalp squamous carcinoma invading the skull, it is effective to reconstruct the skull with titanium mesh and to repair dural defects with artificial dura.