Comparison of immunochemotherapy and chemotherapy alone in conversion therapy for locally advanced unresectable esophageal squamous cell carcinoma.

Background: The clinical value of preoperative immunochemotherapy and simple chemotherapy induction regimen in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma (ESCC) is still unclear. Method: Retrospective analysis was conducted on patients with unresectable cT4b stage ESCC who underwent conversion surgery in our hospital from January 2020 to December 2022. According to the preoperative induction treatment plan, they were divided into induction immunochemotherapy group (iICT group) and induction chemotherapy group (iCT group). The conversion surgery rate, R0 resection rate, radiological and pathological tumor responses, safety, and short-term survival outcomes were analyzed. Results: The results showed that a total of 199 patients with cT4b locally advanced unresectable ESCC who underwent preoperative induction therapy were included in this study. Among them, there were 64 cases (32.2%) in the iICT group, 135 cases (67.8%) in the iCT group. There was a statistically significant difference in objective response rate (73.5% vs 48.9%) and conversion surgery rate (81.3% vs 66.7%), between the iICT and iCT groups (P=0.001 and P=0.019). Among the two groups of patients who underwent surgery, there were statistically significant differences in R0 resection rate (94.2% vs 82.2%) and pathological complete remission rate (23.1% vs 6.7%) between the iICT and iCT groups (P=0.043 and P=0.004). And there was no statistically significant difference in the incidence of grade 3 and above between two groups (P=0.928). The 2-year EFS of the iICT group and iCT group were 76.4% and 42.4%, respectively, with statistically significant differences (P=0.006). Conclusions: Compared with simple chemotherapy, the combination of PD-1 inhibitors and chemotherapy can achieve better conversion surgery rate, tumor response and event-free survival in the conversion therapy of locally advanced unresectable ESCC.

CENPF Upregulation is Associated with Immunosuppressive Status and Poor Clinical Outcomes in Lung Adenocarcinoma Validated by qRT-PCR.

OBJECTIVE: CENPF-differentially expressed in various types of cancers-is a marker of poor prognosis. However, studies on the impact of CENPF on patient prognosis in lung adenocarcinoma regarding immune infiltration are lacking. METHODS: CENPF expression profiles were analyzed in the GEO and TCGA databases. qRT-PCR was used to verify CENPF mRNA expression in lung adenocarcinoma cell lines. The prognostic value of CENPF was evaluated by combining data from clinical samples in the GEPIA2 and TCGA databases. Metascape and WebGestalt were used for enrichment analysis of gene sets most positively associated with CENPF. Immune cell infiltration score data were retrieved from TCGA and the correlation between CENPF expression and immune cell infiltration was analyzed. RESULTS: CENPF expression was elevated in 29 types of cancer. CENPF was highly expressed and increased with tumor grade in lung adenocarcinoma. Immunohistochemical and qRT-PCR analyses revealed that CENPF expression was upregulated in lung adenocarcinoma tissues and cells. High expression of CENPF significantly worsened prognoses in patients with multiple malignancies, including lung adenocarcinoma. Results from gene set enrichment analysis indicated significant enrichment of the progesterone-mediated oocyte maturation pathway. Immune infiltration analysis revealed that CD4+ Th2 cell infiltration was significantly higher in the high CENPF expression group. CONCLUSION: Upregulation of CENPF expression was related to poor progression-free survival, disease- free survival, and overall survival in patients with lung adenocarcinoma. High expression of CENPF was markedly related to genes associated with the immune checkpoint. Lung adenocarcinoma samples with high CENPF expression had increased CD4+ Th2 cell infiltration. Our findings indicate that CENPF promotes CD4+ Th2 cell infiltration through oncogenic activity and may be used as a biomarker for predicting patient outcomes in lung adenocarcinoma.

Dysregulated circRNAs and ceRNA network in esophageal squamous cell carcinoma.

Accumulating evidence suggests that circular RNA (circRNA), once thought to be a transcriptional error, plays an important regulatory role in the tumor biological process. Some circRNAs regulate the protein-coding gene expression by competitive binding with microRNAs (miRNAs). However, functional roles of circRNA-mediated competitive endogenous RNAs (ceRNAs) in esophageal squamous cell carcinoma (ESCC) are rarely reported. To explore the biological functions of circRNAs in ESCC, we surveyed the integrating differential circRNA expression of ESCC and para-cancer tissues using microarray in three patients. Then, we screened out differentially expressed mRNAs obtained from 81 ESCC tissues and 11 normal tissues in The Cancer Genome Atlas (TCGA). Then, we constructed a hypothetical ceRNA network by integrating differential expression of circRNAs and mRNAs. Finally, 32 differentially expressed circRNAs and 98 differentially expressed mRNAs were linked by 64 miRNAs to build the ceRNA network in ESCC. We suggest that the identified ceRNA network can facilitate a better understanding of circRNA-related mechanisms in ESCC.

TSPAN12 is overexpressed in NSCLC via p53 inhibition and promotes NSCLC cell growth in vitro and in vivo.

BACKGROUND: Tetraspanin 12 (TSPAN12), a member of the phylogenetically ancient tetraspanin family, is linked to impaired vascularization of the eye called familial exudative vitreoretinopathy, while the functional role of TSPAN12 in lung cancer has not been well characterized. RESULTS: In our study, TSPAN12 is able to regulate the growth of non-small-cell lung carcinoma (NSCLC) cells both in vitro and in vivo. TSPAN12 mRNA level was significantly increased in human NSCLC samples compared with their corresponding paracancerous histologic normal tissues. In addition, TSPAN12 expression, which is frequently upregulated in NSCLC, is inversely correlated with p53 expression. Furthermore, the expression levels of TSPAN12 were also increased in three human NSCLC cell lines compared to human bronchial epithelial (16HBE) cells. Then, we studied the effects of TSPAN12 silencing by short hairpin ribonucleic acid on NSCLC cell growth in vitro and tumorigenesis in vivo, along with the effect on the p53 pathway. Knockdown of TSPAN12 in NSCLC cells inhibited cell proliferation and colony formation. In addition, knockdown of TSPAN12 increased apoptosis in NSCLC cells. Mechanistically, TSPAN12 could modulate the expression of p53, p21, and p27 in NSCLC cells. In a tumor xenograft model, TSPAN12 silencing inhibits the tumor growth of H1299 cells. CONCLUSION: Taken together, our results reveal that TSPAN12 plays an important role in NSCLC and is a potential biomarker and a promising target in the treatment of NSCLC.

The Diagnostic Value of Routine Contrast Esophagram in Anastomotic Leaks After Esophagectomy.

BACKGROUND: Routine contrast esophagram has been shown to be increasingly limited in diagnosing anastomotic leaks after esophagectomy. METHODS: Patients undergoing esophagectomy from 2013 to 2014 at Huai'an First Peoples' Hospital were identified. We retrospectively analyzed patients who underwent routine contrast esophagram on postoperative day 7 (range 6-10) to preclude anastomotic leaks after esophagectomy. RESULTS: In 846 patients who underwent esophagectomy, a cervical anastomosis was performed in 286 patients and an intrathoracic anastomosis in 560 patients. There were 57 (6.73%) cases with anastomotic leaks, including cervical leaks in 36 and intrathoracic leaks in 21 patients. In the cervical anastomotic leak patients, 13 were diagnosed by early local clinical symptoms and 23 underwent routine contrast esophagram. There were 7 (30.4%) true-positive, 11 (47.8%) false-negative, and five (21.8%) equivocal cases. In the intrathoracic anastomotic leak patients, four (19%) were diagnosed by clinical symptoms, 16 (76.2%) were true positives, and one (4.8%) was a false negative. Aspiration occurred in five patients with cervical anastomoses and in eight patients with intrathoracic anastomoses; aspiration pneumonitis did not occur in these cases. CONCLUSIONS: Gastrografin and barium are safe contrast agents to use in post-esophagectomy contrast esophagram. Because of the low sensitivity in detecting cervical anastomotic leaks, routine contrast esophagram is not advised. For patients with intrathoracic anastomoses, it is still an effective method for detecting anastomotic leaks.

Epigenetic activation of SIN1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition.

Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is an essential component of mTORC2. Previous studies have shown that SIN1 is a key regulator of Akt pathway which plays an important role in various pathological conditions including cancer. While its effects and mechanisms on the progression of NSCLC remain unknown. In this study, we report that SIN1 is able to promote the growth and migration of NSCLC cells both in vitro and in vivo. Overexpression of SIN1 promoted A549 and H1299 cells proliferation by both MTT and colony formation assays. Consistently, knockdown of SIN1 inhibited the proliferation of these cells. In transwell assay, overexpression of SIN1 increased the migration of A549 and H1299 cells, while SIN1 knockdown reduced their migration. In a tumor xenograft model, overexpression of SIN1 promoted tumor growth of A549 cells in vivo, while SIN1 knockdown suppresses the tumor growth. We also found a mechanistic link between SIN1 and H3K4me3, H3K4me3 is involved in SIN1 upregulation. Moreover, SIN1 can significantly promote the in vitro migration and invasion of NSCLC cells via induction epithelial mesenchymal transition (EMT) process, which subsequently leads to transcriptional downregulation of epithelial marker E-cadherin and upregulation of mesenchymal markers N-cadherin and Vimentin expression. Together, our results reveal that SIN1 plays an important role in NSCLC and SIN1 is a potential biomarker and a promising target in the treatment of NSCLC.

[Application of bundles of intervention in the treatment of esophageal carcinoma anastomotic leak].

OBJECTIVE: To investigate the application of bundles of intervention in the treatment of esophageal carcinoma anastomotic leak. METHODS: From January 2014 to May 2015, 44 cases of esophageal carcinoma anastomotic fistula were treated by bundles of intervention (through the collection of a series of evidence-based treatment and care measures for the treatment of diseases) in Department of Thoracic Surgery, Huai'an First Hospital, Nanjing Medical University (bundles of intervention group), and 68 patients with esophageal carcinoma postoperative anastomotic leak from December 2013 to January 2012 receiving traditional therapy were selected as the control group. The clinical and nutritional indexes of both groups were compared. RESULTS: There were no significant differences in general data and proportion of anastomotic leak between the two groups. Eleven patients died during hospital stay, including 3 cases in bundles of intervention group(6.8%) and 8 cases in control group (11.8%) without significant difference(P = 0.390). In bundles of intervention group, 1 case died of type III( intrathoracic anastomotic leak, 2 died of type IIII( intrathoracic anastomotic leak. In control group, 2 cases died of type III( cervical anastomotic leak, 2 died of type III( intrathoracic anastomotic leak and 4 of type IIII( intrathoracic anastomotic leak. The mortality of bundles of intervention group was lower than that of control group. The duration of moderate fever [(4.1±2.4) days vs. (8.3±4.4) days, t=6.171, P=0.001], the time of antibiotic use [(8.2±3.8) days vs.(12.8±5.2) days, t=5.134, P = 0.001], the healing time [(21.5±12.7) days vs.(32.2±15.8) days, t=3.610, P=0.001] were shorter, and the average hospitalization expenses[(63±12) thousand yuan vs. (74±19) thansand yuan, t=3.564, P=0.001] was lower in bundles of intervention group than those in control group. Forty-eight hours after occurrence of anastomotic leak, the levels of hemoglobin, albumin and prealbumin were similar in both groups. However, at the time of fistula healing, the levels of hemoglobin [(110.6±10.5) g/L vs.(103.8±11.1) g/L, t=3.090, P=0.002], albumin [(39.2±5.2) g/L vs.(36.3±5.9) g/L, t=2.543, P=0.013] and prealbumin [(129.3±61.9) g/L vs.(94.1±66.4) g/L, t=2.688, P=0.008] were significantly higher in bundles of intervention group. CONCLUSION: In the treatment of postoperative esophageal carcinoma anastomotic leak, application of bundles of intervention concept can significantly improve the nutritional status and improve the clinical outcomes.

[Application of fast-track surgery in the management of patients with esophageal cancer].

OBJECTIVE: To evaluate the influence of fast-track surgery in perioperative period on the clinical outcomes of patients with esophageal cancer. METHODS: Clinical data of 117 patients with esophageal cancer between January 2011 and June 2011 were retrospectively analyzed. Sixty-three cases (study group) were treated with fast-track surgery and 54 cases(control group) were treated according to routine protocol in the perioperative period. RESULTS: The operative time, time to drainage tube removal, and length of hospital stay were significantly shorter in the study group than those in the control group(all P<0.05). Compared with the control group, the medical cost was lower(P<0.05). The overall postoperative complication rate was 7.9% in the study group and 24.1% in the control group(P<0.05). CONCLUSION: Fast-track surgery in the perioperative period for patients with esophageal cancer can promote bowel function recovery and decrease morbidity.

JAK/STAT signal pathway activation promotes progression and survival of human oesophageal squamous cell carcinoma.

OBJECTIVE: Inappropriate activation of JAK/STAT pathway occurs with high frequency in human cancers and is associated with cancer cell survival and proliferation. However, its role in oesophageal squamous cell carcinoma (ESCC) is unknown. METHODS: By immunohistochemistry, we analysed the expression of two components of this pathway, phosphorylated JAK-1 (pJAK-1) and phosphorylated STAT-3 (pSTAT-3), in 100 ESCC tumours and paired non-neoplastic oesophageal epithelia. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. RESULTS: We found that pJAK-1 and pSTAT-3 expression was not detectable in normal oesophageal squamous cells. Primary ESCC with pJAK-1-positive and pSTAT-3-positive expression was detected in the cancer cell nests of 78 and 72 cases, respectively. In addition, the Pearson's correlation coefficient between pJAK-1 and pSTAT-3 expression was 0.806 (p<0.001). Moreover, pJAK-1 and pSTAT-3 expression was correlated with N stage (lymph node metastasis, both p=0.01), pTNM stage (p=0.008 and 0.009, respectively) and metastatic status (both p=0.01). Furthermore, pJAK-1 and pSTAT-3 expression was associated with shorter overall survival (both p<0.001) and shorter disease-free survival (p=0.005 and 0.006, respectively). By multivariate analysis, TNM clinical classification (T, p<0.001; N, p=0.002; M, p=0.02), pJAK-1 (p=0.002) and pSTAT-3 (p=0.003) were independent prognosis predictors of ESCC. CONCLUSION: These results provide convincing evidence for the first time that the JAK/STAT pathway may participate in the progress of ESCC.