Long-term effect of hospital volume on the postoperative prognosis of 158,618 patients with esophageal squamous cell carcinoma in China.

Background: The impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I-III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China. Aim: To investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China. Methods: The date of 158,618 patients with ESCC were collected from a database (1973-2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality. Results: In both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both P<0.05). And high volume hospital was an independent factor for better prognosis in ESCC patients. The relationship between hospital volume and the risk of all-cause mortality was half-U-shaped, but overall, hospital volume was a protective factor for esophageal cancer patients after surgery (HR<1). The concentration of hospital volume associated with the lowest risk of all-cause mortality was 1027 cases/year in the overall enrolled patients. Conclusion: Hospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year. Core tip: Hospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery.

Down-Regulation of CIDEA Promoted Tumor Growth and Contributed to Cisplatin Resistance by Regulating the JNK-p21/Bad Signaling Pathways in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor prognosis and lack of effective targeted therapies. In this study, we investigated the tumor suppressive role of the cell death inducing DFF like effector A (CIDEA) in ESCC. Firstly, public datasets and ESCC tissue microarray analysis showed that CIDEA was frequently down-regulated at both the mRNA and protein level. This was significantly associated with low differentiation and TNM stage in ESCC, and indicated poor prognosis for ESCC patients. Bisulfite genomic sequencing (BGS) and methylation-specific PCR (MSP) analysis revealed that the down-regulation of CIDEA was associated with hypermethylation of its promoter, which was also correlated with the poor prognosis in ESCC patients. In vitro and in vivo functional studies demonstrated that CIDEA decreased cell growth, foci formation, DNA replication, and tumorigenesis in nude mice. Further study revealed that, during starvation or cisplatin induced DNA damage, CIDEA facilitated the G1-phase arrest or caspase-dependent mitochondrial apoptosis through the JNK-p21/Bad pathway. Therefore, CIDEA is a novel tumor suppressor gene that plays an important role in the development and progression of ESCC, and may provide a potential therapeutic target for patients with ESCC.

LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1.

BACKGROUND: This study aims to clarify the underlying mechanism for the tumor suppressive function of lnc TUSC7 in chemotherapy resistance of esophageal squamous cell carcinoma (ESCC). METHODS: TUSC7, miR-224 and DESC1 expressions in ESCC tissues and cells were detected by qRT-PCR. Protein level of DESC1, EGFR and p-AKT were observed by Western blot. Overall survival was calculated using the Kaplan-Meier method. Dual-luciferase reporter gene assay and RIP assay were used to comfirm TUSC7 binding to miR-224, and miR-224 binding to DESC1. Cell proliferation, apoptosis, and colony formation was detected by MTT, Flow Cytometry and Colony formation assays. RESULTS: TUSC7 was downregulated in ESCC tissues and cells, and low TUSC7 indicated worse overall survival. The analysis of bioinformatics softwares showed that TUSC7 specifically bound to miR-224, and we proved miR-224 was upregulated in ESCC and negatively correlated with TUSC7 expression. Overexpression of TUSC7/inhibition of miR-224 suppressed cell proliferation, colony formation and chemotherapy resistance of ESCC cells, and promoted cell apoptosis. In addition, we confirmed that miR-224 specifically bound to DESC1, and negatively correlated with DESC1. TUSC7 suppressed the proliferation and chemotherapy resistance of ESCC cells by increasing DESC1 expression via inhibiting miR-224. We also confirmed DESC1 inhibited chemotherapy resistance of ESCC cells via EGFR/AKT. Finally, in vivo experiments demonstrated that overexpression of TUSC7 decreased tumor growth and chemotherapy resistance. CONCLUSION: These findings suggested TUSC7 suppressed chemotherapy resistance of ESCC by downregulating miR-224 to modulate DESC1/EGFR/AKT pathway.

Correlations between gastric cancer family history and ROBO2 and RASSF2A gene methylations.

OBJECTIVE: To explore the correlation between ROBO2 and RASSF2A gene methylations and gastric cancer family history. MATERIALS AND METHODS: ROBO2 and RASSF2A gene methylations in gastric cancer tissues and peri.cancerous tissues were detected with methylation.specific PCR in 36. patients with gastric cancer family history and 33 without gastric cancer family history. The correlations of ROBO2 and RASSF2A gene methylations with family history, and clinical and pathological characteristics were analyzed. RESULTS: ROBO2 and RASSF2A gene methylations were all significantly higher in gastric cancer tissues (30% and 26%) than in peri-cancerous tissues (0% and 0%) (all P < 0.05). ROBO2 gene methylation was significantly lower in the patients with gastric cancer family history (17%, 6/36) than in the patients without gastric cancer family history (41%, 15/33) (P < 0.05). CONCLUSION: ROBO2 and RASSF2A gene methylations may be related to gastric tumorigenesis, and ROBO2 gene methylation is associated with sporadic gastric cancer.

PU.1 Is Identified as a Novel Metastasis Suppressor in Hepatocellular Carcinoma Regulating the miR-615-5p/IGF2 Axis.

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

Evaluating ECG-aided tip localization of peripherally inserted central catheter in patients with cancer.

OBJECTIVE: To evaluate ECG-aided tip localization of peripherally inserted central catheter (PICC) in the patients with cancer. METHODS: Between September and December 2014, 170 patients undergoing PICC were divided into observation group and control group (each group with 85 patients). In observation group, patients received ECG-aided tip localization of PICC. In control group, PICC was performed with conventional method. After PICC was performed, all patients took orthophoria chest radiograph (OCR) to check whether the tip position of PICC was appropriate. Finally, successful rate of the first PICC was compared between the two groups. RESULTS: In observation group, OCR showed that the tip of PICC was located in middle and low one-third of superior vena cava in 85 patients. In control group, OCR showed that the tip of PICC was located between superior vena cava and right atrium in 75 patients. The successful rate of the first PICC was significantly higher in observation group than in control group (P < 0.05). CONCLUSION: ECG-aided tip localization of PICC is accurate and safe, and is worth clinically recommending.

Comparison of short-term efficacy and safety of TIROX and DCF regimens for advanced gastric cancer.

OBJECTIVE: To compare the short-term efficacy and safety profile of the S-1 + irinotecan + oxaliplatin (TIROX) and docetaxel + cisplatin + flurouracil (DCF) anticancer regimens in patients with advanced gastric cancer. METHODS: Patients with recurrent or metastatic gastric cancer diagnosed by pathology were randomly divided into two groups to receive six cycles of either the TIROX regimen (21-day cycle) or the DCF regimen (21-day cycle). After six chemotherapy cycles, the short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines and adverse reactions were recorded according to National Cancer Institute Common Toxicity Criteria 2.0 standards. RESULTS: A total of 60 patients were enrolled in the study. The response rate (complete response + partial response) was significantly higher in the TIROX group (18/30 patients; 60.0%) compared with the DCF group (10/30 patients; 33.3%). The rates of grade III-IV leucopenia and neurotoxicity were significantly higher in the TIROX group than the DCF group. CONCLUSION: The TIROX regimen was effective for the treatment of advanced gastric cancer, but it was associated with leucopenia and neurotoxicity.

Meta-analysis of green tea drinking and the prevalence of gynecological tumors in women.

We performed a meta-analysis of the correlation between drinking green tea and the risk of female ovarian tumors. Related literature (2000-2010) was retrieved from PubMed, EMbase, CBMdisc, CNKI, and Wanfang databases. The relationship between the prevalence of ovarian cancer and drinking tea in cohort studies was explored. RevMan5.1.0 software was used for the meta-analysis. A total of 6 case control studies and cohort studies were included. A total of 9113 participants, 3842 cases, and 5271 control cases were included in our analysis. Our analysis indicates that drinking green tea can significantly decrease the risk of ovarian cancer (odds ratio = 0.81; 95% confidence interval = 0.73-0.89; P < .0001). Further research is needed to explore the relationship between drinking green tea and the risk of ovarian tumor in different groups of people and with different tea types and dosages.

Relationship between expression of EGFR in gastric cancer tissue and clinicopathological features.

OBJECTIVE: To investigate the relationship between the expression of epidermal growth factor receptor (EGFR) in gastric cancer and the clinicopathological features and prognosis. METHODS: A total of 78 paraffin specimens of gastric cancer operation were collected. The immunohistochemical method was used to detect the expression of EGFR in 78 cases of gastric cancer and 20 cases of adjacent normal tissue. The relationship between the high expression of EGFR and clinicopathological features was analyzed. RESULTS: EGFR positive expression rate in the 78 cases of gastric cancer tissue was 57.7 % (45/78), while EGFR was not expressed in 20 cases of adjacent normal tissue. The high EGFR expression was positively correlated with the position of gastric cancer, tumor size, cell differentiation, invasive depth, lymph node metastasis and TNM staging, yet having no obvious relation with gender or age. CONCLUSIONS: EGFR expression level in gastric cancer is closely related to the incidence and development of gastric cancer, which can provide a theoretical basis for the targeted therapy for gastric cancer with EGFR as the target.

[Characterization of the changes in comparative genomic hybridization in esophageal cancer patients with family history].

OBJECTIVE: To characterize the profile of chromosomal imbalances in esophageal cancer (EC) with or without family history in Linzhou, Henan Province of China. METHODS: Comparative genomic hybridization (CGH) was used to examine 13 cases with positive family history of EC and 32 cases with negative family history of EC. RESULTS DNA copy number gains on chromosome 10q was observed only in the cases with postivie family history of EC (30%), and none in cases with a negative family history (P<0.05). DNA copy number losses on chromosome 15q were significantly higher in cases with postivie family history (38% vs 6%, P<0.05). The frequency of DNA copy number gains in 3q, 5p, 7p, 8q and DNA copy number losses in 3p, 19q, 9q were similar in the two groups (both beyond 20%) (P>0.05). CONCLUSIONS: Frequent DNA copy number gains on chromosome 10q and losses on chromosome 15q in EC casers with postivie family history indicate that these chromosome sites may harbor the genes related to high susceptibility to EC. Such chromosomal sites as 3q, 5p, 7p, 8q, 3p, 19q, and 9q may contain important genes related with the environmental risk factors of esophageal carcinogenesis.