A modified method for precise anastomosis during laparoscopic low anterior resection for rectal cancer: the first clinical experience and application.

BACKGROUND: There is no criterion to guide and evaluate the anastomosis of laparoscopic low anterior resection (LAR). We developed a new technique for precise anastomosis. This study endeavored to evaluate the effectiveness and safety of this new technology. METHODS: Patients with mid-low rectal cancer who underwent laparoscopic LAR in our department were enrolled retrospectively between January 1, 2021 and July 1, 2023. During the LAR, the distance between the sacral promontory and the rectal stump was measured and used to determine the length of the sigmoid colon, which was preserved for anastomose. The demographic characteristics and short-term outcomes were analyzed. RESULTS: Forty-nine patients (26 men, 23 women) with low and middle rectal cancer were retrospectively enrolled in the study. The distance of the tumor from the anal verge was 6.4 ± 2.7 cm. The operative time was 193 ± 42 min. All patients underwent precise anastomosis, among which 12 patients underwent freeing of the splenic flexure of the colon. According to our criteria, there was no redundant or tense state of the colon anterior to the sacrum after the anastomosis. Only one patient had a postoperative anastomotic leak (Grade B). All 15 patients receiving neoadjuvant chemoradiotherapy underwent terminal ileostomy. No postoperative death occurred within 30 days of the surgery. The median follow-up time in our study was 12 months. One patient developed a single metastasis in the right lobe of the liver in the eighth month after surgery and underwent microwave radiofrequency ablation, which did not recur in the four months of postoperative follow-up, and the rest of the patients survived disease-free without recurrence of metastasis. CONCLUSIONS: Precise measurement of the proximal colon of the anastomosis can ensure accurate and convenient colorectal anastomosis and this may be a technique worthy of clinical application. However, its effectiveness needs to be further verified in a multicenter clinical trial.

Construction of prognostic predictor by comprehensive analyzing alternative splicing events for colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is one of the most common malignant tumors, with high incidence and mortality rates worldwide. Reliable prognostic biomarkers are needed to guide clinical practice. METHODS: Comprehensive gene expression with alternative splicing (AS) profiles for each patient was downloaded using the SpliceSeq database from The Cancer Genome Atlas. Cox regression analysis was conducted to screen for prognostic AS events. The R package limma was used to screen differentially expressed genes (DEGs) between normal and tumor samples in the COAD cohort. A Venn plot analysis was performed between DEGs and prognostic AS events, and the DEGs that co-occurred with prognostic AS events (DEGAS) were identified. The top 30 most-connected DEGAS in protein-protein interaction analysis were identified through Cox proportional hazards regression to establish prognostic models. RESULTS: In total, 350 patients were included in the study. A total of 22,451 AS events were detected, of which 2004 from 1439 genes were significantly associated with survival time. By overlapping these 1439 genes with 6455 DEGs, 211 DEGs with AS events were identified. After the construction of the protein-protein interaction network, the top 30 hub genes were included in a multivariate analysis. Finally, a risk score based on 12 genes associated with overall survival was established (P < 0.05). The area under the curve was 0.782. The risk score was an independent predictor (P < 0.001). CONCLUSIONS: By exploring survival-associated AS events, a powerful prognostic predictor consisting of 12 DEGAS was built. This study aims to propose a novel method to provide treatment targets for COAD and guide clinical practice in the future.

Post-transcriptional up-regulation of PDGF-C by HuR in advanced and stressed breast cancer.

Breast cancer is a heterogeneous disease characterized by multiple genetic alterations leading to the activation of growth factor signaling pathways that promote cell proliferation. Platelet-derived growth factor-C (PDGF-C) is overexpressed in various malignancies; however, the involvement of PDGF-C in breast cancers and the mechanisms underlying PDGF-C deregulation remain unclear. Here, we show that PDGF-C is overexpressed in clinical breast cancers and correlates with poor prognosis. PDGF-C up-regulation was mediated by the human embryonic lethal abnormal vision-like protein HuR, which stabilizes the PDGF-C transcript by binding to two predicted AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR). HuR is up-regulated in hydrogen peroxide-treated or ultraviolet-irradiated breast cancer cells. Clinically, HuR levels are correlated with PDGF-C expression and histological grade or pathological tumor-node-metastasis (pTNM) stage. Our findings reveal a novel mechanism underlying HuR-mediated breast cancer progression, and suggest that HuR and PDGF-C are potential molecular candidates for targeted therapy of breast cancers.

Effectiveness of anastomotic reinforcement sutures in reducing anastomotic leakage risk after laparoscopic rectal cancer surgery: a pooled and integration analysis.

Background and objectives: Anastomotic leakage (AL) is one of the most serious complications after laparoscopic anus-preserving surgery for rectal cancer, which significantly prolongs the patient's hospital stay, leads to dysfunction, and even increases the patient's perioperative morbidity and mortality, and little is known about the effectiveness of anastomotic reinforcement sutures to prevent AL. Thus, this study was conducted to evaluate the efficacy of anastomotic reinforcement sutures as a means to prevent AL during laparoscopic surgery for rectal cancer. Methods: A comprehensive and systematic search was performed in the literature database by combining subject and free terms up to 10 October 2023. The overall literature included was integrated and analyzed using Stata 12.0 software and Review Manager version 5.4 software to assess the effect of anastomotic reinforcement sutures on the incidence of AL. Results: A total of 2,452 patients from 14 studies were included, and an integrated analysis showed that the use of anastomotic reinforcement sutures significantly reduced the incidence of AL [odds ratio (OR) = 0.26; 95% confidence interval (CI), 0.18-0.37; P < 0.00001; I2 = 0%]. However, the findings confirmed whether or not the anastomosis reinforced with sutures did not affect the incidence of anastomotic stenosis (OR = 0.69; 95% CI, 0.37-1.32; P = 0.27; I2 = 0%). We performed subgroup analyses of the results of the study, the randomized controlled studies (OR = 0.31; 95% CI, 0.15-0.65; P < 0.001) as well as retrospective studies (OR = 0.28; 95% CI, 0.19-0.41; P < 0.001), 3-0 sutures (OR = 0.28; 95% CI, 0.17-0.45; P < 0.001) versus 4-0 sutures (OR = 0.26; 95% CI, 0.13-0.53; P < 0.001), barbed wire sutures (OR = 0.26; 95% CI, 0.14-0.48; P < 0.001) versus non-barbed wire sutures (OR = 0.30; 95% CI, 0.20-0.46; P < 0.001), interrupted (OR = 0.30, 95% CI, 0.20-0.46; P < 0.001) versus continuous sutures (OR = 0.29, 95% CI, 0.16-0.51; P < 0.001) to the anastomosis, full-thickness suture (OR = 0.29; 95% CI, 0.16-0.51; P < 0.001) versus sutured with the seromuscular layer (OR = 0.27; 95% CI, 0.14-0.53; P < 0.001), anastomotic sutured in one (OR = 0.27; 95% CI, 0.14-0.53; P < 0.001) versus non-one circle (OR = 0.30; 95% CI, 0.20-0.44; P < 0.001), and reinforcing sutures to the dog-ear area (OR = 0.26; 95% CI, 0.14-0.50; P < 0.001) versus the non-dog-ear area (OR = 0.30; 95% CI, 0.20-0.45; P < 0.001), which have suggested that there is no significant difference between each other and that all of them reduce the incidence of AL. Conclusions: This study provides evidence that performing reinforcement suturing of the anastomosis during laparoscopic rectal surgery significantly lowers the incidence of postoperative AL but has no significant effect on anastomotic stenosis. It is important to note that further randomized controlled studies are required to confirm this conclusion. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022368631.

HuR: a promising therapeutic target for angiogenesis.

Multiple angiogenic factors and inhibitors are becoming potential therapeutic targets for ischemia diseases and cancer. Posttranscriptional regulation through the untranslated region of mRNA is emerging as a critical regulating level in nearly all the biological processes. As a kind of RNA binding proteins, HuR plays important role in augmenting the hypoxic or inflammatory signal, stabilizing the resultant angiogenic factors and promoting the proliferation and migration of endothelial cells. These implicate HuR in the proangiogenic factors mediated angiogenesis in the hypoxia and inflammatory. We consider hypotheses that a more effective angiogenesis can be acquired through strengthened and prolonged effects of angiogenic factors, and that progresses in therapeutic angiogensis might also shed light on the implication of HuR in blocking tumor angiogensis. These considerations may help us to explain HuR as a promising therapeutic target for angiogenesis related disease. It may be a candidate in hypoxia therapy and cancer management.