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PurposeThe incidence of seroma and postoperative pain after Gilbert type III inguinal hernia repair is high. To reduce postoperative complications, this study investigated the clinical efficacy of laparoscopic closed hernia ring combined with a patch repair for Gilbert type III indirect inguinal hernia.MethodsThrough a prospective randomized controlled study, a total of 193 patients with Gilbert type III indirect inguinal hernia admitted to Nanchong Central Hospital affiliated with Chuanbei Medical College from May 2020 to December 2021 were selected and randomly divided into the inner ring closed group (85 patients) and the inner ring non-closed group (95 patients). The patients in both groups underwent laparoscopic tension-free repair of their inguinal hernias. General information such as operative time, postoperative hospital stay, and hospital cost were compared between the two groups, and the patients were followed up at 1, 7, 14, 21, and 28 days and then 3, 6, and 12 months after surgery to compare complications such as incidence of seroma, volume of the seroma fluid, incidence of pain, and visual analogue scale (VAS) pain score.ResultsThere was no conversion to open procedures in any of the patients. The operation time of the closed group was significantly longer than that of the non-closed group (64.2 ± 12.2 vs. 55.3 ± 9.5 min, P P = 0.029 on 7 days; 17 (20%) vs. 33 (35%), P = 0.028 on 14 days; and 6 (7%) vs. 22 (23%), P = 0.003 on 21 days in the postoperative closed group and was significantly lower than that in the non-closed group, while we found that the non-closed group had a higher VAS pain score than that of the closed group (2.36 ± 0.61 vs. 1.95 ± 0.71, P = 0.003 on 7 days and 2.12 ± 0.49 vs. 1.65 ± 0.49, P = 0.002 on 14 days) after surgery according to the statistical results of the VAS pain score. The incidence of postoperative seroma and the amount of seroma fluid decreased gradually in both groups, but when comparing the two groups, the proportion of cases of seroma in the closed group on 7 days [45 (53%) vs. 79 (83%), P P = 0.011]; and 21 days [10 (12%) vs. 29 (31%), P = 0.002] after the operation were significantly less than that in the non-closed group. For the comparison of the amount of seroma fluid between the groups, the seroma fluid volume in the non-closed group was greater than that in the closed group (34.48 ± 20.40 vs. 43.87 ± 16.40 ml, P = 0.006, 7 days) and (21.79 ± 8.42 vs. 30.74 ± 10.39 ml, P = 0.002, 14 days) after surgery. There were no differences in the length of stay, total hospital costs, or postoperative complications (urinary retention, intestinal obstruction, nausea, vomiting, bleeding, and infection) between the two groups, and the differences were not statistically significant (P > 0.05). The postoperative follow-up period was 3–20 months, and no chronic pain or recurrence occurred during the postoperative follow-up period in either group.ConclusionsClosure of the hernia ring is safe and effective for laparoscopic hernia repair for Gilbert type III inguinal hernia, and it significantly reduces the incidence of postoperative seroma and further reduces the postoperative pain without increasing the risk of postoperative infection and recurrence.

BackgroundInhibitors of programmed cell death 1 (PD-1)/programmed cell death ligand 1(PD-L1) checkpoint have been approved for metastatic triple negative breast cancer (mTNBC) in patients positive for PD-L1 expression. Negative results from the recent phase III trials (IMPassion131 and IMPassion132) have raises questions on the efficacy of PD-1/PD-L1 checkpoint inhibitors and the predictive value of PD-L1 expression. Here we attempt to systematically analyze the biomarker value of PD-L1 expression for predicting the response of PD-1/PD-L1 checkpoint inhibitors in mTNBC.Materials and methodsPubMed database was searched until Dec 2021 for studies evaluating PD-1/PD-L1 checkpoint inhibitors plus/minus chemotherapy in mTNBC. Outcome of interest included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Review Manager (RevMan) version 5.4. was used for data-analysis.ResultsIn total, 20 clinical trials comprising 3962 mTNBC patients (ICT: 2665 (67%); CT: 1297 (33%) were included in this study. Overall ORR was 22% (95%CI, 14-30%) and significant improvement was observed for PD-L1+ patients (ORR 1.78 [95%CI, 1.45-2.19], p2 = 0%; 2-year OS: (ORR 2.47 [95%CI, 1.30-4.69], p=0.006; I2 = 63%). Subgroup analysis indicated that PD-L1 expression can successfully predict tumor response and 2-year OS benefit in mTNBC patients regardless of the type of investigating agent, line of treatment administration, and to some extent the type of treatment. Biomarker ability of PD-L1 expression to predict 1-year PFS was slightly better with pembrolizumab (p=0.09) than atezolizumab (p=0.18), and significantly better when treatment was administered in the first-line setting (OR 1.38 [95%CI, 1.02-1.87], p=0.04) and chemotherapy was added (OR 1.38 [95%CI, 1.02-1.86], p=0.03). Immune-related toxicity of any grade and grade≥3 was 39% (95%CI, 26%-52%) and 10% (95%CI, 8%-13%), respectively.ConclusionsPD-L1 expression can predict objective response rate and 2-year OS in mTNBC patients receiving PD-1/PD-L1 checkpoint inhibitors. One-year PFS is also predicted in selected patients. PD-L1 expression can be a useful biomarker of efficacy of PD-1/PD-L1 checkpoint inhibitors in mTNBC.

BackgroundGastric cancer (GC) represents a major global clinical problem with very limited therapeutic options and poor prognosis. Necroptosis, a recently discovered inflammatory form of cell death, has been implicated in carcinogenesis and inducing necroptosis has also been considered as a therapeutic strategy.ObjectiveWe aim to evaluate the role of this pathway in gastric cancer development, prognosis and immune aspects of its tumor microenvironment.Methods and resultsIn this study, we evaluated the gene expression of 55 necroptosis-related genes (NRGs) that were identified via carrying out a comprehensive review of the medical literature. Necroptosis pathway was deregulated in gastric cancer samples (n=375) as compared to adjacent normal tissues (n=32) obtained from the “The Cancer Genome Atlas (TCGA)”. Based on the expression of these NRGs, two molecular subtypes were obtained through consensus clustering that also showed significant prognostic difference. Differentially expressed genes between these two clusters were retrieved and subjected to prognostic evaluation via univariate cox regression analysis and LASSO cox regression analysis. A 13-gene risk signature, termed as necroptosis-related genes prognostic index (NRGPI), was constructed that comprehensively differentiated the gastric cancer patients into high- and low-risk subgroups. The prognostic significance of NRGPI was validated in the GEO cohort (GSE84437: n=408). The NRGPI-high subgroup was characterized by upregulation of 10 genes (CYTL1, PLCL1, CGB5, CNTN1, GRP, APOD, CST6, GPX3, FCN1, SERPINE1) and downregulation of 3 genes (EFNA3, E2F2, SOX14). Further dissection of these two risk groups by differential gene expression analysis indicated involvement of signaling pathways associated with cancer cell progression and immune suppression such as WNT and TGF-β signaling pathway. Para-inflammation and type-II interferon pathways were activated in NRGPI-high patients with an increased infiltration of Tregs and M2 macrophage indicating an exhausted immune phenotype of the tumor microenvironment. These molecular characteristics were mainly driven by the eight NRGPI oncogenes (CYTL1, PLCL1, CNTN1, GRP, APOD, GPX3, FCN1, SERPINE1) as validated in the gastric cancer cell lines and clinical samples. NRGPI-high patients showed sensitivity to a number of targeted agents, in particular, the tyrosine kinase inhibitors.ConclusionsNecroptosis appears to play a critical role in the development of gastric cancer, prognosis and shaping of its tumor immune microenvironment. NRGPI can be used as a promising prognostic biomarker to identify gastric cancer patients with a cold tumor immune microenvironment and poor prognosis who may response to selected molecular targeted therapy.

Supplemental Digital Content is available in the text, Background: Recently, immune checkpoint inhibitors have shown survival advantage over chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). This meta-analysis was conducted to gather and analyze the available evidence (Evidence level I; Randomized Controlled Trials) comparing efficacy and safety of anti-programmed cell death-1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies and chemotherapy in the treatment of advanced NSCLC. Methods: A search strategy was devised to identify the randomized controlled trials (RCTs) using electronic databases of PubMed, Cochrane Library, and Web of Science. Hazard ratios or odds ratios obtained for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment related adverse events (TRAEs) were analyzed using fixed effect model or random effects model. Additionally, subgroup analysis was also performed. Results: A total of seven RCTs (n = 3867) were identified and selected for inclusion in this meta-analysis. Anti-PD1/PD-L1 therapies (nivolumab, pembrolizumab, atezolizumab) resulted in better OS (HR 0.72 [95% confidence interval [CI] 0.63, 0.82; P