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Introduction The survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) has been well defined at the time of interval cytoreductive surgery, but the role of HIPEC remains uncertain for patients with newly diagnosed advanced ovarian cancer in the upfront setting. The present study aimed to report the updated long‐term survival outcomes after 5 years of follow‐up from our previous multicenter retrospective cohort study to compare primary cytoreductive surgery (PCS) plus HIPEC with PCS alone among women with stage III epithelial ovarian cancer. Material and Methods This study was conducted at five high‐volume gynecological medical centers in China from January 2010 to May 2017. Eligible patients with complete data were treated with either PCS combined with HIPEC or PCS alone. The 5‐year overall survival (OS) rate was updated to compare PCS plus HIPEC with PCS alone. The inverse probability of treatment weighting (IPTW) method based on a propensity score model for each patient was used to control the confounding factors and evaluate the effect of HIPEC. Results Data from 789 patients, a total of 584 eligible stage III epithelial ovarian cancer patients were ultimately included in the analysis (PCS‐plus‐HIPEC group, n = 425; PCS‐alone group, n = 159). After IPTW adjustment, the median OS was 44.5 (95% CI, 40.1–49.1) months in the PCS‐plus‐HIPEC group and 32.4 (95% CI, 28.8–40.3) months in the PCS‐alone group (weighted hazard ratio, 0.74; 95% CI, 0.59–0.93; p = 0.006). At 5 years, the OS rates were 37.9% (95% CI, 33.0%–42.8%) in the PCS‐plus‐HIPEC group and 26.4% (95% CI, 18.9%–34.6%) in the PCS‐alone group (p = 0.007). After stratification into optimal and suboptimal cytoreduction subgroups, patients in the PCS‐plus‐HIPEC group maintained a greater association with improved OS than those in the PCS‐alone group. Among the women who underwent optimal cytoreduction in the PCS‐plus‐HIPEC group and PCS‐alone group, the median OS was 49.9 (95% CI, 45.2–58.4) months and 37.8 (95% CI, 30.5–53.0) months (p = 0.042) while the 5‐year OS rate was 43.7% (95% CI, 37.7%–49.6%) and 33.2% (95% CI, 23.3%–43.5%), respectively (p = 0.040). Meanwhile, for those treated with suboptimal cytoreduction subgroup in the PCS‐plus‐HIPEC and PCS‐alone groups, the median OS was 28.4 (95% CI, 22.2–39.9) months and 20.6 (95% CI, 10.6–32.4) months (p = 0.099) while the 5‐year OS rate was 22.4% (95% CI, 15.1%–30.5%) and 12.2% (95% CI, 4.4%–24.2%), respectively (p = 0.060). The median follow‐up period was 87.2 (95% CI, 85.1–92.7) months. Conclusions The updated results indicate that the addition of HIPEC is associated with improved long‐term survival outcomes beyond 5 years for patients with stage III epithelial ovarian cancer in the upfront setting. This study provides further evidence supporting the long‐term efficacy of HIPEC for the primary treatment of advanced ovarian cancer. The PCS‐HIPEC approach achieved superior survival outcomes when optimal cytoreduction was possible.

Background Major depressive disorder (MDD) and anxiety were recognized in treating pancreatic ductal adenocarcinoma (PDAC). This longitudinal study identified risk factors for MDD and anxiety and established associations with patients' quality of life (QoL) and survival outcomes. Materials and Methods We used PHQ‐9 and GAD‐7 questionnaires to diagnose MDD and anxiety in PDAC patients between October 2021 and March 2022 at a Chinese center. Characteristics and clinical data were analyzed for risk factors and EORTC QLQ‐C30 questionnaire was administered for QoL before the first chemotherapy. Furthermore, chemotherapy compliance and 1‐year survival were compared during follow‐up. Results MDD and anxiety occurred in 51.8% and 44.7% of 114 patients over the half‐year period. Employment at work (odds ratio [OR]: 5.514, p = 0.001; OR: 3.420, p = 0.011) was an independent risk factor, while radical surgery (OR: 0.342, p = 0.034; OR: 0.238, p = 0.004) was a protective factor. Several aspects of decreased QoL were discovered after their onsets. Higher incidences of physical disorders (p = 0.004; p < 0.001), mental disorders (p = 0.001; p < 0.001), anti‐therapy emotions (p = 0.002; 0.001), and chemotherapy suspensions (p = 0.001; p = 0.043) were observed. Furthermore, the 1‐year mortalities for all patients and those receiving radical surgeries were correlated with MDD (p = 0.007; 0.036) and anxiety (p = 0.010; 0.031). Conclusions MDD and anxiety are common in PDAC patients and correlated with poor QoL and survivals. Therefore, appropriate mental management is required in future.

The pan-immune-inflammation-value (PIV) is a comprehensive biomarker that integrates different peripheral blood cell subsets. The present study aimed to evaluate the prognostic ability of PIV in patients with nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy. PIV was assessed using the following equation: (Neutrophil count × platelet count × monocyte count)/lymphocyte count. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses. The optimal cut-off values for PIV and systemic immune-inflammation index (SII) were determined using receiver operating characteristic analysis to be 428.0 and 1032.7, respectively. A total of 319 patients were recruited. Patients with a low baseline PIV (≤428.0) accounted for 69.9% (n=223) and patients with a high baseline PIV (>428.0) accounted for 30.1% (n=96). Compared with patients with low PIV, patients with a high PIV had significantly worse 5-year progression-free survival [PFS; 66.8 vs. 77.1%; hazard ratio (HR), 1.97; 95% confidence interval (CI), 1.22-3.23); P=0.005] and 5-year overall survival (OS; 68.7 vs. 86.9%, HR, 2.71; 95% CI, 1.45-5.03; P=0.001). PIV was also a significant independent prognostic indicator for OS (HR, 2.19; 95% CI, 1.16-4.12; P=0.016) and PFS (HR, 1.86; 95% CI, 1.14-3.04; P=0.013) and outperformed the SII in multivariate analysis. In conclusion, the PIV was a powerful predictor of survival outcomes and outperformed the SII in patients with NPC treated with chemoradiotherapy. Prospective validation of the PIV should be performed to better stratify radical treatment of patients with NPC.

Background The features and survival of stage IV breast cancer patients with different metastatic sites are poorly understood. This study aims to examine the clinicopathological features and survival of stage IV breast cancer patients according to different metastatic sites. Methods Using the Surveillance, Epidemiology, and End Results database, we restricted our study population to stage IV breast cancer patients diagnosed between 2010 to 2015. The clinicopathological features were examined by chi-square tests. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients with different metastatic sites by the Kaplan-Meier method with log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors. Results A total of 18,322 patients were identified for survival analysis. Bone-only metastasis accounted for 39.80% of patients, followed by multiple metastasis (33.07%), lung metastasis (10.94%), liver metastasis (7.34%), other metastasis (7.34%), and brain metastasis (1.51%). The Kaplan-Meier plots showed that patients with bone metastasis had the best survival, while patients with brain metastasis had the worst survival in both BCSS and OS ( p  < 0.001, for both). Multivariable analyses showed that age, race, marital status, grade, tumor subtype, tumor size, surgery of primary cancer, and a history of radiotherapy or chemotherapy were independent prognostic factors. Conclusion Stage IV breast cancer patients have different clinicopathological characteristics and survival outcomes according to different metastatic sites. Patients with bone metastasis have the best prognosis, and brain metastasis is the most aggressive subgroup.

Background： Sinonasal inverted papilloma （IP） is a rare benign tumor of the nasal cavities and paranasal sinuses. It is destructive or bone-rcmodeling, tends to recur alter surgical resection, and has a significant malignant potential. The present study aimed to pertbnn a retrospective analysis of patients with squamous cell carcinoma （SCC） arising from IP, including characteristics, survival outcome, and predictors of associated malignancy. Methods： The medical records of 213 patients diagnosed with IP from January 1970 to January 2014 were retrospectively reviewed. Eighty-seven patients were diagnosed with SCC/IP; their clinical characteristics, treatments, and survival outcomes were analyzed. Results： Of the 87 patients with SCC/IP, the 5- and 10-year overall survival outcomes were 39.6% and 31.8%, respectively. Twenty-nine of these patients received surgery and 58 received combined surgery and radiation. Of the patients with stages III-IV, the 5-year survival rate was 30.7% for those treated with surgery only and 39.9% for those given the combination treatment （P = 0.849）. Factors associated with significantly poor prognosis were advanced-stage, metachronous tumors, or with cranial base and orbit invasion. Age, synchronous or metachronous tumors, and pathological stage were independent risk factors for mortality, shown by multivariate analysis. Conclusion： Patients with SCC/IP had low overall survival outcomes. Advanced age, stage, and metachronous tumors are the main factors affecting prognosis. Treatment planning should consider high-risk factors to improve survival outcome.

Background： The effectiveness of neoadjuvant chemoradiotherapy （NCRT） treatment for patients with esophageal carcinoma （EC） remains controversial. The aim of this study was to compare the effect of NCRT followed by surgery （NCRTS） with surgery alone （SA） for EC. Methods： The PubMed, EMBASE, and the Cochrane Library databases were electronically searched up to August 2015 for all the published studies that investigated EC patients receiving either NCRTS or SA, and the reference lists were also manually examined for the eligible studies. The risk ratio （RR） with 95% confidence intervals （CI s） as effective size was determined to assess the 1-, 3-, 5-year survival rates （SRs）, postoperative morbidity, and postoperative mortality. Heterogeneity was determined using the Q-test. The Begg＇s test and Egger＇s test were used for assessing any potential publication bias. Results： Of 1120 identified studies, 16 eligible studies were included in this analysis （involving 2549 patients）. Overall, the pooled results suggested that NCRTS was associated with significantly improved 1-year （RR： 1.07, 95% CI： 1.02–1.13）, 3-year （RR： 1.26, 95% CI： 1.14–1.39）, and 5-year （RR： 1.36, 95% CI： 1.18–1.56） SRs. However, the results also indicated that NCRTS had no or little effect on postoperative morbidity （RR： 0.93, 95% CI： 0.82–1.05） and postoperative mortality （RR： 1.17, 95% CI： 0.56–2.44）. Conclusions： Compared with SA, NCRTS can increase 1-, 3-, and 5-year SRs in patients with EC.

KLK6 is expressed in normal mammary tissues and is aberrantly regulated in breast cancer. At physiological levels of expression, i.e. those found in normal mammary tissues, KLK6 acts as a tumor suppressor in human breast cancer. However, aberrant overexpression of KLK6 (i.e. 50–100-fold higher than normal), a characteristic of a subset of human breast cancers is associated with increased tumorigenicity (Pampalakis et al. Cancer Res 69:3779–3787, 2009). Here, we stably transfected KLK6-non-expressing MDA-MB-231 breast cancer cells with the full-length KLK6 cDNA to overexpress KLK6 at levels comparable to those observed in patients, and investigated potential oncogenic miRNA networks regulated by these abnormally high KLK6 expression levels and increased activity of this serine protease. A number of miRNAs that are upregulated (e.g. miR-146a) or downregulated (e.g. miR-34a) via KLK6-induced alterations in the miRNA biogenesis machinery were identified. Integrated experimental and bioinformatics analyses identified convergent miRNA networks targeting the cell cycle, MYC, MAPK, and other signaling pathways. In large clinical datasets, significant correlations between KLK6 and downstream MAPK and MYC targets at both the RNA and protein levels was confirmed, as well as negative correlation with GATA3. It was also demonstrated that KLK6 overexpression and likely its proteolytic activity is associated with alterations in downstream miRNAs and their targets, and these differ with the molecular subtypes of breast cancer. The data partly explains the different characteristics of breast cancer subtypes. Importantly, we introduce a combined KLK6-CDKN1B+MYC+CDKN1C score for prediction of long-term patient survival outcomes, with higher scores indicating poor survival. •Tumor associated aberrant overexpression of KLK6 alters certain miRNA-regulated networks.•High overexpression of KLK6 suppresses miR-34a, while it induces MAPK and MYC cell signaling pathways by regulating multiple miRNAs.•A KLK6-based combined score is introduced that can predict long-term patient survival outcome.

Background： There has been no external validation of survival prediction models for severe adult respiratory distress syndrome （ARDS） with extracorporeal membrane oxygenation （ECMO） therapy in China. The aim of study was to compare the performance of multiple models recently developed for patients with ARDS undergoing ECMO based on Chinese single-center data. Methods： A retrospective case study was performed, including twenty-three severe ARDS patients who received ECMO from January 2009 to July 2015. The PRESERVE （Predicting death for severe ARDS on VV-ECMO）, ECMOnet, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction （RESP） score, a center-specific model developed lbr inter-hospital transfers receiving ECMO, and the classical risk-prediction scores of Acute Physiology and Chronic Health Evaluation （APACHE） II and Sequential Organ Failure Assessment （SOFA） were calculated. In-hospital and six-month mortality were regarded as the endpoints and model performance was evaluated by comparing the area under the receiver operating characteristic curve （AUC）. Results： The RESP and APACHE II scores showed excellent discriminate performance in predicting survival with AUC of 0.835 （95% confidence interval [CI], 0.659-1 .010, P = 0.007） and 0.762 （95% CI, 0.558-0.965, P = 0.035）, respectively. The optimal cutoff values were risk class 3.5 for RESP and 35.5 for APACHE II score, and both showed 70.0% sensitivity and 84.6% specificity. The excellent performance of these models was also evident for the pneumonia etiological subgroup, for which the SOFA score was also shown to be predictive, with an AUC of 0.790 （95% CI, 0.571-1.009, P = 0.038）. However, the ECMOnet and the score developed for externally retrieved ECMO patients failed to demonstrate significant discriminate power for the overall cohort. The PRESERVE model was unable to be evaluated fully since Conclusions： The RESP, APCHAE 11, and SOFA scorings only one patient died six months postdischarge. systems show good predictive value for intra-hospital survival of ARDS patients treated with ECMO in our single-center evaluation. Future validation should include a larger study with either more patients＇ data at single-center or by integration of domestic multi-center data. Development of a scoring system with national characteristics might be warranted.

Background Survival and drug response are two highly emphasized clinical outcomes in cancer research that directs the prognosis of a cancer patient. Here, we have proposed a late multi omics integrative framework that robustly quantifies survival and drug response for breast cancer patients with a focus on the relative predictive ability of available omics datatypes. Neighborhood component analysis (NCA), a supervised feature selection algorithm selected relevant features from multi-omics datasets retrieved from The Cancer Genome Atlas (TCGA) and Genomics of Drug Sensitivity in Cancer (GDSC) databases. A Neural network framework, fed with NCA selected features, was used to develop survival and drug response prediction models for breast cancer patients. The drug response framework used regression and unsupervised clustering (K-means) to segregate samples into responders and non-responders based on their predicted IC50 values (Z-score). Results The survival prediction framework was highly effective in categorizing patients into risk subtypes with an accuracy of 94%. Compared to single-omics and early integration approaches, our drug response prediction models performed significantly better and were able to predict IC50 values (Z-score) with a mean square error (MSE) of 1.154 and an overall regression value of 0.92, showing a linear relationship between predicted and actual IC50 values. Conclusion The proposed omics integration strategy provides an effective way of extracting critical information from diverse omics data types enabling estimation of prognostic indicators. Such integrative models with high predictive power would have a significant impact and utility in precision oncology.