Predicting surgical efficacy and diagnosing histological inflammation: the clinical significance of prostate exosome proteins in benign prostatic hyperplasia.

Background: Benign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms (LUTS) among the aging male population. Recent studies have shown that histological inflammation (HI) plays a significant role in BPH, with prostatic exosomal protein (PSEP) identified as a potential biomarker for prostate diseases. Therefore, this study aimed to explore the effect of HI on LUTS in patients with BPH, and to further explore the clinical value of PSEP as a diagnostic biomarker of BPH complicated with HI and whether PSEP could be used as an index to predict the improvement of LUTS after operation. Methods: This study was an open-label, cohort study. The study enrolled all patients who were clinical diagnosed as BPH with LUTS and prepared to receive operation of the prostate at the Department of Urology of the Second Hospital of Hebei Medical University. International Prostate Symptom Score (IPSS) were used to evaluate the LUTS of the BPH. And the enrolled patients were divided into four groups, including none, mild HI, moderate HI, and severe HI, based on postoperative pathological results. Then the relationships between HI and IPSS, the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), as well as PSEP were analyzed. Simple and multiple linear regression analyses were performed on the preoperative IPSS and the difference of IPSS before and after surgery was examined. SPSS software version 26 was used for statistical analysis and Prism 9.0 was used to make violin plots. Results: A total of 69 patients were enrolled in the study. The violin plot results indicated IPSS and NIH-CPSI scores exhibited significant increases in correlation with the severity levels of HI (P<0.001; P<0.001). Among BPH patients with total prostate-specific antigen (t-PSA) levels higher than 4.0 ng/mL, a significant correlation was observed between PSEP levels and HI (P=0.04). Besides, simple and multiple linear regression analysis showed that HI (P<0.001) or PSEP (P=0.03) was significantly associated with IPSS and improvement of LUTS, assessed by postoperative and preoperative IPSS differences. Conclusions: The study indicated that IPSS and PSEP (when t-PSA >4 ng/mL) were correlated with the severity of HI in patients with BPH. PSEP was linearly correlated with IPSS and the degree of reduction in IPSS after surgery. Consequently, PSEP may serve as a promising predictor for assessing surgical efficacy and diagnosing the severity of HI in patients with BPH.

Downregulated RBM5 Enhances CARM1 Expression and Activates the PRKACA/GSK3ß Signaling Pathway through Alternative Splicing-Coupled Nonsense-Mediated Decay.

Downregulated RNA-binding motif protein 5 (RBM5) promotes the development and progression of various tumors, including bladder cancer (BC). Alternative splicing (AS) plays a crucial role in the progression of cancer by producing protein isomers with different functions or by promoting nonsense-mediated mRNA decay (NMD). However, whether RBM5 modulates the progression of BC through AS-NMD remains unexplored. In this study, we revealed that the downregulation of RBM5 expression promoted the expression of coactivator-associated arginine methyltransferase 1 (CARM1) in BC cells and tissues. Increased expression of CARM1 facilitated the activation of the Wnt/ß-catenin axis and cell proliferation, which then contributed to the poor prognosis of patients with BC. Interestingly, RBM5 bound directly to CARM1 mRNA and participated in AS-NMD, downregulating the expression of CARM1. In addition, we revealed that protein kinase catalytic subunit alpha (PRKACA) functioned as a phosphorylated kinase of GSK3ß, was regulated by CARM1 at the transcription level, and promoted the growth and progression of BC cells. Furthermore, in this study, we demonstrated a regulatory mechanism of Wnt/ß-catenin activation through the RBM5/CARM1/PRKACA axis and identified a novel potential target for treating BC.

A Practical Nomogram for Predicting the Prognosis of Elderly Patients with Gastric Adenocarcinoma After Gastrectomy.

PURPOSE: To establish a pragmatic prognostic nomogram for predicting the survival of elderly patients undergoing gastrectomy for gastric adenocarcinoma. PATIENTS AND METHODS: Data of elderly patients undergoing gastrectomy for gastric adenocarcinoma between 2004 and 2015 were obtained from the Surveillance, Epidemiology, and End Results database. Prognostic factors were identified by the Kaplan-Meier method and the Cox proportional hazards model. Based on these factors, we developed a nomogram to predict the overall survival (OS) and gastric cancer-specific survival (GCSS). Concordance index (C-index) and calibration curve are employed to assess the predictive accuracy of the model. Decision curve analysis (DCA) and receiver operating characteristic curve (ROC) analysis are applied to further appraise the clinical utility of the model. RESULTS: A total of 8401 cases were incorporated into this research. After univariate and multivariate analyses, nine prognostic factors of OS were identified, including age (P < 0.001), race (P < 0.001), marital status (P < 0.001), tumor site (P < 0.001), tumor size (P = 0.024), differentiation (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), and M stage (P < 0.001); ten prognostic factors of GCSS were identified, including age (P < 0.001), race (P < 0.001), tumor site (P < 0.001), tumor size (P = 0.002), differentiation (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), M stage (P < 0.001), radiotherapy (P < 0.001) and chemotherapy (P < 0.001). The C-index of the constructed nomogram for OS was 0.708 (95% CI: 0.701-0.715) while for GCSS was 0.745 (95% CI: 0.737-0.753). The calibration curves of the nomogram predictions and actual observations displayed good agreement for the 3- and 5-year OS and GCSS probabilities. The results of DCA and the area under the curve calculated by ROC analysis showed that the developed model was superior than TNM stage. CONCLUSION: The nomogram we established could accurately predict the prognosis of individual elderly patients who underwent gastrectomy for gastric adenocarcinoma.

Double Tract Reconstruction Reduces Reflux Esophagitis and Improves Quality of Life after Radical Proximal Gastrectomy for Patients with Upper Gastric or Esophagogastric Adenocarcinoma.

PURPOSE: The aim of the present study was to compare the difference between double tract reconstruction and esophagogastrostomy. MATERIALS AND METHODS: Patients who underwent radical proximal gastrectomy with esophagogastrostomy or double tract reconstruction were included in this study. RESULTS: Sixty-four patients were included in this study and divided into two groups according to reconstruction method. The two groups were well balanced in perioperative safety and 3-year overall survival (OS). The rates of postoperative reflux esophagitis in the double tract reconstruction group and esophagogastrostomy group were 8.0% and 30.8%, respectively (p=0.032). Patients in the double tract reconstruction group had a better global health status (p < 0.001) and emotional functioning (p < 0.001), and complained less about nausea and vomiting (p < 0.001), pain (p=0.039), insomnia (p=0.003), and appetite loss (p < 0.001) based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. Regarding the EORTC QLQ-STO22 questionnaire, patients in the double tract reconstruction group complained less about dysphagia (p=0.030), pain (p=0.008), reflux (p < 0.001), eating (p < 0.001), anxiety (p < 0.001), dry mouth (p=0.007), and taste (p=0.001). The multiple linear regression analysis showed that reconstruction method, postoperative complications, reflux esophagitis, and operation duration had a linear relationship with the global health status score. CONCLUSION: Double tract reconstruction could better prevent reflux esophagitis and improve quality of life without scarifying perioperative safety or 3-year OS.

Effect of Additional Trastuzumab in Neoadjuvant and Adjuvant Treatment for Patients with Resectable HER2-Positive Gastric Cancer.

BACKGROUND: Recent studies have reported a beneficial role of trastuzumab in neoadjuvant treatment (NAT) among resectable gastric cancer (GC) patients; however, the effect of adjuvant treatment (AT) combined with trastuzumab is understudied. We performed a retrospective cohort study to compare chemotherapies with or without trastuzumab among human epidermal growth factor receptor 2-positive (HER2 +) locally advanced GC patients in the AT and NAT settings, respectively. METHODS: We enrolled 208 HER2 + resected GC patients who underwent perioperative/postoperative treatment in 2010-2019 in a single-centered hospital, including 135 AT patients and 73 NAT patients. We used inverse probability of treatment weighting (IPTW) to balance potential confounding factors between the treatment groups, and estimated the treatment effect of trastuzumab. Pathological and survival outcomes were evaluated. RESULTS: The number of trastuzumab-exposed patients in the AT and NAT cohorts was 31 (23.0%) and 34 (46.6%), respectively. After IPTW adjustment, AT combined with trastuzumab showed a better overall survival (OS) over chemotherapy alone (p = 0.023). In IPTW-adjusted NAT analysis, trastuzumab-exposed patients had an improvement in tumor pathological regression and downstaging, with lower tumor regression grade scores (p = 0.002), ypTNM stages (p < 0.001), ypN stages (p = 0.035), and ypT stages (p < 0.001). Loss of HER2 positivity following trastuzumab treatment was observed in NAT patients; however, we did not observe any significant effect of trastuzumab on OS (p = 0.126). CONCLUSIONS: Given the improvement in tumor regression and downstaging among NAT patients, and the OS benefit in AT patients, trastuzumab could be considered a promising treatment for locally advanced HER2 + GC patients. In particular, re-evaluation of HER2 status should be considered following NAT combined with trastuzumab.

[Clinicopathological characteristics and prognostic factor analysis of carcinoma in remnant stomach cancer at Peking University Cancer Hospital].

OBJECTIVE: To investigate the interval time to canceration, clinicopathological characteristics and prognostic factors of carcinoma in remnant stomach (CRS) in patients with primary benign diseases or primary malignant tumors. METHODS: Based on the criteria of the definition of CRS proposed by Japanese Gastric Cancer Association in 2017, a retrospective analysis was conducted on clinicopathological characteristics of patients diagnosed with CRS at Peking University Cancer Hospital from March 1992 to March 2017. Between patients with primary benign diseases (CBS-B group) and primary malignant tumors (CBS-M group), continuous variables were compared using the Student's t-test or the Mann-Whitney U test; categorical variables were compared using the chi-square test or Fisher's exact test. Spearmen-Rho was used to examine correlation. Survival was estimated and compared using Kaplan-Meier methods. Cox proportional hazards regression was applied to identify independent prognostic factors. Area under ROC curve(AUC) was used to evaluate and compare prediction accuracy. RESULTS: A total of 89 patients were included in the study with a male: female ratio of 5.4 to 1.0. The male: female ratio in CRS-B (n=46) and CRS-M (n=43) group was 14.3 to 1.0 and 2.9 to 1.0 respectively with significant difference (χ2=6.091, P=0.019). The interval time to canceration in CRS-B and CRS-M group was 342(36-576) months and 47(12-360) months respectively with significant difference (t=8.887, P=0.000). The interval time to canceration was correlated with the first operative procedure in CRS-B group (r=0.398, P=0.006), while interval time to canceration was correlated with the age at the first operation in CRS-M group (r=0.337, P=0.027). After differentiating the pathological findings of the first operative sample and the second operative sample, 27 patients presented recurrence and 15 patients had new cancer, and the corresponding interval time to canceration was 46(12-132) months and 60(12-360) months respectively with significant difference (t=5.652, P=0.023). In CRS-B group, location of stump carcinoma in gastric intestinal anastomosis, gastric anastomosis, and non-anastomosis area was found in 60.9%(28/46), 23.9%(11/46) and 15.2%(7/46) respectively, and the corresponding percentage in CRS-M group was 39.5%(17/43), 16.3%(7/43) and 44.2%(19/43) respectively without significant difference (χ2=4.726, P=0.096). Among 77 patients with radical gastrectomy, the overall surgical complication rate was 20.8%(16/77), including 8 cases of infection and 7 cases of respiratory system diseases. The 3-year survival rate was 78.4% and 62.6% in CRS-B and CRS-M group respectively with significant difference (χ2=3.969, P=0.046), indicating better prognosis of CRS-B patients. The AUC for the lymph nodes ratio and N staging was 0.725 and 0.639 respectively. Multivariate analysis showed the pathological T staging was an independent risk factor of prognosis (HR=1.192, 95%CI:1.032-1.376, P=0.017). CONCLUSIONS: Men have more CRS than women. The interval time to canceration is correlated to the first operative procedure for CRS-B patients, while it is correlated to the age at the first operation for CRS-M patients. The major location of CRS is in the gastrointestinal anastomosis for CRS-B patients and in non-anastomosis area for CRS-M patients. Main postoperative complications include respiratory and infectious complications. Pathological T staging is an independent prognostic risk factor for CRS patients.