ERAS did not increase 30-day complications compared with CRAS after RC. ERAS may be better than CRAS in terms of bowel movement, tolerance of fluid and regular diet, and ambulation.
ObjectivesTo evaluate the overall efficacy and safety of endoscopic enucleation of the prostate (EP) vs open prostatectomy (OP) for large benign prostatic hyperplasia (BPH).MethodsWe conducted an electronic search of PubMed/Medline, EMBASE, The Cochrane Library, and Web of Science to detect all relevant randomized controlled trials (RCTs) comparing EP with OP. A meta-analysis was performed using Review Manager 5.3.ResultsSeven RCTs (735 patients) were included. At the 3-, 6- and 12-month follow-up, there were no significant differences in the International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), quality of life (QoL) score and post-void residual urine volume (PVR) between EP and OP. The International Index of Erectile Function (IIEF-5) was higher with EP (weighted mean difference [WMD]: 1.00, 95% confidence interval [CI]: 0.21 to 1.78, p=0.01) at the 12-month follow-up. The catheterization time (WMD: 3.80 d, 95%CI: -5.11 to -2.48, P<0.00001) and hospital stay (WMD: 4.93 d, 95%CI: -5.96 to -3.89, P<0.00001) were shorter with EP. The duration of operation was longer for EP compared with OP (WMD: 16.21 min, 95%CI: 3.72 to 28.70, P=0.01). The resected tissue weight (WMD: -9.63 g, 95%CI: -14.46 to -4.81, P<0.0001) and decrease in hemoglobin (WMD: -1.14 g/dL, 95%CI: -1.81 to -0.47, P=0.0008) were less with EP. EP was associated with fewer blood transfusions (risk ratio: 0.22, 95%CI: 0.10 to 0.47, P=0.0001). There were no significant differences between EP and OP when comparing other complications.ConclusionsAlthough only a limited number of RCTs with relatively limited follow-up are available, EP is shown to have a similar postoperative profile and comparable safety to OP. By contrast, EP may have a more desirable perioperative profile. EP appears to be an effective and safe minimally invasive option for treating large prostates that requires only brief convalescence.
Oncolytic virotherapy is a novel and emerging treatment modality that uses replication-competent viruses to destroy cancer cells. Although diverse cancer cell types are sensitive to oncolytic viruses, one of the major challenges of oncolytic virotherapy is that the sensitivity to oncolysis ranges among different cancer cell types. Furthermore, the underlying mechanism of action is not fully understood. Here, we report that activation of cyclic adenosine monophosphate (cAMP) signaling significantly sensitizes refractory cancer cells to alphavirus M1 in vitro, in vivo, and ex vivo. We find that activation of the cAMP signaling pathway inhibits M1-induced expression of antiviral factors in refractory cancer cells, leading to prolonged and severe endoplasmic reticulum (ER) stress, and cell apoptosis. We also demonstrate that M1-mediated oncolysis, which is enhanced by cAMP signaling, involves the factor, exchange protein directly activated by cAMP 1 (Epac1), but not the classical cAMP-dependent protein kinase A (PKA). Taken together, cAMP/Epac1 signaling pathway activation inhibits antiviral factors and improves responsiveness of refractory cancer cells to M1-mediated virotherapy.
PURPOSE:To compare the curative effects of ureteroscopic lithotripsy and laparoscopic ureterolithotomy for unilateral upper ureteral stones, and to explore optimal surgical indications and skills. METHODS: Fifty cases of unilateral upper ureteral stones were randomly divided into two groups: one group underwent ureteroscopic holmium laser lithotripsy under epidural or lumbar anesthesia (n=25), and another group underwent laparoscopic ureterolithotomy under general anesthesia (n=25). Double-J stent was routinely indwelled in both groups. Operating time, postoperative hospitalization time, stone clearance rate and perioperative complications were compared. RESULTS: Operation was successfully performed in all 50 cases, and no open surgery was converted in any case. In the ureteroscopy and laparoscopy groups, the mean operating time was 49.0±10.7 min and 41.8±8.0 min (t=2.68, P=0.00999), respectively, their hospitalization time was 2.8±1.3 days vs. 2.9±0.8 days (t =-0.40, P=0.69413), and stone clearance rate was 88.0% (22/25) vs. 100% (25/25). Stone moved to the renal pelvis in three cases in the ureteroscopy group, and residual stones were removed by extracorporeal shock-wave lithotripsy (ESWL). All patients were followed up for more than three months, and no serious complications such as ureterostenosis occurred. CONCLUSIONS: Laparoscopic ureterolithotomy has a higher stone clearance rate and shorter operation time compared with ureteroscopic lithotripsy. Laparoscopic ureterolithotomy is one safe and effective treatment on unilateral upper ureteral stones. Key words: Ureteral Calculi. Ureteroscopy. Lithotripsy. Laparoscopy. RESUMO OBJETIVO:Comparar os efeitos curativos da litotripsia ureteroscópica e a ureterolitotomia laparoscópica para cálculos unilaterais altos e pesquisar as indicações e resultados. MÉTODOS: Cinquenta casos de cálculos unilaterais altos foram distribuídos aleatoriamente em dois grupos: um grupo submetido a litotripsia ureteroscópica com laser holmium sob anestesia epidural ou lombar (n=25) e outro grupo submetido a ureterolitotomia laparoscópica sob anestesia geral (n=25). Duplo-J stent foi rotineiramente instalado em ambos os grupos. Comparou-se o tempo operatório, tempo de hospitalização pós-operatória, nível de desaparecimento dos cálculos e complicações pós-operatórias. RESULTADOS: Atos operatórios nos 50 casos sem ocorrências e nenhum ato convertido. Nos grupos por ureteroscopia e laparoscopia, o tempo operatório médio foi 49,0±10,7 minutos e 41,8±8,0 minutos (t=2,68, P=0,00999) respectivamente, tempo de hospitalização foi 2,8±1,3 dias vs. 2,9±0,8 dias (t=0,40, P=0,69413) e o nível de desaparecimento dos cálculos foi 88.0% (22/25) vs. 100% (25/25). Cálculo deslocado para pelve renal em três casos no grupo ureteroscópico e cálculos residuais foram removidos por litotripsia por onda de choque extracorpóreo (ESWL). Todos pacientes foram seguidos por mais de três meses e não ocorreram complicações sérias como estenoses ureterais. CONCLUSÕES: A ureterolitotomia laparoscópica teve maio...
Fusion of the prostate-specific and androgen-regulated transmembrane-serine protease gene (TMPRSS2) with the erythroblast transformation-specific (ETS) family members is the most common genetic alteration in prostate cancer. However, the biological and clinical role of TMPRSS2-ETS fusions in prostate cancer, especially in problematic prostate needle core biopsies, has not been rigorously evaluated. We randomly collected 85 specimens including 50 archival prostate cancer tissue blocks, 15 normal prostate specimens, and 20 benign prostatic hyperplasia specimens for TMPRSS2-ETS fusion analyses. Moreover, the fusion status in an additional 20 patients with initial negative biopsies who progressed to biopsy-positive prostate cancer at subsequent follow-ups was also characterized. Fluorescently labeled probes specific for ERG-related rearrangements involving the TMPRSS2-ERG fusion as well as TMPRSS2-ETV1 and TMPRSS2-ETV4 were used to assess samples for gene rearrangements indicative of malignancy under a design of sequential trial. Rearrangements involving TMPRSS2-ETS fusions were detected in 90.0% of the 50 postoperative prostate cancer samples. The positive rate for the rearrangements in the initial prostate cancer-negative biopsies of 20 patients who eventually progressed to prostate cancer was 60.0% (12/20). Our preliminary study demonstrates that the clinical utility of TMPRSS2-ETS fusion detection as a biomarker and ancillary diagnostic tool for the early diagnosis of prostate cancer is promising, given this approach shows significant high sensitivity and specificity in detection.
Accumulating investigations have demonstrated that microRNAs (miRNAs) are promising efficient targets for the next generation of molecular therapeutics. The development of miRNA-based therapies requires the identification and validation of cancer-associated miRNAs. Herein, we identified that miR-197-3p regulates the carcinogenesis and development of prostate cancer (PCa) via bioinformatics analysis. Next, we investigated the function and regulatory mechanisms of miR-197-3p in PCa. Overexpression of miR-197-3p suppressed PCa cell proliferation and colony formation. In contrast, inhibition of miR-197-3p activity enhanced PCa cell proliferation and colony formation. Mechanistic investigations identified that voltage dependent anion channel 1 (VDAC1) is a direct target of miR-197-3p. miR-197-3p targeting of VDAC1 resulted in downregulation of p-Akt and β-catenin. Subsequently, we found that restoration of VDAC1 abolished the effects of miR-197-3p on PCa cell proliferation and AKT signaling pathway. Furthermore, we confirmed that miR-197-3p suppressed tumor xenograft growth in vivo. In conclusion, our study offers an empirical investigation of miR-197-3p, a tumor suppressor that may be a potential therapeutic target in PCa.
The role of cell division cycle 20 (CDC20) was investigated in chemoresistance to decetaxel and the underlying mechanisms in metastatic castration-resistant prostate cancer (mCRPC). MTT assays were performed to determine effects of siRNA-mediated CDC20 knockdown on cell proliferation and anticancer activity of docetaxel. Western blot analyses were conducted to detect changes of Akt and Wnt signaling. Furthermore, in vivo growth of PCa was examined in nude mice treated with siCDC20 or docetaxel alone or in combination. CDC20 was overexpressed in mCRPC cells. Knockdown of CDC20 suppressed cell proliferation and enhanced anticancer effect of docetaxel with IC50 reducing from 0.358 to 0.188 µg/ml in PC3 cells and 0.307 to 0.162 µg/ml in DU145 cells (P<0.01). While no change of Akt signaling was observed, inhibition of Wnt/β-catenin signaling was detected upon CDC20 silencing. Xenograft tumor growth was significantly reduced in nude mice by CDC20 inhibition. The additional treatment of siCDC20 achieved better anticancer effects than that of docetaxel alone. Silencing of CDC20 may be a new strategy to improve chemosensitization to docetaxel in mCRPC.
High-mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors, but its role in renal carcinoma remains unclear. The aim of this study was to examine the expression of HMGA2 and its relationship to the overall survival (OS) of patients with non-metastatic clear cell renal cell carcinoma (ccRCC) following surgery. The expression of HMGA2 was evaluated retrospectively by immunohistochemistry (IHC) in 162 patients with ccRCC who underwent nephrectomy in 2003 and 2004. An IHC analysis revealed that HMGA2 was expressed in the nuclei of tumor cells in 146 (90.1%) patients with ccRCC. The level of HMGA2 was positively correlated with tumor size, lymph node metastasis, and Fuhrman Grade. A Kaplan–Meier analysis with log-rank test found that patients with high HMGA2 expression had a poor outcome and that patients with low HMGA2 expression had better survival. Cox regression analysis showed that HMGA2 expression could serve as an independent prognostic factor for ccRCC patients. The efficacy of the following prognostic models was improved when HMGA2 expression was added: tumor node metastasis stage, UCLA Integrated Scoring System, Mayo Clinic stage, size, grade, and necrosis score. In summary, this study showed that HMGA2 expression is an independent prognostic factor for OS in patients with ccRCC. HMGA2 was found to be a valuable biomarker for ccRCC progression.
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