Active Surveillance for Taiwanese Men with Localized Prostate Cancer: Intermediate-Term Outcomes and Predictive Factors.

PURPOSE: Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS. MATERIALS AND METHODS: This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model. RESULTS: A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL² predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17-2.88) and conversion (HR 1.56, 95% CI 1.05-2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91-2.18; ≥50%: HR 1.97, 95% CI 1.1453-3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06-6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years). CONCLUSIONS: AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.

Laparoendoscopic single-site adrenalectomy in patients with primary hyperaldosteronism: A prospective study with long-term follow up.

OBJECTIVE: Laparoendoscopic single-site (LESS) adrenalectomy is a promising minimally invasive technique, however, the current evidence has not confirmed its long-term effectiveness in primary aldosteronism (PA). We conducted a study to analyze the long-term efficacy of LESS adrenalectomy in patients with PA. METHODS: A total of 49 patients who had been clinically confirmed with PA who had an indication for unilateral adrenalectomy were included in this study. Perioperative data were obtained for all patients. Blood pressure and the levels of serum aldosterone, renin, and potassium were checked periodically. The median follow-up was 16.5 months. RESULTS: No intra- or early post-operative complication occurred. All LESS adrenalectomies were completed successfully, except one with laparoscopic conversion. Hypokalemia was resolved in all cases and no patient required potassium supplements after surgery. Post-operative cure of hypertension was achieved in 63% of our patients. Overall, 84% of our PA patients had clinical improvement in blood pressure control after surgery. CONCLUSIONS: Our long-term experience revealed that LESS adrenalectomy is a safe and effective approach, which demonstrated comparable long-term cure and improvement of hypertension to a conventional laparoscopic series in treating PA.

Laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-access platform and standard laparoscopic instruments: technical considerations and surgical outcomes.

BACKGROUND: We previously reported our initial experience with laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-port device and conventional straight laparoscopic instruments. METHODS: Between December 2010 and February 2012, LESS retroperitoneal partial adrenalectomies were performed in 11 patients. Six patients had aldosterone-producing adenomas (APAs) and five patients had nonfunctioning tumors. A single-port access was created with an Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA) through an incision of 2-3 cm beneath the tip of the 12th rib. All procedures were performed with straight laparoscopic instruments. RESULTS: All LESS procedures were successfully completed without conversion to traditional laparoscopic conversion. The tumors ranged from 1 cm to 4.7 cm (mean, 2.3 cm). The operative time was 71-257 minutes (mean, 121 minutes). Most patients (n = 8) had minimal blood loss; the other three patients had a blood loss of 150 mL, 100 mL, and 100 mL. The mean hospital stay was 3 days (range, 1-6 days). There were no perioperative or postoperative complications. Pathological examinations revealed negative surgical margins in all specimens. All patients with Conn's syndrome had an improvement in blood pressure and normalization of plasma renin activity and serum aldosterone levels; all patients were free of potassium supplementation. CONCLUSION: Our results clearly demonstrate that LESS retroperitoneal partial adrenalectomy can be performed safely and effectively using a custom-made single-access platform and standard laparoscopic instruments.

CKD as a risk factor for bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma.

BACKGROUND: The aim of this study is to examine chronic kidney disease (CKD) as a risk factor for bladder recurrence and cancer-specific and total mortality in a cohort of patients with upper urinary tract (UUT) urothelial carcinoma (UC) treated by means of nephroureterectomy. STUDY DESIGN: Cohort study. SETTINGS & PARTICIPANTS: 150 patients with primary UC of the ureter or renal pelvis treated by means of nephroureterectomy at a single center. PREDICTOR: Presence and severity of CKD according to preoperative markers of kidney damage, estimated glomerular filtration rate calculated using the Modification of Diet in Renal Disease Study equation, and other covariates. OUTCOMES & MEASUREMENTS: Subsequent bladder recurrences, cancer-specific survival, and overall survival. RESULTS: Of 150 patients, 37 (25%) had no CKD, 71 patients (47%) had CKD stages 1 to 4, and 42 patients (28%) had CKD stage 5. 41 (27%) and 31 patients (21%) reported exposure to herbal medicine or tobacco use, respectively. During a mean follow-up of 4 years, 53 patients (35%) developed bladder recurrence and 27 (18%) died, of whom 14 (9.3%) died of cancer. Overall 5-year bladder recurrence-free and cancer-specific survival rates were 62% and 89%, respectively (n = 150). Risks of bladder recurrence were 2.43 (95% confidence interval, 1.00 to 5.93) and 3.95 (95% confidence interval, 1.59 to 9.80), greater in patients with CKD stages 1 to 4 and CKD stage 5 compared with patients without CKD, respectively. Ureteral involvement of the primary tumor (hazard ratio, 1.97; 95% confidence interval, 1.12 to 3.48) also was associated significantly with an increased rate of bladder recurrence. The risk of death from all causes or UC was not significantly greater in patients with CKD stages 1 to 4 or CKD stage 5 compared with those without CKD. Higher tumor stage (pT2 to 4) was associated significantly with overall death (hazard ratio, 5.15; 95% confidence interval, 1.84 to 14.48). LIMITATIONS: A retrospective study in an area of high incidence of both UUT-UC and CKD. CONCLUSIONS: Advancing CKD stage of patients and positive ureteral involvement of the primary tumor (especially in the lower ureter) are associated with greater risk of subsequent bladder recurrence in patients with UUT-UC treated by means of radical surgery.

Alisol B acetate, a triterpene from Alismatis rhizoma, induces Bax nuclear translocation and apoptosis in human hormone-resistant prostate cancer PC-3 cells.

The anti-tumor potential of components from Chinese herbal medicines has been greatly concerned. Alisol B acetate, a triterpene from Alismatis rhizoma, induced apoptotic cell death in human hormone-resistant prostate cancer PC-3 cells in a time- and concentration-dependent manner. A good correlation between loss of mitochondrial membrane potential and apoptotic cell death was apparent indicating the participation of mitochondria-related mechanism. Alisol B acetate induced Bax up-regulation and nuclear translocation; it also induced the activation of initiator caspase-8 and caspase-9, and executor caspase-3, suggesting the involvement of both extrinsic and intrinsic apoptosis pathways. Taken together, it is suggested that alisol B acetate induces apoptosis in PC-3 cells via a mitochondria-mediated mechanism with activation of caspase-8, -9 and -3. Furthermore, the Bax activation and translocation from the cytosol to nucleus might be a crucial response to the apoptotic effect.

Induction of mitotic arrest and apoptosis in human prostate cancer pc-3 cells by evodiamine.

PURPOSE: Although evodiamine, an alkaloid isolated from Evodiae fructus, has been reported to exert anticancer activities, to our knowledge its target and mechanism of action have not yet been explored. We examined the anticancer activities and action mechanism of evodiamine. MATERIALS AND METHODS: Human prostate cancer PC-3 cells were used in this study. The cytotoxic effect and cell growth inhibition were examined using the MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay and sulforhodamine B assay, respectively. The apoptotic effect was determined using TUNEL assay and the progression of cells through the cell cycle and cell apoptosis were examined by FACScan flow cytometry (Becton Dickinson, Sunnyvale, California). In situ mitotic spindle detection and in vitro tubulin polymerization assay were performed by immunofluorescence staining for beta-tubulin and CytoDYNAMIX ScreenTM3 (CDS-03) kits (Cytoskeleton, Denver, Colorado). RESULTS: It was found that treatment of PC-3 cells with evodiamine decreased the cell number in a concentration and time dependent manner, and effectively inhibited PC-3 cell growth via the induction of cell cycle arrest at the G2/M phase and subsequent apoptosis. In an in situ assay we found that evodiamine inhibited microtubule spindle formation. In a cell-free assay system of tubulin polymerization evodiamine inhibited the polymerization of microtubules in a concentration dependent manner. CONCLUSIONS: These data suggest that evodiamine shows anticancer activity through inhibition of tubulin polymerization. This antitubulin activity might make evodiamine a potential anticancer drug.

Modulation of anti-adhesion molecule MUC-1 is associated with arctiin-induced growth inhibition in PC-3 cells.

BACKGROUND: Lignans have been reported to possess anti-tumor activity in various cancer cells. However, their anticancer effects in human prostate cancer have not been well established. Here, we examine the effect of arctiin, a lignan compound, on growth regulation in prostate cancer PC-3 cells. We postulated that arctiin modulates the attachment/detachment of PC-3 cells and we investigated the role of arctiin on MUC-1 expression. METHODS: The effect of arctiin on PC-3 cell growth was examined using an MTT assay method and cell number was calculated by means of a standard regression line. The expressions of MUC-1 and integrins alpha2, alpha5, and beta1 were detected using FACScan flow cytometric analysis. Levels of MUC-1 mRNA were determined using reverse transcriptase PCR (RT-PCR). RESULTS: Treatment of PC-3 cells with arctiin decreased the cell number in a concentration- and time-dependent manner in serum-containing condition. Arctiin preferentially induced cell detachment, but did not have anti-proliferation or cytotoxic effects in PC-3 cells. The arctiin-induced effect was inhibited by cycloheximide, indicating that protein synthesis was required. FACScan flow cytometric analysis demonstrated that arctiin increased the expression of the anti-adhesion mucin MUC-1, but did not affect integrin expression in PC-3 cells. The arctiin-induced increase in MUC-1 protein expression was due to up-regulation of mRNA, as revealed by RT-PCR analysis. CONCLUSIONS: Arctiin significantly induces cell detachment and decreases the cell numbers via the up-regulation of MUC-1 mRNA and protein in PC-3 cells.