Radium-223 for metastatic, castration-resistant prostate cancer: A retrospective chart review study of real-world use in a tertiary hospital in Taiwan.

BACKGROUND: Radium-223 is an alpha-emitting, bone-targeting radiopharmaceutical that confers a survival benefit in patients with confirmed bone-metastatic, castration-resistant prostate cancer with no visceral metastases. We studied real-world use of radium-223 in eligible patients from a tertiary hospital. METHODS: We retrospectively collected clinical data of patients treated with radium-223 in Tungs' Taichung MetroHarbor Hospital by chart review. Data included biochemical parameters, pain scores, other prostate cancer treatments received and adverse events (AEs). RESULTS: Of 36 patients included in the study, 12 patients received radium-223 as first-line therapy, 11 as second-line treatment and 13 as third-line treatment. Prostate-specific antigen significantly increased from baseline in patients who received radium-223 as third-line treatment and in patients who received radium-223 post-chemotherapy. Pain scores significantly decreased when radium-223 was given as second-line and as third-line treatment. In the patients who were naive to novel anti-hormone (NAH) therapy and chemotherapy, mean alkaline phosphatase level significantly decreased from baseline. The most common AE was anemia, found in 16.7% of patients. CONCLUSION: Radium-223 had early biochemical benefits, while in the later stages of the disease, it reduced bone pain in this real-world cohort of chemotherapy-naive, NAH-naive patients, and patients with prior therapy, from a tertiary institution in Taiwan.

Effect of CD44 gene polymorphisms on risk of transitional cell carcinoma of the urinary bladder in Taiwan.

The carcinogenesis of transitional cell carcinoma (TCC) of the urinary bladder involves etiological factors, such as ethnicity, the environment, genetics, and diet. Cluster of differentiation (CD44), a well-known tumor marker, plays a crucial role in regulating tumor cell differentiation and metastasis. This study investigated the effect of CD44 single nucleotide polymorphisms (SNPs) on TCC risk and clinicopathological characteristics. Five SNPs of CD44 were analyzed through real-time polymerase chain reaction in 275 patients with TCC and 275 participants without cancer. In this study, we observed that CD44 rs187115 polymorphism carriers with the genotype of at least one G were associated with TCC risk. Furthermore, TCC patients who carried at least one G allele at CD44 rs187115 had a higher stage risk than did patients carrying the wild-type allele (p < 0.05). In addition, The AATAC or GACGC haplotype among the five CD44 sites was also associated with a reduced risk of TCC. In conclusion, our results suggest that CD44 SNPs influence the risk of TCC. Patients with CD44 rs187115 variant genotypes (AG + GG) exhibited a higher risk of TCC; these patients may possess chemoresistance to developing late-stage TCC compared with those with the wild-type genotype. The CD44 rs187115 SNP may predict poor prognosis in patients with TCC.

Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells.

Timosaponin AIII (TAIII) is a steroidal saponin isolated from Anemarrhena asphodeloides that has been shown to inhibit cell growth and induce apoptosis in cancer. However, the effect of TAIII on acute myeloid leukemia (AML) remains unclear. Here, the molecular mechanism by which TAIII-induced apoptosis affects human AML cells was investigated. The results showed that TAIII significantly inhibited cell proliferation of four AML cell lines (MV4-11, U937, THP-1, and HL-60). Furthermore, TAIII induced apoptosis of HL-60 cells through caspase-3, caspase-8, and caspase-9 activations and PARP cleavage in a dose- and time-dependent manner. Moreover, Western blot analysis also showed that TAIII increased phosphorylation of JNK1/2 and p38 MAPK in a dose-dependent manner. Inhibition of JNK1/2 by specific inhibitors significantly abolished the TAIII-induced activation of the caspase-8. Taken together, our results suggest that TAIII induces HL-60 cell apoptosis through JNK1/2 pathways and could serve as a potential additional chemotherapeutic agent for treating AML.

Using the Water Absorption Ability of Dried Hydrogels to Form Hydrogel-Supported Lipid Bilayers.

The formation of supported lipid bilayers (SLBs) on hydrogels can act as a biocompatible anti-fouling interface. However, generating continuous and mobile SLBs on materials other than conventional glass or mica remains a significant challenge. The interaction between lipid membrane vesicles and a typical hydrogel is usually insufficient to induce membrane vesicle rupture and form a planar lipid membrane. In this study, we demonstrate that the water absorption ability of a dried polyacrylamide (PAAm) hydrogel could serve as a driving force to facilitate the formation of the hydrogel-SLBs. The absorption driving force vanishes after the hydrogels are fully hydrated, leaving no extra interaction hindering lipid lateral mobility in the formed SLBs. Our fluorescence recovery after photobleaching (FRAP) results show that SLBs only form on hydrogels with adequate absorption abilities. Moreover, we discovered that exposure to oxygen during drying could lead to the formation of an oxidized crust on the PAAm hydrogel surface, impeding SLB formation. Therefore, minimizing oxygen exposure during drying is crucial to achieving high-quality hydrogel surfaces for SLB formation. This water absorption method enables the straightforward fabrication of hydrogel-SLBs without the need for additional substrates or charges, thereby expanding their potential applications.

Impact of tissue inhibitor of metalloproteinases-3 genetic variants on clinicopathological characteristics of urothelial cell carcinoma.

To investigate the distribution of single nucleotide polymorphism (SNP) of tissue inhibitor of metalloproteinases-3 (TIMP-3) in patients with/without urothelial cell carcinoma (UCC), three loci of TIMP-3 SNPs (rs9862 C/T, rs9619311 T/C, rs11547635 C/T) were genotyped via TaqMan allelic discrimination for 424 UCC patients and 848 non-UCC participants. Furthermore, the TIMP-3 mRNA expression and its correlation with clinical characters of urothelial bladder carcinoma was analyzed using The Cancer Genome Atlas database (TCGA). The distribution of all 3 studied SNPs of TIMP-3 was insignificantly different between the UCC and non-UCC groups. However, significantly lower tumor T status was found in TIMP-3 SNP rs9862 CT + TT variant than the wild type (OR: 0.515, 95% CI: 0.289-0.917, P = 0.023). Moreover, the muscle invasive tumor type was significantly correlated to the TIMP-3 SNP rs9619311 TC + CC variant in the non-smoker subgroup (OR: 2.149, 95% CI: 1.143-4.039, P = 0.016). With the TIMP-3 expression data provided in TCGA, significantly higher TIMP-3 mRNA expression was observed in UCC with high tumor stage (P < 0.0001), high tumor T status (P < 0.0001) and high lymph node status (P = 0.0005). In conclusions, TIMP-3 SNP rs9862 variant is associated with lower tumor T status of UCC while TIMP-3 SNP rs9619311 variant is correlated to muscle invasive UCC development in non-smoker.

Robotic partial nephrectomy for renal tumor: The pentafecta outcomes of a single surgeon experience.

PURPOSE: This study investigated the oncological and functional surgical outcomes for patients with renal tumor who underwent robot-assisted partial nephrectomy (PN) by a single surgeon in Taiwan from 2006 to 2019. METHODS: This retrospective study assessed patients who underwent robot-assisted PN for renal tumor. Patient data were analyzed for age, sex, body mass index, operative time and total ischemic time, surgical margin (positive/negative), and surgical complications. To evaluate functional and oncological outcomes, achievement of trifecta, and pentafecta criteria was used. Trifecta criteria were defined as a negative surgical margin, no postoperative complications, warm ischemia time <25 min. Pentafecta criteria were the trifecta criteria, >90% preservation of estimated glomerular filtration rate (eGFR) preservation, and no stage progression of chronic kidney disease at 1-year follow-up. RESULTS: Of 101 patients who received robot-assisted PN, the most common type of renal tumor was clear cell renal cell carcinoma (RCC) (38%), followed by angiomyolipoma (26%). Patient characteristics were mean age 54.59 ± 13.8 years; mean RENAL Nephrometry score 6.63 ± 2.16; mean operative time 102.34 ± 50.06 min; and warm ischemia time 20.01 ± 14.12 min. The mean eGFR was 104.43 ± 31.73 mL/min/1.73 m2 preoperatively and 89.39 ± 32.3 mL/min/1.73 m2 postoperatively. Pathologic evaluation showed malignant tumors in 57 patients, among whom achievement of trifecta criteria occurred for 39 (68.42%) and pentafecta criteria for 18 (31.57%). Operation time was the only predictor for pentafecta achievement. CONCLUSION: Robotic PN is a safe and effective approach for patients with renal tumor that can preserve most renal function and achieve oncological control. Pentafecta criteria can be used to more clearly define the surgical outcome of RAPN.

Robot-assisted radical prostatectomy using hugo RAS system: The pioneer experience in Taiwan and Northeast Asia.

BACKGROUND: Among the novel robotic platforms, the Hugo RAS system is the second most studied platform, next to the da Vinci system, and we aim to address our experiences in radical prostatectomy (RP) with the Hugo RAS system. METHODS: We recorded our first 12 cases of prostate cancer undergoing RP with the Hugo RAS system. The median console time was 145 min and median hospital stay was 7 days. Hedge' g was applied to search for the cut-off case in four parameters in surgeries. RESULTS: Pre-console preparation was significantly improved after the first seven cases, and the console time was remarkably shortened after the first two cases. The intraoperative pause for trouble shooting was remarkably shortened after the first three cases. CONCLUSIONS: We found that RP with the Hugo RAS system was feasible, and the learning curve was short as surgeons may benefit from the previous experience with the da Vinci system.

Effects of different tools and working height on physical workload in vertical cleaning tasks applying ambient control techniques.

This study aimed to investigate the effects of different tools and working heights on physical workloads in vertical cleaning tasks. Thirty healthy adults were recruited to use a rag and a long-handle tool (LHT) to simulate cleaning operations on the Wii Fit board surfaces of 3 different heights, respectively. Participants used a lower 50th percentile force but were required to spend a longer time to finish the task while using an LHT than using a rag. The tool preferences were the main factors considered for efficiency and personal subjective workload and physiological load. 76.6% of the participants preferred to use the LHT instead of the rag at a high task height, but 70% preferred to use the rag when working at a medium task height. For low workload cleaning tasks on vertical surfaces, employers should provide cleaners with different handle lengths tools to choose from to reduce the cleaner's workload.

Incidental Prostate Cancer from Prostate with Benign Biopsies: A Predictive and Survival Analysis from Cohort Study.

Purpose: This cohort was to evaluate incidental prostate cancer (iPCa) from men with preoperative benign biopsies and demonstrate their outcomes under different managements. Patients and Methods: Between 2015 and 2017, we analyzed the risk factors having iPCa from surgical specimens from men provided with benign preoperative biopsies of their prostates. Furthermore, we compared the survival outcomes according to the different managements after iPCa was diagnosed. Receiver operating characteristic (ROC) curve was utilized to find the best thresholds. Univariable and multivariable nested logit regression were performed to estimate the effect size of different independent variables. Odds ratio (OR) was expressed with 95% confidence interval, and the alpha level was 5%. Results: In 295 men we enrolled, there were 57 (19%) men having iPCa from surgical specimens. In univariable logit regression, we found significant variables of age, PSA, prostatic volume, PSA velocity ≥ 0.75 ng/mL/year for 3 years, taking 5α reductase inhibitors, abnormal digital rectal examination, cores of biopsy and surgical methods. In multivariable model, PSA was the strongest variable predicting iPCa (OR 3.81 [2.04-7.07]; Wald: 17.75; p < 0.001). In ROC curve, the best threshold was 9.025 ng/mL (area under curve: 0.95; sensitivity: 0.947; specificity: 0.866). In Kaplan-Meier curve of 27.89-month follow-up, robot-assisted simple prostatectomy (RASP) can provide similar PSA progression-free period as robot-assisted radical prostatectomy (RARP) following transurethral surgeries in organ-confined cancer (Log rank test, p = 0.293), and both of them were better than external-beam radiation therapy (RT) following transurethral surgeries (Log rank test, p < 0.001). Conclusion: PSA was the strongest variable to predict iPCa out of prostate with preoperative benign biopsies. RASP was parallel to RARP following transurethral surgeries in organ-confined cancer in the short term.

Validation of robotic-assisted ureteroplasty with buccal mucosa graft for stricture at the proximal and middle ureters: the first comparative study.

Although ureteroplasty with buccal mucosa graft for long-segmental ureteral stenosis has been developed long ago, evidence was still restricted to case series in published literature. This study aims to validate ureteroplasty with buccal mucosa graft (BMG) in long-segment stricture at the proximal and middle ureters under designed comparative methods. From April 2015 to January 2019, we performed robotic-assisted ureteroplasty with BMG with a two-phase design and compared ureteroplasty and BMG (phase 2 surgery) with endoscopic stenting (phase 1 surgery). Paired data of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), hydronephrosis grade, and physical and psychological domains of the World Health Organization Quality of Life (WHOQOL)-BREF were compared. A total of 29 patients were enrolled, and only three (10%) patients had hydronephrosis resolution after treatment with endoscopic stenting (p = 0.250 to baseline). Compared to endoscopic ureteral stent, Hedges' g of ureteroplasty with BMG was 0.56 (95% CI 0.43-0.69), 0.63 (95% CI 0.46-0.80), 0.80 (95% CI 0.56-1.04), and 1.06 (95% CI 0.69-1.43) in EGFR, GFR, physical domain of WHOQOL-BREF, and psychological domain of WHOQOL-BREF, respectively (All significance; p < 0.001). After 12-month follow-ups, no recurrence of stricture was reported. In conclusion, Robotic-assisted ureteroplasty with BMG onlay is efficient in reconstruction of long-segment stricture of the proximal and middle ureters.

Diffusive Ki67 and vimentin are associated with worse recurrence-free survival of upper tract urothelial carcinoma: A retrospective cohort study from bench to bedside.

OBJECTIVES: This study aimed to determine the prognostic values of Ki67 and vimentin in upper tract urothelial carcinoma (UTUC) after extirpative surgery. METHODS AND MATERIALS: Between 2014 and 2019, patients diagnosed with UTUC and receiving radical nephroureterectomy were included retrospectively. Nuclear MIB-1 clones and cytoplasmic VIM 3B4 clones were used to assess Ki67 and vimentin levels, respectively. A unified reading protocol was applied, and the expression level was read by a single pathologist. Receiver operating characteristic curves were utilized to determine the best threshold for Ki67 and vimentin regarding recurrence, and this level was set as the diffusive level. The outcome of recurrence-free survival (RFS) was analyzed via a Cox regression model with univariable and multivariable approaches. Survival outcomes were analyzed via Kaplan-Meier (KM) curves. RESULTS: A total of 247 patients were included, and the mean follow-up was 29.90 ± 6.80 months. Diffusive thresholds were 17.5% for both Ki67 and vimentin. Under multivariable Cox regression, diffusive Ki67 (hazard ratio: 4.20 [2.39-7.37], P < 0.001) and diffusive vimentin (hazard ratio: 5.34 [3.10-9.22], P < 0.001) were significant prognostic indicators of worse RFS. Diffusive Ki67 was accompanied by diffusive vimentin (chi square with Yates' correction, P = 0.015), and vice versa. In the KM curve, there was no difference between diffusive Ki67/nondiffusive vimentin and nondiffusive Ki67/diffusive vimentin (log-rank test, P = 0.073). Significant differences (log-rank test, P < 0.001) were seen in different combinations of diffusive Ki67/vimentin (Mean RFS: 19.76 [18.56-20.96] months), only one diffusive in Ki67 or vimentin (Mean RFS: 22.94 [21.88-24.00] months), and nondiffusive Ki67/vimentin (Mean RFS: 32.96 [32.43-33.50] months). CONCLUSIONS: Diffusive Ki67 and vimentin were related to each other, and they exerted equivalent and synergic effects on predicting worse RFS in UTUC.

Phloretin Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Regulating the Inflammatory Response, Oxidative Stress and Apoptosis.

The inflammatory process is proposed to be one of the factors to benign prostatic enlargement (BPH), and this is the first study examining the anti-inflammatory ability of phloretin in treating rats with testosterone-induced BPH. BPH would be induced by testosterone (10 mg/kg/day testosterone subcutaneously for 28 days), and the other groups of rats were treated with phloretin 50 mg/kg/day or 100 mg/kg/day orally (phr50 or phr100 group) after induction. Prostate weight and prostate weight to body weight ratio were significantly reduced in the Phr100 group. Reduced dihydrotestosterone without interfering with 5α-reductase was observed in the phr100 group. In inflammatory proteins, reduced IL-6, IL-8, IL-17, NF-κB, and COX-2 were seen in the phr100 group. In reactive oxygen species, malondialdehyde was reduced, and superoxide dismutase and glutathione peroxidase were elevated in the phr100 group. In apoptotic assessment, elevated cleaved caspase-3 was observed in rats of the phr100 group. Enhanced pro-apoptotic Bax and reduced anti-apoptotic Bc1-2 could be seen in the phr100 group. In histological stains, markedly decreased glandular hyperplasia and proliferative cell nuclear antigen were observed with reduced expression in the phr100 group. Meanwhile, positive cells of terminal deoxynucleotidyl transferase dUTP nick end labeling were increased in the phr100 group. In conclusion, the treatment of phloretin 100 mg/kg/day could ameliorate testosterone-induced BPH.

Biochemical recurrence of pathological T2+ localized prostate cancer after robotic-assisted radical prostatectomy: A 10-year surveillance.

BACKGROUND: pT2+ prostate cancer (PCa), a term first used in 2004, refers to organ-confined PCa characterized by a positive surgical margin (PSM) without extracapsular extension. Patients with a PSM are vulnerable to biochemical recurrence (BCR) following radical prostatectomy (RP); however, whether adjuvant radiotherapy (aRT) is imperative to PSM after RP remains controversial. This study had the longest follow-up on pT2+ PCa after robotic-assisted RP since 2004. Moreover, we discussed our viewpoints on pT2+ PCa based on real-world experiences. AIM: To conclude a 10-year surveillance on pT2+ PCa and compare our results with those of the published literature. METHODS: Forty-eight patients who underwent robotic-assisted RP between 2008 and 2011 were enrolled. Two serial tests of prostate specific antigen (PSA) ≥ 0.2 ng/mL were defined as BCR. Various designed factors were analyzed using statistical tools for BCR risk. SAS 9.4 was applied and significance was defined as P < 0.05. Univariate, multivariate, linear regression, and receiver operating characteristic (ROC) curve analyses were performed for statistical analyses. RESULTS: With a median follow-up period of 9 years, 25 (52%) patients had BCR (BCR group), and the remaining 23 (48%) patients did not (non-BCR group). The median time for BCR test was 4 years from the first postoperative PSA nadir. Preoperative PSA was significantly different between the BCR and non-BCR groups (P < 0.001), and ROC curve analysis of preoperative PSA suggested a cut-off value of 19.09 ng/mL (sensitivity, 0.600; specificity: 0.739). The linear regression analysis showed no correlation between time to BCR and preoperative PSA (Pearson's correlation, 0.13; adjusted R 2 = 0.026). CONCLUSION: Robotic-assisted RP in pT2+ PCa of worse conditions can provide better BCR-free survival. A surgical technique limiting the PSM in favorable situations is warranted to lower the pT2+ PCa BCR rate. Preoperative PSA cut-off value of 19.09 ng/mL is a predictive factor for BCR. Based on our experiences and review of the literature, we do not recommend routine aRT for pT2+ PCa.

Simultaneous upper and lower urinary tract invasive Lymphoepithelioma-like carcinoma with programmed death-ligand 1 full expression on combined positive score.

Lymphoepithelioma-like carcinoma, named after nasopharyngeal lymphoepithelioma and rarely seen at genitourinary malignancy, accounts for 1%-2% along the upper and lower urinary tract. For its rarity, no published guideline can be adhered to. Roles of surgery and chemotherapy are solid, and rich Programmed Death-Ligand 1 characteristics may furthermore light on the possible immunotherapy. This female case had it at both upper and lower urinary tract simultaneously. No involved regional lymph nodes and no distant metastasis were investigated. No adjuvant chemotherapy was given after robotics-assisted left nephroureterectomy and bladder cuff excision with partial cystectomy, and no recurrence was observed.

Impact of Gene Polymorphisms in GAS5 on Urothelial Cell Carcinoma Development and Clinical Characteristics.

Urothelial cell carcinoma (UCC) is the commonest malignant tumor of the urinary tract and the second most common kidney cancer malignancy. Growth arrest-specific 5 (GAS5), a long noncoding RNA, is encoded by the GAS5 gene and plays a critical role in cellular growth arrest and apoptosis. In the current study, two single nucleotide polymorphisms (SNPs) in the GAS5 gene, rs145204276 and rs55829688, were selected to investigate correlations between these single SNPs and susceptibility to UCC. A total of 430 UCC cases and 860 ethnically matched healthy controls were included. SNP rs145204276 and SNP rs55829688 were determined using a TaqMan genotyping assay. Logistic regression models demonstrated that female patients with UCC carrying the rs145204276 GAS5 Ins/Del or Del/Del genotype had a 3.037-fold higher risk of larger tumor status (95% confidence interval 1.259-7.324) than did rs145204276 wild type (Ins/Ins) carriers (p = 0.011). The Cancer Genome Atlas validation cohort analysis demonstrated that the expression of GAS5 in female patients with bladder urothelial carcinoma (BLCA) with larger tumor size was much lower than that in patients with a smaller tumor size (p = 0.041). Kaplan-Meier curve analysis and the log-rank test revealed that female patients with BLCA and lower GAS5 expression had poorer overall survival than those with higher GAS5 expression. In conclusion, genetic variations in GAS5 rs145204276 may serve as a critical predictor of the clinical status of female patients with UCC.

Robotic Incisional Hernia Repair After Robotic-assisted Radical Prostatectomy (RARP): A 3-port Approach.

BACKGROUND/AIM: Incisional hernia is a complication that occurs occasionally, and surgical intervention is required to prevent more severe sequela. While there are several options for management, robotic-assisted incisional repair has not been well discussed yet. We herein report a case series of 10 patients who underwent robotic-assisted incisional hernia repair (RIHR) after robotic-assisted radical prostatectomy (RARP). The aim of the study was to examine the feasibility of incisional hernia repair with da Vinci® robotics. PATIENTS AND METHODS: We recruited patients from a group of 2,000 consecutive patients who underwent RARP from December, 2005 to June, 2020 by a single surgeon. Patient characteristics included age, body mass index (BMI), PSA level, pathology Gleason score, and pathology TNM staging. The variants regarding the patients' incisional hernia included incisional hernia occurrence time after RARP, defect size, operation time, console time, blood loss, and follow-up time after the herniation occurrence. Furthermore, we established a defect size of 3x2 cm2 as the cutoff value for using mesh reinforcement or not. RESULTS: The mean defect area was 27.7 cm2, and the average operative time was 114.8 min, with a mean console time of 87 min. Blood loss was 32.5 ml, and the hospital stay for all patients was 3 days without complications. The mean follow-up period was 29.5 months, with no recurrence. CONCLUSION: RIHR is a feasible surgical method that is not inferior to the traditional open or laparoscopic repair. Furthermore, RIHR can possibly lessen the burden of both the surgeon and patient.

Building a Nomogram for Prediction of Prostate Cancer in Patients With Preoperatively Suspected Prostate Cancer.

BACKGROUND/AIM: Expanded indications for patients with preoperatively suspected prostate cancer (PC) undergoing theranostic robotic-assisted laparoscopic radical prostatectomy (T-RARP) are reported. We aimed to build a nomogram of T-RARP to predict final pathologically proven PC. This study reviewed data of 153 patients that underwent T-RARP for suspected PC performed by the same surgeon. PATIENTS AND METHODS: Patients' preoperative demographic and clinical characteristics included age, prostate-specific antigen (PSA) level, PSA density (PSAD), history of acute urinary retention (AUR), abnormal digital rectal examination (DRE) of the prostate, and Prostate Imaging Reporting and Data System (PI-RADS) classification at 3-T multiparametric magnetic resonance imaging (MRI). Logistic regression with backward elimination was used to select potential risk factors. RESULTS: Based on Harrell's guidelines, we chose seven variables for our final model: Age, DRE corresponding with MRI, AUR, PSAD, prostate-specific antigen velocity (PSAV), PI-RADS, and biopsy pathology. A nomogram for prediction of adenocarcinoma was developed. The original C-index for the nomogram was 0.80 (95% confidence interval=0.74-0.89). The cut-off of the nomogram score for predicting PC was 50 (sensitivity=55.4%; specificity=91.9%). The receiver operating characteristic curve of the model analysis showed an area under the curve of 0.801. CONCLUSION: A nomogram was produced using age, DRE-corresponding MRI, AUR, PSAD, PSAV, PI-RADS, and biopsy pathology. A preoperative nomogram prediction of prostate adenocarcinoma can help the patient and his family understand the possibility of PC and assist them in their decision-making.

Early Dutasteride Monotherapy in Patients With Elevated Serum Prostate-Specific Antigen Levels Following Robot-Assisted Radical Prostatectomy.

Background: To evaluate the efficacy of early dutasteride administration in patients with a detectable prostate-specific antigen (PSA) levels after robot-assisted radical prostatectomy (RARP). Methods: We retrospectively analyzed RARP patients whose pathological stage is T2a to T3b without lymph node or distant metastasis from 2007 to 2017. All patients received a daily dose of 0.5 mg of dutasteride when post-RARP PSA levels were increasing but had not achieved biochemical recurrence. PSA levels were monitored every 3 months after dutasteride administration. None of the patients received radiotherapy (RT) or androgen-deprivation therapy (ADT) before taking dutasteride. All follow-ups were begun from RARP to January 2019 or to the date of RT/ADT. Results: Thirty-five patients were included in this analysis. The median followed up was 53.6 months. Twenty-two patients (62.9%) showed a PSA response in which the PSA decreased more than 10% at the first follow-up after dutasteride administration. The Pathological stage > T2 (p = 0.012) and positive surgical margin (p = 0.046) were prognostic factors for a PSA response. Twenty-three out of 35 included patients (65.7%) did not require further RT/ADT. The significant risk factor was the PSA level (p = 0.011) at the beginning of dutasteride treatment. The cut-off value of the PSA level to avoid further RT/ADT was 0.195 ng/ml. Conclusions: Early dutasteride administration showed a significant decline in the PSA levels of patients with pathology stage >T2 and positive surgical margin in our retrospective hypothesis-generating study. If dutasteride was provided before the PSA value increased to 0.195 ng/ml after RARP, it would reduce the probability of acquirement of RT/ADT.

Impact of prostatic anterior fat pads with lymph node staging in prostate cancer.

Background: Several reports have revealed the presence of lymph nodes in the prostatic anterior fat pad (PAFP). To date, no study has described the characteristics of Taiwanese patients harboring PAFP lymph nodes with metastatic prostate cancer involvement. Method: Between December 2006 and May 2015, a total of 849 consecutive patients underwent robot-assisted laparoscopic radical prostatectomy with PAFP dissection. Pathological examination of the dissected PAFP was conducted to assess the presence of lymphoid tissue and prostate cancer involvement. Results: Of the 849 patients, 76 (9.0%) had 1-3 PAFP lymph nodes. Moreover, 11 (1.3%) of the 76 patients had positive lymph node metastases of prostate cancer in the PAFP; 5 (0.6%) of the 11 patients, who had negative pelvic lymph node involvement, were upstaged because of positive metastases in PAFP lymph nodes. Among the 76 patients having PAFP lymph nodes, metastatic lymph nodes were associated with the clinical T stage, preoperative Gleason score, pathological T stage, and pathological N stage (p < 0.001). Patients with pathological seminal vesicle invasion and a higher surgical Gleason score also exhibited PAFP lymph node metastases (p < 0.005). Conclusion: Our data show that 9.0% of patients had PAFP lymph nodes and that 1.3% had prostate cancer metastases. Additionally, 0.6% of patients were upstaged because of positive metastases in PAFP lymph nodes. Because of the pathological analysis of the PAFP, a few patients were upstaged. Thus, routine pathological analysis of the PAFP should only be conducted for those with higher preoperative prostate-specific antigen, higher Gleason score, and advanced T stage observations.

Activation of Lysophosphatidic Acid Receptor 3 Inhibits Megakaryopoiesis in Human Hematopoietic Stem Cells and Zebrafish.

Lysophosphatidic acid (LPA) is a membrane-derived lysophospholipid that exists in the plasma and platelets. It exerts its functions through activation of various LPA receptors (LPARs), which belong to the family of G protein-coupled receptors. Activation of LPARs has important roles in stem cell differentiation. However, how LPA affects human hematopoietic stem cell (HSC) differentiation remains elusive. In our previous studies, we have suggested that LPA receptor 2 (LPA2) and LPA receptor 3 (LPA3) play opposing roles and may act as a molecular switch during megakaryocytic differentiation in K562 cells. In this study, human CD34+ HSCs and zebrafish are adopted to investigate the roles of LPA3 during megakaryopoiesis/thrombopoiesis in vitro and in vivo. Our results show that LPAR3 mRNA expression level is decreased upon induction by thrombopoietin and stem cell factor in human HSCs. Using pharmacological activators and shRNA knockdown experiments, we demonstrate that activation of LPA3 inhibits megakaryopoiesis in human HSCs. In addition, pharmacological activation of LPA3 suppressed thrombopoiesis in zebrafish. Furthermore, blockage of LPA3 translation by morpholino increased the number of CD41-GFP+ cells in Tg(CD41:eGFP) zebrafish. Moreover, the mRNA expression level of zCD41 increased significantly in LPA3-knockout zebrafish. These results clarify the negative role of LPA3 during megakaryopoiesis and provide important information for potential treatments of related diseases, such as megakaryopenia.