Cost-effectiveness analysis of different anesthesia strategies for transperineal MRI/US fusion prostate biopsy.

ABSTRACT: This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (<40 ml), TIVA emerged as a more cost-effective strategy. While Chat-LA may generally be the most cost-effective and safer anesthesia method for TP-MUF-PB, personalization of anesthesia strategies is crucial, considering specific patient demographics such as age and prostate volume.

New model of PIRADS and adjusted prostatespecific antigen density of peripheral zone improves the detection rate of initial prostate biopsy: a diagnostic study.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

Effect of Perioperative Dexmedetomidine on Delayed Graft Function Following a Donation-After-Cardiac-Death Kidney Transplant: A Randomized Clinical Trial.

Importance: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown. Objective: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant. Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population. Interventions: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 µg/kg/h intraoperatively and 0.1 µg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine. Main Outcomes and Measures: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30. Results: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit. Conclusions and Relevance: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

Clinical association between pre-treatment levels of plasma fibrinogen and bone metastatic burden in newly diagnosed prostate cancer patients.

BACKGROUND: Due to the different treatments for low-volume metastatic prostate cancer (PCa) as well as high-volume ones, evaluation of bone metastatic status is clinically significant. In this study, we evaluated the correlation between pre-treatment plasma fibrinogen and the burden of bone metastasis in newly diagnosed PCa patients. METHODS: A single-center retrospective analysis, focusing on prostate biopsies of newly diagnosed PCa patients, was performed. A total of 261 patients were enrolled in this study in a 4-year period. All subjects were submitted to single-photon emission computerized tomography-computed tomography to confirm the status of bone metastasis and, if present, the number of metastatic lesions would then be calculated. Clinical information such as age, prostate-specific antigen (PSA), fibrinogen, clinical T stage, and Gleason score were collected. Patients were divided into three groups: (i) a non-metastatic group, (ii) a high volume disease (HVD) group (>3 metastases with at least one lesion outside the spine), and (iii) a low volume disease (LVD) group (metastatic patients excluding HVD ones). The main statistical methods included non-parametric Mann-Whitney test, Spearman correlation, receiver operating characteristic (ROC) curves, and logistic regression. RESULTS: Fibrinogen positively correlated with Gleason score (r = 0.180, P = 0.003), PSA levels (r = 0.216, P < 0.001), and number of metastatic lesions (r = 0.296, P < 0.001). Compared with the non-metastatic and LVD groups, the HVD group showed the highest PSA (104.98 ng/mL, median) and fibrinogen levels (3.39 g/L, median), as well as the largest proportion of Gleason score >7 (86.8%). Both univariate (odds ratio [OR] = 2.16, 95% confidential interval [CI]: 1.536-3.038, P < 0.001) and multivariate (OR = 1.726, 95% CI: 1.206-2.472, P = 0.003) logistic regressions showed that fibrinogen was independently associated with HVD. The ROC curve suggested that fibrinogen acts as a predictor of HVD patients, yielding a cut-off of 3.08 g/L, with a sensitivity of 0.684 and a specificity of 0.760 (area under the curve = 0.739, 95% CI: 0.644-0.833, P < 0.001). CONCLUSIONS: Pre-treatment plasma fibrinogen is positively associated with bone metastatic burden in PCa patients. Our results indicate that fibrinogen might be a potential predictor of HVD.

Diosgenin inhibits the expression of NEDD4 in prostate cancer cells.

Prostate cancer is the second most common malignancy among men and causes a myriad of health problem for males that are diagnosed with the cancer. Although the 5-year relative survival rate of prostate cancer patients has been significantly increased due to prostate-specific antigen testing and treatment advances, patients that develop metastatic castrate-resistant prostate cancer continue to have poor survival rates. Thus, it is critical to discover new therapeutics to treat prostate cancer. Diosgenin is a steroidal saponin from Trigonella foenum graecum, which has been previously identified to exert anti-tumor properties. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) is an E3 ligase that degrades multiple different proteins, and plays an oncogenic role in human cancer. In this study, we explore the molecular mechanism by which diosgenin mediates anti-tumor effects in prostate cancer cells. We found that diosgenin treatment led to cell growth inhibition, apoptosis and cell cycle arrest. Notably, we found that diosgenin inhibited the expression of NEDD4 in prostate cancer cells. Furthermore, overexpression of NEDD4 overcame the diosgenin-mediated anti-tumor activity, while downregulation of NEDD4 promoted the diosgenin-induced anti-cancer function in prostate cancer cells. Our findings indicate that diosgenin is a potential new inhibitor of NEDD4 in prostate cancer cells.

lncRNA MIR503HG functioned as a tumor suppressor and inhibited cell proliferation, metastasis and epithelial-mesenchymal transition in bladder cancer.

Bladder cancer is the most common malignancy with high recurrence. Currently, the long noncoding RNAs (lncRNAs) have been suggested to play vital roles in the pathogenesis of bladder cancer. The present study investigated the role of lncRNA MIR503 host gene (MIR503HG) in the pathogenesis of bladder cancer by using both in vitro and in vivo functional assays. The expression of MIR503HG was downregulated in bladder cancer tissues and cell lines. Low expression of MIR503HG was associated with advanced tumor stage, advanced histological grade, and lymph node metastasis. Ectopic expression of MIR503HG inhibited cell proliferation, cell growth, cell invasion, and migration, and also promoted cell apoptosis and inhibited cell cycle progression in SW780 cells. In parallel, T24 cells were used for loss-of-function studies. Knockdown of MIR503HG promoted the cancer cell proliferation and increased the migration and invasion abilities of T24 cells. In addition, knockdown of MIR503HG reduced the cell apoptotic rate in cancer cells and promoted cell cycle progression. Furthermore, MIR503HG overexpression decreased the epithelial-mesenchymal transition-related mRNA and protein levels of ZEB1, Snail, N-cadherin, and vimentin, with an increase in E-cadherin level. Consistently, knockdown of MIR503HG showed the opposite effects. In vivo xenograft, nude mice results showed that overexpression of MIR503HG suppressed the tumor growth and tumor metastasis. In conclusion, our results identified a novel lncRNA MIR503HG that exhibited significant antiproliferation, antimigration/invasion effects on bladder cancer cells both in vitro and in vivo, which may hold a therapeutic promise to treat bladder cancer.

The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion.

Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of renal cell carcinoma (RCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 307 cases of RCC tissues and 34 normal renal tissues. The Cul1 expression was increased significantly in RCC and was correlated with renal carcinoma histology grade (P = 0.007), tumor size (P = 0.013), and pT status (P = 0.023). Also, we found that silencing of Cul1 leads to increased expression of p21 and p27 that could inhibit the cyclin D1 and cyclin E2 expressions and arrest cell cycle at the G1 phase. Furthermore, knockdown of Cul1 inhibits RCC cell migration and invasion abilities by up-regulating the expression of TIMP-1 which could inhibit the expression of MMP-9. Finally, using bioluminescence imaging, we found that Cul1 knockdown significantly reduced the tumor growth in vivo. Cul1 may constitute a potential therapeutic target in RCC.

Prostate-specific Antigen Density Variation Rate as a Potential Guideline Parameter for Second Prostate Cancer Detection Biopsy.

BACKGROUND: The diagnostic value of current prostate-specific antigen (PSA) tests is challenged by the poor detection rate of prostate cancer (PCa) in repeat prostate biopsy. In this study, we proposed a novel PSA-related parameter named PSA density variation rate (PSADVR) and designed a clinical trial to evaluate its potential diagnostic value for detecting PCa on a second prostate biopsy. METHODS: Data from 184 males who underwent second ultrasound-guided prostate biopsy 6 months after the first biopsy were included in the study. The subjects were divided into PCa and non-PCa groups according to the second biopsy pathological results. Prostate volume, PSA density (PSAD), free-total PSA ratio, and PSADVR were calculated according to corresponding formulas at the second biopsy. These parameters were compared using t-test or Mann-Whitney U-test between PCa and non-PCa groups, and receiver operating characteristic analysis were used to evaluate their predictability on PCa detection. RESULTS: PCa was detected in 24 patients on the second biopsy. Mean values of PSA, PSAD, and PSADVR were greater in the PCa group than in the non-PCa group (8.39 µg/L vs. 7.16 µg/L, 0.20 vs. 0.16, 14.15% vs. -1.36%, respectively). PSADVR had the largest area under the curve, with 0.667 sensitivity and 0.824 specificity when the cutoff was 10%. The PCa detection rate was significantly greater in subjects with PSADVR >10% than PSADVR ≤10% (28.6% vs. 6.5%, P< 0.001). In addition, PSADVR was the only parameter in this study that showed a significant correlation with mid-to-high-risk PCa (r = 0.63, P = 0.03). CONCLUSIONS: Our results demonstrated that PSADVR improved the PCa detection rate on second biopsies, especially for mid-to-high-risk cancers requiring prompt treatment.

N-acetylcysteine Ameliorates Prostatitis via miR-141 Regulating Keap1/Nrf2 Signaling.

Chronic prostatitis was the most common type of prostatitis and oxidative stress was reported to be highly elevated in prostatitis patients. In this study, we determined the effect of N-acetylcysteine (NAC) on prostatitis and the molecular mechanism involved in it. Male Sprague-Dawley rats were divided into three groups: control group (group A, n = 20), carrageenan-induced chronic nonbacterial prostatitis (CNP) model group (group B, n = 20), and carrageenan-induced CNP model group with NAC injection (group C, n = 20). Eye score, locomotion score, inflammatory cell count, cyclooxygenase 2 (COX2) expression, and Evans blue were compared in these three groups. The expression of miR-141 was determined by quantitative real-time PCR (qRT-PCR). Moreover, protein expressions of Kelch-like ECH-associated protein-1 (Keap1) and nuclear factor erythroid-2 related factor 2 (Nrf2) and its target genes were examined by Western blot. Luciferase reporter assay was performed in RWPE-1 cells transfected miR-141 mimic or inhibitor and the plasmid carrying 3'-UTR of Keap1. The value of eye score, locomotion score, inflammatory cell count, and Evans blue were significantly decreased in group C, as well as the expression of COX2, when comparing to that of group B. These results indicated that NAC relieved the carrageenan-induced CNP. Further, we found that NAC increased the expression of miR-141 and activated the Keap1/Nrf2 signaling. Luciferase reporter assay revealed that miR-141 mimic could suppress the activity of Keap1 and stimulate the downstream target genes of Nrf2. In addition, miR-141 inhibitor could reduce the effect of NAC on prostatitis. NAC ameliorates the carrageenan-induced prostatitis and prostate inflammation pain through miR-141 regulating Keap1/Nrf2 signaling.

Comparison of Treatment Outcomes of Different Spermatic Vein Ligation Procedures in Varicocele Treatment.

In this study, 4 different spermatic vein ligation procedures for varicocele (VC) treatment were compared based on recurrence rate, postoperative complications, and semen quality. Between January 2012 and May 2013, a total of 345 male patients with VC were recruited at The First Affiliated Hospital of Soochow University. Patients were performed by different ligation procedures, and they were divided into 4 groups: laparoscopic varicocelectomy group (LV group: n = 84), microscopic inguinal varicocelectomy group (MIV group: n = 85), microscopic retroperitoneal varicocelectomy group (MRV group: n = 86), and microscopic subinguinal varicocelectomy group (MSV group: n = 90). In MSV group, the operative time was 55 ± 6.9 minutes, which was significantly longer than LV, MIV, and MRV groups (P < 0.05). Recurrence rate in LV group was at 11.9%, the highest rate observed compared with the MIV, MRV, and MSV groups (P < 0.05). Scrotal edema and testicular atrophy in MSV group were markedly decreased (P < 0.05), and scrotal pain was relieved in almost all patients in the MSV group at a significantly higher rate than LV, MIV, and MRV groups (P < 0.05). Sperm concentration, sperm count of grades a + b, and sperm motility (%) in the MSV group were sharply higher than LV, MIV, and MRV groups (all P < 0.05). Our study indicates that MSV is the most beneficial of the 4 spermatic vein ligation procedures and may be offered as the first-line treatment for VC in infertile men.

Management of symptomatic caliceal diverticular calculi: Minimally invasive percutaneous nephrolithotomy versus flexible ureterorenoscopy.

OBJECTIVE: To retrospectively evaluate appropriate treatment for patients with symptomatic caliceal diverticular calculi, by comparing the therapeutic outcomes for those undergoing minimally invasive percutaneous nephrolithotomy (MPCNL) and flexible ureterorenoscopy (F-URS). METHODS: From March 2009 to May 2014, 36 consecutive patients with caliceal diverticular calculi were divided into 2 groups: 21 patients underwent MPCNL, and 15 were treated by F-URS. All procedures were performed by one surgical group, which ensured relatively constant parameters. Patient characteristics, operative time, hospital stay after surgery, stone-free rate, symptomatic improvement rate, complications, diverticular obliteration, and stone composition were analyzed retrospectively in the 2 groups. RESULTS: Patient preoperative variables were comparable between the two groups, with no significant difference (P > 0.05). Mean operative time was 136.9 ± 22.8 min in the MPCNL group and 117.3 ± 24.3 min in the F-URS group (P = 0.019). Hospital stay was significantly longer in the MPCNL group than in the F-URS group (9.4 ± 3.1 vs. 6.9 ± 2.1 days, P = 0.010). The stone-free rates after MPCNL and F-URS were 90.5% (19/21) and 60.0% (9/15), respectively (P = 0.046). Additionally, 71.4% (15/21) of patients in the MPCNL group and 46.7% (7/15) of patients in the F-URS group had symptomatic improvement at the 6-month follow-up (P = 0.175); the rates of complications in the 2 groups were 19.0% (4/21) and 13.3% (2/15), respectively (P = 0.650). Complete diverticular obliteration was achieved in 16 (76.2%) cases in the MPCNL group and 5 (33.3%) cases in the F-URS group (P = 0.017). The distributions of calcium oxalate and hydroxyapatite in the stones were 66.7% (14/21) and 33.3% (7/21), respectively, in the MPCNL group; however, the distributions in the F-URS group were 46.7% (7/15) and 53.3% (8/15), respectively (P = 0.310). CONCLUSION: MPCNL is an effective method for the treatment of caliceal diverticular calculi. However, F-URS is an alternative technique in selected patients with a patent infundibulum, despite lower stone-free rates than with MPCNL. Fulguration of the diverticular lining with a high-power holmium laser and permitting the cavity to collapse are useful to increase the chance of diverticular obliteration.

Randomized prospective trial of tubeless versus conventional minimally invasive percutaneous nephrolithotomy.

PURPOSE: To evaluate the effectiveness and safety of minimally invasive percutaneous nephrolithotomy (mPCNL) without nephrostomy drainage tubes. METHODS: We prospectively enrolled 32 eligible patients with kidney stones at our hospital. Patients were randomly assigned to a conventional mPCNL group (ureteric Double-J stents and nephrostomy drainage tubes) or a tubeless mPCNL group (ureteric catheter but no drainage tubes). A single experienced surgeon performed all operations. RESULTS: At baseline, the two groups had similar age, maximum stone diameter, and gender distribution. There were no significant differences in operation time, presence of postoperative fever, stone clearance, and level of postoperative serum hemoglobin. However, the tubeless mPCNL group had significantly shorter hospital stays (3 vs. 4 days, p = 0.032) and significantly less back pain (5 patients vs. 14 patients, p = 0.003) than the conventional mPCNL group. CONCLUSIONS: No significant differences were found between conventional and tubeless mPCNL in safety issues and stone clearance rate. However, patients treated with tubeless mPCNL had shorter hospitalization stays and were less likely to experience back pain.

Variants on ESR1 and their association with prostate cancer risk: a meta-analysis.

BACKGROUND: Epidemiological studies evaluating the association of two variants rs9340799 and rs2234693 on estrogen receptor 1 (ESR1) with prostate risk have generated inconsistent results. METHODS: A meta-analysis was here conducted to systematically evaluate the relationship of these two variants with prostate cancer susceptibility. RESULTS: For rs9340799, heterozygosity of T/C carriers showed a significant increased prostate cancer risk with a pooled odds ratio (OR) of 1.34 (95% CI = 1.06-1.69) while homozygote C/C carriers showed an increased but not statistically significant association with prostate cancer risk (pooled OR = 1.29, 95% CI = 0.94-1.79). Compared to the homozygous TT carriers, the allele C carriers showed a 31% increased risk for prostate cancer (pooled OR = 1.31, 95% CI = 1.06-1.63). No significant association between the rs2234693 and prostate cancer risk was found with the pooled OR of 1.15 (95% CI = 0.97-1.39, T/C and C/C vs. T/T) under the dominant genetic model. Compared to the homozygote T/T carriers, the heterozygous T/C carriers did not show any significantly different risk of prostate cancer (pooled OR = 1.13, 95% CI = 0.94-1.36) and the homozygous C/C carriers also did not show a significant change for prostate cancer risk compared to the wide-type T/T carriers (pooled OR = 1.26, 95% CI = 0.98-1.62). CONCLUSIONS: These data suggested that variant rs9340799, but not rs2234693, on ESR1 confers an elevated risk of prostate cancer.

Clinical application of the adenosine triphosphate-based response assay in intravesical chemotherapy for superficial bladder cancer.

OBJECTIVE: To investigate correlations between adenosine triphosphate chemotherapy response assay (ATP-CRA) and clinical outcomes after ATP-CRA-based chemotherapy for drug selection in patients receiving intravesical chemotherapy to prevent recurrence of superficial bladder cancer after surgery. METHODS: The chemosensitivities of 12 anticancer drugs were evaluated, including 5-Fu ADM, and EPI, using ATP-CRA and primary tumor cell culture in 54 patients. In addition, a further 58 patients were treated according to clinical experience. Differences in post-chemotherapeutical effects between drug sensitivity assay and experience groups were compared. RESULTS: The evaluable rate of the test was 96.3%, the clinical effective rate was 80.8%, the sensitivity rate was 97.6% (41/42), the specificity was 20%, the total predicting accuracy was 74.3%, the positive predictive value was 83.7% (41/49), the negative predictive value was 66.7% (2/3); in the drug sensitivity test group, the clinical effective rate was 80.8%, the experience group response rate was 63.8%, with a significant difference in clinical effects between the ATP-based sensitivity and experience groups (χ2 =7.0153, P<0.01). CONCLUSION: ATP-CRA is a stable, accurate and potentially practical chemosensitivity test providing a predictor of chemotherapeutic response in patients with superficial bladder cancer.

[All-trans retinoic acid enhances bystander effect of suicide-gene therapy against androgen-unresponsive prostate cancer].

OBJECTIVE: To investigate the enhancing effect of all-trans retinoic acid (ATRA) on the bystander effect of the herpes simplex virus thymidine kinase(HSV-TK)/ganciclovir (GCV) against androgen unresponsive prostate cancer. METHODS: The bystander effect of the HSV-TK/GCV system was measured by methyl thiazolyl tetrazolium (MTT) assay on PC-3 cells before and after ATRA treatment. The growth and the histopathology of transplant tumors were observed in 4 groups of nude mice with prostate cancer. RESULTS: ATRA augmented significantly the bystander effect of the HSV-TK/GCV system by reducing TK positive PC-3 cells from 50% to 30% (P < 0.05). HSV-TK showed an inhibiting effect, while ATRA with the HSV-TK/GCV system produced significant effect on prostate cancer 1 week earlier than the former (P < 0.05). CONCLUSION: ATRA can argument the in vivo and in vitro bystander effect of the HSV-TK/GCV system in the treatment of androgen unresponsive prostate cancer.