Clinical Utility of Prostate Health Index for Diagnosis of Prostate Cancer in Patients with PI-RADS 3 Lesions.

The risk of prostate cancer (PCa) in prostate imaging reporting and data system version 2 (PI-RADSv2) score-3 lesions is equivocal; it is regarded as an intermediate status of presented PCa. In this study, we evaluated the clinical utility of the prostate health index (PHI) for the diagnosis of PCa and clinically significant PCa (csPCa) in patients with PI-RADSv2 score-3 lesions. The study cohort included patients who underwent a transrectal ultrasound (TRUS)-guided, cognitive-targeted biopsy for PI-RADSv2 score-3 lesions between November 2018 and April 2021. Before prostate biopsy, the prostate-specific antigen (PSA) derivatives, such as total PSA (tPSA), [-2] proPSA (p2PSA) and free PSA (fPSA) were determined. The calculation equation of PHI is as follows: [(p2PSA/fPSA) × tPSA ½]. Using a receiver operating characteristic (ROC) curve analysis, the values of PSA derivatives measured by the area under the ROC curve (AUC) were compared. For this study, csPCa was defined as Gleason grade 2 or higher. Of the 392 patients with PI-RADSv2 score-3 lesions, PCa was confirmed in 121 (30.9%) patients, including 59 (15.1%) confirmed to have csPCa. Of all the PSA derivatives, PHI and PSA density (PSAD) showed better performance in predicting overall PCa and csPCa, compared with PSA (all p < 0.05). The AUC of the PHI for predicting overall PCa and csPCa were 0.807 (95% confidence interval (CI): 0.710−0.906, p = 0.001) and 0.819 (95% CI: 0.723−0.922, p < 0.001), respectively. By the threshold of 30, PHI was 91.7% sensitive and 46.1% specific for overall PCa, and was 100% sensitive for csPCa. Using 30 as a threshold for PHI, 34.4% of unnecessary biopsies could have been avoided, at the cost of 8.3% of overall PCa, but would include all csPCa.

Utility of Contemporary Health Screening in the Diagnosis of Bladder Cancer.

BACKGROUND: To evaluate the utility of contemporary health screening (HS) in the diagnosis of bladder cancer (BCa). METHODS: We retrospectively reviewed 279,683 individuals who underwent HS between February 1995 and April 2015. Among these individuals, 74 were diagnosed with BCa within a year after the HS and were included in the analysis. Screen-detected BCa was defined as when a referral was made to a urologist due to microscopic hematuria (MH) on urinalysis, abnormal imaging, or any urological symptoms observed at the HS. Screen-undetected BCa was defined as when no referral was made to a urologist because of no abnormality observed at the HS, but a visit to a urological outpatient clinic later was followed by a BCa diagnosis. The incidences of screen-detected BCa and BCa in the Korean population were compared. Clinicopathological characteristics were compared between the screen-detected BCa and screen-undetected BCa groups. RESULTS: The detection rate of BCa was 17.2 per 100,000, which exceeded the 2020 estimated national crude incidence rate of 9.3 per 100,000 by approximately 1.7 times. Among the 74 patients diagnosed with BCa within a year after HS, 48 (64.9%) had screen-detected BCa. The screen-detected BCa group had a higher T stage (p = 0.009) and grade (p = 0.019) than the screen-undetected BCa group. However, the overall survival was not significantly different between the two groups (p = 0.677). A positive correlation between the MH grade and the T stage was identified (p = 0.001). CONCLUSION: Although HS is not focused on BCa screening, contemporary HS can contribute to the detection of BCa.

Preoperative versus Postoperative Compensation of the Contralateral Normal Kidney in Patients Treated with Radical Nephrectomy for Renal Cell Carcinoma.

BACKGROUND: We sought to identify the factors affecting renal compensatory processes that occur preoperatively as well as postoperatively in patients treated with radical nephrectomy (RNx) for renal cell carcinoma (RCC). METHODS: We retrospectively reviewed the records of 906 patients treated with RNx for RCC. We defined the early compensatory process (process 1) as compensatory adaptation of the contralateral normal kidney (CNK) before RNx. We defined the late compensatory process (process 2) as compensatory adaptation of the CNK after RNx. Total compensation was defined as the combination of these two processes. Multivariable logistic regression analyses were used to identify significant factors associated with processes 1, 2 and total compensation. RESULTS: Mean preoperative, 1-week, and 5-year postoperative estimated glomerular filtration rates (eGFR) were 84.5, 57.6 and 63.7 mL/min/1.73 m2, respectively. Female sex (p < 0.001), lower body mass index (BMI) (p < 0.001), absence of hypertension (p = 0.019), lower preoperative eGFR (p < 0.001), larger tumor volume (p < 0.001), and larger CNK volume (p < 0.001) were significantly associated with process 1. Younger age (p = 0.019), higher BMI (p < 0.001), and absence of diabetes mellitus (DM) (p = 0.033) were significantly associated with process 2. Female sex (p < 0.001), younger age (p < 0.001), absence of DM (p = 0.002), lower preoperative eGFR (p < 0.001), and larger tumor (p = 0.001) and CNK volumes (p < 0.001) were significantly associated with total compensation. CONCLUSIONS: Different factors affected each compensatory process. Process 1 made a greater contribution to the entire renal compensatory process than process 2.

Can Prostate-Specific Antigen Density Be an Index to Distinguish Patients Who Can Omit Repeat Prostate Biopsy in Patients with Negative Magnetic Resonance Imaging?

PURPOSE: We evaluated the negative predictive value (NPV) of multiparametric magnetic resonance imaging (mpMRI) in detecting clinically significant prostate cancer (csPCa) according to biopsy setting and prostate-specific antigen density (PSAD) using transperineal template-guided saturation prostate biopsy (TPB) as the reference standard. METHODS: A total of 161 patients with biopsy histories and negative pre-biopsy mpMRI (Prostate Imaging Reporting and Data System version 2 scores of less than 3) participated in the study. TPB was performed on the following indications: "prior negative biopsy" in patients with persistent suspicion of prostate cancer (n = 91) or "confirmatory biopsy" in patients who were candidates for active surveillance (n = 70). The csPCa was defined as a Gleason score of 3 + 4 or greater. We calculated the NPV of mpMRI in detecting csPCa according to biopsy history and prostate-specific antigen density (PSAD) and conducted a logistic regression analysis to determine the clinical predicator for the absence of csPCa. RESULTS: The detection rate of csPCa was 5.5% in the prior negative biopsy group and 14.3% in the confirmatory biopsy group (P = 0.057). None of the variables in the logistic regression models including PSAD <0.15 ng/mL/cc and prior negative biopsy could predict the absence of csPCa. The NPV of mpMRI in detecting csPCa in patients with a prior negative biopsy worsen from 94.5% to 93.3% when combined with PSAD <0.15 ng/mL/cc. CONCLUSION: Patients with negative mpMRI findings may not omit repeat biopsy even if their prior biopsy histories are negative and PSADs are <0.15 ng/mL/cc.

Metastatic renal cell carcinoma to the pancreas: Clinical features and treatment outcome.

BACKGROUND AND OBJECTIVES: Metastatic renal cell carcinoma to the pancreas (PM-RCC) is infrequent; we sought to describe the characteristics of PM-RCC and analyze the outcome following treatment. METHODS: Data of 3107 mRCC patients treated between 1992 and 2007 from the Korean Renal Cancer Study Group database were obtained to identify 300 (9.7%) PM-RCC patients. Characteristics and survival were analyzed and compared to the rest of the mRCC, according to the timing of metastasis and surgical treatments received. RESULTS: PM-RCC was younger at initial diagnosis (55.0 vs. 58.2 years), more frequently in women (30.3% vs. 22.3%), and metachronous (65.3% vs. 41.9%) with a longer disease-free period (82.0 vs. 33.0 months). Overall survival (OS) was significantly better in PM-RCC but pancreas metastasectomy was associated with improved OS only among metachronous PM-RCC. In the 132 metachronous PM-RCC with pancreas metastasectomy, median recurrence-free survival was 17.2 months and we found Heng risk group (hazard ratio [HR] = 2.384, 95% confidence interval [CI] = 1.213-4.684), younger age (HR = 0.965, 95% CI = 0.945-0.987), shorter interval to pancreas metastasis (HR = 0.993, 95% CI = 0.986-0.999), and Eastern Cooperative Oncology Group performance status to be predictive of early progression following pancreas metastasectomy. CONCLUSION: Compared to the other mRCC, PM-RCC demonstrated a favorable prognosis. Pancreas metastasectomy was associated with prolonged survival in the metachronous PM-RCC with a long progression-free period.

Detection rate of clinically insignificant prostate cancer increases with repeat prostate biopsies.

To analyze if clinically insignificant prostate cancer (CIPC) is more frequently detected with repeat prostate biopsies, we retrospectively analyzed the records of 2146 men diagnosed with prostate cancer after one or more prostate biopsies. The patients were divided into five groups according to the number of prostate biopsies obtained, e.g. group 1 had one biopsy, group 2 had two biopsies and group 3 had three biopsies. Of the 2146 patients diagnosed with prostate cancer, 1956 (91.1%), 142 (6.6%), 38 (1.8%), 9 (0.4%) and 1 (0.1%) men were in groups 1, 2, 3, 4 and 5, respectively. Groups 4 and 5 were excluded because of the small sample sizes. The remaining three groups (groups 1, 2 and 3) were statistically analyzed. There were no differences in age or prostate-specific antigen level among the three groups. CIPC was detected in 201 (10.3%), 28 (19.7%) and 9 (23.7%) patients in groups 1, 2 and 3, respectively (P<0.001). A multivariate analysis showed that the number of biopsies was an independent predictor to detect CIPC (OR=2.688 for group 2; OR=4.723 for group 3). In conclusion, patients undergoing multiple prostate biopsies are more likely to be diagnosed with CIPC than those who only undergo one biopsy. However, the risk still exists that the patient could have clinically significant prostate cancer. Therefore, when counseling patients with regard to serial repeat biopsies, the possibility of prostate cancer overdiagnosis and overtreatment must be balanced with the continued risk of clinically significant disease.

Percent tumor volume predicts biochemical recurrence after radical prostatectomy: multi-institutional data analysis.

BACKGROUND: To investigate the prognostic significance of percent tumor volume (PTV) in relation to the surgical margin status in men with prostate cancer after radical prostatectomy (RP). METHODS: Clinical and pathological data from 1,567 patients treated with RP only between 1995 and 2007 at participating institutions were reviewed. PTV was determined by the sum of all visually estimated tumor foci on every section. Biochemical recurrence (BCR) was defined as 2 consecutive increases in prostate-specific antigen (PSA) > 0.2 ng/ml and various clinicopathological variables were tested for prognostication of recurrence-free survival. RESULTS: Serum PSA at surgery was 12.5 ± 16.8 ng/ml and pathological stage was T2 in 899 (57.4%) patients. Surgical Gleason score was 7 in 842 patients (53.7%), higher than 7 in 250 (16%) patients, and in 32% of the patients, surgical margin was positive. Mean PTV was 15.7% and demonstrated a significant positive correlation with serum PSA, all pathological variables and BCR. On multivariate analysis, preoperative PSA (p = 0.012), surgical Gleason score (p < 0.0001, HR 2.183, 95% CI 1.778-2.681), and PTV (≤5, 5.1-15, >15%; p < 0.0001, HR 1.393, 95% CI 1.183-1.641) were independently prognostic of recurrence-free survival. Pathological stage demonstrated a significant relationship with BCR but was not independently prognostic in the multivariate model. CONCLUSION: In men with prostate cancer, preoperative PSA, surgical Gleason score, and PTV are independent predictors of recurrence-free survival after RP.

Prognostic factors and clinical outcomes of urological soft tissue sarcomas.

PURPOSE: The purpose of this study was to elucidate prognostic factors for survival and clinical outcomes of rological soft tissue sarcomas (STSs). MATERIALS AND METHODS: This was a retrospective review of the medical records of 48 patients with urological STS treated from January 1982 to July 2009. Demographic and pathological characteristics were compared. Patients' demographics, clinico-pathological parameters, overall survival, and the factors expected to predict survival, such as sex, age at diagnosis, primary organ, surgical resection, metastasis, and mass size, were analyzed. We evaluated differences in survival on the basis of histological subtype by Kaplan-Meier analysis and multivariate Cox proportional hazards regression. RESULTS: The study included 34 males (70.8%) and 14 females (29.1%). The mean age at diagnosis was 47.1 years (range, 3 to 80). The most common site was the retroperitoneum (n=16), followed by the kidney (n=12), prostate (n=10), bladder (n=7), ureter (n=1), and paratesticular region (n=1). Nineteen patients (39.5%) had other organ metastases at diagnosis. The most common subtypes of sarcoma were leiomyosarcoma (50%), rhabdomyosarcoma (18.7%), and liposarcoma (8%). The remaining 11 cases had other histological subtypes (22.9%). Mean tumor size was 9.5 cm (range, 2.2 to 24). Thirty-three patients (68.7%) underwent surgical resection. The overall survival rate at 5 years was 51.4%. In the univariate and multivariate analysis, surgical resection, primary tumor site, and metastasis at diagnosis remained significant predictors of prognosis. Patients with retroperitoneal sarcoma had a higher overall survival rate by 5 years compared with patients with other organ sarcoma. CONCLUSIONS: The overall survival rate at 5 years was 51.4%. Surgical resection, primary tumor site, and metastasis at diagnosis remained significant predictors of prognosis.

Targeting beta2-microglobulin mediated signaling as a novel therapeutic approach for human renal cell carcinoma.

PURPOSE: We previously reported that the biological functions of beta2-microglobulin include antigen presentation and oncogenic activity. In the current study we investigated the direct role of beta2-microglobulin in the regulation of human renal cell carcinoma cell growth and the possible apoptotic inducing effect of blocking the beta2-microglobulin signaling pathway using an anti-beta2-microglobulin neutralizing antibody. MATERIALS AND METHODS: We examined the effects of recombinant beta2-microglobulin protein and anti-beta2-microglobulin antibody on renal cell carcinoma cell growth and apoptosis in vitro. To seek a molecular understanding of anti-beta2-microglobulin antibody induced apoptosis we analyzed alterations in the growth and survival signaling components in the phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase and c-jun N-terminal kinase mediated pathways using corresponding kinase inhibitors in SN12C cells. RESULTS: Recombinant beta2-microglobulin protein increased the growth of the 3 human renal cell carcinoma cell lines SN12C, Caki-1 and ACHN in a dose and time dependent manner. Treatment of SN12C, Caki-1 and ACHN cells with an anti-beta2-microglobulin polyclonal antibody strongly suppressed the growth of these cells in vitro, also in a dose and time dependent manner. The addition of recombinant beta2-microglobulin protein or anti-beta2-microglobulin antibody increased or decreased, respectively, the anchorage independent growth of SN12C cells. The recombinant beta2-microglobulin protein accelerated cell growth via activating phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase, and induced the phosphorylation of Bcl-xL/Bcl-2-associated death promoter. However, treatment with anti-beta2-microglobulin antibody induced cell death by inhibiting the phosphorylation of Akt and extracellular signal-regulated kinase, and activating c-jun N-terminal kinase, resulting in the induction of phosphorylation of B-cell lymphoma 2 and decreased phosphorylation of Bcl-xL/Bcl-2-associated death promoter, leading to apoptosis. CONCLUSIONS: Our results demonstrate that beta2-microglobulin has an important role in regulating the growth and survival of renal cell carcinoma cells and anti-beta2-microglobulin antibody offers a potential novel therapy for the treatment of human renal cell carcinoma.

Rapid communication: cosmetic circumumbilical incision for extraction of specimen after laparoscopic radical prostatectomy.

Extension of a longitudinal incision at the umbilicus for extraction of a specimen after laparoscopic radical prostatectomy leaves clearly visible scars. We performed a circumumbilical incision in 40 consecutive patients undergoing laparoscopic radical prostatectomy resulting in a favorable cosmetic outcome without complications.

Laparoscopic radical cystectomy with extracorporeal urinary diversion: preliminary experience.

AIM: We present our experience with the fi rst eight patients who underwent laparoscopic radical cystectomy with bilateral pelvic lymphadenectomy and extracorporeal urinary diversion. Patients, operative data and the surgical techniques are presented. METHODS: Between June 2003 and April 2004, seven men and one woman with organ-con fi ned muscle-invasive transitional cell carcinoma of the bladder underwent laparoscopic radical cystectomy with urinary diversion. The age range was 41-73 years. Laparoscopic radical cystectomy and bilateral pelvic lymphadenectomy were performed using fi ve ports by a transperitoneal approach. An ileal conduit diversion or ileal W-neobladder was constructed through the site of specimen retrieval. RESULTS: We performed eight radical cystectomies with ileal conduits (six cases) or orthotopic ileal W-neobladders (two cases). Conversion to open surgery was necessary in one due to technical dif fi culty in urethroneobladder anastomosis. Mean operating time was 560 min (range 455-680). Mean estimated blood loss was 675 mL (range 400-1050). Two of the eight patients needed blood transfusion (800 mL each). Mean days to oral intake and ambulation was 4.4 (range 2-6) and 4.1 (range 3-5), respectively. Mean hospital stay was 12.8 days (range 7-28). Mean follow up was 6.1 months (range 4-14). Histopathological examination of the specimens revealed stage T2N0M0 in fi ve cases, T3aN0M0 in one, T3aN1M0 in one and T3bN1M0 in one. No metastases have been detected and all are alive and free of disease. CONCLUSION: Laparoscopic radical cystectomy is feasible, although dif fi cult and technically demanding, and our results are promising. With more experience and improvement of the surgical technique, laparoscopic radical cystectomy with urinary diversion may become an alternative surgical method for treating the selected patients with localized muscle invasive bladder cancer.

Prevention of tissue injury by ribbon antisense to TGF-beta1 in the kidney.

Transforming growth factor-beta1 (TGF-beta1) is an important mediator of glomerulosclerosis and tubulointerstitial fibrosis in renal diseases. We designed ribbon-type antisense oligos of TGF-beta1, TGF-beta1 RiAS, and combined them with a short peptide of the nuclear localization signal to form a transfection complex of DNA/peptide/liposomes (DPL) for enhanced cellular uptake. When H4IIE cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was reduced by >70%. We then examined the ratio of the kidney weight per body weight in rats. Whereas the weight ratio was 0.47% for the normal kidney, the ratio was 0.99% on day 5 after unilateral ureteric obstruction (UUO). The ratios were 0.95% with PBS injection, 1.07% with scrambled RiAS, and 0.68% with TGF-beta1 RiAS. When examined for TGF-beta1 expression in the tissue, the level of TGF-beta1 mRNA was also significantly reduced following treatment with TGF-beta1 RiAS. Further, physical changes such as diminished dilation, atrophy, as well as apoptosis caused by UUO were also found to be markedly reduced by TGF-beta1 RiAS. The results show that ribbon antisense to TGF-beta1 when combined with efficient uptake can effectively block TGF-beta1 expression and preserve tissue integrity in kidneys with UUO.