Machine learning algorithms can more efficiently predict biochemical recurrence after robot-assisted radical prostatectomy.

OBJECTIVES: To develop a model for predicting biochemical recurrence (BCR) in patients with long follow-up periods using clinical parameters and the machine learning (ML) methods. MATERIALS METHOD: Patients who underwent robot-assisted radical prostatectomy between January 2014 and December 2019 were retrospectively reviewed. Patients who did not have BCR were assigned to Group 1, while those diagnosed with BCR were assigned to Group 2. The patient's demographic data, preoperative and postoperative parameters were all recorded in the database. Three different ML algorithms were employed: random forest, K-nearest neighbour, and logistic regression. RESULTS: Three hundred and sixty-eight patients were included in this study. Among these patients, 295 (80.1%) did not have BCR (Group 1), while 73 (19.8%) had BCR (Group 2). The mean duration of follow-up and duration until the diagnosis of BCR was calculated as 35.2 ± 16.7 and 11.5 ± 11.3 months, respectively. The multivariate analysis revealed that NLR, PSAd, risk classification, PIRADS score, T stage, presence or absence of positive surgical margin, and seminal vesicle invasion were predictive for BCR. Classic Cox regression analysis had an area under the curve (AUC) of 0.915 with a sensitivity and specificity of 90.6% and 79.8%. The AUCs for receiver-operating characteristic curves for random forest, K nearest neighbour, and logistic regression were 0.95, 0.93, and 0.93, respectively. All ML models outperformed the conventional statistical regression model in the prediction of BCR after prostatectomy. CONCLUSION: The construction of more reliable and potent models will provide the clinicians and patients with advantages such as more accurate risk classification, prognosis estimation, early intervention, avoidance of unnecessary treatments, relatively lower morbidity and mortality. The ML methods are cheap, and their powers increase with increasing data input; we believe that their clinical use will increase over time.

Comparison of preoperative locoregional Ga-68 PSMA-11 PET-CT and mp-MRI results with postoperative histopathology of prostate cancer.

BACKGROUND: Conventional imaging modalities are inadequate to evaluate locoregional extension of prostate cancer (PCa). The aim of the current retrospective study was to investigate the diagnostic efficacy of Gallium-68 prostate-specific membrane antigen-11 (Ga-68 PSMA-11) positron emission tomography/computed tomography (PET/CT) and multiparametric magnetic resonance imaging (mp-MRI) for staging preoperative PCa patients with correlating histopathology. MATERIALS AND METHODS: Twenty-four patients with histologically proven PCa underwent both Ga-68 PSMA-11 PET/CT and mp-MRI before robot-assisted laparoscopic radical prostatectomy. For each tumor area, correlations with histopathological results were defined for tumor localization, extraprostatic extension (EPE) of the tumor, invasion of seminal vesicle (SVI) and bladder neck invasion (BNI). In patients with regional lymph node (LN) dissection, histopathological results were also correlated with imaging modalities. RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of EPE and SVI were higher for mp-MRI than Ga-68 PSMA-11 PET/CT. On the other hand Ga-68 PSMA-11 PET/CT had significant successful results for detection of LN metastases when compared with mp-MRI. But for BNI detection both modalities had same insufficient results. Ga-68 PSMA-11 PET/CT had strong results for appropriate tumor localization in the gland. CONCLUSION: Ga-68 PSMA PET/CT has superior results for assessing local LN metastases and for intraprostatic tumor localization. Whereas, mp-MRI must be the preferred modality for determining SVI and EPE. But both imaging modalities failed for determining BNI accurately. Both modalities should be used in conjunction with each other for better treatment planning.

Comparison of antegrade and retrograde laparoscopic radical prostatectomy techniques.

We evaluated the effect of antegrade and retrograde approaches on functional recovery and surgical outcomes of extraperitoneal laparoscopic radical prostatectomy (LRP). We analyzed 135 patients who underwent extraperitoneal LRP, with the retrograde technique performed on 42 (31%; Group 1) and the antegrade technique on 93 (69%; Group 2). Both groups were statistically similar with respect to age, clinical stage, preoperative prostate-specific antigen (PSA) and American Society of Anesthesiologists (ASA) scores, prostate volume, and previous surgical history. Mean operative time was significantly longer in Group 1 (244±18.3 vs. 203.3±18.4 min, p<0.001), whereas mean anastomosis times for both groups were similar (35.8±7.2 vs. 34.7±5.8 min, p=0.155). Estimated blood loss and transfusion rates were significantly lower in Group 2. A significant difference was observed for both hospitalization (6.79±3.3 vs. 5.46±3.08 days, respectively; p=0.026) and catheterization times (12.24±2.1 vs. 11±1.08 days, respectively; p=0.001) for Group 2. The total complication rate was 47.6% in Group 1, and 11.8% in Group 2 (p<0.01). Rates of positive surgical margins were 14.2% and 15% for Groups 1 and 2, respectively. At the 12-month interval from operation, similar recoveries in urinary continence were obtained for both groups (81% in Group 1; 91% in Group 2). Upon comparison of the two LRP techniques, we found that both were effective; however, the latter resulted in lower minor complication rate, lower blood loss, shorter operation time, and shorter length of hospital stay.

Increased testicular 8-hydroxy-2'-deoxyguanosine (8-OHdG) and inducible nitric oxide synthetase (iNOS) and nuclear factor κB (NF-κB) expressions in experimental rat varicocele.

OBJECTIVES: To assess nuclear factor-kappaB (NF-kappaB), inducible NO synthase (iNOS) immunohistochemically, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) biochemically, which are sensitive biological markers of oxidative damage and stress, in testes with experimental varicocele. MATERIALS AND METHODS: Adult rats were randomly divided into three groups. Control group (n: 10), sham group (n: 10), varicocele group (n: 10). Of 14 rats undergoing partial ligation of the left renal vein, 10 rats had developed dilation of the left spermatic vein when evaluated 3 months after varicocele-inducing surgery. The rats were sacrificed after 3 months of the varicocele-inducing surgery. Ipsilateral and contralateral testes were examined for 8-hydroxy-2'-deoxyguanosine (8-OHdG) biochemically, inducible NO synthase (iNOS) and nuclear factor-kappaB (NF-kappaB) expression immunohistochemically. RESULTS: Inducible NO synthase (iNOS), nuclear factor-kappaB (NF-kappaB) expressions and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in both testes of varicocele group were markedly higher compared with control and sham groups (p < 0.01). There was no difference between control and sham groups (p > 0.05). CONCLUSIONS: Regarding to our results, we suggest that varicocele may produce oxidative stress in both of testes, and we believe that this stress may play a role in male fertility.

Stone formation in prostatic urethra after potassium-titanyl-phosphate laser ablation of the prostate for benign prostatic hyperplasia.

We report three cases of stone formation at the prostatic urethra after 80 W potassium-titanyl-phosphate laser ablation of the prostate for benign prostatic hyperplasia. These complications occurred several months after the procedure. The diagnosis was made by ultrasonography, plain radiography of the kidneys, ureters, and bladder, and cystoscopy in patients who were being evaluated after presenting with irritative voiding symptoms. The patients were treated by cystolithotripsy and resection of the calcified prostatic tissue.

Stone formation from intravesical Hem-o-lok clip migration after laparoscopic radical prostatectomy.

Intravesical Hem-o-lok clip (HOLC) migration is a rare complication of prostatic surgery. We report two cases of migration of a HOLC into the bladder leading to stone formation. As such, these devices should be used with caution in the region of the vesicourethral anastomosis.

Curcumin prevents shock-wave lithotripsy-induced renal injury through inhibition of nuclear factor kappa-B and inducible nitric oxide synthase activity in rats.

Shock wave lithotripsy (SWL) is commonly used for treatment of renal stones. Free oxygen radicals are involved in the pathophysiology of renal injury due to SWL. We investigated the protective effects of curcumin, which is an antioxidant and nuclear factor kappa-B (NF-kappaB) inhibitor, against renal injury. Forty-eight rats were included and divided into four groups: group 1, control; group 2, SWL (15 kW-1,500 shocks); group 3, SWL + curcumin (curcumin orally 75 mg/kg/day dissolved in 10% ethyl alcohol, 1 day before and 5 days after SWL); and group 4, SWL + vehicle (10% ethyl alcohol). The kidneys were removed on days 7 and 35 after SWL. A sample was fixed in formaldehyde solution. Renal tissues were examined for proximal tubular injury under light microscope. iNOS activity and active subunit of NF-kappaB, p65, were evaluated immunohistochemically using rat monoclonal antibodies interpreting results semiquantitatively. There were significant differences between SWL and control groups on days 7 and 35, considering histological changes under light microscope (P < 0.02). There was a significant decrease in necrosis and fibrosis in the curcumin group as compared to the SWL group. Expressions of iNOS and p65 on days 7 and 35 were at basal levels with immunohistochemical staining. These parameters had high levels in the SWL group (P < 0.02). No significant difference was present between the control and the curcumin groups (P > 0.02). Curcumin, decreasing expressions of iNOS and p65 and serum nitric oxide levels prevented interstitial, glomerular, tubular epithelial and endothelial cellular injuries. We suggest that curcumin, could be used, especially in high-risk patients, as a protective agent to prevent renal injury due to SWL.

Peritoneal tuberculosis and granulomatous hepatitis secondary to treatment of bladder cancer with Bacillus Calmette-Guérin.

Intravesical administration of Bacillus Calmette-Guérin is used as a treatment method in superficial bladder cancer. While it is generally well tolerated, serious side effects may develop. Granulomatous hepatitis cases have been previously reported; however, only one case with tuberculous peritonitis exists in the current literature. We hereby present two cases, one of which is the second tubercular peritonitis case following Bacillus Calmette-Guérin treatment to be reported, and the other a case with granulomatous hepatitis. Complete cure was achieved in both cases with specific therapy. In the patient who developed peritonitis, intravesical Bacillus Calmette-Guérin therapy was recommenced after antituberculosis treatment, and completed without further complications.

Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population.

We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene (5-HTTLPR) were determined. The 5-HTTLPR (serotonin transporter promoter gene) genotypes in PE patients vs. controls were distributed as follows: L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene: LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the chi2-test. The short (S) allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls (P<0.05). We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup (such as primary and secondary PE) responses to selective serotonin reuptake inhibitors as well as ethnic differences.

Percutaneous versus transurethral cystolithotripsy.

PURPOSE: To compare transurethral cystolithotripsy (TUCL) and percutaneous cystolithotripsy (PCCL) modalities performed during simultaneous transurethral resection of the prostate (TURP) in patients with prostate hyperplasia and large bladder stones. PATIENTS AND METHODS: Sixty-three patients with prostate volume >40 cc and aggregate stone size >2.5 cm were enrolled in the study between August 2003 and February 2007. TUCL (n = 38) or PCCL (n = 25) procedures were performed during simultaneous TURP. In the TUCL group, the stones were removed after fragmentation through a 23F cystolithotripter with pneumatic lithotripsy. This was followed by TURP, performed with a 26F continuous-flow resectoscope. In the PCCL group, the stones were removed through a suprapubic 30F Amplatz sheath after fragmentation. TURP was then performed with the suprapubic sheath providing continuous drainage. RESULTS: Mean age and prostate volumes of the groups were similar. Mean aggregate stone sizes were significantly larger in the PCCL group. The operative time for stone removal was significantly less in the PCCL group while time needed for TURP was statistically similar in the two groups. In the TUCL group, three patients had residual stones necessitating repeated TUCL and urethral stricture developed in three patients. CONCLUSION: The smaller caliber of the working channel during TUCL, compared with PCCL, necessitates disintegration of the stones into smaller fragments. This elongates the duration of the intervention and results in increased urethral and bladder trauma. Combined TURP and PCCL is a safer, more effective, and much faster alternative to combined TURP and TUCL in patients with large bladder stones and prostate hyperplasia.

Quantification of PSA mRNA levels in peripheral blood of patients with localized prostate adenocarcinoma before, during, and after radical prostatectomy by quantitative real-time PCR (qRT-PCR).

OBJECTIVE: To evaluate the clinical value of detected prostate-specific antigen (PSA) mRNA expression levels in circulating cells in patients with prostate cancer by quantitative real-time polymerase chain reaction (qRT-PCR) and to determine the effect of surgical manipulation on hematogenous dissemination. METHODS: Blood samples before, during, and after (24 h) surgery were obtained from 34 patients with prostate cancer who underwent radical prostatectomy for detecting PSA mRNA expression levels. PSA mRNA expression levels, PSA levels, and Gleason scores were then compared. RESULTS: PSA mRNA expression levels were detected in 14 of 34 (41%) patients, and biochemical recurrence of blood PSA was observed in 6 of 34 (17%) patients. Differences of PSA mRNA expression levels in pre-, per-, and postoperative periods were statistically significant (P < 0.001) and differences of PSA mRNA expression levels in pre- and peroperative samples (P < 0.008), pre- and postoperative samples (P < 0.031), and per- and postoperative samples (P < 0.001) were also statistically meaningful. There was significant relationship between the detectable PSA mRNA expression levels in preoperative samples and biochemical recurrence of blood PSA levels. We demonstrated that surgical manipulation had no effect on biochemical recurrence of blood PSA. We also showed that there was significant correlation between high Gleason score and the detectable PSA mRNA expression levels (P < 0.027). CONCLUSIONS: Our results suggest that highly detectable PSA mRNA expression levels in preoperative samples seem to be a significant predictable factor for prostate cancer recurrence.

A single-nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances bladder cancer susceptibility.

OBJECTIVE: To explore the association between the promoter polymorphism (that influences the transcriptional level) of matrix metalloproteinase-1 (MMP-1, associated with tumour cell invasion and metastasis) and bladder cancer in a Turkish population. PATIENTS, SUBJECTS AND METHODS: The MMP-1 polymorphism was assessed in 102 transitional cell carcinomas of the bladder (50 Ta, 52 T2-4) and in 94 age-, smoking- and gender-matched healthy volunteers. The polymerase chain reaction (PCR) assay was used to determine the MMP-1 genotypes. Genomic DNA used for the assay was extracted from peripheral blood lymphocytes. RESULTS: The frequency of the MMP-1 2G/2G genotype, which results in the highest MMP-1 transcriptional level, was compared to that of the 1G/1G plus 1G/2G genotypes. Of the 102 cases with bladder cancer, 49 (48%) showed the 2G/2G genotype, whereas it was found in 22 of the 94 controls (23%); this difference was statistically significant (P < 0.01; odds ratio 2.79, 95% confidence interval, CI, 1.53-5.60). However, there was no significant association between the 2G/2G genotype and tumour grade and pathological stage. We assessed the interaction between smoking status (former and current smokers, by their median pack years) and 2G/2G genotype; there was a significantly increased risk in heavy smokers (P < 0.001; odds ratio 3.21; 95% CI 1.33-5.60). CONCLUSION: These results suggest that the MMP-1 promoter polymorphism might be linked to susceptibility for bladder cancer.

Outcomes of 80 W KTP laser vaporization of the large prostate.

PURPOSE: We evaluated the safety and efficacy of 80 W potassium-titanyl-phosphate (KTP) laser vaporization of the prostate in men with prostate volumes >70 ml. MATERIALS AND METHODS: Laser vaporization of the prostate with an 80 W KTP laser was applied between September 2003 and April 2005. Preoperative evaluation of 100 patients included the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Q(max)), postvoid residual urine volume (PVR), prostate volume, serum sodium, creatinine, hemoglobin, prostate-specific antigen and urinalysis. RESULTS: The mean age of the patients, mean volume of the prostates, mean operative time and mean energy delivery were 67.0 +/- 7.9 (53-90) years, 98.2 +/- 18.9 (74-170) ml, 150.1 +/- 22.7 (100-240) min and 246.1 +/- 77.8 (100-500) kJ, respectively. The serum sodium, creatinine and hemoglobin levels did not change significantly. Urinary retention requiring recatheterization was detected in 10 patients. There was moderate dysuria in 22 patients with a mean duration of 2 months and mild hematuria in 16 patients with a mean duration of 1 month postoperatively. Urinary tract infection occurred in 5 patients. We observed clot retention in 2 patients. The IPSS, Q(max) and PVR values had significantly improved by postoperative months 1, 3, 6 and 12. Reoperation was performed in 5 patients. Internal urethrotomy was performed in 1 patient with bladder neck contracture. CONCLUSIONS: 80 W KTP laser vaporization is a virtually bloodless, safe and effective procedure for surgical treatment of large volume prostates.

Selective nuclear factor kappa-B inhibitors, pyrolidium dithiocarbamate and sulfasalazine, prevent the nephrotoxicity induced by gentamicin.

OBJECTIVE: To investigate the effect of selective nuclear factor kappa-B (NFkappa-B) inhibitors, pyrolidium dithiocarbamate (PD) and sulfasalazine (SZ) on renal tubular necrosis and inducible nitric oxide synthase (iNOS) and NFkappa-B expression induced by gentamicin in rats. MATERIALS AND METHODS: In all, 48 adult male Sprague-Dawley rats were divided into six equal groups; group 1, control; group 2, injected with gentamicin for 10 days (100 mg/kg/day, intraperitoneal, i.p.); group 3, injected with gentamicin plus PD (100 mg/kg/day, i.p.); group 4, injected with gentamicin plus SZ (75 mg/kg/day, i.p.); group 5, injected with gentamicin plus distilled water (vehicle for PD); and group 6, injected with gentamicin plus ammonium hydroxide (75 mg/day, 1 m, vehicle for SZ) for 10 days. At 24 h after the last injection, rats were killed and the renal cortex separated from the medulla. A small sample was fixed in formaldehyde solution for histological and immunohistochemical examination. Blood samples were also taken to assess the serum levels of urea, creatinine, Na(+), K(+) and gamma-glutamyl transpeptidase (GT). Crude extracts of the cortex were used to determine reduced glutathione (GSH-Px), NO and malondialdehyde (MDA). Immunohistochemically, iNOS and the active subunit of NFkappaB, P65, were evaluated using mouse monoclonal antibodies. RESULTS: On haematoxylin and eosin staining, compared with the controls rats, gentamicin caused widespread tubular necrosis (grade 3 and 4) but in group 3 and 4 there was a marked reduction in the extent of tubular damage. Immunohistochemically there was more marked staining for iNOS and P65 expression in rats given gentamicin than in the control and group 3 and 4 (P < 0.001). In groups 3 and 4 iNOS and P65 expression were significantly less than in rats given only gentamicin. There was no significant difference in serum levels of Na(+), K(+), blood urea nitrogen and creatinine. Compared with control rats, gentamicin caused hyperproteinuria, a marked increase in levels of serum gamma-GT, MDA and NO, and a decrease in GSH-Px (P < 0.001). CONCLUSION: These results indicate that gentamicin induces iNOS expression through activation of NFkappa-B (P65). It is possible to prevent gentamicin-induced nephrotoxicity using selective NFkappa-B inhibitors.