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1.
Urol Oncol ; 41(12): 486.e1-486.e13, 2023 12.
Article in English | MEDLINE | ID: mdl-37690934

ABSTRACT

INTRODUCTION: Nonmuscle invasive bladder cancers (NMIBC) are common tumors diagnosed in older individuals and men (median age: 69 years). Immunotherapy is a treatment option in cases resistant to Bacillus-Calmette-Guerin (BCG) therapy. We aimed to evaluate the prognostic role of programmed-cell-death ligand (PD-L)-1 (PD-L1), PD-L2, and signal transducer and activator of transcription 3 (STAT3) expressions, which are closely related to immune mechanisms, in the response to BCG treatment of NMIBC. METHODS: The data of patients at the Ta and T1 stages of the cancer without muscularis propria invasion, who were treated with intravesical BCG therapy between 2017 and 2022 were retrospectively analyzed. Immunohistochemical staining for PD-L1, PD-L2, and STAT3 was performed on transurethral resection materials. RESULTS: The mean age of 59 patients was 66.5 ±7.7 and 83.9% were male. The percentage of patients with complete response to BCG treatment was 66.1% and that of BCG refractory patients was 33.9%. Demographic and clinical data did not differ significantly according to BCG treatment response (P> 0.05). The proportion of patients with tumor-infiltrating lymphocytes (TILs) ≥20% were 9.7% among those with Ta-stage tumors and 46.4% among those with T1-stage tumors (P = 0.0014). The percentages of tumor cell scoring (TCS), immune cell scoring (ICS), combined scoring (CS), and expression levels of PD-L1, PD-L2, and H-score of STAT3 did not differ significantly according to tumor stage and treatment response (P > 0.05). However, the median ICS and CS for PD-L1 and median H-score for STAT3 were significantly higher among patients in T1 stage compared to those in Ta stage (P = 0.0487, 0.0462, 0.0112, respectively). Among BCG refractory patients, median STAT3 of patients in T1 stage was significantly higher than those at stage Ta (P = 0.0356) and the rate of TILs was ≥20% in only 3 patients in T1 stage (P = 0.031). Among all patients, significant positive correlation was found between TCS for PD-L1 and H-score for STAT3 (P = 0.0302); and between ICS for PD-L1 and TCS for PD-L2 (P = 0.0053) and TILs ratio (P < 0.0001). Among BCG-refractory cases, pretreatment and post-treatment TCS for PD-L2 and H-scores for STAT3 were significantly correlated (P = 0.0361 and 0.0021, respectively). CONCLUSIONS: The success of BCG treatment in NMIBC was not related to PD-L1, PD-L2, and STAT3 expression status, but PD-L1 expression was correlated with both PD-L2 and STAT3 as well as TILs rate, but this correlation was lost after BCG treatment.


Subject(s)
Carcinoma, Transitional Cell , Non-Muscle Invasive Bladder Neoplasms , Urinary Bladder Neoplasms , Humans , Male , Aged , Middle Aged , Female , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Prognosis , Retrospective Studies , B7-H1 Antigen/metabolism , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/therapeutic use , BCG Vaccine/therapeutic use
2.
Int Urol Nephrol ; 55(6): 1459-1465, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36966444

ABSTRACT

PURPOSE: We aimed to evaluate the benefits of Comprehensive Complication Index (CCI) compared with the Clavien-Dindo Classification (CDC) in the reporting of radical cystectomy (RC) complications. MATERIALS AND METHODS: We retrospectively analyzed post-operative complications of 251 consecutive RC patients between 2009 and 2021. Patient demographics and causes of mortality were noted. Oncologic outcomes included the recurrence, time to recurrence, cause of all deaths, and time to death. Each complication was graded with CDC and, corresponding and cumulative CCI calculated for each patient. RESULTS: A total of 211 patients are included. Median patient age and follow-up time were 65 (IQR 60-70) years and 20 (IQR 9 - 53) months, respectively. The five-year recurrence and death rates were 39.3% (83/211) and 59.7% (126/211), respectively. Post-operative 521 complications were recorded. Patients with experienced any complication were 69.6% (147/211) and 45.0% (95/211) had > 1 complications. Thirty (14.2%) patients ended up with a cumulative CCI score that corresponded to a higher CDC grade. Severe complications calculated with CDC increased from 18.5% to 19.9% (p < 0.001) with cumulative CCI. Female gender, positive lymph node, and positive surgical margin, presence of severe CDC complication, and CCI score were significant independent predictive factors for overall survival (OS). The contribution of CCI to the multivariable model was 1.8% higher than CDC. CONCLUSIONS: Cumulative morbidity reporting improved with the use of CCI compared to CDC. Both CDC and CCI are significant predictive factors for OS independent of oncologic predictive factors. Reporting the cumulative burden of complications with CCI is more predictive on oncologic survival than reporting complications with CDC.


Subject(s)
Cystectomy , Urinary Bladder Neoplasms , Humans , Female , Cystectomy/adverse effects , Retrospective Studies , Postoperative Complications/etiology , Morbidity , Urinary Bladder Neoplasms/surgery , Urinary Bladder Neoplasms/complications
3.
World J Surg Oncol ; 21(1): 58, 2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36823517

ABSTRACT

PURPOSE: We aimed to evaluate perioperative complications of radical cystectomy (RC) by using standardized methodology. Additionally, we identified independent risk factors associated with perioperative complications. MATERIALS AND METHODS: We retrospectively analyzed 30-day and 90-day perioperative complications of 211 consecutive RC patients. The intraoperative and postoperative complications were defined according to Clavien-Dindo classification (CDC) and reported based on the ICARUS criteria, Martin, and EAU quality criteria. Age-adjusted Charlson comorbidity index (ACCI), systemic inflammatory response index (SIRI), body mass index (BMI) ≥ 25 kg/m2, and neoadjuvant chemotherapy (NAC) were also evaluated. Multivariable regression models according to severe (CDC ≥ IIIb grade) complications were tested. RESULTS: Overall, 88.6% (187/211) patients experienced at least one intraoperative complication. Bleeding during cystectomy was the most common complication observed (81.5% [172/211]). Severe intraoperative complications (EAUiaiC grade > 2) were recorded in 8 patients. Overall, 521 postoperative complications were recorded. Overall, 69.6% of the patients experienced complications. Thirty-nine patients suffered from most severe (CDC ≥ IIIb grade) complications. ACCI (OR: 1.492 [1.144-1.947], p = 0.003), SIRI (OR: 1.279 [1.029-1.575], p = 0.031), BMI (OR: 3.62 [1.58-8.29], p = 0.002), and NAC (OR: 0.342 [0.133-0.880], p = 0.025) were significant independent predictive factors for 90-day most severe complications (CDC ≥ IIIb grade). CONCLUSIONS: RC complications were reported within a standardized manner, concordant with the ICARUS and Martin criteria and EAU guideline recommendations. Complication reporting seems to be improved with the use of standard methodology. Our results showed that ACCI, SIRI, and BMI ≥ 25 kg/m2 and the absence of NAC were significant predictive factors for most severe complications.


Subject(s)
Cystectomy , Urinary Bladder Neoplasms , Humans , Cystectomy/adverse effects , Cystectomy/methods , Urinary Bladder Neoplasms/surgery , Retrospective Studies , Risk Factors , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Intraoperative Complications/epidemiology , Intraoperative Complications/etiology , Treatment Outcome
4.
Urol Oncol ; 41(5): 256.e1-256.e8, 2023 05.
Article in English | MEDLINE | ID: mdl-36577568

ABSTRACT

PURPOSE: We aimed to evaluate the prognostic value of the preoperative systemic inflammation response index (SIRI) to predict the outcomes after open radical cystectomy (RC). MATERIALS AND METHODS: We conducted a retrospective analysis of the institutional cystectomy database and identified 241 consecutive RC patients. Patient demographics and oncologic outcomes were noted. We calculated the SIRI as previously described (NeutrophilxMonocytes/Lymphocytes), based on the blood-tests at the day before surgery and a minimum >30-day later. RESULTS: Median follow-up time was 20 months (interquartile range 9-52). Two, 3 and 5 years recurrence free (RFS) and overall survival (OS) rates were 60.6%, 57.1%, 48.9%, and 54.7%, 47.0%, 37.2%, respectively. Patients with preoperative SIRI >1.91 had significantly higher recurrence rates (P < 0.001) and lower OS (P < 0.001). For internal validation, we evaluated postoperative SIRI >1.91 (repeatability testing), and again found significantly higher recurrence rates (P < 0.001) and lower OS (P = 0.004). Persistently high SIRI increased the recurrence and death risk 5.79 and 2.87 fold, respectively. SIRI was also a significant independent predictive factor for RFS and OS in the multivariable cox regression analyses (P < 0.05). SIRI improved the discriminative ability of the models 1.5% to 4.2% and this was quite higher than other inflammatory markers (NLR, MLR, PLR, SII) in all models. CONCLUSIONS: Patients with SIRI >1.91 had significantly higher recurrence and lower OS rates. The cut-off value is validated internally. SIRI is an independent predictive factor for RFS and OS. The contribution of SIRI in the cox models is higher than other inflammatory markers.


Subject(s)
Urinary Bladder Neoplasms , Humans , Retrospective Studies , Urinary Bladder Neoplasms/surgery , Prognosis , Proportional Hazards Models , Inflammation
5.
Arch Ital Urol Androl ; 95(4): 12130, 2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38193219

ABSTRACT

OBJECTIVE: To report long-term functional and oncological outcomes of OPN Methods: We enrolled 182 patients who underwent consecutive OPN with a diagnosis of kidney tumor in our clinic between April 2002 and February 2020 and were selected from our prospective OPN database. Preoperative demographic and clinical characteristics, intraoperative and pathological results, and patients' postoperative functional and oncological follow-up data were retrospectively analyzed. Overall survival (OS) and disease- free survival (DFS) were evaluated using Kaplan-Meier survival analysis. The time-dependent variation between preoperative and postoperative functional results was statistically analyzed and presented in a graph. RESULTS AND LIMITATIONS: The mean age was 54.4 ± 10.8 yr, and the median age-adjusted Charlson comorbidity index (ACCI) was 1 (interquartile range [IQR] 0-1). The mean tumor size was 3.1 ± 1.2 cm, and the median RENAL score was 6 (IQR 5-8). The most common malign histopathological subtype was clear cell carcinoma with 76.6%, and five cases (3.4%) had positive surgical margins (PSMs). The most common surgical techniques were the retroperitoneal approach (98.9%) and cold ischemia (88.5%). Estimated glomerular filtration rate (eGFR) preservation was 92% (80.8-99.3, IQR), which translates to 32% chronic kidney disease (CKD) upstaging. Acute kidney injury (AKI) was detected in 27 (14.8%) patients according to RIFLE criteria. The intraoperative complication rate was 5.5%, and the postoperative overall complication rate (Clavien-Dindo 1-5) was 30.2%. Major complications (Clavien-Dindo 3-5) were observed in 13 (7.1%) patients. The median oncological follow-up was 42 mo (21.3- 84.6, IQR), and the 5- and 10-yr OS were 90.1% and 78.6%, 5 and 10-yr DFS were 99.4% and 92.1%, respectively. No local recurrence was observed in 5 (3.4%) patients with PSMs; only one had distant metastasis in the 8th postoperative month. The retrospective design, the small number of patients who underwent PN based on mandatory indication, and one type of surgical approach may limit the generalizability of our findings. CONCLUSIONS: This study confirms excellent long-term oncologic and functional outcomes after OPN in a cohort of patients selected from a single institution. In light of the information provided by the literature and our study, our recommendation is to push the limits of PN under every technically feasible condition in the treatment of kidney tumors to protect the kidney reserve and achieve near-perfect oncological results.


Subject(s)
Kidney Neoplasms , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Prospective Studies , Kidney Neoplasms/surgery , Nephrectomy , Kidney
6.
Int Urol Nephrol ; 54(7): 1529-1535, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35438411

ABSTRACT

OBJECTIVES: The aim of the study was to investigate whether a novel simple measurement of pelvic anatomy, the pelvic anatomical index (PAI), which is obtained from simple physical examination, was predictive for potential difficulty and adverse outcome in radical prostatectomy. MATERIALS AND METHODS: Available data from 73 consecutive radical prostatectomy patients were analyzed. The distances between umbilicus and cranial edge of the symphysis pubis (USPD) and between root of the penis and umbilicus (PUD) were measured. PAI was obtained using the formula (PUD/USPD) × body mass index (BMI). Indicators of surgical difficulty assessed were operation time (OT), dorsal vein bleeding (DVB), total blood loss (TBL), and surgical margin (SM) status. Patients with below-median values of the OT, DVB, TBL, and had negative SM were grouped as favorable surgery (n = 18). RESULTS: Median OT, DVB, and TBL were 215 (IQR: 187.5-240) min, 380 (IQR: 200-500) cc, and 1000 (IQR: 700-1300) cc, respectively. Both PAI and BMI were significantly correlated with TBL, DVB, and OT (p < 0.05, for all). PAI and BMI significantly associated with favorable surgery (p = 0,006 and p = 0.048, respectively). However, only PAI was an independent predictor of favorable surgery in multivariable logistic regression analysis. A PAI 36 kg/m2 was determined as the threshold value for favorable surgery with 83.3% sensitivity and 60% specificity. CONCLUSION: PAI significantly correlated with almost all surgical parameters and was a significant independent predictor of favorable surgery. PAI can enable the physician to select and discuss individualized treatment options for patients during preoperative planning.


Subject(s)
Prostate , Prostatectomy , Body Mass Index , Humans , Male , Operative Time , Pelvis , Prostate/surgery , Prostatectomy/adverse effects
7.
Arch Ital Urol Androl ; 94(1): 12-17, 2022 Mar 28.
Article in English | MEDLINE | ID: mdl-35352518

ABSTRACT

OBJECTIVE: To evaluate the impact of Double J stent (DJS) insertion during open partial nephrectomy (OPN) on postoperative prolonged urinary leakage. MATERIALS AND METHODS: A retrospective study was made in consecutive cases of OPN performed between 2002 and 2020 for localized kidney tumors at our tertiary center. Urinary leakage was defined as drainage > 72 hours after surgery by biochemical analysis consistent with urine or radiographic evidence of urine leakage. The patients were divided into two groups according to intraoperative DJS placement, and compared regarding clinicopathologic characteristics, perioperative and postoperative outcomes. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with urinary leakage after the operation. RESULTS: Review of records identified 182 patients who were included in the study. In 73 (40%) patients PN was performed without insertion of a DJS. Thus, 109 (60%) of patients had a DJS inserted. Apart from higher preoperative eGFR values among patients with DJS (96.6 vs. 94.3 mL/min/1.73 m²; p = 0.03), demographic characteristics were similar between groups. The two groups were not different regarding perioperative, postoperative and clinicopathologic outcomes. Patients with DJS had longer ischemia times (31 vs. 23 min; p = 0.02) and longer length of stay (6 vs. 5 days; p = 0.04). Urinary leakage was seen in 7.6% (n = 14) of all patients and it did not differ according to DJS placement (DJS+ 9.2 vs. DJS- 5.5%; p = 0.41). On multivariate analysis, the tumor nearness to the collecting system was the sole independently significant factor (p = 0.04) predicting postoperative urine leak. CONCLUSIONS: Routine intraoperative DJS insertion during OPN does not appear to reduce the probability of postoperative urine leak.


Subject(s)
Kidney Neoplasms , Ureter , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Nephrectomy/adverse effects , Retrospective Studies , Stents
8.
Int Urol Nephrol ; 52(12): 2289-2299, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32761342

ABSTRACT

PURPOSE: We aimed to assess an "Immunological Profile (IP)" including CD8+ and FoxP3+ T lymphocytes for renal cell carcinoma (RCC) to evaluate its effects on tumor pathological characteristics, disease progression, and survival. METHODS: Adjacent normal and intratumoral specimens from 42 patients who had undergone radical nephrectomy for RCC were analyzed for counts of CD8+ and FoxP3+ T lymphocytes by immunohistochemistry. Tissue from both sites were evaluated and scored separately according to low (0) or high (1) expression of CD8 and FoxP3. A total score (min: 0, max: 4) was assigned to each patient. Thereafter, patients were divided into two groups for clinicopathologic and survival stratification based on score (IPWeak 0-2; and IPStrong 3-4). Survival curves were constructed using the Kaplan-Meier method, and a multivariable Cox regression model was used for overall survival (OS) and progression-free survival (PFS). RESULTS: The mean follow-up was 54.73 ± 21.34 months. Poor RCC characteristics including pT3-T4, tumor necrosis, lymphovascular invasion, lymph node involvement, and larger tumor size were significantly more common in the IPWeak patients compared to IPStrong (p < 0.05). Kaplan-Meier analysis showed that IPWeak patients had worse OS (62.5 vs. 100%; p = 0.006) and PFS (50 vs. 94.4%; p = 0.002) compared to IPStrong patients. In multivariable analysis, IPWeak (HR 8.64; 95% CI 1.09-68.05, p = 0.042) and high tumor node metastasis stage (HR 45.33; 95% CI 4.69-437.68, p < 0.001) were significant independent predictors of poor PFS. CONCLUSION: Assessment of IP including CD8+ and FoxP3+ T lymphocytes in adjacent normal and intratumoral sites in RCC may serve as a good predictive marker for PFS.


Subject(s)
CD8-Positive T-Lymphocytes , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/pathology , Forkhead Transcription Factors/immunology , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , T-Lymphocytes/immunology , Adult , Aged , Carcinoma, Renal Cell/mortality , Cohort Studies , Disease Progression , Female , Humans , Kidney Neoplasms/mortality , Male , Middle Aged , Prognosis , Survival Rate
9.
Int. braz. j. urol ; 44(6): 1252-1255, Nov.-Dec. 2018. graf
Article in English | LILACS | ID: biblio-975670

ABSTRACT

ABSTRACT Encrusted cystitis (EC) was first described as chronic cystitis with mucosal calcification in 1914 (1). It is a very rare chronic inflammatory disease presenting with dysuria, pelvic pain and gross hematuria. Voided urine contains mucus or calcified mucopurulent stone like particles. Urinalysis always reveals alkaline pH. It may be present in healthy individuals with no predisposing etiological factors (2-4). Etiologically, previous urological diseases, immunosuppression, urinary infection with urea splitting bacteria, or urological interventions resulting in bladder mucosa trauma may also be present (5, 6). In the present case report, we describe a novel treatment for EC with intravesical dimethyl sulfoxide.


Subject(s)
Humans , Male , Adult , Dimethyl Sulfoxide/therapeutic use , Corynebacterium/classification , Corynebacterium Infections/drug therapy , Cystitis/drug therapy , Administration, Intravesical , Chronic Disease , Treatment Outcome , Corynebacterium/isolation & purification , Corynebacterium Infections/diagnosis , Corynebacterium Infections/microbiology , Cystitis/diagnosis , Cystitis/microbiology
10.
Int Urol Nephrol ; 50(8): 1417-1425, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29931492

ABSTRACT

PURPOSE: Recent studies have shown that Aurora-A expression is associated with bladder cancer initiation and progression. In this study, the effects of intravesical Aurora-A inhibitor Alisertib (ALS) and bacillus Calmette-Guérin (BCG) were compared on bladder carcinogenesis. METHODS: Two mg N-Methyl-N-nitrosourea was administered intravesically to forty of Wistar-albino rats every other week for 8 weeks. At week 10, rats were divided into four groups (10/group): No-treatment (vehicle), ALS-alone, BCG-alone, and ALS + BCG. The intravesical treatment of ALS, BCG, and ALS plus BCG was performed once a week for 6 weeks. At week 16, bladders were collected for immunohistopathological and Western blot analysis. The cell cycle regulators p53, p21, Aurora-A, phosphorylated Aurora-A (p-Aurora-A), and apoptotic marker cleavage of poly [ADP-ribose] polymerase (c-PARP) were determined by Western blot. RESULTS: Histopathologically relatively healthy urothelium was observed in ALS + BCG group (87.5%) compared to the ALS-alone (50%) and the BCG-alone (50%) groups. The lowest expression of p21 and p53 was detected in the BCG-alone, while the highest level of expression was evident in no-treatment group. The ALS treatment alone caused a slight decrease in Aurora-A while there was a dramatic decrease in p-Aurora-A in comparison to no-treatment group. In overall combined treatment with ALS + BCG significantly increased c-PARP compared to all mono-treatments, and decreased all cell cycle parameters compared to no-treatment group. CONCLUSIONS: Although intravesical ALS treatment has similar antiproliferative effects like BCG, ALS + BCG combined treatment led to a best histopathologic and apoptotic response. Consequently, BCG combined with Aurora-A inhibition may provide a new intravesical treatment modality in the prevention of bladder carcinogenesis.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Aurora Kinase A/antagonists & inhibitors , Azepines/administration & dosage , BCG Vaccine/administration & dosage , Precancerous Conditions/drug therapy , Precancerous Conditions/pathology , Pyrimidines/administration & dosage , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/prevention & control , Administration, Intravesical , Animals , Disease Models, Animal , Female , Rats , Rats, Wistar
11.
Int Braz J Urol ; 44(6): 1252-1255, 2018.
Article in English | MEDLINE | ID: mdl-29697935

ABSTRACT

Encrusted cystitis (EC) was first described as chronic cystitis with mucosal calcification in 1914 (1). It is a very rare chronic inflammatory disease presenting with dysuria, pelvic pain and gross hematuria. Voided urine contains mucus or calcified mucopurulent stone like particles. Urinalysis always reveals alkaline pH. It may be present in healthy individuals with no predisposing etiological factors (2-4). Etiologically, previous urological diseases, immunosuppression, urinary infection with urea splitting bacteria, or urological interventions resulting in bladder mucosa trauma may also be present (5, 6). In the present case report, we describe a novel treatment for EC with intravesical dimethyl sulfoxide.


Subject(s)
Corynebacterium Infections/drug therapy , Corynebacterium/classification , Cystitis/drug therapy , Dimethyl Sulfoxide/therapeutic use , Administration, Intravesical , Adult , Chronic Disease , Corynebacterium/isolation & purification , Corynebacterium Infections/diagnosis , Corynebacterium Infections/microbiology , Cystitis/diagnosis , Cystitis/microbiology , Humans , Male , Treatment Outcome
12.
Turk J Urol ; 44(2): 132-137, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29511582

ABSTRACT

OBJECTIVE: The incidence of prostate adenocarcinoma (PCa) is increased with the use of prostate-specific antigen (PSA). In the current study, we aimed to investigate the impact of 5- alpha- reductase inhibitors (5-ARI) on pathological progression in patients followed by active surveillance (AS). MATERIAL AND METHODS: Records of 69 patients with localized prostate cancer under AS (PSA ≤15 ng/mL, PSAD ≤0.20, ≤cT2c, Gleason sum ≤3+3, the number of cancer positive cores ≤3) were evaluated retrospectively. Patients were followed-up with quarterly PSA testing and semiannual digital rectal examination during the first 2 years, and semiannual PSA testing thereafter. Repeat biopsies were done annually and whenever indicated by clinical findings. Pathological progression was defined as increasing Gleason grade, number of cancer-positive cores, and/or increasing percentage of cancer in any core. RESULTS: Patients using (29/69: 42%) and not using (40/69: 58%) 5-ARI were followed for a median of 39 (IQR: 23-45) and 23.5 (IQR: 17-37.5) months, respectively. Pathological progression was observed in 32% (22/69) of the patients at a median of 25 (IQR: 18-39) months. Pathological progression was observed in 34.5% (10/29) and 30% (12/40) of the patients using and not using 5-ARI, respectively (Log-rank p=0.4151). Definitive treatment was done in 31% (9/29) and 47.5% (19/40) of the patients using and not using 5-ARI, respectively. Patients who did not use 5-ARI received definitive treatment earlier than 5-ARI users (Log-rank p=0.0342). On multivariate analysis, more than 2 cancer-positive cores (HR: 11.62) and age (HR: 0.94) were independently associated with pathological progression (p<0.05), rather than 5-ARI use (p=0.148). CONCLUSION: More than 2 cancer- positive cores at the initial biopsy was the strongest covariate associated with pathological progression; these patients should not be offered AS. There was no impact of 5-ARI use on pathological progression in AS.

13.
Cancer Immunol Immunother ; 67(1): 67-77, 2018 01.
Article in English | MEDLINE | ID: mdl-28916862

ABSTRACT

Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. We aimed to monitor changes at the proteome level to identify putative protein biomarkers associated with the response of urothelial precancerous lesions to intravesical BCG treatment. The rats were divided into three groups (n = 10/group): control, non-treated, and BCG-treated groups. The non-treated and BCG-treated groups received N-methyl-N-nitrosourea intravesically. BCG Tice-strain was instilled into bladder in BCG-treated group. At the endpoint of experiment, all surviving rat bladders were collected and equally divided into two portions vertically from dome to neck. Half of each bladder was assessed immunohistopathologically and the other half was used for 2D-based comparative proteomic analysis. Differentially expressed proteins were validated by Western blot analysis. Precancerous lesions of bladder cancer were more common in non-treated group (77.8%) than in BCG-treated group (50%) and the control group (0%). Greater than twofold changes occurred in the expression of a number of proteins. Among them, Rab-GDIß, aldehyde dehydrogenase 2 (ALDH2) and 14-3-3 zeta/delta were important since they were previously reported to be associated with cancer and their expression levels were found to be lower in BCG-treated group in comparison to the non-treated group. ALDH2 and 14-3-3 zeta/delta were also found to be highly expressed in the non-treated group compared to the control group. The down-regulation of these proteins and Rab-GDIß was achieved with BCG; this result indicates that they may be used as putative biomarkers for monitoring changes in bladder carcinogenesis in response to BCG immunotherapy.


Subject(s)
BCG Vaccine/immunology , Cancer Vaccines/immunology , Immunotherapy/methods , Urologic Neoplasms/therapy , Urothelium/metabolism , Administration, Intravesical , Animals , Disease Models, Animal , Female , Guanine Nucleotide Dissociation Inhibitors/genetics , Guanine Nucleotide Dissociation Inhibitors/metabolism , Humans , Precancerous Conditions , Proteome , Rats , Rats, Wistar , Urologic Neoplasms/immunology , Urothelium/pathology
14.
Urol Int ; 100(1): 43-49, 2018.
Article in English | MEDLINE | ID: mdl-29275406

ABSTRACT

INTRODUCTION: To evaluate the pathological outcomes of Turkish men meeting the criteria for Active Surveillance (AS), who elected to undergo immediate radical prostatectomy (RP). MATERIAL AND METHODS: Retrospective analysis including 1,212 patients with clinically localized prostate cancer (PCa) who met the eligibility criteria for AS. The primary outcomes were pathological upstaging and pathological upgrading. RESULTS: Nine hundred ninety-one patients were eligible for analysis after the central review of the submitted data. The mean prostate-specific antigen (PSA) level was 6.89 (0.51-15) ng/mL and the mean biopsy core number was 12 (8-47). The mean tumor positive core on final biopsy pathology was 1.95 (1-6) (16.6% [2.1-33.3%]). Overall, 30.6% of the men experienced a Gleason sum (GS) upgrade and 13.2% had pathological upstaging. For GS upgrade, the percentage of tumor-positive cores and free-to-total-PSA ratio were significant both in univariate analysis and multivariate logistic regression analysis. Variables predicting pathological upstaging were percentage of tumor-positive cores and PSA density, which were significant in univariate analysis. However, only PSA density was significant in multivariate logistic regression. Although biochemical recurrence-free survival was longer in patients without GS upgrade, it was not statistically significant between patients with and without any GS upgrade (mean 133.7 vs. 148.2 months, p = 0.243). A similar observation was made for patients with or without pathological upstaging (mean 117.1 vs. 148.3 months, p = 0.190). CONCLUSIONS: Upgrading and upstaging at RP are quite common among Turkish men with clinically low-risk PCa, who are candidates for AS, and a great majority of them experienced long-term PSA control.


Subject(s)
Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Watchful Waiting , Adult , Aged , Humans , Male , Middle Aged , Prostatectomy/methods , Retrospective Studies , Treatment Outcome , Turkey
15.
Arch Esp Urol ; 70(9): 800-805, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29099383

ABSTRACT

OBJECTIVES: To evaluate the effect of pre-operative alprazolam medication on anxiety and pain in flexible cystoscopy for bladder cancer follow-up. METHODS: A total of 86 male patients who had flexible cystoscopy for bladder cancer follow-up at 6th and 9th months were included in the study. A visual analog scale (VAS) pain score and the State-Trait Anxiety Inventory (STAI) were used. The 6th (VAS-1)and 9th (VAS-2) month pain scores and 6th month STAI score (STAI-1) and, 9th month STAI score before (STAI-2a) and after alprazolam (0.5 mg) intake (STAI-2b) were compared. RESULTS: The mean age was 66.49±12.45 years. Patients were grouped by age≤65 (Group-1) and age≥66 (Group-2). Mean VAS score for VAS-1 and VAS-2 were 2.66±0.96 and 2.44±1.05, respectively (p=0.007). The mean VAS-1 and VAS-2 scores in Group 1 were 3.0±1.05 and 2.73±1.18, respectively (p=0.009). The mean VAS-1 and VAS-2 scores in Group 2 were 2.36±0.77 and 2.17±0.86 respectively (p=0.031). The differences between mean anxiety scores were all statistically significant. All STAI (1, 2a, and 2b) and VAS (1 and 2) scores in Group-1 were statistically significantly higher than Group-2. Increasing STAI score is associated with a statistically significant increase in the VAS scores in the 0.50 and 0.75 quantiles (p=0.021 and p=0.039, respectively). CONCLUSIONS: Using alprazolam before flexible cystoscopy reduces both anxiety (STAI-1 vs STAI-2b) and pain (VAS-1 vs VAS-2). Previous cystoscopy experience reduces anxiety (STAI-2a vs. STAI-2b). Elderly patients have less anxiety and pain scores than younger patients in flexible cystoscopy.


Subject(s)
Alprazolam/therapeutic use , Anti-Anxiety Agents/therapeutic use , Anxiety/prevention & control , Cystoscopy , Pain/prevention & control , Adult , Aged , Aged, 80 and over , Ambulatory Care , Humans , Male , Middle Aged
16.
Arch. esp. urol. (Ed. impr.) ; 70(9): 800-805, nov. 2017. tab, graf
Article in English | IBECS | ID: ibc-168580

ABSTRACT

OBJECTIVES: To evaluate the effect of pre-operative alprazolam medication on anxiety and pain in flexible cystoscopy for bladder cancer follow-up. METHODS: A total of 86 male patients who had flexible cystoscopy for bladder cancer follow-up at 6th and 9th months were included in the study. A visual analog scale (VAS) pain score and the State-Trait Anxiety Inventory (STAI) were used. The 6th (VAS-1) and 9th (VAS-2) month pain scores and 6th month STAI score (STAI-1) and, 9th month STAI score before (STAI-2a) and after alprazolam (0.5 mg) intake (STAI-2b) were compared. RESULTS: The mean age was 66.49±12.45 years. Patients were grouped by age≤65 (Group-1) and age≥66 (Group-2). Mean VAS score for VAS-1 and VAS-2 were 2.66±0.96 and 2.44±1.05, respectively (p = 0.007). The mean VAS-1 and VAS-2 scores in Group 1 were 3.0±1.05 and 2.73±1.18, respectively (p = 0.009). The mean VAS-1 and VAS-2 scores in Group 2 were 2.36±0.77 and 2.17±0.86 respectively (p = 0.031). The differences between mean anxiety scores were all statistically significant. All STAI (1, 2a, and 2b) and VAS (1 and 2) scores in Group-1 were statistically significantly higher than Group-2. Increasing STAI score is associated with a statistically significant increase in the VAS scores in the 0.50 and 0.75 quantiles (p = 0.021 and p = 0.039, respectively). CONCLUSIONS: Using alprazolam before flexible cystoscopy reduces both anxiety (STAI-1 vs STAI-2b) and pain (VAS-1 vs VAS-2). Previous cystoscopy experience reduces anxiety (STAI-2a vs. STAI-2b). Elderly patients have less anxiety and pain scores than younger patients in flexible cystoscopy


OBJETIVOS: Evaluar el efecto del alprazolam preoperatorio sobre la ansiedad y el dolor durante la cistoscopia flexible en el seguimiento del cáncer vesical. Métodos Se incluyeron 86 pacientes varones en seguimiento con cistoscopia flexible por cáncer vesical a los 6 y 9 meses. Se utilizaron una escala visual analógica (EVA) para el dolor y el Formulario STAI (State-trait anxiety Inventory) de ansiedad. Se compararon los resultados de dolor al 6º (EVA1) y 9º mes (EVA2) y los resultados del formulario STAI al 6º (STAI 1) y 9º mes, antes (STAI 2a) y después de la toma de alprazolam (STAI 2b). RESULTADOS: La edad media fue de 66,49±12,45 años. Los pacientes se agruparon por edad ≤ 65 años (Grupo 1) y ≥ 66 (Grupo 2). Las puntuaciones de la EVA 1 y EVA 2 fueron 2,66±0,96 y 2,44±1,05, respectivamente (p = 0,007). La media de las puntuaciones EVA 1 y EVA 2 en el grupo 1 fueron 3,0±1,05 y 2,73±1,18, respectivamente (p = 0,009). La media de las puntuaciones EVA 1 y EVA 2 en el grupo 2 fueron 2,36±0,77 y 2,17±0,86, respectivamente (p = 0,031). Las diferencias entre las puntuaciones medias de ansiedad fueron todas significativas. Todas las STAI (1, 2a y 2b) y EVA (1 y 2) en el grupo 1 fueron superiores a las del grupo 2, con diferencias estadísticamente significativas.Una puntuación del STAI creciente se asocia con un aumento significativo de las puntuaciones de la EVA en los cuartiles 0,50 y 0,75 (p = 0,021 y p = 0,039, respectivamente). CONCLUSIONES: La utilización de alprazolam antes de la cistoscopia flexible reduce tanto la ansiedad (STAI-1 vs STAI-2b) como el dolor (EVA-1 vs EVA-2). La experiencia de cistoscopia previa reduce la ansiedad (STAI-2a vs. STAI-2b). Los pacientes ancianos tienen valores más bajos de ansiedad y dolor en la cistoscopia flexible que los pacientes jóvenes


Subject(s)
Humans , Male , Middle Aged , Aged , Aged, 80 and over , Alprazolam/pharmacokinetics , Cystoscopy/methods , Urinary Bladder Neoplasms/surgery , Pain Management/methods , Anxiety , Test Anxiety Scale/statistics & numerical data , Pain Measurement/statistics & numerical data
17.
Turk J Urol ; 43(3): 297-302, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28861301

ABSTRACT

OBJECTIVE: Only a few papers in the literature aimed to evaluate biopsy core lengths. Additionally, studies evaluated the core length with different approaches. We aimed to determine whether prostate cancer (PCa) detection is affected from core lengths according to three different approaches in a large standard cohort and compare our cut-off values with the published cut-offs. MATERIAL AND METHODS: We retrospectively analyzed 1,523 initial consecutive transrectal ultrasound-guided 12-core prostate biopsies. Biopsies were evaluated with respect to total core length (total length of each patients' core) average core length (total core length divided by total number of cores in each patient), and mean core length (mean length of all cores pooled), and compared our cut-off values with the published cut-offs. The prostate volumes were categorized into four groups (<30, 30-59.99, 60-119.99, ≥120 cm3) and PCa detection rates in these categories were examined. RESULTS: PCa was found in 41.5% patients. There was no difference between benign and malignant mean core lengths of the pooled cores (p>0.05). Total core length and average core length were not significantly associated with PCa in multivariate logistic regression analyses (p>0.05). The core lengths (mean, average and total core lengths) increased (p<0.001) and PCa rates decreased (p<0.001) steadily with increasing prostate volume categories. PCa percentages decreased in all categories above the utilized cut-offs for mean (p>0.05), average (p<0.05), and total core lengths (p>0.05). CONCLUSION: There was no difference between mean core lengths of benign and malignant cores. Total core length and average core length were not significantly associated with PCa. Contrary to the cut-offs used for mean and average core lengths in the published studies, PCa rates decrease as these core lengths increase. Larger studies are necessary for the determination and acceptance of accurate cut-offs.

18.
Exp Anim ; 66(3): 191-198, 2017 Aug 05.
Article in English | MEDLINE | ID: mdl-28228618

ABSTRACT

Although non-muscle invasive bladder cancer (NMIBC) is widely seen in men, most laboratory studies of new intravesical therapies to prevent NMIBC have been conducted on female animals. In addition, ozone (O3) has been shown to be a beneficial agent as an intravesical application in the treatment of various disorders. In the current study, we evaluated the immunohistopathological and oxidative-antioxidative effects of intravesical O3 treatment on n-methyl-n-nitrosourea (MNU)-induced NMIBC. Male Wistar-Albino rats (n=51) were divided into four groups: sham (n=6), O3 only (n=15), MNU only (n=15), and MNU+O3 (n=15). The MNU-only and MNU+O3 groups received MNU, and the O3-only group received saline every other week for 10 weeks. The MNU-only group received 1 ml saline in place of O3 treatment, whereas the O3-only and MNU+O3 groups were treated with 1 ml 25 µg/ml O3 between the 7th and 12th weeks. Rat bladders were collected in the 15th week for immunohistopathology and oxidant-antioxidant quantitation. Oxidant-antioxidant parameters were determined by ELISA. Although all surviving rats in the MNU-only group had preneoplastic (4/11, 36.4%) or neoplastic changes (7/11, 63.6%), a completely normal urothelium was observed in 2 rats (2/12, 16.7%) in the MNU+O3-group (P=0.478). More high-grade lesions were observed in the MNU-only group (4/11, 36.4%) than in the MNU+O3 group (1/12, 8.3%) (P=0.120). All oxidant-antioxidant parameters significantly increased (P<0.05) in the O3-only group compared with the sham group. However, only antioxidant superoxide dismutase was remarkably higher (178.9%, P=0.060) in the MNU+O3 group compared with the MNU-only group. This is the first methodologically and pathologically well-described male rat orthotopic bladder carcinogenesis model with intravesical MNU and administration of O3 in NMIBC.


Subject(s)
Methylnitrosourea/adverse effects , Oxidants, Photochemical/administration & dosage , Ozone/administration & dosage , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/prevention & control , Administration, Intravesical , Animals , Antioxidants/metabolism , Disease Models, Animal , Female , Male , Rats, Wistar , Superoxide Dismutase/metabolism , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/pathology
19.
Prostate ; 75(15): 1783-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26286637

ABSTRACT

BACKGROUND: We aimed to evaluate the relationship between perineural invasion (PNI) and bone metastasis in prostate cancer (PCa). METHODS: We retrospectively reviewed the data of 633 PCas who had whole-body bone scan (WBBS) between 2008 and 2014. We recorded the age, clinical T-stage, total PSA (tPSA) prior to biopsy, Gleason sum (GS), and PNI in transrectal ultrasound guided biopsy (TRUS-Bx) and digital rectal examination findings. Bone metastases were assessed with WBBS and magnetic resonance image if WBBS was suspicious. We divided the patients into two groups according to NCCN criteria: (Group 1) bone scan not indicated, (Group 2) bone scan indicated. RESULTS: There were 262 patients in Group 1 and 371 in 2. There is not significant relationship between PNI and bone metastasis in Group 1. However, there is very limited number of metastatic patients (n = 12) in this group. There is a strong relationship between PNI and bone metastasis in Group 2 (P = 0.001). Sensitivity, specificity and positive predictive value of PNI for bone metastasis were 72.4%, 81.7%, and 77.7%, respectively. In this group, tPSA, GS, positive DRE, and PNI were significant covariates for prediction of bone metastasis in univariate and multivariate analysis (except age). The most powerful predictor was PNI, and it increased the risk of bone metastasis 11-fold. CONCLUSIONS: PNI in the TRUS-Bx specimens is the most powerful predictive histopathological feature for bone metastasis, by increasing the risk of bone metastasis 11-fold in NCCN bone scan indicated patients (Group 2).


Subject(s)
Bone Neoplasms/secondary , Neoplasm Invasiveness/pathology , Prostate/pathology , Prostatic Neoplasms/pathology , Aged , Biopsy , Digital Rectal Examination , Humans , Male , Middle Aged , Neoplasm Grading , Retrospective Studies , Sensitivity and Specificity
20.
Asian J Androl ; 17(6): 892-8; discussion 897, 2015.
Article in English | MEDLINE | ID: mdl-26112487

ABSTRACT

Radiotherapy (XRT) is a curative treatment option for prostate cancer (PCa). Recent XRT technologies allow higher dose therapy that lead to increased local control with less adjacent tissue damage. Additionally, receiving neo-adjuvant or adjuvant hormonotherapy (HT) during radiation therapy increases the curative effect. The aim of this paper is to review the current literature and guidelines on external beam radiation therapy for PCa. However, brachytherapy and radiosurgery, a recently evolving relatively new technology for the radiotherapeutic management of localized PCa, are beyond the scope of this paper.


Subject(s)
Adenocarcinoma/radiotherapy , Prostatectomy , Prostatic Neoplasms/radiotherapy , Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Chemoradiotherapy, Adjuvant , Humans , Male , Patient Selection , Radiation Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Adjuvant
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