Exosomal Prostate-Specific Membrane Antigen (PSMA) and Caveolin-1 as Potential Biomarkers of Prostate Cancer-Evidence from Serbian Population.

Prostate-specific membrane antigen (PSMA) and caveolin-1 are membrane proteins that are overexpressed in prostate cancer (PCa) and are involved in tumor growth and increase in aggressiveness. The aim of the present study is therefore to evaluate PSMA and caveolin-1 proteins from plasma exosomes as effective liquid biopsy biomarkers for PCa. This study included 39 patients with PCa and 33 with benign prostatic hyperplasia (BPH). The shape and size of the exosomes were confirmed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analysis. Immunogold analysis showed that PSMA is localized to the membrane of exosomes isolated from the plasma of both groups of participants. The relative protein levels of PSMA and caveolin-1 in the plasma exosomes of PCa and BPH patients were determined by Western blot analysis. The relative level of the analyzed plasma exosomal proteins was compared between PCa and BPH patients and the relevance of the exosomal PSMA and caveoin-1 level to the clinicopathological parameters in PCa was investigated. The analysis performed showed an enrichment of exosomal PSMA in the plasma of PCa patients compared to the exosomes of men with BPH. The level of exosomal caveolin-1 in plasma was significantly higher in PCa patients with high PSA levels, clinical-stage T3 or T4 and in the group of PCa patients with aggressive PCa compared to favorable clinicopathological features or tumor aggressiveness. Plasma exosomes may serve as a suitable object for the identification of potential biomarkers for the early diagnosis and prognosis of PCa as well as carriers of therapeutic agents in precision medicine of PCa treatment.

Copy number variants within AZF region of Y chromosome and their association with idiopathic male infertility in Serbian population.

Results of numerous studies gave contradictory conclusions when analysing associations between copy number variants (CNVs) within the azoospermia factor (AZF) locus of the Y chromosome and idiopathic male infertility. The aim of this study was to identify the presence and possible association of CNVs in the AZF region of Y chromosome with idiopathic male infertility in the Serbian population. Using the multiplex ligation-dependent probe amplification technique, we were able to detect CNVs in 24 of 105 (22.86%) infertile men and in 11 of 112 (9.82%) fertile controls. The results of Fisher's exact test showed a statistically significant difference between cases and controls after merging g(reen)-r(ed)/g(reen)-r(ed) and b(lue)2/b(lue)3 partial deletions identified in the AZFc region (p = 0.024). At the same time, we observed a trend towards statistical significance for a deletion among gr/gr amplicons (p = 0.053). In addition to these, we identified a novel complex CNV involving inversion of r2/r3 amplicons, followed by b2/b3 duplication and b3/b4 deletion, respectively. Additional analyses on a larger study group would be necessary to draw meaningful conclusions about associations among CNVs that presented with higher frequency in the infertile men than the fertile controls.

Testis sparing surgery for treatment of small testicular lesions: Is it feasible even in germ cell tumors?

BACKGROUND AND OBJECTIVES: To evaluate the results of testis-sparing surgery (TSS) in patients, with small testicular lesions and a normal contralateral testicle. METHODS: In all, 28 patients were treated with TSS for small testicular lesions and a normal contralateral testicle. TSS was considered in patients with testicular lesions smaller than 2 cm and no evidence of metastatic disease. RESULTS: The mean age of patients was 35.3 ± 7.3 years, while the mean diameter of the testicular lesions was 11.4 ± 3.7 mm. After pathological examination, 18 patients (64.3%) were diagnosed with stromal tumors and miscellaneous lesions, while 10 (35.7%) had a germ cell tumor. The median follow-up time for the former group was 33 months and no recurrences were observed. In one patient with germ cell tumor, immediate orchiectomy was performed, while the remaining nine were followed-up (median time, 45 months). One patient developed local recurrence after 39 months. CONCLUSIONS: Excellent outcomes for benign lesions could be achieved using TSS. TSS could be offered safely in highly selected patients with germ cell tumors, specifically within a clinical trial but there is more data needed regarding the potential risks and benefits. J. Surg. Oncol. 2017;115:287-290. © 2016 Wiley Periodicals, Inc.

Testis sparing surgery in the treatment of bilateral testicular germ cell tumors and solitary testicle tumors: A single institution experience.

BACKGROUND AND OBJECTIVE: To assess the oncologic and functional outcomes of testicular sparing surgery (TSS) based on a single institution experience. METHODS: Forty-one patients with bilateral and 3 patients with solitary testicle tumors were referred to our institution. The inclusion criteria for TSS were normal serum testosterone levels, and tumor size (<2 cm). Sperm analysis and hormone status evaluation were performed preoperatively and postoperatively. None of the patients underwent local radiation therapy following TSS for reasons of fertility preservation. RESULTS: A total of 26 TSS were performed in 24 patients. The median follow-up period was 51.0 months. Seven patients developed local recurrence, of which 5 had TIN and were subjected to radical orchiectomy, whereas re-do TSS was done in remaining 2 patients. The overall survival of the study group was 100%, and the presence of testicular intraepithelial neoplasia (TIN) was associated with worse recurrence-free survival (P=0.031, log-rank). Testosterone values were normal in all of the patients, while 4 patients achieved conception. CONCLUSIONS: TSS is acceptable from an oncological point of view, and it enables continuation of a patient's life without lifelong hormonal substitution. Additionally, local irradiation therapy could be delayed in patients with TIN who wish to father children, but with high local recurrence rate.

The Effect of Epidural Analgesia on Quality of Recovery (QoR) after Open Radical Nephrectomy: Randomized, Prospective, and Controlled Trial.

No studies are currently evaluating the quality of recovery (QoR) after open radical nephrectomy (ORN) and epidural morphine analgesia. This was a randomized, prospective, and controlled study that explored the QoR on the first postoperative day after ORN. Eighty subjects were randomized into two groups. The first group received general anesthesia combined with epidural anesthesia and postoperative epidural analgesia with morphine and ropivacaine. The second group received general anesthesia and continuous postoperative intravenous analgesia with tramadol. Both groups received multimodal analgesia with metamizole. The primary outcome measure was the total QoR-40 score. The secondary outcome measures were QoR-15, QoR-VAS, and the visual analog scale (VAS) for pain, anxiety, and nausea. The median difference in the QoR-40 score after 24 postoperative hours between the two groups of patients was 10 (95% CI: 15 to 5), p < 0.0001. The median score and IQR of QoR-40 during the first 24 postoperative hours in the epidural group was 180 (9.5), and in the control group, it was 170 (13). The general independence test for secondary outcomes between groups was significant (p < 0.01). QoR-VAS was correlated with QoR-40 (r = 0.63, p ≤ 0.001) and with QoR-15 (r = 0.54, p ≤ 0.001). The total QoR-40 and QoR-15 alpha coefficients with a 95% CI were 0.88 (0.85-0.92) and 0.73 (0.64-0.81), respectively. There was a significant difference in the QoR between the epidural and the control groups after ORN. The QoR-40 and QoR-15 showed good convergent validity and reliability.

Predictive Value of Inflammatory and Nutritional Indexes in the Pathology of Bladder Cancer Patients Treated with Radical Cystectomy.

In recent years, the focus of numerous studies has been the predictive value of inflammatory and nutritional parameters in oncology patients. The aim of our study was to examine the relationship between the inflammatory and nutritional parameters and the histopathological characteristics of patients with bladder cancer. A retrospective study included 491 patients who underwent radical cystectomy for bladder cancer between 2017 and 2021. We calculated the preoperative values of the neutrophil-to-lymphocyte ratio (NLR), the derived neutrophil-to-lymphocyte ratio (dNLR), the systemic immune-inflammation index (SII), the systemic inflammatory response index (SIRI), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the prognostic nutritional index (PNI), and the geriatric nutritional risk index (GNRI). Statistically significant positive correlations were observed between NLR, dNLR, SII, SIRI, and PLR and the pathological stage of the tumor. We observed statistically significant inverse correlations for LMR, PNI, and GNRI with the tumor stage. SIRI was identified as an independent predictor of the presence of LVI. dNLR was identified as an independent predictor of positive surgical margins. GNRI was identified as an independent predictor of the presence of metastases in the lymph nodes. We noticed the predictive value of SIRI, dNLR, and GNRI in the pathology of bladder cancer patients.

The Impact of Variant Histology in Patients with Urothelial Carcinoma Treated with Radical Cystectomy: Can We Predict the Presence of Variant Histology?

Considering the divergent biological behaviors of certain histological subtypes of urothelial carcinoma, it would be of great importance to examine the impact of variant histology and to predict its presence in patients with bladder cancer. A single-center cohort study included 459 patients who underwent radical cystectomy for urothelial carcinoma between 2017 and 2021. Patients were followed up with until July 2022. We compared clinical, laboratory, and histopathologic characteristics and the overall survival between patients with pure urothelial carcinoma and variant histologies. Our results showed that the patients with variant histology were older and preoperatively more frequently had hydronephrosis and higher values of leukocytes and neutrophils. Also, we found a significant association between variant histology and an advanced stage of tumor disease, the presence of lymphovascular invasion, positive surgical margins, and metastases in surgically resected lymph nodes. The number of neutrophils was identified as an independent preoperative predictor of the presence of variant histology after a radical cystectomy. The overall survival of the patients with variant histology was significantly lower compared to the patients with pure urothelial carcinoma. According to our results, the presence of variant histology represents a more aggressive form of the disease. Preoperative neutrophil counts may indicate the presence of variant histology of urothelial carcinoma in patients with bladder cancer.

Role of Healthcare Professionals and Sociodemographic Characteristics in COVID-19 Vaccination Acceptance among Uro-Oncology Patients: A Cross-Sectional Observational Study.

At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro-oncology patients became a challenge. This was a single-center cross-sectional observational study aimed to investigate the rate of COVID-19 vaccination among uro-oncology patients receiving systemic therapy for metastatic renal cell carcinoma and metastatic castration-resistant prostate cancer. Furthermore, we aimed to assess patients' attitudes and identify factors influencing their decision to vaccinate against COVID-19. Data on patients' sociodemographic characteristics, vaccination status, and awareness and attitudes about COVID-19 vaccination were collected from questionnaires completed by the patients. A total of 173 patients were enrolled in this study, and 124 (71.7%) of them completed the COVID-19 vaccination. Significantly higher vaccination rates were found in male patients, and also in older patients, highly educated patients, and those who lived with one household member. Furthermore, we found significantly higher vaccination rates in patients who had consulted with doctors involved in their treatment, particularly with urologists. A significant association was observed between COVID-19 vaccination and doctor's advice, family member influence, and personal beliefs toward the vaccination. Our study showed multiple associations of patients' sociodemographic characteristics with vaccination rates. Furthermore, consultation with doctors who are particularly involved in oncology treatment and advice received from them were associated with significantly higher vaccination rates among uro-oncology patients.

Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis.

OBJECTIVE: To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT-TCC). PATIENTS AND METHODS: A single-centre series of 189 consecutive patients who were treated surgically for UUT-TCC between January 1999 and December 2009 was evaluated. Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT-TCC were excluded. In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses. RESULTS: The 5-year recurrence-free and cancer-specific survival estimates for the cohort in the present study were 66% and 62%, respectively. The 5-year bladder-only recurrence-free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P = 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non-Balkan endemic nephropathy areas; 95% confidence interval, 1.37-5.98; P = 0.005) were associated with disease recurrence. Tumour location was not associated with disease recurrence in any of the analyses. There was no difference in cancer-specific survival between renal pelvis and ureteral tumours (P = 0.476). Using multivariate analysis, pT classification (HR, 8.04; P = 0.001) and lymph node status (HR, 4.73; P = 0.01) were the only independent predictors associated with a worse cancer-specific survival. CONCLUSION: Tumour location is unable to predict outcomes in a single-centre series of consecutive patients who were treated with radical nephroureterectomy for UUT-TCC.

Midazolam versus Dexmedetomidine in Patients at Risk of Obstructive Sleep Apnea during Urology Procedures: A Randomized Controlled Trial.

Benzodiazepines are the most commonly used sedatives for the reduction of patient anxiety. However, they have adverse intraoperative effects, especially in obstructive sleep apnea (OSA) patients. This study aimed to compare dexmedetomidine (DEX) and midazolam (MDZ) sedation considering intraoperative complications during transurethral resections of the bladder and prostate regarding the risk for OSA. This study was a blinded randomized clinical trial, which included 115 adult patients with a mean age of 65 undergoing urological procedures. Patients were divided into four groups regarding OSA risk (low to medium and high) and choice of either MDZ or DEX. The doses were titrated to reach a Ramsay sedation scale score of 4/5. The intraoperative complications were recorded. Incidence rates of desaturations (44% vs. 12.7%, p = 0.0001), snoring (76% vs. 49%, p = 0.0008), restlessness (26.7% vs. 1.8%, p = 0.0044), and coughing (42.1% vs. 14.5%, p = 0.0001) were higher in the MDZ group compared with DEX, independently of OSA risk. Having a high risk for OSA increased the incidence rates of desaturation (51.2% vs. 15.7%, p < 0.0001) and snoring (90% vs. 47.1%, p < 0.0001), regardless of the sedative choice. DEX produced fewer intraoperative complications over MDZ during sedation in both low to medium risk and high-risk OSA patients.

The Effect of Epidural Analgesia on Quality of Recovery (QoR) after Radical Prostatectomy.

No studies are currently regarding the quality of recovery (QoR) after open radical prostatectomy (ORP) and epidural morphine analgesia. This was a randomized, prospective, and controlled study that explored QoR on the first postoperative day after ORP. Sixty-one men were randomized into two groups. The first (epidural) group received general anesthesia combined with epidural anesthesia and postoperative epidural analgesia with morphine and ropivacaine. The second (control) group received general anesthesia and continuous postoperative intravenous analgesia with tramadol. Both groups received multimodal analgesia with metamizole. The primary outcome measure was the total QoR-40 score. Secondary outcome measures were: QoR-15, QoR-VAS and the visual analogue scale (VAS) for pain, anxiety and nausea. The median difference in the total QoR-40 score after 24 postoperative hours between the two groups of patients was 2 (95% CI: −3 to 8), p = 0.35. The global multivariate inference test for secondary outcomes between groups was not significant p > 0.05). QoR-VAS was correlated with QoR-40 (r = 0.69, p ≤ 0.001) and with QoR-15 (r = 0.65, p ≤ 0.001). The total QoR-40 and QoR-15 alpha coefficient with 95% CI was 0.88 (0.83-0.92) and 0.83 (0.77−0.89), respectively. There was no difference in the QoR between the epidural and the control group after ORP. The QoR-40 and QoR-15 showed good convergent validity and adequate reliability.

MiR-375 and miR-21 as Potential Biomarkers of Prostate Cancer: Comparison of Matching Samples of Plasma and Exosomes.

MiR-21 and miR-375 have been reported as dysregulated in prostate cancer (PCa) in multiple previous studies. Still, variable or even opposing data for the expression of these microRNAs in PCa were found, and their potential biomarker properties remain elusive. In an attempt to clarify their significance as PCa biomarkers, as well as to compare different types of specimens as a source of relevant microRNAs, we used plasma and matching plasma-derived exosomes from patients with PCa and patients with benign prostatic hyperplasia (BPH). Plasma and exosomes were obtained from 34 patients with PCa and 34 patients with BPH, and their levels of expression of miR-21 and miR-375 were determined by RT-qPCR. We found no significant difference in the level of expression of these microRNAs in plasma and exosomes between patients with PCa and BPH. The level of exosomal miR-21 was elevated in PCa patients with high serum PSA values, as well as in patients with aggressive PCa, while for plasma samples, the results remained insignificant. For miR-375, we did not find an association with the values of standard prognostic parameters of PCa, nor with cancer aggressiveness. Therefore, our results support the potential prognostic role of exosomal miR-21 expression levels in PCa.

Optimal threshold of the prostate health index in predicting aggressive prostate cancer using predefined cost-benefit ratios and prevalence.

PURPOSES: The aim of the study was to determine optimal threshold of the Prostate Health Index (Phi) for predicting aggressive prostate cancer (PCa), taking into account misclassification costs, prevalence, and plausible risk factors. METHODS: This prospective cohort study analyzed patients undergoing prostate biopsy and Phi testing. The primary endpoint was aggressive PCa, defined as biopsy Gleason score ≥ 7. The data about age, total prostate-specific antigen (PSA), percentage of free PSA (%fPSA), and digital rectal examination (DRE) were extracted from the patient files. We divided the patients to the low- and high-risk group. The clinical usefulness of the Phi was assessed by the decision curve analysis. The predictive performance was assessed using the area under the receiver operating characteristic curve (AUC), per-class metrics, and the potential reduction in unnecessary biopsies. The uncertain interval of Phi values was also determined. RESULTS: There were 200 men included in the study, 35 (17.5%) of them having aggressive PCa. Important predictors of aggressive PCa were %fPSA, DRE, Phi, and belonging to the high-risk group. With optimal threshold of 30.7, about 32% unnecessary biopsies would be avoided. The optimal threshold of Phi was lower in the high-risk group than in the low-risk group. The AUC for detection of aggressive PCa was 0.791. Per-class metrics showed that the Phi has insufficient diagnostic accuracy. The lower and upper limits of the uncertain interval were 41.8 and 51.4, respectively. CONCLUSION: Different thresholds of the Phi could be optimal, depending on prevalence, patient characteristics, and misclassification costs. Further studies with a larger patient sample are necessary to confirm our conclusions.

Prognostic significance of non-muscle-invasive bladder tumor history in patients with upper urinary tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic factors for survival and disease recurrence in patients treated surgically for upper tract urothelial carcinoma (UTUC), focusing especially on the impact of history of non-muscle-invasive bladder cancer. PATIENTS AND METHODS: A single-center series of 221 consecutive patients who were treated surgically for UTUC between January 1999 and December 2010 was evaluated. Patients who had a history of bladder tumor at a higher stage than the upper tract disease, preoperative chemotherapy, or previous contralateral UTUC were excluded. None of the patients included in this study had distant metastasis at diagnosis of UTUC. In total, 183 patients (mean age 66 years, range 36-88) were then available for evaluation. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location (renal pelvis or ureter). All patients were treated with either open radical nephroureterectomy (RNU) or open conservative surgery. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses. RESULTS: Fifty-one patients (28%) had previous carcinoma not invading bladder muscle. Previous history of non-muscle-invasive bladder cancer was significantly associated with tumor multifocality (P < 0.001), concomitant bladder cancer (P < 0.001), higher tumor stage (P = 0.020), and lymphovascular invasion (P = 0.026). Using univariate analyses, history of non-muscle-invasive bladder cancer was significantly associated with an increased risk of both any recurrence (HR = 2.17; P = 0.003) and bladder-only recurrence (HR = 3.17; P = 0.001). Previous carcinoma not invading bladder muscle (HR = 2.58; P = 0.042) was an independent predictor of bladder-only recurrence. Overall 5-year disease recurrence-free (any recurrence and bladder-only recurrence) survival rates were 66.7% and 77%, respectively. Previous history of non-muscle-invasive bladder cancer was not associated with cancer-specific survival. Our results are subject to the inherent biases associated with high-volume tertiary care centers. CONCLUSIONS: Patients with previous history of non-muscle-invasive bladder cancer had a higher risk of having multifocal and UTUC with higher tumor stages (pT3 or greater). History of bladder tumor was an independent predictor of bladder cancer recurrence but had no effect on non-bladder recurrence, and cancer-specific survival in patients who underwent surgical treatment of UTUC.

Isolated eyeball metastasis of non-seminomatous germ cell testicular tumor.

INTRODUCTION: Testicular tumors most frequently metastasize to regional lymph nodes. Non-seminomatous tumor metastasis of testicle (NSGCTT) to the eyeball is rare. CASE REPORT: We presented a 24-year old man, referred to the ophthalmologist due to acute pain and abrupt loss of sight in the left eye accompanied by its enlargement. Orbital and endocranial computerized tomography (CT) was carried out, indicating the tumor in the left eye. His previous medical history provided the information that the right testicle was painlessly enlarged for 8 months. Ultrasonography showed a completely tumorously altered testis. Abdominal and chest CT failed to reveal any secondary deposits in visceral organs and lymph glands. Tumor markers (AFP - alpha-fetoproteins, beta hCG - human choronic gonadotropin beta) were elevated. Right radical orchiactomy was performed (showed NSGCTT), followed by polychemotherapy with cisplatinum 100 mg/m2, etoposide 120 mg/m2, bleomycin 15 mg/m2 (PEB x 4), resulting in normalization of tumor marker values and significant regression of the left eyeball. Next, the left eye enucleation and ocular prosthesis implantation was carried out. Pathohistological evaluation indicated fibrosis and necrosis only. In a 5-year follow-up period, the patient was free of recurrence. CONCLUSION: Isolated hematogenous metastasis of the NSGCTT to the eye is rare. In our case, the left eye was the only metastatic localization. After chemotherapy and eye enucleation the patient was in a 4-year follow-up period free of the recurrence.

The treatment of stage A testicular seminoma by carboplatin monochemotherapy.

BACKGROUND/AIM: Although radiotherapy is considered to be a standard treatment of stage A testicular seminoma, an increasing number of studies have reported encouraging results of the treatment by carboplatin monochemotherapy (CBDCA). The aim of this study was to analyse the treatment results of patients with clinical stage A seminoma treated by CBDCA on daily basis in the period June 1999 to September 2008. METHODS: A total of 124 patients, mean age 36.63 years (20-62 years), with stage A testicular seminoma were treated, upon radical orchiectomy, by adjuvant CBDCA (400 mg/m2 on day 1 and 22). RESULTS: Chemotherapy was well tolerated, except moderate nausea on the day of the drug administration and the following day. No patient had any serious disorders in blood cells count requiring substitutional treatment. During the mean follow-up period of 37.5 (range 6-111) months, three relapses were noted (2.41%) and none neoplasm of contralateral testicle or any other organ. CONCLUSION: Simple and easy carboplatin administration with excellent treatment results, along with good tolerance and absence of comorbidity, poses itself as a new "gold standard" of treatment for stage A testicular seminoma.

[Induratio penis plastica--localized or diffusive fibromatosis of tunica albuginea penis?].

BACKGROUND/AIM: The part of the tunica albuginea that is not affected by localized pathological fibrosis is excised by the Nesbit contralateral excisional corporalplasty in patients with induratio penis plastica (IPP). The aim of this study was to find out if there were any histological changes of the macroscopically normal tunica albuginea excised during the Nesbit corporalplasty. METHODS: A total of 31 patients, mean age 45 +/- 7.65 years, were surgical treated for extensive penile curvature (impossible or difficult penile imission in the vagina), using the Nesbit surgical technique. The tunica albuginea tissue was manipulated by Allis's clamps and excised in the shape of a diamond and placed in the 4% formaldehyde solution for histological analysis. The excised tunica albuginea was not wider than 1 cm, while the histological preparations were 3 to 5 microm thick, and they were stained with hematoxylin-eosin. The excised tunica albuginea tissue appeared macroscopically (anatomically) normal in all of the operated patients. In 28 (90.3%) patients opperated for dorsal curvature of the penis, the tissue of the tunica albuginea was excised from the urethral ridge, while in 3 (9.7%) patients operated for lateral curvature, the tissue was excised from the lateral corpus cavernosum. RESULTS: The histological results were normal in 12 (38.7%) patients, while in 19 (61.3%) cases the findings indicated fibrosis of tunica albuginea. No significant difference in the patients age was found between these two groups (p = 0.09). The analysis of a total number of histological results of the patients with tunica albuginea fibrosis in relation to the patients with normal results showed that there was no significant difference (chi2 = 1,2; df = 1; p > 0.05), suggesting that the macroscopically normal tunica albuginea is not always expected to yield normal histological result. CONCLUSION: Significantly more reported histological results of tunica albuginea fibrosis in the location that appeared normal macroscopically (chi2 = 27.5; df = 1; p < 0.01) indicated that, in the majority of IPP patients (61.3%), pathological lesion was diffusive with localized phenotypic expression plaque in the tunica albuginea, showing that, in the majority of cases noxa acted diffusely.