The pathway of isolated seminal vesicle invasion has a different impact on biochemical recurrence after radical prostatectomy and pelvic lymphadenectomy.

OBJECTIVE: Prostate cancer with seminal vesicle invasion (SVI) has been considered an aggressive cancer. To evaluate the prognostic significance of different patterns of isolated SVI in patients undergoing radical prostatectomy (RP) and pelvic lymphadenectomy. METHODS AND MATERIALS: We retrospectively analyzed all patients who underwent RP between 2007 and 2019. Inclusion criteria were localized prostate adenocarcinoma, SVI at RP, at least 24-months follow-up, and no adjuvant treatment. Patterns of SVI were following Ohori's classification: type 1: direct spread along the ejaculatory duct from inside; type 2: seminal vesicle invasion outside the prostate, through the capsule; type 3: the presence of cancer island(s) in the seminal vesicle with no continuity from the primary tumor (discontinuous metastases). Patients with type 3 SVI (isolated or in association) were included in the same group. Biochemical recurrence (BCR) was defined as any postoperative PSA ≥0.2 ng/ml. A logistic regression analysis was performed to assess predictors of BCR. Time to BCR was investigated using the Kaplan-Meier analysis with the log-rank test. RESULTS: Sixty-one out of 1,356 patients were included. Median age was 67(7.2) years. Median PSA was 9.4(8.92) ng/ml. Mean follow-up was 85.28 ± 45.27 months. BCR occurred in 28(45.9%) patients. Logistic regression showed that a positive surgical margin (OR 19.964, 95%CI:1.172-29.322, P = 0.038) was predictor of BCR. Kaplan-Meier analysis demonstrated that patients with pattern 3 had a significantly shorter time to BCR compared to other groups (log-rank, P = 0.016). The estimated time to BCR was 48.7 months in type 3, 60.9 months in pattern 1 + 2, 74.8, and 100.8 months in isolated patterns 1 and 2, respectively. In patients with negative surgical margins, pattern 3 confirmed a shorter time to BCR compared to other types of invasions, with an estimated time to BCR of 30.8 months. CONCLUSIONS: Patients with type 3 SVI demonstrated a shorter time to BCR compared to other patterns.

Hidden penis: a rare case of delayed complication after a pelvic blunt trauma.

Penile dislocation following a traumatic pubic bone fracture is a very rare condition. Only a few cases are reported in the literature and the presentation mechanism is still not completely understood. The impact energy on the pelvis usually causes a displaced fracture with concomitant withdrawal of the pubic bone. The retraction of the pubic bone pulls the penis by its suspensory ligament leading to penile dislocation. We describe a rare case of a "hidden" penis 2 months after a blunt pelvic trauma following a motor vehicle accident. Clinical examination revealed a retracted penile skin. The penis was not visible, neither palpable in the expected position. Micturition took place by dripping urine from the opening of the prepubic skin where urine got trapped in the surrounding skin. He also complained of not having erections. A magnetic resonance imaging that showed invaginated penis, located in the anterior pelvic wall, adjacent to the right inguinal canal. Surgical repair was performed trough an inverted "V" suprapubic incision that allowed exploring the pubic area. The degloved penile shaft was identified and isolated from fibrotic adhesions to the surrounding tissue. The invaginated penile skin that was thin and retracted. The point of fixation was located deeply in the right pubic area where the subcutaneous tissue and skin were firmly attached to a spike of the fractured pubic bone. This adhesion was sharply resected and the penis and its skin were restored in their anatomical position. The suspensory ligament was partially detached. Erection was simulated using saline solution injection into the corpora cavernosa to exclude penile curvature. Postoperative course was uneventful. One year after surgery, the penis had a normal appearance without retraction and sexual function was completely restored. Our case pointed out the importance of genitalia evaluation by practitioners involved in the care of pelvic trauma patients.

Detection limits of significant prostate cancer using multiparametric MR and digital rectal examination in men with low serum PSA: Up-date of the Italian Society of Integrated Diagnostic in Urology.

Reasons why significant prostate cancer is still missed in early stage were investigated at the 22nd National SIEUN (Italian Society of integrated diagnostic in Urology, Andrology, Nephrology) congress took place from 30th November to 1st December 2020, in virtual modality. Even if multiparametric magnetic resonance (MR) has been introduced in the clinical practice several, limitations are emerging in patient with regular digital rectal examination (DRE) and serum prostate specific antigen (PSA) levels approaching the normal limits. The present paper summarizes highlights observed in those cases where significant prostate cancer may be missed by PSA or imaging and DRE. The issue of multidisciplinary interest had been subdivided and deepened under four main topics: biochemical, clinical, pathological and radiological point of view with a focus on PI-RADS 3 lesions.

Robot-assisted segmental ureterectomy with psoas hitch ureteral reimplantation: Oncological, functional and perioperative outcomes of case series of a single centre.

INTRODUCTION: According to the Urology guidelines, in selected cases of distal upper tract urothelial carcinoma (UTUC) segmental ureterectomy (SU) can be offered. There is no consensus in the surgical technique of preference. Robot-assisted SU could be an option to overcome all the limitations of open and laparoscopic techniques. We describe our first experience of robot assisted SU with psoas hitch ureteral reimplantation (RAPHUR). MATERIALS AND METHODS: 11 patients underwent RAPHUR for distal UTUC between 2013 and 2017 in a single centre. Pre-, intra-, and postoperative outcomes were assessed. Conventional imaging was performed after 1, 3, 6 months and 1 year from surgery as follow up protocol. We retrospectively evaluated the technical feasibility, oncological and functional outcomes. RESULTS: Median age was 71 years (57-91). The median length of the ureteral defect was 23 mm (10-40). Median preoperative creatinine level was 1.22 mg/dl (0.7-1.85) and median eGFR was 57.5 ml/min/1.73m2 (31-80). Five (45.5%) patients were symptomatic and 7 (63.6%) had hydronephrosis. Median operative time was 185 min (120-240), with a median blood loss of 100 ml (50-300). No case required conversion to open surgery. Overall, only 1 (9%) patient developed Clavien Dindo ≥ 3 postoperative complications. Average hospital stay was 7 (2-9) days. Mean postoperative creatinine was 1.05 mg/dl (0.8-1.85) and mean postoperative eGFR was 72 (36-83). During a median follow up time of 25.5 months (12-53), 4 (36.4%) patients experienced recurrence of urothelial cancer at conventional imaging follow up and 2 (18.2%) died due to its progression. CONCLUSIONS: In our initial experience RAPHUR can be proposed to selected cases of distal ureteral carcinoma with optimal perioperative and functional outcomes. However, cancer control may be undermined compared to nephroureterectomy. Thus, further prospective studies are needed to confirm our findings.

Uretero-iliac artery fistula: a challenge diagnosis for a life-threatening condition: monocentric experience and review of the literature.

INTRODUCTION: Uretero-iliac artery fistulae (UIAF) are the consequence of chronic inflammatory events that create a fibrous and poorly vascularized uretero-vascular adhesion. They often occur in patients with a history of surgery, pelvic radiotherapy, and chronic ureteral stenting. The presentation is usually massive gross hematuria with acute anemia unto to hemorrhagic shock, representing a life-threatening condition. High mortality rate is reported (7-23%). MATERIALS AND METHODS: We present four cases in three patients, treated in our Institution from 2013 to 2018, and reviewed the published literature. UIAF was defined as the ratified presence of an abnormal communication between the ureter and any artery. In all patients, the UIAF was initially evaluated by contrast-enhanced computed tomography (CT) angiography. The management strategy was defined individually based on the specific risk profile of each patient. RESULTS: In all cases, ureteral-iliac artery fistula occurred in female patients with previous surgery or radiation and with presence of indwelling ureteral stent. In every case the hematuria was massive and life-threatening. Diagnosis was delayed because of the poor diagnostic accuracy of CT scan, leading to over-treatment. Angiography resulted the best diagnostic tool. The endovascular treatment proved good outcomes in terms of early complications, with no case of mortality. CONCLUSIONS: In case of gross hematuria during ureteral stent change in female patients with history of previous pelvic surgery and radiation, UIAF must be suspected and immediately treated, since it represents a urological emergency. Angiography can be useful to confirm the diagnosis and endovascular treatment with vascular endoprosthesis is the best therapeutic option.

Approach for Renal Tumors With Low Nephrometry Score Through Unclamped Sutureless Laparoscopic Enucleation Technique: Functional and Oncologic Outcomes.

PURPOSE: We report an unclamped sutureless laparoscopic simple enucleation (LSE) technique for renal tumors with low nephrometry score and analyze complication rates as well as functional and oncologic outcomes. PATIENTS AND METHODS: We reviewed the data of 143 consecutive patients who underwent sutureless laparoscopic tumor enucleation with zero ischemia by a single experienced laparoscopic surgeon. The inclusion criteria for LSE with zero ischemia were tumor size ≤ 5 cm and RENAL nephrometry score of 4 to 6. The following data were collected: age, gender, body mass index, tumor side, renal function, tumor characteristics, American Society of Anesthesiologists score, operative time, positive surgical margins, estimated blood loss, and surgical complications. RESULTS: The median RENAL score of patients was 4.7. Median tumor size was 2.7 cm. Conversion to open surgery and hilum vessels clamped were not necessary in any patient. There were no changes in postoperative creatinine values and estimated glomerular filtration rate. The median operation duration time was 78.2 minutes, and median estimated blood loss was 110.2 mL. The median hospital stay was 3.8 days. A total of 2.8% of the patients had positive surgical margins at pathologic examination. Of the 143 patients, 7% developed fever after surgery requiring an adequate antibiotic regimen, 1.4% developed postoperative bleeding requiring blood transfusions, and 0.7% had postoperative urinary leakage from the drainage requiring double-J stent position. CONCLUSION: The unclamped sutureless LSE is a rational and safe approach to renal tumors with a low nephrometry score. This surgical technique does not increase the complication rate despite the reduction in parenchymal mass excised and the absence of hilar control.

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia

ABSTRACT Purpose We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. Materials and Methods We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. Results Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (p<0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. Conclusions This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

New Prostate Cancer Targets for Diagnosis, Imaging, and Therapy: Focus on Prostate-Specific Membrane Antigen.

The rising incidence rate of the cancer in the prostate gland has increased the demand for improved diagnostic, imaging, and therapeutic approaches. Prostate-specific membrane antigen (PSMA), with folate hydrolase and carboxypeptidase and, internalization activities, is highly expressed in the epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with, metastasis, progression, and androgen independence. Recently, PSMA has been an active target of investigation by several approaches, including the successful utilization of small molecule inhibitors, RNA aptamer conjugates, PSMA-based immunotherapy, and PSMA-targeted prodrug therapy. Future investigations of PSMA in prostate cancer (PCa) should focus in particular on its intracellular activities and functions. The objective of this contribution is to review the current role of PSMA as a marker for PCa diagnosis, imaging, and therapy.

The role of the serum testosterone levels as a predictor of prostate cancer in patients with atypical small acinar proliferation at the first prostate biopsy.

The current literature does not support the usefulness of clinical markers on predicting which patients with atypical small acinar proliferation (ASAP) are more likely to progress to prostate cancer (PCa). Androgens have long been considered to be the potential risk factors for PCa. However, the role of testosterone is controversial. The present study aims to analyze the relationship between serum testosterone (TS) levels and the diagnosis of PCa after a first prostate biopsy in patients affected by ASAP. This retrospective study included 143 patients diagnosed with ASAP in an initial transrectal ultrasound-guided prostate biopsy for suspicious PCa according to the European Association of Urology guidelines. Their TS levels, age, PSA, prostate volume, digital rectal examination, and prostate biopsy Gleason score (GS) were collected retrospectively for statistical analysis. All patients included in the study had a second biopsy and were suitable for further analysis. Re-biopsy was carried out 3-6 months after the first diagnosis of ASAP. Low and normal TS groups were composed of 29 (20.3%) and 114 (79.7%) patients, respectively. The diagnosis of the second biopsy was ASAP in 25.2% and PCa in 36.4% of patients. The comparison between patients with PCa and those with negative or an ASAP result in the second biopsy reported that men with cancer had significantly higher levels of TS (P < 0.001). However, there was no statistically significant association between GS postbiopsy and TS (P = 0.324). Our experience demonstrated that eugonadal patients may be a clinical risk factor for the diagnosis of PCa on re-biopsy after ASAP diagnosis than hypogonadal.

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia.

PURPOSE: We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. MATERIALS AND METHODS: We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. RESULTS: Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (pv0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. CONCLUSIONS: This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

Clinical performance and utility of a NNMT-based urine test for bladder cancer.

BACKGROUND: Bladder cancer (BC) represents the most common neoplasm of the urinary tract. Although cystoscopy and urine cytology represent the gold standard methods to monitor BC, both procedures have limitations. Therefore, the identification of reliable biomarkers for early and noninvasive detection of BC is urgently required. METHODS: In this study, we analyzed nicotinamide N-methyltransferase (NNMT) expression in urine samples from 55 BC patients and 107 controls, using real-time polymerase chain reaction (PCR). Receiver operating characteristic (ROC) analysis was used to identify the best cutoff value to discriminate BC patients from healthy donors, and to evaluate the diagnostic accuracy of a urine-based NNMT test. RESULTS: The results demonstrated that urinary NNMT expression was significantly (p<0.05) higher in BC patients. Moreover, a significant (p<0.05) inverse correlation was found between NNMT expression and histological grade. The ROC analysis revealed that a ΔCq of 13.3 was the best cutoff value, since it was associated with the highest combination of sensitivity and specificity. Moreover, the area under the curve (AUC) value was 0.913 (p<0.05), indicating the excellent diagnostic accuracy of a urine-based NNMT test. CONCLUSIONS: Our data indicate that NNMT is a promising biomarker that could be used to support the early and noninvasive diagnosis of BC.

Pathology and molecular updates in tumors of the prostate: towards a personalized approach.

INTRODUCTION: Treatment planning in patients with prostate neoplasms and prostate cancer (PCa) is generally based on the clinical and pathological molecular markers obtained from prostate needle biopsy and/or radical prostatectomy specimens. Area covered: Pathology of prostate neoplasms is evolving rapidly. Emerging trends include new additions to the 2016 World Health Organization (WHO) tumor classification as well as expanded diagnostic utility of biomarkers and molecular testing in tissue specimens, liquid biopsies and urinary samples, with the following purposes: diagnosis, prognosis and prediction. Expert commentary: The new additions to the 2016 WHO tumor classification, which include pathological definition of Intraductal carcinoma of the prostate (IDC-P) and of a new grading system for PCa, as well as identification of molecular markers, such as TMPRSS2-ERG and AR-V7, may pave the way to personalized therapy for patients with prostate tumors.

Update on histopathological evaluation of lymphadenectomy specimens from prostate cancer patients.

BACKGROUND: Metastases to lymph nodes (LNs) represent an unfavorable prognostic factor in patients with prostate cancer (PCa). Histological examination represents the gold standard in the evaluation of the lymphadenectomy (LND) specimens for the presence of secondary deposits. METHODS AND RESULTS: The metastatic detection rate can vary according to the approach adopted in the microscopic analysis of the LNs, which includes frozen-section examination, total inclusion of the tissue with and without whole-mount sections, serial sectioning, and the application of immunohistochemistry. The assessment of the sentinel LN, the search for micrometastases, and the evaluation of atypical LN metastatic sites further contribute to the detection of the metastatic spread. CONCLUSION: In this review, an update on the histopathological evaluation of LND specimens in patients with PCa is given, and focus is made on their clinical and prognostic significance.

Ultrasound analysis of seminal vesicles in prostate cancer invasion: monocentric experience of an extended prostate biopsy scheme.

PURPOSE: At present, uniformity does not exist with regard to the indication criteria of seminal vesicle (SV) biopsies. The aim of this study was to define the ultrasonographic (US) patterns observed in SV invaded by prostate cancer (PCa), and propose an extended prostate biopsy protocol when SV invasion (SVI) is suspected. METHODS: We reviewed 1.252 patients who underwent an initial transrectal ultrasound-guided prostate biopsy for suspicious PCa. We performed a 14-core biopsy scheme, as first intention, including 1 SV sample on each side when SVI is suspected: a nodule at the base of prostate (determined by digital rectal examination or US) and/or an US pattern that suggests a SVI. US patterns of SVs were classified as abnormal by a variation of the body anterior-posterior diameter, asymmetry of the volume, parietal thickness, distance between the SVs and the rectal surface, and altered echogenicity of SVs and the base of the prostate. RESULTS: Of the 137 biopsies performed in SVs, the SVI by PCa was diagnosed in 66.5% of candidate patients. The overall prevalence of SVI was 28.5%. No significant difference was noted between the patients with SVI and without SVI, when comparing age, prostate volume, and total core length, except for preoperative PSA serum levels. The sensitivity of any abnormal finding on transrectal ultrasound for the presence of SVI by PCa is 90.8%, whereas the specificity is 96%. CONCLUSIONS: We believe that an extended prostate biopsy protocol to provide the possibility of taking one biopsy core of each SV when SVI is suspected should be considered a complementary procedure for PCa staging.

Genitourinary cancers: molecular determinants for personalized therapies.

Recent insights and emerging strategies for individualized therapeutic approaches in patients with genitourinary (GU) cancers are based on patient's genomic and cancer's molecular profiles. This depends on the significant advances made in molecular biology technologies, such as next-generation sequencing and whole-exome sequencing. The rise of such novel techniques has grayly increased our knowledge on cancer cell biology and development, thus allowing to identify complex abnormalities at the genomic level. These findings have paved the way toward what is called precision medicine, thus providing healthcare from an individual perspective in patients with GU tumors.