Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

Double-Layered Hand-Sewn versus Stapled Intestinal Anastomosis in Patients Who Underwent Ileal Urinary Diversion in Radical Cystectomy: A Comparative and Cost Effective Study.

INTRODUCTION: Intestinal anastomosis can be performed by hand suturing (single layer or double layer) or by a mechanical suturing machine. The aim of the study was to compare complications, operative time, and costs of the intestinal anastomosis techniques. METHODS: A retrospective comparative study was conducted including patients who underwent radical cystectomy and uretero-ileo-cutaneostomy or vescica ileale Padovana orthotopic neobladder. Double-layered hand-sewn intestinal anastomosis (HS-IA) were performed using Vicryl stitches. Mechanical-stapled intestinal anastomosis (MS-IA) were performed with a mechanical stapler. RESULTS: Data of 195 patients who underwent were collected. 100 (51.3%) patients underwent HS-IA and 95 (48.7%) patients underwent MS-IA. Considering the complications classified according to Clavien-Dindo, a statistical difference with higher incidence for grade one in the HS-IA both in the ileal conduit group and in the neobladder one than the MS-IA (15.8% and 8.7%, respectively, in HS-IA vs. 1.7% and none in MS-IA). There is not a significant difference in time to flatus and time to defecation. Difference is recorded in the ileal conduit groups for the length of stay (10 days, range 9-12 with HS-IA vs. 13 days range 12-16 days with MS-IA (p < 0.001). The cost of the suture thread used for a single operation was 0.40 euros, whereas the overall cost of a disposable mechanical stapler and one refill was 350.00 €. CONCLUSION: Both HS-IA and MS-IA are safe and effective for patients. The cost for the stapling device is 350 €, in contrast, the cost for Vicryl sutures is negligible.

Retrosigmoid ileal conduit without transposition of the left ureter after open radical cystectomy for bladder cancer.

OBJECTIVES: To assess perioperative outcomes, complications, and rate of uretero-ileal anastomotic stricture (UAS) in patients undergoing retrosigmoid ileal conduit after radical cystectomy (RC). PATIENTS AND METHODS: Clinical records of consecutive patients receiving retrosigmoid ileal conduit after open RC for bladder cancer between March 2016 and June 2020 at two academic centres were prospectively collected. Two expert surgeons performed all cases. Operating room (OR) time, estimated blood loss (EBL), transfusion rate, and 90-day postoperative complications classified according to the Clavien-Dindo system, were assessed. In particular, rate of UAS, defined as upper urinary tract dilatation requiring endourological or surgical management, was evaluated. RESULTS: A total of 97 patients were analysed. The median (interquartile range [IQR]) OR time was 245 (215-290) min, median (IQR) EBL was 350 (300-500) mL, and blood transfusions were given to 15 (15.5%) cases. There were no intraoperative complications. There were 90-day postoperative complications in 33 patients (34%), being major (Grade III-V) in 19 (19.6%). Two patients died from early postoperative complications. At a median (IQR) follow-up of 25 (14-40) months, there was only one case (1%) of UAS, involving the right ureter and requiring an open uretero-ileal re-implantation. CONCLUSION: The retrosigmoid ileal conduit is a safe and valid option for non-continent urinary diversion after RC, ensuring a very low risk of UAS at an intermediate-term follow-up.

Surgical Treatment of Eosinophilic Cystitis in Adults: A Report of Two Cases and a Literature Review.

Eosinophilic cystitis is a rare disease that presents with either urinary frequency, hematuria, suprapubic pain or urinary retention. Although benign, this entity may progress to diffuse bladder involvement with the need for surgical treatment. We report on 2 cases of advanced disease that required cystectomy with very complex lower urinary tract reconstruction, and review the literature of surgically treated cases.

Urethral-fixation technique improves early urinary continence recovery in patients who undergo retropubic radical prostatectomy.

OBJECTIVES: To describe step-by-step an original urethrovesical anastomosis technique (urethral fixation) in patients undergoing retropubic radical prostatectomy (RRP), to compare their early urinary continence recovery with those in a control group receiving a standard anastomosis technique and to identify the predictors of early urinary continence recovery. PATIENTS AND METHODS: We compared 70 patients who underwent RRP with the urethral-fixation technique with a contemporary control group of 51 patients who received RRP with a standard urethrovesical anastomosis. In the urethral-fixation group, the urethrovesical anastomosis was made using eight single sutures. Specifically, to avoid retraction and/or deviations, we fixed the urethral stump laterally to the medial portion of levator ani muscle. Also, to maintain the normal position in the context of the pelvic floor, we fixed the urethral sphincter deeper to the medial dorsal raphe using a 3-0 polydioxanone suture at the 6 o'clock position before completing the incision of the urethral wall. Urinary continence recovery was evaluated at 1, 4, 8 and 12 weeks after catheter removal. Patients self-reporting no urine leak were considered continent. Uni- and multivariable analyses were used to identify predictors of urinary incontinence at the different follow-up time-points. RESULTS: The evaluated groups had comparable preoperative variables. At 1 week after catheter removal, 32 (45.7%) patients in the urethral-fixation group and 10 (19.6%) in the control group were continent (P = 0.01). At 4 weeks after catheter removal, 46 (65.7%) patients in the urethral-fixation group and 16 (31.4%) in the control group were continent (P = 0.001). At 8 weeks after catheter removal, 59 (84.3%) patients in the urethral-fixation group and 21 (41.2%) in the control group were continent (P < 0.001). Finally, at 12 weeks after catheter removal, 63 (90%) patients in the urethral-fixation group and 32 (62.7%) in the control group were continent (P = 0.001). The urethral-fixation technique was an independent predictor of urinary continence recovery at 1 week [odds ratio (OR) 4.305; P = 0.002); 4 weeks (OR 4.784; P < 0.001); 8 weeks (OR 7.678; P < 0.001) and 12 weeks (OR 5.152; P = 0.001) after catheter removal. CONCLUSIONS: The urethral-fixation technique significantly improves early urinary continence recovery in comparison with the standard technique. Moreover, our study confirmed that this surgical technique is an independent predictor of urinary continence recovery at 1, 4, 8 and 12 weeks after catheter removal.

Anatomical study of renal arterial vasculature and its potential impact on partial nephrectomy.

OBJECTIVES: To validate Graves' classification of the intrarenal arteries and to verify the absence of collateral arterial blood supply between different renal segments, in order to maximize peri-operative and functional outcomes of partial nephrectomy. MATERIALS AND METHODS: The study was performed on 15 normal kidneys sampled from eight unembalmed cadavers. Kidneys with the surrounding perirenal fat tissue were removed en bloc with the abdominal segment of the aorta. The renal artery was injected with acrylic and radiopaque resins, with the specimen suspended in water. CT examination of the injected kidneys was performed to analyse the branches located deeply. After imaging acquisition, the specimens were treated with sodium hydroxide for removal of the parenchyma to obtain vascular casts. RESULTS: Ten casts (66.6%) showed the classic subdivision of the main artery into single posterior and anterior branches. With regard to the distribution of the segmental or second-order arteries, only two casts (13%) showed a pattern similar to that described by Graves, characterized by four segmental (second-order) branches coming from the anterior renal artery (apical, superior, middle and inferior). In the remaining 13 kidneys (87%) a different arterial vascular network was detected. In 10 casts (80%) a single renal segment was vascularized by two or more different branches coming from an artery leading to another segment (multiple vascularization). Multiple vascularization was observed in three (20%) apical segments, five (33%) superior segments, six (40%) middle segments, seven (47%) inferior segments and two (13%) posterior segments. CONCLUSIONS: This study shows that in the human kidneys the arterial vasculature is frequently different from that described by Graves. Moreover, in a significant percentage of cases, a single renal segment receives two or more branches that originate from an artery leading to another segment.

Critical analysis of phase II and III randomised control trials (RCTs) evaluating efficacy and tolerability of a ß3-adrenoceptor agonist (Mirabegron) for overactive bladder (OAB).

To critically analyse available phase II and III randomised control trials (RCTs) reporting clinical data about the efficacy and tolerability of Mirabegron (a ß3-adrenoceptor agonist) in the treatment of overactive bladder (OAB) syndrome. A review of the literature was performed in September 2013 using the MEDLINE database. A 'free text' protocol was used for the search strategy using 'overactive bladder' and 'Mirabegron' as keywords. Subsequently, the searches were pooled and limited to phase II and III RCTs. Two phase II and five phase III RCTs were selected and analysed. The available phase II studies showed the efficacy and tolerability of different doses of Mirabegron compared with placebo. Moreover, a dose-ranging study showed that 50 mg once daily should be considered the most promising dose for clinical use. The 12-week phase III studies confirmed the effectiveness of Mirabegron to significantly reduce the mean number of incontinence episodes/24 h and the mean number of micturitions/24 h compared with placebo. A post hoc analysis confirmed that favourable results with Mirabegron were reported both in patients with OAB who were antimuscarinic naïve and in those who had discontinued prior antimuscarinic therapy. Moreover, a phase III trial showed the safety and tolerability of 12-month treatment of Mirabegron. Discontinuation due to adverse events was low both using the 50 and 100 mg dose of Mirabegron. Mirabegron is the first of a new class of drugs for the treatment of OAB able to influence non-voiding activity and produce an increased storage capacity and inter-void interval. Recently published phase II and III RCTs have shown that the ß3-adrenoceptor-selective agonist, Mirabegron, is an effective and safe drug for the symptomatic treatment of OAB syndrome. Mirabegron represents a valid medical option both for patients with OAB who are antimuscarinic naïve, as well as in those where antimuscarinics are ineffective or not tolerated.

Outcomes and limitations of laparoscopic and robotic partial nephrectomy.

PURPOSE OF REVIEW: The objective of this review article is to summarize and critically analyze the studies published in the previous year and report perioperative, functional, and oncologic outcomes after laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN). RECENT FINDINGS: Recent case series studies evaluating LPN confirmed the good oncologic results of this approach at intermediate and long-term follow-ups. Recent studies investigating RAPN confirmed the promising perioperative outcomes reported in the initial case series. Many studies tested and demonstrated the feasibility of both procedures in the treatment of very complex cases represented by tumors larger than 4 cm, hilar/central tumors, endophytic tumors, or tumors located in solitary kidney. Comparative studies confirm advantages in favor of RAPN in comparison with LPN, mainly in terms of warm ischemia time and perioperative outcomes. A recent matched pair analysis showed equivalent perioperative and functional outcomes between RAPN and open partial nephrectomy (OPN). SUMMARY: LPN and above all RAPN represent valid alternatives to OPN in the conservative treatment of renal tumors. Both procedures can be proposed also for the treatment of complex cases. Further, well conducted, comparative studies between RAPN and OPN are needed to test the ability of RAPN as an alternative to OPN in the treatment of more complex cases.

The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy.

A chronic prostatic inflammation seems to play a crucial role in benign prostatic hyperplasia (BPH) pathogenesis and progression. Therefore, inflammation could represent a new potential target for medical therapy of lower urinary tract symptoms (LUTS) due to BPH (LUTS/BPH). This review article analyzes the evidence supporting the role of inflammation in the onset and progression of BPH, and it assesses the potential impact of previous mechanisms on medical therapy of LUTS/BPH. Literature data support the role of inflammation as a relevant factor in the pathogenesis of BPH. Indeed, several data favour the role of infiltrating lymphocytes in the development and progression of prostate adenoma as an effect of a self-maintaining remodeling process. Although available drugs commonly used in the treatment of LUTS/BPH do not exhibit an anti-inflammatory activity, it seems to be obvious considering the inflammation as a new target in the treatment of LUTS/BPH. Drugs currently investigated for the treatment of prostatic inflammation include the hexanic lipidosterolic extract of Serenoa repens, nonsteroidal anti-inflammatory drugs, and vitamin D receptor agonists.

Short-term effects of bowel function on global health quality of life after radical cystectomy.

BACKGROUND: Radical cystectomy (RC) shows an important impact on quality of life (QoL), for various clinical aspects. The aim of our study was to evaluate the short-term bowel function in patients that underwent RC. METHODS: Two hundred and six patients with MIBC underwent RC with ONB or IC urinary diversion. QoL was measured using the EORTC QLQ C30 and the Short-Form SF-36 questionnaires before surgery and at 12 months postoperatively. Baseline characteristics, including demographic profile, BMI, Charlson Comorbidity Index (CCI), modified Frailty Index (m-FI), pathological tumor stage, Clavien-Dindo grade, and neo-adjuvant chemotherapy were recorded and compared. RESULTS: The uni-variate and multivariate analysis (OR) were performed for constipation, diarrhea and m-FI of patients underwent RC for localized MIBC according to global health status score (poor/good vs. very good). Multivariate analysis showed that constipation medium/high was significant associated with global health status poor/good (OR=2.39; 95% CI: 1.22-4.71; P=0.01); Diarrhea medium/high was associated with global health status poor/good (OR=2.85; 95% CI:1.18-6.92; P=0.02), and m-FI ≥2 score (OR=2.13; 95% CI: 0.99-4.57; P=0.05). CONCLUSIONS: Diarrhea and constipation are associated with a lower QoL in cystectomized patients, both with ONB or IC urinary diversion; such association is especially significant in more fragile patients (Frailty Index ≥2).

An update on diabetic women obstetrical outcomes linked to preconception and pregnancy glycemic profile: a systematic literature review.

Women with type 2 diabetes were less likely to have diabetes related complications than women with type 1. Women with type 1 diabetes had a high prepregnancy care and showed a worse glycemic control than women with type 2 both in the preconception period and during pregnancy. Obstetrical outcomes showed that preeclampsia and stillbirth rate is almost doubled in type 1 patients while perinatal deaths and SGA importantly increased in type 2 diabetes. In modern obstetrical care it is mandatory to maintain glucose levels as close to normal as possible particularly in diabetic population. HbA1C no higher than 6% before pregnancy and during the first trimester seems to decrease the risk of adverse obstetrical outcomes. Both the preconceptional counseling and glycemic profile optimization represent a fundamental step to improve pregnancy outcomes in women with preexisting diabetes. A systematic approach to family planning and the availability of preconception care for all diabetic women who desire pregnancy could be an essential step for diabetic management program.

Incidence of Rectal Injury After Radical Prostatectomy: A Systematic Review and Meta-analysis.

Context: Rectal injury (RI) is a dreaded complication after radical prostatectomy (RP), increasing the risk of early postoperative complications, such as bleeding and severe infection/sepsis, and late sequelae, such as a rectourethral fistula (RUF). Considering its traditionally low incidence, uncertainty remains as to predisposing risk factors and management. Objective: To examine the incidence of RI after RP in contemporary series and to propose a pragmatic algorithm for its management. Evidence acquisition: A systematic literature search was performed using the Medline and Scopus databases. Studies reporting data on RI incidence were selected. Subgroup analyses were conducted to assess the differential incidence by age, surgical approach, salvage RP after radiation therapy, and previous benign prostatic hyperplasia (BPH)-related surgery. Evidence synthesis: Eighty-eight, mostly retrospective noncomparative, studies were selected. The meta-analysis obtained a pooled RI incidence of 0.58% (95% confidence interval [CI] 0.46-0.73) in contemporary series with significant across-study heterogeneity (I2 = 100%, p < 0.00001). The highest RI incidence was found in patients undergoing open RP (1.25%; 95% CI 0.66-2.38) and laparoscopic RP (1.25%; 95% CI 0.75-2.08) followed by perineal RP (0.19%; 95% CI 0-276.95) and robotic RP (0.08%; 95% CI 0.02-0.31). Age ≥60 yr (0.56%; 95% CI 0.37-06) and salvage RP after radiation therapy (6.01%; 95% CI 3.99-9.05), but not previous BPH-related surgery (4.08%, 95% CI 0.92-18.20), were also associated with an increased RI incidence. Intraoperative versus postoperative RI detection was associated with a significantly decreased risk of severe postoperative complications (such as sepsis and bleeding) and subsequent formation of a RUF. Conclusions: RI is a rare, but potentially devastating, complication following RP. RI incidence was higher in patients ≥60 yr of age, and in those who underwent open/laparoscopic approach or salvage RP after radiation therapy. Intraoperative RI detection and repair apparently constitute the single most critical step to significantly decrease the risk of major postoperative complications and subsequent RUF formation. Conversely, intraoperatively undetected RI can lead more often to severe infective complications and RUF, the management of which remains poorly standardised and requires complex procedures. Patient summary: Accidental rectum tear is a rare, but potentially devastating, complication in men undergoing prostate removal for cancer. It occurs more often in patients aged 60 yr or older as well as in those who underwent prostate removal via an open/laparoscopic approach and/or prostate removal after radiation therapy for recurrent disease. Prompt identification and repair of this condition during the initial operation are the key to reduce further complications such as the formation of an abnormal opening between the rectum and the urinary tract.

Retzius-sparing vs. standard robot-assisted radical prostatectomy for clinically localised prostate cancer: a comparative study.

BACKGROUND: Retzius-sparing robot-assisted radical prostatectomy (RARP) is not yet universally accepted due to still limited functional data and some concerns on oncological safety compared to the standard one. We assessed perioperative, pathological and early functional outcomes in patients with clinically localised prostate cancer treated with Retzius-sparing versus standard RARP. METHODS: A single-surgeon cohort of 207 consecutive patients undergoing RARP was analysed. A later study group of 102 patients receiving the Retzius-sparing approach was compared with an earlier control group of 105 patients receiving the standard one. Urinary continence recovery 1 week after catheter removal was the primary study outcome. Urinary continence recovery 1, 2, 3 and 6 months after catheter removal, potency recovery 6 months postoperatively, rate of perioperative complications and positive surgical margins were secondary study outcomes. RESULTS: Patients in the study group reported significantly higher urinary continence recovery rates 1 week (91.2% vs. 54.3%, p < 0.001), 1 month (92.2% vs. 66.7%, p < 0.001), 2 months (95.1% vs. 74.3%, p < 0.001), 3 months (96.1% vs. 83.8%, p = 0.01), but not 6 months (97% vs 90.5%, p = 0.09) after catheter removal compared to controls. Potency recovery rates 6 months after catheter removal were significantly higher in the study than the control group (68.2% vs 51.6%, p = 0.03). On multivariable analyses, the Retzius-sparing approach was an independent predictor of 1-week urinary continence recovery, but not of 6-month potency recovery. There were significant differences neither in perioperative complication rate (9.8% in the study vs. 14.3% in the control group, p = 0.28) nor in positive surgical margin rate (9.8% in the study vs. 8.6% in the control group, p = 0.75). CONCLUSIONS: In a comparative study, we observed a significant improvement in immediate urinary continence, but not in early potency recovery, using the Retzius-sparing compared to the standard approach for RARP, with no increase in perioperative complication and positive surgical margin rate.

Outcomes and treatment failure after open or robotic ureteral reconstruction for iatrogenic injuries.

Objectives: The aim of this study is to assess the aetiology, perioperative outcomes and treatment failure of contemporary patients undergoing open or robot-assisted ureteral reconstruction for iatrogenic injuries. Patients and methods: We retrospectively analysed consecutive patients who underwent ureteral reconstruction for iatrogenic injuries at two academic centres 07/2013 and 06/2022. A variety of open or robot-assisted procedures were performed, including uretero-cystoneostomy, Boari bladder flap, uretero-ureterostomy, ileal replacement and pyelo-ureteroplasty. All procedures were performed by a single surgeon with extensive experience in open and robot-assisted surgery and preference-based management. Outcome measures were aetiology, estimated blood loss, length of stay, postoperative complications and treatment failure, defined as upper tract obstruction requiring permanent urinary drainage. We also planned a subgroup analysis comparing the outcomes between open and robot-assisted procedures. Results: Fifty-nine patients were included. Most injuries were consequent to endourological procedures (44%). The most frequently performed procedures were uretero-cystoneostomy (49.2%) and Boari bladder flap (32.2%). Forty (67.8%) were open, and 19 (32.2%) were robot-assisted procedures. Major postoperative complications were recorded in seven (11.9%) patients. After a median follow-up of 42 months (interquartile range 12-24), treatment failure was observed in seven (11.9%) cases. Robot-assisted versus open procedures were associated with decreased estimated blood loss (p = 0.01), length of stay (p < 0.001) and treatment failure (0/19 vs. 7/36, p = 0.04). Conclusion: In our series of iatrogenic ureteral lesions requiring reconstructive surgery, endourological procedures were the most frequent cause. Major postoperative complications were infrequent, and treatment failure rate was low. The robot-assisted approach was associated with improved perioperative outcomes and lower failure rate compared with open.

Minimal Fat Content in Papillary Renal Cell Carcinoma Diagnosed with Dual-Layer Dual-Energy CT.

A 56-year-old man with a previous right nephrectomy for multiple papillary renal cell carcinomas (pRCC) underwent a follow-up CT scan. Using a dual-layer dual-energy CT (dlDECT), we demonstrated the presence of a small amount of fat in a 2.5 cm pRCC that mimicked the diagnosis of angiomyolipoma (AML). Histological examination demonstrated the absence of macroscopic intratumoral adipose tissue, showing a fair amount of enlarged foam macrophages loaded with intracytoplasmic lipids. The presence of fat density in an RCC is an extremely rare occurrence in the literature. To our knowledge, this is the first description using dlDECT of a minimal amount of fat tissue in a small RCC due to the presence of tumor-associated foam macrophages. Radiologists should be aware of this possibility when characterizing a renal mass with DECT. The option of RCCs must be considered, especially in the case of masses with an aggressive character or a positive history of RCC.

Canonical and truncated transglutaminase-2 regulate mucin-1 expression and androgen independency in prostate cancer cell lines.

Androgen independency is associated with poor prostate cancer (PCa) survival. Here we report that silencing of transglutaminase-2 (TG2) expression by CRISPR-Cas9 is associated with upregulation of androgen receptor (AR) transcription in PCa cell lines. Knockout of TG2 reversed the migratory potential and anchorage independency of PC3 and DU145 cells and revealed a reduced level of mucin-1 (MUC1) RNA transcript through unbiased multi-omics profiling, which was restored by selective add-back of the truncated TG2 isoform (TGM2_v2). Silencing of AR resulted into increased MUC1 in TG2KO PC3 cells showing that TG2 affects transcriptional regulation of MUC1 via repressing AR expression. Treatment of PC3 WT cell line with TG2 inhibitor ZDON led to a significant increase in AR expression and decrease in MUC1. ZDON also blocked the formation of MUC1-multimers labelled with TG amine-donor substrates in reducing conditions, revealing for the first time a role for TG2, which we show to be externalised via extracellular vesicles, in MUC1 stabilisation via calcium-dependent transamidation. A specific antibody towards TGM2_v2 revealed its restricted nuclear location compared to the canonical long form of TG2 (TGM2_v1), which is predominantly cytosolic, suggesting that this form contributes to the previously suggested TG2-mediated NF-κB activation and AR transcriptional repression. As TGM2_v2 transcription was increased in biopsies of early-stage prostate adenocarcinoma (PRAD) patients compared to subjects presenting inflammatory prostatitis, and total TG2 protein expression significantly increased in PRAD versus normal tissue, the role of TG2 and its truncated form as a prostate malignancy marker is suggested. In conclusion, this investigation has provided the first unbiased discovery of a novel pathway mediated by TG2 via MUC1, which is shown to contribute to androgen insensitivity and malignancy of PCa cells and be upregulated in PCa biopsies, with potential relevance to cancer immune evasion.

Urethral fixation technique improves urinary continence recovery in men undergoing open radical cystectomy and ileal orthotopic neobladder.

BACKGROUND: We assessed urinary continence recovery and perioperative complications in patients operated on with the novel urethral fixation technique during open radical cystectomy (RC) with ileal orthotopic neobladder (IONB). METHODS: A retrospective cohort of 82 consecutive male patients undergoing open RC with IONB between 07/2013 and 06/2020 was analyzed. A study group of 48 patients operated on with the urethral fixation technique was compared with a control group of 34 patients receiving standard neovesico-urethral anastomosis. In the study group, the urethral stump was fixed to the dorsal median raphe posteriorly and to the medial portion of levator ani muscle postero-laterally in order to avoid urethral retraction/deviation. Urinary continence recovery and perioperative complications were assessed and compared between the two groups. RESULTS: The two groups were comparable with regard to demographic, clinical and pathological variables. At the median follow-up of 36 months, 42 (87.5%) patients in the study, and 22 (64.7%) in the control group during daytime, and 32 (66.7%) patients in the study, and 15 (44.1%) patients in the control group during nighttime used no pads or a safety pad (P=0.01 and P=0.04, respectively). Ninety-day postoperative complications were observed in 14 (29.2%) patients in the study, and in 10 (29.4%) cases in the control group (P=0.77). CONCLUSIONS: In our exploratory case-control study of male patients undergoing open RC with IONB, we observed a significant improvement in daytime and nighttime urinary continence recovery with no increase in perioperative complications using the novel urethral fixation technique compared to the standard neovesical-urethral anastomosis.

Robot-assisted Bladder Diverticulectomy Using a Transperitoneal Extravesical Approach.

Background: Acquired bladder diverticula (BD) are a possible complication of bladder outlet obstruction (BOO) due to benign prostate enlargement (BPE). Robot-assisted bladder diverticulectomy (RABD) has been proposed as an alternative to open removal; however, only a few small series have been published. Objective: To describe our surgical technique for RABD and to assess perioperative results and functional outcomes at 6-mo follow-up. Design setting and participants: A prospective single-centre, single-surgeon cohort of 16 consecutive men with posterior or posterolateral BD due to BOO/BPE undergoing RABD between May 2017 and December 2021 was analysed. Surgical procedure: RABD was performed with a four-arm robotic system via a transperitoneal approach. BD were identified intraoperatively via bladder distension with saline solution through an indwelling catheter with or without concomitant illumination using flexible cystoscopy and fluorescence imaging. Extravesical BD dissection and removal were performed. Outcome measurements and statistical analysis: Operating room time, estimated blood loss, intraoperative and postoperative complications, indwelling catheter time, and timing of associated procedures for BOO/BPE were assessed. The International Prostate Symptom Score (IPSS) and postvoid residual volume (PVR) were compared between baseline and 6 mo after surgery. Results and limitations: Median age and maximum BD diameter were 68 yr (interquartile range [IQR] 54-74) and 69 mm (IQR 51-82), respectively. The median operative time was 126 min (IQR 92-167) and the median estimated blood loss was 20 ml (IQR 15-40). No intraoperative complications were recorded. The urethral catheter was removed on median postoperative day 5 (IQR 5-7). Two men experienced 90-d postoperative complications (persistent urinary infection requiring prolonged antimicrobial therapy). Bipolar transurethral resection of the prostate was performed 3 wk before RABD in seven men and concomitant to RABD in nine men. Median IPSS significantly decreased from 25 (IQR 21-30) to 5 (IQR 5-6), and median PVR from 195 ml (IQR 140-210 ml) to 30 (IQR 28-40) ml (both p < 0.001) at 6-mo follow-up in comparison to baseline. A limitation is the rather small cohort with no control group. Conclusions: RABD is a safe and effective minimally invasive option for treatment of acquired BD in men with BOO/BPE. Validation of our results in larger series with longer follow-up is warranted. Patient summary: We describe our surgical technique for robot-assisted removal of pouches in the bladder wall (called diverticula) in men with bladder outlet obstruction caused by benign prostate enlargement, and report functional results at 6 months after the operation. This minimally invasive technique was found to be safe and effective.

Comparison of Fluoroquinolones and Other Antibiotic Prophylaxis Regimens for Preventing Complications in Patients Undergoing Transrectal Prostate Biopsy.

Our study aimed to compare the incidence of infective complications after transrectal ultrasound-guided prostate biopsy (TRUSBx) when adopting different antimicrobial prophylaxis regimens. A multi-institutional cohort of 1150 patients who underwent TRUSBx was retrospectively analyzed. Procedures were performed between 2017 and 2019 (before and after the EMA warning about the use of fluoroquinolones for the antibiotic prophylaxis of patient candidates to TRUSBx). The primary endpoint was the occurrence of infective complications, including sepsis and/or fever. The population was stratified according to the antibiotic prophylaxis adopted: fluoroquinolones (levofloxacin, ciprofloxacin, prulifloxacin), cephalosporins (cefixime, ceftriaxone) or trimethoprim/sulfamethoxazole. Univariable and multivariable binomial logistic regression models were used to assess the odds ratio (OR) with 95% confidence interval (CI) testing of the risk of infective complication after adjusting for each prebiopsy covariate. In total, 478 (41.6%) patients received fluoroquinolone-based prophylaxis. Among these, 443 (38.5%), 25 (2.2%) and 10 (0.9%) patients received levofloxacin prophylaxis, ciprofloxacin and prulifloxacin, respectively while 14.6% received cefixime, 20.7% received the comedication of ceftriaxone/fosfomycin and 23.1% received trimethoprim/sulfamethoxazole. The trimethoprim/sulfamethoxazole and fluoroquinolone regimens were significantly associated with a lower risk of infective complications (OR 0.15, 95% CI 0.03−0.48, p = 0.003 and OR 0.17, 95% CI 0.06−0.43, p < 0.001, respectively). The ceftriaxone/fosfomycin (OR 0.21, 95% CI 0.04−0.92, p = 0.04) and fluoroquinolone (OR 0.07, 95% CI 0.00−0.70, p = 0.048) prophylaxis were associated with a lower risk of infective sequelae. Fluoroquinolone-based prophylaxis was associated with a lower risk of infective complications after TRUSBx compared to other prophylaxis regimens although its clinical application was recently forbidden by European Medical Agency restrictions.