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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.

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. 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. 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 (  0.01), length of stay (  < 0.001) and treatment failure (0/19 vs. 7/36,  0.04). 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.

Varicocele repair is mainly indicated in young adult patients with clinical palpable varicocele and abnormal semen parameters. Varicocele treatment is associated with a significant improvement in sperm concentration, motility, morphology, and pregnancy rate. Antegrade scrotal sclerotherapy （ASS） represented one of the main alternatives to the traditional inguinal or suprainguinal surgical ligation. This article reviews the use of ASS for varicocele treatment. We provide a brief overview of the history of the procedure and present our methods used in ASS. In addition, we review complication and success of ASS, including our own retrospective data of treating 674 patients over the last 17 years. Herein, we analyzed step by step the ASS technique and described our results with an original modified technique with a long follow-up. Between December 1997 and December 2014, we performed 674 ASS. Mean operative time was 14 min （range 9 to 50 min）. No significant intraoperative complications were reported. Within 90 days from the procedure, postoperative complications were recorded in overall 49 （7.2%） patients. No major complications were recorded. A persistent/recurrent varicocele was detected in 40 （5.9%） cases. In 32/40 （80%） cases, patients showed preoperative grade III varicoceles. In patients with a low sperm number before surgery, sperm count improved from 13 x 106 to 21 x 106 m1-1 （P〈 0.001）. The median value of the percentage of progressive motile forms at 1 h improved from 25% to 45% （P 〈 0.001）. Percentage of normal forms increased from 17% before surgery to 35% 1 year after the procedure （P 〈 0.001）. In the subgroup of the 168 infertile patients, 52 （31%） fathered offspring at a 12-month-minimum follow-up. Therefore, ASS is an effective minimal invasive treatment for varicocele with low recurrence/persistence rate.

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.

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.

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.

BackgroundRetzius-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.MethodsA 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.ResultsPatients 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).ConclusionsIn 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.

Background The urachus is an embryological structure of the urogenital sinus and allantoid that connects the allantois to the early bladder in fetal life and then remains as the median umbilical ligament connecting the umbilicus to the dome of the bladder. An early laparoscopic procedure could trigger a quiescent urachal remnant to become symptomatic, causing a lesion or infection either during carbon oxide contamination or insufflation or a periumbilical or suprapubic port placement. Case presentation A 15-year-old girl complaining of supra-pubic abdominal pain. About 2 months previously, she had undergone laparoscopic appendectomy for acute appendicitis, and early postoperative period was uneventful. She underwent a robotic-assisted excision of a urachal cyst. Conclusions It has been suggested that early laparoscopic procedures could trigger previously asymptomatic urachal remnants to become symptomatic. Robot-assisted excision of a urachal cyst is a safe, effective alternative to open surgery in children.

Kidney cancers represent the 14th most common malignancies with more than 300,000 new cases diagnosed in 2012.In 2012, kidney cancers accounted for 143,000 deaths with a crude rate value of 2% of all cancer deaths.Cigarette smoking, overweight and obesity and arterial hypertension are the most prevalent modifiable risk factors for RCC in both genders.Preoperative variables influencing the decision-making process for T1 renal tumours can be classified as patient-related (age, co-morbidities and performance status) and tumour-related (mode of presentation, clinical tumour size and anatomical/topographic characteristics) factors.The use of nephrometry systems (RENAL or PADUA) to define the anatomical and topographic characteristics of small renal masses should be considered the standard of care for the preoperative evaluation of patients suitable to nephron-sparing surgery.Treatment of cT1N0M0 parenchymal renal tumours should be based on patient-related factors, tumour-related characteristics and surgeon experience.Beyond tumour characterization according to histological subtype, the most important traditional pathological factors dictating the prognosis of patients with RCCs are the pathological size and extent of the primary tumour, nuclear grading, coagulative necrosis, microvascular invasion and sarcomatoid dedifferentiation.Prognosis can be estimated combining clinical and pathological factors in the context of mathematical models. This information can be used to improve the counselling process and to guide the follow-up.