Circulating Tumour DNA and Its Prognostic Role in Management of Muscle Invasive Bladder Cancer: A Narrative Review of the Literature.

Current management of non-metastatic muscle invasive bladder cancer (MIBC) includes radical cystectomy and cisplatin-based neoadjuvant chemotherapy (NAC), offers a 5-year survival rate of approximately 50% and is associated with significant toxicities. A growing body of evidence supports the role of liquid biopsies including circulating tumour DNA (ctDNA) as a prognostic and predictive marker that could stratify patients according to individualised risk of progression/recurrence. Detectable ctDNA levels prior to radical cystectomy have been shown to be correlated with higher risk of recurrence and worse overall prognosis after cystectomy. In addition, ctDNA status after NAC/neoadjuvant immunotherapy is predictive of the pathological response to these treatments, with persistently detectable ctDNA being associated with residual bladder tumour at cystectomy. Finally, detectable ctDNA levels post-cystectomy have been associated with disease relapse and worse disease-free (DFS) and overall survival (OS) and might identify a population with survival benefit from adjuvant immunotherapy.

The definition of ideal training of a urology resident from two different perspectives: trainees vs professors. Is there agreement in their idea of good training?

Introduction: At the end of their residency program, urology trainees should reach the minimum skills required to be able to work by themselves and within a team. To achieve this objective, it is fundamental that the training involves not only surgical activities, but also theoretical, academic, and relational ones. What is the perfect balance between these activities within the ideal urological training? This study aims to evaluate the concordance in different concepts of good urological training between different perspectives (trainees vs professors). Material and methods: Between January and December 2020 the same survey was distributed via email to 967 urology trainees and urology tutors. The survey investigated 5 educational fields: theoretical, clinical, surgical, relational, and simulation. For each field, specific questions investigated the importance of different activities and the training outcomes considered fundamental to be reached by a resident. The questions were evaluated by responders through a Likert 10-point scale. Results: The survey was completed by 155 trainees (58.9%, Group A) and 108 tutors (41.1%, Group B) from 26 different countries. Relative to the tutors, residents assigned statistically significantly lower scores to prostate biopsy (median score 9.11 vs 9.24), robotic simulator training (5.66 vs 5.93), on-call duties with consultants (6.85 vs 7.99), as well as all aspects of relational training (e.g., proper dialogue with colleagues: 7.95 vs 8.88). Conversely, residents assigned statistically significantly higher scores, albeit below sufficiency, to the performance of robotic prostatectomy as a first operator (4.45 vs 4.26). Finally, no discrepancies between residents' and tutors' scores were recorded regarding the remaining items of clinical training (e.g., urodynamics, outpatient clinic, ward duties) and surgical training (e.g., major open, laparoscopic and endoscopic surgical training; all p values >0.05). Conclusions: There was partial concordance between trainees and tutors regarding the activities that should be implemented and the skills that should be achieved during a urological residency. The residents aimed for more surgical involvement, while the tutors and professors, although giving importance to surgical and theoretical training, considered clinical practice as the fundamental basis on which to train future urologists.

The effect of pelvic floor muscle training on urodynamic parameters in women with stress urinary incontinence.

Introduction: Pelvic floor muscle training (PFMT) is suggested for women with stress urinary incontinence (SUI). The aim of our study is to examine the effectiveness of PFMT on urodynamic (UDS) parameters. Material and methods: This is a prospective observational study enrolling women with SUI. Pelvic surgery, prolapse, body mass index >30, and cognitive disability were exclusion criteria. Patients had baseline UDS, then PFMT only (Group A) or PFMT plus biofeedback (BFD) (Group B) for 6 months and UDS 3 months after treatment. The primary investigated parameters were the number of pads used per day and Valsalva leak point pressure (VLPP). Results: Forty-six women completed the study, 22 in Group A and 24 in Group B. At baseline, all patients documented SUI with 3 median pads used per day. Urodynamic SUI was documented with a median Valsalva leak point pressure (mVLPP) of 45 cmH2O. At the re-evaluation, 12 women (26.1%) had SUI in BDs with median number pads per day of 1, which was statistically different to baseline (p = 0.02). Urodynamic SUI was reported in 8 (17.4%) women with a mVLPP of 88 cmH2O.Six patients were from Group A and 6 from Group B. In Group A, the median number of pads per day was 1, and urodynamic SUI was found in 3 women. In Group B, the median number of pads per day was 1, and urodynamic SUI was found in 5 women. Thirty-four women (73.9%) were dry - 16 (47.1%) from Group A and 18 (52.9%) from Group B. Conclusions: PFMT improves urodynamic parameters among women with SUI.

Using machine learning techniques to predict antimicrobial resistance in stone disease patients.

PURPOSE: Artificial intelligence is part of our daily life and machine learning techniques offer possibilities unknown until now in medicine. This study aims to offer an evaluation of the performance of machine learning (ML) techniques, for predicting bacterial resistance in a urology department. METHODS: Data were retrieved from laboratory information system (LIS) concerning 239 patients with urolithiasis hospitalized in the urology department of a tertiary hospital over a 1-year period (2019): age, gender, Gram stain (positive, negative), bacterial species, sample type, antibiotics and antimicrobial susceptibility. In our experiments, we compared several classifiers following a tenfold cross-validation approach on 2 different versions of our dataset; the first contained only information of Gram stain, while the second had knowledge of bacterial species. RESULTS: The best results in the balanced dataset containing Gram stain, achieve a weighted average receiver operator curve (ROC) area of 0.768 and F-measure of 0.708, using a multinomial logistic regression model with a ridge estimator. The corresponding results of the balanced dataset, that contained bacterial species, achieve a weighted average ROC area of 0.874 and F-measure of 0.783, with a bagging classifier. CONCLUSIONS: Artificial intelligence technology can be used for making predictions on antibiotic resistance patterns when knowing Gram staining with an accuracy of 77% and nearly 87% when identifying specific microorganisms. This knowledge can aid urologists prescribing the appropriate antibiotic 24-48 h before test results are known.

Association of metabolic syndrome with prostate cancer diagnosis and aggressiveness in patients undergoing transrectal prostate biopsy.

INTRODUCTION AND OBJECTIVE: Even though the only established risk factors for prostate cancer (PCa) are age, ethnic origin and family history, there are data suggesting that environmental factors, such as the presence of metabolic syndrome (MetS), may also play a role in the etiology of the disease. The aim of this study is to correlate MetS with PCa diagnosis and Gleason score (GS) in patients undergoing transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: This is a prospective, single-center study including 378 patients who underwent transrectal ultrasound guided prostate biopsy in our department during the years from 2018 to 2019. Patients were divided into two groups according to the presence of PCa. Group A included 197 patients diagnosed with PCa while Group B consisted of 181 patients without PCa in their biopsy result. Multiple variables such as the presence of MetS and its components were evaluated in correlation to the presence of PCa and PCa characteristics. Statistical analysis was performed using the IBM SPSS Statistics v.23 program. RESULTS: Mean PSA value was 8.7 ng/dl in the PCa group and 7.1 ng/dl in the non PCa group, respectively. MetS was diagnosed in 108 patients (54.8%) with PCa and 80 patients (44.2%) without PCa and the difference was statistically significant. Hypertriglyceridemia was the MetS component with statistically higher frequency in PCa patients. Furthermore, the prevalence of MetS was higher in higher Gleason score PCa (GS ≥ 4+3) patients vs lower Gleason score PCa (GS ≤ 3+4) patients. More specifically, MetS, hypertriglyceridemia, and low HDL levels were independent factors associated with higher Gleason score PCa (GS ≥ 4+3). CONCLUSIONS: Patients suffering from MetS who undergo prostate biopsy present with higher rates of PCa diagnosis and higher GS in comparison with patients with a normal metabolic profile.

Transdiaphragmatic nephrectomy with synchronous pulmonary and anterior thoracic wall mass metastasectomy in a young male with metastatic renal cell carcinoma; a single-incision approach.

Renal cell carcinoma represents approximately 3% of all cancers, with the highest incidence occurring in the western world. Around 33% of the patients experience metastatic disease at diagnosis. Since the approval of the first targeted therapy, the treatment of metastatic renal cell carcinoma (mRCC) has positively changed, but the surgical treatment of the primary tumor, and metastases if possible, is sometimes crucial in selected patients controlling the burden of cancer sites with the intention to improve survival. We, herein, report on a case of a young male patient presented in the emergency room with gross hematuria which underwent transdiaphragmatic nephrectomy with synchronous pulmonary and anterior thoracic wall mass metastasectomy with a single thoracic incision due to mRCC. Achieving a full response in patients with mRCC is extremely rare only with medical treatment. The role of complete surgical metastasectomy is questioned, but there are several studies that support its efficacy in achieving metastases free status prolonged overall survival and better quality of life. The therapeutic treatment plan for these patients should be discussed within dedicated multidisciplinary cancer centers and focus on each patient individually and they should be offered a closed follow-up strategy.

Fragility index of urological literature regarding medical expulsive treatment.

INTRODUCTION: The role of medical expulsive treatment (MET) is controversial. Fragility index is an additional metric to assess randomized controlled trials (RCTs) outcome validity and indicates how many patients would be required to convert a trial from being statistically significant, to not significant. The larger is the FI, the better the trial's data. The aim of this study is to assess FI of RCTs regarding MET for ureteral stones. MATERIALS AND METHODS: A systematic literature search was performed. RCTs, reporting stone expulsion as a dichotomous outcome, showing statistical significance were eligible. FI (the number of patients needed to change from a non-event to event group, to lose statistical significance) and Fragility quotient (FI divided by total sample size), were calculated while Pearson's correlation and Mann-Whitney U test were used as appropriate. RESULTS: Thirty-six RCTs were eligible, with median FI = 3.5 and fragility quotient = 0.042, median sample size = 81, median journal impact factor = 1.73 and median reported p value = 0.008. In 33.3% of the studies, number of patients lost during follow-up was larger than FI, while in 13.89% of the studies, FI was 0, indicating use of inappropriate statistical method. Pearson's correlation showed significant positive association between FI and sample size (r = 0.981), number of events (r = 0.982) and impact factor (r = 0.731), while no association was found with p value or publication year. CONCLUSIONS: In this analysis, a calculated FI of 3.5 indicates that findings from RCTs on MET for ureteral stones are fragile and should be interpreted in combination with clinical thinking and expertise.

An up-to-date evaluation of darolutamide for the treatment of prostate cancer.

Introduction: Currently, in prostate cancer, an increasing number of novel drugs are being used to delay its advancement to metastatic castration-resistant prostate cancer (mCRPC). Apalutamide, enzalutamide, and most recently, darolutamide (novel androgen receptor antagonists) have been approved for nonmetastatic castration-resistant prostate cancer (nmCRPC).Areas covered: The authors have evaluated darolutamide, covering all aspects of the clinical development, competence, and safety profile of the drug.Expert opinion: The unique structure of darolutamide is characterized by a high affinity for androgen receptors and detainment of antagonist activity in mutant isoforms of androgen receptors. In clinical practice, this is the main reason that makes darolutamide exceptional in terms of safety and efficacy compared to other drugs in this category. Darolutamide is considered to have the lowest probability for adverse events (AEs) compared to apalutamide and enzalutamide. Future studies, along with real-world clinical data are warranted to improve personalized treatment strategies as well as sequencing treatment between approved novel drugs.

Preoperative versus pathological staging of rectal cancer-challenging the indication of neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by surgery is recommended for patients with diagnosed rectal cancer UICC stage II/III. The present study aimed to evaluate the accuracy of preoperative staging with focus on tumor infiltration depth and lymph node status challenging the indication of neoadjuvant CRT. METHOD: All consecutive rectal cancer patients who underwent surgical resection without neoadjuvant CRT at the Klinikum Stuttgart, Germany, between January 2015 and December 2018, were included into the study. Clinicopathologic features focusing on preoperative tumor staging and histological outcome were assessed. RESULTS: A total of 100/162 patients (61.7%) underwent primary surgical rectal resection with curative intent. Among these patients, 54/100 had a correct preoperative T-staging, while 34 were overstaged and 12 understaged. With regard to the nodal status, 68 were accurately staged, while 28 were overstaged and 4 understaged. Only 4/40 perirectal lymph nodes of more than 5 mm in diameter in preoperative MRI histologically revealed to be metastasis. CONCLUSION: For patients without neoadjuvant CRT, a tendency to preoperative overstaging was observed. Lymph node size alone did not reliably predict metastasis. According to current guidelines, 21/62 (33.9%) of these patients would have been overtreated by using CRT. On the background of relevant side effects, complications, and the limited benefit of CRT on overall survival, we suggest that primary surgical resection should be recommended more liberally for stages II and III rectal cancer.

Renal Hematomas After Ureterolithotripsy: Report of Four Cases.

Background: Renal hematomas, although relatively rare, are potentially life-threatening complications after ureterolithotripsy. Case Presentation: We present four cases of renal hematomas that occurred in our department during the past decade (2008-2018). Unstable vital signs, increased inflammatory markers, fever, and flank pain were the commonest postoperative findings. Two patients were treated conservatively and had an uneventful recovery, whereas one patient underwent selective arterial embolization for bleeding control. The fourth patient was diagnosed with contralateral ureteral urothelial tumor and ultimately underwent contralateral radical nephroureterectomy. Conclusion: Application of safety measures during ureteroscopy may reduce the incidence of perirenal hematomas. Prompt diagnosis is based on a thorough clinical examination in combination with imaging to evaluate the location and extent of the hematoma.

A case of cavernosal abscess after neglected penile fracture and bacteremia.

Penile abscess is a urological entity rarely described in the literature. It has been associated with injection therapy for erectile dysfunction, penile instrumentation, trauma and priapism. Identified risk factors include immunosuppresion and pre-existing local or distant infection. Common causal microorganisms include Staphylococcus aureus, Streptococci and Bacteroides. We herein report on a case of penile abscess in a 37-year-old patient occurring after sexual trauma and presenting with bacteremia.

Does the Use of a Robot Decrease the Complication Rate Adherent to Radical Cystectomy? A Systematic Review and Meta-Analysis of Studies Comparing Open with Robotic Counterparts.

Introduction: Radical cystectomy (RC) is the mainstay of treatment for muscle-invasive bladder cancer. In 2003, the first robot-assisted radical cystectomy (RARC) was performed and since then many studies, mainly observational, were conducted to compare robotic and open methods. This study aims to assess perioperative outcomes between the two methods based on pooled data from existing literature. Methods: A literature search of articles in English and French languages was performed in three databases (Medline, Embase, and Cochrane) until 30th of June 2018, as well as in urology conference programs and reference lists of included studies. The study protocol was registered at PROSPERO (CRD42018103063). Terms such as "robotic," "open," and "radical cystectomy" and synonyms were used for the searching algorithm. The primary outcome was the number of minor and major postoperative complications (Clavien grading system). Risk of bias was assessed with the Cochrane tool and Newcastle-Ottawa scale. Comparison of continuous outcomes was performed with weighted mean differences, while for dichotomous outcomes, odds ratios (ORs) were used. Review Manager 5.3 was used. Results: Fifty-four studies (5 randomized trials and 49 observational) were eligible, including 29,697 patients (6500 in the RARC group and 23,197 in the open radical cystectomy group). Minor complications (grade 1-2) in pooled data of 29 studies were fewer in the RARC group (OR = 0.54, 95% confidence interval [CI]: 0.38-0.76, p < 0.001), a difference persisting after sensitivity analysis for 30 and 90 days. Major complications (grade 3-5) in 31 studies were fewer in the RARC group (OR = 0.78, 95% CI: 0.65-0.94, p = 0.009), but this difference disappeared in the 30-day subanalysis. RARC was associated with lower blood transfusion rates (p < 0.001), lower length of stay (p < 0.001), faster return to regular diet (p < 0.001), and lower postoperative mortality rates (p < 0.001), but longer operating time. Conclusions: RARC appears to be associated with fewer complications and favoring perioperative outcomes in comparison with the open method. Due to the observational nature of most studies, larger randomized trials are needed to confirm these findings.

Patient positioning during percutaneous nephrolithotomy: what is the current best practice?

Percutaneous nephrolithotomy (PCNL) is the gold standard procedure for treatment of large stones and complex kidney disorders, but its morbidity remains the highest among stone treatment procedures. In pursuit of minimizing complication rates, surgeons have developed different variations of the classic prone position in which PCNL is usually performed; one among them is supine position. In this study, we review the literature and present all available evidence on different variations in positioning during PCNL, in an effort to identify if there is a position that can minimize the morbidity of this procedure.

A case of penile strangulation after placement of metallic rings.

Penile strangulation following placement of metallic rings is a rare clinical entity that needs urgent attention to avoid potentially severe clinical consequences. Careful handling and occasionally a multidisciplinary approach are the keys to a successful outcome.

Effects of two proprioceptive training programs on ankle range of motion, pain, functional and balance performance in individuals with ankle sprain.

BACKGROUND: Following ankle sprain, residual symptoms are often apparent, and proprioceptive training is a treatment approach. Evidence, however, is limited and the optimal program has to be identified. OBJECTIVE: To investigate the effects of two post-acute supervised proprioceptive training programs in individuals with ankle sprain. METHODS: Participants were recruited from a physiotherapy center for ankle sprain rehabilitation. In a pre-post treatment, blinded-assessor design, 22 individuals were randomly allocated to a balance or a proprioceptive neuromuscular facilitation (PNF) group. Both groups received 10 rehabilitation sessions, within a six-week period. Dorsiflexion range of motion (ROM), pain, functional and balance performance were assessed at baseline, at the end of training and eight weeks after training. RESULTS: Follow-up data were provided for 20 individuals. Eight weeks after training, statistically significant (p< 0.017) improvements were found in dorsiflexion ROM and most functional performance measures for both balance and PNF groups. Eight weeks after training, significant (p< 0.017) improvements in the frontal plane balance test and pain were observed for the balance group. CONCLUSIONS: Balance and PNF programs are recommended in clinical practice for improving ankle ROM and functional performance in individuals with sprain. Balance programs are also recommended for pain relief.

Clinical massage and modified Proprioceptive Neuromuscular Facilitation stretching in males with latent myofascial trigger points.

OBJECTIVES: To determine the immediate effects of modified Proprioceptive Neuromuscular Facilitation (PNF) stretching (group I) versus Myofascial Trigger Point (MTrP) therapy plus modified PNF stretching (group II) in comparison to a control group receiving no treatment. DESIGN: Randomized, assessor-blind, (3 x 4) mixed-model repeated measures. SETTING: University laboratory. PARTICIPANTS: Thirty physically active males with tight hamstrings and at least one latent MTrP on muscles innervated by the lumbosacral, sciatic, tibial and common peroneal nerves. MAIN OUTCOME MEASURES: Knee range of motion (ROM), stretch perception, pressure pain threshold (PPT) and subjective pain intensity. Outcomes were evaluated at baseline, immediately after treatment, at 10 and 30 min. RESULTS: Significant changes over time occurred for group II in all outcomes (p < or = 0.001). Group II also showed lower pain intensity scores than group I immediately post-treatment (p = 0.045) and a strong clinical effect over group I in ROM at all follow-ups (effect sizes = 0.9-1.0, p < or = 0.05). Other differences were found between both stretching groups as compared to the control group (p < or = 0.05). CONCLUSION: The results indicate immediate pre- to post-treatment benefits from MTrP therapy combined with modified PNF stretching in young and physically active males with latent MTrPs.

Effects of intensity of Transcutaneous Electrical Nerve Stimulation (TENS) on pressure pain threshold and blood pressure in healthy humans: A randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Transcutaneous electrical nerve stimulation (TENS) is primarily used for pain relief. However, evidence is beginning to emerge that TENS may also have a lowering effect on systemic blood pressure (BP). The purpose of this study was to investigate the comparative effects of 2 intensities on pressure pain threshold (PPT) and resting BP in healthy humans, using low-frequency stimulation applied segmentally to the pain site. METHODS: In a double-blind design, 40 volunteers, stratified by sex, were randomly allocated to 4 groups: high-intensity ("to tolerance without pain"), low-intensity ("strong but comfortable"), placebo, and control. TENS (2 Hz, 250 mu) was applied over the distribution of the superficial radial nerve of the dominant hand for 30 minutes. The outcome variables were measured at baseline and at 6 subsequent 10-minute intervals. For the PPTs, 2 measurements were taken bilaterally from the first dorsal interosseous muscle using a pressure algometer. The BP was measured in the brachial artery with an automatic monitor. Data difference scores were analyzed using repeated-measures and 1-way analyses of variance. RESULTS: The high-intensity group showed a significant rise in PPT compared with the low-intensity, placebo, and control groups for both measurement sites, which sustained 30 minutes poststimulation. TENS produced no significant effect on BP, regardless of intensity. DISCUSSION: These results affirm that high levels of intensity are of fundamental importance in effective TENS dosage. This also applies for low frequency, segmental stimulation. Resting BP seems not to be dependent on intensity.