An increased body mass index is associated with a worse prognosis in patients administered BCG immunotherapy for T1 bladder cancer.

PURPOSE: The body mass index (BMI) may be associated with an increased incidence and aggressiveness of urological cancers. In this study, we aimed to evaluate the impact of the BMI on survival in patients with T1G3 non-muscle-invasive bladder cancer (NMIBC). METHODS: A total of 1155 T1G3 NMIBC patients from 13 academic institutions were retrospectively reviewed and patients administered adjuvant intravesical Bacillus Calmette-Guérin (BCG) immunotherapy with maintenance were included. Multivariable Cox regression analysis was performed to identify factors predictive of recurrence and progression. RESULTS: After re-TURBT, 288 patients (27.53%) showed residual high-grade NMIBC, while 867 (82.89%) were negative. During follow-up, 678 (64.82%) suffered recurrence, and 303 (30%) progression, 150 (14.34%) died of all causes, and 77 (7.36%) died of bladder cancer. At multivariate analysis, tumor size (hazard ratio [HR]:1.3; p = 0.001), and multifocality (HR:1.24; p = 0.004) were significantly associated with recurrence (c-index for the model:55.98). Overweight (HR: 4; p < 0.001) and obesity (HR:5.33 p < 0.001) were significantly associated with an increased risk of recurrence. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 9.9. For progression, we found that tumor size (HR:1.63; p < 0.001), multifocality (HR:1.31; p = 0.01) and concomitant CIS (HR: 2.07; p < 0.001) were significant prognostic factors at multivariate analysis (C-index 63.8). Overweight (HR: 2.52; p < 0.001) and obesity (HR: 2.521 p < 0.001) were significantly associated with an increased risk of progression. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 1.9. CONCLUSIONS: The BMI could have a relevant role in the clinical management of T1G3 NMIBC, if associated with bladder cancer recurrence and progression. In particular, this anthropometric factor should be taken into account at initial diagnosis and in therapeutic strategy decision making.

High-Grade T1 on Re-Transurethral Resection after Initial High-Grade T1 Confers Worse Oncological Outcomes: Results of a Multi-Institutional Study.

INTRODUCTION: The aim of this multicenter study was to investigate the prognostic impact of residual T1 high-grade (HG)/G3 tumors at re-transurethral resection (TUR of bladder tumor) in a large multi-institutional cohort of patients with primary T1 HG/G3 bladder cancer (BC). PATIENTS AND METHODS: The study period was from January 2002 to -December 2012. A total of 1,046 patients with primary T1 HG/G3 and who had non-muscle invasive BC (NMIBC) on re-TUR followed by adjuvant intravesical Bacillus Calmette-Guerin (BCG) therapy with maintenance were included. Endpoints were time to disease recurrence, progression, and overall and cancer-specific death. RESULTS: A total of 257 (24.6%) patients had residual T1 HG/G3 tumors. The presence of concomitant carcinoma in situ, multiple and large tumors (> 3 cm) at first TUR were associated with residual T1 HG/G3. Five-year recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were 17% (CI 11.8-23); 58.2% (CI 50.7-65); 73.7% (CI 66.3-79.7); and 84.5% (CI 77.8-89.3), respectively, in patients with residual T1 HG/G3, compared to 36.7% (CI 32.8-40.6); 71.4% (CI 67.3-75.2); 89.8% (CI 86.6-92.3); and 95.7% (CI 93.4-97.3), respectively, in patients with NMIBC other than T1 HG/G3 or T0 tumors. Residual T1 HG/G3 was independently associated with RFS, PFS, OS, and CSS in multivariable analyses. CONCLUSIONS: Residual T1 HG/G3 tumor at re-TUR confers worse prognosis in patients with primary T1 HG/G3 treated with maintenance BCG. Patients with residual T1 HG/G3 for primary T1 HG/G3 are very likely to fail BCG therapy alone.

Unilateral Post-Chemotherapy Robot-Assisted Retroperitoneal Lymph Node Dissection for Stage II Non-Seminomatous Germ Cell Tumors: Sexual and Reproductive Outcomes.

We aimed to report sexual and reproductive outcomes following post-chemotherapy robot-assisted retroperitoneal unilateral lymph node dissection (PC-rRPLND) for non-seminomatous germ cell tumors (NSGCTs) at a high-volume cancer center. We collected records regarding sexual and reproductive outcomes of patients undergoing unilateral PC-rRPLND for stage II NSGCTs from January 2018 to November 2021. Preoperative and postoperative (at 12 months) ejaculatory function as well as erectile function, based on the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Score (EHS), were assessed. Only patients with a pre-operative IIEF-5 of ≥22 and EHS of ≥3 were included in this analysis. Overall, 22 patients undergoing unilateral PC-rRPLND met the inclusion criteria. Of these, seven (31.8%) patients presented an andrological disorder of any type after PC-rRPLND. Specifically, retrograde ejaculation was present in three (13.6%) patients and hypospermia was present in one (4.5%) patient. Moreover, three (13.6%) patients yielded erectile dysfunction (IIEF-5 < 22 and/or EHS < 3). Lastly, two (9.1%) succeeded in naturally conceiving a child after PC-rRPLND. Retrograde ejaculation is confirmed to be one of the most common complications of PC-rRPLND. Moreover, a non-negligible number of patients experience erectile dysfunction.

Pelvic floor and sexual male dysfunction.

The pelvic floor is a complex multifunctional structure that corresponds to the genito-urinary-anal area and consists of muscle and connective tissue. It supports the urinary, fecal, sexual and reproductive functions and pelvic statics. The symptoms caused by pelvic floor dysfunction often affect the quality of life of those who are afflicted, worsening significantly more aspects of daily life. In fact, in addition to providing support to the pelvic organs, the deep floor muscles support urinary continence and intestinal emptying whereas the superficial floor muscles are involved in the mechanism of erection and ejaculation. So, conditions of muscle hypotonia or hypertonicity may affect the efficiency of the pelvic floor, altering both the functionality of the deep and superficial floor muscles. In this evolution of knowledge it is possible imagine how the rehabilitation techniques of pelvic floor muscles, if altered and able to support a voiding or evacuative or sexual dysfunction, may have a role in improving the health and the quality of life.

Unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection in Stage II non-seminomatous germ cell tumor: A tertiary care experience.

Objective: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) represents an integral component of the management of patients with non-seminomatous germ cell tumor (NSGCT). Modified templates have been proposed to minimize the surgical morbidity of the procedure. Moreover, the implementation of robotic surgery in this setting has been explored. We report our experience with unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection (PC-rRPLND) for clinical Stages IIA and IIB NSGCTs. Methods: A retrospective single institution review was performed including 33 patients undergoing PC-rRPLND for Stages IIA and IIB NSGCTs between January 2015 and February 2019. Following orchiectomy, patients were scheduled for chemotherapy with three cycles of bleomycin-etoposide-cisplatin. Patients with a residual tumor of <5 cm and an ipsilateral metastatic disease on pre- and post-chemotherapy CT scans were eligible for a unilateral template in absence of rising tumor markers. Descriptive statistics were provided for demographics, clinical characteristics, intraoperative and postoperative parameters. Perioperative, oncological, and functional outcomes were recorded. Results: Overall, 7 (21.2%) patients exhibited necrosis or fibrosis; 14 (42.4%) had mature teratoma; and 12 (36.4%) had viable tumor at final histology. The median lymph node size at surgery was 25 (interquartile range [IQR] 21-36) mm. Median operative time was 180 (IQR 165-215) min and no major postoperative complications were observed. Anterograde ejaculation was preserved in 75.8% of patients. Median follow-up was 26 (IQR 19-30) months and a total of three recurrences were recorded. Conclusion: PC-rRPLND is a reliable and technically reproducible procedure with safe oncological outcomes and acceptable postoperative ejaculatory function in well selected patients with NSGCTs.

Robotic radical cystectomy with concomitant implantation of 3-piece penile prosthesis: a one-step solution.

Radical cystectomy (RC) remains a highly morbid urologic procedure, and erectile dysfunction (ED) represents a significant burden for bladder cancer survivors. While inflatable penile prosthesis (IPP) offers a definitive treatment option for post-RC ED, the hostile postoperative anatomy of RC patients poses some technical challenges for IPP implantation. We report the case of a 54-year-old male with high grade bladder cancer who was managed with a robotic-assisted RC with Bricker ileal conduit urinary diversion and simultaneous implantation of a 3-piece IPP. Operative time was 310 min (230 min for the RC and ileal conduit portion, 80 min for IPP implantation). Estimated blood loss was 300 ml. Postoperative course was regular. The patient was discharged home on postoperative day 6. A robotic RC with concomitant IPP implantation can be offered as "one-step" solution to bladder cancer male patients. This approach can potentially offer the advantage of better outcome in terms of sexual function, while minimizing surgical risks, ultimately improving the quality of life of these patients.

Acute Toxicity in Hypofractionated/Stereotactic Prostate Radiotherapy of Elderly Patients: Use of the Image-guided Radio Therapy (IGRT) Clarity System.

BACKGROUND: The use of intra-fractional monitoring and correction of prostate position with the Image Guided Radio Therapy (IGRT) system can increase the spatial accuracy of dose delivery. Clarity is a system used for intrafraction prostate-motion management, it provides a real-time visualization of prostate with a transperineal ultrasound. The aim of this study was to evaluate the use of Clarity-IGRT on proper intrafraction alignment and monitoring, its impact on Planning Tumor Volume margin and on urinary and rectal toxicity in elderly patients not eligible for surgery. PATIENTS AND METHODS: Twenty-five elderly prostate cancer patients, median age=75 years (range=75-90 years) were treated with Volumetric Radiotherapy and Clarity-IGRT using 3 different schemes: A) 64.5/72 Gray (Gy) in 30 fractions on prostate and seminal vesicles (6 patients); B) 35 Gy in 5 fractions on prostate and seminal vesicles (12 patients); C): 35 Gy in 5 fractions on prostate (7 patients). Ultrasound identification of the overlapped structures to the detected ones during simulation has been used in each session. A specific software calculates direction and entity of necessary shift to obtain the perfect match. The average misalignment in the three-dimensional space has been determined and shown in a box-plot. RESULTS: All patients completed treatment with mild-moderate toxicity. During treatment, genitourinary toxicity was 32% Grade 1; 4% Grade 2, rectal was 4% Grade 1. At follow-up of 3 months, genitourinary toxicity was 20% Grade 1; 4% Grade 2, rectal toxicity was 4% Grade 2. At follow-up of 6 months, genitourinary toxicity was 4% Grade 1; 4% Grade 2. Rectal toxicity was 4% Grade 2. CONCLUSION: Radiotherapy with the Clarity System allows a reduction of PTV margins, the amount of fractions can be reduced increasing the total dose, not exacerbating urinary and rectal toxicity with greater patient's compliance.

Observational study on the effects of a topical formulation in patients with premature ejaculation.

Premature ejaculation (PE) has been defined as the inability to control or delay ejaculation, resulting in dissatisfaction or distress of the patient. Although PE is the most frequent sexual dysfunction, it is still underdiagnosed. An accurate clinical history is the best diagnostic approach that, in the majority of cases, is enough to differentiate between primary and acquired PE. Nowadays, treatment is not curative but is effective in increasing the intravaginal ejaculatory latency time (IELT), improving the sexual satisfaction of the couple [...].

Hyperbaric oxygen therapy reduces mortality in patients with Fournier's Gangrene. Results from a multi-institutional observational study.

BACKGROUND: Evidence about the clinical benefits of Hyperbaric Oxygen Therapy (HBOT) in patients with Fournier's Gangrene (FG) is controversial and inconclusive. We aimed to compare the mortality related to FG between patients undergoing surgical debridement and/or standard antibiotic therapy alone or in combination with HBOT. METHODS: We performed a retrospective multi-institutional observational case-control study. All patients admitted with diagnosis of FG from June 2009 to June 2019 were included into the study. Patients received surgical debridement and/or standard antibiotic therapy alone or in combination with HBOT. Factors associated with FG related mortality were assessed with uni-and multivariate analyses. The main outcome measure was FG related mortality. RESULTS: A total of 161 patients with diagnosis of FG were identified. Mean FG Severity Index was 8.6±4.5. All patients had broad-spectrum parenteral antibiotic therapy. An aggressive debridement was performed in 139 (86.3%) patients. A total of 72 patients (44.7%) underwent HBOT. Mortality due to FG was observed in 32 (36.0%) of patients who do not underwent HBOT and in 14 (19.4%) of patients who underwent HBOT (P=0.01). At the multivariate analysis, surgical debridement and HBOT were independent predictors of lower mortality while higher FG Severity Index was independent predictor of higher mortality. CONCLUSIONS: HBOT and surgical debridement are independent predictors of reduced FG related mortality.

Neuropathic painful complications due to endopelvic nerve lesions after robot-assisted laparoscopic prostatectomy: Three case reports.

RATIONALE: Robot-assisted laparoscopic prostatectomy (RALP) is the most frequent strategy used for the surgical remedy of patients with localized prostate cancer. Although there is awareness about potential patient positioning nerve injuries, iatrogenic nerve lesions are less described in the literature. Here, we report 3 cases of patients who presented with neuropathic painful complications due to RALP-associated nerve lesions. PATIENT CONCERNS: A 62-year-old patient (case 1), a 72-year-old male (case 2), and a 57-year-old patient (case 3) presented at the clinic with symptoms of neuropathic pain after RALP surgery. DIAGNOSIS: Patients were diagnosed with a potential injury of different branches of the pudendal nerve (cases 1 and 2), and left obturator nerve (case 3). INTERVENTIONS: Patients underwent multimodal pharmacologic treatment through pregabalin, weak opioids, strong opioid, paracetamol, and adjuvants. In cases 2 and 3, a multidisciplinary approach was needed. As the patients responded to conservative treatment, invasive approaches were not necessary. OUTCOMES: After treatment, the patients of case 1 showed pain relief after 4 days, paresthesia resolved in 15 days, whereas the anal crushing sensation lasted for approximately 1 month. In case 2, after 4 weeks of treatment, the patient experienced a considerable decrement in pain intensity with complete response after 4 months. In case 3, pain relief was achieved after 2 days, motor symptoms recovery after 2 weeks, and neuropathic features resolved completely after 5 weeks although the obturator sign resolved within 2 months. LESSONS: The RALP-associated neurologic injuries may occur even when performed by highly experienced surgeons. A better understanding of the potential iatrogenic nerve lesions can surely allow an improvement in the surgical technique. A multidisciplinary approach and early multimodal pain strategy are mandatory for managing these complications.

Exploring the molecular aspects associated with testicular germ cell tumors: a review.

Testicular germ cell tumors (TGCTs) represent the most common solid tumors affecting young men. They constitute a distinct entity because of their embryonic origin and their unique biological behavior. Recent preclinical data regarding biological signaling machinery as well as genetic and epigenetic mechanisms associated with molecular patterns of tumors have contribute to explain the pathogenesis and the differentiation of TGCTs and to understand the mechanisms responsible for the development of resistance to treatment. In this review, we discuss the main genetic and epigenetic events associated with TGCTs development in order to better define their role in the pathogenesis of these tumors and in cisplatin-acquired resistance.

Validation of Neutrophil-to-lymphocyte Ratio in a Multi-institutional Cohort of Patients With T1G3 Non-muscle-invasive Bladder Cancer.

INTRODUCTION: The aim of this multicenter study was to investigate the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and to validate the NLR cutoff of 3 in a large multi-institutional cohort of patients with primary T1 HG/G3 non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: The study period was from January 2002 through December 2012. A total of 1046 patients with primary T1 HG/G3 who had NMIBC on re-transurethral bladder resection (TURB) who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance from 13 academic institutions were included. Endpoints were time to disease, and recurrence-free (RFS), progression-free (PFS), overall (OS), and cancer-specific survival (CSS). RESULTS: A total of 512 (48.9%) of patients had NLR ≥ 3 prior to TURB. High pretreatment NLR was associated with female gender and residual T1HG/G3 on re-TURB. The 5-year RFS estimates were 9.4% (95% confidence interval [CI], 6.8%-12.4%) in patients with NLR ≥ 3 compared with 58.8% (95% CI, 54%-63.2%) in patients with NLR < 3; the 5-year PFS estimates were 57.1% (95% CI, 51.5%-62.2%) versus 79.2% (95% CI, 74.7%-83%; P < .0001); the 10-year OS estimates were 63.6% (95% CI, 55%-71%) versus 66.5% (95% CI, 56.8%-74.5%; P = .03); the 10-year CSS estimates were 77.4% (95% CI, 68.4%-84.2%) versus 84.3% (95% CI, 76.6%-89.7%; P = .004). NLR was independently associated with disease recurrence (hazard ratio [HR], 3.34; 95% CI, 2.82-3.95; P < .001), progression (HR, 2.18; 95% CI, 1.71-2.78; P < .001) and CSS (HR, 1.65; 95% CI, 1.02-2.66; P = .03). The addition of NLR to a multivariable model that included established features increased its discrimination for predicting of RFS (+6.9%), PFS (+1.8%), and CSS (+1.7%). CONCLUSIONS: Pretreatment NLR ≥ 3 was a strong predictor for RFS, PFS, and CSS in patients with primary T1 HG/G3 NMIBC. It could help in the decision-making regarding intensity of therapy and follow-up.

Predictors of Residual T1 High Grade on Re-Transurethral Resection in a Large Multi-Institutional Cohort of Patients with Primary T1 High-Grade/Grade 3 Bladder Cancer.

The aim of this multi-institutional study was to identify predictors of residual high-grade (HG) disease at re-transurethral resection (reTUR) in a large cohort of primary T1 HG/Grade 3 (G3) bladder cancer patients. A total of 1155 patients with primary T1 HG/G3 bladder cancer from 13 academic institutions that underwent a reTUR within 6 weeks after first TUR were evaluated. Logistic regression analysis was performed to assess the association of predictive factors with residual HG at reTUR. Residual HG cancer was found in 288 (24.9%) of patients at reTUR. Patients presenting residual HG cancer were more likely to have carcinoma in situ (CIS) at first resection (p<0.001), multiple tumors (p=0.02), and tumor size larger than 3 cm (p=0.02). Residual HG disease at reTUR was associated with increased preoperative neutrophil-to-lymphocytes ratio (NLR) (p=0.006) and body mass index (BMI)>=25 kg/m2. On multivariable analysis, independent predictors for HG residual disease at reTUR were tumor size >3cm (OR = 1.37; 95% CI: 1.02-1.84, p=0.03), concomitant CIS (OR 1.92; 95% CI: 1.32-2.78, p=0.001), being overweight (OR= 2.08; 95% CI: 1.44-3.01, p<0.001) and obesity (OR 2.48; 95% CI: 1.64-3.77, p<0.001). A reTUR in high grade T1 bladder cancer is mandatory as about 25% of patients, presents residual high grade disease. Independent predictors to identify patients at risk of residual high grade disease after a complete TUR include tumor size, presence of carcinoma in situ, and BMI >=25 kg/m2.

Micrornas in prostate cancer: an overview.

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.