BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer: Current Treatment Landscape and Novel Emerging Molecular Targets.

Urothelial carcinoma (UC), the sixth most common cancer in Western countries, includes upper tract urothelial carcinoma (UTUC) and bladder carcinoma (BC) as the most common cancers among UCs (90-95%). BC is the most common cancer and can be a highly heterogeneous disease, including both non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) forms with different oncologic outcomes. Approximately 80% of new BC diagnoses are classified as NMIBC after the initial transurethral resection of the bladder tumor (TURBt). In this setting, intravesical instillation of Bacillus Calmette-Guerin (BCG) is the current standard treatment for intermediate- and high-risk patients. Unfortunately, recurrence occurs in 30% to 40% of patients despite adequate BCG treatment. Radical cystectomy (RC) is currently considered the standard treatment for NMIBC that does not respond to BCG. However, RC is a complex surgical procedure with a recognized high perioperative morbidity that is dependent on the patient, disease behaviors, and surgical factors and is associated with a significant impact on quality of life. Therefore, there is an unmet clinical need for alternative bladder-preserving treatments for patients who desire a bladder-sparing approach or are too frail for major surgery. In this review, we aim to present the strategies in BCG-unresponsive NMIBC, focusing on novel molecular therapeutic targets.

The Utility of Inflammatory Serum Markers in the Assessment of Perioperative Morbidity after Radical Cystectomy for Bladder Cancer.

Background and Objectives: To date, sparse evidence exists about the impact of inflammatory serum markers in predicting perioperative complications after radical cystectomy (RC) for bladder cancer (BC). Here, we evaluated the role of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), C-reactive protein (CRP), and plasma fibrinogen in predicting perioperative morbidity and unplanned 30-days readmission after RC for BC. Materials and methods: We relied on a collaborative database of 271 patients who underwent open RC for cT1-4a N0 M0 BC between January 2012 and December 2022. Univariable and multivariable binomial logistic regression analyses were performed to assess the odds ratio (OR) with 95% confidence intervals (CI) testing the ability of each serum marker to predict postoperative complications (any-grade and major complications), and 30-days unplanned readmission. Results: The median age at RC was 73 yr (IQR 67-79). A total of 182 (67.2%) patients were male and the median BMI was 25.2 (IQR 23.2-28.4). Overall, 172 (63.5%) patients had a Charlson Comorbidity Index (CCI) greater than 2 points and 98 (36.2%) were current smokers at the time of RC. Overall, 233 (86.0%) patients experienced at least one complication after RC. Of these, 171 (63.1%) patients had minor complications (Clavien-Dindo grade 1-2) while 100 (36.9%) experienced major complications (Clavien-Dindo grade ≥ 3). According to multivariable analysis, current smoking status, high plasma fibrinogen, and preoperative anemia were independently associated with major complications (OR 2.10, 95%CI 1.15-4.90, p = 0.02), (OR 1.51, 95%CI 1.26-1.98, p = 0.09), and (OR 1.35, 95%CI 1.17-2.57, p = 0.03), respectively. Overall, 56 (20.7%) patients experienced a 30-days unplanned readmission. According to univariable analysis, high preoperative CRP and hyperfibrinogenemia were significantly associated with an increased risk of unplanned readmission (OR 2.15, 95%CI 1.15-4.16, p = 0.02; OR 2.18, 95%CI 1.13-4.44, p = 0.02, respectively). Conclusions: In our study, the preoperative immune-inflammation signature described by NLR, PLR, LMR, SII, and CRP showed a low reliability in predicting perioperative course after RC. Preoperative anemia and hyperfibrinogenemia were independent predictors of major complications. Further studies are pending in order to draw definitive conclusions.

Plication surgery does not produce additional loss of length in Peyronie's disease patients.

Nesbit's procedure remains a cornerstone in surgical management of Peyronie's disease, despite the subjective loss of penile length. This retrospective study demonstrates that the perceived length loss has already occurred prior to surgery and that the Nesbit's procedure does not produce additional loss of length. Ninety-one patients who had undergone Nesbit's procedure between 2017 and 2022 at the Department of Urology of the University of Trieste were enrolled in the study. Preoperative stretched penile length and postoperative stretched penile length were measured. The curvature was uniplanar in 78 patients and biplanar in the remainder. Mean degree of the main curvature was 52.58° ± 14.13° and mean number of plications was 2.42 ± 1.07. Analysis revealed that the median of the differences between preoperative stretched penile length and postoperative stretched penile length was not significant (p = 0.466). According to our results, no significant penile shortening occurs as immediate consequence of Nesbit's procedure, as length is defined by the shorter side of the shaft affected by Peyronie's disease. Hence the length loss should have to be attributed to Peyronie's disease itself and could have been accurately predicted preoperatively allowing for a more accurate counseling of patients. Further studies are pending to assess potential postoperative loss of length due to scarring contracture.

Procalcitonin as prognostic factor in patients with Fournier's gangrene.

INTRODUCTION: Fournier's Gangrene (FG) has still a mortality rate up to 45%. Several studies identified prognostic factors but there is a knowledge gap concerning procalcitonin (PCT) levels and mortality risk in FG. This study is aimed to assess the role of PCT as prognostic factor in FG. MATERIALS AND METHODS: The medical records of 20 male FG patients admitted at the Department of Urology of "Cattinara" Hospital, University of Trieste between January 2019 and November 2020 were retrospectively reviewed. Clinical, demographic, microbiological data were collected. The Fournier's Gangrene Severity Index (FGSI) was calculated for each patient. RESULTS: Thirteen (65%) of 20 patients survived. Median age was 58 years (IQR 51-88), 15 patients (75%) had a Charlson Comorbidity Index (CCI) score ⩾2, 1 (5%) equal to 0, 4 to 1 (20%). Median FGSI score was 6 (IQR 2-12) and median PCT 0.8 ng/ml (IQR 0.04-2.12). At multivariate analysis PCT levels >0.05 ng/ml were associated with an increased overall mortality risk (OR 2.14, CI 1.25-4.27, p = 0.002). CCI score ⩾2 (OR 1.51, CI 1.01-2.59, p = 0.04), Streptococcical etiology (OR 3.41, CI 2.49-4.61, p = 0.002) and FGSI score >9 (OR 1.41, CI 1.19-2.21, p = 0.004) were associated with unfavorable outcome. CONCLUSION: PCT might be a prognostic factor in FG. CCI and FGSI are useful tools in mortality risk stratification. Streptococcical etiology is associated with unfavorable outcome. Further larger clinical trials are pending.

Neoclitoral location may affect sexual function in transgender women: a preliminary pelvic MRI study.

Assigned female at birth with anorgasmia possess a smaller clitoral glans and clitoral components farther from the vagina lumen than women with normal orgasmic function. There are no studies evaluating this correlation in operated transgender women. We evaluated whether differences in MRI measurements of neoclitoris volume and distance between the neoclitoris and the neovagina were correlated with differences in sexual function. We recruited for a prospective survey study 40 operated male to female patients (oMtF) who had undergone genital gender affirming surgery and postoperative pelvic MRI. Individual pelvic MRIs were reviewed by two blinded investigators, the three axes of the neoclitoris were measured and the volume was calculated using the ellipsoid formula. The distance between the neoclitoris and the neovagina was also measured. Sexual functioning was assessed using the Female Sexual Function Index (FSFI) and the operated Male to Female Sexual Function Index (oMtFSFI). Mean scores differences in FSFI, oMtFSFI were examined; associations with clitoral size, location, sexual functioning and demographical variables were investigated as well. The response rate was 55%, 11 MtFs operated with pubic neoclitoris technique (PNT) and 11 with neo-urethroclitoroplasty according to Petrovic (NCP). The NCP group presented a neoclitoris mean volume of 1.04 (SD 0.39) cc vs 1.31 (SD 0.78) cc of the other group (p = 0.55). The mean distance between neoclitoris and neovagina was 4.20 (SD 0.57) cm in the PNT group and 2.55 (SD 0.45) in the NCP group (p < 0.001). Patients who had undergone NCP achieved a higher FSFI and oMtFSFI mean Total Score than those operated with the previous technique (FSFI 25.81 SD 3.02 vs 18.62 SD 9.92 p = 0.08; oMtFSFI 37.63 SD 8.28 vs 43.36 SD 13.02 p = 0.23). According to pelvic MRI measurements, this study suggests a correlation between neoclitoral location and oMtF sexual satisfaction.

Validation of the Italian version of the Peyronie's Disease Questionnaire (PDQ).

Peyronie's disease (PD) is a connective tissue disorder characterized by the formation of fibrous plaques in the tunica albuginea of the penis which can result in pain, deformity and erectile dysfunction (ED). The Peyronie's Disease Questionnaire (PDQ) assesses the severity of symptoms, including pain, penile curvature and ED, as well as the impact on sexual function, emotional well-being, and overall quality of life of PD patients. Previous studies validated the PDQ in languages other than English and confirmed its test-retest reliability and clinical utility. Despite this, in many countries the unavailability of an adequate PDQ validation in native language hampers its use in clinical practice. In the present non-interventional, observational study we aimed at validating the Italian version of the PDQ (PDQ-I). Between January 2019 and November 2021, 79 PD patients from 6 Italian high-volume centers were administrated the PDQ-I in two separated office visits distanced by a period of 6 months. Intraclass correlation coefficients (ICCs) were used to evaluate the association between the three PDQ scale scores at visit 1 and 2. Paired t-tests were used to evaluate significant score changes between the 2 visits. Cronbach's alpha was used to assess internal consistency reliability. PDQ-I demonstrated an excellent test-retest reliability in the Italian population (ICC 0.78-0.92) as well as a strong internal consistency, with all three scale scores showing a Cronbach's alpha coefficient above 0.70. PDQ-I proved to be a useful tool which allows to reliably evaluate Italian PD patients' quality of life in both everyday andrological practice and clinical research. External validation of our results is pending.

Fluorescence Confocal Microscopy in Urological Malignancies: Current Applications and Future Perspectives.

Fluorescence confocal microscopy (FCM) represents a novel diagnostic technique able to provide real-time histological images from non-fixed specimens. As a consequence of its recent developments, FCM is gaining growing popularity in urological practice. Nevertheless, evidence is still sparse, and, at the moment, its applications are heterogeneous. We performed a narrative review of the current literature on this topic. Papers were selected from the Pubmed, Embase, and Medline archives. We focused on FCM applications in prostate cancer (PCa), urothelial carcinoma (UC), and renal cell carcinoma (RCC). Articles investigating both office and intraoperative settings were included. The review of the literature showed that FCM displays promising accuracy as compared to conventional histopathology. These results represent significant steps along the path of FCM's formal validation as an innovative ready-to-use diagnostic support in urological practice. Instant access to a reliable histological evaluation may indeed significantly influence physicians' decision-making process. In this regard, FCM addresses this still unmet clinical need and introduces intriguing perspectives into future diagnostic pathways. Further studies are required to thoroughly assess the whole potential of this technique.

Sentinel Lymph Node Biopsy in Prostate Cancer: An Overview of Diagnostic Performance, Oncological Outcomes, Safety, and Feasibility.

Sentinel node biopsy (SNB) for prostate cancer (PCa) represents an innovative technique aimed at improving nodal staging accuracy. The routinary adoption of this procedure in patients undergoing radical prostatectomy (RP) might be crucial to identify candidates who could effectively benefit from extensive pelvic lymph nodal dissection (ePLND). Despite some promising results, SNB for PCa is still considered experimental due to the lack of solid evidence and procedural standardization. In this regard, our narrative review aimed to analyze the most recent literature in this field, providing an overview of both the diagnostic accuracy measures and the oncological outcomes of SNB.

Reliable Prediction of Post-Operative Complications' Rate Using the G8 Screening Tool: A Prospective Study on Elderly Patients Undergoing Surgery for Kidney Cancer.

In the last years the incidence of renal neoplasms has been steadily increasing, along with the average age of patients at the time of diagnosis. Surgical management for localized disease is becoming more challenging because of patients' frailty. We conducted a multi-center prospective study to evaluate the role of the G8 as a screening tool in the assessment of intra and post-operative complications of elderly patients (≥70 y.o.) undergoing surgery for kidney cancer. A total of 162 patients were prospectively enrolled between January 2015 to January 2019 and divided into two study groups (frail vs. not-frail) according to their geriatric risk profile based on G8 score. Several factors (i.e., age, CCI, ASA score, preoperative anemia, RENAL score, surgical procedures, and techniques) were analyzed to identify whether any of them would configure as a statistically significant predictor of surgical complications. According to the G8 Score, 90 patients were included in the frail group. A total of 52 frail patients vs. 4 non-frail patients developed a postoperative complication of any kind (p < 0.001). Of these, 11 were major complications and all occurred in the frail group. Our results suggest that the G8 screening tool is an effective and useful instrument to predict the risk of overall complications in elderly patients prior to renal surgery.

An Observational Cohort Study Investigating the Incidence Rate of Infectious Complications After Routine Office Nephrostomy Tube Replacement Without Using Antimicrobial Prophylaxis.

OBJECTIVE: To investigate the incidence of infectious complications after routine office nephrostomy tube replacement (NTR) in patients that did not receive antimicrobial prophylaxis (AMP). METHODS: We prospectively enrolled all patients undergoing routine office NTR between July 2018 and September 2019. Each procedure was considered an independent event. Clinical, microbiological, demographic data were collected. AMP was exclusion criterion. All patients received a questionnaire via phone call within 3 weeks after NTR investigating fever, antibiotics use, hospital admissions. Infectious complications risk was assessed with univariate and multivariate binomial logistic regression analysis. RESULTS: One hundred forty-five routine NTRs were performed. Nineteen patients receiving AMP were excluded. Median age was 78 years (interquartile range 71-81). Charlson Comorbidity Index (CCI) score was ≥5 in 53.2% of patients, 34 had positive urine culture, none received AMP. Seventeen (13.49%) patients reported fever after procedure, 9 received antibiotic therapy while fever resolved spontaneously in 8. Three patients needed hospitalization, 2 for nephrostomy malfunction, 1 for infectious complications. At multivariate analysis only CCI score ≥3 was associated (P < .001) with increased infectious complications risk. CONCLUSION: In this study fever occurs after the 13.5% of the routine NTRs, in almost half cases resolves spontaneously rather than with oral antimicrobial therapy. Avoiding AMP before routine NTR does not expose patients to life-threatening infections.

Analysis of clinical utility of abdominopelvic computed tomography in the follow-up of Stage I seminoma: a single center evaluation.

BACKGROUND: Abdominopelvic computed tomography (CT) is widely used in the follow-up of seminoma patients after radical orchidectomy. The aim of this study was to evaluate the clinical utility of abdominopelvic computed tomography in the follow-up of patients with Stage I seminoma. METHODS: The pathological reports of all patients that have undergone radical orchidectomy in our tertiary referral center between January 2002 and January 2018 have been retrospectively reviewed. All patients with Stage I seminoma and negative serum tumor markers after radical orchidectomy were included. Patients with follow-up shorter than 12 months were excluded. Surveillance records of every patient were reviewed with regard to abdominopelvic imaging. RESULTS: Of the 133 patients who have undergone radical orchidectomy in our center, 55 had Stage I pure seminoma with normal levels of serum tumor markers after surgery. Two patients were excluded as the follow-up was inadequate. Mean follow-up was 63.2 months (IQR: 30-73). The results of 211 abdominopelvic CTs performed as part of the follow-up were reviewed. Two (3,7%) patients developed recurrence; one consisted of a scrotal lump and was diagnosed with ultrasonography (US) while the second appeared as paraaortic nodal metastasis and was diagnosed with abdominopelvic CT. The recurrence was successfully treated in both patients. A single abdominopelvic CT was useful for the detection of recurrent disease in our entire study population. No cancer specific death has been reported in the study population. CONCLUSIONS: Follow-up schedules for Stage I seminoma expose patients to potential risks of radiation-induced tumors, emotional distress and represent a significant burden for the healthcare system. The current series suggests that a better risk adapted patient-tailored follow-up program is needed in order to avoid unnecessary investigations.

Vaginoplasty in Male to Female transgenders: single center experience and a narrative review.

Vaginoplasty in Male to Female (M to F) transgenders is a challenging procedure, often accompanied by numerous complications. Nowadays the most commonly used technique involves inverted penile and scrotal flaps. In this paper the data of 47 M to F patients who have undergone sex affirmation surgery at the Department of Urology of the University of Trieste, Italy since 2014, using our modified vaginoplasty technique with the "Y" shaped urethral flap, have been retrospectively reviewed. Moreover, a non structured review of the literature with regards to short and long-term complications of vaginoplasty has been provided. All patients followed a standardized neo-vaginal dilation protocol. At follow up 2 patients were lost. At 12 months 88.9% of patients (40/45) were able to reach climax, 75.6% (34/45) were having neo-vaginal intercourses and median neo-vaginal depth was 11 cm (IQR 9-13.25): no statistically significant decrease in depth was found at follow up. Only one patient was dissatisfied with aesthetic appearance at 12 months. Our technique provided excellent cosmetic and functional results without severe complications (Clavien-Dindo ≥ 3). The review of the literature has highlighted the need to standardize a postoperative follow up protocol with particular regard to postoperative dilatation regimen. Further, larger randomized clinical trials are pending to draw definitive conclusions.

History vs. legend: Retracing invasion and spread of Oxalis pes-caprae L. in Europe and the Mediterranean area.

Oxalis pes-caprae L. is a South African geophyte that behaves as an invasive in the eurimediterranean area. According to a long-established hypothesis, O. pes-caprae may have invaded Europe and the Mediterranean area starting from a single plant introduced in the Botanical Garden of Malta at the beginning of the 19th century. The aim of this work was to test this hypothesis, to track the arrival of O. pes-caprae in different countries of the Euro-Mediterranean area and to understand the pathways of spreading and particularly its starting point(s). Historical data attesting the presence of the plant in the whole Euro-Mediterranean region were collected from different sources: herbarium specimens, Floras and other botanical papers, plant lists of gardens, catalogs of plant nurseries and plant dealers. First records of the plant (both cultivated and wild) for each Territorial Unit (3rd level of NUTS) were selected and used to draw up a diachronic map and an animated graphic. Both documents clearly show that oldest records are scattered throughout the whole area, proving that the plant arrived in Europe and in the Mediterranean region more times independently and that its spreading started in different times from several different centers of invasion. Botanical gardens and other public or private gardens, nurseries and plant dealers, and above all seaside towns and harbors seemingly played a strategic role as a source of either intentional and unintentional introduction or spread. A geographic profiling analysis was performed to analyse the data. We used also techniques (Silhouette, Kmeans and Voronoi tessellation) capable of verifying the presence of more than one independent clusters of data on the basis of their geographical distribution. Microsatellites were employed for a preliminary analysis of genetic variation in the Mediterranean. Even if the sampling was insufficient, particularly among the populations of the original area, our data supported three main groups of populations, one of them corresponding to the central group of populations identified by GP analysis, and the other two corresponding, respectively, to the western and the eastern cluster of data. The most probable areas of origin of the invasion in the three clusters of observations are characterized by the presence of localities where the invasive plant was cultivated, with the exception of the Iberian cluster of observation where the observations in the field predate the data about known cultivation localities. Alternative possible reasons are also suggested, to explain the current prevalence of pentaploid short-styled plants in the Euro-Mediterranean area.

Traditional alcoholic beverages and their value in the local culture of the Alta Valle del Reno, a mountain borderland between Tuscany and Emilia-Romagna (Italy).

BACKGROUND: Traditional alcoholic beverages (TABs) have only received marginal attention from researchers and ethnobotanists so far, especially in Italy. This work is focused on plant-based TABs in the Alta Valle del Reno, a mountainous area on the border between Tuscany and Emilia-Romagna regions. The aims of our study were to document local knowledge about TABs and to analyze and discuss the distribution of related knowledge within the investigated communities. METHODS: Field data were collected through semi-structured interviews. The relative importance of each plant species used to prepare TABs was assessed by calculating a general Use Value Index (UV general), a current UV (UV current) and a past UV (UV past). We also assessed personal experience of use by calculating effective and potential UV (UV effective, UV potential). A multivariate analysis was performed to compare ingredients in recipes recorded in the Alta Valle del Reno with those reported for neighboring areas. RESULTS: Forty-six plant species, belonging to 20 families, were recorded. Rosaceae was the most significant family (98 citations, 19 species), followed by Rutaceae (15, 3) and Lamiaceae (12, 4). The most important species was Prunus cerasus L. (UV general = 0.44), followed by Juglans regia L. (0.38), Rubus idaeus L. (0.27) and Prunus spinosa L. (0.22). Species with the highest UV current were Juglans regia (0.254), Prunus cerasus (0.238) and Citrus limon L. (0.159). The highest UV effective values were obtained by Prunus cerasus (0.413), Juglans regia (0.254), Rubus idaeus (0.222) and Citrus limon (0.206). We also discuss the results of the multivariate analysis. CONCLUSIONS: TABs proved to occupy an important place in the traditional culture and social life of the studied communities. Moreover, data highlight the local specificity and richness of this kind of tradition in the Alta Valle del Reno, compared to other Italian areas. Some plant ingredients used for TABs have potential nutraceutical and even therapeutic properties that are well known by local people. These properties could constitute an additional economic value for TABs' commercialization, which in turn could promote the local rural economy.