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Background and Objectives: The aim was to compare the intra and postoperative outcomes between the Enhanced Recovery After Surgery (ERAS) protocol versus the standard of care protocol (SCP) in patients who underwent radical cystectomy performed by a single surgeon. Materials and Methods: A retrospective comparative study was conducted including patients who underwent radical cystectomy from 2017 to 2020. Length of stay (LOS), incidence of ileus, early postoperative complications, and number of re-hospitalizations within 30 days were considered as primary comparative outcomes of the study. Results: Data were collected for 91 patients who underwent cystectomy, and 70 and 21 patients followed the SCP and ERAS protocol, respectively. The mean age of the patients was 70.6 (SD 9.5) years. Although there was a statistically significant difference in time to flatus (TTF) [3 (2.7−3) vs. 1 (1−2 IQR) days, p < 0.001, in the SC hospital and in the ERAS center respectively], no difference was reported in time to first defecation (TTD) [5 (4−6) vs. 4 (3−5.8), p = 0.086 respectively]. The median LOS in the SCP group was 12 (IQR 11−13) days vs. 9 (IQR 8−13 p = 0.024). In the postoperative period, patients reported 22 complications (37% in SCP and 42.8% in ERAS group, p = 0.48). Conclusions: The study reveals how even partial adherence to the ERAS protocols leads to similar outcomes when compared to SCP. As a single surgeon series, our study confirmed the role of surgeons in reducing complications and improving surgical outcomes.

Introduction: The world population is ageing and surgical procedures for older patients are associated with higher perioperative morbidity and mortality rates than in younger patients. Segmental ureterectomy (SU) has been proposed as an alternative to radical nephroureterectomy (RNU) for selected upper tract urothelial carcinomas (UTUC), to reduce post-operative morbidity, and preserve renal function. The aim of this study was to compare RNU and SU in terms of post-operative complications, functional outcomes, and overall survival (OS) in older patients treated for UTUC., Materials and Methods: Data of patients aged 75 years or older and treated for UTUC were included. The primary outcome was to compare RNU versus SU according to post-operative complications, the estimated glomerular filtration rate (eGFR) variation, and OS. Complications were defined according to the Clavien-Dindo classification. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Un-adjusted OS curves were plotted using the Kaplan-Meier method., Results: Overall, 177 patients (150 RNU and 27 SU) were eligible for the analysis. Pre- and post-operative characteristics were similar between the 2 groups. RNU patients showed higher incidence of post-operative complications (34.0% vs. 7.4%, P = .011). The mean post-operative serum creatinine was lower in SU patients in comparison with the RNU ones (1.23 vs. 1.69 mg/dL, P = .046), but no differences were found in terms of eGFR variation (P = .258). At 3 years of follow-up, the OS was comparable between the two surgical techniques (P = .129)., Conclusion: In older patients diagnosed with UTUC, SU could offer lower rates of post-operative complications without affecting survival., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: BCG and MMC shortage and Covid-19 pandemic, more recently, limit accessibility to maintenance regimen in intravesical prophylaxis against recurrence of non-muscle invasive bladder cancer (NMIBC). Ellagic acid (EA) and Annona muricata (AM) exert antitumor activity against different human tumours. An observational prospective study on the prophylactic effect of oral administration of EA+AM in patients avoiding maintenance regimen is presented., Materials and Methods: Patients affected by NMIBC and not undergoing maintenance after a 6-week course of intravesical prophylaxis with MMC or BCG were entered. Tis and very high-risk tumours were excluded. After informed consent, the patients were subdivided in relation to the oral assumption or not of EA (100 mg) plus AM (100 mg), daily for 6 months. All patients were submitted to 3-month cytology and cystoscopy., Results: 162 (90%) of 180 entered patients are evaluable, 90 and 72 receiving or not EA+AM. No difference emerged in patients' characteristics between the two groups. BCG was given in 86 (54%) and chemotherapy in 74 (46%) patients. The recurrence free rate at 3, 6 and 12 months in patients assuming or not EA was 96.5% versus 84.6% ( p  = 0.003), 85.4% versus 64.8% ( p  = 0.005) and 74.2% versus 60.6% ( p  = 0.246), respectively. The recurrence free survival at 12 months in patients assuming or not EA was 63.0% versus 34.5% ( p  < 0.0001)., Discussion and Conclusions: Our study suffers several limits: not randomized trial although prospective, limited number of patients and short follow-up, nevertheless it shows the prophylactic effect of oral EA+AM in absence of maintenance after intravesical chemotherapy or immunotherapy induction.

Introduction: Evidence that smoking cessation at first diagnosis of nonmuscle-invasive bladder cancer (NMIBC) reduces the risk of recurrence is lacking. The aim of our prospective study was to analyze the association between patients' changes in smoking habits after diagnosis and recurrence-free survival (RFS)., Patients: After transurethral resection of primary NMIBC, patients were classified as "ex-smokers," i.e., those definitively stopping, and as "active smokers," i.e., those continuing or restarting to smoke. Smoking status was reassessed every 3 months during the first year and every 6 months thereafter. Data on patients' demographics, smoking status, tumor characteristics, treatments, and follow-up were collected. Statistical analysis was performed adopting SPSS 15.0.1 and R3.4.2 software., Results: Out of 194 patients, 67 (34.5%) quit smoking after the diagnosis, while 127 (65.5%) did not. The clinical and pathological characteristics were homogeneously distributed. At a median follow-up of 38 months, 106 patients (54.6%) recurred, 33 (49.2%) ex- and 73 (60.3%) active smokers with a 3-year RFS of 42.3 and 50.7%, respectively (p = 0.55). No statistically significant association between recurrence, pathological features of the primary tumor, and patient smoking habits after diagnosis was detected. Results were not statistically influenced by the intensity (cigarette/day) and duration (years) of smoking. In multivariate analysis, cigarette smoking cessation at diagnosis did not significantly reduce tumor recurrence., Conclusion: In our prospective study, more than half of our patients recurred at 3 years. In multivariate analysis, smoking cessation did not significantly reduce tumor recurrence. However, the 8.4% reduction in favor of the ex-smokers suggests the need of larger studies with longer follow-ups. Surprisingly, only 35% of smokers definitively quit after diagnosis. The urologists should play a more active role to persuade the patients to stop smoking at first cancer diagnosis., (© 2020 S. Karger AG, Basel.)

Aim: Assessing the incidence of immediate postoperative complications and 90-day mortality in high-risk patients who have undergone radical cystectomy; evaluating the correlation between preoperative conditions and surgery outcomes., Materials and Methods: This is a monocentric retrospective observational study in which data of 65 patients have been analyzed. High-risk criteria: (a) Age ≥75 years, (b) obesity, (c) age-adjusted Charlson Comorbidity Index ≥8, (d) anemic status, and (e) pT ≥3. More than 50% of patients had two or more "high-risk" indicators. Postoperative complications were assessed through Clavien-Dindo classification., Results: Average age of patients was 70.4 years, average age-adjusted Charlson Comorbidity Index was 5.8, and average body mass index was 27.5. In 28% of patients, no complications arose, while in 46% grades I-II complications according to Clavien-Dindo occurred, in 23% grades III-IV complications occurred, and in 3% of the patients, death arose in the immediate postoperative period (grade V). Overall, 90-day mortality rate after surgery was 12.3%. The age ≥75 years and an age-adjusted Charlson Comorbidity Index score ≥8 have shown to be risk factors for the onset of severe complications (odds ratio = 3.54, p = 0.028 and odds ratio = 4.7, p = 0.026), while preoperative anemic status was a risk factor for complications in general (odds ratio = 4.1, p = 0.015). No analyzed parameter was a predictor of 90-day mortality ( p > 0.05)., Conclusion: Immediate postoperative complications and 90-day mortality in radical cystectomy in high-risk patients remain significant, but still in line with the data in the literature on comparable populations. Some of the preoperative parameters were able to predict the outcomes of the intervention with regard to the onset of complications but not to the 90-day mortality.

Purpose: The pentose phosphate pathway (PPP) has been shown to play an important role in the metabolism of cancer cells. The transketolase-like 1 gene (TKTL1) encodes an enzyme representing an essential component of this pathway. Its expression has been demonstrated to correlate with stage and outcome in various tumors. The aim of the present study was to assess expression patterns and the prognostic role of TKTL1 in muscle-invasive bladder cancer (MIBC)., Patients and Methods: The expression of TKTL1 was assessed in a tissue microarray consisting of histopathologically benign and malign tissue of 112 patients who underwent radical cystectomy due to MIBC. Cytoplasmatic and nuclear expression were assessed by immunohistochemistry and compared separately with clinicopathologic parameters and outcome., Results: Cytoplasmatic expression of TKTL1 was exclusively present in tumor tissue. In contrast, the proportion of nuclei positive for TKTL1 was higher in histopathologically benign tissue compared with malign tissue. No correlation was observed between cytoplasmatic or nuclear TKTL1 expression and tumor stage, grade or the presence of metastases. Patients with lymph node involvement showed a decreased frequency of cytoplasmatic expression compared with node-negative patients (p = 0.01). However, no further correlation was observed between the expression of TKTL1 and clinical outcome of patients., Conclusions: The present study shows that the cytoplasmatic expression of TKTL1 is specific for MIBC tissue compared with histopathologically benign urothelium. This specific expression is present in a subgroup of MIBC potentially identifying patients with activated PPP suitable for a targeted inhibition of sugar metabolism. In contrast to other malignancies, TKTL1 shows no prognostic significance in MIBC.

Objectives: To study the ablative activity of intravesical gemcitabine against superficial transitional cell carcinoma of the bladder at different doses and concentrations., Methods: A total of 27 patients were treated with intravesical gemcitabine after transurethral resection during which one to three papillary marker lesions were left unresected. Starting 14 days after transurethral resection, six instillations of gemcitabine were given at weekly intervals. Gemcitabine, diluted in 50 mL of saline solution and maintained for 2 hours, was given at the dose of 500 mg, 1000 mg, and 2000 mg in groups of 9 patients each. A complete response (CR) was defined as negative cytology, cystoscopy, and biopsy findings. Patients achieving a CR received monthly maintenance for up to 1 year and underwent cytology and cystoscopy at 3-month intervals., Results: Of the 27 patients, 1 was lost to follow-up, and of the remaining 26 patients, 6 (23%) achieved a CR. A CR was achieved in 1 patient (12.5%), 2 patients (22.2%), and 3 patients (33.3%) at a dose of 500, 1000, and 2000 mg, respectively. A partial response was obtained in 2 additional patients (22%) at a dose of 500 and 1000 mg. Bladder Tis was diagnosed in 2 patients with a CR at 3 and 8 months after treatment. The remaining 4 patients were disease free at a follow-up of up to 22 months. Systemic and local tolerability was excellent, and no treatment interruption was required., Conclusions: Our experience has shown the good tolerability and potential efficacy of intravesical gemcitabine against recurrent transitional cell carcinoma of the bladder. Gemcitabine might be proposed, if our results are confirmed by larger studies, as a second-line therapy in patients who cannot tolerate more aggressive intravesical therapy.

Objectives: To evaluate a highly selected population of patients affected by T1G3 bladder transitional cell carcinoma (TCCB) treated by transurethral resection (TUR) and adjuvant intravesical chemotherapy., Materials and Methods: Between January 1976 and April 1999, 137 patients with T1G3 TCCB were treated by TUR plus intravesical chemotherapy. Particularly, a sequential combination of mitomycin C (MMC) and epirubicin (EPI) was adopted in 91 patients (66.4%). The main exclusion criteria were concomitant or previous Tis, previous T1G3 TCCB, tumor size greater than 3 centimeters and number of tumors more than 3. TUR was repeated if a superficial tumor recurred. Patients went off study if Tis, recurrent T1G3 or invasive tumor were detected during treatment or thereafter. Adjuvant therapy, recurrence and progression were considered in multivariate analysis regarding recurrence, progression and survival respectively., Results: Observation period was up to 240 months with a minimum of 2 years in 112 patients (82%). Seventy patients (51%) recurred. The recurring tumor was again a T1G3 in 22 (16%) patients. Thirteen patients (9.5%) progressed. The 5-year progression-free survival rate was 90%. Median progression-free survival was 149 months. Twenty-two patients (16%) died, 9 (6.6%) of whom due to bladder cancer. Median overall survival was 155 months. The 3- and 5-year disease-free overall survival rates were 89% and 80% respectively. Ten cystectomies (7.3%) were performed. In conclusion, 123 patients (90%) maintained their intact bladder with a mean disease-free overall survival of 104 months. The sequential combination of MMC and EPI adjuvant therapy resulted more effective to be than single drug chemotherapy on recurrence rate (p=0.0021) but had no impact upon progression (p=0.127) and specific survival (p=0.163). Progression (p<0.001) after conservative treatment was the main prognostic factor for survival., Conclusion: A conservative approach is an appropriate therapeutic option for the initial management of selected T1G3 bladder tumors.

Purpose: To study GP-170 in superficial bladder cancer at initial diagnosis and at recurrence and to evaluate if intravesical chemoprophylaxis modifies the expression of GP-170 in tumor recurrences., Materials and Methods: GP-170 was retrospectively assessed in 160 patients affected by primary superficial transitional cell carcinoma of the bladder and followed for up to 10 years. Eighty-four patients (52.5%) recurred after transurethral resection (TUR). Adjuvant intravesical chemotherapy after TUR was adopted in 52 patients. The correlations between GP-170 and G-grade, T-category, risk of recurrence and of progression, and adoption of adjuvant intravesical chemotherapy were investigated. The correlations between variations in grade and stage at recurrence and modifications in GP-170 expression were also studied., Results: No significant correlation between GP-170 expression and G-grade and T-category was found. A significant correlation was detected between GP-170 expression and recurrence ( P=0.0383). It showed a biphasic pattern, i.e., tumors that did not express GP-170 had a higher recurrence rate, but high GP-170 levels were also associated with an increasing risk of recurrence. Intravesical chemotherapy did not induce significative variations in GP-170 expression. No correlation was found between progression and GP-170., Conclusion: GP-170 seems to be an independent prognostic factor for recurrence in superficial bladder tumors. A negative GP-170 pattern and high levels of GP-170 are associated with an increasing risk of recurrence but have no impact upon progression. In our experience, GP-170 is neither induced nor modified by intravesical chemotherapy, although it might represent a factor of chemoresistance when strongly expressed.

Introduction: The glycoprotein P-170, causing drug efflux from the cells, may represent at least one cause of resistance to most drugs used in intravesical chemotherapy of superficial bladder cancer., Materials and Methods: GP-170 was retrospectively assessed in 60 patients affected by superficial transitional cell tumours of the bladder. It was assessed by immunohistochemistry in a semiquantitative way by the intensity of staining and by the percentage of positive cells. Correlation of GP-170 expression with G-grade, T-category, multiplicity, recurrence rate and treatment was investigated. In 44 patients recurrence was analysed in relation to GP-170 basal expression and to its variations. The monoclonal antibody JSB1 (DBA) at 1:20 dilution was employed for the GP-170 assay., Results: GP-170 expression increases with grade but was lower in multiple tumours. No difference between Ta and T1 categories was detected. GP-170 immunohistochemistry from different portions of the same tumour showed a very marked variability in 35.7% of patients. Seven patients (11.6%) were totally negative for GP-170. No statistically significant correlation was found between recurrence, progression and GP-170 basal expression. Similarly no correlation emerged between grade and stage variations at recurrence and modifications in GP-170 expression. One third of the tumours recurring after chemotherapy were negative for GP-170 in spite of an increase in recurrence rate and other risk factors., Conclusion: At the present stage of our experience, we have been unable to show that GP-170 is a useful marker for monitoring chemoresistance to intravesical chemotherapy in superficial bladder cancer. Furthermore, GP-170 determination has shown several technical difficulties.