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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 34593

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Dr. Marco Moschini

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Guest Editor

1. Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Dept Urol, Urol Res Inst, Milan, Italy
2. Luzerner Kantonsspital, Spitalstrasse, CH-6000 Luzern, Switzerland
Interests: bladder cancer; urothelial cancer; non-muscle invasive bladder cancer; muscle invasive bladder cancer; radical cystectomy; transurethral resection of the bladder

Special Issue Information

Dear Colleagues,

Bladder cancer is the second most common genitourinary malignancy, with 81,190 estimated new diagnoses for 2018 in the United States alone. Transurethral resection of the bladder and radical cystectomy with bilateral pelvic lymph node dissection is the standard treatment for non-muscle invasive or very high-risk non-muscle invasive bladder cancer, respectively. However, survival expectations have not shown improvement in the last 20 years, and new diagnostic and therapeutic tools are urgently needed to improve outcomes of this potentially lethal disease.

Dr. Marco Moschini
Guest Editor

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Keywords

bladder cancer
urothelial cancer
non-muscle invasive bladder cancer
muscle invasive bladder cancer
radical cystectomy
transurethral resection of the bladder

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Published Papers (10 papers)

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Editorial

Jump to: Research

3 pages, 158 KiB

Open AccessEditorial

From Basic Science to Clinical Research to Develop New Solutions to Improve Diagnoses and Treatment of Bladder Cancer Patients

by Marco Moschini

J. Clin. Med. 2020, 9(8), 2373; https://doi.org/10.3390/jcm9082373 - 25 Jul 2020

Cited by 1 | Viewed by 1573

Abstract

Bladder cancer (BCa) is the tenth most common form of cancer worldwide, with 549,000 new cases and 200,000 deaths estimated in 2018 [...] Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

Research

Jump to: Editorial

9 pages, 749 KiB

Open AccessArticle

Survival Outcomes of Patients with Pathologically Proven Positive Lymph Nodes at Time of Radical Cystectomy with or without Neoadjuvant Chemotherapy

by Guillaume Ploussard, Benjamin Pradere, Jean-Baptiste Beauval, Christine Chevreau, Christophe Almeras, Etienne Suc, Jean-Romain Gautier, Anne-Pascale Laurenty, Mathieu Roumiguié, Guillaume Loison, Christophe Tollon, Loïc Mourey, Ambroise Salin, Evanguelos Xylinas and Damien Pouessel

J. Clin. Med. 2020, 9(6), 1962; https://doi.org/10.3390/jcm9061962 - 23 Jun 2020

Cited by 14 | Viewed by 2380

Abstract

Background: To compare overall survival (OS) outcomes in pN1-3 disease at the time of radical cystectomy (RC) for muscle invasive bladder according to the neoadjuvant chemotherapy (NAC) status. Materials and Methods: This multicenter study included 450 consecutive patients undergoing RC for muscle-invasive urothelial bladder cancer with pN1-3 pM0 disease from 2010 to 2019. NAC consisted in platinum-based chemotherapy. The primary endpoint was the comparison between NAC and non-NAC in terms of death from any cause. OS was assessed using the Kaplan–Meier method and multivariate Cox proportional hazards regression was used to estimate adjusted hazard ratios. Results: Median age was 69 years. Patients receiving NAC were younger (p = 0.051), and more likely had downstaging to non-muscle invasive disease (10.7% versus 4.3%, p = 0.042). Median OS was 26.6 months. NAC patients had poorer OS compared with those who did receive NAC (Hazard ratio (HR) 1.6; p = 0.019). The persistence of muscle-invasive bladder in RC specimens was also significantly associated with OS (HR 2.40). In the NAC cohort, the two factors independently correlated with OS were the number of positive lymph nodes (p = 0.013) and adjuvant chemotherapy (AC) (HR 0.31; p = 0.015). Conclusions: Persistent nodal disease in RC specimens after NAC was associated with poor prognosis and lower OS rates compared with pN1-3 disease after upfront RC. In this sub-group of NAC patients, AC was independently associated with better OS. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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15 pages, 3624 KiB

Open AccessArticle

Differential Expression and Clinicopathological Significance of HER2, Indoleamine 2,3-Dioxygenase and PD-L1 in Urothelial Carcinoma of the Bladder

by Donghyun Kim, Jin Man Kim, Jun-Sang Kim, Sup Kim and Kyung-Hee Kim

J. Clin. Med. 2020, 9(5), 1265; https://doi.org/10.3390/jcm9051265 - 27 Apr 2020

Cited by 18 | Viewed by 4096

Abstract

Purpose: Evasion of the immune system by cancer cells allows for the progression of tumors. Antitumor immunotherapy has shown remarkable effects in a diverse range of cancers. The aim of this study was to determine the clinicopathological significance of human epidermal growth factor receptor 2 (HER2), indoleamine 2,3-dioxygenase (IDO), and programmed death ligand-1 (PD-L1) expression in urothelial carcinoma of the bladder (UCB). Materials and Methods: We retrospectively studied 97 patients with UCB. We performed an immunohistochemical study to measure the expression levels of HER2, IDO, and PD-L1 in UCB tissue from these 97 patients. Results: In all 97 cases, the PD-L1 expression of tumor-infiltrating immune cells (ICs) was significantly correlated with higher pathologic tumor stage (pT). In pT2–pT4 cases (n = 69), higher levels of HER2 and IDO expression in invasive tumor cells (TCs) were associated with shorter periods of disease-free survival (DFS). Conclusion: These results imply that the expression of PD-L1 in ICs of the UCB microenvironment is associated with cancer invasion and the expression of HER2 or IDO in the invasive cancer cell and suggestive of the potential for cancer recurrence. We suggest that the expression levels of IDO, HER2, and PD-L1 could be useful as targets in the development of combined cancer immunotherapeutic strategies. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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13 pages, 1601 KiB

Open AccessArticle

FOXA1 Gene Expression for Defining Molecular Subtypes of Muscle-Invasive Bladder Cancer after Radical Cystectomy

by Danijel Sikic, Markus Eckstein, Ralph M. Wirtz, Jonas Jarczyk, Thomas S. Worst, Stefan Porubsky, Bastian Keck, Frank Kunath, Veronika Weyerer, Johannes Breyer, Wolfgang Otto, Sebastien Rinaldetti, Christian Bolenz, Arndt Hartmann, Bernd Wullich and Philipp Erben

J. Clin. Med. 2020, 9(4), 994; https://doi.org/10.3390/jcm9040994 - 2 Apr 2020

Cited by 12 | Viewed by 3934

Abstract

It remains unclear how to implement the recently revealed basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) into daily clinical routine and whether molecular marker panels can be reduced. The mRNA expression of basal (KRT5) and luminal (FOXA1, GATA3, KRT20) markers was measured by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and correlated to clinicopathological features, recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS) in 80 patients with MIBC who underwent radical cystectomy. Additionally, the correlation of single markers with the basal and non-basal subtypes defined by a 36-gene panel was examined and then validated in the TCGA (The Cancer Genome Atlas) cohort. High expression of FOXA1 (p = 0.0048) and KRT20 (p = 0.0317) was associated with reduced RFS. In the multivariable analysis, only FOXA1 remained an independent prognostic marker for DFS (p = 0.0333) and RFS (p = 0.0310). FOXA1 expression (AUC = 0.79; p = 0.0007) was closest to the combined marker expression (AUC = 0.79; p = 0.0015) in resembling the non-basal subtype defined by the 36-gene panel. FOXA1 in combination with KRT5 may be used to distinguish the basal and non-basal subtypes of MIBC. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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12 pages, 1553 KiB

Open AccessArticle

A Multiplex Test Assessing MiR663a_me and VIM_me in Urine Accurately Discriminates Bladder Cancer from Inflammatory Conditions

by Sara Monteiro-Reis, Ana Blanca, Joana Tedim-Moreira, Isa Carneiro, Diana Montezuma, Paula Monteiro, Jorge Oliveira, Luís Antunes, Rui Henrique, António Lopez-Beltran and Carmen Jerónimo

J. Clin. Med. 2020, 9(2), 605; https://doi.org/10.3390/jcm9020605 - 24 Feb 2020

Cited by 8 | Viewed by 3560

Abstract

Bladder cancer (BlCa) is a common malignancy with significant morbidity and mortality. Current diagnostic methods are invasive and costly, showing the need for newer biomarkers. Although several epigenetic-based biomarkers have been proposed, their ability to discriminate BlCa from common benign conditions of the urinary tract, especially inflammatory diseases, has not been adequately explored. Herein, we sought to determine whether VIM_me and miR663a_me might accurately discriminate those two conditions, using a multiplex test. Performance of VIM_me and miR663a_me in tissue samples and urines in testing set confirmed previous results (96.3% sensitivity, 88.2% specificity, area under de curve (AUC) 0.98 and 92.6% sensitivity, 75% specificity, AUC 0.83, respectively). In the validation sets, VIM_me-miR663a_me multiplex test in urine discriminated BlCa patients from healthy donors or patients with inflammatory conditions, with 87% sensitivity, 86% specificity and 80% sensitivity, 75% specificity, respectively. Furthermore, positive likelihood ratio (LR) of 2.41 and negative LR of 0.21 were also disclosed. Compared to urinary cytology, VIM_me-miR663a_me multiplex panel correctly detected 87% of the analysed cases, whereas cytology only forecasted 41%. Furthermore, high miR663a_me independently predicted worse clinical outcome, especially in patients with invasive BlCa. We concluded that the implementation of this panel might better stratify patients for confirmatory, invasive examinations, ultimately improving the cost-effectiveness of BlCa diagnosis and management. Moreover, miR663a_me analysis might provide relevant information for patient monitoring, identifying patients at higher risk for cancer progression. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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10 pages, 1307 KiB

Open AccessArticle

Sex-Sparing Robot-Assisted Radical Cystectomy with Intracorporeal Padua Ileal Neobladder in Female: Surgical Technique, Perioperative, Oncologic and Functional Outcomes

by Gabriele Tuderti, Riccardo Mastroianni, Simone Flammia, Mariaconsiglia Ferriero, Costantino Leonardo, Umberto Anceschi, Aldo Brassetti, Salvatore Guaglianone, Michele Gallucci and Giuseppe Simone

J. Clin. Med. 2020, 9(2), 577; https://doi.org/10.3390/jcm9020577 - 20 Feb 2020

Cited by 30 | Viewed by 3588

Abstract

Our aim was to illustrate our technique of sex-sparing (SS)-robot-assisted radical cystectomy (RARC) in female patients receiving an intracorporeal neobladder (iN). From January 2013 to June 2018, 11 female patients underwent SS-RARC-iN at a single tertiary referral center. Inclusion criteria were a cT ≤ 2 N0 M0 bladder tumor at baseline imaging (CT or MRI) and an absence of tumors in the bladder neck, trigone and urethra at TURB. Baseline, perioperative, and outcomes at one year were reported. The median operative time was 255 min and the median hospital stay was seven days. Low-grade Clavien complications occurred in four patients (36.3%), while high-grade complications were not observed in any. Seven patients (63.7%) had an organ-confined disease at the pathologic specimen; nodal involvement and positive surgical margins were not detected in any of the cases. At a median follow-up of 28 months (IQR 14–51), no patients developed new onset of chronic kidney disease stage 3b. After one year, daytime and nighttime continence rates were 90.9% and 86.4% respectively. Quality of life as well as physical and emotional functioning improved significantly over time (all p ≤ 0.04), while urinary symptoms and sexual function worsened at three months with a significant recovery taking place at one year (all p ≤ 0.04). Overall, 8 out of 11 patients (72.7%) were sexually active at the 12-month evaluation. In select female patients, SS-RARC-iN is an oncologically sound procedure associated with favorable perioperative and functional outcomes. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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11 pages, 750 KiB

Open AccessArticle

Clear Cell Adenocarcinoma of the Urinary Bladder Is a Glycogen-Rich Tumor with Poorer Prognosis

by Zhengqiu Zhou, Connor J. Kinslow, Peng Wang, Bin Huang, Simon K. Cheng, Israel Deutsch, Matthew S. Gentry and Ramon C. Sun

J. Clin. Med. 2020, 9(1), 138; https://doi.org/10.3390/jcm9010138 - 3 Jan 2020

Cited by 14 | Viewed by 4571

Abstract

Clear cell adenocarcinoma (CCA) is a rare variant of urinary bladder carcinoma with a glycogen-rich phenotype and unknown prognosis. Using the National Cancer Institute’s surveillance, epidemiology, and end results (SEER) program database, we documented recent trends in incidence, mortality, demographical characteristics, and survival on this rare subtype of urinary bladder cancer. The overall age-adjusted incidence and mortality of CCA was 0.087 (95% confidence interval (CI): 0.069–0.107) and 0.064 (95% CI: 0.049–0.081) respectively per million population. In comparison to non-CCAs, CCAs were more commonly associated with younger age (<60 years old, p = 0.005), female (p < 0.001), black ethnicity (p = 0.001), grade III (p < 0.001), and higher AJCC 6th staging (p < 0.001). In addition, CCA patients more frequently received complete cystectomy (p < 0.001) and beam radiation (p < 0.001) than non-CCA patients. Our study showed a poorer prognosis of CCAs compared to all other carcinomas of the urinary bladder (p < 0.001), accounted for by higher tumor staging of CCA cases. This study adds to the growing evidence that glycogen-rich cancers may have unique characteristics affecting tumor aggressiveness and patient prognosis. Additional mechanistic studies are needed to assess whether it’s the excess glycogen that contributes to the higher stage at diagnosis. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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10 pages, 622 KiB

Open AccessArticle

Recovery from Anesthesia after Robotic-Assisted Radical Cystectomy: Two Different Reversals of Neuromuscular Blockade

by Claudia Claroni, Marco Covotta, Giulia Torregiani, Maria Elena Marcelli, Gabriele Tuderti, Giuseppe Simone, Alessandra Scotto di Uccio, Antonio Zinilli and Ester Forastiere

J. Clin. Med. 2019, 8(11), 1774; https://doi.org/10.3390/jcm8111774 - 24 Oct 2019

Cited by 16 | Viewed by 3163

Abstract

During robot-assisted radical cystectomy (RARC), specific surgical conditions (a steep Trendelenburg position, prolonged pneumoperitoneum, effective myoresolution until the final stages of surgery) can seriously impair the outcomes. The aim of the study was to evaluate the incidence of postoperative nausea and vomiting (PONV) and ileus and the quality of cognitive function at the awakening in two groups of patients undergoing different reversals. In this randomized trial, patients that were American Society of Anesthesiologists physical status (ASA) ≤III candidates for RARC for bladder cancer were randomized into two groups: In the sugammadex (S) group, patients received 2 mg/kg of sugammadex as reversal of neuromuscolar blockade; in the neostigmine (N) group, antagonization was obtained with neostigmine 0.04 mg/kg + atropine 0.02 mg/kg. PONV was evaluated at 30 min, 6 and 24 h after anesthesia. Postoperative cognitive functions and time to resumption of intestinal transit were also investigated. A total of 109 patients were analyzed (54 in the S group and 55 in the N group). The incidence of early PONV was lower in the S group but not statistically significant (S group 25.9% vs. N group 29%; p = 0.711). The Mini-Mental State test mean value was higher in the S group vs. the N group (1 h after surgery: 29.3 (29; 30) vs. 27.6 (27; 30), p = 0.007; 4 h after surgery: 29.5 (30; 30) vs. 28.4 (28; 30), p = 0.05). We did not observe a significant decrease of the PONV after sugammadex administration versus neostigmine use. The Mini-Mental State test mean value was greater in the S group. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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10 pages, 572 KiB

Open AccessArticle

Do Younger Patients with Muscle-Invasive Bladder Cancer have Better Outcomes?

by Florian Janisch, Hang Yu, Malte W. Vetterlein, Roland Dahlem, Oliver Engel, Margit Fisch, Shahrokh F. Shariat, Armin Soave and Michael Rink

J. Clin. Med. 2019, 8(9), 1459; https://doi.org/10.3390/jcm8091459 - 13 Sep 2019

Cited by 16 | Viewed by 3162

Abstract

Urothelial cancer of the bladder (UCB) is usually a disease of the elderly. The influence of age on oncological outcomes remains controversial. This study aims to investigate the impact of age on UCB outcomes in Europe focusing particularly on young and very young patients. We collected data of 669 UCB patients treated with RC at our tertiary care center. We used various categorical stratifications as well as continuous age to investigate the association of age and tumor biology as well as endpoints with descriptive statistics and Cox regression. The median age was 67 years and the mean follow-up was 52 months. Eight patients (1.2%) were ≤40 years old and 39 patients (5.8%) were aged 41–50 years, respectively. In multivariable analysis, higher continuous age and age above the median were independent predictors for disease recurrence, and cancer-specific and overall mortality (all p-values ≤ 0.018). In addition, patients with age in the oldest tertile group had inferior cancer-specific and overall survival rates compared to their younger counterparts. Young (40–50 years) and very young (≤40 years) patients had reduced hazards for all endpoints, which, however, were not statistically significant. Age remains an independent determinant for survival after RC. Young adults did, however, not have superior outcomes in our analyses. Quality of life and complications are endpoints that need further evaluation in patients undergoing RC. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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11 pages, 783 KiB

Open AccessArticle

Open Versus Robotic Cystectomy: A Propensity Score Matched Analysis Comparing Survival Outcomes

by Marco Moschini, Stefania Zamboni, Francesco Soria, Romain Mathieu, Evanguelos Xylinas, Wei Shen Tan, John D Kelly, Giuseppe Simone, Anoop Meraney, Suprita Krishna, Badrinath Konety, Agostino Mattei, Philipp Baumeister, Livio Mordasini, Francesco Montorsi, Alberto Briganti, Andrea Gallina, Armando Stabile, Rafael Sanchez-Salas, Xavier Cathelineau, Michael Rink, Andrea Necchi, Pierre I. Karakiewicz, Morgan Rouprêt, Anthony Koupparis, Wassim Kassouf, Douglas S Scherr, Guillaume Ploussard, Stephen A. Boorjian, Yair Lotan, Prasanna Sooriakumaran and Shahrokh F. Shariat Show full author list Hide full author list

J. Clin. Med. 2019, 8(8), 1192; https://doi.org/10.3390/jcm8081192 - 9 Aug 2019

Cited by 15 | Viewed by 3646

Abstract

Background: To assess the differential effect of robotic assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) on survival outcomes in matched analyses performed on a large multicentric cohort. Methods: The study included 9757 patients with urothelial bladder cancer (BCa) treated in a consecutive manner at each of 25 institutions. All patients underwent radical cystectomy with bilateral pelvic lymphadenectomy. To adjust for potential selection bias, propensity score matching 2:1 was performed with two ORC patients matched to one RARC patient. The propensity-matched cohort included 1374 patients. Multivariable competing risk analyses accounting for death of other causes, tested association of surgical technique with recurrence and cancer specific mortality (CSM), before and after propensity score matching. Results: Overall, 767 (7.8%) patients underwent RARC and 8990 (92.2%) ORC. The median follow-up before and after propensity matching was 81 and 102 months, respectively. In the overall population, the 3-year recurrence rates and CSM were 37% vs. 26% and 34% vs. 24% for ORC vs. RARC (all p values > 0.1), respectively. On multivariable Cox regression analyses, RARC and ORC had similar recurrence and CSM rates before and after matching (all p values > 0.1). Conclusions: Patients treated with RARC and ORC have similar survival outcomes. This data is helpful in consulting patients until long term survival outcomes of level one evidence is available. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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