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Urologie (Heidelberg, Germany) Jul 2022The treatment options for locally advanced and metastatic urothelial carcinoma (UC) are currently limited to established chemotherapy and immunotherapy protocols.... (Review)
Review
BACKGROUND
The treatment options for locally advanced and metastatic urothelial carcinoma (UC) are currently limited to established chemotherapy and immunotherapy protocols. Targeted treatment is so far restricted to a small subgroup of patients. Urothelial organoid systems could make a decisive contribution in establishing effective personalized treatment options by enabling drug response prediction through testing the sensitivity of individual patients. The aim of this article is to describe the state of the science of clinically applicable organoid systems for UC.
METHODOLOGY
A systematic literature search was conducted in several medical databases (Medline, Cochrane Library) and study registers (ClinicalTrials.gov, the EU Clinical Trials Register and the WHO International Clinical Trials Registry). The search terms and the search strategy were adapted to the databases used.
RESULTS
Overall, 7 studies met the inclusion criteria on the topic of UC organoids. These studies describe the fundamental workflow in establishing organoid systems in patients with tumors of the urinary bladder or the renal pelvis. The success rates in generating organoids from non-muscle-invasive bladder cancer were 70-77% and for muscle-invasive bladder cancer 42%. For patient organoids systematic drug testing was carried out.
CONCLUSION
The generation of UC organoids is feasible and the ex vivo testing of individual treatment forms is possible. Due to the lack of a standardized methodology, their implementation remains experimental at the moment. The methodology has a high potential to provide a personalized treatment concept to patients with urothelial cancer.
Topics: Carcinoma, Transitional Cell; Humans; Organoids; Precision Medicine; Urinary Bladder Neoplasms; Urothelium
PubMed: 35925247
DOI: 10.1007/s00120-022-01854-z -
Progres En Urologie : Journal de... Nov 2014To describe natural history and carcinogenesis of upper tract urothelial carcinoma (UTUC). (Review)
Review
[Carcinogenic pathways and natural history of upper tract urothelial carcinomas: state-of-the-art review for the yearly scientific report of the French National Association of Urology].
OBJECTIVE
To describe natural history and carcinogenesis of upper tract urothelial carcinoma (UTUC).
METHODS
A systematic review of the scientific literature was performed in the Medline database (Pubmed) using different associations of the following keywords: upper tract urothelial carcinoma; clonality; carcinogenesis; mutation; chromosomal instability; Lynch syndrome; genetic polymorphism.
RESULTS
Local development of UTUC is characterized by a highly prevalent multifocality that might be explained by the overlap of "field change" and "intraluminal seeding and implantation" theories. UTUC and bladder tumors share common carcinogenesis mechanisms such as mutations of FGFR3 and TP53 defining two distinct pathways of pathogenesis. Epigenetic alterations corresponding to the hypermethylation of different promoters regulating genes expression and chromosomal instability such as chromosome 9 deletions are also involved in UTUC carcinogenesis. Furthermore, specific genetic risk factors fro UTUC including Lynch syndrome and different polymorphisms might explain an individual susceptibility for developing these tumors.
CONCLUSIONS
Significant advances have been done in the field of basic research in UTUCs in recent years and have been of particular interest to provide better descriptions of their natural history. Despite these important findings however, some carcinogenic mechanisms remains not elucidated and unknown in the field of UTUC so far.
Topics: Carcinogenesis; Carcinoma, Transitional Cell; Chromosomal Instability; Decision Trees; Genes, Tumor Suppressor; Genetic Predisposition to Disease; Humans; Lynch Syndrome II; Neoplasm Metastasis; Neoplasm Seeding; Oncogenes; Polymorphism, Genetic; Urologic Neoplasms; Urothelium
PubMed: 25158326
DOI: 10.1016/j.purol.2014.06.010 -
Progres En Urologie : Journal de... Nov 2014To describe the main prognostic factors with an impact on survival of patients diagnosed with upper tract urothelial carcinomas (UTUC). (Review)
Review
[Prognostic factors of upper tract urothelial carcinomas and impact on survival: a systematic review for the yearly scientific report of the French National Association of Urology].
AIM
To describe the main prognostic factors with an impact on survival of patients diagnosed with upper tract urothelial carcinomas (UTUC).
MATERIAL AND METHODS
A systematic review of the literature has been performed using Pubmed without timeline restriction with the following keywords (MeSH): urothelial carcinoma; ureter; renal pelvis; prognosis; recurrence; survival; predictive models; nomogram.
RESULTS
The level of evidence was low (3) in every available studies. There were 4 categories of prognostic factors in UTUCs: clinical (patient and tumor characteristics); surgical; pathological and molecular. The most important pre-operative prognostic factors were: size>3cm, grade (biopsy and cytology); multifocality; important hydronephrosis; co-morbidity (ASA), ECOG status, and a surgical delay of no more than 3months. After surgery, the most important prognostic factors are: stage, grade, carcinoma in situ, lymphovascular invasion and lymph node involvement. Serum markers from inflammation (CRP) could be useful for the prediction of advanced stages. Molecular markers are still under evaluation.
CONCLUSION
The identification of prognostic factors in UTUC has improved over the past years. These prognostic factors can be considered alone but also as a panel or inside predictive tools to predict accurately patient's survival.
Topics: Biomarkers, Tumor; C-Reactive Protein; Carcinoma, Transitional Cell; Humans; Hydronephrosis; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Prognosis; Time-to-Treatment; Urologic Neoplasms; Urothelium
PubMed: 25199726
DOI: 10.1016/j.purol.2014.07.013 -
Progres En Urologie : Journal de... Nov 2014To propose a state-of-the art of current knowledge about clinical, ureteroscopic and photodynamic for the diagnosis of the upper urinary tract cancer (UTUC). (Review)
Review
[Clinical, ureteroscopic and photodynamic diagnosis of urothelial carcinomas of the upper tract: state-of-the art review for the yearly scientific report of the French National Association of Urology].
PURPOSE
To propose a state-of-the art of current knowledge about clinical, ureteroscopic and photodynamic for the diagnosis of the upper urinary tract cancer (UTUC).
MATERIAL AND METHOD
A systematic review of the literature search was performed from the database Medline (NLM, Pubmed), focused on the following keywords: urothelial carcinomas; upper urinary tract; ureter; renal pelvis; diagnosis; fluorescence; ureteroscopy; photodynamic technique; biopsy; cytology.
RESULTS
Gross hematuria and flank pain are the two main clinical symptoms revealing a UTUC in daily clinical practice. Urinary cystoscopy and cystoscopy are mandatory to rule out a concomittant synchronous bladder tumour. Flexible ureteroscopy has revolutionized the management of UTUC by allowing a full exploration of upper urinary tract, an endoscopi vizualization of the tumour and assessment of grade with biopsies. A flexible ureteroscopy is mandatory in diagnostic evaluation of UTUC as soon as a conservative management is being considered. New investigation technologies such as fluorescence, narrow band imaging and optical coherence tomography (± combined with ultra sound), are promising for a near future.
CONCLUSION
It has to be understood that the diagnostic work-up of a UTUC has to be exhaustive and particularly the search of another urothelial carcinoma within the urinary tract. Flexible ureterosocopy has revolutionized the diagnosis and management of UTUC and belongs fully to its initial evaluation.
Topics: Biopsy; Carcinoma, Transitional Cell; Flank Pain; Hematuria; Humans; In Situ Hybridization, Fluorescence; Narrow Band Imaging; Optical Imaging; Tomography, Optical Coherence; Ureteroscopy; Urine; Urography; Urologic Neoplasms; Urothelium
PubMed: 25199724
DOI: 10.1016/j.purol.2014.07.012 -
Progres En Urologie : Journal de... Nov 2014To describe the epidemiology, the risk and genetic factors involved in carcinogenesis pathways of upper urinary tumors UTUCs. (Review)
Review
AIM
To describe the epidemiology, the risk and genetic factors involved in carcinogenesis pathways of upper urinary tumors UTUCs.
MATERIAL
A systematic review of the scientific literature was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM using the following keywords: epidemiology; risk factor; tobacco; aristolochic acid; urothelial carcinoma; ureter; renal pelvis. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned.
RESULTS
The estimated UTUC incidence is 1.2 cases/100,000 inhabitant per year in Europe. The incidence of renal pelvis tumor has been stable for 30years, while the frequency of ureteric locations has increased over time. Locally advanced stage and high grade are more frequent at the time of diagnosis. The median age for diagnosis is 70-years-old. Male-to-female ratio is nearly 2. Main carcinogenic factors are tobacco consumption and occupational exposure. There are specific risk factors for UTUC such acid aristolochic (balkan's nephropathy and Chinese herbs nephropathy). Familial cases are distinct from sporadic cases. UTUCs belong to the HNPCC syndrome and they rank third in its tumor spectrum.
CONCLUSION
UTUCs are scarce tumors with specific epidemiologic characteristics. UTUCs share common risk factors with other urothelial carcinomas such as bladder tumors but have also specific risk factors that clinicians should know.
Topics: Balkan Nephropathy; Benzidines; Carcinoma, Transitional Cell; Genetic Predisposition to Disease; Humans; Hydrocarbons, Chlorinated; Incidence; Inflammation; Occupational Exposure; Polycyclic Aromatic Hydrocarbons; Prevalence; Risk Factors; Sex Distribution; Smoking; Urinary Tract Infections; Urologic Neoplasms; Urothelium
PubMed: 25158329
DOI: 10.1016/j.purol.2014.06.012 -
Cancer Biology & Therapy Sep 2020Colorectal cancer (CRC) is a leading cause of cancer-related death. Epithelial-mesenchymal transition (EMT) is a major process in tumor metastasis development. This...
BACKGROUND
Colorectal cancer (CRC) is a leading cause of cancer-related death. Epithelial-mesenchymal transition (EMT) is a major process in tumor metastasis development. This systematic review aims to describe the role of long non-coding RNA (lncRNA) in EMT in CRC.
METHODS
The electronic databases, PubMed, Cochrane, and EMBASE, were searched from January1990 to June 2019 to identify studies examining lncRNA and their role in mediating EMT in CRC. Studies examining clinical specimens and/or in vitro experiments were included.
RESULTS
In 61 identified studies, 54 lncRNAs were increased in CRC compared to normal colorectal epithelium. Increased lncRNA expression was frequently associated with worse survival. Many lncRNAs mediate their effect through competitive endogenous RNA or transcription factor regulation. The ZEB1, 2/E-cadherin, Wnt/β-catenin signaling, and chromatin remodeling pathways are discussed in particular.
CONCLUSIONS
lncRNAs are major regulators of EMT and predictor adverse outcome in CRC patients. Future research must focus on delineating lncRNA function prior to potential clinical use.
Topics: Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Humans; Neoplasm Metastasis; RNA, Long Noncoding
PubMed: 32730165
DOI: 10.1080/15384047.2020.1794239 -
Diagnostic and prognostic roles of CK20 in the pathology of urothelial lesions. A systematic review.Pathology, Research and Practice Jun 2019Cytokeratin 20 (CK20) is one of the most common immunohistochemical markers in the routine practice of a pathology lab, as biopsies from the urinary tract encompass a...
Cytokeratin 20 (CK20) is one of the most common immunohistochemical markers in the routine practice of a pathology lab, as biopsies from the urinary tract encompass a wide spectrum of lesions which may pose issues in their detection and classification. In this review, we aim to outline the diagnostic accuracy and prognostic value of CK20 in flat urothelial lesions, papillary non-invasive and invasive urothelial carcinoma, molecular subgroups and variant histology, and we briefly discuss its limitations and potential pitfalls.
Topics: Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Transitional Cell; Humans; Keratin-20; Prognosis; Urinary Bladder Neoplasms; Urologic Neoplasms; Urothelium
PubMed: 30987832
DOI: 10.1016/j.prp.2019.04.005 -
The Journal of Urology Jun 2020We sought to assess the prognostic value of variant histology in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. (Meta-Analysis)
Meta-Analysis
PURPOSE
We sought to assess the prognostic value of variant histology in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.
MATERIALS AND METHODS
We searched PubMed®, Web of Science™, Cochrane Library and Scopus® databases in May 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with upper tract urothelial carcinoma with or without variant histology. Formal meta-analyses were performed for these outcomes.
RESULTS
We identified 32 studies with 16,052 patients, including 26 studies with 12,865 patients that were eligible for the meta-analysis. Variant histology was associated with poor outcomes in terms of cancer specific (pooled HR 2.00, 95% CI 1.57 to 2.56), overall (pooled HR 1.76, 95% CI 1.51 to 2.04) and recurrence-free survival (pooled HR 1.64, 95% CI 1.42 to 1.89). Subgroup analyses revealed that micropapillary (pooled HR 3.02, 95% CI 1.71 to 5.34), and squamous and/or glandular variant histologies (pooled HR 1.48, 95% CI 1.14 to 1.92) were also associated with poor cancer specific survival.
CONCLUSIONS
Variant histology in patients with upper tract urothelial carcinoma is associated with an increased risk of cancer specific and overall mortality and disease recurrence. Furthermore, variant histology was independently associated with cancer specific survival in the micropapillary, and squamous and/or glandular variant histology subgroups. It may be useful to incorporate variant histology into prognostic tools that help guide patients and physicians in selecting appropriate treatment strategies for upper tract urothelial carcinoma.
Topics: Carcinoma, Transitional Cell; Clinical Decision-Making; Disease-Free Survival; Feasibility Studies; Humans; Kaplan-Meier Estimate; Kidney; Kidney Neoplasms; Neoplasm Recurrence, Local; Nephroureterectomy; Patient Selection; Predictive Value of Tests; Prognosis; Ureter; Ureteral Neoplasms; Urothelium
PubMed: 31479406
DOI: 10.1097/JU.0000000000000523 -
Progres En Urologie : Journal de... Nov 2014To propose a state of the art regarding imaging techniques for the diagnosis and work-up of upper tract urothelial carcinoma (UTUC). (Review)
Review
OBJECTIVE
To propose a state of the art regarding imaging techniques for the diagnosis and work-up of upper tract urothelial carcinoma (UTUC).
METHODS
A systematic review of the scientific literature was performed in the Medline database (PubMed) until 2014 using different associations of the following keywords: urothelial carcinomas; upper urinary tract; ureter; renal pelvis; CT scan; MRI; ultrasound; urography.
RESULTS
Imaging has a prominent role in the diagnosis, extension and follow-up assessment of upper tract urothelial cancers (UTUC). The couple ultrasound/intravenous urography made way for the multidetector computed tomography urography (MDCTU) and for the magnetic resonance imaging urography (MRU), which can also be combined in some cases. This review of the literature presents available techniques for the exploration of the upper urinary tract, the main protocols (in particular the interest of furosemide addition), details the interpretation techniques for searching UTUC on serial imaging, as well as the main differential diagnoses, and their accuracy. Finally, the role of imaging, according to patient's context is discussed. The combination or fusion of different modalities (CT, MR…) for the same objective is highlighted and presented as the likely evolution of UTUC imaging.
CONCLUSION
MDCTU is nowadays the gold standard imaging modality for the diagnosis of UTUC.
Topics: Carcinoma, Transitional Cell; Diagnosis, Differential; Diagnostic Imaging; Diuretics; Furosemide; Humans; Urologic Neoplasms; Urothelium
PubMed: 25224591
DOI: 10.1016/j.purol.2014.07.009 -
European Journal of Cancer (Oxford,... Jul 2021Platinum-based combination chemotherapy is the standard treatment for patients with chemotherapy-eligible metastatic urothelial carcinoma (mUC). Immune-checkpoint... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Platinum-based combination chemotherapy is the standard treatment for patients with chemotherapy-eligible metastatic urothelial carcinoma (mUC). Immune-checkpoint inhibitors (ICIs) are currently assessed in this setting. This review aimed to assess the role of ICIs alone or in combination as first-line treatment in chemotherapy-eligible patients with mUC.
METHODS
Multiple databases were searched for articles published until November 2020. Studies were deemed eligible if they compared overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), durations of response (DORs) and adverse events (AEs) in chemotherapy-eligible patients with mUC.
RESULTS
Three studies met our eligibility criteria. ICI combination therapy was associated with significantly better OS and PFS, higher CRR and longer DOR than chemotherapy alone (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.76-0.94, P = 0.002; HR: 0.80, 95% CI: 0.71-0.90, P = 0.0002; odds ratio [OR]: 1.48, 95% CI: 1.12-1.96, P = 0.006; and mean difference: 1.39, 95% CI: 0.31-2.46, P = 0.01, respectively). ICI-chemotherapy combination therapy was also associated with significantly better OS and PFS, higher ORR and CRR and longer DOR than chemotherapy alone. Although OS and PFS benefits of ICI combination therapy were larger in patients with high expression of programmed death-ligand 1 (PD-L1), PD-L1 low expression patients also had a benefit; HR for OS (high PD-L1: HR 0.79 versus low PD-L1: HR 0.89) and PFS (high PD-L1: HR 0.74 versus low PD-L1: HR 0.82). ICI monotherapy was not associated with better oncological outcomes but was associated with better safety outcomes than chemotherapy alone.
CONCLUSIONS
Our analysis indicates a superior oncologic benefit to first-line ICI combination therapies in patients with chemotherapy-eligible mUC over standard chemotherapy. In contrast, ICI monotherapy was associated with favorable safety outcomes compared with chemotherapy but failed to show its superiority over chemotherapy in oncological benefits. PD-L1 status alone cannot help guide treatment decision-making. However, caution should be exercised in interpreting the conclusions drawn from this study, given that there is the heterogeneity of the population of interest, risk of bias and the nature of the studies evaluated whose data remain immature or unpublished.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Carcinoma; Clinical Decision-Making; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Patient Selection; Progression-Free Survival; Time Factors; Urinary Bladder Neoplasms; Urothelium
PubMed: 33962359
DOI: 10.1016/j.ejca.2021.03.049