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Actas Urologicas Espanolas Nov 2022Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology. In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis.
MATERIALS AND METHODS
A systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS.
RESULTS
In total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively.
CONCLUSIONS
Our study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma.
Topics: Humans; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Transitional Cell; Hyaluronan Receptors; Keratin-20; Ki-67 Antigen; Tumor Suppressor Protein p53; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium
PubMed: 36216762
DOI: 10.1016/j.acuroe.2022.08.013 -
The Ocular Surface Jan 2023Rho kinase inhibitors (ROCKi) have attracted growing multidisciplinary interest, particularly in Ophthalmology where the question as to how they promote corneal... (Review)
Review
A systematic review on the effects of ROCK inhibitors on proliferation and/or differentiation in human somatic stem cells: A hypothesis that ROCK inhibitors support corneal endothelial healing via acting on the limbal stem cell niche.
Rho kinase inhibitors (ROCKi) have attracted growing multidisciplinary interest, particularly in Ophthalmology where the question as to how they promote corneal endothelial healing remains unresolved. Concurrently, stem cell biology has rapidly progressed in unravelling drivers of stem cell (SC) proliferation and differentiation, where mechanical niche factors and the actin cytoskeleton are increasingly recognized as key players. There is mounting evidence from the study of the peripheral corneal endothelium that supports the likelihood of an internal limbal stem cell niche. The possibility that ROCKi stimulate the endothelial SC niche has not been addressed. Furthermore, there is currently a paucity of data that directly evaluates whether ROCKi promotes corneal endothelial healing by acting on this limbal SC niche located near the transition zone. Therefore, we performed a systematic review examining the effects ROCKi on the proliferation and differentiation of human somatic SC, to provide insight into its effects on various human SC populations. An appraisal of electronic searches of four databases identified 1 in vivo and 58 in vitro studies (36 evaluated proliferation while 53 examined differentiation). Types of SC studied included mesenchymal (n = 32), epithelial (n = 11), epidermal (n = 8), hematopoietic and other (n = 8). The ROCK 1/2 selective inhibitor Y-27632 was used in almost all studies (n = 58), while several studies evaluated ≥2 ROCKi (n = 4) including fasudil, H-1152, and KD025. ROCKi significantly influenced human somatic SC proliferation in 81% of studies (29/36) and SC differentiation in 94% of studies (50/53). The present systemic review highlights that ROCKi are influential in regulating human SC proliferation and differentiation, and provides evidence to support the hypothesis that ROCKi promotes corneal endothelial division and maintenance via acting on the inner limbal SC niche.
Topics: Humans; Endothelium, Corneal; Limbal Stem Cells; Adult Stem Cells; Cell Differentiation; Cell Proliferation; Limbus Corneae; Epithelium, Corneal; Stem Cell Niche
PubMed: 36586668
DOI: 10.1016/j.jtos.2022.12.008 -
Journal of Drugs in Dermatology : JDD Feb 2022Rice bran extracts (RB) derived from Oryza sativa are part of cultural skin and hair care practices in Asia. Given the knowledge gap regarding clinical efficacy,...
BACKGROUND
Rice bran extracts (RB) derived from Oryza sativa are part of cultural skin and hair care practices in Asia. Given the knowledge gap regarding clinical efficacy, marketplace availability, and safety, the growing popularity of nutraceuticals calls for better clinician awareness and scientific understanding of their applications and limitations.
OBJECTIVE
To review available scientific evidence regarding therapeutic efficacy, safety, and consumer availability of RB on hair health.
MATERIALS AND METHODS
A primary literature search was conducted using PubMed to identify articles on RB and hair growth in May 2021. A limited market analysis of rice-derivative-containing hair products was also conducted on Amazon.com.
RESULTS
10 studies were analyzed: six regarding the efficacy of RB for hair growth, and four analyzing the safety profile of RB. Topically applied RB increases expression of growth factors and molecular signals which promote cell proliferation in the anagen phase including β-catenin, while inhibiting enzymes responsible for propagating anagen to catagen/telogen transition including TGFβ and Type I 5α-reductase. RB is non-genotoxic, non-cytotoxic, and appropriate for human use in cosmetics. The Amazon.com search yielded 119 rice-containing hair products, reflecting their over-the-counter popularity.
CONCLUSIONS
Current literature is promising for RB promoting hair growth given its ability to increase expression of growth factors and molecular signals associated with maintaining anagen phase, decreasing inflammation, inhibiting 5α-reductase, and promoting melanogenesis. J Drugs Dermatol. 2022;21(2):177-185. doi:10.36849/JDD.6345.
Topics: Cell Proliferation; Cosmetics; Hair; Hair Follicle; Humans; Oryza
PubMed: 35133117
DOI: 10.36849/jdd.6345 -
Journal of Endourology Feb 2015Developments in optical diagnostics have potential for less invasive diagnosis of upper urinary tract urothelial carcinoma (UUT-UC). This systematic review provides an... (Review)
Review
PURPOSE
Developments in optical diagnostics have potential for less invasive diagnosis of upper urinary tract urothelial carcinoma (UUT-UC). This systematic review provides an overview of technology, applications, and limitations of recently developed optical diagnostics in the upper urinary tract and outlines their potential for future clinical applications. In addition, current evidence was evaluated.
LITERATURE SEARCH
A PubMed literature search was performed and articles on narrow band imaging (NBI), photodynamic diagnosis (PDD), Storz professional imaging enhancement system (SPIES), optical coherence tomography (OCT), and confocal laser endomicroscopy (CLE) regarding UUT-UC were reviewed for data extraction. Study quality was reviewed according to Quality Assessment of Diagnostic Accuracy Studies and Innovation, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) standards.
RESULTS
Four articles available for quality assessment, demonstrated high level of evidence, but low level of IDEAL stage. NBI and SPIES enhance contrast of mucosal surface and vascular structures, improving tumor detection rate. A first in vivo study showed promising results. PDD uses fluorescence to improve tumor detection rate. However, due to the acute angle of the ureterorenoscopes there is an increased risk of false positives. OCT produces cross-sectional high-resolution images, providing information on tumor grade and stage. A pilot study showed promising diagnostic accuracy. CLE allows ultrahigh-resolution microscopy of tissue resulting in images of the cellular structure. CLE cannot be applied in vivo in the upper urinary tract yet, due to technical limitations.
CONCLUSIONS
NBI, SPIES, and PDD aim at improving visualization of UUT-UC through contrast enhancement. OCT and CLE aim at providing real-time predictions of histopathological diagnosis. For all techniques, more research has to be conducted before these techniques can be implemented in the routine management of UUT-UC. All techniques might be of value in specific clinical scenarios and allow for integration, for example, OCT with NBI, and could therefore improve tumor detection and staging and help in selecting the optimal treatment for the individual patient.
Topics: Carcinoma, Transitional Cell; Humans; Microscopy, Confocal; Narrow Band Imaging; Tomography, Optical Coherence; Ureteroscopy; Urinary Tract; Urologic Neoplasms; Urothelium
PubMed: 25178057
DOI: 10.1089/end.2014.0551 -
Frontiers in Endocrinology 2020Abnormal endometrial receptivity is one of the major causes of embryo implantation failure and infertility. The plasma membrane transformation (PMT) describes the...
BACKGROUND
Abnormal endometrial receptivity is one of the major causes of embryo implantation failure and infertility. The plasma membrane transformation (PMT) describes the collective morphological and molecular alterations occurring to the endometrial luminal epithelium across the mid-secretory phase of the menstrual cycle to facilitate implantation. Dysregulation of this process directly affects endometrial receptivity and implantation. Multiple parallels between these alterations to confer endometrial receptivity in women have been drawn to those seen during the epithelial-mesenchymal transition (EMT) in tumorigenesis. Understanding these similarities and differences will improve our knowledge of implantation biology, and may provide novel therapeutic targets to manage implantation failure.
METHODS
A systematic review was performed using the Medline (Ovid), Embase, and Web of Science databases without additional limits. The search terms used were "(plasma membrane* or cell membrane*) and transformation*" and "endometrium or endometrial." Research studies on the PMT or its regulation in women, discussing either the endometrial epithelium, decidualized stroma, or both, were eligible for inclusion.
RESULTS
A total of 198 articles were identified. Data were extracted from 15 studies that matched the inclusion criteria. Collectively, these included studies confirmed the alterations occurring to the endometrial luminal epithelium during the PMT are similar to those seen during the EMT. Such similarities included alterations to the actin cytoskeleton remodeling of adherens junctions, integrin expression and epithelial-stromal communication. These were also some differences between these processes, such as the regulation of tight junctions and mucins, which need to be further researched.
CONCLUSIONS
This review raised the prospect of shared and distinct mechanisms existing in PMT and EMT. Further investigation into similarities between the PMT in the endometrium and the EMT in tumorigenesis may provide new mechanistic insights into PMT and new targets for the management of implantation failure and infertility.
Topics: Animals; Cell Polarity; Embryo Implantation; Endometrium; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Humans
PubMed: 33193109
DOI: 10.3389/fendo.2020.596324 -
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 -
Urology Oct 2020Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of...
Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of urothelial carcinomas. The benefits of such agents include a reduction in morbidity and diseased organ preservation. While numerous agents have shown promise, research is limited due to small patient cohorts, varying follow-up, and no standardized methodology to assess response. Therefore, to date, chemoablation has not been widely adopted. This may change as a novel mitomycin formulation has recently been approved for treating low-grade upper tract urothelial carcinoma. Future studies are ongoing which evaluate other promising chemoablation options in urothelial carcinoma.
Topics: Administration, Intravesical; Antineoplastic Agents; Aziridines; BCG Vaccine; Carcinoma, Transitional Cell; Clinical Trials as Topic; Cystoscopy; Deoxycytidine; Epirubicin; Ethanol; Forecasting; Humans; Indolequinones; Injections, Intralesional; Interferon-alpha; Interleukin-2; Mitomycin; Urinary Bladder Neoplasms; Urothelium; Gemcitabine
PubMed: 32540302
DOI: 10.1016/j.urology.2020.05.066 -
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 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 -
The Journal of Urology Dec 2020The currently available evidence regarding the prognostic and clinical significance of each variant histology subtype of urothelial bladder cancer remains scarce. We... (Meta-Analysis)
Meta-Analysis
PURPOSE
The currently available evidence regarding the prognostic and clinical significance of each variant histology subtype of urothelial bladder cancer remains scarce. We assessed the prognostic value of variant histology in patients with urothelial carcinoma of the bladder treated with radical cystectomy.
MATERIALS AND METHODS
PubMed®, Web of Science™, Cochrane Library and Scopus® databases were searched for articles published before October 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. We identified 39 studies comprising 20,544 patients matching our eligibility criteria.
RESULTS
Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with urothelial carcinoma of the bladder with and without variant histology. Formal meta-analyses were performed for these outcomes. Variant histology was associated with worse cancer specific (pooled HR 1.37, 95% CI 1.24-1.50), overall (pooled HR 1.44, 95% CI 1.26-1.65) and recurrence-free survival (pooled HR 1.32, 95% CI 1.20-1.45). Subgroup analyses demonstrated that "micropapillary" (pooled HR 1.20, 95% CI 1.02-1.41), "plasmacytoid" (pooled HR 2.03, 95% CI 1.17-3.52) and "small cell" variant histology (HR 3.32, 95% CI 1.98-5.59) were also associated with worse overall survival.
CONCLUSIONS
Variant histology in patients with urothelial carcinoma of the bladder is associated with increased risks of disease recurrence as well as cancer specific and overall mortality. Variant histology was independently associated with overall survival in the "micropapillary," "plasmacytoid" and "small cell" subgroups. Variant histology should be integrated into prognostic tools to guide risk stratification, treatment planning and patient counseling. However, caution should be exercised in interpreting the conclusions drawn from this study given the limitations, which include the heterogeneity of the population of interest and the retrospective nature of the primary data evaluated.
Topics: Carcinoma, Transitional Cell; Cystectomy; Disease-Free Survival; Humans; Neoplasm Recurrence, Local; Prognosis; Risk Assessment; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium
PubMed: 32716694
DOI: 10.1097/JU.0000000000001305