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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 Cochrane Database of Systematic... Dec 2012Anal canal intraepithelial neoplasia (AIN) is a pre-malignant condition of the anal canal transitional epithelium that is associated with human papillomavirus (HPV)... (Review)
Review
BACKGROUND
Anal canal intraepithelial neoplasia (AIN) is a pre-malignant condition of the anal canal transitional epithelium that is associated with human papillomavirus (HPV) infection. The incidence and prevalence of AIN and anal cancer are increasing rapidly in HIV-positive men who have sex with men (MSM). Other groups like HIV-negative MSM, immunosuppressed patients and people affected by other HPV diseases like genital warts and cervical intraepithelial neoplasia (CIN) may also develop AIN. The condition is complicated by its multicentric and multifocal nature and high rates of relapse and morbidity. Targeted excisions using ablative treatments such as cautery, infrared coagulation (IRC) and cryotherapy have been used as first-line therapeutic strategies, and there are many other options. There is no consensus about the optimal management of AIN.
OBJECTIVES
To evaluate the effects of therapeutic interventions for anal canal intraepithelial neoplasia (AIN).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4), MEDLINE and EMBASE (to October 2011). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and contacted experts in the field and manufacturers of any AIN and HPV-specific treatments.
SELECTION CRITERIA
Randomized controlled trials (RCTs) that assessed any type of intervention for AIN.
DATA COLLECTION AND ANALYSIS
Two review authors independently abstracted data and assessed risk of bias. If it was possible, the data were synthesised in a meta-analysis.
MAIN RESULTS
We found only one RCT, which included 53 patients, that met our inclusion criteria. This trial reported data on imiquimod versus placebo. There was no statistically significant difference in the risk of disease cure but there was a trend for imiquimod to downgrade the AIN to a low-risk stage. The lack of statistical power of the trial may be due to the small number of patients in each group. The risk of bias was estimated as moderate.
AUTHORS' CONCLUSIONS
The included trial failed to demonstrate any statistically significant efficacy of imiquimod in the management of anal intraepithelial neoplasia (AIN). The absence of reliable evidence for any of the interventions used in AIN precludes any definitive guidance or recommendations for clinical practice. Prospective cohort studies and retrospective studies have not been included in this review as they are considered to provide lower quality evidence. Well designed RCTs are needed.
Topics: Aminoquinolines; Anal Canal; Antineoplastic Agents; Anus Neoplasms; Carcinoma in Situ; Humans; Imiquimod; Precancerous Conditions; Randomized Controlled Trials as Topic
PubMed: 23235673
DOI: 10.1002/14651858.CD009244.pub2 -
BJU International Sep 2012What's known on the subject? and What does the study add? Endoscopic management of upper tract urothelial carcinoma (UTUC) using either ureteroscopy and laser ablation,... (Review)
Review
UNLABELLED
What's known on the subject? and What does the study add? Endoscopic management of upper tract urothelial carcinoma (UTUC) using either ureteroscopy and laser ablation, or percutaneous resection, is a management option for treating selected low-grade tumours with favourable characteristics. However, the evidence base for such practice is relatively weak, as the reported experience is mainly limited to small case series (level of evidence 4), or non-randomised comparative studies that are unmatched for tumour stage (level of evidence 3b), with variability of follow-up duration and reported outcome measures. The present systematic review comprehensively reviews the outcomes of all studies of endoscopic management of UTUC, including the role of topical adjuvant therapy. It establishes for the first time a structured reference for endoscopic management of UTUC, and is a foundation for further clinical studies.
OBJECTIVE
To systematically review the oncological outcomes of upper tract urothelial carcinoma (UTUC) treated with ureteroscopic and percutaneous management. The standard treatment of UTUC is radical nephroureterectomy (RNU). However, over the last two decades several institutions have treated UTUC endoscopically, either via ureteroscopic ablation or percutaneous nephroscopic resection of tumour (PNRT), for both imperative and elective indications.
METHODS
For evidence acquisition the Pubmed database was searched for English language publications in December 2011 using the following terms: upper tract (UT) transitional cell carcinoma (TCC), upper tract TCC, UTTCC, upper tract urothelial cell carcinoma, upper tract urothelial carcinoma, UTUC, endoscopic management, ureteroscopic management, laser ablation, percutaneous management, PNRT, conservative management, ureteroscopic biopsy, biopsy, BCG, mitomycin C, topical therapy.
RESULTS
There are no randomised trials comparing endoscopic management with RNU. Most published studies were retrospective case series (and database reviews), or unmatched comparative studies. There was strong selection bias for favourable tumour characteristics in many endoscopically treated groups. There was variation in medical comorbidity and indication for treatment across different study groups. The biopsy verification of underlying UTUC pathology was inconsistent. The follow-up in most studies was limited, typically to a mean 3 years.
CONCLUSIONS
There is a high rate of UT recurrence with endoscopically managed UTUC, and a grade-related risk of tumour progression and disease-specific mortality. Overall, renal preservation may be high with ≈20% of patients proceeding eventually to RNU. For highly selected Grade 1 (or low-grade) disease managed in experienced centres, 5-year disease-specific survival (DSS) may be equivalent to RNU, although the small study groups and short follow-ups preclude comments on less favourable Grade 1 (or low-grade) tumour characteristics, or DSS, in the longer-term. For Grade 3 (or high-grade) disease, DSS outcomes are poor and endoscopic management should only be considered for compelling imperative indications in the context of the patient's overall life expectancy and competing comorbidity.
Topics: Antibiotics, Antineoplastic; BCG Vaccine; Biopsy; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Disease Progression; Humans; Mitomycin; Neoplasm Recurrence, Local; Nephrectomy; Postoperative Complications; Risk Factors; Treatment Outcome; Ureter; Ureteroscopy; Urologic Neoplasms; Urothelium
PubMed: 22471401
DOI: 10.1111/j.1464-410X.2012.11068.x -
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 -
Alimentary Pharmacology & Therapeutics Nov 2005The incidence of oesophageal adenocarcinoma is increasing in the UK faster than any other malignancy. Despite its relatively poor prognosis and the limited success of... (Review)
Review
The incidence of oesophageal adenocarcinoma is increasing in the UK faster than any other malignancy. Despite its relatively poor prognosis and the limited success of existing treatments, there is enthusiasm that chemopreventive agents might be able to stem the transition from normal squamous epithelium to adenocarcinoma. We discuss gastro-oesophageal reflux as the main risk factor for the development of Barrett's metaplasia, the only known precursor of oesophageal adenocarcinoma. Treatment options for reflux disease are considered with regard to their effects on cancer risk. Recent advances in the molecular and cell biology of Barrett's are outlined, and potential targets for chemoprevention examined. Available treatments for reflux disease have not convincingly altered the likelihood of cancer development. Epidemiological and animal studies support the use of non-steroidal anti-inflammatory drugs as potential chemopreventive agents. Dietary agents, however, have a more favourable side-effect profile and may prove to be an attractive alternative, although more work is needed to fully explore this prospect.
Topics: Adenocarcinoma; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Barrett Esophagus; Diet; Disease Progression; Esophageal Neoplasms; Fatty Acids, Omega-3; Gastroesophageal Reflux; Humans; Nitric Oxide; Oxidative Stress; Proton Pump Inhibitors
PubMed: 16225483
DOI: 10.1111/j.1365-2036.2005.02667.x -
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 -
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 -
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 -
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 -
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