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Deutsches Arzteblatt International May 2016Lichen sclerosus is a chronic inflammatory skin disease. It is thought to be underdiagnosed and undertreated. If it is not treated, lichen sclerosus is associated with a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lichen sclerosus is a chronic inflammatory skin disease. It is thought to be underdiagnosed and undertreated. If it is not treated, lichen sclerosus is associated with a greater degree of scarring and an elevated risk of cancer in the genital area.
METHODS
This review is based on pertinent articles published up to October 2015 that were retrieved by a selective search in PubMed, Embase, and the Cochrane Library and on the European S3 guideline for lichen sclerosus.
RESULTS
Lichen sclerosus is mainly found in the anogenital area but can also be generalized. Extragenital involvement is reportedly present in 6% to 20% of patients. Neighboring mucous membranes, such as the vaginal or oral mucosa, are not typically affected. The disease is more common in women than in men, and occurs more often in adults than in children. About 10% of patients have other family members with the same condition. Anogenital lichen sclerosus often causes itching and pain. Functional impairment due to fissures and scars can arise over the course of the condition. The treatment of first choice is the local application of high-potency corticosteroids as early as possible (1/A). For boys and men in whom the condition does not remit after steroid treatment, circumcision is indicated (3/D).
CONCLUSION
Anogenital itching and clinical features such as erythema, white skin changes (such as hyperkeratosis and sclerosis), and fissures should arouse suspicion of lichen sclerosus. The diagnosis should be confirmed with a skin biopsy, and early, thorough treatment should be initiated. In this way, a mutilating disease course can be averted, and the risk of cancer can be lessened.
Topics: Adrenal Cortex Hormones; Combined Modality Therapy; Diagnosis, Differential; Evidence-Based Medicine; Female; Humans; Lichen Sclerosus et Atrophicus; Male; Treatment Outcome; Urogenital Neoplasms
PubMed: 27232363
DOI: 10.3238/arztebl.2016.0337 -
Advances in Anatomic Pathology Nov 2017Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies... (Review)
Review
Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and...
Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.
Topics: Biomarkers, Tumor; Biopsy; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Endometrial Neoplasms; Female; Gastrointestinal Neoplasms; Head and Neck Neoplasms; Humans; Immunohistochemistry; Lung Neoplasms; Lymphocytes, Tumor-Infiltrating; Melanoma; Mesothelioma; Ovarian Neoplasms; Pathology; Phenotype; Predictive Value of Tests; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck; Urogenital Neoplasms
PubMed: 28777143
DOI: 10.1097/PAP.0000000000000161 -
Journal of Surgical Oncology Oct 2022Memorial Sloan Kettering Cancer Center (MSK) has made many notable contributions to the scientific understanding and care of patients with common urologic cancers. Many... (Review)
Review
Memorial Sloan Kettering Cancer Center (MSK) has made many notable contributions to the scientific understanding and care of patients with common urologic cancers. Many of the advances represented paradigm shifts in management and established new standards of care. This review highlights the surgical procedures and treatment strategies originated and pioneered by urologic surgeons and colleagues at MSK during the past 50 years.
Topics: Humans; Urogenital Neoplasms; Urologic Neoplasms
PubMed: 36087085
DOI: 10.1002/jso.27031 -
The Cochrane Database of Systematic... Mar 2020This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects.
OBJECTIVES
To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes.
SEARCH METHODS
We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies.
SELECTION CRITERIA
We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both.
DATA COLLECTION AND ANALYSIS
Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type.
MAIN RESULTS
In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies.
AUTHORS' CONCLUSIONS
Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk.
Topics: Breast Neoplasms; Camellia sinensis; Case-Control Studies; Female; Flavonoids; Gastrointestinal Neoplasms; Humans; Incidence; Liver Neoplasms; Lung Neoplasms; Male; Mouth Neoplasms; Neoplasms; Phenols; Phytotherapy; Plant Extracts; Polyphenols; Randomized Controlled Trials as Topic; Skin Neoplasms; Tea; Urogenital Neoplasms
PubMed: 32118296
DOI: 10.1002/14651858.CD005004.pub3 -
European Urology Oncology Jun 2023While urothelial and renal cell cancers have exhibited modest responses to novel immune checkpoint inhibitors targeting the programmed death ligand 1 and its receptor,... (Review)
Review
CONTEXT
While urothelial and renal cell cancers have exhibited modest responses to novel immune checkpoint inhibitors targeting the programmed death ligand 1 and its receptor, response rates in patients with prostate cancer have remained poor. The factors underlying suboptimal outcomes observed in patients treated with novel immunotherapies are still to be resolved.
OBJECTIVE
To review the literature and describe the key adaptive immune physiological events associated with cancer progression and therapeutic response in genitourinary (GU) cancers.
EVIDENCE ACQUISITION
We performed a nonsystematic, collaborative narrative review to highlight recent advancements leading to the current state of knowledge on the critical mediators of antitumor adaptive immunity to GU cancers. Further, we discuss the findings on the pre- and post-treatment immunological events that either are unique to each of the three cancer types or exhibit overlapping clinical associations.
EVIDENCE SYNTHESIS
Aging-associated immune function decline is a major factor underlying poor outcomes observed in patients treated with both conventional and novel immunotherapies. Other cancer immunobiological aspects associated with suboptimal responses in GU cancers include the overall tumor mutational burden, mutations in specific tumor suppressor/DNA damage repair genes (KDM6A, PTEN, STAG2, TP53, ATM, and BRCA2), and abundance of multiple functional states of adaptive immune cells and their spatiotemporal localization within the tumor immune microenvironment. Understanding these mechanisms may potentially lead to the development of prognostic and predictive biomarkers such as immune cell infiltration profiles and tertiary lymphoid structures (TLSs) that associate with variable clinical outcomes depending on the nature of the novel immunotherapeutic approach. Implementation of newer immune-monitoring technologies and improved preclinical modeling systems will augment our understanding of the host and tumor intrinsic factors contributing to the variability of responses to immunotherapies.
CONCLUSIONS
Despite the tremendous progress made in the understanding of dynamic and static adaptive immune elements within the tumor immune landscape, several knowledge gaps remain. A comprehensive knowledge thus gained will lead to precision immunotherapy, improved drug sequencing, and a therapeutic response.
PATIENT SUMMARY
We performed a collaborative review by a diverse group of experts in the field to examine our understanding of the events and crosstalk between cancer cells and the patient's immune system that are associated with responses to novel immunotherapies. An evolving understanding of tumor-intrinsic and host-related immune alterations, both before and after therapy, will aid in the discovery of promising markers of responses to immunotherapy as well as the development of unique therapeutic approaches for the management of genitourinary cancers.
Topics: Male; Humans; Urogenital Neoplasms; Prognosis; Prostatic Neoplasms; Adaptive Immunity; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 37069029
DOI: 10.1016/j.euo.2023.03.002 -
Journal of Hematology & Oncology Nov 2023Significant scientific advances in immunotherapy and targeted therapy approaches have improved clinical outcomes and increased treatment options for patients with...
Significant scientific advances in immunotherapy and targeted therapy approaches have improved clinical outcomes and increased treatment options for patients with genitourinary (GU) malignancies. We highlight the clinical trial developments released at the ASCO 2023 annual meeting, including PARP inhibitors for prostate cancer, antibody drug conjugates and fibroblast growth factor receptor inhibitors for urothelial cancer, and HIF2a inhibitors for renal cell carcinoma. Novel agents such as bispecific antibodies, chimeric antigen receptor T-cells, and radiopharmaceuticals are currently in early phase development and also have high potential impact for the GU cancer landscape. With more treatment options, the field will need to define best treatment sequencing to optimize outcomes for each patient.
Topics: Male; Humans; Urogenital Neoplasms; Immunoconjugates; Immunotherapy; Carcinoma, Renal Cell; Kidney Neoplasms
PubMed: 37990343
DOI: 10.1186/s13045-023-01511-8 -
Clinical Genitourinary Cancer Feb 2021
Topics: Artificial Intelligence; COVID-19; Contact Tracing; Global Burden of Disease; Humans; Medical Oncology; Pandemics; Personal Protective Equipment; Physical Distancing; SARS-CoV-2; Smartphone; Telemedicine; Time-to-Treatment; Urogenital Neoplasms; Wireless Technology
PubMed: 33610279
DOI: 10.1016/j.clgc.2021.01.001 -
Journal of Hematology & Oncology Apr 2017Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are... (Review)
Review
Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body's own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.
Topics: Adaptive Immunity; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; B7-H1 Antigen; Biomarkers; CTLA-4 Antigen; Cancer Vaccines; Clinical Trials as Topic; Humans; Immunity, Innate; Immunotherapy; Interferon-alpha; Interleukin-2; Multicenter Studies as Topic; Neoplasm Proteins; Programmed Cell Death 1 Receptor; Urogenital Neoplasms
PubMed: 28434403
DOI: 10.1186/s13045-017-0457-4 -
Clinical Epigenetics Sep 2022DNA 5-hydroxymethylcytosine (5hmC) is produced by dynamic 5mC oxidation process contributing to tissue specification, and loss of 5hmC has been reported in multiple...
BACKGROUND
DNA 5-hydroxymethylcytosine (5hmC) is produced by dynamic 5mC oxidation process contributing to tissue specification, and loss of 5hmC has been reported in multiple cancers including genitourinary cancers. However, 5hmC is also cell-type specific, and its variability may exist between differentiated tumor cells and cancer stem cells. Thus, cancer-associated changes in 5hmC may be contributed by distinct sets of tumor cells within the tumor tissues.
RESULTS
Here, we applied a sensitive immunoprecipitation-based method (hMeDIP-seq) to analyze 5hmC changes during genitourinary carcinogenesis (including prostate, urothelial and kidney). We confirmed the tissue-specific distribution of 5hmC in genitourinary tissues and identified regional gain and global loss of 5hmC coexisting in genitourinary cancers. The genes with gain of 5hmC during tumorigenesis were functionally enriched in regulating stemness and hypoxia, whereas were associated with poor clinical prognosis irrespective of their differences in tumor type. We identified that gain of 5hmC occurred in soft fibrin gel-induced 3D tumor spheres with a tumor-repopulating phenotype in two prostate cancer cell lines, 22RV1 and PC3, compared with conventional two-dimensional (2D) rigid dishes. Then, we defined a malignant signature derived from the differentially hydroxymethylated regions affected genes of cancer stem-like cells, which could predict a worse clinical outcome and identified phenotypically malignant populations of cells from prostate cancer tumors. Notably, an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, restored 5hmC and killed the cancer stem cell-like cells leading to apoptosis in prostate cancer cell lines.
CONCLUSIONS
Collectively, our study dissects the regional gain of 5hmC in maintaining cancer stem-like cells and related to poor prognosis, which provides proof of concept for an epigenetic differentiation therapy with vitamin C by 5hmC reprogramming.
Topics: 5-Methylcytosine; Ascorbic Acid; Carcinogenesis; DNA; DNA Methylation; Fibrin; Humans; Magnesium; Male; Phosphates; Prostatic Neoplasms; Urogenital Neoplasms
PubMed: 36127710
DOI: 10.1186/s13148-022-01333-4 -
Immunotherapy Aug 2020Immune checkpoint inhibitor (ICI) therapy and therapeutic cancer vaccines have continued to demonstrate survival benefit and durable clinical response in patients with... (Review)
Review
Immune checkpoint inhibitor (ICI) therapy and therapeutic cancer vaccines have continued to demonstrate survival benefit and durable clinical response in patients with renal cell cancer, prostate cancer and bladder cancer, with limited responses in testicular cancer. The role of immunotherapy in combination with chemotherapy or other targeted therapies in the neo-adjuvant, adjuvant and metastatic setting is actively being explored. We describe the current immunotherapy-related treatment modalities approved for genitourinary cancers, focusing on immune checkpoint inhibitors, vaccines and other modalities, and highlight ongoing studies involving immunotherapy in these cancer types.
Topics: Animals; Antineoplastic Agents; B7-H1 Antigen; CTLA-4 Antigen; Cancer Vaccines; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Programmed Cell Death 1 Receptor; Urogenital Neoplasms
PubMed: 32594815
DOI: 10.2217/imt-2020-0054