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Immune-checkpoint inhibitors in anal squamous cell carcinoma: a systematic review and meta-analysis.Seminars in Oncology Dec 2023Squamous cell carcinoma of the anus (SCCA) is a rare tumor. While most patients with locally advanced disease are cured with chemo-radiotherapy, about a quarter... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Squamous cell carcinoma of the anus (SCCA) is a rare tumor. While most patients with locally advanced disease are cured with chemo-radiotherapy, about a quarter eventually experience metastatic recurrence. Standard treatment for advanced disease is chemotherapy, but recently evidence on the activity of immunotherapy has been reported. We performed a systematic review and meta-analysis of prospective trials testing immune-checkpoint inhibitors (ICIs) in patients with SCCA.
OBJECTIVE
We aimed to evaluate the overall response rate (ORR) and the disease control rate (DCR) of ICIs in patients with advanced SCCA.
METHODS
We systematically searched PubMed, Embase, and Scopus, through December 31, 2022, for prospective trials assessing ICIs in patients with advanced SCCA. The primary and secondary endpoints were respectively ORR and DCR.
RESULTS
Six prospective trials were included in the analysis, one of which was randomized. Overall, seven treatment arms and 347 patients have been analyzed. Five treatment arms tested ICIs as monotherapy and two arms examined ICIs in combination with cetuximab and bevacizumab, respectively. The pooled ORR was 13% (95%CI, 10%-17%), with a DCR of 57% (95%CI, 40%-74%). Results did not change in a sensitivity analysis, which excluded the two treatment arms testing the combination of ICIs with other drugs.
CONCLUSIONS
The efficacy of ICIs in SCCAs is low. Combination strategies with targeted drugs or chemotherapy might represent a better therapeutic strategy for these patients. Further studies are awaited to identify resistance mechanisms to ICIs and optimize their efficacy.
Topics: Humans; Immune Checkpoint Inhibitors; Prospective Studies; Carcinoma, Squamous Cell; Cetuximab; Bevacizumab
PubMed: 38065801
DOI: 10.1053/j.seminoncol.2023.11.002 -
Colorectal Disease : the Official... Apr 2022Anismus is a common cause of obstructed defaecation syndrome (ODS). The aim of the present review is to assess the efficacy and safety of puborectalis muscle (PRM)... (Meta-Analysis)
Meta-Analysis Review
AIM
Anismus is a common cause of obstructed defaecation syndrome (ODS). The aim of the present review is to assess the efficacy and safety of puborectalis muscle (PRM) division in the treatment of anismus.
METHOD
PubMed, Scopus, Web of Science and the Cochrane Library were searched for studies that assessed the outcome of PRM division in the treatment of anismus. The main outcome measures were subjective improvement in ODS, decrease in the Wexner constipation score and ODS score, and complications, namely faecal incontinence (FI).
RESULTS
Ten studies (204 patients, 63.7% male) were included. The weighted mean rate of initial subjective improvement across randomized trials was 97.6% (95% CI 94%-100%) and across nonrandomized studies it was 63.1 (95% CI 39.3%-87%). The weighted mean rate of 12-month improvement across randomized trials was 64.9% (95% CI 53.3%-76.4%) and across nonrandomized studies it was 55.9% (95% CI 30.8%-81%). The weighted mean rate of FI across randomized trials was 12.1% (95% CI 4.2%-20%) and across nonrandomized studies it was 10.4% (95% CI 1.6%-19.3%). Male sex and unilateral PRM division were significantly associated with recurrence of symptoms after PRM division. Bilateral PRM division, posterior division, complete division and concomitant sphincterotomy were significantly associated with FI after PRM division.
CONCLUSIONS
The use of PRM division for treatment of anismus was followed by some initial improvement in ODS symptoms which decreased to <60% 12 months after PRM division. The mean rate of FI after PRM division, namely 10%-12%, is a limitation of the technique. Further well-designed trials are needed to verify the outcome of PRM division in the treatment of anismus.
Topics: Anus Diseases; Constipation; Female; Humans; Male; Pelvic Floor; Treatment Outcome
PubMed: 34984814
DOI: 10.1111/codi.16040 -
Frontiers in Oncology 2022Observational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the...
BACKGROUND
Observational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the results are inconsistent. We aim to comprehensively estimate the causal relationships between SLE and cancer morbidity and mortality using a meta-analysis of cohort studies and Mendelian randomization.
METHODS
A systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI). In addition, we further evaluated the potentially causal relationships identified by cohort studies using two-sample Mendelian randomization.
RESULTS
A total of 48 cohort studies involving 247,575 patients were included. We performed 31 main meta-analysis to assess the cancer risk and three meta-analyses to evaluate cancer mortality in SLE patients. Through meta-analyses, we observed an increased risk of overall cancer (RR=1.62, 95%CI, 1.47-1.79, <0.001) and cancer-related death (RR=1.52, 95%CI, 1.36-1.70, <0.001) in patients with SLE. Subgroup analysis by site-specific cancer showed that SLE was a risk factor for 17 site-specific cancers, including six digestive cancers (esophagus, colon, anus, hepatobiliary, liver, pancreatic), five hematologic cancers (lymphoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, leukemia, multiple myeloma), as well as cancer in lung, larynx, cervical, vagina/vulva, renal, bladder, skin, and thyroid. In addition, further mendelian randomization analysis verified a weakly association between genetically predisposed SLE and lymphoma risk (odds ratio=1.0004, =0.0035).
CONCLUSIONS
Findings from our study suggest an important role of SLE in carcinogenesis, especially for lymphoma.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, CRD42021243635.
PubMed: 35600353
DOI: 10.3389/fonc.2022.860794 -
The Journal of Infectious Diseases Nov 2023We sought to summarize human papillomavirus (HPV) vaccine efficacy/effectiveness (VE) against anal HPV infection and anal intraepithelial neoplasia (AIN). (Meta-Analysis)
Meta-Analysis
Impact of Human Papillomavirus Vaccine Against Anal Human Papillomavirus Infection, Anal Intraepithelial Neoplasia, and Recurrence of Anal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.
BACKGROUND
We sought to summarize human papillomavirus (HPV) vaccine efficacy/effectiveness (VE) against anal HPV infection and anal intraepithelial neoplasia (AIN).
METHODS
We performed literature review and meta-analysis to estimate VE, stratified by age and analytic population (per-protocol efficacy [PPE] or intention-to-treat [ITT] population in clinical trials, or all participants in real-world studies).
RESULTS
We identified 6 clinical trials and 8 real-world studies. In participants vaccinated at age ≤26 years (mainly human immunodeficiency virus [HIV]-negative individuals), significant VE against incident/prevalent anal HPV infection was reported in clinical trials, with a higher estimate in PPE (2 studies with 2390 participants; VE, 84% [95% confidence interval (CI), 77%-90%]; I2 = 0%) than ITT (2 studies with 4885 participants; 55%, 39%-67%; I2 = 46%) populations or in real-world studies (4 studies with 2375 participants; 77%, 40%-91%; I2 = 81%). HPV vaccination at age ≤26 years was associated with significant VE in preventing persistent anal HPV infection and AIN. No significant VE against anal HPV infection or AIN was found in persons vaccinated at age >26 years (mainly people living with HIV).
CONCLUSIONS
There is strong evidence for high VE against anal HPV infection and AIN in HIV-negative individuals vaccinated at age ≤26 years. However, the lower impact in ITT than in PPE populations and the lack of significant effect in people living with HIV aged >26 years indicates that vaccines have the higher impact in populations with less sexual exposure to anal HPV.
Topics: Humans; Adult; Papillomavirus Vaccines; Papillomavirus Infections; Human Papillomavirus Viruses; Anus Neoplasms; Carcinoma in Situ; HIV Infections; Papillomaviridae
PubMed: 37257044
DOI: 10.1093/infdis/jiad183 -
International Journal of Molecular... Nov 2022Lichen sclerosus (LS) is defined as a chronic mucocutaneous inflammatory disease with a localization predominantly to the anus and genitals (vulvar sclerosus (VLS)).... (Review)
Review
Lichen sclerosus (LS) is defined as a chronic mucocutaneous inflammatory disease with a localization predominantly to the anus and genitals (vulvar sclerosus (VLS)). Pediatric lichen sclerosus (LS) is a chronic inflammatory skin condition with predilection for the anogenital area that if untreated can lead to scarring. Vulvar LS is characterized by two peaks in incidence: it occurs in prepubertal girls and in postmenopausal women. To date, several mechanisms and risk factors have been proposed in the pathogenesis of pediatric vulvar LS; however, the etiology of this condition is still not fully understood and constitutes a challenge for scientists and clinicians. The presented research aimed to systematically review the existing literature on the pathogenesis of pediatric LS and to identify possible underlying autoimmune mechanisms and molecular networks. The clinical presentation of pediatric lichen sclerosus and available treatment modalities are also presented to acquaint a broader audience with this underdiagnosed and undertreated condition. As a result of our review, we discuss several potential mechanisms, molecules, and pathways that have been recognized in this disease. The purpose of our review was also to summarize what we can induce in further studies, which will ultimately help to identify the mechanism responsible for the disease and aid in the development of new, more effective treatment strategies for diagnosis and treatment by clinicians and researchers.
Topics: Humans; Female; Child; Lichen Sclerosus et Atrophicus; Vulva; Immune System Diseases; Genitalia; Treatment Outcome
PubMed: 36430687
DOI: 10.3390/ijms232214212 -
International Journal of Surgery... Mar 2023
Meta-Analysis
Botulinum toxin as a promising surgical strategy for chronic anal fissure: do the dose and injection site matter? Comparison of doses and injection sites of botulinum toxin for chronic anal fissure: A systematic review and network meta-analysis of randomized controlled trials.
Topics: Humans; Fissure in Ano; Network Meta-Analysis; Randomized Controlled Trials as Topic; Botulinum Toxins, Type A; Anal Canal; Chronic Disease; Treatment Outcome
PubMed: 36906767
DOI: 10.1097/JS9.0000000000000022 -
Herz Mar 2024Exercise-based cardiac rehabilitation has positive benefits for patients with chronic heart failure (CHF), but the choice of exercise intensity has been controversial.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Exercise-based cardiac rehabilitation has positive benefits for patients with chronic heart failure (CHF), but the choice of exercise intensity has been controversial. The aim of this systematic review and meta-analysis was to investigate the effects of different exercise intensities on cardiopulmonary function and quality of life (QoL) of patients with CHF.
METHODS
Randomized controlled trials (RCTs) of different exercise intensities applied to patients with CHF were searched in PubMed, Web of Science, the Cochrane Library, and Embase databases from inception to December 2021. Study selection and data extraction were performed simultaneously by two independent reviewers, using the Physiotherapy Evidence Database Scale (PEDro) for quality assessment of the included literature. The weighted mean differences (WMD) or standardized mean difference (SMD) were calculated by employing a fixed or random effects model. Other statistical analyses included subgroup analysis and sensitivity analysis. Quality of evidence was evaluated by the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) method.
RESULTS
Eight RCTs were included. Analyses reported no significant improvement in left ventricular ejection fractions (LVEF; WMD = 0.47, 95% CI [-4.10, 5.03], p = 0.841), peak oxygen uptake (peak VO) (SMD = 0.38, 95% CI [-0.03, 0.80], p = 0.069) and 6‑min walking distance (6MWD) (WMD = 14.10, 95% CI [-9.51, 37.72], p = 0.242). Exercise interventions of varying intensity produced small-to-moderate beneficial effects on QoL (WMD = -4.99, 95% CI [-8.29, -1.68], p = 0.003), which appeared to be attenuated at long-term follow-up (WMD = 2.12, 95% CI [-2.91, 7.16], p = 0.409).
CONCLUSION
High-intensity exercise does not have a significant advantage over moderate-intensity exercise in improving cardiopulmonary function and aerobic capacity in patients with CHF. Beneficial changes in QoL from high-intensity exercise also appeared to decrease during long-term follow-up, indicating a cumulative effect of the efficacy of high-intensity exercise.
Topics: Humans; Exercise Therapy; Exercise; Heart Failure; Quality of Life; Chronic Disease
PubMed: 37552242
DOI: 10.1007/s00059-023-05202-5 -
Reviews in Medical Virology Nov 2021Men who have sex with men (MSM) are at increased risk of human papillomavirus (HPV) infection because of their high-risk sexual behaviours. In this study, a... (Meta-Analysis)
Meta-Analysis Review
Prevalence and genotype distribution of human papillomavirus infection in different anatomical sites among men who have sex with men: A systematic review and meta-analysis.
Men who have sex with men (MSM) are at increased risk of human papillomavirus (HPV) infection because of their high-risk sexual behaviours. In this study, a meta-analytic approach was used to systematically analyse the literature to elucidate the prevalence and genotype distribution of anal, penile, oral and urethral HPV infection among MSM in the world. To carry out this systematic review, five electronic databases including Web of Science, PubMed, Scopus, Embase, and Google Scholar were searched for relevant studies published from January 2012 to November 2019, and pertinent data were collected from the eligible articles. The pooled HPV prevalence was calculated for each anatomical region using a random-effect model weighted by the inverse variance method. The meta-analysis was performed using the "Metaprop" function in the R package Meta. The overall pooled prevalence of anal, penile, oral and urethral HPV infection among MSM were 78.4% (95% confidence interval [CI]: 75.6%-81.0%), 36.2% (95% CI: 29.1%-44.0%), 17.3% (95% CI: 13.6%-21.7%) and 15.4% (95% CI: 7.8%-27.9%), respectively. Stratified analyses showed that the prevalences of HPV were significantly higher in HIV-positive than HIV-negative MSM. The most frequent HPV high-risk type detected in the anus, penis and oral cavity was HPV-16 (19.9%, 4.9% and 3.1%, respectively). HPV infection is rising in MSM because of high-risk sexual behaviours, suggesting an increased future risk of developing HPV-related diseases and malignancies in this population.
Topics: Alphapapillomavirus; Genotype; Homosexuality, Male; Humans; Male; Papillomavirus Infections; Prevalence
PubMed: 33527636
DOI: 10.1002/rmv.2219 -
Arquivos de Gastroenterologia 2023Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal...
BACKGROUND
Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time.
OBJECTIVE
To guide the safest and effective medical treatments of adults with CD.
METHODS
This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate.
RESULTS AND CONCLUSION
The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.
Topics: Adult; Humans; Crohn Disease; Consensus; Brazil; Colitis, Ulcerative; Inflammatory Bowel Diseases
PubMed: 36995888
DOI: 10.1590/S0004-2803.2022005S1-02 -
Radiotherapy and Oncology : Journal of... Apr 2021This systematic review summarised and critically appraised evidence on the efficacy and safety of interventions for anal cancer to support the panel of experts... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
This systematic review summarised and critically appraised evidence on the efficacy and safety of interventions for anal cancer to support the panel of experts developing the national evidence-based anal cancer guideline in Germany.
MATERIALS AND METHODS
We conducted a systematic review and meta-analyses of interventions for the treatment of stage I to III anal squamous cell carcinoma (SCCA). We systematically searched several databases and included any randomised controlled trial (RCT) assessing the pre-specified patient populations, regardless of the interventions studied. Non-randomised controlled studies of selected, pre-specified interventions were included if RCTs were not available or contained insufficient information. Where possible, we conducted meta-analyses and critically assessed confidence in the effect estimates using the GRADE approach.
RESULTS
Our searches yielded 10,325 (25 October 2018) and 889 hits (update search on 18 July 2019). Among the 41 studies (47 publications) included, we identified 19 comparisons of interventions for SCCA, and confidence in the effect estimates ranged from very low to high. Most RCTs compared various chemoradiation regimes. For other treatment options, such as local excision in early stages or different radiotherapies, we mostly identified comparative cohort studies.
CONCLUSION
Our findings indicate that, in most clinical situations, primary chemoradiation based on 5-FU and MMC is still the gold standard. However, treatment options for stage I anal cancer, particularly of the anal margin, as well as newer treatment approaches should be investigated in future RCTs. Overall, our findings may help health care professionals and patients make informed decisions about treatment choices.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Germany; Humans
PubMed: 33549645
DOI: 10.1016/j.radonc.2021.01.031