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Stem Cell Research & Therapy Apr 2023Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn's Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future.
SHORT CONCLUSION
MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs' efficacy.
Topics: Humans; Quality of Life; Mesenchymal Stem Cell Transplantation; Treatment Outcome; Mesenchymal Stem Cells; Rectal Fistula; Crohn Disease
PubMed: 37101285
DOI: 10.1186/s13287-023-03331-6 -
Advances in Therapy Jan 2023Hemorrhoidal disease (HD) is characterized by prolapse of the inflamed and bleeding vascular tissues of the anal canal. Although HD is associated with a high recurrence... (Review)
Review
INTRODUCTION
Hemorrhoidal disease (HD) is characterized by prolapse of the inflamed and bleeding vascular tissues of the anal canal. Although HD is associated with a high recurrence rate, there is a lack of understanding around interventions that can reduce recurrence and improve outcomes for patients. As such, a systematic literature review (SLR) was conducted to summarize evidence on epidemiology, recurrence, and efficacy of interventions in HD.
METHODS
Real-world evidence (RWE) studies evaluating the incidence, prevalence, or recurrence of HD, as well as SLRs including a meta-analytic component reporting on the efficacy of systemic or topical pharmacological treatments for adults with HD, were included. Systematic searches were conducted in MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Database of Systematic Reviews.
RESULTS
The SLR identified 44 eligible publications. Consistent data were limited on the epidemiology of HD or HD recurrence. Specifically, incidence and prevalence reported across geographies were impacted by differences in data collection. Reported risk factors for HD were sedentary behavior, constipation, male gender, and age. Twenty-three RWE studies and one meta-analysis reported HD recurrence rates ranging from 0 to 56.5% following surgery or phlebotonics, with most (n = 19) reporting rates of 20% or less. In addition to time since treatment, risk factors for recurring disease were similar to those for HD in general. With respect to treatment, micronized purified flavonoid fractions significantly improved the main symptoms of HD compared to other pharmacological treatments.
CONCLUSION
The SLRs did not identify any RWE studies reporting recurrence in patients receiving systemic or topical treatments, highlighting the need for future research in this area. Further, more studies are needed to understand the optimum duration of medical treatment to prevent recurrence.
Topics: Adult; Humans; Male; Flavonoids; Hemorrhage; Hemorrhoids; Risk Factors; Meta-Analysis as Topic
PubMed: 36331754
DOI: 10.1007/s12325-022-02351-7 -
The Lancet. HIV Sep 2021Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts....
Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.
BACKGROUND
Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality.
METHODS
We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models.
FINDINGS
The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (p=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (p<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (p=0·0076); the prevalence plateaued thereafter (p=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age.
INTERPRETATION
High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+.
FUNDING
International Agency for Research on Cancer.
Topics: Age Factors; Anal Canal; HIV Infections; Humans; Male; Papillomaviridae; Papillomavirus Infections; Prevalence; Risk Factors; Sexuality; Squamous Intraepithelial Lesions
PubMed: 34339628
DOI: 10.1016/S2352-3018(21)00108-9 -
Cancers Jul 2022(1) Background: Anal canal adenocarcinomas constitute 1% of all gastrointestinal tract cancers. There is a current lack of consensus and NICE guidelines in the United... (Review)
Review
(1) Background: Anal canal adenocarcinomas constitute 1% of all gastrointestinal tract cancers. There is a current lack of consensus and NICE guidelines in the United Kingdom regarding the management of this disease. The overall objective was to perform a systematic review on the multitude of practice and subsequent outcomes in this group. (2) Methods: The MEDLINE, EMBASE, EMCARE and CINAHL databases were interrogated between 2011 to 2021. PRISMA guidelines were used to select relevant studies. The primary outcome measure was 5-year overall survival (OS). Secondary outcome measures included both local recurrences (LR) and distant metastases (DM). The Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies retrieved. The study was registered on PROSPERO (338286). (3) Results: Fifteen studies were included. Overall, there were 11,967 participants who were demographically matched. There were 2090 subjects in the largest study and five subjects in the smallest study. Treatment modalities varied from neoadjuvant chemoradiotherapy (CRT), CRT and surgery (CRT + S), surgery then CRT (S + CRT) and surgery only (S). Five-year OS ranged from 30.2% to 91% across the literature. LR rates ranged from 22% to 29%; DM ranged from 6% to 60%. Study heterogeneity precluded meta-analysis. (4) Conclusions: Trimodality treatment with neoadjuvant chemoradiotherapy (CRT) followed by radical surgery of abdominoperineal excision of rectum (APER) appeared to be the most effective approach, giving the best survival outcomes according to the current data.
PubMed: 35954403
DOI: 10.3390/cancers14153738 -
Colorectal Disease : the Official... May 2022Manometry is the best established technique to assess anorectal function in faecal incontinence. By systematic review, pooled prevalences of anal... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of anal motor and rectal sensory dysfunction in male and female patients undergoing anorectal manometry for symptoms of faecal incontinence.
AIM
Manometry is the best established technique to assess anorectal function in faecal incontinence. By systematic review, pooled prevalences of anal hypotonia/hypocontractility and rectal hypersensitivity/hyposensitivity in male and female patients were determined in controlled studies using anorectal manometry.
METHODS
Searches of MEDLINE and Embase were completed. Screening, data extraction and bias assessment were performed by two reviewers. Meta-analysis was performed based on a random effects model with heterogeneity evaluated by I .
RESULTS
Of 2116 identified records, only 13 studies (2981 faecal incontinence patients; 1028 controls) met the inclusion criteria. Anal tone was evaluated in 10 studies and contractility in 11; rectal sensitivity in five. Only three studies had low risk of bias. Pooled prevalence of anal hypotonia was 44% (95% CI 32-56, I = 96.35%) in women and 27% (95% CI 14-40, I = 94.12%) in men. The pooled prevalence of anal hypocontractility was 69% (95% CI 57-81; I = 98.17%) in women and 36% (95% CI 18-53; I = 96.77%) in men. Pooled prevalence of rectal hypersensitivity was 10% (95% CI 4-15; I = 80.09%) in women and 4% (95% CI 1-7; I = 51.25%) in men, whereas hyposensitivity had a pooled prevalence of 7% (95% CI 5-9; I = 0.00%) in women compared to 19% (95% CI 15-23; I = 0.00%) in men.
CONCLUSIONS
The number of appropriately controlled studies of anorectal manometry is small with fewer still at low risk of bias. Results were subject to gender differences, wide confidence intervals and high heterogeneity indicating the need for international collective effort to harmonize practice and reporting to improve certainty of diagnosis.
Topics: Anal Canal; Fecal Incontinence; Female; Humans; Male; Manometry; Muscle Hypotonia; Rectum
PubMed: 35023242
DOI: 10.1111/codi.16047 -
International Journal of Gynaecology... Jul 2022Women with previous obstetric anal sphincter injuries (OASIs) are at a higher risk of recurrence in the subsequent pregnancy, which may lead to the development or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Women with previous obstetric anal sphincter injuries (OASIs) are at a higher risk of recurrence in the subsequent pregnancy, which may lead to the development or worsening of anal incontinence. Due to a lack of evidence, few recommendations can be made about the factors that may affect the risk of OASI recurrence.
OBJECTIVE
We sought to conduct a systematic review and meta-analysis to investigate potential risk factors for recurrent OASIs.
SEARCH STRATEGY
Studies up to May 2019 were identified from PubMed, Scopus, Cochrane Library, and ISI Web of Science.
SELECTION CRITERIA
Studies assessing the impact of risk factors on OASI recurrence in subsequent pregnancies were included. Reviews, letters to the editor, conference abstracts, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded.
DATA COLLECTION AND ANALYSIS
Data were extracted by two independent reviewers. Odds ratio and standardized mean difference were chosen as effect measures. Pooled estimates were calculated using the random-effects model.
MAIN RESULTS
The meta-analysis showed that maternal age, gestational age, occiput posterior presentation, oxytocin augmentation, operative delivery, and shoulder dystocia were associated with the risk of recurrent OASIs in the subsequent delivery.
CONCLUSION
Prenatal and intrapartum risk factors are associated with recurrence of OASI. PROSPERO registration no. CRD42020178125.
Topics: Anal Canal; Delivery, Obstetric; Fecal Incontinence; Female; Humans; Obstetric Labor Complications; Perineum; Pregnancy; Risk Factors
PubMed: 34559892
DOI: 10.1002/ijgo.13950 -
Techniques in Coloproctology Apr 2021Simple anal fistula is one of the most common causes of proctological surgery and fistulotomy is considered the gold standard. This procedure, however, may cause... (Review)
Review
BACKGROUND
Simple anal fistula is one of the most common causes of proctological surgery and fistulotomy is considered the gold standard. This procedure, however, may cause complications. The aim of this systematic review was to assess the surgical treatment of simple anal fistula with traditional and sphincter-sparing techniques.
METHODS
A literature research was performed using PubMed, Cochrane, and Google Scholar to identify studies on the surgical treatment of simple anal fistulas. Observational studies and randomized clinical trials were included. We assessed the risk of bias of included studies using the Jadad scale for randomized controlled trials, and the MINORS Scale for the remaining studies.
RESULTS
The search returned 456 records, and 66 studies were found to be eligible. The quality of the studies was generally low. A total of 4883 patients with a simple anal fistula underwent a sphincter-cutting procedure, mainly fistulotomy, with a weighted average healing rate of 93.7%, while any postoperative continence impairment was reported in 12.7% of patients. Sphincter-sparing techniques were adopted to treat 602 patients affected by simple anal fistula, reaching a weighted average success rate of 77.7%, with no study reporting a significant postoperative incontinence rate. The postoperative onset of fecal incontinence and the recurrence of the disease reduced patients' quality of life and satisfaction.
CONCLUSIONS
Surgical treatment of simple anal fistulas with sphincter-cutting procedures provides excellent cure rates, even if postoperative fecal incontinence is not a negligible risk. A sphincter-sparing procedure could be useful in selected patients.
Topics: Anal Canal; Fecal Incontinence; Humans; Organ Sparing Treatments; Quality of Life; Rectal Fistula; Treatment Outcome
PubMed: 33387100
DOI: 10.1007/s10151-020-02385-5 -
EClinicalMedicine Aug 2023Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV)...
BACKGROUND
Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV) and men who have sex with men (MSM), and there is not a well-defined guideline for its screening. This systematic review evaluates the accuracy of DNA HRHPV (high-risk human papillomavirus), mRNA HPV, DNA HPV16 isolated and p16 staining biomarkers in anal canal smears for identifying anal intraepithelial neoplasia (AIN) 2 or 3, summarised as anal high-grade squamous intraepithelial lesions (aHSIL), and cancer.
METHODS
We searched the MEDLINE, Cochrane Library and Embase electronic databases as well as Grey literature to identify eligible papers published up to 31st July 2022. This systematic review and meta-analysis included observational studies comparing biomarker tests to histopathology after HRA (High-resolution Anoscopy) as a reference standard. We (ACM, TF) analysed studies in which patients of both sexes were screened for anal cancer using DNA HRHPV, mRNA HPV, DNA HPV16 and/or p16 biomarkers. The analysis was performed in pairs, for instance AIN2 or worse (AIN2+) vs. AIN1, HPV infection and normal (AIN1-). PROSPERO CRD42015024201.
FINDINGS
We included 21 studies with 7445 patients. DNA HR HPV showed a higher sensitivity 92.4% (95% CI 84.2-96.5), specificity 41.7% (95% CI 33.9-44.9) and AUC 0.67, followed by the mRNA HPV test, with a sensitivity 77.3% (95% CI 73.2%-80.9%), specificity 61.9% (95% CI 56.6-66.9) and AUC 0.78. DNA HPV16 showed higher specificity 71.7% (95% CI 55.3-83.8), followed by p16 test, 64.1% (95% CI 51.0-75.4); Sensitivity of DNA HPV16 was 53.3% (95% CI 35.4-70.3) and AUC 0.69, while p16 had a sensitivity of 68.8% (95% CI 47.9-84.1) and AUC 0.74. Subgroup analysis of MSM with HIV, with 13 studies and 5123 patients, showed similar accuracy, with a bit higher sensitivities and lower specificities. Considering the measure of the total between-study variability, mRNA HPV tests showed the smallest area of the 95% prediction ellipse, 6.0%, influenced by the low logit sensitivity, 0.011. All other groups of tests exceed 50% prediction ellipse area, which represent a high heterogeneity.
INTERPRETATION
Our findings suggested that DNA HR HPV can be a useful tool for screening for aHSIL and anal cancer if followed by biomarker with a higher specificity. As an isolated test, mRNA HPV had better performance.
FUNDING
There was no funding source for this study.
PubMed: 37588624
DOI: 10.1016/j.eclinm.2023.102128 -
American Journal of Obstetrics and... Aug 2022We aimed to systematically determine the incidences of wound infection and dehiscence after primary obstetric anal sphincter injury repair. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aimed to systematically determine the incidences of wound infection and dehiscence after primary obstetric anal sphincter injury repair.
DATA SOURCES
MEDLINE, Embase, CINAHL, EmCare, the Cochrane Library, and Trip Pro databases were searched from inception to February 2021.
STUDY ELIGIBILITY CRITERIA
We included observational clinical studies reporting the incidences of wound infection and dehiscence after primary obstetric anal sphincter injury repair. Case series and reports were excluded. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data.
METHODS
Data were analyzed as incidence (percentage) with 95% confidence intervals. Moreover, the prediction intervals were calculated to provide a predicted range for the potential incidence of wound complications when applied to an individual study setting. Study quality and risk of bias were assessed using the relevant tool from the Joanna Briggs Institute.
RESULTS
Of 956 studies found, 39 were selected for full-text review. Moreover, 10 studies (n=4767 women) were eligible and included in the meta-analysis. All 10 studies were conducted in high-income countries (Denmark [n=1], the United Kingdom [n=3], and the United States [n=6]). The incidences of wound infection (n=4593 women) and wound dehiscence (n=3866 women) after primary obstetric anal sphincter injury repair ranged between 0.1% to 19.8% and 1.9% to 24.6%, respectively. The overall incidences were 4.4% (95% confidence interval, 0.4-8.4) for wound infection and 6.9% (95% confidence interval, 1.6-12.2) for wound dehiscence. The prediction intervals were wide and suggested that the true incidences of wound infection and dehiscence in future studies could lie between 0.0% to 11.7% and 0.0% to 16.4%, respectively. Overall, 8 studies had a high or unclear risk of bias across ≥1 assessed element. None of the studies used the same set of clinical parameters to define wound infection or dehiscence. Furthermore, microbiological confirmation with wound swabs was never used as a diagnostic measure.
CONCLUSION
This was a systematic review and meta-analysis of wound infection and dehiscence incidences after primary obstetric anal sphincter injury repair. The incidence estimates from this review will be useful for clinicians when counseling women with obstetric anal sphincter injury and when consenting them for primary surgical repair.
Topics: Anal Canal; Delivery, Obstetric; Fecal Incontinence; Female; Humans; Incidence; Observational Studies as Topic; Obstetric Labor Complications; Perineum; Pregnancy; United Kingdom; Wound Infection
PubMed: 35550375
DOI: 10.1016/j.ajog.2022.05.012 -
Updates in Surgery Dec 2023Anal fistula (AF) is a common disease with high prevalence and surgical operations are effective treatments in clinical work. There exist many well-known surgical... (Meta-Analysis)
Meta-Analysis Review
Anal fistula (AF) is a common disease with high prevalence and surgical operations are effective treatments in clinical work. There exist many well-known surgical techniques treating complex anal fistula (CAF), however, none is ideal. To compare the superiority of Anal fistula plug (AFP) and Endoanal advancement flap repair (EAFR) for complex anal fistula. We searched worldwide databases including Pubmed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and SinoMed from their inception to March 2023. Studies comparing the outcomes of AFP and EAFR were included according to the PICO principles. The indicators of the healing rate, recurrence rate, wound infection rate, and complication rate, et al. were extracted and compared between different surgical methods. 5 RCTS and 7 non-RCTs were included in the meta-analysis with a total of 847 patients (341 patients conducted with AFP and 506 patients with EAFR). By combining the total effect of the 12 articles, we found that there was a statistical difference reporting the healing rate of AFP 48.3% and EAFR 64.4% treating the CAF (OR 0.68, 95% CI 0.30,1.55, P = 0.03), and EAFR has a better healing rate. However, there was no significant difference in terms of the recurrence rate (OR 1.68, 95% CI 0.80,3.54, P = 0.17), the wound infection rate (OR 1.82, 95% CI 0.95,3.52, P = 0.07), and the complication rate (OR 1.06, 95% CI 0.70,1.61, P = 0.77) either in the 12 articles or in the subgroup. The meta-analysis indicated that the EAFR was superior to AFP in terms of the healing rate treating the CAF, however, there were no significant differences between the two groups when it came to the recurrence rate, the wound infection rate, and the complication rate. EAFR might be one initial treatment for the complex cryptoglandular anal fistulas compared with AFP.
Topics: Humans; alpha-Fetoproteins; Rectal Fistula; Treatment Outcome; Surgical Flaps; Fecal Incontinence; Wound Infection; Anal Canal
PubMed: 37882975
DOI: 10.1007/s13304-023-01674-6