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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 -
Techniques in Coloproctology Mar 2021Faecal incontinence (FI) affects 1-19% of the general population and carries significant physical and psychological morbidity. Treatment strategies vary greatly with... (Review)
Review
BACKGROUND
Faecal incontinence (FI) affects 1-19% of the general population and carries significant physical and psychological morbidity. Treatment strategies vary greatly with respect to morbidity and efficacy and relatively little is known regarding the role of mechanical devices such as anal and vaginal inserts. This is an up-to-date systematic review of the use of these devices in the management of patients with FI.
METHODS
A systematic electronic search was performed of the Medline, Pubmed and Embase databases using the key words and/or MeSH 'anal plug', 'anal insert', 'vaginal insert' and 'faecal incontinence'. Only articles that reported clinical outcomes for these devices for FI in the English language were included. Review articles were excluded to avoid duplication of data.
RESULTS
Thirteen articles fulfilled the eligibility criteria. Two articles reported outcomes for the Eclipse vaginal insert and 11 articles reported on three types of anal inserts; the Coloplast 'Tulip' design (6), the Procon/ProTect device (2) and the Renew insert (3). When tolerated, both anal and vaginal inserts significantly improved continence, bowel function and quality of life where reported. Adverse effects included discomfort, leakage and slippage. Long-term compliance and benefit are yet to be determined.
CONCLUSIONS
Vaginal and anal inserts may be a useful treatment for FI. Better quality of evidence is needed to define its effectiveness.
Topics: Anal Canal; Fecal Incontinence; Female; Humans; Quality of Life
PubMed: 32870438
DOI: 10.1007/s10151-020-02317-3 -
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 -
European Journal of Nuclear Medicine... Dec 2023To provide comprehensive data on the diagnostic and prognostic value of [F]-FDG PET (PET) in anal canal cancer patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To provide comprehensive data on the diagnostic and prognostic value of [F]-FDG PET (PET) in anal canal cancer patients.
METHODS
This study was designed following the PRISMA-DTA guidelines. For the meta-analysis, published original articles (until December 2022) that met the following criteria were included: Evaluated PET for locoregional and/or distant disease detection in patients with histopathology-proven anal canal cancer; Compared PET with a valid reference standard; Provided crude data to calculate meta-analytic estimates. Diagnostic measurements from subgroups were calculated in evaluating primary tumour detection, T stage, lymph node and distant metastases. Articles providing prognostic information on PET were also reported as a systematic review. For pooled meta-analytic calculations, the hierarchical method was used. The bivariate model was conducted to find the summary estimates. Analyses were performed using STATA 16.
RESULTS
After the screening, 28 studies were eligible to enter the meta-analytic calculations, and data from 15 were reported descriptively. For distinguishing T3/T4 from other T-stages, PET had pooled sensitivity and specificity of 91%(95%CI:72%-97%) and 96%(95%CI:88%-98%), respectively. The sensitivity and specificity for detecting metastatic (regional and/or distant) disease were 100% (95%CI:82%-100%) and 95% (95%CI:90%-98%), respectively. For therapy response assessment, the sensitivity and specificity of PET were 96%(95%CI:78%-99%) and 86%(95%CI:75%-93%), respectively. Higher pre-treatment total metabolic tumour volume was predictive of poorer survival. Conversely, for those achieving complete metabolic response, the 2-year PFS was 94%(95%CI:91%-97%) versus 51%(95%CI:42%-59%) for others (p-value < 0.001).
CONCLUSION
PET may be a useful tool for anal canal cancer therapy planning and provides valuable prognostic information.
Topics: Humans; Fluorodeoxyglucose F18; Positron-Emission Tomography; Anal Canal; Radiopharmaceuticals; Sensitivity and Specificity; Positron Emission Tomography Computed Tomography; Neoplasms
PubMed: 37592085
DOI: 10.1007/s00259-023-06393-z -
Neurogastroenterology and Motility Sep 2022Diagnosing anal incontinence (AI) based on manometry results is challenging due to the variation of the normal values and overlap between patients with and without AI.... (Review)
Review
BACKGROUND
Diagnosing anal incontinence (AI) based on manometry results is challenging due to the variation of the normal values and overlap between patients with and without AI. This study aimed to perform a systematic review on the difference in sphincter fatigability between patients with and without AI.
METHODS
MEDLINE, EMBASE, SCOPUS, and Google Scholar were searched. Studies were included if they included adult patients and assessed anal sphincter fatigability between using manometry. The effect size was estimated as the standardized mean difference (SMD) with 95% confidence intervals. A random-effects model was used.
RESULTS
The database searches identified 125 unique articles, and five additional articles were identified from the reference list of articles. One hundred thirteen were excluded through title and abstract review. Nine articles were included in the final analysis. There was no statistically significant difference in the resting pressure between the two groups. Patients with AI had significantly lower squeeze pressure. There was no statistically significant difference between the groups in the fatigue rate. The FRI was significantly lower in patients with AI (SMD 1.636, p = 0.001). Approximately a third of the patients in one study were able to maintain a contraction for 20s without reducing pressure. There was significant heterogeneity in the studies. The data available were inadequate for more robust calculations.
CONCLUSIONS
Sphincter fatigability, measured by the Fatigability Rate Index, has good discriminating power for anal incontinence. A standardized protocol needs to be followed by future researchers. Graphical Abstract The analysis used six studies with 413 patients to compare Fatigue Rate Index between patients with AI and controls. All studies reported a lower FRI in patients with incontinence and the FRI was significantly lower in patients with AI (standardized mean difference [SMD] 1.636, p= 0.001). Conflicting results were reported on the correlation between FRI and AI symptom scores.
Topics: Adult; Anal Canal; Fatigue; Fecal Incontinence; Humans; Manometry
PubMed: 35246890
DOI: 10.1111/nmo.14342 -
Techniques in Coloproctology Dec 2023A common and debilitating complication of low anterior resection for rectal cancer is low anterior resection syndrome (LARS). As a multifactorial entity, LARS is poorly...
BACKGROUND
A common and debilitating complication of low anterior resection for rectal cancer is low anterior resection syndrome (LARS). As a multifactorial entity, LARS is poorly understood and challenging to treat. Despite this, prevention strategies are commonly overlooked. Our aim was to review the pathophysiology of LARS and explore current evidence on the efficacy and feasibility of prophylactic techniques.
METHODS
A literature review was performed between [1st January 2000 to 1st October 2023] for studies which investigated preventative interventions for LARS. Mechanisms by which LARS develop are described, followed by a review of prophylactic strategies to prevent LARS. Medline, Cochrane, and PubMed databases were searched, 189 articles screened, 8 duplicates removed and 18 studies reviewed.
RESULTS
Colonic dysmotility, anal sphincter dysfunction and neorectal dysfunction all contribute to the development of LARS, with the complex mechanism of defecation interrupted by surgery. Transanal irrigation (TAI) and pelvic floor rehabilitation (PFR) have shown benefits in preventing LARS, but may be limited by patient compliance. Intraoperative nerve monitoring (IONM) and robotic-assisted surgery have shown some promise in surgically preventing LARS. Nerve stimulation and other novel strategies currently used in treatment of LARS have yet to be investigated in their roles prophylactically.
CONCLUSIONS
To date, there is a limited evidence base for all preventative strategies including IONM, RAS, PFP and TAI. These strategies are limited by either access (IONM, RAS and PFP) or acceptability (PFP and TAI), which are both key to the success of any intervention. The results of ongoing trials will serve to assess acceptability, while technological advancement may improve access to some of the aforementioned strategies.
Topics: Humans; Anal Canal; Low Anterior Resection Syndrome; Postoperative Complications; Quality of Life; Rectal Neoplasms; Robotic Surgical Procedures
PubMed: 38091118
DOI: 10.1007/s10151-023-02872-5 -
Surgery Jul 2022There are multiple treatments for anal fissures. These range from medical treatment to surgical procedures, such as sphincterotomy. The aim of this study was to compare... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are multiple treatments for anal fissures. These range from medical treatment to surgical procedures, such as sphincterotomy. The aim of this study was to compare the relative clinical outcomes and effectiveness of interventional treatments for anal fissure.
METHODS
Randomized controlled trials were identified by means of a PRISMA-compliant systematic review using the Medline, EMBASE, and CENTRAL databases. Inclusion criteria were randomized controlled trials comparing treatments for anal fissure. A Bayesian network meta-analysis was performed using BUGSnet package in R. Outcomes of interest were healing (6-8-, 10-16-, and >16-week follow-up), symptom recurrence, pain (measured on a visual analog scale), and fecal or flatus incontinence. PROPSERO Registration: CRD42021229615.
RESULTS
Sixty-nine randomized controlled trials were included in the analysis. Lateral sphincterotomy remains the treatment with the highest odds of healing compared to botulinum toxin and medical therapy at all follow-up time points. There was no significant difference in healing between botulinum toxin and medical therapy at any time point. Advancement flap showed similar effectiveness compared to lateral sphincterotomy. Medical treatment and botulinum toxin had the highest pain scores at follow-up. Sphincterotomy had the highest odds of fecal and flatus incontinence.
CONCLUSION
Lateral sphincterotomy had the highest rates of healing and should be considered as the definitive treatment after failed initial therapy with botulinum toxin or medical treatment. Botulinum toxin was equally effective compared to medical treatment. Advancement flap shows similar effectiveness compared to lateral sphincterotomy, but more studies are needed to evaluate its efficacy.
Topics: Anal Canal; Bayes Theorem; Botulinum Toxins; Chronic Disease; Fissure in Ano; Flatulence; Humans; Network Meta-Analysis; Pain; Treatment Outcome
PubMed: 34998619
DOI: 10.1016/j.surg.2021.11.030 -
Ultrasound in Obstetrics & Gynecology :... Oct 2023The primary objective was to perform a systematic review of predictive factors for obstetric anal sphincter injury (OASI) occurrence at first vaginal delivery, with the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The primary objective was to perform a systematic review of predictive factors for obstetric anal sphincter injury (OASI) occurrence at first vaginal delivery, with the diagnosis made by ultrasound (US-OASI). The secondary objective was to report on incidence rates of sonographic anal sphincter (AS) trauma, including trauma that was not clinically reported at childbirth, among the studies providing data for our primary objective.
METHODS
We conducted a systematic search of MEDLINE, EMBASE, Web of Science, CINAHL, The Cochrane Library and ClinicalTrials.gov databases. Both observational cohort studies and interventional trials were eligible for inclusion. Study eligibility was assessed independently by two authors. Random-effects meta-analyses were performed to pool effect estimates from studies reporting on similar predictive factors. Summary odds ratio (OR) or mean difference (MD) is reported with 95% CI. Heterogeneity was assessed using the I statistic. Methodological quality was assessed using the Quality in Prognosis Studies tool.
RESULTS
A total of 2805 records were screened and 21 met the inclusion criteria (16 prospective cohort studies, three retrospective cohort studies and two interventional non-randomized trials). Increasing gestational age at delivery (MD, 0.34 (95% CI, 0.04-0.64) weeks), shorter antepartum perineal body length (MD, -0.60 (95% CI, -1.09 to -0.11) cm), labor augmentation (OR, 1.81 (95% CI, 1.21-2.71)), instrumental delivery (OR, 2.13 (95% CI, 1.13-4.01)), in particular forceps extraction (OR, 3.56 (95% CI, 1.31-9.67)), shoulder dystocia (OR, 12.07 (95% CI, 1.06-137.60)), episiotomy use (OR, 1.85 (95% CI, 1.11-3.06)) and shorter episiotomy length (MD, -0.40 (95% CI, -0.75 to -0.05) cm) were associated with US-OASI. When pooling incidence rates, 26% (95% CI, 20-32%) of women who had a first vaginal delivery had US-OASI (20 studies; I = 88%). In studies reporting on both clinical and US-OASI rates, 20% (95% CI, 14-28%) of women had AS trauma on ultrasound that was not reported clinically at childbirth (16 studies; I = 90%). No differences were found in maternal age, body mass index, weight, subpubic arch angle, induction of labor, epidural analgesia, episiotomy angle, duration of first/second/active-second stages of labor, vacuum extraction, neonatal birth weight or head circumference between cases with and those without US-OASI. Antenatal perineal massage and use of an intrapartum pelvic floor muscle dilator did not affect the odds of US-OASI. Most (81%) studies were judged to be at high risk of bias in at least one domain and only four (19%) studies had an overall low risk of bias.
CONCLUSION
Given the ultrasound evidence of structural damage to the AS in 26% of women following a first vaginal delivery, clinicians should have a low threshold of suspicion for the condition. This systematic review identified several predictive factors for this. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Anal Canal; Retrospective Studies; Prospective Studies; Delivery, Obstetric; Episiotomy; Anus Diseases; Perineum; Risk Factors; Obstetric Labor Complications
PubMed: 37329513
DOI: 10.1002/uog.26292