-
International Journal of Cancer Dec 2022To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta-analysis of the diagnostic accuracy of anal cancer screening tests... (Meta-Analysis)
Meta-Analysis
To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta-analysis of the diagnostic accuracy of anal cancer screening tests in different populations with elevated risk for anal cancer. We conducted a literature search of studies evaluating tests for anal precancer and cancer (anal intraepithelial neoplasia grade 2 or worse, AIN2+) published between January 1, 1997 to September 30, 2021 in PubMed and Embase. Titles and abstracts were screened for inclusion and included articles underwent full-text review, data abstraction and quality assessment. We estimated the prevalence of AIN2+ and calculated summary estimates and 95% confidence intervals (CI) of test positivity, sensitivity and specificity and predictive values of various testing strategies, overall and among population subgroups. A total of 39 articles were included. The prevalence of AIN2+ was 20% (95% CI, 17-29%), and ranged from 22% in men who have sex with men (MSM) living with HIV to 13% in women and 12% in MSM without HIV. The sensitivity and specificity of cytology and HPV testing were 81% and 62% and 92% and 42%, respectively, and 93% and 33%, respectively for cytology and HPV co-testing. AIN2+ risks were similar among those testing positive for cytology, HPV, or co-testing. Limited data on other biomarkers (HPV E6/E7 mRNA and p16/Ki-67 dual stain), suggested higher specificity, but lower sensitivity compared with anal cytology and HPV. Our findings provide important evidence for the development of clinical guidelines using anal cytology and HPV testing for anal cancer screening.
Topics: Anus Neoplasms; Early Detection of Cancer; Female; HIV Infections; Homosexuality, Male; Humans; Ki-67 Antigen; Male; Papillomaviridae; Papillomavirus Infections; RNA, Messenger; Sexual and Gender Minorities
PubMed: 35793241
DOI: 10.1002/ijc.34199 -
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 -
Journal of Clinical Virology : the... Jul 2023Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA; cHPV DNA) in blood referred to as "liquid biopsy" may support the early diagnosis and monitoring of affected individuals.
METHODS
A systematic review, including meta-analysis of studies available in the literature on the utilization of ctDNA and cHPV DNA as diagnostic, predictive, and monitoring biomarker tests of HPV associated anogenital cancers was performed following the criteria of PRISMA.
RESULTS
A total of 31 studies were eligible for systematic review; 20 used cHPV DNA in cervical cancers; 7 used ctDNA in cervical cancer; 5 used cHPV DNA in anal cancer; no eligible studies on vulva, vaginal or penile cancer were available. The meta-analysis identified low sensitivity (0.36) and high specificity (0.96) of cHPV DNA as diagnostic for cervical cancer. Comparatively, there was high sensitivity (0.95) and specificity (1.0) of cHPV DNA for the diagnosis of anal cancer. cHPV DNA and/or ctDNA in cervical cancer were prognostic markers associated with poor clinical outcomes. Additionally, in anal cancer the post treatment detection of cHPV DNA was informative in the prediction of treatment response or progression-free survival.
CONCLUSION
ctDNA and cHPV DNA are promising diagnostic and prognostic biomarkers for the detection of anogenital disease. Evolution and refinement of molecular tools is likely to improve performance further. Additionally the comparative absence of studies in the vulval, vaginal and penile context warrants further exploration and research.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Human Papillomavirus Viruses; Anus Neoplasms; DNA
PubMed: 37163963
DOI: 10.1016/j.jcv.2023.105469 -
International Journal of Colorectal... Jan 2022Anal fissure is a common condition that can be treated medically or surgically. Chemical sphincterotomy is often used before surgical intervention. This study aims to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anal fissure is a common condition that can be treated medically or surgically. Chemical sphincterotomy is often used before surgical intervention. This study aims to evaluate the effectiveness of topical agents for chemical sphincterotomy on healing of anal fissures and side-effects.
METHODS
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant systematic review was performed using MEDLINE, EMBASE, Scopus, and CENTRAL databases. Eligible studies included randomized controlled trials which compared topical sphincterotomy agents with topical placebo agents or each other. Studies that included surgical treatments were excluded. Overall evidence was synthesized according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.
RESULTS
Thirty-seven studies met the study selection criteria. Seventeen studies show that glyceryl trinitrate (GTN) was significantly more likely to heal anal fissure than placebo (relative risk (RR) = 1.96, 95% confidence interval (95%CI) = 1.35-2.84, I2 = 80%). Eleven studies showed a marginally significant difference between healing rates for diltiazem vs GTN, RR = 1.16, (1.01-1.33) I2 = 48%. There was no significant difference in healing between diltiazem and placebo, RR = 1.65, (0.64-4.23), I2 = 92%. GTN significantly reduced pain on the visual analog scale compared to the placebo group, MD-0.97 (-1.64 to -0.29) I2 = 92%. There was high certainty of evidence that GTN was significantly more likely to cause headache than placebo (RR = 2.73 (1.82-4.10) I2 = 58%) and diltiazem RR = 6.88 (2.19-21.63) I2 = 17%.
CONCLUSION
There is low certainty evidence topical nitrates are an effective treatment for anal fissure healing and pain reduction compared to placebo. Despite widespread use of topical diltiazem, more evidence is required to establish the effectiveness of calcium channel blockers compared to placebo.
Topics: Administration, Topical; Chronic Disease; Diltiazem; Fissure in Ano; Humans; Nitroglycerin; Sphincterotomy; Treatment Outcome; Vasodilator Agents
PubMed: 34608561
DOI: 10.1007/s00384-021-04040-3 -
Radiotherapy and Oncology : Journal of... Jun 2022To conduct a systematic review evaluating the impact of high dose rate (HDR) brachytherapy (BT) on the clinical outcomes and toxicities of patients with anal cancer. (Review)
Review
PURPOSE
To conduct a systematic review evaluating the impact of high dose rate (HDR) brachytherapy (BT) on the clinical outcomes and toxicities of patients with anal cancer.
METHODS AND MATERIALS
A search of Medline, Embase, and Cochrane Library databases was performed using search terms: "anal", "anal canal", "squamous", "adenocarcinoma", "cancer", "neoplasm", in combination with "brachytherapy", "high dose rate brachytherapy" or "HDR brachytherapy". Additional studies were identified after scanning references. Studies published in English with ≥10 patients were included.
RESULTS
Ten studies (n = 448) were included in this review. 321 patients were treated with curative intent external beam radiotherapy (EBRT), chemotherapy (CT) and HDRBT; of those, 312 and 9 received interstitial and intraluminal BT, respectively. Mean follow up was 39.9 months (range (R): 24-61 months). Complete response was noted between 80%-93% and local control ranged between 81%-88%. Mean rate of local failure was 12.3% (SD 3.6%, R: 8%-18%). Distant failure rate was reported between 2%-3% and metastasis free survival ranged between 82%-88%. Mean disease free survival and overall survival were 77.3% (SD 6.6%, R: 66%-100%) and 82.5% (SD 13.7%, R: 70%-87.7%). Acute toxicity was mostly grade 1/2 dermatitis, proctitis or cystitis; G3 or higher toxicity was reported only in 4 patients in 2 studies (dermatitis n = 3 and sphincter necrosis n = 1). Most common long term toxicities were incontinence (2.5%-9%) and proctitis (2.5%-19%); G3/4 toxicity ranged between 2.2%-7.1%. Mean sphincter preservation rate and colostomy free survival was 88.0% and 80.4%, respectively.
CONCLUSION
Pooled analysis in this review suggests excellent response, local control and survival with HDRBT in combination with EBRT and CT, with limited toxicity. Prospective well conducted trials are needed to further establish role of HDRBT management of anal cancer with future focus on development of international consensus on patient selection, dosimetric parameters, treatment sequencing as well as defining uniform outcome and toxicity assessment.
Topics: Anus Neoplasms; Brachytherapy; Dermatitis; Humans; Proctitis; Prospective Studies; Radiotherapy Dosage; Retrospective Studies
PubMed: 35381275
DOI: 10.1016/j.radonc.2022.03.019 -
Journal of Gastroenterology and... Feb 2021Although surveillance colonoscopy is recommended by several guidelines for Crohn's disease (CD), the evidence is insufficient to support the validity of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Although surveillance colonoscopy is recommended by several guidelines for Crohn's disease (CD), the evidence is insufficient to support the validity of this recommendation. Moreover, the efficacy of surveillance colonoscopy for anorectal cancer remains unclear. Therefore, we performed a systematic review of cancer in patients with CD before considering the proper surveillance methods.
METHODS
We conducted a systematic review and meta-analysis examining the incidence of intestinal cancer and a literature review to clarify the characteristic features of cancer in CD. We performed the systematic literature review of studies published up to May 2019.
RESULTS
Overall, 7344 patients were included in eight studies. The standardized incidence ratios (95% confidence intervals) of colorectal cancer (CRC) and small bowel cancer (SBC) were 2.08 (1.43-3.02) and 22.01 (9.10-53.25), respectively. The prevalence of CRC and SBC was 57/7344 (0.77%) and 17/7344 (0.23%), respectively, during a median follow-up of 12.55 years. Additionally, 54 studies reporting 208 anorectal cancer cases were identified. In patients with anorectal cancer, the prognosis for survival was 2.1 ± 2.3 years, and advanced cancer greater than stage T3 occurred in 46/74 patients (62.1%). Many more reports of anorectal cancer were published in Asia than in Western countries.
CONCLUSION
Although we were unable to state a recommendation for surveillance for SBC, we should perform cancer surveillance for CRC in patients with CD. However, the characteristics of cancer may differ according to geography or race. We must establish proper and effective surveillance methods that are independently suitable to detect these differences.
Topics: Anus Neoplasms; Chronic Disease Indicators; Colonoscopy; Colorectal Neoplasms; Crohn Disease; Escherichia coli Proteins; Exodeoxyribonucleases; Follow-Up Studies; Humans; Intestine, Small; Neoplasm Staging; Rectal Neoplasms; Survival Rate; Time Factors
PubMed: 32865278
DOI: 10.1111/jgh.15229 -
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 -
Clinical Gastroenterology and... Jun 2024Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and... (Review)
Review
BACKGROUND AND AIMS
Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.
METHODS
We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach.
RESULTS
Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on six structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with longstanding (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus(SCCA) and anorectal carcinoma. Risk factors for SCCA, notably human papilloma virus (HPV), should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an exam under anesthesia (EUA) with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers.
CONCLUSION
Inflammatory bowel disease (IBD) clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.
PubMed: 38871152
DOI: 10.1016/j.cgh.2024.05.029 -
Journal of Crohn's & Colitis Apr 2023The aim of this systematic review was to assess the literature on the incidence and risk factors for colorectal cancer and anal cancer in patients with perianal Crohn's... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The aim of this systematic review was to assess the literature on the incidence and risk factors for colorectal cancer and anal cancer in patients with perianal Crohn's disease.
METHOD
A systematic review of the literature was performed using PubMed, Embase and Google Scholar. A meta-analysis was then conducted using a random-effects model.
RESULTS
Five studies were included in the systematic review. Of the total patients, 26.5% had perianal Crohn's disease. The median follow-up was 6 years. In total, 127 cases of colorectal cancer were found [0.43% of the included Crohn's disease patients]. Perianal involvement was present in 50% of colorectal cancer patients [0.89% of the population]. Three of the studies specified the cancer to be rectal or anal, which were present in 68 and 24 cases [0.3% and 0.1% of patients], respectively. In a subgroup analysis of rectal and anal cancer, perianal involvement was most frequent in anal cancer, accounting for 46% of the cases. In the rectal cancer group, 37% had perianal involvement. The higher incidence of colorectal cancer in patients with perianal Crohn's disease was confirmed in a meta-analysis.
CONCLUSION
Half of the patients with colorectal cancer and anal cancer were found to have perianal Crohn's disease. In patients with perianal involvement, there was a higher percentage of anal cancer compared with rectal cancer. These results support the theory that patients with perianal Crohn's disease are at increased risk for developing colorectal and anal cancer. Studies collecting more detailed data regarding patients and their cancers are needed to further specify the disease course.
Topics: Humans; Crohn Disease; Anus Neoplasms; Rectal Neoplasms; Rectum; Anal Canal; Rectal Fistula
PubMed: 36130090
DOI: 10.1093/ecco-jcc/jjac143 -
International Journal of Molecular... Dec 2022Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the... (Review)
Review
Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus and has a significant clinical and economic impact. Although oral and intestinal mucositis can occur concurrently in the same individual, these conditions are often studied independently using organ-specific models that do not mimic human disease. Hence, the purpose of this scoping review was to provide a comprehensive yet systematic overview of the animal models that are utilised in the study of chemotherapy-induced mucositis. A search of PubMed/MEDLINE and Scopus databases was conducted to identify all relevant studies. Multiple phases of filtering were conducted, including deduplication, title/abstract screening, full-text screening, and data extraction. Studies were reported according to the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. An inter-rater reliability test was conducted using Cohen's Kappa score. After title, abstract, and full-text screening, 251 articles met the inclusion criteria. Seven articles investigated both chemotherapy-induced intestinal and oral mucositis, 198 articles investigated chemotherapy-induced intestinal mucositis, and 46 studies investigated chemotherapy-induced oral mucositis. Among a total of 205 articles on chemotherapy-induced intestinal mucositis, 103 utilised 5-fluorouracil, 34 irinotecan, 16 platinum-based drugs, 33 methotrexate, and 32 other chemotherapeutic agents. Thirteen articles reported the use of a combination of 5-fluorouracil, irinotecan, platinum-based drugs, or methotrexate to induce intestinal mucositis. Among a total of 53 articles on chemotherapy-induced oral mucositis, 50 utilised 5-fluorouracil, 2 irinotecan, 2 methotrexate, 1 topotecan and 1 with other chemotherapeutic drugs. Three articles used a combination of these drugs to induce oral mucositis. Various animal models such as mice, rats, hamsters, piglets, rabbits, and zebrafish were used. The chemotherapeutic agents were introduced at various dosages via three routes of administration. Animals were mainly mice and rats. Unlike intestinal mucositis, most oral mucositis models combined mechanical or chemical irritation with chemotherapy. In conclusion, this extensive assessment of the literature revealed that there was a large variation among studies that reproduce oral and intestinal mucositis in animals. To assist with the design of a suitable preclinical model of chemotherapy-induced alimentary tract mucositis, animal types, routes of administration, dosages, and types of drugs were reported in this study. Further research is required to define an optimal protocol that improves the translatability of findings to humans.
Topics: Animals; Rats; Mice; Humans; Rabbits; Swine; Zebrafish; Reproducibility of Results; Mucositis; Irinotecan; Fluorouracil; Antineoplastic Agents; Stomatitis; Methotrexate
PubMed: 36499758
DOI: 10.3390/ijms232315434