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Clinical Oncology (Royal College of... Aug 2014Squamous cell cancer of the anal canal is a rare tumour for which there remains uncertainty regarding optimal therapy. A systematic review was conducted to summarise the... (Review)
Review
Squamous cell cancer of the anal canal is a rare tumour for which there remains uncertainty regarding optimal therapy. A systematic review was conducted to summarise the evidence examining concurrent chemotherapy and radiotherapy or different chemotherapy regimens in combination with radiotherapy. MEDLINE, EMBASE and conference proceedings were searched for relevant randomised controlled trials. Outcomes of interest were colostomy rate, local failure, overall survival, disease-free survival, adverse effects and quality of life. Six randomised controlled trials were identified. Two trials reported lower colostomy and local failure rates for concurrent 5-fluorouracil (5-FU) plus mitomycin C (MMC) and radiotherapy compared with radiotherapy alone. The omission of MMC from this regimen resulted in higher colostomy and local failure rates and lower disease-free survival. Induction chemotherapy followed by concurrent 5-FU plus cisplatin and radiotherapy resulted in a higher colostomy rate than concurrent 5-FU plus MMC and radiotherapy. Haematological toxicity rates were lower in patients who received radiotherapy with 5-FU alone or 5-FU plus cisplatin compared with 5-FU plus MMC. No benefit was seen for the addition of induction or maintenance chemotherapy to concurrent chemoradiotherapy. The available evidence continues to support the use of radiotherapy with concurrent 5-FU and MMC as standard treatment for cancer of the anal canal to decrease colostomy and local failure rates.
Topics: Anus Neoplasms; Chemoradiotherapy; Humans; Neoplasms, Squamous Cell
PubMed: 24721444
DOI: 10.1016/j.clon.2014.03.005 -
The Cochrane Database of Systematic... Dec 2011Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily affects the genital area and around the anus, where it causes persistent itching and soreness. Scarring after inflammation may lead to severe damage by fusion of the vulval lips (labia); narrowing of the vaginal opening; and burying of the clitoris in women and girls, as well as tightening of the foreskin in men and boys, if treatments are not started early. Affected people have an increased risk of genital cancers.
OBJECTIVES
To assess the effects of topical interventions for genital lichen sclerosus and adverse effects reported in included trials.
SEARCH METHODS
We searched the following databases up to 16 September 2011: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (from 1982), CINAHL (from 1981), British Nursing Index and Archive (from 1985), Science Citation Index Expanded (from 1945), BIOSIS Previews (from 1926), Conference Papers Index (from 1982), and Conference Proceedings Citation Index - Science (from 1990). We also searched ongoing trial registries and scanned the bibliographies of included studies, published reviews, and papers that had cited the included studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of topical interventions in genital lichen sclerosus.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion.
MAIN RESULTS
We included 7 RCTs, with a total of 249 participants, covering 6 treatments. Six of these RCTs tested the efficacy of one active intervention against placebo or another active intervention, while the other trial tested three active interventions against placebo.When compared to placebo in one trial, clobetasol propionate 0.05% was effective in treating genital lichen sclerosus in relation to the following outcomes: 'participant-rated improvement or remission of symptoms' (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.45 to 5.61) and 'investigator-rated global degree of improvement' (standardised mean difference (SMD) 5.74, 95% CI 4.26 to 7.23).When mometasone furoate 0.05% was compared to placebo in another trial, there was a significant improvement in the 'investigator-rated change in clinical grade of phimosis' (SMD -1.04, 95% CI -1.77 to -0.31).Both trials found no significant differences in reported adverse drug reactions between the corticosteroid and placebo groups. The data from four trials found no significant benefit for topical testosterone, dihydrotestosterone, and progesterone. When used as maintenance therapy after an initial treatment with topical clobetasol propionate in another trial, topical testosterone worsened the symptoms (P < 0.05), but the placebo did not.One trial found no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (itching) (SMD -0.33, 95% CI -0.99 to 0.33) and burning/pain (SMD 0.03, 95% CI -0.62 to 0.69). However, pimecrolimus was less effective than clobetasol propionate with regard to the 'investigator-rated global degree of improvement' (SMD -1.64, 95% CI -2.40 to -0.87). This trial found no significant differences in reported adverse drug reactions between the pimecrolimus and placebo groups.
AUTHORS' CONCLUSIONS
The current limited evidence demonstrates the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital lichen sclerosus. Further RCTs are needed to determine the optimal potency and regimen of topical corticosteroids, examine other topical interventions, assess the duration of remission or prevention of flares, evaluate the reduction in the risk of genital squamous cell carcinoma or genital intraepithelial neoplasia, and examine the efficacy in improving the quality of the sex lives of people with this condition.
Topics: Adult; Anti-Inflammatory Agents; Child; Clobetasol; Dermatologic Agents; Dihydrotestosterone; Female; Genital Diseases, Male; Humans; Lichen Sclerosus et Atrophicus; Male; Mometasone Furoate; Pregnadienediols; Randomized Controlled Trials as Topic; Tacrolimus; Testosterone Propionate; Vulvar Lichen Sclerosus
PubMed: 22161424
DOI: 10.1002/14651858.CD008240.pub2 -
Journal of the American Academy of... Sep 2017Cryotherapy is one of the most commonly used therapeutic modalities to treat anogenital warts (AGWs), but this treatment was not clearly established in the recent... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Cryotherapy is one of the most commonly used therapeutic modalities to treat anogenital warts (AGWs), but this treatment was not clearly established in the recent international recommendations.
OBJECTIVE
To compare the efficacy and safety of cryotherapy versus other AGW treatments.
METHODS
Through a systematic search of 12 electronic databases, we identified 11 randomized controlled trials, screened from database inception through October 2016, that met the inclusion criteria (including immunocompetent adults with AGWs receiving cryotherapy in 1 of the comparison groups). Primary endpoint was complete clearance of AGW. Risk-for-bias assessment was based on Cochrane Handbook recommendations. Meta-analyses used Review Manager v5.3 software.
RESULTS
Cryotherapy efficacy did not appear to differ from that of trichloroacetic acid, podophyllin, or imiquimod. Electrosurgery was weakly associated with better AGW clearance than cryotherapy (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.65-0.99). Cryotherapy was associated with more immediate low-level adverse events (erythema, stinging, or irritation; RR 3.02, 95% CI 1.38-6.61) and immediate pain requiring oral analgesics (RR 2.11, 95% CI 1.07-4.17) but fewer erosions (RR 0.57, 95% CI 0.36-0.90).
LIMITATIONS
All but 1 randomized-controlled trial had a high risk for bias.
CONCLUSION
With low-level quality of the evidence, cryotherapy is an acceptable first-line therapy to treat AGWs.
Topics: Anus Diseases; Condylomata Acuminata; Cryotherapy; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Male; Randomized Controlled Trials as Topic
PubMed: 28651824
DOI: 10.1016/j.jaad.2017.04.012 -
International Journal of Surgery... Aug 2022There are no consensus guidelines on the optimal dose or injection site of botulinum toxin (BT) for chronic anal fissure (CAF). The objective of this study was to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are no consensus guidelines on the optimal dose or injection site of botulinum toxin (BT) for chronic anal fissure (CAF). The objective of this study was to determine the appropriate dose and injection site of BT for CAF by comparing healing rate and adverse effects (incontinence and recurrence).
METHODS
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus were searched from inception through May 31, 2021. Randomized controlled trials evaluating healing and adverse effects of BT injection for CAF published in any language were selected. Multiple treatment comparisons and ranking were performed using a two-stage network meta-analysis, and results were graded by Confidence in Network Meta-Analysis tool.
RESULTS
Twenty-seven trials involving 1880 patients were included. The results demonstrated that high-dose-BT had significantly higher short-term healing when injected out of the fissure (OF) site than each side of the fissure (SF) site, with a risk ratio (RR) of 2.12 (1.08, 4.15); low-dose-BT did not show any difference across OF and SF site with RR of 1.20 (0.85, 1.68). High-dose-BT at the OF site showed similar healing to low-dose-BT at the same site (RR of 1.02 (0.79, 1.31)) but with a higher risk of incontinence with RR of 3.54 (0.85, 14.76). In contrast, high-dose-BT at the SF site showed lower healing compared to low-dose-BT at the same site with RR of 0.57 (0.29, 1.14). Both high-dose-BT and low-dose-BT at the OF site had higher recurrence than high-dose-BT or low-dose-BT at the SF site with RR of 2.08 (0.33, 13.11) and 1.89 (0.60, 5.94), respectively.
CONCLUSIONS
Given moderate level of evidence, low-dose BT is optimal; injection out of the fissure site improves short-term outcomes while injection each side of the fissure site tends to reduce recurrence in the longer term.
Topics: Anal Canal; Botulinum Toxins, Type A; Chronic Disease; Fissure in Ano; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35934283
DOI: 10.1016/j.ijsu.2022.106798 -
BMC Infectious Diseases Jun 2016Human papillomavirus (HPV) vaccines were designed to prevent cervical cancer in women and their provision remains a major public health need. However, HPV is also a... (Review)
Review
BACKGROUND
Human papillomavirus (HPV) vaccines were designed to prevent cervical cancer in women and their provision remains a major public health need. However, HPV is also a major cause of non-cervical anogenital and oropharyngeal cancers and the potential benefit of vaccination likely extends beyond cervical cancer.
METHODS
A systematic literature search of PubMed (1995-2014) identified publications assessing the incidence, persistence, and clearance of non-cervical anogenital/oral HPV infections. Comparability with cervical HPV was assessed by identifying articles assessing the same or similar populations.
RESULTS
Available data suggest high incidence rates of non-cervical HPV infection in men and women, with HPV-16 predominating in all sites. The incidence of high risk HPV per 100 person-years ranged from 11.4 to 72.9 for penile infections, 6.7-47.9 at other male genital sites, and 4.4-36.7 and 5.3-23.4 for anal infections in men and women, respectively. The incidence per 100 person-years of oral infection with any HPV type ranged from 5.7 to 6.7 in men and 6.8-39.6 in women. Within the limitations of the data, there was a general pattern of higher incidence and clearance of non-cervical genital HPV infections, compared to cervical infections. HIV status, circumcision, number of sex partners and partner HPV status significantly influenced high-risk HPV incidence/clearance at male anogenital sites. Few studies assessed risk factors for oral HPV.
CONCLUSIONS
Parallels appear to exist between the epidemiology of cervical and non-cervical HPV infections in terms of incidence, HPV-type distribution, and risk factors for infection. Available data suggest that non-cervical genital HPV infections may occur more frequently, with higher clearance rates, than cervical infections. More extensive studies could provide useful information for estimating vaccine impact, the wider cost-benefit of HPV vaccination, and guiding vaccination policy.
TRIAL REGISTRATION
Not applicable, as systematic review of the literature.
Topics: Anus Diseases; Female; Genital Diseases, Male; Human papillomavirus 16; Humans; Incidence; Male; Mouth Diseases; Papillomavirus Infections; Papillomavirus Vaccines; Sexual Partners; Sexually Transmitted Diseases; Vaginal Diseases
PubMed: 27301867
DOI: 10.1186/s12879-016-1633-9 -
Alimentary Pharmacology & Therapeutics Oct 2015Temporary faecal diversion is sometimes used for management of refractory perianal Crohn's disease (CD) with variable success. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Temporary faecal diversion is sometimes used for management of refractory perianal Crohn's disease (CD) with variable success.
AIMS
To perform a systematic review with meta-analysis to evaluate the effectiveness, long-term outcomes and factors associated with success of temporary faecal diversion for perianal CD.
METHODS
Through a systematic literature review through 15 July 2015, we identified 16 cohort studies (556 patients) reporting outcomes after temporary faecal diversion. We estimated pooled rates [with 95% confidence interval (CI)] of early clinical response, attempted and successful restoration of bowel continuity after temporary faecal diversion (without symptomatic relapse), and rates of re-diversion (in patients with attempted restoration) and proctectomy (with or without colectomy and end-ileostomy). We identified factors associated with successful restoration of bowel continuity.
RESULTS
On meta-analysis, 63.8% (95% CI: 54.1-72.5) of patients had early clinical response after faecal diversion for refractory perianal CD. Restoration of bowel continuity was attempted in 34.5% (95% CI: 27.0-42.8) of patients, and was successful in only 16.6% (95% CI: 11.8-22.9). Of those in whom restoration was attempted, 26.5% (95% CI: 14.1-44.2) required re-diversion because of severe relapse. Overall, 41.6% (95% CI: 32.6-51.2) of patients required proctectomy after failure of temporary faecal diversion. There was no difference in the successful restoration of bowel continuity after temporary faecal diversion in the pre-biological or biological era (13.7% vs. 17.6%, P = 0.60), in part due to selection bias. Absence of rectal involvement was the most consistent factor associated with restoration of bowel continuity.
CONCLUSIONS
Temporary faecal diversion may improve symptoms in approximately two-thirds of patients with refractory perianal Crohn's disease, but bowel restoration is successful in only 17% of patients.
Topics: Anus Diseases; Colectomy; Crohn Disease; Feces; Humans; Ileostomy; Proctocolectomy, Restorative; Recurrence
PubMed: 26264359
DOI: 10.1111/apt.13356 -
Langenbeck's Archives of Surgery Mar 2017The incidence of anal abscess and fistula is relatively high, and the condition is most common in young men. (Review)
Review
BACKGROUND
The incidence of anal abscess and fistula is relatively high, and the condition is most common in young men.
METHODS
This is a revised version of the German S3 guidelines first published in 2011. It is based on a systematic review of pertinent literature.
RESULTS
Cryptoglandular abscesses and fistulas usually originate in the proctodeal glands of the intersphincteric space. Classification depends on their relation to the anal sphincter. Patient history and clinical examination are diagnostically sufficient in order to establish the indication for surgery. Further examinations (endosonography, MRI) should be considered in complex abscesses or fistulas. The goal of surgery for an abscess is thorough drainage of the focus of infection while preserving the sphincter muscles. The risk of abscess recurrence or secondary fistula formation is low overall. However, they may result from insufficient drainage. Primary fistulotomy should only be performed in case of superficial fistulas. Moreover, it should be done by experienced surgeons. In case of unclear findings or high fistulas, repair should take place in a second procedure. Anal fistulas can be treated only by surgical intervention with one of the following operations: laying open, seton drainage, plastic surgical reconstruction with suturing of the sphincter (flap, sphincter repair, LIFT), and occlusion with biomaterials. Only superficial fistulas should be laid open. The risk of postoperative incontinence is directly related to the thickness of the sphincter muscle that is divided. All high anal fistulas should be treated with a sphincter-saving procedure. The various plastic surgical reconstructive procedures all yield roughly the same results. Occlusion with biomaterial results in lower cure rate.
CONCLUSION
In this revision of the German S3 guidelines, instructions for diagnosis and treatment of anal abscess and fistula are described based on a review of current literature.
Topics: Abscess; Anus Diseases; Germany; Humans; Practice Guidelines as Topic; Rectal Fistula
PubMed: 28251361
DOI: 10.1007/s00423-017-1563-z -
Clinical Infectious Diseases : An... Jul 2006Individuals with human immunodeficiency virus (HIV) infection are at increased risk for human papillomavirus-related squamous cell cancer of the anus. Screening... (Review)
Review
Individuals with human immunodeficiency virus (HIV) infection are at increased risk for human papillomavirus-related squamous cell cancer of the anus. Screening HIV-infected patients for squamous cell cancer of the anus and human papillomavirus-related anal dysplasia may prevent excess morbidity and mortality. We have conducted a systematic review of the indirect evidence in the literature regarding the utility of anal Papanicolau (Pap) smear screening of HIV-infected individuals in the highly active antiretroviral therapy era. Although there are no published studies evaluating the efficacy of anal Pap smear screening for preventing squamous cell cancer of the anus or anal intraepithelial neoplasia, we reviewed data regarding the burden of disease, anal Pap smear sensitivity and specificity, the prevalence of anal dysplasia, and 1 cost effectiveness study. The available evidence demonstrates that HIV-infected individuals have an increased risk for squamous cell cancer of the anus and anal intraepithelial neoplasia. This review identifies important areas for further study before routine anal Pap smear screening can be recommended.
Topics: Antiretroviral Therapy, Highly Active; Anus Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; HIV Infections; Humans; Male; Mass Screening; Papanicolaou Test; Papillomaviridae; Papillomavirus Infections; Precancerous Conditions; Vaginal Smears
PubMed: 16779751
DOI: 10.1086/505219 -
International Journal of Colorectal... Sep 2020In most cases, squamous cell carcinoma of the anus (SCCA) is treated with chemo-radiotherapy preserving sphincter function and offering good long-term survival and low... (Review)
Review
PURPOSE
In most cases, squamous cell carcinoma of the anus (SCCA) is treated with chemo-radiotherapy preserving sphincter function and offering good long-term survival and low recurrence rates. However, chemo-radiotherapy has several side effects: dyspareunia, impotence, fecal incontinence, pain, and skin symptoms. Small/T1 tumors, without metastatic disease, can be treated with local excision alone. We aimed to systematically review the literature regarding outcome following local excision of T1 SCCA.
METHODS
PubMed and Embase databases were searched for studies that investigated outcome following local excision of SCCA.
RESULTS
Twenty-three studies were included. Twenty of the studies were retrospective, and three studies included more than 100 patients. Most of the studies were published before the 1980s. Overall there was great heterogeneity and missing data across the included studies when comparing patient demographics, resection margins, definitions on tumor location, and outcome. Overall 5-year survival was 69% (95% CI 66-72) following local excision. Overall 5-year recurrence was 37% (95% CI 30-45) following local excision. No complications were reported following local excision.
CONCLUSION
The current literature on outcome following local excision of T1 anal cancers consists predominantly of smaller, retrospective, and heterogenous studies. Overall 5-year survival is acceptable, but worse than following chemo-radiation therapy. However, local excision seems to have no or only few minor complications. Recurrence rates are high. Therefore, a thorough follow-up program is needed when performing local excision as primary treatment for T1 SCCA. There is an evident need for further studies.
Topics: Anal Canal; Anus Neoplasms; Digestive System Surgical Procedures; Female; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 32671458
DOI: 10.1007/s00384-020-03687-8 -
The Cochrane Database of Systematic... Oct 2006Because of the disability associated with surgery for anal fissure and the risk of incontinence, medical alternatives for surgery have been sought. Most recently,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Because of the disability associated with surgery for anal fissure and the risk of incontinence, medical alternatives for surgery have been sought. Most recently, pharmacologic methods that relax the anal smooth muscle, to accomplish reversibly what occurs in surgery, have been used to obtain fissure healing.
OBJECTIVES
To assess the efficacy and morbidity of various medical therapies for anal fissure.
SEARCH STRATEGY
Search terms include "anal fissure randomized". Timing from 1966 to May 2006. Further details of the search below.
SELECTION CRITERIA
Studies in which participants were randomized to a non-surgical therapy for anal fissure. Comparison groups may include an operative procedure, an alternate medical therapy or placebo. Chronic fissure, acute fissure and fissure in children are included in the review. Atypical fissures associated with inflammatory bowel disease or cancer or anal infection are excluded.
DATA COLLECTION AND ANALYSIS
Data were abstracted from published reports and meeting abstracts, assessing method of randomization, blinding, "intention to treat" and drop-outs, therapies, supportive measures (applied to both groups), dosing and frequency and cross-overs. Dichotomous outcome measures included Non-healing of the fissure (a combination of persistence and recurrence), and Adverse events (including incontinence, headache, infection, anaphylaxis). Continuous outcome measures included measures of pain relief and anorectal manometry.
MAIN RESULTS
48 different comparisons of the ability of medical therapies to heal anal fissure have been reported in 53 RCTs. Eleven agents were used (nitroglycerin ointment (GTN), isosorbide dinitrate, Botulinum toxin (Botox), diltiazem, nifedipine (Calcium channel blockers or CCBs), hydrocortisone, lignocaine, bran, minoxidil, indoramin, and placebo) as well as anal dilators and surgical sphincterotomy.GTN was found to be marginally but significantly better than placebo in healing anal fissure (48.6% vs. 37%, p < 0.004), but late recurrence of fissure was common, in the range of 50% of those initially cured. Botox and CCBs were equivalent to GTN in efficacy with fewer adverse events. No medical therapy came close to the efficacy of surgical sphincterotomy, though none in these RCTs was associated with the risk of incontinence.
AUTHORS' CONCLUSIONS
Medical therapy for chronic anal fissure, acute fissure and fissure in children may be applied with a chance of cure that is marginally better than placebo, and, for chronic fissure in adults, far less effective than surgery.
Topics: Fissure in Ano; Humans; Randomized Controlled Trials as Topic
PubMed: 17054170
DOI: 10.1002/14651858.CD003431.pub2