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International Journal of Colorectal... Jan 2012The main purpose of this study was to investigate the efficacy and safety of botulinum toxin in the treatment of anal fissure. An answer was attempted to the following... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The main purpose of this study was to investigate the efficacy and safety of botulinum toxin in the treatment of anal fissure. An answer was attempted to the following research questions: (i) what is the efficacy of botulinum toxin in healing of anal fissure compared to placebo, (ii) what is the efficacy of botulinum toxin in healing of anal fissure compared to other means of chemical sphincterotomy, (iii) what is the efficacy of botulinum toxin in healing of anal fissure compared to surgical sphincterotomy, (iv) what is the short term safety of botulinum toxin injections and (v) what is the long term safety of botulinum toxin injections.
METHODS
Clinical trials investigating the effect of botulinum toxin in the treatment of anal fissure met inclusion criteria. Case reports and case series were also included for the estimation of safety. Meta-analysis was not performed due to clinical heterogeneity.
RESULTS
The comparator could be placebo, nitroglycerin ointment, or lateral internal sphincterotomy, with dosage ranging from 20 IU to 50 IU of botulinum toxin. Fissure healing was the most commonly reported primary endpoint but the time period from botulinum toxin injection to fissure healing ranged from 2 weeks to 4 months. Accordingly, outcome data were also heterogenous.
CONCLUSIONS
Botulinum toxin injections should be considered a minimally invasive therapeutic option for the treatment of chronic anal fissure. However, well designed randomized trials are needed for the valid estimation of the efficacy and safety of botulinum toxin in this therapeutic indication.
Topics: Botulinum Toxins; Dose-Response Relationship, Drug; Fissure in Ano; Humans; Lidocaine; Nitrates; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome; Wound Healing
PubMed: 21822595
DOI: 10.1007/s00384-011-1286-5 -
The Lancet. Infectious Diseases Feb 2018Data on carcinogenicity of human papillomavirus (HPV) types in the anus are needed to inform anal cancer prevention through vaccination and screening. This is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Data on carcinogenicity of human papillomavirus (HPV) types in the anus are needed to inform anal cancer prevention through vaccination and screening. This is particularly the case for people infected with HIV, who are at an increased risk of anal cancer.
METHODS
We did a systematic review of studies published from January, 1986, to July, 2017, in MEDLINE, Embase, and the Cochrane Library on anal HPV infection, without any language restrictions. Eligible studies reported type-specific HPV prevalence by strata of cytopathological or histopathological anal diagnosis, sex, and HIV status. Data requests were made to authors when necessary. We did a meta-analysis of type-specific HPV prevalence across the full spectrum of anal diagnoses, from normal cytology to anal cancer. We assessed the main outcome of type-specific HPV prevalence ratios [PR], calculated across strata of anal diagnoses, gender, or HIV status, by use of generalised linear models.
FINDINGS
95 studies were identified from the search, published between 1992-2017, from which 18 646 individuals fulfilled the criteria for inclusion in the analyses: 8534 people with normal cytology, 5730 with low-grade lesions, 2024 with high-grade lesions, and 2358 with anal cancer. HPV prevalence varied in normal cytology from 42% in HIV-negative women to 76% in HIV-positive men and, for each diagnosis, was higher in individuals who were HIV positive than those who were HIV negative. HPV16 positivity increased with diagnosis severity, being the only HPV type accounting for more HPV infection in anal cancer than normal cytology, both in individuals who were HIV negative (PR 5·0, 95% CI 3·8-6·6, p<0·0001) and those who were HIV positive (2·3, 1·9-2·7, p<0·0001). HPV16 positivity increased even between high-grade lesions and anal cancer, whereas other high-risk HPV types accounted for high proportions of low-grade or high-grade lesions but their prevalence decreased in anal cancer. However, HPV16 was less frequent in HIV-positive than HIV-negative anal cancer, both in men (PR 0·8, 95% CI 0·7-0·9, p<0·0001) and women (0·8, 0·6-1·0, p=0·063), and in HIV-positive versus HIV-negative high-grade lesions in women (0·6, 0·5-0·9, p=0·0077). Type-specific attribution of the non-HPV16 fraction of HIV-positive anal cancer is hindered by a high prevalence of multiple HPV infections.
INTERPRETATION
HPV16 is by far the most carcinogenic HPV type in the anus, with enrichment of HPV16 even from high-grade lesions to anal cancer, both in individuals who are HIV negative and those who are HIV positive. Nevertheless, the fraction of anal cancer attributable to HPV16 is smaller in the HIV-positive population.
FUNDING
International Agency for Research on Cancer.
Topics: Anal Canal; Anus Neoplasms; Female; Genotype; HIV Infections; Humans; Male; Papillomaviridae; Papillomavirus Infections; Prevalence
PubMed: 29158102
DOI: 10.1016/S1473-3099(17)30653-9 -
The Journal of Infectious Diseases Nov 2023We sought to summarize human papillomavirus (HPV) vaccine efficacy/effectiveness (VE) against anal HPV infection and anal intraepithelial neoplasia (AIN). (Meta-Analysis)
Meta-Analysis
Impact of Human Papillomavirus Vaccine Against Anal Human Papillomavirus Infection, Anal Intraepithelial Neoplasia, and Recurrence of Anal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.
BACKGROUND
We sought to summarize human papillomavirus (HPV) vaccine efficacy/effectiveness (VE) against anal HPV infection and anal intraepithelial neoplasia (AIN).
METHODS
We performed literature review and meta-analysis to estimate VE, stratified by age and analytic population (per-protocol efficacy [PPE] or intention-to-treat [ITT] population in clinical trials, or all participants in real-world studies).
RESULTS
We identified 6 clinical trials and 8 real-world studies. In participants vaccinated at age ≤26 years (mainly human immunodeficiency virus [HIV]-negative individuals), significant VE against incident/prevalent anal HPV infection was reported in clinical trials, with a higher estimate in PPE (2 studies with 2390 participants; VE, 84% [95% confidence interval (CI), 77%-90%]; I2 = 0%) than ITT (2 studies with 4885 participants; 55%, 39%-67%; I2 = 46%) populations or in real-world studies (4 studies with 2375 participants; 77%, 40%-91%; I2 = 81%). HPV vaccination at age ≤26 years was associated with significant VE in preventing persistent anal HPV infection and AIN. No significant VE against anal HPV infection or AIN was found in persons vaccinated at age >26 years (mainly people living with HIV).
CONCLUSIONS
There is strong evidence for high VE against anal HPV infection and AIN in HIV-negative individuals vaccinated at age ≤26 years. However, the lower impact in ITT than in PPE populations and the lack of significant effect in people living with HIV aged >26 years indicates that vaccines have the higher impact in populations with less sexual exposure to anal HPV.
Topics: Humans; Adult; Papillomavirus Vaccines; Papillomavirus Infections; Human Papillomavirus Viruses; Anus Neoplasms; Carcinoma in Situ; HIV Infections; Papillomaviridae
PubMed: 37257044
DOI: 10.1093/infdis/jiad183 -
Alimentary Pharmacology & Therapeutics Mar 2006Gastrointestinal dysmotility in systemic sclerosis (scleroderma) is prevalent in 90% of patients, increasing morbidity and in some cases mortality. The resultant... (Review)
Review
Gastrointestinal dysmotility in systemic sclerosis (scleroderma) is prevalent in 90% of patients, increasing morbidity and in some cases mortality. The resultant gastrointestinal complications are usually extensive, involving many regions of the gut from the oesophagus to the anus. Collagen replacement of vascular and enteric smooth muscle results in hypomotility, lumen dilatation, tensile rigidity and eventual loss of organ functions. The aim of this paper is to provide an overview of systemic sclerosis-related gastrointestinal dysmotility and available/potential therapeutic options. We evaluated published data on the pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis patients using the MEDLINE database for English and non-English articles from 1966 to July 2005. Based on this systematic review, lifestyle and medical therapy approaches are preferred as they often improve and/or ameliorate symptoms. Surgery is only recommended with serious, rare complications such as bowel perforation or ischaemia. Alternative therapies such as acupuncture-based therapies are well tolerated, with clinical improvement and may be of potential therapeutic benefit for systemic sclerosis gastrointestinal dysmotility. Further elucidation of initiating and persistent mechanisms of systemic sclerosis-related gastrointestinal dysmotility will optimize the development of a multidisciplinary and more directed treatment regimen.
Topics: Colon; Esophageal Diseases; Esophagus; Gastric Emptying; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Intestinal Diseases; Intestine, Small; Life Style; Proton Pump Inhibitors; Scleroderma, Systemic; Stomach; Stomach Diseases
PubMed: 16556171
DOI: 10.1111/j.1365-2036.2006.02804.x -
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 -
Journal of Gastrointestinal and Liver... Sep 2013The pathological condition of inguinal lymph nodes is an independent prognostic factor in predicting tumor recurrence and overall survival in anal canal cancer. Sentinel... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
The pathological condition of inguinal lymph nodes is an independent prognostic factor in predicting tumor recurrence and overall survival in anal canal cancer. Sentinel node mapping is a non-invasive method for the detection of inguinal lymph node involvement in anal cancer. In the current study, we conducted a comprehensive search of literature in this regard and then interpreted the final results in a systematic review and meta-analysis format.
METHODS
Medline, SCOPUS, and ISI Web of Knowledge were searched with the following search terms: (anal OR anus) AND sentinel. Outcomes of interest were inguinal detection rate and inguinal recurrence in patients receiving inguinal sparing radiotherapy due to pathologically negative inguinal sentinel nodes (false negative cases).
RESULTS
Overall 16 studies (323 patients) were included in the meta-analysis. Pooled inguinal detection rate was 86.2%: 73.4-93.4%: for studies using both blue dye and radiotracer it was 90.1% [78.7-95.8] and for studies using radiotracer alone it was 72.4% [46.3-88.9]. Pooled sensitivity was 90% [79-97%].
CONCLUSIONS
Sentinel node biopsy is a promising method for inguinal lymph node staging in anal cancer. Combined blue dye and radiotracer technique can maximize the inguinal detection rate. Location of the tumor is highly associated with the detection of inguinal sentinel nodes. Despite fairly high pooled sensitivity, no definite conclusion can be made regarding false negative rate of this technique due to low sample size and sub-optimal quality of the included studies. Large multicenter studies with long and consistent follow up are needed to definitely validate this technique in the future.
Topics: Anus Neoplasms; Coloring Agents; Dye Dilution Technique; Humans; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Predictive Value of Tests; Sentinel Lymph Node Biopsy
PubMed: 24078990
DOI: No ID Found -
Radiation Oncology (London, England) Jan 2014Anal canal carcinoma is a rare gastro-intestinal cancer. Radiochemotherapy is the recommended primary treatment for patients with non-metastatic carcinoma; surgery is... (Review)
Review
Anal canal carcinoma is a rare gastro-intestinal cancer. Radiochemotherapy is the recommended primary treatment for patients with non-metastatic carcinoma; surgery is generally reserved for persistent or recurrent disease. Follow-up and surveillance after primary treatment is paramount to classify patients in those with complete remission, persistent or progressive disease. Locally persistent disease represents a clinically significant problem and its management remains subject of some controversy.The aim of this systematic review is to summarise recommendations for the primary treatment of anal canal carcinoma, to focus on the optimal time to consider residual disease as genuine persistence to proceed with salvage treatment, and to discern how this analysis might inform future clinical trials in management in this class of patients.
Topics: Anus Neoplasms; Combined Modality Therapy; Humans; Neoplasm Recurrence, Local; Neoplasm, Residual; Practice Guidelines as Topic; Radiotherapy; Salvage Therapy; Treatment Failure
PubMed: 24472223
DOI: 10.1186/1748-717X-9-39 -
Annals of Surgical Oncology Oct 2015The aim of this systematic review and meta-analysis was to compare the role of FDG-positron emission tomography (PET) or PET/computed tomography (CT) with conventional... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
The aim of this systematic review and meta-analysis was to compare the role of FDG-positron emission tomography (PET) or PET/computed tomography (CT) with conventional imaging in the detection of primary and nodal disease in anal cancer, and to assess the impact of PET or PET/CT on the management of anal cancer.
METHODS
A systematic review of the literature was performed. Eligible studies included those comparing PET or PET/CT with conventional imaging in the staging of histologically confirmed anal squamous cell carcinoma (SCC), or studies that performed PET or PET/CT imaging to assess response following treatment.
RESULTS
Twelve studies met the inclusion criteria. For the detection of primary disease, CT and PET had a sensitivity of 60 % (95 % confidence interval [CI] 45.5-75.2) and 99 % (95 % CI 96-100), respectively. Compared with conventional imaging, PET upstaged 15 % (95 % CI 10-21) and downstaged 15 % (95 % CI 10-20) of nodal disease. This led to a change in nodal staging in 28 % of patients (95 % CI 18-38). When only studies performing contemporary PET/CT were considered, the rate of nodal upstaging was 21 % (95 % CI 13-30) and the TNM stage was altered in 41 % of patients. Following chemoradiotherapy, 78 % (95 % CI 65-88) of patients had a complete response on PET.
CONCLUSION
Compared with conventional imaging, PET or PET/CT alters the nodal status in a sufficient number of cases to justify its routine use in the staging of patients with anal SCC.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Fluorodeoxyglucose F18; Humans; Lymphatic Metastasis; Multimodal Imaging; Neoplasm Staging; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 25652048
DOI: 10.1245/s10434-015-4391-9 -
European Journal of Cancer (Oxford,... Jan 2014Overexpression of the human papillomavirus (HPV) oncogenes E6 and E7 is necessary for the development of distinct lower genital tract cancers. However, secondary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Overexpression of the human papillomavirus (HPV) oncogenes E6 and E7 is necessary for the development of distinct lower genital tract cancers. However, secondary cellular genomic alterations are mandatory to promote progression of HPV-induced premalignant stages. We aimed at identifying the chromosomal regions most frequently gained and lost and the disease stage at which the latter occurs. These regions might be relevant for carcinogenesis and could serve as diagnostic markers to identify premalignant lesions with high progression risk towards invasive cancer.
METHODS
We performed a systematic literature review and meta-analysis of studies listed in PubMed that analysed chromosomal copy number alterations by comparative genomic hybridisation (CGH) in HPV-positive and -negative cancers or premalignant lesions of the anogenital tract (cervix, anus, vagina, penis and vulva).
FINDINGS
Data were extracted and analysed from 32 studies. The most common alterations in cervical squamous cell carcinoma (SCC) (12 studies, 293 samples) were gains at 3q with a rate of 0.55 (95% confidence interval (CI) 0.43-0.70), losses at 3p (0.36, 95%CI 0.27-0.48) and losses at 11q (0.33, 95%CI 0.26-0.43). Gains at 3q were particularly frequent in HPV16-positive cervical SCC (0.84, 95%CI 0.78-0.90). Also more than one quarter of high grade cervical intraepithelial neoplasia (CIN) harboured gains of 3q (0.27, 95%CI 0.20-0.36), but the rate in low grade CIN was low (0.02, 95%CI 0.00-0.09). For HPV-associated vulvar SCC (four studies, 30 samples) the same common alterations as in cervical SCC were reported. Studies on non-cervical and non-vulvar SCC and premalignant lesions of the lower genital tract are scarce.
INTERPRETATION
3q gains were most frequently found in HPV16-positive cervical SCC. The results suggest the selection of HPV-transformed cell clones harbouring 3q gains in high grade premalignant lesions, while alterations in low grade lesions are rare.
Topics: Chromosome Aberrations; Female; Genomic Instability; Humans; Papillomaviridae; Papillomavirus Infections; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 24054023
DOI: 10.1016/j.ejca.2013.08.022 -
International Journal of Surgery... Mar 2023
Meta-Analysis
Botulinum toxin as a promising surgical strategy for chronic anal fissure: do the dose and injection site matter? Comparison of doses and injection sites of botulinum toxin for chronic anal fissure: A systematic review and network meta-analysis of randomized controlled trials.
Topics: Humans; Fissure in Ano; Network Meta-Analysis; Randomized Controlled Trials as Topic; Botulinum Toxins, Type A; Anal Canal; Chronic Disease; Treatment Outcome
PubMed: 36906767
DOI: 10.1097/JS9.0000000000000022