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International Journal of Colorectal... Feb 2021Anal intraepithelial neoplasia (AIN) is the accepted precursor of anal squamous cell carcinoma (ASCC). There has long been a hypothesis that treating AIN may prevent... (Review)
Review
PURPOSE
Anal intraepithelial neoplasia (AIN) is the accepted precursor of anal squamous cell carcinoma (ASCC). There has long been a hypothesis that treating AIN may prevent ASCC. Many different treatment modalities have been suggested and studied. We conducted this systematic review to evaluate their efficacy and the evidence as to whether we can prevent ASCC by treating AIN.
METHODS
MEDLINE and EMBASE were electronically searched using relevant search terms. All studies investigating the use of a single treatment for AIN that reported at least one end outcome such as partial or complete response to treatment, recurrence after treatment and/or ASCC diagnosis after treatment were included.
RESULTS
Thirty studies were included in the systematic review investigating 10 treatment modalities: 5% imiquimod, 5-fluorouracil, cidofovir, trichloroacetic acid, electrocautery, surgical excision, infrared coagulation, radiofrequency ablation, photodynamic therapy and HPV vaccination. All treatment modalities demonstrated some initial regression of AIN after treatment; however, recurrence rates were high especially in HIV-positive patients. Many of the studies suffered from significant bias which prevented direct comparison.
CONCLUSIONS
Although the theory persists that by inducing the regression of AIN, we may be able to reduce the risk of ASCC, there was no clinical evidence within the literature advocating that treating AIN does prevent ASCC.
Topics: Anus Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; HIV Infections; Humans; Imiquimod; Neoplasm Recurrence, Local; Papillomavirus Infections
PubMed: 32979069
DOI: 10.1007/s00384-020-03740-6 -
American Journal of Transplantation :... Dec 2020The number of solid organ transplant recipients (SOTR), and their life expectancy, is increasing, with higher risk for long-term complications from immunosuppression. We... (Meta-Analysis)
Meta-Analysis
The number of solid organ transplant recipients (SOTR), and their life expectancy, is increasing, with higher risk for long-term complications from immunosuppression. We carried out a systematic review describing the burden of anal squamous cell carcinoma (SCC), and its surrogates, in SOTR. We conducted mixed effect model-based meta-analyses evaluating incidence of anal SCC (standardized incidence ratio [SIR] vs general population, and absolute incidence rate [IR]), prevalence of anal squamous abnormalities, and human papillomavirus (HPV) 16. Generalized I statistics were calculated, quantifying heterogeneity. Anal SCC incidence in SOTR was elevated vs the general population (pooled SIR = 6.8, 95% confidence interval [CI], 4.3-10.9; 6 studies including 241 106 SOTR; I = 82.3%), with an absolute IR of 12.3 (95% CI, 10.4-14.7) per 100 000 person-years (5 studies including 1 079 489 person-years; I = 0%). Prevalence of abnormal anal cytology was 12.9% (95% CI, 9.2%-17.7%; 6 studies including 328 SOTR; I = 17.4%). For histology, the pooled prevalence estimate of anal squamous intraepithelial lesions was 22.4% (95% CI, 17.3%-28.5%; 3 studies including 214 SOTR; I = 0%), with 4.7% (95% CI, 2.5%-8.5%; I = 0%) high-grade squamous intraepithelial lesions. Pooled anal HPV16 prevalence was 3.6% (95% CI, 1.6%-7.8%; 4 studies including 254 SOTR; I = 17.6%). There was substantial and consistent evidence of elevated anal SCC incidence in SOTR.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Human papillomavirus 16; Humans; Organ Transplantation; Papillomavirus Infections; Squamous Intraepithelial Lesions
PubMed: 32343489
DOI: 10.1111/ajt.15942 -
Supportive Care in Cancer : Official... Jun 2020Due to increasing numbers of colorectal and anal cancer survivors, more individuals are living with long-term symptoms after treatment. A systematic review was...
Systematic review of clinical practice guidelines for colorectal and anal cancer: the extent of recommendations for managing long-term symptoms and functional impairments.
PURPOSE
Due to increasing numbers of colorectal and anal cancer survivors, more individuals are living with long-term symptoms after treatment. A systematic review was undertaken to assess the extent to which practice guidelines for colorectal and anal cancer provide recommendations for managing long-term symptoms and functioning impairments.
METHODS
Four electronic databases and websites of 30 international cancer societies were searched for clinical practice guidelines, consensus statements, or best practice recommendations for colorectal or anal cancer. Quality of included guidelines was evaluated with the Appraisal of Guidelines for Research & Evaluation II tool. Results were narratively summarized.
RESULTS
We included 51 guidelines or consensus statements. Recommendations for managing long-term symptoms or functioning impairments were reported in 13 guidelines (25.4%). All 13 recommend a healthy lifestyle, diet, body weight, and physical activity. The ASCO Colorectal Cancer Survivorship Care Guideline is the most comprehensive, including interventions targeting sexual and bowel function to pain and cognitive issues, and also highlights limited evidence for informing management strategies. Other guidelines recommend treating incontinence, chronic diarrhea, and distress, and stress the need for greater awareness for sexual dysfunction, survivorship clinics, and referrals to specific supportive care interventions.
CONCLUSIONS
Few clinical practice guidelines include recommendations for managing long-term symptoms and functioning impairments. It is unclear if this is due to limited evidence or absence of management strategies and interventions. Clear recommendations for managing long-term symptoms and functioning to help health professionals in supporting colorectal and anal cancer survivors are needed.
Topics: Anus Neoplasms; Cancer Survivors; Colorectal Neoplasms; Consensus; Databases, Factual; Exercise; Healthy Lifestyle; Humans; Practice Guidelines as Topic
PubMed: 32025805
DOI: 10.1007/s00520-020-05301-7 -
BMJ Open Oct 2019To generate estimates of comparative clinical effectiveness for interventions used in the treatment of anogenital warts (AGWs) through the systematic review, appraisal... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To generate estimates of comparative clinical effectiveness for interventions used in the treatment of anogenital warts (AGWs) through the systematic review, appraisal and synthesis of data from randomised controlled trials (RCTs).
DESIGN
Systematic review and network meta-analysis of RCTs. Search strategies were developed for MEDLINE, Embase, the Cochrane Library and the Web of Science. For electronic databases, searches were run from inception to March 2018. The systematic review was carried out following the general principles recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
PARTICIPANTS
People aged ≥16 years with clinically diagnosed AGWs (irrespective of biopsy confirmation).
INTERVENTIONS
Topical and ablative treatments recommended by the British Association for Sexual Health and HIV for the treatment of AGWs, either as monotherapy or in combination versus each other.
OUTCOME MEASURES
Complete clearance of AGWs at the end of treatment and at other scheduled visits, and rate of recurrence.
RESULTS
Thirty-seven RCTs met inclusion criteria. Twenty studies were assessed as being at unclear risk of bias, with the remaining studies categorised as high risk of bias. Network meta-analysis indicates that, of the treatment options compared, carbon dioxide laser therapy is the most effective treatment for achieving complete clearance of AGWs at the end of treatment. Of patient-applied topical treatments, podophyllotoxin 0.5% solution was found to be the most effective at achieving complete clearance, and was associated with a statistically significant difference compared with imiquimod 5% cream and polyphenon E 10% ointment (p<0.05). Few data were available on recurrence of AGWs after complete clearance. Of the interventions evaluated, surgical excision was the most effective at minimising risk of recurrence.
CONCLUSION
Of the studies assessed, as a collective, the quality of the evidence is low. Few studies are available that evaluate treatment options versus each other.
TRIAL REGISTRATION NUMBER
CRD42013005457.
Topics: Administration, Topical; Antineoplastic Agents; Anus Diseases; Catechin; Caustics; Condylomata Acuminata; Cryosurgery; Electrosurgery; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Imiquimod; Laser Therapy; Male; Network Meta-Analysis; Papillomaviridae; Podophyllotoxin; Treatment Outcome; Trichloroacetic Acid
PubMed: 31676644
DOI: 10.1136/bmjopen-2018-027765 -
World Journal of Gastrointestinal... Aug 2019The anorectal leiomyosarcoma (LMS) is an aggressive malignant neoplasm. Owing to the rarity of LMSs, an optimal treatment modality has yet to be determined.
BACKGROUND
The anorectal leiomyosarcoma (LMS) is an aggressive malignant neoplasm. Owing to the rarity of LMSs, an optimal treatment modality has yet to be determined.
AIM
To collect all published data on anorectal LMS characteristics, explore current treatment options, and review recent cases of postradiation LMS.
METHODS
A literature search of the PubMed electronic database was conducted using the MeSH terms "rectal neoplasms", "anus neoplasms" and "gastrointestinal neoplasms" combined with "leiomyosarcoma". The search was limited to English language and human studies. All available case reports and case series of anal or rectal LMSs that were published from the beginning of January 1996 to May 2017 were included if the diagnosis of LMS had been confirmed by histopathologic examination. Data were analyzed using simple statistics (mean, median, and standard deviation). Independent sample -test was used to compare means for continuous variables.
RESULTS
A total of 27 articles reporting on 51 cases of anorectal LMS were identified. Among these cases, 11.7% had undergone previous pelvic radiotherapy (developing LMS at 13-35 years afterwards). Anorectal LMS affected the rectum in 92.2% of the cases, and no sex-based predominance was observed. Surgical resection with negative margins remains the mainstay of treatment, which can be accomplished with wide local excision or radical resection. The local recurrence rate was higher among cases who received wide local excision (30%), as compared to radical resection (20%); however, the overall rate of metastasis was 51.61% regardless of the treatment approach. The use of neoadjuvant radiation lowers the risk of local recurrence compared to adjuvant radiotherapy, and facilitates R0 resection of the tumor. Cases treated with adjuvant chemotherapy showed better rates of distant recurrence and overall survival. Nonetheless, multidisciplinary team discussion is necessary to determine the optimal management plan whilst considering patient- and disease-related factors.
CONCLUSION
A multidisciplinary team approach, considering the underlying patient- and disease- related factors, is necessary for optimal management of these complex tumors.
PubMed: 31523383
DOI: 10.4240/wjgs.v11.i8.334 -
International Journal of Radiation... Nov 2019
Topics: Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Capecitabine; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Consensus; Delphi Technique; ErbB Receptors; Female; Humans; Male; Margins of Excision; Mitomycin; Precision Medicine; Radiotherapy; Salvage Therapy; Sex Factors; Societies, Medical; Treatment Outcome; United States
PubMed: 31288054
DOI: 10.1016/j.ijrobp.2019.06.2544 -
The Lancet. Infectious Diseases Aug 2019Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely...
BACKGROUND
Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer.
METHODS
We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL.
FINDINGS
Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16·5, 95% CI 14·2-19·2, p<0·0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4·4, 3·7-5·3, p<0·0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14·1, 11·1-17·9, p<0·0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12·9, 95% CI 6·7-24·8, p<0·0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2·3, 1·6-3·4, p<0·0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23·1, 9·4-57·0, p<0·0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3·6, 2·5-5·3, p<0·0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women).
INTERPRETATION
HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women.
FUNDING
International Agency for Research on Cancer.
Topics: Anus Neoplasms; Early Detection of Cancer; Female; Global Health; HIV Seropositivity; Human papillomavirus 16; Humans; Papillomavirus Infections; Prevalence; Uterine Cervical Neoplasms
PubMed: 31204304
DOI: 10.1016/S1473-3099(19)30164-1 -
BMC Cancer Jun 2019Human papilloma virus (HPV) associated cervical cancer remains a global concern particular, in Sub-Saharan Africa (SSA) where the impact is felt most. Evidence show that...
BACKGROUND
Human papilloma virus (HPV) associated cervical cancer remains a global concern particular, in Sub-Saharan Africa (SSA) where the impact is felt most. Evidence show that many other cancers such as vaginal, anal, oropharyngeal, penile are because of persistent infection with HPV especially, high-risk types.
AIM
We mapped evidence on the incidence, prevalence, mortality, and the trends of human papillomavirus-related cancers in SSA.
METHODS
A comprehensive literature search was conducted from several databases including PubMed, Google scholar, Science Direct, and CINAHL and MEDLINE via EBSCOhost as well as World Health Organization website for grey literature. Studies reporting HPV-related cancers in SSA outcomes including prevalence, incidence, mortality, and trends were included in this study. The risk of bias of the included studies were assessed using the mixed methods appraisal tool version 2011. We employed PRISMA (preferred reporting items for systematic reviews and meta-analyses) to report the search results. Thematic analysis used to reveal the emerging themes from the included studies.
RESULTS
Seventy-four (74) studies were retrieved at full article screening, eight of them (six reviews, and two quantitative study) were eligible for data extraction. The degree of agreement between the two independent reviewers following full article screening, was 86.49% agreement versus 64.57% likely by chance which constituted moderate to significant agreement (Kappa statistic = 0.62, p-value< 0.05). Of the eight included studies, four (50%) studies generalized about SSA with no country of interest; two (25%) studies were conducted in Nigeria; one (12.5%) reported about Uganda, Zambia, Guinea, Malawi Tanzania, Mali, Mozambique, Zimbabwe; and one (12.5%) reported about Ethiopia, Senegal, Zimbabwe and Uganda. These eight included studies reported evidence on more than one outcome of interest. Four studies reported about the prevalence of HPV-related cancers, seven studies reported about the incidence, four studies reported about mortality, and four studies reported about the trends of HPV-related cancers.
CONCLUSION
This study observation highlighted a gap of knowledge regarding the epidemiological data on the recent HPV prevalence in SSA, which will have a potential impact in determining the distribution of HPV on different body sites (cervix, penis, vagina, vulva, anus and oropharynx). Ongoing research projects are recommended in SSA to enhance the value of HPV, and HPV-associated cancers epidemiological data to inform strategies or/and policies on prevention, diagnosis, and treatment of HPV-related conditions.
Topics: Africa South of the Sahara; Anus Neoplasms; Female; Humans; Incidence; Male; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Penile Neoplasms; Prevalence; Uterine Cervical Neoplasms; Vaginal Neoplasms
PubMed: 31185951
DOI: 10.1186/s12885-019-5781-3 -
Journal of Gastrointestinal Oncology Feb 2019Definitive chemoradiation (CRT) is the standard treatment for localized squamous cell carcinoma of the anus (SCCA). Because most phase III trials in SCCA have excluded...
BACKGROUND
Definitive chemoradiation (CRT) is the standard treatment for localized squamous cell carcinoma of the anus (SCCA). Because most phase III trials in SCCA have excluded patients with HIV, the evidence on treatment outcomes of these patients is lacking. We performed a systematic review and meta-analysis on the efficacy and toxicity profiles of HIV-positive SCCA patients treated with definitive CRT.
METHODS
The systematic search was conducted Embase, Medline, Cochrane Libary, Scopus, Lilacs and Opengrey, from inception until September 2017. Eligible studies were clinical trials, prospective or retrospective cohort studies. The main outcome variables were 3-year disease-free survival (DFS) and overall survival (OS) rates and frequency of grade 3 or 4 (G3/4) treatment-related toxicities, according to HIV status. Meta-analyses using pooled risk ratios were performed for binary outcomes from comparative studies from the antiretroviral therapy (HAART) era with the fixed effects model.
RESULTS
Out of 3,951 studies, 40 were deemed eligible, with a total of 3,720 patients. One third (N=1,298; 34%) were HIV-positive and their median pre CRT CD4 count was 347 µm/L. HIV-positive patients presented higher risk of G3/4 cutaneous toxicities [risk ratio (RR) =1.34; 95% CI, 1.10-1.64; P=0.004; I=77.7%], worse 3-year DFS rate (RR =1.32; 95% CI, 1.01-1.74; P=0.043; I=52.19%), and 3-year OS rate (RR =1.77; 95% CI, 1.35-2.32; P<0.001; I=6%).
CONCLUSIONS
Patients with localized SCCA and HIV infection treated with CRT tend to experience higher risk of toxicities and worse DFS and OS rates. Our findings suggest that future trials should be tailored to HIV-positive patients.
PubMed: 30788159
DOI: 10.21037/jgo.2018.10.08 -
Contrast Media & Molecular Imaging 2018Prognostic significance of fluorine-18 fluorodeoxyglucose positron emission tomography (F-FDG-PET) in anal squamous cell carcinoma (SCC) has been evaluated in several... (Meta-Analysis)
Meta-Analysis
PURPOSE
Prognostic significance of fluorine-18 fluorodeoxyglucose positron emission tomography (F-FDG-PET) in anal squamous cell carcinoma (SCC) has been evaluated in several studies; however, the results seem to be controversial and no consensus exists about its predictive capability. The current meta-analysis was carried out to comprehensively investigate the prognostic significance of F-FDG-PET parameters in patients with anal SCC.
METHODS
A comprehensive literature search of PubMed/MEDLINE and Scopus databases was performed to retrieve pertinent articles published until August 5th 2018, concerning the prognostic significance of F-FDG-PET in patients with anal SCC. No language restriction was used. Several prognostic factors were reported for progression-free survival (PFS) and overall survival (OS) including pretreatment maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), inguinal nodal uptake, and metabolic response to therapy.
RESULTS
Eleven studies (741 patients) were included. The pooled hazard ratio (HR) for the probability of PFS was 5.36 (95% confidence interval (95% CI): 3.12-9.21, < 0.001) for metabolic response to therapy and 1.98 (95% CI: 1.26-3.12, =0.003) for SUVmax. The pooled HR for the probability of OS was 5.87 (3.02-11.39, < 0.0001) for metabolic response to therapy. On the other hand, the study revealed that the pooled HRs of MTV and inguinal nodal uptake for PFS were 1.56 (95% CI: 0.96-2.53, =0.072) and 1.79 (95% CI: 1-3.21, =0.051), respectively.
CONCLUSIONS
Our findings propose that some F-FDG-PET parameters could serve as prognostic indicators in anal SCC, but further larger studies are needed in this setting.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Fluorodeoxyglucose F18; Humans; Positron-Emission Tomography; Prognosis; Survival Analysis; Tumor Burden
PubMed: 30627062
DOI: 10.1155/2018/9760492