Anal pruritus: Don't look away.

Anal pruritus is a common anorectal symptom that can significantly impair a patient's quality of life, including their mental health. It can be one of the most difficult proctological conditions to treat. Patients often delay seeking medical attention, since it is an embarrassing but non-life-threatening situation. Pruritus ani can be associated with idiopathic and secondary causes, such as anorectal diseases, cancer (anal or colorectal), dermatological and sexually transmitted diseases, fungal infections and systemic diseases. If patients are referred for a colonoscopy, this can sometimes provide the first opportunity to evaluate the perianal area. Classifications of anal pruritus are based on the abnormalities of the perianal skin, one of the most commonly used being the Washington classification. A proper digital anorectal examination is important, as well as an anoscopy to help to exclude anorectal diseases or suspicious masses. Endoscopists should be aware of the common etiologies, and classification of the perianal area abnormalities should be provided in the colonoscopy report. Information on treatment possibilities and follow-up can also be provided. The treatment normally consists of a triple approach: proper hygiene, elimination of irritants, and skin care and protection. Several topical therapies have been described as possible treatments, including steroids, capsaicin, tacrolimus and methylene blue intradermal injections.

Argon Plasma Coagulation as Treatment for Anal Condylomas: A Narrative Review.

OBJECTIVES: Anal condylomas are a manifestation of anal human papillomavirus infection and can be associated with precancerous lesions and squamous cell carcinomas. Several methods have been described for treatment, including argon plasma coagulation. A narrative review of the evidence published on this topic was conducted. METHODS: A search was conducted using PubMed, Scopus, and Web of Science databases. RESULTS: Five studies reported on anal/perianal condyloma treatment with argon plasma coagulation. In 3 of these studies, there was a comparison with other treatment methods (addition of imiquimod, electrofulguration, and electrocautery, respectively). Argon plasma coagulation settings varied between studies. This type of treatment was effective for ablation. Recurrence rates and follow-up times varied largely between studies. No major complications, such as pain, scarring, sexual dysfunction, or severe bleeding were described. CONCLUSION: Studies indicate that argon plasma coagulation is an effective and safe therapy for anal and perianal condylomas.

Future Directions for Research on Anal Precancerous Lesion Treatment.

ABSTRACT: The benefit of treating anal precancerous lesions to reduce anal cancer progression was recently shown in people living with HIV. This will certainly impact the future development of recommendations on anal cancer prevention by including anal precancerous lesions screening and treatment for people living with HIV. However, by bringing this topic to the spotlight, it has also uncovered data that are still missing in this field and that need to be addressed by research.This article will discuss the many unanswered questions about treatment of anal precancerous lesions and future directions for research.

Identification and reporting of anal pathology during routine colonoscopies

The gold-standard procedure for anal canal examination is anoscopy. Nonetheless, patients are referred for a colonoscopy for many reasons, and a routine exam might provide an opportunity to diagnose anal pathologies, such as hemorrhoids, anal fissures, anal polyps, condylomas, and anal squamous cell carcinoma. It is important to know the main features of these conditions and relevant information to report in order to help guide patient treatment and follow-up.

Anal Intraepithelial Neoplasia and Anal Squamous Cell Carcinoma: Updates From the Last 3 Years.

ABSTRACT: In the last 3 years, new and relevant information has been published on anal cancer and anal precancerous lesions epidemiology, screening, treatment, and vaccination. This information will likely change prevention and treatment strategies for these patients in the upcoming years.

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.

Anal High-risk Human Papillomavirus Infection, Squamous Intraepithelial Lesions, and Anal Cancer in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Ulcerative colitis [UC] and Crohn's disease [CD] can be associated with severe comorbidities, namely opportunistic infections and malignancies. We present the first systematic review and meta-analysis evaluating the burden of anal human papillomavirus disease in patients with UC and CD. METHODS: PubMed, Web of Science, and Scopus were searched until November 2022. Meta-analyses were performed using random effects models. The protocol was recorded at PROSPERO register with the number CRD42022356728. RESULTS: Six studies, including 78 711 patients with UC with a total follow-up of 518 969 person-years, described the anal cancer incidence rate. For anal cancer incidence rate in CD, six studies were selected, including 56 845 patients with a total follow-up of 671 899 person-years. The incidence of anal cancer was 10.2 [95% CI 4.3 - 23.7] per 100 000 person-years in UC and 7.7 [3.5 - 17.1] per 100 000 person-years in CD. A subgroup analysis of anal cancer in perianal CD, including 7105 patients, was calculated with incidence of 19.6 [12.2 - 31.6] per 100 000 person-years [three studies included]. Few studies described prevalence of anal cytological abnormalities [four studies including 349 patients] or high-risk human papillomavirus [three studies including 210 patients], with high heterogeneity. Prevalence of cytological abnormalities or high-risk human papillomavirus was not associated with pharmacological immunosuppression in the studies included. CONCLUSION: The incidence of anal cancer is higher in UC than in CD, with the exception of perianal CD. There are limited and heterogeneous data on anal high-risk human papillomavirus infection and squamous intraepithelial lesions prevalence in this population.

Vulvar High-Grade Squamous Intraepithelial Lesions and Cancer as a Risk Factor for Anal Cancer: A Review.

OBJECTIVES: Anal squamous cell carcinoma (ASCC) has a higher incidence described in certain groups, namely, in women with vulvar high-grade squamous intraepithelial lesions (vHSILs) and/or human papillomavirus squamous cell carcinoma (VSCC). This review describes terminology, vHSIL, and VSCC in their association with ASCC and the published recommendations for early detection of this cancer in these women. MATERIALS AND METHODS: A narrative review was conducted by the authors on vHSIL and VSCC as risk factors for ASCC. RESULTS: The ASCC and VSCC incidence are increasing. Women with vHSIL and/or VSCC can present with ASCC at diagnosis, being one of the highest-risk groups. Suspicious symptoms include rectal bleeding, pain, and a sensation of an anal mass. Digital anorectal examination can help detect early ASCC. Sensitivity of anal cytology in women with vHSIL and VSCC seems low, with the exception of immunosuppressed women with genital neoplasia (cervix, vagina, and vulva). There are still insufficient data on high-resolution anoscopy in women with vHSIL and/or VSCC as a screening method. CONCLUSIONS: Clinicians need be aware that women with vHSIL and VSCC comprise one of the highest-risk groups for ASCC. Inquiring suggestive symptoms of ASCC and a digital anorectal examination can help in the early detection of this type of cancer.

Evaluation of Anorectal Function in Perianal Crohn's Disease: A Pilot Study.

BACKGROUND: Perianal Crohn's disease is a disabling condition, with little known about anorectal function in healed/inactive perianal Crohn's disease; Aim: To evaluate anorectal function in a cohort of patients with treated/healed perianal Crohn's disease; Methods: Prospective cohort study, including high-resolution anorectal manometry, balloon expulsion test, and 3D-endoanal ultrasound in all patients; Results: Of the 16 patients studied (mean age ± SD, 42 ± 13 years), 12 (75%) were men. A laceration of the internal anal sphincter and/or anal scarring was seen in nine (56%) patients; there was no laceration of the external anal sphincter. Five (56%) of these nine patients had never experienced faecal incontinence. All had normal anal resting and squeeze pressures. Manometry suggested dyssynergia in 11 (69%) patients, with only one (6%) fulfilling the criteria for obstructed defecation. Hyposensitivity for at least one sensory parameter was seen in 11 (69%) patients and hypersensitivity in five (31%) patients; Conclusions: This study detected sphincter abnormalities in more than half of patients, many of whom were asymptomatic. Alterations in rectal sensation were frequently seen, more commonly with rectal hyposensitivity. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03819257).

High-risk human papilloma virus, precancerous lesions and cancer in anal condylomas.

INTRODUCTION: Anal condylomas are associated with human papillomavirus (HPV) infection and are a risk factor for anal squamous cell carcinoma (SCC). OBJECTIVE: To conduct a meta-analysis evaluating the prevalence of anal high-risk HPV, high-grade squamous intraepithelial lesions (HSIL) and SCC in patients with condylomas. The standardized incidence ratio (SIR) and the incidence rate of anal SCC were also calculated. METHODS: Three electronic databases were searched until April 2020. Meta-analyses were performed using random effects models. RESULTS: Pooled prevalence estimate of high-risk HPV (HR-HPV) in anal condylomas was 40.2% (21.0-63.1) in immunocompromised and 16.4% (10.7-24.3) in nonimmunocompromised patients, with an odds ratio (OR) of 3.79 (1.51-9.52, P = 0.005) for immunocompromised patients. HR-HPV in condylomas with HSIL was 73.8% (39.1-92.5) and in non-HSIL cases was 17.7% (9.6-30.2), corresponding to an OR of 12.33 (2.97-51.21, P = 0.001) for those with HSIL. The prevalence of HSIL in condylomas was 24.0% (16.4-33.7) in immunocompromised and 11.8% (7.2-18.8) in nonimmunocompromised patients, with an OR of 2.51 (1.72-3.65, P < 0.001) for immunocompromised patients. The overall prevalence of anal SCC in anal condylomas was 0.3% (0.0-1.7). The SIR of anal SCC was 10.7 (8.5-13.5), 20.1 (14.4-28.2) in men and 7.7 (5.6-10.5) in women. The overall incidence rate of anal SCC was 6.5 per 100 000 person-years (3.6-11.7), 12.7 (9.1-17.8) in men and 4.7 (1.7-13) in women. CONCLUSION: Patients with a history of anal condylomas have a high risk of anal SCC, especially men. The prevalence of HR-HPV and HSIL in condylomas from immunocompromised patients is high. This information can change patient follow-up and treatment.

Multizonal anogenital neoplasia in women: a cohort analysis.

BACKGROUND: There is currently a lack of information on full anogenital evaluation of women with a previous history of anogenital neoplasia. METHODS: Retrospective analysis of the Homerton Anogenital Neoplasia Service records from January 2012 to March 2017, to identify all new referrals of women with previous anogenital neoplasia, who had had at least one complete examination of all anogenital sites. Multizonal anogenital disease (MZD) was defined as the presence of high-grade squamous intraepithelial lesions (HSIL)/carcinoma concurrently at two or more of the following sites/zones: perianus, anal canal, vulva, vagina or cervix. RESULTS: 253 women were included, mean age was 47 (SD=15) years and median duration of follow-up was 12 (IQR=21) months. Fifty-six women (22%) were diagnosed with MZD at first assessment and/or during follow-up. Current smokers (RR=1.84, 95% CI 1.21-2.79, p=0.004) and women on immunodulators/immunosuppressive drugs (RR=2.57, 95% CI 1.72-3.86, p<0.001) had an increased risk for MZD. The risk was lower for women without a previous history of anogenital high-grade lesions/cancer compared to those with this history (RR=0.06, 95% CI 0.01-0.45, p=0.006). CONCLUSIONS: Multizonal assessment was important to diagnose occult areas of disease and should be especially considered in current smokers, pharmacologically immunocompromised and those with a previous history of anogenital HSIL/cancer.

Anal cancer and precancerous lesions: a call for improvement.

Anal squamous cell carcinoma is the most common type of anal cancer and is largely associated with anal human papillomavirus infection. The incidence of anal squamous cell carcinoma is increasing, and although still uncommon in the general population, a high incidence has been noted in specific population groups (eg, patients with HIV, men who have sex with men [MSM], recipients of solid organ transplants, women with genital neoplasia, and patients with systemic lupus erythematosus or inflammatory bowel disease). The higher incidence among individuals who are HIV-positive makes anal squamous cell carcinoma one of the most common non-AIDS-defining cancers among HIV-positive individuals. Anal cancer screening in high-risk groups aims to detect high-grade squamous intraepithelial lesions, which are considered anal precancerous lesions, and for which identification can provide an opportunity for prevention. A blind anal cytology is normally the first screening method, and for patients with abnormal results, this approach can be followed by an examination of the anal canal and perianal area under magnification, along with staining-a technique known as high-resolution anoscopy. Digital anorectal examination can enable early anal cancer detection. Several societies are in favour of screening for HIV-positive MSM and recipients of transplants. There are no current recommendations for screening of anal precancerous lesions via endoscopy, but in high-risk groups, a careful observation of the squamocolumnar junction should be attempted. Several treatments can be used to treat high-grade squamous intraepithelial lesions, including argon plasma coagulation or radiofrequency ablation, which are largely limited by high recurrence rates. Gastroenterologists need to be aware of anal squamous cell carcinoma and anal precancerous lesions, given that patients at high risk are frequently encountered in the gastroenterology department. We summarise simple procedures that can help in early anal squamous cell carcinoma detection.

A meta-analysis of anal cancer incidence by risk group: Toward a unified anal cancer risk scale.

Certain population groups are known to have higher than average anal cancer risk, namely persons living with HIV (PLHIV), men who have sex with men (MSM), women diagnosed with human papillomavirus (HPV)-related gynecological precancerous lesions or cancer, solid organ transplant recipients (SOTRs) and patients with autoimmune diseases. Our aim was to provide robust and comparable estimates of anal cancer burden across these groups. Summary incidence rates (IRs), as cases per 100 000 person-years (py), were calculated by fixed-effects meta-analysis. IRs were 85 (95% confidence interval [CI] = 82-89) for HIV-positive MSM (n = 7 studies; 2 229 234 py), 32 (95% CI = 30-35) for non-MSM male PLHIV (n = 5; 1626 448 py) and 22 (95% CI = 19-24) for female PLHIV (n = 6; 1 472 123 py), with strong variation by age (eg, from 16.8 < 30 years to 107.5 ≥ 60 years for HIV-positive MSM). IR was 19 (95% CI = 10-36) in HIV-negative MSM (n = 2; 48 135 py). Anal cancer IRs were much higher after diagnosis of vulvar (IR = 48 [95% CI = 38-61]; n = 4; 145 147 py) than cervical (9 [95% CI = 8-12]; n = 4; 779 098 py) or vaginal (IR = 10 [95% CI = 3-30]; n = 4; 32 671) cancer, with equivalent disparity after respective precancerous lesions. IR was 13 (95% CI = 12-15) in SOTRs (n = 5; 1 946 206 py), reaching 24.5 and 49.6 for males and females >10 years after transplant. Anal cancer IRs were 10 (95% CI = 5-19), 6 (95% CI = 3-11) and 3 (95% CI = 2-4) for systemic lupus erythematosus, ulcerative colitis and Crohn's disease, respectively. In conclusion, a unifying anal cancer risk scale, based upon comprehensive meta-analysis, can improve prioritization and standardization in anal cancer prevention/research initiatives, which are in their public health infancy.

Burden of anal squamous cell carcinoma, squamous intraepithelial lesions and HPV16 infection in solid organ transplant recipients: A systematic review and 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 I2 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; I2  = 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; I2  = 0%). Prevalence of abnormal anal cytology was 12.9% (95% CI, 9.2%-17.7%; 6 studies including 328 SOTR; I2  = 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; I2  = 0%), with 4.7% (95% CI, 2.5%-8.5%; I2  = 0%) high-grade squamous intraepithelial lesions. Pooled anal HPV16 prevalence was 3.6% (95% CI, 1.6%-7.8%; 4 studies including 254 SOTR; I2  = 17.6%). There was substantial and consistent evidence of elevated anal SCC incidence in SOTR.

Cytology in Anal Cancer Screening: Practical Review for Clinicians.

The incidence and mortality of anal squamous cell carcinoma (SCC) are expected to continue to increase in the next 20 years. High-risk groups for anal SCC, i.e., human immunodeficiency virus (HIV)-positive patients, men who have sex with men (MSM), women with previous genital neoplasia, and solid-organ transplant recipients, have been identified. HIV-positive MSM have the highest risk, and some societies have advocated for anal cancer screening to be done in this population. Screening for anal SCC follows the same principles as that for cervical cancer since there are similarities between the two types of cancers. Anal cytology has been recommended as an initial screening method for high-risk groups, e.g., HIV-positive MSM. Normally, the cytology is liquid based and collected blindly by a clinician using a Dacron swab and it is especially used for internal lesions detection. The sensitivity to predict anal high-grade squamous intraepithelial lesions is higher in immunosuppressed patients with a high burden of the disease. The report should include the classification, normally according to the Bethesda terminology and the sample adequacy, in a manner similar to that for cervical cytology. In cases involving unsatisfactory samples, it is important to repeat the procedure given the prevalence of anal squamous cytological abnormalities in follow-up cytology procedures. The absence of transformation zone cells in anal cytology seems to increase the risk of false-negative results.

Recommendations Favoring Anal Cytology as a Method for Anal Cancer Screening: A Systematic Review.

Clinicians are increasingly facing the decision of performing anal cancer screening in high-risk groups. Anal cytology is commonly the first approach. We systematically reviewed recommendations favoring anal cytology for anal cancer screening. Three databases were searched: PubMed, Scopus, and Embase, from January 2007 to 12 September 2019. The references cited by the retrieved articles and the websites of relevant organizations were also searched without language restrictions. Studies reporting guidelines from regional or national societies, institutes, or groups were included. Eight papers met the inclusion criteria and were selected, five were from the United States of America (USA) and three from Europe. There were no national recommendations published. There was one guideline specifically for solid-organ transplant recipients. The other seven targeted HIV-positive patients, with HIV-positive men who have sex with men (MSM) included as a screening group in all of these. Two recommendations favored screening in all HIV-positive patients. Five recommendations targeting HIV-positive patients made considerations about the cytology follow-up, recommending at least annual cytology in case of a normal result, and in case of squamous cytological abnormalities, a referral for anoscopy/high-resolution anoscopy. There were no recommendations for upper and lower age limits for screening. In conclusion, several societies recommend anal cancer screening using anal cytology in HIV-positive MSM patients. There is a lack of screening recommendations for other high-risk groups, with only one society recommending screening in transplant recipients.

Predictive models of mortality and hospital readmission of patients with decompensated liver cirrhosis.

INTRODUCTION: Complications of cirrhosis are one the major causes of hospital admission associated with high morbimortality rates and social and economic charges. The aims of this study were to evaluate hospital readmission and mortality rates and predictive factors for hospital readmission and mortality. METHODS: Patients with decompensated cirrhosis admitted to our institution between 2008-2014 were retrospectively analyzed. RESULTS: Included 427 admissions from 177 patients with cirrhosis with mean age of 59.0 ± 12.3 years. The major cause was alcoholic-related liver disease and the median duration of admission was 9.0 days (IQR 6.0-14.0). During the follow-up period,there were 250 readmissions from 95 patients, with a median of 58 (IQR27-134) days for readmission, representing 58.5% of the total number of admissions.The 180-day mortality rate was 35.0%. In the multivariate analysis, ascites, smoking and MELD Na were associated with 180-day mortality. Creatinine, albumin, esophageal variceal bleeding, previous variceal banding, lactulose, rifaximin and proton pump inhibitors use were independently associated with need of readmission. Based on regression analysis, two models were calculated to predict 180-day mortality (AUROC 0.74 (0.682-0.794)) and need for readmission(AUROC 0.821 (0.781-0.861)), p < 0.001. CONCLUSION: The readmission rate and mortality of cirrhotic patients are still very high and it is a priority to determine preventable risk factors to improve patient outcome. Two models were created to predict 180-day mortality(AUROC 0.74) and need for readmission(AUROC 0.821), that could guide the management of the patients at the time of admission.