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.

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 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.

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.

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.

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.

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.

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.

Performance of Anal Cytology Compared With High-Resolution Anoscopy and Histology in Women With Lower Anogenital Tract Neoplasia.

Background: Information on the performance of anal cytology in women who are high risk for human papillomavirus-related lesions and the factors that might influence cytology are largely lacking. Methods: Retrospective study including all new referrals of women with a previous history of anogenital neoplasia from January 2012 to July 2017, with concomitant anal cytology and high-resolution anoscopy with or without biopsies. Results: Six hundred and thirty six anal cytology samples and 323 biopsies obtained from 278 women were included. Overall sensitivity and specificity of "any abnormality" on anal cytology to predict any abnormality in histology was 47% (95% confidence interval [CI], 41%-54%) and 84% (95% CI, 73%-91%), respectively. For detecting high-grade squamous intraepithelial lesions (HSIL)/cancer, sensitivity was 71% (95% CI, 61%-79%) and specificity was 73% (95% CI, 66%-79%). There was a poor concordance between cytological and histological grades (κ = 0.147). Cytology had a higher sensitivity to predict HSIL/cancer in immunosuppressed vs nonimmunosuppressed patients (92% vs 60%, P = .002). The sensitivity for HSIL detection was higher when 2 or more quadrants were affected compared with 1 (86% vs 57%, P = .006). A previous history of vulvar HSIL/cancer (odds ratio [OR], 1.71, 1.08-2.73; P = .023), immunosuppression (OR, 1.88, 1.17-3.03; P = .009), and concomitant genital HSIL/cancer (OR, 2.51, 1.47-4.29; P = .001) were risk factors for abnormal cytology. Conclusions: Women characteristics can influence the performance of anal cytology. The sensitivity for detecting anal HSIL/cancer was higher in those immunosuppressed and with more extensive disease.

p16 immunostaining in histological grading of anal squamous intraepithelial lesions: a systematic review and meta-analysis.

p16 is the most widely studied biomarker in lower anogenital tract squamous intraepithelial lesions and, currently the only recommended biomarker for histological grade assessment. The aim of this systematic review and meta-analysis was to evaluate p16-positive rates according to anal squamous intraepithelial lesions/anal intraepithelial neoplasia (AIN) grade. Two investigators independently searched four electronic databases: PubMed, Web of Sciences, Scopus, and Embase from inception until August 2017. Studies that evaluated p16 immunostaining in histological samples of anal and/or perianal squamous intraepithelial lesions and defined a p16-positive result as diffuse block staining with nuclear or nuclear plus cytoplasmic staining were included. A meta-analysis was performed using a random effects model. Fifteen studies consisting of 790 samples were included. The proportion of p16 expression increased with the severity of histological grade. p16 positivity was 2% (95% CI: 0.2-5%) in normal histology, 12% (95% CI: 2-27%) in low-grade squamous intraepithelial lesions (LSILs)/AIN1 (excluding condylomas), 7% (95% CI: 2-13%) in all LSIL (AIN1/LSIL/condyloma), 76% (95% CI: 61-88%) in AIN2, and 90% (95% CI: 82-95%) in AIN3. For anal high-grade squamous intraepithelial lesions (HSILs), in studies using a two-tiered nomenclature, p16 positivity was 84% (95% CI: 66-96%) and for all HSIL (AIN2, AIN3, HSIL combined) it was 82% (95% CI: 72-91%). In summary, p16 positivity in anal squamous intraepithelial lesions appears to be in a similar range to the commonly described cervical squamous intraepithelial lesions, however, for anal low-grade lesions positivity seems to be lower.

Anal High-Grade Squamous Intraepithelial Lesions in Pharmacologically Immunocompromised Patients Followed in a Referral Center.

BACKGROUND: Information is lacking regarding anal/perianal precancerous lesions in referral cohorts of pharmacologically immunocompromised patients. OBJECTIVE: The aim of this study is to evaluate the prevalence of anal/perianal high-grade squamous intraepithelial lesions in a referral cohort of patients on immunomodulator/immunosuppressive medications, who were assessed and followed with high-resolution anoscopy. DESIGN: This is a retrospective study. SETTING: This study was conducted in a single anal neoplasia service from January 2012 to June 2017. PATIENTS: Patients on chronic immunomodulator/immunosuppressive medications were included. Cases of concomitant immunosuppression due to HIV infection were excluded, and immunosuppression due to chemotherapy was not considered for this analysis. INTERVENTION: High-resolution anoscopy was performed. MAIN OUTCOME: The primary outcome measured was the prevalence of anal/perianal high-grade squamous intraepithelial lesions in a referral cohort of pharmacologically immunocompromised patients. RESULTS: Fifty-four patients were included, of whom 40 were women (74%), with a mean age of 48 ± 17 years. A total of 232 high-resolution anoscopy examinations were performed in this cohort. At the first evaluation, 28 patients (52%) were diagnosed with anal and/or perianal high-grade squamous intraepithelial lesions (including 2 cases of perianal squamous cell carcinoma); 11 cases (20%) were new diagnoses. Ten of 46 patients (22%) with follow-up developed a new lesion (high-grade/cancer) during a median follow-up period of 17 (interquartile range, 6-28) months. Overall, 37 patients (69%) in our cohort had anal/perianal high-grade squamous intraepithelial lesions ever diagnosed (including previous history, first visit, and follow-up); 5 patients had perianal squamous cell carcinoma. At our center, 6% of the new referrals were known to be pharmacologically immunocompromised patients. LIMITATIONS: The retrospective nature of this study, the heterogeneity of the cohort, and the absence of human papillomavirus testing were limitations of this study. CONCLUSIONS: The presence of anal and/or perianal high-grade squamous intraepithelial lesions or cancer detected by high-resolution anoscopy in this referral population was high, and the detection of new lesions suggests that long-term follow-up is needed. Patients on immunomodulator/immunosuppressive drugs represented only a small percentage of the new referrals to our center. See Video Abstract at http://links.lww.com/DCR/A748.

Anal Sphincters Evaluation by Endoanal Ultrasound in Obstructed Defecation.

OBJECTIVES: To evaluate anal sphincter abnormalities detected by endoanal ultrasound in obstructed defecation due to rectocele and rectal intussusception. METHODS: The retrospective analysis includes 45 patients with obstructed defecation syndrome due to rectocele and/or rectal intussusception with or without fecal incontinence, and submitted to endoanal ultrasound. RESULTS: Ninety-three percent (n = 42) were women (mean age of 63 ± 12 years), and 47% (n = 21) of the patients had fecal incontinence. In total, 29% (n = 13) had a previous anorectal surgery, and 93% (n = 39) of the women had a previous vaginal delivery. An isolated rectal intussusception was diagnosed in 20% (n = 9) of the patients, an isolated rectocele in 24% (n = 11), and rectal intussusception and rectocele in 56% (n = 25). Thirty-six percent of patients had anal sphincter lacerations (n = 16): 12% (n = 2) had only internal laceration, 69% (n = 11) had only external laceration, and 19% (n = 3) had both. Two patients had a thinner internal anal sphincter with 0.9 and 1.2 mm, respectively. In total, 25% of the patients without fecal incontinence had an occult anal sphincter laceration, and all were women with an external sphincter laceration in the anterior quadrant and a previous vaginal delivery. In patients with obstructed defecation and fecal incontinence, 48% had sphincter lacerations. Previous anorectal surgery was a predictor of anal sphincter laceration (odds ratio [OR] 4.8; 95% confidence interval [CI] = 1.214-18.971; P = .025), but fecal incontinence (OR 2.7; 95% CI = 0.774-9.613; P = .119) and previous vaginal delivery (OR 1.250; 95% CI = 0.104-15.011; P = .860) were not. CONCLUSIONS: Endoanal ultrasound should be considered in obstructed defecation with or without fecal incontinence, especially if surgical correction is planned.

High levels of immunoglobulin A anti-tissue transglutaminase antibodies at diagnosis are a predictive factor for celiac hepatitis.

INTRODUCTION: Celiac hepatitis is characterized by the presence of liver injury in patients with celiac disease that resolves after gluten-free diet. AIM: To evaluate predictive factors of celiac hepatitis at celiac disease diagnosis. METHODS: Retrospective study including 46 adult patients with the diagnosis of celiac disease. RESULTS: Eighty-seven percent were women, with a mean age of 33 ± 11 years, 87% had a Marsh 3 and 46% (n = 21) had celiac hepatitis. These patients had a median Immunoglobulin A anti-tissue transglutaminase antibody (TTG-IgA) level of 208.0 U/ml (p25-p75: 89-1316 U/ml), a mean aspartate aminotransferase of 42 ± 24 U/L, alanine aminotransferase 50 ± 28 U/L, alkaline phosphatase 111 ± 64 U/L, at the time of diagnosis. Median TTG-IgA one year after diagnosis was 9U/ml (p25-p75: 4.5-30.5 U/ml) and 33% of the patients had normal values. At diagnosis, patients without celiac hepatitis had a median TTG-IgA of 77U/ml (p25-p75: 24-288 U/ml), mean aspartate aminotransferase of 23 ± 4 U/L, alanine aminotransferase 20 ± 6 U/L, alkaline phosphatase 69 ± 17 U/L. Median of TTG-IgA one year after diagnosis was 6 U/ml (p25-p75: 3-19 U/ml) and 48% had normal values. The celiac hepatitis group patients had higher values of TTG-IgA (p = 0.007) at diagnosis. There was a statistically significant positive correlation between TTG-IgA and alanine aminotransferase (r = 0.324, p = 0.028) at diagnosis. The odds of having celiac hepatitis was almost 5-fold higher in patients with a TTG-IgA level higher than 310 U/ml (OR = 4.8, 95%CI = 1.213-18.781, p = 0.025). CONCLUSIONS: Higher TTG-IgA levels are a predictive factor for celiac hepatitis in adult patients with celiac disease at diagnosis.

The missing piece.

A 59-year-old female was admitted due to the suspicion of food impactation after having eaten bread. An upper endoscopy revealed an indeterminate, bluish foreign body in the mid esophagus that was extracted with a forceps. After removal, it was clear that it was a puzzle piece. The patient then recalled that she had been playing with a puzzle with her granddaughter, while eating bread.

Gastric inflammatory fibroid polyp mimicking a gastrointestinal stromal tumour.

Inflammatory fibroid polyp of the gastrointestinal tract is a rare, benign neoplasm, most frequently located in the gastric antrum. Symptoms depend on the location and the size of the lesion. Biopsies are limited for the diagnosis of inflammatory fibroid polyps and diagnosis may not be possible until resection. The authors present a case of a 55-year-old woman, presenting with an upper gastrointestinal bleeding due to a large gastric inflammatory fibroid polyp imitating a gastrointestinal stromal tumor.

Predictive factors of small bowel patency in Crohn's disease patients.

BACKGROUND: Patency capsule was developed to avoid small bowel video capsule endoscopy retention, namely in patients with Crohn's disease. AIMS: To evaluate the predictive factors of small bowel patency in Crohn's disease patients. PATIENTS AND METHODS: Retrospective analysis including 151 Crohn's disease patients submitted to patency capsule (Agile® Patency Capsule) from 2011 to 2012. Patients that excreted the intact patency capsule were classified as having a patent small bowel (without patency capsule retention), other patients were considered to have negative patency of the small bowel (patency capsule retention). RESULTS: Patients had a mean age of 41±14 years, 54% were female and 25% had been previously submitted to surgery. Stricturing disease was seen in 20% of cases and penetrating disease in 16% of cases. Left-sided colonic lesions and ileal strictures were observed at colonoscopy in 13% and 9% of patients, respectively. In our sample, 28% of patients had negative patency of the small bowel (patency capsule retention). In multivariate analysis, independent factors that were associated with negative patency of the small bowel in Crohn's disease patients were stricturing (OR 10.16, p < 0.001) and penetrating phenotypes (OR 11.73, p = 0.001), left-sided colonic lesions (OR 3.77, p = 0.038), ileal stricture (OR 9.76, p = 0.003); previous intestinal surgery was found to be protective (OR 0.16, p = 0.006). CONCLUSIONS: Stricturing or penetrating disease, ileal strictures, no previous surgery and left-sided colonic lesions were the factors associated with negative small bowel patency in Crohn's disease patients.

In Vitro Susceptibility of Leishmania infantum to Artemisinin Derivatives and Selected Trioxolanes.

Leishmaniasis is among the world's most neglected diseases. Currently available drugs for treatment present drawbacks, urging the need for more effective, safer, and cheaper drugs. A small library of artemisinin-derived trioxanes and synthetic trioxolanes was tested against promastigote and intramacrophage amastigote forms of Leishmania infantum. The trioxolanes LC50 and LC95 presented the best activity and safety profiles, showing potential for further studies in the context of leishmanial therapy. Our results indicate that the compounds tested exhibit peroxide-dependent activity.

Prognostic Role of a Multimarker Analysis of Circulating Tumor Cells in Advanced Gastric and Gastroesophageal Adenocarcinomas.

OBJECTIVE: We aimed to assess the prognostic value of circulating tumor cells (CTC) in patients with advanced gastric and gastroesophageal adenocarcinomas. METHODS: The presence of CTC was evaluated in 62 patients with advanced gastric and gastroesophageal adenocarcinomas before systemic therapy and at follow-up through immunomagnetic enrichment for mucin 1- and epithelial cell adhesion molecule (EpCAM)-positive cells, followed by real-time RT-PCR of the tumor-associated genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5. RESULTS: The patients were stratified into groups according to CTC detection (CTC negative: with all marker genes negative; CTC positive: with at least 1 of the marker genes positive). Patients who were CTC positive at baseline had a significantly shorter median progression-free survival (PFS; 3.5 months, 95% CI: 2.9-4.2) and overall survival (OS; 5.8 months, 95% CI: 4.5-7.0) than patients lacking CTC (PFS 10.7 months, 95% CI: 6.9-14.4, p<0.001; OS 13.3 months, 95% CI: 8.0-18.6, p=0.003). Alterations in the marker profile during the course of chemotherapy were not predictive of clinical outcome or response to therapy. Yet, a favorable clinical response depended significantly on CTC negativity (p=0.03). CONCLUSION: Our data suggest that the presence of CTC is a major predictor of outcome in patients with gastric and gastroesophageal malignancies.