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Journal of the National Cancer Institute Jan 2024Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the...
BACKGROUND
Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the general population in the United States. We describe trends in anal intraepithelial neoplasia grade III diagnosis and risk of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III by HIV status and sex.
METHODS
We used data from a population-based linkage between cancer and HIV registries in 11 US states; Puerto Rico; and Washington, DC, during 1996-2019. We identified all individuals with a diagnosis of anal intraepithelial neoplasia grade III and determined their HIV status. We estimated the average annual percentage change of anal intraepithelial neoplasia grade III using Poisson regression stratified by HIV status and sex. We estimated the 5-year cumulative incidence of squamous cell carcinoma of the anus following an anal intraepithelial neoplasia grade III diagnosis stratified by sex, HIV status, and prior AIDS diagnosis.
RESULTS
Among people with HIV, average annual percentage changes for anal intraepithelial neoplasia grade III were 15% (95% confidence interval [CI] = 12% to 17%) per year among females and 12% (95% CI = 11% to 14%) among males. Average annual percentage changes for those without HIV were 8% (95% CI = 7% to 8%) for females and 8% (95% CI = 6% to 9%) for males. Among people with HIV, a prior AIDS diagnosis was associated with a 2.7-fold (95% CI = 2.23 to 3.40) and 1.9-fold (95% CI = 1.72 to 2.02) increased risk of anal intraepithelial neoplasia grade III diagnosis for females and males, respectively. Five-year cumulative incidence of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III for people with HIV with a prior AIDS diagnosis were 3.4% and 3.7% for females and males, respectively.
CONCLUSIONS
Rates of anal intraepithelial neoplasia grade III diagnoses have increased since 1996, particularly for people with HIV, likely influenced by increased screening. A prior AIDS diagnosis was strongly associated with risk of anal intraepithelial neoplasia grade III diagnosis.
Topics: Male; Female; Humans; United States; HIV Infections; Acquired Immunodeficiency Syndrome; Risk Factors; Anal Canal; Carcinoma in Situ; Anus Neoplasms; Carcinoma, Squamous Cell; Papillomavirus Infections
PubMed: 37632787
DOI: 10.1093/jnci/djad176 -
Asian Journal of Surgery Oct 2023
Topics: Humans; Anus Neoplasms; Rectal Fistula; Anal Canal; Treatment Outcome
PubMed: 37344312
DOI: 10.1016/j.asjsur.2023.05.085 -
The Journal of Surgical Research Feb 2024There have been no significant changes in anal cancer treatment options in 4 decades. In this study, we highlight two preclinical models designed to assess anal cancer...
INTRODUCTION
There have been no significant changes in anal cancer treatment options in 4 decades. In this study, we highlight two preclinical models designed to assess anal cancer treatments.
MATERIALS AND METHODS
Transgenic K14E6/E7 mice were treated with 7, 12-dimethylbenz(a)anthracene until anal tumors developed. Mice were treated with localized radiation in addition to chemotherapy (combined-modality therapy [CMT]) and compared to no treatment control (NTC). K14E6/E7 mouse anal spheroids with and without Pik3ca mutations were isolated and treated with vehicle, LY3023414 (LY3) (a drug previously shown to be effective in cancer prevention), CMT, or CMT + LY3.
RESULTS
In the in vivo model, there was a significant increase in survival in the CMT group compared to the NTC group (P = 0.0392). In the ex vivo model, there was a significant decrease in the mean diameter of CMT and CMT + LY3-treated spheroids compared to vehicle (P ≤ 0.0001). For LY3 alone compared to vehicle, there was a statistically significant decrease in spheroid size in the K14E6/E7 group without mutation (P = 0.0004).
CONCLUSIONS
We have provided proof of concept for two preclinical anal cancer treatment models that allow for the future testing of novel therapies for anal cancer.
Topics: Mice; Animals; Mice, Transgenic; Combined Modality Therapy; Anus Neoplasms; Anal Canal; Carcinoma, Squamous Cell
PubMed: 37864962
DOI: 10.1016/j.jss.2023.09.053 -
MedRxiv : the Preprint Server For... Oct 2023Squamous cell carcinoma of the anus (SCCA) annual incidence among sexual minority men (SMM) with and without HIV is 85/100,000 and 19/100,000 persons, respectively,...
BACKGROUND
Squamous cell carcinoma of the anus (SCCA) annual incidence among sexual minority men (SMM) with and without HIV is 85/100,000 and 19/100,000 persons, respectively, which is significantly higher than the overall incidence (2/100,000). Since SCCA tumours average ≥30 mm at diagnosis, we assessed the accuracy of individuals to self-detect anal abnormalities.
METHODS
The study enrolled 714 SMM and transgender women (SMM/TW), aged 25 to 81 years, in Chicago, Illinois and Houston, Texas during 2020-2022. Individuals were taught the anal self- and companion examinations (ASE/ACE). Then, a clinician performed a digital anal rectal examination (DARE) before participants conducted the ASE or ACE. Accuracy was measured along with factors associated with ASE/ACE and DARE concordance.
FINDINGS
The median age was 40 years (interquartile range, 32-54), 36.8% were living with HIV, and 47.0%, 23.4%, and 23.0% were non-Hispanic white, non-Hispanic Black, and Hispanic. Clinicians detected 245 individuals with abnormalities (median diameter 3 mm). Sensitivity and specificity of the ASE/ACE was 59.6% (95%CI 53.5-65.7%) and 80.2% (95%CI 76.6-83.8%), respectively. Overall concordance was 0.73 (95% CI 0.70-0.76) between ASE/ACE and DARE and increased with increasing anal canal lesion size (p=0.02). However, concordance was lower for participants aged ≥55 years (compared to 25-34 years) and when the ASE/ACE trainer was a lay person rather than a clinician.
INTERPRETATION
SMM/TW who complete an ASE or ACE are likely to detect SCCA at an early stage when malignant lesions are much smaller than the current median dimension at presentation of ≥30 mm.
FUNDING
National Cancer Institute.
RESEARCH IN CONTEXT
While squamous cell carcinoma of the anus (SCCA) incidence is substantially elevated in people with HIV, there are currently no consensus recommendations on how to screen for it, nor is there widespread technological infrastructure for one prevailing method, high-resolution anoscopy. In the absence of screening programs, the size of SCCA tumours at diagnosis are > 30 mm. We searched PubMed for articles between January 1, 2000 and June 15, 2023 using the search terms 'anus neoplasm' and 'self-examination'. We found no studies assessing the accuracy of self-examinations to detect anal masses other than our prior feasibility study. The primary goal of the Prevent Anal Cancer Palpation Study was to assess the accuracy of lay self-examinations and companion examinations to recognise abnormalities in the anal region. Clinicians conducted a digital anal rectal examination and recorded all lesions observed at the perianus or anal canal. The median size of lesions was 3 mm. Participants conducted lay examinations and these results were judged against a clinician's examination. The sensitivity and specificity of the lay examinations, for any lesion at the anal canal or perianal region was 59.6% and 80.1%, respectively. As lesions increased in size, concordance increased between clinician's exam and the lay exam. It is now known that high-resolution anoscopy can reduce the risk for SCCA but the infrastructure using this technology is very limited in high-resource settings and almost non-existent in low resource settings, especially where HIV prevalence is highest. The evidence suggests that self- and partner examination of the anal region is feasible and that lay persons can detect lesions that are much smaller than the prevailing size of SCCA tumours.
PubMed: 37905024
DOI: 10.1101/2023.10.19.23297209 -
BMC Surgery Oct 2023The aim of these evidence-based guidelines is to present a consensus position from members of the Italian Unitary Society of Colon-Proctology (SIUCP: Società Italiana...
INTRODUCTION
The aim of these evidence-based guidelines is to present a consensus position from members of the Italian Unitary Society of Colon-Proctology (SIUCP: Società Italiana Unitaria di Colon-Proctologia) on the diagnosis and management of anal fissure, with the purpose to guide every physician in the choice of the best treatment option, according with the available literature.
METHODS
A panel of experts was designed and charged by the Board of the SIUCP to develop key-questions on the main topics covering the management of anal fissure and to performe an accurate search on each topic in different databanks, in order to provide evidence-based answers to the questions and to summarize them in statements. All the clinical questions were discussed by the expert panel in different rounds through the Delphi approach and, for each statement, a consensus among the experts was reached. The questions were created according to the PICO criteria, and the statements developed adopting the GRADE methodology.
CONCLUSIONS
In patients with acute anal fissure the medical therapy with dietary and behavioral norms is indicated. In the chronic phase of disease, the conservative treatment with topical 0.3% nifedipine plus 1.5% lidocaine or nitrates may represent the first-line therapy, eventually associated with ointments with film-forming, anti-inflammatory and healing properties such as Propionibacterium extract gel. In case of first-line treatment failure, the surgical strategy (internal sphincterotomy or fissurectomy with flap), may be guided by the clinical findings, eventually supported by endoanal ultrasound and anal manometry.
Topics: Humans; Fissure in Ano; Colorectal Surgery; Lidocaine; Colon; Chronic Disease; Anal Canal; Treatment Outcome
PubMed: 37833715
DOI: 10.1186/s12893-023-02223-z -
Cancers May 2024High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC). Artificial intelligence (AI)...
Deep Learning and High-Resolution Anoscopy: Development of an Interoperable Algorithm for the Detection and Differentiation of Anal Squamous Cell Carcinoma Precursors-A Multicentric Study.
High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC). Artificial intelligence (AI) algorithms have shown high levels of efficiency in detecting and differentiating HSIL from low-grade squamous intraepithelial lesions (LSIL) in HRA images. Our aim was to develop a deep learning system for the automatic detection and differentiation of HSIL versus LSIL using HRA images from both conventional and digital proctoscopes. A convolutional neural network (CNN) was developed based on 151 HRA exams performed at two volume centers using conventional and digital HRA systems. A total of 57,822 images were included, 28,874 images containing HSIL and 28,948 LSIL. Partial subanalyses were performed to evaluate the performance of the CNN in the subset of images acetic acid and lugol iodine staining and after treatment of the anal canal. The overall accuracy of the CNN in distinguishing HSIL from LSIL during the testing stage was 94.6%. The algorithm had an overall sensitivity and specificity of 93.6% and 95.7%, respectively (AUC 0.97). For staining with acetic acid, HSIL was differentiated from LSIL with an overall accuracy of 96.4%, while for lugol and after therapeutic manipulation, these values were 96.6% and 99.3%, respectively. The introduction of AI algorithms to HRA may enhance the early diagnosis of ASCC precursors, and this system was shown to perform adequately across conventional and digital HRA interfaces.
PubMed: 38791987
DOI: 10.3390/cancers16101909 -
PloS One 2023Ablation or surgical excision is the typical treatment of anal high-grade squamous intraepithelial lesions (HSIL). Recurrences are common due to the persistence of...
BACKGROUND
Ablation or surgical excision is the typical treatment of anal high-grade squamous intraepithelial lesions (HSIL). Recurrences are common due to the persistence of underlying human papillomavirus (HPV) infection. Additional well-tolerated and effective non-surgical options for HPV-associated anal disease are needed.
METHODS
This 3+3 dose escalation Phase I clinical trial evaluated the safety and tolerability of artesunate suppositories in the treatment of patients with biopsy-proven HSIL.
RESULTS
The maximal tolerated dose was 400 mg, administered in 3 cycles. All adverse events associated with the use 200- and 400-mg artesunate suppositories were Grade 1. At the 600-mg dose, patients experienced clinically significant nausea.
CONCLUSION
Artesunate suppositories are a safe treatment option for anal HSIL.
Topics: Humans; Male; Artesunate; Suppositories; Papillomavirus Infections; Squamous Intraepithelial Lesions; Anal Canal; Anus Neoplasms; HIV Infections; Homosexuality, Male
PubMed: 38100463
DOI: 10.1371/journal.pone.0295647 -
Cureus Nov 2023Anal mucinous adenocarcinomas are very rare and usually arise from anal fistulas. We report a case of a 73-year-old man with a past medical history of hypertension...
Anal mucinous adenocarcinomas are very rare and usually arise from anal fistulas. We report a case of a 73-year-old man with a past medical history of hypertension admitted to our facility for evaluation of bleeding from a large, tender, left gluteal perianal mass. The patient reported the mass had been growing for over six years. On examination, an ulcerated, fungating large exophytic lesion was found extending from the anal verge laterally engulfing the left gluteus. The patient was anemic with low hemoglobin and hematocrit, as well as an elevated carcinoembryonic antigen level. A colonoscopy was performed during which an internal opening of a left-sided anal fistula was identified. The mass was biopsied and returned positive for a mucinous adenocarcinoma. Staging imaging including a computed tomography scan of the chest abdomen and pelvis did not show any metastatic disease. A magnetic resonance image of the pelvis revealed a locally invasive, heterogeneous tumor extending from the perianal soft tissue to the posterior wall of the anal canal and lower rectum. The patient was discussed at the interdisciplinary tumor board and completed five weeks of concurrent chemotherapy and radiation with 5-fluorouracil and a total of 28 fractions of radiation. He then underwent abdominoperineal resection with a vertical rectus abdominis myocutaneous flap. The patient was placed in the surgical intensive care unit and subsequently discharged in stable condition on postoperative day 14. This case highlights the presentation, diagnosis, and management of anal mucinous adenocarcinoma.
PubMed: 38058344
DOI: 10.7759/cureus.48314 -
Clinics in Colon and Rectal Surgery Jan 2024Restorative proctocolectomy with ileal pouch-anal anastomosis remains the gold standard treatment for patients with ulcerative colitis who desire restoration of... (Review)
Review
Restorative proctocolectomy with ileal pouch-anal anastomosis remains the gold standard treatment for patients with ulcerative colitis who desire restoration of intestinal continuity. Despite a significant cancer risk reduction after surgical removal of the colon and rectum, dysplasia and cancers of the ileal pouch or anal transition zone still occur and are a risk even if an anal canal mucosectomy is performed. Surgical care and maintenance after ileoanal anastomosis must include consideration of malignant potential along with other commonly monitored variables such as bowel function and quality of life. Cancers and dysplasia of the ileal pouch are rare but sometimes difficult-to-manage sequelae of pouch surgery.
PubMed: 38188063
DOI: 10.1055/s-0043-1762562