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OBJECTIVES: Anal cancer risk is elevated in MSM with HIV (MSMWH). Anal high-risk human papillomavirus (hr-HPV) infection is necessary but insufficient to develop high-grade squamous intraepithelial lesion (HSIL), the anal cancer precursor, suggesting additional factors. We sought to determine whether the microbiome of the anal canal is distinct by comparing it with the microbiome of stool. We also sought to determine whether changes in the anal microbiome are associated with HSIL among MSMWH. DESIGN: Cross-sectional comparison of the microbiome of the anal canal with the microbiome of stool in MSMWH and cross-sectional comparison of the anal microbiome of MSMWH with anal HSIL with the anal microbiome of MSMWH without anal HSIL. METHODS: Sterile swabs were used to sample the anus of MSMWH for microbiome and HPV testing, followed by high-resolution anoscopy. Stool samples were mailed from home. 16S sequencing was used for bacterial identification. Measures of alpha diversity, beta diversity, and differential abundance analysis were used to compare samples. RESULTS: One hundred sixty-six anal samples and 103 matching stool samples were sequenced. Beta diversity showed clustering of stool and anal samples. Of hr-HPV-positive MSMWH, 31 had HSIL and 13 had no SIL. Comparison of the microbiome between these revealed 28 different species. The highest-fold enrichment among MSMWH/hr-HPV/HSIL included pro-inflammatory and carcinogenic Prevotella, Parasuterella, Hungatella, Sneathia, and Fusobacterium species. The anti-inflammatory Anaerostipes caccae showed the greatest reduction among MSMWH/hr-HPV/HSIL. CONCLUSION: The anal microbiome is distinct from stool. A pro-inflammatory and carcinogenic environment may be associated with anal HSIL.

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.

L'actualité en oncologie radiothérapie est marquée par les résultats d'essais stratégiques particulièrement pour les cancers de l'œsophage et du rectum. Pour l'adénocarcinome de l'œsophage, en situation préopératoire, les résultats de l'étude ESOPEC ont montré un bénéfice de survie de la chimiothérapie périopératoire par 5-fluoro-uracile, leucovorine oxaliplatine, taxotère en comparaison à la chimioradiothérapie (irradiation de 41,4 Gy avec une chimiothérapie concomitante par carboplatine/paclitaxel). En situation exclusive, l'étude CONCORDE n'a pas montré de bénéfice de l'escalade de dose et la dose standard reste 50 Gy. Pour le cancer du pancréas opérable, l'étude NRG/RTOG0848 qui comparait la chimiothérapie adjuvante avec ou sans chimioradiothérapie complémentaire a retrouvé une augmentation significative de la probabilité de survie sans maladie à 5 ans dans le sous-groupe de patients sans atteinte ganglionnaire. Pour les cancers du rectum, l'actualisation à 7 ans des résultats de l'étude PRODIGE 23 a confirmé le bénéfice non seulement en termes de survie sans récidive mais également de survie globale d'une chimiothérapie néoadjuvante par 5-fluoro-uracile, acide folinique, irinotécan et oxalipalatine avant la chimioradiothérapie, alors que l'actualisation de l'étude RAPIDO a montré un taux de rechute locale inacceptable dans le bras expérimental. L'actualisation de l'étude OPRA a montré un taux de survie avec conservation d'organe à 5 ans significativement supérieur en faveur du bras chimioradiothérapie suivie de la chimiothérapie en comparaison à la chimiothérapie d'induction première suivie de chimioradiothérapie. Une étude de phase 2 incluant 41 patients atteints d'un cancer du rectum localement avancé avec défaillance du système de réparation de l'ADN, a montré qu'un traitement exclusif par immunothérapie anti-PDL1 (dostarlimab) pendant 6 mois permettait une réponse clinique complète sans recours à un traitement complémentaire (ni radiothérapie, ni chirurgie). Pour le carcinome épidermoïde du canal anal, la survie et les profils de toxicité des patients inclus dans la cohorte anabase traités pour une tumeur de petit stade (T1 ou T2) ont été comparés selon qu'ils aient reçu exclusivement de la radiothérapie ou de la chimioradiothérapie. L'ajout d'une chimiothérapie à la radiothérapie ne montrait pas de bénéfice mais augmentait la toxicité et le risque d'allongement du traitement en raison d'interruption. Current events in radiotherapy oncology are marked by the results of strategic trials, particularly for esophageal and rectal cancers. For resectable esophageal adenocarcinoma, results of the ESOPEC study showed a benefit in overall survival from the perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin and docetaxel compared to chemoradiotherapy (41.4 Gy radiotherapy and carboplatin/paclitaxel chemotherapy). In definitive setting, the CONCORDE study did not show any benefit from dose escalation and the standard dose remains 50 Gy. For resectable pancreatic cancer, the NRG/RTOG0848 study that compared adjuvant chemotherapy with or without chemoradiotherapy found a significant increase of the 5-year disease-free survival rate in the subgroup of node-negative patients. For rectal cancers, the 7-year update of PRODIGE 23 study confirmed the benefit in disease-free- and overall survival of neoadjuvant folinic acid, fluorouracil, irinotecan and oxaliplatin chemotherapy before chemoradiotherapy of T3, T4 or N+ adenocarcinoma, while the update of the RAPIDO study revealed an unacceptable local recurrence rate in the experimental arm. The update of the OPRA study shows a significantly higher 5-year organ preservation rate in favor of the chemoradiotherapy arm followed by consolidation chemotherapy compared to induction chemotherapy followed by CRT. A phase 2 study, including 41 patients with mismatch repair deficient, locally advanced rectal cancer reported that exclusive treatment with anti-PDL1 immunotherapy (dostarlimab) for 6 months resulted in complete clinical response without the need of additional treatment (neither radiotherapy nor surgery). For anal carcinoma, the analysis of survival and toxicity profiles of patients treated for a small stage T1 or T2 tumor were compared depending on whether they received exclusive radiotherapy or chemoradiotherapy. The addition of chemotherapy to radiotherapy did not show any survival benefit but significantly increased toxicity and the risk of radiotherapy disruption. [ABSTRACT FROM AUTHOR]

Background: In placebo‐controlled clinical trials, reboxetine, a selective noradrenaline reuptake inhibitor, increases urethral pressure and relieves stress urinary incontinence symptoms in women. Considering the close connection in neural regulation of the external urethral and anal sphincters, we hypothesized that reboxetine may also enhance anal sphincter pressure. Conversely, it is believed that selective serotonin reuptake inhibitors may contribute to fecal incontinence by reducing anal sphincter pressure. In this study, we investigated the effect of reboxetine and citalopram on anal opening pressure in healthy female volunteers. Methods: In a double‐blind, three‐way crossover trial, 24 female participants received single doses of 40 mg citalopram, 8 mg reboxetine, and matching placebos, with a minimum of 8‐day washout between sessions. Using anal acoustic reflectometry, we measured anal opening pressure during both resting and squeezing conditions at the estimated time of peak plasma concentration for both study drugs. Key Results: Compared with placebo, reboxetine increased anal opening pressure with 23.4 cmH2O (95% confidence interval [CI] 16.5–30.2, p < 0.001) during rest and with 22.5 cmH2O (95% CI 15.2–29.8, p < 0.001) during squeeze. Citalopram did not change anal opening pressure statistically significantly compared to placebo. Conclusions & Inferences: An 8‐mg dose of reboxetine increased anal opening pressure substantially in healthy women, suggesting potential benefits for fecal incontinence symptoms. In contrast, a 40‐mg dose of citalopram showed a marginal and statistically insignificant effect on anal opening pressure, indicating that selective serotonin reuptake inhibitors do not contribute to fecal incontinence by reducing anal sphincter tone. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: Despite the high prevalence of fecal incontinence, existing treatment options may be inadequate. Drugs that enhance the tone of the anal sphincter complex could potentially be an effective pharmacological approach. This study investigated the effect of the tricyclic antidepressant imipramine on anal sphincter tone in healthy women, employing anal acoustic reflectometry as the evaluating method. Methods: In a double-blind, randomized, placebo-controlled crossover study, 16 healthy female volunteers were randomized to one of two treatment sequences. The participants attended two study visits separated by at least 7 days' washout. At each visit, they received a single dose of 50 mg imipramine or matching placebo, in alternating order. We assessed the anal opening pressure under the resting state and during voluntary squeezing of the pelvic floor. Measurements were performed pre-dose and 1 h after drug administration, corresponding to the estimated time of peak plasma concentration of imipramine. Results: All participants completed the study. In total, 44% of the participants reported at least one adverse effect, primarily anticholinergic. Compared with placebo, imipramine increased anal opening pressure by 15.2 cmH2O (95% confidence interval [CI] 2.0–28.2 cmH2O, p = 0.03) in the resting state and 15.1 (95% CI 4.2–26.0 cmH2O, p = 0.01) cmH2O during squeezing. Conclusions: The findings indicate that imipramine increases anal sphincter tone in healthy women. However, further research is required to evaluate its clinical impact on individuals with fecal incontinence. This research also demonstrates the effectiveness of using anal acoustic reflectometry for assessing pharmacological effects on anal sphincter function. [ABSTRACT FROM AUTHOR]

Objectives: To assess the feasibility of acquiring adequate transperineal ultrasound (TPUS) volumes of the anal sphincter (AS) immediately after vaginal birth, the reproducibility of its measurements, and detecting defects therein. Methods: Secondary analysis of TPUS volumes of the AS, acquired immediately after vaginal birth with a transversely oriented convex probe. Two independent experts ranked off‐line image quality as "inadequate," "adequate," or "ideal" using the Point‐of‐Care Ultrasound Image Quality scale. On "adequate" and "ideal" quality volumes, the length of the external AS at 6 and 12 o'clock, and the volume of the external and internal AS were measured. Additionally, volumes were screened for AS defects on tomographic ultrasound imaging. Subsequently, we rated the intra‐ and interrater agreement on those findings. Results: Of 183 volumes, 162 were considered "adequate" or of "ideal" quality (88.5%). Reasons for "inadequacy" were shadow artifacts (16/21), poor resolution (3/21), incomplete acquisition (1/21), or aberrant AS morphology (1/21). The intrarater reliability of two‐dimensional (2D) and three‐dimensional (3D) measurements was excellent, whereas interrater reliability was fair to good for 2D measurements and good for 3D measurements. In those tomographic ultrasound imaging (TUI) sequences including AS defects, the intra‐ and interrater reliability of the defect measurement were excellent [intraclass correlation coefficient (ICC) = 0.92 (0.80–0.94)] and moderate [ICC = 0.72 (0.63–0.79)]. In this cohort, there were only few (4/48; 8.3%) AS defects. However, grading them was poorly reproducible between experts. Conclusion: TPUS of the AS immediately after vaginal birth yields adequate image quality and allows for reproducible measurements. In the few patients with AS defects, there was good agreement on the presence, but it was poor for the extent of defects. [ABSTRACT FROM AUTHOR]

Abstract Purpose To share our experience in the management of a specific type of mild anorectal anomaly presenting with severe constipation. Methods Data of patients with idiopathic constipation who were referred to our pediatric surgical facility during the period from 2013 to 2023 were retrospectively analyzed. The study included patients with significant symptoms of constipation associated with a minor degree of unrecognized anterior anal misplacement. MRI was ordered in most cases to confirm the presence of deeper structural abnormalities. Results Data from 16 cases were available for retrospective analysis. All included cases underwent posterior anoplasty with posterior sphincterotomy. Postoperative recovery was uneventful in all cases with no wound complications. Almost all cases reported obvious improvement of symptoms regarding frequency of defecation and relief of straining which was the most distressing preoperative complaint. After 1 month, 12 cases were off laxatives with regular defecation; 3 cases still required lower doses of laxatives. Only one case reported unsatisfactory response up to 3 months postoperatively, and unfortunately was lost to follow-up. Five cases responded to messages sent to them through registered phone numbers and were available for longer-term follow-up. Conclusion Mild unrecognized forms of anorectal anomalies may present with idiopathic constipation. Severe straining at defecation is an important clue. The subtle abnormality on perineal examination can be supported by pelvic MRI unveiling more structural abnormalities at a deeper level. Posterior anoplasty offered relief of symptoms in most cases.

Background: Superficially invasive squamous cell carcinoma (SISCC) and high-grade squamous intraepithelial lesions (HSIL) involving the anal canal are rare, and their surgical management involves local excision. Endoscopic submucosal dissection (ESD) has recently emerged as a promising treatment. This study aimed to evaluate the feasibility and safety of ESD for SISCC and HSIL in the anal canal. Methods: All patients diagnosed with SISCC or HSIL in the anal canal who underwent ESD between November 2018 and May 2023 were included. Patient age, sex, pathology, human immunodeficiency virus (HIV) status, human papillomavirus (HPV) status, T stage, en bloc rate, and R0 resection rate were analyzed. Results: Ten patients, including two men and eight women, with a median age of 61 (51–68) years were enrolled. All patients were HIV-negative, but five (50%) were HPV-positive. Pathological examination showed tumor stage of two patients as T2, one as T0 of SISCC, and seven as Tis of HSIL. The median specimen and tumor sizes were 24 (6–65) mm and 18 (6–55) mm, respectively. The en bloc and R0 resection rates were 100% and 80%, respectively. No severe complications occurred and no recurrence was observed at the follow-up (median follow-up period, 9 (1–35) months). Conclusions: ESD is a reliable and minimally invasive procedure that enables more individualized treatment options for specific groups. As we were limited by the length of the observation period, the long-term performance of ESD for SISCC and HSIL involving the anal canal requires further investigation. [ABSTRACT FROM AUTHOR]

Objectives: To elucidate the male urethral muscular structure and its relationship with the anorectal canal muscles, as establishing an anatomical foundation for urethral function will contribute to the prevention, diagnosis, and treatment of urinary incontinence. Methods: Eight male cadavers were used. Using a multifaceted approach, we performed macroscopic anatomical examination, histological analysis of wide‐range serial sectioning and immunostaining, and three‐dimensional (3D) reconstruction from histological sections. In the macroscopic anatomical examination, pelvic halves were meticulously dissected in layers from the medial aspect. In the histological analysis, the tissue, including the urethra and anorectal canal, was serially sectioned in the horizontal plane. The muscular structures were reconstructed and visualised in 3D. Results: The membranous portion of the urethra had three muscle layers: the longitudinal and circular muscles (smooth muscle) and the external urethral sphincter (skeletal muscle). The circular muscle was connected posteriorly to the longitudinal rectal muscle. The external urethral sphincter had a horseshoe shape, with its posterior ends continuing to the external anal sphincter, forming a 3D ring‐like sphincter. Conclusion: This study revealed skeletal and smooth muscle connections between the male urethra and anorectal canal, enabling urethral compression and closure. These anatomical muscle connections suggest a functional linkage between them. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Extensive studies are required to understand the behavior as well as prognosis of SS in the colorectal region. IHC staining is essential for the accurate diagnosis when a lesion is encountered at an unusual site. [ABSTRACT FROM AUTHOR]

BACKGROUND: Autologous fat grafting (AFG) has shown promise in the treatment of complex wounds, with trials reporting good healing rates and safety profile. We aim to investigate the role of AFG in managing complex anorectal fistulas. METHODS: This was a retrospective review of a prospectively maintained IRB-approved database. We examined the rates of symptom improvement, clinical closure of fistula tracts, recurrence, complications, and worsening fecal incontinence. Perianal disease activity index (PDAI) was obtained for patients undergoing combination of AFG and fistula plug treatment. RESULTS: In total, 52 unique patients underwent 81 procedures, of which Crohns was present in 34 (65.4%) patients. The majority of patients previously underwent more common treatments such as endorectal advancement flap or ligation of intersphincteric fistula tract. Fat-harvesting sites and processing technique were selected by the plastic surgeons based on availability of trunk fat deposits. When analyzing patients by their last procedure, 41 (80.4%) experienced symptom improvement, and 29 (64.4%) experienced clinical closure of all fistula tracts. Recurrence rate was 40.4%, and complication rate was 15.4% (7 postoperative abscesses requiring I&D and 1 bleeding episode ligated at bedside). The abdomen was the most common site of lipoaspirate harvest at 63%, but extremities were occasionally used. There were no statistically significant differences in outcomes when comparing single graft treatment to multiple treatments, Crohns and non-Crohns, different methods of fat preparation, and diversion. CONCLUSION: AFG is a versatile procedure that can be done in conjunction with other therapies and does not interfere with future treatments if recurrence occurs. It is a promising and affordable method to safely address complex fistulas.

An ongoing debate exists regarding the feasibility of placing self-expanding metallic stents (SEMS) within 5 cm of the anal verge. Traditionally, SEMS have been considered contraindicated for patients with a malignant rectal obstruction within this region due to potential impact on the anorectal ring or anal canal, which can cause incontinence, proctalgia, and tenesmus. However, in the case of a 63-year-old female who presented with distention, abdominal pain, and diminishing stool output, the rectal exam identified a bulky fixed mass. Imaging studies revealed large bowel obstruction and high-grade stricture, with a minuscule residual lumen. Endoscopy identified a bulky mass obscuring the lumen at 5 cm from the anal verge, and biopsy confirmed adenocarcinoma. Despite the traditionally held contraindication, a 2.5 cm × 9.0 cm colonic stent was successfully deployed, leading to brisk colonic decompression. This allowed the patient to promptly undergo chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Transanal excision of benign lesions, moderately or well-differentiated rectal T1 adenocarcinomas is typically completed via transanal endoscopic microsurgery (TEM) or laparoscopic transanal minimally invasive surgery (TAMIS). Robotic platforms provide ergonomic comfort in an enclosed space, enhanced range of motion, and superior 3D visualization. This study sought to perform a literature review of robotic TAMIS (R-TAMIS) and provide expert commentary on the technique. A Pubmed literature search was performed. Study design, robot type, indication, techniques compared, surgical margins, conversion, complications, operative time, estimated blood loss, patient positioning, and defect closure were collected from included articles. Expert opinion on pre-operative planning, technical details, and possible pitfalls was provided, with an accompanying video. Twelve articles published between 2013 and 2022 were included. Five were case reports, three case series, two prospective cohort studies, one retrospective cohort study, and one Phase II trial. The Da Vinci Si (n = 3), Xi (n = 2), single port (n = 3) and flex robotic system (n = 2) were used. Five studies reported negative surgical margins, one reported positive margins, and six did not comment. Operating room time ranged from 45 to 552 min and EBL ranged from 0 to 100 mL. Patient positioning varied based on lesion location but included supine, prone, modified lithotomy, and prone jackknife positions. 11/12 studies reported defect closure, most commonly with V-Loc absorbable suture. We recommend pre-operative MRI abdomen/pelvis, digital rectal exam, and rigid proctoscopy; prone jackknife patient positioning to avoid collisions with robotic arms; and defect closure of full-thickness excisions with backhanded running V-Loc suture.

The current standard of care for anal squamous cell carcinoma (ASCC) is definitive concurrent chemoradiotherapy (CRT). However, about a third of patients may experience treatment failure. Recently, immunotherapy has emerged as a novel strategy for metastatic ASCC patients. We evaluated the efficacy and safety of surgery, CRT alone, and CRT with immunotherapy (CRT-I) in 100 nonmetastatic ASCC patients, treated from April 2012 through May 2023, by determining survival outcomes and acute adverse events. The median (range) follow-up was 30.7 (7.6 to 134.9) months. The study cohort 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were 80.7 %, 62.2 %, 71.1 %, and 67.6 %, respectively. The Surgery group had significantly lower rates than the CRT and CRT-I groups for 3-year PFS (33.1% vs. 65.2% vs. 92.9 %, P < 0.001), DMFS (46.7% vs. 74.6% vs. 92.9 %, P = 0.002) and LRFS (37.0% vs. 73.3% vs. 92.9 %, P < 0.001), respectively. All patients receiving CRT-I were alive at last follow-up. Of 100 patients, 26 (26.0 %) experienced severe (≥ grade 3) acute toxicity. Of 24 patients receiving CRT-I, 8 (33.3 %) had severe acute toxicity. Using immunohistochemistry, peritumoural stromal infiltration by CD8+ T cells was significantly higher after CRT-I compared to before CRT-I and to after CRT alone. The addition of immunotherapy to CRT may be an effective first-line treatment option with favourable survival outcomes and acceptable toxicity for patients with ASCC. A prospective, randomized trial assessing the efficacy of CRT combined with a PD-1 inhibitor in patients with locally advanced ASCC is in progress.

BackgroundUnderstanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized.MethodsWe reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants.ResultsHuman papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection.ConclusionsThis robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

BackgroundAge-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention.MethodsWe centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology.ResultsIn HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+.ConclusionsAge-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

Many mammals rely on volatile organic chemical compounds (VOCs) produced by bacteria for their communication and behavior, though little is known about the exact molecular mechanisms or bacterial species that are responsible. We used metagenomic sequencing, mass-spectrometry based metabolomics, and culturing to profile the microbial and volatile chemical constituents of anal gland secretions in twenty-three domestic cats (Felis catus), in attempts to identify organisms potentially involved in host odor production. We found that the anal gland microbiome was dominated by bacteria in the genera Corynebacterium, Bacteroides, Proteus, Lactobacillus, and Streptococcus, and showed striking variation among individual cats. Microbiome profiles also varied with host age and obesity. Metabolites such as fatty-acids, ketones, aldehydes and alcohols were detected in glandular secretions. Overall, microbiome and metabolome profiles were modestly correlated (r = 0.17), indicating that a relationship exists between the bacteria in the gland and the metabolites produced in the gland. Functional analyses revealed the presence of genes predicted to code for enzymes involved in VOC metabolism such as dehydrogenases, reductases, and decarboxylases. From metagenomic data, we generated 85 high-quality metagenome assembled genomes (MAGs). Of importance were four MAGs classified as Corynebacterium frankenforstense, Proteus mirabilis, Lactobacillus johnsonii, and Bacteroides fragilis. They represent strong candidates for further investigation of the mechanisms of volatile synthesis and scent production in the mammalian anal gland.

Purpose: The JCOG (Japan Clinical Oncology Group) 0212 study did not confirm the noninferiority of mesorectal excision (ME) alone to ME with LLND for rectal or anal adenocarcinomas. Furthermore, the significance of LLND for SCCs remains unknown. We evaluated the significance of lateral lymph node dissection (LLND) of squamous cell carcinoma (SCC) of the anal canal. Methods: This retrospective cohort study was conducted in 435 patients with SCCs among 1,781 patients with anal canal tumors. In 40 patients who underwent LLND, the 5-year relapse-free survival (5y-RFS) and 5-year overall survival (5y-OS) were compared between groups with positive and negative histopathological findings. In 71 patients with negative lateral lymph node metastasis in the preoperative diagnosis, the 5y-RFS, 5y-OS, and 5-year local recurrence-free survival were compared between patients who did and did not undergo LLND. Results: The clinical and pathological T stages predicted pathological lateral pelvic lymph node metastasis. There was no statistically significant difference in 5y-RFS and 5y-OS between patients who did and did not undergo LLND. Among patients who underwent LLND, 5y-RFS in those with positive histopathological findings (15.0%) was worse than that in those without (59.2%) (p = 0.002). Conclusions: In patients who underwent LLND, 5y-RFS in those with positive histopathological findings than in those without LLND did not contribute to prognosis. [ABSTRACT FROM AUTHOR]

Objective: This study explores the role of pelvic floor (PF) muscles in individuals with anal area diseases and defecation irregularities. Materials and Methods: Anorectal angle (ARA), pubococcygeal line (PCL), and the distance between ARA and PCL were measured retrospectively in 392 images from patients over 18 years old who underwent lower abdomen magnetic resonance (MR) defecography (sagittal, T2 sequence). The patients presented with complaints of fecal incontinence, chronic constipation, anal fissures, hemorrhoids, anal abscesses, and anal or perianal fistulas. Measurements were taken during three phases: rest, Valsalva maneuver, and the final phase of defecation. Patients were categorized according to the World Health Organization's age classification, and average ages for childbirth and menopause were determined using data from the Turkish Statistical Institute. Results: Across all patients, the ARA did not sufficiently constrict during Valsalva, and was wider in women during all defecation phases. The ARA was wider at rest in patients aged 65 and over, and during the final defecation phase in the 45-64 age group compared to other age groups. Throughout all phases of defecation, the PCL was longer in women and in the 45-64 age group than in others; PF descent during Valsalva and the final phase was greater in these groups as well. Conclusion: The findings highlight that PF insufficiency is more pronounced in the postmenopausal period. Evaluation of the PF should be integrated into the diagnostic and treatment protocols for anal area diseases, with an emphasis on PF rehabilitation. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of anal squamous cell carcinoma (ASCC) is increasing worldwide, with a significant proportion of patients treated with curative intent having recurrence. The ability to accurately predict progression-free survival (PFS) and overall survival (OS) would allow for development of personalised treatment strategies. The aim of the study was to train and external test radiomic/clinical feature derived time-to-event prediction models. Methods: Consecutive patients with ASCC treated with curative intent at two large tertiary referral centres with baseline FDG PET-CT were included. Radiomic feature extraction was performed using LIFEx software on the pre-treatment PET-CT. Two distinct predictive models for PFS and OS were trained and tuned at each of the centres, with the best performing models externally tested on the other centres' patient cohort. Results: A total of 187 patients were included from centre 1 (mean age 61.6 ± 11.5 years, median follow up 30 months, PFS events = 57/187, OS events = 46/187) and 257 patients were included from centre 2 (mean age 62.6 ± 12.3 years, median follow up 35 months, PFS events = 70/257, OS events = 54/257). The best performing model for PFS and OS was achieved using a Cox regression model based on age and metabolic tumour volume (MTV) with a training c-index of 0.7 and an external testing c-index of 0.7 (standard error = 0.4). Conclusions: A combination of patient age and MTV has been demonstrated using external validation to have the potential to predict OS and PFS in ASCC patients. Clinical relevance statement: A Cox regression model using patients' age and metabolic tumour volume showed good predictive potential for progression-free survival in external testing. The benefits of a previous radiomics model published by our group could not be confirmed on external testing. Key Points: • A predictive model based on patient age and metabolic tumour volume showed potential to predict overall survival and progression-free survival and was validated on an external test cohort. • The methodology used to create a predictive model from age and metabolic tumour volume was repeatable using external cohort data. • The predictive ability of positron emission tomography-computed tomography–derived radiomic features diminished when the influence of metabolic tumour volume was accounted for. [ABSTRACT FROM AUTHOR]

Key Clinical Message Extensive studies are required to understand the behavior as well as prognosis of SS in the colorectal region. IHC staining is essential for the accurate diagnosis when a lesion is encountered at an unusual site.

Introduction: Anal canal melanoma is a rare form of both anal cancer and skin melanoma, representing 1% of all anal cancers. Diagnosis is often made at an advanced disease stage. Because of late diagnosis and aggressive clinical course, anal canal melanoma has a very poor prognosis. Case Presentation: We present the case of a 61-year-old female with anal canal melanoma and lung, liver, pelvic and central nervous system (CNS) metastasis, BRAF V600E mutated. Combined BRAF/MEK inhibition and CNS radiation therapy were able to achieve excellent local and distant disease control. Conclusion: Anal canal melanoma is a rare and aggressive form of melanoma. Multidisciplinary management in experienced centers is mandatory for good clinical outcomes.

Anorectal mucosal melanoma is rare entity. There is currently no consensus on optimal surgical treatment for loco-regional anorectal melanoma that has a favourable outcome. Abdominoperineal resection has not shown a survival benefit over wide local excision due to the inevitable distant recurrence. With local excision considered favourable given reduced surgical morbidity and avoidance of permanent stoma. However, anorectal melanomas are often diagnosed late, with an increased tumour size and depth of primary lesions, increasing the risk of local recurrence and subsequent disease morbidity when excised locally. The decision to proceed to local excision versus abdominoperineal resection is complex, it needs to be individualized, based on primary tumour clinicopathological features and driven by multidisciplinary discussion, with the goal to improve quality and quantity of life. We present a case of a 66-year-old female with anorectal mucosal melanoma with locoregional disease and our surgical approach. [ABSTRACT FROM AUTHOR]

BackgroundRisk of anal squamous cell carcinoma (anal cancer) is greater among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). We describe the frequency of and factors associated with abnormal anal cytology results in Colombian MSM living with HIV.MethodsThis retrospective observational cohort study included MSM ≥18 years old living with HIV screened with anal cytology at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2019 and February 2020. A multivariable log-binomial regression model estimated associations with abnormal anal cytology.ResultsA total of 211 patients were included. Mean age was 35.6 years. Sixty-eight (32.3%) had an abnormal anal cytology result: ASC-US 33.8% (n = 23); LSIL 60.3% (n = 41); and HSIL 5.9% (n = 4). MSM with an STI diagnosis in the previous 12 months (RR 1.48, [95% CI 1.03-2.12], p = 0.032) or with a CD4+ T cell count

The purpose of the present trial was to determine the feasibility of the daily topical application of the piperidine nitroxide, MTS‑01, combined with chemoradiotherapy in the treatment of patients with anal carcinoma. The secondary study endpoints were the description of the effects of this agent on skin toxicity and rectal‑associated lymphoid tissue. The participants received radiotherapy concurrent with mitomycin‑C and 5‑fluorouracil for carcinoma of the anal canal. MTS‑01 was applied to the bilateral inguinal area and the gluteal cleft. Dermatologic and non‑dermatologic toxicity was graded throughout the treatment period. Circulating lymphocytes were serially collected for phenotyping. Rectal mucosal snag biopsies were collected at baseline and at 1 year of follow‑up. A total of 5 patients received topical MTS‑01. Adverse events attributed to MTS‑01 included asymptomatic grade 1 hypoglycemia and grade 1‑2 diarrhea. Dermatitis within untreated, radiated skin was not more severe than dermatitis in MTS‑01‑treated, unirradiated skin. Circulating CD4+ lymphocyte suppression was noted at >1 year following treatment in human immunodeficiency virus‑negative participants. CD4+ lymphocytes remained suppressed in the irradiated rectal mucosa at 1 year, whereas the CD8+ lymphocyte numbers recovered or increased. On the whole, the present study demonstrates that the MTS‑01 topical application was tolerable with minimal toxicity. Chemoradiation for anal cancer led to prolonged CD4+ lymphocytopenia in the circulation and gut mucosa.

Anal squamous intraepithelial lesions (ASILs) correspond to premalignant changes preceding the development of anal squamous cell carcinoma. To describe a new endoscopic technique to detect and remove ASILs in non-anesthetized patients and compare it with standard surgical treatment. For endoscopic treatment, high resolution (HR) flexible endoscopes with a distal attachment were used. Underwater inspection of the anal canal was performed in near-focus mode with white light and narrow-band imaging. Detected lesions were resected with a diathermia snare after local injection of xylocaine/adrenaline. We did a retrospective comparison of all patients who underwent endoscopic or standard surgical treatment for ASILs at Ersta hospital in Stockholm between 2018 and 2020. Patient files were reviewed for number of lesions, treatments until macroscopic radicality, degree of dysplasia, bleeding, pain and other complications. Endoscopic (n = 37) and surgical (n = 43) treatment displayed comparable number of lesions per patient (p =.37). The number of procedures until macroscopic radicality was higher for endoscopy than surgery (p =.04). However, in endoscopic follow up of 12 of the surgically treated patients, residual ASIL was found in 10 cases. Post-procedural bleeding requiring healthcare occurred in two endoscopy patients and one surgically treated patient. Underwater resection using a HR flexible endoscope in non-anesthetized is a new, feasible and well tolerated method for ASILs treatment. Its efficacy and risk of complications seem comparable to standard surgical treatment while avoiding general anesthesia. However, minor lesions might be overlooked at surgery. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical characteristics and treatments of anal canal duplication (ACD) in children. Methods The relevant clinical data were retrospectively reviewed for two ACD children. More related cases were retrieved from the relevant Chinese and English literature reports of the databases of PubMed, Medline, Web of Science, CNKI and Wanfang from 1993 to 2022. Results Two neonates presented with sagittal anal orifice discovered by their mothers. There were no other associated anomalies. Fistulography revealed a tubular structure in two cases and proximal end of lumen communicated with rectum in case 2. Dissection was performed via a posterior sagittal approach. Histological examination hinted at squamous epithelium with smooth muscle bundles. Both cases achieved excellent cosmetics with normal sphincter control. A total of 76 cases of ACD have been reported. There were 9 boys and 67 girls with a mean diagnostic age of 3.5(0-16) year; 93%(71/76) of lesion were located at 6 o'clock behind anus; 91%(69/76) was tubular and 9%(69/76) cystic. And 87%(66/76) were asymptomatic or mildly symptomatic (a mean age of 2.8 year); 13%(10/76) developed presacral abscesses (a mean age of 7.7 year); 33%(25/76) presented associated anomalies, including presacral mass (44%); 70 children underwent surgical removal (perineal approach, n=34; posterior sagittal approach, n=36) and postoperative complications occurred (4%, 3/70). Bowel function normalized during a mean follow-up period of 3.6 years (1 month to 19 years). Conclusions A clinical diagnosis of ACD should be suspected for an opening in posterior anal midline, particularly in girls. Associated anomalies should be ruled out. Early surgery is recommended. ACD removal via a posterior sagittal approach is both safe and effective. [ABSTRACT FROM AUTHOR]

Background: Despite increases in the lifetime prevalence of anal intercourse, little is known about the safety of inflatable penile prosthesis use during anal intercourse or the forces required for anal penetration. Aim: We sought to determine the force required for anal penetration. Methods: A digital force gauge device was secured to a silicone phallus with a length and girth representative of the average male phallus in the United States and inserted into the anal canal of 6 male participants for a total of 5 measurements per participant. The maximum axial forces on insertion were recorded. Participants then completed a survey eliciting demographic information and past experience with receptive anal intercourse. Outcomes: The outcome measure was the force recorded during insertion of a force gauge device into the anal canal. Results: The median maximal force recorded on anal penetration was 26.5 N (2.7 kg; range: 16.1-51.7 N or 1.64-5.27 kg). Participants who engaged in receptive anal intercourse more than once per month tended to use lesser median maximal forces (25.7 N or 2.62 kg) than participants who engaged less frequently in receptive anal intercourse (41.6 N or 4.24 kg). Clinical Implications: Compared with the forces required for vaginal penetration, anal penetration forces may cause additional mechanical stress to the phallus. Strengths and Limitations: While the study is limited primarily in its small sample size and in the use of a single device for anal penetration with a set size and rigidity, the resulting findings presented here are to our knowledge the first reported data pertaining the force required for anal penetration. Conclusion: As the forces required for anal penetration exceeded those for vaginal penetration, clinicians may need to carefully counsel patients on the safe use of an inflatable penile prosthesis for anal intercourse. [ABSTRACT FROM AUTHOR]

Introduction: Anal canal melanoma is a rare form of both anal cancer and skin melanoma, representing 1% of all anal cancers. Diagnosis is often made at an advanced disease stage. Because of late diagnosis and aggressive clinical course, anal canal melanoma has a very poor prognosis. Case Presentation: We present the case of a 61-year-old female with anal canal melanoma and lung, liver, pelvic and central nervous system (CNS) metastasis, BRAF V600E mutated. Combined BRAF/MEK inhibition and CNS radiation therapy were able to achieve excellent local and distant disease control. Conclusion: Anal canal melanoma is a rare and aggressive form of melanoma. Multidisciplinary management in experienced centers is mandatory for good clinical outcomes. [ABSTRACT FROM AUTHOR]

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Human papillomavirus (HPV) is the most common sexually transmitted infection, linked to several types of lesions. HPV, specifically HPV 16, accounts for most of anal cancer cases. In this study, we evaluated the proportion of samples tested positive for HPV and characterized genotypes distribution in anal specimens collected from individuals at risk of anal HPV infection attending from 2018 to 2022 a large Infectious Diseases Department in Italy. The presence of HPV DNA was investigated through a commercial kit detecting 12 HR‐HPV, 8 probable/possible HR‐HPV, and 8 LR‐HPV genotypes. Among 1514 samples, 84% (1266/1514) resulted positive for any type of HPV. The prevalence of high‐risk HPV types remained high during all the years of the study period, from 2018 to 2022, ranging from 65% to 73%. Most of HR‐HPV, LR‐HPV and HPV 16 positive samples were collected from men >45 years. HPV 16 was also the most frequent type in men and women. We did not observe significant variations between years in detection of HR‐HPV, instead of LR‐HPV, that significantly decreased. In conclusion, the high prevalence of oncogenic HPV genotypes underlines the necessity of clear anal HPV screening guidelines and, along with frequent HR‐HPV coinfections, reinforces the urge to intensify the anti‐HPV vaccination campaign. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 ribonucleic acid (RNA) has been detected in feces, but RNA is not infectious. This systematic review aims to answer if fecal SARS-CoV-2 is experimentally infectious and if evidence of human fecal-oral SARS-CoV-2 transmission exists. On September 19, 2022, we searched PubMed, Embase, Web of Science, medRxiv, and bioRxiv. Biomedical studies inoculating SARS-CoV-2 from feces, rectal, or anal swabs in cells, tissue, organoids, or animals were included. Epidemiological studies of groups differing in exposure to fecal SARS-CoV-2 were included. Risk of bias was assessed using standardized tools. Results were summarized by vote counting, tabulation, and a harvest plot. PROSPERO registration no. CRD42020221719. A total of 4,874 studies were screened; 26 studies were included; and 13 out of 23 biomedical studies (56.5%) succeeded in infection. Two (66.7%) epidemiological studies found limited evidence suggesting fecal-oral transmission. All studies had concerns about the risk of bias. It is possible to experimentally infect cell cultures, organoids, and animals with fecal SARS-CoV-2. No strong epidemiologic evidence was found to support human fecal-oral transmission. We advise future research to study fecal infectivity at different time points during infection, apply appropriate controls, use in vivo models, and study fecal exposure as a risk factor of transmission in human populations. • Fecal-oral transmission of SARS-CoV-2 poses a major knowledge gap. • Cell, organoid, and animal infection by SARS-CoV-2 from feces has been observed. • Circumstantial evidence suggesting human SARS-CoV-2 fecal-oral transmission exists. • No strong evidence of human SARS-CoV-2 fecal-oral transmission was found. [ABSTRACT FROM AUTHOR]

Summary: Background: Squamous cell carcinoma of the anus (SCCA) annual incidence among sexual minority men 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). Incidence may also be higher in transgender women. Since SCCA tumours average ≥30 mm at diagnosis, we assessed the accuracy of individuals to self-detect smaller anal abnormalities. Methods: Using convenience sampling, the study enrolled sexual minority men and transgender women, aged 25–81 years, in Chicago, Illinois and Houston, Texas, USA, during 2020–2022. Individuals were taught the anal self-examination and anal companion examination (ASE/ACE). Then, a clinician performed a digital anal rectal examination (DARE) before participants conducted the ASE or ACE. The sensitivity, specificity and concordance of the ASE/ACE to detect an abnormality were measured along with factors associated with ASE/ACE and DARE concordance. Findings: Among 714 enrolled individuals, the median age was 40 years (interquartile range, 32–54), 36.8% (259/703) were living with HIV, and 47.0% (334/710), 23.4% (166/710), and 23.0% (163/710) were non-Hispanic white, non-Hispanic Black, and Hispanic, respectively. A total of 94.1% (671/713) identified as cisgendered men, and 5.9% (42/713) as gender minorities. A total of 658 participants completed an ASE and 28 couples (56 partners) completed an ACE. Clinicians detected abnormalities in 34.3% (245/714) of individuals. The abnormalities were a median of 3 mm in diameter. 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). Concordance was lower when participants were older and received ASE/ACE training from a lay person rather than a clinician. Interpretation: Sexual minority men/transgender women may self-detect SCCA when malignant lesions are much smaller than the current mean dimension at presentation of ≥30 mm. Funding: National Cancer Institute.

BackgroundMultiple anal human papillomavirus (HPVs) may increase the risk of anal cancer among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). The Jaccard Similarity Index (JSI) was explored as a measure of multiple HPV persistence.MethodsThe TRUST/RV368 cohort enrolled MSM living with and without HIV in Abuja and Lagos, Nigeria. Participants with anal swabs at baseline, 3- and 12-month visits were tested for high- and low-risk HPVs using a next-generation sequencing assay. Persistence of the same HPV genotypes over time was calculated using the JSI and categorized into high, medium, and low similarity tertiles. Factors associated with higher versus lower similarity were estimated with multivariable ordinal logistic regression and reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs).ResultsOf the 225 participants, median age was 25 years (interquartile range, 22-29 years), 62% were living with HIV, median HPVs was 3 (interquartile range, 2-5), and HPV6 (28%), HPV16 (26%), HPV11 (23%), and HPV45 (20%) were most prevalent. Fifty-three percent of participants had highly similar HPVs at 3 months, and the similarity was associated with HIV (aOR, 3.11; 95% CI, 1.6-5.9) and recent receptive sex (aOR, 1.9; 95% CI, 1.0-3.5). By 12 months, 20% had highly similar HPVs, and it was associated with 12 years or longer since anal coital debut (aOR, 6.8; 95% CI, 3.1-5.2), self-reported genital warts (aOR, 3.1; 95% CI, 1.5-6.6), and 200 or less CD4 cells/mm3 (aOR, 13.3; 95% CI, 2.7-65.2) for those living with HIV.ConclusionsStudies evaluating the JSI as a predictor of high-grade intraepithelial lesions would further confirm its applicability as a quantitative measure of multiple HPV persistence.

ObjectiveOur study aim was to validate the use of computer-aided narrative content analysis in the extraction of standard diagnostic categories using an archived cytology database that included individually overread reference classification.DesignA retrospective analysis of narrative anal cytology results collected on HIV-infected patients at the University of California, San Diego between January and December 2001.MethodsWe used computer-assisted content analysis extraction methodology using Wordstat 8.0 (Provalis Research) that operated using a classification dictionary that we developed for the following diagnostic categories: NAMC, ASCUS, LSIL, HSIL. We compared its accuracy to a physician overread manually extracted method: that classified each report into the most severe diagnostic category referenced in the narrative report. Agreement between content analysis mapped diagnostic categories and the reference category was evaluated using kappa agreement.ResultsDuring 2001, 901 patients underwent 997 anal cytological examinations as routine screening. By reference diagnostic category: 54 (5.4%) were unsatisfactory, 460 (46.1%) were NAMC, 291 (29.2%) were ASCUS, 131 (13.1%) were LSIL, and 61 (6.1%) were HSIL. Computer-aided content analysis extracted a single diagnosis from each report in 963 (96.2%) cases and two diagnoses in 38 (3.8%) cases. The Kappa agreement was 0.96 (0.019 s.e.). There were 29 cases classified ASCUS by reference category but LSIL by adjudicated content analysis. A focused review indicated that the over reader assigned reference category was in error.ConclusionComputer-aided narrative content analysis of anal cytology results yielded accurate and time-efficient classification into meaningful diagnostic categories that can be used to evaluate screening programs and modeling natural history.

BackgroundRobotic transanal minimally invasive surgery (R-TAMIS) is an appealing alternative to transanal minimally invasive surgery (TAMIS) and transanal endoscopic microsurgery (TEM) for benign and early malignant rectal lesions that are not amenable to traditional open transanal excision. However, no studies to our knowledge have directly compared the three techniques. This study sought to compare peri-operative and pathologic outcomes of the three approaches.MethodsThe records of 29 consecutive patients who underwent TEM, TAMIS, or R-TAMIS at a single academic center between 2016 and 2020 were reviewed. Intra-operative details, pathological diagnosis and margins, and post-operative outcomes were recorded. The three groups were compared using chi-square and Kruskal-Wallis tests.ResultsOverall, 16/29 patients were women and the median age was 57 (interquartile range (IQR): 28-81). Thirteen patients underwent TEM, six had TAMIS, and 10 had R-TAMIS. BMI was lower in the R-TAMIS patients (24.7; IQR 23.8-28.7), than in TEM (29.3; IQR 19.9-30.2), and TAMIS (30.4; IQR 26.6-32.9) patients. High grade dysplasia and/or invasive cancer was more common in TAMIS (80%) and R-TAMIS (66.7%) patients than in TEM patients (41.7%). The three groups did not differ significantly in tumor type or distance from the anal verge. No R-TAMIS patients had a positive surgical margin compared to 23.1% in the TEM group and 16.7% in the TAMIS group. Length of stay (median 1 day for TEM and R-TAMIS patients, 0 days for TAMIS patients) and 30-day readmission rates (7.7% of TEM, 0% of TAMIS, 10% of R-TAMIS patients) also did not differ among the groups. Median operative time was 110 min for TEM, 105 min for TAMIS, and 76 min for R-TAMIS patients.ConclusionsR-TAMIS may have several advantages over other advanced techniques for transanal excisions. R-TAMIS tended to be faster and to more often result in negative surgical margins compared to the two other techniques.

Anal cancer is a rare disease, but its incidence has been increasing steadily. Primary staging and assessment after chemoradiation therapy are commonly performed using MRI, which is considered to be the preferred imaging modality. CT and PET/CT are useful in evaluating lymph node metastases and distant metastatic disease. Anal squamous-cell carcinoma (ASCC) and rectal adenocarcinoma are typically indistinguishable on MRI, and a biopsy prior to imaging is necessary to accurately stage the tumor and determine the treatment approach. This review discusses the histology, MR technique, diagnosis, staging, and treatment of anal cancer, with a particular focus on the differences in TNM staging between anal and rectal carcinomas. Purpose: This review discusses the histology, MR technique, diagnosis, staging, and treatment of anal cancer, with a particular focus on the differences in TNM staging between anal squamous-cell carcinoma (ASCC) and rectal adenocarcinoma. Methods and materials: To conduct this updated review, a comprehensive literature search was performed using prominent medical databases, including PubMed and Embase. The search was limited to articles published within the last 10 years (2013–2023) to ensure their relevance to the current state of knowledge. Inclusion criteria: (1) articles that provided substantial information on the diagnostic techniques used for ASCC, mainly focusing on imaging, were included; (2) studies reporting on emerging technologies; (3) English-language articles. Exclusion criteria: articles that did not meet the inclusion criteria, case reports, or articles with insufficient data. The primary outcome of this review is to assess the accuracy and efficacy of different diagnostic modalities, including CT, MRI, and PET, in diagnosing ASCC. The secondary outcomes are as follows: (1) to identify any advancements or innovations in diagnostic techniques for ASCC over the past decade; (2) to highlight the challenges and limitations of the diagnostic process. Results: ASCC is a rare disease; however, its incidence has been steadily increasing. Primary staging and assessment after chemoradiation therapy are commonly performed using MRI, which is considered to be the preferred imaging modality. CT and PET/CT are useful in evaluating lymph node metastases and distant metastatic disease. Conclusion: ASCC and rectal adenocarcinoma are the most common histological subtypes and are typically indistinguishable on MRI; therefore, a biopsy prior to imaging is necessary to stage the tumor accurately and determine the treatment approach.

We aimed to evaluate the effects of postpartum progesterone on obstetric anal sphincter injury (OASI) healing in female rats using an experimental OASI model. Twenty-eight female rats were divided into four groups after birth: sham-30, sham-90, progesterone (P4)-30, and P4-90. Moreover, OASI model was established in all groups. Subsequently, except for the sham groups, medroxyprogesterone acetate (0.15 mg) was intramuscularly injected into the P4 groups. After 30 and 90 days, the rats were euthanized under general anesthesia after recording the data. The anal sphincter region was collected for histopathological examination. Progesterone and thiol/disulfide homeostasis studies were performed on blood samples. No significant differences were observed between the groups regarding the external anal sphincter (EAS), internal anal sphincter (IAS), or connective tissue thickness (p = 0.714, p = 0.135, and p = 0.314, respectively). No statistically significant differences in the total thiol, native thiol, disulfide, and progesterone levels were found between the groups (p = 0.917, p = 0.503, p = 0.361, and p = 0.294, respectively). The endometrial thickness was lower in the P4 groups than in the sham groups (p = 0.031). Postpartum progesterone administration did not affect IAS and EAS or connective tissue thickness or disrupt the thiol–disulfide balance. However, this administration led to endometrial thinning.

Anal human papillomavirus (HPV) disproportionately affects men who have sex with men (MSM), particularly those who are older and those living with HIV. After experiencing difficulty recruiting older MSM into a study on aging and anal HPV, we conducted a sub-study to gain feedback on our recruitment methods and explore barriers and facilitators to participating in anal HPV research. We conducted focus groups with 30 men who have sex with men (MSM), both HIV-negative and MSM living with HIV, ages 50-75. We identified multiple themes that were barriers to participation including: (1) lack of knowledge about human papillomavirus and anal cancer; (2) research focused on anal cancer or discomfort with topics or procedures concerning the anus; (3) stigma including stigma associated with being men who have sex with men, being out, being a receptive partner, and being considered "older" in the gay community; and (4) confidentiality concerns including a fear of breach of confidentiality. Facilitators to participation were also identified; these motivational factors include altruism, wanting recommendations from a doctor, and desire to receive the best available care. Researchers seeking to enroll older men who have sex with men should be aware of these barriers and facilitators to participation in order to maximize recruitment.

BackgroundMen who have sex with men (MSM) living with human immunodeficiency virus (HIV) are at increased risk of anal cancer. Anal cytology can be used to screen for dysplasia, with high-resolution anoscopy (HRA) required for diagnostic confirmation. We describe the impact lack of HRA had on management of abnormal screening results in Bogotá, Colombia.Material and methodsThis retrospective cohort study includes MSM with HIV who underwent anal cytology screening between January 2019February 2020, with colorectal surgery (CRS) follow-up through July 2020. Cytology results included atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). Categorical and continuous variables were compared via Fisher's exact test and Wilcoxon rank-sum, respectively.ResultsOf 211 MSM screened, 68 had abnormal cytology: ASC-US (n = 23), LSIL (n = 41), HSIL (n = 4). Sixty (88.2%) were referred to CRS, and 51 (75.0%) attended ≥ 1 appointment. At initial assessment, 17 were referred for anal exam under anesthesia (EUA) for tissue resection, and 21 for rectosigmoidoscopy. Having perianal condyloma was associated with recommendation for EUA (P < 0.001), while cytology grade of dysplasia was not (P = 0.308). Eleven (16.2%) underwent EUA for condyloma resection.ConclusionsFew studies have described anal cancer screening in settings without HRA. We found lack of HRA limited management of abnormal cytology in Colombia. Those with condyloma underwent resection, but HRA remains necessary to localize and treat microscopic disease. Next steps include implementation of HRA in order to further develop the anal cancer screening program for MSM with HIV in Bogotá.

BackgroundMen who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied.MethodsTwo hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24.ResultsAmong 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events.Conclusions18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

Introduction Anal examination and videoanoscopy (VA) are rarely performed during colonoscopies. In recent years, there has been a considerable increase in lesions of sexually transmitted anal and rectal infections, but these conditions are not noticed or reported during routine colonoscopy. Objective To raise awareness regarding the fortuitous findings of lesions and sexually transmitted infections (STIs) in colonoscopy exams and to demonstrate that anal examination and VA provide important information and should be routinely performed. Methods We conducted a descriptive retrospective study in 16,132 patients screened by colonoscopy and VA between 2006 and 2018. Among numerous other findings, the presence of anal condylomata and sexually transmitted retitis or perianal dermatitis was observed. The rates of each finding were calculated, and the patients were subdivided by sex and into age groups by blocks of ten years. Results Among the 16,132 colonoscopies performed, 26 cases of condyloma (0.16%) and 50 cases of proctitis or perianal dermatitis suspicious for STI (0.33%) were found. Conclusion Performing anal examination and VA systematically in all routine colonoscopies enabled the identification of numerous anal conditions, including several fortuitous cases of STIs. The study proposes that anal examination and VA should be performed in all routine colonoscopies and, in suspected cases, complementary tests for STIs.

Abstract Background Anal lymphomas are extremely rare. There are no relevant descriptions in professional books, and there are only a few case reports in the literature. Here, we report a new case and review the literature to summarize the clinical and pathological features of anal lymphoma. Methods We described a case of anal lymphoma confirmed by pathological diagnosis, then searched the PubMed database, and finally selected 12 reported cases to be included in the study. We described the clinical and pathological characteristics of the patients. Results Thirteen patients with anal lymphoma were confirmed. Seven men and six women with a median age of 50. There were four cases of HIV- and EBV-infected patients. The size of the tumor was 1–13 cm, all of which were diagnosed as B-cell lymphoma, and 61.5% were diffuse large B-cell lymphomas. Among the 13 patients, eight received chemotherapy or immunochemotherapy, two received radiotherapy, one received chemotherapy combined with radiotherapy, one received surgery, and one gave up treatment. Three patients died, and only 2 of 10 surviving patients had complete remission. Conclusion Anal lymphoma is extremely rare. Patients with persistent abscess complicated with HIV or EBV infection should undergo pathological biopsy to exclude anal lymphoma.

Background: Endoscopic submucosal dissection (ESD) of rectal tumors involving the dentate line (RT-DL) is challenging because of the anatomical features of the anal canal. This study aimed to identify optimal techniques and sedation and to determine the clinical outcomes of ESD for RT-DL. Methods: We retrospectively collected medical records and endoscopic results of patients who underwent ESD for rectal tumors between January 2012 and April 2021. Patients were divided into RT-DL and rectal tumors not involving the dentate line (RT-NDL) groups, as per involvement of the dentate line. The treatment results and clinical outcomes of the two groups were evaluated and analyzed. Additionally, subgroup analysis was performed in the RT-DL group for the sedation method involved. Results: In total, 225 patients were enrolled and 22 were assigned to the RT-DL group. The complete resection rate (90.9% vs. 95.6%, P =0.336), delayed bleeding (13.6% vs. 5.9%, P =0.084), perforation (0% vs. 3.9%, P = 0.343), hospital stays (4.55 vs. 4.48 days, P = 0.869), and recurrence (0% vs. 0.5%) showed no significant group differences. However, in RT-DL group, the procedure time (78.32 vs. 51.10 min, P = 0.002) was longer and there was more perianal pain (22.7% vs. 0%, P = 0.001). The subgroup analysis revealed that deep sedation using propofol reduced perianal pain during the procedure (0/14 vs. 5/8, P = 0.002). Conclusions: ESD of RT-DL is a safe and effective treatment despite the challenges of requiring a high level of technique and longer procedure time. In particular, ESD under deep sedation should be considered in patients with RT-DL to control perianal pain. [ABSTRACT FROM AUTHOR]

Context: Concurrent chemoradiotherapy is considered a standard of care for patients with carcinoma anal canal. Being an unusual malignancy, there is limited Indian data regarding survival outcomes and prognostic factors. Aim: To evaluate survival outcomes and associated prognostic factors in patients with carcinoma anal canal treated with radical intent. Methods and Material: Patients with squamous cell carcinoma of the anal canal, treated with radical intent between 2015 and 2019 were included in the study. Data regarding the baseline characteristics of the patients and treatment outcomes were collected and analyzed. Survival rates were estimated using Kaplan–Meier method. To determine survival difference between the groups, log-rank test was used. Multivariate analyses were performed with Cox proportional hazard models and P value < 0.05 was considered significant. Results: Forty-two patients were identified after applying suitable eligibility criteria. The median age was 55 years (range: 26–80 years).The median follow-up duration was 23.5 months (range: 1.9–51.9 months). The 3-year overall survival (OS), disease-free survival (DFS), and locoregional (LRC) were 78.5%, 53.1%, and 66.4%, respectively. On multivariate analysis, inferior DFS was significantly affected by lack of concurrent chemotherapy (CT) (hazard ratio [HR], 11.50; 95% confidence interval [CI], 1.92–68.78; P = 0.007) and radiotherapy (RT) dose of 45 Gy or less (HR, 35.96; 95% CI, 6.32–204.56; P = 0.000). Conclusion: For patients of carcinoma anal canal, concurrent CT and RT dose are independent prognostic factors influencing DFS. [ABSTRACT FROM AUTHOR]