Adenocarcinoma within anorectal fistulae is rare and is sometimes associated with Crohn's disease. Crohn's disease-associated adenocarcinoma within anorectal fistulae has a poor prognosis; however, little is known about the clinicopathological differences between Crohn's disease-associated adenocarcinoma within anorectal fistulae and usual adenocarcinoma within anorectal fistulae. We retrospectively searched patients' charts and pathology archives at Tokyo Yamate Medical Center and Tokyo Medical and Dental University Hospital for adenocarcinoma within anorectal fistulae. Clinical and pathological data were collected and immunohistochemical examinations were conducted. Overall survival rate was estimated using the Kaplan-Meier method. Prognostic factors of overall survival were assessed using univariate and multivariate Cox regression analyses. We examined 82 cases of adenocarcinoma within anorectal fistulae. Fifty-nine of 82 cases (72%) had usual adenocarcinoma within anorectal fistulae, while the remaining 23 cases (28%) had Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae were diagnosed at a younger age and at a more advanced stage than those with usual adenocarcinoma within anorectal fistulae. Macroscopic and histological types were also different between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Crohn's disease-associated adenocarcinoma within anorectal fistulae included more ulcerative types and high-grade adenocarcinomas. The rate of lymphovascular invasion was higher in Crohn's disease-associated adenocarcinoma within anorectal fistulae. Immunohistochemically, the expression of E-cadherin, p53, and MUC5AC differed between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae exhibited worse overall survival than those with usual adenocarcinoma within anorectal fistulae, and vascular invasion was the strongest significant independent predictor of overall survival in patients with adenocarcinoma within anorectal fistulae. In conclusion, usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae have different clinicopathological characteristics and should be considered separate clinical entities.

Human papillomavirus (HPV) infection is known to cause anal condyloma acuminatum (CA) and squamous cell carcinoma. Men who have sex with men (MSM) with HIV infection are frequently co-infected with HPV, especially high risk HPV (HR-HPV) that causes anal squamous cell carcinoma. However, there are few reports of HPV genotype studies in anal lesion of Japanese men. We tried to estimate the distribution of HPV genotypes in anal CA tissue specimens from the Japanese men to elucidate the risk of anal cancer. A total of 62 patients who had anal CA surgically excised were enrolled. They included 27 HIV-positive MSM, 18 HIV-negative MSM, 1 HIV-positive man who have sex with women (MSW), and 16 HIV-negative MSW. HPV genotypes in anal CA tissue were determined by the polymerase chain reaction technique with reverse line blot hybridization. HR-HPV was detected in 45.2% of the CA tissue specimens and high grade squamous intraepithelial lesion (HSIL) was observed in 15.3%. Moreover, the prevalence of HR-HPV in the HIV-positive MSM (70.4%) was higher than the HIV-negative MSM (33.3%, p = .0311) or the HIV-negative MSW (18.8%, p = .0016). The conditional logistic regression analysis suggested HIV positivity as the primary risk factor for the HR-HPV infection in CA. In addition, HSIL was detected in higher frequency in CA tissues from HIV-positive MSM (25.9%) than HIV-negative MSW (0.0%, p = .0346). HR-HPV and HSIL were frequently detected in anal CA tissues from Japanese MSM patients with HIV infection, suggesting the necessity of surveillance for this population.

Background and Aims Previous studies conducted in Europe suggested that darvadstrocel, a suspension of expanded allogeneic adipose-derived mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn’s disease. The aim of this study was to evaluate the efficacy and safety of darvadstrocel for the treatment of complex perianal fistulas in Japanese adults with Crohn’s disease. Methods This is a phase 3, open-label, single-arm study conducted at 9 sites in Japan. Adult patients with non-active or mildly active Crohn’s disease and complex perianal fistulas received a single 24mL intralesional injection of darvadstrocel (120×10 6 cells). The primary endpoint was combined remission (clinically confirmed closure of all treated external openings that were draining at screening and absence of collections >2 cm [confirmed by magnetic resonance imaging] among treated fistulas) at Week 24. Results Between March 6, 2019 and February 1, 2021, 22 patients received darvadstrocel and completed the 52-week follow-up. The proportion of patients achieving combined remission at Week 24 was 59.1% (95% CI, 38.5–79.6). The effect was maintained at Week 52, with 68.2% (95% CI, 48.7–87.6) of patients achieving combined remission. Treatment-related adverse events included: 1 (4.5%) patient with worsening of Crohn’s disease and diarrhea and 1 (4.5%) patient with blood bilirubin increase. No new safety findings were identified in this study. Conclusions The efficacy and tolerability of darvadstrocel in Japanese adult patients with treatment-refractory complex perianal fistulas in Crohn’s disease were similar to those observed in the previous European study.

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