Fistula-Associated Anal Adenocarcinoma: A 20-Year Single-Center Experience.

BACKGROUND: Fistula-associated anal adenocarcinoma (FAAC) is a rare consequence in patients with long-standing perianal fistulas. A paucity of data are available for this patient collective, making clinical characterization and management of this disease difficult. OBJECTIVE: This study aimed to describe a single-center experience with FAAC patients, their clinical course, and histopathological and molecular pathological characterization. METHODS: All patients receiving surgery for an anal fistula in 1999-2019 at a tertiary university referral hospital were included in this retrospective analysis. Patients with FAAC were eligible for histopathological analysis, including immunohistochemistry and molecular profiling. RESULTS: This study included 1004 patients receiving surgical treatment for an anal fistula, of whom 242 had an underlying inflammatory bowel disease (IBD). Ten patients were diagnosed with a fistula-associated anal carcinoma (1.0%), and six of these patients had an FAAC (0.6%). The mean overall survival of FAAC patients was 24 ± 3 months. FAAC immunohistochemistry revealed positive staining for CK20, CDX2 and MUC2, while stainings for CK5/6 and CK7 were negative. All FAAC specimens revealed microsatellite stability. Molecular profiling detected mutations in 35 genes, with the most frequent mutations being TP53, NOTCH1, NOTCH3, ATM, PIK3R1 and SMAD4. CONCLUSION: FAAC is rare but associated with poor clinical outcome. Tissue acquisition is crucial for early diagnosis and therapy and should be performed in long-standing, non-healing, IBD-associated fistulas in particular. The immunophenotype of FAAC seems more similar to the rectal-type mucosa than the anal glands.

Moral injury, posttraumatic stress disorder, and religious involvement among U.S. veterans.

BACKGROUND: Traumatic experiences can cause ethical conflicts. "Moral injury" (MI) has been used to describe this emotional/cognitive state, and could contribute to the development of posttraumatic stress disorder (PTSD) or block its recovery. We examine the relationship between MI and PTSD, and the impact of religious involvement (RI) on that relationship. METHODS: We conducted a study of 120 veterans enrolled at the Charlie Norwood VA Medical Center in Augusta, Georgia. Standard measures of PTSD symptoms, MI, and RI were administered. Regression models were used to examine correlates of PTSD symptoms and the moderating or mediating effects of RI. RESULTS: A strong relationship was found between MI and PTSD symptoms (r = 0.54, P ≤ .0001), and between MI and RI (r = -.41, P ≤ .0001), but only a weak relationship was found between RI and PTSD symptoms (r = -.17, P = .058). RI did not mediate or moderate the relationship between MI and PTSD symptoms in the overall sample. However, among non-Middle Eastern war theater veterans, a significant buffering effect of religiosity was found. CONCLUSIONS: MI has a strong positive relationship with PTSD symptoms and an inverse relationship with RI. RI did not mediate or moderate the relationship between MI and PTSD in the overall sample, but it moderated this relationship in non-Middle Eastern war theater veterans.