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.

Teduglutide in short bowel syndrome patients: A way back to normal life?

BACKGROUND: The glucagon-like peptide 2 analogue teduglutide is an effective drug for the treatment of short bowel syndrome patients with intestinal failure (SBS-IF). This intestinotrophic peptide improves intestinal capacity for fluid and nutrient absorption through induction of mucosal growth and reduction of gastrointestinal motility. Clinical trials demonstrated the efficacy of teduglutide in reducing the need for parenteral support (PS). This study describes an SBS-IF patient population receiving teduglutide therapy in a specialized medical care setting. METHOD: A retrospective analysis was performed using data of patients experiencing nonmalignant SBS-IF. They were treated with teduglutide in a multidisciplinary SBS-IF program at a single university medical center between June 2016 and June 2020. RESULTS: Thirteen patients under teduglutide treatment were included in the final analysis. Mean small bowel length was 82 ± 31 cm, with 77% of patients having their colon in continuity. Over a median follow-up of 107 weeks, all patients (13 of 13, 100%) responded to the therapy with a clinically significant reduction of PS volume. Mean PS reduction increased with therapy duration and ranged from -82.5% at week 24 (n = 13) to -100% in patients (n = 5) who were treated for 144 weeks. Enteral autonomy was achieved in 12 of 13 (92%) patients. Teduglutide therapy improved stool frequency and consistency, changed dietary habits, and reduced disease-associated sleep disruptions. CONCLUSION: Integrating SBS-IF patients treated with teduglutide in a proactive and tight-meshed patient care program significantly improves the clinical outcome, leading to an increased proportion of patients reaching enteral autonomy.