Molecular and genomic characterisation of a panel of human anal cancer cell lines.

Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.

Combined treatment approach to chronic anal fissure with associated anal fistula.

BACKGROUND: Anal fistula in association with chronic anal fissure (fissure-fistula) is infrequently described. Recognizing this association and managing both components may help prevent some treatment failures seen with chronic anal fissure. This study aims to report on the outcomes of 20 consecutive patients with fissure-fistula managed with fistulotomy and injection of botulinum A toxin. METHODS: The study is a retrospective, observational study, assessing the success of symptom resolution following fistulotomy with botulinum A toxin, in patients identified as having a chronic anal fissure with associated anal fistula. The study included all patients with this condition treated with combination treatment by a single surgeon at a tertiary care hospital between January 2013 and January 2016. RESULTS: Twenty patients with fissure-fistula treated with fistulotomy and botulinum toxin A were identified. The median cohort age was 44 years (range 25-78), with a predominance of males (80%) and posterior fissure position (80%). The most common presenting symptoms were anal pain (70%), rectal bleeding (55%), anal discharge (35%) and anal pruritus (35%). Mean follow-up was 10.5 weeks and all patients who attended follow-up appointments reported resolution of symptoms. There were no cases of incontinence and none of the cohort required further surgical intervention for the condition. CONCLUSION: Chronic anal fissure with associated anal fistula can be successfully managed with fistulotomy and injection of botulinum toxin A. Further studies would be helpful in determining if recognition and management of the fistula component in isolation with fistulotomy is as effective as fistulotomy plus botulinum A toxin.