Risks Factors Associated with the Development of Crohn's Disease After Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Following ileal pouch-anal anastomosis [IPAA] for ulcerative colitis [UC], up to 16% of patients develop Crohn's disease of the pouch [CDP], which is a major cause of pouch failure. This systematic review and meta-analysis aimed to identify preoperative characteristics and risk factors for CDP development following IPAA. METHODS: A literature search of the MEDLINE, EMBASE, EMCare and CINAHL databases was performed for studies that reported data on predictive characteristics and outcomes of CDP development in patients who underwent IPAA for UC between January 1990 and August 2022. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed. RESULTS: Seven studies with 1274 patients were included: 767 patients with a normal pouch and 507 patients with CDP. Age at UC diagnosis (weighted mean difference [WMD] -2.85; 95% confidence interval [CI] -4.39 to -1.31; p = 0.0003; I2 54%) and age at pouch surgery [WMD -3.17; 95% CI -5.27 to -1.07; p = 0.003; I2 20%) were significantly lower in patients who developed CDP compared to a normal pouch. Family history of IBD was significantly associated with CDP (odds ratio [OR] 2.43; 95% CI 1.41-4.19; p = 0.001; I2 31%], along with a history of smoking [OR 1.80; 95% CI 1.35-2.39; p < 0.0001; I2 0%]. Other factors such as sex and primary sclerosing cholangitis were found not to increase the risk of CDP. CONCLUSIONS: Age at UC diagnosis and pouch surgery, family history of IBD and previous smoking have been identified as potential risk factors for CDP post-IPAA. This has important implications towards preoperative counselling, planning surgical management and evaluating prognosis.

Comparing and contrasting clinical consensus and guidelines for anal intraepithelial neoplasia in different geographical regions.

Anal Squamous Cell Carcinoma (ASCC) is an uncommon cancer with a recognised precursor Anal Intraepithelial Neoplasia (AIN). Although there are consistent evidence-based guidelines for the management of ASCC, historically this has not been the case for AIN and as a result there have been geographical variations in the recommendations for the treatment of AIN. More recently there have been updates in the literature to the recommendations for the management of AIN. To assess whether we are now closer to achieving an international consensus, we have completed a systematic scoping review of available guidelines for the screening, treatment and follow-up of AIN as a precursor to ASCC. MEDLINE and EMBASE were systematically searched for available clinical guidelines endorsed by a recognised clinical society that included recommendations on either the screening, treatment or follow-up of AIN. Nine clinical guidelines from three geographical areas were included. The most recent guidelines agreed that screening for AIN in high-risk patients and follow-up after treatment was necessary but there was less consensus on the modality of screening. Six Guidelines recommended the treatment of high-grade AIN and four guidelines describe a follow-up protocol of patients diagnosed with AIN. There appears to be increasing consensus on the treatment and follow-up of patients despite a poor evidence base. There is still significant discrepancy in guidance on the method to identify patients at risk of ASCC and AIN despite consensus between geographical regions on which patient subgroups are at the highest risk.

The Role of Demographics, Social Deprivation and Ethnicity on Anal Squamous Cell Carcinoma Incidence in England.

Anal Squamous Cell Carcinoma (ASCC) is an HPV-related malignancy with increasing incidence in high-income economies. Although ethnicity and social deprivation are known to be risk factors in other malignancies, little is known about socioeconomic status and risk of ASCC. This is a cross-sectional study following the STROBE Statement. Demographic data from the English Clinical Outcomes and Services Dataset (COSD) were extracted for all patients diagnosed with ASCC in England between 2013 and 2018. Outcomes included ethnicity, social deprivation, staging and treatment. This study included 5457 patients. Incidence increased by 23.4% in 5 years, with female incidence increasing more rapidly than male incidence (28.6% vs. 13.5%). Men were more likely to present with early staging (p < 0.001) and have surgery as their only treatment (p < 0.001). The rate of incidence of Stage 1 tumours in men was 106.9%; however, women had the greatest increase in metastatic tumours (76.1%). Black Caribbean and Black African patients were more likely to present at an earlier age with later staging (p < 0.001) and social deprivation was associated with younger age (p < 0.001). ASCC incidence is rapidly increasing in patterns consistent with two separate populations: one male with early staging, the other female and related to social deprivation and ethnicity factors.

Anal squamous cell carcinoma in a high HIV prevalence population.

Anal Squamous Cell Carcinoma (ASCC) is a rare cancer that has a rapidly increasing incidence in areas with highly developed economies. ASCC is strongly associated with HIV and there appears to be increasing numbers of younger male persons living with HIV (PLWH) diagnosed with ASCC. This is a retrospective cohort study of HIV positive and HIV negative patients diagnosed with primary ASCC between January 2000 and January 2020 in a demographic group with high prevalence rates of HIV. One Hundred and seventy six patients were included, and clinical data was retrieved from multiple, prospective databases. A clinical subgroup was identified in this cohort of younger HIV positive males who were more likely to have had a prior diagnosis of Anal Intraepithelial Neoplasia (AIN). Gender and HIV status had no effect on staging or disease-free survival. PLWH were more likely to develop a recurrence (p < 0.000) but had a longer time to recurrence than HIV negative patients, however this was not statistically significant (46.1 months vs. 17.5 months; p = 0.077). Patients known to have a previous diagnosis of AIN were more likely to have earlier staging and local tumour excision. Five-year Disease-Free Survival was associated with tumour size and the absence of nodal or metastatic disease (p < 0.000).

Joint ACPGBI and The Duke's Club statement on colonoscopy training.

Colorectal surgeons across the UK currently undertake a large proportion of routine diagnostic and therapeutic colonoscopy in most NHS Trusts [1]. Meanwhile, the new UK General Surgical curriculum now includes an indicative requirement of 200 diagnostic colonoscopies for surgical trainees who have declared a colorectal subspecialty interest (hereafter termed 'colorectal trainees'), indicating the JCST's (Joint Committee on Surgical Training) commitment to colonoscopy training. However, several studies have reported a marked deficiency in colonoscopy training opportunities and accreditation for surgical trainees compared with gastroenterology trainees [2-4].

Evaluating the efficacy of treatment options for anal intraepithelial neoplasia: a systematic review.

PURPOSE: Anal intraepithelial neoplasia (AIN) is the accepted precursor of anal squamous cell carcinoma (ASCC). There has long been a hypothesis that treating AIN may prevent ASCC. Many different treatment modalities have been suggested and studied. We conducted this systematic review to evaluate their efficacy and the evidence as to whether we can prevent ASCC by treating AIN. METHODS: MEDLINE and EMBASE were electronically searched using relevant search terms. All studies investigating the use of a single treatment for AIN that reported at least one end outcome such as partial or complete response to treatment, recurrence after treatment and/or ASCC diagnosis after treatment were included. RESULTS: Thirty studies were included in the systematic review investigating 10 treatment modalities: 5% imiquimod, 5-fluorouracil, cidofovir, trichloroacetic acid, electrocautery, surgical excision, infrared coagulation, radiofrequency ablation, photodynamic therapy and HPV vaccination. All treatment modalities demonstrated some initial regression of AIN after treatment; however, recurrence rates were high especially in HIV-positive patients. Many of the studies suffered from significant bias which prevented direct comparison. CONCLUSIONS: Although the theory persists that by inducing the regression of AIN, we may be able to reduce the risk of ASCC, there was no clinical evidence within the literature advocating that treating AIN does prevent ASCC.

All You Need to Know About DPYD Genetic Testing for Patients Treated With Fluorouracil and Capecitabine: A Practitioner-Friendly Guide.

Fluoropyrimidines (fluorouracil, capecitabine, and other analogs) are highly used anticancer drugs worldwide. However, patients with cancer treated with these drugs might experience severe, life-threatening toxicity because of germline genetic variation in the DPYD gene. This is a genetic predisposition with an established mechanistic basis that links genetic variation in the DPYD gene to an increase in systemic drug exposure, resulting in an increased risk of toxicity. Pharmacology guidelines provide recommendations on avoiding treatment with fluoropyrimidines or reducing their dose in patients carrying DPYD genetic variants conferring an increased risk of toxicity. However, oncology societies in the United States do not recommend systematic testing. Instead, on April 30, 2020, the European Society for Medical Oncology issued a document recommending genetic testing. In this scenario of contradicting information, practicing oncologists struggle with reaching an informed decision on whether genetic testing should be applied before treatment. This is mostly due to uncertainty about the clinical relevance of genetic testing from the perspective of a practicing oncologist. To reach an informed decision, practicing oncologists need access to concise information on the genetic variants to be tested and a practitioner-friendly interpretation of the test results. We believe this information is currently lacking. To our knowledge, for the first time, we provide a single guide for health care professionals to make an evidence-based decision about DPYD testing for patients with cancer. This article provides the essential knowledge base for oncologists to have an informed discussion with their patients about the genetic testing for DPYD. This document assists practitioners in quickly evaluating whether, when, where, and how to order a DPYD genetic test.

Crohn's disease.

INTRODUCTION: Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments to induce remission in adults with Crohn's disease? What are the effects of surgical interventions to induce and maintain remission in adults with small-bowel Crohn's disease? What are the effects of surgical interventions to induce remission in adults with colonic Crohn's disease? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? What are the effects of lifestyle interventions to maintain remission in adults with Crohn's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 93 systematic reviews, RCTs, or observational studies that met our inclusion criteria. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty.

Crohn's disease.

INTRODUCTION: Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments to induce remission in adults with Crohn's disease? What are the effects of surgical interventions to induce and maintain remission in adults with small-bowel Crohn's disease? What are the effects of surgical interventions to induce remission in adults with colonic Crohn's disease? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? What are the effects of lifestyle interventions to maintain remission in adults with Crohn's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 93 systematic reviews, RCTs, or observational studies that met our inclusion criteria. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty.