Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome predisposing affected individuals to gastrointestinal (GI) cancers through a high burden of polyposis. Colorectal cancer rates reach 100% by the age of 45, making early colectomy a mainstay of treatment. While most patients undergo colectomy at an early age, ongoing screening and surveillance of the upper gastrointestinal tract and rectal pouch must continue throughout adulthood. Endoscopic therapy of gastric, duodenal, ampullary and rectal pouch polyps is critical to reduce morbidity and cancer related mortality. Management of these lesions is not uniform, and is dependent on their location, size, histology, and risk of malignant potential. Medical therapies targeting pathways that reduce the malignant progression of pre-cancerous lesions have been studied for many years. While studies on the use of aspirin and non-steroidal anti-inflammatories (NSAIDs) in chemoprevention have shown encouraging results in Lynch syndrome and primary colorectal cancer, the potential benefits of these medications have not been duplicated in FAP cohorts. While data remains limited on chemoprevention in FAP, a number of randomized trials are currently underway examining targeted therapies with the potential to slow the progression of the disease. This review aims to provide an in-depth review of the literature on current endoscopic options and chemopreventive therapies targeting FAP. While the endoscopic management has robust data for its use, chemoprevention in FAP is still in its infancy. The complementary use of chemopreventive agents and endoscopic therapy for FAP patients is quickly becoming a growing and exciting area of research.

The Phenotypic Spectrum of New-onset IBD in Canadian Children of South Asian Ethnicity: A Prospective Multi-Centre Comparative Study.

BACKGROUND: Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. METHODS: Patients aged <17 years, enrolled in a Canadian nationwide inception cohort study, were included. Baseline demographic and IBD phenotypic features were compared between SA and Caucasian children. Longitudinal outcomes through 18 months of follow-up were compared matched by propensity scores. RESULTS: Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2-14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p <0.001]. Additionally, a greater proportion of SA CD patients present with colonic-only disease [colonic-only CD/UC/IBD-U in SAs 67% vs 57% for Caucasians, p = 0.001], and among those with CD, colonic CD in SAs 31% vs 23% in Caucasians, p = 0.20]. Perianal fistulising disease was also numerically more common in SAs (14 [27%] vs 64 [18%], p = 0.06]. Adjusting for differences in phenotypic presentation, anti-tumour necrosis factor [TNF] exposure, and time to initiation was similar, and two-thirds of children, whether anti-TNF exposed or naïve, were in corticosteroid-free clinical remission at 18 months irrespective of ethnicity. CONCLUSIONS: The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.

Phenotypic Variation in Paediatric Inflammatory Bowel Disease by Age: A Multicentre Prospective Inception Cohort Study of the Canadian Children IBD Network.

BACKGROUND AND AIMS: Incidence of paediatric inflammatory bowel disease [IBD] in Canada is among the highest worldwide, and age of onset may be decreasing. In a multicentre nationwide inception cohort study, we examined variation in phenotype of IBD throughout the paediatric age spectrum. METHODS: Children aged ≥2 years [y] and <17y [A1 age at diagnosis], with new onset IBD, were systematically evaluated at sites of the Canadian Children IBD Network. Prospectively recorded phenotypic data were compared between age groups. RESULTS: Among 1092 children (70% Caucasian; 64% Crohn's disease [CD], 36% ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U]; median age 13 y, interquartile range [IQR] 11-15 y), 210 [19%] were diagnosed before the age of age 10 y [Paris A1a] and 43 [4%] before age 6 y (very-early-onset [VEO-IBD]). CD was less common in younger children [42%, 56%, 66%, respectively, of VEO-IBD, A1a; A1b]. Colon-only IBD [UC/IBDU or CD-colon] was present in 81% of VEO-IBD and 65% of A1a; ileal disease increased progressively, reaching plateau at age 10 y. CD location was ileocolonic [L3] in 53% overall. Ileitis [L1] increased with age [6% of VEO-IBD; 13% of A1a; 21% of A1b], as did stricturing/penetrating CD [4% of A1a; 11% of A1b]. At all ages UC was extensive [E3/E4] in >85%, and disease activity moderate to severe according to Physician's Global Assessment [PGA] and weighted Paediatric Crohn's Disease Activity Index/Paediatric Ulcerative Colitis Activity Index [wPCDAI/PUCAI] in >70%. Heights were modestly reduced in CD [mean height z score -0.30 ± 1.23], but normal in UC/IBD-U. CONCLUSIONS: Paris classification of age at diagnosis is supported by age-related increases in ileal disease until age 10 years. Other phenotypic features, including severity, are similar across all ages. Linear growth is less impaired in CD than in historical cohorts, reflecting earlier diagnosis.

Successful therapy for protein-losing enteropathy caused by chronic neuronopathic Gaucher disease.

Gaucher disease (OMIM #230800) is caused by ß-glucosidase deficiency and primarily involves the mononuclear phagocyte system (also called Reticuloendothelial System or Macrophage System). The disease is classified into three main phenotypes based on the presence or absence of neurological manifestations: non-neuronopathic (type 1), acute neuronopathic (type 2) and chronic neuronopathic (type 3). Typical manifestations include hepatosplenomegaly, skeletal deformities, hematological abnormalities, interstitial lung fibrosis and neurodegeneration in neuronopathic cases. Mesenteric lymphadenopathy with resultant protein losing enteropathy (PLE) has only been rarely described. Mesenteric lymphadenopathy may lead to intestinal lymphatic obstruction and secondary lymphangiectasia resulting in chronic diarrhea, abdominal pain and weight loss. Fecal protein loss with secondary hypoalbuminemia can be significant. We report a male with Chronic Neuronopathic Gaucher disease (GD) (homozygous for c.1448T > C (NM_000157.3) GBA mutation) who at 16 years of age developed intractable abdominal pain, diarrhea and weight loss. This was caused by PLE secondary to intestinal lymphangiectasia caused by calcified mesenteric lymphadenopathy despite prior long term enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT). His older similarly affected sister who had been receiving treatment with ERT and/or SRT remains stable on these treatments with no evidence of mesenteric lymphadenopathy. Medical management with total parenteral nutrition, daily medium chain triglyceride-oil (MCT) supplementation, low dose oral budesonide, continued oral SRT and an increased dose of parenteral ERT has stabilized his condition with resolution of the gastrointestinal symptoms and appropriate weight gain.

Systematic review: thalidomide and thalidomide analogues for treatment of inflammatory bowel disease.

BACKGROUND: It has been reported that thalidomide may be effective in treating inflammatory bowel disease (IBD). AIM: To review the evidence examining the efficacy and safety of thalidomide for inducing and maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed (1950-August 2014), EMBASE (1984-August 2014), Scopus, and Web of knowledge were searched for randomised controlled trials (RCTs), observational studies and case series. The primary outcomes were induction of remission or response for active IBD or relapse rate for patients in remission and subsequently on thalidomide/analogues for at least 3 months. RESULTS: Twelve studies (2 RCTs and 10 case series) met the inclusion criteria for inducing remission and included 248 patients (10 with UC, 238 with CD). Only one RCT of paediatric CD achieved high quality scores (remission rate thalidomide: 46%, placebo: 12%; p=0.01). The crude pooled remission rate for thalidomide was 49% and 25% in luminal and perianal CD respectively. For UC, 50% achieved remission and 10% had partial response. One case series reported 21 patients (17 CD, four UC) who maintained remission for 6 months. Many adverse events were reported including sedation (32%) and peripheral neuropathy (20%). CONCLUSIONS: One high quality RCT showed that thalidomide is effective for inducing remission in paediatric CD. The current evidence is insufficient to support using thalidomide to induce remission in UC or adult CD, or to maintain remission in IBD. Significant adverse events may occur, necessitating discontinuation of thalidomide.

Systematic review: the role of tacrolimus in the management of Crohn's disease.

BACKGROUND Several published studies have evaluated the efficacy of tacrolimus in the management of Crohn's disease with variable conclusions. AIM To review systematically the evidence examining the efficacy and safety of tacrolimus in treating Crohn's disease. METHODS The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PUBMED) and EMBASE (1984 to January 2011) were searched. Also, references from selected articles were examined. Case series (five or more patients), cohort and randomised controlled trials were eligible for inclusion, incorporating oral, intravenous or topical tacrolimus therapy. The primary outcome was induction of remission of active Crohn's disease. RESULTS Eleven studies met the inclusion criteria which included 163 patients, of which 127 received tacrolimus therapy. In patients with luminal Crohn's disease, the crude pooled remission rate for tacrolimus was 44.3% (range, 7-69%) and the crude pooled response rate was 37.1% (range, 14-57%). For patients with perianal disease using systemic tacrolimus, crude pooled remission rate was 28.6% (range, 0-64%) and crude pooled response rate was 38.8% (range, 0-57%). Combining data from two studies using topical tacrolimus, 35.7% of patients achieved remission and 28.6% partial response. Nonserious adverse effects are common, particularly tremor, paraesthesia and headache. Reversible nephrotoxity occurred in 16% of patients. CONCLUSIONS The current evidence; although of a poor quality, appears to support the use of tacrolimus in Crohn's disease. High quality randomised controlled trials are needed.

Predictors of medication adherence in pediatric inflammatory bowel disease patients at the Stollery Children's Hospital.

BACKGROUND: Patients with inflammatory bowel disease (IBD) often do not take their medications as prescribed. OBJECTIVE: To examine self-reported adherence rates in IBD patients at the Stollery Children's Hospital (Edmonton, Alberta) and to determine predictors of medication adherence. METHODS: A survey was mailed to 212 pediatric IBD patients of the Stollery Children's Hospital. A chart review was completed for those who returned the survey. RESULTS: A total of 119 patients completed the survey. The nonresponders were significantly older than responders (14.5 years versus 13.2 years; P=0.032). The overall adherence rate was 80%. Nonadherence was associated with older age (14.6 years versus 13.0 years; P=0.04), longer disease duration (5.0 years versus 3.1 years; P=0.004) and reported use of herbal medications (40.0% versus 13.6%; P=0.029). The most common reasons reported for missing medications were forgetfulness, feeling better and too many medications. In addition, patients reported being more likely to take anti-inflammatory medications and less likely to take herbal medicines. CONCLUSION: Identified predictors of nonadherence such as age, disease duration and use of herbal treatments may enable the development of specific strategies to improve adherence in adolescents with IBD.