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Genetic Predictors of Quality of Life Post Ileal Pouch Anal Anastomosis for Ulcerative Colitis

TM Connelly MB, BCh , MS; B Sanders BS; A Berg PhD; L Harris III BS, E Williams MD, S Deiling, BA; A Tinsley MD, MS WA Koltun MD. Genetic Predictors of Quality of Life Post Ileal Pouch Anal Anastomosis for Ulcerative Colitis. No Disclosures. INTRODUCTION.

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Genetic Predictors of Quality of Life Post Ileal Pouch Anal Anastomosis for Ulcerative Colitis

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  1. TM Connelly MB, BCh, MS; B Sanders BS; A Berg PhD; L Harris III BS, E Williams MD, S Deiling, BA; A Tinsley MD, MS WA Koltun MD Genetic Predictors of Quality of Life Post Ileal Pouch Anal Anastomosis for Ulcerative Colitis

  2. No Disclosures

  3. INTRODUCTION • Total proctocolectomy and Ileal Pouch Anal • Anastomosis (IPAA) for ulcerative colitis (UC) allows • for the resection of the diseased rectum and colon • whilst preserving continence • Procedure outcomes and patient satisfaction are • varied • Many studies have attempted to predict pouch function • preoperatively or evaluate pouch function through • objective measures such as pouchitis and frequency of • bowel motions

  4. Ileal Pouch Anal Anastomosis

  5. INTRODUCTION • Regardless of pouch function, patient • satisfaction or well-being post IPAA is what is • desired • Factors to predict such well-being post IPAA are not well defined • We hypothesized that a correlation between a genetic marker and pouch satisfaction may be • identifiable

  6. AIM To determine predictors of post IPAA well-being or satisfaction in the form of: Demographic and perioperative variables Genetic markers

  7. To determine ‘patient satisfaction’ we created a modified questionnaire based on the validated: 1. Modified Pouchitis Activity Score 2. IBD quality of life questionnaire (IBDQ) Added questions on steroid and antibiotic use Adapted to be pouch specific by adding the phrase “Since yourpouch operation…” METHODS: Questionnaire Design

  8. The Modified Pouchitis Activity Score=4 questions on clinical condition: stool frequency, rectal bleeding, urgency and pyrexia IBDQ=32 questions covering 4 categories Bowel symptoms Emotional well-being Social well-being Systemicsymptoms METHODS: Questionnaire Design **These 4 categories were combined for an ‘overall QOL’ score

  9. The 220 adult UC-IPAA patients with stored DNA samples were identified from our divisional Biobank and mailed surveys -Excluded pouch failure/excision patients 14 surveys were returned to sender and 142 (69%) patients responded METHODS: Patient Selection

  10. Patient DNA was genotyped on the HMC Division of Colon and Rectal Surgery’s custom designed Illumina® BeadExpressVeraCode platform -307 IBD associated SNPs Genotyping was performed at the HMC Genomics Core Facility METHODS: Genotyping

  11. Questionnaire Analysis For each category, the median overall score of all patients was calculated Individual patient scores were then separated into above or below the median Fisher’s exact test and the Mann Whitney test were used Variables with a p<.05 in each category were entered into multivariate analyses METHODS: Statistical Evaluation

  12. Genotyping Analysis Logistic Regression Bonferroni correction to correct for multiple comparisons of 307 SNPs METHODS: Statistical Evaluation

  13. RESULTS

  14. Patient Demographics

  15. FACTORS CORRELATING WITH POOR OVERALL QOL

  16. FACTORS CORRELATING WITH POOR OVERALL QOL SCORE

  17. FACTORS CORRELATING WITH POOR EMOTIONAL WELL-BEING

  18. FACTORS CORRELATING WITH POOR EMOTIONAL WELL-BEING

  19. FACTORS CORRELATING WITH POOR SOCIAL WELL-BEING

  20. FACTORS CORRELATING WITH POOR SOCIAL WELL-BEING

  21. OVERALL QOL : GENETICS

  22. BOWEL SYMPTOMS: GENETICS

  23. EMOTIONAL WELL-BEING: GENETICS

  24. TNFSF14 and POU5F1B TNFSF14 (LIGHT) -Stimulation of T cell proliferation -VEGF induced apoptosis of macrophagesfor the resolution of inflammation -Increased in colonic mucosa of IBD patients POU5F1 (OCT4) -Embryonic stem cell pluripotency -Inhibits the differentiation of progenitor cells -Adult stem cell renewal -Associated with UC and CRC

  25. CONCLUSIONS:

  26. CONCLUSIONS: • Worse overall QOL (emotional and social well-being + bowel and systemic symptoms) was associated with: • Female gender, readmission post colectomy, pouchitis • intermittent pyrexia • SNP rs2279627 within the TNFSF14 gene • Poor emotional well-being was associated with: • Readmission post colectomy, pouchitis, urgent colectomy • SNPs within the TNFSF14 and POU5F1 genes • Poor social well-being was associated with: • Pouchitis and a smoking history

  27. CONCLUSIONS: • Outcomes of patients with pouches are largely determined by postoperative variables • However, genetic markers such as POU5F1 and TNFSF14 SNPs are present preoperatively and may potentially be used to assist in surgical decision making

  28. THANK YOU

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