genetic predictors of quality of life post ileal pouch anal anastomosis for ulcerative colitis
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
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
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
INTRODUCTION
Ileal Pouch Anal Anastomosis
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
INTRODUCTION
To determine predictors of post IPAA well-being or satisfaction in the form of:1. Demographic and
perioperative variables2. Genetic markers
AIM
To determine ‘patient satisfaction’ we created a modified questionnaire based on the validated:
1. Modified Pouchitis Activity Score2. IBD quality of life questionnaire (IBDQ)
Added questions on steroid and antibiotic use
Adapted to be pouch specific by adding the phrase “Since your pouch operation…”
METHODS: Questionnaire Design
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 • Systemic symptoms
METHODS: Questionnaire Design
**These 4 categories were combined for an ‘overall QOL’ score
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
Patient DNA was genotyped on the HMC Division of Colon and Rectal Surgery’s custom designed Illumina® BeadExpress VeraCode platform
-307 IBD associated SNPs
Genotyping was performed at the HMC Genomics Core Facility
METHODS: Genotyping
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
Genotyping Analysis
Logistic Regression
Bonferroni correction to correct for multiple comparisons of 307 SNPs
METHODS: Statistical Evaluation
RESULTS
FEMALE 39%EX OR CURRENT SMOKER 41%AGE AT DX (YEARS, SD) 32 ± 12
POUCH DURATION (YEARS, SD) 10 ± 6
DURATION BETWEEN DIAGNOSIS AND COLECTOMY (YEARS, SD)
8 ± 8
Patient Demographics
UNIVARIATE MULTIVARIATE
p value OR 95% CI pFemales .003 2.6 1.1-6.0 .02Readmitted within 30 days post colectomy
.05 5.3
1.8-16.7 .005
History of pouchitis
.00008 5.6 1.12-20 .003
Intermittent pyrexia .009 5.9 1.3-50 .03
Intermittent steroid use
.03
Intermittent antibiotic use
.04
Urgency .004
FACTORS CORRELATING WITH POOR OVERALL QOL
UNIVARIATE MULTIVARIATE
p value OR 95% CI pFemales .003 2.6 1.1-6.0 .02Readmitted within 30 days post colectomy
.05 5.3
1.8-16.7 .005
History of pouchitis
.00008 5.6 1.12-20 .003
Intermittent pyrexia .009 5.9 1.3-50 .03
Intermittent steroid use
.03
Intermittent antibiotic use
.04
Urgency .004
FACTORS CORRELATING WITH POOR OVERALL QOL SCORE
UNIVARIATEp value
Urgent Colectomy .0063Readmitted within 30 days post colectomy
.05
History of pouchitis
.00002
Intermittent pyrexia .05
Intermittent steroid use .03
Intermittent antibiotic use
.04
Urgency .0065
Younger age at colectomy .05
Shorter duration between UC diagnosis and colectomy
.006
FACTORS CORRELATING WITH POOR EMOTIONAL WELL-BEING
UNIVARIATE MULTIVARIATEp value OR 95% CI p
Urgent Colectomy .0063 3.6 1.2-12.5 .02
Readmitted within 30 days post colectomy
.05 5.6
1.8-20 .004
History of pouchitis
.00002 5.6
1.8-20 .004
Intermittent pyrexia .05
Intermittent steroid use .03
Intermittent antibiotic use
.04
Urgency .0065
Younger age at colectomy .05
Shorter duration between UC diagnosis and colectomy
.006
FACTORS CORRELATING WITH POOR EMOTIONAL WELL-BEING
UNIVARIATEp value
Positive Smoking History .02History of pouchitis
.02
Intermittent pyrexia .02
Urgency .007
FACTORS CORRELATING WITH POOR SOCIAL WELL-BEING
UNIVARIATE MULTIVARIATE
p value OR 95% CI pPositive Smoking History .02 2.1 .99-4.5 .053
History of pouchitis
.02 2.1 1.0-4.3 .04
Intermittent pyrexia .02
Urgency .007
FACTORS CORRELATING WITH POOR SOCIAL WELL-BEING
SNP Gene p value Bonferroni corrected p value
rs2279627 TNFSF14 .0001 .033rs7837328 8q24 .00034 NSDrs7014346 8q24 .0018 NSDrs7712957 S100Z .002 NSD
OVERALL QOL : GENETICS
BOWEL SYMPTOMS: GENETICS
SNP Gene p value
Bonferroni corrected p value
rs2279627 TNFSF14 .0001 .033rs7712957 S100Z .0004 NSDrs1297265 Gene Desert .002 NSDrs9647373 CLDN1 .005 NSD
SNP Gene p value Bonferroni corrected p value
rs7837328 POU5F1B .00002 .0061
rs2279627 TNFSF14 .00014 .046
rs7014346 POU5F1B .00014 .0146
rs7712957 S100Z .002 NSD
EMOTIONAL WELL-BEING: GENETICS
TNFSF14 and POU5F1BTNFSF14 (LIGHT) -Stimulation of T cell proliferation-VEGF induced apoptosis of macrophages for 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
CONCLUSIONS:
CONCLUSIONS:1. 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
2. Poor emotional well-being was associated with:Readmission post colectomy, pouchitis, urgent colectomySNPs within the TNFSF14 and POU5F1 genes
3. Poor social well-being was associated with: Pouchitis and a smoking history
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
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