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A prospective evaluation of health-related quality of life after ileal pouch anal anastomosis for ulcerative colitis
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2001 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 96, No. 5, 2001 ISSN 0002-9270/01/$20.00 PII S0002-9270(01)02364-4
A Prospective Evaluation of Health-Related Quality of Life After Ileal Pouch Anal Anastomosis for Ulcerative Colitis A. J. Muir, M.D., L. J. Edwards, Ph.D., L. L. Sanders, M.S., R. R. Bollinger, M.D., Ph.D., M. J. Koruda, M.D., D. R. Bachwich, M.D., and D. Provenzale, M.D. Division of Gastroenterology, Division of Biometry, Department of Community and Family Medicine, Department of Medicine, Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Surgery, University of North Carolina, Chapel Hill, North Carolina; Rapid City Medical Center, Rapid City, South Dakota; and Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, North Carolina
OBJECTIVES: The ileal pouch anal anastomosis is a safe and effective procedure but is also associated with pouchitis, small bowel obstruction, and incontinence. We prospectively evaluated the health-related quality of life using generic and disease-specific measures in a cohort of patients with ulcerative colitis undergoing ileal pouch anal anastomosis. METHODS: Health-related quality of life measures included the Time Trade-off, Rating Form of IBD Patient Concerns, and the Short-Form 36. Assessments occurred preoperatively and 1, 6, and 12 months postoperatively. RESULTS: Time Trade-off scores had significantly improved at the 1-month postoperative assessment and approached perfect health at the 12-month postoperative assessment. The Rating Form of IBD Patient Concerns revealed a significant reduction in patient concerns at 1 month, and this difference persisted at 6 and 12 months. Seven of the eight subscales of the Short-Form 36 revealed improved healthrelated quality of life postoperatively. CONCLUSIONS: Health-related quality of life improved after ileal pouch anal anastomosis when assessed with both generic and disease-specific measures. Improvements were observed as early as 1 month postoperatively. These results may guide patients and physicians as they consider and prepare for the impact of ileal pouch anal anastomosis. (Am J Gastroenterol 2001;96:1480 –1485. © 2001 by Am. Coll. of Gastroenterology)
firmed that the procedure is safe and effective but have also revealed significant rates of pouchitis, small bowel obstruction, and incontinence (1, 2). The benefits coupled with complications naturally raise questions about the functional status and health-related quality of life (HRQL) of these patients. Although both series included data that suggested a good functional outcome for most patients, they did not use standardized HRQL instruments. Previous cross-sectional studies found that HRQL scores of patients after IPAA were similar to patients with UC in remission (3, 4), but the studies lacked a comparison with the preoperative status. Studies that prospectively examined HRQL after IPAA in UC did find improvement in HRQL, but they used generic measures and not a disease-specific measure (5, 6). In an earlier cross-sectional study, we evaluated a group of patients who had undergone IPAA with both generic and disease-specific measures. We used the Sickness Impact Profile (SIP) (7), the Short Form 36 (SF36) (8), and the Time Trade-off (TTO) (9) as our generic measures of HRQL, and we chose the Rating Form of IBD Patient Concerns (RFIPC) (10) for our disease-specific measure. Compared with a national sample of inflammatory bowel disease (IBD) patients, we found that patients undergoing IPAA had better HRQL scores on both the generic and disease-specific measures (11). Using the same measures, we studied a cohort of patients prospectively. The aim of this study was to prospectively evaluate the HRQL in patients with UC undergoing IPAA by comparing their preoperative and postoperative states using both generic and disease-specific HRQL measures.
INTRODUCTION In the last 20 yr, the ileal pouch anal anastomosis (IPAA) procedure has gained wide acceptance as an option for ulcerative colitis (UC) patients who have failed medical therapy or developed dysplasia. Two large series have con-
MATERIALS AND METHODS Patients The cohort included patients from Duke University, the University of North Carolina, and the University of Penn-
AJG – May, 2001
sylvania who underwent IPAA for ulcerative colitis. Patients underwent a two-stage procedure. The first stage was a proctocolectomy with formation of a J-pouch and a Brooke ileostomy. The second stage was takedown of the ileostomy. All patients were contacted and asked to participate by the research coordinator at each institution. All patients gave informed consent. The study was approved by the institutional review board of each institution. Assessments We measured HRQL with the SF-36, TTO, and the RFIPC. The instruments were administered preoperatively and then 1, 6, and 12 months after takedown of the ileostomy. The SF-36 is a 36-item questionnaire that measures three major health attributes: 1) health status (physical functioning, social functioning, role limitations because of energy problems); 2) well-being (mental health, energy and fatigue, pain); and 3) an overall evaluation of health. Higher scores are associated with improved HRQL. Validated as part of the Medical Outcomes Study (12), the SF-36 was created for clinicians as a practical method for monitoring patient outcomes in routine practice settings. The SF-36 has measured disease severity and has also predicted subsequent transitions in health status, expenditures, use, and mortality. The scale has been validated in multiple populations, including dialysis patients (13), diabetics (14), and elderly veterans (15). The TTO is a utility measure that asks the respondent to choose between a longer life expectancy (time t) in a less healthy state (state i), versus a shorter life expectancy (time x) in a perfect or excellent state of health. Preference values are derived implicitly based on individual responses to decision situations, e.g., “Would you rather live 10 yr in your current health state or 5 yr in perfect health?” The time in the state of perfect health (time x) is varied until the responder is indifferent between the two alternatives. At the point of indifference, the required preference value for state i is given by hi ⫽ x/t. For example, if the individual believes that living 10 yr in his or her current health state is equivalent to living 5 yr in perfect health, the TTO score is 5/10 or 0.5. A score of 0 is equivalent to being dead, and a score of 1 is equivalent to a state of perfect health. The RFIPC is a disease-specific 25-item measure of perceived health status that was standardized in a national study of patients with IBD. The overall scale ranged from zero to 100, and lower scores suggest fewer concerns and improved HRQL. Factor analysis revealed the following four indices: 1) impact of disease, 2) sexual intimacy, 3) complication of disease, and 4) body stigma. The RFIPC was designed specifically for patients with IBD. The severity of the concerns correlated with the patient’s psychological well-being and daily function. Statistical Analysis Patient characteristics were described in terms of medians and interquartile ranges (IQR) when they were continuous
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Table 1. Patient Characteristics (n ⫽ 20) Age (yr), median (IQR) Gender, no. (%) female Race, no. (%) white Indication, no (%) severe colitis Duration of diagnosis (yr), median (IQR) Admissions last 2 yr, median (IQR) Location, no. (%) pancolitis Prednisone use, no. (%) Immunomodulator use, no. (%) Not working because of UC, no. (%)
38 (33–46.5) 10 (50) 18 (90) 19 (95) 7.5 (3–14.5) 1 (0–2.5) 16 (80) 14 (70) 9 (45) 6 (30)
(e.g., age, duration of diagnosis) and in terms of the number and percent with the characteristic when categorical (e.g., gender, race). Means and standard deviations (SD) were found for each of the scale measurements at the preoperative stage and at each follow-up time. Differences between preoperative scores and each follow-up were evaluated using paired t tests. Pearson correlation coefficients were used to evaluate the association between each of the different HRQL instruments. The mixed general linear model (16), a multivariate data analysis technique used for analyzing longitudinal data, was used to assess the change in HRQL measurements over time. All models had measurement score at 1, 6, and 12 months as the outcome, and had baseline score and time from baseline as predictor variables. The time from baseline measurement was centered at the average of the 6-month measurements. Additionally, the models describing the change over time in RFIPC and the Role Physical component of the SF-36 contained time (centered) squared as a predictor variable.
RESULTS Table 1 contains patient characteristics. The cohort included 10 men and 10 women with a median age of 38 yr. For the majority, the indication for colectomy was severe colitis. In this group of patients, 70% were taking prednisone preoperatively, whereas 45% were receiving immunomodulator therapy. All 20 patients participated in the four interviews for TTO assessments. In all, 18 patients completed the questionnaires at 1 month after takedown of the ileostomy, and 17 patients completed all of the 6- and 12-month questionnaires. Table 2 includes the TTO scores at each assessment point. There was a statistically and clinically significant improvement in TTO scores by 1 month after takedown of the ileostomy. Of note, these differences remained significant after accounting for multiple comparisons. When compared with the preoperative score, the difference persisted at 6 and 12 months. By 12 months after takedown, the mean TTO score of 0.93 approached perfect health (1.0). Table 3 lists the coefficients for each regression equation. The TTO regression equation coefficients for both predictor variables are statistically significant, demonstrating a continued im-
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Table 2. Time Trade-Off and Rating Form of IBD Patient Concern Scores at the Preoperative and Postoperative Intervals Time trade-off, mean ⫾ SD RFIPC, mean ⫾ SD
Preop
1 Mo
6 Mo
12 Mo
0.59 ⫾ 0.28 53.3 ⫾ 25.1
0.80 ⫾ 0.24* 28.3 ⫾ 17.8*
0.91 ⫾ 0.14* 24.6 ⫾ 16.7*
0.93 ⫾ 0.09* 23.2 ⫾ 12.6*
* p ⬍ 0.001 for paired t test with preoperative score. Tests remained significant after accounting for multiple comparisons.
provement in TTO score between months 1 and 12. Therefore, whereas the most substantial change in TTO score occurred by 1 month after takedown of the ileostomy, we observed continued improvement between months 1 and 12. Table 2 also includes the scores for the disease-specific measure, the RFIPC. Paired t tests compared preoperative and postoperative concerns, and found a statistically and clinically significant reduction in patient concerns by 1 month after takedown. The difference persisted at 6 and 12 months after takedown. These differences also remained significant after accounting for multiple comparisons. Figure 1 displays the plots of the individual and overall mean RFIPC scores derived from the mixed general linear model equation. The overall mean is represented by the thick line. Once again, the regression equation coefficients are statistically different from zero. The greatest reduction in concerns seems to have developed by 1 month after takedown, and then the RFIPC scores decline for the remainder of the year, suggesting continued improvement in HRQL. The results of the SF-36, the generic HRQL instrument, are shown in Table 4. The subscales of Social Functioning, Mental Health, General Health, and Vitality had improved significantly by 1 month after takedown (p ⬍ 0.05). The subscales of Physical Functioning, Role Physical, and Bodily Pain showed significant improvements by 6 months after takedown (p ⬍ 0.05). All of these improvements persisted at the 12-month assessment. Only the Role Emotional subscale did not improve in this analysis. With the number of subscales and the small sample size, these differences were not significant after accounting for multiple comparisons. A mixed general linear model was constructed to examine the change in the subscales between 1 and 12 months, and the coefficients of these equations are listed in Table 3. The baseline score was a significant predictor for all subscales except Social Functioning and Bodily Pain. Time was a significant predictor of all the subscales except
Role Emotional. Thus, seven of the eight subscales improved between months 1 and 12. For comparison, the final column of Table 4 lists the scores of a healthy population. Our patients’ scores were similar to the healthy population at 12 months. We also examined the correlations between the various instruments. The results are shown in Table 5. Preoperatively, the correlations between TTO and both RFIPC and the SF-36 standardized mental composite score (MCS) were good (⬎0.5), whereas the correlation between the TTO and the SF-36 standardized physical composite score (PCS) was fair. Interestingly, the postoperative pattern reversed with good correlation between TTO and PCS and fair correlations with both RFIPC and MCS.
DISCUSSION Using both disease-specific and generic instruments, we found that HRQL improved significantly after IPAA for patients with chronic UC. Seven of the eight subscales of the SF-36 improved after IPAA and were similar to those of a healthy population at 12 months after takedown. TTO scores improved dramatically after IPAA and approached perfect health 12 months after takedown of the ileostomy. Finally, the RFIPC scores also improved with a significant reduction in concerns by 1 month after takedown of the ileostomy. Although patients have traditionally been counseled to expect a full year to recover after IPAA, improvements in most of the measures occurred by 1 month after takedown of the ileostomy. We observed statistically significant improvements in the TTO, RFIPC, and four of the eight SF-36 subscales at 1 month after takedown of the ileostomy. The correlations between the generic and disease-specific instruments demonstrated that preoperative TTO scores correlated with emotional aspects of HRQL, suggesting that emotional factors are a major component of preoperative
Table 3. Mixed Model Regression Equation Coefficients Measure
Intercept
p Value
Preop Score
p Value
Time
p Value
Time2
TTO RFIPC PF SF RP RE MH BP GH VT
0.7025 0.9098 44.47 66.34 59.66 54.47 41.57 58.78 38.10 38.89
0.0001 0.2058 0.0001 0.0001 0.0001 0.0001 0.0015 0.0001 0.0009 0.0001
0.2934 0.3212 0.6322 0.2149 0.4991 0.3876 0.5444 0.1855 0.5122 0.4073
0.0008 0.0117 0.0001 0.1138 0.0006 0.0064 0.0032 0.1909 0.013 0.0116
0.0101 ⫺0.070 2.237 1.482 4.392 ⫺0.4804 0.7014 1.763 1.013 1.397
0.0151 0.0108 0.0001 0.0144 0.0001 0.5574 0.0321 0.0014 0.013 0.006
N/A N/A ⫺0.2566 N/A ⫺0.5535 N/A N/A N/A N/A N/A
N/A ⫽ not applicable; other abbreviations as in text.
p Value
0.0103 0.0081
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Figure 1. Plots of the Rating Form of IBD Patient Concerns (RFIPC) scores for individual patients after the last surgery (regular lines) and then the score derived from the mixed general linear model equation (boldface line). The baseline score is a predictor variable in the model and therefore is not shown on this graph. Lower RFIPC scores suggest fewer concerns and improved health-related quality of life. The greatest reduction in concerns seems to have developed by 1 month after takedown, after which the RFIPC scores decline for the remainder of the year.
HRQL. Meanwhile, postoperative TTO scores more highly correlated with physical factors, suggesting that physical function is a major component of postoperative HRQL. To date, two large series have shown excellent results with the IPAA procedure. In a series of 1005 patients between 1983 and 1993, Fazio et al. reported their results (2). In examining functional results, the patients reported a median of six bowel movements in a 24-h period. Of the patients, 10% experienced urgency, 29% seepage, and 44% a dietary restriction. When considering quality of life, 93% of patients rated theirs as good or excellent. They reported an early mortality rate of 0.4%. With a median follow-up of 28 months, complication rates included small bowel obstruction (25.3%), pouchitis (23.5%), anal stricture (14%),
parapouch abscess or peritonitis (8.2%), pouch-cutaneous fistula (5.2%), and pouch-vaginal fistula (4.2% of women). Meagher et al. recently reported their experience with 1310 patients undergoing IPAA for ulcerative colitis between 1981 and 1994 (3). Of their patients, 10% of their patients experienced pouch failure. The patients reported a mean of six bowel movements in a 24-h period. One year after the procedure, symptoms included incontinence (20%) and sexual dysfunction (14%). In addition, 48% of patients were taking an antidiarrheal medication. Although both series show impressive results and, overall, an excellent functional outcome, significant numbers of patients experienced complications. As a result, the overall assessment of HRQL is a natural consideration for patients
Table 4. Mean Values of SF-36 Scores* at the Preoperative and Postoperative Intervals Subscale
Preop (n ⫽ 20)
1 Mo (n ⫽ 18)
6 Mo (n ⫽ 17)
12 Mo (n ⫽ 18)
Healthy Population
PF (Physical functioning) SF (Social functioning) RP (Role physical) RE (Role emotional) MH (Mental health) BP (Bodily pain) GH (General Health) VT (Vitality)
59.0 ⫾ 30.7 53.1 ⫾ 33.2 36.2 ⫾ 44.0 58.3 ⫾ 41.7 61.0 ⫾ 19.1 53.4 ⫾ 27.4 41.2 ⫾ 22.7 31.5 ⫾ 25.3
66.7 ⫾ 28.0 69.8 ⫾ 29.2† 47.6 ⫾ 41.7 81.5 ⫾ 30.7 72.0 ⫾ 19.1† 57.6 ⫾ 20.9 56.7 ⫾ 21.3† 45.3 ⫾ 23.0†
81.5 ⫾ 27.6† 80.9 ⫾ 27.6† 75.0 ⫾ 43.3† 78.4 ⫾ 39.0 75.3 ⫾ 21.8† 74.4 ⫾ 25.0† 61.1 ⫾ 28.4† 52.6 ⫾ 25.4†
85.3 ⫾ 22.3† 86.1 ⫾ 17.6† 80.6 ⫾ 31.6† 75.9 ⫾ 35.8 79.1 ⫾ 16.3† 77.7 ⫾ 18.9† 66.8 ⫾ 19.2† 61.7 ⫾ 20.9†
84.2 ⫾ 23.3 83.3 ⫾ 22.7 81.0 ⫾ 34.0 81.3 ⫾ 33.0 74.7 ⫾ 18.0 75.2 ⫾ 23.7 72.0 ⫾ 20.3 60.9 ⫾ 21.0
* Higher SF-36 scores are associated with improved HRQL. † p ⬍ 0.05 for paired t test with preoperative score. Tests were not significant after accounting for multiple comparisons.
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Table 5. Correlations of Time Trade-Off Scores Versus RFIPC Scores and the Standardized Physical (PCS) and Mental (MCS) Scores of the SF-36 Time Period
TTO vs RFIPC
TTO vs PCS
TTO vs MCS
Preop 1 mo postop 6 mo postop 12 mo postop
⫺0.59 ⫺0.44 ⫺0.79 ⫺0.44
0.30 0.56 0.78 0.66
0.52 0.31 0.85 0.36
Preop ⫽ preoperative; postop ⫽ postoperative; other abbreviations as in text.
contemplating IPAA. Multiple series have now shown good HRQL after IPAA. In a retrospective study of 55 patients who underwent IPAA for UC or familial adenomatous polyposis, 47 (87%) of patients described their quality of life as “always” better since IPAA (17). Recently, Brunel et al. extended these results to patients with distal ulcerative colitis. HRQL was assessed by restrictions on social activities, work, recreation, sex life, and travel. They noted a dramatic improvement in the social life of 26 of 27 patients (18). These series, however, did not use validated HRQL measures. McLeod et al. examined HRQL with the TTO and the SIP in a group of 20 patients (6). The TTO results were similar to our cohort with an increase from 0.58 to 0.98 from the preoperative to the postoperative state. The SIP scores also significantly improved in the group. However, the postoperative assessment occurred at a mean of 14 months. We found the substantial increase in HRQL 1 month after takedown to be an especially interesting finding that may help guide patients when considering IPAA. Thirby et al. followed-up 24 patients who underwent IPAA for UC (6). The evaluations occurred preoperatively and then every 3 months postoperatively with Health Status Questionnaire (a variant of the SF-36). Significant improvements occurred in six of eight subscales by the 9-month evaluation. Although statistical comparisons were not reported, several of the subscales also showed improvements by the 3-month evaluation. Both of these studies, however, used generic HRQL measures but did not include a disease-specific measure. Martin et al. studied HRQL after IPAA with a diseasespecific measure (5). They developed a 29-item instrument for 29 patients with UC who underwent IPAA. The patients were evaluated at a mean of 3.8 yr after the surgery. When compared with other patient groups, the IPAA patients had similar scores to UC patients in remission or with mild disease. In a similar study, Sagar et al. developed a diseasespecific measure and found that a group of patients at least 12 months after IPAA had similar HRQL scores to a group of UC patients on medical treatment (4). Our study was the first, however, to prospectively study IPAA patients with a disease-specific measure. HRQL and functional status are important issues for the patient for whom IPAA is recommended. Our study was prospective and therefore allowed us to compare the patients with their preoperative status. Our assessment examined all aspects, using a disease-specific measure as well as a ge-
neric and a utility measure. The use of both disease-specific and generic measures of HRQL increases the potential application of these results. Although the disease-specific measure may be more helpful to the individual patient evaluating the treatment, the generic measure allows comparisons with other disease states and the general population. In any case, all of these instruments demonstrated significant improvements after IPAA, with many patients experiencing significant improvements as early as 1 month after takedown of the ileostomy. These results can be used to guide patients and physicians as they consider and then prepare for the impact of IPAA.
ACKNOWLEDGMENTS Supported in part by National Institutes of Health Training Grant in Digestive Diseases (to A.J.M.) and VA HSR&D Career Development Award (to D.P.). Reprint requests and correspondence: Andrew J. Muir, M.D., DUMC Box 3913, Durham, NC 27710. Received Oct. 12, 2000; accepted Jan. 5, 2001.
REFERENCES 1. Fazio VW, Ziv Y, Church JM, et al. Ileal pouch-anal anastomoses complications and function in 1005 patients. Ann Surg 1995;222:120 –7. 2. Meagher AP, Farouk R, Dozois RR, et al. J ileal pouch-anal anastomosis for chronic ulcerative colitis: Complications and long-term outcome in 1310 patients. Br J Surg 1998;85:800 –3. 3. Sagar PM, Lewis W, Holdsworth PJ, et al. Quality of life after restorative proctocolectomy with a pelvic ileal reservoir compares favorably with that of patients with medically treated colitis. Dis Colon Rectum 1993;36:584 –92. 4. Martin A, Dinca M, Leone L, et al. Quality of life after proctocolectomy and ileo-anal anastomosis for severe ulcerative colitis. Am J Gastroenterol 1998;93:166 –9. 5. McLeod RS, Churchill DN, Lock AM, et al. Quality of life of patients with ulcerative colitis preoperatively and postoperatively. Gastroenterology 1991;101:1307–13. 6. Thirby RC, Land JC, Fenster LF, et al. Effect of surgery on health-related quality of life in patients with inflammatory bowel disease. Arch Surg 1998;133:826 –32. 7. Bergner M, Bobbitt RA, Carter WB, et al. The sickness impact profile: Development and final revision of a health status measure. Med Care 1981;19:787– 805. 8. Stewart AL, Hays RD, Ware JE. The MOS short-form general health survey: Reliability and validity in a patient population. Med Care 1988;36:925–30. 9. Torrance GW. Utility approach to measuring health-related quality of life. J Chron Dis 1987;40:593– 600. 10. Drossman DA, Lesserman J, Mitchell CM, et al. The rating form of IBD patient concerns: A new measure of health status. Psychosom Med 1991;53:701–12. 11. Provenzale D, Shearin M, Phillips-Bute BG, et al. Healthrelated quality of life after ileoanal pull-through. Evaluation and assessment of new health status measures. Gastroenterology 1997;113:7–14. 12. Tarlov AR, Ware JE, Greenfield S. The medical outcomes
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study: An application of methods for monitoring the results of medical care. JAMA 1989;262:724 –35. 13. Kurtin PS, Davies AR, Meyer KB, et al. Patient-based measures in outpatient dialysis. Early experiences in developing outcomes assessment program. Med Care 1992;30:136 – 49S. 14. Nerenz DR, Repasky DP, Whitehouse FW, et al. Ongoing assessment of health status in patients with diabetes mellitus. Med Care 1992;30:MS112–24. 15. Weinberger M, Samsa GP, Hanlon JT, et al. An evaluation of
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a brief health status measure in elderly veterans. J Am Geriatr Soc 1991;39:691– 4. 16. Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics 1982;38:963–74. 17. Seidel PA, Peach SE, Newman M, et al. Ileoanal pouch procedures: Clinical outcomes and quality-of-life assessment. Am Surg 1999;65:40 – 6. 18. Brunel M, Penna C, Tiret E, et al. Restorative proctocolectomy for distal ulcerative colitis. Gut 1999;45:542–5.
Vol. 96, No. 5, 2001 ISSN 0002-9270/01/$20.00 PII S0002-9270(01)02364-4
A Prospective Evaluation of Health-Related Quality of Life After Ileal Pouch Anal Anastomosis for Ulcerative Colitis A. J. Muir, M.D., L. J. Edwards, Ph.D., L. L. Sanders, M.S., R. R. Bollinger, M.D., Ph.D., M. J. Koruda, M.D., D. R. Bachwich, M.D., and D. Provenzale, M.D. Division of Gastroenterology, Division of Biometry, Department of Community and Family Medicine, Department of Medicine, Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Surgery, University of North Carolina, Chapel Hill, North Carolina; Rapid City Medical Center, Rapid City, South Dakota; and Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, North Carolina
OBJECTIVES: The ileal pouch anal anastomosis is a safe and effective procedure but is also associated with pouchitis, small bowel obstruction, and incontinence. We prospectively evaluated the health-related quality of life using generic and disease-specific measures in a cohort of patients with ulcerative colitis undergoing ileal pouch anal anastomosis. METHODS: Health-related quality of life measures included the Time Trade-off, Rating Form of IBD Patient Concerns, and the Short-Form 36. Assessments occurred preoperatively and 1, 6, and 12 months postoperatively. RESULTS: Time Trade-off scores had significantly improved at the 1-month postoperative assessment and approached perfect health at the 12-month postoperative assessment. The Rating Form of IBD Patient Concerns revealed a significant reduction in patient concerns at 1 month, and this difference persisted at 6 and 12 months. Seven of the eight subscales of the Short-Form 36 revealed improved healthrelated quality of life postoperatively. CONCLUSIONS: Health-related quality of life improved after ileal pouch anal anastomosis when assessed with both generic and disease-specific measures. Improvements were observed as early as 1 month postoperatively. These results may guide patients and physicians as they consider and prepare for the impact of ileal pouch anal anastomosis. (Am J Gastroenterol 2001;96:1480 –1485. © 2001 by Am. Coll. of Gastroenterology)
firmed that the procedure is safe and effective but have also revealed significant rates of pouchitis, small bowel obstruction, and incontinence (1, 2). The benefits coupled with complications naturally raise questions about the functional status and health-related quality of life (HRQL) of these patients. Although both series included data that suggested a good functional outcome for most patients, they did not use standardized HRQL instruments. Previous cross-sectional studies found that HRQL scores of patients after IPAA were similar to patients with UC in remission (3, 4), but the studies lacked a comparison with the preoperative status. Studies that prospectively examined HRQL after IPAA in UC did find improvement in HRQL, but they used generic measures and not a disease-specific measure (5, 6). In an earlier cross-sectional study, we evaluated a group of patients who had undergone IPAA with both generic and disease-specific measures. We used the Sickness Impact Profile (SIP) (7), the Short Form 36 (SF36) (8), and the Time Trade-off (TTO) (9) as our generic measures of HRQL, and we chose the Rating Form of IBD Patient Concerns (RFIPC) (10) for our disease-specific measure. Compared with a national sample of inflammatory bowel disease (IBD) patients, we found that patients undergoing IPAA had better HRQL scores on both the generic and disease-specific measures (11). Using the same measures, we studied a cohort of patients prospectively. The aim of this study was to prospectively evaluate the HRQL in patients with UC undergoing IPAA by comparing their preoperative and postoperative states using both generic and disease-specific HRQL measures.
INTRODUCTION In the last 20 yr, the ileal pouch anal anastomosis (IPAA) procedure has gained wide acceptance as an option for ulcerative colitis (UC) patients who have failed medical therapy or developed dysplasia. Two large series have con-
MATERIALS AND METHODS Patients The cohort included patients from Duke University, the University of North Carolina, and the University of Penn-
AJG – May, 2001
sylvania who underwent IPAA for ulcerative colitis. Patients underwent a two-stage procedure. The first stage was a proctocolectomy with formation of a J-pouch and a Brooke ileostomy. The second stage was takedown of the ileostomy. All patients were contacted and asked to participate by the research coordinator at each institution. All patients gave informed consent. The study was approved by the institutional review board of each institution. Assessments We measured HRQL with the SF-36, TTO, and the RFIPC. The instruments were administered preoperatively and then 1, 6, and 12 months after takedown of the ileostomy. The SF-36 is a 36-item questionnaire that measures three major health attributes: 1) health status (physical functioning, social functioning, role limitations because of energy problems); 2) well-being (mental health, energy and fatigue, pain); and 3) an overall evaluation of health. Higher scores are associated with improved HRQL. Validated as part of the Medical Outcomes Study (12), the SF-36 was created for clinicians as a practical method for monitoring patient outcomes in routine practice settings. The SF-36 has measured disease severity and has also predicted subsequent transitions in health status, expenditures, use, and mortality. The scale has been validated in multiple populations, including dialysis patients (13), diabetics (14), and elderly veterans (15). The TTO is a utility measure that asks the respondent to choose between a longer life expectancy (time t) in a less healthy state (state i), versus a shorter life expectancy (time x) in a perfect or excellent state of health. Preference values are derived implicitly based on individual responses to decision situations, e.g., “Would you rather live 10 yr in your current health state or 5 yr in perfect health?” The time in the state of perfect health (time x) is varied until the responder is indifferent between the two alternatives. At the point of indifference, the required preference value for state i is given by hi ⫽ x/t. For example, if the individual believes that living 10 yr in his or her current health state is equivalent to living 5 yr in perfect health, the TTO score is 5/10 or 0.5. A score of 0 is equivalent to being dead, and a score of 1 is equivalent to a state of perfect health. The RFIPC is a disease-specific 25-item measure of perceived health status that was standardized in a national study of patients with IBD. The overall scale ranged from zero to 100, and lower scores suggest fewer concerns and improved HRQL. Factor analysis revealed the following four indices: 1) impact of disease, 2) sexual intimacy, 3) complication of disease, and 4) body stigma. The RFIPC was designed specifically for patients with IBD. The severity of the concerns correlated with the patient’s psychological well-being and daily function. Statistical Analysis Patient characteristics were described in terms of medians and interquartile ranges (IQR) when they were continuous
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Table 1. Patient Characteristics (n ⫽ 20) Age (yr), median (IQR) Gender, no. (%) female Race, no. (%) white Indication, no (%) severe colitis Duration of diagnosis (yr), median (IQR) Admissions last 2 yr, median (IQR) Location, no. (%) pancolitis Prednisone use, no. (%) Immunomodulator use, no. (%) Not working because of UC, no. (%)
38 (33–46.5) 10 (50) 18 (90) 19 (95) 7.5 (3–14.5) 1 (0–2.5) 16 (80) 14 (70) 9 (45) 6 (30)
(e.g., age, duration of diagnosis) and in terms of the number and percent with the characteristic when categorical (e.g., gender, race). Means and standard deviations (SD) were found for each of the scale measurements at the preoperative stage and at each follow-up time. Differences between preoperative scores and each follow-up were evaluated using paired t tests. Pearson correlation coefficients were used to evaluate the association between each of the different HRQL instruments. The mixed general linear model (16), a multivariate data analysis technique used for analyzing longitudinal data, was used to assess the change in HRQL measurements over time. All models had measurement score at 1, 6, and 12 months as the outcome, and had baseline score and time from baseline as predictor variables. The time from baseline measurement was centered at the average of the 6-month measurements. Additionally, the models describing the change over time in RFIPC and the Role Physical component of the SF-36 contained time (centered) squared as a predictor variable.
RESULTS Table 1 contains patient characteristics. The cohort included 10 men and 10 women with a median age of 38 yr. For the majority, the indication for colectomy was severe colitis. In this group of patients, 70% were taking prednisone preoperatively, whereas 45% were receiving immunomodulator therapy. All 20 patients participated in the four interviews for TTO assessments. In all, 18 patients completed the questionnaires at 1 month after takedown of the ileostomy, and 17 patients completed all of the 6- and 12-month questionnaires. Table 2 includes the TTO scores at each assessment point. There was a statistically and clinically significant improvement in TTO scores by 1 month after takedown of the ileostomy. Of note, these differences remained significant after accounting for multiple comparisons. When compared with the preoperative score, the difference persisted at 6 and 12 months. By 12 months after takedown, the mean TTO score of 0.93 approached perfect health (1.0). Table 3 lists the coefficients for each regression equation. The TTO regression equation coefficients for both predictor variables are statistically significant, demonstrating a continued im-
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Table 2. Time Trade-Off and Rating Form of IBD Patient Concern Scores at the Preoperative and Postoperative Intervals Time trade-off, mean ⫾ SD RFIPC, mean ⫾ SD
Preop
1 Mo
6 Mo
12 Mo
0.59 ⫾ 0.28 53.3 ⫾ 25.1
0.80 ⫾ 0.24* 28.3 ⫾ 17.8*
0.91 ⫾ 0.14* 24.6 ⫾ 16.7*
0.93 ⫾ 0.09* 23.2 ⫾ 12.6*
* p ⬍ 0.001 for paired t test with preoperative score. Tests remained significant after accounting for multiple comparisons.
provement in TTO score between months 1 and 12. Therefore, whereas the most substantial change in TTO score occurred by 1 month after takedown of the ileostomy, we observed continued improvement between months 1 and 12. Table 2 also includes the scores for the disease-specific measure, the RFIPC. Paired t tests compared preoperative and postoperative concerns, and found a statistically and clinically significant reduction in patient concerns by 1 month after takedown. The difference persisted at 6 and 12 months after takedown. These differences also remained significant after accounting for multiple comparisons. Figure 1 displays the plots of the individual and overall mean RFIPC scores derived from the mixed general linear model equation. The overall mean is represented by the thick line. Once again, the regression equation coefficients are statistically different from zero. The greatest reduction in concerns seems to have developed by 1 month after takedown, and then the RFIPC scores decline for the remainder of the year, suggesting continued improvement in HRQL. The results of the SF-36, the generic HRQL instrument, are shown in Table 4. The subscales of Social Functioning, Mental Health, General Health, and Vitality had improved significantly by 1 month after takedown (p ⬍ 0.05). The subscales of Physical Functioning, Role Physical, and Bodily Pain showed significant improvements by 6 months after takedown (p ⬍ 0.05). All of these improvements persisted at the 12-month assessment. Only the Role Emotional subscale did not improve in this analysis. With the number of subscales and the small sample size, these differences were not significant after accounting for multiple comparisons. A mixed general linear model was constructed to examine the change in the subscales between 1 and 12 months, and the coefficients of these equations are listed in Table 3. The baseline score was a significant predictor for all subscales except Social Functioning and Bodily Pain. Time was a significant predictor of all the subscales except
Role Emotional. Thus, seven of the eight subscales improved between months 1 and 12. For comparison, the final column of Table 4 lists the scores of a healthy population. Our patients’ scores were similar to the healthy population at 12 months. We also examined the correlations between the various instruments. The results are shown in Table 5. Preoperatively, the correlations between TTO and both RFIPC and the SF-36 standardized mental composite score (MCS) were good (⬎0.5), whereas the correlation between the TTO and the SF-36 standardized physical composite score (PCS) was fair. Interestingly, the postoperative pattern reversed with good correlation between TTO and PCS and fair correlations with both RFIPC and MCS.
DISCUSSION Using both disease-specific and generic instruments, we found that HRQL improved significantly after IPAA for patients with chronic UC. Seven of the eight subscales of the SF-36 improved after IPAA and were similar to those of a healthy population at 12 months after takedown. TTO scores improved dramatically after IPAA and approached perfect health 12 months after takedown of the ileostomy. Finally, the RFIPC scores also improved with a significant reduction in concerns by 1 month after takedown of the ileostomy. Although patients have traditionally been counseled to expect a full year to recover after IPAA, improvements in most of the measures occurred by 1 month after takedown of the ileostomy. We observed statistically significant improvements in the TTO, RFIPC, and four of the eight SF-36 subscales at 1 month after takedown of the ileostomy. The correlations between the generic and disease-specific instruments demonstrated that preoperative TTO scores correlated with emotional aspects of HRQL, suggesting that emotional factors are a major component of preoperative
Table 3. Mixed Model Regression Equation Coefficients Measure
Intercept
p Value
Preop Score
p Value
Time
p Value
Time2
TTO RFIPC PF SF RP RE MH BP GH VT
0.7025 0.9098 44.47 66.34 59.66 54.47 41.57 58.78 38.10 38.89
0.0001 0.2058 0.0001 0.0001 0.0001 0.0001 0.0015 0.0001 0.0009 0.0001
0.2934 0.3212 0.6322 0.2149 0.4991 0.3876 0.5444 0.1855 0.5122 0.4073
0.0008 0.0117 0.0001 0.1138 0.0006 0.0064 0.0032 0.1909 0.013 0.0116
0.0101 ⫺0.070 2.237 1.482 4.392 ⫺0.4804 0.7014 1.763 1.013 1.397
0.0151 0.0108 0.0001 0.0144 0.0001 0.5574 0.0321 0.0014 0.013 0.006
N/A N/A ⫺0.2566 N/A ⫺0.5535 N/A N/A N/A N/A N/A
N/A ⫽ not applicable; other abbreviations as in text.
p Value
0.0103 0.0081
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Figure 1. Plots of the Rating Form of IBD Patient Concerns (RFIPC) scores for individual patients after the last surgery (regular lines) and then the score derived from the mixed general linear model equation (boldface line). The baseline score is a predictor variable in the model and therefore is not shown on this graph. Lower RFIPC scores suggest fewer concerns and improved health-related quality of life. The greatest reduction in concerns seems to have developed by 1 month after takedown, after which the RFIPC scores decline for the remainder of the year.
HRQL. Meanwhile, postoperative TTO scores more highly correlated with physical factors, suggesting that physical function is a major component of postoperative HRQL. To date, two large series have shown excellent results with the IPAA procedure. In a series of 1005 patients between 1983 and 1993, Fazio et al. reported their results (2). In examining functional results, the patients reported a median of six bowel movements in a 24-h period. Of the patients, 10% experienced urgency, 29% seepage, and 44% a dietary restriction. When considering quality of life, 93% of patients rated theirs as good or excellent. They reported an early mortality rate of 0.4%. With a median follow-up of 28 months, complication rates included small bowel obstruction (25.3%), pouchitis (23.5%), anal stricture (14%),
parapouch abscess or peritonitis (8.2%), pouch-cutaneous fistula (5.2%), and pouch-vaginal fistula (4.2% of women). Meagher et al. recently reported their experience with 1310 patients undergoing IPAA for ulcerative colitis between 1981 and 1994 (3). Of their patients, 10% of their patients experienced pouch failure. The patients reported a mean of six bowel movements in a 24-h period. One year after the procedure, symptoms included incontinence (20%) and sexual dysfunction (14%). In addition, 48% of patients were taking an antidiarrheal medication. Although both series show impressive results and, overall, an excellent functional outcome, significant numbers of patients experienced complications. As a result, the overall assessment of HRQL is a natural consideration for patients
Table 4. Mean Values of SF-36 Scores* at the Preoperative and Postoperative Intervals Subscale
Preop (n ⫽ 20)
1 Mo (n ⫽ 18)
6 Mo (n ⫽ 17)
12 Mo (n ⫽ 18)
Healthy Population
PF (Physical functioning) SF (Social functioning) RP (Role physical) RE (Role emotional) MH (Mental health) BP (Bodily pain) GH (General Health) VT (Vitality)
59.0 ⫾ 30.7 53.1 ⫾ 33.2 36.2 ⫾ 44.0 58.3 ⫾ 41.7 61.0 ⫾ 19.1 53.4 ⫾ 27.4 41.2 ⫾ 22.7 31.5 ⫾ 25.3
66.7 ⫾ 28.0 69.8 ⫾ 29.2† 47.6 ⫾ 41.7 81.5 ⫾ 30.7 72.0 ⫾ 19.1† 57.6 ⫾ 20.9 56.7 ⫾ 21.3† 45.3 ⫾ 23.0†
81.5 ⫾ 27.6† 80.9 ⫾ 27.6† 75.0 ⫾ 43.3† 78.4 ⫾ 39.0 75.3 ⫾ 21.8† 74.4 ⫾ 25.0† 61.1 ⫾ 28.4† 52.6 ⫾ 25.4†
85.3 ⫾ 22.3† 86.1 ⫾ 17.6† 80.6 ⫾ 31.6† 75.9 ⫾ 35.8 79.1 ⫾ 16.3† 77.7 ⫾ 18.9† 66.8 ⫾ 19.2† 61.7 ⫾ 20.9†
84.2 ⫾ 23.3 83.3 ⫾ 22.7 81.0 ⫾ 34.0 81.3 ⫾ 33.0 74.7 ⫾ 18.0 75.2 ⫾ 23.7 72.0 ⫾ 20.3 60.9 ⫾ 21.0
* Higher SF-36 scores are associated with improved HRQL. † p ⬍ 0.05 for paired t test with preoperative score. Tests were not significant after accounting for multiple comparisons.
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Table 5. Correlations of Time Trade-Off Scores Versus RFIPC Scores and the Standardized Physical (PCS) and Mental (MCS) Scores of the SF-36 Time Period
TTO vs RFIPC
TTO vs PCS
TTO vs MCS
Preop 1 mo postop 6 mo postop 12 mo postop
⫺0.59 ⫺0.44 ⫺0.79 ⫺0.44
0.30 0.56 0.78 0.66
0.52 0.31 0.85 0.36
Preop ⫽ preoperative; postop ⫽ postoperative; other abbreviations as in text.
contemplating IPAA. Multiple series have now shown good HRQL after IPAA. In a retrospective study of 55 patients who underwent IPAA for UC or familial adenomatous polyposis, 47 (87%) of patients described their quality of life as “always” better since IPAA (17). Recently, Brunel et al. extended these results to patients with distal ulcerative colitis. HRQL was assessed by restrictions on social activities, work, recreation, sex life, and travel. They noted a dramatic improvement in the social life of 26 of 27 patients (18). These series, however, did not use validated HRQL measures. McLeod et al. examined HRQL with the TTO and the SIP in a group of 20 patients (6). The TTO results were similar to our cohort with an increase from 0.58 to 0.98 from the preoperative to the postoperative state. The SIP scores also significantly improved in the group. However, the postoperative assessment occurred at a mean of 14 months. We found the substantial increase in HRQL 1 month after takedown to be an especially interesting finding that may help guide patients when considering IPAA. Thirby et al. followed-up 24 patients who underwent IPAA for UC (6). The evaluations occurred preoperatively and then every 3 months postoperatively with Health Status Questionnaire (a variant of the SF-36). Significant improvements occurred in six of eight subscales by the 9-month evaluation. Although statistical comparisons were not reported, several of the subscales also showed improvements by the 3-month evaluation. Both of these studies, however, used generic HRQL measures but did not include a disease-specific measure. Martin et al. studied HRQL after IPAA with a diseasespecific measure (5). They developed a 29-item instrument for 29 patients with UC who underwent IPAA. The patients were evaluated at a mean of 3.8 yr after the surgery. When compared with other patient groups, the IPAA patients had similar scores to UC patients in remission or with mild disease. In a similar study, Sagar et al. developed a diseasespecific measure and found that a group of patients at least 12 months after IPAA had similar HRQL scores to a group of UC patients on medical treatment (4). Our study was the first, however, to prospectively study IPAA patients with a disease-specific measure. HRQL and functional status are important issues for the patient for whom IPAA is recommended. Our study was prospective and therefore allowed us to compare the patients with their preoperative status. Our assessment examined all aspects, using a disease-specific measure as well as a ge-
neric and a utility measure. The use of both disease-specific and generic measures of HRQL increases the potential application of these results. Although the disease-specific measure may be more helpful to the individual patient evaluating the treatment, the generic measure allows comparisons with other disease states and the general population. In any case, all of these instruments demonstrated significant improvements after IPAA, with many patients experiencing significant improvements as early as 1 month after takedown of the ileostomy. These results can be used to guide patients and physicians as they consider and then prepare for the impact of IPAA.
ACKNOWLEDGMENTS Supported in part by National Institutes of Health Training Grant in Digestive Diseases (to A.J.M.) and VA HSR&D Career Development Award (to D.P.). Reprint requests and correspondence: Andrew J. Muir, M.D., DUMC Box 3913, Durham, NC 27710. Received Oct. 12, 2000; accepted Jan. 5, 2001.
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