Restorative proctocolectomy with ileal pouch anal anastomosis

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1 ORIGINAL ARTICLE Biosychosocial Determinants of Health-Related Quality of Life After Ileal Pouch Anal Anastomosis for Ulcerative Colitis* Winfried Häuser, MD,* Nadine Dietz, Ulf Steder-Neukamm, Karl-Heinz Janke, MD, MPH, and Andreas Stallmach, Prof. MD Background: In atients with ileal ouch anal anastomosis (IPAA) the influences of sychosocial variables and of extraintestinal manifestations of ulcerative colitis (UC) on health-related quality of life (HRQOL) have not been studied so far. Methods: 61 atients with UC (age 52.7 ± 13.9 years; 47% female) comleted the German version of the Inflammatory Bowel Disease Questionnaire (IBDQ-D), the Short Form Health Survey (SF 36), the German version of the Hosital Anxiety and Deression Scale (HADS-D) and the Giessener Symtom List (GBB 24). Indeendent of their current clinical activity 37 atients underwent endoscoies. Pouchitis was defined by the Pouch Disease Activity Score (PDAI) 7. Where ossible, IPAA-atients were comared with the data for the German general oulation and with a clinical samle of atients with UC and no IPAA. Results: Patients with IPAA comlained more about fatigue and arthralgia and a reduced hysical and mental health (SF-36) than the German general oulation (P < 0.01). The IBDQ-total score could be redicted (adjusted R 2 = 29.1, P < 0.01) by the number of oerations due to IPAA-related comlications ( = 18.8) and HADS-D- Anxiety scores 11 ( = 29.1). The IBDQ-subscale score Bowel could be redicted (adjusted R 2 = 13.7, P = 0.04) by PDAI 7( = 9.2) and the subscale score Systemic (adjusted R 2 = 13.3, P = 0.04) by the number of extraintestinal manifestations ( = 1.9). Conclusions: HRQOL of atients with UC and IPAA is determined not only by IPAA-related factors but also by anxiety and extraintestinal manifestations with associated musculoskeletal ain. Received for ublication August 19, 2003; acceted November 7, From the *Deartment of Internal Medicine I, Klinikum Saarbrücken, D Saarbrücken, Germany, Deutsche Morbus Crohn /Colitis ulcerosa Foundation DCCV, D Leverkusen, Germany, Deartment of Internal Medicine, Universitätsklinikum Tübingen, D Tübingen, Germany, Deartment of Gastroenterology, Heatology and Nutrition Theray, Katholische Kliniken Essen Nord, D Essen, Germany. Rerints: Winfried Häuser, MD, Deartment of Internal Medicine I, Klinikum Saarbrücken ggmbh, Winterberg 1, D Saarbrücken, Germany ( w.haeuser@klinikum-saarbruecken.de). *This investigation is art of the Cometence Network IBD, sonsored by the German Ministry of Education and Research (BMBF D ) Coyright 2004 by Liincott Williams & Wilkins Key Words: health-related quality of life, ulcerative colitis, ileal ouch anastomosis, extraintestinal manifestations, anxiety, ouch disease activity index, PDAI (Inflamm Bowel Dis 2004;10: ) Restorative roctocolectomy with ileal ouch anal anastomosis (IPAA) has established its lace as an oeration of choice for ulcerative colitis (UC) refractory to medical treatment or with malignant transformations (1). In UC refractory to medical treatment the indication for IPAA is influenced by the reduced health-related quality of life HRQOL of the atients. Most studies on long term functional results of IPAA, satisfaction with surgery and HRQOL in IPAA-atients used generic instruments 1 4 as the widely used Short Form Health Survey (SF-36, 5) or the Cleveland Global Quality of life score. 6 IBD-secific instruments such as the Inflammatory Bowel Disease Questionnaire (IBDQ, 7) and its modifications 8 or the Rating Form of IBD Patients Concerns (RFIPC, 9) were also administered to atients with IPAA to assess the outcomes of IPAA. 3,10 Most studies reorted a high satisfaction of the atients with the surgical outcome and a HRQOL of IPAAatients comarable with the general oulation. 1,4,10 Yet u to 16% of the IPAA-atients with a history of UC comlained a reduced HRQOL. 1 The main factors identified so far as having a negative imact on HRQOL after IPAA were a history of ouchitis and an unfavorable functional outcome (number of bowel movements er day, fecal incontinence). 1,6 Although some authors stress that HRQOL could be influenced also by non-ouch-related factors such as extraintestinal symtoms 1 and life style variables 6 these issues have not been studied systematically. The aims of the study therefore were to assess the redictive value of disease-related, sociodemograhic and sychologic variables for HRQOL of IPAA-atients with a history of UC. Measuring HRQOL simultaneously by generic and disease-secific instruments allows comarisons with the general oulation and UC-atients without IPAA. METHODS Particiants for this study were recruited in three ways. The attendants of a meeting of the working grou IPAA of the Inflamm Bowel Dis Volume 10, Number 4, July

2 Häuser et al Inflamm Bowel Dis Volume 10, Number 4, July 2004 German Morbus Crohn /Colitis ulcerosa Foundation (DCCV), October 24 th 2002, Kassel, Germany, were asked to fill out a set of questionnaires. Members of the above mentioned working grou who did not take art in the meeting mentioned and atients with IPAA and UC who had been oerated in the deartment of general surgery or has been treated in the medical IBD-outatient deartment of the Universitätskliniken des Saarlandes (Germany) from January 1993 to December 2002 were contacted by a letter inviting them to take art in a study on HRQOL and ouchitis. The address lists of the DCCV included not only atients with IPAA but also IBD atients without IPAA and relatives. Due to German laws on data rotection a selective addressing of IPAA atients was not ossible. The atients of the DCCV had been oerated on other surgical centers than the university of the Saarland. Inclusion criteria were age > 18 years, UC in history confirmed by biosy and an ability to read German. Patients who showed interest to take art in the study were contacted by a second letter scheduling the examination which included hysical examination, endoscoy of the ouch with biosies indeendent of the macroscoic asects and clinical symtoms and the answering of a set of questionnaires The questionnaires were to be answered 8 days before the examination. All atients gave their voluntary informed consent after full written exlanation of the aims of the study, including considerations regarding ethics and data rotection and the anonymous deosition of the questionnaires aart from the medical charts. To estimate the enrollment rate we suosed that 70 of the 280 members of the working grou IPAA of the DCCV were IPAA atients, the others being either members rior to surgical intervention or relatives. Fortyfive of these 70 were interested in getting further information regarding the study. From 18 of these 70 atients (25.7%) a comlete data set (endoscoy, questionnaires) was available. Thirty-four of 61 (55.7%) atients of the university of the Saarland were interested in getting further information regarding the study. From 19 of these 34 atients (55.8%) a comlete data set (endoscoy, questionnaires) was available. Fourteen of 30 articiants (46.6%) of the meeting of the working grou IPAA of the DCCV answered the distributed questionnaires. From these atients no endoscoy findings were available. Altogether the estimated enrollment rate was 61/161 (37.9%). From 37 atients endoscoy findings are available. Endoscoy scores were determined by endoscoists who were aware of the atients clinical history. No atient had an anastomotic stricture, ouch outlet obstruction, erianal abscess or external fistula. A single athologist blinded to the clinical resentation and clinical findings assessed ouch biosies for the grade of inflammation based on the criteria of Sandborn. 11 Pouchitis was diagnosed if the Pouchitis Activity Index (PDAI) was Patients in which no ouchoscoy could be carried out were assumed to have ouchitis if they scored 3 in the clinical items of the PDAI within the medical questionnaire. Clinical data and the HRQOL were comared with reresentative samles of the German oulation and a samle of 65 atients with UC from a study on HRQOL with the IBDQ-D of the university of Tuebingen, Germany (Janke et al, submitted for ublication). In this samle activity of the UC was assessed by the German Inflammatory Bowel Disease Activity Index for UC (GIBDI uc ) which has been develoed and is scheduled for validation within the German cometence network Inflammatory Bowel Diseases. The GIBDI uc uses 7 items/dimensions (number of loose stools/24h, general well being, abdominal ain, amount of blood in stools, fever, extraintestinal manifestations and hemoglobin). A GIBDI score of 0 3 oints indicates remission, 4 7 oints a slight, 8 11 oints a moderate and 12 oints a severe disease activity. 12 No SF-36 and GBB 24 data were available for this samle. QUESTIONNAIRES The following questionnaires were used Modified medical questionnaire of the German cometence network inflammatory bowel diseases: Added to basic medical questions regarding the history of the IBD, current symtoms necessary to calculate activity scores and resent medication it included questions on the history of IPAA. Patients were asked to give an overall judgement of their current quality of life comared with the time rior to IPAA on a 7-oint Likert scale (0 = very much worse 3 = unchanged. 6 = very much better). Sociodemograhic questionnaire of the German cometence network inflammatory bowel diseases 12 : Including standard demograhic questions to assess gender, marital status, age, religion, life style variables (regular cigarette smoking, regular intake of alcohol, regular sorts) and occuational status. Questions on education, the occuational status and the available income were used to calculate a social index. Data of this social index can be comared with a reresentative samle of the general German. 13 The Medical Outcome Study Short-Form 36 (SF-36 Items) 5 is a reliable and valid instrument to measure all domains of the health status. It looks at 4 domains in the area of hysical health (hysical functioning, role limitation hysical, bodily ain and general health) and 4 domains in the area of mental health (role limitation emotional, vitality, mental health and social functioning). Two comrehensive indexes of HRQOL can also be comuted (hysical comonent summary and mental comonent summary). The resonses to the questions in each domain are added to rovide eight scores between 0 and 100 with higher scores reflecting better HRQOL. The mean of the two comrehensive scores is 50 with a standard error of the mean (SEM) of 10. Data from reresentative oulation samles of different countries including Germany are available as well as data for different grous with diseases and sychiatric disorders. 5, Liincott Williams & Wilkins

3 Inflamm Bowel Dis Volume 10, Number 4, July 2004 Ileal Pouch Anal Anastomosis The Inflammatory Bowel Disease Questionnaire IBDQ is a disease-secific HRQOL-questionnaire designed as an outcome measure for clinical trials. It consists of 32 items in 4 domains Emotional (12 items), Bowel (10 items), Social (5 items) and Systemic (5 Items) - each rated on a 7-oint Likert scale. The total score may range from 32 to 224, with a higher score indicating better HRQOL. It has been translated and culturally adated for several languages and has been shown to be a valid, reliable instrument resonsive to change 7. We used the German version of the IBDQ (IBDQ-D), which has been validated for German seaking atients with IPAA. 15 The Hosital Anxiety and Deression Scale (HADS) was secifically designed for the assessment of anxiety and deression in atients with hysical illness. With 7 items each on a 4-oint Likert scale ranging from 0 (not resent) to 3 (always resent), subscale scores for anxiety and deression can be calculated. Resondents who score 11 on either subscale have a symtom severity of deression or anxiety indicative of a robable sychiatric disorder (i.e. clinical deression or anxiety disorder). The HADS is a reliable and valid sychological screening tool in hysical ill ersons. 16 For the German version HADS-D normative data for a German general oulation are available, as well as international data from large hysically ill oulations. 17 The Giessener Symtom List (GBB 24) was designed to assess fatigue, muscle and bone ain, dysetic and cardiovascular symtoms. With 24 items on a 5-oint Likert scale ranging from 0 (no suffering from this symtom) to 4 (severe suffering from this symtom) bodily symtoms can be assessed in 4 subscales (fatigue, dysetic symtoms, myalgia/arthralgia symtoms, cardioresiratory symtoms) and one total score. Within the subscales the scores range from 0 to 24 and in the total score from 0 to 144. Data from a reresentative samle of the German oulation as well as studies in medically ill and mentally affected oulations have shown good reliability and validity. 18 Ethics This study was aroved by the ethics committees of the university of Tübingen and of the board of hysicians of the Saarland. STATISTICAL ANALYSIS U to one missing item of the IBDQ-D, HADS-D, SF-36 and GBB 24 were relaced by the median of the items of the resective subscale. If more than one item was missing the resective questionnaire was excluded form further analysis. All data were analyzed using Winstat for Excel (Version , R. Fitch Software, Germany) and the Statistical Package for Social Sciences for Windows (SPSS Version 11.0, Chicago, USA). Data derived from descritive statistical analysis are resented in the form of ercentages for categoric variables and of mean, one standard deviation (SD) and range for continuous variables. Categoric data were comared using the Chi 2 -Test and continuous data by two-tailed non-arametric tests, or if aroriate, by arametric tests. The Kruskal-Wallis one-way analysis of variance was used for comarison of continuouos data between more than two grous. If a significant result was found, further airwise comarisons were made using the Mann-Whitney U test. The level of significance was set at = 0.05 in case of single comarisons. In case of multile comarisons the reset P value was set = Stewise multile regression analysis was erformed to identify indeendent variables (redictors) contributing to the HRQOL as measured by the summary scale and the subscales of the IBDQ-D. The following variables were entered into regression analysis based on the literature and clinical exerience: Medical variables: PDAI 7 (Pouchitis); number of extraintestinal manifestations; number of other medical diseases; number of oerations because of ouch comlications; current medication with analgetics, sychoharmacological agents; Body Mass Index (BMI). Because only few atients were treated with antibiotics, corticosteroids, azathiorin or infliximab these ossible redictors had to be excluded because of low statistical ower. Sociodemograhic variables: Age, sex, social, resent working status and artnershi. Psychologic variables: Probable sychiatric disorder with a HADS-D-score 11 in at least one scale. Lifestyle variables: Regular smoking, hysical fitness, membershi in a self hel organisation. RESULTS Patients Sociodemograhic and medical data of the IPAA atients are listed in Tables 1 and 2. The mean age of the 65 atients with UC without IPAA was 45.2 ± 13.5 years with 63% male atients. 58% atients were in remission, 37% had a slight and 5% a moderate disease activity (Janke et al, submitted for ublication). HRQOL, Extraintestinal Symtoms and Anxiety/Deression In their global judgment of their current HRQOL comared with the time rior to IPAA no atient alleged a (very) much worse HRQOL, 2 atients (3.5%) a slightly worse, 1 (1.7%) an unchanged, 5 (8.7%) atients a slightly better, 22 atients (38.6%) a better and 27 atients (47.4%) a very much better HRQOL. The HRQOL, further somatic symtoms and the amount of anxiety and deression of the IPAA-atients measured by the SF-36 and comarisons with the general German oulation and atients with UC without IPAA are resented in Figures 1 and 2. The ercentage of atients with IPAA with a HADS-D anxiety score 11 indicative of a robable anxiety disorder 2004 Liincott Williams & Wilkins 401

4 Häuser et al Inflamm Bowel Dis Volume 10, Number 4, July 2004 TABLE 1. Sociodemograhic Characteristics of the Study Samle Variable Absolute (%) Mean (±SD) Range Sex (%) Female 29 (47) Male 32 (53) Age (years) 46.6 (11.4) Marital status Living alone 9 (14.8) Living with family/artner 52 (85.2) Current occuational status In work 36 (59.0) House wife/house man 2 (3.3) Without job 1 (1.6) Pension 20 (32.8) Missing data 2 (3.3) Social index Lower 3 (4.9) Middle 32 (52.5) Uer 9 (14.8) Missing data 17 (27.9) Life style variables Regular smoking 35 (57.4) No sorts 26 (42.6) Member of self-hel 46 (75.4) organisation (19.7%) is significantly higher than in the German general oulation (5.9%) (Chi 2 = 19.1; P < 0.001) and not different than in atients with UC without IPAA (13.8%) (Chi 2 = 0.9). The ercentage of atients with IPAA with a HADS-D deression score 11 (1.6%) indicative of a robable deressive disorder is significantly lower than in the German general oulation (8.4%) (Chi 2 = 3.6; P = 0.05) and than in atients with UC without IPAA (11.3%) (Chi 2 = 4.8; P = 0.03). The ercentage of UC atients which score 11 in at least one HADS-D subscale without (20.2%) and with IPAA (19.7%) indicative of a robable sychiatric disorder is not significantly different. Comared with the German general oulation atients with IPAA comlained more about fatigue (GBB 24: t = 10.5; P < 0.001), arthralgia/myalgia (GBB 24: t = 4.2; P < 0.001) and a lowered hysical (SF 36: t = 4.2; P < 0.001) and mental health (SF 36: t = 5.3; P < 0.001). TABLE 2. Medical Data of the Study Samle Variable Absolute (%) Mean (±SD) Range Body Mass Index 25.7 (4.00) Years since first diagnosis IBD 16.9 (8.5) 4 31 Years since IPAA 6.7 (3.5) 1 13 Pouch tye Kock-Pouch 2 (3.3) J-Pouch 59 (96.7) Oerations due to ouch related comlications 20 (32.8) 3.0 (3.1) 1 12 Current disease activity PDAI clinical 3 49 (83.3) PDAI clinical < 3 12 (19.7) PDAI <7 22/37 (59.5) PDAI 7 15/37 (40.5) Current extraintestinal manifestations Joints and/ore sine 30 (49.2) Skin 19 (31.1) Eyes 5 (8.2) Liver/bile ducts 7 (11.5) Current IBD-medication 5-ASA (oral, local) 5 (8.2) Corticosteroids (oral, local) 8 (13.1) Azathiorin 1 (1.6) Infliximab 1 (1.6) Antibiotics 0 (0.0) Probiotics 4 (6.6) Boswellia 11 (18.0) Antidiarrhoics 37 (60.6) Psychoharmacological Agents 24 (39.3) Analgetics 11 (18.0) Medical comorbidities (Lung, Diabetes, Hyertension, Allergies, Other diseases) None 15 (24.6) 1 34 (55.7) 2 9 (14.8) >2 3 (4.9) HRQOL of IPAA Patients With and Without Pouchitis and Comarison With UC-Patients Without IPAA Patients with ouchitis according to the clinical score of the PDAI, scored lower in all subscales of the IBDQ than atients without ouchitis (all P < 0.001). PDAI atients with ouchitis according to the full PDAI, scored lower only in the IBDQ-subscale Bowel than atients without ouchitis (see Table 3). There were no significant differences between atients with and without ouchitis defined by the clinical PDAI Liincott Williams & Wilkins

5 Inflamm Bowel Dis Volume 10, Number 4, July 2004 Ileal Pouch Anal Anastomosis FIGURE 1. Fatigue, arthralgia/myalgia and anxiety/deression of the general German oulation and ulcerative colitis with IPAA (data as mean and standard deviation). score (z = 0.3) and the PDAI-total score (z = -0.1) regarding musculoskeletal ain measured by the GBB 24 (Mann- Whitney U test). Comaring CU-IPAA atients with and without ouchitis and CU atients in remission and with mild or moderate disease activity showed significant differences in the IBDQ-D subscales (Bowel, Social and Total P < 0.001, Systemic P = 0.001, Emotional P = 0.006; Kruskal Wallis Test). IPAA atients with ouchitis did not differ from UC atients with mild and moderate disease activity but from UC atients in remission in the subscales Bowel (P < 0.001) and Total score (P = 0.002). IPAA without ouchitis did not differ in any IBDQ-D subscale from UC atients in remission and from atients with mild activity only in the subscale Bowel (P = 0.005) (see Table 4). FIGURE 2. Physical and mental summary scores of the Short Form Health Survey SF 36 of the general German oulation and ulcerative colitis with IPAA (data as mean and standard deviation) Liincott Williams & Wilkins 403

6 Häuser et al Inflamm Bowel Dis Volume 10, Number 4, July 2004 TABLE 3. Health-Related Quality of Life Measured by the Inflammatory Bowel Disease Questionnaire German Version (IBDQ-D) in Patients With Ileal Pouch Anal Anastomosis (IPAA) With Clinical (PDAI3-6) or PDAI-Total (PDAI 7) Pouchitis and Without Clinical (PDAI < 3) or PDAI-Total (PDAI < 7) Pouchitis (Means and Standard Deviation; Mann-Whitney U-Test) IBDQ- Subscale PDAI clinical 3 n=12 PDAI clinical <3 n=49 z Bowel ± ± <0.001 Systemic ± ± <0.001 Emotional ± ± <0.001 Social ± ± <0.001 Total ± ± <0.001 PDAI Total 7 n=15 PDAI Total <7 n=22 Bowel ± ± Systemic ± ± n.s. Emotional ± ± n.s. Social ± ± n.s. Total ± ± n.s. Predictors of HRQOL Table 5 shows the results of stewise multile regression analysis when each of the subscale scores of the IBDQ-D were used as deendent variable. Each row indicates the variables best redicting the IBDQ-D subscale scores. Thirteen ercent to forty ercent of the variance of the subscale scores of the IBDQ-D could be exlained by 4 indeendent variables with ouchitis (PDAI 7), number of oerations due to IPAArelated local comlications, number of extraintestinal manifestations and robable sychiatric disorder (HADS-D anxiety scores 11) (P < 0.05), all having a negative imact on IBDQ scores. Yet only in the subscales Emotional, Social and in the IBDQ-D total score the redictors exlain a substantial ercentage of the variance. DISCUSSION This is the first study with simultaneous assessment of the influence of somatic as well as sychosocial variables on the HRQOL in UC atients with IPAA, measured both by a generic and by an IBD- secific instrument. The main results and conclusions of our study can be summarized as follows: Although our atients reorted a lower mental and hysical HRQOL comared with the general German oulation their overall judgement of their current HRQOL comared with the re-roctocolectomy time was higher. The clinical score of the PDAI differentiated better between atients with reduced HRQOL in the IBDQ subscale scores than the PDAI total score. Patients with and without ouchitis did not differ in the amount of musculoskeletal ain. Extraintestinal manifestations, oerations due to IPAArelated comlications and increased anxiety all had a higher negative imact on HRQOL than the resence of ouchitis (defined by the PDAI total score). Some asects of our study have to be ket in mind when comaring the results with former studies. The atients of other HRQOL studies were recruited from one gastroenterological center, where they were oerated. 1,2,3,4,6,8,10 Our atients had been oerated in different centers thus minimizing a center-based selection bias. On the other hand institutional variations on surgery and management of the atients that might have influence on HRQOL could not be assessed. The enrollment rate of 37.9% was less than the ones of the studies of Tiainen et al with 62% 1 and of Fazio et al with 85% 4 who did not erform endoscoy in their atients within the HRQOL study. Because most of our atients were recruited via a collaboration with an IBD self hel organization and our study included an endoscoic examination indeendent of clinical symtoms it is obvious that we included in our study highly motivated atients, maybe they suffer from a worse than average disease condition, but this is something we cannot confirm. The number of atients who showed a reduced quality of life comared with the time before IPAA with 3.5% was low and corresonds to the high satisfaction of atients with IPAA concerning the surgical outcome in other studies. 4,19,20 Yet the mental and hysical health of our atients was lower than that of the general German oulation. This finding stands in contrast to the results of Tiainen et al who, using the SF-36, found a similar HRQOL comared with the Finish oulation 1 and to the results of Fazio et al as well as Provenzale et al who comared their atients to the US-American general oulation. 4,10 Yet none of these studies described the ercentage of atients with ouchitis, because no clinical or endoscoic screening for ouchitis was carried out at the time of HRQOLassessment. The influence of ouchitis on HRQOL as measured by the SF-36 is highlighted by the Finish study, seeing significant differences in the SF-36 subscales Health ercetion and Physical functioning in atients with a history of ouchitis comared with atients with no history of ouchitis in the last year. Unfortunately it is not mentioned there, whether the atients suffered from ouchitis at the time of the study. 1 Another reason for the reduced HRQOL in our study samle could be the high ercentage of atients with extraintestinal manifestations of the UC (48%), an asect not taken into account in revious studies on IPAA HRQOL. For the urose of giving a rognostic estimate of ossible benefits of surgical intervention with roctocolectomy and IPAA for an individual atient, it is imortant not only to know the ostoerative HRQOL in IPAA and how it comares to the HRQOL in the general oulation, but to look at HRQOL in IPAA comaring it to UC atients without IPAA. Martin et al found in a samle of IPAA atients without ouchitis HRQOL values comarable to UC atients with mild Liincott Williams & Wilkins

7 Inflamm Bowel Dis Volume 10, Number 4, July 2004 Ileal Pouch Anal Anastomosis TABLE 4. Health-Related Quality of Life of Patients With Ileal Pouch Anal Anastomosis (IPAA) Comared With Patients With Ulcerative Colitis UC Without IPAA Measured by the German Version of the Inflammatory Bowel Disease Questionnaire IBDQ-D (Means and Standard Deviation; Kruskal-Wallis-H-Test With Post Hoc -Adjusted Pairwise Comarisons by Mann-Whitney-U-Test; = 0.005) IPAA Without Pouchitis PDAI < 7 n=22 IPAA With Pouchitis PDAI 7 n=15 UC in Remission n=38 UC With Mild Activity n=24 UC With Moderate Activity n=3 Bowel ± ± ± ± ± 6.4 Systemic ± ± ± ± ± 6.4 Emotional ± ± ± ± ± 5.9 Social ± ± ± ± ± 2.1 Total score ± ± ± ± ± 16.8 UC in Remission n=38 UC with Mild Activity n=24 IPAA Without Pouchitis n = 22 Comared With Bowel Systemic Emotional Social Total score UC in Remission n=38 UC with Mild Activity n=24 UC with Moderate Activity n=3 IPAA with Pouchitis n = 15 Comared With Bowel Systemic Emotional Social Total score disease activity, using an IBD- secific instrument develoed by themselves. 8 In our study the IBDQ-D subscale scores of IPAA atients without ouchitis were comarable to those of UC atients without IPAA in remission. The IBDQ-S subscale scores of IPAA atients with ouchitis were comarable to those of UC atients with mild or moderate disease activity. The differences of both studies can be due the different HRQOL-instruments used. TABLE 5. Results of Searate Stewise Multile Regression Analyses for Each of the Five Domains of the German Version of the Inflammatory Bowel Disease Questionnaire IBDQ-D IBDQ-D Score ANOVA F Significance P Predictor Adjusted R 2 -Coefficient Ste Bowel PDAI Systemic Number of extraintestinal manifestations Emotional HADS-D Anxiety Number of IPAA-related oerations Social Number of IPAA-related oerations Number of extraintestinal manifestations Total Number of IPAA-related oerations HADS-D Anxiety HADS-D = German Version of the Hosital Anxiety and Deression Scale HADS 2004 Liincott Williams & Wilkins 405

8 Häuser et al Inflamm Bowel Dis Volume 10, Number 4, July 2004 Pouchitis, defined by the PDAI clinical score, better differentiated between atients with reduced HRQOL than ouchitis as defined by the PDAI total score. Taking into consideration that the correlations between the clinical, endoscoic and histologic scores of the PDAI are near zero 21 and that HRQOL measures based on the ersonal exerience of atients correlate little with so-called objective measures, 9,12 this finding is not surrising. Most studies on the determinants of HRQOL in IPAA focus on ouch function and ouch-related local comlications. The imortance of the ouch-related local comlications could be confirmed in our study by the significant redictive caacity that the number of oerations because of IPAArelated local comlications has for the IBDQ-D total score and the Emotional and Social subscale. By the use of the GBB 24 we could demonstrate that IPAA atients are also afflicted in their HRQOL by extraintestinal symtoms such as fatigue and myalgia/arthralgia. The ercentage of arthralgia in IPAA atients with a history of UC in other studies was between 31% (22) and 55% (23), 40% to 43% of which indicated an interference with daily life. Extraintestinal manifestations may develo de novo or aggravate after IPAA (22). Patients with IPAA due to familial adenomatous olyosis reort much less arthralgia between 8 and 20% than UC atients (22,23). Yet in one study a benefit from roctocolectomy for most UC atients regarding their extraintestinal symtoms including arthralgia was found (24). Polyarticular arthralgia was reorted not to be associated with ouch inflammation. 22 In our study too the amount of arthralgia/myalgia did not differ in atients with and without ouchitis. In studies on anxiety/deression in chronic somatic diseases such as IBD, the rate of atients with increased scores indicating a robable sychiatric disorder is usually increased comared with the general oulation. 16 In a study of British IBD atients (UC and Crohn s disease) without IPAA 25.9% of the atients scored 11 on one or both subscales of the HADS (25). In our samle we found a reduced rate of HADS-D deression scores 11 comared with the general German oulation and an increased rate HADS-D anxiety scores 11 comared with the general German oulation. The ercentage of UC atients with IPAA which scored scored 11 on one or both subscales of the HADS indicative of a sychiatric disorder is comarable to the one of British and German IBD atients without IPAA (25; Janke et al, submitted for ublication). The imortance of the burden of anxiety in IPAA atients is highlighted by the results of the multile regression analysis showing that HADS-Anxiety scores 11 contribute indeendently and negatively to the HRQOL as measured by total score of the IBDQ. The fact that IPAA atients suffer mainly from symtoms of anxiety might be interreted as resulting from fears of fecal incontinence and social restrictions, but in our exerience the remaining threat that a stoma might still become necessary is most disturbing for atients with IPAA. We conclude that to imrove the HRQOL of atients with UC and IPAA not only otimal surgical outcome and effective medical treatment of ouchitis are imortant. The medical management of extraintestinal symtoms must not be discontinued after roctocolectomy. Pain and anxiety have major influences on the quality of life after IPAA, thus they should come into clinical focus. 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