- Email: [email protected]
Long-term quality of life associated with early surgical complications in patients with ulcerative colitis after ileal pouch–anal anastomosis: A single-center retrospective study
International Journal of Surgery 48 (2017) 174–179
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.elsevier.com/locate/ijsu
Original Research
Long-term quality of life associated with early surgical complications in patients with ulcerative colitis after ileal pouch–anal anastomosis: A singlecenter retrospective study
MARK
Weimin Xua,1, Hairong Yeb,1, Yilian Zhua,1, Wenjun Dinga, Jihong Fua, Long Cuia,∗∗, Peng Dua,∗ a b
Department of Colorectal Surgery, Xin-Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China Department of Anesthesia, Xin-Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
A R T I C L E I N F O
A B S T R A C T
Keywords: Ileal pouch–anal anastomosis Quality of life Surgical complications Ulcerative colitis
Background: Ileal pouch-anal anastomosis (IPAA) is recommended for patients with ulcerative colitis (UC) in terms of surgical treatment. Measuring surgical complications of IPAA and long-term quality of life (QOL) are important to achieve an acceptable risk/benefit ratio for patients with UC. Materials and methods: Patients with UC who underwent total proctocolectomy (TPC) with IPAA from February 2008 to July 2016 at our institute were included. Early surgical complications were defined as mechanical/ infectious events within one month after IPAA. Assessment of QOL was performed using the Cleveland Global Quality of Life instrument (CGQL), with 50% improvement as a cut-off value. Demographic and clinical variables were compared with univariable analysis and step-wise logistic regression models were also performed. Results: A total of 58 eligible patients had a median follow-up time of 78.5 months [interquartile range (IQR), 34.4–92.8] from February2008 to March 2017, including 25 cases (43.1%) developed early surgical complications. Age at pouch surgery and excessive blood loss were risk factors associated with early surgical complications (p < 0.05). In multivariate analysis, older age at surgery [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.01–1.1] and significant blood loss (≧400 ml) (OR, 4.31; 95% CI, 1.21–16.87) were contributing factors for developing early surgical complications. The CGQL score was significantly increased after IPAA (0.728 ± 0.151 vs. 0.429 ± 0.173, p < 0.001). Early surgical complications (OR, 5.55; 95%CI, 1.44–21.37), older age at surgery (OR, 1.06; 95% CI, 1.01–1.12) and use of immunomodulatory (OR, 17.50; 95% CI, 1.52–201.39) were associated with poor long-term QOL. Conclusion: The study demonstrated that early surgical complications might contribute to develop a poor CGQL score, suggesting intentional control of risk factors associated with early surgical complications should be taken into consideration for patients with UC for pouch surgery.
1. Introduction As a major form of inflammatory bowel disease (IBD), ulcerative colitis (UC) is characterized by a chronic course of recurrent relapse and remission and the need for long-term medical management. Approximately 25–30% of patients with UC eventually need to undergo colectomy for medically refractory disease or colitis-associated neoplasia [1]. The restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA), described in 1978 [2], has become the procedure of choice for the surgical treatment of the UC patients, which not only removes the affected colon and rectum, but also restores intestinal
continuity with sphincter conservation while avoiding a permanent ostomy. However, the procedure is a technically demanding operation which can be associated with serious surgical complications (pelvic sepsis, anastomotic leakage, etc.), which may have a detrimental effect on function, quality of life (QOL) and health status, including high stool frequency and fecal incontinence. Previous studies have shown that IPAA improves QOL for UC patients [3,4], while the risk factors of postoperative complications and its relationship with long-term QOL are still unclear. Mostly patients with UC undergoing pouch surgery are young and have a long life expectancy. Thus, measuring surgical complications and functional long-term QOL are important in order to
∗
Corresponding author. Department of Colorectal Surgery, Xin-Hua Hospital, 1665 Kongjiang Road, Shanghai 200092, China. Corresponding author. Department of Colorectal Surgery, Xin-Hua Hospital, 1665 Kongjiang Road, Shanghai 200092, China. E-mail addresses: [email protected] (W. Xu), [email protected] (H. Ye), [email protected] (Y. Zhu), [email protected] (W. Ding), [email protected] (J. Fu), [email protected] (L. Cui), [email protected] (P. Du). 1 Weimin Xu, Hairong Ye and Yilian Zhu contributed equally to this work. ∗∗
http://dx.doi.org/10.1016/j.ijsu.2017.10.070 Received 7 September 2017; Received in revised form 23 October 2017; Accepted 25 October 2017 1743-9191/ © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
Table 1 Baseline characteristics of Patients and Univariable Analysis of risk factors for early surgical complications. Variables
Clinical data Postoperative follow-up time [mo, median (IQR)] Preoperative CGQL score (mean ± SD) Postoperative CGQL score (mean ± SD) Disease duration [yr, median (IQR)] Median age at surgery [yr, median (IQR)] Male: female Body mass index (kg/m2, mean ± SD) Stage of surgery, n (%) Ⅱ-stage IPAA Ⅲ-stage IPAA Surgical urgency, n (%) Urgent surgery Elective surgery History of abdominal surgery, n (%) Surgical approach, n (%) Open Laparoscopic Steroids, n (%) Immunomodulators, n (%) Extent of UC, n (%) Left side Pancolitis Laboratory and anesthetic Data ASA Grade, n (%) Ⅰ Ⅱ Opioids, n (%) Blood transfusion, n (%) Anesthesia method, n (%) General anesthesia (GA) General and Epidural anesthesia (EP) Preoperative hemoglobin (g/L, mean ± SD) Preoperative albumin (g/L, mean ± SD) Blood loss (ml, mean ± SD) Urine volume (ml, mean ± SD) Transfusion volume (ml, mean ± SD) Colloidal amount (ml, mean ± SD)
All cases
Early surgical complications group (Group A) n = 25
Non-complications group (Group B) n = 33
78.5 (34.4–92.8) 0.429 ± 0.173 0.728 ± 0.151 3.5 (2.0–8.0) 37.5 (27.8–52.0) 19:39 20.2 ± 3.4
0.474 ± 0.185 0.696 ± 0.135 3.0 (2.0–8.0) 45.0 (35.0–56.0) 10:15 20.0 ± 2.8
0.398 ± 0.160 0.751 ± 0.159 4.0 (1.8–7.5) 30.0 (26.0–50.5) 9:24 20.3 ± 3.8
42 (72.4) 16 (27.6)
18 (72.0) 7 (28.0)
24 (72.7) 9 (27.3)
4 (6.9) 54 (93.1) 10 (17.2)
3 (12.0) 22 (88.0) 2 (7.7)
1 (3.0) 32 (97.0) 8 (25.0)
39 (67.2) 19 (32.8) 30 (51.7) 7 (12.1)
19 (76.0) 6 (24.0) 13 (52.0) 2 (8.0)
20 (60.6) 13 (39.4) 20 (60.6) 5 (15.2)
10 (17.2) 48 (82.8)
5 (20.0) 20 (80.0)
5 (15.2) 28 (84.8)
8 (13.8) 50 (86.2) 50 (86.2%) 6 (10.3)
4 (16.0) 21 (84.0) 21 (84.0) 1 (4.0)
4 (12.0) 29 (87.9) 29 (87.9) 5 (15.2)
54 (93.1) 4 (6.9) 38.4 ± 5.7 114.8 ± 22.4 259.3 ± 185.4 378.6 ± 251.8 2100.0 ± 548.8 637.9 ± 257.4
23 (92.0) 2 (8.0) 116.2 ± 20.9 38.0 ± 7.0 325.2 ± 167.8 378.0 ± 275.4 226.0 ± 671.6 680.0 ± 244.9
31 (93.9) 2 (6.1) 113.7 ± 23.7 38.7 ± 4.4 223.0 ± 189.3 379.1 ± 236.8 2004.5 ± 420.1 606.1 ± 265.7
p value
0.823 0.015 0.306 0.683 0.951
0.305
0.160 0.216
0.512 0.687 0.731
0.674
0.715 0.222 1.000
0.676 0.668 0.037 0.987 0.156 0.283
impaired general health status, and/or lost follow-up.
achieve an acceptable risk to benefit ratio for both surgeons and UC patients. In this study, we mainly assessed risk factors associated with longterm functional outcome by using the Cleveland Global Quality of Life (CGQL) instrument and evaluated the early surgical complications of UC patients after IPAA. It is important to explore treatment strategies and methods to reduce the incidence of postoperative adverse events and to improve the long-term QOL.
2.3. Quality of life scale We used the questionnaires to obtain both pre- and postoperative CGQL score, which has been determined to assess long-term QOL in UC patients after IPAA [3,5]. Patients were asked to score each of the three items (current quality of life, current quality of health, and current energy level), each on a scale of 0–10 (0, worst; 10, best). The scores were added and the cumulative score is divided by 30 to obtain the ultimate CGQL score. In the present study, we used the CGQL instrument before surgery to evaluate the preoperative status, then we subtracted the preoperative score from the latest postoperative CGQL score and the difference is divided by preoperative score so as to obtain the improvement of CGQL scores in percentage. We then respectively divided into two groups based on the improvement percentage of CGQL scores, with 50% improvement as a cut-off value.
2. Methods 2.1. Participants and setting Patients who underwent total proctocolectomy (TPC) with pouch creation between January 2008 and July 2016 at our institute were eligible for inclusion. Patients were identified, and their clinical data was obtained from a prospectively maintained, institutional review board-approved pouch database. Long-term CGQL scores were conducted by telephone interview and outpatient examination.
2.4. Statistical analysis Statistics to describe the data are appropriately represented by the numbers and percentages, mean and standard deviations (SD), or the median and interquartile range (IQR). Continuous variables were described according to the median and IQR or mean and SD. Two-sample Student's t-test was used to compare the population means between two different continuous variables and Wilcoxon's rank-sum test was used for ranked variables respectively. Categorical variables were evaluated using Chi-squared or Fisher's exact test, as appropriate. Multivariable
2.2. Inclusion and exclusion criteria Inclusion criteria were patients who: (1) diagnosed as UC; (2) received TPC with pouch creation; (3) underwent pouch surgery at 16–65 years old; and (4) received a regular follow-up at our department. Exclusion criteria were patients who: (1) underlying as familial adenomatous polyposis (FAP) or indeterminate colitis (IC); (2) were with status of temporary or permanent diverting ileostomy; and (3) had 175
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
logistic regression was further used to evaluate the association of clinical factors with early surgical complications and the long-term QOL. All hypothesis testing was two-sided, with a p-value of < 0.05 considered statistically significant.
Table 2 Postoperative complications of IPAA (N = 58).
3. Results 3.1. Demographics and clinical characteristics A total of 58 patients who underwent TPC with IPAA at our institution were eligible for the current analysis. Demographics, clinical, laboratory and anesthetic characteristics are shown in Table 1. The median follow-up time for the cohort was 78.5 months (IQR, 34.4–92.8) from February 2008 to March 2017. Two patients were died during the follow-up and were excluded from the analysis of long-term QOL. Median age of patients at the time of surgery was 37.5 years old (IQR, 27.8–52.0) with a median disease duration of 3.5 years (IQR, 2.0–8.0). Forty-two patients (72.4%) underwent II-stage surgery and 19 patients (32.8%) underwent laparoscopic procedure for pouch surgery. QOL improved significantly from a preoperative mean CGQL value of 0.429–0.728 after pouch construction (p < 0.001). Detailed improvements in long-term QOL can be seen in Fig. 1.
Complications
N (%)
Early postoperative complications Early postoperative Intestinal obstruction Pouch and anastomotic bleeding Pouch-anal anastomotic leak Leak at the tip of the J-pouch. Sacrococcygeal abscess Perianal sinus Wound infection Sepsis Late complications Postoperative long term intestinal obstruction Pouchitis Cuffitis Pouch-vagina leak Incision hernia Defecation dysfunction Pouch failure Anastomotic stricture Sexual dysfunction Infertility
25 (43.1) 8 (13.8) 8 (13.8) 1 (1.7) 2 (3.4) 2 (3.4) 1 (1.7) 8 (13.8) 1 (1.7) 23 (39.7) 5 (8.6) 12 (20.7) 1 (1.7) 2 (3.4) 3 (5.2) 4 (6.9) 3 (5.2) 3 (5.2) 1 (1.7) 1 (1.7)
died from severe sepsis. During the entire follow-up period, there were 23 patients (39.7%) developed late complications (details were shown in Table 2). Pouch failure occurred in 3 patients (5.2%), due to two of them developed Crohn's disease (CD) of pouch and one for severe pouchitis.
3.2. Postoperative complications of IPAA Table 2 shows various post-IPAA complications noted during the investigation. Early surgical complications in the present study refer to the complications which occurred within one month after pouch surgery. Postoperative complications were diagnosed based on clinical manifestations, laboratory results along with endoscopic and imaging findings. A total of 25 patients (43.1%) experienced early surgical complications, of which 8 patients (13.8%) had intestinal obstruction, 8 (13.8%) experienced bleeding at pouch or anastomotic site, 3 (5.2%) underwent pouch leaks (two leaks at the tip of “J” and one at pouchanal anastomosis), 2 (3.4%) developed sacrococcygeal abscess, 1 (1.7%) had perianal sinus, 8 (13.8%) had wound infection and 1 (1.7%)
3.3. Risk factors for early surgical complications in patients with IPAA We then analyzed the risk factors of early surgical complications in the group of 25 patients who developed early complications (Group A) compared with the others (Group B). Significant differences were observed for age at pouch surgery (p = 0.015) and intraoperative blood loss (p = 0.037) between groups. There were no statistical differences in terms of gender, body mass index (BMI), stage of surgery, history of Fig. 1. Comparison of pre- and post-IPAA CGQL scores. Three items of the CGQL instrument, current quality of life (A) current quality of health (B) and current energy level (C) were respectively compared between pre-and post-IPAA status. (D) Ultimate overall CGQL scores between the different status was performed. Scores are presented as mean ± SD. *** means P < 0.001.
176
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
Table 3 Multivariate logistic regression analysis of risk factors for early postoperative complications after IPAA. Variables
Odds Ratio
95% Confidence Interval
p value
Age at surgery Blood loss≧400 ml Open surgery Gender
1.05 4.51 1.49 0.542
1.01–1.10 1.21–16.87 0.43–5.18 0.16–1.89
0.025 0.025 0.531 0.337
Table 5 Multivariate logistic regression analysis of influencing factors for CGQL. Variables
Odds Ratio
95% Confidence Interval
p value
Early surgical complications Immunomodulators Age at surgery Gender
5.55 17.50 1.06 0.74
1.44–21.37 1.52–201.39 1.01–1.12 0.17–3.28
0.013 0.022 0.023 0.689
1.01–1.12), and use of immunomodulators (OR, 17.50; 95%CI, 1.52–201.39) were independent factors of poor long-term QOL after IPAA for patients with UC (Table 5).
Table 4 Possible influencing factors for CGQL of UC patients accepted IPAA (N = 56). Characteristics
Group C (n = 30)
Group D (n = 26)
p value
Median age at surgery [yr, median (IQR)] Male: female BMI (kg/m2) History of abdominal surgery, n (%) Surgical urgency, n (%) Urgent surgery Elective surgery Surgical approach, n (%) Open Laparoscopic Steroids, n (%) Immunomodulators, n (%) Extent of UC, n (%) Left-sided colitis Pancolitis Stage of surgery, n (%) Ⅱ-stage IPAA Ⅲ-stage IPAA Blood transfusion, n (%) Opioids, n (%) Early surgical complications, n (%)
29.0 (26.0–43.5)
50.0 (35.0–55.3)
0.002
8:22 20.7 ± 4.1 4 (13.3)
11:15 19.6 ± 2.3 6 (23.1)
0.218 0.192 0.487
1 (3.3) 29 (96.7)
2 (7.7) 24 (92.3)
17 (56.7) 13 (43.3) 17 (56.7) 1 (3.3)
20 (76.9) 6 (23.1) 15 (57.7) 6 (23.1)
4 (13.3) 26 (86.7)
5 (9.2) 21 (80.8)
21 (70.0) 9 (30.0) 5 (16.7) 26 (86.7) 7 (23.3)
19 (73.1) 7 (26.9) 1 (3.8) 23 (88.5) 16 (61.5)
4. Discussion It is a significant advantage of IPAA that it can avoid the permanent stoma by maintaining bowel continuity and creating a continent fecal reservoir. Current practice proves that IPAA has been a rather safe procedure for most UC patients through creating a long-term functional pouch. Favorable gastrointestinal function and QOL could be achieved through IPAA for patients with UC [6,7]. Assessing by using CGQL instrument in the study, we found that pouch surgery may significantly improve the long-term QOL (pre-vs. post-, 0.429 vs. 0.728, p < 0.001). Despite IPAA generally brings about excellent functional results and high satisfaction in patients, multiple kinds of postoperative complications may be encountered after there has been reports presenting respective morbidity and mortality rates [8], which cause the adverse outcome and compromise patients' QOL. One study reported that the proportion of patients who require permanent ileostomy for pouch failure was 11.3% [9]. The morbidity rate varies greatly (30%–60%) with surgical complications distressing both the patients and surgeons [10]. In our study, early postoperative complications occurred in 43.1% of the cohort patients, including intestinal obstruction, pouch and anastomotic bleeding, leakage, etc. Late complications occurred in 39.7% of the patients. Pouch failure developed in 3 patients (5.2%) during a mean follow-up of 78.5 months, with similar incidence (6.8%) reported in one pooled data from 43 studies with a mean follow-up time of 36.7-month [12]. In our study, 2 cases of pouch failure were due to CD of pouch and one for severe pouchitis. Indeterminate diagnosis of UC before surgery may be one explanation for occurrence of this severe outcome. Pouch surgery for CD or IC may be detrimental to patient's long-term outcome. Late complications also may cause troublesome results and reduce the satisfaction of surgical treatments. Poor outcome after IPAA includes multiple functional problems such as stool frequency, incontinence or sexual dysfunction, leading to further distress. Starting from postoperative complications, there still remained some patients with an unsatisfied feeling or poor outcome after IPAA. The definite influence and relationship of surgical complications with longterm outcome for patients with UC after pouch surgery remain unclear. Thus, the aim of this retrospective study was to explore the risk factors associated with the long-term QOL and search for strategies and methods to improve it in clinical practice. Several QOL assessment systems in the form of questionnaires have been used to assess outcome after surgery, such as Short Form 36 (SF36). Of these, CGQL instrument was designed specifically for patients undergoing RPC [13]. Compared with SF-36, CGQL instrument deemed to be reliable, responsive, and is a simpler instrument, which has been used to assess long-term quality of life in UC patients after IPAA [3,5]. In the present study, we demonstrated that early surgical complications were significantly associated with the long-term outcome for UC patients by analysis from the improvement of CGQL scores. One explanation is that additional surgical procedures required to treat early postoperative complications may cause adverse outcomes such as abdominal adhesions, pelvic abscess, injury of anal sphincter etc.
0.592
0.110
0.938 0.041 0.719
0.799
0.200 1.000 0.004
abdominal surgery, surgical urgency, surgical approach, use of steroids and immunomodulators, volume of opioids use, American Society of Anesthesiologists (ASA) grade, anesthesia method, extent of UC, preoperative hemoglobin and albumin level and intraoperative infusion volume (p > 0.05) (Table 3). To further analyze the risk factors associated with early surgical complications after IPAA, we performed a multivariate logistic analysis. Table 4 showed a step-wise logistic regression model for the description of risk factors. In the multivariate analysis, older age at surgery [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.01–1.10] and significant intraoperative blood loss (≧400 ml) (OR, 4.51; 95% CI, 1.21–16.87) were contributing factors for developing early surgical complications. 3.4. Analysis of long-term QOL Based on each patient's CGQL score difference between preoperative and postoperative value, patients with ≧50% improvement were included in the good outcome group (Group C, n = 30) and those with < 50% improvement were listed in the poor outcome group (Group D, n = 26). Two patients died were excluded from this analysis. In univariate analysis, age at pouch surgery (p = 0.002), use of immunomodulators for UC (p = 0.041), and presence of early surgical complications (p = 0.004) were significantly associated with long-term QOL. No statistical differences were observed between 2 groups in baseline characteristics, including BMI, stage of surgery, history of abdominal surgery, surgical urgency, use of steroids or opioids, ASA grade, anesthesia method and extent of UC (Table 5). In the multivariate analysis, early surgical complications (OR, 5.55; 95% CI, 1.44–21.37), older age at pouch surgery (OR, 1.06; 95%CI, 177
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
health or nutritional status and likely affect the long-term QOL. Detailed mechanism needs further identification. There are some limitations to the study. Firstly, insufficient sample size has the potential to increase the referral bias due to the nature of our practice from one single center. A sizeable number of patients referred to the assessment of CGQL values from more hospitals are needed in further studies. Secondly, despite the fact that this was a long-term study, there were still some CGQL scores obtained from a relative shorter follow-up for different pouch patients. Therefore, it might have had an individual heterogeneity bias due to a different follow-up period in the cohort patients. To get more accurate CGQL value from a larger sample size may obtain more meaningful conclusions.
Secondly, previous studies have reported that the occurrence of pouch bleeding is one definite contributing factor for developing acute or chronic pouchitis, which are the most common manifestation of complications of IPAA [14]. Of the 58 patients in our study, 2 with pouch or anastomosis bleeding developed pouchitis. Severe pouchitis may lead to worst outcome of pouch failure and a poor long-term QOL. Thirdly, occurrence of multiple complications during the immediate postoperative periods may likely have a negative impact on the UC patients' mental health and therefore have adverse effect on the QOL to a certain extent. In order to further explore the risk factors for early surgical complications associated with the poor long-term QOL, we analyzed various factors, including clinical characteristics, medical management histories, operative details, and anesthesia data from a medical record system. By univariate and multivariate analysis, we found older age at surgery and excessive blood loss (≧400 ml) were contributing factors for early surgical complications. Older patients undergoing pouch surgery are more likely to suffer from the early surgical complications. Similar results could be found in other studies [15,16]. Ridzuan Farouk [17] found that older patients had a higher frequency of nocturnal stool and more episodes of fecal incontinence compared with younger patients. During the most of IPAA procedures in clinical practice, we performed the double-stapling technique for pouch construction with the remnant columnar cuff less than 2–3 cm above the anal margin. This surgical procedure is demanding in term of patients' anal function while older patients are disadvantaged compared with young patients. Also, older patients with UC have relatively poor health status due to longer course of disease which leads to slower recovery postoperatively. Excessive bleeding and/or fulminant colitis could deteriorate the general physical conditions of the patients and many reports have asserted that pouch surgery should be treated with caution under these circumstances [18]. Previous retrospective studies found that excessive blood loss (> 500 ml) significantly increased mortality after colorectal surgery [19] and estimated blood loss (> 200 ml) were found to be associated with increased length of hospital stay [20]. In our study, intraoperative blood loss (≧400 ml) proved closely associated with surgical complications. Nowadays, minimally invasive surgery has become widely available. Laparoscopy has been reported as an effective minimally invasive procedure with lower incidence of surgical complications [21,22]. A single institutional case-matched study demonstrated that IPAA performed laparoscopically confers several significant benefits including significantly smaller incision with less postoperative pain, earlier return of bowel function and shorter length of hospital stay [23]. Multicenter randomized controlled trial with large sample size should be carried out prospectively to further establish the potential advantage of laparoscopic IPAA. The clinical implication suggested that strategies such as employing minimally invasive surgery with better surgical skills to minimize intraoperative blood loss may help reduce the incidence of early surgical complications, which will be beneficial to improve the long-term QOL. In addition, appropriate IPAA stage and surgical timing should be taken into consideration in the clinical practice, which may be beneficial for patients. Long-term and regular follow-up combined with colonoscopy in outpatient examination could help detect pouch function and reduce the incidence of pouch failure, which should also attract our attention. Some medical treatments during the disease course of UC may be associated with the occurrence of surgical complications of IPAA and its impact on long-term outcome is still unclear. In the present study, we found use of immunomodulators was an independent adverse factor for long-term QOL after IPAA. In clinical practice, thiopurine drugs, such as azathioprine and mercaptopurine are the common treatment for steroid-dependent CD and UC patients [24]. Immunomodulators have many adverse reactions including liver damage [25], lung damage [26], bone marrow suppression and a small risk of developing congenital malformation in pregnancy [27], which may be associated with poor
5. Conclusion The results of this study have several clinical implications. Our study shows that the risk factors for developing surgical mechanical/ infectious complications within one month after IPAA are possibly age at time of surgery and intraoperative blood loss. Moreover, the early surgical complications contribute to developing a poor CGQL score during follow-up time after IPAA, suggesting intentional control of the risk factors associated with early surgical complications should be taken into consideration for patients with UC. The result also helps both surgeons and patients to make informed decisions. Standard surgical procedure of IPAA to reduce intraoperative blood loss, reasonable selection of immunomodulators therapy course and early recruitment of patients should be emphasized in clinical practice. Ethical approval None. Funding This work was supported by grants from the National Natural Science Foundation of China [grant numbers 81570474]. Author contribution Peng Du and Long Cui conceived the study. Data was collected by all authors. Wenjun Ding and Jihong Fu completed the follow-up. Weimin Xu performed analyses of the data. Weimin Xu and Yilian Zhu wrote the manuscript. Hairong Ye finished the revision of the manuscript. Weimin Xu, Hairong Ye and Yilian Zhu contributed equally to this work. All authors reviewed the manuscript. Conflicts of interest None of the authors have any conflict of interest. Research registration unique identifying number (UIN) researchregistry2937. Guarantor Peng Du. References [1] R. Marchioni Beery, S. Kane, Current approaches to the management of new-onset ulcerative colitis, Clin. Exp. Gastroenterol. 7 (2014) 111–132. [2] A.G. Parks, R.J. Nicholls, Proctocolectomy without ileostomy for ulcerative colitis, Br. Med. J. 2 (6130) (1978) 85–88. [3] V.W. Fazio, M.G. O'Riordain, I.C. Lavery, J.M. Church, P. Lau, S.A. Strong, et al., Long-term functional outcome and quality of life after stapled restorative proctocolectomy, Ann. Surg. 230 (4) (1999) 575–584.
178
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
of life after ileal pouch-anal anastomosis, Ann. Surg. 238 (2) (2003) 221–228. [17] J.H.P. Ridzuan Farouk, Bruce G. Wolff, Roger R. Dozois, Scott Browning, Dirk Larson, Functional outcomes after ileal pouch-anal anastomosis for chronic ulcerative colitis, Ann. Surg. 231 (6) (2000) 919–926. [18] A. Grucela, R.M. Steinhagen, Current surgical management of ulcerative colitis, Mt. Sinai J. Med. A J. Transl. Personal. Med. 76 (6) (2009) 606–612. [19] K. Skala, P. Gervaz, N. Buchs, I. Inan, M. Secic, B. Mugnier-Konrad, et al., Risk factors for mortality-morbidity after emergency-urgent colorectal surgery, Int. J. Colorectal Dis. 24 (3) (2009) 311–316. [20] Z. Aga, M. Machina, S.A. Mccluskey, Greater intravenous fluid volumes are associated with prolonged recovery after colorectal surgery: a retrospective cohort study, Bja Br. J. Anaesth. 116 (6) (2016) 804–810. [21] H. Zhang, S. Hu, G. Zhang, K. Wang, B. Chen, B. Li, et al., Laparoscopic versus open proctocolectomy with ileal pouch-anal anastomosis, Minim. Invasive Ther. Allied Technol. MITAT Off. J. Soc. Minim. Invasive Ther. 16 (3) (2007) 187–191. [22] F.J. Fleming, T.D. Francone, M.J. Kim, D. Gunzler, S. Messing, J.R. Monson, A laparoscopic approach does reduce short-term complications in patients undergoing ileal pouch-anal anastomosis, Dis. Colon Rectum 54 (2) (2011) 176–182. [23] D.W. Larson, R.R. Cima, E.J. Dozois, M. Davies, K. Piotrowicz, S.A. Barnes, et al., Safety, feasibility, and short-term outcomes of laparoscopic ileal-pouch-anal anastomosis: a single institutional case-matched experience, Ann. Surg. 243 (5) (2006) 667–670. [24] J.P. Gisbert, P.M. Linares, A.G. Mcnicholl, J. Maté, F. Gomollón, Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis, Aliment. Pharmacol. Ther. 30 (2) (2009) 126–137. [25] E. Petit, S. Langouet, H. Akhdar, C. Nicolas-Nicolaz, A. Guillouzo, F. Morel, Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes, Toxicol. In Vitro 22 (3) (2008) 632–642. [26] A.N. Ananthakrishnan, T. Attila, M.F. Otterson, R.J. Lipchik, B.T. Massey, R.A. Komorowski, et al., Severe pulmonary toxicity after azathioprine/6-mercaptopurine initiation for the treatment of inflammatory bowel disease, J. Clin. Gastroenterol. 41 (7) (2007) 682–688. [27] C.G. Su, R.B. Stein, J.D. Lewis, G.R. Lichtenstein, Azathioprine or 6-mercaptopurine for inflammatory bowel disease: do risks outweigh benefits? Dig. Liver Dis. 32 (6) (2000) 518–531.
[4] A.J. Muir, L.J. Edwards, L.L. Sanders, R.R. Bollinger, M.J. Koruda, D.R. Bachwich, et al., A prospective evaluation of health-related quality of life after ileal pouch anal anastomosis for ulcerative colitis, Am. J. Gastroenterol. 96 (5) (2001) 1480–1485. [5] J.C. Coffey, D.C. Winter, P. Neary, A. Murphy, H.P. Redmond, W.O. Kirwan, Quality of life after ileal pouch-anal anastomosis: an evaluation of diet and other factors using the Cleveland Global Quality of Life instrument, Dis. Colon Rectum 45 (1) (2002) 30–38. [6] V.W. Fazio, R.P. Kiran, F.H. Remzi, J.C. Coffey, H.M. Heneghan, H.T. Kirat, et al., Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients, Ann. Surg. 257 (4) (2013) 679–685. [7] A. de Buck van Overstraeten, A.M. Wolthuis, S. Vermeire, G. Van Assche, A. Laenen, M. Ferrante, et al., Long-term functional outcome after ileal pouch anal anastomosis in 191 patients with ulcerative colitis, J. Crohn's Colitis 8 (10) (2014) 1261–1266. [8] F. Alexander, Complications of ileal pouch anal anastomosis, Seminars Pediatr. Surg. 16 (3) (2007) 200–204. [9] C. Leowardi, U. Hinz, M. Tariverdian, P. Kienle, C. Herfarth, A. Ulrich, et al., Longterm outcome 10 years or more after restorative proctocolectomy and ileal pouch–anal anastomosis in patients with ulcerative colitis, Langenbeck's Arch. Surg. 395 (1) (2010) 49–56. [10] S. Ross, R.E. Kornbrekke, Complications after ileal pouch-anal anastomosis in Korean patients with ulcerative colitis, World J. Gastroenterol. 20 (23) (2014) 7488–7496. [12] W.E. Hueting, E. Buskens, dTI. Van, H.G. Gooszen, C.J. van Laarhoven, Results and complications after ileal pouch anal anastomosis: a meta-analysis of 43 observational studies comprising 9,317 patients, Dig. Surg. 22 (1–2) (2005) 69. [13] V.W. Fazio, Y. Ziv, J.M. Church, J.R. Oakley, I.C. Lavery, J.W. Milsom, et al., Ileal pouch-anal anastomoses complications and function in 1005 patients, Ann. Surg. 222 (2) (1995) 120–127. [14] A. Cheifetz, S. Itzkowitz, The diagnosis and treatment of pouchitis in inflammatory bowel disease, J. Clin. Gastroenterol. 38 (5 Suppl 1) (2004) S44. [15] E. Carmon, A. Keidar, A. Ravid, G. Goldman, M. Rabau, The correlation between quality of life and functional outcome in ulcerative colitis patients after proctocolectomy ileal pouch anal anastomosis, Colorectal Dis. 5 (3) (2003) 228. [16] C.P. Delaney, V.W. Fazio, F.H. Remzi, J. Hammel, J.M. Church, T.L. Hull, et al., Prospective, age-related analysis of surgical results, functional outcome, and quality
179
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.elsevier.com/locate/ijsu
Original Research
Long-term quality of life associated with early surgical complications in patients with ulcerative colitis after ileal pouch–anal anastomosis: A singlecenter retrospective study
MARK
Weimin Xua,1, Hairong Yeb,1, Yilian Zhua,1, Wenjun Dinga, Jihong Fua, Long Cuia,∗∗, Peng Dua,∗ a b
Department of Colorectal Surgery, Xin-Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China Department of Anesthesia, Xin-Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
A R T I C L E I N F O
A B S T R A C T
Keywords: Ileal pouch–anal anastomosis Quality of life Surgical complications Ulcerative colitis
Background: Ileal pouch-anal anastomosis (IPAA) is recommended for patients with ulcerative colitis (UC) in terms of surgical treatment. Measuring surgical complications of IPAA and long-term quality of life (QOL) are important to achieve an acceptable risk/benefit ratio for patients with UC. Materials and methods: Patients with UC who underwent total proctocolectomy (TPC) with IPAA from February 2008 to July 2016 at our institute were included. Early surgical complications were defined as mechanical/ infectious events within one month after IPAA. Assessment of QOL was performed using the Cleveland Global Quality of Life instrument (CGQL), with 50% improvement as a cut-off value. Demographic and clinical variables were compared with univariable analysis and step-wise logistic regression models were also performed. Results: A total of 58 eligible patients had a median follow-up time of 78.5 months [interquartile range (IQR), 34.4–92.8] from February2008 to March 2017, including 25 cases (43.1%) developed early surgical complications. Age at pouch surgery and excessive blood loss were risk factors associated with early surgical complications (p < 0.05). In multivariate analysis, older age at surgery [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.01–1.1] and significant blood loss (≧400 ml) (OR, 4.31; 95% CI, 1.21–16.87) were contributing factors for developing early surgical complications. The CGQL score was significantly increased after IPAA (0.728 ± 0.151 vs. 0.429 ± 0.173, p < 0.001). Early surgical complications (OR, 5.55; 95%CI, 1.44–21.37), older age at surgery (OR, 1.06; 95% CI, 1.01–1.12) and use of immunomodulatory (OR, 17.50; 95% CI, 1.52–201.39) were associated with poor long-term QOL. Conclusion: The study demonstrated that early surgical complications might contribute to develop a poor CGQL score, suggesting intentional control of risk factors associated with early surgical complications should be taken into consideration for patients with UC for pouch surgery.
1. Introduction As a major form of inflammatory bowel disease (IBD), ulcerative colitis (UC) is characterized by a chronic course of recurrent relapse and remission and the need for long-term medical management. Approximately 25–30% of patients with UC eventually need to undergo colectomy for medically refractory disease or colitis-associated neoplasia [1]. The restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA), described in 1978 [2], has become the procedure of choice for the surgical treatment of the UC patients, which not only removes the affected colon and rectum, but also restores intestinal
continuity with sphincter conservation while avoiding a permanent ostomy. However, the procedure is a technically demanding operation which can be associated with serious surgical complications (pelvic sepsis, anastomotic leakage, etc.), which may have a detrimental effect on function, quality of life (QOL) and health status, including high stool frequency and fecal incontinence. Previous studies have shown that IPAA improves QOL for UC patients [3,4], while the risk factors of postoperative complications and its relationship with long-term QOL are still unclear. Mostly patients with UC undergoing pouch surgery are young and have a long life expectancy. Thus, measuring surgical complications and functional long-term QOL are important in order to
∗
Corresponding author. Department of Colorectal Surgery, Xin-Hua Hospital, 1665 Kongjiang Road, Shanghai 200092, China. Corresponding author. Department of Colorectal Surgery, Xin-Hua Hospital, 1665 Kongjiang Road, Shanghai 200092, China. E-mail addresses: [email protected] (W. Xu), [email protected] (H. Ye), [email protected] (Y. Zhu), [email protected] (W. Ding), [email protected] (J. Fu), [email protected] (L. Cui), [email protected] (P. Du). 1 Weimin Xu, Hairong Ye and Yilian Zhu contributed equally to this work. ∗∗
http://dx.doi.org/10.1016/j.ijsu.2017.10.070 Received 7 September 2017; Received in revised form 23 October 2017; Accepted 25 October 2017 1743-9191/ © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
Table 1 Baseline characteristics of Patients and Univariable Analysis of risk factors for early surgical complications. Variables
Clinical data Postoperative follow-up time [mo, median (IQR)] Preoperative CGQL score (mean ± SD) Postoperative CGQL score (mean ± SD) Disease duration [yr, median (IQR)] Median age at surgery [yr, median (IQR)] Male: female Body mass index (kg/m2, mean ± SD) Stage of surgery, n (%) Ⅱ-stage IPAA Ⅲ-stage IPAA Surgical urgency, n (%) Urgent surgery Elective surgery History of abdominal surgery, n (%) Surgical approach, n (%) Open Laparoscopic Steroids, n (%) Immunomodulators, n (%) Extent of UC, n (%) Left side Pancolitis Laboratory and anesthetic Data ASA Grade, n (%) Ⅰ Ⅱ Opioids, n (%) Blood transfusion, n (%) Anesthesia method, n (%) General anesthesia (GA) General and Epidural anesthesia (EP) Preoperative hemoglobin (g/L, mean ± SD) Preoperative albumin (g/L, mean ± SD) Blood loss (ml, mean ± SD) Urine volume (ml, mean ± SD) Transfusion volume (ml, mean ± SD) Colloidal amount (ml, mean ± SD)
All cases
Early surgical complications group (Group A) n = 25
Non-complications group (Group B) n = 33
78.5 (34.4–92.8) 0.429 ± 0.173 0.728 ± 0.151 3.5 (2.0–8.0) 37.5 (27.8–52.0) 19:39 20.2 ± 3.4
0.474 ± 0.185 0.696 ± 0.135 3.0 (2.0–8.0) 45.0 (35.0–56.0) 10:15 20.0 ± 2.8
0.398 ± 0.160 0.751 ± 0.159 4.0 (1.8–7.5) 30.0 (26.0–50.5) 9:24 20.3 ± 3.8
42 (72.4) 16 (27.6)
18 (72.0) 7 (28.0)
24 (72.7) 9 (27.3)
4 (6.9) 54 (93.1) 10 (17.2)
3 (12.0) 22 (88.0) 2 (7.7)
1 (3.0) 32 (97.0) 8 (25.0)
39 (67.2) 19 (32.8) 30 (51.7) 7 (12.1)
19 (76.0) 6 (24.0) 13 (52.0) 2 (8.0)
20 (60.6) 13 (39.4) 20 (60.6) 5 (15.2)
10 (17.2) 48 (82.8)
5 (20.0) 20 (80.0)
5 (15.2) 28 (84.8)
8 (13.8) 50 (86.2) 50 (86.2%) 6 (10.3)
4 (16.0) 21 (84.0) 21 (84.0) 1 (4.0)
4 (12.0) 29 (87.9) 29 (87.9) 5 (15.2)
54 (93.1) 4 (6.9) 38.4 ± 5.7 114.8 ± 22.4 259.3 ± 185.4 378.6 ± 251.8 2100.0 ± 548.8 637.9 ± 257.4
23 (92.0) 2 (8.0) 116.2 ± 20.9 38.0 ± 7.0 325.2 ± 167.8 378.0 ± 275.4 226.0 ± 671.6 680.0 ± 244.9
31 (93.9) 2 (6.1) 113.7 ± 23.7 38.7 ± 4.4 223.0 ± 189.3 379.1 ± 236.8 2004.5 ± 420.1 606.1 ± 265.7
p value
0.823 0.015 0.306 0.683 0.951
0.305
0.160 0.216
0.512 0.687 0.731
0.674
0.715 0.222 1.000
0.676 0.668 0.037 0.987 0.156 0.283
impaired general health status, and/or lost follow-up.
achieve an acceptable risk to benefit ratio for both surgeons and UC patients. In this study, we mainly assessed risk factors associated with longterm functional outcome by using the Cleveland Global Quality of Life (CGQL) instrument and evaluated the early surgical complications of UC patients after IPAA. It is important to explore treatment strategies and methods to reduce the incidence of postoperative adverse events and to improve the long-term QOL.
2.3. Quality of life scale We used the questionnaires to obtain both pre- and postoperative CGQL score, which has been determined to assess long-term QOL in UC patients after IPAA [3,5]. Patients were asked to score each of the three items (current quality of life, current quality of health, and current energy level), each on a scale of 0–10 (0, worst; 10, best). The scores were added and the cumulative score is divided by 30 to obtain the ultimate CGQL score. In the present study, we used the CGQL instrument before surgery to evaluate the preoperative status, then we subtracted the preoperative score from the latest postoperative CGQL score and the difference is divided by preoperative score so as to obtain the improvement of CGQL scores in percentage. We then respectively divided into two groups based on the improvement percentage of CGQL scores, with 50% improvement as a cut-off value.
2. Methods 2.1. Participants and setting Patients who underwent total proctocolectomy (TPC) with pouch creation between January 2008 and July 2016 at our institute were eligible for inclusion. Patients were identified, and their clinical data was obtained from a prospectively maintained, institutional review board-approved pouch database. Long-term CGQL scores were conducted by telephone interview and outpatient examination.
2.4. Statistical analysis Statistics to describe the data are appropriately represented by the numbers and percentages, mean and standard deviations (SD), or the median and interquartile range (IQR). Continuous variables were described according to the median and IQR or mean and SD. Two-sample Student's t-test was used to compare the population means between two different continuous variables and Wilcoxon's rank-sum test was used for ranked variables respectively. Categorical variables were evaluated using Chi-squared or Fisher's exact test, as appropriate. Multivariable
2.2. Inclusion and exclusion criteria Inclusion criteria were patients who: (1) diagnosed as UC; (2) received TPC with pouch creation; (3) underwent pouch surgery at 16–65 years old; and (4) received a regular follow-up at our department. Exclusion criteria were patients who: (1) underlying as familial adenomatous polyposis (FAP) or indeterminate colitis (IC); (2) were with status of temporary or permanent diverting ileostomy; and (3) had 175
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
logistic regression was further used to evaluate the association of clinical factors with early surgical complications and the long-term QOL. All hypothesis testing was two-sided, with a p-value of < 0.05 considered statistically significant.
Table 2 Postoperative complications of IPAA (N = 58).
3. Results 3.1. Demographics and clinical characteristics A total of 58 patients who underwent TPC with IPAA at our institution were eligible for the current analysis. Demographics, clinical, laboratory and anesthetic characteristics are shown in Table 1. The median follow-up time for the cohort was 78.5 months (IQR, 34.4–92.8) from February 2008 to March 2017. Two patients were died during the follow-up and were excluded from the analysis of long-term QOL. Median age of patients at the time of surgery was 37.5 years old (IQR, 27.8–52.0) with a median disease duration of 3.5 years (IQR, 2.0–8.0). Forty-two patients (72.4%) underwent II-stage surgery and 19 patients (32.8%) underwent laparoscopic procedure for pouch surgery. QOL improved significantly from a preoperative mean CGQL value of 0.429–0.728 after pouch construction (p < 0.001). Detailed improvements in long-term QOL can be seen in Fig. 1.
Complications
N (%)
Early postoperative complications Early postoperative Intestinal obstruction Pouch and anastomotic bleeding Pouch-anal anastomotic leak Leak at the tip of the J-pouch. Sacrococcygeal abscess Perianal sinus Wound infection Sepsis Late complications Postoperative long term intestinal obstruction Pouchitis Cuffitis Pouch-vagina leak Incision hernia Defecation dysfunction Pouch failure Anastomotic stricture Sexual dysfunction Infertility
25 (43.1) 8 (13.8) 8 (13.8) 1 (1.7) 2 (3.4) 2 (3.4) 1 (1.7) 8 (13.8) 1 (1.7) 23 (39.7) 5 (8.6) 12 (20.7) 1 (1.7) 2 (3.4) 3 (5.2) 4 (6.9) 3 (5.2) 3 (5.2) 1 (1.7) 1 (1.7)
died from severe sepsis. During the entire follow-up period, there were 23 patients (39.7%) developed late complications (details were shown in Table 2). Pouch failure occurred in 3 patients (5.2%), due to two of them developed Crohn's disease (CD) of pouch and one for severe pouchitis.
3.2. Postoperative complications of IPAA Table 2 shows various post-IPAA complications noted during the investigation. Early surgical complications in the present study refer to the complications which occurred within one month after pouch surgery. Postoperative complications were diagnosed based on clinical manifestations, laboratory results along with endoscopic and imaging findings. A total of 25 patients (43.1%) experienced early surgical complications, of which 8 patients (13.8%) had intestinal obstruction, 8 (13.8%) experienced bleeding at pouch or anastomotic site, 3 (5.2%) underwent pouch leaks (two leaks at the tip of “J” and one at pouchanal anastomosis), 2 (3.4%) developed sacrococcygeal abscess, 1 (1.7%) had perianal sinus, 8 (13.8%) had wound infection and 1 (1.7%)
3.3. Risk factors for early surgical complications in patients with IPAA We then analyzed the risk factors of early surgical complications in the group of 25 patients who developed early complications (Group A) compared with the others (Group B). Significant differences were observed for age at pouch surgery (p = 0.015) and intraoperative blood loss (p = 0.037) between groups. There were no statistical differences in terms of gender, body mass index (BMI), stage of surgery, history of Fig. 1. Comparison of pre- and post-IPAA CGQL scores. Three items of the CGQL instrument, current quality of life (A) current quality of health (B) and current energy level (C) were respectively compared between pre-and post-IPAA status. (D) Ultimate overall CGQL scores between the different status was performed. Scores are presented as mean ± SD. *** means P < 0.001.
176
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
Table 3 Multivariate logistic regression analysis of risk factors for early postoperative complications after IPAA. Variables
Odds Ratio
95% Confidence Interval
p value
Age at surgery Blood loss≧400 ml Open surgery Gender
1.05 4.51 1.49 0.542
1.01–1.10 1.21–16.87 0.43–5.18 0.16–1.89
0.025 0.025 0.531 0.337
Table 5 Multivariate logistic regression analysis of influencing factors for CGQL. Variables
Odds Ratio
95% Confidence Interval
p value
Early surgical complications Immunomodulators Age at surgery Gender
5.55 17.50 1.06 0.74
1.44–21.37 1.52–201.39 1.01–1.12 0.17–3.28
0.013 0.022 0.023 0.689
1.01–1.12), and use of immunomodulators (OR, 17.50; 95%CI, 1.52–201.39) were independent factors of poor long-term QOL after IPAA for patients with UC (Table 5).
Table 4 Possible influencing factors for CGQL of UC patients accepted IPAA (N = 56). Characteristics
Group C (n = 30)
Group D (n = 26)
p value
Median age at surgery [yr, median (IQR)] Male: female BMI (kg/m2) History of abdominal surgery, n (%) Surgical urgency, n (%) Urgent surgery Elective surgery Surgical approach, n (%) Open Laparoscopic Steroids, n (%) Immunomodulators, n (%) Extent of UC, n (%) Left-sided colitis Pancolitis Stage of surgery, n (%) Ⅱ-stage IPAA Ⅲ-stage IPAA Blood transfusion, n (%) Opioids, n (%) Early surgical complications, n (%)
29.0 (26.0–43.5)
50.0 (35.0–55.3)
0.002
8:22 20.7 ± 4.1 4 (13.3)
11:15 19.6 ± 2.3 6 (23.1)
0.218 0.192 0.487
1 (3.3) 29 (96.7)
2 (7.7) 24 (92.3)
17 (56.7) 13 (43.3) 17 (56.7) 1 (3.3)
20 (76.9) 6 (23.1) 15 (57.7) 6 (23.1)
4 (13.3) 26 (86.7)
5 (9.2) 21 (80.8)
21 (70.0) 9 (30.0) 5 (16.7) 26 (86.7) 7 (23.3)
19 (73.1) 7 (26.9) 1 (3.8) 23 (88.5) 16 (61.5)
4. Discussion It is a significant advantage of IPAA that it can avoid the permanent stoma by maintaining bowel continuity and creating a continent fecal reservoir. Current practice proves that IPAA has been a rather safe procedure for most UC patients through creating a long-term functional pouch. Favorable gastrointestinal function and QOL could be achieved through IPAA for patients with UC [6,7]. Assessing by using CGQL instrument in the study, we found that pouch surgery may significantly improve the long-term QOL (pre-vs. post-, 0.429 vs. 0.728, p < 0.001). Despite IPAA generally brings about excellent functional results and high satisfaction in patients, multiple kinds of postoperative complications may be encountered after there has been reports presenting respective morbidity and mortality rates [8], which cause the adverse outcome and compromise patients' QOL. One study reported that the proportion of patients who require permanent ileostomy for pouch failure was 11.3% [9]. The morbidity rate varies greatly (30%–60%) with surgical complications distressing both the patients and surgeons [10]. In our study, early postoperative complications occurred in 43.1% of the cohort patients, including intestinal obstruction, pouch and anastomotic bleeding, leakage, etc. Late complications occurred in 39.7% of the patients. Pouch failure developed in 3 patients (5.2%) during a mean follow-up of 78.5 months, with similar incidence (6.8%) reported in one pooled data from 43 studies with a mean follow-up time of 36.7-month [12]. In our study, 2 cases of pouch failure were due to CD of pouch and one for severe pouchitis. Indeterminate diagnosis of UC before surgery may be one explanation for occurrence of this severe outcome. Pouch surgery for CD or IC may be detrimental to patient's long-term outcome. Late complications also may cause troublesome results and reduce the satisfaction of surgical treatments. Poor outcome after IPAA includes multiple functional problems such as stool frequency, incontinence or sexual dysfunction, leading to further distress. Starting from postoperative complications, there still remained some patients with an unsatisfied feeling or poor outcome after IPAA. The definite influence and relationship of surgical complications with longterm outcome for patients with UC after pouch surgery remain unclear. Thus, the aim of this retrospective study was to explore the risk factors associated with the long-term QOL and search for strategies and methods to improve it in clinical practice. Several QOL assessment systems in the form of questionnaires have been used to assess outcome after surgery, such as Short Form 36 (SF36). Of these, CGQL instrument was designed specifically for patients undergoing RPC [13]. Compared with SF-36, CGQL instrument deemed to be reliable, responsive, and is a simpler instrument, which has been used to assess long-term quality of life in UC patients after IPAA [3,5]. In the present study, we demonstrated that early surgical complications were significantly associated with the long-term outcome for UC patients by analysis from the improvement of CGQL scores. One explanation is that additional surgical procedures required to treat early postoperative complications may cause adverse outcomes such as abdominal adhesions, pelvic abscess, injury of anal sphincter etc.
0.592
0.110
0.938 0.041 0.719
0.799
0.200 1.000 0.004
abdominal surgery, surgical urgency, surgical approach, use of steroids and immunomodulators, volume of opioids use, American Society of Anesthesiologists (ASA) grade, anesthesia method, extent of UC, preoperative hemoglobin and albumin level and intraoperative infusion volume (p > 0.05) (Table 3). To further analyze the risk factors associated with early surgical complications after IPAA, we performed a multivariate logistic analysis. Table 4 showed a step-wise logistic regression model for the description of risk factors. In the multivariate analysis, older age at surgery [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.01–1.10] and significant intraoperative blood loss (≧400 ml) (OR, 4.51; 95% CI, 1.21–16.87) were contributing factors for developing early surgical complications. 3.4. Analysis of long-term QOL Based on each patient's CGQL score difference between preoperative and postoperative value, patients with ≧50% improvement were included in the good outcome group (Group C, n = 30) and those with < 50% improvement were listed in the poor outcome group (Group D, n = 26). Two patients died were excluded from this analysis. In univariate analysis, age at pouch surgery (p = 0.002), use of immunomodulators for UC (p = 0.041), and presence of early surgical complications (p = 0.004) were significantly associated with long-term QOL. No statistical differences were observed between 2 groups in baseline characteristics, including BMI, stage of surgery, history of abdominal surgery, surgical urgency, use of steroids or opioids, ASA grade, anesthesia method and extent of UC (Table 5). In the multivariate analysis, early surgical complications (OR, 5.55; 95% CI, 1.44–21.37), older age at pouch surgery (OR, 1.06; 95%CI, 177
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
health or nutritional status and likely affect the long-term QOL. Detailed mechanism needs further identification. There are some limitations to the study. Firstly, insufficient sample size has the potential to increase the referral bias due to the nature of our practice from one single center. A sizeable number of patients referred to the assessment of CGQL values from more hospitals are needed in further studies. Secondly, despite the fact that this was a long-term study, there were still some CGQL scores obtained from a relative shorter follow-up for different pouch patients. Therefore, it might have had an individual heterogeneity bias due to a different follow-up period in the cohort patients. To get more accurate CGQL value from a larger sample size may obtain more meaningful conclusions.
Secondly, previous studies have reported that the occurrence of pouch bleeding is one definite contributing factor for developing acute or chronic pouchitis, which are the most common manifestation of complications of IPAA [14]. Of the 58 patients in our study, 2 with pouch or anastomosis bleeding developed pouchitis. Severe pouchitis may lead to worst outcome of pouch failure and a poor long-term QOL. Thirdly, occurrence of multiple complications during the immediate postoperative periods may likely have a negative impact on the UC patients' mental health and therefore have adverse effect on the QOL to a certain extent. In order to further explore the risk factors for early surgical complications associated with the poor long-term QOL, we analyzed various factors, including clinical characteristics, medical management histories, operative details, and anesthesia data from a medical record system. By univariate and multivariate analysis, we found older age at surgery and excessive blood loss (≧400 ml) were contributing factors for early surgical complications. Older patients undergoing pouch surgery are more likely to suffer from the early surgical complications. Similar results could be found in other studies [15,16]. Ridzuan Farouk [17] found that older patients had a higher frequency of nocturnal stool and more episodes of fecal incontinence compared with younger patients. During the most of IPAA procedures in clinical practice, we performed the double-stapling technique for pouch construction with the remnant columnar cuff less than 2–3 cm above the anal margin. This surgical procedure is demanding in term of patients' anal function while older patients are disadvantaged compared with young patients. Also, older patients with UC have relatively poor health status due to longer course of disease which leads to slower recovery postoperatively. Excessive bleeding and/or fulminant colitis could deteriorate the general physical conditions of the patients and many reports have asserted that pouch surgery should be treated with caution under these circumstances [18]. Previous retrospective studies found that excessive blood loss (> 500 ml) significantly increased mortality after colorectal surgery [19] and estimated blood loss (> 200 ml) were found to be associated with increased length of hospital stay [20]. In our study, intraoperative blood loss (≧400 ml) proved closely associated with surgical complications. Nowadays, minimally invasive surgery has become widely available. Laparoscopy has been reported as an effective minimally invasive procedure with lower incidence of surgical complications [21,22]. A single institutional case-matched study demonstrated that IPAA performed laparoscopically confers several significant benefits including significantly smaller incision with less postoperative pain, earlier return of bowel function and shorter length of hospital stay [23]. Multicenter randomized controlled trial with large sample size should be carried out prospectively to further establish the potential advantage of laparoscopic IPAA. The clinical implication suggested that strategies such as employing minimally invasive surgery with better surgical skills to minimize intraoperative blood loss may help reduce the incidence of early surgical complications, which will be beneficial to improve the long-term QOL. In addition, appropriate IPAA stage and surgical timing should be taken into consideration in the clinical practice, which may be beneficial for patients. Long-term and regular follow-up combined with colonoscopy in outpatient examination could help detect pouch function and reduce the incidence of pouch failure, which should also attract our attention. Some medical treatments during the disease course of UC may be associated with the occurrence of surgical complications of IPAA and its impact on long-term outcome is still unclear. In the present study, we found use of immunomodulators was an independent adverse factor for long-term QOL after IPAA. In clinical practice, thiopurine drugs, such as azathioprine and mercaptopurine are the common treatment for steroid-dependent CD and UC patients [24]. Immunomodulators have many adverse reactions including liver damage [25], lung damage [26], bone marrow suppression and a small risk of developing congenital malformation in pregnancy [27], which may be associated with poor
5. Conclusion The results of this study have several clinical implications. Our study shows that the risk factors for developing surgical mechanical/ infectious complications within one month after IPAA are possibly age at time of surgery and intraoperative blood loss. Moreover, the early surgical complications contribute to developing a poor CGQL score during follow-up time after IPAA, suggesting intentional control of the risk factors associated with early surgical complications should be taken into consideration for patients with UC. The result also helps both surgeons and patients to make informed decisions. Standard surgical procedure of IPAA to reduce intraoperative blood loss, reasonable selection of immunomodulators therapy course and early recruitment of patients should be emphasized in clinical practice. Ethical approval None. Funding This work was supported by grants from the National Natural Science Foundation of China [grant numbers 81570474]. Author contribution Peng Du and Long Cui conceived the study. Data was collected by all authors. Wenjun Ding and Jihong Fu completed the follow-up. Weimin Xu performed analyses of the data. Weimin Xu and Yilian Zhu wrote the manuscript. Hairong Ye finished the revision of the manuscript. Weimin Xu, Hairong Ye and Yilian Zhu contributed equally to this work. All authors reviewed the manuscript. Conflicts of interest None of the authors have any conflict of interest. Research registration unique identifying number (UIN) researchregistry2937. Guarantor Peng Du. References [1] R. Marchioni Beery, S. Kane, Current approaches to the management of new-onset ulcerative colitis, Clin. Exp. Gastroenterol. 7 (2014) 111–132. [2] A.G. Parks, R.J. Nicholls, Proctocolectomy without ileostomy for ulcerative colitis, Br. Med. J. 2 (6130) (1978) 85–88. [3] V.W. Fazio, M.G. O'Riordain, I.C. Lavery, J.M. Church, P. Lau, S.A. Strong, et al., Long-term functional outcome and quality of life after stapled restorative proctocolectomy, Ann. Surg. 230 (4) (1999) 575–584.
178
International Journal of Surgery 48 (2017) 174–179
W. Xu et al.
of life after ileal pouch-anal anastomosis, Ann. Surg. 238 (2) (2003) 221–228. [17] J.H.P. Ridzuan Farouk, Bruce G. Wolff, Roger R. Dozois, Scott Browning, Dirk Larson, Functional outcomes after ileal pouch-anal anastomosis for chronic ulcerative colitis, Ann. Surg. 231 (6) (2000) 919–926. [18] A. Grucela, R.M. Steinhagen, Current surgical management of ulcerative colitis, Mt. Sinai J. Med. A J. Transl. Personal. Med. 76 (6) (2009) 606–612. [19] K. Skala, P. Gervaz, N. Buchs, I. Inan, M. Secic, B. Mugnier-Konrad, et al., Risk factors for mortality-morbidity after emergency-urgent colorectal surgery, Int. J. Colorectal Dis. 24 (3) (2009) 311–316. [20] Z. Aga, M. Machina, S.A. Mccluskey, Greater intravenous fluid volumes are associated with prolonged recovery after colorectal surgery: a retrospective cohort study, Bja Br. J. Anaesth. 116 (6) (2016) 804–810. [21] H. Zhang, S. Hu, G. Zhang, K. Wang, B. Chen, B. Li, et al., Laparoscopic versus open proctocolectomy with ileal pouch-anal anastomosis, Minim. Invasive Ther. Allied Technol. MITAT Off. J. Soc. Minim. Invasive Ther. 16 (3) (2007) 187–191. [22] F.J. Fleming, T.D. Francone, M.J. Kim, D. Gunzler, S. Messing, J.R. Monson, A laparoscopic approach does reduce short-term complications in patients undergoing ileal pouch-anal anastomosis, Dis. Colon Rectum 54 (2) (2011) 176–182. [23] D.W. Larson, R.R. Cima, E.J. Dozois, M. Davies, K. Piotrowicz, S.A. Barnes, et al., Safety, feasibility, and short-term outcomes of laparoscopic ileal-pouch-anal anastomosis: a single institutional case-matched experience, Ann. Surg. 243 (5) (2006) 667–670. [24] J.P. Gisbert, P.M. Linares, A.G. Mcnicholl, J. Maté, F. Gomollón, Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis, Aliment. Pharmacol. Ther. 30 (2) (2009) 126–137. [25] E. Petit, S. Langouet, H. Akhdar, C. Nicolas-Nicolaz, A. Guillouzo, F. Morel, Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes, Toxicol. In Vitro 22 (3) (2008) 632–642. [26] A.N. Ananthakrishnan, T. Attila, M.F. Otterson, R.J. Lipchik, B.T. Massey, R.A. Komorowski, et al., Severe pulmonary toxicity after azathioprine/6-mercaptopurine initiation for the treatment of inflammatory bowel disease, J. Clin. Gastroenterol. 41 (7) (2007) 682–688. [27] C.G. Su, R.B. Stein, J.D. Lewis, G.R. Lichtenstein, Azathioprine or 6-mercaptopurine for inflammatory bowel disease: do risks outweigh benefits? Dig. Liver Dis. 32 (6) (2000) 518–531.
[4] A.J. Muir, L.J. Edwards, L.L. Sanders, R.R. Bollinger, M.J. Koruda, D.R. Bachwich, et al., A prospective evaluation of health-related quality of life after ileal pouch anal anastomosis for ulcerative colitis, Am. J. Gastroenterol. 96 (5) (2001) 1480–1485. [5] J.C. Coffey, D.C. Winter, P. Neary, A. Murphy, H.P. Redmond, W.O. Kirwan, Quality of life after ileal pouch-anal anastomosis: an evaluation of diet and other factors using the Cleveland Global Quality of Life instrument, Dis. Colon Rectum 45 (1) (2002) 30–38. [6] V.W. Fazio, R.P. Kiran, F.H. Remzi, J.C. Coffey, H.M. Heneghan, H.T. Kirat, et al., Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients, Ann. Surg. 257 (4) (2013) 679–685. [7] A. de Buck van Overstraeten, A.M. Wolthuis, S. Vermeire, G. Van Assche, A. Laenen, M. Ferrante, et al., Long-term functional outcome after ileal pouch anal anastomosis in 191 patients with ulcerative colitis, J. Crohn's Colitis 8 (10) (2014) 1261–1266. [8] F. Alexander, Complications of ileal pouch anal anastomosis, Seminars Pediatr. Surg. 16 (3) (2007) 200–204. [9] C. Leowardi, U. Hinz, M. Tariverdian, P. Kienle, C. Herfarth, A. Ulrich, et al., Longterm outcome 10 years or more after restorative proctocolectomy and ileal pouch–anal anastomosis in patients with ulcerative colitis, Langenbeck's Arch. Surg. 395 (1) (2010) 49–56. [10] S. Ross, R.E. Kornbrekke, Complications after ileal pouch-anal anastomosis in Korean patients with ulcerative colitis, World J. Gastroenterol. 20 (23) (2014) 7488–7496. [12] W.E. Hueting, E. Buskens, dTI. Van, H.G. Gooszen, C.J. van Laarhoven, Results and complications after ileal pouch anal anastomosis: a meta-analysis of 43 observational studies comprising 9,317 patients, Dig. Surg. 22 (1–2) (2005) 69. [13] V.W. Fazio, Y. Ziv, J.M. Church, J.R. Oakley, I.C. Lavery, J.W. Milsom, et al., Ileal pouch-anal anastomoses complications and function in 1005 patients, Ann. Surg. 222 (2) (1995) 120–127. [14] A. Cheifetz, S. Itzkowitz, The diagnosis and treatment of pouchitis in inflammatory bowel disease, J. Clin. Gastroenterol. 38 (5 Suppl 1) (2004) S44. [15] E. Carmon, A. Keidar, A. Ravid, G. Goldman, M. Rabau, The correlation between quality of life and functional outcome in ulcerative colitis patients after proctocolectomy ileal pouch anal anastomosis, Colorectal Dis. 5 (3) (2003) 228. [16] C.P. Delaney, V.W. Fazio, F.H. Remzi, J. Hammel, J.M. Church, T.L. Hull, et al., Prospective, age-related analysis of surgical results, functional outcome, and quality
179