Appropriate J-pouch volume associated with improved clinical outcomes and long-term quality of life in patients with ulcerative colitis after ileal pouch-anal anastomosis: results from China UC Pouch Center Union
Article information
Abstract
Background/Aims
A well-functioning and well-constructed pouch is crucial for the long-term quality of life (QOL) in ulcerative colitis (UC) patients after ileal pouch-anal anastomosis (IPAA). What pouch volume is appropriate to construct to maintain satisfactory pouch function for better long-term prognosis remains unknown.
Methods
UC patients who underwent IPAA from January 2008 to January 2024 in our pouch surgery centers affiliated with the China UC Pouch Center Union were enrolled. The primary outcomes were the occurrence of postoperative complications and impaired long-term QOL.
Results
A total of 222 eligible UC patients with a median follow-up time of 8.0 years (interquartile range, 4.0–10.3 years) were enrolled. Among the patients, 117 (52.7%) had a pouch with volume <120 mL, whereas 105 (47.3%) had a pouch volume ≥120 mL. We found that patients with pouch volume ≥120 mL were more likely to achieve significantly improved long-term QOL (P=0.013), better bowel function (P=0.030) as well as have decreased risk of late postoperative complications (P=0.005), mainly presented as pouchitis (P=0.039). Furthermore, we demonstrated that a small pouch with volume < 120 mL is an independent risk factor for the development of late postoperative complications (odds ratio, 2.157; P=0.013) and impaired long-term QOL (odds ratio, 2.049; P=0.018).
Conclusions
A J-pouch volume ≥120 mL could be a considerable option for colorectal surgeons in pouch configurations to achieve better long-term prognosis.
INTRODUCTION
Total proctocolectomy with ileal pouch-anal anastomosis (IPAA), first proposed in 1978 [1], has been accepted as the radical surgery for ulcerative colitis (UC). Numerous pieces of evidence have demonstrated that IPAA can significantly improve long-term prognosis [2-4] as this surgical procedure removes the inflammatory colorectum as well as restores the intestinal continuity to prevent permanent ileostomy by creating an ileal reservoir, which is constructed from varying lengths of the distal ileum. However, IPAA is a complicated and technically demanding procedure, which is associated with several serious postoperative complications. Our previous studies indicated that intraoperative intravenous fluid administration and postoperative complications had detrimental effects on long-term quality of life (QOL) [5,6].
Among all pouch configurations, the J pouch is the most commonly used configuration due to its relatively easy construction and promising long-term outcomes [7,8]. The J pouch was joined, using varying methods, to the anorectal ring with sphincter conservation to recreate intestinal continuity and maintain normal physiology in IPAA. Thus, a well-functioning and well-constructed J pouch is decisive for the long-term QOL in UC patients after IPAA. Furthermore, appropriate pouch volume is crucial for a well-functioning J pouch as it is associated with bowel function after the operation. Although the volume is mainly determined by the length of ileum used for pouch creation [9], the radius of the transverse section of the terminal ileum and the compliance of the ileum itself also affect the volume. Thus, it is not accurate enough to determine the pouch volume only by detecting the pouch length. Our most recent study indicated that patients with a J-pouch length of 22±2 cm could achieve better clinical outcomes [10], but we ignored to analyze the effect of pouch volume on outcomes. Current evidence about the issue of what volume of pouch could make patients achieve the best long-term prognosis is lacking. Few studies with a long-term follow-up period comprehensively assess the relationship between pouch volume and clinical outcomes and long-term prognosis after IPAA.
In this study, we mainly aimed to explore whether pouch volume was associated with postoperative complications and long-term QOL and further determine the appropriate pouch volume for achieving better long-term prognosis, so as to provide clinicians with decision-making suggestions for pouch construction.
METHODS
1. Patients and Study Design
A retrospective multicenter study with all UC patients who received IPAA from January 2008 to January 2024 in our 4 pouch surgery centers affiliated with the China UC Pouch Center Union was performed. Clinical data were retrospectively collected from hospital electronic medical records, and follow-up information was obtained from regular postoperative outpatient examination and questionnaire investigation regarding QOL improvement. In this study, patients diagnosed as UC with complete data were ultimately included for analysis, whereas those who underwent subtotal colectomy with permanent diverting ileostomy without pouch construction or had poor compliance with irregular follow-up and incomplete clinical data were excluded from this study. Our research protocol has been reviewed and approved by the Ethics Committee of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine (No. XHEC-C-2024-187-1). The requirement for written informed consent was waived by the Ethics Committee.
2. Pouch Construction and Pouch Volume Measurement
As our institute is affiliated with the China UC Pouch Center Union, the procedure of IPAA is homogenized, standardized and performed by 3 experienced colorectal surgeons specialized in pouch surgery in each center. Briefly, after removing the affected colorectum, we used different numbers of endoscopic linear cutter reloads, by using a laparoscopic stapler, (Endo GIA60; Medtronic, Minneapolis, MN, USA), to construct a J pouch. The length of the cutting line of the side-to-side anastomosis of ileum was measured to record as the pouch length [10]. After the construction was completed, a 50-mL syringe was used to inject normal saline into the pouch until its maximum tolerated volume was reached to check for leak or bleeding at the anastomosis of the pouch body. The volume of injected normal saline was recorded intraoperatively as the pouch volume.
3. Clinical and Long-Term QOL Evaluation
The primary outcomes were the occurrence of postoperative complications and impaired long-term QOL improvement. Based on the Montreal classification system, we categorized UC as proctitis (E1), left-sided colitis (E2), and pancolitis (E3) according to the extent of affected colorectum [11]. Complications that developed within one month were considered early postoperative complications, whereas those that developed after one month were classified as late postoperative complications, mainly including pouchitis, postoperative late intestinal obstruction and anastomotic stricture. Wexner continence scores were measured to assess the bowel and defecation function. As we previously reported [5,10], the improvement of long-term QOL was evaluated by the difference between the pre-IPAA Cleveland Global Quality of Life (CGQL) instrument [12] after admission and the post-IPAA CGQL collected from the latest postoperative follow-up. Based on our previous research, the improvement percentage of CGQL of more than or less than 50% was considered as significantly improved long-term QOL or impaired long-term QOL in this study [5,10]. Briefly, the cumulative score of 3 items, current QOL (0–10 scores), current quality of health (0–10 scores), and current energy level (0–10 scores), was divided by 30 to obtain the ultimate CGQL scores.
4. Statistical Analysis
SPSS version 22.0 (IBM Corp., Armonk, NY, USA) and Graph Pad Prism 8.0 (San Diego, CA, USA) were used for statistical analysis. Continuous and categorical variables were presented as the mean and standard deviation and the median and interquartile range and analyzed by two-sample Student t-test and chi-square or Fisher exact test. Whereas the ranked data were analyzed using the Wilcoxon rank-sum test. Multivariate logistic regression analysis was performed to determine the risk factors for the development of late postoperative complications and impaired long-term QOL. The receiver-operating characteristic (ROC) curve was used to explore the best threshold evaluation for reflecting the long-term outcomes in J-pouch volume. The Kaplan-Meier method with the log-rank test was further performed to compare the overall late postoperative complications-free survival. The confidence interval (CI) was set at 95%. In this study, all statistics were two-sided, with a P-value <0.05 considered statistically significant.
RESULTS
1. Baseline Characteristics
A total of 239 UC patients who underwent IPAA in the China UC Pouch Center Union were initially enrolled. Of the patients, 8 patients were lost to follow-up and 9 patients with permanent diverting ileostomy without pouch construction were excluded. Thus, 222 eligible UC patients with complete data were ultimately included for further analysis (Fig. 1). Among the patients, the median follow-up time was 8.0 years (interquartile range, 4.0–10.3 years) and 117 patients (52.7%) had a pouch with volume <120 mL, whereas 105 patients (47.3%) received greater pouch construction with volume ≥120 mL (Table 1). In the whole cohort, most patients received IPAA due to medical treatment failure (86.9%) and a comparable proportion (5.4%) of patients who underwent IPAA due to malignant transformation. The detailed demographics and clinical characteristics are listed in Table 1.
The flowchart of this study. UC, ulcerative colitis; IPAA, ileal pouch-anal anastomosis; QOL, quality of life.
Main Baseline Characteristics of Patients
2. Postoperative Complications
In the whole cohort, 59 patients (26.6%) developed the early postoperative complications, mainly presented as early postoperative intestinal obstruction (13.5%), pouch and anastomotic bleeding (5.0%), pouch-anal anastomotic leak (4.1%), wound infection (7.2%), and incisional hernia (1.4%). Whereas a total of 76 patients (34.2%) developed late postoperative complications. Among them, 61 (27.5%) developed pouchitis, 3 (1.4%) developed pouch failure, 11 (5.0%) had postoperative long-term intestinal obstruction, 4 (1.8%) underwent pouchvagina leak, 7 (3.2%) had anastomotic stricture and only 1 (0.5%) developed sexual dysfunction (Table 2).
Main Postoperative Complications of Ileal Pouch-Anal Anastomosis
3. Clinical Outcomes in Patients with J Pouch Configuration of Different Volume
To determine the best threshold value of J-pouch volume for reflecting the late complications, the ROC analysis was performed. As shown in Supplementary Fig. 1, pouch volume had the most significant area under the ROC curve (AUC) of 0.654 with a sensitivity of 56.9% and specificity of 73.9% at the cutoff value of 120 mL (P=0.002). Based on the above results, we chose a pouch volume of 120 mL as the cutoff value for further analysis. To this end, we compared the postoperative complications and long-term QOL in patients with J pouch configuration with a cutoff value of 120 mL. As shown in Table 3, patients with J-pouch volume ≥120 mL had a lower risk late postoperative complications (P=0.005), mainly presented as less pouchitis (P=0.039), less defecation frequency (P=0.001) and had better bowel function assessed by Wexner scores (P=0.030). To further explore whether pouch volume could affect the late postoperative complications-free survival, the Kaplan-Meier method with the log-rank test analysis was performed. As shown in Fig. 2, patients with pouch volume <120 mL were prone to have shorter overall late postoperative complications-free survival than patients whose pouch volume ≥120 mL (P=0.023).
Analysis of the Clinical Outcome and Long-Term QOL in Patients with Pouches of Different Volumes
Analysis of overall late postoperative complications-free survival in patients with pouch volume ≥120 mL or <120 mL by Kaplan-Meier method with the log-rank test.
Furthermore, we determined whether a pouch volume ≥120 mL contributed to significantly improved long-term QOL. To this end, we first demonstrated the obvious improvements of post-IPAA scores CGQL in both pouches with different volumes (Fig. 3A and B). Whereas the ultimate postoperative CGQL scores (0.731 vs. 0.773; P=0.015), the current QOL (7.145 vs. 7.657; P=0.018) and the current quality of health (7.188 vs. 7.600; P=0.043) more significantly improved in patients with pouch volume ≥120 mL (Table 3, Fig. 3C-F). Moreover, significantly improved long-term QOL was more common in patients with pouch volume ≥120 mL (Table 3). Collectively, these data indicated that pouch volume ≥120 mL was associated with a lower risk of late postoperative complications, better bowel function, and more significantly improved long-term QOL.
A greater pouch with a volume ≥120 mL promoted better long-term QOL. The pre- and post-IPAA CGQL scores in patients with pouch volume <120 mL (A) and ≥120 mL (B). The postoperative current QOL (C), the current quality of health (D), current energy level (E), and CGQL scores (F) in patients with pouch volume <120 mL and ≥120 mL. QOL, quality of life; IPAA, ileal pouch-anal anastomosis; CGOL, Cleveland Global Quality of Life.
4. J-Pouch Volume <120 mL Increased the Risk of Late Postoperative Complications
Based on the above results, we speculated whether a pouch volume <120 mL could contribute to late postoperative complications. To this end, the univariate analysis was performed and the results indicated that J-pouch volume (P=0.005), the length of hospital stay (P=0.004), preoperative white blood cell counts (P=0.023), intraoperative blood loss (P=0.016), and operative duration (P=0.035) were associated with late postoperative complications (Table 4). Then these variables with significant differences in univariate analysis were further analyzed by the multivariate logistic regression. As shown in Table 5, J-pouch volume <120 mL (odds ratio [OR], 2.157; 95% CI, 1.175–3.960; P=0.013), preoperative white blood cell counts ≥10×109/L (OR, 2.205; 95% CI, 1.122–4.335; P=0.022) and operative duration ≥5 hours (OR, 1.927; 95% CI, 1.040–3.569; P=0.037) were independent risk factors for the development of late postoperative complications.
Analysis of Risk Factors for Late Postoperative Complications in UC Patients after IPAA
Logistic Regression Analysis of Risk Factors for Late Postoperative Complications in UC Patients after IPAA
5. J-Pouch Volume <120 mL Affected the Improvement of Long-Term QOL
Next, we further explored whether J-pouch volume <120 mL contributed to the impaired long-term QOL. According to the results from the univariate analysis, age at diagnosis (P=0.045), surgical approach (P=0.001), J-pouch volume (P=0.013), preoperative level of albumin (P=0.030) and the length of hospital stay (P=0.017) were significantly associated with impaired long-term QOL (Table 6). Multivariate logistic regression further demonstrated that age at diagnosis ≥40 years old (OR, 1.977; 95% CI, 1.100–3.555; P=0.023), open surgery (OR, 2.590; 95% CI, 1.284–5.222; P=0.008), J-pouch volume <120 mL (OR, 2.049; 95% CI, 1.130–3.715; P=0.018), and preoperative albumin <35 g/L (OR, 2.310; 95% CI, 1.270–4.203; P=0.006) were contributing factors for impaired long-term QOL (Table 7).
Analysis of Influencing Factors for Long-Term QOL Improvement in UC Patients after IPAA
Logistic Regression Analysis of Risk Factors for Impaired Long-Term QOL in UC Patients after IPAA
DISCUSSION
Compared with the W and S pouches, the J pouch has become the most popular pouch configuration due to its technical simplicity and overall satisfactory functional characteristics [13]. Currently, a structured approach to the surgical procedure of pouch surgery is still indefinite, diversified and lack of consistent standards. What volume of pouch should be constructed to make patients achieve better benefits remains unclear. The present multicenter study with the largest sample size and longest follow-up period based on the China UC Pouch Center Union first explored the relationship between pouch volume and clinical outcomes after IPAA and determined the appropriate pouch volume for patients. Based on the results, we demonstrated that patients with the pouch volume ≥120 mL were more likely to achieve better long-term QOL and had a lower risk of late postoperative complications, mainly including reduced risk for pouchitis and better bowel function. Moreover, we indicated that relatively small pouch volume (<120 mL) could be an independent risk factor for the development of late postoperative complications and impaired long-term QOL. Thus, a J-pouch volume ≥120 mL could be a considerable option for colorectal surgeons in pouch configurations to make patients achieve better long-term prognosis.
The side-to-side anastomosis of the distal ileum is the critical step of pouch surgery. Although pouch volume is mainly determined by the length of side-to-side anastomosis of the pouch body, it does not mean a pouch with a longer length necessarily has a larger volume. The radius of the transverse section of the terminal ileum and the compliance of the ileum itself also determined the pouch volume. Thus, the measurement of pouch volume only by pouch length is inadequate. In addition, an appropriate pouch volume is closely associated with satisfactory pouch function. An excessively small pouch volume may compromise pouch compliance and function, resulting in increased stool frequency or even incontinence, thereby significantly affecting long-term QOL. Thus, constructing a pouch with an appropriate volume is important for colorectal surgeons to make patients achieve better long-term prognosis. However, the current evidence mainly focused on pouch length, few studies explored what pouch volume is appropriate for patients to achieve better long-term prognosis. We previously reported that patients with a pouch length of 22±2 cm had a lower risk of postoperative complications and more significantly improved long-term QOL than those with a pouch length of 14±2 cm [10]. In contrast, Miratashi Yazdi et al. [14] reported that patients with short J-pouch configuration (8±2 cm) were likely to obtain better postoperative QOL. Moreover, another study done by Shibata et al. [15] indicated that there was no significant correlation between J-pouch length and the functional outcome by the multivariate analysis. The inconsistency between pouch length and clinical outcomes reported in various studies further indicated that it is insufficient to assess outcomes only based on the pouch length. A previous randomized controlled trial reported that a 4-limb W pouch with greater maximum tolerated volume contributed to better bowel function and fewer nighttime defecations [16]. In the present study, we demonstrated that patients with J pouch of greater volume (≥120 mL) had less late postoperative complications, better bowel function, and long-term QOL, which provided supporting evidence for pouch configurations of greater pouch volume (≥120 mL) in UC patients with IPAA to make patients achieve better long-term prognosis.
Consistent with the previous study, pouchitis was the most common late complication after IPAA [10,17-20]. Pouchitis arises as a result of the complicated interactions between genetic factors, immune dysregulation and the imbalance in the gut microbiota [21]. The abundance of specific microbiota in patients with healthy pouch was different from patients with inflamed pouch [22-24]. Antibiotics and faecal microbiota transplantation were considered as the therapeutic strategies for pouchitis, which further provided plausibility that microbiota dysbiosis could affect the course of pouchitis [25,26]. Moreover, Machiels et al. [27] reported that an abundance of multiple intestinal gut microbiota before colectomy with IPAA was associated with the development of pouchitis, hence indicating that gut microbiota dysbiosis could influence the pouch function. Increased defecation frequency even incontinence could lead to the disruption of intestine homeostasis and further microbiota dysbiosis. A previous study also indicated that dysbiosis could be characterized as a directed alteration of the microbiome composition in patients with diarrhea-predominant irritable bowel syndrome [28]. Our previous studies reported pouches with short lengths contributed to more defecation frequency to promote the development of pouchitis, even the severe diffuse pouchitis [10,19], which could be explained that greater pouches were prone to have better function of ileal reservoir for feces to decrease defecation frequency and further prevent pouchitis. Consistent with our results, Miratashi Yazdi et al. [14] also demonstrated that a short J pouch led to worse bowel function. However, what pouch volume is appropriate for construct to maintain satisfactory pouch function and decrease the risk of pouchitis remains unknown. Based on previous results, the predominant finding of this study was that a greater J pouch (≥120 mL) significantly improved bowel function, decreased the defecation frequency as well as prevented the development of late complications, especially pouchitis.
Our study had several limitations. First, the loss of follow-up and incomplete clinical data were almost inevitable due to the nature of the retrospective study. Second, although we provided supporting evidence for pouch configuration with appropriate volume, prospective studies with a larger sample size should be performed to further confirm our results. Third, using CGQL and Wexner scores to assess patients with an ileal pouch is suboptimal. Recently, Cavallaro and Bordeianou [29] reported a patient-centered, clinically useful scoring system that can quantify the range and severity of symptoms experienced by ileoanal pouch patients and their correlation with QOL. However, as this study was retrospective, some data pertaining to the above pouch-specific patient-reported outcome measure were missing or were not obtained during follow-up. In future studies, we will improve the completeness of clinical data and use the above measures to better assess the clinical outcomes of patients after IPAA. Fourth, the IPAA procedures were performed by experienced surgeons, the potential influence of inter-surgeon variability on the study outcomes was not evaluated.
In conclusion, this study first indicated that greater pouch volume (≥120 mL) is appropriate for UC patients and found that patients with pouch volume ≥120 mL were more likely to achieve more significantly improved long-term QOL, better bowel function as well as a decreased risk of late postoperative complications, mainly presented as pouchitis. Furthermore, we demonstrated that a small pouch with a volume <120 mL is an independent risk factor for the development of late postoperative complications and impaired long-term QOL. Thus, our study first provided supporting evidence for pouch configuration with appropriate volume in UC patients to make patients achieve better long-term prognosis.
Notes
Funding Source
This work was supported by the National Natural Science Foundation of China (Nos. 82570638, 82470549, 82270549), Natural Science Foundation of Shanghai (Nos. 25ZR1402360, 22ZR1440500), the Clinical Research Special Project of Shanghai Municipal Health Commission (20254Y0118), the Interdisciplinary Program of Shanghai Jiaotong University (No. YG2025QNB40), and the Qingfeng Scientific Research Fund of the China Crohn’s & Colitis Foundation (CCCF) (No. CCCF-QF-2022C14-21).
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Data Availability Statement
Data analyzed in this study are available from the corresponding author upon reasonable request.
Author Contributions
Conceptualization: Du P. Data curation: Xu W, Dai Z. Formal analysis: Xu W, Ding W. Funding acquisition: Xu W, Du P. Investigation: Xu W, Dai Z, Ding W, Cui L, Wu X, Zhou W, Ding Z. Methodology: all authors. Project administration: Xu W, Cui L, Wu X, Zhou W, Ding Z, Du P. Supervision: Du P. Validation: Xu W, Dai Z, Ding W, Du P. Visualization: Xu W, Dai Z. Writingoriginal draft: all authors. Approval of final manuscript: all authors.
Supplementary Material
Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).
Supplementary Fig. 1.
Receiver-operating characteristic (ROC) curves of pouch volume in predicting late complications after IPAA. Pouch volume had the most significant area under the ROC curve (AUC) of 0.654 with a sensitivity of 56.9% and specificity of 73.9% at the cutoff value of 120 mL.