Causes Of Pouch Failure Research Articles

P0423 Anastomotic leakage after ileoanal pouch surgery: risk factors and salvage

Abstract Background Chronic anastomotic leakage (AL) is the most common cause of pouch failure after restorative proctocolectomy with ileal pouch-anal anastomosis for Ulcerative Colitis. This study aims to investigate the factors associated with AL and successful salvage of leaking anastomoses after ileoanal pouch surgery. Methods This multicentre retrospective cohort study included patients ≥18 years old with Ulcerative Colitis or unclassified Inflammatory Bowel Disease who underwent ileoanal pouch surgery between 2016 and 2021 in six European centres, with >12 months follow-up. The primary outcome was AL rate. Secondary outcomes included factors associated with the occurrence of AL, diagnosis, management and salvage of AL and stoma-free survival. Results 411 patients were included, of which 13.6% (n=56) had a diagnosed AL with a significantly higher rate in low-volume centres. Of the 56 AL, 44 were diagnosed early and 12 late. Three-stage approach was associated with late diagnosis and treatment. AL were managed using various techniques. The overall AL salvage rate was 85.4%, 92% when diagnosed and treated early and 60% when diagnosed and treated late (p=0.010). Successful AL salvage was associated with long-term stoma-free status (p=0.002). The long-term stoma-free rate was 95.5% in patients with early diagnosed and treated leaks, but only 41.7% when diagnosed and treated late (p<0.001). Conclusion Early diagnosis and treatment of AL diminishes the negative effect of AL after ileoanal pouch surgery. Pro-active anastomotic assessment is mandatory to enable early diagnosis and management especially in patients at increased risk of silent leaks such as three-staged patients.

Long Rectal Cuff and Remnant Mesorectum Are Major Preventable Causes of Ileal Pouch Failure.

Long rectal cuff (>2 cm) and remnant mesorectum are known causes of pouch dysfunction due to obstructive defecation, as well as pelvic sepsis after prolonged obstruction. The aim of this study is to report the rates and the management of patients who underwent re-do ileal pouch anal anastomosis due to pouch failure associated with retained mesorectum and long rectal cuff. This is a retrospective study. The investigation is based on a quaternary inflammatory bowel disease center. Patients undergoing re-do ileal pouch anal anastomosis surgery and had long rectal cuff and/or remnant mesorectum between September 2016 and September 2023 were included in the study. The main outcomes were functioning pouch rate and functional results. Of the 245 patients who underwent re-do ileal pouch anal anastomosis surgery, 98 (40%) patients had long rectal cuff and/or remnant mesorectum. Re-do ileal pouch anal anastomosis in this patient group was successful (92%) at a median follow-up of 28 (18-52) months. The retrospective nature of the study and this is the experience of a single specialized center. Long rectal cuff and remanent mesorectum are major causes of pouch failure which can be successfully managed with re-do ileal pouch anal anastomosis surgery. Nearly half of pouch failure patients who had successful re-do ileal pouch anal anastomosis surgery initially received unnecessary biologic therapy before coming to our center. See Video abstract.

Comprehensive systematic review and pooled analysis of real-world studies evaluating immunomodulator and biologic therapies for chronic pouchitis treatment.

Pouchitis is a common complication after restorative ileal pouch-anal anastomosis following proctocolectomy for ulcerative colitis. Antibiotic-dependent or antibiotic-refractory chronic pouchitis (CP), which is a common cause of pouch failure affecting 15-20% of patients, is challenging to treat. The efficacy of second-line immunomodulator and biologic therapy remains poorly defined. We present a pooled analysis of real-world efficacy data from peer-reviewed full-text manuscripts, focusing on immunomodulator and biologic therapies in CP. Embase and PubMed databases were searched for full-text articles describing the treatment of CP. We performed a systematic review and pooled analysis of published studies to assess the efficacy of immunomodulators, including thiopurines and methotrexate, and biologics including antitumor necrosis factor, anti-integrin, and interleukin-12/23 antagonists. Clinical and endoscopic response and remission rates were combined for pooled analyses. Rates of treatment discontinuation and safety were also assessed. Pooled analysis comprised 20 full-text articles (485 patients). Overall clinical response rate was 46% (95% CI: 35-59%) and clinical remission rate was 35% (95% CI: 21-52%). Overall endoscopic response and remission rates were 41% (95% CI: 18-68%) and 15% (95% CI: 5-39%), respectively. Individual agents' safety profile was reassuring, with vedolizumab being the most favorable. The real-world efficacy data of immunomodulators in the treatment of CP is insufficient. Vedolizumab and ustekinumab appeared effective and safe for CP, whereas anti-TNFs showed higher rates of adverse events. The high heterogeneity within the studies is attributed to the real-world study design, obfuscating drug efficacy comparisons across the studies. Further studies are required to define the comparative effectiveness of available treatments of CP.

Surgical Options for the Treatment of Perianal and Anovaginal Fistulas in the Setting of Ileoanal Pouch Crohn’s Disease: Experience of a Tertiary Center

BackgroundThe leading cause of pouch failure following ileal pouch-anal anastomosis are peri-pouch fistulas and pelvic sepsis. ObjectiveDetermine the overall efficacy of current surgical therapy for the treatment of perianal and anovaginal fistulizing disease related to Crohn’s disease phenotype of the pouch. DesignRetrospective cohort study of a prospectively maintained, IRB-approved database. Settings/PatientsNinety-one (2.3%) patients of 3058 patients with an original diagnosis of ulcerative colitis who underwent proctocolectomy with ileal pouch-anal anastomosis between 2000 and 2021 at the Cleveland Clinic and underwent postoperative surgery for Crohn’s-related perianal disease. InterventionsTwo hundred thirty-one operations for perianal or anovaginal fistula(s). Main Outcome and MeasuresHealing rate of surgical therapy for peri-pouch fistulizing disease, impact of recurrent interventions on outcomes, and predictors of surgical failure. ResultsOverall mean age was 39.1 (± 11.6) years, with a BMI of 25.3 (± 6.3) kg/m2. More than half of the patients were female (n = 52, 57.1%). Sixty-three patients (69.2%) had a perianal fistula, 25 (27.5%) had an anovaginal fistula, and 3 (3.3%) patients had both. Overall success rate for healing was 59.3% (n = 54/91) at a mean follow-up of 6.4 (± 4.8) years. Seventeen (18.7%) patients underwent a concomitant diverting loop ileostomy. Among them, eight (47.0%) patients had the ileostomy closure after a mean time of 9.7 (± 2.8) months. In the multivariable logistic regression model, patients who had seton insertions in any operation were significantly less likely to heal (OR 0.11 95%, CI 0.03–0.43, p = 0.001). Overall pouch failure rate was 12.1%. LimitationsRetrospective single-center study which lacks a control arm and consistent long-term follow-up specific to a population-based dataset. ConclusionsPouch patients who develop perianal disease are difficult to treat, sometimes requiring pouch excision. However, when medical treatment alone is not effective, a multidisciplinary approach including surgical intervention can result in complete fistula healing in more than half of the cases.

Risks factors associated with the development of Crohn's disease after ileal pouch-anal anastomosis for ulcerative colitis: a systematic review and meta-analysis.

Following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), up to 16% of patients develop Crohn's disease of the pouch (CDP) which is a major cause of pouch failure. This systematic review and meta-analysis aimed to identify preoperative characteristics and risk factors for CDP development following IPAA. A literature search of MEDLINE, EMBASE, EMCare and CINAHL databases was performed for studies that reported data on predictive characteristics and outcomes of CDP development in patients who underwent IPAA for UC between January 1990 and August 2022. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed. Seven studies with 1,274 patients were included: 767 patients with a normal pouch and 507 patients with CDP. Age at UC diagnosis (WMD -2.85; 95% CI -4.39 to -1.31; p=0.0003; I2 54%) and age at pouch surgery (WMD -3.17; 95% CI -5.27 to -1.07; p=0.003; I2 20%) were significantly lower in patients who developed CDP compared to a normal pouch. Family history of IBD was significantly associated with CDP (OR 2.43; 95% CI 1.41 to 4.19; p=0.001; I2 31%), along with a history of smoking (OR 1.80; 95% CI 1.35 to 2.39; p<0.0001; I2 0%). Other factors including sex, primary sclerosing cholangitis and current smoking were found not to increase risk of CDP. Age at UC diagnosis and pouch surgery, family history of IBD and previous smoking have been identified as potential risk factors for CDP post-IPAA. This has important implications towards preoperative counselling, planning surgical management and evaluating prognosis.

Dealing with Complications of Colorectal Surgery Using the Transanal Approach-When and How?

The transanal approach is a new and exciting addition to the surgeons' repertoire to deal with complications after colorectal surgery. Improved exposure, accessibility, and visibility greatly facilitate adequate dissection of the affected area with potential increase in effectiveness and reduced morbidity. An essential component in salvaging anastomotic leaks of low colorectal, coloanal, or ileoanal anastomoses is early diagnosis and early treatment, especially when starting with endoscopic vacuum therapy, followed by early surgical closure (endoscopic vacuum-assisted surgical closure). Redo surgery using a transanal minimally invasive surgery platform for chronic leaks after total mesorectal excision surgery or surgical causes of pouch failure successfully mitigates limited visibility and exposure by using a bottom-up approach.

Pouchitis: Clinical Features, Diagnosis, and Treatment.

Procto-colectomy with an ileal pouch anal anastomosis is the procedure of choice for ulcerative colitis patients that require colectomy. Pouchitis is a non-specific inflammation of the ileal reservoir, and the most common, inflammatory and long-term, complication after pouch surgery for ulcerative colitis. The aetiology is still unknown, but many risk factors have been individuated. Pouchitis can be classified based on aetiology, duration, clinical course, and response to antibiotic therapy. Accurate diagnosis and classification is the key factor for an adequate management, and exclusion of secondary causes of pouchitis is pivotal. Most of the patients consistently respond to antibiotic therapy, but management of the subgroup of patients with chronic-antibiotic-resistant-pouchitis is still challenging, being this entity one of the major causes of pouch failure.

Inflammatory, infectious, and ischemic disorders of the pelvic pouch

Pouchitis refers to a spectrum of inflammatory disorders affecting the ileal reservoir following restorative proctocolectomy and can be classified as idiopathic or secondary if a specific identifiable entity is identified. Pouchitis is a principal complication of the ileal pouch-anal anastomosis (IPAA) procedure and understanding the evaluation, diagnosis, and treatment of pouchitis is essential for the physician managing IPAA patients. Diagnosis and treatment of pouchitis is typically aided with multidisciplinary coordinated care leveraging specialized medical, pathological, and pharmacological expertise. While most mild and acute episodes of idiopathic pouchitis are easily treated, the gravity of the disease is clear – pouchitis significantly impairs the quality of life for IPAA patients and is a common cause of pouch failure.

Outcome and functional prognosis of pelvic sepsis after ileal pouch-anal anastomosis in patients with ulcerative colitis.

Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure for ulcerative colitis, but pouch failure or pelvic sepsis still occurs in some patients. We conducted this study to investigate the cause of pouch failure and evaluate defecatory function after pelvic sepsis. A total of 234 patients who underwent restorative proctocolectomy were enrolled. We analyzed the cause of pouch failure, as well as defecatory function and manometric outcomes, with and without the complication of pelvic sepsis. Pelvic sepsis developed in 29 (12.3%) of the 234 patients who underwent restorative proctocolectomy (pelvic sepsis group). The pelvic sepsis led to pouch failure in two of these patients (as a vaginal fistula in one and ileo-anal anastomotic leakage in one). Of the remaining majority of patients who did not suffer pelvic sepsis (control group), nine suffered pouch failure (as vaginal fistula in four, perianal abscess in two, pouch-spinal marrow fistula in one, and chronic pouchitis in two). There were no significant differences in defecatory function or manometric outcomes between the two groups. In the pelvic sepsis group, stool frequency was significantly correlated with white blood cell count (P=0.01) and the duration until onset of pelvic sepsis (P<0.01). Pelvic sepsis after restorative proctocolectomy for ulcerative colitis does not affect defecatory and manometric function, but control of the inflammation caused by pelvic sepsis is integral for defecatory function.

Serologic Markers Associated with Development of Crohn’s Disease After Ileal Pouch Anal Anastomosis for Ulcerative Colitis

One of the causes of pouch failure after ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) is the development of de novo Crohn's disease (CD). Our aim was to clearly define factors associated with post-IPAA CD. We conducted a cross-sectional study to compare demographic, clinical, and serological characteristics of patients with and without post-IPAA CD. All subjects underwent testing for anti-neutrophil cytoplasm antibodies, anti-Saccaromyces cerevisiae antibodies, anti-outer membrane porin C antibodies, and anti-CBir1 flagellin (anti-CBir1). A multivariable model assessed factors associated with post-IPAA CD. Thirty-nine subjects were enrolled in the study: 20 cases and 19 controls. Patients who developed post-IPAA CD were significantly younger (median 22 ± 9.9 vs. 30 ± 11.3, p = .027) at the time of UC diagnosis and exhibited more extraintestinal manifestations compared to controls (p = .023). No significant difference between the groups was found with respect to family history, smoking, duration of illness prior to colectomy, time to the onset of pouchitis, preoperative treatment, and indication for surgery. However, the post-operative serologic profile differed significantly with far more cases having elevated anti-CBir1 titers (p = .016, OR 8.81), the latter being the only independent predictor in the combined model. Patients with Crohn's disease of the pouch were more likely to have elevated CBir1 antibodies titers than those with simple pouchitis and healthy pouches. The stability of the CBir1 antibodies (pre- and post-colectomy) must be further assessed to establish its value as an independent predictor for development of post-IPAA CD.

Pros and cons of antibiotic therapy for pouchitis

Restorative proctocolectomy with ileal pouch–anal anastomosis has become the surgical treatment of choice for patients with medically refractory ulcerative colitis or ulcerative colitis with dysplasia and for the majority of patients with familial adenomatous polyposis. However, pouchitis and other pouch-associated complications frequently occur following surgery. Pouchitis is the most common long-term complication of ileal pouch–anal anastomosis in patients with ulcerative colitis, with a cumulative prevalence of up to 50%. The pathogenesis of pouchitis is probably associated with alterations in commensal bacterial flora, and most patients with pouchitis respond favorably to antibiotic therapy. Antibiotic therapy is the mainstay of treatment for active pouchitis, with ciprofloxacin or metronidazole traditionally being first-line agents. Some patients may develop dependency on antibiotics, thus requiring long-term maintenance therapy. In a subset of patients, the disease course may be refractory to antibiotic therapy, which is one of the common causes of pouch failure, requiring permanent ileostomy or pouch excision. On the other hand, long-term antibiotic use is expensive and can be associated with adverse effects and bacterial resistance. There may also be the risk of secondary infections, such as Clostridium difficile and fungal infections. The risks and benefits should be carefully balanced in patients who require long-term antibiotic therapy, and safe, efficacious, non-antibiotic-based agents are needed.

Risk factors for pouch failure in patients with different phenotypes of Crohnʼs disease of the pouch

Crohn's disease (CD) of the pouch is one of the leading causes of pouch failure in patients with restorative proctocolectomy. Risk factors for pouch failure in these patients are yet to be identified. The aim of the study was to assess risk factors associated with pouch failure in patients with CD of the pouch. All patients with a confirmed diagnosis of CD of the pouch in the Pouchitis Clinic between 2002 and 2007 were evaluated. Patients with familial adenomatous polyposis, normal pouches, pouchitis, cuffitis, surgical complications, and other diseased pouch conditions were excluded. Pouch failure was defined as the requirement for a permanent diversion or pouch resection. Demographic and clinical factors were studied with univariable and multivariable analyses. A total of 137 patients with CD of the pouch were included. Twenty-two patients (16%) developed pouch failure a median of 6 years after ileostomy takedown. Four of 50 patients (8.0%) with inflammatory CD, 4 of 30 (13.3%) with fibrostenotic CD, and 14 of 57 (24.6%) with fistulizing CD had pouch failure. A Kaplan-Meier plot for time to pouch failure by CD phenotype showed a trend toward association (P = 0.054) in patients with fistulizing CD. Adjusting for age, smoking status, and the use of immunomodulators or biologics, fistulizing CD was not found to be significantly associated with a higher hazard for pouch failure. Younger age, being an ex-smoker, and the use of immunomodulators or biologics were found to increase the hazard of pouch failure. Younger age, being an ex-smoker, and the requirement for immunomodulators or biologics were associated with pouch failure. The identification of these risk factors may help delineate the natural history of CD of the pouch and shed light on proper clinical management and prognosis.

Cumulative failure rate of ileal pouch-anal anastomosis and quality of life after failure.

The aim of the study was to calculate the cumulative occurrence of pouch failure among 486 patients who had undergone proctocolectomy and ileoanal anastomosis for ulcerative colitis or familial adenomatous polyposis. The other goal was to compare the quality of life in the failure group of 21 patients, the successful group, and the healthy population. Data were collected from patient histories, with the probability of pouch failure being calculated by the Kaplan-Meier method. Patients with pouch failure and controls were sent a Short-Form 36-item quality-of-life questionnaire, and data were analyzed with paired -test. The overall failure rate was 5.3 percent (26), including 24 pouch excisions and 2 early deaths (0.4 percent). Cumulative probabilities of pouch failure were 1, 5, and 7 percent at 1, 5, and 10 years, respectively. Neither pouchitis, gender, nor diagnosis correlated with pouch failure, but fistula formation ( p< 0.001) did. Patients with failure had lower quality-of-life scores for physical function (p < 0.02), social function ( p< 0.04), energy ( p< 0.02), and physical role function ( < 0.03) than the healthy population. Scores for physical function ( p< 0.01), energy ( p< 0.01), and physical role function ( p< 0.05) were also lower than those of control patients. The most common cause of pouch failure is fistula, whereas pouch excision is rarely caused by pouchitis. The impaired quality of life of patients in the failure group was caused by impairment of physical function and restrictions in social life.

Outcome after septic complications in J pouch procedures.

Despite the wide range of surgical approaches for pouch salvage, septic complications are among the main causes of pouch failure. This study analysed the mode and outcome of various therapeutic approaches for pouch salvage and the impact of time of diagnosis, localization and form of septic complications on the risk of pouch failure in 131 patients with septic complications of a total of 706 patients undergoing a J pouch procedure. Septic complications consisted of 76.3 per cent fistulas, 15.3 per cent anastomotic breakdowns and 8.4 per cent pelvic abscesses. A total of 107 patients (81.7 per cent) with septic complications required a mean of 2.2 surgical procedures. The frequency of permanent defunctioning and excision of the pouch in the 131 patients with septic complications was 23.7 and 6.1 per cent respectively. The estimated cumulative 3-, 5- and 10-year rate of pouch failure in patients with septic complications was 19.6, 31.1 and 39.2 per cent respectively. The risk of pouch failure was significantly affected by the site of origin of septic complications (P = 0.02). The 5-year pouch failure rate increased in a subgroup of patients with septic complications at the pouch-anal anastomosis when the anal sphincter was involved (50.1 versus 29.2 per cent; P = 0.18). Pouch failure as a result of septic complications may occur several years after ileal pouch-anal anastomosis. For prevention of pouch failure, surgery for septic complications is required in a high percentage of patients and repeated attempts are justified. Follow-up studies are required for further analysis of pouch failure.

Functional outcomes after ileal pouch-anal anastomosis for chronic ulcerative colitis.

To assess long-term outcomes after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (CUC) with specific emphasis on patient sex, childbirth, and age. Childbirth and the process of aging affect pelvic floor and anal sphincter function independently. Early function after IPAA is good for most patients. Nonetheless, there are concerns about the impact of the aging process as well as pregnancy on long-term functional outcomes after IPAA. Functional outcomes using a standardized questionnaire were prospectively assessed for each patient on an annual basis. Of the 1,454 patients who underwent IPAA for CUC between 1981 and 1994, 1,386 were part of this study. Median age was 32 years. Median length of follow-up was 8 years. Pelvic sepsis was the primary cause of pouch failure irrespective of sex or age. Functional outcomes were comparable between men and women. Eighty-five women who became pregnant after IPAA had pouch function, which was comparable with women who did not have a child. Daytime and nocturnal incontinence affected older patients more frequently than younger ones. Incontinence became more common the longer the follow-up in older patients, but this was not found in younger patients. Poor anal function led to pouch excision in only 3 of 204 older patients. Incontinence rates were significantly higher in older patients after IPAA for CUC compared with younger patients. However, this did not contribute to a greater risk of pouch failure in these older patients. Patient sex and uncomplicated childbirth did not affect long-term functional outcomes.

Pouch salvage. Long-term outcome.

The aim of this study was to determine the outcome of pouch salvage operations and the factors that may influence successful reconstructions. This retrospective review includes data from 198 patients who had undergone restorative proctocolectomy at a single institution during an 11-year period. All patients who had undergone attempted pouch salvage and who still had a pouch in situ were reviewed by both postal questionnaire and at interview in the outpatients clinic. Of 198 patients who underwent restorative proctocolectomy and ileal pouch-anal anastomosis, 27 (13.6 percent) presented with pouch-specific complications requiring pouch salvage. A further five patients requiring pouch salvage were referred from other centers. Of 32 patients who underwent attempted pouch salvage, 16 (50 percent) had a successful outcome, 12 (37.5 percent) had pouch excision, and 3 (9 percent) are still defunctioned. There was one death (3 percent) in this series. Pelvic sepsis was a major cause of pouch failure, being present in 50 percent (8/16) of failed salvage procedures, and accounting for 58 percent (7/12) of pouch excisions. Salvage surgery for major complications following ileoanal pouch construction is worthwhile in the absence of major pelvic sepsis. Overall success rate is 50 percent, and these results may be acceptable to highly motivated patients.

Ileal pouch-anal anastomosis. Patterns of failure.

During the period from 1980 through 1990, our institution constructed 253 ileoanal reservoirs in 253 patients, of whom 25 (9.9%) experienced pouch failure. A poor functional result was the most common cause of pouch failure (seven [28%] of 25 patients). Unsuspected Crohn's disease became manifest in 13 (5%) of the 253 patients, resulting in pouch loss due to perianal sepsis or pouch fistulas in six patients (24% of 25 failures), and resulted in a significantly increased risk of pouch failure compared with that of the non-Crohn's population. Pouchitis occurred in 78 patients (31%) and accounted for four (16%) of 25 failures, but patients with pouchitis were not at higher risk for pouch failure than were patients who did not have pouchitis (failure rates of 6.4% vs 10.4%, respectively; not significant). Significant pelvic sepsis in the absence of Crohn's disease developed in 13 patients, five (38%) of whom lost their pouches. Poor functional results, pelvic sepsis, and unsuspected Crohn's disease were the major causes of pouch failure, while pouchitis was not.