Fecal incontinence and defecatory dyssynergia after ileoanal pouch in ulcerative colitis: Frequently underdiagnosed complications.

Although increasingly appreciated, little is known about the prevalence of fecal urgency, fecal incontinence and differences between patients' and physicians' perception in inflammatory bowel disease (IBD). We performed an online patient and physician survey to evaluate the assessment, prevalence and impact of fecal urgency and incontinence in IBD. A total of 593 patients (44.0% ulcerative colitis (UC), 53.5% Crohn's disease (CD), 2.2% indeterminate colitis, 2 not specified) completed the survey (65.8% females, mean age 47.1years). Fecal urgency was often reported (UC: 98.5%, CD: 96.2%) and was prevalent even during remission (UC: 65.9%, CD: 68.5%). Fecal urgency considerably impacted daily activities (visual analog scale [VAS] 5, IQR 3-8). Yet, 22.8% of patients have never discussed fecal urgency with their physicians. Fecal incontinence was experienced by 44.7% of patients and 7.9% on a weekly basis. Diapers/pads were required at least once a month in 20.4% of patients. However, 29.7% of patients never talked with their physician about fecal incontinence. UC was an independent predictor for the presence of moderate-severe fecal urgency (OR 1.65, 95% CI 1.13-2.41) and fecal incontinence (OR 1.77, 95% CI 1.22-2.59). All physicians claimed to regularly inquire about fecal urgency and incontinence. However, the impact of these symptoms on daily activities was overestimated compared with the patient feedback (median VAS 8 vs. 5, p=0.0113, and 9 vs. 5, p=0.0187). Fecal urgency and incontinence are burdensome symptoms in IBD, with a similar prevalence in UC and CD. A mismatch was found between the physician and patient perception. These symptoms should be addressed during outpatient visits.

Diagnosis and management of pouchitis

Background Fecal incontinence commonly occurs in patients with ulcerative colitis and ileal pouch–anal anastomosis. There is a paucity of manometric data in pouch patients. We aimed to better define manometric parameters in pouch patients with fecal incontinence. Methods We compared clinical and manometric variables in ulcerative colitis patients with pouch and fecal incontinence to ulcerative colitis patients with pouch without fecal incontinence and to non-ulcerative colitis patients with fecal incontinence. Manometric data for the 3 cohorts were compared to established normative data. An independent-samples t-test was performed for continuous variables, and chi-square test was used for categorical variables. Logistic regression was performed to identify predictors of incontinence in pouch patients (P < .05). Results Among 26 pouch patients with fecal incontinence (73% female), 26 pouch patients without fecal incontinence (35% female), and 84 patients with fecal incontinence without ulcerative colitis (68% female), there were no differences in anorectal pressures between patients with fecal incontinence. Lower pressures were observed in pouch patients with fecal incontinence compared to those without fecal incontinence. Resting pressure was similar between pouch patients with fecal incontinence and healthy controls (60.9 ± 36.1 mmHg vs. 66.9 ± 3.2 mmHg, P = .40). Female sex (P = .019) and defecatory disorders (P = .033) each independently predicted fecal incontinence in pouch patients. Conclusions Pouch patients with fecal incontinence have lower anorectal pressures compared to pouch patients without incontinence, though have similar pressures to non-ulcerative colitis patients with fecal incontinence. Pouch patients with fecal incontinence have similar resting pressures as healthy controls. Distinct manometric normative values for pouch patients are needed.

Inflammation and dysplasia may affect the ileal pouch after restorative proctocolectomy and ileal pouch-anal anastomosis. The aim of this prospective study was to evaluate the morphologic changes and the risk of dysplasia within the pouch after ileal pouch-anal anastomosis. Thirty-seven patients with ileal pouch-anal anastomosis underwent endoscopies and biopsies of the pouch: 21 patients were affected by ulcerative colitis and 16 by Crohn's colitis. The mucosal biopsy specimens were studied to investigate the degree of acute and chronic inflammation and the occurrence of dysplasia. A score system was calculated for each patient and correlated with the histologic diagnosis of ulcerative colitis or Crohn's colitis. After a median follow-up of 85 (range, 7-198) months, the inflammation histologic score evaluated was 3.8 (95 percent confidence interval, 2.4-5.1) and 3.5 (95 percent confidence interval, 2.6-4.3), respectively, in patients with Crohn's colitis and ulcerative colitis (mean and 95 percent confidence interval; P = 0.74, not significant), and no patient developed mucosal dysplasia. Fifteen patients (40.5 percent) developed clinical pouchitis that occurred in Crohn's colitis (9/16 patients or 56 percent) and in ulcerative colitis (6/21 patients or 28 percent; P not significant). The score was 4.1 (95 percent confidence interval, 3.2-5) in patients with pouchitis and 3.2 (95 percent confidence interval, 2.1-4.3) in patients without clinical pouchitis (P = 0.012) and was 4.1 (95 percent confidence interval, 2.6-5.5) and 4 (95 percent confidence interval, 2.9-5.3), respectively, in pouchitis patients with Crohn's colitis and ulcerative colitis. No difference in the inflammation histologic score was observed in ileal pouches after restorative proctocolectomy for ulcerative and Crohn's colitis. In our series, which includes those patients with longer follow-up (>5 years) or with chronic unremitting pouchitis, no case of dysplasia was found. The occurrence of pouchitis was higher in the case of ileal pouch-anal anastomosis for Crohn's disease than for ulcerative colitis, but no difference in the severity of the histologic score was noted.

Infliximab for Ulcerative Colitis: Finally Some Answers

Fecal continence following colectomy and ileoanal anastomosis through extramucosal rectal tube

The Soave procedure is an increasingly popular procedure for the definitive therapy of patients with ulcerative colitis. The authors present their experience with 100 patients in whom total proctocolectomy, rectal mucosal stripping, and ileoanal anastomosis (generally using an S-pouch) were carried out. The physiological and anatomical basis of continence is presented, and anastomosis at the top of the columns of Morgagni is recommended. Of the 100 patients in whom this procedure was performed, there was no mortality either in-hospital or later. Of the 12 patients in whom the anastomosis was done 1 cm above the top of the columns (and thus columnar epithelium was retained), six have recurrent anorectal disease, but all are continent both day and night. Three patients in whom the anastomosis was done at the dentate line have had difficulty with continence; two are now continent, but one, after being totally incontinent for 4 years, has required a permanent ileostomy. Of the 69 patients in whom the anastomosis was done at the top of the columns of Morgagni, five are incontinent at night only and two have seepage during both day and night. Thus, if the anastomosis is done at the level recommended, namely, at the top of the columns of Morgagni, retaining no columnar epithelium and anastomosing the ileal pouch to transitional epithelium (which the authors believe not to be subject to the disease of ulcerative colitis), daytime continence will be achieved in 97% and total day and night continence in 90%. The evidence presented suggests that a properly done pull-through procedure with ileoanal anastomosis is the procedure of choice for ulcerative colitis.

Despite advances in ulcerative colitis (UC) therapies, a relatively undefined proportion of patients experience faecal incontinence (FI) in the absence of active inflammation. For this group, there remains a significant unmet need with a limited evidence base. We aimed to estimate the prevalence and impact of FI in UC. In a prospective cross-sectional study, patients with UC completed a series of validated questionnaires, including Rome IV FI criteria, an inflammatory bowel disease (IBD)-specific FI questionnaire (ICIQ-IBD), Hospital Anxiety and Depression Scale and IBD-Control. UC remission was defined as faecal calprotectin (FCP) ≤250 μg/g, or IBD-control 8 score ≥13 and IBD-Control-VAS ≥ 85. Of 255 patients with UC, overall, 20.4% fulfilled Rome IV criteria for FI. Rome IV FI prevalence did not differ between active and quiescent UC regardless of whether disease activity was defined by IBD-Control scores ± FCP (p = 0.25), or objectively with FCP thresholds of 250 μg/g (p = 0.86) and 100 μg/g (p = 0.95). Most patients (75.2%) reported FI when in 'remission' and during 'relapse' (90.6%) according to ICIQ-IBD. Those who reported FI according to both ICIQ-IBD and Rome IV definitions had higher anxiety, depression and worse quality-of-life (QoL) scores (p < 0.05). In those with Rome IV FI, there was a strong correlation between FI symptom severity and impaired QoL (r = 0.809, p < 0.001). The prevalence of FI in UC is high, even in remission, and associated with significant psychological distress, symptom burden and impaired QoL. These findings highlight the urgent need for further research and development of evidence-based treatments for FI in UC.

Variables associated with loss of ileoanal pouches constructed in childhood

Fecal incontinence is experienced by some patients with an ileoanal reservoir pouch. The alpha1-adrenergic agonist phenylephrine raises resting anal sphincter pressure in healthy volunteers and may be of value in these patients. Twelve patients (7 female), median age 44 (range, 29-67) years were studied. All had fecal incontinence despite a noninflamed pouch of normal size and ultrasonographically structurally normal anal sphincter muscles. Patients were treated with topical 10 percent phenylephrine and placebo gels, allocated in random order in a double-blind, crossover study for two four-week periods. Before and during treatment, maximum resting anal sphincter pressure and anodermal blood flow were measured, a symptom questionnaire was completed, and incontinence score was determined using a validated scale. Six of 12 (50 percent) patients improved subjectively after phenylephrine compared with one on placebo (P = 0.07). Four patients had complete cessation of incontinence with active treatment. Phenylephrine significantly reduced the incontinence score (P = 0.015). It also resulted in a significant rise in mean maximum resting anal sphincter pressure when compared with placebo (P = 0.012). For all 12 patients, mean percent subjective improvement was higher after phenylephrine compared with placebo (P = 0.04). There were no side effects. Topical phenylephrine significantly improves fecal continence in patients with an ileoanal pouch. In some patients it totally eliminates nocturnal episodes. The mechanism of benefit is likely to be one of altered neural sphincter control. This is the first study of the use of a topical pharmacologic agent to treat fecal incontinence and may have a wider application.

Patients with ulcerative colitis are reported to be at increased risk of colorectal cancer and are also at high risk of postoperative complications. However, the incidence of postoperative complications in these patients and how the type of surgery performed affects prognosis are not well understood. Data collected by the Japanese Society for Cancer of the Colon and Rectum on ulcerative colitis patients with colorectal cancer between January 1983 and December 2020 were analyzed according to whether total colorectal resection was performed with ileoanal anastomosis (IAA), ileoanal canal anastomosis (IACA), or permanent stoma creation. The incidence of postoperative complications and the prognosis for each surgical technique were investigated. The incidence of overall complications was not significantly different among the IAA, IACA, and stoma groups (32.7%, 32.3%, and 37.7%, respectively; p=0.510). The incidence of infectious complications was significantly higher in the stoma group (21.2%) than in the IAA (12.9%) and IACA (14.6%) groups (p=0.048); however, the noninfectious complication rate was lower in the stoma group (13.7%) than in the IAA (21.1%) and IACA (16.2%) groups (p=0.088). Five-year relapse-free survival was higher in patients without complications than in those with complications in the IACA group (92.8% vs. 75.2%; p=0.041) and the stoma group (78.1% vs. 71.2%, p=0.333) but not in the IAA group (90.3% vs. 90.0%, p=0.888). The risks of infectious and noninfectious complications differed according to the type of surgical technique used. Postoperative complications worsened prognosis.

INTRODUCTION: Despite advances in Ulcerative Colitis (UC) therapies, many patients suffer refractory defecatory symptoms in the absence of active inflammation. For this group, treatment is challenging, with a paucity of research and limited therapeutic options. In this prospective, ongoing study, we aim to determine the prevalence of faecal incontinence (FI) in patients with quiescent UC. METHODS: In a cross-sectional study, consecutive patients with UC attending Inflammatory Bowel Disease (IBD) clinics completed a series of validated questionnaires; including an IBD-specific FI questionnaire (ICIQ-IBD questionnaire), Hospital Anxiety and Depression Scale (HADS), the Rome IV diagnostic questionnaire, and the IBD-control questionnaire. Participants were requested to return a Faecal Calprotectin (FCP) within 2 weeks of completing questionnaires. Quiescent UC was defined as IBD-control 8 score ≥13 and IBD-control-VAS ≥85, and/or FCP levels ≤250 (where available, FCP data were used in preference to IBD-control to classify UC activity). Data were compared between active and quiescent groups using chi-square and non-parametric tests. RESULTS: Overall, n = 97 UC patients (n = 50 males, mean age 48 (range 18-82) participated. ICIQ-IBD data revealed that most patients experience FI (84/97 (87%) during 'relapses'. Interestingly, 58/97 (60%) reported FI when in 'remission', and this group had higher median HADS depression (P = 0.0002), poorer QoL scores (P &lt; 0.0001), and trend towards higher HADS anxiety (P = 0.09) scores, compared to those without FI. Disease activity data (IBD-control and/or FCP) were available for all patients, and based on these 61/97 (63%) had quiescent UC. The prevalence of FI based on ICIQ-IBD did not differ between those with active (22/36, 61%) and quiescent UC (36/61, 59%), P = NS. In those with FI on ICIQ-IBD, median IBD-FI symptom scores, IBD-FI QoL scores and HADS (anxiety: P = 0.47, depression: P = 0.18) id not differ between disease activity groups. However, within the quiescent group, patients that met the more stringent Rome IV criteria for FI (n = 13) had higher median IBD-FI symptom scores (P = 0.007) and HADS-depression scores (P = 0.05), a trend to worse IBD-FI QoL (P = 0.07), but similar HADS-anxiety (P = 0.68). CONCLUSION: This is one of the first studies to identify that FI affects most patients with UC, regardless of disease activity, with a detrimental impact on patients' psychological wellbeing and QoL. FI be screened for in IBD clinics. There is an urgent need for further research in this area.

Introduction: Total retocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment and with familial adenomatous polyposis (FAP) with many rectal polyps.Pouchitis is one of the most common complications after this procedure in UC patients.Defects in autophagy have been reported in inflammatory bowel diseases.However, there are no studies on the ileal pouch (IP).Aim: To evaluate markers for autophagy in the IP mucosa of UC or FAP patients comparing them to controls with a normal distal ileum.Patients and Method: Sixteen patients with IP in "J" shape, asymptomatic and with endoscopically normal IP were evaluated.The control group consisted of eight patients with normal colonoscopy.The specimens were snap-frozen and the protein and transcriptional levels of autophagy markers were determined by immunoblot of total protein extract and by Real-Time PCR, respectively.The absence of pouchitis was assessed by clinical, histological and endoscopic parameters, according to the Pouchitis Disease Activity Index (PDAI).The Unicamp ethical committee approved the study and informed consent was signed by all participants.Non-parametric tests were applied for statistical analysis.The level of significance was p<0.05.Results: There was a significant decrease in the transcriptional levels of ATG5, MAP1LC3A and BAX in the FAP group.There was also a decrease in the protein level of Beclin-1 in the UC and FAP patients compared to the control group.Although the LC3-II levels by immunoblot were higher in the UC group, LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group.Corroborating these results, there was an increase of p62 by immunoblot in the UC group.Conclusion: These findings indicated a modulation of macroautophagy markers in the IP, from both UC and FAP, which may contribute to the inflammatory process of the mucosa in the pouch.

BACKGROUND: Total rectocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment and for familial adenomatous polyposis (FAP) with many rectal polyps. The main complication after this procedure is the pouch inflammation (pouchitis) that can affect up to 45 percent of patients who are submitted to IPAA for UC, and only five percent of the FAP patients who undergo the same procedure. Previous studies have shown increased pro-inflammatory cytokines in the ileal pouch (IP) mucosa of UC patients, even in the absence of clinical, endoscopic and histological inflammation. Autophagy is an evolutionarily conserved catabolic pathway that consists of selective degradation of cellular components and a homeostatic mechanism that protects cells exposed to stress situations (toxins, starvation), and defects in this pathway have been reported in inflammatory bowel diseases. However, there are no studies on the IP. Therefore, we studied markers for autophagy in the IP mucosa of UC and FAP patients comparing them to controls with a normal distal ileum. METHODS: Sixteen patients with IP in "J" shape, asymptomatic and with endoscopically normal mucosa were evaluated. The control group consisted of eight patients with normal colonoscopy. Gene expression was analyzed by qPCR and protein levels by immunoblotting and immunofluorescence. This study was approved by the Ethics Committee of the University of Campinas and was performed in accordance with the Declaration of Helsinki. All results were reported as means ± SEM. Data were analyzed by non-parametric Test, comparing all groups. The level of significance was set at P<0.05. RESULTS: There was a significant decrease in the transcriptional levels of ATG5, MAP1LC3A and BAX in the FAP group (P<0.05). There was also a decrease in the protein level of Beclin-1 in the UC and FAP compared to the control group (P<0.05). Although the LC3II levels by immunoblot were higher in the UC group, total LC3 and LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group (P<0.05). Corroborating to these results, there was an increase of p62 by immunoblot in the UC group, compared to controls (P<0.05). CONCLUSION(S): These results indicate impaired macroautophagy mechanism in the IP. In FAP, decreased autophagy may be related to impaired apoptosis, otherwise in UC, may be mainly due to increased Toll-Like Receptors (TLR) activation. These findings may explain the inflammation predisposition, mainly in the IP mucosa of UC patients. Acknowledgments: We thank FAPESP (São Paulo Research Foundation) for financial support. Negreiros LMV (co-author) received scholarship from FAPESP. We are grateful to Prof. Tristan Torriani for English grammar revision. We thank Francesca Ramos and José Diego Botezelli for technical assistance and the staff of the Life Sciences Core Facility (LaCTAD) from State University of Campinas (UNICAMP), for the Cell Biology analysis.

Colonic pouch can improve fecal continence after low anterior resection in the short-term, but its superiority would disappear in the long-term (2 years after surgery), since fecal continence improves gradually with time in the non-pouch group. Furthermore, the incidence of incomplete defecation increases gradually with time, and a lot of patients would have difficulty in defecation and require long-term use of suppositories and enemas. Pouch enforcement will result in prolonged operation time and increased treatment cost. Therefore, the value of colonic pouch in low rectal anastomosis is being questioned, and its application diminishes gradually. For patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) after total colectomy, ileal pouch anal anastomosis (IPAA) can reduce fecal frequency and improve patients' quality of life in both short-term and long-term, by increasing the volume of the neo-rectum and altering intestinal motility. For these reasons, IPAA is the first surgical choice for UC and FAP.