Introduction

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum. Surgical intervention is often required in cases of medically refractory disease, dysplasia, or colorectal cancer. Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical procedure for these patients. The transanal approach to IPAA has emerged as a minimally invasive alternative to conventional surgery. However, the safety, efficacy, and long-term outcomes of transanal IPAA remain unclear.

Aims & Methods

This systematic review and meta-analysis aimed to assess the safety, efficacy, and long-term outcomes of transanal ileal pouch-anal anastomosis in adult patients with ulcerative colitis and compare it with the conventional approach. A comprehensive literature search was conducted using PubMed, EMBASE, and the Cochrane Library from inception to October 2022. Comparative studies were included for adult patients with UC who underwent transanal IPAA versus conventional IPAA. Outcomes analyzed included anastomotic leak, major and minor complications, using relative risk (RR). Meta-analysis was performed using R 4.0.3 and its packages metafor and meta.

Results

Our search identified 4 comparative studies, including a total of 858 patients (338 transanal and 520 conventional IPAA). The meta-analysis showed no significant differences in anastomotic leak (pooled RR 1.72, 95% confidence interval [CI] 0.77-3.79, I2=3%), minor complications (pooled RR 0.97, 95% CI 0.68-1.37, I2=75%), or major complications (pooled RR 0.81, 95% CI 0.52-1.27, I2=56%) between the two groups.

Conclusion

This systematic review and meta-analysis suggest that transanal ileal pouch-anal anastomosis is a safe and effective alternative to conventional IPAA for patients with ulcerative colitis, with similar rates of complications. More high-quality RCTs are needed to confirm these findings and to further evaluate the long-term outcomes of this procedure.

Introduction

Acute severe ulcerative colitis (UC) refractory to intravenous corticosteroids is a serious form of severe UC and may result in colectomy. In this network meta-analysis, we aim to assess the efficacy of biologics and other immunotherapies as rescue treatments for patients with acute severe UC unresponsive to standard therapy, with a focus on their ability to prevent colectomy.

Aims & Methods

On March 1, 2025, a data search was conducted using PubMed, Scopus, and the Cochrane Library. We included controlled clinical trials that evaluated the use of biologics and other immunotherapies in patients with severe ulcerative colitis refractory to intravenous steroids. The primary outcomes were clinical response at week 1 and the colectomy rate at week 12. We used the odds ratio with the 95% confidence interval to estimate the effect size, and a random-effects model was applied. Data analysis was performed in RStudio using the netmeta package.

Results

Out of 2,186 articles screened, only 5 met our eligibility criteria, with a total of 734 patients. Four treatment strategies were included in the network meta-analysis: infliximab intensified dosing (10 mg/kg at week 0 and week 1 if responsive, or earlier if not), standard infliximab dosing (5 mg/kg at weeks 0, 2, and 6), accelerated infliximab dosing (5 mg/kg at weeks 0, 1, and 3), and cyclosporine. For preventing colectomy, infliximab 10 mg/kg (OR 0.11; 95% CI: 0.02–0.79), infliximab 5 mg/kg standard dose (OR 0.21; 95% CI: 0.06–0.73), and cyclosporine (OR 0.20; 95% CI: 0.05–0.79) were all associated with a statistically significant reduction in colectomy risk compared to placebo at week 12. Accelerated infliximab dosing did not show a statistically significant difference.
For clinical response at week 1, infliximab 10 mg/kg, infliximab 5 mg/kg (standard dose), and cyclosporine had similar response rates, with no significant differences observed.

Conclusion

Infliximab (both standard and intensified doses) and cyclosporine, as rescue therapies, had lower rates of colectomy at week 12 in patients with acute severe ulcerative colitis refractory to corticosteroids. Clinical response at week 1 was comparable across these therapies.

References

1. Laharie D, Bourreille A, Branche J, et al. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet. 2012;380(9857):1909-1915. doi:10.1016/S0140-6736(12)61084-8
2. Choy MC, Li Wai Suen CFD, Con D, et al. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol. 2024;9(11):981-996. doi:10.1016/S2468-1253(24)00200-0
3. Williams JG, Alam MF, Alrubaiy L, et al. Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomised trial. Lancet Gastroenterol Hepatol. 2016;1(1):15-24. doi:10.1016/S2468-1253(16)30003-6
4. Järnerot G, Hertervig E, Friis-Liby I, et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005;128(7):1805-1811. doi:10.1053/j.gastro.2005.03.003

Introduction

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum. In some cases, surgical intervention such as colectomy may be necessary. Following colectomy, the creation of an ileal pouch-anal anastomosis (IPAA) provides an alternative to permanent ostomy. However, pouchitis is a well-recognized complication of IPAA, causing inflammation and symptoms similar to those of ulcerative colitis. Despite its frequency, there remains a paucity of reliable data on the incidence and long-term disease course of pouchitis, especially from population-based cohorts

Aims & Methods

We aim to investigate the incidence and disease course pouchitis in UC patients who’ve underwent an IPAA between 11th November 1993 and 26th April 2021 at Copenhagen University Hospital Hvidovre, Gastrounit. Due to centralization of IPAA, the department covers approx. 46 % of the Danish population. All patients were manually screened through their electronic medical record. All events of pouchitis and the duration was registered.

Results

In total, 239 UC patients had ileal pouch-anal anastomosis (IPAA) performed between 11th November 1993 and 26th April 2021. However, 6 patients did not have their relieving ileostomy put back and their constructed pouch taken into usage and were therefore excluded from the analysis. The median follow-up time was 8.36 years (IQR: 4.33 – 11.16) for the 233 patients. During the observation period, a total of 122 (52.36 %) UC patients, experienced 421 events of pouchitis ranging from 1-25 episodes per patient. Of the 421 events, 329 (78.15 %) were defined as acute (≤ 28 days) and 92 (21.85 %) as chronic pouchitis (>28 days). Looking at the frequency of the flares, 311 (73.87 %) of these could be categorised as episodic pouchitis (<3 episodes per year) and 110 (26.13 %) as relapsing pouchitis (≥3 episodes per year). The episodes of relapsing pouchitis were distributed among 31 patients (26.19 %). The mean time from IPAA construction to the first episode of pouchtitis was 27.24 (SD: 36.20) months. The mean length of each episode of pouchitis until remission was 25.69 (SD: 59.70) days. While the time between each pouchitis episode was a mean of 373.53 (SD: 620.14) days.
The survival rate, referring to time to pouchitis, at 6 months, 1,2,5, and 10 years are shown in table 1

Conclusion

This study highlights the high incidence of pouchitis in UC patients who have undergone an IPAA. Approximately half of the patients experienced at least one episode of pouchitis. The time from IPAA construction to the first episode of pouchitis was around 2 years, with a mean duration of each episode being around 3 weeks. The frequency of relapsing pouchitis was seen in a quarter of the patients. These findings emphasize the importance of identifying preventive and therapeutic strategies for pouchitis in this patient population to improve long-term outcomes.

Disclosure

This study was supported by Takeda Pharma A/S

Introduction

Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) performed in two or three stages has become the standard surgical treatment in patients with ulcerative colitis (UC) in which the medical management fails. It is a technically complex operation associated with significant morbidity that can be performed with a laparoscopic or robotic approach. Robotic colorectal surgery is gaining popularity because it overcomes many of the mechanical and optical disadvantages of laparoscopy, although limited data are available regarding its safety, efficacy, and costs.

Aims & Methods

This study compares the postoperative short-terms surgical outcomes of the two surgical approaches. Robotic and laparoscopic restorative proctocolectomy procedures with IPAA consecutively performed between June 2015 and May 2023 were retrospectively collected. Inclusion criteria was UC not responders to medical therapy. Exclusion criteria was conversion to open surgery.
Primary analyzed outcome were complications rate in the first month (30 days) according to Clavien Dindo Score and length of hospital stay (days). Statistical analysis was performed with a dedicated software (SPSS).

Results

A total of 54 patients with UC refractory to medical therapy were included, with 31 laparoscopic procedure and 23 robotic procedures.
Demographic data were comparable between two groups in terms of age (48.7 vs 45.7 years; p= 0.62), BMI (22,0 vs 23,7 Kg/m2; p= 1.311) and ASA score (p=0,72).Short-term complications defined as Clavien Dindo scores 2-3, (compared with score 1) were 13% in the robotic group and 31% in the laparoscopic group (RR= 0.27, 95% conf. interval. 0.11-1.06).
In particular, no high-grade Clavien-Dindo complications occurred in the robotic group while 3 events (grade 3) occurred in the laparoscopic group. No surgical intervention was needed in both groups.
Length of hospital stay was a mean of 7.3 days in lap-group and 6.3 days in rob-group with no statistical significativity (p=0,09).

Conclusion

This preliminary study concludes that robot-assisted surgery allows a reduction of short-term complications compared to laparoscopic approach. Moreover, robotic surgery allows a reduction of length of hospital stay although not statistically significant. Limits of the study were the retrospective design and the low numerosity of the sample, although comparable with the experiences already published.

Introduction

Steroid-refractory acute severe ulcerative colitis (SR-ASUC) is a life-threatening emergency that results in colectomy in approximately 40% of cases.¹ Several medical therapies have emerged as rescue treatments aimed at reducing the need for colectomy.^2-3However, direct comparative studies evaluating the relative efficacy of these therapies remain limited.⁴ This network meta-analysis aims to systematically review and compare the efficacy and safety of available rescue therapies for SR-ASUC, including biologics and small molecule treatments.

Aims & Methods

A systematic literature search was conducted using the MEDLINE, SCOPUS, and CENTRAL databases. Colectomy-free survival probabilities were extracted from Kaplan-Meier curves. A one-stage network meta-analysis using parametric Weibull regression was performed to estimate and compare the relative treatment effects of biologics and small molecule therapies. The primary outcome was colectomy-free survival at 4 and 12 weeks. This study was registered in PROSPERO (CRD420251030353).

Results

A total of 18 studies (5 randomized controlled trials and 13 cohort studies), including 1,706 patients with SR-ASUC, were included. Compared to placebo, standard-dose infliximab [hazard ratio (HR) 0.34, 95% CI: 0.20–0.60, p < 0.001], accelerated-dose infliximab [HR 0.38, 95% CI: 0.21–0.68, p = 0.001], and tofacitinib [HR 0.36, 95% CI: 0.19–0.69, p = 0.002] significantly improved colectomy-free survival. Cyclosporine also showed a trend toward reduced colectomy risk, though it did not reach statistical significance [HR 0.57, 95% CI: 0.31–1.01, p = 0.056]. There were no significant differences in overall adverse events or infection rates among the therapies. Based on SUCRA rankings, colectomy-free survival at both 4 and 12 weeks was highest for tofacitinib (SUCRA: 0.90 and 0.87), followed by accelerated-dose infliximab (0.95 and 0.85), standard-dose infliximab (0.87 and 0.83), and cyclosporine (0.81 and 0.74). (Figure 1 Colectomy free survival probability ; Kaplan-Meier curves)
Table 1. Pairwise table showing comparative efficacy in reducing colectomy risk of biologics and small molecule for SR-ASUC

Conclusion

Tofacitinib and accelerated-dose infliximab appear to be the most effective rescue therapies for improving colectomy-free survival in patients with SR-ASUC.

References

1. Dong C, Metzger M, Holsbø E, et al. Aliment Pharmacol Ther. 2020 Jan;51(1):8-33.
2. Honap S, Jairath V, Sands BE, et al. Gut. 2024 Sep 9;73(10):1763-1773.
3. Calméjane L, Laharie D, Kirchgesner J, et al. United European Gastroenterol J. 2023 Oct;11(8):722-732.
4. Choy MC, Seah D, Faleck DM, et al. Inflamm Bowel Dis. 2019 Jun 18;25(7):1169-1186.

Introduction

There is a small but recognised risk of malignant transformation in ileal-pouch anal anastomosis (IPAA). The risk of pouch dysplasia and pouch cancer increases over time and the reported incidence is approximately 5% after 20 years.[1] For this reason, current guidelines suggest patients to undergo pouchoscopy surveillance. However, the frequency of surveillance is still widely debated.

Aims & Methods

The primary aim of this study is to investigate the incidence of high-grade dysplasia and cancers in patients with IPAA for UC in the long-term.
All patients within 8 hospitals, under a single health board, with IPAA for UC, created between 1980 and 2019 and undergoing pouchoscopy surveillance, were reviewed.
Data collected included patient demographics, such as sex, age at diagnosis of UC, age at pouch creation and those with any identifiable risk factors. It also included specific pouch data such as date of IPAA creation, mean number of days between UC diagnosis, IPAA creation and first pouchoscopy. Surveillance data included the indication for pouchoscopy as well as pouchoscopy findings.

Results

187 patients (107 male) were under surveillance. The median age of IPAA creation was 38 years old (range 11-63).
The median duration of patient follow up was 192.2 months (range 13.1-464.9 months), with 106 patients (56.7%) having >15 years of follow up. The median interval between pouchoscopies was 27.3 months (IQR: 21.4-39.2).
A total of 574 pouchoscopies were performed on the 187 patients, by a total of 115 endoscopists. The median number of pouchoscopies per endoscopist was 2. 1 endoscopist performed 147 of the 574 pouchoscopies (25.6%). Patients averaged 3.07 scopes per person. The indication for scopes were surveillance (305, 53.1%), symptoms (248, 43.2%) and positive bowel screening (19, 3.3%).
There were no high-grade dysplasia. One cancer (0.005%) was found in the rectal cuff at 330.6 months. 18 patients (9.6%) were considered “high-risk” according to the BSG guidelines; 9 with Primary Sclerosing Cholangitis (PSC), 2 with PSC/autoimmune hepatitis overlap syndrome, 5 with a long rectal cuff, 1 with a previous colorectal malignancy and 1 with PSC and a previous colorectal malignancy. None of them developed high-grade dysplasia nor cancer. These high-risk patients had a median follow up of 158.4 months (range 64.4-405.7 month).
Other findings included pouchitis (151, 26.3%), chronic pouchitis (84, 14.6%), non-specific inflammation (144, 25.1%) and stenosis (82, 14.3%). 10 patients had their IPAA excised.

Conclusion

The incidence of high-grade dysplasia or cancer in IPAA is extremely low and may not warrant the intense surveillance.
Further protocols are needed to ensure that patients with IPAA are not undergoing national bowel screening and are having unnecessary pouchoscopies for false positive results.

References

Pouw RE, Bisschops R, Gecse KB, de Hertogh G, Iacucci M, Rutter M, Barret M, Biermann K, Czakó L, Hucl T, Jansen M, Savarino E, Spaander MCW, Schmidt PT, Dinis-Ribeiro M, Vieth M, van Hooft JE. Endoscopic tissue sampling - Part 2: Lower gastrointestinal tract. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2021 Dec;53(12):1261-1273.