Creation of an institutional preoperative checklist to support clinical risk assessment in patients with ulcerative colitis (UC) considering ileoanal pouch surgery.

Background: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the most established restorative operative approach for patients with ulcerative colitis. It has associated morbidity and the potential for major repercussions on quality of life. As such, patient selection is crucial to its success. The main aim of this paper is to present an institutional preoperative checklist to support clinical risk assessment and patient selection in those considering IPAA. Methods: A literature review was performed to identify the risk factors associated with surgical complications, decreased functional outcomes/quality of life, and pouch failure after IPAA. Based on this, a preliminary checklist was devised and modified through an iterative process. This was then evaluated by a consensus group comprising the pouch multidisciplinary team (MDT) core members. Results: The final preoperative checklist includes assessment for risk factors such as gender, advanced age, obesity, comorbidities, sphincteric impairment, Crohn's disease and pelvic radiation therapy. In addition, essential steps in the decision-making process, such as pouch nurse counselling and discussion regarding surgical alternatives, are also included. The last step of the checklist is discussion at a dedicated pouch-MDT. Discussion: A preoperative checklist may support clinicians with the selection of patients that are suitable for pouch surgery. It also serves as a useful tool to inform the discussion of cases at the MDT meeting.

An early experience in robotic ileoanal pouch surgery with robotic intracorporeal single-stapled anastomosis (RiSSA) at a tertiary referral centre.

AIM: A robotic approach to ileal pouch-anal anastomosis (IPAA) surgery offers advantages over other approaches in terms of precision, improved access to the pelvis and less muscular fatigue for the surgeon. The integrity of the anastomosis is also fundamental to successful IPAA surgery. The robotic platform can permit intracorporeal suturing deep within the pelvis to create a single-stapled, double purse-string anastomosis, which may reduce the risk of anastomotic complications. This study describes the safety and early outcomes of robotic intracorporeal single-stapled anastomosis (RiSSA) amongst patients operated consecutively at a tertiary centre immediately before and following the pandemic. METHOD: A retrospective study of prospectively collected data analysing the outcome of patients undergoing robotic IPAA between 2019 and 2022 was conducted. All procedures were performed with the da Vinci Xi Surgical System (with a hand-assisted suprapubic incision to fashion the pouch). All pouch-anal anastomoses were performed using a double purse-string, single-stapled (RiSSA) method. Demographic, clinical and outcome data were collected. RESULTS: Twenty consecutive patients (nine with ulcerative colitis and 11 with familial adenomatous polyposis) were included with a median age of 25 years (range 16-52); 18 had American Society of Anesthesiologists classification II, and mean body mass index was 24 kg/m2 (range 18.1-34.3). Nine patients (eight ulcerative colitis and one familial adenomatous polyposis) had undergone prior subtotal colectomy and therefore underwent restorative proctectomy with IPAA. Eleven patients underwent restorative proctocolectomy. All procedures were completed robotically. The median length of stay was 9 days (5-49). There were no unplanned admissions to intensive care and no deaths. Three patients were readmitted following hospital discharge for (i) an ileus managed conservatively, (ii) small bowel obstruction managed conservatively and (iii) small bowel obstruction due to constriction at the stoma site necessitating surgery. There were two additional reoperations both for drain complications, one for drain removal and one for drain erosion. On mobilization of the pouch in the latter case, an anastomotic defect was observed. In total, 19/20 patients underwent RiSSA without postoperative anastomotic problems. DISCUSSION: RiSSA offers a safe and feasible alternative technique to other minimally invasive approaches with low rates of anastomosis-related complications.

Factors associated with stoma formation in ileocolic resection for Crohn's disease and the development of a predictive scoring system.

PURPOSE: The likelihood of a stoma following ileocolic resection (ICR) for Crohn's disease (CD) is an important consideration. This study aims to identify the factors associated with an increased likelihood of a stoma and develop a predictive scoring system (SS). METHODS: Patient data were collected from St. Marks Hospital, London, UK and Humanitas Clinical and Research Center, Milan, Italy, on all patients who underwent an ICR for CD from 2005 to 2017. A logistic regression analysis was used for multivariate analysis. The SS was developed from the logistic regression model. The performance of the SS was evaluated using receiver operating characteristics area under the curve (AUROC). RESULTS: A total of 628 surgeries were included in the analysis. Sixty-nine surgeries were excluded due to missing data. The remaining 559 were divided into two cohorts for the scoring system's development (n = 434) and validation (n = 125). The regression model was statistically significant (p < 0.0001). The statistically significant independent variables included sex, preoperative albumin and haemoglobin levels, surgical access and simultaneous colonic resection. The AUROC for the development and validation cohorts were 0.803 and 0.905, respectively (p < 0.0001). Youden's index suggested the cut-off score of - 95.9, with a sensitivity of 87.6% and a specificity of 62.9%. CONCLUSIONS: Male sex, low preoperative albumin, anaemia, laparoscopic conversion and simultaneous colonic resection were associated with an increased likelihood of requiring a stoma and were used to develop an SS. The calculator is available online at https://rebrand.ly/CrohnsStoma .

The use of, and outcomes for, inflammatory bowel disease services during the Covid-19 pandemic: a nationwide observational study.

BACKGROUND: Inflammatory bowel disease (IBD) services have been particularly affected by the Covid-19 pandemic. Delays in referral to secondary care and access to investigations and surgery have been exacerbated. AIMS: To investigate the use of and outcomes for emergency IBD care during the Covid-19 pandemic. METHODS: Nationwide observational study using administrative data for England (2015-2020) comparing cohorts admitted from 1 January 2015, to 31 January 2020 (pre-pandemic) and from 1 February 2020, to 31 January 2021 (pandemic). Autoregressive integrated moving average forecast models were run to estimate the counterfactual IBD admissions and procedures for February 2020 to January 2021. RESULTS: Large decreases in attendances to hospital for emergency treatment were observed for both acute ulcerative colitis (UC, 16.4%) and acute Crohn's disease (CD, 8.7%). The prevalence of concomitant Covid-19 during the same episode was low [391/16 494 (2.4%) and 349/15 613 (2.2%), respectively]. No significant difference in 30-day mortality was observed. A shorter median length of stay by 1 day for acute IBD admissions was observed (P < 0.0001). A higher rate of emergency readmission within 28 days for acute UC was observed (14.1% vs 13.4%, P = 0.012). All IBD procedures and investigations showed decreases in volume from February 2020 to January 2021 compared with counterfactual estimates. The largest absolute deficit was in endoscopy (17 544 fewer procedures, 35.2% reduction). CONCLUSION: There is likely a significant burden of untreated IBD in the community. Patients with IBD may experience clinical harm or protracted decreases in quality of life if care is not prioritised.

Lack of anti-TNF drugs levels in fistula tissue - a reason for nonresponse in Crohn's perianal fistulating disease?

INTRODUCTION: Anti-TNF therapy is recommended as treatment for patients with Crohn´s perianal fistulas. However, a significant proportion of patients have a sub-optimal response to anti-TNF therapy. Higher serum levels of anti-TNF agents have been associated with improved outcomes in perianal Crohn's disease. Currently, it is unknown whether anti-TNF agent levels can be detected in tissue from fistula tracts themselves and whether this is associated with response. AIMS AND METHODS: We undertook a pilot study to measure fistula tissue levels of anti-TNF medication (infliximab and adalimumab). We used a previously validated targeted proteomic technique, employing ultraperformance liquid chromatography-mass spectrometry, to detect/quantify anti-TNF drugs. Biopsies were obtained from fistula tracts of patients with Crohn's disease on maintenance treatment; with idiopathic (cryptoglandular) fistula tissues used as negative controls as well as positive controls (by spiking the latter tissues with anti-TNF drugs). RESULTS: Tissue was sampled from the fistula tracts of seven patients with Crohn's perianal disease (five patients were on adalimumab and two patients were on infliximab). The anti-TNF drugs, infliximab and adalimumab, were not detected in fistula samples from any of the Crohn's patients despite detection in 'spiked' positive control samples. CONCLUSION: Absence of detection of the anti-TNF drugs in fistula tissue raises the question on the role of tissue penetrance of anti-TNF drugs in response to therapy. Further work is required in a larger number of patients to validate the findings observed and investigate if any correlation exists between tissue and serum levels of anti-TNF and clinical outcome. SUMMARY: Predicting response in Crohn's fistula patients on biologic therapy is difficult with no reliable biomarkers. This pilot study uses targeted proteomics to investigate the potential role of tissue drug levels in acting as a biomarker of treatment response.

Emerging Data on Fistula Laser Closure (FiLaC) for the Treatment of Perianal Fistulas; Patient Selection and Outcomes.

Fistula laser closure (FiLaC) is a relatively new sphincter-sparing technique in fistula surgery that was initially reported in 2011. It involves the radial dissipation of laser energy in the fistula tract and, through a combination of coagulation and shrinkage of the tract, is proposed to result in progressive sealing of fistulas. Early studies have suggested minimal impact on continence and touted the advantage of minimal morbidity with potential of repeat procedures if the technique fails initially. Despite early promising results, ten years on, questions remain on the technique, patient selection and long-term outcomes. This narrative review assesses the evidence reported to-date of radially emitting laser fistula surgery in the treatment of perianal fistulas.

Quantitative Magnetic Resonance Imaging in Perianal Crohn's Disease at 1.5 and 3.0 T: A Feasibility Study.

Perianal Crohn's Disease (pCD) is a common manifestation of Crohn's Disease. Absence of reliable disease measures makes disease monitoring unreliable. Qualitative MRI has been increasingly used for diagnosing and monitoring pCD and has shown potential for assessing response to treatment. Quantitative MRI sequences, such as diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and magnetisation transfer (MT), along with T2 relaxometry, offer opportunities to improve diagnostic capability. Quantitative MRI sequences (DWI, DCE, MT and T2) were used in a cohort of 25 pCD patients before and 12 weeks after biological therapy at two different field strengths (1.5 and 3 T). Disease activity was measured with the Perianal Crohn's Disease Activity index (PDAI) and serum C-reactive protein (CRP). Diseased tissue areas on MRI were defined by a radiologist. A baseline model to predict outcome at 12 weeks was developed. No differences were seen in the quantitative MR measured in the diseased tissue regions from baseline to 12 weeks; however, PDAI and CRP decreased. Baseline PDAI, CRP, T2 relaxometry and surgical history were found to have a moderate ability to predict response after 12 weeks of biological treatment. Validation in larger cohorts with MRI and clinical measures are needed in order to further develop the model.

Current review of the management of fistulising perianal Crohn's disease.

Perianal manifestations of Crohn's disease constitute a distinct disease phenotype commonly affecting patients and conferring an increased risk of disability and disease burden. Much research has gone into management of fistulising manifestations, with biological therapy changing the landscape of treatment. In this article, we discuss the up-to-date surgical and medical management of perianal fistulas, highlighting current consensus management guidelines and the evidence behind them, as well as future directions in management.

Is fistulotomy with immediate sphincter reconstruction (FISR) a sphincter preserving procedure for high anal fistula? A systematic review and meta-analysis.

AIM: This systematic review aimed to assess the outcomes of fistulotomy or fistulectomy and immediate sphincter repair (FISR) in relation to healing, incontinence and sphincter dehiscence both overall and in patients with high anal fistulae. METHODS: Medline, Embase and The Cochrane library were searched for studies of patients undergoing FISR for anal fistula. Data regarding healing, continence and sphincter dehiscence were extracted overall and for high anal fistulae. The DerSimonian-Laird random-effects method was used for pooled analysis, heterogeneity between studies was assessed based on the significance of between-study heterogeneity, and on the size of the I2  value. Risk of bias was assessed using the Cochrane risk of bias tool and the Newcastle-Ottawa scale. RESULTS: We identified 21 studies evaluating 1700 patients. Pooled analysis of healing reached 93% (95% CI: 91%-95%, I2  = 51% p-value for heterogeneity = 0.004), with continence disturbance and worsening continence reaching 11% (95% CI: 6%-18%, I2  = 87% p < 0.001) and 8% (95% CI: 4%-13%, I2  = 74% p < 0.001), respectively. Subgroup analysis according to fistula height could only be conducted on limited data. Pooled healing in high anal fistulae was 89% (95% CI: 84%-94%, I2  = 76% p < 0.001), 16% suffered disturbance of continence (95% CI: 7%-27%, I2  = 89% p < 0.001), 8% worsening continence from baseline (95% CI: 2%-16%, I2  = 80% p < 0.001) and 2% suffered sphincter dehiscence (95% CI: 0%-10%, I2  = 89% p < 0.001). CONCLUSION: The evidence suggests FISR is a safe, effective procedure. However, data are limited by inconsistencies in reporting of continence and definition of fistula height, particularly high anal fistulae. Significant heterogeneity means that outcomes in high fistulae remain uncertain.

Perioperative safety of tofacitinib in surgical ulcerative colitis patients.

AIM: The literature regarding monoclonal antibodies and increased postoperative complications in inflammatory bowel disease remains controversial. There have been no studies investigating tofacitinib. The aim of this work was to determine preoperative exposure to the small-molecule inhibitor tofacitinib and postoperative outcomes. METHOD: We conducted a retrospective review of all adult patients exposed to tofacitinib within 4 weeks of total abdominal colectomy for medically refractory ulcerative colitis between 1 January 2018 and 1 September 2020 at four inflammatory bowel disease referral centres. Data collected included patient demographics and 90-day postoperative morbidity, readmission and reoperation rates. RESULTS: Fifty-three patients (32 men, 60%) with ulcerative colitis underwent a total abdominal colectomy (n = 50 laparoscopic, 94%) for medically refractory disease. Previous exposure to monoclonal antibodies included infliximab (n = 34), adalimumab (n = 35), certolizumab pegol (n = 5), vedolizumab (n = 33) and ustekinumab (n = 10). Twenty-seven (51%) patients were on concurrent prednisone at a median daily dose of 30 mg by mouth (range 5-60 mg). There were no postoperative deaths. Ninety-day postoperative complications included ileus (n = 7, 13.2%), superficial surgical site infection (n = 4, 7.5%), intra-abdominal abscess (n = 2, 3.8%) and venous thromboembolism (VTE) (n = 7, 13.2%). Locations of VTE included portomesenteric venous thrombus (n = 4), internal iliac vein (n = 2) and pulmonary embolism (n = 1). Nine (17%) patients were readmitted to hospital and five (9%) patients had a reoperation. CONCLUSION: Mirroring the recently issued US Food and Drug Administration black box warning of an increased risk of VTE in medically treated ulcerative colitis patients taking tofacitinib, preoperative tofacitinib exposure may present an increased risk of postoperative VTE events. Consideration should be given for prolonged VTE prophylaxis on hospital discharge.

Prognostic factors associated with unhealed perineal wounds post-proctectomy for perianal Crohn's disease: a two-centre study.

AIM: The aim of this work was to determine the factors associated with poor wound healing in patients with perianal Crohn's disease (pCD) who had undergone proctectomy in the era of biologic therapies. METHOD: Case record review was performed on 103 patients with pCD who underwent proctectomy at St Mark's Hospital, Harrow and the Western General Hospital, Edinburgh between 2005 and 2017. Healing rates at 6 and 12 months post-proctectomy were considered; univariate analysis was performed. RESULTS: Sixty out of 103 patients (58.3%) had failure of wound healing at 6 months and 41/103 (39.8%) at 12 months. In total, 63.1% (65/103) patients received biologic therapies prior to proctectomy; however, exposure to biologics was not a significant factor in predicting failure of wound healing at 12 months (infliximab p = 0.255; adalimumab p = 0.889; vedolizumab p = 0.153). Male gender was the only variable associated with poor wound healing at 12 months on univariate analysis (p = 0.017). A lower pre-operative C-reactive protein was associated with early wound healing at 6 months compared with at 12 months (p = 0.041) on univariate analysis. Other parameters not associated with rates of wound healing included smoking status, corticosteroid exposure, thiopurine exposure, number of previous biologics, perianal sepsis on MRI within the last 12 months, duration of CD prior to proctectomy and pre-operative albumin. CONCLUSION: More than a third of patients had unhealed wounds 12 months after proctectomy. We report that unhealed wounds are more common in male patients. Importantly, our results also suggest that exposure to biologics does not affect rates of wound healing.

A scoring system to predict a prolonged length of stay after surgery for Crohn's disease.

AIM: Many factors influence the postoperative length of stay (LOS) in Crohn's disease (CD). This study aims to identify the factors associated with a prolonged LOS after ileocolic resection (ICR) for CD and to develop a scoring system to predict the postoperative LOS in CD. METHOD: Patient data were collected from St Marks Hospital, London, UK, and the Humanitas Clinical and Research Center Milan, Italy, for all patients who underwent an ICR for CD from 2005 to 2017. Logistic regression was used for multivariate analysis. The scoring system was developed from the logistic regression model. The performance of the scoring system was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: A total of 628 surgeries were included in the analysis. Eighty eight surgeries were excluded due to missing data. The remaining 543 were divided into two cohorts for the development (n = 418) and validation (n = 125) of the scoring system. The regression model was statistically significant (p < 0.0001). The statistically significant independent variables included the time since diagnosis, American Society of Anesthesiologists (ASA) grade, perioperative use of steroids, surgical access, strictureplasty and platelet count. The AUROCs for the development and validation cohorts were 0.732 and 0.7, respectively (p < 0.0001). The cut-off score suggested by Youden's index was 50, with a sensitivity of 65.6% and a specificity of 73.3%. CONCLUSION: The time since diagnosis, ASA grade, steroid use, surgical access, strictureplasty and platelet count were associated with a prolonged LOS and were used to develop a scoring system. The calculator is available online at https://rebrand.ly/Crohnscal.

Differences in amino acid and lipid metabolism distinguish Crohn's from idiopathic/cryptoglandular perianal fistulas by tissue metabonomic profiling and may offer clues to underlying pathogenesis.

INTRODUCTION: Few studies have investigated perianal fistula etiopathogenesis, and although the cryptoglandular theory is widely accepted in idiopathic cases, in Crohn's disease, it is thought to involve the interplay between microbiological, immunological and genetic factors. A pilot study was conducted to assess for metabolic variations in Crohn's perianal fistula tissue that might differ from that of idiopathic (cryptoglandular) perianal fistula tissue as a comparator. The goal was to identify any potential biomarkers of disease, which may improve the understanding of pathogenesis. AIMS AND METHODS: Fistula tract biopsies were obtained from 30 patients with idiopathic perianal fistula and 20 patients with Crohn's anal fistula. Two different assays were used in an ultra-high-performance liquid chromatography system coupled with a mass spectrometric detector to achieve broad metabolome coverage. Univariate and multivariate statistical data analyses were used to identify differentiating metabolic features corresponding to the perianal fistula phenotype (i.e. Crohn's disease vs. idiopathic). RESULTS: Significant orthogonal partial least squares discriminant analysis predictive models (validated with cross-validated-analysis of variance P value <0.05) differentiated metabolites from tissue samples from Crohn's vs. idiopathic anal fistula patients using both metabolic profiling platforms. A total of 41 metabolites were identified, suggesting alterations in pathways, including amino acid, carnitine and lipid metabolism. CONCLUSION: Metabonomics may reveal biomarkers of Crohn's perianal fistula. Further work in larger numbers is required to validate the findings of these studies as well as cross-correlation with microbiome work to better understand the impact of host-gut/environment interactions in the pathophysiology of Crohn's and idiopathic perianal fistulas and identify novel therapeutic targets.

Development and initial psychometric validation of a patient-reported outcome measure for Crohn's perianal fistula: the Crohn's Anal Fistula Quality of Life (CAF-QoL) scale.

INTRODUCTION: Crohn's perianal fistulas are challenging for patients and clinicians. Many do not respond to available treatments and despite recommendations by a global consensus, there are currently no specific patient-derived quality of life tools to measure response to treatment. We present a new validated patient-reported outcome measure (PROM) for this complicated disease phenotype. METHODS: A draft questionnaire was generated using unstructured qualitative patient interviews on the experience of living with Crohn's perianal fistula, a nationwide multidisciplinary consensus exercise, a systematic review of outcomes assessing medical/surgical/combined treatment and a patient and public involvement day. Psychometric properties were assessed including construct validity (by comparison with the Hospital Anxiety and Depression Scale (HADS) and the UK Inflammatory Bowel Disease Questionnaire (UK-IBDQ)), and reliability and responsiveness was assessed by test-retest analysis. RESULTS: Data from 211 patients contributed to development of a final 28-item questionnaire. The Crohn's Anal Fistula Quality of Life (CAF-QoL) demonstrated good internal consistency (Cronbach's alpha 0.88), excellent stability (intraclass correlation 0.98) and good responsiveness and construct validity, with positive correlation with the UK-IBDQ and HADS. CONCLUSION: The CAF-QoL scale is ready for use as a PROM in research and clinical practice. It complements objective clinical evaluation of fistula by capturing impact on the patient.

Burden of disease and adaptation to life in patients with Crohn's perianal fistula: a qualitative exploration.

BACKGROUND: Perianal fistulas are a challenging manifestation of Crohn's disease. Best medical and surgical therapy results in only about a third of patients remaining in remission at one year on maintenance treatment and sustained healing is often elusive. There is little published data on patient perspective of living with the condition or coping strategies in the face of non-curative/non-definitive treatment. We aimed to understand the experience of living with perianal fistula(s) and their impact on quality of life and routine functioning. METHODS: This exploratory qualitative study used purposive sampling to recruit participants with current / previous diagnosis of Crohn's anal fistulas, from national IBD / bowel disease charities. The "standards for reporting qualitative research" (SRQR) recommendations were followed. Unstructured individual face-to-face interviews were audio recorded, transcribed and analysed thematically. Early themes were reviewed by the study team including patient advocates, clinicians and qualitative researchers. RESULTS: Twelve interviews were conducted, achieving apparent data saturation. Three broad themes were uncovered: Burden of symptoms; Burden of treatment; and Impact on emotional, physical and social well-being. Each included several sub-themes, with considerable interplay between these. The impact of perianal fistula(s) on patients with CD is intense and wide reaching, negatively affecting intimate, close and social relationships. Fistulas cause losses in life and work-related opportunities, and treatments can be difficult to tolerate. CONCLUSION: Crohn's perianal fistulas exert a heavy negative physical and emotional impact on patients. These findings will inform development of a patient reported outcome measure to assess treatment effectiveness and quality of life for patients living with this challenging condition.

Enhanced Recovery Deviation and Failure After Pancreaticoduodenectomy: Causative Factors and Impact.

BACKGROUND: Enhanced recovery after surgery (ERAS) following pancreaticoduodenectomy (PD) is popular and safe. This study aimed to describe the incidence, causative factors, and clinical impact of deviation from and failure of an ERAS protocol. MATERIALS AND METHODS: A prospective cohort analysis of elective PD patients managed according to an ERAS protocol between October 2015 and June 2018 was performed. Univariate and multivariate analyses identified variables associated with protocol deviation and failure. The relationship between protocol deviation and failure was also explored. RESULTS: A total of 97 patients were identified comprising of 46 females and 51 males. The median age was 68 y (range 17-85). Twenty-one patients (21.6%) suffered serious complications, whereas two (2.1%) died perioperatively. The median length of stay (LoS) was 14 d (6-36). In total, 73 (75.3%) patients deviated, whereas 39 (40.2%) failed the protocol. On univariate analysis, protocol deviation was associated with male gender, surgery time ≥270 min, and prolonged LoS. On multivariate analysis only prolonged LoS remained significant. Only serious complications were associated with protocol failure on multivariate analysis. Protocol deviation was not associated with significant complications nor ERAS protocol failure. CONCLUSIONS: ERAS protocol deviation does not alter the course of those destined to protocol failure. Greater understanding into the causative factors of either protocol deviation or failure may be the only way to personalize care and realize the maximal benefit of ERAS in this specific group of patients.

Medical-surgical Combined Approach in Perianal Fistulizing Crohn's Disease (CD): Doing it Together.

Fistulising perianal Crohn's disease (pCD) is an aggressive phenotype, and patients not only suffer from perianal manifestations but also a worsening course for their luminal disease. This article describes the 6 key steps clinicians need to consider when managing patients with pCD which include; (i) ensuring a prompt diagnosis, (ii) multi-disciplinary management, (iii) psychological support, (iv) using multimodal medical and surgical treatment strategies, (v) continually monitoring and optimising therapy and (vi) ensuring that patients have a way of accessing care if required. Patients with fistulising pCD often have an unpredictable disease course and complete remission can be elusive. As such, a considered and nuanced approach is essential keeping the wider multi-disciplinary team and the patient involved in all decision making.