Introduction

Anastomotic ulcers are a common finding in Crohn’s disease (CD) patients undergoing ileocolonic resection (ICR). The clinical significance of these lesions remains debated, as some studies have suggested that they may be associated with a higher risk of postoperative recurrence (POR), while others have not found a significant association. Also, the pathogenesis of anastomotic ulcers is poorly understood.

Aims & Methods

We aimed to assess the risk of CD postoperative recurrence (POR) after ICR in patients with and without isolated anastomotic ulcers among those with otherwise healthy neo-terminal ileum (TI). Also, we aimed to assess the mucosa-associated microbiome composition on either side of the anastomosis.
CD patients undergoing ICR were prospectively recruited as part of the multicenter NIDDK Inflammatory Bowel Disease Genetics Consortium CD Ileal Post-Op Study. In this analysis, we included subjects recruited at Mount Sinai Hospital Toronto without any ulcerations in the neo-TI (simple endoscopic score for CD ≤2) at the first postoperative colonoscopy (FC). Patients with ulcerations limited to the anastomotic line were classified as modified Rutgeerts score (mRS) i2a, whereas those without any ulceration as i0. Biopsies were taken on both sides of the anastomosis at FC, and the mucosa-associated microbiome was assessed by sequencing the 16S rRNA gene. POR was retrospectively defined as a composite of clinical recurrence (symptomatic worsening with objective evidence of inflammation within 6 months of symptom onset), change in CD-related therapy, endoscopic balloon dilation, or intestinal resection. We used Cox proportional hazards models to assess the risk of POR since FC. Alpha and beta diversity were analyzed at the ileal and colonic sides of the anastomosis using the phyloseq package. Differential abundance analysis between groups was performed employing MaAsLin2. False discovery rate of q<0.2 was considered significant.

Results

Sixty patients were included. Median age was 32.5 years [IQR 26-40.5], 53.3% were female, median disease duration was 9 years [IQR 2-15.5], median time from surgery to FC was 198 days [IQR 172-262], median follow-up was 4.2 years [IRQ 2.6-6.6]. 34 (56.7%) were mRS i0 group, and 26 (43.3%) were mRS i2a group. There were no significant differences in Montreal classification, smoking status, previous resection, biologic or non-biologic medication use at FC.
In multivariate analysis, mRS i2a was associated with a higher risk of POR after adjusting for previous surgical resection, penetrating behavior, and biologic use at FC (adjusted HR 5.15, 95% CI 2.24-11.87, p= 0.00012).
There were no differences in alpha or beta diversity on either side of the anastomosis. In the neo-TI, after adjusting for age, sex, and biologic use at FC, the genera Lachnospiraceae NK4A136 (p=0.004, q=0.17) and Klebsiella (p=0.005, q=0.17) were more abundant in i0 and i2a, respectively. On the colonic side, the genera Fusobacterium (p=0.0012, q=0.038) and Lachnospira (p=0.01, q=0.15) were more abundant in i2a.

Conclusion

In CD patients with otherwise healthy neo-TI, we found a significantly higher risk of POR in those with anastomotic ulcerations. We found a differential microbiome composition on both sides of the anastomosis, suggesting putative taxa to be related to these lesions.

Introduction

Capsule endoscopy is the first-line examination for digestive bleeding with likely origin in the small bowel, in hemodynamically stable patients. In the 2022 update, ESGE guidelines recommend that, in the context of overt bleeding, capsule enteroscopy should be performed as soon as possible, ideally within the first 48 hours. In the previous guidelines, published in 2015, the recommended window was 14 days.

Aims & Methods

This study aimed to evaluate the improvement in yield offered by the new recommendations regarding the timing of urgent capsule enteroscopy. Patients with suspected overt middle gastrointestinal bleeding between January 2005 and November 2022 were retrospectively analyzed. Diagnostic and therapeutic yield, rebleeding rate, and mortality were compared when capsule enteroscopy was performed within the first 48 hours, within the first 14 days, or between the 3rd and 14th day after admission.

Results

A total of 138 patients were included (58.7% men, median age 66 years), 87 of whom (63.0%) underwent capsule enteroscopy within the first 48 hours after hospital admission. The median follow-up was 55 months (5-180). The diagnostic yield (presence of blood or lesions with bleeding potential) was slightly higher when capsule enteroscopy was performed within the first 48 hours (81.6% versus 76.5%, p=0.349). On the other hand, capsule enteroscopy within the first 48 hours was significantly associated with higher therapeutic yield (endoscopic, radiologic, or surgical treatment) - 54.0% versus 39.2%, p=0.02. The rebleeding rate was significantly lower in patients undergoing enteroscopy within 48 hours after admission (19.5% versus 29.4%, p=0.04). On the other hand, overall mortality at 36 months did not differ between strategies (21.8% and 25.5%, p=0.401).

Conclusion

Performing capsule endoscopy within the first 48 hours, as recommended by recently published guidelines, is associated with favourable short- and long-term clinical outcomes.

Introduction

Sporadic neoplasias (SNs) and ulcerative colitis-associated neoplasias (UCANs) can occur in patients with UC. Differences in the characteristics and prognoses between UCANs in patients with UC and SNs in patients without UC have been assessed in numerous previous studies. However, only a few studies have focused on the characteristics and prognoses of SNs in patients with UC. It is important to distinguish between UCANs and SNs, because they have different prognoses and therefore need different treatment strategies.

Aims & Methods

This study aimed to evaluate the clinical features and prognoses of SNs detected in patients with UC, both within and outside the affected area. A total of 141 SNs in 59 patients with UC, which were detected by surveillance colonoscopy (SCS) at Hiroshima University Hospital between January 1999 and December 2021, were included. In our hospital, we perform SCS for UC patients with left-sided or total colitis and with a disease duration of more than 7 years, if possible, in the remission stage. SNs were diagnosed based on their location, endoscopic features, and histopathological findings. The final diagnosis was made by histopathological evaluation of the excised specimens and confirmed by more than one gastrointestinal pathologist. The histopathological diagnosis of SN was made according to the pathological features described in the recent European Crohn's and Colitis Organization and the European Society of Pathology statement on histopathology. Immunohistochemical evaluation of Ki67 and p53 was performed in all cases. SNs, especially sporadic adenomas, have regular neoplastic glands with low amounts of stroma, and rarely have a mixture of benign/dysplastic crypts. Although UCANs sometimes have a surrounding flat area with overexpression of p53, SNs have no such area and have a distinct border between the neoplastic glands and non-neoplastic mucosa. SNs have Ki67 expression mainly in the superficial zone and have low levels of p53 expression.

Results

The mean age at first SN detection was 58.8 years, and the mean duration of UC was 9.9 years. Male patients represented 64.4% of the enrolled patients. The most common type of UC was the total colitis type (47.5%). With regard to their clinical course, approximately half of the patients (49.2%) presented with the relapse-remitting type. Among the 141 SNs, 129 lesions (91.5%) were diagnosed as adenomas, five (3.5%) as Tis carcinomas, two (1.5%) as T1a carcinomas (superficially submucosal invasive carcinoma: <1,000 µm), and five (3.5%) as T1b carcinomas (deeply submucosal invasive carcinoma: ≥1,000 µm). There were 86 (61.0 %) SNs in the right colon, 44 (31.2%) in the left colon, and 11 (7.8%) in the rectum. When classified as outside or within the affected area of UC, 100 (70.9%) SNs occurred outside and 41 (29.1%) within. Most SNs (135 lesions, 95.7%) underwent endoscopic resection, and only six lesions (4.3%) underwent surgical resection. Among the 59 patients included in this study, synchronous SNs occurred in 14 (23.7%), and metachronous multiple SNs occurred in 24 (40.7%) patients. The 5-year cumulative incidence of metachronous multiple SNs was higher in patients with synchronous multiple SNs (54.2%) than in those without (46.4%). The histology, size, and background mucosa of the initial SNs were not associated with the incidence of metachronous SNs in our study.

Conclusion

UC patients with synchronous multiple SNs were at higher risk of developing metachronous multiple SNs and may require close follow-up compared to patients without synchronous SNs.

Introduction

Double-headed capsules enable the non-invasive one-step endoscopic evaluation of both the small bowel and colon (pan-intestinal capsule endoscopy, PCE).

Aims & Methods

We aim to evaluate the diagnostic accuracy and safety of PCE vs. the current standard of care (conventional colonoscopy) as the first-line examination in patients with iron deficiency anaemia (IDA) and/or overt bleeding after a non-diagnostic upper endoscopy (suspected mid or lower gastrointestinal bleeding, MLGIB).
We conducted a prospective, single-centre, single-blinded cohort study including consecutive patients with suspected MLGIB. All patients were submitted to PCE, followed by same-day colonoscopy under deep sedation. The physicians performing PCE and conventional colonoscopies were independent and blinded to each other’s observations. The diagnostic yield for potentially haemorrhagic lesions (PHL) was compared for efficacy analysis, and adverse events were assessed for both examinations. The gold standard diagnosis was defined by consensus panel. This trial has been registered in ClinicalTrials.gov (ID NCT04782986).

Results

We included 100 consecutive patients with suspected MLGIB, mean age 66.5 (18-92) years, 65% female gender, presenting with IDA (81%) or overt bleeding (19%). Mean haemoglobin level was 8.4 (4.1-12.8) g/dL and 40% were inpatients. For PCE, the PillCam Crohn’s® capsule was used in 88 patients, and PillCam COLON® 2 in the remaining. Patients with overt bleeding performed PCE within 2 weeks in 70% of cases, 15% in the first 72h after the bleeding episode. PCE was complete in 76% of cases, vs. colonoscopy 95% (p<0.01). The quality of bowel preparation was adequate in 72% of PCE vs. 85% of colonoscopies (p=0.012). Overall, PHL were diagnosed, based on the combination of PCE + colonoscopy, in 46% of patients, corresponding to small bowel and/or colon angioectasias in more than two-thirds (69.6%) of cases. PHL were detected by both examinations in 13/46 (28.3%), only by colonoscopy in 3/46 (6.5%), and only by PCE in 30/46 (65.2%) of cases (p<0.01). Overall, colonoscopy detected PHL in 23% of the entire cohort, which means 50% (23/46) of all patients with PHL according to the consensus panel, while for PCE the overall diagnostic yield was 44%, meaning 95.7% (44/46) of all PHL (p<0.01). Considering the gold standard diagnosis for PHL, colonoscopy had a sensitivity of 23/46=50%, specificity 54/54=100%, positive predictive value (PPV) 23/23=100% and negative predictive value (NPV) 54/77=70,1%, while for PCE the sensitivity was 44/46=95.7%, specificity 54/54=100%, PPV 44/44=100% and NPV 54/56=96.4%. Thirty-one percent of patients had PHL accessible to ileocolonoscopy; in those cases, the PCE was able to make the diagnosis in 29/31 (93.5%) vs. conventional colonoscopy in 23/31 (74.2%) of cases, p<0.01. Regarding safety, no significant adverse events occurred with PCE, vs. 2% (cardiopulmonary) with conventional colonoscopy.

Conclusion

PCE is safe and more effective than conventional colonoscopy in identifying PHL both in the small bowel and the colon, and could be considered as a first-line examination in patients with IDA or overt bleeding after a non-diagnostic upper endoscopy. In more than half of patients with suspected MLGIB, PCE does not detect any PHL either in the small bowel or the colon, dismissing any further invasive endoscopic investigations.

Disclosure

Medtronic provided financial support to the acquisition of some of the capsules which were used in the trial

Introduction

Initial reports suggested a high mortality associated with peri-operative COVID-19 infection resulting in delayed surgery and a global change in surgical pathways. The impact of COVID-19 variants and vaccinations on surgical outcomes is yet to be described.

Aims & Methods

We aimed to define the risk of COVID-19 infection in the 30 days following surgery and the associated mortality. With the approval of NHS England we identified all registered adult patients in an OpenSAFELY-TPP primary care general practice within England whilst having an abdominal, obstetric, orthopaedic, thoracic or vascular procedure defined using OPCS codes between 01/02/2020 and 01/03/2022.COVID vaccinations and COVID waves were defined. Crude 30 day risks were calculated using Kaplan Meier curves. A competing risks Cox proportional survival analysis was used to adjust the cumulative risk of COVID-19 infection by the competing risk of death and subsequent non COVID-19 emergency readmissions.
Primary care records managed by the GP software provider TPP were linked to ONS death data, Hospital Episodes Statistics, and Second Generation Surveillance System Public Health England test data through OpenSAFELY. All data were linked, stored and analysed securely within the OpenSAFELY platform: https://opensafely.org/. Data include pseudonymised data such as coded diagnoses, medications and physiological parameters. No free text data are included. All code is shared openly for review and re-use under MIT open license https://github.com/opensafely/PostOpCovid. Detailed pseudonymised patient data is potentially re-identifiable and therefore not shared.
This study was approved by the Health Research Authority [REC reference 21/EE/0278] by the East of England Research Ethics Committee.

Results

We identified 1,213,890 patients within the study period who underwent at least one surgical procedure. Following surgery 11,950 (0.9%) patients developed COVID-19 infection within 30 days. Post-operative COVID infections were greatest in wave 4 with 2.5% of patients having a post-operative infection. Adjusting for all factors post-operative COVID infection risk was 4.9 (aHR 4.88 95% CI 4.65-5.12) fold greater in the fourth wave compared to the first wave.
Within 90 days of surgery there were 820 (0.06%) deaths. A recent COVID infection increased crude morality to 1.42%, and a post-operative COVID infection increased crude mortality to 1.82%. The risk of death reduced following a first and second vaccination (aHR 0.11 95% CI 0.09-0.13). A recent COVID infection (7-42 days prior to admission) increased mortality 4 fold (aHR 3.84 95% CI 3.31-4.45) and a post-operative COVID infection increased mortality 8 fold (aHR 8.49 95% CI 7.6-9.48) compared to those without a COVID-19 infection. This increased 90 day mortality risk was highest in the second wave following a post-operative COVID infection, but then decreased to the non-covid baseline for both emergency and elective procedures in the 3^rd and 4^th waves.

Conclusion

The risk of post-operative COVID infection is low but has increased as strains have been become more transmissible. The absolute risk of death following peri-operative COVID-19 infection is greater than those who have not had infection however this risk has become attenuated during the latter waves of the pandemic.

Acknowledgements: We are very grateful for all the support received from the TPP Technical Operations team throughout this work, and for generous assistance from the information governance and database teams at NHS England and the NHS England Transformation Directorate.

Disclosure

None to declare

Introduction

There are no prediction models for a diagnosis of inflammatory bowel disease (IBD) in primary care. Our aim was to develop an IBD risk prediction tool to reduce the length of time patients have undiagnosed IBD symptoms and improve IBD clinical outcomes.

Aims & Methods

We developed and internally validated a risk prediction tool for the diagnosis of IBD, ulcerative colitis (UC) and Crohn’s disease (CD).
A population-based retrospective open cohort study using Clinical Practice Research Datalink (CPRD) database was undertaken between 1st January 2010 and 31st December 2019 of all the patients aged 18 years or older. Patients were followed from first presentation with lower gastrointestinal (GI) symptoms potentially related to IBD to IBD diagnosis. Candidate predictors were chosen based on clinical and substantive knowledge. Cox proportional hazards regression with backward elimination was used for model development of IBD, UC and CD risk prediction models. The predictive performance of the models was assessed using discrimination (C-statistic). Internal validation using 1000 bootstrap sampling repetitions was used to estimate the optimism-corrected measures of predictive performance.

Results

Of 2,056,398 patients with lower GI symptoms: 11,192 patients had an IBD diagnosis (7033 UC (62.8%) and 4138 CD (37.0%)). The final IBD model included demographic factors (age, sex, ethnicity, smoking, index of multiple deprivation, body mass index, Charlson comorbidity index, loperamide use) co-existing conditions (anxiety, depression, irritable bowel syndrome (IBS), haemorrhoids), extraintestinal (EIM) manifestations (mouth ulcers, ophthalmic, primary sclerosing cholangitis, dermatological), laboratory investigations (low haemoglobin (Hb), low Mean Corpuscular volume (MCV), low albumin, low ferritin, raised C-reactive protein (CRP), raised Erythrocyte Sedimentation Rate (ESR), raised calprotectin level). The UC model included all above except mouth ulcers, IBS, ophthalmic EIM. Depression and ferritin were excluded in the CD model though low vitamin B12 level was included. The risk score for each patient was the sum of individual risk factors. In the development dataset, models showed moderate discrimination. For the IBD prediction tool: C-statistic 0.71 (95% CI 0.70-0.71),UC prediction tool: C-statistic 0.70 (95% CI 0.69-0.70) and CD prediction tool: C-statistic 0.75 (95% CI 0.74-0.76). The C-statistics of the models showed that the IBD, UC and CD prediction tools reliably differentiated patients with and without IBD,UC and CD respectively.

Conclusion

A risk score of patient demographics, symptoms and investigations performs well for IBD,UC and CD and may help in prioritising suspected IBD referrals in symptomatic subjects in primary care.

Disclosure

No conflict of interest to declare