Introduction

Celiac disease (CeD) may affect the interplay between the duodenal mucosa and exocrine pancreatic function as a consequence of intestinal inflammation, and could potentially increase the risk of acute pancreatitis (AP). However, the association between these two conditions remain largely unexplored.

Aims & Methods

This Swedish nationwide cohort study in ESPRESSO aimed to investigate the risk of incident AP in patients with CeD without previous pancreatic disease. Patients with biopsy-confirmed CeD were identified between 1969 and 2023 (n=57,221) and were individually matched with ≤5 general population reference individuals (n= 279,126) by sex, birth year, calendar year, and county of residence. Included individuals were followed until 31 August 2024. The primary outcome was any incident AP. Secondary outcomes included (1) specific AP types (i.e., gallstone-related, non-gallstone-related, potential alcohol-related AP); (2) severe AP, defined as (i) any hospitalization for AP that lasts for ≥14 days or being combined with diagnostic or procedural code implying a complicated episode, or (ii) all-cause death <90 days after being discharged for AP); as well as (3) second episode of any AP that occurred ≥90 days after being discharged for incident AP. Flexible parametric survival models were used to estimate the adjusted hazard ratios (aHRs) for investigated outcomes. Familial risk factors were additionally accounted for in the comparison with CeD-free full siblings (n=70,016).

Results

During a median follow-up of 15.5 years, incident AP was observed in 549 patients with CeD (incidence rate (IR)=59 per 100,000 person-years) and 1,732 reference individuals (IR=38). Patients with CeD had a higher hazard of developing any AP than reference individuals (aHR=1.50, 95% confidence interval:1.35 to 1.67). The hazard elevation remained significant for more than 25 years after the diagnosis of CeD, resulting in one extra AP event per 185 CeD patients until then. CeD was significantly associated with gallstone-related AP (aHR=1.31 [1.12 to 1.54]), non-gallstone-related AP (aHR=1.65 [1.41 to 1.93]), severe AP (aHR=1.68 [1.32 to 2.14]), but not with potential alcohol-related AP (aHR=1.22 [0.89 to 1.67]). The association between CeD and any AP was attenuated but remained significant in the sibling comparison and in sensitivity analyses that respectively accounted for the potential influence of cancer, medications that may induce AP (i.e., steroids, mesalamine, and immunosuppressants), and the COVID-19 pandemic.
Restricting our data to patients who had experienced a first AP, the risk of second-time AP was not higher in patients with CeD (aHR=0.81 [0.61 to 1.07]) than in reference individuals.

Conclusion

Patients with CeD were at an increased risk of incident AP, especially non-gallstone-related AP, for more than 25 years after diagnosis. However, the risk was no longer elevated beyond the first AP episode. Further research is needed to investigate the underlying mechanism linking CeD to AP.

Disclosure

All authors have completed the ICMJE uniform disclosure form and declare:
FE has served as an advisory board member for Boehringer Ingelheim.
DAL is an employee of Takeda Pharmaceuticals and owns stock in this company.
JFL has coordinated a study on behalf of the Swedish IBD quality register (SWIBREG). That study received funding from Janssen Corporation. JFL has also received financial support from MSD/Merck developing a paper reviewing national healthcare registers in China, and for a collaboration on inflammatory bowel disease. JFL also has a research collaboration on celiac disease with Takeda.
The other authors report no disclosures relevant to the manuscript.

Introduction

Post endoscopy upper gastrointestinal cancers (PEUGIC) are often missed opportunities to diagnose earlier or even prevent cancer. PEUGIC in patients undergoing surveillance for pre-malignant conditions are a potentially important surveillance quality indicator. A national process for identifying all PEUGIC in the English National Health Service and performing root cause analysis was developed.

Aims & Methods

Potential PEUGIC between 2017 and 2023 occurring 3-36 months after an index endoscopy which did not result in a cancer diagnosis were identified from National Cancer Registration Dataset and Hospital Episode Statistics held by the National Cancer Registration and Analysis Service. Data from local root cause analysis were uploaded onto a secure portal for national analysis. Only PEUGIC following surveillance endoscopy were included in this analysis. Logistic regression analysis was used to identify associations.

Results

3151 potential PEUGIC were examined by local reviewers in 144 English hospitals. 635 (20%) were excluded and data were available for 2516 PEUGIC. 618 PEUGIC (24.6%) were undergoing surveillance for: Barrett’s oesophagus (83%); chronic atrophic gastritis (7%) or other conditions (10%). PEUGIC sites were oesophagus 85%, stomach 13% and duodenum 1%. 5% of PEUGIC were not related to the pre-malignant condition under surveillance.
Table 1 summarises the PEUGIC root cause analysis results based on the World Endoscopy Organisation categorisation. Inadequate endoscopy or decision making occurred in 30% of PEUGIC (categories B/D) and was associated with patient harm OR 2.61 (95% CI 1.74 -3.92).
Seattle biopsy protocol compliance was only 58% in Barrett’s surveillance PEUGIC. Additional focal or cancer associated lesions were present at index endoscopy in the PEUGIC segment in 23%.
Oesophageal and gastric PEUGIC often presented with stage 2 cancers or greater (48% and 43% respectively). 45.2% of oesophageal and 47.0% of gastric PEUGIC were considered at least possibly avoidable. Treatment was adversely affected with palliative treatment in 22% of oesophageal and 30% of gastric PEUGIC. 6% led to premature death.
Endoscopy practices associated with stage ≥2 cancer were: sedation without opioids OR 1.75 (95% CI 1.03-2.97); lack of image enhancement OR 1.78 (95% CI 1.18-2.70) and lack of dedicated surveillance sessions OR 2.08 (95% CI 1.46-2.98).

Table 1 Root causes of all surveillance PEUGIC

Conclusion

Inadequate assessment or decision making was noted in 30% of surveillance PEUGIC, which adversely affected treatment in 20% of oesophageal and 30% of gastric PEUGIC. 48% of oesophageal and 43% of gastric PEUGIC patients presented with stage 2 cancer or greater suggesting potential failures of surveillance. Optimal sedation practice, image enhancement and dedicated surveillance sessions were associated with stage 1 PEUGIC and better outcomes.