Introduction

The incidence of acute pancreatitis is rising globally and current studies show that around one in four acute pancreatitis cases labelled as idiopathic are of biliary etiology¹. As a cause of biliary pancreatitis, microlithiasis and sludge play a decisive role alongside classic gallstones². However, the pathomechanism of microlithiasis and sludge, in contrast to classic gallstones, causing acute pancreatitis is not yet understood. Gallstone-induced duct obstruction is mimicked in many animal models via duct ligation and is considered to be a critical trigger of pancreatitis. Nonetheless, biliary microlithiasis does not lead to bile duct obstruction, and thus the trigger of biliary pancreatitis remains elusive.

Aims & Methods

The aim of this study was to identify the mechanism of microlithiasis-induced acute pancreatitis. Assuming that biliary microlithiasis induces mechanical damage while passing through the papilla, human papilla biopsies were studied (acute pancreatitis (n = 4) and control patients without any pancreatobiliary pathology (n = 4)). Papilla biopsies were stained for CD45 and NLRP3. In vitro, bone marrow-derived and yolk-sac-derived macrophages were treated with cholesterol monohydrate and calcium billirubinate crystals and the NLRP3 inflammasome activation was quantified. In vivo, microlithiasis formation was induced and sonographically monitored over 6-8 weeks in 8-10 weeks-old female mice using a lithogenic high-fat diet and twice daily i.p. devazepide injections. After caerulein-induced acute pancreatitis, low-dose CCK i.p. injections (40 ng/kg; 8 x) induced microlithiasis ejection from the gallbladder and the pancreatitis phenotype was compared with caerulein-induced pancreatitis and control mice.

Results

Significantly higher CD45 and NLRP3 expression levels were found in the papilla biopsies of microlithiasis-induced acute pancreatitis patients. In line with this, significantly higher IL-1ß secretion and caspase-1 activation were observed in vitro in bone marrow-derived macrophages stimulated with cholesterol monohydrate and calcium billirubinate crystal, but not in yolk-sac-derived macrophages. Likewise, crystal-induced increased NLRP3 inflammasome recruitment was shown. In vivo microlithiasis formation and sonographic monitoring was achieved in all mice with high fat diet and devazepide injections. Compared to the caerulein-induced pancreatitis group, the caerulein + microlithiasis pancreatitis group showed higher LDH, GPT and ALP levels in serum but without a correlating microlithiasis-aggravated pancreatitis phenotype in HE damage scoring or CD45 staining.

Conclusion

We describe for the first time a mechanism in which biliary microlithiasis leads to a local inflammatory reaction at the papilla (acute papillitis) via NLRP3 inflammasome activation driven by bone marrow-derived macrophages. Secondarily, this may lead to pancreatic duct obstruction and acute pancreatitis through papillary edema.

References

1. Umans DS et al. Prospective multicentre study of indications for surgery in patients with idiopathic acute pancreatitis following endoscopic ultrasonography (PICUS). Br J Surg. 2023 Nov 9;110(12):1877-1882.
2. Żorniak M, Sirtl S et al. Consensus definition of sludge and microlithiasis as a possible cause of pancreatitis. Gut. 2023 Oct;72(10):1919-1926.

Introduction

Incidence of sporadic ductal pancreatic adenocarcinoma (PDAC) in the Czech Republic is the third highest in Europe (23.1/100,000 population). New-onset diabetes mellitus with weight loss (> 5% within < 6 months) in patients over sixty can be an early sign of PDAC. New-onset diabetes mellitus was recorded in 12.2% subjects three years prior to the diagnosis of PDAC (in the 60-74+ age group:13.8%) in the Czech Republic in the period 2017-2021 [ref. 1].

Aims & Methods

The aim of this study was to evaluate the standardized incidence ratio (SIR) of PDAC in patients with diabetes mellitus with and without previous history of any other malignancy within a 12-year period.
Methods: The analysis was based on individual population data from the Czech National Registry of Reimbursed Health Services, the National Cancer Registry, and the Death Certificate Information System in the period 2010 - 2021. Patients were divided into two groups: the first one included subjects with diabetes mellitus who had a history of any malignancy prior to the diagnosis of diabetes (follow-up 865,956 person-years); the second cohort consisted of people with diabetes mellitus who had no history of malignancy prior to the diagnosis of diabetes (7,971,090 person-years). The calculated person-years at risk were stratified by sex, age and time periods (2010-2013; 2014-2017; 2018-2021). Subgroup analyses were performed considering follow-up and age at diagnosis of diabetes. The first report of any antidiabetic drug (ATC group A10) was the determinant for the diagnosis of diabetes mellitus in a particular individual. SIR was calculated as the ratio of observed to expected (estimated from incidence in the general population) cases of PDAC.

Results

Selected SIRs stratified according to age and follow-up are displayed in Table 1.
A significantly higher risk of PDAC in diabetes mellitus with a history of previous malignant diseases (compared to the general population) was found for the following: head and neck cancer (SIR 2.54), gastric cancer (2.12), colorectal cancer (1.38), laryngeal cancer (2,51), malignant melanoma (1.65), breast cancer (1.61), cervical cancer (2.22), uterine cancer (1.72), prostate cancer (1.59), testicular cancer (3.1), kidney cancer (1.75), urinary bladder cancer (1.74), thyroid cancer (2.13), Hodgkin lymphoma (2.74), non-Hodgkin lymphoma (2.15) and leukaemias (1.93).

Table 1
Risk of PDAC in diabetes mellitus

Conclusion

Risk of PDAC in patients with diabetes mellitus was higher in subjects with a history of various malignant diseases compared to those with no previous history of any malignancy. Particular attention should be paid to new-onset diabetes (diagnosis made within one last year). History of a malignancy, as an important risk factor for PDAC, should be taken into account when surveilling patients with diabetes mellitus.

Funding: Research projects MO1012 (DZVRO) and MH CZ-DRO (UHHK, 00179906).

References

Ref. 1: UEG Journal 2024; 12 (Suppl S8): 565.

Disclosure

There is conflict of interest.

Introduction

Recent developments in diagnostic imaging have increased the detection rate of lymphoma, for which a clear, histopathological diagnosis is critical for the subsequent choice of therapeutic regimen. Over the past decade, endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/B) has become widely-used means of tissue collection. However the open lymph node biopsy has conventionally been used to diagnose lymphoma histologically, and the evidence backing the use of EUS-FNA/B for this purpose is still limited.

Aims & Methods

The present study aimed to compare the performance of EUS-FNA/B and the open biopsy for diagnosing lymphoma by retrospectively analyzing 1113 patients with 1224 lesions who underwent either of the two methods at the study center between 2012 and 2024. The patients’ background, pathological diagnosis, procedural factors, and complications were evaluated. The performance of the open biopsy was compared with that of EUS-FNAB in diagnosing lymphoma in accordance with the 5^th edition of the World Health Organization classification of hematolymphoid tumours ¹⁾ (WHO classification).

Results

An open biopsy was performed for 943 lesions, 621 of which were malignant lymphomas, with the face, head, neck, axilla or groin, limb, and other areas being the site of 46, 556, 96, 225, 4, and 16 lesions, respectively. EUS-FNAB was performed for 281 lesions, 82 of which were malignant lymphomas, with the intra-abdominal area, mediastinum, and rectum being the site of 270, 10, and 1 lesion, respectively. The needle gauge used for FNA was 19G, 22G, and 25G in 1, 143, and 36 lesions, respectively, while and the needle gauge for FNB was 20G, 22G, and 25G in 3, 74, and 3 lesions, respectively. The mean number of punctures was 2.3 (range 1-9). EUS-FNAB involved significantly fewer, procedural complications than the open biopsy (14/943 vs 0/281; p=0.04). According to the WHO classification, the diagnostic performance (95% confidence interval) of the open biopsy has sensitivity 93.4 % (91.1-95.2), specificity 100.0 % (98.3-100.0), positive predictive value 100.0 % (99.0-100.0), and negative predictive value 88.7 % (85.0-91.8). The diagnostic performance (95% confidence interval) of EUS-FNAB according to the same classification has sensitivity 79.3 % (68.9-87.4), specificity 100.0 % (97.2-100.0), positive predictive value 100 % (91.8-100.0), and negative predictive value 92.1 % (87.7-95.3 %). Between the groups, there was no significant difference in the proportion of lesions for which immunostaining was able to be performed (615/621 vs 80/82; p = 0.24). The positive diagnosis rate was significantly higher for the open biopsy (580/621 vs 27/40; p < 0.001) but did not differ significantly for the EUS-FNB (580/621 vs 38/42; p = 0.52). Univariate and multivariate analyses found that needle type (FNB needle) was a procedural factor in EUS (needle type, gauge, number of punctures, stroke length) contributing to the diagnosis of lymphoma (odds ratio: 3.83; p = 0.037).

Conclusion

EUS was less complicated than the open biopsy as means of collecting tissue for histologically diagnosing lymphoma, and EUS-FNB had a positive diagnosis rate comparable to that of the open biopsy.

References

1. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022 Jul;36(7):1703-1719.

Introduction

Patients with Crohn’s disease (CD) are at risk of progressing from inflammatory to stricturing and penetrating phenotypes. The influence of the type of remission on phenotype progression has not been adequately evaluated.

Aims & Methods

Retrospective cohort study including surgically naïve CD patients with inflammatory or stricturing phenotype evaluated concomitantly by magnetic resonance enterography and colonoscopy. The degree of remission was correlated with the risk of progressing to stricturing and penetrating phenotypes.

Results

381 CD patients were included, 21.8% with transmural remission, 21.3% with isolated endoscopic remission, 10.5% with isolated radiologic remission, and 46.5% without remission. Patients with transmural remission presented the lowest rates of phenotype progression (1.2%), with a significant difference compared to isolated endoscopic remission (18.3%, P≤ 0.001), isolated radiologic remission (17.5%, P=0.002), and no remission (36.9%, P≤0.001). In multivariate regression analysis, transmural remission (OR 0.023 95%CI 0.003-0.171, P<0.001), isolated radiologic remission (OR 0.342 95%CI 0.141-0.826, P=0.017), and isolated endoscopic remission (OR 0.441 95%CI 0.220-0.881, P=0.020) resulted in lower rates of phenotype progression compared to no remission.
Figure 1 presents the Kaplan-Meier estimates of remaining free of penetrating complication (upper curve) and free of stricturing and/or penetrating complication (lower curve) after the baseline assessment in patients with no remission (A), isolated endoscopic remission (B), isolated radiologic remission (C), and transmural remission (D).

Conclusion

The degree of intestinal remission correlates with the risk of phenotype progression. Patients with transmural remission are at the lowest risk of progressing to stricturing and penetrating phenotypes.