Introduction

Acute pancreatitis (AP) is one of the most common and widely increasing gastrointestinal diseases leading to hospitalization without specifically available therapy [1]. It is mainly caused by gallstones, possibly by increasing the pressure in pancreatic duct with refluxing of bile acids (BAs) or changing of serum BA concentration due to bile duct obstruction [2]. So far, few existing reports only mentioned total BA measurements without considering their hydrophilic potential. Our data from experimental work showed that systemic BAs can modulate severity of AP depending on their hydrophobicity and the involvement of cholecystokinin [3]. As a further translational step, we aimed to investigate the role of systemic BAs profiles and analysed their association with the etiology and severity of AP in human.

Aims & Methods

Serum from AP patients and a healthy control group was collected and stored at -80⁰C. A profile of 20 different BAs was quantified by liquid chromatography tandem mass spectrometry-based assay using the AbsoluteIDQBAs kit according to the manufacturer’s instruction. The workflow was managed by MetIDQ and the data was analyzed by Oracle database XE software. Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated for each patient at the first and third day of hospitalization and were compared by subtraction of the values (Δ APACHE II). Diagnosis criteria and severity of pancreatitis were assessed according to the Revised Atlanta classification and the APACHE II score.

Results

There were 214 AP patients with mean age of 60±16 (range 26-87) years and 50.4 % were female. Biliary origin was diagnosed in 133 (62.1%) patients and non-biliary pancreatitis (mainly alcoholic AP) in 81 (37.9 %) cases. In non-biliary AP, profiles of both hydrophobic and hydrophilic BAs did not differ from controls. In biliary AP, significantly elevated levels were detected for hydrophobic BAs but not hydrophilic one. The total concentrations of hydrophobic BAs were 33.86±4.51 μM in biliary AP and 8.068±1.98 μM in non-biliary AP (p < 0.0001). Cut-off values were 0.30 μM and 3.78 μM for hydrophilic and hydrophobic BAs, respectively. The total amount of hydrophilic BAs was not different between the groups of deteriorated (Δ APACHE II >0) and ameliorated or stable AP (Δ APACHE II ≤ 0). Conversely, total hydrophobic BAs concentrations were significantly higher in the worsened AP (55.8±12.3 μM) group than in those who recovered or at least did not deteriorate (5.9±0.6 μM). However, ursodeoxycholic acid (UDCA), a hydrophilic BA, was significantly decreased in severe disease and showed a reduced trend in moderately severe AP.
Hydrophobic BAs had more predictive potential with an area under the curve (AUC) of 0.762, a sensitivity of 83.75% and a specificity of 60% at the cut-off value 11.84 μM, whereas hydrophilic BAs were only of limited use for the prediction of AP deterioration, as AUC was 0.57 with a sensitivity of 65% and a specificity of 44% at the cut-off 0.7 μM. Additionally, UDCA concentrations of less than 19 nM can be used to distinguish biliary AP from non-biliary AP with an AUC of 0.723, sensitivity 75%, and specificity 65%. For detection of deterioration, UDCA alone with cut-off concentration 18 nM showed a value with an AUC of 0.68, sensitivity 76%, and specificity 61%.

Conclusion

In patients, the sum of hydrophobic but not total hydrophilic BAs associated with the etiology and severity of AP. Serum levels of UDCA, a particular type of hydrophilic BAs, inversely associated with the severity of AP, which suggests a protective role.

References

[1]. Iannuzzi, J.P.; King, J.A.; Leong, J.H.; Quan, J.; Windsor, J.W.; Tanyingoh, D.; Coward, S.; Forbes, N.; Heitman, S.J.; Shaheen, A.A.; et al. Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis. Gastroenterology 2022, 162, 122-134, doi:10.1053/j.gastro.2021.09.043
[2]. Lerch, M.M.; Aghdassi, A.A. The role of bile acids in gallstone-induced pancreatitis. Gastroenterology 2010, 138, 429-433, doi:10.1053/j.gastro.2009.12.012
[3]. Tran, Q.T.; Sendler, M.; Wiese, M.L.; Doller, J.; Zierke, L.; Gischke, M.; Glaubitz, J.; Tran, V.H.; Lalk, M.; Bornscheuer, U.T.; Weiss F.U; Lerch, M.M and Aghdassi A.A. Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis. International journal of molecular sciences 2022, 23, 13592. doi: 10.3390/ijms232113592

Disclosure

The authors declared no Conflict of Interest.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is frequently indicated in patients who underwent Roux-en-Y gastric bypass (RYGB) surgery. (1, 2) However, due to the altered anatomy, it is challenging to gain pancreatobiliary access in patients following a RYGB. Several strategies are currently available, but all have their disadvantages. Laparoscopy-assisted ERCP (LA-ERCP), the current golden standard, has higher success rates but also comes with logistical challenges of intraoperative ERCP, peri-operative complications and high costs. (3 - 5) Endoscopic ultrasound directed ERCP (EDGE) is a technique used to create a gastro-gastrostomy by placing a lumen apposing metal stent (LAMS) between the gastric pouch and the excluded stomach, facilitating subsequent ERCP.(6) Although EDGE gained more popularity over the last few years, prospective studies are lacking.

Aims & Methods

The aim of this study is to provide prospective evidence for the efficacy and safety of EDGE, including fistula closure.This multicentre prospective cohort study included all consecutive patients scheduled for elective ERCP after RYGB surgery. EDGE was performed as a two-step procedure. Primary endpoint was overall technical success. Secondary endpoints were technical success of LAMS placement and ERCP individually, persistent fistula and other procedure-related adverse events (AEs).

Results

Between January 2021 and August 2024, 26 patients were included in 4 Dutch hospitals. Overall technical success was achieved in 25/26 patients (96.2%). Median LAMS indwelling time was 14 days [IQR 11 – 28 days]. Two EDGE-related AEs occurred (7.7%); one perforation of the contralateral duodenal wall following scope insertion and one bleeding after LAMS placement. Two ERCP-related AEs occurred (7.7%): one CBD perforation and one post-ERCP pancreatitis. Two patients were lost to follow-up. None of the remaining patients had a persistent fistula, based on radiologic or endoscopic evidence (0/24). No mortality occurred.

Conclusion

This prospective study shows that two-step EDGE is relatively safe and associated with high technical success, without any cases of a persistent fistula. However, AEs occurred in 4 patients (15.4%), of which two were EDGE-related (7.7%).

References

1. Yang H, Petersen GM, Roth MP, Schoenfield LJ. Risk factors for gallstone formation during rapid loss of weight. Digestive diseases and sciences. 1992;37(6):912-8.
2. Haal S, Guman MSS, Boerlage TCC, Acherman YIZ, de Brauw LM, Bruin S, et al. Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial. Lancet Gastroenterol Hepatol. 2021;6(12):993-1001.
3. Gangwani MK, Aziz M, Haghbin H, Iqbal A, Dillard J, Dahiya DS, et al. Comparing EUS-directed Transgastric ERCP (EDGE) Versus Laparoscopic-Assisted ERCP Versus Enteroscopic ERCP: A Network Meta-analysis. J Clin Gastroenterol. 2024;58(2):110-9.
4. da Ponte-Neto AM, Bernardo WM, de ACLM, Josino IR, Brunaldi VO, Moura DTH, et al. Comparison between Enteroscopy-Based and Laparoscopy-Assisted ERCP for Accessing the Biliary Tree in Patients with Roux-en-Y Gastric Bypass: Systematic Review and Meta-analysis. Obes Surg. 2018;28(12):4064-76.
5. Abbas AM, Strong AT, Diehl DL, Brauer BC, Lee IH, Burbridge R, et al. Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass. Gastrointestinal endoscopy. 2018;87(4):1031-9.
6. van Wanrooij RLJ, Bronswijk M, Kunda R, Everett SM, Lakhtakia S, Rimbas M, et al. Therapeutic endoscopic ultrasound: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review. Endoscopy. 2022;54(3):310-32.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease of the pancreas with a high mortality rate due to late diagnosis at an advanced stage for its asymptomatic progression. Chronic pancreatitis, one of the risk factors for the development of PDAC, complicates the diagnostic process as both conditions sometimes share overlapping clinical and pathological features. Identifying individuals at higher risk of developing the disease and detecting pancreatic cancer at an early, curable stage is critical to improving overall patient outcomes. This study investigates the potential of relative telomere length (RTL) in peripheral blood and microbiome composition as biomarkers for PDAC. These biomarkers could support a minimally invasive liquid biopsy approach for early diagnosis of PDAC, differentiation from chronic pancreatitis, and screening of high-risk individuals.

Aims & Methods

A total of 239 participants were enrolled in the study and were divided into four groups: patients with PDAC (n = 36), chronic pancreatitis (n = 60), type II diabetes mellitus (n = 91) and cancer-free individuals (n = 52). Peripheral blood samples were collected to estimate relative telomere length using the multiplex monochrome qPCR method. Stool samples from a subset comprising chronic pancreatitis patients (n = 13), PDAC patients (n = 12), and healthy controls (n = 7) were analysed using 16S rRNA sequencing for metataxonomic analysis of the gut microbiome.

Results

Microbiome analysis revealed dysbiosis in a subset of patients, with an overrepresentation of bacterial species such as Prevotella copri and Akkermansia muciniphila in chronic pancreatitis and PDAC patients. A trend towards reduced microbial diversity was observed in PDAC patients, with changes in bacterial composition already detectable in chronic pancreatitis patients. No significant differences were found in RTL between the PDAC and cancer-free patient groups, and the only risk factors associated with changes were age, gender and smoking.

Conclusion

The pilot findings suggest a general trend towards reduced microbial diversity in PDAC patients, with alterations in bacterial proportions already observed in individuals diagnosed with chronic pancreatitis. These data ptovide a basis for the development of non-invasive diagnostic strategies to improve early detection and clinical outcomes for patients with PDAC. However, relative telomere length has not been shown to be a reliable biomarker.

References

Wu H, Zou WB, Zhou DZ, Gu YT, Liao Z, Li ZS. Longer Leukocyte Telomere Length is Associated With an Increased Risk of Chronic Pancreatitis. Pancreas. 2017;46(8):e65-e66. doi:10.1097/MPA.0000000000000887
Riquelme E, Zhang Y, Zhang L, et al. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019;178(4):795-806.e12. doi:10.1016/j.cell.2019.07.008
Antwi SO, Petersen GM. Leukocyte Telomere Length and Pancreatic Cancer Risk: Updated Epidemiologic Review. Pancreas. 2018;47(3):265-271. doi:10.1097/MPA.0000000000000995
Campa D, Felici A, Corradi C, et al. Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review. Mutagenesis. 2025;40(1):39-47. doi:10.1093/mutage/gead034
Sexton RE, Uddin MH, Bannoura S, et al. Connecting the Human Microbiome and Pancreatic Cancer [published correction appears in Cancer Metastasis Rev. 2022 Jun;41(2):333. doi: 10.1007/s10555-022-10037-3.]. Cancer Metastasis Rev. 2022;41(2):317-331. doi:10.1007/s10555-022-10022-w

Clinical Case Summary

A 71-year-old female presented to the gastroenterology clinic following a two year history of dysphagia and sensation of food sticking in the oesophagus. Her dysphagia was limited to solid foods, and symptoms were not exacerbated by positional change. Pain was mostly localised around the sternal notch where she would have the sensation of a food bolus. Over the preceding 2 years, she had experienced about 7.5kg of weight loss with no constitutional symptoms of fevers or fatigue. Her past medical history included hypertension, dyslipidaemia, lower back pain, cold agglutinin disease, monoclonal B lymphocytosis and peripheral arterial disease. On examination, there were no signs of malnourishment or palpable lymph nodes in the axilla, neck or supraclavicular region. Her abdomen was soft and non-tender. Given largely non-illuminating blood results, an oesophageal-gastroduedonoscopy was performed. However, no findings were noted, specifically no oesophageal webs, Zenker diverticulum, gastroparesis, trachealisation of the oesophagus or corrosive pathology. H. pylori was also not isolated on histopathology. A barium swallow was then performed which showed extensive external compression of the proximal third of the oesophagus at the level of the arch of the aorta, most indicative of dysphagia lusoria (Fig 1). Computed tomography angiography (CTA) showed retroesophageal aberrant right subclavian artery bifurcating from the ascending aorta independent of a brachiocephalic artery and causing external oesophageal compression (Fig 2 & 3). Given this definitive diagnosis, the patient was then seen in clinic where management of dysphagia lusoria was explained. Despite ongoing symptoms, the patient decided to continue with conservative management and lifestyle modifications, which included eating smaller bites and increase in fluid intake. Although an extensive compression typically requires surgical intervention, our patient was stable at two-year follow-up (Fig 4 A-B).

References

Figure 1: Barium swallow examination showing extrinsic compression of the proximal third of the oesophagus at the level of the aortic arch (white arrow).
Figure 2: Axial view of computed tomography angiography (CTA) showing the posterior course of the retroesophageal aberrant right subclavian artery.
Figure 3: Axial view of computed tomography angiography (CTA) showing compression of oesophagus (white arrow) by the retroesophageal aberrant right subclavian artery (white arrowhead).
Figure 4: Computed tomography angiography (CTA) multi-planar reconstruction (MPR) showing the posterior course of the right subclavian artery (white arrow), crossing the mediastinum and compressing the oesophagus. A. coronal view B. Sagittal view

Disclosure

None.

Clinical Case Summary

An 18-year-old female was diagnosed with very early-onset Crohn’s disease (CD) in 2008. Due to steroid dependence, adalimumab 40 mg biweekly was initiated in 2019, with escalation to 40 mg weekly in February 2023 following secondary loss of response. In November 2023, despite clinical and biochemical remission (CRP <0.5 mg/L, fecal calprotectin <50 µg/g), the patient developed painful purpuric and ulcerated lesions on both lower limbs. Histological examination of a skin biopsy confirmed leukocytoclastic vasculitis (LCV), revealing perivascular neutrophilic infiltrates, nuclear debris, and fibrinoid necrosis in post-capillary venules. Infectious and autoimmune screening, including ANA, antiphospholipid antibodies, p-ANCA, and c-ANCA, were negative. Following consultation with an immunologist, adalimumab was discontinued, and oral prednisone 25 mg/day was initiated. However, the clinical course was complicated by a skin abscess, which was treated with oral amoxicillin/clavulanate (1 g three times daily for 3 days). As vasculitic lesions worsened, the patient was hospitalized, and prednisone was increased to 50 mg/day. Intravenous cefazolin (2 g every 8 hours for 5 days) was also administered, resulting in stabilization and partial clinical improvement. A multidisciplinary team, including a gastroenterologist, immunologist, and dermatologist, opted to initiate off-label treatment with upadacitinib 30 mg/day, a selective Janus kinase 1 (JAK1) inhibitor. After four weeks, the patient showed improvement in the vasculitic lesions, and corticosteroid therapy was tapered. At the six-month follow-up, the patient remained on upadacitinib monotherapy, with sustained clinical and biochemical remission of both CD and LCV, without any adverse events. This case highlights the potential of JAK1 inhibition as an effective and safe therapeutic option for leukocytoclastic vasculitis in patients with Crohn’s disease.

References

Photographic documentation of the clinical case:
1. Images showing the initial presentation of petechial and purpuric lesions on the lower limbs.
2. Images of severe vasculitis characterized by confluent and ulcerated lesions.
3. Images documenting cutaneous healing following upadacitinib treatment.