Introduction

Autoimmune pancreatitis (AiP) is a rare form of chronic pancreatitis. Studies from Japan and Germany suggest that AiP patients may have a higher incidence of malignancies compared to the general population. However, reliable data in this regard are still lacking.

Aims & Methods

We initiated a retrospective, multicenter observational study within the Pancreas 2000 framework to investigate the incidence of malignancy in AiP Patients.In our global multicenter retrospective observational trial, we are currently collecting data from patients with AiP diagnosed after 2005, including type 1, type 2, and not-otherwise-specified (NOS) AIP, regardless of the diagnostic criteria used. Patients with less than 12 months of follow-up after AIP diagnosis and those with immune checkpoint inhibitor-induced pancreatitis are excluded. Our primary outcome is to determine the occurrence of the first invasive cancer in AiP patients. The secondary outcome is to evaluate the characteristics of AiP patients with distinct pancreatic and/or extrapancreatic cancers and the prevalence of all cancer diagnoses within 12 months prior to AiP diagnosis. The standardized incidence ratio of any first invasive cancer after AiP diagnosis will be compared to age-grouped and gender-matched controls in the general population. The expected number of cancers in the general population will be determined using the Cancer Incidence in Five Continents Volume XI (CI5XI) registry.

Results

We will present the current status of recruitment and preliminary data. To date, 16 centers from Europe and America have entered 321 cases. Ethics submissions have already been applied for in an additional 45 centers across four continents (Europe, Asia, America, and Oceania).

Conclusion

To the best of our knowledge, this is the first global observational trial analyzing the risk of developing cancer in patients with AiP.

Clinical Case Summary

A 67 old male patient with Hx of DM, HTN, IHD and previous repair of paraumbilical hernial defect. He had history of multiple previous ERCP with difficult stone extraction and stent placement to secure biliary drainage.
He presented with fever and abdominal pain mainly at re-herniated defect at paraumbilical region. By examination we found ulcerated skin over the hernial sac with a small foreign body protruding from it. He was sent for radiology and performed abdominal CT examination which commented on a mispositioned/slipped biliary stent along with CBD dilatation. Initial labs showed elevated TLC and bilirubin. he admitted that he neglected the instructions to make an appointment for stent exchange after 3 months as he was told after the last ERCP 2 years ago.
Surgical consultation was done to inspect the ectopic stent, they removed it and recommended for follow up of the fistulous opening only as the CT didn't show serious injuries or any abdominal free fluid.
The ectopic stent was impacted inside an intestinal loop inside the hernial sac and couldn't take the natural pathway out of the body with the excreta.
When we saw the slipped stent that punctured its own way out through the hernia out of the patient's body, we thought that this strange finding was the only surprise that the patient can give us.
Patient was planned for ERCP to secure biliary drainage.
After cannulation while performing ERCP, the cholangiogram revealed another surprise, The patient had another hidden stent, an internally migrated one.
It was removed by balloon sweeping and another new double pigtail stent was inserted to ensure more stability.
Upon our request we brought the previous ERCP reports to be revised. We found that the last procedure 2 years ago reported a missed stent already and he put a new one. This means that the hernial stent was the older slipped one and kept in place for this whole time till it decided to get out and the newer stent was internally migrated.

Clinical Case Summary

A 45 y/o female patient complained from fatigue and dyspnea, her CBC showed MHA (Hb 6.5 g/dl, MCV 62 fl/cell) with normal WBCs and PLTs and she denied any apparent bleeding or menstrual abnormalities. Upon investigating, her virology profile was negative, she had +ve FOB, low levels of iron (25.6 ug/dl), low ferritin (10.3 ng/ml) and high Reticulocyte count (3.5%). She underwent upper and lower GI endoscopies without significant findings. She received packed RBCs to correct her general condition but the symptoms recurred. Repeated upper and lower endoscopies didn’t show any source of bleeding. Capsule enteroscopy was ordered and showed multiple red spots, dilated vessels and small varices. We thought of angiodysplasia so we ordered CT enterography but the scan couldn’t detect vascular abnormalities in small intestinal wall and showed an aneurismal dilation at portal vein confluence (3x3.7cm) along with dilated both portal vein and splenic vein. The interventional radiology team described the aneurysm as fusiform not saccular, so it wasn’t suitable for coiling and embolization.
Portal vein aneurysm (PVA) was discovered incidentally in this case. The turbulence of the portal blood flow is believed to be causing congestion in the drained intestinal segments. As a result, we found the described spots and dilated vessels in the jejunum. DBE was suggested to apply APC to the telangiectatic spots, but this won’t address the dilated veins that’s why we preferred consulting intervention radiology to deal with both the intestinal lesions and the aneurysm itself as the main cause of this condition, but unfortunately no definitive intestinal lesions were seen in the angiography CT and the aneurysmal anatomy wasn’t suitable for intervention, also endovascular surgical consultation declined the portal vein reconstruction possibilities due to the difficulty and procedural risks. We advised the patient to continue on supportive treatment and blood transfusion when needed.

References

Kurtcehajic, A., Zerem, E., Alibegovic, E., Kunosic, S., Hujdurovic, A. and Fejzic, J.A., 2023. Portal vein aneurysm-etiology, multimodal imaging and current management. World Journal of Clinical Cases, 11(4), p.725.

Clinical Case Summary

Bouveret syndrome is a rare type of ileus caused by the impaction of large gallstones that pass through a cholecystoenteric fistula in the duodenum.Although endoscopic treatment is preferable over surgery for patients with Bouveret,1 some difficulties in endoscopic procedures must be overcome.2 Herein, we describe the usefulness of combined endoscopic procedures of electrohydraulic lithotripsy (EHL) and new technique by using the guide wire as a snare (Figure1).72 years old female patient known chronic liver disease and splenomegaly came to the emergency department by progressive abdominal pain, persistent vomiting, and weight loss two months ago. Upper Endoscopy was arranged next day and showed hugely dilated stomach with remnant food (signs of Gastric outlet obstruction) down to large stone at second part of duodenum totally obstructing lumen and a fistulous opening. MRCP was done and revealed: dilated Common Bile Duct about 10 mm down to its lower with extensive air in the biliary tree, dilated IHBRs with extensive pneumobilia, collapsed thick-walled gall bladder with air inside and large 35x55 mm impacted stone in the second part of the duodenum. An attempt using Biliary Electrohydraulic lithotripsy (EHL) was done, EHL over 3 hours was with minimal effect as the stone was hard and decreased the stone size to about 4 cm but it is still lodged in the angle, and we couldn’t grasp it by snare.We used Boston scientific guidewire 0.035 to create an open snare which overlapped the stone in its place then gradually pulled to the stomach. Over another 4 hours we used EHL and Lithotripsy stone extractor to destroy the stone into small fragments less than 1 cm.The stone was destroyed. The duodenum was reevaluated and circumferential ulcerations was noted with complete healing of fistula. The patient started oral intake 24 hours after the procedure with no abdominal pain or vomiting. Long term follow up of the patient showed marked weight gain with no adverse effects.

References

1. Cappell MS, Davis M. Characterization of Bouveret’s syndrome: A comprehensive review of 128 cases. A m J G a s t r o e n t e r o l 2006;
101: 2139–46.
2. Caldwell KM, Lee SJ, Leggett PL, Bajwa KS, Mehta SS, Shah SK. Bouveret syndrome: Current management strategies. C l i n E x p
69–75.

Introduction

Intraductal papillary mucinous neoplasms (IPMN) is one of the main pancreatic ductal adenocarcinoma precursors, characterized by a remarkable morphological and spatial heterogeneity. This phenotypical heterogeneity is reflected in IPMN prognosis, with gastric phenotype IPMNs being more often branch-duct and low-grade lesions. There is no biomarker to predict which lesion will progress, complexifying the clinical surveillance scheme. Infiltration of immune cells and fibroblasts in tumor microenvironment (TME) may play a role in this phenotypic heterogeneity.

Aims & Methods

The aim of the present study was to describe the molecular heterogeneity of IPMN lesions at a transcriptional level and their TME. All histological slides from 135 paraffin embedded (FFPE) surgical pancreatic resections for IPMN (2013-2023) were reviewed for selection of regions of morphological interest (ROI) depending on IPMN phenotype and dysplasia. A total of 420 morphologically homogeneous ROI were microdissected for RNA sequencing and 22 from mixed phenotype for DNA sequencing. Additionally, 127 regions adjacent to IPMN lesions were annotated for immunochemistry to quantify immune cell and fibroblast infiltration. Proliferation index was quantified for all microdissections by Ki67 immunostaining.

Results

Among the 135 resections, 49 (36%) were pure gastric, 54 (40%) pure intestinal, 6 (4%) pure pancreatobiliary (PB) and 26 (19%) displayed a mixed phenotype (2 or 3 different phenotypes within the same specimen). Out of the 420 microdissections, 181 were gastric (22% high grade), 195 intestinal (40% high grade) and 44 PB (all high grade). Unsupervised analysis showed an important overlap of gastric and PB phenotype in contrast with intestinal IPMNs. Samples from mixed phenotypes tended to cluster independently and 8 out of 22 showed a common clonal origin. In non-intestinal samples, HG lesions clustered in 2 groups, one purely composed of gastric phenotype and a distinct one composed of gastric and PB. In intestinal samples, HG samples poorly clustered suggesting a biological continuum. Indeed, genes overexpressed in intestinal samples were enriched for cell division and proliferation pathways and the ki67 was significantly higher in intestinal (mean 24% ± 16) compared to gastric samples (mean 6% ± 6.4, p<0.0001). Overexpressed genes in gastric samples were highly enriched in immune response pathways. In fact, TME CD4 and CD8 T cell infiltration was significantly higher in gastric and PB compared to intestinal samples and this, independently of grade of dysplasia. Yet, PB samples displayed a significantly higher TME infiltration of active fibroblasts, regulatory T cells, M2 macrophages and neutrophils compared to gastric and intestinal phenotypes.

Conclusion

Our findings highlight the transcriptomic and microenvironmental heterogeneity of IPMN phenotypes, with distinct molecular programs and immune landscapes associated with each subtype. While intestinal IPMN are characterized by a proliferative, immune-cold profile irrespective of dysplasia grade, gastric and PB lesions show marked immune infiltration, with PB lesions enriched in immunosuppressive cell populations. These results suggest that TME composition may contribute to the differential progression potential of IPMN subtypes and provide a rationale for phenotype-specific biomarkers and interception strategies.

Introduction

Predicting choledocholithiasis in acute pancreatitis is challenging. Existing predictive models typically rely on the common bile duct (CBD) width, a parameter difficult to assess reliably. We aimed to develop a model based solely on easily available clinical and laboratory markers, excluding CBD width.

Aims & Methods

We conducted a retrospective cohort study of 348 patients treated for acute pancreatitis at the LMU University Hospital in Munich, Germany, between 2005 and 2021. A Random Forrest (RF) model was developed using the TensorFlow Decision Forests (TFDF) library with 14 clinical and laboratory features, excluding CBD width. Model performance was assessed using sensitivity, specificity, predictive values, and area under the receiver operating characteristic curve (AUC-ROC).

Results

Of 348 patients with acute biliary pancreatitis, 167 (48.0%) had CBD stones. Our model achieved a sensitivity of 92.3%, a negative predictive value (NPV) of 83.3%, and an AUC-ROC of 0.739. Compared to using CBD width ≥8 mm or bilirubin ≥4 mg/dl as predictors (as guidelines recommend), our model demonstrated superior sensitivity (92.3% vs. 79.5% vs. 30.8%, respectively) and NPV (83.3% vs. 74.3% vs. 54.8%, respectively). The rate of missed intraductal concrements was substantially lower with our model (4.3% vs. 41.4%). In subgroup analysis, our model performed better in predicting stones (AUC=0.8) than microlithiasis or sludge (AUC=0.623).

Conclusion

We developed the first machine learning-based score to predict choledocholithiasis in acute pancreatitis without relying on CBD width. The model's high sensitivity and NPV make it a promising tool for clinical decision-making, specifically for hospitals without the option of endosonography.

Disclosure

SS is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 413635475 - and the LMU Munich Clinician Scientist Program (MCSP).