Introduction

EUS-guided pancreatic duct drainage (EUS-PDD) is an endoscopic procedure which is indicated in symptomatic patients with evidence of pancreatic duct obstruction after failure or impossibility to perform transpapillary drainage or EWSL in the contest of chronic pancreatitis or altered anatomy causes (e.g. Whipple or Roux-en-Y surgery). Nowadays, it is a challenging procedure performed by few endoscopist. Clinical and technical success rate is still lacking and heterogenous, therefore acquisition of new data and experience is necessary.

Aims & Methods

This study aims to describe our initial endoscopic experience evaluating also some clinical aspects. This is a retrospective observational single-center study including patients (pts) undergone EUS-PDD from March 2018 to July 2023 using plastic stent (7Fr 10cm), delivered with an electrocautery-enhanced catheter, after failure or impossibility to transpapillary drainage. It was evaluated exocrine pancreatic function by fecal elastase (FE-1) and nutritional markers (prealbumin and magnesium).

Results

Total of 15 pts with median age of 72 years old. 13 pts (86.6%) had a chronic pancreatitis diagnosis with radiological evidence duct pancreatic alterations (5 stenosis, 3 lithiasis, 4 both, 1 duct rupture); 2 pts had a post-surgical stenosis. All pts were symptomatic: 6 pts (40%) shows multiple episodes of acute pancreatitis and 9 (60%) had abdominal pain non responder to medical therapy. Pancreatic duct had median dilatation of 7 mm (4-15.6 mm). Every transmural access was performed through gastric wall with single plastic stent (7Fr 10cm) placement. Technical success was obtained in 11 pts (73%) of which 2 pts had early stent migration; in 4 pts (26.6%) EUS-PDD failed. No other adverse events. 13 (86.6%) had a condition of pancreatic exocrine insufficiency: FE-1 between 200 µg/g and 100 µg/g in 8 pts and FE-1 < 100 µg/g in 5 pts under pancreatic enzyme replacement therapy. Magnesium median value was 0.74 mmol/L (0.5-0.8 mmol/L) and prealbumin median value was 0.22 g/L (0.11-0.26 g/L), both at the low normal serum level. After 4 weeks, it was placed a second plastic stent in 8 pts and during clinical follow-up (3 and 6 months), pts had no pain and described improvement of general quality of life and nutritional markers.

Conclusion

EUS-guided pancreatic duct drainage remains a challenging endoscopic procedure indicated only for selected cases and performed by expert endoscopists. However, it seems to have a reasonable clinical success rate but we need further data to improve endoscopic experience and clinical awareness.

References

1. Chandan S et al. Efficacy and safety of endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD): A systematic review and meta-analysis of 714 patients. Endosc Int Open. 2020 Nov;8(11):E1664-E1672.
2. Teh JL et al. Techniques and Outcomes of Endoscopic Ultrasound Guided-Pancreatic Duct Drainage (EUS- PDD). J Clin Med. 2023 Feb 17;12(4):1626.

Introduction

Pancreatic exocrine insufficiency (PEI) is defined as a reduction of pancreatic exocrine activity in the intestine at a level that prevents normal digestion(1). PEI leads to malnutrition-related complications and a reduced quality of life. Faecal pancreatic elastase is an ideal biomarker to assess pancreatic function in patients experiencing PEI. Due to its high stability, faecal pancreatic elastase is concentrated during intestinal passage, thus reflecting the total overall pancreatic secretion.

Aims & Methods

The aim of this work was to evaluate the clinical performance of a particle-enhanced turbidimetric immunoassay (PETIA) that allows automated quantification of pancreatic elastase in faecal extracts on clinical chemistry analyzers. Hundred and eighty-nine samples from 76 controls and 113 diagnosed patients were used to compare the turbidimetric immunoassay and a reference ELISA assay performance. For both assays, sensitivity and specificity were determined using a cutoff of 200 μg/g. Moreover, for samples within the measuring range for both assays, a kappa value and the overall agreement were assessed.

Results

A better clinical performance was obtained by the turbidimetric immunoassay compared to the reference ELISA assay. The turbidimetric immunoassay revealed a sensitivity and specificity of 78% and 74%, respectively, while the reference ELISA assay revealed a sensitivity and specificity of 74% and 68%, respectively. The hundred and twelve samples used to perform a method comparison showed a relative bias at the cutoff (200 μg/g) of -5.72% and an overall analytical agreement between the turbidimetric immunoassay and the reference ELISA assay of 85.7%. Cohen’s kappa agreement showed a substantial agreement of 0.70.

Conclusion

The turbidimetric immunoassay showed good diagnostic performance and a strong agreement with the reference ELISA assay. The particle-enhanced turbidimetric immunoassay is an accurate, non-invasive, automated test and an ideal assay for large-scale determination of pancreatic elastase levels in fecal extracts.

References

(1) Philips ME, et al. BMJ Open Gastro 2021; 8: e000643

Disclosure

“All authors are employees of BÜHLMANN Laboratories AG”

Clinical Case Summary

54-year-old male, with gastroesophageal reflux disease medicated with PPIs, was admitted due to acute exacerbation of watery chronic-diarrhea (>10 bowel movements/day). The patient was dehydrated, hypotensive and presented acute-kidney-injury AKIN-3. Abdominal CT-scan identified diffuse gastric wall-thickening and a 20 mm nodule at the gastroduodenal junction. Due to suspicion of Zollinger-Ellison Syndrome (ZES), the PPI-dose was optimized with symptomatic improvement. Subsequently, for hormonal assay, PPI was switched to an H2 blocker. Approximately 72h after the switch, melena with hemodynamic instability was identified, and upper-endoscopy revealed extensive duodenal peptic ulcer disease (Forrest-IIc and III ulcers). After 72h without PPI, gastrin 4390 ng/L and gastric-pH 2.9 were documented.
The hospitalization was marked by two episodes of upper gastrointestinal haemorrhage (UGIH), with hemodynamic instability and admission in the intensive care unit. Besides PPI and endoscopic-hemostatic-therapy (EHT), octreotide was initiated. PET-DOTATOC-Ga-68 scan revealed nodal metastasis. The patient underwent antrectomy with Y-Roux-reconstruction (neuroendocrine-tumor, mitotic-index < 1/2mm², ki67 <3%, pT2N1-R2). On the 2nd postoperative-day, UGIH recurrence with hemodynamic instability occurred, leading to re-laparotomy and intraoperative retrograde-enteroscopy with EHT (Over-the-scope-Clip) and gastroduodenal artery ligation. The patient remained stable, without UGIH, and gastrin 20 ng/L. After 2-months, he was discharged and referred to Oncology (N1R2).
ZES caused by gastrinomas, is a rare condition requiring high clinical suspicion and symptoms typically begin years before diagnosis. Metastatic disease determines prognosis, but complications are associated with considerable morbimortality. This case illustrates the diagnostic/treatment dilemmas of ZES and gastrinoma staging/treatment, as well as the therapeutic challenge of one of its most feared complications, UGIH.

References

Image 1 - Abdominopelvic CT scan showing gastric wall thickening and a nodule in the gastrinoma triangle.
Image 2 - Upper gastrointestinal endoscopy – upper gastrointestinal haemorrhage.
Image 3 - PET-DOTATOC-Ga-68 scan result – tumor and nodal metastasis
Image 4 - Histopathological study of the surgical specimen compatible with neuroendocrine tumor - H&E as well as neuroendocrine markers.

Disclosure

Nothing to declare

Introduction

Drug-induced liver injury (DILI) caused by metamizole has gained increasing attention in recent years^{1, 2}. However, causality assessment remains a challenge, in particular in patients with multiple drug intake.

Aims & Methods

We further characterized metamizole DILI cases with the goal to identify typical patterns that can help adjudication. To this end, the data of 88 patients with metamizole intake from our prospective study on acute liver injury with potential drug-related cause were analysed. DILI diagnosis and causality assessment was based on clinical, laboratory and histological features as well as expert adjudication³. Alternative causes of liver injury were identified or ruled out by a thorough hepatological work-up.

Results

DILI was associated with metamizole in 63 of 324 DILI patients from our cohort (prevalence 19.4%). Out of the remaining 25 patients with metamizole intake, nine patients suffered from non-metamizole DILI and 16 patients from an alternative cause for liver injury (mainly autoimmune hepatitis [n=10] and biliary obstruction [n=4]). A distinctive phenotype was observed in 45 of the 63 metamizole DILI cases, which was characterized by a relatively long latency from the start of drug intake until recognition of liver injury (median: 51 days), high transaminases at onset (aspartate aminotransferase [AST] 36.9xULN, alanine aminotransferase [ALT] 42.5xULN) and a delayed peak of bilirubin with a median of 7 days after DILI recognition. Patients with this phenotype had higher rates of jaundice (100.0% vs. 62.8%, p<0.001), coagulopathy (73.7% vs. 20.9%, p<0.001) and acute liver failure (40.0% vs. 7.0%, p<0.001) when compared to metamizole DILI cases without this clinical picture, non-metamizole DILI and non-DILI controls, however remission rates did not differ significantly when compared to the controls (71.1% vs. 76.7%, p=0.481) or to the recovery rates described in larger registry studies on DILI in general⁴. Overall, adverse outcome as defined by death or liver transplantation was observed in nine patients with metamizole DILI (14.3%). On multivariate analysis, AST and INR at DILI recognition were the only parameters independently associated with this endpoint. Regarding prediction of an adverse outcome INR had the highest discrimination (c-statistic 0.89, 95% confidence interval [CI]: 0.74-0.99) and with this performed better than Hy’s law, transaminases, bilirubin or the model for end-stage liver disease (MELD) score at baseline in terms of prognosis. INR at a cut-off of ≥1.95 showed a sensitivity and specificity as high as 77.8% and 93.5% for an adverse outcome.

Conclusion

Patients with DILI due to metamizole can present with a specific pattern which can help to identify metamizole as the causative agent and avoid erroneous association of liver injury with innocent bystander medication. Outcome, however, is not associated with this clinical picture and should rather be predicted by AST and especially INR at onset.

References

1 Sebode M, Reike-Kunze M, Weidemann S, et al. Metamizole: An underrated agent causing severe idiosyncratic drug-induced liver injury. Br J Clin Pharmacol. 2020;86(7):1406-15.
2 Weber S, Benesic A, Neumann J, et al. Liver injury associated with metamizole exposure: features of an underestimated adverse event. Drug Saf. 2021;44(6):669-80.
3 Bjornsson ES, Stephens C, Atallah E, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115-26.
4 Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study. Gastroenterology. 2015;148(7):1340-52 e7.

Disclosure

Sabine Weber and Alexander L. Gerbes received funding from TransBioLine (Translational Safety Biomarker Pipeline (TransBioLine): Enabling development and implementation of novel safety biomarkers in clinical trials and diagnosis of disease; Grant Agreement ID: 821283). The TransBioLine project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 821283. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.