Introduction

Despite advances with chemotherapy regimens, Pancreatic adenocarcinoma (PDAC) is becoming the 2^nd cause of cancer-related death. Personalized medicine will be the game changer, but molecular characterization of pancreatic neoplasms is yet extremely cumbersome and has been performed on surgical samples or few EUS-tissue acquisition (TA) cases, mostly for DNA analysis. Our aim was to evaluate DNA and RNA extracted for research purposes from pancreatic neoplasms employing Endoscopic Ultrasound (EUS) Fine needle aspiration (FNA) and biopsy (FNB) and adequacy to molecular analyses.

Aims & Methods

From Oct 2022, patients with solid pancreatic neoplasms suggestive of either PDAC or neuroendocrine neoplasm (NEN) undergoing diagnostic EUS-TA were considered for enrollment. Employed needles were either FNA, or Franseen, Fork-tip or Three-prong, either 22G or 25G based on operator’s preference, with Rapid on Site Evaluation and, in case of adequacy within the first 2 passes, 1 additional pass with the same needle was performed for molecular analyses. DNA and RNA were then extracted with a new technique and nucleic acids were quantified and evaluated for adequacy for molecular analysis. Mann-Whitney was employed for comparison of continuous variables, and Kruskal-Wallis test for comparison between multiple groups; Logistic regression was applied to determine factors associated with adequacy to molecular tests.

Results

351 patients underwent sampling for molecular analyses, 309 with a definitive diagnosis of PDAC and 42 with NEN. 92,9% of patients were sampled with 25G FNA needles. Median quantity of DNA extracted was significantly lower in PDAC 2048 ng (95%CI: 1470 -3651) compared to NEN 6752 ng (95%CI: 3502-9655)(p<0.0144). Mean quantity of RNA extracted was similar, 312 ng for PDAC, and 444 ng for NEN (p=0.07), with a higher median RIN of 6,4 (95%CI:6,2-6,5) for PDAC versus 4,7 (95%CI:3,9-5) for NEN (p<0.0001). In terms of needle type, concerning DNA extraction, 25G FNA needles retrieved a median of 3384 ng, 25G Franseen needles (4312 ng), 22G Franseen (73864 ng), 25G Fork-tip or Three-prong (3104 ng), with no significant difference. In terms of needle type, concerning RNA extraction, 25G FNA needles retrieved a median of 310 ng (RIN 6,3), 25G Franseen needles 460 ng (RIN 5,5), 22G Franseen 884 ng (RIN 5,9), 25G Fork-tip or Three-prong 301 ng (RIN 5,15), with no significant difference. 295 (95,5%) of PDAC samples and 34 (80,9%) of NEN samples were considered adequate for sequencing. The only factor associated to adequacy for molecular analysis was tumor type, with PDAC having an OR of 5,44 (95%CI 2,06-14,37)(p=0.0006), while the type of employed needle was not

Conclusion

Molecular analysis on EUS-acquired tissue of pancreatic neoplasms will be the mainstay of personalized therapies but how to best perform tissue acquisition and sample handling for this specific purpose is yet to be defined. This is the largest study ever performed on DNA and RNA extraction from EUS-acquired samples, demonstrating superior adequacy for molecular analysis in PDAC compared to NEN. All needle types result similar in terms of performance despite the low number of needles other than 25G FNA needles.

Introduction

In patients with chronic pancreatitis (CP), pancreatic exocrine insufficiency (PEI) and poor nutritional intake may cause nutritional deficiencies. Guidelines advise monitoring key nutrients and supplementing is case of deficiency to prevent malnutrition-related complications. However, adherence remains low, possibly due to limited evidence on the clinical relevance of single nutrient deficiencies and the benefit of targeted supplementation. The aim of this study is to evaluate the prevalence of nutritional deficiencies in patients with CP and to identify predictors of those at highest risk. Secondary, we seek to explore association between nutritional deficiencies and malnutrition-related complications, and to provide insight into the natural course of nutritional deficiencies.

Aims & Methods

We analyzed data from the COMBO-trial, a nationwide stepped-wedged cluster randomized trial to evaluate the effect of an evidence-based algorithm for the management of CP. Measurements of fat-soluble vitamins, minerals, and albumin conducted in the outpatient clinic during the 35-month study period were included. PEI was defined as fecal elastase-1 concentration <200 µg/g or the use of pancreatic enzyme replacement therapy (PERT). The Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q), designed to evaluate the severity of PEI symptoms, was administered at four distinct time points throughout the study. Supplement use was collected from health records and patient questionnaires. Multivariate logistic regression analysis was performed for the presence of multiple deficiencies. Potential predictors included patient and disease characteristics at baseline and the mean score of the PEI-Q during follow-up.

Results

In total 409 patients were included in this study. At baseline 327 (80.0%) had PEI and PERT was used by 297 (72.6%). Nutritional deficiencies were present in 195 patients (47.7%) of which 81 (19.8%) had multiple deficiencies. The prevalence of deficiencies included vitamin A in 13/172 (7.6%) patients, vitamin D 111/289 (38.4%), vitamin E 15/168 (8.9%), vitamin K 52/88 (59.1%), iron 44/137 (32.1%) calcium 4/198 (2.0%), magnesium 24/132 (18.2%) zinc 13/67 (19.4%), selenium 4/42 (9.5%), and albumin in 41/288 (14.2%) patients. No abnormal coagulation was observed in the 20 patients with vitamin K deficiency and available INR measurements. Osteopenia was diagnosed in 110/236 (46.6%) and osteoporosis in 56/236 (23.7%). Deficiencies in vitamin K and vitamin D, micronutrients critical to bone metabolism, were not associated with osteopenia or osteoporosis. Of 44 patients with an iron deficiency, 22 (50%) were anemic. Deficiency resolved without single nutrient supplementation in 71.4% (vitamin A), 75.0% (vitamin D), 50.0% (vitamin E) , 33.3% (vitamin K), 63.6% (iron), 100% (magnesium), 80.0% (zinc) of cases. Independent predictors for multiple deficiencies were more severe PEI symptoms (OR 1.86, 1.09 – 3.17) and daily alcohol consumption (OR 2.80, 1.27 – 6.18).

Conclusion

Nutritional deficiencies are present in approximately half of the patients with CP. Most nutritional deficiencies resolve without single nutrient supplementation. Predictors for multiple nutritional deficiencies were severity of PEI symptoms and daily alcohol consumption. Therefore, nutritional deficiencies should be considered a marker of malnutrition, with treatment focused on addressing the underlying cause rather than isolated correction through single nutrient supplementation.

Introduction

Pain in acute pancreatitis is the symptom to be treated urgently. There are currently no recommendations for analgesic management. Intravenous lidocaine has both analgesic and anti-inflammatory effects. Its use has never been evaluated for analgesia in acute pancreatitis. The aim of our study was therefore to evaluate the efficacy and safety of intravenous lidocaine in the management of acute pancreatitis resistant to level I and II analgesics.

Aims & Methods

We conducted a retrospective, monocentric study between January 2015 and December 2021. Patients visiting the emergency department for proven acute pancreatitis and presenting with pain resistant to group I and II analgesics, hospitalized in the hepato-gastroenterology department and treated with intravenous lidocaine, were included. Pain was assessed by retrospective collection of numerical pain scales (NPS) at the emergency department, and at each analgesic re-evaluation. Treatment efficacy was defined as the absence of need for a Level III analgesic (opioids).

Results

154 patients, hospitalized in our gastroenterology unit for acute pancreatitis and presenting with pain refractory to level I and II analgesics treated with intravenous lidocaine were included. Patients were predominantly male, with a median age of 48.5 years [37.0; 58.0]. The main etiology of acute pancreatitis was ethylic in 36% of cases. Acute necrotizing pancreatitis was present in 69% of patients. 44/154 patients received a bolus of opioid morphine in the emergency department before the administration of lidocaine. Lidocaine was prescribed in a continuous way at the dose of 2g/24h (intravenous administration with electric syringe). The median NPS before prescription of lidocaine was 8.0 [7.00; 9.00]. Lidocaine treatment was effective in 88.7% of patients (136/154). 1.3% of patients experienced lidocaine-related adverse events such as skin rash and dysgeusia. In univariate analysis, patients requiring intensive care or developing an acute respiratory distress syndrome were significantly more likely to fail lidocaine (respectively OR = 5.83; CI [1.69; 20.06]; p=0.01 and OR = 4.23; CI [1.44; 12.43]; p=0.009).

Conclusion

Intravenous lidocaine administration appears to be effective and safe for pain control in 89% of patients failing to level I and II analgesia. Further prospective studies are needed to confirm these results.
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Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a cornerstone in the diagnosis and treatment of pancreatobiliary diseases. However, it carries the risk of complications including potentially fatal post-ERCP pancreatitis (PEP). Despite ongoing efforts, effective strategies for managing PEP remain unestablished. Current guidelines define PEP based on symptoms and findings occurring within 24 hours after ERCP; however, early diagnosis and intervention may prevent its incidence and severity. Recently, urinary trypsinogen-2 (UT2) has emerged as a potential biomarker for early acute pancreatitis, but its role and the optimal timing for PEP remain unclear. Therefore, we aimed to evaluate the diagnostic performance of UT2 at multiple time points following ERCP.

Aims & Methods

This is a single-center prospective observational study conducted at The University of Tokyo Hospital. Patients who underwent their initial ERCP at our institution between February 2022 and June 2024 were enrolled. Patients with choledochojejunostomy, biliary pancreatitis, or those undergoing hemodialysis were excluded. UT2 levels were measured using a rapid dipstick test before ERCP, immediately after, and at 1 and 3 hours post-procedure. Serum amylase (AMY) levels were measured 3 hours after ERCP. We evaluated the diagnostic performance (sensitivity, specificity, and accuracy) of UT2 at multiple time points, for the diagnosis of PEP. PEP was defined as an elevation in pancreatic enzyme >3x upper limit of normal with abdominal pain at 24 hours post-pocedure.

Results

A total of 521 patients underwent initial ERCP during the study period, and 337 were included in the final analysis. The median age was 74 years, and 64% were male. A naïve papilla was present in 89% of patients. The indications for ERCP included bile duct stones (39%), malignant biliary obstruction due to pancreatic cancer (13%) or non-pancreatic cancer (18%), benign biliary stricture (5%), diagnostic pancreatogram (24%), and others (1.2%). EST, EPBD, and EPLBD were performed in 37%, 6.5%, and 4.5%, respectively. Prophylactic pancreatic stent placement and rectal NSAIDs administration were performed in 29% and 20%, respectively. PEP occurred in 10% (mild 8.6%, moderate 1.2%, and severe 0.3%) of patients. UT2 demonstrated a trend toward higher sensitivity compared to AMY (AMY: 52.9% vs. UT2 at 0 h: 52.9%, 1 h: 64.7%, 3 h: 64.7%), while AMY exhibited significantly higher specificity (AMY: 92.7% vs. UT2 at 0 h: 65.3%, 1 h: 64.7%, 3 h: 65.0%) and accuracy (AMY: 88.7% vs. UT2 at 0 h: 64.1%, 1 h: 64.7%, 3 h: 65.0%). Notably, 28.5% of patients were positive for UT2 prior to undergoing ERCP. These patients were significantly older (79 vs. 71 years, P < 0.01), more likely to have pancreatic cancer (19.8% vs. 9.5%, P = 0.02), and less likely to have chronic pancreatitis (3.1% vs. 12.9%, P = 0.01). After excluding 96 cases (28.5%) who were UT2-positive before ERCP, we further evaluated the diagnostic performance of UT2 and AMY. UT2 at 0 h had lower sensitivity compared to AMY (AMY: 54.2% vs. UT2 at 0 h: 37.5%, 1 h: 54.2%, 3 h: 54.2%). In contrast, specificity was similarly high across all markers (AMY: 91.7% vs. UT2 at 0 h: 88.9%, 1 h: 87.1%, 3 h: 87.1%). Diagnostic accuracy was comparable between AMY and UT2 (AMY: 88.0% vs. UT2 at 0 h: 83.8%, 1 h: 83.8%, 3 h: 83.8%).

Conclusion

UT2 showed slightly lower predictive performance for PEP compared to AMY. However, excluding UT2-positive pre-ERCP improved the diagnostic accuracy. The diagnostic performance plateaued at 1 hour after ERCP, suggesting its potential utility in predicting PEP earlier.

Disclosure

The author is affiliated with Nipro Corporation through a labor-related arrangement, but has received no financial support or remuneration related to this study.

Introduction

Autoimmune pancreatitis (AIP) is a rare disease that can be diagnosed, according to the International Consensus Diagnostic Criteria (ICDC). Contrast-enhanced MRI with MRCP has now largely replaced other imaging techniques and ERCP for the assessment of ductal morphology in AIP. A number of MRI-criteria have been proposed, but due to the rarity of the disease the diagnostic imaging criteria have not yet been systematically validated. Aim of the study is to review and optimize the MR-morphologic diagnostic criteria for AIP in terms of specificity and sensitivity in the diagnosis and differential diagnosis of the pancreaticobiliary system.

Aims & Methods

We analyzed retrospectively hundred-fiftysix (n=156) high-quality MRIs: AIP n=56, chronic pancreatitis (CP) n=25, pancreatic cancer (PDAC) n=25, primary sclerosing cholangitis (PSC) n=25, Non-HPB subjects n=25. The MRI reading was conducted in a blinded fashion, using defined criteria by at least two radiological experts. The statistical analysis was performed by means of Proportion test, Chi-square test or Fisher’s exact test, One-way ANOVA and Cohen’s Kappa Statistic of the level of agreement.

Results

The level of agreement between two readers was moderate to substantial agreement (κ 0.23-0.85). Sausage-like enlargment (Reader 1: Sens 30.91%, Spec 98.98%, NPV 71.85%, accuracy 74.51%; Reader 2: Sens 26.79%, Spec 98.00%, NPV 70.50%, accuracy 72.43%), restricted diffusion (Reader 1: Sens 47.83%, Spec 89.29%, NPV 75.76%, accuracy 74.51%; Reader 2: Sens 56.86%, Spec 73.26%, NPV 74.12%, accuracy 72.30%), delayed enhancement in the venous phase (Reader 1: Sens 8.70%, Spec 83.15%, NPV 63.79%, accuracy 74.10%; Reader 2: Sens 32.61%, Spec 79.31%, NPV 69.00%, accuracy 75.19%), the icicle sign (Reader 1: Sens 10.91%, Spec 100%, NPV 66.67%, accuracy 65.30%; Reader 2: Sens 37.50%, Spec 91.00%, NPV 72.22%, accuracy 71.79%) and hyperenhancement of ductal wall (Reader 1: Sens 14.29%, Spec 96.67%, NPV 67.44%, accuracy 71.90%; Reader 2: Sens 8.51%, Spec 95.45%, NPV 66.14%, accuracy 74.10%) show a good accuracy distinguishing AIP from controls. Apparent diffusion coefficient (ADC) was significantly different between AIP, PDAC and CP (ANOVA). The area under the receiver operating characteristic curve (AUROC) was 0.85 (CI 0.73 – 0.97) and 0.68 (CI 0.51 – 0.85) respectively for CP and PDAC.

Conclusion

Our study showed that the Sausage-like enlargment, restricted diffusion, delayed enhancement in the venous phase, the icicle sign and hyperenhancement of ductal wall show a good accuracy distinguishing AIP from controls.

Introduction

Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy of the pancreas due to limited treatment response and lack of early diagnosis. PDAC accounts for more than 90% of all pancreatic neoplasms and early PDAC may be missed on Computed Tomography (CT) scan due to similar attenuation as healthy pancreas, small size and hidden location.

Aims & Methods

The current study aims at improving detection of PDAC with CT scans using a deep learning model. It uses three different Convolutional Neural Network (CNN) models namely, Visual Geometry Group 19 (VGG19), Residual Neural Network 50 (ResNet-50) and Inception-v3. A compendium of 129,910 abdomen CT images (107 patients) of PDAC patients and 18,942 abdomen CT images (80 patients) of healthy controls were considered from The Cancer Imaging Archive. Additionally, several pre-processing and image augmentation methods were used to prevent overfitting and improve accuracies.

Results

The current model showed high construct validity with markedly lowered computational power. The Inception-v3 model showed the highest accuracy in the detection of PDAC with an accuracy of 97.93%. Specificity of the VGG-19 model was the highest at 98.77 whereas sensitivity was the highest for the Inception-v3 model at 98.75%. Data on the CNN models’ Performance Metrics (accuracy, sensitivity, specificity and area under ROC) ​were all compared.

Conclusion

The deep learning enabled tool accurately detected PDAC on CT scans versus healthy controls. The models were also reasonably sensitive for tumours below 2 cm.

References

1. Ushio J, Kanno A, Ikeda E, et al. Pancreatic Ductal Adenocarcinoma: Epidemiology and Risk Factors. Diagnostics (Basel). 2021;11(3):562. doi:10.3390/diagnostics11030562
2. Qureshi TA, Gaddam S, Wachsman AM, et al. Predicting pancreatic ductal adenocarcinoma using artificial intelligence analysis of pre-diagnostic computed tomography images. Cancer Biomark. 2022;33(2):211-217. doi:10.3233/CBM-210273
3. Ahmed HS. BEYOND TRADITIONAL TOOLS: EXPLORING CONVOLUTIONAL NEURAL NETWORKS AS INNOVATIVE PROGNOSTIC MODELS IN PANCREATIC DUCTAL ADENOCARCINOMA. Arq Gastroenterol. 2024;61:e23107. doi:10.1590/S0004-2803.24612023-117