Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers for which few curative therapies are available to date. Acute pancreatitis (AP) is uncommon manifestation of PDAC. Heat shock proteins are important for a dynamic range of cellular processes that include protection against cell stress and inflammation. The inducible heat shock proteins-90 (HSP90) are anti-oxidative, anti-inflammatory and cytoprotective enzymes, however their upregulating role remains unknown in AP leading to PDAC. We hypothesize that the elevation of HSP90 during acute pancreatitis could accelerate the development of PDAC. Method: Patients with acute pancreatitis (n= 50) and age-and sex-matched PDAC patients (n=48) were studied. Peripheral blood samples from AP and PDAC patients were collected on admission and stored -80C. Heat shock protein 90 alpha (HSP90 alpha) in human patient serum was quantitatively detected by a double-antibody sandwich enzyme-linked immunosorbent assay (Invitrogen, USA). Statistical analysis was performed using SAS 9.4. Results: The subjects were categorized into 2 groups based on HSP-90 levels results. For the AP group high HSP-90 was defined as adjusted HSP-90 > 26.5 ng/ml and low HSP-90 as adjusted HSP-90 <= 26.5 ng/ml. For the PDAC group, high HSP-90 as adjusted HSP-90 > 14.25 ng/ml and low HSP-90 as adjusted HSP90 <= 14.25 ng/ml. Furthermore, univariable and multivariable hazard model analysis revealed that high HSP-90 levels implied the probability of death significant increase by about three times (P-value = 0.0445) by adjusting with covariates of gender, age, race, ethnicity, marital status, BMI, pancreatitis, treatment, and max tumor size. Conclusion: High serum levels of HSP-90 may be a risk factor and independent prognostic indicator for tumorigenesis in pancreatic ductal adenocarcinoma.

Purpose: Liver transplantation is the only treatment for patients with liver failure. It remains a challenge in surgical decision making for the best donor-to-recipient match during allocation processes, and to foresee postoperative complications and outcomes. In this study, we evaluate the utilization of machine learning models and establish for predicting short term mortality and survival in liver transplant recipients. Method: In a cohort study, the clinical findings of 134 patients who underwent liver transplant surgery (January, 2012-January, 2022) were analyzed. To model the three months to one year survival of such patients, different machine learning models (classifiers) were applied, prediction accuracy was compared using the area under the receiver operating characteristic curve (ROC). Furthermore, Kaplan-Meier method was used to estimate the survival probabilities in different years duration. The optimal set for the prediction of the mortality was selected by a wrapper method based on binary measures. Results: Data is currently being analyzed. Conclusion: Our preliminary approach could serve as an accurate method to assess preoperative mortality risk, postoperative outcomes and short term survival in liver transplantation.

Description and comparison of cohort characteristics and outcome of adult patients with out-of-hospital cardiac arrest (OHCA) attributed to poisoning (P-OHCA) versus patients with OHCA attributed to other medical causes (NP-OHCA).We included all patients who received cardiopulmonary resuscitation after OHCA between January 2011 and December 2020 from German emergency medical services with good data quality in the German Resuscitation Registry. Exclusion criteria: patients < 18 years of age or OHCA attributed to trauma, drowning, intracranial bleeding or exsanguination.Patients with P-OHCA (n = 574) were significantly younger compared to NP-OHCA (n = 40,146) (median age of 43 (35–54) years vs. 73 (62–82) years; p < 0.001). Cardiac arrest in P-OHCA patients was significantly less often witnessed by bystanders (41.8 % vs. 66.2 %, p < 0.001). Asystole was the predominant initial rhythm in P-OHCA patients (73.5% vs. 53.7%, p < 0.001) while ventricular fibrillation (VF) and pulseless electrical activity (PEA) were less common (9.2% vs. 25.1% and 16.2 % vs. 20.5%, p < 0.001). P-OHCA had a higher chance of survival with good neurological outcome at hospital discharge (15.2 vs. 8.8 % p < 0.001) and poisoning was an independent protective prognostic factor in multivariate analysis (OR 2.47, 95%-CI [1.71–3.57]). P-OHCA patients with initial PEA survival with good neurological outcome was comparable to initial VF (34.3 % vs. 37.7%).Patients in the P-OHCA group had a significantly higher chance of survival with good neurological outcome and PEA as initial rhythm was as favourable as initial VF. Therefore, in P-OHCA patients resuscitation efforts should be extended.

Aims Ampullary lesions (AL) can be resected by endoscopic-papillectomy (EP), surgical-ampullectomy (SA) and pancreaticoduodenectomy (PDD). However, consistent data analyzing the different methods are lacking. We compared outcome and complications of EP and surgery in matched patients of a large retrospective multicenter study.

Introduction: Genome assessment shows promise as a potential method for predicting acute pancreatitis (AP) severity. We hypothesized that Heat Shock Protein 70 (HSP70) single nucleotide polymorphisms (SNPs) and expression changes may play a role in early detection of acute pancreatitis severity. Methods: A total of 57 AP patients and 52 age- and sex-matched healthy controls were studied. Peripheral blood samples from pancreatitis patients were collected upon admission. Two SNPs of the HSP70-gene family were selected. RNA was extracted parallel to genomic DNA from AP patients (N=12) and healthy controls (N=21).Gene expression of two HSP70 family members HSPA1A and HSPA1L was measured using TaqMan gene expression assays via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: Major allele frequency in HSPA1A gene was 1 (A>G) for AP patients and 1 (A>G) for controls. For HSPA1A, the gene major allele frequency was 0.672 (A>C) for patients and 0.7 (A>C) for controls, the major allele frequencies were 0.638 (A>G) and 0.672 (G>C) for patients and 0.85 (A>G) and 0.65 (G>C) for controls, respectively. The allele frequencies differed between AP patients with organ failure and those with mild disease. Following gene expression of HSPA1L and SNP relationship analysis, AP patients with heterozygous genotype had higher expression levels as compared to non-AP patients (p=0.014). Conclusions: Our data suggest that polymorphism of the HSP70 promoter region may be a risk factor for developing severe acute pancreatitis. Further study to determine the urine levels of HSP70 protein expression is needed to confirm the protective mechanism of HSP70.

Hintergrund Ampulläre Läsionen (AL) können entweder endoskopisch via Papillektomie (EP), via chirurgischer Ampullektomy (SA) oder Pankreatikoduodenektomie (PD) reseziert werden. Da vergleichende Studien nicht verfügbar sind führten wir eine retrospective multizentrische Studie durch, um gematchte Daten zu EP und PD zu vergleichen.

Aims Ampullary lesions (AL) are a rare condition but may be clinically significant by obstruction, jaundice, bleeding or malignant transformation. Main resection techniques comprise the endoscopic papillectomy (EP), the surgical ampullectomy (SA) and pancreaticoduodenectomy (PD). Since consistent comparative data are lacking, we performed a retrospective multicenter center study (Endoscopic-Papillectomy-versus-Surgical-Ampullectomy-versus-Pancreaticoduodectomy (ESAP)) comparing the most frequent procedures, i.e. EP and PD.

Ampullary lesions (ALs) can be treated by endoscopic (EA) or surgical ampullectomy (SA) or pancreaticoduodenectomy (PD). However, EA carries significant risk of incomplete resection while surgical interventions can lead to substantial morbidity. We performed a systematic review and meta-analysis for R0, adverse-events (AEs) and recurrence between EA, SA and PD. Electronic databases were searched from 1990 to 2018. Outcomes were calculated as pooled means using fixed and random-effects models and the Freeman-Tukey-Double-Arcsine-Proportion-model. We identified 59 independent studies. The pooled R0 rate was 76.6% (71.8–81.4%, I2 = 91.38%) for EA, 96.4% (93.6–99.2%, I2 = 37.8%) for SA and 98.9% (98.0–99.7%, I2 = 0%) for PD. AEs were 24.7% (19.8–29.6%, I2 = 86.4%), 28.3% (19.0–37.7%, I2 = 76.8%) and 44.7% (37.9–51.4%, I2 = 0%), respectively. Recurrences were registered in 13.0% (10.2–15.6%, I2 = 91.3%), 9.4% (4.8–14%, I2 = 57.3%) and 14.2% (9.5–18.9%, I2 = 0%). Differences between proportions were significant in R0 for EA compared to SA (p = 0.007) and PD (p = 0.022). AEs were statistically different only between EA and PD (p = 0.049) and recurrence showed no significance for EA/SA or EA/PD. Our data indicate an increased rate of complete resection in surgical interventions accompanied with a higher risk of complications. However, studies showed various sources of bias, limited quality of data and a significant heterogeneity, particularly in EA studies.

Background: During pancreatitis, autophagy is activated, but lysosomal degradation of dysfunctional organelles including mitochondria is impaired, resulting in acinar cell death. Retrospective cohort analyses demonstrated an association between simvastatin use and decreased acute pancreatitis incidence. Methods: We examined whether simvastatin can protect cell death induced by cerulein and the mechanisms involved during acute pancreatitis. Mice were pretreated with DMSO or simvastatin (20 mg/kg) for 24 h followed by 7 hourly cerulein injections and sacrificed 1 h after last injection to harvest blood and tissue for analysis. Results: Pancreatic histopathology revealed that simvastatin reduced necrotic cell death, inflammatory cell infiltration and edema. We found that cerulein triggered mitophagy with autophagosome formation in acinar cells. However, autophagosome-lysosome fusion was impaired due to altered levels of LAMP-1, AMPK and ULK-1, resulting in autophagosome accumulation (incomplete autophagy). Simvastatin abrogated these effects by upregulating LAMP-1 and activating AMPK which phosphorylated ULK-1, resulting in increased formation of functional autolysosomes. In contrast, autophagosomes accumulated in control group during pancreatitis. The effects of simvastatin to promote autophagic flux were inhibited by chloroquine. Mitochondria from simvastatin-treated mice were resistant to calcium overload compared to control, suggesting that simvastatin induced mitochondrial quality control to eliminate susceptible mitochondria. Clinical specimens showed a significant increase in cell-free mtDNA in plasma during pancreatitis compared to normal controls. Furthermore, genetic deletion of parkin abrogated the benefits of simvastatin. Conclusion: Our findings reveal the novel role of simvastatin in enhancing autophagic flux to prevent pancreatic cell injury and pancreatitis.