Autophagy-mediated ferroptosis is involved in development of severe acute pancreatitis.

BACKGROUND: Ferroptosis is a newly recognized form of regulatory cell death characterized by severe lipid peroxidation triggered by iron overload and the production of reactive oxygen species (ROS). However, the role of ferroptosis in severe acute pancreatitis(SAP) has not been fully elucidated. METHODS: We established four severe acute pancreatitis models of rats including the sham control group, the SAP group, the Fer -1-treated SAP (SAP + Fer-1) group, the 3-MA-treated SAP (SAP + 3-MA) group. The SAP group was induced by retrograde injection of sodium taurocholate into the pancreatic duct. The other two groups were intraperitoneally injected with ferroptosis inhibitor (Fer-1) and autophagy inhibitor (3-MA), respectively. The model of severe acute pancreatitis with amylase crest-related inflammatory factors was successfully established. Then we detected ferroptosis (GPX4, SLC7A1 etc.) and autophagy-related factors (LC3II, p62 ect.) to further clarify the relationship between ferroptosis and autophagy. RESULTS: Our study found that ferroptosis occurs during the development of SAP, such as iron and lipid peroxidation in pancreatic tissues, decreased levels of reduced glutathione peroxidase 4 (GPX 4) and glutathione (GSH), and increased malondialdehyde(MDA) and significant mitochondrial damage. In addition, ferroptosis related proteins such as GPX4, solute carrier family 7 member 11(SLC7A11) and ferritin heavy chain 1(FTH1) were significantly decreased. Next, the pathogenesis of ferroptosis in SAP was studied. First, treatment with the ferroptosis inhibitor ferrostatin-1(Fer-1) significantly alleviated ferroptosis in SAP. Interestingly, autophagy occurs during the pathogenesis of SAP, and autophagy promotes the occurrence of ferroptosis in SAP. Moreover, 3-methyladenine (3-MA) inhibition of autophagy can significantly reduce iron overload and ferroptosis in SAP. CONCLUSIONS: Our results suggest that ferroptosis is a novel pathogenesis of SAP and is dependent on autophagy. This study provides a new theoretical basis for the study of SAP.

Close relationship between mediators of inflammation and pancreatic cancer: Our experience.

In this editorial, we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer. Cancer of the pancreas remains one of the deadliest cancer types. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends of pancreatic cancer incidence and mortality vary considerably worldwide. A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this editorial, we highlight the foundational studies that have driven our understanding of these processes. In our experimental center, we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer. We focused on the role of mast cells (MCs). MCs contain pro-angiogenic factors, including tryptase, that are associated with increased angiogenesis in various tumors. In this editorial, we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue. The assessment includes the density of c-Kit receptor-positive MCs, the density of tryptase-positive MCs, the area of tryptase-positive MCs, and angiogenesis in terms of microvascularization density.

Establishment and Diagnostic Value of an Early Prediction Model for Acute Pancreatitis Complicated With Acute Kidney Injury.

OBJECTIVES: To establish an early prediction model for acute pancreatitis (AP) complicated with acute kidney injury (AKI) and evaluate its diagnostic value. METHOD: AP patients were recruited from the Emergency Department at Peking University People's Hospital in 2021 and stratified into AKI and control (no AKI) groups. Their clinical data were analyzed. The risk for AKI development was determined using logistic analyses to establish a risk prediction model, whose diagnostic value was analyzed using a receiver operating characteristic curve. RESULTS: There was no significant difference in the basic renal function between the AKI (n = 79) and control (n = 179) groups. The increased triglyceride glucose index (odds ratio [OR], 2.613; 95% confidence interval [CI], 1.324-5.158; P = 0.006), age (OR, 1.076; 95% CI, 1.016-1.140; P = 0.013), and procalcitonin (OR, 1.377; 95% CI, 1.096-1.730, P = 0.006) were associated with AKI development. A model was established for prediction of AKI (sensitivity 79.75%, specificity 96.65%). The area under the receiver operating characteristic curve was 0.856 which was superior to the Ranson, Bedside Index for Severity in AP, and Acute Physiology and Chronic Health Evaluation II scores (0.856 vs 0.691 vs 0.745 vs 0.705). CONCLUSIONS: The prediction model based on age, triglyceride glucose, and procalcitonin is valuable for the prediction of AP-related AKI.

Certolizumab Has Favorable Efficacy on Preventing Pancreas and Target Organs Damage in Acute Pancreatitis.

OBJECTIVE: It was targeted to assess the efficacy of certolizumab on pancreas and target organs via biochemical parameters and histopathologic scores in experimental acute pancreatitis (AP). MATERIALS AND METHODS: Forty male Sprague Dawley rats were divided into the following 5 equal groups: group 1 (sham group), group 2 (AP group), group 3 (AP + low-dose certolizumab group), group 4 (AP + high-dose certolizumab group), and group 5 (placebo group). Rats in all groups were sacrificed 24 hours after the last injection and amylase, tumor necrosis factor α, transforming growth factor ß, interleukin 1ß, malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were studied in blood samples. Histopathological investigation of both the pancreas and target organs (lungs, liver, heart, kidneys) was performed by a pathologist blind to the groups. In silico analysis were also accomplished. RESULTS: The biochemical results in the certolizumab treatment groups were identified to be significantly favorable compared to the AP group (P < 0.001). The difference between the high-dose group (group 4) and low-dose treatment group (group 3) was found to be significant in terms of biochemical parameters and histopathological scores (P < 0.001). In terms of the effect of certolizumab treatment on the target organs (especially on lung tissue), the differences between the low-dose treatment group (group 3) and high-dose treatment group (group 4) with the AP group (group 2) were significant. CONCLUSIONS: Certolizumab has favorable protective effects on pancreas and target organs in AP. It may be a beneficial agent for AP treatment and may prevent target organ damage.

X-Box binding protein 1 downregulates SIRT6 to promote injury in pancreatic ductal epithelial cells.

OBJECTIVE: Acute pancreatitis (AP) stands as a frequent cause for clinical emergency hospital admissions. The X-box binding protein 1 (XBP1) was found to be implicated in pancreatic acinar cell apoptosis. The objective is to unveil the potential mechanisms governed by XBP1 and SIRT6 in the context of AP. METHODS: Caerulein-treated human pancreatic duct epithelial (HPDE) cells to establish an in vitro research model. The levels and regulatory role of SIRT6 in the treated cells were evaluated, including its effects on inflammatory responses, oxidative stress, apoptosis, and endoplasmic reticulum stress. The relationship between XBP1 and SIRT6 was explored by luciferase and ChIP experiments. Furthermore, the effect of XBP1 overexpression on the regulatory function of SIRT6 on cells was evaluated. RESULTS: Caerulein promoted the decrease of SIRT6 and the increase of XBP1 in HPDE cells. Overexpression of SIRT6 slowed down the secretion of inflammatory factors, oxidative stress, apoptosis level, and endoplasmic reticulum stress in HPDE cells. However, XBP1 negatively regulated SIRT6, and XBP1 overexpression partially reversed the regulation of SIRT6 on the above aspects. CONCLUSION: Our study illuminates the role of XBP1 in downregulating SIRT6 in HPDE cells, thereby promoting cellular injury. Inhibiting XBP1 or augmenting SIRT6 levels holds promise in preserving cell function and represents a potential therapeutic avenue in the management of AP.

The Long Non-Coding RNA SNHG1 Predicts Severity of Acute Pancreatitis and Stimulates Pancreatic Cell Apoptosis and Inflammatory Response.

Acute pancreatitis (AP) is a common digestive emergency, needs early prediction and recognition. The study examined the clinical value of long non-coding RNA SNHG1 in AP, and explored its related mechanism for AP. A total of 288 AP cases and 150 healthy persons were recruited, the AP patients were grouped based on AP severity. AR42J cells were treated with 100nM caerulein to stimulate AP in vitro. qRT-PCR was performed for mRNA detection. Receiver operating characteristic (ROC) curve was drawn for diagnostic significance evaluation. The relationship of SNHG1 and miR-140-3p was verified via luciferase reporter and RNA immunoprecipitation (RIP) assay. AP cases had high expression of SNHG1, and it can differentiate AP cases from healthy people with the area under the curve (AUC) of 0.899. Severe AP cases had high values of SNHG1, which was independently related to AP severity. SNHG1 knockdown relieved caerulein-induced AR42J cell apoptosis and inflammatory response. miR-140-3p interacted with SNHG1, and reversed the role of SNHG1 in caerulein-induced AR42J cell injury. RAB21 was a candidate target of miR-140-3p, and was at high expression in AP cell models. SNHG1 may be a promising biomarker for the detection of AP, and serves as a potential biological marker for further risk stratification in the management of AP. SNHG1 knockdown can relieve inflammatory responses and pancreatic cell apoptosis by absorbing miR-140-3p.

Pancreatitis with Intraabdominal Venous Thrombosis as an Initial Presentation of Parathyroid Adenoma: A Rare Clinical Presentation.

BACKGROUND Benign parathyroid adenoma is a cause of hypercalcemia, which can lead to acute pancreatitis. Patients with acute pancreatitis are at risk for venous thrombosis. This report describes a 34-year-old woman with hypercalcemia due to parathyroid adenoma and acute pancreatitis associated with splenic vein and superior mesenteric vein thrombosis. CASE REPORT A previously healthy 34-year-old woman presented with severe epigastric pain that radiated to the back, associated with vomiting. Her abdominal examination was soft and lax, with epigastric and left upper quadrant tenderness. Pancreatitis with splenic and superior mesenteric veins thrombosis was diagnosed. The diagnosis was confirmed by an elevated serum lipase level and contrast-enhanced computed tomography (CT) of abdomen. Her serum calcium level was elevated. However, further workup revealed elevated parathyroid hormone (PTH) levels and radiological imaging showed parathyroid adenoma. She was diagnosed with hypercalcemia-induced pancreatitis secondary to hyperparathyroidism with intraabdominal venous thrombosis. The patient was initially treated conservatively, and later underwent parathyroidectomy after her condition was stabilized. The patient is currently in good condition, after a 2-year follow-up period. CONCLUSIONS Acute pancreatitis and thrombosis secondary to primary hyperparathyroidism (PHPT) are rare, but can lead to potentially fatal complications, especially in patients without symptoms of PHPT. This report highlights the importance of recognizing that hypercalcemia associated with parathyroid adenoma can result in acute pancreatitis, leading to hypercoagulable states and inflammation of adjacent vessels, including the splenic and mesenteric veins. To the best of our knowledge, this is second case report of acute pancreatitis with intraabdominal venous thrombosis secondary to PHPT.

FASTING INCREASES THE SEVERITY OF ACUTE PANCREATITIS IN A MOUSE MODEL: IMPLICATIONS FOR PREOPERATIVE INTERVENTIONS TO REDUCE COMPLICATIONS OF PANCREATIC SURGERY.

BACKGROUND: Acute pancreatitis following surgical or endoscopic procedures on the pancreas can compromise the outcome and lead to severe complications and even death. The aim of this study was to determine whether prolonged fasting affects the severity of acute pancreatitis (AP). METHODS: Male mice were divided into 4 groups: Group CF (n=5) control animals that fasted for 24 hours; Group CNF (n=5) control animals that did not fast; Group APF (n=7) that fasted for 24 hours and underwent induction of acute pancreatitis (AP) and Group APNF (n=7) that did not fast and underwent AP. Eight hours after AP blood was collected for evaluation of cytokines: IL-1ß, IL-6, IL-10, TNF-α and MCP-1. Liver tissue was collected for determination of Malondialdehyde, pancreatic tissue for determination of enzyme content and lung tissue for determination of myeloperoxidase. RESULTS: Significant increase in pancreatic amylase content was observed in group CF and increased serum levels of IL -6, Il-10 and MCP-1 were in group APF. Liver malondialdehyde was also increased in APF animals. APF group showed much more necrosis of the pancreatic acinar cells. CONCLUSION: In the present study, we observed an increase in the severity of acute pancreatitis with prolonged fasting in a severe acute pancreatitis model. These results suggest that in clinical practice, the preoperative fasting time should be shortened before pancreatic procedures.

Acute pancreatitis and refractory hypercalcemia in the third trimester caused by parathyroid carcinoma.

BACKGROUND: Hypercalcemia can be a rare contributor to acute pancreatitis (AP) in pregnancy. This is primarily due to primary hyperparathyroidism (PHPT), resulting from parathyroid carcinoma. We exhibited a case report to analyze the diagnosis and treatment during the onset of hypercalcemia-induced AP. CASE PRESENTATION: A 32-year-old primigravida presented with acute pancreatitis near full-term gestation. Following a cesarean delivery, there was a reduction in serum amylase and peripancreatic exudate, but her serum calcium concentrations persistently elevated over 4.0 mmol/L. Interventions to lower the hypercalcemia were only temporarily effective, until a high serum parathyroid hormone (PTH) concentration of 1404 pg/mL was detected. Ultrasound revealed a 31 mm × 24 mm hypoechoic oval nodule in the left lower lobe of the thyroid gland. She underwent a parathyroidectomy, resulting in a dramatic decrease in serum PTH level, from preoperative levels of 2051 pg/mL to 299 pg/mL just 20 minutes after removal. Similarly, her serum calcium declined from 3.82 mmol/L to 1.73 mmol/L within 24 hours postoperatively. The final histopathology suggested parathyroid carcinoma. CONCLUSION: When refractory hypercalcemia is present, serum PTH levels should be measured to determine PHPT. Parathyroidectomy is the optimal strategy for alleviating hypercalcemia and clarifying the underlying pathology.

Social disparity is associated with an increased risk of acute and chronic pancreatitis.

AIM: To study social disparity in acute pancreatitis (AP) and chronic pancreatitis (CP).We also aimed at exploring whether an interaction exists between alcohol intake and socioeconomic factors. METHODS: Prospective cohort study based on data from 271 696 men and women participating in the Danish National Health Surveys 2010, and 2013. Information on alcohol and smoking parameters, body mass index (BMI), diet, and education, were self-reported and information on family income was obtained from administrative registers. Outcome variables (acute and chronic pancreatitis) were obtained from national health registers. RESULTS: The incidence rate ratio (IRR) of developing AP and CP increased with decreasing family income. Compared to participants in the highest income quintile, participants in the lowest income quintile had 43 (95% CI: 14-80%), 99 (95% CI: 26-214%), and 56% (95% CI: 26-94%) higher incidence rates of AP, CP, and all pancreatitis, respectively. The associations persisted after adjustment for alcohol intake, smoking, BMI, and diet.Likewise, participants with only primary school education had an IRR for an AP of 1.30 (95% CI: 1.06-1.59) compared to those with higher education after adjustment for baseline year, age, and sex. We found no interactions between alcohol intake and income or between alcohol intake and education in relation to neither AP, CP, nor all pancreatitis. CONCLUSION: This large prospective population study showed a significant social disparity in incidence rates of pancreatitis by family income, with higher rates among those with the lowest income and education independent of risk factors such as alcohol intake, smoking, BMI, and diet.

Symptomatic uncomplicated gallstone disease is associated with a high short-term risk of gallstone-related complications: a contemporary cohort study.

BACKGROUND: The natural history of symptomatic uncomplicated gallstone disease is largely unknown. We examined the risk of progressing from symptomatic uncomplicated to complicated gallstone disease in a large regional cohort of patients, where disruptions in elective surgical capacities have led to the indefinite postponement of surgery for benign conditions, including cholecystectomies. METHODS: Patients with radiologically diagnosed incident symptomatic and uncomplicated gallstone disease were identified from outpatient clinics and emergency departments on the Island of Funen, Denmark. The absolute risk of complications (cholecystitis, cholangitis, pancreatitis, acute cholecystectomy for unremitting pain) was calculated using death and elective cholecystectomies as competing risks using the Aalen-Johansen method. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) of gallstone complications associated with patient and gallstone characteristics. RESULTS: Two hundred eighty-six patients diagnosed with incident symptomatic, uncomplicated gallstone disease from 1 January 2020 to 1 July 2023 were identified. During 79,170 person-years of observation, 176 (61.5%) patients developed a gallstone-related complication. The 6-, 12- and 24-month risk of developing gallstone-related complications were 36%, 55% and 81%. The risk of developing complications related to common bile duct stones was lowest with larger stones (aHR per millimeter increase = 0.89 (0.82-0.97), p < 0.01), while no covariates were statistically significantly associated with the risk of cholecystitis. Eighty-five (30%) patients underwent elective laparoscopic cholecystectomy, with one patient (1.2%) developing a gallstone-related complication afterward. CONCLUSIONS: The risk of developing complications to symptomatic gallstones in a general Scandinavian population is high, and prophylactic cholecystectomy should be considered.

Cholecystectomy in Mild and Moderate Acute Pancreatitis: A Retrospective Study.

Background: Cholecystectomy has been a subject of debate regarding its timing and utility in cases of mild and moderately severe acute pancreatitis (AP). We aimed to critically evaluate the role of early cholecystectomy in the management of mild and moderate AP, considering patient's characteristics, associated procedures, and overall impact on patient outcomes. Methods: The study compared the outcomes between patients admitted in a tertiary care surgical center undergoing early ( 96h) versus delayed ( 96h) laparoscopic cholecystectomy (LC) for mild and moderately severe acute gallstone pancreatitis between January 2019 and December 2022. Results: The study included 54 cases [mean (standard deviation) age, 59.4 (16.5) years; 31 (57.4%) years females]. All patients underwent LC, with 29 cases undergoing a two-phase therapeutic regimen for common bile duct (CBD) lithiasis, consisting of endoscopic retrograde cholangiopancreatography followed by sequential LC. The early cholecystectomy group (EC) comprised 17 patients (31.5%), while the delayed cholecystectomy group (DC) included 37 patients (68.5%). EC was significantly correlated with lower length of stay (p-value 0.0001) and significantly lower rate of ERCP usage during perioperative period. Conclusions: EC in the first 4 days after admission provides significant benefits such as prevention of recurrent pancreatitis, reduction in complications, and decreased length of stay for patients with mild and moderately severe AP.

A 42-Year-Old Woman with Recurrent Pancreatitis Associated with Gallstones and Phrygian Cap Gallbladder.

BACKGROUND Gallbladder anomalies are rare congenital defects with an incidence rate of approximately 2% in the general population. Phrygian cap gallbladder is a common anatomical variant in which the fundus of the gallbladder folds on itself. Gallstone impaction is rare, and it can be associated with acute pancreatitis. This report describes a 42-year-old woman with recurrent pancreatitis associated with gallstones and Phrygian cap gallbladder. CASE REPORT We report the case of a 42-year-old woman with acute biliary pancreatitis and a history of repeated hospitalizations for episodes of pancreatitis. A preoperative MRI was conducted, which revealed the presence of a Phrygian cap gallbladder that had not been previously reported in imaging studies. The patient underwent cholecystectomy surgery with a laparo-endoscopic approach (rendezvous technique). No intra- or postoperative complications occurred. CONCLUSIONS We report a case of acute biliary pancreatitis caused by stone migration and describe the anatomical variant of the Phrygian cap gallbladder with its clinical implications. The literature contains very few reports of cholecystitis or pancreatitis in patients with a gallbladder anomaly. Continuous reporting of anatomical variations of the gallbladder and biliary tract improves clinical knowledge, and knowledge of gallbladder anomalies is crucial to avoid injury to the biliary tract during laparoscopic cholecystectomy. This case emphasizes the importance of accurate preoperative evaluation to prevent serious surgical complications.

ERCP-Related adverse events in pediatric patients: a 10-years single-site review.

PURPOSE: This retrospective analysis aimed to assess the feasibility and safety of endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients by examining ERCP-related adverse events (AEs) occurring over a decade at a single center. METHODS: Pediatric patients under 18 years old who underwent ERCP at the Second Hospital of Hebei Medical University from 1/2013 to 11/2023 were included. ERCP-related AEs were defined according to ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Clinical data of patients experiencing ERCP-related AEs were obtained from electronic medical records for analysis. RESULTS: Over the past decade, a total of 76 pediatric patients underwent 113 ERCP procedures, including 26 patients who underwent repeat ERCP, totaling 63 procedures. There were 32 males and 44 females, with a median age of 13 years (range 3 years and 5 months-17 years and 9 months). Among all ERCP procedures, 14 (12.4%) were diagnostic and 99 (87.6%) were therapeutic, with a 100% success rate. 16 cases (14.2%) of ERCP-related AEs, all post-ERCP pancreatitis (PEP), were observed, while no other AEs defined by ESGE such as bleeding, perforation, cholangitis, cholecystitis, or sedation-related events were noted. Additionally, 23 cases (20.4%) of ERCP-related AEs not included in the ESGE definition were observed, including post-ERCP abdominal pain in 20 cases (17.7%), post-ERCP nausea and vomiting in 2 cases (1.8%), and unplanned reoperation in 1 case (0.9%). In the 26 cases of pediatric patients who underwent repeat ERCP, we observed that AEs occurred in 15 cases (57.7%) during their initial ERCP, which was much higher than the overall average level. CONCLUSIONS: Post-ERCP abdominal pain and PEP are the most common ERCP-related AEs in pediatric patients, while severe AEs such as bleeding and perforation are rare. The incidence of AEs after initial ERCP in pediatric patients who received repeat ERCP is higher than the overall average level. Based on our center's experience, we believe that ERCP can be safely performed in children over 3 years old with biliary and pancreatic diseases and obtain reliable clinical benefits. However, active monitoring and management of ERCP-related AEs are essential to improve the clinical outcomes of pediatric ERCP.

Early laparoscopic cholecystectomy in acute mild gallstone pancreatitis. Is there a role for routine admission contrast-enhanced CT Scan?

PURPOSE: This study aims to evaluate the efficacy of admission contrast-enhanced CT scans in formulating strategies for performing early laparoscopic cholecystectomy in cases of acute gallstone pancreatitis. METHODS: Patients diagnosed with acute gallstone pancreatitis underwent a CT scan upon admission (after at least 24 h from symptom onset) to confirm diagnosis and assess peripancreatic fluid, collections, gallstones, and common bile duct stones. Patients with mild acute gallstone pancreatitis, following the Atlanta classification and Baltazar score A or B, were identified as candidates for early cholecystectomy (within 72 h of admission). RESULTS: Within the analyzed period, 272 patients were diagnosed with mild acute gallstone pancreatitis according to the Atlanta Guidelines. A total of 33 patients (12.1%) were excluded: 17 (6.25%) due to SIRS, 10 (3.6%) due to local complications identified in CT (Balthazar D/E), and 6 (2.2%) due to severe comorbidities. Enhanced CT scans accurately detected gallstones, common bile duct stones, pancreatic enlargement, inflammation, pancreatic collections, and peripancreatic fluid. Among the cohort, 239 patients were selected for early laparoscopic cholecystectomy. Routine intraoperative cholangiogram was conducted in all cases, and where choledocholithiasis was present, successful treatment occurred through common bile duct exploration. Only one case required conversion from laparoscopic to open surgery. There were no observed severe complications or mortality. CONCLUSION: Admission CT scans are instrumental in identifying clinically stable patients with local tomographic complications that contraindicate early surgery. Patients meeting the criteria for mild acute gallstone pancreatitis, as per Atlanta guidelines, without SIRS or local complications (Baltazar D/E), can safely undergo early cholecystectomy within the initial 72 h of admission.

[Risk factors for pancreatitis after endoscopic retrograde cholangiopancreatography in children]. / å„¿ç«¥ç»å† é•œé€†è¡Œèƒ°èƒ†ç®¡é€ å½±æœ¯åŽèƒ°è ºç‚Žå‘ç”Ÿçš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the application of endoscopic retrograde cholangiopancreatography (ERCP) in children and the risk factors for post-ERCP pancreatitis (PEP). METHODS: A retrospective analysis was conducted on the clinical data of 66 children, aged ≤16 years, who underwent ERCP for pancreaticobiliary diseases at the Gastrointestinal Endoscopy Center of the Second Affiliated Hospital of Kunming Medical University from September 2013 to September 2023. The incidence rate of PEP and the risk factors for the development of PEP were analyzed. RESULTS: A total of 78 ERCP procedures were performed on 66 children, with 5 diagnostic ERCPs, 69 therapeutic ERCPs, and 4 failed procedures. The success rate of ERCP operations was 95% (74/78). There were 17 cases of PEP in total, with an incidence rate of 22%. In the PEP group, the proportion of children with normal preoperative bilirubin and the proportion of guidewire insertion into the pancreatic duct during surgery were higher than in the non-PEP group (P<0.05). The multivariate logistic regression analysis showed that guidewire insertion into the pancreatic duct was an independent risk factor for PEP (P<0.05). CONCLUSIONS: With the increasing application of ERCP in children with pancreaticobiliary diseases, it is important to select an appropriate intubation technique during surgery to avoid blindly entering the guidewire into the pancreatic duct and reduce the occurrence of PEP.

A deep learning-powered diagnostic model for acute pancreatitis.

BACKGROUND: Acute pancreatitis is one of the most common diseases requiring emergency surgery. Rapid and accurate recognition of acute pancreatitis can help improve clinical outcomes. This study aimed to develop a deep learning-powered diagnostic model for acute pancreatitis. MATERIALS AND METHODS: In this investigation, we enrolled a cohort of 190 patients with acute pancreatitis who were admitted to Sichuan Provincial People's Hospital between January 2020 and December 2021. Abdominal computed tomography (CT) scans were obtained from both patients with acute pancreatitis and healthy individuals. Our model was constructed using two modules: (1) the acute pancreatitis classifier module; (2) the pancreatitis lesion segmentation module. Each model's performance was assessed based on precision, recall rate, F1-score, Area Under the Curve (AUC), loss rate, frequency-weighted accuracy (fwavacc), and Mean Intersection over Union (MIOU). RESULTS: Upon admission, significant variations were observed between patients with mild and severe acute pancreatitis in inflammatory indexes, liver, and kidney function indicators, as well as coagulation parameters. The acute pancreatitis classifier module exhibited commendable diagnostic efficacy, showing an impressive AUC of 0.993 (95%CI: 0.978-0.999) in the test set (comprising healthy examination patients vs. those with acute pancreatitis, P < 0.001) and an AUC of 0.850 (95%CI: 0.790-0.898) in the external validation set (healthy examination patients vs. patients with acute pancreatitis, P < 0.001). Furthermore, the acute pancreatitis lesion segmentation module demonstrated exceptional performance in the validation set. For pancreas segmentation, peripancreatic inflammatory exudation, peripancreatic effusion, and peripancreatic abscess necrosis, the MIOU values were 86.02 (84.52, 87.20), 61.81 (56.25, 64.83), 57.73 (49.90, 68.23), and 66.36 (55.08, 72.12), respectively. These findings underscore the robustness and reliability of the developed models in accurately characterizing and assessing acute pancreatitis. CONCLUSION: The diagnostic model for acute pancreatitis, driven by deep learning, exhibits excellent efficacy in accurately evaluating the severity of the condition. TRIAL REGISTRATION: This is a retrospective study.

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance.

We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P (n = 9 studies, N = 1375) involved as a starting point parathyroid NETs (n = 7) or pancreatitis (n = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies (n = 7) included MEN1-related insulinomas (n = 2) or MEN1-associated PHP (n = 2) or analyses of genetic profile (n = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, p < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). MEN1 pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline MEN1 pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: CDC73 gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified (n = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome (n = 1). Normocalcemic and mildly symptomatic hyperparathyroidism (n = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.

Diagnostic and Prognostic Markers for Pancreatitis and Pancreatic Ductal Adenocarcinoma.

Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.