Chronic Pancreatitis Research Articles

Risk factors for acute pancreatitis after endoscopic retrograde cholangiopancreatography: a retrospective single-center study

Background. Endoscopic retrograde cholangiopancreatography (ERCP) is an important procedure in the diagnosis and management of pancreaticobiliary diseases. Post-ERCP pancreatitis (PEP) is the most common and serious adverse event after ERCP. Purpose – to evaluate retrospectively PEP incidence and to identify independent risk factors of PEP. Materials and Methods. The analysis of 578 ERCP cases was done. A number of potential risk factors for PEP were taken into uni- and multivariate analisys: age, gender, common bile duct (CBD) size, bilirubin level, presence of cholangitis, Sphincter of Oddi dysfunction (SOD), malignant biliary obstruction, chronic pancreatitis, biliary obstruction, history of cholecystectomy, history of endoscopic papillosphincterotomy (EPST), initial ERCP success, therapeutic success, selective biliary cannulation, pancreatic cannulation/injection, Precut and EPST. Results. PEP was in 29 (5%) cases. Six factors with р < 0,05 by univariate analysis (CBD ≤ 10 mm, normal bilirubin level, SOD, history of cholecystectomy, pancreatic cannulation/injection, precut) were included into multivariate logistic regression model. The independent risk factor for PEP were CBD ≤ 10 mm (OR 2,416; 95% ДІ, 1,037–5,629; p = 0,041), SOD (OR 4,107; 95% ДІ, 1,726–9,771; p = 0,001) та pancreatic cannulation/injection (OR 3,447; 95% ДІ, 1,455–8,166; p = 0,005); and precut was an independent protective factor for PEP (OR 0,129; 95% ДІ, 0,047–0,354; p = 0,014). Conclusions. The incidence of PEP was 5%. Small CBD and SOD are independent PEP risk factors as well as pancreatic cannulation/injection. Early precut technique is an independent factor preventing PEP.

Results of interventions on the celiac plexus in treating patients with chronic pharmacoresistant abdominal pain

Patients with chronic abdominal pain are a complex cohort of patients who undergo treatment by many specialists for a long time: surgeons, urologists, gynecologists, neurologists, psychiatrists, etc. However, despite all diagnostic and treatment measures, the pain syndrome persists or worsens. Objective ‒ evaluation of the effectiveness, safety and long-term results of treating patients with abdominal pain syndromes, which includes the use of various methods of minimally invasive interventions on the celiac plexus (CP) taking into account the peculiarities of the origin, nature and localization of pain. Materials and methods. An analysis of the results of 26 interventions on CP in 21 patients was performed. Inclusion criteria for participants in the study were individuals with persistent pharmacoresistant abdominal pain for ≥3 months, aged 19 to 73 years. There were 13 (62.0%) male and 8 (38.0%) were female. Mean age was 55.2±15.2 years. Patients were divided into two groups. The first (n=16) included patients with pancreatic cancer, the second (n=5) included patients with non-oncological chronic abdominal pain syndromes: functional abdominal pain syndrome was diagnosed in three cases, and one observation each of solaritis and chronic pancreatitis. All procedures were performed under CT. To assess the intensity of the pain syndrome, a visual analogue scale (VAS) of pain from 1 to 10 cm was used, where 0 cm is the absence of pain, 10 cm is unbearable pain; functional status (FS) - according to the Karnofsky scale (KS) from 0 to 100%. Estimation of the daily dose of opioid analgesics was estimated using the oral morphine equivalent daily dose (oMEDD). Patients were observed for 6 months, evaluations were carried out after 1 week, 1, 3 and 6 months, respectively. Results. In the first group, 17 interventions on CP were performed in 16 participants, sympatholysis was performed twice in one patient. In the second group - 9 interventions in 5 patients: 4 Celiac Plexus Blocks (CPBs) of the central nervous system using "Depo-Medrol®" (methylprednisolone) and 5 neurolysis with 96% ethyl alcohol. Two patients were initially treated with CPB and then sympatholysis due to the recurrence of pain syndrome with the aim of a more stable sympatholytic and analgesic effect. In one patient, neurolysis of CP was performed three times. In all cases, no complications were recorded during the procedures. VAS before the procedure in the general group (n=26) was 9.6±0.6 cm, one week after the intervention it was 4.5±1.6 cm (P<0.0001), after one month it was 3.2±1 .5 cm (P<0.0001), after 3 months – 3.0±1.6 cm (P<0.0001), after six months – 4.4±1.6 cm (P<0.0001). The FS indicator according to the KS before the procedure in the general group was 65.8±7.0%, one week after the intervention – 80.8±8.0% (P<0.0001), one month later – 81.5±8.3 % (P<0.0001), after 3 months – 75.0±9.5% (P<0.0010), after six months – 68.0±9.4% (P=0.4042). The oral morphine equivalent daily dose before the procedure in the general group was 123.8±86.0 mg per day, one week after the intervention on CP oMEDD was 57.3±61.2 mg (P<0.0001), after 1 month – 41.0±47.3 mg (P<0.0001), after 3 months – 44.0±51.3 mg (P<0.0001), after 6 months – 80.6±77.2 mg (P<0,0001). Conclusions. Computed tomography-guided celiac plexus neurolysis is a useful and effective tool in treating patients with both abdominal pain caused by inoperable pancreatic cancer and chronic non-oncological pharmacoresistant abdominal pain. Minimally invasive interventions on CP provide a significant reduction of pain syndrome according to the VAS scale (p<0.001), reduce the need to take opioids analgesics (p<0.001) after 1, 3, 6 months and increase the FS of patients according to the KS (p<0.001) after 1, 3 months. Taking into account the high percentage of recurrence of pain syndrome in the studied patients of the group of non-oncology pain, the need for repeated interventions for the purpose of long-term pain control, interventions on CP in this cohort of patients require further research with an increase in the number of observations.

Diagnostic Yield of Endoscopic Ultrasound in Common Bile Duct Dilation: A Real Breakthrough.

Endoscopic ultrasound (EUS) is important for the evaluation of patients with common bile duct (CBD) dilation. The purpose of this study was to evaluate the diagnostic performance of EUS for CBD dilation in patients with negative initial studies. This was a retrospective cohort study that included patients who underwent EUS for CBD dilation (≥ 7 mm if intact anatomy or ≥ 10 mm if prior cholecystectomy) in the absence of pathology on previous ultrasonography (US), computed tomography (CT), and/or magnetic resonance cholangiopancreatography (MRCP). A total of 109 patients were included, among whom 41 had a positive EUS: 33 choledocholithiasis (30.3%), 6 chronic pancreatitis (5.5%), and 2 ampullary cancer (1.8%). If the EUS was negative, no pathology was found during 1-year follow-up. Older age was associated with positive EUS (79 versus 71 years, p = 0.030). Patients with jaundice, cholelithiasis, and altered liver biochemistry were 16.2 (p = 0.002), 3.1 (p = 0.024), and 2.9 (p = 0.009) times more likely to have positive EUS, respectively. A total of 53 patients had a negative MRCP (48.6%); those with biliary abdominal pain and jaundice were 15.5 (p < 0.001) and 20.0 (p = 0.007) times more likely to have positive EUS, respectively. Considering asymptomatic patients with normal liver tests, CBD diameter ≥ 10 mm in US and ≥ 11 mm in CT can predict a positive EUS (AUC 0.754, p = 0.047 and AUC 0.734, p = 0.048). EUS is a useful diagnostic method for patients with unexplained CBD dilation, even if negative MRCP, and especially in patients with older age, abdominal pain, jaundice, cholelithiasis, and/or altered liver biochemistry. CBD diameter in US and CT had a moderate discriminative ability in predicting positive EUS in asymptomatic patients without altered liver biochemistry.

Progress in treatment of chronic pancreatitis: A review based on the ClinicalTrials.gov database

Progress in treatment of chronic pancreatitis: A review based on the ClinicalTrials.gov database

Misdiagnosis of pancreatic intraductal papillary mucinous neoplasms and the challenge of mimicking lesions: imaging diagnosis and differentiation strategies.

The rising prevalence of pancreatic cystic lesions (PCLs), particularly intraductal papillary neoplasms (IPMNs), has been attributed to increased utilization of advanced imaging techniques. Incidental detection of PCLs is frequent in abdominal CT and MRI scans, with IPMNs representing a significant portion of these lesions. Surveillance of IPMNs is recommended due to their malignant potential; however, their overlapping imaging features with benign entities can lead to misdiagnosis, overtreatment, and overutilization of healthcare resources. This paper aims to highlight and differentiate lesions often mistaken for IPMNs, providing insight into their imaging characteristics, diagnostic challenges, and distinctive features while highlighting the incidence of wrong diagnosis for these lesions. These lesions include serous cystadenomas, cystic pancreatic neuroendocrine tumors, mucinous cystic neoplasms, lymphoepithelial cysts, duodenal diverticula, pancreatic schwannomas, chronic pancreatitis, retention cysts, intrapancreatic accessory spleens, pancreatic lipomas, choledochal cysts, and others. Utilizing various imaging modalities, including contrast-enhanced CT, MRI, and EUS, alongside histological and molecular analyses, can aid in accurate diagnosis and appropriate management. Understanding these mimicry scenarios is crucial to avoid unnecessary surveillance, interventions, and the burden they place on both patients and healthcare systems. Improved recognition of these lesions can lead to better patient outcomes and resource allocation.

REDOX SIGNALLING IN THE PANCREAS IN HEALTH AND DISEASE.

This review addresses oxidative stress and redox signaling in the pancreas under physiological conditions as well as in acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. Physiological redox homeodynamics is maintained mainly by NRF2/KEAP1, NF-κB, protein tyrosine phosphatases, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and normal autophagy. Depletion of reduced glutathione in the pancreas is a hallmark of acute pancreatitis and is initially accompanied by disulfide stress, which is characterized by protein cysteinylation without increased glutathione oxidation. A cross-talk between oxidative stress, MAPKs, and NF-κB amplifies the inflammatory cascade, acting PP2A and PGC1α as key redox regulatory nodes. In acute pancreatitis, nitration of cystathionine-β synthase causes blockade of the trans-sulfuration pathway leading to increased homocysteine levels, whereas p53 triggers necroptosis in the pancreas through downregulation of sulfiredoxin, PGC1α, and peroxiredoxin 3. Chronic pancreatitis exhibits oxidative distress mediated by NADPH oxidase 1 and/or CYP2E1, which promotes cell death, fibrosis, and inflammation. Oxidative stress cooperates with mutant KRAS to initiate and promote pancreatic adenocarcinoma. Mutant KRAS increases mitochondrial ROS, which trigger acinar-to-ductal metaplasia and progression to PanIN. ROS are maintained at sufficient level to promote cell proliferation, whilst avoiding cell death or senescence through formation of NADPH and GSH, and activation of NRF-2, HIF-1/2α, and CREB. Redox signalling also plays a fundamental role in differentiation, proliferation, and insulin secretion of β-cells. However, ROS overproduction promotes β-cell dysfunction and apoptosis in type 1 and type 2 diabetes.

A rare case of Pancreatic lesion: Pancreatic mass and chronic pancreatitis caused by parasitic infection

A middle-age male patient was hospitalized for six-months upper abdominal pain. The patient had experienced 3 episodes of acute pancreatitis in the past 6 years. All the examination pointed to chronic pancreatitis and tumor, which, however, covering up the truth that the patient was in infection with Clonorchis sinensis in his pancreas. As the condition met the surgical indications, we performed pancreaticoduodenectomy and found the infection of Clonorchis sinensis in the postoperative pathological report. The patient maintain healthy during subsequent follow-up. Pancreatic mass with Clonorchis sinensis infected were rarely seen clinically, here we report the case which indicate us that further study on parasite and pancreatic lesion should be implemented. This case report is in accordance with Strengthening the reporting of Clinical Case Report and Helsinki Declaration.

A50-year-old patient with pancreatitis revealing pancreatitis, panniculitis, and polyarthritis syndrome-acase report and review of the literature.

The combination of pancreatitis, panniculitis, and polyarthritis (PPP) is arare systemic syndrome that occurs in patients with acute or chronic pancreatitis or pancreatic malignancies. A50-year-old male patient presented with polyarthritis increasing for 1week and consequent inability to walk unaided. In addition, the patient had several isolated nodules on the lower extremities without any tenderness to pressure. Laboratory tests showed elevated pancreatic enzymes indicative of pancreatitis, which was thereafter confirmed by abdominal CT scan, with signs of chronic pancreatitis and concrements in the pancreatic duct. The diagnosis of panniculitis was established by dermatological consultation. Considering all these clinical features, PPP syndrome was diagnosed. In accordance with the pre-existing literature, oral glucocorticoid therapy and nonsteroidal anti-inflammatory drugs (NSAIDs) were given but failed to improve pain and polyarthritis. In the further clinical course, due to the persistent increase in lipase and amylase, endoscopic retrograde cholangiopancreatography (ERCP) was performed, showing small concrements in the pancreatic duct. During the intervention, the pancreatic duct was widened, the small concrements were removed, and apancreatic duct stent was then implanted. Following ERCP, an instant decrease in pancreatic enzymes was observed, accompanied by aclear and sustained improvement of joint swellings and pain. With the typical triad of clinical findings in mind, one should consider PPP syndrome in the context of acute or chronic pancreatitis as well as in pancreatic malignancies. All involved disciplines (gastroenterology, dermatology, and rheumatology) should be familiar with this rare but severe condition. The prognosis depends on the extent of the functional deficit of the extremities and the progression of the underlying disease.

Somatostatin in Treatment of Acute Recurrent Pancreatitis and Role of Endoscopic Ultrasonography in The Diagnostic Workup

The pancreas is an elongated, soft, flat, lobulated, and yellowish gland located on the posterior abdominal wall in a transverse orientation. The structure is located in the retroperitoneum and has a thin capsule. An abrupt response to pancreatic injury is known as acute pancreatitis (AP). Chronic pancreatitis can lead to enduring harm to the composition and the pancreas' endocrine and exocrine functions. The term idiopathic RAP (IRAP) is employed when the reason cannot be readily identified by the assessment of physical examination, medical history, basic laboratory tests (calcium and serum triglyceride levels, for example), and diagnostic imaging studies (e.g., CT scans and transabdominal ultrasounds). With endoscopic ultrasonography (EUS), you may see the inside of your digestive tract and any surrounding tissues in high resolution and real time. When it comes to evaluating a wide variety of benign and malignant GI illnesses, this technique is both efficient and cost-effective. Somatostatin inhibits the release and manufacture of certain enzymes, which in turn decreases the pancreas' ability to absorb amino acids. The release of somatostatin from the pancreatic islets is stimulated by high glucose concentration.

The Clinical Significance of Pancreatic Steatosis in Pancreatic Cancer: A Hospital-Based Study.

Background/Objectives: Pancreatic cancer remains one of the deadliest malignancies worldwide with a pressing need for early detection and intervention strategies. Emerging evidence has suggested a potential link between pancreas steatosis, characterized by excessive pancreatic fat accumulation, and an increased risk of pancreatic cancer development. This retrospective imaging study aims to elucidate the association between pancreatic steatosis and the subsequent development of pancreatic cancer. In the study, we aimed to determine the characteristics of pancreatic cancer with pancreatic steatosis. Methods: During the period of January 2022 to December 2022, we conducted a retrospective study, collecting 101 newly diagnosed pancreas cancer cases from the available image datasets. A comprehensive database of retrospective abdominal imaging studies, comprising computed tomography (CT) and magnetic resonance imaging (MRI), was established from a diverse patient population and subsequently analyzed. Inclusion criteria encompassed patients having available baseline imaging data, allowing for the assessment of pancreatic fat content. Pancreatic fat content was quantified using validated radiological techniques, while demographic, clinical, and histopathological data were all collected. The clinical data and patient characteristics were collected from medical records and analyzed. Results: Preliminary analysis revealed a significant correlation between elevated pancreatic fat content and an increased incidence of subsequent pancreatic cancer. Moreover, subgroup analysis based on age, gender, and comorbidities provided valuable insight into potential risk factors associated with this progression. Additionally, the study identified novel radiological markers that may serve as early indicators of pancreatic cancer development in individuals with pancreatic steatosis. Conclusions: In the imaging study, approximately 30% (30/101) of pancreatic cancer patients presented with pancreatic steatosis. Chronic pancreatitis emerged as the primary factor contributing to pancreatic steatosis in these patients. Importantly, pancreatic steatosis did not significantly impact the prognosis of pancreatic cancer. Follow-up data revealed no significant differences in survival duration between patients with or without pancreatic steatosis. Additionally, no association was found between pancreatic steatosis and hepatic steatosis.

Image J as the quantification tool in endosonography strain elastography may be reflected in the disturbance of endocrine pancreatic dysfunction.

Pancreatic fibrosis is one of the main pathological features of chronic pancreatitis (CP), suggesting a strong relationship between CP and pancreatic ductal cancer. There was no available data about pancreatic fibrosis and pancreatic dysfunction in the early CP (ECP) using endosonography (EUS). Asymptomatic patients with pancreatic enzyme abnormalities (AP-P; n = 56) and patients with ECP (n = 21) were determined by the absence of abnormal findings on upper gastrointestinal endoscopy, abdominal ultrasonography, and abdominal computed tomography. An Olympus EUS (GF-UCT 260; Olympus) was used to perform EUS. Open software "Image J", developed by NIH, was used to measure the surface area fraction of the designated elastic blue region. The maximum value among the pancreatic head, pancreatic body, and pancreatic tail was defined as the ELST-blue score. The exocrine and endocrine pancreatic functions were evaluated using the N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA) test and homeostasis model assessment of β-cell function (HOMA-β) value, respectively. EUS score, lobularity, and hyperechoic foci/strands in patients with ECP were significantly (p < 0.001) higher than those in patients with AP-P. In addition, there were no significant differences in the BT-PABA test (73.1 ± 25.5, 68.5 ± 15.6) and HOMA-β (93.1 ± 67.4, 73.5 ± 139.7) between patients with ECP and AP-P. The ELST-blue score measured by image J as the quantification tool in EUS strain elastography in patients with ECP was significantly higher (p = 0.002) than that in patients with AP-P. Interestingly, the ELST-blue score was significantly associated with HOMA-β in patients with ECP. The ELST-blue score may be a useful tool for the evaluation of endocrine pancreatic dysfunction in the ECP.

Pain in chronic pancreatitis: What can we do today?

The aim of this study is to illustrate the complexity of pain management in chronic pancreatitis (CP). In this context, pain represents the most common and debilitating symptom, and it deeply affects patient's quality of life. Multiple rating scales (unidimensional, bidimensional and multidimensional) have been proposed to quantify CP pain. However, it represents the result of complex mechanisms, involving genetic, neuropathic and neurogenic factors. Considering all these aspects, the treatment should be discussed in a multidisciplinary setting and it should be approached in a stepwise manner. First, a lifestyle change is recommended and nonsteroidal anti-inflammatory drugs represent the gold standard among medical treatments for CP patients. The second step, after medical approach, is endoscopic therapy, especially for complicated CP. In case of failure, tailored surgery represents the third step and decompressive or resection procedures can be chosen. In conclusion, CP pain's management is challenging considering all these complex aspects and the lack of international protocols.

Dachaihu Decoction alleviates chronic pancreatitis by regulating MAPK signaling pathway: Insights from network pharmacology and experimental validation

Ethnopharmacological relevanceChronic pancreatitis (CP), a syndrome characterized by inflammatory fibrosis, can impair both the internal and external secretory functions of the pancreas. The global incidence of this disease is gradually increasing. However, the exact pathogenesis remains unclear, resulting in a lack of targeted clinical therapies. According to the principles of traditional Chinese medicine, CP can be attributed to Shaoyang and Yangming syndromes, which manifest as abdominal pain and hypochondriac distension. Dachaihu Decoction (DCHD) is a classic formula from the “Treatise on Febrile and Miscellaneous Disease.” It is frequently prescribed for conditions associated with combined Shaoyang and Yangming syndromes. However, the specific mechanisms by which DCHD prevents and treats CP remain unclear and require further investigation. Aim of the studyUsing a holistic methodology, including network pharmacology, molecular docking, transcriptomic profiling, and animal experimentation, we explored the potential therapeutic mechanisms of DCHD in CP. Materials and methodsIn a mouse model, caerulein was used to induce CP, and DCHD was administered via gastric lavage to assess its therapeutic effect on pancreatic injury caused by caerulein-induced CP. Subsequently, pancreatic tissues were collected for transcriptomic analysis. Screening of DCHD-active ingredient-target pathways for CP treatment was conducted using network pharmacology and further preliminary validation was performed using molecular docking techniques. Additionally, in vivo and in vitro validation was conducted using animal and cells experiments based on the predicted results. ResultsOur findings suggest that DCHD ameliorates pancreatic acinar cell injury, pancreatic inflammation, and fibrosis in mice with CP. Network pharmacology identified 385 potential targets of DCHD associated with CP. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the therapeutic effect of DCHD on CP may be linked to the mitogen-activated protein kinase (MAPK) signaling pathway. Transcriptomic data supported this finding, as it confirmed that DCHD inhibited the pancreatic MAPK signaling pathway in CP. Molecular docking studies further revealed that the top ten active components of DCHD exhibited strong docking activity with key molecules within the MAPK signaling pathway. Finally, animal experiments confirmed that DCHD effectively reduced the phosphorylation of P38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in pancreatic tissues. In addition, the expression of p-P38, p-JNK, and p-ERK was reduced in pancreatic stellate cells and macrophages in the DCHD group. We further treated CP mice, human pancreatic stellate cell line (hPSCs), and macrophage cell line RAW264.7 with the active component baicalin from DCHD, and found that baicalin effectively reduced pancreatic damage in CP. Additionally, the expression of key proteins in the MAPK signaling pathway was significantly decreased in both hPSCs and RAW264.7. ConclusionIn summary, DCHD plays an important role in the treatment of chronic pancreatitis, and it may become a promising drug against the progression of CP. The role of DCHD in alleviating pancreatic inflammatory cell infiltration and fibrosis may be related to the regulation of the MAPK signaling pathway.

Determination of asprosin levels and analysis of correlative relationships with carbohydrate metabolism indicators in patients with type 2 diabetes and chronic pancreatitis

Objective — to investigate asprosin levels in patients with type 2 diabetes mellitus (DM) and chronic pancreatitis (CP) and to analyze the correlations between asprosin levels and carbohydrate metabolism indicators in these patients. Materials and methods. The study was conducted on 100 patients treated at the Kharkiv Regional Clinical Hospital from 2020 to 2022. Patients were divided into two groups. The first group (n=30) included patients with type 2 DM, and the second group (n=70) comprised patients with comorbid type 2 DM and CP. The control group consisted of 20 healthy persons of comparable age. Diagnoses of CP and type 2 DM were established according to the approved protocols of the Ministry of Health of Ukraine. Asprosin levels in the blood were determined using enzyme‑linked immunosorbent assay (ELISA). Fasting blood glucose and insulin concentrations were studied, and the HOMA‑IR index was calculated. Results. The obtained results showed statistically significant differences in the level of asprosin between the groups of patients and the control group. Patients with comorbid type 2 DM and CP had significantly higher asprosin levels (10.06±3.56 ng/ml) compared to those with type 2 DM alone (7.34±2.08 ng/ml) and the control group (2.81±1.34 ng/ml). Correlation analysis revealed moderate positive correlations between asprosin and insulin levels (r=0.41) and HOMA index (r=0.47) in patients with type 2 DM without CP. In patients with comorbid type 2 DM and CP, moderate correlations were observed between asprosin levels and insulin (r=0.52) and HOMA index (r=0.53). Conclusions. Asprosin is an important adipokine that influences the development of insulin resistance and inflammatory processes in type 2 DM and CP. The highest asprosin levels were observed in the group with comorbid type 2 DM and CP. Moderate positive correlations were established between asprosin levels and insulin levels, as well as the HOMA‑IR index in patients from both groups. This suggests asprosin as a potential target for therapeutic intervention in type 2 DM and its complications.

Endoscopic Retrograde Cholangio-Pancreatography and Endoscopic Ultrasound in the Management of Paediatric Acute Recurrent Pancreatitis and Chronic Pancreatitis.

Objectives: To evaluate the role of ERCP (endoscopic retrograde cholangio-pancreatography) and EUS (endoscopic ultrasound) and to describe the efficacy and safety of these procedures in a paediatric cohort with chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). Methods: All patients (<18 years) undergoing an ERCP or EUS for ARP and CP between January 2008 and December 2022 were included. Data collection included indications for the procedure, technical success, adverse events and outcome data. Results: A total of 222 ERCPs were performed in 98 patients with CP and ARP (60% female, median age 10 years). The commonest indications were a main pancreatic duct stricture (PD) with or without a stone within the main PD. Successful cannulation was achieved in 98% of cases. Improved stricture resolution was demonstrated in 63% of patients. The overall adverse event rate for ERCP was low (n = 8/222, 3.6%). An improvement in abdominal pain was demonstrated in (75/98) 76% of patients. Their Body Mass Index also significantly improved post ERCP (15.5 ± 1.41 vs. 12.9 ± 1.16 kg/m2, p = 0.001). A total of 54 EUS procedures were undertaken in 48 individuals. Moreover, 35 individuals underwent a therapeutic EUS procedure, for which the commonest indication was the drainage of a pancreatic fluid collection. The overall complication rate was low (n = 2.4%) in all EUS cases. Conclusions: ERCP and EUS can be safely and effectively used in a paediatric population with indications analogous to an adult cohort.

Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain.

Background and Aims: This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Methods: A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease (N = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) (N = 22), acute pancreatitis (N = 33), recurrent acute pancreatitis (N = 57), and definite CP (N = 63). Results: Circulating AEA concentrations were higher in women than in men (p = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight (p = 0.003). Asymptomatic controls with no pancreatic disease had significantly (p = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly (p = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower (p = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Conclusions: Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.

Hydrophobic solid lipid-based microparticles for the protection of gastric-sensitive hydrophilic active biomolecules for oral administration in the treatment of EPI

Exocrine Pancreatic Insufficiency (EPI), induced by conditions such as cystic fibrosis, chronic pancreatitis, and Crohn’s disease, is a frequently overlooked and underdiagnosed gastrointestinal disorder. It leads to inadequate intestinal digestion due to insufficient secretion of pancreatic juice, resulting in discomfort, pain, and ultimately severe malnutrition. Despite numerous treatments proving ineffective over the past three decades, a strictly hydrophobic solid lipid formulation, administered orally, is proposed in this study to restore digestive function. This technology relies on the hydrophobic nature of the matrix to physically protect the hydrophilic active principle from the gastric environment while enabling its immediate release in the duodenum by targeting the amphiphilic nature of bile salts. Results demonstrate that this formulation effectively protects an acid-sensitive active ingredient during gastric passage (Simulated Gastric Fluid or SGF), facilitating its rapid release upon entering an artificial duodenal environment (Simulated Intestinal Fluid or SIF). Furthermore, it has been demonstrated that the preservation of a protein-based active ingredient extends beyond its primary protein structure to include its functional aspects, such as enzymatic activity. This drug delivery technology could enable the protection of hydrophilic active biomolecules, such as pancreatin, which are sensitive to gastric acidity, while promoting their immediate release upon contact with bile salts in the proximal duodenum, with the ultimate goal of correcting the digestive defect induced by EPI.

A systematic review of yoga for the treatment of gastrointestinal disorders.

Several studies have reviewed yoga for the treatment of disorders of gut-brain interaction (DGBI) with most demonstrating a benefit for symptom reduction; however, yoga has been studied beyond DGBI. The aim of this systematic review is to provide a comprehensive summary of yoga as treatment for gastrointestinal conditions. We conducted literature searches in PubMed and Embase and included yoga trials of adults with a diagnosis of a gastrointestinal disorders and diseases. We identified 1275 articles; 12 studies were eligible. Most studies compared yoga to controls, for patients with different GI conditions (irritable bowel syndrome, ulcerative colitis, chronic pancreatitis, and gastrointestinal cancer). The type, method, and duration of yoga used varied. Across IBS studies, most demonstrated that yoga improved IBS symptom severity, mood-related symptoms, and quality of life compared with controls. In one study of inflammatory bowel disease, yoga improved quality of life compared to controls. Two studies of gastrointestinal cancer demonstrated that yoga led to a reduction in sleep disturbance and mood symptoms. One study of chronic pancreatitis found that yoga led to improvements in quality of life, stress, mood changes, alcohol dependence, and appetite. Yoga was generally safe, and no serious adverse events were attributed to the intervention. In conclusion, yoga appears to be safe and has potential to improve functioning across a spectrum of gastrointestinal diseases; however, current studies are limited by heterogeneity and methodological weaknesses. Further research is needed to evaluate the impact of yoga on health outcomes for a broader range of gastrointestinal conditions.

Abstract B024: Multiplexed 3D atlas of state transitions and potential prognostic role of poly- ADP ribose glycohydrolase (PARG) in chronic pancreatitis and PDAC

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC), a disease predominantly associated with chronic inflammation, ranks as the third-leading cause of cancer-related mortality. The limited efficacy of current PDAC therapies is, in part, attributed to the challenges posed by late- stage diagnosis, highlighting the urgent need for early detection techniques to improve treatment outcomes. Sustained pancreatic inflammation induces the production of reactive oxygen species, leading to the activation of the DNA damage repair network, including enzymes such as poly-ADP ribose glycohydrolase (PARG). PARG is crucial for degrading poly-ADP ribose (PAR) chains catalyzed by PARP and, thus, regulating key cellular responses to DNA damage. However, the role of PARG in the molecular etiology of pancreatic diseases remains unclear. As a first step, we conducted a single-cell spatial analysis on a multiplex immunofluorescence cyclic dataset focusing on pathways involved in: immune and stromal alterations influencing cell-state transitions; differentiation; and critical cellular signaling pathways. Specifically, we evaluated the expression patterns of DNA damage enzymes (i.e., PARG), to elucidate their potential roles in the transformation from chronic inflammation to malignancy. Method: The human pancreatitis tissue microarray (TMA), consisting of 6 normal, 36 pancreatitis, 36 pancreatic intraepithelial neoplasia (PanINs), and 6 PDAC samples in duplicate, obtained from patients with pancreatitis or pancreatic cancer diagnosed at Oregon Health and Science University. We generated a comprehensive 48-plex image dataset that was processed through unsupervised clustering and manual gating to identify common cell types across different stages of pancreatic disease, including epithelial, stromal, immune, and endothelial. Result and conclusion: We observed moderate to strong cytoplasmic PARG expression in pancreatitis samples compared to normal tissue (p &amp;lt; 0.001), which significantly decreased in PanINs (p &amp;lt; 0.001) and PDAC samples (p &amp;lt; 0.001). Notably, the PARG expression was primarily in CK19-positive epithelial cells. Further evaluation showed that DNA damage markers, such as pRPA and γH2AX, increased as the disease progressed from pancreatitis to PanINs to PDAC. Therefore, there was an inverse correlation between PARG expression and DNA damage marker expression in cells exhibiting DNA damage. Additionally, PARG expression was inversely correlated with proliferating cells, marked by Ki67 and PCNA, at the single-cell level. In conclusion, our single-cell spatial analysis supports the notion that PARG expression correlates with resolution of DNA damage and that its reduced expression associates with disease progression and cellular proliferation. Overall, these findings support early phase clinical trials using PARG inhibitors in the oncologic space, and as a potential target for early detection of PDAC and treatment of other pancreatic diseases. Mechanistically, PARG loss may provide a setting for faulty DNA repair and thus, an accumulation of driver mutations. Citation Format: Vidhi M Shah, Jennifer Eng, Koei Chin, Brett C. Sheppard, Jonathan R. Brody, Rosalie C. Sears. Multiplexed 3D atlas of state transitions and potential prognostic role of poly- ADP ribose glycohydrolase (PARG) in chronic pancreatitis and PDAC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B024.

Abstract C059: Regulatory Elements of Pancreas Development License the Initiation of Pancreatic Ductal Adenocarcinoma

Abstract Mutations in DNA are a known cause of cancer. However, they become oncogenic only under specific cellular conditions and within certain tissue contexts. Tissue injury often leads to the aberrant activation of developmental pathways, eroding markers of cellular differentiation and giving rise to transient cellular states. These states resemble developmental progenitors, characterized by higher transcriptional plasticity. Oncogenes, particularly KRAS, co-opt cellular plasticity by acting on tissue-specific enhancers, preventing the resolution of acinar plasticity and maintaining the pancreas in a pro-inflammatory phase that progresses to cancer1,2. However, the specific role of tissue-specific enhancers in pancreas regeneration and cancer initiation remains unexplored, and strategies to target these regenerative processes are yet to be developed. Our laboratory investigates non-mutational mechanisms of cancer, with a special interest in the intersection of developmental biology and cancer, aiming to elucidate the processes of cellular plasticity and cancer initiation. Recent studies have shown that acinar cells possess remarkable cellular plasticity, giving rise to a diverse population of cellular states in pancreas regeneration and cancer contexts3-5. We have discovered that the transcription factor Sox4 is necessary for the specification of tuft cells and gastric metaplasia found in chronic pancreatitis and in pancreatic intraepithelial lesions (PanINs). Moreover, we have shown that cellular plasticity has a non-cell autonomous protective effect; losing Sox4 and cellular heterogeneity in PanINs results in a fibrotic and immunosuppressive tumor microenvironment and disease progression. Our results demonstrated that targeting cellular plasticity accelerates or prevents cancer initiation through autonomous and non-autonomous cellular processes6. In this study, we leverage a comprehensive resource of ncRNAs transcribed from enhancer elements of pancreas development, together with their inferred target genes and correlations with clinical outcomes. We focused on an ncRNA associated with the risk of pancreatic cancer. To study its function, we developed two novel mouse strains for tissue-specific deletion, enabling precise manipulation and study of its role in the pancreas and other tissues. Our phenotypic analysis demonstrates that the ncRNA is activated following tissue injury and is essential for developing PanINs. Moreover, we show that it regulates cell-cell communication after tissue injury. This mechanism operates independently of cellular plasticity but significantly creates a pro-inflammatory environment that favors cancer development. Our results demonstrate that enhancer elements are actionable targets to regulate cell fate decisions in regeneration and cancer. Additionally, KRAS-induced cancer initiation depends on developmental regulatory elements, opening the window to develop prophylactic interventions to delay tumor onset. Citation Format: Luis Arnes. Regulatory Elements of Pancreas Development License the Initiation of Pancreatic Ductal Adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C059.