Chronic Pancreatitis Research Articles

Effect of endoscopic ultrasound guided celiac plexus block on the palliation of pain in chronic pancreatitis (EPOCH Trial): study protocol for a randomized multicenter sham-controlled trial {1}

BackgroundCeliac plexus block has been commonly utilized for the treatment of chronic pancreatitis-associated abdominal pain. Prospective studies suggest efficacy in 30 to 50% of patients, although no randomized sham-controlled trials have been performed. The objective of this study is to assess the effect of endoscopic ultrasound (EUS)-guided celiac plexus block on abdominal pain in patients with documented chronic pancreatitis. MethodsThis is a two-arm randomized sham-controlled trial with blinded evaluators. The study will be conducted at multiple academic sites in the United States who are members of the United States Pancreatic Disease Study Group (USPG). Patients referred for EUS to exclude chronic pancreatitis as a cause of abdominal pain as well as those with established painful chronic pancreatitis undergoing EUS for another indication will be eligible. At the time of EUS with confirmation of chronic pancreatitis by standard EUS diagnostic criteria, patients will be randomized to either celiac plexus block or sham whereby an anesthetic and steroid combination will be injected into the celiac plexus or saline will be injected into the gastric lumen with the same type of needle as used for celiac plexus block, respectively. The main outcome measure will be a 50% reduction in abdominal pain using the Brief Pain Inventory Short Form (BPI-SF) at 1 month post-intervention. A number of secondary outcomes will be measured including visual analog scale (VAS), Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) pain scores, and quality of life using a pancreas-specific validated measure (PANQOLI).DiscussionIn this study, the effect of celiac plexus block on abdominal pain in patients with chronic pancreatitis will be compared to a sham intervention. This randomized trial will offer a definitive assessment of the role of celiac plexus block for the treatment of abdominal pain in this setting.Trial registration {2}ClinicalTrials.gov NCT 06178315. Registered on December 21, 2023

Results of surgical treatment of chronic pancreatitis with a high risk of developing pancreatic cancer

Objective. To analyze the results of surgical treatment of patients with pancreatic insufficiency and a high risk of developing pancreatic cancer. Materials and methods. The study included 39 patients treated in 2019–2023. In 20 (51%) patients, it was difficult to clearly differentiate between chronic pancreatitis and pancreatic cancer. In 19 (49%) patients, the diagnosis of chronic pancreatitis was not in doubt. All patients with complicated forms of chronic pancreatitis and suspected pancreatic tumor underwent a set of laboratory tests, and routine screening methods of instrumental diagnostics were used. In addition to standard methods of examination, the levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases in the blood plasma were studied. Results. The method of intraoperative multiple biopsy, improved by us, was an obligatory component of surgical care for a clear differential diagnosis of chronic pancreatitis and pancreatic cancer. In the presence of complicated chronic pancreatitis, during surgery, the biopsy was taken using a special punch instrument that resembles a pen, along the entire length of the main pancreatic duct along the upper and lower edges of the dissection in a checkerboard pattern. There were no complications of punch biopsy. Of the 20 patients in whom it was not possible to clearly differentiate between chronic pancreatitis and pancreatic cancer, 12 (60%) were diagnosed with diabetes mellitus. The characteristic changes in the pancreatic tissue gave grounds for performing extended resection interventions in these patients. In the remaining 8 (40%) patients without morphological changes inherent in malignancy, Whipple operation (2), longitudinal pancreaticoduodenectomy (2), Frey operation (2), and our proposed central pancreatic resection with preservation of the left anatomical segment (2) were performed. Drainage and resectional surgical interventions were performed in 19 (49%) patients with complicated forms of chronic pancreatitis. After radical surgical interventions for pancreatic cancer, 1 patient developed gastrostasis, and on the 11th day he underwent a relaparotomy with reconstruction of the gastroenteroanastomosis, and on the 30th day a subhepatic abscess was diagnosed in 1 patient, who underwent drainage with a subcostal mini–access with a positive effect. In 2 patients, after left–sided pancreatic resection, subdiaphragmatic abscesses were diagnosed on the left, they were treated minimally invasively with punctures and drainage under ultrasound control. Multiple organ failure occurred in 1 patient after surgery for internal pancreatic fistula, infected ascites as a complication of neglected chronic pancreatitis. The patient died. Infection of the median laparotomy wound occurred in 4 patients, and healing was achieved by controlled primary tension. Class B pancreatic fistulas occurred in 3 patients: 2 – after left–sided pancreatic resection, 1 – after longitudinal pancreaticoduodenostomy. In 1 patient, a class C permanent pancreatic fistula was formed after a combined (resection and drainage) intervention. Relaparotomy, subtotal resection with Roux–en–Y loop closure was performed. Conclusions. Morphological changes in the pancreatic tissue in chronic pancreatitis in combination with diabetes mellitus, corresponding to the development of PanIN, are direct predictors of adenocarcinoma. Multiple intraoperative pancreatic biopsies are effective in verifying pancreatic malignancy. Pre– and intraoperative diagnostics make it possible to optimize the surgical treatment of complicated forms of chronic pancreatitis and prevent the development of postoperative pancreatic fistula.

Metagenomic Study Reveals Phage–Bacterial Interactome Dynamics in Gut and Oral Microbiota in Pancreatic Diseases

Individuals with pancreatic-related health conditions usually show lower diversity and different composition of bacterial and viral species between the gut and oral microbiomes compared to healthy individuals. We performed a thorough microbiome analysis, using deep shotgun sequencing of stool and saliva samples obtained from patients with chronic pancreatitis (CP), pancreatic ductal adenocarcinoma (PDAC), and healthy controls (HCs).We observed similar microbiota composition at the species level in both the gut and oral samples in PDAC patients compared to HCs, among which the most distinctive finding was that the abundance of oral-originated Fusobacterium nucleatum species did not differ between the oral and the gut samples. Moreover, comparing PDAC patients with HCs, Klebsiella oxytoca was significantly more abundant in the stool samples of PDAC patients, while Streptococcus spp. showed higher abundance in both the oral and stool samples of PDAC patients. Finally, the most important finding was the distinctive gut phage–bacterial interactome pattern among PDAC patients. CrAssphages, particularly Blohavirus, showed mutual exclusion with K. oxytoca species, while Burzaovirus showed co-occurrence with Enterobacteriaceae spp., which have been shown to be capable of inducing DNA damage in human pancreatic cells ex vivo. The interactome findings warrant further mechanistic studies, as our findings may provide new insights into developing microbiota-based diagnostic and therapeutic methods for pancreatic diseases.

Chronic Pancreatitis with Unilateral Pleural Effusion: An Atypical Presentation

Chronic Pancreatitis with Unilateral Pleural Effusion: An Atypical Presentation

Sarcopenia Prevalence in Liver Cirrhosis Patients Using MRI and Handgrip Strength Measurements

Background: Cirrhosis, a leading cause of mortality worldwide, is histologically represented as formation of regenerative nodules encircled by fibrous bands caused by chronic liver injury. Nutritional status in cirrhotic patients is challenging to assess due to fluid accumulation resulting from impaired protein synthesis. Factors such as reduced food intake, malabsorption, and altered macronutrient metabolism negatively impact the nutritional status, leading to sarcopenia. The development of sarcopenia is multifactorial and is linked to lower survival rates. Aim: To assess sarcopenia prevalence in liver cirrhosis patients using MRI and handgrip strength measurements. Discussion: Impaired food intake in liver cirrhosis results from a combination of factors including loss of appetite, hormonal changes, early satiety, ascites, nausea, taste disturbances, and functional dyspepsia. Malabsorption can also occur due to portosystemic shunting, reduced bile production, chronic pancreatitis, and small intestinal bacterial overgrowth, all of which contribute to sarcopenia. It also arises from complex interactions involving impaired glycogen synthesis, inadequate nutrition, disrupted skeletal muscle protein synthesis and underlying hypermetabolism. Conclusion: MRI-based assessments indicate there is a significant occurrence of sarcopenia in individuals with cirrhosis. Our findings reveal that handgrip strength, when correlated with MRI results, is a reliable predictor of sarcopenia in these patients.

Focal Pancreatitis Mimicking Neuroendocrine Tumor on DOTATATE PET/CT With Radiology-Pathology Correlation.

A 54-year-old man presented with left lower quadrant pain. CT showed no cause for his pain but identified an incidental 2.0-cm enhancing lesion in the pancreatic tail. On MRI, this lesion was hyperenhancing and diffusion-restricting, suspicious for a neuroendocrine tumor. However, EUS-guided biopsy yielded only benign pancreatic tissue. Due to this discordance, 64 Cu-DOTATATE PET/CT was performed. The pancreatic tail lesion was tracer-avid, suggesting a well-differentiated neuroendocrine tumor. Based on the PET findings, the patient underwent distal pancreatectomy. Surgical pathology revealed only focal chronic pancreatitis with islet aggregation, a previously undescribed mimic of neuroendocrine tumor on DOTATATE PET/CT.

An intensified trans-sectoral nutritional intervention in malnourished patients with chronic pancreatitis improves diseases prognosis and identifies potential biomarkers of nutritional status.

Malnutrition is a common complication in chronic pancreatitis and associated with reduced quality of life and life expectancy. Nutritional support is considered mandatory in malnourished patients with chronic pancreatitis but there is only scarce evidence on optimal treatment modalities and the efficacy of nutrition therapy. Here, we investigated the feasibility and efficacy of an intensified nutritional intervention in malnourished patients with chronic pancreatitis and aimed to identify suitable indicators for monitoring nutritional status. We performed a single-arm feasibility study, in which malnourished patients with chronic pancreatitis received an intensified trans-sectoral nutritional intervention for 6 months. Multimodal treatment comprised face-to-face dietary counseling, oral nutritional supplementation, and a complementary telephone-based nutrition and exercise coaching. Patients underwent follow-up examinations after 28, 90, and 180 days, when we assessed changes in anthropometric and body composition measures, muscle function, Chronic Pancreatitis Prognosis Score (COPPS), as well as blood parameters and intestinal microbiota composition. Eleven out of 73 patients initially screened for study participation were enrolled in the trial of which 9 subjects (age (mean ± SD): 56.2 (±14.8) years; male: 67%; alcoholic etiology: 44%) underwent the complete intervention. Patients gained a median of 5.3 kg (8.6%) body weight, including 1.6 kg skeletal muscle mass, and significantly increased gait speed (p < 0.001). Ameliorated nutritional status and muscle function were associated with increased blood levels of IGF-1 and cholinesterase as well as altered gut microbiota composition on the phyla and genera level. Moreover, significant improvements in COPPS indicated reduced disease severity after 90 and 180 days. Malnourished patients with chronic pancreatitis benefit from intensified nutritional therapy. Besides ameliorated nutritional status, a multimodal intervention can improve muscle function as well disease prognosis. Future studies are needed to prove superiority to standard-of-care and to validate potential biomarkers for prospective monitoring of nutritional status. https://clinicaltrials.gov/study/NCT04476056, NCT04476056.

Effects of asparaginase-associated pancreatitis in children with haematological tumours.

Asparaginase-associated pancreatitis (AAP) is a major challenge for continuing asparaginase therapy. We aimed to investigate the acute and long-term complications and survival rates related to first and second AAP episodes in Chinese children with haematological malignancies. We retrospectively analysed clinical data of children with pancreatitis who received asparaginase chemotherapy for acute lymphoblastic leukaemia (ALL), acute mixed cell leukaemia, and non-Hodgkin's lymphoma at Shanghai Children's Medical Center from November 2013 to November 2023. Of the 76 children included in the study, 12 had local complications (15.79%), with no deaths recorded. Systemic complications manifested in 28 patients (36.84%), resulting in 3 deaths (3.95%). Four patients (5.26%) developed long-term complications (chronic pancreatitis or insulin-dependent diabetes mellitus). No significant differences in local or long-term complications were recorded between children in the asparaginase re-exposed (n=39) and non-re-exposed (n=45) groups. Among the re-exposed patients, eight (25.81%) experienced a second attack without fatalities or complications. Survival analysis of intermediate- to high-risk patients revealed a significantly higher event-free survival (EFS) rate for the re-exposed group than for the non-re-exposed group. The second AAP episode's occurrence and severity had no relation to the first AAP episode's severity, and the second AAP episode was significantly less severe than the first (p<0.001). The second AAP episode's occurrence is unrelated to the first AAP episode's severity, and the second AAP episode's severity is significantly lower than that of the first. Further, asparaginase therapy could improve EFS in children with intermediate and high-risk ALL.

Impact of asprosin, interleukin-6, and adiponectin on exocrine pancreatic insufficiency in patients with type 2 diabetes mellitus and chronic pancreatitis

Exocrine pancreatic insufficiency (EPI) is a clinical condition often associated with chronic pancreatitis (CP) and type 2 diabetes mellitus (T2DM) leads to malabsorption and nutritional deficiencies, severely impacting patients’ quality of life. It has been identified that asprosin, a glucogenic protein, is a key player in carbohydrate metabolism and chronic inflammation. Elevated levels of asprosin, along with changes in interleukin‑6 (IL‑6) and adiponectin, may contribute to the pathophysiology of EPI in patients with T2DM and CP. Objective — to investigate the levels of asprosin, IL‑6, and adiponectin and their correlation with exocrine pancreatic function in patients with T2DM and CP. Materials and methods. The study included 100 patients treated at Kharkiv Regional Clinical Hospital from 2020 to 2022. Patients were divided into two groups: Group 1 (n=70) with comorbid T2DM and CP, and Group 2 (n=30) with T2DM alone. The control group included 20 healthy individuals. Blood levels of asprosin, IL‑6, and adiponectin were measured using immunoassays. Fecal elastase‑1 (FE‑1) levels were used to assess exocrine pancreatic function. Pearson’s correlation coefficient was calculated to determine the relationships between these markers. Results. Asprosin levels were significantly higher in Group 1 compared to Group 2 and the control group, with the highest levels observed in patients with comorbid T2DM and CP (10.06±3.56 ng/ml). IL‑6 levels were also elevated in Group 1 (64.44±4.35 pg/ ml), indicating heightened inflammation. Adiponectin levels were lower in Group 1 (2.80±0.38 ng/ml), correlating with worse metabolic profiles. FE‑1 levels were markedly reduced in Group 1 (142.2±6.3 mg/ g), confirming severe EPI. Significant correlations were found between asprosin levels and IL‑6 (positive correlation, r=0.49, p&lt;0.01), as well as between asprosin levels and FE‑1 (negative correlation, r=–0.52, p&lt;0.01). In the group of patients with isolated T2DM, significant moderate negative correlations were found between asprosin levels and adiponectin (r=–0.47, p&lt;0.05) and FE‑1 (r=–0.44, p&lt;0.05). The study also demonstrated a strong negative correlation between adiponectin and IL‑6 (r=–0.61, p&lt;0.01) in patients with comorbid T2DM and CP. Conclusions. Elevated asprosin levels in patients with T2DM and CP are associated with increased inflammation and reduced exocrine pancreatic function. The significant correlations between asprosin, IL‑6, and FE‑1 suggest that asprosin could serve as a clinically valuable biomarker for assessing metabolic and inflammatory status in these patients. The findings highlight the complex interaction between metabolic and inflammatory pathways in the development of EPI.

Correlating tissue and plasma‑specific piRNA changes to predict their possible role in pancreatic malignancy and chronic inflammation.

The aggressiveness of pancreatic ductal adenocarcinoma is primarily due to lack of effective early detection biomarkers. Circulating non-coding RNAs serve as diagnostic or prognostic biomarkers in multiple types of cancer. Comparison of their expression between diseased tissue and relevant body fluids such as saliva, urine, bile, pancreatic juice, blood etc. may reveal mechanistic involvement of common non-coding RNAs. piwi-interacting RNAs (piRNAs) are a class of non-coding RNAs. The aim of the present study was to investigate plasma and tumour tissue piRNA changes in patients with pancreatic cancer (PC) and explore the possible role in tumorigenesis and pancreatic inflammation. Sequencing of circulating plasma small RNAs from patients with PC and chronic pancreatitis (CP) was performed and differentially expressed piRNAs were compared with those in tissues. Subsequent search for target genes for those piRNAs was performed followed by pathway and cluster analysis. A total of 36 piRNAs were shown to be deregulated in pancreatic tumour tissue and alteration of 11 piRNAs was detected in plasma of patients with PC. piRNAs hsa-piR-23246, hsa-piR-32858 and hsa-piR-9137 may serve a key role in PC development as their expression was correlated in both plasma and tumour tissue. Key piRNA-target interactions interfering with key biological pathways were also characterized. A total of 19 deregulated piRNAs in plasma samples of patients with CP was identified; these targeted genes responsible for chronic inflammation. Therefore, the present study provides a comprehensive description of piRNA alteration in pancreatic malignancy and inflammation; these may be explored for biomarker potential in future.

8182 New Mouse Model Mirrors Human MODY8: Opening Doors to Understanding Exocrine-Endocrine Crosstalk in the Diabetic Pancreas

Abstract Disclosure: K. El Jellas: None. V. Salerno: None. L.S. Katz: None. J. Hu: None. G. Fogarty: None. A. Mandal: None. A. DiStefano-Forti: None. D. Scott: None. M. Lowe: None. A. Molven: None. R.N. Kulkarni: None. Maturity-onset diabetes of the young, type 8 (MODY8) is a dominantly inherited form of monogenic diabetes, caused by heterozygous mutations in the carboxyl ester lipase (CEL) gene expressed in pancreatic acinar cells. MODY8 is characterized by chronic pancreatitis and exocrine dysfunction. Despite the intimate anatomical relationship between the endocrine and exocrine pancreas, little is known about the biological components mediating exocrine-endocrine communication in regulating glucose homeostasis. Here, we report a refined mouse model that bears the mutation present in MODY8 patients on one allele, and the humanized normal variable number of tandem repeat (VNTR) of CEL with 16 repeats (16R) on the other, mimicking the genetic make-up seen in MODY8 patients. Examination of glucose homeostasis revealed that inducing stress (e.g. by high-fat diet) leads to glucose intolerance in MODY8/16R mice and a blunted glucose-stimulated insulin-secretion compared to their control littermates. Histopathological analyses demonstrated features of chronic pancreatitis in some pancreatic lobes, including inflammation, acinar atrophy, acinar-to-ductal metaplasia, fibrosis and fat infiltration, mirroring the morphology of the human disease. Moreover, we applied immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO) to intact pancreata and found that beta-cell mass was significantly decreased in the MODY8/16R mice, with a large number of islets located within fatty lobes. These results are coupled with comparative proteomics and lipidomic profiling with the aim of understanding the molecular signatures of exocrine and endocrine cells during pathogenesis. In conclusion, we have generated a mouse that recapitulates several features of the exocrine and endocrine phenotype characteristic of human MODY8. This novel model provides a unique opportunity, not possible in humans, to characterize pancreatic endocrine-exocrine communication in a longitudinal manner as a response to diverse environmental stressors. Presentation: 6/2/2024

Current status and future perspectives for endoscopic treatment of local complications in chronic pancreatitis.

Chronic pancreatitis is a progressive disease characterized by irregular fibrosis, cellular infiltration, and parenchymal loss within the pancreas. Chronic pancreatitis treatment includes lifestyle modifications based on disease etiology, dietary adjustments appropriate for each stage and condition, drug therapy, endoscopic treatments, and surgical treatments. Although surgical treatments of symptomatic chronic pancreatitis provide good pain relief, endoscopic therapies are recommended as the first-line treatment because they are minimally invasive. In recent years, endoscopic therapy has emerged as an alternative treatment method to surgery for managing local complications in patients with chronic pancreatitis. For pancreatic stone removal, a combination of extracorporeal shock wave lithotripsy and endoscopic extraction is used. For refractory pancreatic duct stones, intracorporeal fragmentation techniques, such as pancreatoscopy-guided electrohydraulic lithotripsy and laser lithotripsy, offer additional options. Interventional endoscopic ultrasound has become the primary treatment modality for pancreatic pseudocysts, except in the absence of disconnected pancreatic duct syndrome. This review focuses on the current status of endoscopic therapies for common local complications of chronic pancreatitis, including updated information in the past few years.

The complex interplay of Selenoprotein P, NO metabolites, and pancreatic enzymes in chronic pancreatitis and hypothyroidism is partially orchestrated by the SEPP1 gene’s rs7579 polymorphism: focus on gender aspect

Objective To establish the association of the SEPP1 gene’s (rs7579) polymorphism with enzymatic, metabolic and hormonal activity in patients with chronic pancreatitis (CP) and primary hypothyroidism. Materials and methods Eighty CP patients (40 with comorbid hypothyroidism) and 30 healthy controls participated in the case-control study. Pancreatic enzymes, Selenoprotein P, NO metabolites (NO2 -+NO3 -), glucose, total cholesterol (TC), triglycerides (TG) and low/high density lipoprotein cholesterol (LDL-, HDL-C), Atherogenicity Index (AI), thyroid-stimulating hormone (TSH), Thyroxine (T4), glomerular filtration rate (GFR) were studied. SEPP1 (rs7579) genotyping performed by PCR (FlexCycler BU). Results and discussion SEPP1 (rs7579) gene’s A-allele increases the risk of hypothyroidism twice in CP [OR=2.0; OR 95%CI:1.09-3.66; р=0.023]. Pancreatic patients with hypothyroidism and SEPP1 gene’s (rs7579) AA-genotype had 60.0% (рАА=0.013) lower elastase and 13.78% (р=0.003) higher α-amylase as well as TSH by 10.81% (рАА=0.009) and 15.64% (рАА=0.009), especially in women 14.55-45.18% (р&lt;0.001) at a lower value of Selenoprotein P – by 28.65-48.08% (р≤0.048) regardless of the SEPP1 gene (rs7579) variants. Women have 17.43-18.14% (pW≤0.032) higher NO metabolites than men; A-allele women have free T4 value 2.62 times lower (рGG=0.01) than GGwomen and 2.97 times lower (рW=0.011) than men. Comorbid patients with A-allele had elevated TC and LDL-C, by 11.77-26.45% (рАА≤0.01) and 18.06-26.21% (рАА≤0.019), respectively. Women have 54.50% (pW=0.002) higher AI with 39.30% lower (pW=0.034) Selenoprotein P and 21.96-24.56% (pW≤0.033) GFR than men. Conclusion SEPP1 (rs7579) gene polymorphism influences the risk of hypothyroidism in CP patients, changes of pancreatic enzymes, dyslipidaemia particular in AA-genotype carriers, mainly women. There was no dependence of SEPP1 and total NO metabolites values on the SEPP1 gene (rs7579) polymorphism. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1038-1047

Surgical treatment of chronic pancreatitis with an inflammatory pancreatic head mass: a retrospective study

BackgroundConservative treatment of chronic pancreatitis has only a limited effect in most patients. Surgery offers very good long-term results, even in the early stages of the disease. Unfortunately, only a minority of patients undergo surgical treatment. The aim of this work was to summarise the current treatment options for patients with an inflammatory mass of the pancreatic head. Data from patients in our study demonstrates that the surgery is a safe method, and here we compare the perioperative and early postoperative outcomes of patients who underwent a pancreatoduodenectomy and duodenum-preserving pancreatic head resection for chronic pancreatitis.MethodsAll patients who underwent a pancreaticoduodenectomy or a duodenum-preserving pancreatic head resection in our department between 2014 and 2022 were included in this study. Perioperative and early postoperative results were statistically analysed and compared.ResultsThirty-eight pancreaticoduodenectomies and 23 duodenum-preserving pancreatic head resections were performed. The overall mortality was 3%, whereas the in-hospital mortality after pancreaticoduodenectomy was 5%. The mortality after duodenum-preserving pancreatic head resection was 0%. No statistically significant differences in the hospital stay, blood loss, and serious morbidity were found in either surgery. Operative time was significantly shorter in the duodenum-preserving pancreatic head resection group.ConclusionsBoth pancreatoduodenectomy and duodenum-preserving pancreatic head resection are safe treatment options. Duodenum-preserving pancreatic head resection showed a statistically significant superiority in the operative time compared to pancreaticoduodenectomy. Although other monitored parameters did not show a statistically significant difference, the high risk of complications after pancreaticoduodenectomy with a mortality of 5%; maintenance of the duodenum and upper loop of jejunum, and lower risk of metabolic dysfunctions after duodenum-preserving pancreatic head resection may favour duodenum-preserving pancreatic head resection in recommended diagnoses. Attending physicians should be more encouraged to use a multidisciplinary approach to assess the suitability of surgical treatment in patients with chronic pancreatitis.

Utility of dual-energy CT and advanced multiparametric MRI based imaging biomarkers of pancreatic fibrosis in grading the severity of chronic pancreatitis.

To non-invasively quantify pancreatic fibrosis and grade severity of chronic pancreatitis (CP) on dual-energy CT (DECT) and multiparametric MRI (mpMRI). We included 72 patients (mean age:30years; 59 men) with suspected or confirmed CP from December 2019 to December 2021 graded as equivocal(n = 20), mild(n = 18), and moderate-marked(n = 34) using composite imaging and endoscopic ultrasound criteria. Study patients underwent multiphasic DECT and mpMRI of the abdomen. Normalized iodine concentration(NIC) and fat fraction(FF) on 6-minute delayed DECT, and T1 relaxation time(T1Rt), extracellular volume fraction(ECVf), intravoxel incoherent motion-based perfusion fraction(PF), and magnetization transfer ratio(MTR) on mpMRI of pancreas were compared. 20 renal donors(for DECT) and 20 patients with renal mass(for mpMRI) served as controls. NIC of pancreas in controls and progressive grades of CP were 0.24 ± 0.05, 0.80 ± 0.18, 1.06 ± 0.23, 1.40 ± 0.36, FF were 9.28 ± 5.89, 14.19 ± 5.29, 17.31 ± 5.99, 29.32 ± 12.22, T1Rt were 590.11 ± 61.13, 801.93 ± 211.01, 1006.79 ± 352.18, 1388.01 ± 312.23ms, ECVf were 0.07 ± 0.03, 0.30 ± 0.12, 0.41 ± 0.12, 0.53 ± 0.13, PF were 0.38 ± 0.04, 0.28 ± 0.07, 0.25 ± 0.09, 0.21 ± 0.05 and MTR were 0.12 ± 0.03, 0.15 ± 0.06, 0.21 ± 0.07, 0.26 ± 0.06, respectively. There were significant differences for all quantitative parameters between controls and mild CP; for NIC, PF, and ECVf between controls and progressive CP grades (p < 0.05). Area under curve for NIC, FF, T1Rt, ECVf, PF, and MTR in differentiating controls and mild CP were 1.00, 0.86, 0.95, 1.00, 0.90 and 0.84 respectively and for NIC, FF, ECVf and PF in differentiating controls and equivocal CP were 1.00, 0.76, 0.95 and 0.92 respectively. DECT and mpMRI were useful in quantifying pancreatic fibrosis and grading the severity of CP. NIC was the most accurate marker.

A causal relationship between distinct immune features and acute or chronic pancreatitis: results from a mendelian randomization analysis

ObjectivesThis study aimed to thoroughly examining the causal link between immune traits and four types of pancreatitis, using mendelian randomization. MethodsData on 731 immune traits were collected from the genome-wide association study (GWAS) database as exposure. Information regarding acute pancreatitis (AP), alcohol-induced acute pancreatitis (AAP), chronic pancreatitis (CP), and alcohol-induced chronic pancreatitis (ACP) were acquired from the FinnGen Consortium as outcomes. Mendelian randomization (MR) using inverse variance weighting (IVW) evaluated the links between immune traits and pancreatitis. We evaluated the robustness of the IVW results through sensitivity analyses and validated them using meta-analysis with AP and CP data from the UK Biobank in the GWAS catalog. ResultsA total of 36 immune traits showed significant associations with susceptibility of four types of pancreatitis, including AP (7 traits), AAP (8 traits), CP (14 traits), and ACP (7 traits). Twenty characteristics were found to be potential risk factors for pancreatitis, identified in B Cells (5 traits), conventional dendritic cells (cDCs, 2 traits), maturation stage of T cells (2 traits), monocytes (2 traits), myeloid cells (2 traits), T cells, B cells, natural killer cells (TBNK, 2 traits), and regulatory T cells (Treg cells, 5 traits). Multiple sensitivity analyses confirmed the validity of the findings. Meta-analysis confirmed a solid causal relationship between CX3CR1 on CD14− CD16−of monocyte panel and the susceptibility of CP. ConclusionsOur MR study identified immune traits causally linked to acute and chronic pancreatitis, offering new insights for early clinical intervention and immune cell-targeted therapies.

T1 signal intensity ratio correlation with T1 mapping in pediatric pancreatitis.

Our primary purpose was to understand the correlation between pancreas T1-weighted signal intensity ratio (SIR) and T1 relaxation time in children. We also sought to characterize differences in T1 SIR between children without and with pancreatitis. Retrospective study of patients < 18-years-old. SIR-pancreas:spleen (SIR-PS) and SIR-pancreas:paraspinal muscle (SIR-PM) were generated from T1-weighted gradient recalled echo images. Subdivided by field strength, T1 SIR was correlated (Spearman's) with T1 relaxation time. 220 participants were included, 144 imaged at 1.5T (mean: 11.4 ± 4.2 years) and 76 imaged at 3T (mean: 10.9 ± 4.5 years). At 1.5T, SIR-PS (rho=-0.62, 95% CI: -0.71 to -0.51, p < 0.0001) and SIR-PM(rho=-0.57, 95% CI: -0.67 to -0.45, p < 0.0001) moderately negatively correlated with T1 relaxation time. At 3T, correlations between T1 SIR and T1 relaxation time were moderate (rho=-0.40 to -0.43, p ≤ 0.0003). SIR-PS was significantly different between patient groups at 1.5T (p < 0.0001) with pairwise differences between: normal vs. acute on chronic pancreatitis (1.52 vs. 1.13; p < 0.0001). SIR-PM was also significantly different between groups at 1.5T (p < 0.0001) with differences between: normal vs. acute pancreatitis (1.65 vs. 1.40; p = 0.0006), normal vs. acute on chronic pancreatitis (1.65 vs. 1.18; p < 0.0001), and normal vs. chronic pancreatitis (1.65 vs. 1.52; p = 0.0066). A SIR-PS cut-off of ≤ 1.31 had 44% sensitivity and 95% specificity and SIR-PM cut-off of ≤ 1.53 had 69% sensitivity and 70% specificity for pancreatitis. At 3T, SIR-PS was significantly different between groups (p = 0.033) but without significant pairwise differences. At 1.5T pancreas T1 SIR moderately to strongly correlates with estimated T1 relaxation time and is significantly lower in children with pancreatitis.

An unusual type of diabetes “not 1” and “not 2”

Type 3c diabetes mellitus (T3cDM) is a secondary form of diabetes caused by pancreatic disease, such as chronic pancreatitis, that impairs insulin and glucagon secretion and results in poor glycemic control. Often misdiagnosed as type 2 diabetes, this pancreatic diabetes requires specific management due to elevated hemoglobin A1c levels, early insulin requirements, and increased risk of hypoglycemia. This case report discusses a 24-year-old man with hereditary chronic pancreatitis associated with the PRSS1 mutation, without typical symp­toms of exocrine pancreatic insufficiency, who presented with early insulin therapy and increased glycemic variability. The complexity of diagnosing this type of diabetes highlights the importance of diabetes screening in patients with chronic pancreatitis and the risk of inappropriate diagnosis and medical treatment.

Immortalized mesenchymal stromal cells overexpressing alpha-1 antitrypsin protect acinar cells from apoptotic and ferroptotic cell death.

Chronic pancreatitis (CP) is a progressive inflammatory disorder that impairs endocrine and exocrine function. Our previous work showed that mesenchymal stem/stromal cells (MSCs) and MSCs overexpressing alpha-1 antitrypsin (AAT-MSCs) could be therapeutic tools for CP. However, primary MSCs are predisposed to undergo senescence during culture expansion, which limits their therapeutic applications. We generated and characterized immortalized human MSCs (iMSCs) and AAT-MSCs (iAAT-MSCs) and tested their protective effect on 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced acinar cell death in an invitro cell culture system. Primary MSCs were immortalized by transduction with simian virus 40 large T antigen (SV40LT), and the resulting iMSC and iAAT-MSC lines were analysed for proliferation, senescence, phenotype and multi-differentiation potential. Subsequently, apoptosis and ferroptosis pathways were investigated by assessing changes before and after TNBS treatment. Coculture of iMSCs and iAAT-MSCs with acinar cell lines inhibited early cell death induced by TNBS, reduced ER stress and reversed TNBS-induced protein reduction at tight junctions. Additionally, iMSCs and iAAT-MSCs exerted such protection by regulating mitochondrial respiration, ATP content and ROS production in TNBS-induced acinar cells. Furthermore, iMSCs and iAAT-MSCs ameliorated TNBS-induced ferroptosis by modulating iron generation and ROS production and regulating the ferritin heavy chain 1 (FTH1)/protein disulfide isomerase (PDI)/glutathione peroxide 4 (GPX4) signalling pathways in acinar cells. These findings identify ferroptosis as an unrecognized mechanism that leads to TNBS-induced cell death and offer mechanistic insights relevant to using stem cell therapy to treat acinar cell death associated with CP.

S174 Pulmonary Embolism in Chronic Pancreatitis: A Retrospective Analysis of Predictors and Clinical Outcomes

S174 Pulmonary Embolism in Chronic Pancreatitis: A Retrospective Analysis of Predictors and Clinical Outcomes