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BACKGROUND & AIMS: Heterozygous SPINK1 mutations are strong risk factors for chronic pancreatitis in humans, yet heterozygous disruption of mouse Spink1 yielded no pancreatic phenotype. To resolve this contradiction, we used CRISPR/Cas9-mediated genome editing to generate heterozygous Spink1-deleted mice (Spink1-KOhet) in the C57BL/6N strain and studied the effect of this allele in trypsin-independent and trypsin-dependent pancreatitis models. METHODS: We investigated severity of acute pancreatitis and progression to chronic pancreatitis in Spink1-KOhet mice after transient (10 injections) and prolonged (2 × 8 injections) cerulein hyperstimulation. We crossed Spink1-KOhet mice with T7D23A and T7D22N,K24R mice that carry strongly autoactivating trypsinogen mutants and exhibit spontaneous chronic pancreatitis. RESULTS: Prolonged but not transient cerulein stimulation resulted in increased intrapancreatic trypsin activity and more severe acute pancreatitis in Spink1-KOhet mice relative to the C57BL/6N control strain. After the acute episode, Spink1-KOhet mice developed progressive disease with chronic pancreatitis-like features, whereas C57BL/6N mice recovered rapidly. Trypsinogen mutant mice carrying the Spink1-KOhet allele exhibited strikingly more severe chronic pancreatitis than the respective parent strains. CONCLUSIONS: Heterozygous Spink1 deficiency caused more severe acute pancreatitis after prolonged cerulein stimulation and promoted chronic pancreatitis after the cerulein-induced acute episode, and in two strains of trypsinogen mutant mice with spontaneous disease. In contrast, acute pancreatitis induced with limited cerulein hyperstimulation was unaffected by heterozygous Spink1 deletion, in agreement with recent observations that trypsin activity does not mediate pathologic responses in this model. Taken together, the findings strongly support the notion that loss-of-function SPINK1 mutations in humans increase chronic pancreatitis risk in a trypsin-dependent manner.

Background: The comorbidity of chronic pancreatitis (CP) in patients with osteoarthritis (OA) is insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of CP in OA patients, as well as associated complications. Methods: A cohort of 181 patients was categorized into four groups: a control group (n=30), patients with OA (n=68), patients with CP (n=31), and patients with OA and comorbid CP (n=52). All four groups had no statistical differences in age and gender. The study utilized the WOMAC index, Visual Analog Scale (VAS), Lequesne index, biochemical assays, and advanced statistical methods to assess joint status in OA patients with comorbid CP. It explored potential predictors of comorbidity development and associated complications. Results: The study revealed that concurrent CP in OA exacerbates progression and contributes to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for CP comorbidity development in OA patients. Factors such as the WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxyvitamin D3, and BMI were found to influence the development of comorbidity of CP in OA. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation Syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency Domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors comorbidity CP with exocrine pancreatic insufficiency in OA patients. Conclusion: The presence of CP in OA patients exacerbates disease progression and complications, necessitating further investigation. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Endoscopic ultrasound (EUS) is the most sensitive method for evaluation of pancreatic lesions but is limited by significant operator dependency. Artificial intelligence (AI), in the form of computer‐aided detection (CADe) systems, has shown potential in increasing accuracy and bridging operator dependency in several endoscopic domains. However, the complexity of integrating AI into EUS is far more challenging. This aims to develop and test the basis for a CADe system for real‐time detection and segmentation of all pancreatic lesions.In this single‐center study EUS studies of pancreatic findings were included. Lesions were outlined by two expert (>5 years performing EUS) endoscopists, and the two leading types of models were benchmarked. The models' performance was evaluated through per‐pixel intersection over union (IoU).A total of 1497 EUS images from 165 patients were evaluated. The dataset included malignancies, neuroendocrine tumors, benign cysts, chronic and acute pancreatitis, normal fatty pancreas, and benign lesions. The best model demonstrated detection and segmentation on the test set with a mean IoU of 0.73, achieving a PPV, NPV, total accuracy, and ROC of 0.82, 0.96, 0.95, and 0.95, respectively. The algorithm is adaptable for real‐time processing.We developed and tested deep learning models for real‐time detection and segmentation of pancreatic lesions during EUS with promising results. This constitutes the basis for a CADe system for EUS, which could be valuable in future detection and evaluation of pancreatic lesions. Further studies for validation and generalization are underway. [ABSTRACT FROM AUTHOR]

Background: The pancreas plays an important role in the nutrition and metabolism of the whole body. Many disease processes including obesity, diabetes mellitus (DM), acute or chronic pancreatitis, and pancreatic carcinoma result in abnormality of pancreas morphology and function. Magnetic resonance imaging (MRI) provides quantitative parameters including T1, T2, and apparent diffusion coefficient (ADC) values for evaluating normal and abnormal pancreas. Based on the normal range of these quantitative parameters, pancreatic abnormality could be detected early. However, the range and the relationship of T1, T2, and ADC values with gender and age groups using the same dataset have not been explored. Purpose: To establish the ranges of MRI tissue and functional parameters, including T1, T2, and ADC values, in healthy adult pancreas and their correlations with gender, subregion, and age. Materials and methods: The T1, T2, and ADC values of healthy pancreas in 86 adults were measured using a 3.0-T MRI scanner. The average T1, T2, and ADC values were obtained in the whole pancreas and subregions (head, neck, body, and tail). Their correlations with gender and age were investigated. Results: The T1, T2, and ADC values of the whole pancreas from all subjects were 870.07 ± 61.86 ms, 44.07 ± 6.14 ms, and 1.072 ± 0.212 × 10−3 mm2/s, respectively. T2 values were significantly different between genders (P < 0.05). No significant differences were found between subregions. The T1, T2, and ADC values differed significantly among the age groups (P < 0.05). The T1 value revealed a moderately positive correlation, while the T2 and ADC values displayed negative correlations with age (r = 0.31, −0.45, and −0.39, respectively). The combination of T1, T2, and ADC values achieved the highest AUC value and showed a significant difference compared to T1, T2, and ADC values alone in predicting age older than 45 years. Conclusion: This study established the normal ranges of T1, T2, and ADC. We found that T2 is different between men and women, and T1, T2, and ADC are age-dependent. These results could be useful for quantitative MRI of pancreatic disease. [ABSTRACT FROM AUTHOR]

Total pancreatectomy and islet autotransplantation (TPIAT) is an effective treatment for chronic and recurrent acute pancreatitis, and it provides a significant potential additional benefit of insulin independence. Spontaneous hypoglycemia in the absence of insulin therapy following TPIAT is a recognized complication, which has been attributed to lack of protective glucagon responses to hypoglycemia, following intrahepatic islet autotransplantation. We describe the use of liraglutide to treat spontaneous hypoglycemia following TPIAT. Continuous glucose monitoring was used to identify timing of hypoglycemia in relation to meals and monitor treatment effect. Liraglutide has been used for management of hypoglycemia following bariatric surgery, but, to our knowledge, this is the first application of its effective use to treat spontaneous severe hypoglycemia following TPIAT. [ABSTRACT FROM AUTHOR]

Background/Objectives: The clinical utility of body composition in the development of complications of acute pancreatitis (AP) remains unclear. We aimed to describe the associations between body composition and the recurrence of AP. Methods: We performed a retrospective study of patients hospitalized with AP at three tertiary care centers. Patients with computer tomography (CT) imaging of the abdomen at admission were included. A previously validated and fully automated abdominal segmentation algorithm was used for body composition analysis. Hospitalization for a recurrent episode of AP was the primary endpoint. Secondary endpoints included the development of chronic pancreatitis (CP) or diabetes mellitus (DM) in patients who were evaluated. Cox Proportional Hazards regression was used. Results: From a total of 347 patients, 89 (25.6%) were hospitalized for recurrent AP (median time: 219 days). Thirty-four of 112 patients (30.4%) developed CP (median time: 311 days) and 22 of 88 (25.0%) developed DM (median time: 1104 days). After adjusting for age, male sex, first episode of AP, BUN, and severity of AP, we found that obesity, body mass index, alcohol pancreatitis, and gallstone pancreatitis were significantly associated with a recurrent episode of AP. Body composition was not associated with recurrent AP. In unadjusted analysis, subcutaneous adipose tissue (SAT) (HR 0.87 per 10 cm2, p = 0.002) was associated with CP. Skeletal muscle (SM) mass approached significance for CP (p = 0.0546). Intermuscular adipose tissue (IMAT) (HR 1.45 per 5 cm2, p = 0.0264) was associated with DM. Conclusion: Body composition was not associated with having a recurrent AP. At follow-up, 30% and 25% of evaluated patients developed CP and DM, respectively. A higher SAT and IMAT were associated with a lower incidence of CP and higher incidence of DM, respectively. [ABSTRACT FROM AUTHOR]

Sphingosine-1-phosphate (S1P) is a sphingolipid metabolic product produced via the phosphorylation of sphingosine by sphingosine kinases (SPHKs), serving as a powerful modulator of various cellular processes through its interaction with S1P receptors (S1PRs). Currently, this incompletely understood mechanism in pancreatic diseases including pancreatitis and pancreatic cancer, largely limits therapeutic options for these disorders. Recent evidence indicates that S1P significantly contributes to pancreatic diseases by modulating inflammation, promoting pyroptosis in pancreatic acinar cells, regulating the activation of pancreatic stellate cells, and affecting organelle functions in pancreatic cancer cells. Nevertheless, no review has encapsulated these advancements. Thus, this review compiles information about the involvement of S1P signaling in exocrine pancreatic disorders, including acute pancreatitis, chronic pancreatitis, and pancreatic cancer, as well as prospective treatment strategies to target S1P signaling for these conditions. The insights presented here possess the potential to offer valuable guidance for the implementation of therapies targeting S1P signaling in various pancreatic diseases. [ABSTRACT FROM AUTHOR]

Purpose: To characterize T1 relaxation times of the pancreas, liver, and spleen in children with and without abdominal pathology. Methods: This retrospective study included pediatric patients (< 18-years-old). T1 mapping was performed with a Modified Look-Locker Inversion Recovery sequence. Patients were grouped based on review of imaging reports and electronic medical records. The Kruskal–Wallis test with Dunn's multiple comparison was used to compare groups. Results: 220 participants were included (mean age: 11.4 ± 4.2 years (1.5 T); 10.9 ± 4.5 years (3 T)). Pancreas T1 (msec) was significantly different between subgroups at 1.5 T (p < 0.0001). Significant pairwise differences included: normal (median: 583; IQR: 561–654) vs. acute pancreatitis (731; 632–945; p = 0.0024), normal vs. chronic pancreatitis (700; 643–863; p = 0.0013), and normal vs. acute + chronic pancreatitis (1020; 897–1099; p < 0.0001). Pancreas T1 was also significantly different between subgroups at 3 T (p < 0.0001). Significant pairwise differences included: normal (779; 753–851) vs. acute pancreatitis (1087; 910–1259; p = 0.0012), and normal vs. acute + chronic pancreatitis (1226; 1025–1367; p < 0.0001). Liver T1 was significantly different between subgroups only at 3 T (p = 0.0011) with pairwise differences between normal (818, 788–819) vs. steatotic (959; 848–997; p = 0.0017) and normal vs. other liver disease (882; 831–904; p = 0.0455). Liver T1 was weakly correlated with liver fat fraction at 1.5 T (r = 0.39; 0.24–0.52; p < 0.0001) and moderately correlated at 3 T (r = 0.64; 0.49–0.76; p < 0.0001). There were no significant differences in splenic T1 relaxation times between subgroups. Conclusion: Pancreas T1 relaxation times are higher at 1.5 T and 3 T in children with pancreatitis and liver T1 relaxation times are higher in children with steatotic and non-steatotic chronic liver disease at 3 T. [ABSTRACT FROM AUTHOR]

Background: Pancreatic fibrosis is the main pathological feature of chronic pancreatitis. There is a lack of medications that effectively alleviate or reverse pancreatic fibrosis and thus cure chronic pancreatitis. Methods: We screened drugs that could alleviate pancreatic fibrosis from 80 traditional Chinese medicine monomers and verified their efficacy and mechanisms. Results: We preliminarily identified corynoline as an antifibrotic candidate by drug screening among 80 compounds. In vitro, corynoline dose-dependently reduces collagen I synthesis in pancreatic stellate cells induced by TGF-β1 and inhibits its activation. Furthermore, we found that corynoline could alleviate the morphological disruption, such as acinar cell atrophy, collagen deposition etc., as well as reduced pancreatic weight in mice with chronic pancreatitis. We further validated the antifibrotic effect of corynoline in mRNA and protein levels. We also found that corynoline could inhibit NF-κB signaling pathway in vitro and in vivo. Next, we identified PSMA2 as the binding protein of corynoline by Lip-SMap and validated it using DARTS. Moreover, the siRNA of PSMA2 disrupts the anti-fibrotic effect of corynoline. Conclusion: In conclusion, corynoline is a promising agent for the treatment of pancreatic fibrosis and chronic pancreatitis. [ABSTRACT FROM AUTHOR]

Objective: The timely identification of both malignant and nonmalignant pancreatic lesions has the potential to significantly enhance prognosis and implement risk management strategies across various levels. microRNAs (miRs) and their corresponding targets play a crucial role in the development of pancreatic lesions and can serve as valuable diagnostic and therapeutic targets. The objective of our study was to investigate potential diagnostic markers that can effectively differentiate between malignant and nonmalignant pancreatic lesions. Methods: Gene Expression Omnibus (GEO) database with GSE24279 dataset was utilized to screen differentially expressed miRNAs (DEMs). We utilized the TargetScanHuman database to predict the target genes associated with hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p. Furthermore, a cohort comprising healthy individuals (n = 52), chronic pancreatitis (CP; n = 34), and pancreatic adenocarcinoma (PAAD; n = 53) patients was recruited to ascertain the levels of plasma markers. Results: We identified 3 miRNAs (hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p) and 2 proteins (PCDH1 and AMN) as potential diagnostic markers for distinguishing between CP and PAAD. The area under the curve (AUC) values for all markers exceeded .800. Notably, a combination of plasma PCDH1 and AMN demonstrated excellent diagnostic performance (AUC = .921; 95% CI: .866-.977; sensitivity = .792; specificity = .941) in discriminating between CP and PAAD. In addition, the model of hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p yielded an AUC of .928, sensitivity of .830, and specificity of .912, respectively. Conclusion: Plasma levels of miRNAs (hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p) and their corresponding targets (PCDH1 and AMN) hold promise as potential biomarkers for predicting PAAD in patients with CP. [ABSTRACT FROM AUTHOR]

A 10-y-old spayed female Cavalier King Charles Spaniel dog was presented to the Veterinary Teaching Hospital because of recurrent chronic abscesses on the distal pelvic limbs, fever, lethargy, lameness of unknown etiology, and chronic pancreatitis. Sterile nodular panniculitis was diagnosed after an extensive workup, and the dog initially responded to immunosuppressive therapy, but relapse and spread of cutaneous lesions and acute lameness occurred after 11 mo, and euthanasia was elected. Postmortem examination confirmed hyalinizing pancreatic adenocarcinoma with pancreatitis, panniculitis, polyarthritis (PPP), and osteomyelitis. Histopathology and bacterial and fungal cultures were supportive of a sterile process, specifically the PPP syndrome, which is a rare, potentially life-threatening, systemic manifestation of pancreatic disease in both people and animals. To our knowledge, a clinicopathologic description of a hyalinizing pancreatic adenocarcinoma associated with this rare syndrome has not been reported previously in a dog. [ABSTRACT FROM AUTHOR]

Debilitating abdominal pain is a common symptom affecting patients with chronic pancreatitis (CP). CP pain is dynamic due to multiple underlying mechanisms. The objective of this study was to 1) evaluate changes in pain phenotype at one year follow-up and 2) validate putative pain biomarkers in a prospective cohort study. The Neuropathic and Nociceptive PROMIS-PQ questionnaires were used to classify pain for participants with in the PROCEED study. Putative serum biomarkers were measured via immunoassay. At enrollment, 17.6 % (120/681) subjects with CP reported no pain in the previous year. Of those, 29 % experienced pain during the 1 yr follow-up whereas 18 % of those with pain prior to enrollment reported no pain during the 1 yr follow-up period. Of the 393 subjects with PROMIS-PQ data at enrollment, 212 also had follow-up data at 1 yr. Approximately half (53.3 %) of those individuals changed pain phenotype between baseline and follow-up. At 1 yr, serum TGFβ1 level was negatively correlated with nociceptive T-scores (p = 0.006). GP130 was significantly correlated with both nociceptive (p = 0.012) and neuropathic T-scores (p = 0.043) at 1 yr, which is consistent with the previously published findings. The positive association between TGFβ1 and pain is not maintained over time, suggesting it is a poor pain biomarker. However, serum GP130 is a consistent biomarker for mixed-type pain in CP. Preclinical studies show that targeting TGFβ1 or IL-6 (ligand for GP130) is sufficient to inhibit CP pain supporting further investigation of this as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) is associated with increased risk of calcium-oxalate kidney stones, likely due to enteric hyperoxaluria. However, the risk of kidney stones for patients with CP after total pancreatectomy with islet autotransplantation (TPIAT) is unknown. We aimed to evaluate kidney stone risk in patients with CP after TPIAT. A retrospective analysis of 629 patients who underwent TPIAT was conducted to identify patients who developed kidney stones post-TPIAT. Kaplan-Meier analysis estimated time to first event. An Anderson-Gill proportional-hazards analysis of all kidney stone events described key clinical associations. Mean age at TPIAT was 33 years (SD 15.3, range 3–69); 69.8 % (n = 439) were female. The estimated chance of any kidney stone episodes by 5 years post-TPIAT was 12.8 % (95 % CI: 8.8–16.6 %); by 10 years, 23.2 % (CI: 17.5–28.6 %); by 15 years, 29.4 % (CI: 21.8–36.2 %). Significant associations with kidney stones post-TPIAT included older age (HR 1.25 per 10 years), smoking history (HR 1.72), mild chronic kidney disease (HR 1.96), renal cysts (HR 3.67), pre-TPIAT kidney stones (HR 4.06), family history of kidney stones (HR 4.10), and Roux-en-Y reconstruction (HR 2.68). Of the 77 patients who developed kidney stones, 34 (44.1 %) had recurrent episodes. Of 143 total kidney stone events, 35 (24.5 %) required stone removal, 79 (55.2 %) resolved spontaneously, and 29 (20.3 %) were missing this data. Patients with CP post-TPIAT commonly have kidney stones: nearly 3 in 10 have ≥1 kidney stone episodes within 15 years. Clinicians should be aware of this risk and counsel patients on prevention. [ABSTRACT FROM AUTHOR]

Objectives: Pancreatic steatosis (PS) and pancreatic fibrosis (PF) both show increased pancreatic echogenicity on conventional B‐mode ultrasound. In this study, we assessed the applicability of two‐dimensional shear‐wave elastography (2D‐SWE) for their discrimination. Methods: We gathered data from 120 adults with valid 2D‐SWE measurements, comprising 40 healthy individuals, 55 individuals diagnosed with PS via non‐enhanced computed tomography (CT), and 25 patients clinically diagnosed with non‐calcific chronic pancreatitis. The participants were divided into three groups: normal pancreas (NP), PS, and PF. pancreatic echogenicity, pancreatic stiffness, and CT values between groups were analyzed. Results: The 2D‐SWE and CT values among the NP, PS, and PF groups all showed significant differences (P <.001). For the diagnosis of PS and PF using 2D‐SWE, the area under the curve (AUC) values were 0.9100 and 0.9940, respectively, with optimal cut‐off values of 5.7 kPa for predicting PS and 8.2 kPa for predicting PF. Conclusions: The 2D‐SWE technique enabled rapid and quantitative assessment of the hardness of hyperechoic pancreas visualized on conventional B‐mode ultrasound, which holds certain value in distinguishing PS from PF. Access the CME test here and search by article title. [ABSTRACT FROM AUTHOR]

Background: Pancreatitis is a serious and complex inflammatory disease that imposes a severe effect on quality of life. Links between plasma lipidome and pancreatitis have been reported, some of which have not yet been clearly elucidated. Methods: Therefore, our study aimed to investigate the causal relationships between plasma lipidome and four types of pancreatitis by conducting a bidirectional, two-sample Mendelian randomization (MR) analysis. We obtained genetic variants associated with 179 lipid species from a Genome-wide association analysis of plasma lipidome. The aggregated statistical data of acute pancreatitis (AP), alcohol-induced acute pancreatitis (AAP), chronic pancreatitis (CP), and alcohol-induced chronic pancreatitis (ACP) from the FinnGen consortium were exploited as the outcome. The inverse variance weighted (IVW) technique as the main method was used for MR analysis and sensitivity analyses were used to evaluate heterogeneity and pleiotropy. Results: After FDR correction, SE (27:1/20:4) (OR = 0.938, 95%CI = 0.906-0.972, P = 4.38 × 10-4, PFDR = 0.039) was identified to be significantly associated with AP risk. Eight lipid species were identified to be significantly associated with CP risk: SE (27:1/20:4) (OR = 0.911, 95%CI = 0.869-0.954, P = 8.89 × 10-5, PFDR = 0.016), LPC (20:4) (OR = 0.892, 95%CI = 0.843-0.945, P = 9.74 × 10-5, PFDR = 0.009), PC (16:0_22:5) (OR = 0.880, 95%CI = 0.818-0.947, P = 6.29 × 10-4, PFDR = 0.028), PC (17:0_20:4) (OR = 0.893, 95%CI = 0.842-0.948, P = 1.76 × 10-4, PFDR = 0.010), PC (18:0_20:4) (OR = 0.920, 95%CI = 0.874-0.969, P = 1.70 × 10-3, PFDR = 0.038), PC (O-16:0/20:4) (OR = 0.871, 95%CI = 0.804-0.943, P = 6.95 × 10-4, PFDR = 0.025), PC (O-16:1/20:4) (OR = 0.890, 95%CI = 0.832-0.953, P = 7.85 × 10-4, PFDR = 0.023), and PE (O-18:1/20:4) (OR = 0.866, 95%CI = 0.791-0.947, P = 1.61 × 10-3, PFDR = 0.041). Furthermore, genetically predicted increased LPC (20:4) (OR = 0.862, 95%CI = 0.796-0.934, P = 3.00 × 10-4, PFDR = 0.027) and SM (34:2;O2) (OR = 0.753, 95%CI = 0.659-0.860, P = 2.97 × 10-5, PFDR = 0.005) levels were associated with decreased risk of ACP. Conclusions: Our findings provide evidence of causal associations between the specific types of lipidome and pancreatitis, offering new insights into future clinical research. [ABSTRACT FROM AUTHOR]

Elastography is a non-invasive imaging modality that has been developed for the evaluation of the stiffness of various organs. It is categorized into two main types: strain elastography and shear wave elastography. While strain elastography offers valuable information on the mechanical properties of the organ being studied, it is limited by the qualitative nature of its measurements and its reliance on operator skills. On the other hand, shear wave elastography overcomes these limitations as it provides a quantitative assessment of tissue stiffness, offers more reproducibility, and is less operator-dependent. Endoscopic ultrasound-guided shear wave elastography (EUS-SWE) is an emerging technique that overcomes the limitations of transabdominal ultrasound in the evaluation of the pancreas. A growing body of literature has demonstrated its safety and feasibility in the evaluation of pancreatic parenchyma. This article provides a comprehensive review of the current state of the literature on EUS-SWE, including its technical aspects, clinical applications in the evaluation of various pancreatic conditions, technological limitations, and future directions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next‐generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26–2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67–4.50) and in a biobank meta‐analysis (OR, 1.16; 95% CI, 1.04–1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9‐edited HEK293T cell lines show that loss‐of‐function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/− mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein‐stimulated pancreatitis models, Sec16a+/− mice display heightened pancreatic inflammation and fibrosis compared to wild‐type mice. These findings implicate a novel pathogenic mechanism predisposing to CP. [ABSTRACT FROM AUTHOR]

Background: Celiac 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. Methods: This 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). Discussion: In 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 [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Extracorporeal shock wave lithotripsy for pancreatic stones (P‐ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferred therapeutic approaches for painful chronic pancreatitis (CP) with pancreatic stones. This study aimed to report the short‐ and long‐term outcomes following P‐ESWL and ERCP in a large cohort with CP. Methods: Patients with painful CP and pancreatic stones >5 mm in size, who underwent P‐ESWL and subsequent ERCP between March 2011 and June 2018, were included in this retrospective‐prospective mixed observational study. The total stone clearance rates were recorded. All patients were followed up until the end of March 2024, with the visual analogue scale (VAS) for pain, pain type, quality‐of‐life scores and other relevant information recorded. Results: A total of 2071 patients underwent P‐ESWL, and 93.1% of them subsequently underwent ERCP during the study period. Patients were followed up for an average of 11.8 years from the onset of CP and 6.7 years from the first P‐ESWL procedure. Complete stone clearance was achieved in 73.7% of the patients. At the end of the follow‐up period, 70.1% of the patients achieved complete pain remission. Significant pain type conversion and lower VAS scores were observed in the patients after treatment. Quality‐of‐life scores and body mass indices increased after P‐ESWL and ERCP. Conclusions: P‐ESWL and ERCP are effective and minimally invasive treatments for pancreatic stones in patients with painful CP. Most patients achieved complete pain relief, and pain‐type conversion was common after treatment. (ClinicalTrials.gov: NCT05916547). [ABSTRACT FROM AUTHOR]

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 in vitro 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. [ABSTRACT FROM AUTHOR]

Objective: Unknown etiology Background: Chylous ascites is defined as the development of lipid-rich ascitic fluid in the peritoneal cavity. The formation of chylous ascites revolves around non-portal-based and portal-based etiologies, and the diagnosis is made via paracentesis revealing an elevated triglyceride level and milky-white appearance. Chylous ascites is often reported as a postoperative complication in surgical procedures, but it has also been documented in cases of cirrhosis, malignancy, and tuberculosis. However, chylous ascites is rarely seen in chronic pancreatitis and noncirrhotic portal hypertension. This report presents the case of a 65-year-old man with a history of necrotizing pancreatitis and portal hypertension amidst an incidental finding of chylous ascites upon elective umbilical hernia repair. Case Report: We present the case of a patient with chylous ascites discovered during hernia repair. A 65-year-old man with no alcohol or tobacco use and a history of recurrent episodes of acute necrotizing pancreatitis was admitted for umbilical hernia repair. However, upon entering the abdominal cavity, an enlarging mass of ascitic fluid was encountered and tracked into the hernia sac. The fluid was drained via paracentesis and cytology revealed chylous ascites. The patient was discharged in stable condition and was advised to consume a high-protein, lowfat diet. Postoperative computed topography (CT) demonstrated an unchanged necrotic mass in the head of the pancreas. Conclusions: This report demonstrates that when dealing with unexpected findings, it is important to consider the existence of multiple pathologies as the driving cause. We describe a complex cause of chylous ascites, along with a review of the literature on the relationship between chylous ascites and chronic pancreatitis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Chronic pancreatitis is a long-standing inflammation of the pancreas that leads to permanent damage and impairment of its functions. Accurate diagnosis is crucial for effective management. This study aims to evaluate and compare the effectiveness of ultrasonography (US) and computed tomography (CT) in diagnosing chronic pancreatitis, highlighting their respective advantages and limitations. Materials and Methods: This observational study was conducted over 18 months in the Department of Radiodiagnosis at a tertiary care hospital. The study included 10 patients presenting with clinical symptoms suggestive of chronic pancreatitis. Initial evaluations were performed using a Samsung HS 40 ultrasonography machine, followed by CT scans using a Philips MX 16-slice CT scanner. The pancreas was assessed for size, echogenicity, duct dilatation, calcifications, and parenchymal changes. Data were analyzed using SPSS 22.0 software to determine the sensitivity, specificity, and diagnostic accuracy of both imaging modalities. Results: The study population consisted of 10 patients with a mean age of 29 years, predominantly male (70%). The most common etiologies were idiopathic (50%) and alcoholism (30%). Ultrasonography visualized the pancreas in all cases, identifying duct dilatation (90%) and calcifications (80%) as common findings. CT confirmed these findings and provided additional details, detecting calcifications in 90% of patients and pancreatic atrophy in 60%. Both modalities effectively visualized the pancreas, but CT demonstrated higher sensitivity in detecting calcifications and structural changes. Conclusion: Ultrasonography is valuable for the initial evaluation of chronic pancreatitis due to its non-invasive nature and accessibility. However, CT provides a more detailed and comprehensive assessment, essential for confirming the diagnosis and identifying complications. The complementary use of both imaging modalities enhances diagnostic accuracy and aids in effective management of chronic pancreatitis. [ABSTRACT FROM AUTHOR]

Pancreatic lipase (PNLIP) is the major lipolytic enzyme secreted by the pancreas. A recent study identified human PNLIP variants P245A, I265R, F300L, S304F, and F314L in European cohorts with chronic pancreatitis. Functional analyses indicated that the variants were normally secreted but exhibited reduced stability when exposed to pancreatic proteases. Proteolysis of the PNLIP variants yielded an intact Cterminal domain, while the N-terminal domain was degraded. The protease-sensitive PNLIP phenotype was strongly correlated with chronic pancreatitis, suggesting a novel pathological pathway underlying the disease. To facilitate preclinical mouse modeling, here we investigated how the human mutations affected the secretion and proteolytic stability of mouse PNLIP. We found that variants I265R, F300L, S304F, and F314L were secreted at high levels, while P245A had a secretion defect and accumulated inside the cells. Proteolysis experiments indicated that wild-type mouse PNLIP was resistant to cleavage, while variant I265R was readily degraded by mouse trypsin and chymotrypsin C. Variants F300L, S304F, and F314L were unaffected by trypsin but were slowly proteolyzed by chymotrypsin C. The proteases degraded the N-terminal domain of variant I265R, leaving the C-terminal domain intact. Structural analyses suggested that changes in stabilizing interactions around the I265R mutation site contribute to the increased proteolytic susceptibility of this variant. The results demonstrate that variant I265R is the best candidate for modeling the protease-sensitive PNLIP phenotype in mice. [ABSTRACT FROM AUTHOR]

" State-target-cause-result" is a new clinical theory combining macroscopic and microscopic syndrome differentiation based on the holistic view of traditional Chinese medicine combined with Western medical research. The "inflammation-cancer transformation " of chronic pancreatitis is a complex pathological process that is associated with the interaction between the pancreas and various pathological factors and multiple objects, involving the imbalance of multiple homeostasis. The microscopic process of " inflammation-cancer transformation" in chronic pancreatitis is the " target," whereas various factors that could induce its occurrence under chronic inflammatory conditions are the " state. " The " inflammationcancer transformation" of chronic pancreatitis is summarized as yin and yang imbalance, qi movement disorder, endogenous dampness, heat, blood stasis, and turbid phlegm stagnation, unresolved congestion resulting in deficiency caused by stagnation, intermingled deficiency and excess, and internal cancer toxin generation. This paper elucidates the pathogenesis and intervention strategies of the " inflammation-cancer transformation " of chronic pancreatitis from a macro perspective of "state," focusing on reducing the impact of " state" imbalance on the " target" to establish a balanced pancreas-immune-microbiota state. The aim is to broaden the theory for exploring the mechanism and drug development related to chronic pancreatitis " inflammation-cancer transformation " in both traditional Chinese and Western medicine. [ABSTRACT FROM AUTHOR]

Mangiferin is a bioactive substance present in high concentration in mangoes and also in some other fruits. Owing to its potential as a chemopreventive and chemotherapeutic agent against several types of cancer, this unique, significant, and well‐researched polyphenol has received a lot of attention recently. It possesses the ability to treat cancers, including rectal cancer, prostate cancer, ovarian cancer, leukemia, gastric cancer, liver cancer, chronic pancreatitis, and lung cancer. It can control/regulate multiple key signaling pathways, such as signal transducer and activator of transcription 3 (STAT3), second mitochondria‐derived activator of caspases/direct inhibitor of apoptosis (IAP)‐binding protein with low propidium iodide (pl) (Smac/DIABLO) nuclear factor kappa B (NF‐κB), phosphatidylinositol 3 kinase/protein 3 kinase (PI3K/Akt), transforming growth factor beta/suppressor of mothers against decapentaplegic (TGF‐β/SMAD), c‐jun N‐terminal kinase/p38 mitogen‐activated protein kinase (JNK/p38‐MAPK), and phosphor‐I kappa B kinase (p‐IκB), which are crucial to the development of cancers. By triggering apoptotic signals and halting the advancement of the cell cycle, it can also prevent some cancer cell types from proliferating and developing. It has been revealed that mangiferin targets a variety of adhesion molecules, cytokines, pro‐inflammatory transcription factors, kinases, chemokines, growth factors, and cell‐cycle proteins. By means of preventing the onset, advancement, and metastasis of cancer, these targets may mediate the chemopreventive and therapeutic effects of mangiferin. Mangiferin has confirmed potential benefits in lung, cervical, breast, brain, and prostate cancers as well as leukemia whether administered alone or in combination with recognized anticancer compounds. More clinical trials and research investigations are required to completely unleash the potential of mangiferin, which may lower the risk of cancer onset and act as a preventive and therapeutic alternative for a number of cancers. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) is a progressive fibroinflammatory disease characterized by destruction of pancreatic acinar cells, infiltration of inflammatory cells, activation of pancreatic stellate cell (PSC), and pancreatic fibrosis. Autophagy participates in the maintenance of cell homeostasis. Recent studies have shown that autophagy closely related to the occurrence and development of CP. However, several autophagy types in the pancreatic microenvironment play different roles in the progression of CP. The autophagy of acinar cells has a "double-edged sword" effect. PSC autophagy is positively correlated with its activation, while the role of autophagy of inflammatory cells is still unclear. This study focused on some key cells in the CP microenvironment and explored the role and mechanism of autophagy in the progression of CP. [ABSTRACT FROM AUTHOR]

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; p=0.023]. Pancreatic patients with hypothyroidism and SEPP1 gene's (rs7579) AA-genotype had 60.0% (pAA=0.013) lower elastase and 13.78% (p=0.003) higher α-amylase as well as TSH by 10.81% (pAA=0.009) and 15.64% (pAA=0.009), especially in women 14.55-45.18% (p<0.001) at a lower value of Selenoprotein P - by 28.65-48.08% (p≤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 (pGG=0.01) than GG-women and 2.97 times lower (pW=0.011) than men. Comorbid patients with A-allele had elevated TC and LDL-C, by 11.77-26.45% (pAA≤0.01) and 18.06-26.21% (pAA≤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. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP. METHODS: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors. RESULTS: Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of followup. Children with a SPINK1 mutation (P50.005) and those with ARP (compared with CP, P50.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 (P < 0.001). DISCUSSION: In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP. [ABSTRACT FROM AUTHOR]

Background: Conservative 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. Methods: All 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. Results: Thirty-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. Conclusions: Both 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. [ABSTRACT FROM AUTHOR]

• Chronic pancreatitis is the most frequent cause of diabetes secondary to pancreatic disease. • Alterations in insulin secretion can only be detected by comparisons within the same glucose tolerance range. • Chronic pancreatitis does not induce specific alterations of insulin secretion. • Diabetes with chronic pancreatitis presents a reduced functional beta-cell mass. Chronic pancreatitis (CP) is – along with acute pancreatitis - the most frequent cause of diabetes of the exocrine pancreas (DEP). Although insulin deficiency is widely accepted as the major feature of DEP, it is still unclear whether diabetes associated with CP is characterized by additional or different functional defects of the insulin secretory machinery. To identify possible functional defects specifically induced by CP, we performed a cross-sectional study in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM) comparing patients with and without CP (CP vs. NCP). We administered an oral glucose tolerance test (OGTT) to all participants and, according to their glucose tolerance, classified them as NGT, IGT and DM. Insulin sensitivity and beta-cell functional parameters were derived from OGTT, hyperglycemic clamp and hyperinsulinemic euglycemic clamp. Studying 146 subjects, we found that beta-cell function and insulin secretion were significantly lower in CP compared to NCP patients. However, when we classified the subjects according to OGTT-derived glucose tolerance, we found no differences in beta-cell function or in insulin sensitivity between CP and NCP with the same glucose tolerance status. Of note, we found that arginine-stimulated insulin secretion is reduced only in subjects with CP and DM compared to NCP subjects with DM. Patients with CP had no specific alterations in insulin secretion and beta-cell function. However, in patients diagnosed with diabetes, we found a lower arginine-stimulated insulin secretion, a marker of reduced functional mass. [Display omitted] [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aims to evaluate the possible clinical application of interleukin 8 (IL-8) as a single biomarker and its capabilities in combination with carbohydrate antigen (CA19-9), carcinoembryonic antigen (CEA), and carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as diagnostic and prognostic tools for pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 170 serum samples from patients with PDAC (n = 100), chronic pancreatitis (CP) (n = 39), and healthy individuals (n = 31) were analysed. IL-8 and CEACAM6 were measured by an enzyme-linked immunosorbent assay (ELISA). CA19-9 and CEA were determined by chemiluminescent microparticle immunoassay, and bilirubin was quantified using a diazonium salt reaction. Receiver operating characteristic curve analysis, logistic regression, and Kaplan–Meier analyses were performed to evaluate the properties of a single IL-8 and in combination with other biomarkers. Results: The concentrations of IL-8 were statistically significantly higher in the PDAC group compared to the CP and control groups. Heterogeneous levels of IL-8 correlated with PDAC stages (p = 0.007). IL-8 had good and satisfactory diagnostic efficacy in differentiating PDAC from controls (0.858; p < 0.001) and patients with CP (0.696; p < 0.001), respectively. High and low expressions of IL-8 were not significantly associated with overall survival (OS) or disease-free survival (DFS). A combination of IL-8, CEACAM6, and CA19-9 reached the highest AUC values for differentiating PDAC from the control group. The best classification score between PDAC and the control group with CP patients was obtained by merging IL-8 and CA19-9 (0.894; p < 0.001). Conclusions: These results provide compelling evidence of IL-8 as a promising diagnostic biomarker. Nonetheless, due to the high complexity of PDAC, only the conjunction of IL-8, CA19-9, and CEACAM6 integrates sufficient diagnostic capabilities. [ABSTRACT FROM AUTHOR]

Introduction: There is sparse data from India on indications, technical success, safety and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) using standard adult duodenoscope in the pediatric population. Methods: Retrospective analysis of prospectively maintained electronic endoscopy and clinical database was performed to identify pediatric patients (age ≤ 18 years) who underwent ERCP between January 2017 and December 2022. Demographics and procedural details including indications, cholangio-pancreatogram findings, endotherapy type performed, technical and clinical success and complications were noted. Results: As many as 150 pediatric patients were included of whom 88 had pancreatic (mean age-13.7 years) and 62 had biliary disease (mean age- 14.9 years). Common pancreatic ERCP indications were chronic pancreatitis (n = 45 [51.1%]), pancreatic duct disruption fistula (n = 21 [23.9%]) and recurrent acute pancreatitis (n = 16 [18.2%]). Among biliary indications were choledocholithiasis (n = 29 [46.8%]), benign bile duct strictures (n = 13 [21%]), bile duct injury/leak and biliary stent removal (n = 7 [11.3%]) , choledochal cyst (n = 5 [8.1%]) and pancreatic mass causing biliary compression (n = 1 [1.6%]). Technical success in pancreatic and biliary ERCP was 94.3% and 95.2%, respectively, and clinical success was 84.1% and 93.5%, respectively. Most common complications following pancreatic ERCPs were acute pancreatitis (n = 9 [10.2%]) (mild = 5, moderate = 4) patients and post sphincterotomy bleed in one (1.1%). Among biliary ERCPs, post ERCP pancreatitis was seen in (n = 3 [4.8%]) (mild = 2, moderate = 1). Conclusion: ERCP can be safely and effectively performed in children using standard duodenoscope. Chronic pancreatitis, choledocholithiasis and pancreatic divisum are common pediatric ERCP indications. [ABSTRACT FROM AUTHOR]

Acute obstructive suppurative pancreatic ductitis (AOSPD) is an acute suppuration of the pancreatic duct. Endoscopic retrograde cholangiopancreatography (ERCP) drainage and intravenous antibiotics treatment is the mainstay of therapy. Herein we describe an extremely rare case of AOSPD leading to pyogenic spondylitis. A 61-year-old male with a past medical history of chronic pancreatitis and diabetes mellitus presented to our hospital with abdominal and dorsal pain, fever, and shock status. Laboratory data showed severe inflammation, disseminated intravascular coagulation, and normal pancreatic enzymes. Computed tomography showed dilated main pancreatic duct and surrounding pancreatic abscesses. Spinal abnormalities were not detected at this point. He was initially diagnosed as infected pancreatic pseudocyst, but did not respond well to conservative intravenous antibiotic treatment. ERCP performed one week later revealed purulent pancreatic juice and the diagnosis was changed to AOSPD. Upon ERCP, we experienced technical difficulty in passing obstructing calculi. However, successful pancreatic drainage was achieved using new dilation and penetration devices. The patient responded quickly to drainage, but later developed pyogenic spondylitis. Our case highlights the difficulty of diagnosing AOSPD, the usefulness of new devices in urgent endoscopic drainage, and underscores the possibility of progression of pyogenic spondylitis even after adequate treatment. [ABSTRACT FROM AUTHOR]

Highlights: What are the main findings? CP and ARP are common in paediatric populations with varied aetiologies. ERCP is more commonly used compared to EUS in paediatrics and is limited to specialist centres. What is the implication of the main finding? ERCP and EUS are safe and efficacious, with minimal complications in the management of CP and ARP in a paediatric cohort. Indications for both diagnostic and therapeutic EUS are increasing. ERCP and EUS offer a more 'patient-friendly', minimally invasive approach to CP and ARP. 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. [ABSTRACT FROM AUTHOR]

Background Purpose Method Results Conclusion 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 FROM AUTHOR]

Background and Aim Methods Results Conclusions Stent‐induced ductal change is a complication of endoscopic pancreatic stent placement for chronic pancreatitis, potentially leading to irreversible changes that may contribute to pancreatic dysfunction. This study aimed to examine the long‐term outcomes of stent‐induced ductal change and evaluate factors that correlate with the development of irreversible ductal changes.Between January 2008 and December 2022, 52/223 patients with chronic pancreatitis in whom an S‐type plastic stent was successfully placed from the main papilla for duct stricture were detected with stent‐induced ductal change on pancreatography at stent removal. We retrospectively investigated the clinical features of patients whose main pancreatic duct was reassessed by endoscopic pancreatography after >1 month without stent and whose residual stent‐induced ductal change was irreversible.The patients with chronic pancreatitis with stent‐induced ductal change (n = 28) (elevated change, 15; stricture change, 13) were evaluated using follow‐up pancreatography. Eleven patients (39.3%) showed residual change associated with stent‐induced ductal change, the degree of which was partial improvement, no change, and obstructive change in one, seven, and three patients, respectively. Stricture changes during stent removal and duration of stent placement that triggered ductal changes were significantly associated with the development of residual ductal changes.Irreversible stent‐induced ductal change in patients with chronic pancreatitis was associated with stricture changes in the main pancreatic duct and continued plastic‐stent placement. Careful evaluation of the pancreatic duct is required during plastic‐stent placement. Early plastic‐stent removal may result in an effective response to the development of stent‐induced ductal change. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to address the diagnostic challenges associated with pancreatic disorders, such as chronic pancreatitis (CP) and pancreatic cancer (PC) and highlight the importance of protease activity as a crucial prognostic marker for these conditions. METHODS: Total proteolytic activity was determined using casein as a substrate. To measure the activity of metal-dependent and serine proteases, ethylenediaminetetraacetic acid and phenylmethylsulfonyl fluoride were used. The content of low- and middle-molecular-weight (LMMW) substances was determined spectrophotometrically. The protein profile was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), while zymography was performed to indicate the molecular weight of active enzymes. RESULTS: The pathogenesis of both pancreatic disorders was found to be accompanied by a proteolytic imbalance in pancreatic tissues, manifested in either the increase in the total proteolytic activity under pancreatitis or the decrease in the total proteolytic activity under pancreatic cancer. The increase in the levels of both metal-dependent and serine proteases was indicated in the blood plasma of patients in both studied groups. This proteolytic imbalance was accompanied by the accumulation of protein degradation fragments and LMMW substances. Results of zymography were also informative: pancreatic tissue and plasma samples from patients with either CP or PC were characterized by the presence of additional bands, indicating altered proteolytic activity in both pathological conditions. CONCLUSIONS: This study underscores the importance of proteolytic features in distinguishing CP and PC, offering potential diagnostic markers. Proteolytic shifts may aid in differentiating pathologies, detecting transitions, and developing specific protease inhibitors. Further research is crucial for advancing diagnostic and therapeutic strategies for CP and PC. [ABSTRACT FROM AUTHOR]

Pseudoaneurysm of the splenic artery is a rare vascular complication of chronic pancreatitis, with a high mortality rate. Haemorrhage and abdominal pain are the most common manifestations, and so far there are no literature reviews on the rare complication of splenic artery pseudoaneurysm due to chronic pancreatitis. Therefore, we describe a male patient with worsening haemochezia and upper abdominal pain, who had been hospitalized repeatedly for 'pancreatitis' 1 year ago, and relevant investigations confirmed a pseudoaneurysm of the splenic artery, which was successfully treated by transarterial embolization, and a literature review is also presented. [ABSTRACT FROM AUTHOR]

Background & Aims: Adipokines are among the biomarkers that have been studied in chronic pancreatitis (CP), as well as in pancreatic cancer (PC). So far, the existing findings are contradictory and inconclusive. Therefore, we assessed the levels of three major adipokines in CP in comparison to controls and PC, adiponectin, leptin, and resistin. Methods: A systematic electronic search was carried out in November 2022 using PubMed, Embase, and Scopus, reviewing observational studies. By using the Newcastle-Ottawa Scale, the included studies' quality was evaluated (NOS). In the examination of the estimated overall effect size, we employed the random-effects model in conjunction with the mean difference (MD) analysis. The MD with 95% confidence interval (CI) served as the primary summary outcome. Results: Our systematic review included a total of 14 studies, out of which nine were considered in our metaanalysis. A significant MD related to leptin levels in CP patients vs. controls (-1.299, 95%CI: -2.493 - -0.105), resistin levels in CP patients vs. controls (8.356, 95%CI: 3.700-13.012), and adiponectin levels in PC patients vs. controls (11.240, 95%CI: 5.872-16.60) was reported. However, no significant MD was reported in leptin levels between CP vs. PC patients (-0.936, 95%CI: -3.325-1.454), as well as adiponectin levels in CP patients vs. controls (0.422. 95%CI -5.651-6.535]) and in CP vs. PC patients (-6.252, 95%CI -13.269-0.766). Conclusions: CP was significantly associated with decreased leptin levels and increased resistin levels. Furthermore, increased levels of adiponectin are associated with PC. Yet, no significant MD was seen for leptin and adiponectin levels between CP and PC patients, and likewise for adiponectin levels between CP patients and controls. Results should be interpreted with caution due to the high heterogeneity among the included studies. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Superoxide dismutase (SOD) is an enzyme that plays a crucial role in protecting cells from oxidative damage. Our study aims to address the lack of papers simultaneously analyzing the immunoreactivity of all three distinct isoforms of SOD in human exocrine pancreas cells. BACKGROUND: Superoxide dismutases (SODs) facilitate the conversion of superoxide radicals into less harmful substances. By neutralizing superoxide radicals, SODs help prevent the formation of highly reactive and destructive species that can adversely affect manifold cellular components. METHODS: The study analyzed immunoreactivity of SODs in samples of six healthy adult human pancreases, while using the indirect immunohistochemical method under a light microscope. RESULTS: SOD1 was predominantly found in centroacinar cells and epithelial cells of the duct system while SOD2 was mainly detected in the epithelial cells of interlobular ducts. Both enzymes were prominently present in the basal region of acinar cells near the cell nucleus. The expression of SOD3 was observed to be rare. CONCLUSION: Understanding the intracellular metabolism of SODs in healthy exocrine pancreas cells serves as a basis for determining the precise role of oxidative damage and SOD signaling in the pathogenesis of various pancreatic diseases, including chronic pancreatitis and pancreatic cancer [ABSTRACT FROM AUTHOR]

Background/Aims: Coaxial placement of double pigtail plastic stents (DPPS) through lumen-apposing metal stents (LAMSs) is commonly performed to reduce the risk of LAMS obstruction, bleeding, and stent migration when used for the drainage of pancreatic fluid collections (PFCs). A systematic review and meta-analysis were performed to compare the outcomes of LAMS alone and LAMS with coaxial DPPS placement in the management of PFCs. Methods: A systematic review was conducted to identify studies comparing LAMS and LAMS/DPPS for PFC drainage. Primary outcomes included the rate of clinical success, overall adverse events (AEs), bleeding, infection, occlusion, and stent migration. The pooled effect size was summarized using a random-effects model and compared between LAMS and LAMS/DPPS by calculating odds ratios (ORs). Results: Nine studies involving 709 patients were identified (338 on LAMS and 371 on LAMS/DPPS). LAMS/DPPS was associated with a reduced risk of stent obstruction (OR, 0.59; p=0.004) and infection (OR, 0.55; p=0.001). No significant differences were observed in clinical success (OR, 0.96; p=0.440), overall AEs (OR, 0.57; p=0.060), bleeding (OR, 0.61; p=0.120), or stent migration (OR, 1.03; p=0.480). Conclusions: Coaxial DPPS for LAMS drainage of PFCs is associated with a reduced risk of stent occlusion and infection; however, no difference was observed in the overall AE rates or bleeding. [ABSTRACT FROM AUTHOR]

Surgeries for chronic pancreatitis are tailored based on disease process and either include parenchymal-preserving surgeries or total pancreatectomy with or without islet cell autotransplantation. It is critical to account for vascular variants as injuries to these are associated with short- and long-term morbidity and mortality. There is a lack of contemporary data on the true incidence of aberrant arterial anatomy, and it is likely to be underreported by nonhepatobiliary radiologists. This study is a retrospective analysis of all patients undergoing pancreatic resections for chronic pancreatitis at the single center. The presence of vascular variants was compared between standard reporting and preoperative imaging review by a hepatobiliary radiologist and surgeon. Primary outcomes were operative time and blood loss. Of the 72 pancreatic resections for chronic pancreatitis, 50 (69%) satisfied inclusion criteria. Three of fifty (6%) had vascular anomalies reported on standard reporting while 11 (22%) had vascular anomalies identified on preoperative imaging review and confirmed at surgery. Hence, only 27% of patients with variant vascular anatomy were reported on standard imaging. There was no significant difference in operative times or blood loss between those with and without known vascular anomalies. Pancreatic resection is a complex undertaking as long-standing inflammation distorts anatomic planes and increases opportunity for inadvertent vascular injury especially if there are aberrant vessels. In this study, we found that anatomic vascular variants are oftentimes not reported. Dedicated surgical planning with review of cross-sectional imaging identified all cases of anatomic variants resulting in no difference in operative time or incidence of intraoperative hemorrhage. [ABSTRACT FROM AUTHOR]

The serine protease chymotrypsin protects the pancreas against pancreatitis by degrading trypsinogen, the precursor to the digestive protease trypsin. Taking advantage of previously generated mouse models with either the Ctrb1 gene (encoding chymotrypsin B1) or the Ctrl gene (encoding chymotrypsin-like protease) disrupted, here we generated the novel Ctrb1-del × Ctrl-KO strain in the C57BL/6N genetic background, which harbors a naturally inactivated Ctrc gene (encoding chymotrypsin C). The newly created mice are devoid of chymotrypsin, yet the animals develop normally, breed well, and show no spontaneous phenotype, indicating that chymotrypsin is dispensable under laboratory conditions. When given cerulein, the Ctrb1-del × Ctrl-KO strain exhibited markedly increased intrapancreatic trypsin activation and more severe acute pancreatitis, relative to wild-type C57BL/6N mice. After the acute episode, Ctrb1-del × Ctrl-KO mice spontaneously progressed to chronic pancreatitis, whereas C57BL/6N mice recovered rapidly. The cerulein-induced pancreas pathology in Ctrb1-del × Ctrl-KO mice was highly similar to that previously observed in Ctrb1-del mice; however, trypsin activation was more robust and pancreatitis severity was increased. Taken together, the results confirm and extend prior observations demonstrating that chymotrypsin safeguards the pancreas against pancreatitis by limiting pathologic trypsin activity. In mice, the CTRB1 isoform, which constitutes about 90% of the total chymotrypsin content, is responsible primarily for the anti-trypsin defenses and protection against pancreatitis; however, the minor isoform CTRL also contributes to an appreciable extent. NEW & NOTEWORTHY: Chymotrypsins defend the pancreas against the inflammatory disorder pancreatitis by degrading harmful trypsinogen. This study demonstrates that mice devoid of pancreatic chymotrypsins are phenotypically normal but become sensitized to secretagogue hyperstimulation and exhibit increased intrapancreatic trypsin activation, more severe acute pancreatitis, and rapid progression to chronic pancreatitis. The observations confirm and extend the essential role of chymotrypsins in pancreas health. [ABSTRACT FROM AUTHOR]

Alcohol and nicotine are the two most important risk factors of chronic pancreatitis, and they often occur together. It is still unclear how much they influence the severity of the disease and which of the two addictions should be treated with priority. We performed a single-center, retrospective, cross-sectional study in a mixed medicosurgical cohort of 870 patients diagnosed with chronic pancreatitis (CP). We analyzed the impact of the drinking pattern and abstinence for alcohol and nicotine on the course of the disease. Patients with alcoholic CP were subdivided into 1) patients with "life-time drinking history" (LTDH), 2) "current drinkers" with current alcohol abuse without signs of LTDH, and 3) "former drinkers" who stopped or reduced alcohol intake dramatically. Compared to patients with LTDH, "former drinkers" had a lower rate of exocrine insufficiency (29% vs. 59%) and pseudocysts (33% vs. 49%), were more often relapse-free (37% vs. 5%), and had less abdominal pain. There was no correlation detected between the quantity of alcohol consumption and the severity or progression of the disease. Regarding nicotine, 29 pack-years are the threshold for developing the early stage of CP. Under nicotine abstinence, only slightly more patients were relapse-free (37% vs. 22%). In contrast, the cumulative amount of nicotine consumed correlated with overall disease severity and the development of pseudocysts. The need for surgery was increased, with odds ratios of 1.8, for both alcohol and nicotine abuse. Alcohol cessation in chronic pancreatitis reduces exocrine insufficiency, abdominal pain, and local complications. The effect of nicotine cessation is less pronounced in our cohort. However, nicotine abuse represents an important factor for the development of the disease. • Alcohol cessation results in a lower rate of exocrine insufficiency, pseudocysts, and acute pancreatitis episodes. • The drinking pattern, but not the absolute amount of alcohol, correlates with the disease severity. • We were able to identify a threshold of 29 pack-years for the development of chronic pancreatitis. • Smoking cessation only reduced the relapse frequency of acute pancreatitis episodes without affecting the disease severity. [ABSTRACT FROM AUTHOR]

Purpose of Review: Extracorporeal shockwave lithotripsy (ESWL) is a non-invasive approach for the management of uncomplicated symptomatic pancreatic calculi in patients with chronic pancreatitis (CP). It can be used to achieve long term pain relief, with or without ERCP. The efficacy of ESWL in treating pancreatic ductal calculi is addressed in detail in this article. Recent Findings: In more than 70% of patients, ESWL treatment leads to total ductal clearance. This relieves pain in more than half of the patients with symptomatic chronic pancreatitis caused by ductal obstruction. In CP patients, ESWL reduces the proportion of patients requiring analgesics and decreases the requirement of surgery. The safety profile of ESWL is favourable, with mild and self-limiting complications that typically do not necessitate intervention. ESWL should be adhered to as a first alternative to conventional endoscopic techniques, as long as there is no convincing data about EHL or laser lithotripsy efficacy. Summary: In view of its high efficiency, non-invasive nature, and low complications rates, ESWL should be offered as the first-line therapy for selected patients with large painful pancreatic calculi. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS) is the most sensitive method for diagnosing chronic pancreatitis (CP) in its early stages, and Rosemont Classification (RC) is used for its evaluation. Data on the correlation between EUS features and pancreatic exocrine insufficiency (PEI) are limited. We investigated the correlation between the EUS findings and PEI. This was a retrospective, monocentric cohort study involving patients prospectively enrolled from 2018 to 2022, with definite or probable CP according to the M-ANNHEIM criteria. All the patients underwent EUS and exocrine function investigations within 12 months of diagnosis. PEI was diagnosed using fecal elastase (FE) or when overt steatorrhea was reversed by pancreatic enzyme replacement therapy. Logistic regression analyses, rank correlation, ROC curve, and area under the curve (AUROC) were performed to evaluate the association between EUS features and PEI, and the accuracy of RC in predicting PEI. Among 128 patients examined (63.3 % male; mean age, 47 years), 69.5 % were diagnosed with PEI. In multivariate logistic regression among all the RC criteria, only lithiasis in the main pancreatic duct (MPD) was associated with increased risk of PEI (OR 2.92, 95 % CI 1.29–6.61; p = 0.01). Rank analysis showed a weak inverse correlation between RC and FE (Spearman's rho = −0.02; p = 0.03). The accuracy of RC was moderate (AUROC 0.62, p = 0.014). Among RC EUS features, lithiasis in the MPD is helpful for predicting the risk of PEI, while other findings are of limited utility in evaluating exocrine function. [ABSTRACT FROM AUTHOR]

Spontaneous pancreatic portal vein fistula (PPVF) - a rare complication of pancreatic inflammation – varies widely in presentation and means of diagnosis but has been previously associated with bleeding complications and mortality. A systematic review of published literature was performed to assess the frequency of outcomes. A search of electronic databases (PubMed, Ovid MEDLINE, Scopus, EMBASE, gray literature) resulted in 1667 relevant unique manuscripts; 52 met inclusion criteria. A total of 74 unique (male n = 47, 63.5 %) patients were included. Mean age was 53.5 (±11.9) years. History of alcohol use was reported in 55 (74.3 %). Underlying chronic pancreatitis (CP) was present in 49 (66.2 %). In cases where presenting symptoms were reported (n = 57, 77.4 %), the most frequent were abdominal pain (63.5 %), weight loss (14.9 %), rash (12.2 %), nausea/vomiting (12.2 %), and polyarthritis (9.5 %). Computed tomography was the most common imaging modality used to confirm the diagnosis (n = 20, 27.0 %), followed by magnetic resonance cholangiopancreatography (n = 14, 18.9 %). Portal vein thrombosis was reported in 57 (77.0 %), and bleeding events (luminal, variceal, or intra-pseudocyst) were reported in 13(17.6 %) patients. Younger age was associated with higher risk of bleeding events. Mortality was reported in 12 (16.2 %) patients at any time during follow up. Older age and polyarthritis at presentation were associated with mortality. PPVF is a rare and potentially fatal condition, though rates of bleeding complication and death were relatively low in this population. High-quality observational studies are needed to better understand the pathophysiology and natural history of this diagnosis. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) is characterized by debilitating pain which affects patients' quality of life. Early surgical intervention has been shown to mitigate pain and prevent a decline in quality of life. The present study evaluated the impact of bile duct and duodenum preserving pancreatic head resection (BDPPHR), an innovative technique, on pain relief, functional outcomes, postoperative morbidity, and mortality in patients with CP. Between March 2019 and July 2022, a total of 37 patients underwent bile duct and duodenum preserving pancreatic head resection (BDPPHR) for pain relief in patients with CP. Post-operative outcomes were assessed by Izbicki pain score, exocrine insufficiency, endocrine insufficiency, and return to work. The safety of the surgical procedure was determined by evaluation of postoperative morbidity and mortality as per Clavien-Dindo scores. BDPPHR showed a significant reduction in Izbicki pain scores with 30 (81 %) patients experiencing complete or partial pain relief up to 18 months of follow up. 32(86 %) patients ceased narcotic use by the end of the 18-month follow-up period. 33 (89 %) patients were able to resume regular work at the end of 18 months. There were no significant alterations in both exocrine and endocrine statuses post-surgery. The median duration of hospital stay was 4.5 days (3-11). Major complications occurred in 2 (5 %) patients. There was no post-operative mortality. BDPPHR is a novel and safe technique of near total head resection which results in very good pain relief in 81 % of patients. [ABSTRACT FROM AUTHOR]