Plasma metabolite levels in patients with pancreatic cancer (PC) have changed, but the relationship between the altered plasma metabolites and the risk for PC occurrence is not fully clear, as well as the predictive value of the specific metabolites.

In this study, we obtained the metabolomics data of 243,145 people from the UK Biobank. An extreme gradient boosting (XGBoost) model, least absolute shrinkage and selection operator (Lasso) regression, and covariate-adjusted Cox proportional hazard regression models were used to evaluate the relationship between metabolites and PC risk. We also evaluated conventional risks, metabolites, and combination models for PC risk by comparing the area under the receiver operating characteristic curve (AUC).

The average follow-up time was 13.8 (± 2.1) years; 1,026 of 243,145 participants developed PC. Fourteen metabolites were significantly associated with PC, including glucose-related metabolites, lipids, lipoproteins, and amino acids. Increased PC risk was associated with citrate, glucose, and the percentage of triglycerides to total lipids in intermediate-density lipoprotein or small low-density lipoprotein. Glycine, histidine, cholesterol, and cholesterol ester subclasses were associated with lower PC risk. Predicting PC risk improved when the newly identified metabolites were added to conventional PC risk factors (AUC: 0.705 vs 0.711, p = 0.037). The Kaplan-Meier cumulative incidence curves showed that these metabolites were good predictors of PC risk (all log-rank p < 0.05).

We identified novel metabolites that were significantly associated with the occurrence of PC, which may aid in the early diagnosis of PC.

Extracorporeal shock wave lithotripsy (ESWL) with endotherapy (ET) is the first-line treatment in patients with chronic pancreatitis (CP) and main pancreatic duct stone (PDS). Our study aimed to evaluate factors that predict the outcome of ESWL in CP patients with PDS.

We retrospectively analyzed data of 166 patients with CP and radiopaque PDS. Computed tomography (CT) images were evaluated for stone density, stone size, main pancreatic duct (MPD) size, and skin-to-stone distance (SSD). Long-term pain relief results were determined via telephone interview in 100 patients.

Mean stone density (MSD) > 1336 HU predicted the need to perform more than one ESWL session (odds ratio [OR]: 1.002; 95% confidence interval [CI]: 1.001 to 1.003; p = 0.002), cut-off 1336 HU yielding 71% sensitivity and 65% specificity. Denser stones required more ESWL and following ET, with ≥4 ET sessions resulting in better technical success. (OR: 3.222; 95% CI: 1.240 to 8.371; p = 0.016). Overall technical success (complete stone fragmentation in ESWL or placing a stent past the stone in ET) rate was 81.3%. Clinical success (complete or partial pain relief at the end of the treatments) rate was 83.7% and remained at the same level also in the long-term follow-up (median 5.5 years). Stone size, MPD size, or SSD were not associated with any of the study outcomes.

Higher MSD than 1336 HU predicts the need for more than one ESWL and ET sessions to fragment the stone and clear the duct, but when successful the long-term result is favorable.

To investigate the epidemiology and burden of adult-onset chronic pancreatitis (CP) in South Australia.

Retrospective case-control study; data linkage.

All public adult hospitals in SA.

Administrative data linkage from South Australia-Northern Territory DataLink was used to ascertain an index cohort of all adults with an initial diagnosis of CP aged >19 years between June 2000 and June 2019. Age- and sex-matched controls were drawn from the general population of SA, adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus (defined by International Classification of Diseases 10th Revision coding).

Hospital visits, days in hospital, emergency department visits, intensive care unit admissions, incidence, prevalence.

A total of 2503 incident index cases with CP were identified. The crude prevalence and incidence were estimated as 195.1 per 100 000 and 10.4 per 100 000 per annum, respectively. Cases of CP averaged more hospital visits for any reason (median 11, IQR 5 to 21.75) than the general population (median 1, IQR 0 to 4) and had a higher healthcare burden than controls with type 1 diabetes or type 2 diabetes (all p<0.001). Indigenous individuals were over-represented in the cohort (n=358; 14.8% vs 1.5% of the general population) and had higher healthcare utilisation than other patients with CP (p<0.001).

CP is a significant burden on the SA healthcare system and was more prevalent and more burdensome in Indigenous adults. CP consumes a disproportionate level of public health services. Our findings support further research and preventive efforts, particularly in the Indigenous population.

Chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are diseases with overlapping features, both requiring complex management strategies. CP is characterized by pancreatic exocrine insufficiency (PEI) and pain, with treatment focused on symptom relief through pancreatic enzyme replacement therapy (PERT), pain control, and lifestyle and nutritional changes. However, the standard therapy does not address the underlying inflammation or fibrosis, which drives disease progression. AIP, on the other hand, presents with obstructive jaundice and fibrosis and is classified into two subtypes: Type 1 (AIP-1), linked to IgG4-related disease, and Type 2 (AIP-2), associated with inflammatory bowel disease. Treatment for AIP typically involves oral steroids. Immunomodulators and rituximab are used for recurrent or refractory cases. Novel therapies targeting the inflammation and fibrotic components of CP are being explored. A multidisciplinary approach is essential to optimize care and improve patients' outcomes.

Common indications to evaluate exocrine pancreatic function in children include chronic diarrhea, steatorrhea, failure to thrive, cystic fibrosis and those with chronic abdominal pain due to chronic pancreatitis where imaging studies are normal [1]. Exocrine Pancreatic Insufficiency (EPI) has a spectrum of severity. In children often remains an underdiagnosed condition, particularly in its mild, partial, and isolated enzyme deficiency forms. The purpose of this review is to help understand the different varieties of EPI including isolated pancreatic enzyme deficiencies as possible causes of malnutrition and growth failure in pediatric patients.

Among the indirect diagnostic methods, the fecal elastase-1 (FE-1) testing is the most widely used one. While it has good sensitivity and specificity in severe pancreatic damage, like cystic fibrosis in children, its performance in the diagnosis of mild, partial, and isolated enzyme deficiencies is poor. Direct pancreatic function testing performed during endoscopy (ePFT), has emerged as a more sensitive and specific method for assessing all forms of exocrine pancreatic function. Notably, recent guidelines from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) emphasize the importance of ePFT in pediatric patients.  Most of the pediatric practitioners taught that the pancreas has only two diseases, cystic fibrosis and pancreatitis. They are missing the fact that pancreas, like other digestive organs, can have different, many times secondary, dysfunctions that influence the growth of children. Most pediatric gastroenterologists still use the fecal elastase-1 (FE-1) test, however, this lacks sufficient specificity and sensitivity [2-5] especially in patients with mild or early pancreatic disease or those with isolated enzyme deficiencies [5]. The most accurate diagnostic modality to explore these conditions is ePFT. In this review we highlighted the critical importance of direct pancreatic function testing. Enhancing clinical awareness and incorporating direct testing methods can ultimately improve outcomes for affected children.

The pancreas, an organ with dual functions, regulates blood glucose levels through the endocrine system by secreting hormones such as insulin and glucagon. It also aids digestion through the exocrine system by secreting digestive enzymes. Complex interactions and signaling mechanisms between the endocrine and exocrine functions of the pancreas play a crucial role in maintaining metabolic homeostasis and overall health. Compelling evidence indicates direct and indirect crosstalk between the endocrine and exocrine parts, influencing the development of diseases affecting both. From a developmental perspective, the exocrine and endocrine parts share the same origin-the "tip-trunk" domain. In certain circumstances, pancreatic exocrine cells may transdifferentiate into endocrine-like cells, such as insulin-secreting cells. Additionally, several pancreatic diseases, including pancreatic cancer, pancreatitis, and diabetes, exhibit potential relevance to both endocrine and exocrine functions. Endocrine cells may communicate with exocrine cells directly through cytokines or indirectly by regulating the immune microenvironment. This crosstalk affects the onset and progression of these diseases. This review summarizes the history and milestones of findings related to the exocrine and endocrine pancreas, their embryonic development, phenotypic transformations, signaling roles in health and disease, the endocrine-exocrine crosstalk from the perspective of diseases, and potential therapeutic targets. Elucidating the regulatory mechanisms of pancreatic endocrine and exocrine signaling and provide novel insights for the understanding and treatment of diseases.

Recent studies have increasingly emphasized the strong correlation between the lipidome and the risk of pancreatic diseases. To determine causality, a Mendelian randomization (MR) analysis was performed to identify connections between the lipidome and pancreatic diseases.

Statistics from a genome-wide association study of the plasma lipidome, which included a diverse array of 179 lipid species, were obtained from the GeneRISK cohort study with 7,174 participants. Genetic associations with four types of pancreatitis and pancreatic cancer were sourced from the R11 release of the FinnGen consortium. Two pancreatitis datasets from UK Biobank were employed as the validation cohort. MR analysis was conducted to assess the relationship between the genetically predicted plasma lipidome and these pancreatic diseases. Inverse variance weighted was adopted as the main statistical method. Bayesian weighted MR was employed for further verification. The MR-Egger intercept test for pleiotropy and Cochrane's Q statistics test for heterogeneity were performed to ensure the robustness.

MR analysis yielded significant evidence that 26, 25, 2, and 19 lipid species were correlated with diverse outcomes of pancreatitis, and 8 lipid species were correlated with pancreatic cancer. Notably, sterol ester (27:1/20:2) levels (OR: 0.84, 95% CI: 0.78-0.90, P = 5.79 × 10-7) were significantly associated with acute pancreatitis, and phosphatidylcholine (17:0_20:4) levels (OR: 0.89, 95% CI: 0.84-0.94, P = 1.78 × 10-4) and sterol ester (27:1/20:4) levels (OR: 0.90, 95% CI: 0.86-0.95, P = 2.71 × 10-4) levels were significantly associated with chronic pancreatitis after the Bonferroni-corrected test. As for validation, 14 and 9 lipid species were correlated with acute and chronic pancreatitis of UK Biobank. Some lipid classes showed significant effects both in the FinnGen consortium and UK Biobank datasets.

The findings of this study indicate a potential genetic predisposition linking the plasma lipidome to pancreatic diseases and good prospects for future pancreatic disease clinical trials.

Chronic pancreatitis is a benign disease which causes recurrent abdominal pain and loss of pancreatic function. Lateral pancreaticojejunostomy (LPJ) is a commonly performed drainage procedure for this condition. While usually performed through an open approach, there have been few cases of laparoscopic approaches for this condition. A literature review was conducted to understand the current status of laparoscopic longitudinal pancreatojejunostomy (LLPJ). We conducted a comprehensive literature search using PubMed, Embase and Cochrane Library to find the articles published until 1 st October 2023. We excluded studies involving paediatric patients or robotic assisted surgeries. Our evaluation focussed on pain relief scores, morbidity, hospital stay length, mortality rates and the development of endocrine and exocrine deficiencies in the patients. The patients in the analysis had a mean age of 36.5 and a male to female ratio of 1.4:1. The mean main pancreatic duct diameter was 11.5 mm. Tropical pancreatitis was identified as the primary cause. The surgical procedure was performed using 4 ports with minimal bleeding and a 13% morbidity rate. The conversion rate was 15%. The average operative time was 260 min and the mean hospital stay was 5.7 days. The results for pain control were excellent, as 90% of patients did not report pain in most series at the end of 3 years. The laparoscopic surgical management of chronic calcific pancreatitis with LPJ offers a safe and effective solution for pain relief in carefully chosen patients. However, further comprehensive studies with large sample sizes are essential to establish a more conclusive comparison between LLPJ and open surgery.

Visceral artery pseudoaneurysms, particularly those in the gastroduodenal artery (GDA), are rare but serious complications associated with chronic pancreatitis, posing a significant risk of rupture due to their structural fragility. In this case, a 61-year-old male with a history of chronic pancreatitis, alcohol cirrhosis, duodenal ulcer, and COPD presented with persistent abdominal pain and recurrent fevers. Imaging revealed a 7 cm pseudoaneurysm between the GDA and superior mesenteric vein, which was successfully treated with coil embolization. This case highlights the importance of prompt recognition and intervention in managing GDA pseudoaneurysms, particularly when complicated by an arterioportal fistula, and demonstrates the efficacy of endovascular therapy as a minimally invasive treatment option that can significantly improve patient outcomes in complex vascular complications associated with chronic pancreatitis.

Background: The role of diet on the risk of chronic pancreatitis (CP) is understudied. The health benefits of the Mediterranean diet (MedDiet) pattern have long been recognized, but its association with CP risk is unclear. We aimed to investigate the association between adherence to MedDiet and the incidence of CP in a large-scale cohort. Methods: 190 790 participants from the UK Biobank were involved, all free of CP and with typical diet recall data at recruitment. The diagnosis of CP was ascertained by the combination of hospital inpatient data, primary care data, and death registry data. Multivariable Cox regression models were used to evaluate the associations between MedDiet adherence, measured by the Mediterranean Diet Adherence Screener (MEDAS) continuous score, and the incidence of CP. The mediating role of inflammation (assessed by C-reactive protein) and metabolic status between MedDiet adherence and CP risk was also investigated. Results: During a mean of 10.8 years of follow-up, 214 participants developed CP. Individuals with the highest adherence to MedDiet, defined by continuous MEDAS scores, exhibited significantly lower risk of developing CP (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.40-0.82; p = 0.002) compared to those in the lowest tertiles. Metabolic status mediated 4.74% of the association between MedDiet adherence and CP risk, while the mediating role of C-reactive protein was not significant. Conclusion: Greater Mediterranean diet adherence is associated with reduced chronic pancreatitis risk.

The pancreas is involved in digestion and glucose regulation in the human body. Given the recognized link between chronic pancreatitis and pancreatic cancer, addressing pancreatic disorders and pancreatic cancer is particularly challenging. This review aims to highlight the limitations of traditional methods in diagnosing pancreatic disorders and cancer and explore several next-generation sequencing (NGS) approaches as a promising alternative. There are distinct clinical symptoms that are shared by a number of clinical phenotypes of pancreatic illness induced by particular genetic mutations. Traditional diagnostic methods encompass computed tomography, magnetic resonance imaging, contrast-enhanced Doppler ultrasound, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, transabdominal ultrasound, laparoscopy, and positron emission tomography have a prognostic ability of only 5% or less and a 5-year survival rate. Genetic sequencing can be employed as an alternative to conventional diagnostic techniques. Sanger sequencing and NGS are currently largely operated genome analysis, with no exception for pancreatic disease diagnosis. The NGS methods can sequence millions to billions of short DNA fragments, enabling enormous sample screening in a short amount of time with low-abundance detection, like in 0.1%-1% mutation prevalence declining approximate cost. Whole-genome sequencing, whole-exome sequencing, RNA sequencing, and single-cell NGS are a few NGS methods utilized to diagnose pancreatic disease. For both research and clinical applications, the NGS techniques can provide a precise diagnosis of pancreatic disorders in a short amount of time at a reasonable expenditure.

Total pancreatectomy with islet autotransplant (TPIAT) is important therapy for select chronic pancreatitis (CP) patients. The specialized technique of islet isolation limits widespread TPIAT use. We hypothesized that remote islet isolation provides satisfactory islet yield and perioperative outcomes.

A retrospective review of TPIAT patients between 2020 and 2022 was conducted. Islet isolation was performed off-site, with percutaneous intraportal islet autotransplant (IAT) completed the morning following pancreatectomy. Demographics and perioperative outcomes were analyzed.

Fourteen patients underwent TPIAT; median age was 43 (interquartile range, 12.5) years. Operation occurred 7.5 (14.8) years after pancreatitis diagnosis. The most common pancreatitis etiology was genetic (50%). All patients underwent preoperative endoscopic therapy; three underwent prior pancreatectomy. Operative time was 236 (51) minutes; subsequent percutaneous IAT time was 87 (35) minutes. The islet equivalent (IEQ)/kilogram (kg) yield was 3456 (3815) IEQ/kg. Nine patients had positive islet cultures. Two thromboembolic events and one bacteremia occurred. One perihepatic hematoma occurred after percutaneous portal venous access. The median postoperative length of stay was 14.5 days, and five patients (36%) were readmitted within 90 days. All patients were discharged home on insulin. No mortality occurred.

Total pancreatectomy with remote islet isolation provides excellent islet yield for autotransplant and satisfactory perioperative outcomes.

Hereditary pancreatitis (HP) is an unusual form of pancreatitis inherited as an autosomal dominant disorder. Patients typically present with recurrent acute pancreatitis-like symptoms that eventually progress to chronic pancreatitis, resulting in pancreatic exocrine insufficiency or diabetes mellitus, and a high risk of developing pancreatic cancer. As such, early diagnosis is crucial. Herein, we present the case of an 11-year-old boy with no significant medical history, but a family history of type 1 diabetes and pancreatic cancer, who presented with intermittent epigastric pain and nausea. Imaging revealed multiple pancreatic pseudocysts, pancreatic stones, and pancreatic duct dilation, resulting in the diagnosis of acute-on-chronic pancreatitis. Genetic testing confirmed the presence of a mutation in the PRSS1 gene, ultimately resulting in the diagnosis of HP. The patient remained symptom-free for five years during follow-up post-treatment. This case highlights the importance of considering HP in young patients presenting with pseudocysts and other signs of chronic pancreatitis even during the initial acute episode.

The increasing availability of patient-derived multimodal biological data for various diseases has opened up avenues for finding the optimal methods for jointly leveraging the information extracted in a customizable and scalable manner. Here, we propose the Proximogram, a graph-based representation that provides a joint construct for embedding independently obtained omics and spatial data. To evaluate the representation, we generated proximograms from 2 distinct biological sources, namely, multiplexed immunofluorescence images and single-cell RNA-seq data obtained from patients across two pancreatic diseases that include normal and chronic Pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). The generated proximograms were used as inputs to 2 distinct graph deep-learning models. The improved classification results over simpler spatial-data-based input graphs point to the increased discriminatory power obtained by integrating structural information from single-cell ligand-receptor signaling data and the spatial architecture of cells in each disease class, which can help point to markers of high diagnostic significance.

Chronic pancreatitis (CP) in young individuals may lead to disease-related secondary sarcopenia (SSARC), characterized by muscle loss and systemic inflammation. In this study, CP was induced in young pigs, and serum levels of key hormones, muscle fiber diameters in various muscles, and the mRNA expression of genes related to oxidative stress and programmed cell death were assessed. A decrease in muscle fiber diameters was observed in SSARC pigs, particularly in the longissimus and diaphragm muscles. Hormonal analysis revealed alterations in dehydroepiandrosterone, testosterone, oxytocin, myostatin, and cortisol levels, indicating a distinct hormonal response in SSARC pigs compared to controls. Oxytocin levels in SSARC pigs were significantly lower and myostatin levels higher. Additionally, changes in the expression of catalase (CAT), caspase 8 (CASP8), B-cell lymphoma 2 (BCL2), and BCL2-associated X protein (BAX) mRNA suggested a downregulation of oxidative stress response and apoptosis regulation. A reduced BAX/BCL2 ratio in SSARC pigs implied potential caspase-independent cell death pathways. The findings highlight the complex interplay between hormonal changes and muscle degradation in SSARC, underscoring the need for further research into the apoptotic and inflammatory pathways involved in muscle changes due to chronic organ inflammation in young individuals.

To assess the association between pancreatic enzyme replacement therapy (PERT) and resource utilization among patients with chronic pancreatitis (CP) in a large Midwestern US healthcare system.

This retrospective cohort study used electronic medical record data. Eligible patients (N = 2445) were aged ≥18 years and diagnosed with non-cystic fibrosis CP between January 2005 and December 2018, with ≥6 months' follow-up; study initiation was first encounter with the healthcare system. Patients in the PERT group were prescribed PERT at ≥1 encounter; patients in the non-PERT group were not prescribed PERT at any encounter.

In total, 62,899 encounters were reviewed (PERT, n = 22,935; non-PERT, n = 39,964). More patients in the PERT group were younger, male, White, married/partnered and with private insurance than those in the non-PERT group. They also received longer care and had more overall encounters, fewer outpatient and day surgery/24-hour observation encounters, and more inpatient encounters. Emergency room encounters were similar between groups. Average cost by encounter was similar between groups ($225 and $213, respectively).

Despite similar average costs per encounter, the groups had very different encounter types. More inferential research on PERT use among patients with CP is needed, particularly regarding resource utilization and long-term outcomes.

The pancreas is an organ with both exocrine and endocrine functions, comprising a highly organized and complex tissue microenvironment composed of diverse cellular and non-cellular components. The impairment of microenvironmental homeostasis, mediated by the dysregulation of cell-to-cell crosstalk, can lead to pancreatic diseases such as pancreatitis, diabetes, and pancreatic cancer. Macrophages, key immune effector cells, can dynamically modulate their polarization status between pro-inflammatory (M1) and anti-inflammatory (M2) modes, critically influencing the homeostasis of the pancreatic microenvironment and thus playing a pivotal role in the pathogenesis of the pancreatic disease. This review aims to summarize current findings and provide detailed mechanistic insights into how alterations mediated by macrophage polarization contribute to the pathogenesis of pancreatic disorders. By analyzing current research comprehensively, this article endeavors to deepen our mechanistic understanding of regulatory molecules that affect macrophage polarity and the intricate crosstalk that regulates pancreatic function within the microenvironment, thereby facilitating the development of innovative therapeutic strategies that target perturbations in the pancreatic microenvironment.

Chronic inflammation of the pancreas is considered to be one of the causes of pancreatic cancer. However, the diagnosis of chronic pancreatitis (CP) is very difficult in the pancreas, where biopsies are difficult to perform. The prevalence of CP is estimated to be many times more common than in patients with actual symptomatic CP. In recent years, abnormal cleavage of certain proteins has attracted attention as a biomarker for CP other than pancreatic enzymes. Connective tissue growth factor (CTGF) is one of the growth factors involved in tissue repair and other processes and is increased by stimulation of transforming growth factor-β, suggesting a relationship of CTGF with fibrosis. In this study, we measured the total length of CTGF in blood and N-terminal fragment CTGF in 48 cases of chronic pancreatitis, 64 cases of pancreatic cancer and 45 healthy volunteers (HV). Interestingly, we found that blood N-terminal fragment CTGF level was significantly increased in CP and pancreatic cancer patients. Multiple logistic regression analysis showed serum levels of N-terminal fragment CTGF, CRP and amylase were significant and independent variables for the differential diagnosis of CP from HV. Receiver operating characteristic analysis showed that area under the curve (AUC) value of serum N-terminal fragment CTGF level was 0.933, which can differentiate between CP and HV. Several factors would be involved in the increase in serum N-terminal fragment CTGF level. In conclusion, serum N-terminal fragment CTGF level is a promising new biomarker for CP.

As a progressive fibroinflammatory disease, chronic pancreatitis (CP) often manifests as recurrent bouts of abdominal pain with or without complications, causing a heavy burden of health care. In recent years, some meaningful insights into the management of CP have been obtained from randomized controlled trials, systematic reviews, and meta-analyses, which were of great importance. Based on this research, it is shown that there are various treatments for CP. Therefore, it is of great importance to choose a suitable strategy for patients with CP individually. Relevant evidence on the management of CP was summarized in this review, including nutrition supplements, medication, endoscopy, surgery, exploration of novel therapies as well as evaluation and prediction of treatment response.

Pancreatitis is a severe inflammation in the pancreas and accounts for one of the leading gastrointestinal disorders worldwide, and presently pacing up with the morbidity and mortality rates. It has been noted that severe recurrences of acute pancreatitis lead to chronic inflammation and fibrosis of the pancreas which may further result to a long-term risk of pancreatic carcinogenesis which has a lower survival rate and worse prognosis. Several genetic and epigenetic mechanisms have been reported to orchestrate disease development. Intriguingly, concurrent epigenetic alterations can also control the genes responsible for the pathophysiology of several inflammatory pathways. Deciphering how epigenetic changes affect the inflammatory processes in pancreatitis and body's response to various therapeutic modalities may help to manage the condition more effectively. The current review will concentrate on several epigenetic changes in general and how specifically they are implicated in pancreatitis pathogenesis. Further, this review summarizes the involvement of inflammation in pancreatitis from an epigenetic perspective.

Both acute and chronic pancreatitis are frequent diseases of the pancreas, which, despite being of benign nature, are related to a significant risk of malnutrition and may require nutritional support. Acute necrotizing pancreatitis is encountered in 20 % of patients with acute pancreatitis, is associated with increased morbidity and mortality, and may require artificial nutrition by enteral or parenteral route, as well as additional endoscopic, radiological or surgical interventions. Chronic pancreatitis represents a chronic inflammation of the pancreatic gland with development of fibrosis. Abdominal pain leading to decreased oral intake, as well as exocrine and endocrine failure are frequent complications of the disease. All of the above represent risk factors related to malnutrition. Therefore, patients with chronic pancreatitis should be considered at risk, screened and supplemented accordingly. Moreover, osteoporosis and increased facture risk should be acknowledged in patients with chronic pancreatitis, and preventive measures should be considered.

The treatment of chronic pancreatitis (CP) and symptomatic pancreatic duct (PD) calculi often involves techniques like endoscopic retrograde cholangiopancreatography (ERCP), extracorporeal shock wave lithotripsy (ESWL), or a combination of both. However, identifying predictive factors for the successful removal of these calculi remains variable. This study aimed to determine the factors predicting successful ESWL and endoscopic removal in CP and PD calculi patients.

We examined data from CP patients who underwent complete PD calculi removal via ESWL combined with ERCP between July 2012 and 2022, and assessed baseline characteristics, imaging findings, and treatment details. Patients were categorized into early- and late-endoscopic complete removal groups (EER and LER groups, respectively).

Of the 27 patients analyzed, 74.1% were male with an average age of 44 ± 9.6 years. EER was achieved in 74% of the patients. Patients in the EER group exhibited smaller PD calculi diameter (8.5 vs. 19 mm, p = 0.012) and lower calculus density (964.6 vs. 1313.3 HU, p = 0.041) compared to the LER group. Notably, PD stricture and the rate of PD stent insertion were not different between the groups. A calculus density threshold of 1300 HU on non-contrast CT demonstrated 71% sensitivity and 80% specificity in predicting EER.

Smaller and low-density PD calculi may serve as predictors for successful EER, potentially aiding in the management of CP patients with PD calculi.

Chronic pancreatitis (CP) causes suffering and socioeconomic burden. This study evaluated perioperative results and patient-reported outcomes (PRO) in CP patients treated with duodenum-preserving pancreatic head resection (DPPHR).

Data were analyzed of CP patients undergoing DPPHR between 01/2001-10/2014. PROs were measured using a specifically designed questionnaire and the EORTC QLQ-C30/PAN26. Associations between treatment variables and PROs were examined.

Of 332 patients who received DPPHR, most (n = 251, 75.6%) underwent the Berne modification. Surgical morbidity was 21.5% (n = 71) and 90-day mortality 1.5% (n = 5). Median follow-up was 79.9 months, 5-year survival 90.5%, and 1.8% of patients developed pancreatic cancer. Of 283 patients alive, 178 (62.9%) returned questionnaires. Referral for surgery was self-initiated (38.0% of cases), by gastroenterologists (27.5%) and by general practitioners (21.1%). QoL improved in 78.7% of patients, remained stable in 12.1%, and worsened in 9.1%. Median Izbicki scores decreased from 90 to 5 points after surgery (p < 0.0001). Time from diagnosis to DPPHR was an independent, proportional predictor of a higher postoperative Izbicki score (p = 0.04).

DPPHR is an effective, safe treatment for CP. A delay in surgery decreases surgical effectivity, hence CP patients should be referred to surgery early to ensure satisfactory outcomes.

Opioids, such as morphine and oxycodone, are widely used for pain management associated with chronic pancreatitis (CP); however, their impact on the progression and pain sensitivity of CP has never been evaluated. This report investigates the impact of opioid use on the severity of CP, pain sensitivity, and the gut microbiome. C57BL/6 mice were divided into control, CP, CP with morphine/oxycodone, and either morphine or oxycodone alone groups. CP was induced by administration of caerulein (50ug/kg/h, i.p. hourly x7, twice a week for 10 weeks). The mouse-to-pancreas weight ratio, histology, and Sirius red staining were performed to measure CP severity. Tail flick and paw pressure assays were used to measure thermal and mechanical pain. DNA was extracted from the fecal samples and subjected to whole-genome shotgun sequencing. Germ-free mice were used to validate the role of gut microbiome in sensitizing acute pancreatic inflammation. Opioid treatment exacerbates CP by increasing pancreatic necrosis, fibrosis, and immune-cell infiltration. Opioid-treated CP mice exhibited enhanced pain hypersensitivity and showed distinct clustering of the gut microbiome compared to untreated CP mice, with severely compromised gut barrier integrity. Fecal microbiota transplantation (FMT) from opioid-treated CP mice into germ-free mice resulted in pancreatic inflammation in response to a suboptimal caerulein dose. Together, these analyses revealed that opioids worsen the severity of CP and induce significant alterations in pain sensitivity and the gut microbiome in a caerulein CP mouse model. Microbial dysbiosis plays an important role in sensitizing the host to pancreatic inflammation.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Differentiation from chronic pancreatitis (CP) is currently inaccurate in about one-third of cases. Misdiagnoses in both directions, however, have severe consequences for patients. We set out to identify molecular markers for a clear distinction between PDAC and CP.

Genome-wide variations of DNA-methylation, messenger RNA and microRNA level as well as combinations thereof were analysed in 345 tissue samples for marker identification. To improve diagnostic performance, we established a random-forest machine-learning approach. Results were validated on another 48 samples and further corroborated in 16 liquid biopsy samples.

Machine-learning succeeded in defining markers to differentiate between patients with PDAC and CP, while low-dimensional embedding and cluster analysis failed to do so. DNA-methylation yielded the best diagnostic accuracy by far, dwarfing the importance of transcript levels. Identified changes were confirmed with data taken from public repositories and validated in independent sample sets. A signature of six DNA-methylation sites in a CpG-island of the protein kinase C beta type gene achieved a validated diagnostic accuracy of 100% in tissue and in circulating free DNA isolated from patient plasma.

The success of machine-learning to identify an effective marker signature documents the power of this approach. The high diagnostic accuracy of discriminating PDAC from CP could have tremendous consequences for treatment success, once the result from still a limited number of liquid biopsy samples would be confirmed in a larger cohort of patients with suspected pancreatic cancer.

In patients with chronic pancreatitis, pancreatic calcification is a risk factor for diabetes development, poor islet yield, and metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT). We investigated whether calcification pattern based on computed tomography is associated with outcomes using our database of 200 consecutive TPIAT procedures. Three groups were compared: noncalcification (NC); focal calcification, limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections. Maximum changes in outcomes were seen in the DC vs focal calcification group. In the DC group, preoperative hemoglobin A1c levels were higher (P < .01), and stimulated C-peptide levels were lower (P < .01) than in the NC group. Islet isolation from the DC pancreas resulted in the lowest islet equivalent (IEQ) yield and IEQ/kg among the 3 groups (P < .0001), with no insulin independence 12 months posttransplant (P < .05 vs NC group). Notably, at 12 months, the DC group was 91.7% narcotic-free, significantly higher than the NC group (P < .05). Although DC is a sign of diabetes risk after TPIAT, the DC group showed exceptional pain relief. These findings suggest that TPIAT can be beneficial for patients with chronic pancreatitis with severe calcification.

Pancreatic stones are the result of pathophysiologic changes in chronic pancreatitis with an incidence of more than 90%. At present, pancreatic extracorporeal shock wave lithotripsy (P-ESWL) can be used as the first-line treatment for large or complex stones. Although a large number of studies have proven the safety and effectiveness of P-ESWL, we should also pay attention to postoperative adverse events, mainly due to the scattering of shock waves in the conduction pathway. Adverse events can be classified as either complications or transient adverse events according to the severity. Because the anatomic location of organs along the shock wave conducting pathway differs greatly, adverse events after P-ESWL are varied and difficult to predict. This paper outlines the mechanism, definition, classification, management and risk factors for adverse events related to P-ESWL. It also discusses the technique of P-ESWL, indications and contraindications of P-ESWL, and adverse events in special populations.

The pancreas is a vital intra-abdominal organ with dual exocrine and endocrine function. This article provides an overview of several common pancreatic pathologies including pancreatitis, pancreatic cysts, and pancreatic cancer with a focus on clinical presentation as well as initial diagnosis and management.

Individuals with chronic pancreatitis (CP) are at increased risk for nutritional complications during their clinical course. We appraised the literature to provide updated estimates of the prevalence and predictors of osteoporosis, osteopenia, and osteopathy in CP using a systematic review and meta-analysis.

Search strategies were developed for major databases from inception through October 2021. Outcomes of interest included rates of osteopenia and osteoporosis based on dual-energy X-ray absorptiometry scans and risk factors. A random-effects model was used for analysis, and results were expressed as pooled cumulative rates along with 95% confidence interval (CI).

From an initial total of 1,704 identified articles, we ultimately selected 17 studies that involved 1,659 subjects (n = 1,067 men) with CP. The pooled rate of osteopathy was 58% (95% CI: 49%-67%; P < 0.001; I 2 = 91.8%). The pooled rate of osteoporosis was 18% (95% CI: 12%-23%; P < 0.001; I 2 = 86.3%), and the pooled rate of osteopenia was 39% (95% CI: 31%-48%; P < 0.001; I 2 = 91.53%). In the systematic review, factors associated with decreased bone mineral density included smoking, alcohol consumption, older age, female sex, low body mass index, decreased vitamins D and K, and fecal elastase levels.

Patients with CP have high rates of osteopathy when assessed with dual-energy X-ray absorptiometry imaging. Additional studies with longitudinal follow-up are needed to understand the observed heterogeneity, the cumulative burden of disease, and rate of bone loss in CP.

This study evaluated the dependence of the signal characteristics of time-spatial labeling inversion pulse (time-SLIP) on flow velocity and tag thickness to depict the pancreatic juice flow by analyzing signal profile using a tube phantom study. The tag edge property was evaluated by edge rise distance (ERD). For various slow flow velocities and tag thicknesses, the signal profile characteristics were evaluated using two indices: the tag center value (RTCV) reduction rate and the total signal value along the tube (TSVT). ERD, which was about 10% of the tag thickness, was higher for thicker tags, making slow flow detection difficult. TSVT was proportional to the thickness of the tag and was preserved irrespective of the flow velocity. RTCV became lower with higher flow velocity and decreased significantly with thinner tags. These results suggest that the visualization of pancreatic juice flow might improve stability by considering the appropriate tag thickness.

In recent years, the terms sarcopenia, sarcopenic obesity, and osteosarcopenic obesity (OSO) were coined to define a situation in elderly people strongly associated with frailty and increased mortality. Possibly, a complex interplay of several hormones and cytokines are involved in its development. Ongoing research detected that OSO may occur at any age and in several conditions. The prevalence of OSO in alcoholism was poorly analyzed. The aim of this study was to analyze the prevalence of OSO in alcoholism and its relationship with proinflammatory cytokines and/or common complications of alcoholism, such as cirrhosis, cancer, or vascular disease. We included 115 patients with alcoholic use disorder. Body composition analysis was performed by double X-ray absorptiometry. Handgrip strength was recorded using a dynamometer. We assessed liver function according to Child's classification, and determined serum levels of proinflammatory cytokines (TNF-α, IL-6, IL-8), routine laboratory variables, and vitamin D. People with alcoholic use disorder showed a high prevalence of OSO, especially regarding OSO obesity (60%), OSO osteopenia (55.65%), and OSO lean mass (60.17%). OSO handgrip was closely, independently, related to the presence of vascular calcification (χ² = 17.00; p < 0.001). OSO handgrip was related to several proinflammatory cytokines and vitamin D. Vitamin D deficiency kept a close correlation with OSO handgrip (rho = -0.54, p < 0.001). Therefore, among people with alcohol use disorder, OSO prevalence was high. OSO handgrip is related to serum proinflammatory cytokine levels supporting the possible pathogenetic role of these cytokines on OSO development. Vitamin D deficiency is related to OSO handgrip suggesting its pathogenetic involvement in sarcopenia in patients with alcohol use disorder. The close association between OSO handgrip and vascular calcification is clinically relevant and suggests that OSO handgrip may constitute a prognostic tool in these patients.

Pancreatitis poses a serious medical problem worldwide. This study aims to explore the epidemiological trends of pancreatitis from 1990 to 2019, analyze the association between disease burden and age, period and birth cohort, and subsequently present a forecast of pancreatitis incidence and deaths.

Epidemiologic data were gathered from the Global Health Data Exchange query tool. Joinpoint regression model was used to calculate the average annual percentage changes (AAPCs). Age-period-cohort analysis was utilized to estimate the independent effects of age, period and birth cohort. We also predicted the global epidemiological trends to 2044.

Globally, the incident cases and deaths of pancreatitis increased 1.63-and 1.65-fold from 1990 to 2019, respectively. Joinpoint regression analysis showed that the age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) decreased over the past three decades. The age effect indicates that older people have higher age-specific incidence and death rates. The period effect on incidence and deaths showed downward trends from 1990 to 2019. The cohort effect demonstrated that incidence and death risk peaked in the earlier birth cohort and were lower in the latest birth cohort. Incident cases and deaths of pancreatitis may significantly increase in the next 25 years. The ASIRs were predicted to slightly increase, while the ASDRs were predicted to decrease.

Epidemiologic patterns and trends of pancreatitis across age, period and birth cohort may provide novel insight into public health. Limitations of alcohol use and prevention strategies for pancreatitis are necessary to reduce future burden.

The clinical course of chronic pancreatitis is unpredictable and there is no globally accepted score to predict the disease course. We developed a clinical score to estimate pancreatitis-related hospitalisation in patients with newly diagnosed chronic pancreatitis.

We conducted a retrospective cohort study using two clinical chronic pancreatitis databases held in tertiary referral centres in Dublin, Ireland, and in Tarragona, Spain. Individuals diagnosed with chronic pancreatitis between 2007 and 2014 were eligible for inclusion. Candidate predictors included aetiology, body mass index, exocrine dysfunction, smoking and alcohol history. We used multivariable logistic regression to develop the model.

We analysed data from 154 patients with newly diagnosed chronic pancreatitis. Of these, 105 patients (68%) had at least one hospital admission for pancreatitis-related reasons in the 6 years following diagnosis. Aetiology of chronic pancreatitis, body mass index, use of pain medications and gender were found to be predictive of more pancreatic-related hospital admissions. These predictors were used to develop a clinical score which showed acceptable discrimination (area under the ROC curve = 0.70).

We developed a clinical score based on easily accessible clinical parameters to predict pancreatitis-related hospitalisation in patients with newly diagnosed chronic pancreatitis.

Chronic pancreatitis (CP) is an irreversible and progressive inflammatory disease. Knowledge on the development and progression of CP is limited. The goal of the study was to define the serum profile of pro-inflammatory cytokines and the cell antioxidant defense system (superoxidase dismutase-SOD, and reduced glutathione-GSH) over time in a cerulein-induced CP model and explore the impact of these changes on selected cytokines in the intestinal mucosa and pancreatic tissue, as well as on selected serum biochemical parameters. The mRNA expression of CLDN1 and CDH1 genes, and levels of Claudin-1 and E-cadherin, proteins of gut barrier, in the intestinal mucosa were determined via western blot analysis. The study showed moderate pathomorphological changes in the pigs' pancreas 43 days after the last cerulein injection. Blood serum levels of interleukin (IL)-1-beta, IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGTP), SOD and GSH were increased following cerulein injections. IL-1-beta, IL-6, TNF-alpha and GSH were also increased in jejunal mucosa and pancreatic tissue. In duodenum, decreased mRNA expression of CDH1 and level of E-cadherin and increased D-lactate, an indicator of leaky gut, indicating an inflammatory state, were observed. Based on the current results, we can conclude that repetitive cerulein injections in growing pigs not only led to CP over time, but also induced inflammation in the intestine. As a result of the inflammation, the intestinal barrier was impaired.

Chronic Pancreatitis (CP) is a fibroinflammatory condition with debilitating symptoms. Quality of life is severely affected in patients with CP and they are likely to suffer from mental health disorders, including depression. We conducted a systematic review and meta-analysis assessing the prevalence of depressive symptoms and depression in patients with CP.

MEDLINE (OVID), PsycINFO, Cochrane Library, Embase, CINAHL Complete, Scopus and Web of Science were searched until July 2022 to identify manuscripts reporting the prevalence of depressive symptoms and depression (diagnosed clinically or with a validated scale without language restriction) in patients with Chronic Pancreatitis. The pooled prevalence was calculated using a random effects model. Heterogeneity was assessed by the inconsistency index (I2).

Among 3647 articles identified, 58 studies were identified for full text review, and ultimately nine studies were included. A total of 87136 patients were included in the studies. Depression was diagnosed clinically or symptoms were identified using validated scales including Center for Epidemiological Studies 10-item Depression Scale (CESD), Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS). The overall prevalence of depression in patients with chronic pancreatitis was 36.2% (95%CI: 18.8-55.7). In the stratified analysis, depression prevalence according to the clinical diagnosis, BDI and HADS was 30.10%, 48.17% and 36.61%, respectively.

The high prevalence of depression among patients with CP deserves a call-to-action due to its medical implications and worsening quality of life. Our findings raise awareness of the importance of screening patients with CP for mental health disorders. Further well-designed studies are needed to further characterize these findings.

The activation of pancreatic stellate cells (PSCs) plays a key role in the occurrence and development of chronic pancreatitis (CP) and pancreatic fibrosis, which is related to the process of epithelial-mesenchymal transition (EMT). This study was designed to investigate the effect and mechanism of Tcf21 (one of tumor suppressor genes) on pancreatic inflammation and fibrosis in vivo and in vitro.

C57BL/6 male mice were intraperitoneally injected with caerulein for 6 weeks to establish CP animal model. Fixed pancreatic tissue paraffin-embedded sections were used for immunohistochemistry staining of Tcf21, fibrosis-related markers (α-SMA), interstitial markers (Vimentin) and epithelial markers (E-cadherin). Western blotting and qRT-PCR assay were performed to analyze the change of expression of the above markers after stimulation of TGF-β1 or overexpressed Tcf21 lentivirus transfection in human pancreatic stellate cells (HPSCs).

The pancreatic expression of α-SMA and Vimentin of CP mice significantly increased, while the expression of Tcf21 and E-cadherin significantly decreased. TGF-β1 could promote activation and EMT process of HPSCs, and inhibited the expression of Tcf21. Overexpression of Tcf21 could significantly down-regulate the expression of α-SMA, Fibronectin and Vimentin, and up-regulated the expression of ZO-1 of HPSCs. Cell Counting Kit-8 assay and scratch wound-healing assay results showed that overexpression of Tcf21 could significantly inhibit the cell migration and proliferation of HPSCs.

Overexpression of Tcf21 could significantly alleviate the activation, proliferation, migration of PSCs by regulating the EMT process. Tcf21 had a potential prospect of a new target for CP therapy.

Pediatric patients with exocrine pancreatic insufficiency (EPI) have symptoms that include abdominal pain, weight loss or poor weight gain, malnutrition, and steatorrhea. This condition can be present at birth or develop during childhood for certain genetic disorders. Cystic fibrosis (CF) is the most prevalent disorder in which patients are screened for EPI; other disorders also are associated with pancreatic dysfunction, such as hereditary pancreatitis, Pearson syndrome, and Shwachman-Diamond syndrome. Understanding the clinical presentation and proposed pathophysiology of the pancreatic dysfunction of these disorders aids in diagnosis and treatment. Testing pancreatic function is challenging. Directly testing aspirates produced from the pancreas after stimulation is considered the gold standard, but the procedures are not standardized or widely available. Instead, indirect tests are often used in diagnosis and monitoring. Although indirect tests are more widely available and easier to perform, they have inherent limitations due to a lack of sensitivity and/or specificity for EPI.

To analyze treatment outcomes in patients with various forms of chronic pancreatitis.

We analyzed 434 patients with chronic pancreatitis. These ones underwent 2879 different examinations to determine morphological type of pancreatitis and dynamics of pathological process, as well as substantiate treatment strategy and functional monitoring of various organs and systems. Morphological type A (Buchler et al. 2002) was present in 51.6% of cases, type B - 40.0%, type C - 4.3%. Cystic lesions were detected in 41.7% of cases, pancreatic calculi - 45.7%, choledocholithiasis - 19.1%, tubular stricture of distal choledochus - 21.4%, pancreatic duct enlargement - 95.7%, narrowing or interruption of the duct - 93.5%, communication of the duct with the cyst - in 17.4% of patients. Induration of pancreatic parenchyma was noted in 97% of patients, heterogeneous structure - 94.4%, enlargement of the pancreas - 10.8%, shrinkage of the gland - in 49.5% of cases. Surgical treatment was performed in 186 patients: ERCP + EPST in 8 patients, ERCP + EPST + pancreatic duct stenting in 2 patients, ERCP + EPST + wirsungotomy with stenting in 2 patients, laparotomy with hepaticocholedochojejunostomy in 6 patients, laparotomy with gastropancreatoduodenal resection in 19 patients, laparotomy with Puestow I procedure in 18 patients, Puestow II procedure in 34 patients, laparotomy + pancreatic tail resection + Duval procedure in 3 patients, laparotomy with Frey surgery in 19 cases, laparotomy and Beger procedure in 2 patients, external drainage of pseudocyst in 21 patients, endoscopic internal drainage of pseudocyst in 9 patients, laparotomy with cystodigestive anastomosis in 34 patients, excision of fistula and distal pancreatectomy in 9 cases).

Postoperative complications developed in 22 (11.8%) patients. Mortality rate was 2.2%.

Gut bacteria facilitate nutrient metabolism and generate small molecules that form part of the broader "metabolome". It is unclear whether these metabolites are disturbed in chronic pancreatitis (CP). This study aimed to evaluate the gut microbial-host cometabolites and their relationship in patients with CP.

Fecal samples were collected from 40 patients with CP and 38 healthy family members. Each sample was examined with 16S rRNA gene profiling and gas chromatography time-of-flight mass spectrometry to estimate the relative abundances of specific bacterial taxa between the two groups and to profile any changes in the metabolome, respectively. Correlation analysis was used to evaluate the differences in metabolites and gut microbiota between the two groups.

The abundance of Actinobacteria was lower at the phylum level, and that of Bifidobacterium was lower at the genus level in the CP group. Eighteen metabolites had significantly different abundances and the concentrations of 13 metabolites were significantly different between the two groups. Oxoadipic acid and citric acid levels were positively correlated with Bifidobacterium abundance (r = 0.306 and 0.330, respectively, both P < 0.05), while the 3-methylindole concentration was negatively correlated with Bifidobacterium abundance (r = -0.252, P = 0.026) in CP.

Gut microbiome and host microbiome metabolic products might be altered in patients with CP. Evaluating gastrointestinal metabolite levels may further enhance our understanding of the pathogenesis and/or progression of CP.