To systematize data on the prevalence and risk of malnutrition in patients with chronic pancreatitis (CP).

MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, Scopus, and the Russian Science Citation Index were searched for studies published between January 1, 1985, and October 23, 2024 (inclusive) based on an analysis of the titles and abstracts of articles in these databases. The study included relevant publications in peer-reviewed periodicals in English or Russian, publications with data on the prevalence of malnutrition in patients with CP and control subjects (if any), studies on adult patients with CP, and publications with detailed descriptive statistics that allow using the data in the meta-analysis.

The final analysis included 13 studies involving 3,812 subjects (3,401 patients with CP and 411 controls). The overall prevalence of malnutrition in patients with CP was 43.43% (95% confidence interval [CI] 32.419-54.780), whereas in controls, it was 10.843% (95% CI 1.360-27.698). When analyzing the association in the overall pool of studies, a significant risk of malnutrition in CP patients compared to controls was shown (relative risk [RR] 3.635, 95% CI 1.409-9.373; p=0.008). The analysis used a random effect model, as there was high heterogeneity between the groups (I2=88.09%, 95% CI 74.76-94.38). A review of studies that used only validated instrumental methods for the diagnosis of malnutrition (criteria of the Global Leadership Initiative on Malnutrition) showed a total prevalence of malnutrition of 38.348% (95% CI 14.975-65.047) in patients with CP and 12.22% (95% CI 5.985-67.238) in control subjects.

This meta-analysis demonstrated that malnutrition is a common complication of CP and occurs in approximately 40% of CP patients. A modern clinician should promptly assess malnutrition markers in a CP patient and correct them using enzyme replacement therapy if detected.

Observational studies have shown that human digestive function declines naturally with age. Oral enzyme supplementation is a candidate strategy to enhance macronutrient digestion in older adults. The objective of this study was to test the effects of a mixture of six microbial enzyme preparations (ENZ) on nutrient bioaccessibility from a mixed meal in an in vitro model of digestive senescence. The mixed meal included chicken meat, peas, and potatoes. The INFOGEST 2.0 static simulation of oro-gastric digestion was used to model human digestive physiology along with a consensus protocol to model aging. Analytical testing of gastric digesta included measurements of free amino nitrogen (FAN), amino acid (AA), fatty acid (FA), glycerol, maltose, and glucose concentrations. Peptide distribution profiles were evaluated by size exclusion chromatography (SEC) and gel electrophoresis. After simulating digestion of the mixed meal, all nutrient bioaccessibility outcomes compared to pepsin-only controls, except glycerol, were further enhanced by ENZ in the aging condition compared to the standard condition (FAN: 77.1 vs. 39.3%; essential AA: 100.4 vs. 57.6%; total FA: 12.8- vs. 8.0-fold; maltose: 142.1 vs. 0.7%). SEC confirmed ENZ's proteolytic capacity to generate more lower molecular weight peptides and free AAs in standard and aging conditions compared to pepsin alone. Gel electrophoresis confirmed proteolytic enhancement with ENZ. These data showcase ENZ's hydrolytic activity toward macronutrients and suggest ENZ's capacity to compensate for reduced pepsin activity in an aging-adapted oro-gastric digestion simulation.

Exocrine pancreatic insufficiency (EPI) is a major cause of maldigestion and malnutrition, resulting from primary pancreatic diseases or other conditions. As the prevalence of EPI continues to rise, accurate identification of its etiology has become critical for the diagnosis and treatment of pancreatic secretory insufficiency. EPI can result from both pancreatic and non-pancreatic disorders. Pancreatic disorders include acute and chronic pancreatitis, pancreatic tumors, cystic fibrosis, procedures that involve pancreatic resection, and other rare causes. Non-pancreatic disorders of EPI include diabetes mellitus, celiac disease, inflammatory bowel disease, gastrointestinal and esophagectomy surgery, as well as advanced patient age. This review aims to provide a comprehensive analysis of the literature on EPI etiology, with a thorough overview to support its consideration as a potential diagnosis.

Patients with chronic pancreatitis (CP) may develop pancreatic exocrine insufficiency (PEI) but data regarding subclinical PEI are scarce. Our objective was to detect subclinical PEI in patients with CP and its functional consequences.

We prospectively included patients with CP from April 2018-December 2021. Mild PEI and severe PEI were diagnosed if fecal elastase (FE) was 100-200 μg/g and <100 μg/g stool respectively. Vitamin levels and DEXA scan were done to assess functional consequences of PEI. Presence of subclinical PEI in CP (low FE-1 but without steatorrhea) with consequent osteopathy was the primary outcome.

Of 120 patients with CP, subclinical PEI (low FE-1 but no steatorrhea) was present in 84/120(70%) patients: 6/8(75%) in early CP, 41/53(77%) in definite CP and 37/55(67.2%) in advanced CP. Overall, 72.1% patients had osteopathy including 53(62%) among patients with subclinical PEI. There was no difference in osteopathy between subclinical and severe PEI. Patients with severe PEI had lower vitamin A levels as compared to mild PEI and no PEI patients [1.3 ± 0.5 mg/ml vs. 1.7 ± 0.6 mg/ml vs. 1.8 ± 0.5 mg/ml; p = 0.04]. There was no difference in vitamin D levels. Osteopathy was present in 40/56 (71.4%) in advanced, 26/56 (46.4%) in definite and 2/8 (25%) in early CP patients (p = 0.09). On multivariable analysis, patients with advanced CP had the higher risk of osteopathy (odds ratio 7.6, 95% CI 1.9-29.7).

Subclinical PEI was present even in early CP with increased risk of osteopathy and fat-soluble vitamin deficiency.

Assessing the digestive and absorptive capacity of the gastro-intestinal tract (GIT) using minimally- or non-invasive methods, particularly in children, has been difficult owing to the complex physiology and variability in functional measurements. However, measuring GIT function is increasingly important with the emerging relevance of childhood environmental enteropathy (EE) as a mediating factor in linear growth faltering, severe acute malnutrition, poor oral vaccine uptake and impaired cognition. In EE, sub-optimal nutrient digestion and absorption (malabsorption) forms the critical link to the conditions mentioned above. The present narrative review discusses probable mechanisms that can cause malabsorption of macronutrients, along with mechanistic and experimental evidence, in children (if not, in adults) with EE. The strengths and limitations of the human experimental studies are examined in relation to a battery of existing and potential tests that are used to measure malabsorption. From the available studies conducted in children, lactose and fat malabsorption are more likely to occur in EE. Breath tests (non-invasive) measuring carbohydrate (13C-starch/sucrose/lactose), fat (13C-mixed triglyceride) and dipeptide (benzoyl-L-tyrosyl-L-1-13C-alanine) malabsorption with modifications to the existing protocols seem suitable for use in children with EE. Future research should focus on understanding the degree of macronutrient malabsorption using these tests, in different settings, and link them to functional outcomes (such as growth, muscle strength, cognition).

Pancreatic exocrine insufficiency (PEI) is defined as a reduction in pancreatic exocrine secretion below the level that allows the normal digestion of nutrients. Pancreatic disease and surgery are the main causes of PEI. However, other conditions and upper gastrointestinal surgery can also affect the digestive function of the pancreas. PEI can cause symptoms of nutritional malabsorption and deficiencies, which affect the quality of life and increase morbidity and mortality. These guidelines were developed following the United European Gastroenterology framework for the development of high-quality clinical guidelines. After a systematic literature review, the evidence was evaluated according to the Oxford Center for Evidence-Based Medicine and the Grading of Recommendations Assessment, Development, and Evaluation methodology, as appropriate. Statements and comments were developed by the working groups and voted on using the Delphi method. The diagnosis of PEI should be based on a global assessment of symptoms, nutritional status, and a pancreatic secretion test. Pancreatic enzyme replacement therapy (PERT), together with dietary advice and support, are the cornerstones of PEI therapy. PERT is indicated in patients with PEI that is secondary to pancreatic disease, pancreatic surgery, or other metabolic or gastroenterological conditions. Specific recommendations concerning the management of PEI under various clinical conditions are provided based on evidence and expert opinions. This evidence-based guideline summarizes the prevalence, clinical impact, and general diagnostic and therapeutic approaches for PEI, as well as the specifics of PEI in different clinical conditions. Finally, the unmet needs for future research are discussed.

Acute pancreatitis is an inflammatory condition of the exocrine pancreas that is a common indication for hospital admission and has had an increasing incidence in the last few decades. The diagnosis of acute pancreatitis requires the satisfaction of two out of three criteria: (1) abdominal pain radiating to the back, (2) serum lipase or amylase levels three or more times the upper limit of the normal level, and (3) findings indicating pancreatitis obtained via a computed tomography (CT) scan or magnetic resonance imaging (MRI). The different etiologies include gallstones, autoimmune disorders, alcohol abuse, smoking, hypertriglyceridemia, obesity, drugs, and post-endoscope retrograde cholangiopancreatography (ERCP). The initial investigation includes serum amylase and lipase analysis, a lipid panel including triglycerides, analysis of immunoglobulins, a full blood count, electrolyte analysis, a hemoglobin A1c test, a complete metabolic panel, and transabdominal ultrasound. The initial therapy includes oxygen supplementation, the provision of intravenous fluids, pain control, and a nutrition regime. Early oral feeding is encouraged if tolerated; if not, liquid supplement provision or enteral tube feeding within 48 h of admission has shown better outcomes. Some complications of acute pancreatitis are necrosis, infection, insulin resistance leading to diabetes mellitus, and pancreatic exocrine insufficiency requiring enzyme supplementation. Patients need to attend regular follow-ups and abstain from alcohol and smoking (if warranted) to prevent the recurrence of acute pancreatitis. The mortality rate of acute pancreatitis has decreased in the past few decades because of better management skills, but the recent rise in acute pancreatitis episodes is concerning. Sustained endeavors through clinical trials are required to establish a broad variety of drugs that can be used for acute pancreatitis episodes.

The association between pancreatic exocrine insufficiency (PEI) and morphologic findings in chronic pancreatitis has not yet been fully studied. Thus, the aim of this study was to investigate the correlation between PEI severity and computed tomography (CT)-based morphological severity in patients with chronic pancreatitis. This nationwide survey included 180 Korean participants with chronic pancreatitis aged 18 years or older between January 2018 and December 2021. PEI severity was measured by the PEI questionnaire (PEI-Q). Morphological severity was measured using a CT-based scoring system, which included pancreatic duct caliber, pancreatic duct stricture or intraductal obstructing calculus, pancreatic atrophy, and pancreatic calcification. In addition, 35 patients who received pancreatic enzyme replacement therapy (PERT) were evaluated by PEI-Q to determine whether PEI improved after PERT. PEI severity was normal (n = 89), mild (n = 69), moderate (n = 14), or severe (n = 8). Severities of pancreatic duct caliber and pancreatic duct stricture or intraductal obstructing calculus had small but significant associations with PEI severity (Cramer V = 0.121 and 0.141, respectively). Severities of pancreatic atrophy and pancreatic calcification were not significantly associated with PEI severity. PEI severity showed a significant improvement after PERT (P < .001). In conclusion, PEI severity had significant associations with CT-based morphological severities, including severities of pancreatic duct caliber and pancreatic duct stricture or intraductal obstructing calculus. In addition, PEI-Q could be a useful indicator for evaluating the therapeutic effect of PERT in clinical practice.

Protein maldigestion and malabsorption lead to malnutrition and are a feature of exocrine pancreatic insufficiency (EPI). Although it is the current standard, measurement of nitrogen in stool to assess protease activity is indirect. Up to 80% of hydrolysed proteins appear in blood in the form of peptides, so we developed a method to measure peptide-derived amino acids in plasma as a relevant measure of proteolysis, verified its accuracy, precision, and linearity, and validated it in a porcine model. We modified a ninhydrin method. Large proteins were eliminated from plasma with 10 kDa-cut-off centrifugal filters. Free and total amino acids were measured in permeate before and after its hydrolysis. Peptide-derived amino acids were quantified by subtracting free amino acids from total amino acids. We verified the method in vitro and by comparing results in healthy and EPI pigs. The accuracy of the analysis was close to 100%, with excellent precision (mean relative standard deviation for low, medium, and high amino acid levels = 0.88%) and with stringent linearity (r2  = 0.986, %RE = 5.23). The high-throughput ninhydrin method detected levels of peptide-derived amino acids in vivo with maximal changes seen approximately 2 hours postprandially in young pigs. The AUC and Cmax were significantly higher in healthy compared to EPI pigs (P = .0026 and P = .0037, respectively). The high-throughput ninhydrin method is a sensitive, reliable, and practical method for the estimation of dietary peptide-derived amino acids. This assay endpoint could serve as a direct biomarker of protein digestion and absorption.

Historically, the intestinal lymphatics were considered passive conduits for fluids, immune cells, dietary lipids, lipid soluble vitamins, and lipophilic drugs. Studies of intestinal lymphatic drug delivery in the late 20th century focused primarily on the drugs' physicochemical properties, especially high lipophilicity, that resulted in intestinal lymphatic transport. More recent discoveries have changed our traditional view by demonstrating that the lymphatics are active, plastic, and tissue-specific players in a range of biological and pathological processes, including within the intestine. These findings have, in turn, inspired exploration of lymph-specific therapies for a range of diseases, as well as the development of more sophisticated strategies to actively deliver drugs or vaccines to the intestinal lymph, including a range of nanotechnologies, lipid prodrugs, and lipid-conjugated materials that "hitchhike" onto lymphatic transport pathways. With the increasing development of novel therapeutics such as biologics, there has been interest in whether these therapeutics are absorbed and transported through intestinal lymph after oral administration. Here we review the current state of understanding of the anatomy and physiology of the gastrointestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. We summarize the current state-of-the-art approaches to deliver drugs and quantify their uptake into the intestinal lymphatic system. Finally, and excitingly, we discuss recent examples of significant pharmacokinetic and therapeutic benefits achieved via intestinal lymphatic drug delivery. We also propose approaches to advance the development and clinical application of intestinal lymphatic delivery strategies in the future. SIGNIFICANCE STATEMENT: This comprehensive review details the understanding of the anatomy and physiology of the intestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. It highlights current state-of-the-art approaches to deliver drugs to the intestinal lymphatics and the shift toward the use of these strategies to achieve pharmacokinetic and therapeutic benefits for patients.

The digestion of starch-based foods in the intestinal tract is important for human health. Modeling the details enhances fundamental understanding and glycemic prediction accuracy. It is, however, a challenge to take granular properties into account. A multiscale digestion model has been proposed to characterize mass transfer and hydrolysis reaction at both the intestine and particle scales, seamlessly integrating inter-scale mass exchange. A specific grid scheme was formulated for the shrinkage and transport of the particle computational domain. By incorporating additional glycemic-related processes, e.g., intestinal absorption, a dietary property-based glycemic prediction system has been developed. Its effectiveness was validated based on a human tolerance experiment of cooked rice particles. The model-based investigation comprehensively reveals the impact of initial size on digestion behavior, specifically in terms of enzyme distribution and particle evolution. This work also demonstrates the significance of modeling both particle-scale diffusion and intestine-scale transport, a combination not previously explored. The results indicate that ignoring the former mechanism leads to an overestimation of the glycemic peak by at least 50.8%, while ignoring the latter results in an underestimation of 16.3%.

Gastrointestinal (GI) sequelae, such as vomiting, hyperacidity, dysphagia, dysmotility, and diarrhea, are nearly universal among patients with nephropathic cystinosis. These complications result from disease processes (e.g., kidney disease, cystine crystal accumulation in the GI tract) and side effects of treatments (e.g., cysteamine, immunosuppressive therapy). GI involvement can negatively impact patient well-being and jeopardize disease outcomes by compromising drug absorption and patient adherence to the strict treatment regimen required to manage cystinosis. Given improved life expectancy due to advances in kidney transplantation and the transformative impact of cystine-depleting therapy, nephrologists are increasingly focused on addressing extra-renal complications and quality of life in patients with cystinosis. However, there is a lack of clinical data and guidance to inform GI-related monitoring, interventions, and referrals by nephrologists. Various publications have examined the prevalence and pathophysiology of selected GI complications in cystinosis, but none have summarized the full picture or provided guidance based on the literature and expert experience. We aim to comprehensively review GI sequelae associated with cystinosis and its treatments and to discuss approaches for monitoring and managing these complications, including the involvement of gastroenterology and other disciplines.

Exocrine pancreatic insufficiency (EPI) is highly prevalent among individuals with cystic fibrosis (CF). Individuals diagnosed with EPI are often labeled as having "pancreas insufficient cystic fibrosis (PI-CF)" while those with normal exocrine function are labeled as "pancreas sufficient CF (PS-CF)." This diagnosis of EPI relies on clinical and laboratory features and management involves consumption of pancreas enzyme replacement therapy. In this review, we discuss the nuances of diagnosis and management of EPI in CF. We also present emerging evidence on the effects of CFTR modulating agents on the management of EPI, and speculate that these medications may lead to greater heterogeneity in management of EPI in CF moving forward.

Pancreas serves endocrine and exocrine functions in the body; thus, their pathology can cause a broad range of irreparable consequences. Endocrine functions include the production of hormones such as insulin and glucagon, while exocrine functions involve the secretion of digestive enzymes. Disruption of these functions can lead to conditions like diabetes mellitus and exocrine pancreatic insufficiency. Also, the symptoms and causality of pancreatic cancer very greatly depends on their origin: pancreatic ductal adenocarcinoma is one of the most fatal cancer; however, most of tumor derived from endocrine part of pancreas are benign. Pancreatitis, an inflammation of the pancreatic tissues, is caused by excessive alcohol consumption, the bile duct obstruction by gallstones, and the premature activation of digestive enzymes in the pancreas. Hereditary pancreatic diseases, such as maturity-onset diabetes of the young and hereditary pancreatitis, can be a candidate for disease modeling using human pluripotent stem cells (hPSCs), due to their strong genetic influence. hPSC-derived pancreatic differentiation has been established for cell replacement therapy for diabetic patients and is robustly used for disease modeling. The disease modeling platform that allows interactions between immune cells and pancreatic cells is necessary to perform in-depth investigation of disease pathogenesis.

Latent associations between low serum amylase and reduced plasma insulin levels and increased adiposity have been described previously in a small study of asymptomatic middle-aged humans. In the present study, we sought to determine the nature of such changes during the longitudinal progression from metabolically normal to overt type 2 diabetes mellitus (T2DM) in nonhuman primates (NHPs), a disease that appears to be the same in both pathophysiology and underlying mechanisms as that which most commonly develops in middle-aged adult humans. Amylase and lipase levels were characterized in 157 unrelated adult rhesus monkeys (Macaca mulatta); 38% developed T2DM while under study. In all monkeys, multivariable linear regression analysis revealed that amylase could be negatively predicted by % body fat (β -0.29; p = 0.002), age (β -0.27; p = 0.005), and HbA1c (β -0.18; p = 0.037). Amylase levels were positively predicted by lipase levels (β = 0.19; p = -0.024) in all NHPs included in the study. Amylase was significantly lower in NHPs with metabolic syndrome (p < 0.001), prediabetes (PreDM) (p < 0.001), and T2DM (p < 0.001) compared to metabolically normal adult NHPs. Lipase increased in NHPs with PreDM (p = 0.005) and T2DM (p = 0.04) compared to normal NHPs. This is the first longitudinal study of any species, including humans, to show the dynamics of amylase and lipase during the metabolic progression from normal to metabolic syndrome, to PreDM and then to overt T2DM. The extraordinary similarity between humans and monkeys in T2DM, in pancreatic pathophysiology and in metabolic functions give these findings high translational value.

Exocrine pancreatic dysfunction (EPD) is a malabsorptive complication of pancreatic disorders that can lead to a host of symptoms ranging from flatulence to diarrhea and contribute to weight loss and metabolic bone disease. It is increasingly recognized to occur after acute pancreatitis (AP), including episodes with mild severity. The risk of developing EPD after AP is influenced by a range of factors, including the degree of acinar cell destruction and inflammation during AP, and persistent structural derangements following AP. In this article, we discuss the epidemiology, pathophysiology, and clinical management of EPD after AP while highlighting key knowledge gaps.

Pancreatic exocrine insufficiency (PEI) can be induced by various kinds of diseases, including chronic pancreatitis, acute pancreatitis, and post-pancreatectomy. The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis, disorder of pancreatic fluid flow, and imbalance of secretion feedback. Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis, with the abundance of Lactobacillus and Bifidobacterium increasing the most, which could be partially reversed by pancreatic enzyme replacement therapy. Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota. Pancreatic exocrine secretions and changes in duodenal pH as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota. In turn, the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk. Going forward, more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.

This study investigated the antidiabetic effect of vanillin using in vitro, in silico, and in vivo experimental models.

Type 2 diabetes (T2D) was induced in male Sprague-Dawley (SD) rats using fructose-streptozotocin (STZ), then orally administered low (150 mg/kg bodyweight) or high (300 mg/kg bodyweight) dose of vanillin for 5 weeks intervention period.

Vanillin suppressed the levels of blood glucose, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-c), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, uric acid, when elevated serum insulin, HDL-cholesterol, and concomitantly improved pancreatic β-cell function, glucose tolerance, and pancreatic morphology. It also elevated both serum and pancreatic tissue GSH level, SOD and catalase activities, and hepatic glycogen level, while depleting malondialdehyde level, α-amylase, lipase, acetylcholinesterase, ATPase, ENTPDase and 5'-nucleotidase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glycogen phosphorylase activities.

The results indicate the potent antidiabetic effect of vanillin against T2D and its associated complications.

Exocrine pancreatic insufficiency (EPI) is common in pancreatic ductal adenocarcinoma (PDAC) and may lead to significant nutrition compromise. In the setting of cancer cachexia and gastrointestinal toxicities of cancer treatments, untreated (or undertreated) EPI exacerbates weight loss, sarcopenia, micronutrient deficiencies, and malnutrition. Together, these complications contribute to poor tolerance of oncologic therapies and negatively impact survival. Treatment of EPI in PDAC involves the addition of pancreatic enzyme replacement therapy, with titration to improve gastrointestinal symptoms. Medical nutrition therapies may also be applicable and may include fat-soluble vitamin replacement, medium-chain triglycerides, and, in some cases, enteral nutrition. Optimizing nutrition status is an important adjunct treatment approach to improve quality of life and may also improve overall survival.

Fat digestion and absorption play crucial roles in maintaining energy homeostasis and supporting essential physiological functions. The initial stage of fat digestion occurs in the stomach, where gastric lipase begins the hydrolysis of triglycerides. However, most fat digestion takes place in the small intestine via pancreatic enzymes and bile salts. Emulsification of fat by bile acids facilitates enzymatic action, breaking down triglycerides into free fatty acids and monoglycerides, which are then able to be absorbed by enterocytes. Fat malabsorption can result from various underlying conditions, such as exocrine pancreatic insufficiency, bile acid disorders, or intestinal diseases. The clinical manifestations of fat malabsorption include steatorrhea, malnutrition, and deficiencies of fat-soluble vitamins. Diagnostic approaches involve assessing fecal fat levels, imaging studies, and various functional tests to identify the specific etiology. This review article will describe the normal physiologic process of fat digestion and absorption and discuss various pathophysiology that can lead to fat malabsorption within the gastrointestinal tract as well as their respective diagnostic testing modalities. Effective digestion of fat is essential for overall health, because it allows for absorption of many essential nutrients, plays an integral role in cellular and structural function, and supplies energy to the body. When this is dysfunctional, disorders of malabsorption can occur. This article will give a brief overview of the physiologic process of fat digestion and absorption in healthy individuals as well as review important pathophysiology that can lead to fat malabsorption within the gastrointestinal tract and current diagnostic testing modalities.

Exocrine pancreatic insufficiency (EPI) is a complex condition that disrupts normal digestion and absorption. Patients with EPI may suffer from mild to debilitating malabsorption with a constellation of symptoms that can have a significant effect on quality of life and nutrition status. Pancreatic enzyme replacement therapy (PERT) is effective and safe to treat EPI and is the standard of care for this condition. A wide variety and various forms of these products exist, as well as numerous guidelines and recommendations. Obtaining PERT for patients can oftentimes be cost prohibitive. Determining the presence and extent of EPI can be challenging and patient specific, making it difficult for practitioners. This narrative review will explore these issues, as well as several disease states potentially affected by EPI, and review current management strategies.

Mouse models of diet-induced type 2 diabetes mellitus provide powerful tools for studying the structural and physiological changes that are related to the disease progression. In this study, diabetic-like glucose dysregulation was induced in mice by feeding them a western diet, and light and transmission electron microscopy were used to study the ultrastructural changes in the pancreatic acinar cells. Acinar necrosis and vacuolization of the cytoplasm were the most prominent features. Furthermore, we observed intracellular and extracellular accumulation of lipid compounds in the form of lipid droplets, structural enlargement of the cisternae of the rough endoplasmic reticulum (RER), and altered mitochondrial morphology, with mitochondria lacking the typical organization of the inner membrane. Last, autophagic structures, i.e., autophagosomes, autolysosomes, and residual bodies, were abundant within the acinar cells of western diet-fed mice, and the autolysosomes contained lipids and material of varying electron density. While diets inducing obesity and type 2 diabetes are clearly associated with structural changes and dysfunction of the endocrine pancreas, we here demonstrate the strong effect of dietary intervention on the structure of acinar cells in the exocrine part of the organ before detectable changes in plasma amylase activity, which may help us better understand the development of non-alcoholic fatty pancreas disease and its association with endo- and exocrine dysfunction.

The pancreas has two main functions: to produce and secrete digestive enzymes (exocrine function) and to produce hormones that regulate blood glucose and splanchnic secretion (endocrine function). The endocrine and exocrine portions of the pancreas are central regulators in digestion and metabolism, with continuous crosstalk between their deeply interconnected components, which plays a role in disease. Pancreatic neoplasms, inflammation, trauma, and surgery can lead to the development of type 3c diabetes when an insult simultaneously damages both acini and islets, leading to exocrine and endocrine dysfunction. In diabetes mellitus patients, pancreatic exocrine insufficiency is highly prevalent, yet little is known about the associations between diabetes mellitus and pancreatic exocrine function. This review aims to provide an overview of the physiology of the pancreas, summarize the pathophysiology and diagnostic work-up of pancreatic exocrine insufficiency, and explore the relationships between exocrine pancreatic insufficiency and diabetes mellitus.

Pancreatic ductal adenocarcinoma (PDAC), a neoplasm of the gastrointestinal tract, is the most common pancreatic malignancy (90%) and the fourth highest cause of cancer mortality worldwide. Surgery intervention is currently the only strategy able to offer an advantage in terms of overall survival, but prognosis remains poor even for operated patients. Therefore, the development of robust biomarkers for early diagnosis and prognostic stratification in clinical practice is urgently needed. In this work, we investigated deregulated microRNAs (miRNAs) in tissues from PDAC patients with high (G3) or low (G2) histological grade and with (N+) or without (N-) lymph node metastases. miRNA expression profiling was performed by a comprehensive PCR array and subsequent validation by RT-qPCR. The results showed a significant increase in miR-1-3p, miR-31-5p, and miR-205-5p expression in G3 compared to G2 patients (** p < 0.01; *** p < 0.001; *** p < 0.001). miR-518d-3p upregulation and miR-215-5p downregulation were observed in N+ compared to N- patients. A statistical analysis performed using OncomiR program showed the significant involvement (p < 0.05) of two miRNAs (miR-31 and miR-205) in the histological grade of PDAC patients. Also, an expression analysis in PDAC patients showed that miR-31 and miR-205 had the highest expression at grade 3 compared with normal and other tumor grades. Overall, survival plots confirmed that the overexpression of miR-31 and miR-205 was significantly correlated with decreased survival in TCGA PDAC clinical samples. A KEGG pathway analysis showed that all three miRNAs are involved in the regulation of multiple pathways, including the Hippo signaling, adherens junction and microRNAs in cancer, along with several target genes. Based on in silico analysis and experimental validation, our study suggests the potential role of miR-1-3p, miR-31-5p, and miR-205-5p as useful clinical biomarkers and putative therapeutic targets in PDAC, which should be further investigated to determine the specific molecular processes affected by their aberrant expression.

Food allergies are becoming ever more prevalent around the world. This pathology is characterized by the breakdown of oral tolerance to ingested food allergens, resulting in allergic reactions in subsequent exposures. Due to the possible severity of the symptoms associated with this pathology, new approaches to prevent it and reduce associated symptoms are of utmost importance. In this framework, dietary phenolic compounds appear as a tool with a not fully explored potential. Some phenolic compounds have been pointed to with the ability to modulate food allergies and possibly reduce their symptoms. These compounds can modulate food allergies through many different mechanisms, such as altering the bioaccessibility and bioavailability of potentially immunogenic peptides, by modulating the human immune system and by modulating the composition of the human microbiome that resides in the oral cavity and the gastrointestinal tract. This review deepens the state-of-the-art of the modulation of these mechanisms by phenolic compounds. While this review shows clear evidence that dietary supplementation with foods rich in phenolic compounds might constitute a new approach to the management of food allergies, it also highlights the need for further research to delve into the mechanisms of action of these compounds and decipher systematic structure/activity relationships.

The 13 C mixed triglyceride breath test (13 C MTGT) is a diagnostic test for pancreatic exocrine insufficiency (PEI). It is poorly standardised with much heterogeneity of the test meal, the commonest being toast and butter. A standardised oral nutritional supplement that could be easily transported, stored and made up would be valuable for making this test accessible outside of specialist centres.

A prospective, randomised, two-arm crossover study of different test meals was carried out in 14 healthy controls. The 13 C MTGT was performed in identical conditions on two separate days. Two test meals were given in random order, either standard (toast and butter) or novel (oral nutritional supplement), with 250 mg of 13 C-labelled mixed triglyceride incorporated. Breath samples were taken postprandially to calculate cumulative percentage dose recovery (cPDR) of 13 C at 6 h.

All 14 participants completed both arms of the study with no protocol deviations. The mean cPDR was 39.39% (standard deviation [SD] 5.19) for the standard test meal and 39.93% (SD 5.20) for the novel test meal. A one-way repeated measures analysis of variance (ANOVA) found no significant difference in cPDR between the two meals, F(1, 13) = 0.18, p = 0.68 (minimum detectable difference of 0.81 at 80% power).

This study demonstrates that a standardised oral nutritional supplement can be used without compromising 13 C recovery. Using this test meal provides a standardised dietary stimulus to the pancreas, avoiding possible variation in quantity of dietary components with other test meals. Further, the ease of use of this method would help establish the 13 C MTGT test more widely.

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.

Pancreatic exocrine insufficiency (PEI) is common after gastric resection for cancer or ulcers but is under-recognized and undertreated. Although pancreatic enzyme replacement therapy (PERT) is the mainstay of PEI management, robust evidence supporting its use after gastric surgery is limited.

In the absence of guideline recommendations specific for patients with pancreatic insufficiency after gastrectomy, a panel of experts from different geographical regions convened in a virtual meeting to discuss their approach to patient management.

Pancreatic insufficiency after gastrointestinal surgery is not a simple post-surgical complication as several factors contribute to its development. Although the pancreas is unimpaired after gastrectomy, it cannot function normally in the altered environment. Pancreatic insufficiency can be challenging to diagnose in gastrectomy patients due to nonspecific symptoms and the absence of a simple diagnostic test. Fecal elastase appears to be the default test, although it is not sufficiently sensitive nor reliable for diagnosing or monitoring PEI. Patients with maldigestion symptoms after gastrectomy are treated pragmatically: those with clinical suspicion of pancreatic insufficiency receive a trial of PERT and are monitored for symptom improvement. There is a clear need for high-quality evidence from clinical trials to guide the management of this patient population.

Chronic pancreatitis is a heterogeneous and complex syndrome that, in most cases, causes pain as a cardinal symptom and affects both the morphology and function of the pancreas, leading to several serious complications.

The present review, based on a non-systematic PubMed search updated to June 2023, aims to present the current available evidence on the role of gastroenterologists in the diagnosis and treatment of both local and systemic complications by either endoscopic or medical treatments.

At diagnosis and during chronic pancreatitis follow-up, particular care is needed to consider not only the clinically manifest signs and symptoms of the disease, such as pain, jaundice, gastrointestinal obstruction, and pseudocysts, which require multidisciplinary discussion to establish the best treatment option (endoscopic or surgical), but also less evident systemic complications. Pancreatic exocrine and endocrine insufficiency, together with chronic inflammation, addiction, and dysbiosis, contribute to malnutrition, sarcopenia, and osteopathy. These complications, in turn, increase the risk of infection, thromboembolic events, and death. Patients with chronic pancreatitis also have an increased risk of psychiatric disorders and pancreatic cancer onset. Overall, patients with chronic pancreatitis should receive a holistic evaluation, considering all these aspects, possibly through multidisciplinary care in dedicated expert centers.

Being an underdiagnosed and under or insufficiently treated condition, surgical pancreatic exocrine insufficiency (PSP) is the condition in which pancreatic enzymes are insufficient for digestion because of gastrointestinal (GI) surgery involving the upper GI tract, biliary ducts, or the pancreas, and and leading to potential malnutrition and deterioration in quality of life. Age, obesity, history of tobacco use, family history of diabetes, surgery due to a malignant tumor, presence of steatorrhea, jaundice, weight loss, and intraoperative findings of hard pancreatic texture have been associated with a higher risk of PSP. Pancreatoduodectomy (PD) has demonstrated an increased risk of developing PSP, with a prevalence between 19-100%. Distal pancreatectomy (DP) and central pancreatectomy (CenP) are associated with less risk of PSP, with a prevalence of 0-82% and 3.66-8.7%, respectively. In patients with chronic pancreatitis (CP), PSP was associated with 80% in Partington-Rochelle procedure, 86% in Frey procedure, 80% in duodenum preserving pancreatic head procedure, >60% in PD and 27.5-63% in DP. Fecal elastase-1 (FE-1) is a generally accepted tool for diagnosis. Treatment is recommended to start as soon as a diagnosis is achieved, or clinical suspicion is high. Pancreatic enzyme replacement therapy improves symptoms of malabsorption, facilitates weight gain, and ultimately improves patients' quality of life. Starting dosage is between 10,000-50,000 units in snacks and 50,000-75,000 units in main meals, administered throughout food intake, though further data specifically on PSP are needed. Follow-up in PSP is recommended on an on-demand basis, where malnutrition should be assessed.

The finding of pancreatic cystic lesions (PCL) on incidental imaging is becoming increasingly common. International studies report a prevalence of 2.2-44.7% depending on the population, imaging modality and indication for imaging, and the prevalence increases with age. Patients with PCL are at risk of developing pancreatic cancer, a disease with a poor prognosis. This publication summarizes recommendations for the diagnosis and management of PCL and post-operative pancreatic exocrine insufficiency (PEI) from a group of local specialists.

Clinical evidence was consolidated from narrative reviews and consensus statements formulated during two online meetings in March 2022. The expert panel included gastroenterologists, hepatobiliary surgeons, oncologists, radiologists, and endocrinologists.

Patients with PCL require careful investigation and follow-up due to the risk of malignant transformation of these lesions. They should undergo clinical investigation and pancreas-specific imaging to classify lesions and understand the risk profile of the patient. Where indicated, patients should undergo pancreatectomy to excise PCL. Following pancreatectomy, patients are at risk of PEI, leading to gastrointestinal dysfunction and malnutrition. Therefore, such patients should be monitored for symptoms of PEI, and promptly treated with pancreatic enzyme replacement therapy (PERT). Patients with poor response to PERT may require increases in dose, addition of a proton pump inhibitor, and/or further investigation, including tests for pancreatic function. Patients are also at risk of new-onset diabetes mellitus after pancreatectomy; they should be screened and treated with insulin if indicated.

These statements are an accurate summary of our approach to the diagnosis and management of patients with PCL and will be of assistance to clinicians treating these patients in a similar clinical landscape.

In insulin resistance (IR), it is thought that pancreatic fat accumulation may decrease pancreatic volume, cause an impaired endocrine function, and simultaneously lead to an exocrine dysfunction before diabetes develops.

The association between pancreatic exocrine function and insulin resistance (IR) was assessed in a population with insulin resistance.

This was a descriptive cross-sectional study that included 43 IR cases with no other comorbid diseases or pregnancy and 41 healthy controls. Fasting blood adiponectin, leptin, pancreatic amylase, lipase, and stool fecal elastase-1 (FE-1) were studied and compared in both groups.

The IR group consisted of 38 females (88.3%) and five males (11.6%), while the control group consisted of 31 females (75.6%) and ten males (24.3%). FE-1 levels were significantly lower in the IR group (P-value <0.01). Blood glucose, insulin, and HbA1c levels were significantly higher in the IR group than in the control (P-value of <0.01, <0.01, <0.01, respectively). Leptin levels were significantly higher in the IR group compared to the controls (P-value = 0.013). After dividing the whole group (n: 84) into two groups as FE-1 <200 μg/g (n: 61) and FE-1 ≥200 μg/g (n: 23), logistic regression analysis was performed; the significant predictor of low FE-1 was HOMA-IR (ODD ratio: 4.27, P-value <0.01, 95% confidence interval for ODD ratio: 1.95-9.30).

This study showed that IR is associated with pancreatic exocrine dysfunction.

The joint work of the stomach and the small intestine plays a fundamental role in human digestion. In the stomach, food is turned into a semi-fluid mixture that is slowly released into the small intestine, where most enzymatic reactions occur, and nutrients are absorbed as they become available. This whole process is closely related to glucose homeostasis, mainly because of the appearance of glucose in the portal system and the energetic expenditure of the process itself. The current phenomenological-based model describes such effects of the digestive process on blood glucose concentration. It considers enzymatic and mechanical transformations, energetic expenditure, and the impact of macro-nutrients, fiber, and water on overall digestion and glucose absorption. The model estimates the rate of glucose appearance in the portal vein and is intended to be further integrated into existing models for other human organs and used in model-based systems such as an artificial pancreas with automated insulin delivery.

Arthritis is a chronic disease that affects, approximately, 1 % of the total global population. It is characterized by chronic inflammation, accompanied in most of the cases of motor disability and sever pain. The main therapies available have high risk of failure and advanced treatments are scarce and highly cost. In this scenario, search for effective, safe and low-cost treatments is quite desirable. Methyl gallate (MG) is a plant-derived phenolic compound described to present remarkable anti-inflammatory effect in experimental models of arthritis. Thus, in this study we formulated nanomicelles of MG using Pluronic (F-127) as matrix and evaluated in vivo the pharmacokinetic, biodistribution and its effect in the mice model of zymosan-induced arthritis. The nanomicelles were formed with a size 126 nm. The biodistribution showed a ubiquitous tissue deposition with a renal excretion. The pharmacokinetics showed elimination half-life of 1.72 h and a clearance of 0.006 L/h. The oral pretreatment with nanomicelles containing MG (3.5 or 7 mg/kg) demonstrated a reduction in total leukocytes, neutrophils, and mononuclear cells from the inflammation site. The data supports the use of methyl gallate nanomicelles as an alternative drug for arthritis. DATA AVAILABILITY: All the data of this study are transparent.

Exocrine pancreatic insufficiency (EPI) is a condition defined as pancreatic loss of exocrine function, including decreased digestive enzymes and bicarbonate secretion, which leads to maldigestion and malabsorption of nutrients. It is a common complication in many pancreatic disorders. If left undiagnosed, EPI can cause poor digestion of food, chronic diarrhea, severe malnutrition and related complications. Nutritional status and fat-soluble vitamins should be carefully assessed and monitored in patients with EPI. Early diagnosis of EPI is clinically important for appropriate nutritional support and initiating pancreatic enzyme replacement therapy (PERT) which could significantly improve patient outcomes. The evaluation of nutritional status and related unique management in children with EPI will be discussed in this review.

Pancreatic exocrine insufficiency is a cause of malabsorption. It is generally diagnosed if faecal elastase-1 (FE-1) levels are below 200 µg/g. Pancreatic function is assumed to be normal when faecal elastase levels are >500 µg/g. The significance of faecal elastase levels above 200 µg/g but less than 500 µg/g is unclear.

This retrospective study reports the response to treatment in patients who had an FE-1 level between 200 and 500 µg/g.

Of these 82 patients, 28 were offered pancreatic enzyme replacement therapy (PERT). A clinical response, defined as an improvement in their initial symptoms after commencing PERT, was seen in 20 patients (71%), 7 with potentially predisposing conditions and 13 with functional diarrhoea. PERT particularly abolished or improved diarrhoea, steatorrhoea and flatulence.

Clinicians should, therefore, be aware that a trial of PERT given to patients with FE-1 levels between 200 and 500 µg/g may lead to improvement in gastrointestinal symptoms.