Untargeted Metabolomics for the Diagnosis of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis.

Background and Objectives: The clinical manifestations and course of chronic pancreatitis (CP) are often nonspecific and variable, hampering diagnosis of the risk of exocrine pancreatic insufficiency (EPI). Development of new, reproducible, and non-invasive methods to diagnose EPI is therefore a major priority. The objective of this metabolomic study was to identify novel biomarkers associated with EPI. Materials and Methods: We analyzed 53 samples from patients with CP, 32 with and 21 without EPI, using an untargeted metabolomics workflow based on hydrophilic interaction chromatography coupled to high-resolution mass spectrometry. Principal component and partial least squares-discriminant analyses showed significant between-group differentiation, and univariate and multivariate analyses identified potential candidate metabolites that significantly differed between samples from CP patients with EPI and those without EPI. Results: Excellent results were obtained using a six-metabolic panel to diagnose the presence of EPI in CP patients (area under the ROC curve = 0.785). Conclusions: This study confirms the usefulness of metabolomics in this disease setting, allowing the identification of novel biomarkers to differentiate between the presence and absence of EPI in CP patients.

State of the Art in Exocrine Pancreatic Insufficiency.

Exocrine pancreatic insufficiency (EPI) is defined as the maldigestion of foods due to inadequate pancreatic secretion, which can be caused by alterations in its stimulation, production, transport, or interaction with nutrients at duodenal level. The most frequent causes are chronic pancreatitis in adults and cystic fibrosis in children. The prevalence of EPI is high, varying according to its etiology, but it is considered to be underdiagnosed and undertreated. Its importance lies in the quality of life impairment that results from the malabsorption and malnutrition and in the increased morbidity and mortality, being associated with osteoporosis and cardiovascular events. The diagnosis is based on a set of symptoms, indicators of malnutrition, and an indirect non-invasive test in at-risk patients. The treatment of choice combines non-restrictive dietary measures with pancreatic enzyme replacement therapy to correct the associated symptoms and improve the nutritional status of patients. Non-responders require the adjustment of pancreatic enzyme therapy, the association of proton pump inhibitors, and/or the evaluation of alternative diagnoses such as bacterial overgrowth. This review offers an in-depth overview of EPI in order to support the proper management of this entity based on updated and integrated knowledge of its etiopathogenesis, prevalence, diagnosis, and treatment.

Splenic rupture: an infrequent but potentially severe complication after colonoscopy.

Splenic rupture is an infrequent compilation and can be severe without an early diagnosis. We present the case of a 53-year-old female who had undergone colonoscopy 24 hours previously and presented to the ER due to pain in left hemithorax and hypotension. She was diagnosed with a splenic rupture via abdominal computed tomography (CT). An urgent splenectomy was performed with a favorable postoperative evolution. The clinical recognition of splenic rupture is vital due to the fact that we are not as familiarized with this condition as we are with hemorrhage and perforation after colonoscopy.

Sarcoidosis onset simulating a unique hepatic metastasis.

Sarcoidosis is a systemic granulomatous disease with an uncertain etiology, characterized by the production of non-necrotizing granulomas. The most frequent presentation is pulmonary and mediastinal, although it might affect any other organ. Hepatic alterations occur in 50 to 65% of the cases. Nevertheless, it is commonly subclinical or detected during a study of the alteration of liver enzymes. It is very unusual that disease onset occurs as an isolated hepatic tumor. A hepatic biopsy is usually required to confirm the diagnosis. A differential diagnosis must be established via any hepatic granulomatous disease, infectious or autoimmune disease as well as the exclusion of malignancy. We present a clinical case of a female diagnosed with an isolated hepatic sarcoidosis that simulated a unique hepatic metastatic lesion. The hepatic biopsy was diagnostic.

Acute gastric dilatation after dietary violation.

Acute gastric dilatation is a rare disease for which an early diagnosis and treatment are crucial in order to avoid potential serious complications. We present the case report of a woman with acute gastric dilatation after dietary violation.

Serum biomarkers for the differentiation of autoimmune pancreatitis from pancreatic ductal adenocarcinoma.

Autoimmune pancreatitis (AIP), a chronic inflammation caused by the immune system attacking the pancreas, usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma (PDAC). Serum biomarkers, substances that quantitatively change in sera during disease development, are a promising non-invasive tool with high utility for differentiating between these diseases. In this way, the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4 (IgG4) antibody are elevated. However, this approach has some drawbacks. Notably, IgG4 antibody concentrations are also elevated in sera from some patients with PDAC. This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC, evaluating the usefulness of immunoglobulins, autoantibodies, chemokines, and cytokines. The proposed serum biomarkers have proven useful, although most studies had a small sample size, did not examine their presence in patients with PDAC, or did not test them in humans. In addition, current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity, either alone or in combination with clinical data and/or radiological images.

Novel Biomarkers to Distinguish between Type 3c and Type 2 Diabetes Mellitus by Untargeted Metabolomics.

Pancreatogenic diabetes mellitus (T3cDM) is a highly frequent complication of pancreatic disease, especially chronic pancreatitis, and it is often misdiagnosed as type 2 diabetes mellitus (T2DM). A correct diagnosis allows the appropriate treatment of these patients, improving their quality of life, and various technologies have been employed over recent years to search for specific biomarkers of each disease. The main aim of this metabolomic project was to find differential metabolites between T3cDM and T2DM. Reverse-phase liquid chromatography coupled to high-resolution mass spectrometry was performed in serum samples from patients with T3cDM and T2DM. Multivariate Principal Component and Partial Least Squares-Discriminant analyses were employed to evaluate between-group variations. Univariate and multivariate analyses were used to identify potential candidates and the area under the receiver-operating characteristic (ROC) curve was calculated to evaluate their diagnostic value. A panel of five differential metabolites obtained an area under the ROC curve of 0.946. In this study, we demonstrate the usefulness of untargeted metabolomics for the differential diagnosis between T3cDM and T2DM and propose a panel of five metabolites that appear altered in the comparison between patients with these diseases.

Role of Exocrine and Endocrine Insufficiency in the Management of Patients with Chronic Pancreatitis.

BACKGROUND: Exocrine pancreatic insufficiency results from the destruction of the pancreatic parenchyma and is diagnosed by using direct or indirect tests, both of which have shortcomings. Chronic pancreatitis is the most frequent cause of this pathology in adults. METHODS: Patients meeting radiological or histological diagnostic criteria of chronic pancreatitis are enrolled and the stool elastase test is conducted, considering fecal elastase levels >200 µg/g to represent normal pancreatic function, and levels <200 µg/g to indicate the presence of exocrine pancreatic insufficiency. Additionally, we determine the body mass index of the patients and study their nutritional status and main biochemical and hematological variables, including their glucose and hemoglobin A1c (HbA1c) levels. RESULTS: Exocrine pancreatic insufficiency is detected in 60% of the patients. Among these, 83.3% are severe cases, and 72% of the latter also are diagnosed with endocrine pancreatic insufficiency (diabetes mellitus). During the nutritional status study, HbA1c levels are significantly higher, and magnesium and prealbumin levels are significantly lower in patients with exocrine pancreatic insufficiency than in those without this disease. CONCLUSIONS: Exocrine and endocrine pancreatic insufficiency are highly prevalent among patients with chronic pancreatitis and an early diagnosis of these diseases is vital to improve the clinical management of these patients and reduce their risk of mortality.