Pancreatic Hyperenzymemia Research Articles

A clinical case of asymptomatic pancreatic hyperenzymemia on the background of taking a Glucagon-like peptide-1 analogue (GLP-1)

According to current statistics, the incidence of type 2 diabetes has increased significantly over the past few years. The number of drugs prescribed to correct carbohydrate metabolism is also increasing, and new groups of hypoglycemic drugs are appearing. This prompts a more detailed study and analysis of the possible side effects of the prescribed therapy. One of the modern groups of medications f or treating type 2 diabetes are analogues of glucagon-like peptide-1 receptor agonists, which, in addition to correcting carbohydrate metabolism, have a beneficial effect on the risk of developing cardiovascular events. Despite this, there is evidence that their use may be associated with the development of undesirable adverse effects from the pancreas, particularly acute pancreatitis, pancreatopathy, or asymptomatic hyperenzymemia. The aim of our work was the analysis of a clinical case of an asymptomatic increase in the level of pancreatic enzymes (Gullo's syndrome) in a patient with type 2 diabetes, who used a glucagon-like peptide-1 receptor analogue for treatment according to the usual scheme (dulaglutide 0.75 mg subcutaneously once a week during 2 years). As a result, the patient developed a side effect that could be related to taking this medicine. This did not lead to the withdrawal of the drug but required a more thorough examination of the patient and regular further screening for the timely detection of the development of possible organic pathology of the pancreas in the future. So, after analyzing this clinical case, it is possible to see the possibility of developing asymptomatic pancreatic hyperenzymopathy during the treatment of type 2 diabetes mellitus with glucagon-like peptide-1 receptor agonist analogues, which should be taken into account when determining the treatment tactics.

A Clinical and Pathophysiological Overview of Intestinal and Systemic Diseases Associated with Pancreatic Disorders: Causality or Casualty?

The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.

Circulating IgG4+ Plasmablast Count as a Diagnostic Tool in Autoimmune Pancreatitis.

Type 1 autoimmune pancreatitis (AIP) is an IgG4-related disease whose diagnosis is challenging. The aim of this study was to investigate the diagnostic value of circulating total and IgG4+ plasmablasts in differentiating this condition from the other main pancreatic diseases. Patients with type 1 AIP (n= 19) were prospectively enrolled in a tertiary center together with patients suffering from type 2 or not otherwise specified (NOS) AIP (n= 10), pancreatic adenocarcinoma (n= 17), chronic pancreatitis (n= 20), and intraductal papillary mucinous neoplasia or chronic asymptomatic pancreatic hyperenzymemia (n= 21) as control groups. Flow cytometry was used to measure the total plasmablast and IgG4+ plasmablast number by gating peripheral blood CD45+CD19+CD38hiCD20-CD24-CD27+ and CD45+CD19+CD38hiCD20-CD24-CD27+IgG4+ cells, respectively. In patients with AIP, these cell populations were also evaluated after 1 month of therapy, after 2-4 months from the end of treatment, and after 1 year from the enrollment. The study was approved by the local ethics committee (protocol number: 59133, 30/11/2017). Total plasmablast quantification was capable of discriminating type 1 AIP from all the other pancreatic disorders with a sensitivity of 47% and a specificity of 81%, according to a cutoff of 4500 cells/mL (AUC= 0.738), whereas IgG4+ plasmablast count distinguished type 1 AIP from all the other pancreatic disorders with a sensitivity of 80% and a specificity of 97% when applying a cutoff of 210 IgG4+ cells/mL (AUC= 0.879). The basal IgG4+ plasmablast number was significantly higher (P= .0001) in type 1 AIP than in type 2/NOS AIP, decreased after steroid therapy, and increased at disease relapse. IgG4+ plasmablast count represents a potentially useful biomarker to differentiate type 1 from type 2/NOS AIP and from other pancreatic diseases.

Клинические особенности патогенного варианта нуклеотидной последовательности L138ins в гене CFTR при муковисцидозе

In this study, we analyzed phenotypic manifestations and clinical course of cystic fibrosis (CF) in patients with the pathogenic variant L138ins of the CFTR gene. The L138ins variant is rarely detected in CF patients worldwide, but is quite common in different regions of the Russian Federation, particularly in the Middle Urals. Before the neonatal screening implementation, the majority of CF patients with the L138ins variant were diagnosed late because of the mild disease course and dubious results of sweat tests. Such patients usually have elevated levels of immunoreactive trypsinogen (IRT) in the neonatal period, which enables early diagnosis; however, false-negative results in CF patients have also been reported. There were cases of male infertility among CF patients with the L138ins variant, while women had their reproductive function preserved. There were also cases of asymptomatic pancreatic hyperenzymemia in children. Respiratory infections caused by Pseudomonas aeruginosa are not very common in this group of patients. However, adult patients have more severe respiratory manifestations (even with a fatal outcome) than children. Thus, despite the mild disease phenotype in patients with the L138ins variant, the residual function of the protein is not sufficient to ensure normal functioning of lungs. Key words: cystic fibrosis, pathogenic CFTR variants, L138ins

Patients With Coronavirus Disease 2019 Interstitial Pneumonia Exhibit Pancreatic Hyperenzymemia and Not Acute Pancreatitis.

ObjectivesGastrointestinal manifestations of coronavirus disease 19 (COVID-19) have been well established, but pancreatic involvement is under debate. Our aims were to evaluate the presence of acute pancreatitis in COVID-19 patients and to assess the frequency of pancreatic hyperenzymemia.MethodsFrom April 1, 2020, to April 30, 2020, 110 consecutive patients (69 males, 41 females; mean age, 63.0 years; range, 24–93 years) met these criteria and were enrolled in the study. The clinical data and serum activity of pancreatic amylase and lipase were assayed in all patients using commercially available kits.ResultsNone of the patients studied developed clinical signs or morphological alterations compatible with acute pancreatitis. However, it was found that 24.5% of the patients had amylase values above 53 IU/L and 16.4% had lipase values above 300 IU/L. Only 1 patient (0.9%) had both amylase and lipase values in excess of 3-fold the upper normal limit without clinical signs of pancreatitis.ConclusionsThe presence of pancreatic hyperenzymemia in a patient with COVID-19 requires the management of these patients be guided by clinical evaluation and not merely by evaluation of the biochemical results.

Markedly elevated lipase as the first manifestation of celiac disease: Case Report

Lipase is a hydrolytic enzyme and commonly used for the diagnosis of pancreatitis with amylase. Except for pancreatitis, lipase is elevated in many clinical conditions such as hepatobiliary disorders, bowel diseases, malignancies, renal impairment. Celiac disease (CD) should be considered as one of the causes. In patients with CD, the frequency of pancreatic hyperenzymemia and possible pathophysiological mechanisms are not well studied. To date, several mechanisms explaining pancreatic hyperenzymemia in CD are reported. Malnutrition, disease bowel induced pancreatic dysfunction, autoimmune pancreatic inflammation, and macroenzymemia are the main ones. Herein, we report a patient with newly diagnosed CD, representing markedly elevated serum lipase level with normal amylase.

Familial Gullo’s Syndrome: a clinical case report

This case report describes a male patient born in 1953 presenting an occasional increase in serum amylase and lipase forty years ago. The monitoring of enzymes was accompanied by radiological investigations, which did not reveal pancreatic pathology. In his family, including 10 siblings, half were carriers of this isolated anomaly; multiple cysts in pancreas, kidneys, and liver were present in some family members, in addition to a pancreatic neoplasia in a sister who did not carry the enzymatic abnormality. Our patient developed colon adenocarcinoma at the age of 67.Here we examine the characteristics of non-pathological chronic pancreatic hyperenzymemia defined as such by the main Italian pioneer Professor Gullo.

Gullo's syndrome - what do we know?

Benign pancreatic hyperenzymemia (Gullo’s syndrome) is characterized by a more than threefold increase of the serum pancreatic enzymes lipase and amylase activity in the absence of any pancreatic disease. Recently, there is an increase in describing cases of Gullo’s syndrome in medical literature. Gullo’s syndrome is a diagnosis of exclusion, and clinicians should be aware of various other conditions which can cause elevation of pancreatic enzymes. However, the diagnostic pathway should be done with the right accuracy to avoid unnecessary examinations.

Hyperlipasemia and Potential Pancreatic Injury Patterns in COVID-19: A Marker of Severity or Innocent Bystander?

Hyperlipasemia and Potential Pancreatic Injury Patterns in COVID-19: A Marker of Severity or Innocent Bystander?

Benign pancreatic hyperenzymemia-Gullo's syndrome: focus on this clinical challenge. A monocentric retrospective study.

An abnormal and chronic rise of pancreatic enzymes in the blood is most often due to pancreatic diseases, primarily inflammatory or neoplastic, or to numerous extra-pancreatic pathologies. Benign chronic pancreatic hyperenzymemia was described for the first time - as a separate nosological entity - in 1996 by Lucio Gullo et al. They demonstrated the existence of a benign chronic pancreatic hyperenzymemia in asymptomatic subjects and without clinical implications; however, a follow-up of at least 1-2 years is necessary during which no specific symptomatology or morpho-functional impairment of the pancreas should occur, also evaluated through the aid of instrumental diagnostic investigations such as ultrasonography (US), computed tomography (CT) or magnetic resonance cholangio pancreatography (MRCP). This study was performed with the analysis of a group of 43 subjects arrived at the observation of the Gastroenterology Team of Policlinico Hospital G. Rodolico in Catania-Italy which presented a chronic pancreatic hyperenzymemia, in order to establish the actual benignity of this condition over time. During the follow-up, pancreatic alterations and hyperenzymemia were found in 10 patients, while hyperenzymemia was not associated with pancreatic modification in 33 patients. Because of this enzymatic elevation - often conspicuous and lasting - the patient is often particularly anxious. For the same reason, the patient frequently undergoes very expensive laboratory and instrumental diagnostic methods. Good knowledge of the syndrome makes it possible to manage the event more rationally, also to reduce management costs to a minimum.

Gullos Syndrome (Benign Pancreatic Hyperenzymemia): Report of the First Two Cases in Basque Country

Gullos Syndrome (Benign Pancreatic Hyperenzymemia): Report of the First Two Cases in Basque Country

Sa1397 – Chronic Asymptomatic Pancreatic Hyperenzymemia (CAPH): Meta-Analysis of Pancreatic Findings At Second-Level Imaging

Sa1397 – Chronic Asymptomatic Pancreatic Hyperenzymemia (CAPH): Meta-Analysis of Pancreatic Findings At Second-Level Imaging

Association between chronic asymptomatic pancreatic hyperenzymemia and pancreatic ductal anomalies: a magnetic resonance cholangiopancreatography study.

Elucidating the association between pancreatic ductal anomalies and chronic asymptomatic pancreatic hyperenzymemia using magnetic resonance cholangiopancreatography. We conducted a single-center, retrospective, case-control study. The healthy community group comprised 554 subjects who participated in a paid, whole-body health checkup program. The patient group comprised 14 subjects with idiopathic pancreatic hyperamylasemia or hyperlipasemia. All subjects underwent magnetic resonance cholangiopancreatography. The clinical features and incidence rates of pancreatic ductal anomalies were then compared between the groups. Compared to the healthy community group, the patient group was significantly more likely to be ≥ age 65 (71.4% of patient group vs. 22.1% of healthy community group), have a history of diabetes mellitus (21.4% vs. 5.4%) or hypertension (35.7% vs. 11.4%), and to have pancreas divisum (21.4% vs. 2.7%), meandering main pancreatic duct (21.4% vs. 4.1%), Wirsungocele (14.3% vs. 1.1%), or dilated main pancreatic duct (14.3% vs. 2.3%). Multivariate analysis found that age ≥ 65 (odds ratio 8.76), presence of pancreas divisum (odds ratio 13.2), meandering main pancreatic duct (odds ratio 8.95), and Wirsungocele (odds ratio 17.6) were independent factors significantly associated with chronic asymptomatic pancreatic hyperenzymemia. Pancreas divisum, meandering main pancreatic duct, and Wirsungocele were independently associated with chronic asymptomatic pancreatic hyperenzymemia.

Chronic Asymptomatic Pancreatic Hyperenzymemia: A Long-term Follow-up.

Chronic asymptomatic pancreatic hyperenzymemia (CAPH) was described as a benign disease. However, we already described clinically relevant findings requiring surgery or follow-up in half of the subjects. The aim of this study was to evaluate the long-term outcome of CAPH in terms of symptoms and evolution toward chronic pancreatitis. Subjects previously enrolled in the first phase of the study (from 2005 to 2010) were reinvestigated from December 2013 to January 2017 with a phone call ± magnetic resonance cholangiopancreatography with secretin stimulation. A total of 133 subjects were eligible for the follow-up study (75 males, 58 females; age, 48.4 [standard deviation {SD}, 14] years); 24 (18%) of them dropped out. During a mean follow-up of 9.3 (SD, 5.2) years after the first diagnosis of CAPH, no episode of acute pancreatitis or abdominal pain was reported. Sixty-three subjects (58%) of 109 underwent magnetic resonance cholangiopancreatography with secretin stimulation with a mean follow-up of 5.7 [SD, 3.1] years (range, 1-11 years). Secretin stimulation-MRCP resulted unchanged in 54 (90%) of 60 subjects, worsened in 3 (5%) and improved in 3 (5%). Two subjects died from causes unrelated to pancreatic disease. Excluding subjects with a pancreatic disease at index magnetic resonance imaging, CAPH is a benign condition.

Do Patients with Pancreatic Hyperenzymemia without Abnormal Imaging Need Additional Endoscopic Ultrasound?

Do Patients with Pancreatic Hyperenzymemia without Abnormal Imaging Need Additional Endoscopic Ultrasound?

Prevalence and correlates of Benign Pancreatic Hyperenzymemia in a large general population sample: The Damocles sword perception

BackgroundBenign Pancreatic Hyperenzymemia (BPH) is characterized by a long-term increase of serum pancreatic enzymes (PE) in otherwise healthy subjects. The study investigates the prevalence and correlates of the condition using data from Electronic Health Records (EHR) in a large sample of general population, to identify subjects potentially affected by BPH. MethodsCross-sectional retrospective observational study integrated by a follow-up visit. ResultsThe database of a reference laboratory identified, out of 577.251 admittances from 2011 to 2015, 4964 patients tested at least for one PE assay and 1688 subjects who had at least 3 PE tests (normal or increased) over two years. Forty-two individuals showed an increase of PE at least three times throughout 2 years without any evidence of pancreatic disease, even after matching with the ICD 9-CM code in the GPs database. Data retrieved at follow-up visit showed that for 34 the diagnosis of BPH could be made. ConclusionsOur data indicate that BPH prevalence among subjects underwent blood testing for multiple PE testing is 2%. This condition, even if not a disease, is perceived by nearly all the BPH patients as a serious threat to their life. Further studies are needed to manage its heavy psychological impact.

Chronic Asymptomatic Pancreatic Hyperenzymemia (CAPH): Meta-analysis of pancreatic findings at second-level imaging

Background/ObjectivesData estimating the prevalence of significant findings during the investigation of patients with Chronic Asymptomatic Pancreatic Hyperenzymemia (CAPH) are scanty and heterogeneous, and the diagnostic approach is therefore uncertain. The aim of this study was to meta-analyze pancreatic abnormalities detected at second-level imaging in patients with CAPH. MethodsPubmed database was searched until September 2018 for articles evaluating CAPH patients through MRI-Cholangio-Pancreatography with/without secretin (MRCP or s-MRCP) or Endoscopic Ultrasound (EUS). The methodology was developed from PRISMA checklist. Pooled prevalences of pancreatic findings were calculated, with subgroup analyses according to imaging modality. Quality of the studies, publication bias and heterogeneity were analyzed. ResultsIn 8 articles describing 521 patients with CAPH, pooled prevalence of normal imaging was 56.6% [95%CI (CI) 41.9–70.2; I2 = 88.6%). Prevalences of neoplasia, chronic pancreatitis, pancreatic cysts and benign abnormalities were 2.2% [CI1.2–4.1; I2 = 0%], 16.2% [CI10.2–24.8; I2 = 71.5%], 12.8% [CI8.2–19.3; I2 = 64.7%] and 17.2% [CI11.9–24.2; I2 = 71.5%] respectively. In sub-analyses, EUS and s-CPRM were less frequently normal and diagnosed more “early” chronic pancreatitis, while neoplastic lesions were still rare. ConclusionsIn CAPH patients, second-level pancreatic imaging is normal in 56% of the cases, neoplastic lesions are rare and the rate of pancreatic cysts is similar to that seen as incidental findings. More than one third of patients are diagnosed with abnormalities whose prognostic significance is uncertain. Despite the superior sensitivity of EUS or s-CPRM, the less costly/invasive and more available contrast-enhanced MRCP does not seem to miss relevant findings in this setting.

The importance of pancreatic inflammation in endosonographic diagnostics of solid pancreatic masses

Endosonography (EUS) is one of the main diagnostic tools for the differential diagnosis of pancreatic masses. Theaim of our study was to describe the value of this technique in the work-up of solid pancreatic lesions, considering the influenceof the morphological evidence of pancreatic inflammation in the diagnostic process. Retrospectiveanalysis of prospectively collected data in our tertiary University center. From March 2007 to October 2015, 218 patientsunderwent EUS for a suspected solid pancreatic neoplasm (based on previous cross-sectional imaging results, idiopatic acutepancreatitis, weight loss, pancreatic hyperenzymemia, painless jaundice or elevated Ca 19-9 values). Malignantlesions were diagnosed in 98 (45%) patients. Sensitivity of EUS for malignancy was 91% and specificity 89.2%. Signs ofpancreatic inflammation in the surrounding pancreatic parenchyma around the focal lesion were present in 97 patients (44.4%)(more often in men, smokers and drinkers, and the most common etiology was focal chronic pancreatitis) and in these patientsthe sensitivity and sensibility dropped to 44% and 87.1%, respectively. In patients without signs of pancreatic inflammation,the pancreatic focal lesions were adenocarcinoma, neuroendocrine tumor, ventral/dorsal split, non-pancreatic pathology, pancreaticlipomatosis and autoimmune pancreatitis. Pancreatic inflammation (either focal or involving the wholegland) lowers the diagnostic sensibility of EUS in the work- up of pancreatic masses suspected for cancer, requiring furtherinvasive diagnostic methods. Focal autoimmune pancreatitis and paraduodenal pancreatitis are still confused with pancreaticcancer, even in the absence of pancreatic inflammation.

There Is No Association between Coeliac Disease and Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) is a rare disorder whose association with coeliac disease (CD) has never been investigated, although CD patients display a high prevalence of both endocrine and exocrine pancreatic affections. Therefore, we sought to evaluate the frequency of CD in patients with AIP and in further medical pancreatic disorders. The screening for CD was carried out through the detection of tissue transglutaminase (tTG) autoantibodies in sera of patients retrospectively enrolled and divided in four groups: AIP, chronic pancreatitis, chronic asymptomatic pancreatic hyperenzymemia (CAPH), and control subjects with functional dyspepsia. The search for anti-endomysium autoantibodies was performed in those cases with borderline or positive anti-tTG values. Duodenal biopsy was offered to all cases showing positive results. One patient out of 72 (1.4%) with AIP had already been diagnosed with CD and was following a gluten-free diet, while one case out of 71 (1.4%) with chronic pancreatitis and one out of 92 (1.1%) control subjects were diagnosed with de novo CD. No cases of CD were detected in the CAPH group. By contrast, a high prevalence of cases with ulcerative colitis was found in the AIP group (13.8%). Despite a mutual association between CD and several autoimmune disorders, our data do not support the serologic screening for CD in AIP. Further studies will clarify the usefulness of CD serologic screening in other pancreatic disorders.

Clinical study in safety of enteral nutrition in critically ill children with pancreatic hyperpancreorrhea

Objective To investigate the safety and efficacy of enteral nutrition in critically ill children with hyperpancreorrhea including hyperamylasemia and hyperlipasemia in order to provide the rationale of nutritional support for such critically ill children. Methods A total of 90 critically ill children with hyperpancreorrhea admitted in pediatric intensive care unit were enrolled for prospective study in a period from January 2014 to December 2015. The patients were randomly(random number) divided into fasting group (n=30), and in those with fasting time exceeded three days, intravenous nutrition was given; ordinary milk group (n=30) and special milk group (n=30) and in this group, those with age 1 year were given small hundred peptides in addition to the basis of routine treatment. Clinical data and biochemical findings in different groups were analyzed by χ2test, t test, F test or non-parametric test to evaluate the safety and efficacy of enteral nutrition in critically ill children with hyperpancreorrhea. Results (1) There were statistically significant differences in rates of nutrition support-related symptoms such as diarrhea, electrolyte imbalance, blood glucose disorder among groups (χ2=6.975,6.074,6.300, P=0.031,0.048,0.043). (2) There were statistically significant difference in rates of serum amylase or lipase levels more than upper limit on the third day among different groups ( χ2=7.081, P=0.029). There was no statistically significant difference in rates of fecal elastase-1 0.05). There was statistically significant difference in procalcitonin on the 7th day among different groups (H=6.251, P=0.044). There was statistically significant difference in oxygenation index on the 3rd day among different groups (F=3.119, P=0.049). There was statistically significant difference in lactate on the 7th day among different groups (F=6.449, P=0.040). There was statistically significant differences in albumin on the 3rd day and on the 7th among different groups (F=5.451, P=0.006; H=24.861, P<0.01). (3) There were statistically significant differences in PICU stay and hospital stay among different groups (F=3.222,3.891, P=0.045; 0.024). There was statistically significant difference in survival rate among different groups ( χ2=6.240, P=0.044). Conclusions Early and right enteral nutrition was safe and effective for critically ill children with hyperpancreorrhea, and the special milk powder such asr AiReShu and small hundred peptides suitable for children with hyperpancreorrhea could effectively support nutrition for critically ill children with hyperpancreorrhea, improve the status of illness, promote disease recovery, shorten hospital stay and improve the prognosis. Key words: Critically ill children; Pancreatic hyperenzymemia; Sepsis; Enteral nutrition; Nutritional support; Safety; Efficacy; Prognosis