Pancreatic Hyperenzymemia Research Articles

Preoperative biliary stenting is associated with detrimental perioperative morbidity – a propensity matched analysis of over 900 patients from the German pancreas registry

Benign 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.Cross-sectional retrospective observational study integrated by a follow-up visit.The 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.Our 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.

Clinical observation of family benign pancreatic hyperenzymemia

The article provides a brief literature review on the problem of asymptomatic pancreatic hyperenzymemia and an algorithm for examining patients. The authors for the first time in Ukraine have described the clinical observation of family with Gullo’s syndrome — family benign pancreatic hyperenzymemia. Family members were carefully examined, structural changes in the pancreas were excluded, and its normal functional state was proved. The results of a genetic examination are presented.

Benign pancreatic hyperenzymemia: Gullo's syndrome

Carlo, a 2-year-old boy, was referred to our Unit for a chronic diarrhoea. His medical history revealed a San Diego hemoglobinopathy and Gilbert disease, family history was also positive for celiac disease. Clinical examination was normal. Laboratory investigations revealed unexpected hyperamylasemia (total amylase 257 U/L and pancreatic amylase 196 U/L), hyperlipasemia (199 U/L), and mild hyperbilirubinemia, mainly indirect. Celiac disease was excluded. Further investigation as TORCH and EBV serology, coagulation, insulin, C-peptide and islet cell antibodies, erythrocyte sedimentation rate, C-reactive protein, autoimmunity, sweat test and urinary amylase were negative. Abdominal echography and MRI were normal. During the 5 years follow-up, laboratory investigations confirmed the hyperamylasemia with fluctuating values, but always above the standard values for age. Excluding pancreatic and extra pancreatic pathologies, Gullo's syndrome has been suggested. This condition may occur sporadically or in a familial form. It is asymptomatic and the hyperenzymemia can persist for years. Etiology is still not clear, it has been reported defects in the passage of enzymes from Golgi network to the basolateral cell membrane. As in our patient, it has been reported in the literature that subjects with benign pancreatic hyperenzymemia have also a Gilbert's syndrome. The relationship is still unclear. A proper diagnosis of Gullo's syndrome is important to aid clinician in the management of this children and to reassure family about the benignancy of the disease. The recognition of this syndrome may also prevent multiple and complex diagnostic evaluations or hospital admissions for children.

Benign Pancreatic Hyperenzymemia (Gullo Syndrome), Histamine Intolerance, and Carbohydrate Malabsorption

Benign pancreatic hyperenzymemia (Gullo syndrome) is characterized by a more than threefold increase of the pancreatic enzymes lipase and amylase in the absence of a pancreatic disease over a period of more than 1 year, with elevations and significant undulations of pancreatic enzyme serum concentrations occurring on a day-to-day basis for 5 consecutive days. Nonspecific abdominal complaints may be caused by carbohydrate and/or protein malabsorption. We report a patient with benign pancreatic hyperenzymemia with lactose and histamine malabsorption; the symptoms of gastrointestinal malabsorption were treated successfully with an individually tailored lactose- and histamine-free diet.

Endoscopic Ultrasonography May Select Subjects Having Asymptomatic Chronic Pancreatic Hyperenzymemia Who Require a Stricter Follow-up.

We have previously shown that at least 50% of patients with asymptomatic chronic pancreatic hyperenzymemia (ACPH) may develop morphological pancreatic alterations. Endoscopic ultrasonography (EUS) may detect small lesions, and its sensitivity seems to be higher than other imaging techniques. The aim of this study was to evaluate whether EUS may modify the management of patients having ACPH. In 2 referral centers for pancreatic disease, a retrospective analysis of prospectively enrolled patients with ACPH was conducted. Seventy-three patients with ACPH were enrolled for the purpose of this study. Endoscopic ultrasonography was performed as the last examination in 45 subjects who resulted negative at previous imaging studies (abdominal ultrasound, computed tomography, magnetic resonance imaging associated with cholangiopancreatography). Using EUS in 7 subjects, abnormalities were found in the following: 3 branch-duct intraductal papillary mucinous neoplasms, 1 duodenal diverticulum, 1 annular pancreas, 1 findings suggestive of chronic pancreatitis, and 1 undefined cyst (<5 mm). Endoscopic ultrasonography is able to detect alteration not found by other imaging technique in 15.5% of patients with ACPH and may be useful to select those patients who require a more strict follow-up.

Endoscopic ultrasonography in chronic asymptomatic pancreatic hyperenzymemia: The more we see, the less we know

Endoscopic ultrasonography in chronic asymptomatic pancreatic hyperenzymemia: The more we see, the less we know

Can Serum Pancreatic Amylase and Lipase Levels Be Used as Diagnostic Markers to Distinguish Between Patients With Mucinous Cystic Lesions of the Pancreas, Chronic Pancreatitis, and Pancreatic Ductal Adenocarcinoma?

This study aimed to assess the presence of pancreatic hyperenzymemia in patients with pancreatic cystic lesions as compared to other chronic diseases of the pancreas. Ninety-one patients were studied: 32 had mucinous cystic lesions, 35 had chronic pancreatitis (CP), and 24 had pancreatic ductal adenocarcinoma (PDAC). Surgery was carried out in 10 of the 32 patients with mucinous cystic lesion (7 of them had severe dysplasia), in 5 patients with CP, and in 9 patients with PDAC. Abnormally high serum pancreatic isoamylase activity was present in 11 (34.4%) patients with mucinous cystic lesions, in 14 (40.0%) patients with CP, and none in patients with PDAC (P = 0.002); whereas serum lipase activity was abnormally high in 8 (25.0%) patients with mucinous cystic lesion, in 17 (48.6%) patients with CP, and in 3 (12.5%) patients with PDAC (P = 0.009). In 7 patients with mucinous cystic lesions and histologically confirmed severe dysplasia, abnormally high levels of both serum pancreatic amylase and lipase were present in 3 (42.9%) patients. High serum concentrations of pancreatic amylase and lipase were found in no more than half of the patients with mucinous cystic lesions. High levels of pancreatic enzymes were not associated with a greater risk of malignancy.

Pancreatic morpho-functional imaging as a diagnostic approach for chronic asymptomatic pancreatic hyperenzymemia

BackgroundMagnetic resonance cholangio-pancreatography (MRCP) findings in people with chronic asymptomatic pancreatic hyperenzymemia (CAPH) have shifted the hypothesis that CAPH is always non-pathological. However, there have been no studies including both secretin-MRCP (S-MRCP) and endoscopic ultrasonography (EUS) to examine the pancreatic morphology in these subjects. AimTo prospectively assess the diagnostic approach for CAPH using both pancreatic EUS and S-MRCP. MethodsIn a case-control prospective study from January 2010 to December 2014, 68 consecutive subjects with CAPH were scheduled to undergo S-MRCP and EUS (CAPH group) in a tertiary care setting. In the same period, the EUS findings of this group were compared with 68 patients examined by EUS alone for submucosal lesions of the gastric fundus, matched for sex and age (control group). ResultsEUS detected pancreatic alterations in 60.3% of the CAPH group and 13.2% of controls (p<0.001). S-MRCP showed pancreatic alterations in 51.5% in the CAPH group. With the combined procedures, pancreatic abnormalities were detected in 63.3%. The diagnoses established by the two techniques were concordant in 51 (75%) of the 68 CAPH subjects; in the remaining 17 (25%) the two methods gave additional information. ConclusionsIn people with CAPH S-MRCP and EUS are both recommended in order to detect pancreatic abnormalities before this biochemical alteration is confirmed as benign CAPH, or Gullo's syndrome.

Diabetes and Pancreas: Why So Difficult? Potential Mechanisms of Elevated Serum Pancreatic Enzymes.

Diabetes mellitus has been associated with a higher risk of exocrine pancreas disorders despite inconsistencies among studies, presumably due to the presence of several (often unmeasured) confounding factors. As a direct consequence of this uncertainty, the relationship between anti-diabetic therapies and pancreatic adverse reactions is difficult to evaluate and remains far from being clarified. Indeed, the on going debate on the safety of incretin-based therapies does not lie in any definite conclusion. Serum level of amylases and lipase reflects the balance between production from different tissues and clearance, but it may be also influenced by numerous molecular, cellular, and systems mechanisms. The present review tries to provide an overview of potential biochemical pathways that may underlie pancreatic hyperenzymemia in health and diabetes mellitus.

Healthy Chinese with benign pancreatic hyperenzymemia

Benign pancreatic hyperenzymemia, or Gullo's syndrome, is an uncommon syndrome characterized by a long-term increase of serum pancreatic enzyme in the absence of pancreatic diseases. It is primarily discovered incidentally and occurs in either sporadic or familial form. Herein, we report the first case of benign pancreatic hyperenzymemia in Taiwan. A 57-year-old Chinese male was incidentally noted with elevated serum amylase and lipase levels during a health check-up and was diagnosed with benign pancreatic hyperenzymemia using a series of image and serological tests. Although this is the first case of benign pancreatic hyperenzymemia in Taiwan, its prevalence may be underestimated due to the diagnostic difficulties. Correct diagnosis of this disease is important to avoid costly test duplication, unfounded anxieties, and multiple consultations.

Pancreatic involvement in pediatric inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs) are a group of chronic diseases affecting the gastrointestinal tract, with a disabling course. The incidence of IBDs is increasing in different geographical areas, indicating its emergence as a global disease, especially in children. Many patients with IBDs develop extraintestinal manifestations (EIMs) during follow-up, as IBDs have a potential risk of systemic involvement.. A systematic review of the literature was made to analyze latest studies on pancreatic involvement in children with IBD including our experience in assessing possible implications and its future application. The involvement of the hepatobiliary system is considered a rare EIM of children with IBD, with an incidence much higher than that in the general population. Isolated pancreatic hyperenzymemia, which occurs in the absence of typical symptoms and/or characteristic imaging findings, may be found in many patients with IBD. The frequent causes of pancreatitis are drugs, bilio-pancreatic disorders, immunologic disturbances and pancreatic auto-antibodies, although in some cases idiopathic forms have been described. It is important to establish a correct diagnostic approach based on etiology and to assess the most appropriate therapeutic strategy, thus avoiding complications and improving the quality of life of children with IBD.

Quality of life in patients with long-standing chronic non-pathological pancreatic hyperenzymemia

BackgroundChronic non-pathological pancreatic hyperenzymemia is a benign condition characterized by the persistent elevation of serum pancreatic enzymes without morphological alterations of the pancreas. No information is available regarding the quality of life of these subjects. AimTo evaluate the physical, mental and psychological status of these subjects using SF-12 Health Survey questionnaire and the 12-item General Health Questionnaire. MethodsFifty-one consecutive subjects having long-standing chronic non-pathological pancreatic hyperenzymemia (duration: 11.0 years, range 5–21) were studied. The Italian version of the SF-12 questionnaire and the General Health Questionnaire were compiled by the subjects studied. ResultsRegarding the SF-12 questionnaire, the physical component scores and the mental component scores were 50.1 ± 8.0 and 44.7 ± 11.7, respectively and these figures were not statistically different from those of reference Italian population. Regarding the psychological status, seven subjects (13.7%) had non-psychotic-psychiatric problems. No statistical differences in the physical component score, mental component score and general health questionnaire were found between patients having non-familial or familial chronic non-pathological pancreatic hyperenzymemia. ConclusionsSubjects with long-standing chronic non-pathological pancreatic hyperenzymemia had a quality of life no different from that of the Italian population. The explanation provided by the physician regarding the benignity of long-standing chronic non-pathological pancreatic hyperenzymemia is enough to reassure this type of patient.

A 5-year experience of benign pancreatic hyperenzymemia.

Benign pancreatic hyperenzymemia is characterized by a long-term increase of serum pancreatic enzymes in otherwise healthy subjects. This study was designed to determine (a) whether all pancreatic enzymes are elevated, (b) the extent of each enzyme increase, (c) the relative frequency of the familial form, and (d) the relative frequencies of pancreatic and salivary hyperamylasemia and macroamylasemia. Two hundred seven asymptomatic subjects with benign pancreatic hyperenzymemia were studied during the 5-year period. Serum amylase, isoamylase, and lipase levels were assessed by immunoenzymatic assays. Most (n = 183; 88.4%) patients had benign pancreatic hyperenzymemia; 155 (74.9%) patients had an abnormal increase of all 3 enzymes, 15 (7.2%) patients of only lipase, and 13 (6.3%) patients of only amylase and pancreatic isoamylase. Lipase levels were the highest (1.1-21 times above upper limit). Of the 183 subjects, 72 were members of 35 different families, 15 (7.2%) had increased salivary amylase, and 9 (4.3%) had macroamylasemia. Wide day-to-day fluctuations of pancreatic enzymes, including falls within the reference ranges, were recorded. All enzymes were increased in benign pancreatic hyperenzymemia, with lipase showing the highest elevation. Doctors should reassure patients about the benign nature of this condition and limit repeating useless examinations.

Pancreatic hyperenzymemia is associated with bacterial culture positivity, more severe and right-sided colitis.

Several studies reported pancreatic hyperenzymemia (PHE) related to acute colitis. However, there is no consensus on its clinical significance. This study was addressed to find the clinical significance of PHE in acute colitis. Pancreatic hyperenzymemia was defined as abnormal increase in serum concentrations of the pancreatic enzymes by three times of normal upper range without definite pancreatic symptoms and evidence of pancreatitis at abdominal CT imaging of pancreatic disease. And clinical and laboratory and biologic parameters of PHE group and normal pancreatic enzymemia (NPE) group were compared. A total of 1,069 patients admitted to hospitals due to acute colitis were analyzed. Of these patients, 2.99 % (32/1,069) showed PHE. PHE group showed more severe symptoms and had longer hospital stays than the NPE group (12.15 vs. 4.59 days; P < 0.001). Multivariable analysis showed that right-sided colitis (OR 2.846; 95 % CI 1.122-7.224; P = 0.028) and culture positivity (OR 3.346; 95 % CI 1.119-10.008; P = 0.031) are associated with PHE during acute colitis. Also, PHE group was more common when a microorganism could be identified in the cultures (28.1 vs. 7.0 %; P = 0.003), especially blood culture. Among patients with positive cultures, Salmonella spp. had a positive correlation with the right-sided colitis and PHE (amylase P = 0.002; lipase P = 0.029), Salmonella serovar typhimurium (group B) was especially related to increased serum lipase but not to increased serum amylase (lipase; P = 0.041: amylase; P = 0.485). Pancreatic hyperenzymemia is associated with right-sided colitis, bacterial culture positivity, and severe acute colitis.

Two rare cases of benign hyperlipasemia in children

Gullo's syndrome is a newly identified condition characterized by a chronic elevation of pancreatic amylase and/or lipase in the absence of pancreatic disease. Until now, only one case of benign isolated hyperlipasemia in children has been recorded. We describe two children with benign and not familial increase of serum lipase. Case 1: a six year old girl presented with occasional discovery of serum lipase elevation. Medical history was silent for pancreatic hyperenzymemia. The screening for possible causes for elevated lipase (genetic, autoimmune and infectious diseases) was normal. The serum lipase increased three fold over the upper limit (193 U/L; reference range 0-60 U/L), with daily fluctuation of values. Both ultrasound scan and magnetic resonance imaging were normal. The genetic mutation associated with chronic pancreatitis was negative. We followed up this patient for two years with blood tests every six months and she did not show any signs or symptoms of pancreatic disease, except for the high level of lipase serum. Case 2: an eight year old girl complained of nausea, vomiting and severe abdominal pain in the epigastric region after eating for the last two weeks. Full blood count, electrolytes, C-reactive protein, liver and renal function were normal. Serum lipase was 96 U/L (reference range 0-60 U/L). The screening for the possible causes of pancreatic disease was negative. Endoscopy of the upper gastrointestinal tract, ultrasound, computed tomography scan and magnetic resonance imaging were normal. One year after the presentation of the symptoms, the patient became asymptomatic although the level of serum lipase continued to be high.

EUS And s-MRCP Findings In Asymptomatic Subjects with Chronic Pancreatic Hyperenzymemia

Context A long-standing increase of serum pancreatic enzymes in asymptomatic subjects is considered a benign idiopathic condition called “non-pathological chronic pancreatic hyper­enzymemia” (CPH). However, recent studies showed secretin-MRCP (s-MRCP) has brought to light abnormal pancreatic findings in a significant proportion of these subjects. Objective To evaluate pancreatic morphological abnormalities using s-MRCP and EUS in CPH patients. Methods Consecutive patients affected by CPH were investigated with s-MRCP and EUS. EUS findings were compared with consecutive age- and sex-matched controls who underwent EUS investigation for unrelated to pancreaticobiliary disease (CTR). Results Fifty-five CPH subjects and 55 CTR patients were enrolled. Abnormal s-MRCP pancreatic findings were present in 23 CPH cases (41.8%): 10 chronic pancreatitis, according to Cambridge classification; 5 pancreas divisum; 3 pancreatic cyst; 5 Vater’s papilla dysfunction. Pathological EUS pancreatic findings were present in 28 CPH cases (50.9%): 7 pancreatic cystic lesion, 5 pancreas divisum, 1 papillitis, 1 NET, 14 chronic pancreatitis (CP) defined by presence of “consistent with CP” or “suggestive of CP” findings using Rosemont criteria. All cases of CP who undergone s-MRCP had pathological EUS findings suggestive for CP too. Normal EUS findings were more significantly frequent in control patients (n=45) than CPH patient (n=27) (P<0.05). The two groups have same frequencies in detection of cystic lesions, pancreas divisum, papillitis, NET, but chronic pancreatitis was more common in CPH (25.5% vs . 7.3%; P<0.05). Conclusions About half of the patients with asymptomatic chronic pancreatic hyper­enzymemia had some pancreatic abnormalities using s-MRCP and EUS. Both these procedures should characterize the diagnostic work-up of these subjects before the hyperenzymemia can be defined with certainly as non-pathological or benign.

Clinical and Radiological Follow-up of Subjects with Chronic Asymptomatic Pancreatic Hyperenzymemia

Context Chronic asymptomatic pancreatic hyperenzymemia (CAPH) has been described since 1996 as a benign disease. Pathological findings at magnetic resonance cholangiopancreatography (MRCP) with secretin stimulation (s-MRCP) have been found in 50% of CAPH subjects, but in 30% their clinical meaning remains undefined. Objective To investigate subjects with CAPH during the follow-up to assess the clinical and radiological outcome. Methods From January 2012 to March 2013, a cohort of 160 subjects previously studied for CAPH were re-evaluate with s-MRCP and biochemical tests. Results Clinical data relative to 108 subjects were collected, whereas 68 (47 males, 21 females; mean age: 49.8 ± 12.2 years) underwent s-MRCP. Clinically, acute pancreatitis was observed in one subject out of 108 (0.9%) after 5 years from the first detection of hyperenzymemia. Among the 68 subjects who underwent s-MRCP, 23 (33.8%) had previous s-RMCP normal and 45 (66.2%) pathological. No radiological alterations in 23 subjects with normal s-MRCP at first evaluation were observed at follow-up, whereas unchanged s-MRCP was documented in 41 out of 45 (91.1%) subjects with pathological s-MRCP at first evaluation after mean follow-up of 3±2 years. One out of 11 subject with IPMN had progression of the size of the cyst, 1 out of 11 with suspected sphincter of Oddi dysfunction showed an increase of Wirsung duct diameter, while a worsening of ductal morphology was observed in 2 out of 20 subjects with suspected chronic pancreatitis. Conclusion CAPH subjects remain asymptomatic during the follow-up. Subjects with previous normal MRCP-s did not show pathological findings at follow-up whereas only a small percentage of those with previous suspected sphincter of Oddi dysfunction or chronic pancreatitis, showed a progression at imaging in a short term follow-up.

Celiac Disease and CFTR Mutations in Patients With Chronic Asymptomatic Pancreatic Hyperenzymemia

Celiac Disease and CFTR Mutations in Patients With Chronic Asymptomatic Pancreatic Hyperenzymemia

Familial Pancreatic Hyperenzymemia

Asymptomatic chronic pancreatic hyperenzymemia is characterized by an increase in serum amylase and/or lipase concentrations and was first described by Pieper-Bigelow et al. [1], in 1990 who called the condition ‘‘asymptomatic chronic hyperamylasemia’’; in 1991, Ventrucci et al. [2] found that, in some patients, pancreatic hyperamylasemia may also be associated with hyperlipasemia and, finally, in 1996, Gullo [3] found that other pancreatic enzymes may be increased and that there was a fluctuation of these molecules. A special form of asymptomatic chronic pancreatic hyperenzymemia is Chronic Non-Pathological Pancreatic Hyperenzymemia (CNPH) defined as persistent hyperenzymemia exclusively of pancreatic origin without pancreatic disease [4]. A patient with persistent hyperenzymemia exclusively of pancreatic origin without pancreatic disease with at least one member of the family having the same enzyme alteration can be diagnosed as having familial pancreatic hyperenzymemia [5]. We revised the current medical literature in order to evaluate the epidemiology, pathophysiology and genetic alteration of this particular group of subjects. Finally, we also report the possible link between familial pancreatic hyperenzymemia and familial pancreatic cancer.

Asymptomatic and Persistent Elevation of Pancreatic Enzymes in an Ulcerative Colitis Patient

Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis at imaging. This evidence brought us to reassess the drug dosage, without achieving a normalization of biochemical analysis. Autoimmune pancreatitis was excluded. One year after the suspension of azathioprine, we still face persistent high levels of amylase/lipase. Normalization of enzymatic values in patients who develop intolerance to azathioprine, in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis, is usually achieved in about two months after stopping drug intake. Asymptomatic elevation in serum pancreatic enzymes in the absence of pancreatic disease is reported in the literature and defined as “Gullo's syndrome,” but nobody of the subjects studied had been treated in the past with pancreatotoxic drugs. Might this case be defined as “benign pancreatic hyperenzymemia”?