Chronic Asymptomatic Pancreatic Hyperenzymemia Research Articles

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

<h3>Background & Aims</h3> 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. <h3>Methods</h3> 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⁺CD38^hiCD20^-CD24^-CD27⁺ and CD45⁺CD19⁺CD38^hiCD20^-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). <h3>Results</h3> 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 (<i>P</i> = .0001) in type 1 AIP than in type 2/NOS AIP, decreased after steroid therapy, and increased at disease relapse. <h3>Conclusion</h3> IgG4⁺ plasmablast count represents a potentially useful biomarker to differentiate type 1 from type 2/NOS AIP and from other pancreatic diseases.

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.

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.

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.

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

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.

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

A specific diagnostic work-out has a high diagnostic rate in patients with chronic asymptomatic pancreatic hyperenzymemia

A specific diagnostic work-out has a high diagnostic rate in patients with chronic asymptomatic pancreatic hyperenzymemia

Prospective Evaluation of Subjects With Chronic Asymptomatic Pancreatic Hyperenzymemia

Chronic asymptomatic pancreatic hyperenzymemia (CAPH) has been described since 1996 as a benign disease. Recent studies described pathological findings at magnetic resonance cholangiopancreatography with secretin stimulation (s-MRCP) in more than half of the CAPH subjects. The aim of this study was to investigate the frequency and clinical relevance of s-MRCP findings in patients with CAPH. Subjects prospectively enrolled from January 2005 to December 2010 underwent s-MRCP and biochemical tests routinely performed. Data relative to 160 subjects (94 males, 66 females, age 49.6±13.6 years) were analyzed. In all, 51 (32%) subjects had hyperamylasemia, 9 (6%) hyperlipasemia, and 100 (62%) an increase in both enzyme levels. The time between the first increased dosage of serum pancreatic enzymes and our observation was 3.3±3.9 years (range: 1-15). Familial pancreatic hyperenzymemia was observed in 26 out of 133 subjects (19.5%). Anatomic abnormalities of the pancreatic duct system at s-MRCP were found in 24 out of 160 subjects (15%). Pathological MRCP findings were present in 44 subjects (27.5%) before and in 80 subjects (50%) after secretin administration (P<0.0001). Five subjects (3.1%) underwent surgery, 3 for pancreatic endocrine tumor, 1 for pancreatic adenocarcinoma, and 1 for intraductal papillary-mucinous neoplasia (IPMN) involving the main pancreatic duct, and 18 patients (11.3%) needed a follow-up (17 for IPMN and 1 for endocrine tumor). Alterations of the pancreatic duct system at s-MRCP in subjects with CAPH can be observed in 50% of the subjects and are clinically relevant in 14.4% of cases.

Chronic asymptomatic pancreatic hyperenzymemia is a benign condition in only half of the cases: A prospective study

Objective. Prospectively to evaluate patients with chronic asymptomatic pancreatic hyperenzymemia in order to identify possible pancreatic and non-pancreatic diseases. Material and methods. Seventy-five asymptomatic subjects with long-standing pancreatic hyperenzymemia (45 M, 30 F; mean age±SD 51.5±16.0 years, range 19–78 years, mean duration±SD of pancreatic hyperenzymemia 14.7±7.0 months, range 7–34 months) and normal ultrasonographic evaluation were included in this study. The subjects enrolled were carefully interviewed and prospectively evaluated. All patients underwent blood screening. An additional abdominal ultrasound was also carried out and, if considered necessary, other imaging and endoscopic evaluation procedures were used. Results. The follow-up of the patients after enrolment in the study was 3.3±1.8 years (mean±SD). In 38 patients (50.7%), pancreatic or extrapancreatic disease was diagnosed: 20 patients had chronic pancreatitis, 1 had autoimmune chronic pancreatitis, 1 had a benign cyst of the pancreas, 2 had serous cystadenomas, 5 had an intraductal papillary mucinous tumor of the pancreas, 3 had a ductal pancreatic adenocarcinoma, 4 patients had chronic viral hepatitis, and 2 had Crohn's disease. In 37 subjects (49.3%), no pancreatic or extrapancreatic diseases were found (3 subjects had macroamylasemia, 3 had familial hyperenzymemia, 31 had chronic non-pathological pancreatic hyperenzymemia). Conclusions. Subjects having an increase of either amylase or lipase serum levels should undergo a thorough diagnostic work-up prior to establishing the existence of chronic non-pathological pancreatic hyperenzymemia.