Chronic pancreatitis is characterized by progressive, irreversible morphologic and functional changes that are most commonly attributed to environmental insults, particularly when there is a genetic ...or anatomic predisposition. Heavy alcohol use and cigarette smoking are the most common environmental risk factors, but both may be absent. Antecedent episodes of acute pancreatitis occur in about half of patients. Abdominal pain is the most common symptom and requires a tailored approach depending on the anatomic changes in the pancreas. Other clinical manifestations include diabetes mellitus, exocrine pancreatic insufficiency, metabolic bone disease, pancreatic cancer, and anatomic complications. Current disease management is centered on risk factor reduction and screening for and treating disease complications. There are no current therapies to delay or retard disease progression, but there are ongoing efforts to more fully understand the natural history of chronic pancreatitis and underlying mechanisms of disease. These studies are expected to provide insights that will transform our approach to disease management and provide increased hope to patients.
Recent Advances in Autoimmune Pancreatitis Hart, Phil A; Zen, Yoh; Chari, Suresh T
Gastroenterology (New York, N.Y. 1943),
07/2015, Volume:
149, Issue:
1
Journal Article
Peer reviewed
Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that is characterized clinically by frequent presentation with obstructive jaundice, histologically by a dense lymphoplasmacytic ...infiltrate with fibrosis, and therapeutically by a dramatic response to corticosteroid therapy. Two distinct diseases, type 1 and type 2 AIP, share these features. However, these 2 diseases have unique pancreatic histopathologic patterns and differ significantly in their demographic profiles, clinical presentation, and natural history. Recognizing the popular and long-standing association of the term “AIP” with what is now called “type 1 AIP,” we suggest using “AIP” solely for type 1 AIP and to acknowledge its own distinct disease status by using “idiopathic duct-centric chronic pancreatitis” (IDCP) for type 2 AIP. AIP is the pancreatic manifestation of immunoglobulin G4–related disease (IgG4-RD). The etiopathogenesis of AIP and IgG4-RD is largely unknown. However, the remarkable effectiveness of B-cell depletion therapy with rituximab in patients with AIP and IgG4-RD highlights the crucial role of B cells in its pathogenesis. IDCP is less commonly recognized, and little is known about its pathogenesis. IDCP has no biomarker but is associated with inflammatory bowel disease in ∼25% of patients. Recently, the international consensus diagnostic criteria for AIP identified combinations of features that are diagnostic of both diseases. Both AIP and IDCP are corticosteroid responsive; however, relapses are common in AIP and rare in IDCP. Therefore, maintenance therapy with either an immunomodulator (eg, azathioprine, 6-mercaptopurine, or mycophenolate mofetil) or rituximab is often necessary for patients with AIP. Long-term survival is excellent for both patients with AIP and patients with IDCP.
Objective
IgG4‐related disease (IgG4‐RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serologic, radiologic, and pathologic data is required for diagnosis. ...This work was undertaken to develop and validate an international set of classification criteria for IgG4‐RD.
Methods
An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises, existing literature, derivation and validation cohorts of 1,879 subjects (1,086 cases, 793 mimickers), and multicriterion decision analysis to identify, weight, and test potential classification criteria. Two independent validation cohorts were included.
Results
A 3‐step classification process was developed. First, it must be demonstrated that a potential IgG4‐RD case has involvement of at least 1 of 11 possible organs in a manner consistent with IgG4‐RD. Second, exclusion criteria consisting of a total of 32 clinical, serologic, radiologic, and pathologic items must be applied; the presence of any of these criteria eliminates the patient from IgG4‐RD classification. Third, 8 weighted inclusion criteria domains, addressing clinical findings, serologic results, radiology assessments, and pathology interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% confidence interval 95% CI 97.2–99.8%) and a sensitivity of 85.5% (95% CI 81.9–88.5%). In the second, the specificity was 97.8% (95% CI 93.7–99.2%) and the sensitivity was 82.0% (95% CI 77.0–86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds.
Conclusion
ACR/EULAR classification criteria for IgG4‐RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiologic, and basic science investigations.
Pancreatic cancer is a lethal disease that is commonly diagnosed at a late stage. Screening asymptomatic patients is necessary for early detection, but this is not currently recommended in the ...general population. As demonstrated in the current study, an important number of patients at increased risk can be diagnosed using either MRI/magnetic resonance cholangiopancreatography or endoscopic ultrasound. Further collaborative efforts are needed to define the ideal population for testing and refine the current approach to pancreatic cancer surveillance.
The epidemiological trends contributing to increasing acute pancreatitis (AP) hospitalizations remain unknown. We sought to analyze etiological factors and outcomes of increasing AP hospitalizations.
...Utilizing the Nationwide Inpatient Sample, retrospective analyses of adult (≥18 years) inpatient admissions with a primary diagnosis of AP (N = 2,016,045) were performed. Patient hospitalizations from 2009 to 2012 were compared with those from 2002 to 2005.
Compared with 2002-2005, there was a 13.2% (P < 0.001) increase in AP admissions in 2009-2012. Multivariate analysis adjusted for "period," patient and hospital demographics, AP etiologies, and disease associations demonstrated an increase in the odds of associated chronic pancreatitis (CP) 2002-2005: odds ratio, (OR), 32.04; 95% confidence interval (CI), 30.51-33.64; 2009-2012: OR, 35.02; 95% CI, 33.94-36.14, whereas associated odds of gallstones (2002-2005: OR, 36.37; 95% CI, 35.32-37.46; 2009-2012: OR, 29.85; 95% CI, 29.09-30.64) decreased. Compared with 2002-2005, the AP-related mortality decreased in 2009-2012 (1.62%-0.79%, P < 0.001) and was lower in AP with associated CP (0.65%-0.26%; P < 0.001) compared with AP without CP.
In the preceding decade, AP hospitalizations increased, but associated mortality declined. Associated CP has emerged as a leading contributor for AP-related hospitalizations. Further research is needed to identify novel interventions to prevent disease progression of AP.
Complications of Chronic Pancreatitis Ramsey, Mitchell L.; Conwell, Darwin L.; Hart, Phil A.
Digestive diseases and sciences,
07/2017, Volume:
62, Issue:
7
Journal Article
Peer reviewed
Open access
Chronic pancreatitis is a disease that leads to irreversible changes in the pancreatic morphology and function. The loss of function can lead to diabetes mellitus and exocrine pancreatic ...insufficiency. The inflammation and fibrosis can also lead to other complications including a chronic abdominal pain syndrome, metabolic bone disease, and pancretic cancer. This article reviews our current understanding of the mechanisms and management of these complications of chronic pancreatitis.
Objective
IgG4‐related disease (IgG4‐RD) can cause fibroinflammatory lesions in nearly any organ, leading to organ dysfunction and failure. The IgG4‐RD Responder Index (RI) was developed to help ...investigators assess the efficacy of treatment in a structured manner. The aim of this study was to validate the RI in a multinational investigation.
Methods
The RI guides investigators through assessments of disease activity and damage in 25 domains, incorporating higher weights for disease manifestations that require urgent treatment or that worsen despite treatment. After a training exercise, investigators reviewed 12 written IgG4‐RD vignettes based on real patients. Investigators calculated both an RI score as well as a physician's global assessment (PhGA) score for each vignette. In a longitudinal assessment, 3 investigators used the RI in 15 patients with newly active disease who were followed up over serial visits after treatment. We assessed interrater and intrarater reliability, precision, validity, and responsiveness.
Results
The 26 physician investigators included representatives from 6 specialties and 9 countries. The interrater and intrarater reliability of the RI was strong (0.89 and 0.69, respectively). Correlations (construct validity) between the RI and PhGA were high (Spearman's r = 0.9, P < 0.0001). The RI was sensitive to change (discriminant validity). Following treatment, there was significant improvement in the RI score (mean change 10.5 95% confidence interval (95% CI) 5.4–12, P < 0.001), which correlated with the change in the PhGA. Urgent disease and damage were captured effectively.
Discussion
In this international, multispecialty study, we observed that the RI is a valid and reliable disease activity assessment tool that can be used to measure response to therapy.
Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by ...an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps.
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