Chronic pancreatitis Majumder, Shounak, MD; Chari, Suresh T, Dr
The Lancet (British edition),
05/2016, Volume:
387, Issue:
10031
Journal Article
Peer reviewed
Summary Chronic pancreatitis describes a wide spectrum of fibro-inflammatory disorders of the exocrine pancreas that includes calcifying, obstructive, and steroid-responsive forms. Use of the term ...chronic pancreatitis without qualification generally refers to calcifying chronic pancreatitis. Epidemiology is poorly defined, but incidence worldwide seems to be on the rise. Smoking, drinking alcohol, and genetic predisposition are the major risk factors for chronic calcifying pancreatitis. In this Seminar, we discuss the clinical features, diagnosis, and management of chronic calcifying pancreatitis, focusing on pain management, the role of endoscopic and surgical intervention, and the use of pancreatic enzyme-replacement therapy. Management of patients is often challenging and necessitates a multidisciplinary approach.
Most patients with pancreatic ductal adenocarcinoma (PDAC) present with symptomatic, surgically unresectable disease. Although the goal of early detection of PDAC is laudable and likely to result in ...significant improvement in overall survival, the relatively low prevalence of PDAC renders general population screening infeasible. The challenges of early detection include identification of at-risk individuals in the general population who would benefit from longitudinal surveillance programs and appropriate biomarker and imaging-based modalities used for PDAC surveillance in such cohorts. In recent years, various subgroups at higher-than-average risk for PDAC have been identified, including those with familial risk due to germline mutations, a history of pancreatitis, patients with mucinous pancreatic cysts, and elderly patients with new-onset diabetes. The last 2 categories are discussed at length in terms of the opportunities and challenges they present for PDAC early detection. We also discuss current and emerging imaging modalities that are critical to identifying early, potentially curable PDAC in high-risk cohorts on surveillance.
The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological ...data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest to the oncology community as the differentiation of new-onset diabetes caused by PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address these relationships and raise awareness of the relationships between PDAC and diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer was held at the American Diabetes Association's 76th Scientific Sessions in June 2016. This article summarizes the data presented at that symposium, describing the current understanding of the interrelationships between diabetes, diabetes management, and pancreatic cancer, and identifies areas where additional research is needed.
It is unclear how long pancreatic ductal adenocarcinomas (PDACs) are present before diagnosis. Patients with PDAC usually develop hyperglycemia and diabetes before the tumor is identified. If early ...invasive PDACs are associated with hyperglycemia, the duration of hyperglycemia should associate with the time that they have had the tumor.
We collected data on patients with PDACs from medical databases in Olmsted County, Minnesota, from 2000 through 2015 and from the Mayo Clinic’s tumor registry from January 1, 1976, through January 1, 2017. We compared glycemic profiles of patients with PDAC (cases) compared with patients without cancer, matched for age and sex (controls). We analyzed temporal fasting blood glucose (FBG) profiles collected for 60 months before patients received a PDAC diagnosis (index date) (n = 219) (cohort A), FBG profiles of patients with resected PDAC (n = 526) stratified by tumor volume and grade (cohort B), and temporal FBG profiles of patients with resected PDACs from whom long-term FBG data were available (n = 103) (cohort C). The primary outcome was to estimate duration of presence of invasive PDAC before its diagnosis based on hyperglycemia, defined as significantly higher (P < .05) FBG levels in cases compared with controls.
In cohort A, the mean FBG did not differ significantly between cases and controls 36 months before the index date. Hyperglycemia was first noted 36 to 30 months before PDAC diagnosis in all cases, those with or without diabetes at baseline and those with or without resection at diagnosis. FBG level increased until diagnosis of PDAC. In cohort B, the mean FBG did not differ significantly in controls vs cases with PDACs below 1.0 mL. The smallest tumor volume associated with hyperglycemia was 1.1 to 2.0 mL; FBG level increased with tumor volume. FBG varied with tumor grade: well- or moderately differentiated tumors (5.8 mL) produced the same FBG levels as smaller, poorly differentiated tumors (1.5 mL) (P < .001). In cohort C, the duration of prediagnostic hyperglycemia for cases with large-, medium-, or small-volume PDACs was 36 to 24, 24 to 12, and 12 to 0 months, respectively. PDAC resection resolved hyperglycemia, regardless of tumor location.
In a case–control study of patients with PDAC from 2 databases, we associated FBG level with time to PDAC diagnosis and tumor volume and grade. Patients are hyperglycemic for a mean period of 36 to 30 months before PDAC diagnosis; this information might be incorporated into strategies for early detection.
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Autoimmune pancreatitis (AIP) is a recently defined form of chronic pancreatitis. While numerous case reports and small case series of AIP have been reported from Japan, there have been relatively ...few from the West. Based on a retrospective review of our experience with resected AIP and a review of the literature, we have identified five cardinal features of AIP in histology, imaging, serology, other organ involvement, and response to steroid therapy, which are summarized in the mnemonic HISORt. A combination of the HISORt criteria can be used to definitively diagnose a wide spectrum of manifestations of AIP.
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.
Of patients with new-onset diabetes (NOD; based on glycemic status) older than 50 years, approximately 1% are diagnosed with pancreatic cancer (PC) within 3 years. We aimed to develop and validate a ...model to determine risk of PC in patients with NOD.
We retrospectively collected data from 4 independent and nonoverlapping cohorts of patients (N = 1,561) with NOD (based on glycemic status; data collected at date of diagnosis and 12 months previously) in the Rochester Epidemiology Project from January 1, 2000 through December 31, 2015 to create our model. The model weighed scores for 3 factors identified in the discovery cohort to be most strongly associated with PC (64 patients with PC and 192 with type 2 diabetes): change in weight, change in blood glucose, and age at onset of diabetes. We called our model Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC). We validated the locked-down model and cutoff score in an independent population-based cohort of 1,096 patients with diabetes; of these, 9 patients (82%) had PC within 3 years of meeting the criteria for NOD.
In the discovery cohort, the END-PAC model identified patients who developed PC within 3 years of diabetes onset (area under receiver operating characteristic curve 0.87); a score of at least 3 identified patients who developed PC with 80% sensitivity and specificity. In the validation cohort, a score of at least 3 identified 7 of 9 patients with PC (78%) with 85% specificity; the prevalence of PC in patients with a score of at least 3 (3.6%) was 4.4-fold greater than in patients with NOD. A high END-PAC score in patients who did not have PC (false positives) was often due to such factors as recent steroid use or different malignancy. An ENDPAC score no higher than 0 (in 49% of patients) meant that patients had an extremely low risk for PC. An END-PAC score of at least 3 identified 75% of patients in the discovery cohort more than 6 months before a diagnosis of PC.
Based on change in weight, change in blood glucose, and age at onset of diabetes, we developed and validated a model to determine risk of PC in patients with NOD based on glycemic status (END-PAC model). An independent prospective study is needed to further validate this model, which could contribute to early detection of PC.
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IgG4-related systemic disease (ISD) is a recently recognized syndrome affecting multiple organs. Autoimmune pancreatitis (AIP) is the pancreatic manifestation of ISD and mimics pancreatic cancer. ...Current data show frequent association with serum IgG4 elevation and other serologic abnormalities. Here we explore the diagnostic and possible prognostic utility and pathogenetic implications of serologic abnormalities in ISD.
Serum IgG4 elevations (>140 mg/dl) are seen in 70-80% of AIP patients and also in 5% of normal population and 10% of pancreatic cancer making it an unsuitable single marker for diagnosis. However, when combined with other features of AIP, it can be of great diagnostic value though its utility in monitoring of therapy or as a marker or predictor of relapse is limited. Several other antibodies have been identified in AIP against pancreas-specific antigens like trypsinogens I and II, pancreatic secretory trypsin inhibitor (PSTI) and plasminogen binding protein (PBP) and other nonpancreas-specific antigens. Anti-PBP antibodies appear to have potential diagnostic utility but require further validation.
No single serologic marker is diagnostic of ISD. Serum IgG4 elevation has convincing diagnostic utility when combined with other disease features although its value in disease monitoring may be limited.
Pancreatic ductal adenocarcinoma is an aggressive malignancy with a high mortality rate. Proper determination of the extent of disease on imaging studies at the time of staging is one of the most ...important steps in optimal patient management. Given the variability in expertise and definition of disease extent among different practitioners as well as frequent lack of complete reporting of pertinent imaging findings at radiologic examinations, adoption of a standardized template for radiology reporting, using universally accepted and agreed on terminology for solid pancreatic neoplasms, is needed. A consensus statement describing a standardized reporting template authored by a multi-institutional group of experts in pancreatic ductal adenocarcinoma that included radiologists, gastroenterologists, and hepatopancreatobiliary surgeons was developed under the joint sponsorship of the Society of Abdominal Radiologists and the American Pancreatic Association. Adoption of this standardized imaging reporting template should improve the decision-making process for the management of patients with pancreatic ductal adenocarcinoma by providing a complete, pertinent, and accurate reporting of disease staging to optimize treatment recommendations that can be offered to the patient. Standardization can also help to facilitate research and clinical trial design by using appropriate and consistent staging by means of resectability status, thus allowing for comparison of results among different institutions.
Autoimmune Pancreatitis Majumder, Shounak; Takahashi, Naoki; Chari, Suresh T.
Digestive diseases and sciences,
07/2017, Volume:
62, Issue:
7
Journal Article
Peer reviewed
Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with ...obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP. Histologically, lymphoplasmacytic acinar inflammation and storiform fibrosis are seen in both. In addition, the histologic hallmark of IDCP is the granulocyte epithelial lesion: intraluminal and intraepithelial neutrophils in medium-sized and small ducts with or without granulocytic acinar inflammation often associated with destruction of ductal architecture. Initial treatment of both AIP and IDCP is with oral corticosteroids for duration of 4 weeks followed by a gradual taper. Relapses are common in AIP and relatively uncommon in IDCP, a relatively rare disease for which the natural history is not well understood. For patients with relapsing AIP, treatment with immunomodulators and more recently rituximab has been recommended. Although rare instances of pancreaticobiliary malignancy has been reported in patients with AIP, overall the lifetime risk of developing pancreatic cancer does not appear to be elevated.
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