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Rochester, MN, United States

Sinicrope F.,Mayo Medical School | Sinicrope F.,Fiterman Center for Digestive Diseases | Foster N.R.,Mayo Medical School | Sargent D.J.,Mayo Medical School | And 3 more authors.
Cancer | Year: 2010

BACKGROUND: Colon cancers with defective DNA mismatch repair (MMR) have a favorable prognosis and may lack benefit from 5-fluorouracil-based adjuvant chemotherapy. The authors developed models to predict MMR deficiency in sporadic colon cancer patients using routine clinical and pathological data. METHODS: TNM stage II and III colon carcinomas (n=982) from 6 5-fluorouracil-based adjuvant therapy trials were analyzed for microsatellite instability and/or MMR protein expression. Tumor-infiltrating lymphocytes (TILs) were quantified (n=326). Logistic regression and a recursive partitioning and amalgamation analysis were used to identify predictive factors for MMR status. RESULTS: Defective MMR was detected in 147 (15%) cancers. Tumor site and histologic grade were the most important predictors of MMR status. Distal tumors had a low likelihood of defective MMR (3%; 13 of 468); proximal tumors had a greater likelihood (26%; 130 of 506). By using tumor site, grade, and sex, the logistic regression model showed excellent discrimination (c statistic=0.81). Proximal site, female sex, and poor differentiation showed a positive predictive value (PPV) of 51% for defective MMR. In a patient subset (n=326), a model including proximal site, TILs (>2/ high-power field), and female sex showed even better discrimination (c statistic=0.86), with a PPV of 81%. CONCLUSIONS: Defective MMR is rare in distal, sporadic colon cancers, which should generally not undergo MMR testing. Proximal site, poor differentiation, and female sex detect 51% of tumors with defective MMR; substituting TILs for grade increases the PPV to 81%. These data can increase the efficiency of MMR testing to assist in clinical decisions. © 2010 American Cancer Society.

Treeprasertsuk S.,Fiterman Center for Digestive Diseases | Treeprasertsuk S.,Chulalongkorn University | Lopez-Jimenez F.,Mayo Medical School | Lindor K.D.,Fiterman Center for Digestive Diseases
Digestive Diseases and Sciences | Year: 2011

Background: Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and is recognized as part of the metabolic syndrome (MetS). Patients with NAFLD have a lower life expectancy compared to the general population, with coronary artery disease (CAD) as the leading cause of death. Aims: We aim to address the epidemiological data of CAD, the possible pathogenesis or linkage mechanisms of NAFLD and atherosclerosis and the strategies to reduce the CAD risk in NAFLD patients. Methods: We reviewed data from a Medline and PubMed search which was performed to identify relevant literature using search terms "NAFLD," "metabolic syndrome" and "coronary artery disease." Results: Patients with steatohepatitis, a part of the spectrum of NAFLD, have more cardiovascular events than patients without steatohepatitis. However, the association between liver histological progression and the risk of CAD events is not linear. A multidisciplinary approach to NAFLD patients based on controlling related risk factors and monitoring for CAD risks and liver complications is necessary. The combination of lifestyle modification with pharmacological treatment tailored to each individual's risk factors needs to be considered. There is a need for more research on primary prevention for CAD in NAFLD patients and interventional studies for determining the nature of the relationship between NAFLD and CAD. Conclusions: NAFLD is recognized as part of the MetS and increases cardiovascular risks. Therefore, a multidisciplinary approach to these patients of controlling the related risk factors and monitoring for cardiovascular and liver complications must be done. © 2010 Springer Science+Business Media, LLC.

Sah R.P.,Fiterman Center for Digestive Diseases | Chari S.T.,Fiterman Center for Digestive Diseases
Current Opinion in Rheumatology | Year: 2011

Purpose of review: 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. Recent findings: 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. Summary: 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. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Sah R.P.,Fiterman Center for Digestive Diseases | Chari S.T.,Fiterman Center for Digestive Diseases | Chari S.T.,Miles and Shirley Fiterman Center for Digestive Diseases
Current Gastroenterology Reports | Year: 2012

Autoimmune Pancreatitis (AIP) is a recently recognized chronic fibro-inflammatory disease of the pancreas. Although rare, its recognition continues to increase worldwide. Patients often present with painless obstructive jaundice mimicking pancreatic cancer. Two subtypes of AIP are known-type 1 is a multi-organ disease associated with IgG4; type 2 appears to be a pancreas-specific disorder. Dramatic response to steroid treatment is characteristic of both forms. A non-invasive diagnosis of type 1 AIP may be possible using diagnostic criteria (in ~70% cases) while diagnosis of type 2 requires histology. These subtypes differ in natural history- type 1 often relapses while initial reports suggest that type 2 does not. Long term complications include endocrine and exocrine insufficiency and in case of type 1, disease relapses and complications from extra-pancreatic involvement. Neither form affects long term survival. The treatment and follow-up guidelines continue to evolve with our increasing experience in AIP. © Springer Science+Business Media, LLC 2012.

Sah R.P.,Fiterman Center for Digestive Diseases | Pannala R.,Fiterman Center for Digestive Diseases | Chari S.T.,Fiterman Center for Digestive Diseases | Sugumar A.,Fiterman Center for Digestive Diseases | And 8 more authors.
Clinical Gastroenterology and Hepatology | Year: 2010

Background & Aims: Little is known about how many patients with features of acute pancreatitis (AP) or chronic pancreatitis (CP) have autoimmune pancreatitis (AIP); most information comes from case reports. We explored the clinical profiles and relationship between these diseases. Methods: We evaluated 178 patients presenting to our Pancreas Clinic between January 2005 and June 2006 for evaluation of the etiology of their suspected pancreatitis; AIP was diagnosed when patients met HISORt (Histology, Imaging features, Serology, Other organ involvement and Response to steroid treatment) criteria. In a separate cohort of patients with AIP from our database, we identified patients who presented with features of AP (≥2 of abdominal pain, increased pancreatic enzymes, pancreatic inflammation determined by imaging analyses) or CP (≥1 of pancreatic calcification, irregular main pancreatic duct dilation, or marked atrophy) and determined their clinical profile. Results: Only 7/178 (3.9%) patients evaluated for etiology of suspected pancreatitis had AIP. Among 63 AIP patients in our database, 22 (34.9%) had features of AP (n = 15) or CP (n = 7) at presentation (average age 53.4 ± 19.0 years, all males). Patients with AIP and pancreatitis were characterized by presence of obstructive jaundice (59.1%), increased levels of liver enzymes (81.8%), increased levels of serum immunoglobulin G4 (80.9%), and other organ involvement (69.1%). All 19 patients presenting with pancreatitis who were treated with steroids responded to treatment. Conclusions: While AIP is an uncommon etiology for acute or chronic pancreatitis, >33% of AIP have features of acute or chronic pancreatitis at presentation. © 2010 AGA Institute.

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