Can We Detect Chronic Pancreatitis With Low Serum Pancreatic Enzyme Levels?
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ABSTRACT:
SUBMITTER: Kwon CI
PROVIDER: S-EPMC5544969 | biostudies-other | 2016 Sep
REPOSITORIES: biostudies-other
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Project description:Finland ranks sixth among the countries having highest incidence rate of pancreatic cancer with mortality roughly equaling incidence. The average age of diagnosis for pancreatic cancer is 69 years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis is 40-50 years, however, many cases overlap in age. By radiology, the evaluation of a pancreatic mass, that is, the differential diagnosis between chronic pancreatitis and pancreatic cancer is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret. New blood based biomarkers are needed. The accuracy of the only established biomarker for pancreatic cancer, CA 19-9 is rather poor in differentiating between benign and malignant mass of the pancreas. In this study, we have performed mass spectrometry analysis (High Definition MSE ) of serum samples from patients with chronic pancreatitis (13) and pancreatic cancer (22). We have quantified 291 proteins and performed detailed statistical analysis such as principal component analysis, orthogonal partial least square discriminant analysis and receiver operating curve analysis. The proteomic signature of chronic pancreatitis versus pancreatic cancer samples was able to separate the two groups by multiple statistical techniques. Some of the enriched pathways in the proteomic dataset were LXR/RXR activation, complement and coagulation systems and inflammatory response. We propose that multiple high-confidence biomarker candidates in our pilot study including Inter-alpha-trypsin inhibitor heavy chain H2 (Area under the curve, AUC: 0.947), protein AMBP (AUC: 0.951) and prothrombin (AUC: 0.917), which should be further evaluated in larger patient series as potential new biomarkers for differential diagnosis.
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Project description:ObjectivesSmall intestinal bacterial overgrowth (SIBO) is often present in patients with chronic pancreatitis (CP) with persistent steatorrhea, despite pancreatic enzyme replacement therapy. Overall prevalence of SIBO, diagnosed by glucose breath test (GBT), varies between 0% and 40% but 0%-21% in those without upper gastrointestinal (GI) surgery. We investigated the prevalence and nonsurgical independent predictors of SIBO in CP without upper GI surgery.MethodsTwo hundred seventy-three patients ≥18 years old had a presumptive diagnosis of CP and a GBT between 1989 and 2017. We defined CP by Mayo score (0-16) ≥4 and a positive GBT for SIBO by Rome consensus criteria and retrospectively collected data for 5 a priori variables (age, opiates, alcohol use, diabetes mellitus (DM), gastroparesis) and 41 investigational variables (demographics, GI symptoms, comorbidities, CP etiologies and cofactors, CP symptom duration, Mayo score and nondiabetes components, and biochemical variables).ResultsNinety-eight of 273 patients had definite CP and 40.8% had SIBO. Five of 46 variables predicted SIBO: opiates, P = 0.005; DM, P = 0.04; total Mayo score, P < 0.05; zinc, P = 0.005; and albumin, P < 0.05). Multivariable analysis of 3 noncorrelated variables identified zinc level (odds ratio = 0.0001; P = 0.03) as the sole independent predictor of SIBO (model C-statistic = 0.89; P < 0.001).DiscussionSIBO, diagnosed by GBT, occurs in 40.8% of patients with CP without upper GI surgery. In patients with CP, markers of more severe CP (low zinc level, DM and increased Mayo score) and opiate use should raise clinical suspicion for SIBO, particularly in patients with persistent steatorrhea or weight loss despite pancreatic enzyme replacement therapy.
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Project description:microRNAs have emerged as powerful regulators of many biological processes, and their expression in many cancer tissues has been shown to correlate with clinical parameters such as cancer type and prognosis. Present in a variety of biological fluids, microRNAs have been described as a 'gold mine' of potential noninvasive biomarkers. Release of microRNA content of blood cells upon hemolysis dramatically alters the microRNA profile in blood, potentially affecting levels of a significant number of proposed biomarker microRNAs and, consequently, accuracy of serum or plasma-based tests. Several methods to detect low levels of hemolysis have been proposed; however, a direct comparison assessing their sensitivities is currently lacking. In this study, we evaluated the sensitivities of four methods to detect hemolysis in serum (listed in the order of sensitivity): measurement of hemoglobin using a Coulter® AcT diff™ Analyzer, visual inspection, the absorbance of hemoglobin measured by spectrophotometry at 414 nm and the ratio of red blood cell-enriched miR-451a to the reference microRNA miR-23a-3p. The miR ratio detected hemolysis down to approximately 0.001%, whereas the Coulter® AcT diff™ Analyzer was unable to detect hemolysis lower than 1%. The spectrophotometric method could detect down to 0.004% hemolysis, and correlated with the miR ratio. Analysis of hemolysis in a cohort of 86 serum samples from cancer patients and healthy controls showed that 31 of 86 (36%) were predicted by the miR ratio to be hemolyzed, whereas only 8 of these samples (9%) showed visible pink discoloration. Using receiver operator characteristic (ROC) analyses, we identified absorbance cutoffs of 0.072 and 0.3 that could identify samples with low and high levels of hemolysis, respectively. Overall, this study will assist researchers in the selection of appropriate methodologies to test for hemolysis in serum samples prior to quantifying expression of microRNAs.
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Project description:Age-standardized incidence rates for pancreatic cancer (PC) in men have increased by 25% from 1957 to 2011 in Finland. The average age of diagnosis for PC is 69 years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis (CP) is 40-50 years, but the cases overlap in age. By radiology the evaluation of a pancreatic mass, i.e. the differential diagnosis between CP and PC is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret. New blood based biomarkers are needed. The accuracy of the only established biomarker for PC, CA 19-9 is rather poor in differentiating between benign and malignant mass of the pancreas. In this study, we have performed mass spectrometry HDMSE analysis of serum samples from patients with chronic pancreatitis and pancreatic cancer. We have quantified 652 proteins and performed detailed statistical analysis such as principal component analysis, orthogonal partial least square discriminant analysis and receiver operating curve analysis.
2017-06-09 | PXD005144 | Pride
Project description:Background:Periostin is a matricellular protein that induces fibrillogenesis and activates cell migration. It is overexpressed in common fibrotic diseases and is also associated with abdominal adiposity/ectopic fat phenotypes. The study aimed to investigate circulating levels of periostin in health and after an attack of pancreatitis, as well as their associations with abdominal adiposity/ectopic fat phenotypes. Methods:Blood samples were obtained from healthy controls, as well as definite chronic pancreatitis (CP) and acute pancreatitis (AP) individuals during follow-up visits. Fat depositions in the pancreas, liver, skeletal muscle, as well as visceral and subcutaneous fat volumes, were quantified with the use of magnetic resonance imaging. A series of multivariable analyses were conducted, accounting for possible confounders. Results:A total of 121 individuals were included. Periostin levels were significantly higher in the CP group compared with the other groups in both unadjusted (F = 3.211, P = 0.044) and all adjusted models (F = 4.165, P = 0.019 in the most adjusted model). Intra-pancreatic fat deposition (but not the other fat phenotypes) was significantly associated with periostin concentration in the CP group (? = 49.63, P = 0.034) and explained most of its variance (32.0%). Conclusions:Individuals with CP, but not healthy individuals or those after clinical resolution of AP, are characterized by elevated circulating levels of periostin that are positively associated with intra-pancreatic fat deposition.
| S-EPMC7430919 | biostudies-literature
Project description:Age-standardized incidence rates for pancreatic cancer (PC) in men have increased by 25% from 1957 to 2011 in Finland. The average age of diagnosis for PC is 69 years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis (CP) is 40-50 years, but the cases overlap in age. By radiology the evaluation of a pancreatic mass, i.e. the differential diagnosis between CP and PC is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret. New blood based biomarkers are needed. The accuracy of the only established biomarker for PC, CA 19-9 is rather poor in differentiating between benign and malignant mass of the pancreas. In this study, we have performed mass spectrometry HDMSE analysis of serum samples from patients with chronic pancreatitis and pancreatic cancer. We have quantified 652 proteins and performed detailed statistical analysis such as principal component analysis, orthogonal partial least square discriminant analysis and receiver operating curve analysis.
2018-08-31 | MSV000082883 | MassIVE
Project description:Pancreatitis is a fibro-inflammatory disorder of the pancreas that can occur acutely or chronically as a result of the activation of digestive enzymes that damage pancreatic cells, which promotes inflammation. Chronic pancreatitis with persistent fibro-inflammation of the pancreas progresses to pancreatic cancer, which is the fourth leading cause of cancer deaths across the globe. Pancreatic cancer involves cross-talk of inflammatory, proliferative, migratory, and fibrotic mechanisms. In this review, we discuss the role of cytokines in the inflammatory cell storm in pancreatitis and pancreatic cancer and their role in the activation of SDF1?/CXCR4, SOCS3, inflammasome, and NF-?B signaling. The aberrant immune reactions contribute to pathological damage of acinar and ductal cells, and the activation of pancreatic stellate cells to a myofibroblast-like phenotype. We summarize several aspects involved in the promotion of pancreatic cancer by inflammation and include a number of regulatory molecules that inhibit that process.
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