Low serum trypsinogen levels in chronic pancreatitis: Correlation with parenchymal loss, exocrine pancreatic insufficiency, and diabetes but not CT-based cambridge severity scores for fibrosis.

BACKGROUND: Chronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas affecting acinar cells, duct cells, islet cells and inflammatory cells including fibrosis-producing stellate cells. Serum trypsinogen is a biomarkers of acinar cell function. AIM: To define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP. METHODS: Serum samples from previously ascertained and well phenotyped case and control subjects from the North American Pancreatitis Study II (NAPS2) were used to measure serum trypsinogen levels in a commercial laboratory. Control samples were used to define normal ranges and compared with levels in CP patients with defined features. RESULTS: A final cohort of 279 CP patients and 262 controls from the NAPS2 studies were evaluated. In controls trypsinogen had a mean of 34.96 ng/ml and SD = 11.99. Cut-off values for low trypsinogen ranged from <20 to 10 ng/ml and very low trypsinogen at <10 ng/ml. Compared to controls, CP was associated with very low trypsinogen levels (p < 0.0001). Within CP, very low trypsinogen levels correlated with parenchymal loss (pancreatic surgery [p < 0.05]; atrophy with calcifications, [p < 0.001]), EPI (p < 0.01, trend p < 0.001) and diabetes (trend p < 0.01) but not CT-based criteria for fibrosis (pancreatic duct dilation, irregularity, strictures). CONCLUSIONS: Very low serum trypsinogen levels correlate with measures of acinar cell loss including surgical resection, atrophic-calcific CP, diabetes and functional symptoms EPI but not duct morphology criteria. Serum trypsinogen levels correlate with decreased acinar cell function and therefore have biomarker utility clinical management.

Nutrition and Inflammatory Biomarkers in Chronic Pancreatitis Patients.

BACKGROUND: Chronic pancreatitis (CP) patients frequently experience malabsorption and maldigestion, leading to micronutrient and macronutrient deficiencies. Comorbid diabetes and lifestyle habits, such as alcohol consumption, may impact nutrition status. METHODS: We compared micronutrient antioxidant, bone metabolism, serum protein, and inflammatory marker levels in 301 CP patients and 266 controls with no known pancreatic disease. We analyzed serum prealbumin and retinol binding protein; vitamins A, D, E, and B12; osteocalcin; tumor necrosis factor-α; and C-reactive protein (CRP). We also evaluated biomarkers among subsets of patients, examining factors including time since diagnosis, body mass index, alcohol as primary etiology, diabetes mellitus, vitamin supplementation, and pancreatic enzyme replacement. RESULTS: After correcting for multiple comparisons, CP patients had significantly lower levels than controls of the following: vitamin A (40.9 vs 45.4 µg/dL) and vitamin E (α-tocopherol [8.7 vs 10.3 mg/L] and γ-tocopherol [1.8 vs 2.2 mg/L]), as well as osteocalcin (7.9 vs 10 ng/mL) and serum prealbumin (23 vs 27 mg/dL). Both patients and controls who took vitamin supplements had higher serum levels of vitamins than those not taking supplements. Compared with controls, in controlled analyses, CP patients had significantly lower levels of vitamins A, D, and E (both α-tocopherol and γ-tocopherol). CP patients also had significantly lower levels of osteocalcin, serum prealbumin, and retinol binding protein, and higher CRP. CONCLUSIONS: CP patients demonstrated lower levels of selected nutrition and bone metabolism biomarkers than controls. Diabetes and alcohol did not impact biomarkers. Vitamin supplements and pancreatic enzyme replacement therapy improved nutrition biomarkers in CP patients.

Association Between Endoscopist Personality and Rate of Adenoma Detection.

BACKGROUND & AIMS: There is significant variation among endoscopists in their adenoma detection rates (ADRs). We explored associations between ADR and characteristics of endoscopists, including personality traits and financial incentives. METHODS: We collected electronic health record data from October 2013 through September 2015 and calculated ADRs for physicians from 4 health systems. ADRs were risk-adjusted for differences in patient populations. Physicians were surveyed to assess financial motivations, knowledge and perceptions about colonoscopy quality, and personality traits. Of 140 physicians sent the survey, 117 responded. RESULTS: The median risk-adjusted ADR for all surveyed physicians was 29.3% (interquartile range, 24.1%-35.5%). We found no significant association between ADR and financial incentives, malpractice concerns, or physicians' perceptions of ADR as a quality metric. ADR was associated with the degree of self-reported compulsiveness relative to peers: among endoscopists who described themselves as much more compulsive, the ADR was 33.1%; among those who described themselves as somewhat more compulsive, the ADR was 32.9%; among those who described themselves as about the same as others, the ADR was 26.4%; and among those who described themselves as somewhat less compulsive, the ADR was 27.3%) (P = .0019). ADR was also associated with perceived thoroughness (much more thorough than peers, ADR = 31.5%; somewhat more, 31.9%; same/somewhat less, 27.1%; P = .0173). Physicians who reported feeling rushed, having difficulty pacing themselves, or having difficulty in accomplishing goals had higher ADRs. A secondary analysis found the same associations between personality and adenomas per colonoscopy. CONCLUSIONS: We found no significant association between ADR and financial incentives, malpractice concerns, or perceptions of ADR as a quality metric. However, ADRs were higher among physicians who described themselves as more compulsive or thorough, and among those who reported feeling rushed or having difficulty accomplishing goals.

Endoscopist factors that influence serrated polyp detection: a multicenter study.

BACKGROUND: Serrated polyps are important colorectal cancer precursors that are variably detected during colonoscopy. We measured serrated polyp detection rate (SPDR) in a large, multicenter, cross-sectional study of colonoscopy quality to identify drivers of SPDR variation. METHODS: Colonoscopy and pathology reports were collected for a 2-year period (10/2013-9/2015) from four sites across the United States. Data from reports, including size, location, and histology of polyps, were abstracted using a validated natural language processing algorithm. SPDR was defined as the proportion of colonoscopies with ≥ 1 serrated polyp (not including hyperplastic polyps). Multivariable logistic regression was performed to determine endoscopist characteristics associated with serrated polyp detection. RESULTS: A total of 104 618 colonoscopies were performed by 201 endoscopists who varied with respect to specialty (86 % were gastroenterologists), sex (18 % female), years in practice (range 1 - 51), and number of colonoscopies performed during the study period (range 30 - 2654). The overall mean SPDR was 5.1 % (SD 3.8 %, range 0 - 18.8 %). In multivariable analysis, gastroenterology specialty training (odds ratio [OR] 1.89, 95 % confidence interval [CI] 1.33 - 2.70), fewer years in practice (≤ 9 years vs. ≥ 27 years: OR 1.52, 95 %CI 1.14 - 2.04)], and higher procedure volumes (highest vs. lowest quartile: OR 1.77, 95 %CI 1.27 - 2.46)] were independently associated with serrated polyp detection. CONCLUSIONS: Gastroenterology specialization, more recent completion of training, and greater procedure volume are associated with serrated polyp detection. These findings imply that both repetition and training are likely to be important contributors to adequate detection of these important cancer precursors. Additional efforts to improve SPDR are needed.

Variation in Pathologist Classification of Colorectal Adenomas and Serrated Polyps.

OBJECTIVES: Endoscopist quality measures such as adenoma detection rate (ADR) and serrated polyp detection rates (SPDRs) depend on pathologist classification of histology. Although variation in pathologic interpretation is recognized, we add to the literature by quantifying the impact of pathologic variability on endoscopist performance. METHODS: We used natural language processing to abstract relevant data from colonoscopy and related pathology reports performed over 2 years at four clinical sites. We quantified each pathologist's likelihood of classifying polyp specimens as adenomas or serrated polyps. We estimated the impact on endoscopists' ADR and SPDR of sending their specimens to pathologists with higher or lower classification rates. RESULTS: We observed 85,526 colonoscopies performed by 119 endoscopists; 50,453 had a polyp specimen, which were analyzed by 48 pathologists. There was greater variation across pathologists in classification of serrated polyps than in classification of adenomas. We estimate the endoscopist's average SPDR would be 0.5% if all their specimens were analyzed by the pathologist in our sample with the lowest classification rate and 12.0% if all their specimens were analyzed by the pathologist with the highest classification rate. In contrast, the endoscopist's average ADR would be 28.5% and 42.4% if their specimens were analyzed by the pathologist with lowest and highest classification rate, respectively. CONCLUSIONS: There is significant variation in pathologic interpretation, which more substantially affects endoscopist SPDR than ADR.

Physician characteristics associated with higher adenoma detection rate.

BACKGROUND AND AIMS: Patients who receive a colonoscopy from a physician with a low adenoma detection rate (ADR) are at higher risk of subsequent colorectal cancer. It is unclear what drives the variation across physicians in ADR. We describe physician characteristics associated with higher ADR. METHODS: In this retrospective cohort study a natural language processing system was used to analyze all outpatient colonoscopy examinations and their associated pathology reports from October 2013 to September 2015 for adults age 40 years and older across physicians from 4 diverse health systems. Physician performance on ADR was risk adjusted for differences in patient population and procedure indication. Our sample included 201 physicians performing at least 30 colonoscopy examinations during the study period, totaling 104,618 colonoscopy examinations. RESULTS: The mean ADR was 33.2% (range, 6.3%-58.7%). Higher ADR was seen among female physicians (4.2 percentage points higher than men, P = .020), gastroenterologists (9.4 percentage points higher than nongastroenterologists, P < .001), and physicians with ≤9 years since their residency completion (6.0 percentage points higher than physicians who have had 27-51 years of practice, P = .004). CONCLUSIONS: Gastroenterologists, female physicians, and more recently trained physicians had higher performance in adenoma detection.

Management and outcomes of acute pancreatitis patients over the last decade: A US tertiary-center experience.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) management remains largely supportive and can be challenging in patients with severe disease. This study aims to describe a ten-year US tertiary-center experience in managing AP patients. METHODS: Clinical management and outcomes of 400 prospectively enrolled AP patients stratified by the Revised Atlanta Classification were analyzed; trends in management between early (2004-2008) and late enrollment phase (2009-2014) were assessed. RESULTS: Fifty-two% of patients were classified as mild AP (MAP); moderately severe (MoAP) and severe (SAP) grades contained 23.5% and 24.5% of participants. Intravenous fluid administration during the first 24 h (MAP 3.7, MoAP 4.7, and SAP 4.8 L), need for ICU (6%, 23%, 93%), and nutritional support (7%, 51%, 90%) increased significantly with greater AP severity (p < 0.001). One hundred fifty five (39%) patients developed necrotizing AP, of which 41% received prophylactic antibiotics, and 44% underwent pancreatic drainage/debridement. Prophylactic antibiotics (58% vs. 27%) and interventions (63% vs. 27%) were noted more frequently in SAP than MoAP (p < 0.001). Enteral nutrition (18% vs. 30%) and minimally invasive pancreatic interventions (19% vs. 41%) were more commonly used in the late phase (p < 0.05). The overall median length of hospitalization was 7 days reaching 29 days in SAP group. Mortality was 5%; all deaths occurred in SAP group. CONCLUSIONS: This study provides an extensive report on clinical management of AP and its trends overtime. Pancreatic intervention is required in less than 50% of patients with necrotizing pancreatitis. Utilization of enteral nutrition and minimally invasive pancreatic interventions has been increasing over time.

Etiology and Treatment of Pain and Psychosocial Issues in Patients With Inflammatory Bowel Diseases.

There is increasing evidence that brain-gut interactions are altered during development of inflammatory bowel diseases (IBDs). Understanding the relationship between the neurobiology, psychological symptoms, and social ramifications of IBD can guide comprehensive care for the whole patient. The most common psychological conditions in patients with IBD are chronic abdominal pain, anxiety, and depression. We review the evidence-based data and rates of these conditions and their respective relationship to IBD and the diagnostic approaches to identify patients with these conditions. Different treatment options for pain and psychosocial conditions are discussed, and new models of team-based IBD care are introduced. Providing the health care provider with tools to diagnose and manage psychological conditions in patients with Crohn's disease or ulcerative colitis is necessary for their total care and should be part of quality-improvement initiatives.

The Inflammatory Bowel Disease Specialty Medical Home: A New Model of Patient-centered Care.

New models of health care have emerged over the past decade. Accountable care organizations and patient-centered medical homes are designed to improve the patient experience, enhance health care quality, and decrease cost. These models have been developed in the primary care domain and have yet to be tested in specialty care. Certain chronic diseases require principal care by a specialist or health care team. The specialty medical home would provide patient-centered care for specific populations of patients whose health care derives from a single chronic disease. This article defines the parameters for a specialty medical home and provides a specific payer-provider experience for the comprehensive care of an inflammatory bowel disease population.

Chronic pancreatitis: An international draft consensus proposal for a new mechanistic definition.

BACKGROUND: A definition of chronic pancreatitis (CP) is needed for diagnosis and distinguishing CP from other disorders. Previous definitions focused on morphology. Advances in epidemiology, genetics, molecular biology, modeling and other disciplines provide new insights into pathogenesis of CP, and allow CP to be better defined. METHODS: Expert physician-scientists from the United States, India, Europe and Japan reviewed medical and scientific literature and clinical experiences. Competing views and approaches were debated until a new consensus definition was reached. RESULTS: CP has been defined as 'a continuing inflammatory disease of the pancreas, characterized by irreversible morphological change, and typically causing pain and/or permanent loss of function'. Focusing on abnormal morphology makes early diagnosis challenging and excludes inflammation without fibrosis, atrophy, endocrine and exocrine dysfunction, pain syndromes and metaplasia. A new mechanistic definition is proposed--'Chronic pancreatitis is a pathologic fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress.' In addition, "Common features of established and advanced CP include pancreatic atrophy, fibrosis, pain syndromes, duct distortion and strictures, calcifications, pancreatic exocrine dysfunction, pancreatic endocrine dysfunction and dysplasia." This definition recognizes the complex nature of CP, separates risk factors from disease activity markers and disease endpoints, and allows for a rational approach to early diagnosis, classification and prognosis. CONCLUSIONS: Initial agreement on a mechanistic definition of CP has been reached. This definition should be debated in rebuttals and endorsements, among experts and pancreatic societies until international consensus is reached.

Epidemiologic and Mechanistic Associations Between Smoking and Pancreatitis.

OPINION STATEMENT: Alcohol has long been associated with pancreatitis. Although first described more than three decades ago, smoking has been widely accepted as an important risk factor for all forms of pancreatitis only in the past few years. Empiric data has confirmed smoking as an independent and dose-dependent risk for both acute and chronic pancreatitis. Smoking also increases the risk of recurrences and progression of established chronic pancreatitis. The effects of smoking are enhanced in the presence of alcohol consumption. Indirect evidence suggests that smoking cessation may be beneficial in preventing disease progression. Smoking cessation can therefore be an important strategy for primary as well as secondary prevention of pancreatitis. Therefore, in addition to alcohol, physicians should routinely counsel patients for the benefits of smoking cessation. The mechanisms through which cigarette smoke triggers pathological cellular events, resulting in pancreatitis, are unresolved. Although cigarette smoke contains greater than 4000 compounds, principally nicotine and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) have been broadly studied with regard to pancreatic diseases. Both nicotine and NNK have been shown to induce morphological changes in the pancreas consistent with those seen in pancreatitis. Furthermore, nicotine affects pancreatic secretion and NNK induces premature zymogen activation, two well-known features of pancreatitis. These cigarette toxins may mediate both pro- and anti-inflammatory pathways and can induce changes in pancreatic acinar cell function at the level of transcription, leading to conditions such as thiamin deficiency and mitochondrial dysfunction. Such circumstances could leave the pancreas prone to the development of pancreatitis. This review summarizes relevant research findings and focuses on the epidemiologic links between smoking and pancreatitis, and the cellular pathways that may be significant in induction and evolution of smoking-related pancreatitis.