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OBJECTIVES: To determine if RNA collected from pancreatic tissue, without the use of RNAlater, is useful for RNA sequencing (RNA-seq) despite degradation, and if so, then, via RNA-seq analysis, how does gene expression vary between pancreatitis etiologies. METHODS: Data were assessed in 2 dimensions, based on RNA-seq signal shape assessed by RSeQC v.2.6.4 and RNA expression after accounting for different degrees of degradation. RESULTS: Six measures of RNA characteristics (median RNA fragment size, reads per million kilobases saturation, transcript integrity number, distribution of hexamers, percentage of nucleotides that are guanine or cytosine, and duplicated reads) were significantly different between hereditary pancreatitis and idiopathic pancreatitis. Differential expression analysis revealed that 150 genes were differentially expressed between hereditary and idiopathic etiologies, 197 genes were differentially expressed between alcoholic and idiopathic etiologies, and 200 genes were differentially expressed between alcoholic and hereditary etiologies. We then determined that many enriched pathways between hereditary and idiopathic etiologies are related to the matrisome, and many of the enriched pathways between alcoholic and idiopathic etiology or hereditary etiology are related to ion transport. CONCLUSIONS: We found distinct RNA-seq signals between different pancreatitis etiologies in both of the dimensions in critical pathways for pancreas biology.
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Perfilación de la Expresión Génica/métodos , Trasplante de Islotes Pancreáticos/métodos , Páncreas/cirugía , Pancreatitis Crónica/cirugía , Pancreatitis/cirugía , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas/metabolismo , Páncreas/patología , Pancreatitis/etiología , Pancreatitis Crónica/genética , Estudios Prospectivos , RNA-Seq/métodos , Trasplante Autólogo , Adulto JovenRESUMEN
OBJECTIVE: The aim of the study was to report the prevalence and predictors of abdominal pain and disability 1 year after an acute pancreatitis (AP) attack. METHODS: Patients were prospectively enrolled between December 2012 and April 2016. Enrolled subjects were contacted at a median of 13 months after enrollment. Multivariable regression models were used to determine factors independently associated with abdominal pain at follow-up. RESULTS: Response rate was 71% (110/155). Of respondents, median age was 51 years, 58% were female, and 14% had severe AP. At follow-up, 24% of patients reported abdominal pain (65% intermittent, 35% constant), 10% used analgesics regularly, and 6% had regular opioids use. Furthermore, 41% of patients experienced pain-related interference with work or daily activities, and 8% developed disability. On regression analysis, idiopathic etiology (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.1-13.6) persistent organ failure (OR, 3.3; 95% CI, 1.1-7.9), and recurrent AP (OR, 2.9; 95% CI, 1.1-10.6) were independently associated with abdominal pain at follow-up. Disability at follow-up was associated with younger age, current smoking, and intensive care unit admission (all P < 0.05). CONCLUSIONS: Abdominal pain and disability are potential long-term sequelae of AP. Certain pre-existing factors and pancreatitis features are associated with these outcomes at one-year follow-up of AP.
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Dolor Abdominal/etiología , Pancreatitis/complicaciones , Dolor Abdominal/epidemiología , Actividades Cotidianas , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios ProspectivosRESUMEN
BACKGROUND: The effect of diet on risk of acute pancreatitis (AP) has been suggested by prior studies, but the association of dietary habits with severity of AP has not been previously evaluated. OBJECTIVE: The objective of the study was to assess differences in reported dietary habits in patients with severe AP compared with those with mild or moderate AP. METHODS: A prospectively maintained cohort of patients with AP was utilized. A brief questionnaire on dietary habits was implemented. Dietary habits were categorized based on the overall type of diet, fruit/vegetable servings, fat content, dairy consumption, dessert/sweets consumption, and fluid intake. Patients were grouped into mild/moderate and severe AP. Multivariate analysis was used to determine whether dietary habits have an independent association with AP severity. RESULTS: 407 patients with AP were studied. Mean patient age was 51 y, and 202 (50%) were men. 29% of patients were smokers and 46% actively consumed alcohol. 225 patients had mild AP, 103 moderate AP, and 79 developed severe AP. The 3 groups were comparable in race, body mass index, etiology of AP, and comorbidities. Dietary factors were overall comparable between the groups except for diet type: subjects with severe AP had a higher percentage of consuming a meat-rich diet (84%) than patients with mild AP (72%) and moderate AP (67%) (P = 0.04). Based on multivariable logistic regression, the OR of developing severe AP was 2.5 (95% CI: 1.24-5.32, P = 0.01) between patients who eat a meat-rich diet and those who consume a vegetable-based diet. CONCLUSIONS: A meat-rich diet is independently associated with the development of persistent organ failure (severe disease) in patients with AP. These findings require further evaluation and could be useful for patient counseling, risk stratification, and disease prevention. This study is registered at clinicaltrials.gov as NCT03075605.
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GOALS: To report the clinical profile and natural course in a large series of patients with hypertriglyceridemia (HTG) and acute pancreatitis (AP). BACKGROUND: The natural history of HTG-related pancreatitis is poorly defined. STUDY: Medical records of 121 patients with serum triglycerides (TG) levels of ≥500 mg/dL suffering 225 attacks of AP between January 2001 to August 2013 treated at the University of Pittsburgh Medical Center were retrospectively studied. Structured data were collected on initial presentation and long-term outcomes (mean follow-up 64.7±42.8 mo). AP severity was classified using Revised Atlanta Classification. RESULTS: Most patients were young-middle aged (mean 44±12.7 y), male (70%), white (78%), and had sentinel AP (63%). Peak serum TG recorded was ≥1000 mg/dL in 48%. At least 1 secondary risk factor (diabetes, high-risk drinking, obesity, offending medications) was present in the majority (78%). Sentinel AP attack varied in severity between mild (41%), moderate (26%), and severe (33%). Recurrent AP attacks occurred in 32%, often in patients with poorly controlled diabetes, alcoholism, and TG levels. A cumulative increase in prevalence of pancreatic and/or peripancreatic necrosis was observed, with 45% patients having it at some time during observation. Local complications were higher in patients with serum TG ≥1000 mg/dL. Chronic pancreatitis was noted in 16.5% patients (new-onset in 9%). CONCLUSIONS: Patients with HTG-related pancreatitis have a high prevalence of secondary risk factors. Frequent recurrences in them are usually due to poor control of secondary factors or TG. Serum TG ≥1000 mg/dL increases the risk of local complications. A subset can have or develop chronic pancreatitis.
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Hipertrigliceridemia/sangre , Pancreatitis/sangre , Triglicéridos/sangre , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/sangre , Estudios de Cohortes , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/complicaciones , Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Femenino , Humanos , Hipertrigliceridemia/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Obesidad/epidemiología , Pancreatitis/etiología , Prevalencia , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
GOALS: To explore the diagnostic challenges, management, and clinical outcomes of patients with isolated peripancreatic necrosis (PPN), with emphasis on the extent of involvement, and compare them to pancreatic necrosis (PN). BACKGROUND: PPN, a relatively new term, has been included as a separate entity in the Revised Atlanta Classification. STUDY: Clinical data of recruited acute pancreatitis patients were recorded prospectively. Contrast-enhanced computed tomographic scans were reviewed by expert radiologists blinded to clinical outcomes. RESULTS: In total, 271 of the 400 acute pancreatitis patients underwent contrast-enhanced computed tomography, of which 29 (11%) had PPN (14: limited; 15: extensive) and 124 (46%) PN (40: <30%, 16: 30% to 50%, 68: >50% of parenchyma). Patients with PPN were similar to PN in age (56 y), gender (55% male), and body mass index (29 kg/m(2)). Nutritional support was provided in 18 (62%) patients with PPN and 97 (78%) with PN (P=0.12). Drainage/debridement was required in 2 patients (7%) with PPN and 64 (53%) with parenchymal necrosis (P<0.001). Persistent organ failure rates did not differ significantly (34% vs. 51%, P=0.17), but hospital stay was shorter in patients with PPN (15 vs. 20 d, P=0.05). Limited PPN required no intervention and had similar persistent organ failure rates and hospitalization length with interstitial pancreatitis (both P≥0.12). Extensive PPN mainly developed in patients with persistent organ failure (60%) and rarely required drainage (2/15). CONCLUSIONS: PPN prevalence was lower than PN with a ratio of 1:4. PPN rarely required intervention. Utilizing the extent of involvement has the potential to classify PPN and PN with escalating clinical significance and guide management.
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Hospitalización/estadística & datos numéricos , Páncreas/fisiopatología , Pancreatitis Aguda Necrotizante/epidemiología , Tomografía Computarizada por Rayos X , Adulto , Anciano , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/epidemiología , Apoyo Nutricional , Páncreas/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/fisiopatología , Estudios Prospectivos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria , Estados UnidosAsunto(s)
Diabetes Mellitus/etiología , Pancreatitis/complicaciones , Enfermedad Aguda , Adulto , Anciano , Diabetes Mellitus/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/diagnóstico , Pancreatitis/terapia , Pennsylvania , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: In considering whether medications that increase insulin levels accelerate pancreatic adenocarcinoma (PC) development, we hypothesized that PC patients with diabetes mellitus (DM) who used exogenous insulin or insulin-stimulating medications should have an earlier age at diagnosis or present with more advanced disease. METHODS: Patients enrolled in our PC registry from June 1, 2003, to May 31, 2012, were stratified according to treatment solely with insulin, insulin-stimulating medications, or insulin-independent medications. Age at PC diagnosis, PC stage, and years between DM and PC diagnoses were analyzed among the cohorts. RESULTS: Of 122 DM patients (mean age, 67.4 ± 10.2 years), the mean ages at PC diagnosis within the insulin-only (n = 40), insulin-stimulating (n = 11), insulin-independent (n = 71), and non-DM (n = 321) cohorts were 68.7 ± 10.5, 69.6 ± 10.8, 66.3 ± 9.7, and 65.5 ± 10.5 years, respectively. No significant difference among the age at PC diagnosis was observed based on duration or type of DM treatment. There was no correlation between PC stage and increased insulin exposure. CONCLUSIONS: Anti-DM medications that increase exposure to insulin do not appear to accelerate PC development using outcomes of mean age at PC diagnosis, PC stage, or duration between DM and PC diagnoses.
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Adenocarcinoma/sangre , Diabetes Mellitus/sangre , Insulina/sangre , Neoplasias Pancreáticas/sangre , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamiento farmacológico , Edad de Inicio , Anciano , Consumo de Bebidas Alcohólicas , Índice de Masa Corporal , Estudios de Cohortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Femenino , Humanos , Hipoglucemiantes/sangre , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Modelos Lineales , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Estadificación de Neoplasias , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamiento farmacológico , Fumar , Factores de TiempoAsunto(s)
Biomarcadores/análisis , Enfermedades Pancreáticas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Enfermedad Aguda , Predisposición Genética a la Enfermedad/genética , Humanos , Enfermedades Pancreáticas/genética , Neoplasias Pancreáticas/genética , Pancreatitis/diagnóstico , Pancreatitis/genética , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/genética , Recurrencia , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Hereditary pancreatitis is an autosomal dominant disorder with 80% penetrance and variable expressivity. The vast majority of cases have been linked to mutations within the cationic trypsinogen gene, also referred to as serine protease 1 (PRSS1). Other than inheritance, PRSS1 pancreatitis has been considered clinically and pathologically indistinguishable from other etiologies of chronic pancreatitis. However, to date, the histologic findings of PRSS1 pancreatitis have not been well described. We, therefore, collected pancreatic specimens from 10 PRSS1 patients of various ages and examined their clinicopathologic features. Patients at the time of resection ranged in age from 9 to 66 years (median, 29 y), with a slight female predominance (60%). All patients reported a history of intermittent abdominal pain, with an age of onset ranging from infancy to 21 years of age. Examination of the gross and microscopic findings suggested a sequential pattern of changes with increasing patient age. In pediatric patients (n=4), although in most cases the pancreas was grossly normal, there was microscopic variation in lobular size and shape. Although the central portions of the pancreas displayed parenchymal loss accompanied by loose perilobular and interlobular fibrosis, the periphery was remarkable for replacement by mature adipose tissue. These changes were more developed in younger adults (n=2), in whom fatty replacement seemed to extend from the periphery to the central portions of the pancreas. With older patients (n=4), the pancreas showed marked atrophy and extensive replacement by mature adipose tissue with scattered islets of Langerhans and rare acinar epithelium concentrated near the main pancreatic duct. In summary, PRSS1 hereditary pancreatitis is characterized by progressive lipomatous atrophy of the pancreas.
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Mutación , Páncreas/patología , Pancreatitis Crónica/genética , Pancreatitis Crónica/patología , Tripsina/genética , Adolescente , Adulto , Anciano , Atrofia , Niño , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Lipomatosis/enzimología , Lipomatosis/genética , Lipomatosis/patología , Masculino , Persona de Mediana Edad , Páncreas/enzimología , Páncreas/cirugía , Pancreatectomía , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/enzimología , Pancreatitis Crónica/cirugía , Fenotipo , Resultado del TratamientoRESUMEN
CONTEXT: Hereditary pancreatitis is typically caused by the PRSS1 R122H or N29I mutations resulting in high penetrance (about 80%) autosomal dominant disorder that is usually reported in North America, Northern Europe and Northeast Asia, but not South America, Africa or India. CASE REPORT: Here we report a kindred from Venezuela, South America with the PRSS1 R122H variant. Only the proband, an 11-year old boy with severe chronic pancreatitis, and a maternal grandmother with pancreatitis at age 60 years (confirmed PRSS1 R122H), are symptomatic. CONCLUSIONS: Issues of mutation prevalence, non-penetrance, and disease recognition in various countries are discussed.
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Mutación Missense , Pancreatitis Crónica/genética , Penetrancia , Tripsina/genética , Sustitución de Aminoácidos/fisiología , Arginina/genética , Niño , Familia , Femenino , Histidina/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense/fisiología , Linaje , Fenotipo , VenezuelaRESUMEN
Chronic pancreatitis is not one disease; it is a pathway of injury and fibrosis driven by many factors. The role of genetics is emerging as a major factor, both in terms of understand pathogenesis, and in terms of identifying risk factors and mechanisms. Use of the TIGAR-O classification system, or others will be useful research tools to determine gene-gene, gene-environment, and other interactions that contribute to development of an otherwise mysterious disease