Objectives Hypertriglyceridemia-induced pancreatitis is an important cause of acute pancreatitis (AP) in children, which lacks established guidelines. The aim of this study was to review management approaches at a single pediatric center. Methods This retrospective study included all inpatients younger than 21 years with AP and triglycerides (TG) of 1000 mg/dL or greater. A linear mixed effect model was used to calculate drop in TGs. The patient's diet, intravenous fluid (IVF) rate, insulin, and plasmapheresis were included in the model. Results Seventeen admissions were identified among 8 patients, average age 15 years (range, 6-19 years). Fifty percent had recurrent AP and 29% of admissions had complications including 1 death. The population was primarily female (75%), white (75%), and overweight, and 63% had diabetes. The median stay was 5.4 days. There were 14 approaches used with variations in IVF rates, insulin, plasmapheresis, and nill per os (NPO) versus feeds. Variables that reduced TG's were NPO, higher IVF rates, plasmapheresis, and insulin (P < 0.05). Importantly, NPO reduced TGs faster than those who started early nutrition. Conclusions Hypertriglyceridemia is an important cause of pancreatitis in children. This study shares a management algorithm from a single institution. Larger studies are needed for more evidence-based guidelines.

Since the introduction of Sodium-glucose cotransporter 2 (SGLT2) inhibitors as guideline therapy for both uncontrolled type 2 diabetes mellitus and heart failure, these medications have become popular options as add-on therapy. This class of medication reduces blood glucose levels via inhibition of glucose reabsorption in the proximal convoluted tubules leading to enhanced renal excretion. Not only do SGLT2 inhibitors provide advantages in improved glucose control, but also have proven to reduce cardiovascular mortality. Generally, SGLT2 inhibitors are well tolerated, however adverse reactions of genitourinary tract infections secondary to glucosuria and hypotension from associated osmotic diuresis have been reported. Less commonly, pancreatitis has been associated with use of SGL2 inhibitors. We present a case of suspected empagliflozin induced pancreatitis notable for delayed onset at approximately 120 days since SGLT2 inhibitor initiation.

Pancreatic cancer is the product of microenvironment alterations which emerge from inflammatory signaling and progress to more devastating cases such as Pancreatic Ductal Adenocarcinoma (PDAC). PDAC is extremely aggressive with a statistical five-year survival rate of merely 3%-5%, and is more than relevant to cancer research being that it is the fourth leading cause of cancer-related deaths in the US. Unfortunately pancreatic cancer is often unnoticed until reaching its hardly treatable end stages, which perpetuates the low survival rate. The onset of PDAC may be facilitated by the activation of pancreatic stellate cells (PSCs), which secrete collagen and markedly contribute to tissue fibrosis. Inflammatory factors and activation of PSCs are hallmarks of pancreatitis and could increase occurrence rates of pancreatic cancer. The purpose of this thesis is to elucidate inflammatory signaling patterns starting with the onset of acute pancreatitis and through future studies of the more damaging states of chronic pancreatitis and cancer progression. Through the induction of acute pancreatitis in oncogenic and wild type mouse models and evaluating cytokine expression levels via RT-PCR a link between inflammatory signaling and disease state progression will be delineated. This model utilizes mice with mutant KRas, a gene activated in nearly all PDAC incidences, and constitutively active Akt, an oncogene activated in nearly all cancers. Preliminary results indicate that when experimentally inducing pancreatitis in mice predisposed to pancreatic cancer tissue remodeling and leukocyte infiltration is observed as a result of cytokine expression. Furthermore, macrophage and neutrophil stains are positive with one round of cerulein injections proving that acute inflammation is induced by these methods. Pancreatitis is a risk factor for pancreatic cancer which can be caused by environmental factors including smoking, alcohol consumption, and obesity. By understanding the mechanism by which inflammation occurs and the cytokine signaling involved we can attempt inhibit tumor-promoting signaling pathways in the pancreas stroma.

INTRODUCCION: La mayoría de los pacientes con pancreatitis aguda exhibe una evolución clínica autolimitante y relativamente libre de complicaciones mayores. Varios scores han sido creados con la intensión de lograr predecir adecuada y precozmente la gravedad de la pancreatitis para así poder disminuir esta mortalidad. El score BISAP fue validado en el 2008 como predictor de mortalidad para pancreatitis aguda, mientras que la obesidad es un factor de riesgo independiente que incrementa el riesgo de severidad en pacientes que presentan pancreatitis aguda. El objetivo del presente estudio es determinar si la obesidad añadida a un score BISAP mejora la predicción de severidad en pacientes con pancreatitis aguda MATERIAL Y METODOS: El presente estudio fue realizado en el Hospital Nacional Daniel Alcides Carrión, provincia del Callao, departamento de Lima, Perú. Los datos de los pacientes fueron recolectados en el servicio de emergencia de dicho nosocomio, se trató de un estudio retrospectivo transversal, realizado entre enero del 2009 y junio del 2010. RESULTADOS: Se evaluaron un total de 99 pacientes con diagnóstico de pancreatitis aguda. La etiología de las 99 pancreatitis fueron catalogadas como biliares. Solo 2 terminaron en defunción (2%). La mayoría de casos se presentaron en pacientes del sexo femenino 77 (77,8%). Dieciséis de los 99 pacientes (16%), fueron considerados como pancreatitis aguda grave. El 90% de los pacientes (89 /99), tuvieron un BISAP < 3, 10% un BISAP ≥ 3, quince de los 99 pacientes tuvieron un BISAP-O > 3, de ellos 12 fueron realmente considerados como una pancreatitis severa. De 16 pacientes con pancreatitis severa, 14 pacientes tuvieron un IMC > 25. (p = 0,03; OR = 4,39). BISAP-O tiene una sensibilidad, especificidad, Valor predictivo positivo VPP y Valor predictivo negativo VPN de 75%; 96,4%; 80% y 95,2% respectivamente con una exactitud de 92,3%. El área bajo la curva para el BISAP-O fue 0,94 (IC 95%: 0,89 a 0,99). No hubo diferencias cuando se comparó con los otros scores estudiados (p=0,45). CONCLUSIONES: El score de BISAP es un método sencillo y rápido que puede ser utilizado para predecir la gravedad de los pacientes con pancreatitis aguda al momento del ingreso a un servicio de emergencia. BISAP asociado a Obesidad (BISAP-O) otorga una mayor sensibilidad y exactitud diagnóstica al score BISAP y puede servir como un parámetro de ayuda para predecir la severidad en los pacientes con pancreatitis aguda. No fue posible evaluar el score de BISAP-O como predictor de mortalidad para los pacientes con pancreatitis aguda, debido a la baja tasa de mortalidad en el presente estudio. Se requieren más estudios para poder validar el score BISAP asociado a la Obesidad para predecir severidad. / INTRODUCTION: Most patients with acute pancreatitis exhibits a self-limiting clinical course and relatively free of major complications. Several scores have been created with the intention of achieving adequate and early predict the severity of pancreatitis in order to reduce this mortality. BISAP score was validated in 2008 as a predictor of mortality for acute pancreatitis, obesity is an independent risk factor that increases the risk of severity in patients with acute pancreatitis. The aim of this study is to determine whether obesity BISAP added a score improves prediction of severity in patients with acute pancreatitis MATERIAL AND METHODS: This study was conducted in Daniel Alcides Carrión Hospital, Lima, Peru. The patient data were collected in the Emergency Service, it was a cross-sectional retrospective study, between January 2009 and June 2010. RESULTS: We evaluated a total of 99 patients with acute pancreatitis. Etiology of the 99 were biliary pancreatitis. Only 2 ended in death (2%). Most cases occurred in female patients 77/22 (77.8%). Sixteen of the 99 patients (16%) were considered severe acute pancreatitis. 90% (89/99) had a BISAP <3, 10% a BISAP ≥ 3, fifteen of the 99 patients had a BISAP-O> 3, of them 12 were actually considered a severe pancreatitis. Of 16 patients with severe pancreatitis, 14 patients had a BMI> 25. (P = 0.03, OR = 4.39). BISAP-O has a sensitivity, specificity, PPV and NPV of 75%, 96.4%, 80% and 95.2% respectively, with an accuracy of 92.3%. The area under the curve for BISAP-O was 0.94 (95% CI 0.89 to 0.99). There was no difference when compared with the other studied scores (p = 0.45). CONCLUSIONS: BISAP The score is a simple method that can be used to predict the severity of acute pancreatitis. Obesity associated BISAP (BISAP-O) provides higher sensitivity and diagnostic accuracy to score BISAP and can serve as a parameter to help predict severity in patients with acute pancreatitis. It was not possible to assess the BISAP-O score as a predictor of mortality for patients with acute pancreatitis, due to the low mortality rate in the present study. Further studies are required to validate the score BISAP associated with obesity in predicting severity.

Conclusion. These data provide a clue that AT1 receptor blocker could effectively attenuate severe form of pancreatitis and its-associated systemic inflammation in experimental models of AP. The underlying mechanisms may be involved in Ang II-induced NADPH oxidase derived oxidative stress, particularly NFkappaB and ERK1/2-dependent CREB activation. The pro-inflammatory pathways would commonly converge to transcribe an array of genes such as IL-6, thus regulating the severity of pancreatitis and the onset of its complications. All these in vivo and in vitro data provide substantial evidence that Ang II is involved in AT1 receptor-mediated signaling cascade in regulating the pathogenesis of AP. The findings provide a new insight on potential application of AT 1 receptor blockade for a therapeutic approach in the management of AP. (Abstract shortened by UMI.) / Recent advance in basic research has revealed that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of AP. In this regard, the present study aimed at investigating the effectiveness of RAS blockade in clinically relevant AP animal model and AP-associated systemic inflammation. More importantly, the underlying mechanistic pathways involved in angiotensin II (Ang II)-induced pro-inflammatory actions were elucidated using both in vivo and in vitro systems. / Results. Major components of RAS were up-regulated in obstructive pancreatitis model. Blockade of AT1 receptor attenuated pancreatic injury induced by the two models. Moreover, losartan could significantly ameliorate AP-associated systemic inflammation. Analysis of protein expression levels revealed that losartan treatment improved AP-associated elevation of NADPH oxidase p67 and p22 subunits. Double-immunostaining confirmed that expression of NADPH oxidase was localized to pancreatic acinar cells. AT1 receptor antagonism not only reduced oxidative stress but also suppressed nuclear factor kappaB (NFkappaB) activation, as evidenced by reversal effects on IkappaBbeta depletion, augmentation of phosphor NFkappaB p65, and enhanced nuclear kappaB binding activity. Blockade of AT1 receptor could also suppress the levels of kappaB-related protein expression, including intercellular adhesion molecule-1, cyclooxygenase-2, and IL-1. On the other hand, pancreatic mRNA and protein levels of IL-6 were enhanced by obstructive AP, which were antagonized by AT1 receptor blocker. Losartan treatment could reverse extracellular-regulated kinase (ERK) 1/2 and cAMP-responsive element binding protein (CREB) phosphorylation brought by obstructive AP. In vitro studies, exogenous application of Ang II induced ERK1/2 and CREB activation in AR42J cells. Concomitantly, IL-6 expression was augmented dose- and time-dependently in response to Ang II, which was reversed by treatment of AT1 receptor blocker (losartan) and ERK1/2 inhibitor (PD98059). Ang II induced NFkappaB activation was reversed by pre-treatment of AT1 receptor blocker and NADPH oxidase inhibitor but not ERK1/2 inhibitor in vitro. Moreover, Ang II-induced superoxide generation was detected. Treatment of antioxidant prevented Ang II-induced ERK1/2 activation. On top of these, in vitro experiments revealed that Ang II could sustain the activation of caerulein-induced NFkappaB and ERK1/2 in an AT1 receptor-mediated manner, but not secretagogue-induced hypersecretion. / Chan, Yuk Cheung. / Adviser: Po Siny Lzung. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3246. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 228-262). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Introdução: A litíase biliar e o consumo de álcool são as etiologias mais frequentes para pancreatite aguda (PA), sendo reportadas como responsáveis por cerca de 40 e 30% dos casos respectivamente. No entanto, no Rio Grande do Sul - BR observamos uma frequência de pancreatite aguda biliar (PAB) em torno de 77% dos casos e pancreatite aguda alcoólica (PAA) em apenas 8%. Além da possibilidade de diferenças próprias da nossa população, é possível que a incidência de PAB esteja aumentando. Objetivo: Estimar as frequências globais da PAB, PAA e dos casos considerados pancreatite aguda idiopática (PAI) em estudos publicados de 2006 a 18 de outubro de 2017. Comparar as frequências de PAB, PAA e PAI entre os estudos que realizaram revisão de prontuários individuais dos pacientes ou foram prospectivos e os que utilizaram apenas os códigos de alta hospitalar para o diagnóstico etiológico. Comparar as frequências de PAB, PAA, PAI de acordo com região geográfica da população dos estudos. Métodos: Uma revisão sistemática de estudos observacionais em Inglês, Espanhol e Português, de 2006 a 18 de outubro de 2017 foi realizada. Metanálise pelo modelo de efeitos randômicos foi utilizada para calcular as frequências de PAB, PAA e PAI globais e nos subgrupos (diagnóstico por código da alta hospitalar, diagnóstico por avaliação individualizada do prontuário do paciente, estudos dos EUA, estudos da América Latina, estudos da Europa e estudos da Ásia). Resultado: Foram incluídos quarenta e seis estudos representando 2.341.007 casos de PA em 36 países. A estimativa global para a pancreatite aguda biliar (PAB) foi 41,6% (IC 95% 39,2-44,1), seguido por PA alcoólica (PAA) com 20,5% (IC 95% 3 16,6-24,6) e PA idiopática (PAI) em 18,3% (IC 95% 15.1 - 21,7). Em estudos com diagnóstico etiológico por código de alta a PAI foi a mais frequente com 37,9% dos casos (IC 95% 35,1 - 40,8). Nos estudos que revisaram os prontuários dos pacientes a PAB foi a mais frequente com 46% (IC 95% 42,3 - 49,8). Nos EUA a PAI foi a mais frequente com 34,7% (IC 95% 32,3 - 37,2). Na América Latina a estimativa de PAB foi de 68,5% (IC de 95% 57,8 - 78,3). Na Europa, na Ásia e em 1 estudo Australiano, a etiologia mais frequente foi a PAB em 41,3% (IC 95% 37,9 - 44,7), 42% (IC 95% 28,8 - 55,8) e 40% (IC 95% 36,8 - 43,2), respectivamente. Na África do Sul 1 artigo apresentou frequência de 70,2% (IC de 95% 64,5 - 75,4) para PAA. Conclusão: A PAB é a etiologia mais prevalente da PA, sendo 2 vezes mais frequente que o segundo lugar. A América Latina apresenta uma frequência para PAB muito maior do que o resto do mundo. Grandes estudos populacionais que utilizam diagnósticos codificados e estudos americanos apresentam elevadas taxas de PA sem classificação. A importância do diagnóstico etiológico consiste no tratamento da causa para prevenção da recorrência. / Background: Gallstones and alcohol are the most common etiology of acute pancreatitis (AP) and is reported to account for about 40% and 30% of cases respectively. However, in Rio Grande do Sul - BR, we observed a frequency of acute biliary pancreatitis (ABP) around 77% of cases and alcoholic acute pancreatitis (AAP) in only 8%. Besides the possibility of differences of our own population, it is possible that the incidence of PAB is increasing. Objective: estimate the global frequency of ABP, AAP and the cases considered idiopathic pancreatitis (IAP) in published studies from 2006 to October 18 2017. Compare the frequencies for ABP, AAP and AIP among studies that performed review of individual records of patients or collected data prospectively and those using only the hospital discharge diagnostic codes for etiologic diagnosis. Compare the frequency of ABP, AAP and IAP by geographic region. Methods: A systematic review of observational studies in English, Spanish and Portuguese, from 2006 to October 18, 2017 was done. Random-effects metaanalysis was used to assess the frequency of biliary, alcoholic and idiopathic AP worldwide and to perform the analysis of 6 subgroups (hospital discharge coded diagnosis, individual patient chart review, studies from US, Latin America, Europe and studies from Asia). Results: Forty-six studies were included representing 2.341.007 cases of PA in 36 countries. The overall estimate for ABP was 41.6% (95% CI 39.2 to 44.1), followed by AAP with 20.5% (95% CI 16.6 to 24 6) and IAP with 18.3% (95% CI 15.1 - 21.7). In studies with hospital discharge coded diagnosis IAP was the most frequent with 37.9% (95% CI 35.1 to 40.8). In studies with individual patient chart review PAB 5 was more frequent with 46% (95% CI 42.3 to 49.8). In US studies IAP was he most frequent etiology with 34.7% (95% CI 32.3 to 37.2). In Latin America PAB was estimated 68.5% of the cases (95% CI 57.8 to 78.3). In Europe, Asia and one Australian study, the most frequent cause was the ABP in 41.3% (95% CI 37.9 to 44.7), 42% (95% CI 28.8 to 55.8) and 40% (95% CI 36.8 to 43.2) of the cases respectively. One study from South Africa had AAP in 70.2% (95% CI 64.5 to 75.4) of the cases. Conclusion: Gallstones are the main etiology of AP globally, twice as frequent as the second one. Latin America has a frequency for ABP much higher than the rest of the world. Large population studies using coded diagnoses and American studies show high rates IAP. The importance of the etiological diagnosis resides in treating the cause in order to prevent recurrence.

Introdução: A litíase biliar e o consumo de álcool são as etiologias mais frequentes para pancreatite aguda (PA), sendo reportadas como responsáveis por cerca de 40 e 30% dos casos respectivamente. No entanto, no Rio Grande do Sul - BR observamos uma frequência de pancreatite aguda biliar (PAB) em torno de 77% dos casos e pancreatite aguda alcoólica (PAA) em apenas 8%. Além da possibilidade de diferenças próprias da nossa população, é possível que a incidência de PAB esteja aumentando. Objetivo: Estimar as frequências globais da PAB, PAA e dos casos considerados pancreatite aguda idiopática (PAI) em estudos publicados de 2006 a 18 de outubro de 2017. Comparar as frequências de PAB, PAA e PAI entre os estudos que realizaram revisão de prontuários individuais dos pacientes ou foram prospectivos e os que utilizaram apenas os códigos de alta hospitalar para o diagnóstico etiológico. Comparar as frequências de PAB, PAA, PAI de acordo com região geográfica da população dos estudos. Métodos: Uma revisão sistemática de estudos observacionais em Inglês, Espanhol e Português, de 2006 a 18 de outubro de 2017 foi realizada. Metanálise pelo modelo de efeitos randômicos foi utilizada para calcular as frequências de PAB, PAA e PAI globais e nos subgrupos (diagnóstico por código da alta hospitalar, diagnóstico por avaliação individualizada do prontuário do paciente, estudos dos EUA, estudos da América Latina, estudos da Europa e estudos da Ásia). Resultado: Foram incluídos quarenta e seis estudos representando 2.341.007 casos de PA em 36 países. A estimativa global para a pancreatite aguda biliar (PAB) foi 41,6% (IC 95% 39,2-44,1), seguido por PA alcoólica (PAA) com 20,5% (IC 95% 3 16,6-24,6) e PA idiopática (PAI) em 18,3% (IC 95% 15.1 - 21,7). Em estudos com diagnóstico etiológico por código de alta a PAI foi a mais frequente com 37,9% dos casos (IC 95% 35,1 - 40,8). Nos estudos que revisaram os prontuários dos pacientes a PAB foi a mais frequente com 46% (IC 95% 42,3 - 49,8). Nos EUA a PAI foi a mais frequente com 34,7% (IC 95% 32,3 - 37,2). Na América Latina a estimativa de PAB foi de 68,5% (IC de 95% 57,8 - 78,3). Na Europa, na Ásia e em 1 estudo Australiano, a etiologia mais frequente foi a PAB em 41,3% (IC 95% 37,9 - 44,7), 42% (IC 95% 28,8 - 55,8) e 40% (IC 95% 36,8 - 43,2), respectivamente. Na África do Sul 1 artigo apresentou frequência de 70,2% (IC de 95% 64,5 - 75,4) para PAA. Conclusão: A PAB é a etiologia mais prevalente da PA, sendo 2 vezes mais frequente que o segundo lugar. A América Latina apresenta uma frequência para PAB muito maior do que o resto do mundo. Grandes estudos populacionais que utilizam diagnósticos codificados e estudos americanos apresentam elevadas taxas de PA sem classificação. A importância do diagnóstico etiológico consiste no tratamento da causa para prevenção da recorrência. / Background: Gallstones and alcohol are the most common etiology of acute pancreatitis (AP) and is reported to account for about 40% and 30% of cases respectively. However, in Rio Grande do Sul - BR, we observed a frequency of acute biliary pancreatitis (ABP) around 77% of cases and alcoholic acute pancreatitis (AAP) in only 8%. Besides the possibility of differences of our own population, it is possible that the incidence of PAB is increasing. Objective: estimate the global frequency of ABP, AAP and the cases considered idiopathic pancreatitis (IAP) in published studies from 2006 to October 18 2017. Compare the frequencies for ABP, AAP and AIP among studies that performed review of individual records of patients or collected data prospectively and those using only the hospital discharge diagnostic codes for etiologic diagnosis. Compare the frequency of ABP, AAP and IAP by geographic region. Methods: A systematic review of observational studies in English, Spanish and Portuguese, from 2006 to October 18, 2017 was done. Random-effects metaanalysis was used to assess the frequency of biliary, alcoholic and idiopathic AP worldwide and to perform the analysis of 6 subgroups (hospital discharge coded diagnosis, individual patient chart review, studies from US, Latin America, Europe and studies from Asia). Results: Forty-six studies were included representing 2.341.007 cases of PA in 36 countries. The overall estimate for ABP was 41.6% (95% CI 39.2 to 44.1), followed by AAP with 20.5% (95% CI 16.6 to 24 6) and IAP with 18.3% (95% CI 15.1 - 21.7). In studies with hospital discharge coded diagnosis IAP was the most frequent with 37.9% (95% CI 35.1 to 40.8). In studies with individual patient chart review PAB 5 was more frequent with 46% (95% CI 42.3 to 49.8). In US studies IAP was he most frequent etiology with 34.7% (95% CI 32.3 to 37.2). In Latin America PAB was estimated 68.5% of the cases (95% CI 57.8 to 78.3). In Europe, Asia and one Australian study, the most frequent cause was the ABP in 41.3% (95% CI 37.9 to 44.7), 42% (95% CI 28.8 to 55.8) and 40% (95% CI 36.8 to 43.2) of the cases respectively. One study from South Africa had AAP in 70.2% (95% CI 64.5 to 75.4) of the cases. Conclusion: Gallstones are the main etiology of AP globally, twice as frequent as the second one. Latin America has a frequency for ABP much higher than the rest of the world. Large population studies using coded diagnoses and American studies show high rates IAP. The importance of the etiological diagnosis resides in treating the cause in order to prevent recurrence.

Introdução: A litíase biliar e o consumo de álcool são as etiologias mais frequentes para pancreatite aguda (PA), sendo reportadas como responsáveis por cerca de 40 e 30% dos casos respectivamente. No entanto, no Rio Grande do Sul - BR observamos uma frequência de pancreatite aguda biliar (PAB) em torno de 77% dos casos e pancreatite aguda alcoólica (PAA) em apenas 8%. Além da possibilidade de diferenças próprias da nossa população, é possível que a incidência de PAB esteja aumentando. Objetivo: Estimar as frequências globais da PAB, PAA e dos casos considerados pancreatite aguda idiopática (PAI) em estudos publicados de 2006 a 18 de outubro de 2017. Comparar as frequências de PAB, PAA e PAI entre os estudos que realizaram revisão de prontuários individuais dos pacientes ou foram prospectivos e os que utilizaram apenas os códigos de alta hospitalar para o diagnóstico etiológico. Comparar as frequências de PAB, PAA, PAI de acordo com região geográfica da população dos estudos. Métodos: Uma revisão sistemática de estudos observacionais em Inglês, Espanhol e Português, de 2006 a 18 de outubro de 2017 foi realizada. Metanálise pelo modelo de efeitos randômicos foi utilizada para calcular as frequências de PAB, PAA e PAI globais e nos subgrupos (diagnóstico por código da alta hospitalar, diagnóstico por avaliação individualizada do prontuário do paciente, estudos dos EUA, estudos da América Latina, estudos da Europa e estudos da Ásia). Resultado: Foram incluídos quarenta e seis estudos representando 2.341.007 casos de PA em 36 países. A estimativa global para a pancreatite aguda biliar (PAB) foi 41,6% (IC 95% 39,2-44,1), seguido por PA alcoólica (PAA) com 20,5% (IC 95% 3 16,6-24,6) e PA idiopática (PAI) em 18,3% (IC 95% 15.1 - 21,7). Em estudos com diagnóstico etiológico por código de alta a PAI foi a mais frequente com 37,9% dos casos (IC 95% 35,1 - 40,8). Nos estudos que revisaram os prontuários dos pacientes a PAB foi a mais frequente com 46% (IC 95% 42,3 - 49,8). Nos EUA a PAI foi a mais frequente com 34,7% (IC 95% 32,3 - 37,2). Na América Latina a estimativa de PAB foi de 68,5% (IC de 95% 57,8 - 78,3). Na Europa, na Ásia e em 1 estudo Australiano, a etiologia mais frequente foi a PAB em 41,3% (IC 95% 37,9 - 44,7), 42% (IC 95% 28,8 - 55,8) e 40% (IC 95% 36,8 - 43,2), respectivamente. Na África do Sul 1 artigo apresentou frequência de 70,2% (IC de 95% 64,5 - 75,4) para PAA. Conclusão: A PAB é a etiologia mais prevalente da PA, sendo 2 vezes mais frequente que o segundo lugar. A América Latina apresenta uma frequência para PAB muito maior do que o resto do mundo. Grandes estudos populacionais que utilizam diagnósticos codificados e estudos americanos apresentam elevadas taxas de PA sem classificação. A importância do diagnóstico etiológico consiste no tratamento da causa para prevenção da recorrência. / Background: Gallstones and alcohol are the most common etiology of acute pancreatitis (AP) and is reported to account for about 40% and 30% of cases respectively. However, in Rio Grande do Sul - BR, we observed a frequency of acute biliary pancreatitis (ABP) around 77% of cases and alcoholic acute pancreatitis (AAP) in only 8%. Besides the possibility of differences of our own population, it is possible that the incidence of PAB is increasing. Objective: estimate the global frequency of ABP, AAP and the cases considered idiopathic pancreatitis (IAP) in published studies from 2006 to October 18 2017. Compare the frequencies for ABP, AAP and AIP among studies that performed review of individual records of patients or collected data prospectively and those using only the hospital discharge diagnostic codes for etiologic diagnosis. Compare the frequency of ABP, AAP and IAP by geographic region. Methods: A systematic review of observational studies in English, Spanish and Portuguese, from 2006 to October 18, 2017 was done. Random-effects metaanalysis was used to assess the frequency of biliary, alcoholic and idiopathic AP worldwide and to perform the analysis of 6 subgroups (hospital discharge coded diagnosis, individual patient chart review, studies from US, Latin America, Europe and studies from Asia). Results: Forty-six studies were included representing 2.341.007 cases of PA in 36 countries. The overall estimate for ABP was 41.6% (95% CI 39.2 to 44.1), followed by AAP with 20.5% (95% CI 16.6 to 24 6) and IAP with 18.3% (95% CI 15.1 - 21.7). In studies with hospital discharge coded diagnosis IAP was the most frequent with 37.9% (95% CI 35.1 to 40.8). In studies with individual patient chart review PAB 5 was more frequent with 46% (95% CI 42.3 to 49.8). In US studies IAP was he most frequent etiology with 34.7% (95% CI 32.3 to 37.2). In Latin America PAB was estimated 68.5% of the cases (95% CI 57.8 to 78.3). In Europe, Asia and one Australian study, the most frequent cause was the ABP in 41.3% (95% CI 37.9 to 44.7), 42% (95% CI 28.8 to 55.8) and 40% (95% CI 36.8 to 43.2) of the cases respectively. One study from South Africa had AAP in 70.2% (95% CI 64.5 to 75.4) of the cases. Conclusion: Gallstones are the main etiology of AP globally, twice as frequent as the second one. Latin America has a frequency for ABP much higher than the rest of the world. Large population studies using coded diagnoses and American studies show high rates IAP. The importance of the etiological diagnosis resides in treating the cause in order to prevent recurrence.

Chronic pancreatitis is considered a risk factor for pancreatic cancer. An exact mechanism how chronic inflammation of the pancreas leads to pancreatic cancer is not yet understood; the possibility of a shared genetic predisposition for both diseases is also assumed. A similar association in patients with AIP has not yet been demonstrated. The aim of our work was to expand the knowledge about relationship between chronic pancreatitis and pancreatic cancer. We studied the association of the diseases in two synchronous projects. In the first one, we examined the occurrence of pancreatic cancer in patients with autoimmune pancreatitis. In the second project, we investigated the presence of genetics variants associated with chronic pancreatitis in patients with pancreatic cancer. In the retrospective study of our cohort of patients, we were one of the very first in the world to show occurrence of pancreatic cancer in patients with autoimmune pancreatitis, and as the only one, we have defined the characteristics of such patients. To assess the association of the diseases, we performed a systematic review where we identified all reported cases of coincidence of pancreatic cancer and autoimmune pancreatitis; the incidence of cancer in patients with autoimmune pancreatitis was similar to that of patients...

Die Hämoxygenase-1 (HO-1) ist das geschwindigkeitsbestimmende Enzym des Hämabbaus und ist wichtiger Regulator inflammatorischer Prozesse. Der Verlauf einer experimentellen akuten Pankreatitis (AP) konnte im Tiermodell durch HO-1 Induktion abgemildert werden. Die Aktivierung und Proliferation pankreatischer Stellatum Zellen (PSC) wird durch eine experimentelle HO-1 Induktion inhibiert und kann so möglicherweise vor der Fibrosierung des Pankreasparenchyms bei chronischer Pankreatitis (CP) schützen. Die Transkription der HO-1 wird durch einen GT-Repeat beeinflusst, der im Promoter lokalisiert ist. Diese Arbeit untersuchte, ob Varianten des GT-Repeat oder weitere genetische Varianten der HO-1 mit verschiedenen Pankreatitisformen assoziiert sind. Der GT-Repeat und der SNP rs2071746 wurden mit fluoreszensmarkierten Primern bzw. mit Schmelzkurvenanalyse bei 285 Patienten mit AP, bei 208 Patienten mit alkoholischer CP (ACP), bei 207 mit idiopathischer/hereditärer CP (ICP/HCP), 147 Patienten mit Alkoholischer Leberzirrhose (ALZ) und bei 289 Kontrollen untersucht. Bei den ACP Patienten wurde die GT-Repeat Analyse auf insgesamt 446 Patienten erhöht. Zusätzlich wurden die kodierenden HO-1 Abschnitte mittels DNA-Sequenzierung bei 145 Patienten mit ACP, 138 Patienten mit ICP/HCP, 147 Patienten mit ALZ und bei 151 Kontrollen analysiert. Das Exon 3 wurde darüber hinaus bei zusätzlichen ICP/HP Patienten und Kontrollen untersucht. Die Längenverteilungen des GT-Repeat, die Allelverteilung des SNP rs2071746 und die Verteilung der bei der DNA-Sequenzierung gefundenen synonymen und nicht synonymen Varianten waren bei allen untersuchten Gruppen nicht signifikant unterschiedlich. Obwohl die funktionellen Daten einen Einfluss von HO-1 Varianten auf die Pathogenese der verschiedenen Pankreatitis-Formen nahelegen, konnte unsere umfangreiche genetische Analyse keine Assoziation nachweisen. Genetische Varianten der HO-1 haben keinen Einfluss auf die Entwicklung einer AP, ACP, ICP/HCP und ALZ.:Inhaltsverzeichnis Vorbemerkung ..................................................................................................... 3 Bibliographische Beschreibung.......................................................................... 4 Abkürzungen/Abbildungen ................................................................................ 6 1. Einleitung........................................................................................................9 1.1 Akute Pankreatitis ......................................................................................................................... 9 1.2 Chronische Pankreatitis ............................................................................................................... 11 1.3 Genetische Aspekte der Chronischen Pankreatitis ...................................................................... 12 1.3.1 Kationisches Trypsinogen (PRSS1) ...................................................................................... 12 1.3.2 Anionisches Trypsinogen (PRSS2) ....................................................................................... 14 1.3.3 Serinproteaseinhibitor, Kazal Typ1 (SPINK1)..................................................................... 14 1.3.4 Chymotrypsin C (CTRC) ...................................................................................................... 15 1.3.5 CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) ...................................... 15 1.4 Hämoxygenase-1 ......................................................................................................................... 16 1.4.1 Physiologische Bedeutung der Hämoxygenase-1 (HO-1) .................................................... 16 1.4.2 Genetische Varianten der Hämoxygenase-1 ........................................................................ 18 1.4.3 Hämoxygenase-1 und Pankreatitis....................................................................................... 20 1.5 Hypothese/Fragestellung ............................................................................................................. 21 2. Publikation ..................................................................................................... 22 3. Zusammenfassung der Arbeit ...................................................................... 23 4. Literaturverzeichnis...................................................................................... 28 5. Danksagung.................................................................................................... 35 6. Erklärung über die eigenständige Abfassung der Arbeit .......................... 36 7. Lebenslauf ...................................................................................................... 37