Evolution and progress of surgical intervention strategies for acute pancreatitis / 中华外科杂志

Acute pancreatitis is one of the common surgical acute abdominal diseases. Since people first recognized acute pancreatitis in the middle of the nineteenth century, a diversified minimally invasive treatment model with standardization has been formed today. According to the main line of surgical intervention of acute pancreatitis treatment,this period can be roughly divided into five stages:exploration stage, conservative treatment stage, pancreatectomy stage, debridement and drainage of the pancreatic necrotic tissue stage, and minimally invasive treatment as the first choice led by the multidisciplinary team mode stage. Throughout history, the evolution and progress of surgical intervention strategies for acute pancreatitis cannot be separated from the progress of science and technology, the update of treatment concepts and the further understanding of the pathogenesis. This article will summarize the surgical characteristics of acute pancreatitis treatment at each stage to explain the development of surgical treatment of acute pancreatitis,to help investigate the development of surgical treatment of acute pancreatitis in the future.

Ameliorative effect of certolizumab on experimentally induced acute necrotic pancreatitis in rats

SUMMARY OBJECTIVE: The effects of Certolizumab, a pegylated monoclonal antibody to tumor necrosis factor α, on experimentally induced acute pancreatitis (AP) were examined. METHODS: Thirty-six Wistar Albino male rats were randomly divided into four groups. Group I was the control group and no medication administered to this group. Group II was the Certolizumab group, and 100 ml/kg serum physiologic administered into the biliopancreatic duct and a single dose of 10 μg Certolizumab was simultaneously administered intraperitoneally. Acute pancreatitis was induced with a retrograde injection of 3% Na taurocholate into the common biliopancreatic duct in the study (Group III) and treatment (Groups IV) groups. Rats were sacrificed 72 hours later. Serum amylase, lipase, lactate dehydrogenase activities, along with pancreatic histopathology, were examined. RESULTS: Certolizumab treatment significantly decreased serum amylase, lipase, and LDH levels; histopathologically edema, hemorrhage, parenchymal necrosis, fat necrosis, and infiltration scores; immunohistochemically MDA, MPO, TNF-α and Caspase-3 activity. CONCLUSION: The results support the idea that certolizumab might be beneficial for the severity of AP.

RESUMO OBJETIVO: Os efeitos de Certolizumab, um anticorpo monoclonal pegilado para o fator de necrose tumoral α, na pancreatite aguda induzida experimentalmente (PA) foram examinados. MÉTODO: Trinta e seis ratos Wistar Albino foram divididos aleatoriamente em quatro grupos. O Grupo I foi considerado o grupo controle e não recebeu medicação; o Grupo II foi o grupo Certolizumab e recebeu 100 ml/kg de soro fisiológico administrado no ducto biliopancreático e dose única de 10 mg Certolizumab administrada por via intraperitoneal simultaneamente. A pancreatite aguda foi induzida com uma injeção retrógrada de uma solução de 3% taurocolato de sódio aplicada no ducto biliopancreático comum nos grupos de estudo (Grupo III) e tratamento (Grupos IV). Os ratos foram sacrificados 72 horas depois. As atividades séricas de amilase, lipase, lactato desidrogenase, juntamente com a histopatologia pancreática, foram examinadas. RESULTADOS: O tratamento com Certolizumab diminuiu significativamente os níveis séricos de amilase, lipase e LDH; edema histopatológico, hemorragia, necrose paranquimatosa, necrose gordurosa e escores de infiltração; atividade imuno-histoquímica de MDA, MPO, TNF-α e Caspase-3. CONCLUSÃO: Estes resultados suportam a ideia de que o Certolizumab pode ser benéfico para a gravidade da PA.

Glycogen synthase kinase-3 beta inhibitors protectagainst the acute lung injuries resulting from acute necrotizing pancreatitis

Abstract Purpose The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3β inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats. Methods Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3β, phospho-GSK-3β (Ser9), iNOS, ICAM-1, TNF-α, and IL-10 were detected in lung tissues by Western-blot. Results The outcomes revealed that the intervention of GSK-3β inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1β and IL-6 (P<0.01), inhibited the activation of NF-κB, and abated expression of iNOS, ICAM-1 and TNF-α protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups. Conclusions Inhibition of GSK-3β weakens acute lung injury related to ANP via the inhibitory function of NF-κB signaling pathway. Different kinds of GSK-3β inhibitors have different effects to ANP acute lung injury.

Effects of diazoxide in experimental acute necrotizing pancreatitis

OBJECTIVE: We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis. METHODS: Male Wistar rats (200-400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n=38) was observed for 72 h and analyzed by the Mantel-Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt's scale. Cytokine expression in plasma was evaluated by the multiplex method. RESULTS: Mortality at 72 h was 33% in the control group and 60% in the treatment group (p=0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p=0.015). CONCLUSIONS: Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h.

Role of high mobility group box-1 and protection of growth hormone and somatostatin in severe acute pancreatitis

In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP.

Is there a therapeutic window for pentoxifylline after the onset of acute pancreatitis? / Existe uma janela terapêutica para a pentoxifilina após o início da pancreatite aguda?

PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.

OBJETIVO: Investigar os efeitos da pentoxifilina (PTX) na pancreatite aguda (PA) experimental administrando a droga após a indução da doença. MÉTODOS: Cem ratos machos Wistar foram submetidos à indução da PA através da infusão de taurocolato de sódio e divididos em três grupos: Grupo Sham: sham-operated ratos, Grupo Salina: AP e solução salina, e Grupo PTX: AP e PTX. Solução salina e PTX foram administradas 1 hora após a indução da PA. Três horas após indução da PA os níveis de fator de necrose tumoral (TNF)-α no líquido peritoneal e os níveis séricos de interleucina (IL)-6 e IL-10 foram analisados pelo método de Enzima Imunoensaio (ELISA). A atividade da mieloperoxidase (MPO) foi analisada no pulmão e foram realizadas análises histológicas do pulmão e pâncreas, além do estudo da mortalidade. RESULTADOS: A administração de PTX 1 hora após a indução da PA reduziu significativamente os níveis de TNF-α peritoneal e os níveis séricos de IL-6 e IL-10 quando comparado ao grupo salina. Redução na mortalidade foi observado após o tratamento com PTX comparado ao grupo salina. CONCLUSÃO: A administração de PTX após a indução da PA diminuiu os níveis sistêmicos de citocinas pró-inflamatórias, sugerindo a possibilidade de que existe uma janela terapêutica para PTX após o início do PA.

Identificando a la Pancreatitis aguda severa / Identifying the severe acute pancreatitis

OBJETIVOS: Comparar a pacientes con pancreatitis aguda con necrosis que no presentan complicaciones adicionales durante su hospitalización (Grupo A) versus aquellos pacientes con pancreatitis aguda con necrosis que presenten complicaciones adicionales durante su hospitalización (Grupo B). MÉTODOS: Se realizó el análisis sobre una base de datos preexistente de registros de pacientes hospitalizados con diagnóstico de pancreatitis aguda con necrosis de la Unidad de Pancreatitis Aguda Grave del Hospital Nacional Edgardo Rebagliati Martins entre 2000 y 2010. Se utilizaron los registros de todos los pacientes criterios diagnósticos de pancreatitis aguda severa con presencia de necrosis mayores de 18 años. RESULTADOS: Se incluyeron 215 registros de pacientes con PA con necrosis. Los pacientes del Grupo A representaron un 32% (68) y los del Grupo B el 68%(147). Grupo A tuvo un promedio de 39 días de hospitalización y el Grupo B tuvo un promedio de 56 días (p = 0.01). Del Grupo A 22% tuvieron más de 50% de necrosis mientras 43% del Grupo B tuvieron esta extensión de necrosis (p <0.05, OR 3.4, IC (1.12-10)). De los 14 casos fallecidos de toda la población, encontrándose todos ellos en el Grupo B, 12 de ellos tuvieron más de 50% de necrosis. CONCLUSIONES: No todos los casos clasificados como pancreatitis aguda severa, basados en la presencia de necrosis pancreática, se comportan de manera uniforme. Es la extensión de la necrosis pancreática (mayor a 50%) y no la sola presencia de la misma, la que determinaría una evolución con complicaciones adicionales y mayor mortalidad.

AIMS: To compare patients with acute necrotizing pancreatitis without any additional complications during their hospital stay (Group A) versus patients with Acute Necrotizing Pancreatitis with additional complications during their hospital stay (Group B) METHODS: Data obtained from a pre-existing base from hospitalized patients with diagnosis of acute necrotizing pancreatitis in the specialized unit of "Unidad de Pancreatitis Aguda Grave del Hospital Nacional Edgardo Rebagliati Martins" between 2000 and 2010. Data included patients with diagnosis of acute necrotizing pancreatitis, of ages 18 and over. RESULTS: Data from 215 patients with acute necrotizing pancreatitis was included. Patients from Group A represented 32% (68) and from Group B 68% (147). Group A had a average of 39 hospitalized days and Group B had an average of 56 days (p=0.01). From Group A 22% had more than 50% of necrosis while 43% of Group B had this extension of necrosis (p <0.05, OR 3.4, IC (1.12-10)). Of the 14 deaths of the population, all part of Group B, 12 of them had more than 50% of necrosis. CONCLUSIONS: Not every patient classified as severe acute pancreatitis, based on the presence of necrosis, behave likewise. It is an extended necrosis, described as more than 50% of pancreatic necrosis, and not the presence itself which will determine additional complications during the course of disease and a greater mortality.

Elevación de creatinina sérica como indicador de necrosis pancreática / Elevation of serum creatinine as an indicator of pancreatic necrosis

La Pancreatitis Aguda (PA) es una patología que se autolimita en el 80% de los casos; estos casos en general evolucionan hacia la recuperación total. Su evolución puede ser de leve a severa. La forma grave varía desde un 10% a un 25% y se asocia con falla orgánica y/o complicaciones locales como necrosis pancreática. En Venezuela, la PA Severa es un importante problema de salud pública, encontrándose entre las primeras 25 causas de muerte. Este estudio plantea la utilización de una prueba de laboratorio ampliamente disponible, de fácil uso e interpretación, para pronosticar la aparición de complicaciones como necrosis pancreática. Objetivo: Determinar la utilidad de la creatinina sérica como factor predictivo de necrosis pancreática en pancreatitis aguda. Materiales y Metodos: Estudio de tipo analítico, transversal y retrospectivo. Se revisaron las historias clínicas de los pacientes que ingresaron al hospital “Dr. Miguel Pérez Carreño”, con diagnóstico de pancreatitis aguda entre 2008 y 2009. Se registró creatinina sérica y se relacionó con la clasificación de severidad tomográfica según Balthazar. Resultados: La población estuvo conformada por 50 casos, de éstos se excluyeron 4, por embarazo o enfermedad renal crónica. Treinta de sexo femenino (65%) y 16 masculino (35%). Edades comprendidas entre 18 a 77 años, con media de 40,2. La estancia hospitalaria media fue de 8,74 días. Del total de 46 pacientes, presentó Balthazar A 63% (n=29), B 17,39% (n=8), C 14,04% (n= 6) y D 6,5% (n=3). No se obtuvo ningún E. Al aplicar un análisis de varianza se observó relación estadística significativa directamente proporcional de la creatinina sérica de ingreso (p=0,001) y de las 48 horas (p=0,001) con el Balthazar y el hematocrito. Conclusiones: La evaluación de los niveles y variaciones de creatinina sérica son de utilidad para predecir la aparición de necrosis pancreática en pacientes con pancreatitis aguda.

Acute Pancreatitis (AP) is a self-limited pathology in 80% of the cases; these cases generally evolve towards total recovery. Its evolution can be mild or severe. The severe form varies from a 10% to a 25%, and is associated with organ failure and/or local complications as pancreatic necrosis. In Venezuela severe AP is an important public health problem, being in the first 25 causes of death. The present study proposes the use of a widely available laboratory test, of easy use and interpretation, to predict the appearance of complications as pancreatic necrosis. Objective: To determine the usefulness of the serum creatinine as predictive factor of pancreatic necrosis in acute pancreatitis. Materials and Methods: An analytic, transversal and retrospective study. Clinical histories of patients admitted to the “Dr. Miguel Perez Carreño” hospital with a diagnosis of acute pancreatitis between years 2008 and 2009 were reviewed. Serum creatinine was registered and compared according to the Balthazar classification of tomographic severity. Results: The sample was comprised by 50 cases, from which 4 were excluded, due to pregnancy or chronic renal disease. Thirty were female (65%) and 16 male (35%). Between the ages of 18 and 77, with mean age of 40,2. The median hospital stay was 8,74 days. From total of 46 patients, 63% had Balthazar A (n=29); B 17.39% (n=8); C 14,04% (n= 6) and D 6.5% (n=3). No Balthazar E was obtained. When applying a variance analysis, a significant statistical relation was observed, directly proportional to the serum creatinine upon admission (p=0,001) and the 48 hours (p=0,001) with the Balthazar and hematocrit. Conclusions: The evaluation of the levels and variations of serum creatinine is a useful tool for predicting the appearance of pancreatic necrosis in patients with acute pancreatitis.

Acute necrotizing pancreatitis and postmortem autolysis of pancreas / 法医学杂志

OBJECTIVE@#To compare the pathomorphologic changes between the pancreas in acute necrotizing pancreatitis (ANP) and that in acute deaths of rats (within 48 hours) so as to find the distinctions.@*METHODS@#The animal models of ANP and other acute deaths (electroshock, mechanic asphyxia/strangle, and acute poisoning with tetramine) were established according to the criteria. Half-quantitative grading and image quantitative analysis methods were employed to observe the gross and microscopic changes of the pancreases.@*RESULTS@#Three features including inflammation infiltrate, fat necrosis and calcium deposit in the ANP group were considerably different from that in other acutely died rat group (P<0.05).@*CONCLUSION@#Inflammation infiltrate, fat necrosis and calcium deposit are the most important pathologic features found in ANP by common light microscope, distinguishing ANP from postmortem pancreatic autolysis.

Pancreatitis aguda: experiencia en el Hospital Jesús Yerena: Lídice / Acute pancreatitis: Hospital Jesús Yerena experience: Lídice

Presentar la experiencia en el diagnóstico y manejo de la pancreatitis aguda en el servicio de cirugía del Hospital Jesús Yerena de Lídice, en Caracas, al igual que los aspectos epidemiológicos relacionados con esta enfermedad y comparar los resultados con la bibliografía mundial. Se realizó un estudio de tipo retrospectivo, revisándose 106 historias clínicas de pacientes que ingresaron a la emergencia del hospital por presentar un cuadro de pancreatitis aguda, en un período de 10 años, desde enero de 1993 hasta enero de 2003. De un total de 106 pacientes con pancreatitis aguda, 83 fueron de sexo masculino (78,30 por ciento) y 39 de sexo femenino (21,70 por ciento). El grupo etario más afectado fue el comprendido entre los 27 y 37 años de edad (49 por ciento). Las causas de la pancreatitis fueron: litiasis biliar en 42,45 por ciento de los casos, trauma abdominal en 23,58 por ciento e ingesta excesiva de alcohol en 18,86 por ciento de los pacientes. Los principales síntomas presentados por estos pacientes fueron: dolor abdominal, náuseas, vómitos, ictericia y en algunos casos rigidez abdominal. Del total de pacientes, 44 fueron sometidos a intervención quirúrgica, realizándose diferentes procedimientos como: desbridamento pancreático, colecistostomía y coledocostomía, lavado peritoneal, irrigación de la cavidad abdominal. Las complicaciones más frecuentes fueron las fístulas pancreáticas (22,72 por ciento), absceso intraabdominal (13,63 por ciento), diabetes (4,54 por ciento), y pseudoquistes pancreáticos (2,72 por ciento). En total fallecieron 9 pacientes (8,49 por ciento). Preocupa el considerable número de personas jóvenes afectas por esta patología, ya que se consideran una población en edad productiva o económicamente activa. Dentro de los antecedentes patológicos de importancia presentados por estos pacientes, no difieren de manera significativa, en comparación con los descritos en la bibliografía mundial, pero se destaca que una población importante.

Pancreatite aguda experimental induzida pela L-arginina: avaliação histológica e bioquímica / Experimental acute pancreatitis induced by L-arginine: a histological and biochemical evaluation

RACIONAL: Doses excessivas de aminoácidos básicos como a L-arginina têm a capacidade de lesar o pâncreas de ratos. OBJETIVO: Descrever e avaliar as características bioquímicas e histológicas da pancreatite aguda induzida pela L-arginina em ratos durante a instalação, desenvolvimento e reparação do processo inflamatório pancreático. MATERIAL E MÉTODOS: A amostra constituiu-se de 105 ratos machos, da linhagem Wistar. Aos ratos do grupo experimento (n = 70) administrou-se injeção intraperitonial de 500 mg/100 g de peso corporal de L-arginina. No grupo controle (n = 35) foi injetada solução salina isotônica. Analisaram-se 10 animais do grupo experimento e 5 do grupo controle em cada período de 6 h, 12 h, 24 h, 48 h, 72 h, 7 dias e 14 dias. Durante os tempos determinados coletou-se sangue para exames laboratoriais e o pâncreas para análise em microscopia óptica. RESULTADOS: Doze a 24 horas após a injeção de L-arginina os níveis séricos de amilase atingiram valores máximos, comparados àqueles dos ratos controle, decrescendo gradualmente, alcançou-os na 48ªhora sendo significativamente menor após 72 horas e 7 dias. A atividade enzimática retornou a níveis basais após 14 dias. Os valores de amilase estavam normais em todos os tempos avaliados nos animais do grupo controle. Na microscopia óptica, após injeção de L-arginina, observou-se arquitetura pancreática histologicamente preservada no período de 6 horas, evidenciando-se em 24 horas importante edema intersticial. Após 48 horas, a arquitetura acinar estava parcialmente destruída com necrose celular focal, atingindo sua máxima severidade ao ultrapassar 72 horas. No 7° dia a necrose tecidual e o edema haviam diminuído, iniciando-se a regeneração da arquitetura acinar. Observou-se a reconstrução estrutural pancreática após 14 dias. No grupo controle não se encontraram alterações histológicas pancreáticas. CONCLUSÃO: A pancreatite aguda experimental induzida pela L-arginina induz a necrose pancreática, apresentando evolução auto-limitada com regeneração do pâncreas em 2 semanas.

Necrosectomy followed by closed cavity lavage for necrotising pancreatitis--report of three cases.

Necrotizing Pancreatitis is a life threatening condition involving pancreas, peripancreatic and retroperitoneal tissues. It's serious regional and systemic involvement causes multiple organ or system failure. Planned and carefully performed necresectomy followed by closed cavity lavage can significantly reduce the mortality and morbidity of this catastrophic condition. Meticulous preoperative resuscitation, preparation and operative necrosectomy followed by continuos irrigation in the postoperative period were done in three consecutive patients. The operative procedure including postoperative management and follow up is reported and analyzed.

Pancreatitis aguda / Acute pancreatitis

La pancreatitis aguda es una inflamación del páncreas producida por una activación enzimática intrínseca. Se relaciona con una amplia gama de asociaciones etiológicas, hallazgos patológicos y cursos clínicos. Las causas asociadas se pueden clasificar como obstructivas y no-obstructivas, siendo alcohol y litiasis biliar las más frecuentes. Su patogenia se basa en la activación intrínseca de proenzimas lo que lleva a una respuesta inflamatoria precedida de la liberación de factores y mediadores proinflamatorios y en la generación de radicales libres en su proceso. Desde el punto de vista patológico se clasifica en intersticial y necrotizante, pudiendo complicarse con la presencia de colección de fluído, seudo quiste o absceso. Estas formas patológicas constituyen el substrato de las formas clínicas leve y severa respectivamente, esta última caracterizada por la presencia de complicaciones sistémicas y/o locales. El diagnóstico se basa en la confirmación de la presencia de la enfermedad y en su grado de severidad. Estos objetivos se logran en función del cuadro clínico-auxiliar establecido en la determinación del aclaramiento de la amilasa y su relación con el aclaramiento de la creatinina y de los factores pronósticos de riesgo como los principales parámetros diagnósticos. El tratamiento de la pancreatitis aguda reside en el manejo de sus complicaciones. Los objetivos primarios son optimizar la hemodinámica del paciente, monitorizar y mantener su status respiratorio, darle soporte nutricional y manejar adecuadamente las infecciones que se puedan presentar. Una vez estabilizado el paciente, se procederá a la evaluación y tratamiento etiológico.