NLRP3 inflammasome inhibitor MCC950 can reduce the damage of pancreatic and intestinal barrier function in mice with acute pancreatitis.

PURPOSE: Abnormal activation of NOD-like receptor protein 3 (NLRP3) inflammasome can lead to the occurrence and progression of acute pancreatitis. This study investigated the protective effect of MCC950 on pancreatitis mice. METHODS: Eighteen mice were randomly divided into control group, severe acute pancreatitis (SAP) group and SAP+MCC950 group. Serum interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA. Hematoxylin and eosin (HE) staining was used to evaluate the pathological damage. Western blotting was used to detect the expression of NLRP3 inflammasome and tight junction proteins in the small intestine and pancreas. RESULTS: MCC950 could reduce the levels of IL-6 and IL-1ß in SAP mice. After treatment with MCC950, the expression levels of NLRP3 inflammasome in the pancreas of SAP mice were significantly reduced and the pathological damage to the pancreas and intestine was alleviated. Compared with the control group, the expression of tight junction protein (ZO-1,occludin and claudin-4) in the intestinal mucosa of SAP mice was decreased, and the expression of claudin-4 and occludin were upregulated after MCC950 treatment. CONCLUSIONS: MCC950 can inhibit NLRP3 inflammasome activation and significantly reduce the inflammatory response and delay the process of pancreatitis. It has therapeutic potential in the treatment of acute pancreatitis.

Canine pancreatitis: the development of the pancreatic inflammatory condition and the clinical-therapeutic approach / Pancreatite canina: o desenvolvimento da condição inflamatória pancreática e a abordagem clínico-terapêutica / Pancreatitis canina: el desarrollo de la condición inflamatoria pancreática y el enfoque clínico-terapéutico

La pancreatitis, aguda o crónica, es una enfermedad grave para los perros, debido a su potencial nocivo y a la existencia de infradiagnóstico. La enfermedad sigue siendo objeto de estudios en cuanto a su fisiopatología y mecanismos terapéuticos, debido a que los signos que presentan los animales son inespecíficos y van desde presentaciones leves a severas. Puede provocar cambios morfofuncionales en el páncreas y órganos adyacentes. El diagnóstico puede ser una tarea muy difícil, ya sea por los síntomas variables y la gravedad de la enfermedad, o por los callejones sin salida experimentados en el momento de los exámenes complementarios. El manejo terapéutico se define en base a los síntomas que presentan los animales, que van desde la infusión de líquidos para reposición de volumen, analgésicos, antieméticos, antibióticos, alimentos especiales, entre otros.(AU)

Pancreatitis, acute or chronic, is a serious disease for dogs, due to its harmful potential and the existence of underdiagnosis. The disease is still the target of studies regarding its pathophysiology and therapeutic mechanisms, because the signs presented by the animals are nonspecific, ranging from mild to severe presentations. It can cause morphofunctional changes in the pancreas and adjacent organs. The diagnosis can be a very difficult task, either due to the variable symptoms and severity of the disease, or the impasses experienced at the time of the complementary exams. Therapeutic management is defined based on the symptoms presented by the animals, ranging from fluid infusion for volume replacement, analgesics, antiemetics, antibiotics, special food, among others.(AU)

A pancreatite é uma doença grave para os cães, tanto pelo seu potencial deletério quanto pela existência de subdiagnósticos, e pode ser classificada em aguda ou crônica. A doença ainda é alvo de estudos no que diz respeito a sua patofisiologia e mecanismos terapêuticos, uma vez que os sinais apresentados pelos animais são inespecíficos, variando desde apresentações brandas a graves. Pode causar alteração morfofuncional do pâncreas e órgãos adjacentes. O diagnóstico pode ser uma tarefa bastante difícil, seja pela sintomatologia variável e gravidade da doença como também pelos impasses vivenciados no momento da realização dos exames complementares. O manejo terapêutico é definido com base na sintomatologia apresentada pelos animais, variando desde a infusão de fluidos para reposição volêmica, analgésicos, antieméticos, antibióticos, alimentação especial, entre outros.(AU)

Canine pancreatitis: the development of the pancreatic inflammatory condition and the clinical-therapeutic approach / Pancreatite canina: o desenvolvimento da condição inflamatória pancreática e a abordagem clínico-terapêutica / Pancreatitis canina: el desarrollo de la condición inflamatoria pancreática y el enfoque clínico-terapéutico

La pancreatitis, aguda o crónica, es una enfermedad grave para los perros, debido a su potencial nocivo y a la existencia de infradiagnóstico. La enfermedad sigue siendo objeto de estudios en cuanto a su fisiopatología y mecanismos terapéuticos, debido a que los signos que presentan los animales son inespecíficos y van desde presentaciones leves a severas. Puede provocar cambios morfofuncionales en el páncreas y órganos adyacentes. El diagnóstico puede ser una tarea muy difícil, ya sea por los síntomas variables y la gravedad de la enfermedad, o por los callejones sin salida experimentados en el momento de los exámenes complementarios. El manejo terapéutico se define en base a los síntomas que presentan los animales, que van desde la infusión de líquidos para reposición de volumen, analgésicos, antieméticos, antibióticos, alimentos especiales, entre otros.

Pancreatitis, acute or chronic, is a serious disease for dogs, due to its harmful potential and the existence of underdiagnosis. The disease is still the target of studies regarding its pathophysiology and therapeutic mechanisms, because the signs presented by the animals are nonspecific, ranging from mild to severe presentations. It can cause morphofunctional changes in the pancreas and adjacent organs. The diagnosis can be a very difficult task, either due to the variable symptoms and severity of the disease, or the impasses experienced at the time of the complementary exams. Therapeutic management is defined based on the symptoms presented by the animals, ranging from fluid infusion for volume replacement, analgesics, antiemetics, antibiotics, special food, among others.

A pancreatite é uma doença grave para os cães, tanto pelo seu potencial deletério quanto pela existência de subdiagnósticos, e pode ser classificada em aguda ou crônica. A doença ainda é alvo de estudos no que diz respeito a sua patofisiologia e mecanismos terapêuticos, uma vez que os sinais apresentados pelos animais são inespecíficos, variando desde apresentações brandas a graves. Pode causar alteração morfofuncional do pâncreas e órgãos adjacentes. O diagnóstico pode ser uma tarefa bastante difícil, seja pela sintomatologia variável e gravidade da doença como também pelos impasses vivenciados no momento da realização dos exames complementares. O manejo terapêutico é definido com base na sintomatologia apresentada pelos animais, variando desde a infusão de fluidos para reposição volêmica, analgésicos, antieméticos, antibióticos, alimentação especial, entre outros.

Calcium channels blockers toxins attenuate abdominal hyperalgesia and inflammatory response associated with the cerulein-induced acute pancreatitis in rats.

Agents that modulate the activity of high-voltage gated calcium channels (HVCCs) exhibit experimentally and clinically significant effect by relieving visceral pain. Among these agents, the toxins Phα1ß and ω-conotoxin MVIIA effectively reduce chronic pain in rodent models. The molecular mechanisms underlying the chronic pain associated with acute pancreatitis (AP) are poorly understood. Hypercalcemia is a risk factor; the role of cytosolic calcium is considered to be a modulator of pancreatitis. Blockade of Ca2+ signals may be useful as a prophylactic treatment of pancreatitis. We explored the pathophysiological roles of three peptide toxins: Phα1ß and its recombinant form CTK 01512-2-blockers of TRPA1 receptor and HVCCs and ω-conotoxin MVIIA, a specific blocker of N-type calcium channels in cerulein-induced AP. Cerulein injection elicits AP in rats, evidenced by an increase in hyperalgesic pain, inflammatory infiltration, amylase and lipase secretion, and reactive oxygen species, TNF-α, and p65 NF-κB levels. These effects of cerulein-induced AP were abolished by Phα1ß and its recombinant form CTK 01512-2, whereas ω-conotoxin MVIIA had no effect on the induced increase in pancreatic enzyme secretion. Our results demonstrate that Phα1ß and CTK 01512-2 toxins-antagonists of HVCCs and TRPA1 receptor presented an effective response profile, in the control of nociception and inflammatory process in the AP model in rats, without causing changes in spontaneous locomotion of the rats.

Controversias en la terapia nutricional de la pancreatitis aguda grave / Controversies in nutrition therapy of severe acute pancreatitis

La clasificación de la severidad de la pancreatitis aguda ha cambiado con la actualización de Atlanta del 2012. Las recomendaciones de terapia nutricional en los casos de pancreatitis aguda grave no están sustentadas en estudios con alto nivel de evidencia, en los estudios se incluyen pacientes con los diferentes grados de severidad, se usa la clasificación de Atlanta 2002 para definir la pancreatitis aguda grave y, en la mayoría de los estudios experimentales, los controles son pacientes con nutrición parenteral. Se realiza una revisión narrativa de la evidencia actual publicada, analizando las características clínico epidemiológica de los pacientes y los resultados obtenidos. Así, se proponen características que deben ser consideradas en estudios futuros sobre el tema.

The classification of the severity of acute pancreatitis has changed with respect to the Atlanta update of 2012. The recommendations for nutritional therapy in cases of severe acute pancreatitis are not supported by high-level studies, as studies contain a mix of patients with different degrees of severity. The Atlanta 2002 classification is used to define severe acute pancreatitis and, in most of experimental studies, controls are patients with parenteral nutrition. A narrative review of the current published evidence is carried out analyzing the clinical and epidemiological characteristics of the patients in these results and characteristics to be included in future studies are proposed.

Páncreas divisum y pancreatitis: su importancia en la práctica cotidiana / Pancreas divisum and pancreatitis: its importance in everyday practice

Pancreas divisum (PD) is the most common congenital anatomical variant of the pancreas. Its etiological implication in recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) has been recurrently questioned. Normal anatomy and variants: 80-90% of the population has normal anatomy, with excretion of exocrine pancreatic secretion to the duodenum by the major papilla. Three anatomical variants of PD have been described: classic PD with visible ventral duct, but total absence of fusion; PD with absence of ventral duct; and incomplete PD, with a rudimentary connection between the ventral and dorsal ducts. Clinical implication: This anatomical variant is symptomatic in less than 5% of the carriers, being associated to higher prevalence in patients with RAP However, the relationship between PD and RAP is considered probable, only in cases of association with mutation of the CFTR gene. Obstructive CP can develop in the segment drained by the dorsal duct. Diagnosis: Magnetic resonance cholangiopancreatography (MRCP) is the most sensitive diagnostic method. Other non-invasive diagnostic methods are endosonography and computed tomography (CT), the latter with lower performance. Treatment: The current trend in acute pancreatitis (AP) where PD is assumed as an etiological factor, is endoscopic resolution, with papillotomy with or without a pancreatic stent.

El páncreas divisum (PD) es la variante anatómica congénita más frecuente del páncreas. Su implicancia etiológica en pancreatitis aguda recurrente (PAR) y pancreatitis crónica (PC) ha sido frecuentemente cuestionada. Anatomía normal y variantes: 80-90% de la población presenta anatomía normal, con salida de secreción pancreática exocrina al duodeno por la papila mayor. Se han descrito 3 variantes anatómicas: PD clásico con conducto ventral visible, pero ausencia total de fusión; PD con ausencia de conducto ventral; y PD incompleto, con conexión rudimentaria entre los conductos ventral y dorsal. Implicancia clínica: Esta variante anatómica da síntomas en menos de 5% de los portadores, asociándose a mayor prevalencia en pacientes con PAR. Sin embargo, se considera probable la relación entre PD y PAR, solo en casos de asociación con mutación del gen CFTR. Pancreatitis crónica (PC) obstructiva se puede desarrollar en el segmento drenado por el conducto dorsal. Diagnóstico: La colangiopancreatografía por resonancia magnética (CPRM) es el método diagnóstico más sensible. Otros métodos diagnósticos no invasivos son la endosonografía y tomografía computada (TC), este último de menor rendimiento. Tratamiento: La tendencia actual en PA donde se asume PD como factor etiológico, es la resolución endoscópica, con papilotomía con o sin stent.

Abnormal Cardiovascular Findings in Acute Pancreatitis: Are They Associated with Disease Severity?

BACKGROUND: Acute pancreatitis (AP), a disease that commonly requires in-hospital treatment, has been associated with a high incidence of abnormal cardiovascular findings (ACFs). We conducted a prospective study to explore the association of these findings with severity of the disease. METHODS: Adult patients with AP diagnosis were prospectively enrolled in an observational study during an 8-month period in a tertiary care center. AP and its severity were defined according to the Revised Atlanta Classification of AP. Subjects were submitted to electrocardiographic, echocardiographic, and serologic testing during the acute period and a 3-month follow-up. The incidence of ACF was compared between two groups: (1) Mild and (2) moderate/severe cases. RESULTS: Twenty-seven patients (mean age 48 ± 17 years) with AP were enrolled; 15 (55%) had mild and 12 (45%) had moderate/severe AP. During the acute episode, 67% had increased pro-brain natriuretic peptide levels; 52% had abnormal electrocardiographic findings; 48% had abnormal echocardiographic findings; and 18% had increased troponin I levels. There was no significant difference in the incidence of ACF between mild and moderate/severe groups. Nineteen patients (70%) had repeated follow-up testing, and most of the initial ACF did not persist. CONCLUSION: ACFs occur in an important proportion of patients during AP episodes. Future research should continue to focus in the association of ACFs and the severity of the disease.

[Recurrent pancreatitis secondary to sphincter of Oddi dysfunction: case report]. / Pancreatitis recurrente secundaria a disfunción del esfínter de Oddi: presentación de un caso.

Dysfunction of the sphincter of Oddi is a rare disease that causes about 20% of recurrent idiopathic pancreatitis. In order to suspect its existence, it is mandatory to have ruled out all other causes of acute pancreatitis. Then, the disease needs to be classified by degree of dysfunction and have a manometry performed as it is considered the gold standard of diagnosis. Manometry is used to guide treatment and its method of choice is usually an endoscopic sphincterotomy. In this article a case of recurrent pancreatitis is discussed, which after a thorough study that ruled out other etiologies, was diagnosed as a pancreatic-type dysfunction of the sphincter of Oddi. The dysfunction was resolved by endoscopic sphincterotomy and the patient had a favorable course without any recurrence of symptoms.

La disfunción del esfínter de Oddi es una patología poco frecuente que es causa de aproximadamente el 20% de las pancreatitis recurrentes idiopáticas. Para sospechar de su existencia es obligatorio haber descartado todas las otras causas de pancreatitis aguda. Luego, sobre la base de la historia clínica, exámenes de laboratorio y estudio con imágenes, se debe realizar una clasificación del tipo de disfunción. Según ello, es necesario llevar a cabo una manometría, considerada el gold estándar para el diagnóstico, y guiar el método de tratamiento, siendo el de elección la esfinterotomía endoscópica. En el presente artículo se discute un caso de pancreatitis recurrente, que luego de un minucioso estudio, y habiendo descartado otras etiologías, se diagnosticó como causa la disfunción del esfínter de Oddi tipo pancreática. Se resolvió mediante esfinterotomía endoscópica, presentando una evolución favorable y sin recurrencia de la sintomatología.

Is there a role for glutamine supplementation in the management of acute pancreatitis? / ¿Tiene algún rol la suplementación con glutamina en el manejo de la pancreatitis aguda?

There is no consensus about the effects of glutamine supplementation for acute pancreatitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified 15 systematic reviews including 31 randomized controlled trials addressing the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded glutamine supplementation might decrease infectious complications in acute pancreatitis, but it is not clear if it affects mortality or length of hospital stay because the certainty of the evidence is very low.

No existe claridad sobre el efecto del uso de glutamina en pacientes con pancreatitis aguda. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos 15 revisiones sistemáticas que en conjunto incluyen 31 estudios aleatorizados pertinentes a la pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la glutamina podría disminuir las complicaciones infecciosas en la pancreatitis aguda, pero no está claro si tiene algún efecto sobre la mortalidad o el tiempo de hospitalización porque la certeza de la evidencia es muy baja.

[Acute pancreatitis in pregnancy]. / Pancreatitis aguda durante el embarazo.

BACKGROUND: Acute pancreatitis is an inflammatory disease that affects the pancreatic tissue, which have been proposed numerous causes, with unpredictable results, it appears as a complication of rare occurrence, so the information on maternal and fetal complications is limited. Objective: Exposing obstetric and perinatal outcomes of patients diagnosed with pancreatitis complicating pregnancy. METHODOLOGY: A retrospective, observational, transverse and descriptive study; data were obtained and analyzed by reviewing medical records of patients diagnosed with pancreatitis and pregnancy. RESULTS: A total of 9 cases were included, corresponding to an incidence of 39/100,000 live births in the time period analyzed. The median age was 22, the mean gestational age at diagnosis was 31 weeks. 4 patients had cesarean delivery and 2 patients natural delivery. 3 patients had Ranson 3, a 2 and other Ranson Ranson 1 the remaining 4 Ranson 0. All products had adequate evolution. A case of maternal death as a complication of the disease was presented, because of metabolic acidosis and ARDS. CONCLUSION: Acute pancreatitis is an entity of variable incidence, which increases their appearance with advancing pregnancy, and can lead to serious complications for pregnant women. It is extremely important to pay attention to early symptoms of the disease, and achieve an accurate diagnosis and provide adequate multidisciplinary management for a better prognosis for maternal-fetal binomial.

Macrophage activation syndrome: A severe and frequent manifestation of acute pancreatitis in 362 childhood-onset compared to 1830 adult-onset systemic lupus erythematosus patients.

OBJECTIVE: We previously reported a case series of acute pancreatitis (AP) and macrophage activation syndrome (MAS) in childhood (cSLE) patients; however, there are no data regarding the comparison of AP and MAS in large populations of cSLE and adult SLE (aSLE). METHODS: A study included 362 cSLE and 1830 aSLE patients. MAS was diagnosed according to preliminary diagnostic guidelines and AP according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Demographic data, clinical features, SLEDAI-2K, SLICC/ACR-DI, and treatment were assessed. RESULTS: Age in MAS patients was significantly lower compared with those without this complication [15 (8.8-55) vs. 33.5 (10.2-45.7) years, p = 0.007]. The frequencies of fever (94% vs. 37%, p = 0.001), leucopenia (82% vs. 19%, p = 0.0001), thrombocytopenia (65% vs. 19%, p = 0.013), hypertriglyceridemia (87% vs. 42%, p = 0.037), and hyperferritinemia (93% vs. 37%, p = 0.011) were also more frequently observed in AP patients with MAS compared in AP patients without MAS. Fever and hyperferritinemia concomitantly were more frequent in the former group (86% vs. 12%, p = 0.0015). Higher and significant frequency of AP in cSLE compared to aSLE patients [12/362 (3.3%) vs. 20/1830 (1.1%), p = 0.003], with similar AP duration [22 (6-60) vs. 15 (4-90) days, p = 0.534]. MAS (85% vs. 30%, p = 0.003) and death by MAS complication (31% vs. 0%, p = 0.017) were significantly higher in children compared with aSLE. CONCLUSIONS: This study provides novel data demonstrating that MAS occur in the majority of cSLE with AP with a higher mortality compared to aSLE. In addition, we identified in AP patients, a cluster of MAS clinical and laboratorial parameters more associated with this complication.

Inverted U-Shaped Relationship between Central Venous Pressure and Intra-Abdominal Pressure in the Early Phase of Severe Acute Pancreatitis: A Retrospective Study.

OBJECTIVE: Many studies have indicated that intra-abdominal pressure (IAP) is positively correlated with central venous pressure (CVP) in severe cases. However, although elevated IAP is common in patients with severe acute pancreatitis (SAP), its relationship with CVP remains unclear. Our study aimed to investigate the association of IAP with CVP in early-phase SAP patients. METHODS: In total, 116 SAP patients were included in this retrospective study. On the first day of hospitalization, blood samples were collected for biochemical examination and cytokine concentration monitoring. Additionally, a urinary catheter and right subclavian vein catheter were inserted for IAP and CVP measurement, respectively. Other routine clinical data were also recorded. RESULTS: Within 24 hours after hospitalization, CVP fluctuated and increased with increasing IAP up to 15.7 mmHg (P = 0.054) but decreased with increasing IAP when the IAP was > 15.7 mmHg (P < 0.001). After adjusting for abdominal perfusion pressure (APP) and mean arterial pressure (MAP), a similar distribution was observed. An inverted U-shaped trend between IAP and CVP was also present in the groups classified according to the patient's sex, local complications, ascites, and serum amylase levels. CONCLUSIONS: CVP and IAP have an inverted U-shaped relationship, with a peak at an IAP of 15.7 mmHg in the early phase of SAP. After this peak, CVP decreases as IAP increases. These results have crucial implications for clinical fluid resuscitation in SAP patients. In particular, because one CVP value might be correlated with different IAP values in patients with the same CVP, the volume of fluid needed might be different.

Clinical and radiological indicators of severity in patients with acute pancreatitis.

UNLABELLED: The purpose of this study was to estimate the degree of association between clinical (Ranson criteria) and radiological variables (Abdominal CT scan) with degree of severity in patients with a diagnosis of acute pancreatitis. METHOD: All patients discharged with the diagnosis of acute pancreatitis from January 1, 2010 through December 31, 2012 in a community hospital were selected (N=174). The following variables were studied: sex; age; weight; height; admission and discharge dates; presence of several chronic conditions; laboratory results included in Ranson criteria; abdominal CT category; outcome, including fatality surgery, and other complications. Analysis included descriptive statistics and Risk-Ratios for complications for different groups of subjects, using clinical and radiological criteria. RESULTS: The incidence rate of complications, including fatality, surgery and organ failure was 36.2%. Factors that showed significant associations with the risk of complication on crude analysis were gallbladder disease with a RR=1.78 ($95% CI: 1.22, 2.60) and abnormal abdominal CT with a RR=1.85 (95% CI: 1.11, 3.07). with multivariate analysis, gallbladder disease, abnormal abdominal CT, and presence of 3 or more Ranson's criteria showed increased risk for complications, but the results did not reach statistical significance. DISCUSSION: The factors that seemed to be associated with increased rate of complications in subjects with acute pancreatitis were gallbladder disease, abnormal abdominal CT, and 3 or more Ranson's criteria. The Results did not show statistical significance probably because of low statistical power of the study.

[Is antibiotic prophylaxis in acute pancreatitis beneficial?]. / ¿Es beneficiosa la profilaxis antibiótica en la pancreatitis aguda?

There is controversy about the effects of prophylactic antibiotics in acute pancreatitis. Searching in Epistemonikos database, which is maintained by screening 19 databases, we identified 15 systematic reviews including 19 randomised studies overall. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded that prophylactic antibiotics may reduce mortality and length of hospitalization in patients with acute pancreatitis, but the quality of the evidence is low. The probability that future evidence change what we know is high.

Acute pancreatitis: the stress factor.

Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications. Etiologies of pancreatitis vary, with gallstones accounting for the majority of all cases, followed by alcohol. Other causes of pancreatitis include trauma, ischemia, mechanical obstruction, infections, autoimmune, hereditary, and drugs. The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion, intracellular activation of proteases, and generation of inflammatory mediators. Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells, whose systemic action ultimately determined the severity of the disease. Indeed, severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome, characterized by a progressive physiologic failure of several interdependent organ systems. Stress occurs when homeostasis is threatened, and stressors can include physical or mental forces, or combinations of both. Depending on the timing and duration, stress can result in beneficial or harmful consequences. While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis, the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention. This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis.

Tratamiento médico de la pancreatitis aguda / Medical treatment of acute pancreatitis

Se revisan los últimos avances en el manejo médico de la pancreatitis aguda. Estos se basan en los cambios que van desde el mayor conocimiento de la fisiopatología y la clínica y el desarrollo de técnicas para el manejo de las complicaciones. El reconocimiento del mal pronóstico dado por la falla persistente de órganos (mayor a 48 horas) y la evolución lenta pero sin severidad de los pacientes con complicaciones locales, ha hecho redefinir la clasificación de la pancreatitis, estratificándose al paciente con cuadros leves, moderados y severos. De los múltiples scores de severidad disponibles para predecir la severidad, APACHE II y BISAP son los que demuestran mayor valor en los trabajos realizados en el Perú. El uso de hidratación enérgica al inicio del cuadro, para evitar el daño a nivel de la microcirculación pancreática, la nutrición enteral precoz cuando se predice un cuadro severo o prolongado, además de la analgesia con narcóticos, son algunas de las medidas que se preconizan en la actualidad. Se discute además la evidencia de realimentar con sólidos en vez de dieta líquida desde el primer día de inicio de dieta a pacientes con pancreatitis leve. Por último se presenta la evidencia del uso de necrosectomía endoscópica como alternativa a la necrosectomía quirúrgica.

We review recent advances in medical management of acute pancreatitis. These are based on changes ranging from increased knowledge of the pathophysiology and clinical development of techniques for the management of complications. The recognition of poor prognosis given persistent organ failure (more than 48 hours) and the slow evolution without severity of patients with local complications, has redefined the classification of pancreatitis, stratifying the patient with mild, moderate and severe. Of the many available severity scores to predict severity, APACHE II and BISAP are demonstrating greater value on work done in Peru. Using vigorous hydration to avoid damage to the pancreatic microcirculation level, early enteral nutrition when it predicts a severe or prolonged disease in addition to narcotic analgesia, are some of the measures advocated in the present. I also discuss the evidence of refeeding with solid rather than liquid diet to patients with mild pancreatitis. Finally, evidence of safety and good outcomes of endoscopic necrosectomy is presented as an alternative to surgical necrosectomy.

Nitric oxide synthase inhibition reduces albumin induced lung damage in acute pancreatitis.

BACKGROUND/OBJECTIVES: Colloid resuscitation in acute pancreatitis (AP) is a matter of controversy due to the possible deleterious effect on lung function. A previous study demonstrates that albumin administration increases lung damage in burns and this effect can be reversed by inducible nitric oxide synthase (iNOS) inhibition. This study evaluates the effects of S-methylisothiourea (SMT), a specific iNOS inhibitor, on lungs and pancreas of rats with AP receiving intravenous albumin. METHODS: AP was induced in Wistar rats by intraductal 5% taurocholate injection. To evaluate the effect of albumin on lung damage, animals received IV saline or human albumin immediately after AP (Groups: Saline and Albumin). To evaluate the effect of iNOS inhibition on lung damage, SMT was given immediately after AP (Group Saline+SMT, and Group Albumin+SMT). At 12 h after AP induction, serum amylase activity, lung vascular permeability and myeloperoxidase (MPO) activity were evaluated. Lung and pancreas histological analysis were performed. RESULTS: Serum amylase activity, pancreatic edema, lung vascular permeability, MPO activity, and inflammatory infiltration were significantly increased after AP. Albumin administration increased lung vascular permeability, inflammatory infiltration, and pancreatic edema compared to saline administration (p < 0.05). Albumin administration with SMT reduced lung vascular permeability, MPO activity, and inflammatory infiltration compared to albumin administration alone (p < 0.05). CONCLUSION: Lung and pancreatic damage induced by albumin administration for restoration of plasma volume in AP are reduced by iNOS inhibition. Awareness of this fact may be useful in high-risk patients who need to receive albumin for volume replacement.

Abdominal hyperalgesia in secretory phospholipase A2-induced rat pancreatitis: distinct roles of NK1 receptors.

We investigated the potential of secretory phospholipase A(2) (sPLA(2))-induced pancreatitis to promote abdominal hyperalgesia, as well as to depolarize sensory fibres in vitro using a grease-gap technique. Pancreatitis was induced by the injection of sPLA(2) from Crotalus durissus terrificus (sPLA(2)Cdt, 300µgkg(-1)) venom into the common bile duct of rats. Pancreatic inflammatory signs, serum amylase levels and abdominal hyperalgesia were evaluated in rats treated or not with SR140333, a tachykinin NK(1) receptor antagonist. Injection of sPLA(2)Cdt caused pancreatic oedema formation and increased pancreatic neutrophil infiltration and serum amylase at 4h, which returned to normality by 24h, except for the neutrophil infiltration, which was still increased at this time point. Animals injected with sPLA(2) exhibited a lower withdrawal threshold to electronic von Frey stimulation in the upper abdominal region at 4h, but not 24h, post-injection when compared with saline-injected rats. Pre-treatment of animals with SR140333 significantly reduced the sPLA(2)Cdt-induced abdominal hyperalgesia, without affecting the other parameters. Neither sPLA(2)Cdt nor sPLA(2) from Naja mocambique mocambique venom depolarized capsaicin-sensitive sensory fibres from rat vagus nerve, but they decreased the propagated compound action potentials in both A and C fibres. These data show for the first time that NK(1) receptors play an important role in the early abdominal hyperalgesia in a rat model of sPLA(2)-induced pancreatitis, suggesting that these receptors are of importance in the development of pain in the pancreatitis condition. We also provide evidence that sPLA(2)s do not directly depolarize sensory fibres in vitro.