Immune-Related Pancreatitis Caused by Immune Checkpoint Inhibitor Nivolumab:Report of One Case / 中国医学科学院学报

In recent years,great progress has been achieved in the application of immune checkpoint inhibitors (ICI) in tumor immunotherapy.However,a variety of adverse reactions induced by ICI have been reported.Despite the high overall incidence of adverse reactions caused by ICI,some adverse reactions,such as immune-related pancreatitis,are rare in clinical practice.In this paper,a case of immune-related pancreatitis after treatment of advanced gastric cancer with nivolumab was identified.We analyzed the cause,treatment,incidence,and risk factors of the adverse reaction,aiming to improve the clinical diagnosis,treatment,and safe medication of rare adverse reactions associated with ICI.

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.

Comparación entre uso y no uso de antibióticos profilácticos en pancreatitis aguda grave: ensayo clínico aleatorizado: reporte preliminar / Comparison between use and non-use of prophylactic antibiotics in severe acute pancreatitis: randomized clinical trial: preliminary report

Resumen Introducción: La pancreatitis aguda es una enfermedad frecuente en el país, con una tasa de mortalidad de 10%-30%. La administración profiláctica de antibióticos ha sido parte del tratamiento de pancreatitis aguda grave (PAG), por la teórica prevención de complicaciones infecciosas y reducción de mortalidad. Sin embargo, la evidencia científica disponible es controversial. Objetivo: Demostrar que los antibióticos profilácticos no disminuyen las complicaciones locales y/o sistémicas, requerimiento de Unidad de Paciente Crítico (UPC), ni mortalidad en PAG. Definimos PAG como APACHE II ≥ 8 o PCR ≥ 150 o falla multiorgánica. Material y Método: Ensayo clínico aleatorizado, con aleatorización simple mediante tabla electrónica (uso o no uso de antibióticos profilácticos) de pacientes con PAG. En el grupo que usó antibióticos profilácticos se utilizó ciprofloxacino y metronidazol por 7 días. El resto del manejo no tuvo variación. Resultados: n = 71, dos grupos aleatorizados; Grupo 1 (n = 35), sin uso de antibióticos profilácticos, y grupo 2 (n = 36) con uso de profilaxis antibiótica. 12 pacientes (16%) requirieron UPC; 6 pacientes del grupo 1, y 6 del grupo 2 (p = 0,957). Siete pacientes (9,8%) tuvieron algún tipo de complicación, 3 en el grupo 1 y 4 en el grupo 2 (p = 0,516). El promedio de estancia hospitalaria fue 18,2 ± 9,5 días en el grupo 1, y 22,6 ± 29.2 días en el grupo 2 (p = 0,495). Mortalidad: 1 paciente (1,41%) en el grupo 2 (p = 0,493). Conclusión: En este reporte preliminar, el uso de antibióticos profilácticos en PAG no mostró reducir las complicaciones, necesidad de cama en UPC, ni la mortalidad.

Introduction: Acute pancreatitis is a common disease in the country, with a mortality rate of 10%-30%. The prophylactic administration of antibiotics has been part of the treatment of severe acute pancreatitis (SAP), due to the theoretical prevention of infectious complications and mortality reduction. However, the available scientific evidence is controversial. Objective: To demonstrate that prophylactic antibiotics do not reduce local and/or systemic complications, critical patient unit (CPU) requirement, or mortality in SAP. We define SAP as APACHE II ≥ 8 or PCR ≥ 150° or multiorgan failure. Material and Method: Randomized clinical trial, with simple randomization by electronic table (use or non-use of prophylactic antibiotics) of patients with SAP. In the group that used prophylactic antibiotics, ciprofloxacin and metronidazole were used for 7 days. Results: n = 71, two randomized groups; Group 1 (n = 35), without the use of prophylactic antibiotics, and group 2 (n = 36) with the use of antibiotic prophylaxis. 12 patients (16%) required CPU; 6 patients from group 1, and 6 from group 2 (p = 0.957). Seven patients (9.8%) had some type of complication, 3 in group 1 and 4 in group 2 (p = 0.516). The average hospital stay was 18.2 ± 9.5 days in group 1, and 22.6 ± 29.2 days in group 2 (p = 0.495). Mortality: 1 patient (1.41%) in group 2 (p = 0.493). Conclusion: In this preliminary report, the use of prophylactic antibiotics in SAP was not shown to reduce complications, need for bed in CPU, or mortality.

The Effect of Thymosin Alpha 1 on Severe Acute Pancreatitis in Rats / Estudios sobre el efecto de la timosina alfa 1 sobre la pancreatitis aguda grave en ratas

ABSTRACT Objective: To observe the effect of thymosin alpha l (Tα1) on severe acute pancreatitis (SAP) in rats. Methods: Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups (eight in each group): control group (Group A), SAP group (Group B) and Tα1 treatment group (Group C). Animal models of SAP were made by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Rats in Group C were treated with Tα1 (6 mg/kg) via intraperitoneal administration prior to SAP modelling. Eight rats in each group were sacrificed at 12 hours, respectively, after modelling. The serum levels of amylase, tumour necrosis factor-α (TNF-α), interleukin-lβ (IL-lβ and interleukin-6 (IL-6) were detected in each group. The pathological scores of the tissue in the pancreas head were observed by light microscopy. Results: The levels of serum amylase of Group B were 6378 ± 538 U/L, which were significantly higher than those (4587 ± 478 U/L) of Group C (p < 0.05). The levels of serum TNF-α of Group B were 360.32 ± 28.67 pg/mL, which were higher than those (269.99 ± 26.11 pg/mL) of Group C (p < 0.05). The levels of serum IL-lβ of Group B were 435.93 ± 36.00 pg/mL, which were higher than those (312.42 ± 17.89 pg/mL) of Group C (p < 0.05). The levels of serum IL-6 of Group B were 433.90 ± 28.36 pg/mL, which were higher than those (289.98 ± 23.00 pg/mL) of Group C (p < 0.05). The pancreatic pathological scores of Group B were 13.34 ± 2.19, which were higher than those (6.39 ± 1.86) of Group C (p < 0.05). Conclusion: Thymosin alpha 1 could decrease proinflammatory cytokines and reduce pancreas injury and had a protective effect in rats with SAP. This provides a new strategy for the clinical treatment of SAP.

RESUMEN Objetivo: Observar el efecto de la timosina alfa l (Tα1) sobre la pancreatitis aguda grave (PAG) en ratas. Métodos: Veinticuatro ratas Sprague-Dawley adultas machos fueron divididas aleatoriamente en tres grupos (ocho en cada grupo): grupo de control (grupo A), grupo de PAG (grupo B) y grupo de tratamiento con Tα1 (grupo C). Los modelos animales de PAG fueron creados mediante inyección retrógrada de taurocolato de sodio al 5% en el conducto biliopancreático. Las ratas del grupo C se trataron con Tα1 (6 mg/kg) via administración intraperitoneal antes del modelado de PAG. Las ocho ratas en cada grupo fueron sacrificadas a las 12 horas, respectivamente, después del modelado. Los niveles séricos de amilasa, factor-α de necrosis tumoral (TNF-α), interleucina-β (Il-β) e interleucina-6 (IL-6) fueron detectados en cada grupo. Las puntuaciones patológicas del tejido en la cabeza del páncreas fueron observadas mediante microscopía de luz. Resultados: Los niveles de amilasa sérica del grupo B fueron 6378 ± 538 U/L, y resultaron significativamente más altos (p < 0.05) que los niveles 4587 ± 478 U/L del grupo C. Los niveles séricos de TNF-α del grupo B fueron 360.32 ± 28.67 pg/mL, y resultaron ser más altos (p < 0.05) que los 269.99 ± 26.11 pg/mL del grupo C. Los niveles séricos de Il-β del grupo B fueron 435.93 ± 36.00 pg/mL, y fueron más altos (p < 0.05) que los 312.42 ± 17.89 pg/mL) del grupo C. Los niveles de suero IL-6 del grupo B fueron 433.90 ± 28.36 pg/mL, y resultaron ser más altos (p < 0.05) que los 289.98 ± 23.00 pg/mL del grupo C. Las puntuaciones patológicas pancreáticas del grupo B fueron 13.34 ± 2.19, y resultaron ser más altas (p < 0.05) que las puntuaciones 6.39 ± 1.86 del grupo C. Conclusión: La timosina alfa pudo disminuir las citoquinas proinflamatorias y reducir la lesión del páncreas, y tuvo un efecto protector en las ratas con PAG. Esto ofrece una nueva estrategia para el tratamiento clínico de PAG.

Effects of baicalin on inflammatory reaction, oxidative stress and PKDl and NF-kB protein expressions in rats with severe acute pancreatitis

Abstract Purpose: To investigate the effects of baicalin on inflammatory reaction, oxidative stress and protein kinase D1 (PKD1) and nuclear factor-kappa B (NF-κB) protein expressions in severe acute pancreatitis (SAP) rats. Methods: Sixty rats were divided into sham operation, model, and low-, medium- and high-dose baicalin group. SAP model was established in later 4 groups. The later 3 groups were injected with 0.1, 0.2 and 0.4 ml/100 g 5% baicalin injection, respectively. At 12 h, the serum SAP related indexes and inflammatory factors, peripheral blood CD3 and γδT cell percentages, wet/dry ratio and pancreas ascites volume, oxidative stress indexes and PKD1 and NF-κB protein expressions in pancreatic tissue were determined. Results: Compared with model group, in high-dose baicalin group the wet/dry ratio and ascites volume, serum amylase level, phospholipase A2 activity, TNF-α, IL-1 and IL-6 levels, and pancreatic malondialdehyde level and PKD1 and NF-κB protein expression were significantly decreased (P < 0.05), and peripheral blood CD3 and γδT cell percentages and pancreatic superoxide dismutase and glutathione peroxidase levels were significantly increased (P < 0.05). Conclusion: Baicalin can resist the inflammatory reaction and oxidative stress, and down-regulate protein kinase D1 and nuclear factor-kappa B protein expressions, thus exerting the protective effects on severe acute pancreatitis in rats.

Individualized vancomycin dosing for a patient diagnosed as severe acute pancreatitis with concurrent extracorporeal membrane oxygenation and continuous veno-venous hemofiltration therapy: a case report / 北京大学学报(医学版)

Pharmacokinetic parameters can be significantly altered for acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO) and continuous veno-venous hemofiltration therapy (CVVH). Here we reported a case of individualized vancomycin dosing for a patient diagnosed as severe acute pancreatitis treated with concurrent ECMO and CVVH. A 65 kg 32-year-old woman was admitted to hospital presented with severe acute pancreatitis (SAP), respiratory failure, metabotropic acidosis and hyperkalemia. She was admitted to intensive care unit (ICU) on hospital day 1 and was initiated on CVVH. She progressed to multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) on ICU day 2, and veno-venous ECMO was instituted. Several catheters were inserted into the body to support ECMO, CVVH and pulse indicator continuous cardiac output (PiCCO), so vancomycin was prescribed empirically on ICU day 3 for prevention of catheter-related infection. Given the residual renal function and continuous hemofiltration intensity on day 3, vancomycin bolus of 1 000 mg was prescribed, followed by a maintenance dose of 500 mg every 8 hours. On ICU day 4, a vancomycin trough serum concentration of 14.1 mg/L was obtained before the fourth dose, which was within the target range of 10-20 mg/L. By ICU day 7, vancomycin dosage was elevated to 1.0 g every 12 hours because of aggravated infection and improved kidney function. On ICU day 14, a vancomycin trough serum concentration of 17 mg/L was obtained. Her white blood cell (WBC) and neutrophil percentage (Neut%) dropped to the normal level by ICU day 19. This vancomycin regimen was successful in providing a target attainment of trough serum concentration ranging from 10-20 mg/L quickly and in controlling infection-related symptoms and signs properly. With the help of this case report we want to call attention to the clinically significant alteration in vancomycin pharmacokinetics among critically ill patients. Individualized vancomycin dosing regimens and therapeutic drug monitoring are necessary for critically ill patients receiving CVVH and ECMO to ensure that the target serum vancomycin levels are reached to adequately treat the infection and avoid nephrotoxicity.

[RETRACTED ARTICLE] Therapeutic effect and potential mechanism of pioglitazone in rats with severe acute pancreatitis

Caspase recruitment domain-containing protein 9 (Card9) is located upstream of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) inflammatory pathways. This study investigated the therapeutic effect and potential mechanism of pioglitazone in rats with severe acute pancreatitis (SAP). SAP was induced by a retrograde infusion of 5.0% sodium taurocholate into the biliopancreatic duct of Sprague Dawley rats (n=54), which were then treated with pioglitazone. Blood and pancreatic tissues were harvested at 3, 6, and 12 h after SAP induction. Pancreatic pathological damage was evaluated by hematoxylin and eosin staining. Serum amylase, serum pro-inflammatory cytokines, and pancreatic myeloperoxidase (MPO) activities were determined by enzyme-linked immunosorbent assay. The expression of Card9 mRNA and protein in pancreatic tissues was detected by real-time polymerase chain reaction and western blotting. Pioglitazone had a therapeutic effect in treating rats with SAP by decreasing the level of amylase activity, ameliorating pancreatic histological damage, decreasing serum pro-inflammatory cytokine levels and tissue MPO activity, and downregulating the expression of NF-κB, p38MAPK, and Card9 mRNAs and proteins (P<0.05). The present study demonstrated that the inhibition of Card9 expression could reduce the severity of SAP. Card9 has a role in the pathogenic mechanism of SAP.

Pancreatitis inducida por drogas / DRUG-INDUCED ACUTE PANCREATITIS

Introducción. Las Reacciones Adversas Medicamentosas (RAM) son una de las principales causas de hospitalización y mortalidad en el sistema de salud (en países desarrollados y en vías de desarrollo), y la relevancia va creciendo año tras año. El objetivo de este estudio fue determinar la incidencia de pancreatitis aguda inducida por drogas y los grupos de drogas que más frecuentemente se ven involucrados. Material y Métodos: Se realizó un estudio retrospectivo tomando como fuente una base de datos de farmacovigilancia del Hospital General de Agudos ¨Dr. Cosme Argerich¨ con información de los últimos cinco años. Resultados: Se detectaron siete casos de pancreatitis inducida por drogas de los cuales fueron dos por quimioterápicos (lapatinib e imatinib), tres por antirretrovirales, uno por inmunosupresores y uno por antihipertensivos (enalapril). En cinco casos fue necesaria la hospitalización y un evento fue mortal. Conclusión: De acuerdo a la bibliografía internacional, a pesar de que los fármacos son solo responsables del 1-2% de casos de pancreatitis aguda inducida por drogas, es importante destacar que es difícil encontrar la causalidad entre el fármaco y el cuadro del paciente, lo que lleva muchas veces a un subdiagnóstico como una pancreatitis idiopática. En el presente estudio, estos casos deben considerarse por su impacto, no solo a nivel de la salud del paciente

Adverse Drug Reactions (ADR) are nowadays an increasing problem in health systems and represents between the 4th and the 6th cause of death in developing countries. Drug induced pancreatitis in a rare ADR but reports are increasing with antiretroviral drugs and new antiviral and anticancer drugs. The aim of this study was to determine the incidence of drug ­ induced pancreatitis in a tertiary care hospital. We used a pharmacovigilance database applying de Naranjo Score for drug causality in adverse medical events. From a total of 2990 ADR we detected 7 cases of pancreatitis. Antiretroviral and anticancer drugs were the drugs most frequently involved.

Heparin and insulin in the management of hypertriglyceridemia-associated pancreatitis: case series and literature review

SUMMARY Severe hypertriglyceridemia accounts for up to 7% of all cases of acute pancreatitis. Heparin and insulin activate lipoprotein lipase (LPL), thereby reducing plasma triglyceride levels. However, the safety and efficacy of heparin and insulin in the treatment of hypertriglyceridemia-associated acute pancreatitis have not been well established yet. We successfully used heparin and insulin as first-line therapy in four consecutive patients with acute pancreatitis secondary to hypertriglyceridemia. In a literature search, we revised almost all reports published to date of patients managed successfully with this combination. Heparin and insulin appear to be a safe, effective, and inexpensive first-line therapy for hypertriglyceridemia-associated acute pancreatitis.

Neoplasia mucinosa papilar intraductal como hallazgo en paciente con pancreatitis / Intraductal papillary mucinous neoplasm as a finding in a patient with pancreatitis

Introducción: La neoplasia mucinosa intraductal papilar (NMIP) del páncreas es una masa quística dependiente del sistema ductal pancreático. Presentación del caso: Paciente de 65 años, femenino, antecedentes mórbidos de diabetes mellitus tipo 2 sin tratamiento e hipertensión arterial esencial en tratamiento. Consulta por cuadro clínico de 9 horas caracterizado por epigastralgia opresiva/urente de inicio súbito, con irradiación en faja a dorso, intensidad EVA 10/10, asociado a náuseas, sin vómitos, diarrea ni fiebre. Ingresa hemodinámicamente estable, afebril, hidratada, sin signos de irritación peritoneal, sin masas palpables y con ruidos hidroaéreos presentes. Destaca en exámenes de laboratorio: amilasa 390 UI/L, lipasa 1760.9 U/L.Se diagnostica pancreatitis aguda y por sospecha de etiología biliar se realiza colangiopancreatografia por resonancia magnética (CPRM). Como hallazgo se describe formación quística de 13mm a nivel de la transición entre cuerpo y cola del páncreas, compatible con NMIP de rama secundaria y se diagnostica pancreatitis aguda leve Balthazar B de etiología litiásica. Se realiza manejo de la pancreatitis y debido a las características del NMIP encontrado el plan es seguimiento tomográfico en 2 a 3 años. Discusión: Las NMIP son hallazgos imagenológicos frecuentemente incidentales, pues la mayoría de los pacientes se mantienen asintomáticos. La característica imagenológica habitual corresponde a una lesión quística multilocular lobulada situada en el proceso unciforme y en contigüidad con el conducto pancreático principal dilatado. Según las características de la lesión, el manejo puede ser quirúrgico o seguimiento. Las tasas de supervivencia global a 5 años se acercan a 61-87%

Introduction: Pancreatic intraductal papillary mucinous neoplasm (IPMN) is a cystic mass dependent on the pancreatic ductal system. Case report: Female, 65 years old, with morbid history of type 2 diabetes without treatment and essential hypertension under treatment. Consults by clinical profile of 9 hours characterized by oppressive/ burning epigastralgia of sudden onset, with irradiation in sash to back, intensity EVA 10/10, associated with nausea, without vomiting, diarrhea or fever. Is hemodynamically stable, afebrile, hydrated, with no signs of peritoneal irritation, with no palpable masses and with bowel sounds present. Highlights in laboratory tests: amylase 390 UI / L, lipase 1760.9 U / L. Acute pancreatitis is diagnosed and due the suspicion of biliary etiology a magnetic resonance cholangiopancreatography is performed. A cystic formation of 13mm is described at the transition level between body and tail of the pancreas, compatible with branch duct type IPMN and acute mild pancreatitis Balthazar B of lithiasic etiology is diagnosed. Management of pancreatitis is performed and because of the characteristics of the IPMN found the plan is tomographic follow-up in 2 to 3 years. Discussion: IPMN are frequently incidental imaging findings, as most patients remain asymptomatic. The usual imaging characteristic corresponds to a lobulated multilocular cystic lesion located in the unicular process and in contiguity with the main dilated pancreatic duct. Depending on the characteristics of the lesion, the management may be surgical or follow-up. The 5-year survival rates approach 61-87%.

Therapeutic effects of ellagic acid on L-arginin induced acute pancreatitis

ABSTRACT PURPOSE: To investigate the therapeutic effects of ellagic acid on L-arginin ınduced acute pancreatitis in rats. METHODS: Thirty-two were split into four groups. Group 1 (control) rats were performed only laparotomy, no drugs were administered. Group 2 (control+EA) rats were administered 85mg/kg EA orally. Rats were sacrificed by cardiac puncture 24 hours after the administration. Group3 (AP) 24 hours after intraperitoneal L-arginine administration, rats were sacrificed by cardiac puncture. Group 4 (EA)-(AP): 85mg/kg EA was administered orally after the L-arginine administration. 24 hours later, rats were sacrificed by cardiac puncture. Serum TNF-α, IL-1β, IL-6, total oxidative status (TOS), total antioxidant capacity (TAC), amylase levels were determined in all groups. RESULTS: Group 3 (AP) rats showed significantly raised TOS level as compared to Group1 (control) rats (p<0.001). Following the EA therapy, a decrease in TOS was observed in Group 4 (AP+EA). TAC levels were significantly raised in the Group 4 (AP+EA) compared to the Group 3 (AP) (p=0.003). Group 3 (AP) showed significantly increased TNF-α, IL-1β and IL-6 serum levels as compared to Group 4 (AP+EA). Histopathological changes were supported our result. CONCLUSION: The healing effects of ellagic acid on inflammatory and oxidative stress were confirmed by histopathological and biochemical evaluations of the pancreatic tissue.

Sucessfull management of bilateral presumed Candida endogenous endophtalmitis following pancreatitis / Tratamento bem sucedido de caso de endoftalmite endógena bilateral presumida por Candida pós pancreatite

ABSTRACT Endogenous endophthalmitis is a rare, and frequently devastating, ophthalmic disease. It occurs mostly in immunocompromised patients, or those with diabetes mellitus, cancer or intravenous drugs users. Candida infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within days to weeks of fungemia. The association of treatment for pancreatitis with endophthalmitis is unusual. Treatment with broad-spectrum antibiotics and total parenteral nutrition may explain endogenous endophthalmitis. We report the case of a patient with pancreatitis treated with broad-spectrum antibiotics and total parenteral nutrition who developed bilateral presumed Candida endogenous endophthalmitis that was successfully treated with vitrectomy and intravitreal amphotericin B.

RESUMO Endoftalmite endógena é uma condição oftalmológica rara e frequentemente devastadora. Ocorre principalmente em pacientes imunocomprometidos, diabéticos, com neoplasias ou usuários de drogas intravenosas. Infecção por Candida é a causa mais comum de endoftalmite endógena. A candidíase ocular ocorre de dias a semanas após a fungemia. A associação de endoftalmite e o tratamento para pancreatite é rara. O tratamento com antibióticos de amplo espectro e alimentação parenteral total podem explicar uma endoftalmite endógena. Neste estudo, reportamos o caso de um paciente com pancreatite tratado com antibióticos de amplo espectro e alimentação parenteral total que desenvolveu endoftalmite endógena bilateral presumida por Candida que foi tratado com sucesso com vitrectomia e injeção intravítrea de amfotericina B.

Galunisertib (LY2157299), a transforming growth factor-β receptor I kinase inhibitor, attenuates acute pancreatitis in rats

Galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGF-βRI), is the only known TGF-β pathway inhibitor. In the present study, we investigated the effect of galunisertib on taurocholate (TAC)-induced acute pancreatitis (AP) in rats, and the role of TGF-β and NF-κB signaling pathways. AP was induced by infusion of TAC into the pancreatic duct of Sprague-Dawley male rats (n=30). The rats (220±50 g) were administered galunisertib intragastrically [75 mg·kg-1·day-1 for 2 days (0 and 24 h)]. Serum IL-1β, IL-6, TNF-α, amylase (AMY), lipase (LIP), and myeloperoxidase (MPO) levels were measured by ELISA. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA); NF-κBp65 and TGF-β1 proteins, as well as TGF-βRI and p-Smad2/3 proteins, were detected by western blot assay. Cell apoptosis was detected by TUNEL assay. H&E staining was used to evaluate the histopathological alterations of the pancreas. Galunisertib treatment attenuated the severity of AP and decreased the pancreatic histological score. In addition, number of apoptotic cells were significantly increased in the galunisertib-treated group (16.38±2.26) than in the AP group (8.14±1.27) and sham-operated group (1.82±0.73; P<0.05 and P<0.01, respectively). Galunisertib decreased the expression levels of TGF-βRI and p-Smad2/3 and inhibited NF-κB activation and p65 translocation compared with the sham-operated group. Furthermore, serum IL-1β, IL-6, TNF-α, AMY and LIP levels and tissue MPO activity were significantly decreased in the galunisertib-treated group. Our data demonstrate that galunisertib attenuates the severity of TAC-induced experimental AP in rats by inducing apoptosis in the pancreas, inhibiting the activation of TGF-β signals and NF-κB as well as the secretion of pro-inflammatory cytokines.

Pancreatitis aguda en paciente con lupus eritematoso sistémico / Acute pancreatitis in a patient with systemic lupus erythematosus

Se presenta caso de mujer joven portadora de lupus eritematoso sistémico que consulta por síntomas gastrointestinales y fiebre. Por laboratorio y tomografía abdominal se llega a diagnóstico de pancreatitis aguda que mejora con corticoides.

Report case of a young women carrier of systemic lupus erythematosus who comes to consult with gastrointestinal symptoms and fever. The diagnosis of Acute Pancreatitis is reached with laboratory exams and abdominal CT. Corticosteroids have afficacy for the treatment.

Un desafío clínico: diagnóstico diferencial de pancreatitis autoinmune y cáncer de páncreas. El valor del tratamiento esteroidal de prueba / Focal autoimmune pancreatitis versus pancreatic cancer: value of steroid treatment in the diagnosis

Background: The differential diagnosis of pancreatic cancer and focal forms of autoimmune pancreatitis is complicated since serological tests, IgG4 and CA 19-9 have a low sensibility and specificity. CT scan and magnetic resonance imaging provide clear differentiation in the majority, but not in all cases. Endosonography is the most precise diagnostic procedure and allows to obtain samples for cytology or even histological studies. Aim: To report the experience with 18 cases of focal autoimmune pancreatitis and three cases of pancreatic cancer. Material and Methods: Review of medical records of 18 patients with focal autoimmune pancreatitis and 3 cases of pancreatic cancer. Results: The eighteen patients with focal autoimmune pancreatitis were treated with prednisone 0.5 mg/kg/day obtaining a complete clinical and morphological recovery in all. However, 3 had a relapse and one was operated. During follow up, none has developed a pancreatic cancer. The 3 patients with pancreatic cancer did not respond to steroidal treatment. Conclusions: The quick and dramatic response to steroids of autoimmune pancreatitis, may be useful and is recommended for the differential diagnosis with pancreatic cancer.

Aggravation of Hypertriglyceridemia and Acute Pancreatitis in a Bipolar Patient Treated with Quetiapine

Pancreatitis is a very rare adverse effect of quetiapine treatment, with only 5 cases of quetiapine-associated pancreatitis reported in the English literature to date. Herein, we report one patient who developed severe hypertriglyceridemia (>1000 mg/dL) after quetiapine administration, resulting in acute pancreatitis. An analysis of the underlying pathogenic mechanisms and a review of relevant literature are also presented. Clinicians should be aware of the potentially life-threatening metabolic disturbances and/or pancreatitis associated with quetiapine therapy.

Pancreatitis autoinmune: sospecha, diagnóstico diferencial y manejo / Autoimmune pancreatitis: suspicion, differential diagnosis and management

Autoimmune pancreatitis was described only in the second half of the last century. Two types of the disease have been identified: Type 1; Lymphoplasmacytic sclerosing pancreatitis (LPSP), and Type 2, idiopathic duct centric pancreatitis (IDCP). Type 1 AIP is characterized by IgG4 positive lymphoplasmacytic infiltration, storiform periductal fibrosis and obstructive venulitis. It is frequently associated with other autoimmune diseases, it forms part of a systemic IgG4 dependent autoimmune disease, with a tendency of recurrence or progressive pancreatic damage in about 30 percent of the cases. In Type 2, histology reveals ductal destruction by granulocytic epithelial lesions. This type is considered as a pancreas-specific disease, the only association observed is with inflammatory bowel disease. After a successful treatment, recurrence of this disease is an exception. The basis of the diagnosis of AIP is serology and imaging methods. Computed Tomography (CT) scan and magnetic resonance have a good sensibility in the differential diagnosis of pancreatic lesions. Endosonography (EUS) with fine-needle aspiration (FNA) would be the best method to exclude pancreatic cancer. However, its limited accessibility in Chile and high costs make its use rather exceptional. The treatment of AIP is steroids, 0.5-1 mg/kg/day Prednisone for a relatively short period, without the need of permanent treatment in most cases. While possibility of recurrence or progressive pancreatic damage exists, the prognosis is generally good.

La pancreatitis autoinmune es una enfermedad descrita en la segunda mitad del siglo pasado. Se diferencian dos tipos, la pancreatitis esclerosante linfoplasmocítica (PELP-Tipo 1) y la pancreatitis idiopática conducto-destructivo (PICD-Tipo 2). El Tipo 1 está caracterizado por infiltración linfoplasmocitaria por células IgG4 positivas, fibrosis periductal y venulitis obstructiva. Se asocia con otras enfermedades autoinmunes, probablemente forma parte de una enfermedad sistémica IgG4 dependiente, clínicamente tiene la tendencia de recaídas o progresión del daño pancreático en 30 por ciento de los casos. En el Tipo 2 se ve la destrucción de conductos por lesiones granulocíticas epiteliales, considerada como enfermedad específica del páncreas, se asocia sólo con enfermedad inflamatoria intestinal. Después de su recuperación, la recaída es una excepción. El diagnóstico de la PAI se basa en métodos serológicos y morfológicos. Tomografía computada y resonancia nuclear magnética son de buen rendimiento en el diagnóstico diferencial de las enfermedades pancreáticas. Endosonografía con biopsia con aguja fina sería el mejor método para descartar cáncer de páncreas; su disponibilidad en Chile es más bien de excepción. El tratamiento es prednisona 0,5- 1,0 mg/kg/día por un período relativamente corto, sin necesidad de tratamiento de mantención en la gran mayoría de los casos. El pronóstico es bueno, aunque existe posibilidad de recaída o progresión hacia la cronicidad.

Intensive insulin therapy in severe acute pancreatitis: a meta-analysis and systematic review / Terapia intensiva de insulina en la pancreatitis aguda severa: meta-análisis y revisión sistemática

OBJECTIVE: To assess the effect of intensive insulin therapy on outcomes of patients with severe acute pancreatitis. METHODS: Relevant literatures cited in these electronic databases: Medline, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI) database, and Excerpta Medical database (Embase) were systematically searched for randomized controlled trials (RCTs) in which intensive insulin therapy was used in severe acute pancreatitis. Length of hospitalization, acute physiology and chronic health evaluation II (APACHE II) score, incidence of complications, and adverse effects were recorded for statistical analysis. The methodological quality of the eligible studies was assessed by Jadad scale. The results were analysed by Revman 4.3 software. RESULTS: Three studies, which included a total of 118 cases, were finally reviewed. The methodological quality of the trials varied substantially. In patients with severe acute pancreatitis, intensive insulin therapy was associated with shorter length of hospitalization (weighted mean difference (WMD) = -12.13, 95% confidence interval (CI) [-15.48,8.78], p > 0.00001) and lower APACHE II score after 72 hours treatment (WMD = -3.80, 95% CI [-4.88,2.72], p> 0.00001). One study reported insulin-related adverse event. CONCLUSION: In patients with severe acute pancreatitis, intensive insulin therapy could relieve the patient's condition earlier and shorten the length of hospitalization without serious adverse effect.

OBJETIVO: Evaluar el efecto de la terapia intensiva de insulina en la evolución clínica de los pacientes afligidos de pancreatitis aguda severa. MÉTODOS: La literatura pertinente citada a partir de las siguientes bases electrónicas de datos: Medline, Base de datos de literatura biomédica china, Base de datos de la infraestructura nacional china de conocimientos (CNKI), y la Excerpta Medical Database (Embase). Todas estas bases de datos fueron investigadas sistemáticamente en busca ensayos controlados aleatorios (RCT), en los cuales la terapia de insulina intensiva se usó en la pancreatitis aguda severa. El tiempo de hospitalización, la fisiología aguda, y la puntuación de la evaluación de salud crónica II (APACHE II), la incidencia de complicaciones, así como los efectos adversos, fueron registrados para el análisis estadístico. La calidad metodológica de los estudios elegibles fue evaluada mediante la escala de Jadad. Los resultados se analizaron mediante el software Revman 4.3. RESULTADOS: Finalmente se examinaron tres estudios que incluyeron un total de 118 casos. La calidad metodológica de los ensayos varió sustancialmente. En los pacientes con pancreatitis aguda severa, la terapia de insulina intensiva estuvo asociada con una estadía hospitalaria más corta (diferencia media ponderada WMD = -12.13, 95% intervalo de confianza (CI) [-15.48, 8.78], p < 0.00001) y una puntuación APACHE II más baja después de 72 horas de tratamiento (WMD = -3.80, 95% CI [-4.88, 2.72], p < 0.00001). Un estudio reportó eventos adversos relacionados con la insulina. CONCLUSIÓN: En los pacientes con pancreatitis aguda severa, la terapia intensiva de insulina podría aliviar la condición del paciente más rápidamente, y acortar el tiempo de hospitalización sin serios efectos adversos.

Effect of Proton Pump Inhibitor in Patients with Acute Pancreatitis: Pilot Study / 대한소화기학회지

BACKGROUND/AIMS: Oxygen free radicals play an important role in acute pancreatitis. Pantoprazole as a proton pump inhibitor (PPI) has pancreatic anti-secretory effect and a pronounced inhibitory reactivity towards hydroxyl radicals. The objective of the study was to investigate the effect of pantoprazole on the course of acute pancreatitis. METHODS: We conducted a prospective randomized trial involving 40 patients with acute pancreatitis. Patients were divided into two groups. One group received PPI and the other group did not receive PPI. In the PPI group, patients received pantoprazole 40 mg intravenously twice a day for fasting time, and then 40 mg orally twice a day until discharge. RESULTS: There were no significant differences in baseline characteristics and laboratory markers between two groups. In the pantoprazole group, mean hospital stay was 7.4 days, time to start oral intake was 69.0 hours, and time to pain relief was 59.7 hours. Acute physiology and chronic health evaluation (APACHE) II score was 3.15 at admission day and 2.35 at discharge. On the other hand, in the non-pantoprazole group, mean hospital stay was 7.6 days, time taken to start oral intake was 71.4 hours, and time taken to pain relief was 61.8 hours. APACHE II score was 4.4 at admission and 2.85 at discharge. However, there were no significant differences between two groups. CONCLUSIONS: Treatment with pantoprazole did not have influence on the clinical course of acute pancreatitis. But, considering it was a pilot study, large scale prospective trials will be needed.