[Surgical management of duodenal atresia due to annular pancreas and intestinal atresia IIIb]. / Manejo quirúrgico de atresia duodenal por páncreas anular y atresia intestinal IIIb.

Background: The presence of duodenal atresia related to type IIIb intestinal atresia is a rare association, with few cases reported in the literature, representing a surgical challenge considering that even isolated cases of type IIIb intestinal atresia are a challenge. The objective was to report the successful surgical management of a case of a complex intestinal malformation, characterized by duodenal occlusion secondary to annular pancreas and type IIIb intestinal atresia, with intestinal malrotation by definition and the presence of Meckel's diverticulum. Clinical case: We present the case report of a newborn sent to the second level of care with a diagnosis of duodenal obstruction not diagnosed prenatally, which resulted in duodenal atresia due to annular pancreas and type IIIb intestinal atresia according to the Grosfeld classification. The presence of duodenal atresia with type IIIb intestinal atresia is an extremely rare condition, even more so associated with annular pancreas. These cases are a challenge considering the short length of the small intestine and its consequent need for total parenteral nutrition for a prolonged period. Conclusions: The surgical management of this complex intestinal malformation resulted in a case with an adequate post-surgical evolution, based on the immediate start of enteral feeding with a short period of need for total parenteral nutrition that finally resulted in a short hospital stay.

Introducción: la presencia de atresia duodenal relacionada con atresia intestinal tipo IIIb es una asociación rara, con pocos casos reportados en la literatura, y representa un reto quirúrgico si se toma en cuenta que incluso los casos aislados de atresia intestinal tipo IIIb lo representan. El objetivo fue reportar el manejo quirúrgico exitoso del caso de una malformación intestinal compleja, caracterizada por una oclusión duodenal secundaria a páncreas anular y atresia intestinal tipo IIIb, con una malrotación intestinal por definición y la presencia de divertículo de Meckel. Caso clínico: reportamos el caso de un recién nacido enviado de segundo nivel de atención con un diagnóstico de obstrucción duodenal no diagnosticado prenatalmente, que resultó en atresia duodenal por páncreas anular y atresia intestinal tipo IIIb, según la clasificación de Grosfeld. La presencia de atresia duodenal con atresia intestinal tipo IIIb es una condición extremadamente rara y todavía lo es más asociada con páncreas anular. Estos casos son un desafío si se toma en cuenta la corta longitud de intestino delgado y su consiguiente necesidad de nutrición parenteral total por un periodo prolongado. Conclusiones: el manejo quirúrgico de esta malformación intestinal compleja resultó en un caso con una adecuada evolución postquirúrgica, basada en el inicio mediato de alimentación enteral con un periodo corto de necesidad de nutrición parenteral total que finalmente resultó en una corta estancia hospitalaria.

Annular pancreas in neonate patients Vomiting and weight loss in a 13-day newborn / Pâncreas Anular no período neonatal Vômitos e perda de peso em neonato com 13 dias de vida

Objective: Reinforce that, despite being a rare condition, the annular pancreas must be considered a differential diagnosis for intestinal obstructions in the newborn period. Case description: This case report refers to a 13-days newborn admitted to the emergency room presenting with postprandial vomiting and progressive weight loss since maternity discharge. The patient did not respond to initial interventions that included IV antibiotics and nasogastric tube insertion. A contrast study of the upper digestive tract (esophagus, stomach, and duodenum) found a luminal narrowing on the second duodenal portion. The patient was submitted to an exploratory laparotomy which found a pancreatic-tissue ring involving the second part of the duodenum. Despite rare, we reinforce that the annular pancreas must be considered a differential diagnosis for intestinal obstructions in the newborn period. Comments: Annular pancreas is a rare congenital defect in which a ring of pancreatic tissue encircles the duodenum, causing different degrees of intestinal obstruction. (AU)

Objetivo: Evidenciar que, apesar de condição rara, o pâncreas anular deve se firmar como diagnóstico dife-rencial das obstruções intestinais no período neonatal. Descrição do caso: Este relato aborda o caso de uma paciente de 13 dias de vida admitida no pronto atendimento com queixa de volumosos vômitos pós-prandiais e perda de peso progressiva desde a alta da maternidade. Apesar das medidas iniciais, com ressuscitação volêmica, antibioticoterapia e passagem de sonda nasogástrica para descompressão, a paciente evolui sem melhora. Exame contrastado de esôfago-estômago-duodeno detectou estreitamento luminal da segunda porção duodenal. Paciente submetida à laparotomia exploradora, que evidenciou anel de tecido pancreático estreitando o trânsito intestinal na região. Comentários: O pâncreas anular é uma anomalia congênita rara na qual um anel de tecido pancreático envolve a porção descendente do duodeno, causando graus variados de obstrução intestinal extrínseca. (AU)

Agenesia del páncreas dorsal: reporte de caso y revisión del tema / Agenesis of the dorsal pancreas: case report and topic review

Complete agenesis of the dorsal pancreas (ADP) is an exceedingly rare congenital anomaly, compatible with life. It may be asymptomatic and usually incidentally diagnosed. In symptomatic cases, the clinical manifestations vary from abdominal pain, pancreatitis and diabetes mellitus to exocrine insufficiency with steatorrhea. We present a case report of a 28 year old female with ADP, diagnosed incidentally during radiological evaluation for hyperglycemias in SARS COV2 concomitant affection. Magnetic resonance cholangiopancreatography confirmed the absence of, neck, body and tail of the pancreas. Knowing the pancreatic embryogenesis, the clinical presentation of their malformations and the main radiological characteristics is important for the proper diagnosis of these anomalies.

Páncreas ectópico, una posible y rara causa de hipoglucemia postprandial / Ectopic pancreas, a possible rare cause of postprandial hypoglycemia

Introducción: El páncreas ectópico es la segunda anomalía congénita pancreática más frecuente después del páncreas divisum. Fue descrito por primera vez en 1729 por Schultz y se define como la presencia de tejido pancreático que carece de comunicación anatómica o vascular con el cuerpo principal del páncreas. La localización más frecuente es en el estómago (25 - 38 por ciento), seguido de duodeno, yeyuno e íleon. El 40 por ciento de los casos son sintomáticos y es más frecuente su presentación en varones en torno a la 5ª y 6ª década de la vida. Objetivo: Presentar un caso de páncreas ectópico diagnosticado a través de un estudio histológico tras realizada la cirugía. Presentación de caso: Presentamos el caso de una paciente compatible con hipoglucemia y cuyo estudio definitivo mostró la presencia de tejido pancreático ectópico en estómago, con resolución completa de los síntomas tras tratamiento quirúrgico. La anatomía patológica mostró una lesión nodular tumoral benigna (2,5 cm), constituida por tejido pancreático heterotópico, con presencia de páncreas exocrino con acinos. Páncreas endocrino con presencia de islotes de Langerhans y componente epitelial con ductos. Afectación desde la submucosa hasta la subserosa, con una pared muscular propia con hiperplasia muscular en relación a la heterotopía pancreática. La mucosa gástrica mostraba inflamación crónica leve con escasos folículos linfoides. Conclusiones: La presencia de páncreas ectópico es una entidad poco frecuente, pero a tener en cuenta en pacientes con clínica de hipoglucemia, una vez descartadas otras causas. No existe consenso con respecto a indicaciones en el manejo de lesiones pequeñas y asintomáticas, por lo que se recomienda individualizar cada caso teniendo en cuenta el tamaño, la localización y el tipo histológico(AU)

Introduction: Ectopic pancreas is the second most frequent congenital anomaly after pancreas divisum. It was described for the first time in 1729 by Schultz and it is defined as the presence of pancreatic tissue with no anatomical or vascular communication with the main body of pancreas. The most common location is in the stomach (25-38 percent), followed by the duodenum, jejunum and ileum ones. 40 percent of the cases are symptomatic and is more frequent their presentation in males in the fifth or sixth decade of life. Objective: To present a case of ectopic pancreas diagnosed through a histological study after surgery. Case presentation: Case of a patient with clinical features compatible with hypoglycemia that after being studied showed the presence of ectopic pancreatic tissue in the stomach, with a complete solution of the symptoms after surgical treatment. The pathological anatomy showed a benign tumor nodular lesion (2.5 cm), made up of heterotopic pancreatic tissue, with the presence of exocrine pancreas with acini. Endocrine pancreas with the presence of islets of Langerhans and epithelial component with ducts. Involvement from the submucosa to the subserosa, with a proper muscular wall with muscular hyperplasia in relation to pancreatic heterotopia. The gastric mucosa showed mild chronic inflammation with few lymphoid follicles. Conclusions: The presence of ectopic pancreas is a rare condition, but it should be taken into account in patients with clinical features of hypoglycemia once ruled out other causes. There is no consensus in regards to the indications for the management of small and asymptomatic lesions, so, it is recommended to individualize each case taking into account the size, location and histological type(AU)

Annular pancreas, cause of abdominal pain: Case report / Páncreas anular, causa de dolor abdominal. Reporte de caso

Background: Annular pancreas is a congenital abnormality which causes duodenal obstruction in neonates. It befalls upon 1 patient amongst every 12 000-15 000 newborns. It often appears in adulthood. Clinical traits include abdominal pain, intestinal obstruction, vomiting, and pancreatitis. The diagnosis requires image studies and surgical exploration. Clinical case: Female patient, 11 years of age, presenting intermittent chronic abdominal pain, underweight for her age. Treated by a private physician with ranitidine (4 mg/kg/day) and ibuprofen (5 mg/kg/dose) orally, for one month, due to acid-peptic disease. On December 31, 2017, she was attended at Pediatric Emergency presenting epigastric pain, and nausea. She vomited bile contents 4 times over a 24 hour span. Other symptoms included painful reaction to epigastric palpation, positive pancreatic points, negative Murphy's sign, no hepatomegaly or splenomegaly, decreased peristaltic noises. Reported: amylase 2163 U/L, lipase 821 U/L, lactic dehydrogenase 461 U/L. Pancreatic ultrasound: 19.3 mm head, 23.2 mm body and 10 mm tail. She was admitted to pediatrics, where the annular pancreas condition was confirmed through ultrasound and computed tomography scan. She then underwent conservative treatment. Conclusion: The patient displayed typical annular pancreas symptoms. Image studies were key to the diagnosis.

Introducción: el páncreas anular es una anomalía congénita que causa obstrucción duodenal en el neonato. Se reporta en 1 por cada 12 000-15 000 recién nacidos, a menudo se revela en la edad adulta. Clínicamente incluye obstrucción intestinal, dolor abdominal, vómitos y puntos pancreáticos positivos. El diagnóstico requiere estudios de imagenología y exploración quirúrgica. Caso clínico: paciente del sexo femenino, de 11 años de edad, con dolor abdominal crónico intermitente, de bajo peso para su edad. Tratada por médico privado con ranitidina (4 mg/kg/día) e ibuprofeno (5 mg/kg/dosis) vía oral, durante un mes, por enfermedad acido-péptica. El 31 de diciembre del 2017 fue atendida en urgencias pediátricas, por dolor en epigastrio, náuseas y vómitos de contenido gastrobiliar en número de 4 en 24 horas. Abdomen doloroso a la palpación en epigastrio, puntos pancreáticos positivos, Murphy negativo, sin hepatomegalia ni esplenomegalia, ruidos peristálticos disminuidos. Se reportó: amilasa 2163 U/L, lipasa 821 U/L, deshidrogenasa láctica 461 U/L. Ultrasonido de páncreas: cabeza de 19.3 mm, cuerpo de 23.2 mm y cola de 10 mm. Fue internada en pediatría, confirmándose páncreas anular por ultrasonido y tomografía; recibió tratamiento conservador. Conclusión: la paciente presentó síntomas típicos del páncreas anular, su estudio mediante imágenes fue decisivo para establecer el diagnóstico.

Heterotaxy syndrome with agenesis of dorsal pancreas and diabetes mellitus: case report and review of the literature

SUMMARY Heterotaxy syndrome (HS) is a rare congenital condition with multifactorial heritance, characterized by an abnormal arrangement of thoraco-abdominal organs and vessels. Patients present with multiple cardiac, gastrointestinal, hepatosplenic, pancreatic, renal, neurological and skeletal disorders without any pathognomonic alteration. Despite the described increased risk of diabetes mellitus (DM) in patients with altered pancreatic anatomy, just one case was reported in Korea regarding the association of HS and DM in a 13-year-old girl. Our report refers to a 40-year-old female Brazilian patient with a history of DM and HS with polysplenia and agenesis of dorsal pancreas without cardiac abnormalities. She presented a worsening glycemic control associated with weight gain and signs of insulin resistance. After a proper clinical management of insulin and oral medications, our patient developed an improvement in glycemic control. Although it is a rare disease, HS with polysplenia and pancreatic disorders can be associated with an increased risk of DM. This case highlights the importance of investigating DM in patients with HS, especially those with pancreatic anatomical disorders, for proper clinical management of this rare condition.

Heterotaxy syndrome with agenesis of dorsal pancreas and diabetes mellitus: case report and review of the literature.

Heterotaxy syndrome (HS) is a rare congenital condition with multifactorial heritance, characterized by an abnormal arrangement of thoraco-abdominal organs and vessels. Patients present with multiple cardiac, gastrointestinal, hepatosplenic, pancreatic, renal, neurological and skeletal disorders without any pathognomonic alteration. Despite the described increased risk of diabetes mellitus (DM) in patients with altered pancreatic anatomy, just one case was reported in Korea regarding the association of HS and DM in a 13-year-old girl. Our report refers to a 40-year-old female Brazilian patient with a history of DM and HS with polysplenia and agenesis of dorsal pancreas without cardiac abnormalities. She presented a worsening glycemic control associated with weight gain and signs of insulin resistance. After a proper clinical management of insulin and oral medications, our patient developed an improvement in glycemic control. Although it is a rare disease, HS with polysplenia and pancreatic disorders can be associated with an increased risk of DM. This case highlights the importance of investigating DM in patients with HS, especially those with pancreatic anatomical disorders, for proper clinical management of this rare condition.

PDX1 -MODY and dorsal pancreatic agenesis: New phenotype of a rare disease.

Maturity-Onset Diabetes of the Young (MODY) type 4 or PDX1 -MODY is a rare form of monogenic diabetes caused by heterozygous variants in PDX1 . Pancreatic developmental anomalies related to PDX1 are reported only in neonatal diabetes cases. Here, we describe dorsal pancreatic agenesis in 2 patients with PDX1 -MODY. The proband presented with diabetes since 14 years of age and maintained regular glycemic control with low doses of basal insulin and detectable C-peptide levels after 38 years with diabetes. A diagnosis of MODY was suspected. Targeted next-generation sequencing identified a heterozygous variant in PDX1 : c.188delC/p.Pro63Argfs*60. Computed tomography revealed caudal pancreatic agenesis. Low fecal elastase indicated exocrine insufficiency. His son had impaired glucose tolerance, presented similar pancreatic agenesis, and harbored the same allelic variant. The unusual presentation in this Brazilian family enabled expansion upon a rare disease phenotype, demonstrating the possibility of detecting pancreatic malformation even in cases of PDX1 -related diabetes diagnosed after the first year of life. This finding can improve the management of MODY4 patients, leading to precocious investigation of pancreatic dysgenesis and exocrine dysfunction.

Um caso raro de destruição total do pâncreas por pancreatite em cão / A rare case of total pancreatic destruction due to pancreatitis in a dog

A 16-year-old female Poodle entered UFMG's Veterinary Hospital with severe prostration, lack of appetite, and vomit. During physical examination, abdominal pain, dehydration, and hyperglycemia (448mg/dl) were found, therefore the animal was admitted under the suspicion of diabetic ketoacidosis. Screening revealed metabolic acidosis, hyperkalemia, glycosuria, ketonuria, and proteinuria. Leukocytosis, thrombocytosis, increase in the number of hepatic enzymes and hyperglycemia were also present in these tests. The ultrasound images showed a smaller and hypoechogenic pancreas, irregularity and folds in duodenum and reactivity of the surrounding tissue, indicating pancreatitis. Thirty days after the dog had been discharged for treatment at home, it was taken back to the veterinary hospital due to status epilepticus, which motivated the owner's decision of euthanasia. During post mortem examination no trace of pancreas was found. On histological examination of the adipose tissue next to the duodenum, only one pancreatic duct was seen, together with inflamatory cells , thus characterizing a rare case of total pancreatic destruction due to pancreatitis.(AU)

Um caso raro de destruição total do pâncreas por pancreatite em cão / A rare case of total pancreatic destruction due to pancreatitis in a dog

A 16-year-old female Poodle entered UFMG's Veterinary Hospital with severe prostration, lack of appetite, and vomit. During physical examination, abdominal pain, dehydration, and hyperglycemia (448mg/dl) were found, therefore the animal was admitted under the suspicion of diabetic ketoacidosis. Screening revealed metabolic acidosis, hyperkalemia, glycosuria, ketonuria, and proteinuria. Leukocytosis, thrombocytosis, increase in the number of hepatic enzymes and hyperglycemia were also present in these tests. The ultrasound images showed a smaller and hypoechogenic pancreas, irregularity and folds in duodenum and reactivity of the surrounding tissue, indicating pancreatitis. Thirty days after the dog had been discharged for treatment at home, it was taken back to the veterinary hospital due to status epilepticus, which motivated the owner's decision of euthanasia. During post mortem examination no trace of pancreas was found. On histological examination of the adipose tissue next to the duodenum, only one pancreatic duct was seen, together with inflamatory cells , thus characterizing a rare case of total pancreatic destruction due to pancreatitis.(AU)

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.

Terapia fotodinâmica em células de tumores pancreáticos humanos: eficiência e análise das vias mediadoras de citotoxicidade / Photodynamic therapy in human pancreatic tumors: efficiency and analysis of cytotoxicity mediator pathways

O adenocarcinoma de ducto pancreático (PDAC) é a quarta causa de morte em decorrência de neoplasias nos países ocidentais. Atualmente, a cirurgia ressectiva é a única possibilidade de cura para a doença, porém, a recidiva tumoral acontece em menos de um ano após a intervenção cirúrgica, mesmo com a quimioterapia adjuvante. A terapia fotodinâmica (PDT) é uma alternativa promissora no tratamento do câncer. No entanto, pouco se sabe sobre o uso da PDT em tumores pancreáticos. Portanto, o objetivo deste trabalho foi avaliar a eficiência da PDT com o azul de metileno (MB) como fotossensibilizador (MB-PDT) em induzir a morte de linhagens de PDAC humanas (AsPC-1, Panc-1, MIAPaCa-2 e BxPC-3) e estudar a contribuição de vias de necrose regulada nos efeitos citotóxicos da terapia sobre estes modelos. Os resultados obtidos mostraram que a MB-PDT foi capaz de induzir a morte massiva das células de PDAC. Além disso, eles indicaram que há dois perfis de susceptibilidade entre as quatro linhagens estudadas quando submetidas a MBPDT com 4,5 J/cm2 de energia e 6min de irradiação. De acordo com os dados apresentados, a diferença nas sensibilidades das linhagens à terapia não está associada à diferenças na capacidade de incorporação do MB ou na localização sub-celular do fotossensibilizador nas diferentes células, uma vez que a localização é, predominantemente, lisossomal em todas elas. Adicionalmente, mostrou-se que as linhagens menos susceptíveis ao tratamento, MIAPaCa-2 e Panc-1, apresentam níveis significativamente menores de RIPK3 e MLKL, dois dos componentes do necrossomo, essenciais para a execução da necroptose. Além disso, foi visto que a MB-PDT induz um aumento de fosforilação de MLKL em AsPC-1, demonstrando a ativação da necroptose após a terapia nestas células, mas não em MIAPaCa-2 (menos responsiva à terapia com 4,5 J/cm2 deenergia e 6min de tempo de irradiação). Ainda, a inibição da via de sinalização necroptótica diminuiu significativamente as porcentagens de morte das células mais susceptíveis (BxPC-3 e AsPC-1), não alterando a resposta de Panc-1 e MIAPaCa-2, corroborando a ativação e importância da necroptose para a citotoxicidade da MB-PDT. Finalmente, neste trabalho foi mostrado que o aumento do tempo de irradiação, mantendo-se a quantidade total de energia aplicada no tratamento, melhora a eficiência da MB-PDT em induzir a morte das células que apresentam limitações para executar a necroptose, sugerindo que mais de uma via de morte esteja sendo ativada após a terapia e que o tempo de irradiação atuaria modulando esta ativação. Complementarmente, foi mostrado que os tempos maiores de irradiação aumentam o estresse oxidativo intracelular que é acompanhado por uma diminuição significativa do conteúdo intracelular de glutationa reduzida (GSH), indicando, preliminarmente, que a ferroptose pode estar sendo acionada após os protocolos mais longos de irradiação. Coletivamente, os resultados apresentados neste trabalho confirmam a eficiência da MB-PDT no tratamento de diferentes linhagens de PDAC, indicando que a necroptose está sendo ativada e contribuindo para a citotoxicidade da terapia sobre as células que não apresentam resistência à esta via de morte. Ainda, eles demonstram que o aumento do tempo de irradiação pode transpor a barreira de resistência de algumas linhagens à terapia, provavelmente por induzir a ativação de outras vias de necrose regulada, mostrando a importância da otimização do protocolo de tratamento no aumento da eficiência da MB-PDT sobre os tumores de pâncreas. Finalmente, os resultados confirmam a MB-PDT como alternativa eficaz no tratamento do PDAC, apresentando um amplo espectro de atuação sobre subtipos tumorais resistentes à vias clássicas de morte celular, uma característica importante no contexto de uma terapia anti-cancer

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death due to neoplasms in western countries. Currently, resective surgery is the only therapetical approach to cure this disease, but tumor´s recurrence occurs less than one year after the surgery, even with adjuvant chemotherapy. Photodynamic therapy (PDT) is a promising alternative for the cancer treatment. However, the efficacy of PDT to treat pancreatic tumors as well as the mechanisms involved in the induction of tumorigenic cell death remain unclear. For this purpose, in this study, we set out to evaluate the efficacy of PDT using methylene blue (MB) as a photosensitizer (MB-PDT), in inducing death of human PDAC derived cell lines (AsPC-1, Panc-1, MIAPaCa-2 and BxPC-3) and to deeper investigate the contribution of necroptosis to the cytotoxic effects of the therapy. We observed that MB-PDT was able to induce massive death of PDAC cells. Moreover, our results indicated that upon MB-PDT (4.5 J/cm2 energy and 6min of irradiation time), there were two susceptibility profiles among the four cell lines studied. Data also showed that this differential profile of cell response was neither associated with the differences in the MB incorporation capacity nor with the subcellular location of the photosensitizer, since the localization was predominantly lysosomal in all of tested cell lines. In addition, less susceptible cells, MIAPaCa-2 and Panc-1, showed significantly lower levels of RIPK3 and MLKL, two of the necrosome components, essential for triggering necroptosis. Furthermore, while MB-PDT (4.5 J/cm2 and 6min of irradiation) has been able to increase MLKL´s phosphorylation levels, an essential step in necroptosis induction, in AsPC-1cells, less responsive MIAPaCa-2 cells presented no variations on the phosphorylation state of this pseudokinase. Moreover, pharmacological inhibition of the necroptotic signaling pathway significantly decreased cell death percentages of the most susceptible cells (BxPC-3 andAsPC-1), without altering the response of Panc-1 and MIAPaCa-2, corroborating that activation of necroptosis was strongly involved in the cytotoxicity of MB-PDT. Finally, this work showed that increasing the irradiation time improved the efficacy of MB-PDT in killing cells which display limitations to perform necroptosis, suggesting that the irradiation time would be modulating the degree of oxidative stress generated and this stimuli would in turn, be responsible for triggering other regulated cell death pathways in a RIKP3 and MLKL independent way. Indeed, this increase in oxidative stress was accompanied by a significant decrease in GSH, a global indicatior of less antioxidant cell capacity, preliminarily pointing at the induction of ferroptosis by longer irradiation protocols. In summary, we demonstrated that MB-PDT is able to induce cell death in different PDAC cell lines and that different regulated cell death mechanisms are being activated upon MB-PDT induction. Furthermore, it was demonstrated that increased irradiation time may overcome the resistance barrier of some cell lines, probably inducing the activation of other regulated cell death pathways, showing the importance of optimizing the irradiation protocol in order to maximize the efficacy of the therapy. Finally, our observations point MB-PDT as an alternative and effective therapy for pancreatic cancer treatment, displaying a broad-spectrum action on tumors displaying different resistance mechanisms to classic cell death pathways, a desired property for improving an anticancer therapy

Um caso raro de destruição total do pâncreas por pancreatite em cão / A rare case of total pancreatic destruction due to pancreatitis in a dog

A 16-year-old female Poodle entered UFMG's Veterinary Hospital with severe prostration, lack of appetite, and vomit. During physical examination, abdominal pain, dehydration, and hyperglycemia (448mg/dl) were found, therefore the animal was admitted under the suspicion of diabetic ketoacidosis. Screening revealed metabolic acidosis, hyperkalemia, glycosuria, ketonuria, and proteinuria. Leukocytosis, thrombocytosis, increase in the number of hepatic enzymes and hyperglycemia were also present in these tests. The ultrasound images showed a smaller and hypoechogenic pancreas, irregularity and folds in duodenum and reactivity of the surrounding tissue, indicating pancreatitis. Thirty days after the dog had been discharged for treatment at home, it was taken back to the veterinary hospital due to status epilepticus, which motivated the owner's decision of euthanasia. During post mortem examination no trace of pancreas was found. On histological examination of the adipose tissue next to the duodenum, only one pancreatic duct was seen, together with inflamatory cells , thus characterizing a rare case of total pancreatic destruction due to pancreatitis.(AU)

Factores de riesgo para pancreatitis aguda en el Hospital Comandante Faustino Pérez de Matanzas / Risk factors for acute pancreatitis in the Hospital Comandante

Introducción: la pancreatitis aguda constituye causa de ingresos frecuentes en las unidades de atención al grave del Hospital "Comandante Faustino Pérez Hernández" de Matanzas. En ocasiones presentan complicaciones que prolongan la estadía y elevan la mortalidad. Objetivo: determinar el comportamiento clínico epidemiológico de la Pancreatitis Aguda en unidades de atención al grave. Materiales y Métodos: se realizó un estudio descriptivo, observacional, prospectivo desde enero 2013 a diciembre 2014, en el Hospital Universitario "Comandante Faustino Pérez Hernández" de Matanzas, a los pacientes ingresados con diagnóstico de Pancreatitis Aguda. Se operacionalizaron las variables: edad, factores de riesgos y estado del paciente al egreso. Resultados: predominaron los hombres y el grupo etario de 35 - 44 años (25,40 %); el alcoholismo fue el factor de riesgo más representado (38,10 %). La mortalidad fue de un 9,6 %. Conclusiones: en el estudio predominaron los jóvenes, el sexo masculino y el alcoholismo como factor de riesgo más frecuente. La pancreatitis aguda crítica constituyó la forma más frecuente. La sobrevida constatada fue favorable, siendo superior a los reportes de la literatura (AU).

Introduction: acute pancreatitis is the cause of frequent admissions in the units of seriously-ill patients' care of the Hospital "Comandante Faustino Pérez Hernández" of Matanzas. Sometimes they have complications causing extension staying and increasing mortality. Objective: to determine the clinical epidemiological behavior of acute pancreatitis in seriously-ill patients´ care units. Materials and Methods: a prospective, observational, descriptive study was carried out from January 2013 to December 2014, in the University Hospital "Comandante Faustino Pérez Hernández" of Matanzas, with patients who entered the hospital diagnosed with acute pancreatitis. The studied variables were age, risk factors, and patient´s status at discharging. Results: men predominated and also the age group ranging between 35 and 44 years (25,40 %). Alcoholism was the most represented risk factor (38,10 %). Mortality was 9,6 %. Conclusions: there they were predominant young people, male sex and alcoholism was the most frequent risk factor. Acute critical pancreatitis was the most frequent form. The showed survival was favorable, being higher than the one reported in the literature (AU).

Factores de riesgo para pancreatitis aguda en el Hospital Comandante Faustino Pérez de Matanzas / Risk factors for acute pancreatitis in the Hospital Comandante

Introducción: la pancreatitis aguda constituye causa de ingresos frecuentes en las unidades de atención al grave del Hospital "Comandante Faustino Pérez Hernández" de Matanzas. En ocasiones presentan complicaciones que prolongan la estadía y elevan la mortalidad. Objetivo: determinar el comportamiento clínico epidemiológico de la Pancreatitis Aguda en unidades de atención al grave. Materiales y Métodos: se realizó un estudio descriptivo, observacional, prospectivo desde enero 2013 a diciembre 2014, en el Hospital Universitario "Comandante Faustino Pérez Hernández" de Matanzas, a los pacientes ingresados con diagnóstico de Pancreatitis Aguda. Se operacionalizaron las variables: edad, factores de riesgos y estado del paciente al egreso. Resultados: predominaron los hombres y el grupo etario de 35 - 44 años (25,40 %); el alcoholismo fue el factor de riesgo más representado (38,10 %). La mortalidad fue de un 9,6 %. Conclusiones: en el estudio predominaron los jóvenes, el sexo masculino y el alcoholismo como factor de riesgo más frecuente. La pancreatitis aguda crítica constituyó la forma más frecuente. La sobrevida constatada fue favorable, siendo superior a los reportes de la literatura (AU).

Introduction: acute pancreatitis is the cause of frequent admissions in the units of seriously-ill patients' care of the Hospital "Comandante Faustino Pérez Hernández" of Matanzas. Sometimes they have complications causing extension staying and increasing mortality. Objective: to determine the clinical epidemiological behavior of acute pancreatitis in seriously-ill patients´ care units. Materials and Methods: a prospective, observational, descriptive study was carried out from January 2013 to December 2014, in the University Hospital "Comandante Faustino Pérez Hernández" of Matanzas, with patients who entered the hospital diagnosed with acute pancreatitis. The studied variables were age, risk factors, and patient´s status at discharging. Results: men predominated and also the age group ranging between 35 and 44 years (25,40 %). Alcoholism was the most represented risk factor (38,10 %). Mortality was 9,6 %. Conclusions: there they were predominant young people, male sex and alcoholism was the most frequent risk factor. Acute critical pancreatitis was the most frequent form. The showed survival was favorable, being higher than the one reported in the literature (AU).

¿Tiene el páncreas divisum un rol determinante en la pancreatitis aguda? / Does Pancreas divisum have any determinant role in acute pancreatitis?

Resumen Objetivo: Las anomalías pancreáticas del desarrollo son un espectro de variaciones anatómicas, entre las que se destaca el páncreas divisum; su asociación con la pancreatitis aguda continúa siendo controversial. Materiales y métodos: En primer término se realizó una investigación no experimental de corte transversal sobre 100 piezas duodenopancreáticas cadavéricas y en segunda instancia se analizó el reporte de caso de un paciente con colestasis extrahepática y pancreatitis aguda asociadas a la portación de páncreas divisum. El objetivo fue determinar la prevalencia del sistema descompresivo pancreático. Resultados: Existe diferencia estadísticamente significativa entre las dimensiones del conducto pancreático accesorio y su relación con la permeabilidad. En cuanto a la volumetría pancreática, la sección correspondiente al tercio superior cefálico, cuello, cuerpo y cola del órgano registró una dimensión media de 21,99 cm3, mientras que la sección de los dos tercios cefálicos restantes fue de 8,17 cm3. Simultáneamente, el paciente reportado presentó cuadro clínico de pancreatitis con amilasa de 280 UI/l y lipasa de 173 UI/l asociado a colestasis. Al segundo día de internación se realizó colangiopancreatografía retrógrada endoscópica con papilotomía duodenal mayor y extracción de múltiples cálculos coledocianos, evidenciando un páncreas divisum completo. Discusión: El caso expuesto exhibe que la pancreatitis, en presencia de páncreas divisum, tendría la denominación de una pancreatitis ventral subclínica. Conclusión: El páncreas divisum sería un predictor determinante de pancreatitis aguda al perder el mecanismo descompresivo protector pancreático.

Abstract Purpose: Pancreatic developmental anomalies are a spectrum of anatomical variations, including the pancreas divisum, where its association with acute pancreatitis continues being controversial. Materials and methods: Firstly, a non-experimental cross-sectional study was carried out on one hundred cadaveric duodenpancreatic pieces, and secondly was analyzed the case report of a patient with extrahepatic cholestasis and acute pancreatitis associated with pancreas divisum. The objective was to determinate the prevalence of the decompressive pancreatic system. Results: There is a statistically significant difference between the dimensions of the accessory pancreatic duct and its relation with the permeability. In terms of pancreatic volumetry, the section corresponding to the upper third cephalic, neck, body and tail of the organ registers an average dimension of 21.99 cm3, while the section of the last two thirds cephalic was 8.17 cm3. Simultaneously, the patient reported presented a pancreatitis with amylase 280 UI/l, lipase 173 UI/l, associated with cholestasis. On the second day of hospitalization, endoscopic retrograde cholangiopancreatography was performed with a greater duodenal papillotomy and extraction of multiple common bile duct stones, evidencing a complete pancreas divisum. Discussion: The exposed case shows that pancreatitis, in presence of pancreas divisum, would have the denomination of a subclinical ventral pancreatitis. Conclusion: The pancreas divisum would be a predictor of acute pancreatitis by losing the decompressive pancreatic protective mechanism.