Oxidative damage and exocrine dysfunction of ovine fetal pancreas are induced by maternal nutritional restriction

This study investigated oxidative damage and exocrine dysfunction of fetal pancreas caused by maternal nutritional restriction. Eighteen ewes carrying singleton fetus were randomly divided into control group (CG, ad libitum, 0.67 MJ ME/BW0.75/d, n = 6), restricted group 1 (RG1, 0.33 MJ ME/BW0.75/d, n = 6), and restricted group 2 (RG2, 0.18 MJ ME/BW0.75/d, n = 6) at d 90 of pregnancy. Maternal undernutrition was imposed from d 90 to 140 of pregnancy. At 140 d of gestation, fetal blood and pancreas tissue were collected to determine fetal pancreatic extracellular matrix, antioxidant capacity, and indicators of exocrine dysfunction. With the decrease of maternal nutrition, the fetal body weight, pancreatic weight, and DNA content were reduced in RG2 compared with CG, and increased and thickened collagen fibers were observed in RG2. Fetuses in RG2 exhibited increased collagen 3 (COL3) and fibronectin (FN) levels relative to CG, and the COL1:COL3 ratio was lower than that of the CG. For RG1, we found increased COL3 compared with CG. Malondialdehyde, serum amylase, and serum lipase in fetal pancreas in RG2 increased, but the total antioxidant capacity (T-AOC) decreased compared with the CG. The impaired ovine fetal pancreas growth, antioxidant imbalance, and pancreatic exocrine dysfunction are induced by maternal undernutrition during late pregnancy.

Diabetes of the Exocrine Pancreas Related to Hereditary Pancreatitis, an Update.

PURPOSE OF REVIEW: The aim was to review evidence about diabetes secondary to hereditary pancreatitis, seeking novel diagnostic and treatment features. RECENT FINDINGS: Hereditary pancreatitis (HP) is an autosomal dominant condition, characterized by recurrent episodes of acute pancreatitis, progression to fibrosis, and chronic pancreatitis. Clinical presentation includes diabetes of the exocrine pancreas (DEP). HP prevalence ranges from 0.3 to 0.57 per 100,000 people, with up to 80% of these develop DEP. This condition often requires specific interventions: with regard to metabolic control, metformin is the first choice for those with mild DEP, and for those in advanced disease, insulin is considered the first-line therapy. Insulin analogues and insulin pump therapy are preferred due to the brittle glycemic pattern and risk of hypoglycemia. In case of exocrine insufficiency, pancreatic enzyme replacement therapy is recommended. Pancreatic polypeptide administration is a promising novel treatment feature. DEP due to HP appears to be a misdiagnosed condition. The requirement of specific management demonstrates the importance of this matter; therefore, appropriate recognition and classification are important.

Pancreatic multifocal necrosis in female cat: case report / Necrose multifocal pancreática em gata: relato de caso

Pancreatitis is the inflammatory process of the exocrine pancreas, with necrosis and fibrosis as the main structural alterations. Felines may present the acute and chronic forms of the disease. A domestic, female, undefined feline (srd) was taken to a Private Veterinary Hospital in the city of Guarulhos, state of São Paulo. The animal had signs of apathy, prostration, inappetence, anorexia and bilateral exposure of the third eyelid. After the physical examination, blood was collected for haematological and biochemical exams. Abdominal ultrasonography was also requested, where reverberation was detected in the region of the intestinal loop, hyperechogenicity of the duodenal wall and reverberation of the pancreas. According to the results of the blood tests and ultrasonographic findings, we opted for exploratory laparotomy. During the surgical procedure a pancreatic fragment was collected for histopathological analysis. The histopathologic result was compatible with moderate multifocal pancreatic necrosis. Therefore, was instituted antibiotic therapy with Enrofloxacin (5 mg / kg, BID, IM for 5 days), analgesia with Tramadol Hydrochloride (2 mg/kg, BID, IV for 4 days) and Betamethasone (0.3 mg/kg, SID, IV). After the beginning of treatment with corticosteroid, the animal began to improve and eat. Many cases are diagnosed as acute or chronic pancreatitis only due to changes in pancreatic enzymes and ultrasonographic changes in the pancreas, using histopathological examination, which is a more instructive technique. It is very likely that pancreatic necrosis is not a pathology of low incidence, but rather poorly diagnosed due to difficulties in performing a biopsy.

A pancreatite é o processo inflamatório do pâncreas exócrino, tendo a necrose e a fibrose como principais alterações estruturais. Felinos podem apresentar as formas aguda e crônica da doença. Foi levado a um Hospital Veterinário Particular na cidade de Guarulhos, estado de São Paulo, um felino doméstico, fêmea, sem raça definida (srd). O animal apresentava sinais de apatia, prostração, inapetência, anorexia e exposição bilateral da terceira pálpebra. Após o exame físico, foi feita coleta de sangue para realização de exames hematológicos e bioquímicos. Foram solicitados ainda ultrassonografia abdominal, onde foi detectada reverberação em região de alça intestinal, hiperecogenicidade de parede duodenal e reverberação de pâncreas. De acordo com os resultados dos exames de sangue e os achados ultrassonográficos, optou-se pela laparotomia exploratória. Durante o procedimento cirúrgico foi coletado um fragmento pancreático para análise histopatológica. O resultado do histopatológico foi compatível com necrose pancreática multifocal moderada. Sendo assim, foi instituída antibióticoterapia com Enrofloxacina (5 mg/kg, BID, IM, durante 5 dias), analgesia com Cloridrato de Tramadol (2 mg/kg, BID, IV, durante 4 dias) e Betametasona (0,3 mg/kg, SID, IV). Após o início do tratamento com corticosteróide, o animal começou a apresentar melhora, voltando a se alimentar. Muitos casos são diagnosticados como pancreatite aguda ou crônica apenas por conta das alterações em enzimas pancreáticas e alterações ultrassonográficas em pâncreas, lançando mão do exame histopatológico, que é uma técnica mais elucidativa. Muito provável que a necrose pancreática não seja uma patologia de baixa incidência, e sim, pouco diagnosticada, devido às dificuldades em se realizar biópsia.

Pancreatic multifocal necrosis in female cat: case report / Necrose multifocal pancreática em gata: relato de caso

Pancreatitis is the inflammatory process of the exocrine pancreas, with necrosis and fibrosis as the main structural alterations. Felines may present the acute and chronic forms of the disease. A domestic, female, undefined feline (srd) was taken to a Private Veterinary Hospital in the city of Guarulhos, state of São Paulo. The animal had signs of apathy, prostration, inappetence, anorexia and bilateral exposure of the third eyelid. After the physical examination, blood was collected for haematological and biochemical exams. Abdominal ultrasonography was also requested, where reverberation was detected in the region of the intestinal loop, hyperechogenicity of the duodenal wall and reverberation of the pancreas. According to the results of the blood tests and ultrasonographic findings, we opted for exploratory laparotomy. During the surgical procedure a pancreatic fragment was collected for histopathological analysis. The histopathologic result was compatible with moderate multifocal pancreatic necrosis. Therefore, was instituted antibiotic therapy with Enrofloxacin (5 mg / kg, BID, IM for 5 days), analgesia with Tramadol Hydrochloride (2 mg/kg, BID, IV for 4 days) and Betamethasone (0.3 mg/kg, SID, IV). After the beginning of treatment with corticosteroid, the animal began to improve and eat. Many cases are diagnosed as acute or chronic pancreatitis only due to changes in pancreatic enzymes and ultrasonographic changes in the pancreas, using histopathological examination, which is a more instructive technique. It is very likely that pancreatic necrosis is not a pathology of low incidence, but rather poorly diagnosed due to difficulties in performing a biopsy.(AU)

A pancreatite é o processo inflamatório do pâncreas exócrino, tendo a necrose e a fibrose como principais alterações estruturais. Felinos podem apresentar as formas aguda e crônica da doença. Foi levado a um Hospital Veterinário Particular na cidade de Guarulhos, estado de São Paulo, um felino doméstico, fêmea, sem raça definida (srd). O animal apresentava sinais de apatia, prostração, inapetência, anorexia e exposição bilateral da terceira pálpebra. Após o exame físico, foi feita coleta de sangue para realização de exames hematológicos e bioquímicos. Foram solicitados ainda ultrassonografia abdominal, onde foi detectada reverberação em região de alça intestinal, hiperecogenicidade de parede duodenal e reverberação de pâncreas. De acordo com os resultados dos exames de sangue e os achados ultrassonográficos, optou-se pela laparotomia exploratória. Durante o procedimento cirúrgico foi coletado um fragmento pancreático para análise histopatológica. O resultado do histopatológico foi compatível com necrose pancreática multifocal moderada. Sendo assim, foi instituída antibióticoterapia com Enrofloxacina (5 mg/kg, BID, IM, durante 5 dias), analgesia com Cloridrato de Tramadol (2 mg/kg, BID, IV, durante 4 dias) e Betametasona (0,3 mg/kg, SID, IV). Após o início do tratamento com corticosteróide, o animal começou a apresentar melhora, voltando a se alimentar. Muitos casos são diagnosticados como pancreatite aguda ou crônica apenas por conta das alterações em enzimas pancreáticas e alterações ultrassonográficas em pâncreas, lançando mão do exame histopatológico, que é uma técnica mais elucidativa. Muito provável que a necrose pancreática não seja uma patologia de baixa incidência, e sim, pouco diagnosticada, devido às dificuldades em se realizar biópsia.(AU)

The exocrine pancreas is an extracardiac source of atrial natriuretic peptide.

Previous studies have shown that atrial natriuretic peptide (ANP) regulates exocrine pancreatic function in health and disease. As extracardiac sources of ANP have been identified and ANP-like immunoreactivity has been reported in the exocrine pancreas, in the present work we sought to establish whether ANP was produced in the rat exocrine pancreas and if conditions like fasting/feeding or acute pancreatitis were reflected on ANP expression. By using RT-PCR, immunoblotting, and immunofluorescence microscopy assays, it was found that both mRNA and protein ANP were present in the acinar cells of the exocrine pancreas. The amount of ANP in the pancreas was lower in than the atrium but similar to other tissues like the kidney and liver. Immunogold labeling electron microscopy studies revealed that ANP was localized in zymogen granules and the endoplasmic reticulum suggesting local synthesis and package into granules. ANP protein expression was significantly increased not only in fasting but also in acute pancreatitis, the latter probably related to impaired secretion. Natriuretic peptide receptor type C which mediates ANP biological effects in the exocrine pancreas was also present in acinar cells and its expression did not change with either fasting or acute pancreatitis. Present findings show that the exocrine pancreas is a relatively important extracardiac source of ANP and further support previous studies strongly suggesting the active role of the peptide in pancreatic physiology and pathophysiology.

Clinico-pathological features and survival of patients with malignant exocrine pancreatic neoplasms: The AC Camargo Cancer Center experience.

BACKGROUND: Pancreatic cancer plays an important role in cancer-related mortality. Few studies have been performed in Brazil to characterize patients affected by this disease. We aimed to describe the clinico-pathological characteristics and the survival of patients with pancreatic cancer seen at AC Camargo Cancer Center (ACCCC). METHODS: We included patients ≥ 18-year old, with a histologically confirmed diagnosis of exocrine pancreatic cancer, that attended at least one visit at ACCCC from 2008 to 2016. RESULTS: The study included 739 patients. Median age at diagnosis was 64 years. Most patients were male. About 5% presented a family history of pancreatic cancer. A total of 40% had diabetes and 51.4% presented with ECOG performance status 1. Tumors most often arose in the pancreatic head and roughly half of the patients had metastatic disease at presentation. Median overall survival of patients with potentially resectable disease submitted to surgery at ACCCC was 35.4 months. Median overall survival times of patients with the unresectable and metastatic disease were 14.1 and 9.3 months, respectively. CONCLUSIONS: The features of our population match those of studies done in developed countries. We believe multicentric data from patients with pancreatic cancer in Brazil could enable more effective preventive and therapeutic approaches to the disease.

Paracrine Secretion of Transforming Growth Factor ß by Ductal Cells Promotes Acinar-to-Ductal Metaplasia in Cultured Human Exocrine Pancreas Tissues.

OBJECTIVE: We aimed to evaluate the contribution of acinar-to-ductal metaplasia (ADM) to the accumulation of cells with a ductal phenotype in cultured human exocrine pancreatic tissues and reveal the underlying mechanism. METHODS: We sorted and cultured viable cell populations in human exocrine pancreatic tissues with a flow cytometry-based lineage tracing method to evaluate possible mechanisms of ADM. Cell surface markers, gene expression pattern, and sphere formation assay were used to examine ADM. RESULTS: A large proportion of acinar cells gained CD133 expression during the 2-dimensional culture and showed down-regulation of acinar markers and up-regulation of ductal markers, assuming an ADM phenotype. In a serum-free culture condition, ADM induction was mainly dependent on transforming growth factor ß (TGF-ß) secreted from cultured ductal cells. Human acinar cells when cultured alone for a week in a serum-free condition do not undergo ADM. However, serum may contain other factors besides TGF-ß to induce ADM in human acinar cells. In addition, we found that TGF-ß cannot induce ADM of murine acinar cells. CONCLUSIONS: Ductal cells are the major source of TGF-ß that induces ADM in cultured human exocrine pancreatic tissues. This culture system might be a useful model to investigate the mechanism of ADM in human cells.

Secretin-Enhanced Magnetic Resonance Cholangiopancreatography for Assessing Pancreatic Secretory Function in Children.

OBJECTIVE: To assess the accuracy and interrater reproducibility of measurements of pancreatic secretory function by magnetic resonance cholangiopancreatography in response to secretin administration and to describe our experience using the technique to noninvasively assess pancreatic secretory function in a pediatric population. STUDY DESIGN: In the accuracy study, phantoms with varying fluid volume (47-206 mL) were imaged using the clinical quantification sequence. Fluid volume was measured by image segmentation (ImageJ). Measurement accuracy was expressed in terms of error (absolute and percent) relative to known fluid volume. In the reproducibility study and clinical experience, 31 patients with suspected pancreatic disease underwent 33 secretin-enhanced magnetic resonance cholangiopancreatography exams. Two-dimensional T2-weighted, fat-saturated single shot fast spin echo sequences were acquired before and after secretin injection (0.2 µg/kg, max 16 µg). Secreted fluid volume (postsecretin minus presecretin) was independently measured by 2 blinded reviewers. Between reviewer measurement reproducibility was assessed based on correlation (Spearman) and bias (Bland-Altman analysis). RESULTS: For the accuracy study, fluid volumes were measured with mean volume errors of -0.3 to +12.5 mL (percent error -0.03% to +9.0%). For the reproducibility study, the mean secreted fluid volumes measured by reviewer 1 and reviewer 2 were 79.1 ± 54.3 mL (range 5.5-215.4) and 77.2 ± 47.1 mL (range 6.7-198.1 mL), respectively. Measured secreted fluid volumes were very strongly correlated (r = 0.922) between reviewers with a bias of only 1.9 mL (95% limits of agreement -40.5 to 44.2). CONCLUSIONS: Measurement of fluid volume by magnetic resonance imaging is highly accurate with <10% (<13 mL) error in measured volume. Measurements of pancreatic secreted fluid volume in response to secretin by magnetic resonance cholangiopancreatography are highly reproducible with a bias of <2 mL between reviewers.

Carcinoma indiferenciado de páncreas exocrino en perro: descripción de caso / Carcinoma indiferenciado de pâncreas exócrino em cão: relato de caso / Undifferentiated carcinoma of the exocrine pancreas in dog: case report

El presente trabajo tiene como objetivo describir un caso de carcinoma de páncreas exocrino en un paciente canino, macho, raza Poodle de 10 años de edad. El motivo de la consulta fue orina oscura e ictericia. El animal presentaba sintomatología inespecífica junto con hallazgos físicos inconclusos. En ecografía abdominal se logró visualizar un nódulo en cuerpo de páncreas que fue confirmado bajo laparotomía exploratoria. El diagnóstico se corroboró con biopsia del tejido pancreático y marcación inmunohistoquímica. El tejido fue negativo para insulina, glucagón, somastatina y vimentina; y positivo para citoqueratina (AE1/AE3) y citoqueratina 19. El diagnóstico fue de carcinoma de páncreas exocrino. El paciente evidenció una respuesta clínica desfavorable que lo llevo a la muerte siete días después. En la necropsia se observó un notable cambio estructural en páncreas y evidencia de metástasis en órganos adyacentes no antes percibidos en la laparotomía demostrando así la agresividad de este tipo de tumor.

O presente trabalho tem como objetivo descrever um caso de carcinoma de pâncreas exócrino em um paciente canino, macho, da raça Poodle de 10 anos de idade. A queixa principal foi de urina escura e ictericia. O animal apresentava sinais inespecíficos além de achados físicos inconclusivos. No ultrassom abdominal conseguiu-se observar um nódulo no corpo do pâncreas que foi confirmado na laparotomia exploratória. O diagnóstico foi feito por biopsia do tecido pancreático e marcação imuno-histoquímica. O tecido foi negativo para insulina, glucagon, somastatina e vimentina, e positivo para citoqueratina (AE1/AE2) e citoqueratina 19. O diagnóstico foi de carcinoma de pâncreas exócrino. O paciente desenvolveu uma resposta clínica desfavorável e foi a óbito após sete días da cirurgia. Na necropsia foi observada uma acentuada mudança estrutural no pâncreas como também evidencia de metástase em órgãos adjacentes não antes percebidos na laparotomia exploratória, demostrando assim, a agressividade deste tipo de tumor.

The aim of this article is to describe a case of carcinoma of the exocrine pancreas in a 10 year old, male, Poodle dog. The main complaint informed by the owner was dark urine and icterus. The animal was presented with an unspecified symptomatology and physical exam inconclusive. On abdominal ultrasound a nodule in the pancreas body was seen and confirmed under exploratory laparotomy. Final diagnosis was confirmed by biopsy of the tissue and immunohistochemistry evaluation. The tissue was negative for insulin, glucagon, somastatin and vimentin; and positive for cytokeratin (AE1/AE3) and cytoqueratin 19. Final diagnosis was carcinoma of the exocrine pancreas. The dog had a poor clinical response and died after seven days post-surgery. On necropsy a remarkable structural change of pancreas and regional metastatic disease were revealed; these findings were not seen on previously exploratory surgery, describing the aggressiveness of this type of tumor.

Carcinoma indiferenciado de páncreas exocrino en perro: descripción de caso / Carcinoma indiferenciado de pâncreas exócrino em cão: relato de caso / Undifferentiated carcinoma of the exocrine pancreas in dog: case report

El presente trabajo tiene como objetivo describir un caso de carcinoma de páncreas exocrino en un paciente canino, macho, raza Poodle de 10 años de edad. El motivo de la consulta fue orina oscura e ictericia. El animal presentaba sintomatología inespecífica junto con hallazgos físicos inconclusos. En ecografía abdominal se logró visualizar un nódulo en cuerpo de páncreas que fue confirmado bajo laparotomía exploratoria. El diagnóstico se corroboró con biopsia del tejido pancreático y marcación inmunohistoquímica. El tejido fue negativo para insulina, glucagón, somastatina y vimentina; y positivo para citoqueratina (AE1/AE3) y citoqueratina 19. El diagnóstico fue de carcinoma de páncreas exocrino. El paciente evidenció una respuesta clínica desfavorable que lo llevo a la muerte siete días después. En la necropsia se observó un notable cambio estructural en páncreas y evidencia de metástasis en órganos adyacentes no antes percibidos en la laparotomía demostrando así la agresividad de este tipo de tumor.(AU)

O presente trabalho tem como objetivo descrever um caso de carcinoma de pâncreas exócrino em um paciente canino, macho, da raça Poodle de 10 anos de idade. A queixa principal foi de urina escura e ictericia. O animal apresentava sinais inespecíficos além de achados físicos inconclusivos. No ultrassom abdominal conseguiu-se observar um nódulo no corpo do pâncreas que foi confirmado na laparotomia exploratória. O diagnóstico foi feito por biopsia do tecido pancreático e marcação imuno-histoquímica. O tecido foi negativo para insulina, glucagon, somastatina e vimentina, e positivo para citoqueratina (AE1/AE2) e citoqueratina 19. O diagnóstico foi de carcinoma de pâncreas exócrino. O paciente desenvolveu uma resposta clínica desfavorável e foi a óbito após sete días da cirurgia. Na necropsia foi observada uma acentuada mudança estrutural no pâncreas como também evidencia de metástase em órgãos adjacentes não antes percebidos na laparotomia exploratória, demostrando assim, a agressividade deste tipo de tumor.(AU)

The aim of this article is to describe a case of carcinoma of the exocrine pancreas in a 10 year old, male, Poodle dog. The main complaint informed by the owner was dark urine and icterus. The animal was presented with an unspecified symptomatology and physical exam inconclusive. On abdominal ultrasound a nodule in the pancreas body was seen and confirmed under exploratory laparotomy. Final diagnosis was confirmed by biopsy of the tissue and immunohistochemistry evaluation. The tissue was negative for insulin, glucagon, somastatin and vimentin; and positive for cytokeratin (AE1/AE3) and cytoqueratin 19. Final diagnosis was carcinoma of the exocrine pancreas. The dog had a poor clinical response and died after seven days post-surgery. On necropsy a remarkable structural change of pancreas and regional metastatic disease were revealed; these findings were not seen on previously exploratory surgery, describing the aggressiveness of this type of tumor.(AU)

Derivación exocrina al duodeno en trasplante simultáneo de riñón y páncreas, experiencia en la Fundación Valle de Lili, Cali, Colombia / Exocrine bypass to the duodenum in simultaneous kidney and pancreas transplant, experience at Fundación Valle de Lili, Cali, Colombia

Introducción: El trasplante simultáneo de riñón y páncreas es reconocido como un tratamiento eficaz para el manejo de pacientes con diabetes mellitus, principalmente de tipo I, e insuficiencia renal crónica. Sin embargo, hoy en día aún existe dificultad para el seguimiento del injerto pancreático, ya que no existe un marcador serológico definitivo que lo permita y persiste la dificultad para la toma de biopsias. Se ha descrito una modificación en la técnica quirúrgica que permitiría el acceso endoscópico mediante una duodeno-duodenostomía. Material y métodos. Se seleccionaron los pacientes que recibieron un trasplante simultáneo de riñón y páncreas con derivación exocrina al duodeno, evaluando la seguridad del procedimiento, la evolución y las complicaciones médico-quirúrgicas. Resultados. Nueve pacientes fueron sometidos a trasplante simultáneo de riñón y páncreas con derivación exocrina al duodeno. La mediana de la edad fue de 36 años y la mayoría era del sexo masculino. El tiempo de isquemia en frío fue de 10 horas para el injerto pancreático y de 11 horas para el renal. El tiempo total de hospitalización fue de 21 días. Se presentó una pérdida del injerto pancreático y una pérdida del injerto renal. Hubo una sola muerte, causada por aspergilosis pulmonar. Conclusiones. La derivación exocrina duodenal permite y facilita la evaluación y el seguimiento endoscópico del injerto pancreático. No supone una mayor exigencia técnica en el trasplante simultáneo de riñón y páncreas, ni un incremento en el número de complicaciones en relación directa con la modificación del procedimiento quirúrgico.

Introduction: Despite its recognition as an effective therapy for the management of patients with Type I diabetes mellitus and chronic renal failure, simultaneous kidney and pancreas transplant encounters difficulties in monitoring the pancreatic graft, and there is no strong serologic marker coupled with the difficulties in taking biopsies. We describe a modification of a surgical technique that allows endoscopic access through a duodenostomy. Material and methods. Patients who received simultaneous kidney-pancreas transplantation with exocrine bypass to the duodenum were selected to evaluate the safety of the procedure, the clinical postoperative course, and the medical and surgical complications. Results: Nine patients were submitted to simultaneous kidney-pancreas transplantation with exocrine bypass to the duodenum. Median age was 36, most patients where male. Cold ischemia time was 10 hours for the pancreatic graft and 11 hours for the kidney graft. Total hospital stay was 21 days. There was one death caused by pulmonary aspergillosis. Conclusion: The duodenal exocrine derivation permits and facilitates the evaluation and endoscopy follow-up of the pancreatic graft. It neither imposes greater technical demands in simultaneous kidney-pancreas transplantation, nor an increase in the number of complications directly related to the modification of the surgical procedure.

Exocrine pancreatic carcinoma with hypoglycemia in a dog / Carcinoma de pâncreas exócrino com hipoglicemia em um cão

Background: Primary pancreas neoplasms are rare, representing less than 0.5% of all veterinary tumors. They are highly aggressive, and most of the patients have unspecific clinical signs until diagnosis. Although the treatment of choice is surgical resection, only 15 to 20% of the patients may undergo surgery and be cured. Survival is variable after diagnosis, ranging from 4 to 10 months. Prognosis is poor due to the aggressiveness and advanced stage of the disease at the moment of diagnosis, and the weak response to all existing treatments. The objective of this study was to report a case of exocrine pancreatic carcinoma in a dog with hypoglycemia. Case: The present study describes a clinical case of exocrine pancreatic carcinoma in the Clínica Escola de Veterinária (CEVET) at UNICENTRO-PR. The patient was taken to the CEVET and the main complaint of the owner was a volume increase in the ventral thoracic region. During the physical examination, it was observed that this increased volume was a mammary tumor in the third gland of the right side of the body. The animal showed no other symptoms and the diagnosis of exocrine pancreatic cancer was only possible because glucose levels in routine examination were below the normal reference value for the species (47 mg/dL). After the glycemic curve was determined, it was observed that glucose levels were below reference values, even [...]

Exocrine pancreatic carcinoma with hypoglycemia in a dog / Carcinoma de pâncreas exócrino com hipoglicemia em um cão

Background: Primary pancreas neoplasms are rare, representing less than 0.5% of all veterinary tumors. They are highly aggressive, and most of the patients have unspecific clinical signs until diagnosis. Although the treatment of choice is surgical resection, only 15 to 20% of the patients may undergo surgery and be cured. Survival is variable after diagnosis, ranging from 4 to 10 months. Prognosis is poor due to the aggressiveness and advanced stage of the disease at the moment of diagnosis, and the weak response to all existing treatments. The objective of this study was to report a case of exocrine pancreatic carcinoma in a dog with hypoglycemia. Case: The present study describes a clinical case of exocrine pancreatic carcinoma in the Clínica Escola de Veterinária (CEVET) at UNICENTRO-PR. The patient was taken to the CEVET and the main complaint of the owner was a volume increase in the ventral thoracic region. During the physical examination, it was observed that this increased volume was a mammary tumor in the third gland of the right side of the body. The animal showed no other symptoms and the diagnosis of exocrine pancreatic cancer was only possible because glucose levels in routine examination were below the normal reference value for the species (47 mg/dL). After the glycemic curve was determined, it was observed that glucose levels were below reference values, even [...](AU)

Pancreatic polypeptide: a review of its involvement in neuro-endocrine reflexes, islet-acinar interactions and ethanol-evoked physiopatologic pancreatic gland changes.

prevents, in pancreocytes, the evolving of a "supramaximalecbolic-stimulation" process. The PP involvement as a modulating agent of pancreon's reactivity is reflected by the progressive increment of its plasma values in the first week of an evolving AP episode. In the AP associated to a large meal, an overpowering of the pancreon's brake might have a pivotal role. In experimental and clinical chronic alcoholism, a vagal neuropathy of the Pavlov inhibitory fibers that, as a consequence, impairs the pancreon's brake through a depression of PP secretion is at the basis of an enhanced reactivity of the duodeno-pancreatic reflexes. The latter leads to intrapancreatic cholinergic hypertonus and to Vater papilla's dysfunction. These changes, plus an enhanced pancreocyte's response to CCK, are at the core of acinar cell "supramaximal stimulation" with the organelle disruption that process implies. The intrapancreatic cholinergic hypertonus, the enhanced exocrine cell reactivity to CCK stimulation, and the augmented resistance to the pancreatic secretion flow at Oddi sphincter, explain the aggravating influence of chronic alcoholism on an episode of acute biliary pancreatitis. As the PP secretion, normally elicited by secretin, CCK, food and insulin hypoglycemia, is depressed in the presence of an augmented number of PP cells, as it is in the cases of chronic alcoholics, cystic fibrosis patients and, also, in dogs with pancreatic fibrosis (ductal ligation), it has been inferred, besides our postulated impairment of the Pavlov inhibitory fibers in the vagus nerves, that the defect of PP release is localized to the common final pathway of the above stimuli, probably in or near the PP cell itself This review was prompted by the unexpected experimental finding in canines that Tissucol-induced pancreatic ductal blockade elicits Pancreatic Polypeptide (PP) release and seems to be at the basis of the beneficial effects on taurocho- late-induced acute pancreatitis (AP). In the release mechanism of this regulatory peptide secreted by PP cells located in the periphery of Langerhans islets and scattered in the ductal epithelium, two neuroendocrine reflexes (NER) are involved. The "short" NER is evoked from the duodenum by an unknown component of bile-pancreatic secretion. The "long" NER is triggered by a vagovagal reflex. PP induces a depression of the intrapancreatic cholinergic tone. On the one hand suppressing, hormonally, nervous impulses discharge from the vagal nuclear complex in the brainstem. On the other, interfering paracrinically on the cholinergic transmission by acting, presynaptically, on post-ganglionic cholinergic neurons. The resulting PP-evoked fall of the intrapancreatic cholinergic tone depresses the hormone induced (secretin, CCK) pancreons secretory response. PP, with other agents, contributes to the "fail-safe" system or pancreon's brake that

Variants in Solute Carrier SLC26A9 Modify Prenatal Exocrine Pancreatic Damage in Cystic Fibrosis.

OBJECTIVES: To test the hypothesis that multiple constituents of the apical plasma membrane residing alongside the causal cystic fibrosis (CF) transmembrane conductance regulator protein, including known CF modifiers SLC26A9, SLC6A14, and SLC9A3, would be associated with prenatal exocrine pancreatic damage as measured by newborn screened (NBS) immunoreactive trypsinogen (IRT) levels. STUDY DESIGN: NBS IRT measures and genome-wide genotype data were available on 111 subjects from Colorado, 37 subjects from Wisconsin, and 80 subjects from France. Multiple linear regression was used to determine whether any of 8 single nucleotide polymorphisms (SNPs) in SLC26A9, SLC6A14, and SLC9A3 were associated with IRT and whether other constituents of the apical plasma membrane contributed to IRT. RESULTS: In the Colorado sample, 3 SLC26A9 SNPs were associated with NBS IRT (min P=1.16×10(-3); rs7512462), but no SLC6A14 or SLC9A3 SNPs were associated (P>.05). The rs7512462 association replicated in the Wisconsin sample (P=.03) but not in the French sample (P=.76). Furthermore, rs7512462 was the top-ranked apical membrane constituent in the combined Colorado and Wisconsin sample. CONCLUSIONS: NBS IRT is a biomarker of prenatal exocrine pancreatic disease in patients with CF, and a SNP in SLC26A9 accounts for significant IRT variability. This work suggests SLC26A9 as a potential therapeutic target to ameliorate exocrine pancreatic disease.

TTD consensus document on the diagnosis and management of exocrine pancreatic cancer.

Exocrine pancreatic cancer (PC) is a very aggressive and heterogeneous tumor with several cellular signaling pathways implicated in its pathogenesis and maintenance. Several risk factors increase the risk of developing PC. Therapeutic strategies used are dictated by the extent of disease. Supportive treatment is critical because of the high frequency of symptoms. For localized disease, surgery followed by adjuvant gemcitabine is the standard. Neoadjuvant and new adjuvant chemotherapy regimens are being evaluated. Locally advanced disease should respond best guided by a multidisciplinary team. Various treatment options are appropriate such as chemotherapy alone or chemoradiotherapy with integration of rescue surgery if the tumor becomes resectable. In metastatic disease, chemotherapy should be reserved for patients with ECOG 0-1 using Folfirinox or gemcitabine plus nab-paclitaxel as the most recommended options. Several therapeutic strategies targeting unregulated pathways are under evaluation with an unmet need for biomarkers to guide management.

Avances en la cirugía de tumores del páncreas exocrino en niños / Advances in the surgical management of pancreatic exocrine tumors in children

Introducción: Los tumores pancreáticos en la infancia son infrecuentes y diversos. Dentro de ellos, el pan-creatoblastoma es el más frecuente en niños pequeños, seguido por el tumor sólido pseudopapilar (TSP), que es una neoplasia de bajo grado de malignidad que predomina en niñas y mujeres jóvenes. La resección quirúrgica completa, es su tratamiento de elección. En la medida del progreso de la cirugía mínimamente invasiva , la pancreatectomía laparoscópica parece ser factible y segura en niños. Objetivo: Comunicar el caso clínico de un niño con TSP para alertar sobre esta patología y actualizar acerca de su manejo quirúrgico. Caso clínico: Niño de 10 años portador de un tumor pancreático diagnosticado por presentar dolor abdominal luego de un traumatismo menor. La ultrasonografía y TAC de abdomen mostraron un tumor de 8 cm en el cuerpo y cola del páncreas, sin metástasis. La a-feto proteína fue normal. Se realizó pancreatectomía córporo caudal laparoscópica y esplenectomía, siendo dado de alta al sexto día postoperatorio, sin incidentes. La biopsia confirmó TSP. Discusión: Se expone acerca de las características y clasificación de los tumores del páncreas en la infancia. En particular de discute acerca del TSP, su enfrentamiento diagnóstico y las ventajas de la cirugía mínimamente invasiva en su tratamiento.

Introduction: Pancreatic tumors in childhood are rare and diverse. Among them, pancreatoblastoma is the most common pancreatic tumor in young children, followed by the solid pseudopapillary tumor (SPT), which is an uncommon neoplasm characterized by low potential for malignancy that mainly occurs in young women. Complete surgical resection is the treatment of choice. Following the advances in minimally invasive surgery, laparoscopic distal pancreatectomy appears to be feasible and safe in children. Objective: To report a case of a child with SPT to create awareness on this topic and update its surgical management. Case report: The case of a 10 year old boy carrying a pancreatic tumor, who sought medical attention due to abdominal pain after minor trauma, is reported. Ultrasonography and CT scan of the abdomen showed an 8 cm tumor in the body and tail of the pancreas, no metastases. The alpha-fetoprotein was normal. Laparoscopic corporocaudal pan-createctomy and splenectomy were performed, and the patient was discharged on the sixth postoperative day without incident. Biopsy confirmed SPT. Discussion: This study exposes the characteristics and classification of pancreatic tumors in childhood. In particular, SPT is discussed regarding diagnosis and the advantages of minimally invasive surgery as part of the treatment.

Pancreatic ultrastructural enhancement due to telmisartan plus sitagliptin treatment in diet-induced obese C57BL/6 mice.

OBJECTIVE: We sought to evaluate the effects of telmisartan, sitagliptin, or their combination on pancreatic ultrastructural alterations in high-fat-fed C57BL/6 mice. METHODS: Three-month-old C57BL/6 mice were fed with standard chow (SC, 10% lipids) or high-fat diet (HF, 60% lipids) during 10 weeks to induce obesity and its comorbidities. After this period, treatment began (lasted 6 weeks), and the HF group was divided into 4 subgroups: untreated HF, HF plus telmisartan (5 mg/kg per day), HF plus sitagliptin (1.1 g/kg per day), and HF plus telmisartan plus sitagliptin. Drugs were mixed with diet. Biochemical analyses, radioimmunoassay, immunofluorescence, stereology, and transmission electron microscopy were performed to assess pancreatic remodeling. RESULTS: Overweight, hyperinsulinemia, hyperglycemia, and dyslipidemia were found in the HF group, but these outcomes were controlled by the different treatments. Untreated HF animals also showed alterations concerning distribution of α/ß cell followed by large and numerous lipid droplets within pancreas. Telmisartan and sitagliptin as monotherapy alleviated these findings, and a complete reversal of pancreatic steatosis was observed after treating with the combination of the 2 drugs. CONCLUSIONS: AT1 receptor blockade, partial peroxisome proliferator-activated receptor gamma activation, and extended incretin action emerge as feasible strategies to control pancreatic steatosis and avoid progression of pancreatic diseases due to lipotoxicity.

Atrial natriuretic factor stimulates efflux of cAMP in rat exocrine pancreas via multidrug resistance-associated proteins.

BACKGROUND & AIMS: Atrial natriuretic factor (ANF) prevents increases in intracellular levels of cAMP that are induced by secretin in the exocrine pancreas. We investigated the contribution of cyclic adenosine monophosphate (cAMP) efflux to ANF inhibition of secretin signaling. METHODS: Intracellular and extracellular cAMP were measured by radio-binding assays in isolated pancreatic acini exposed to secretin and other secretagogues, alone or with ANF. Levels of messenger RNA for multidrug resistance-associated protein (MRP)4, MRP5, and MRP8 were measured by real-time polymerase chain reaction. MRP4 was knocked down in AR42J cells by small interfering RNA. In vivo studies were performed in rats. RESULTS: Pancreatic secretagogues increased levels of intracellular cAMP, but only secretin and vasoactive intestinal peptide promoted cAMP efflux; efflux was increased by ANF, through signaling via natriuretic peptide receptor-C and phospholipase C-protein kinase C. In time-course studies with active phosphodiesterases, levels of intracellular and extracellular cAMP increased earlier after the addition of secretin and ANF (1 min) than after the addition of secretin alone (3 min). Similar kinetic patterns occurred with a phosphodiesterase inhibitor. A probenecid-sensitive transporter mediated cAMP egression. The main cAMP transporter, MRP4, was expressed in AR42J cells and pancreas. cAMP egression occurred in AR42J cells exposed to secretin, but this response was reduced in cells that expressed MRP4 small interfering RNA. In rats, levels of cAMP in plasma and pancreatic juice increased after infusion with secretin alone or secretin plus ANF. CONCLUSIONS: ANF signals via natriuretic peptide receptor-C coupled to the phospholipase C-protein kinase C pathway to increase secretin-induced efflux of cAMP, probably through MPR-4. Cyclic AMP extrusion might be a mechanism, in addition to phosphodiesterase action, to regulate intracellular cAMP levels in pancreatic acinar cells.