Effect of exosomes as drug carriers in chemotherapy of pancreatic cancer / 中南大学学报(医学版)

Pancreatic cancer (PC) is a malignant tumor of the digestive tract with poor patient prognosis. The PC incidence is still increasing with a 5-year survival rate of only 10%. At present, surgical resection is the most effective method to treat PC, however, 80% of the patients missed the best time for surgery after they have been diagnosed as PC. Chemotherapy is one of the main treating methods but PC is insensitive to chemotherapy, prone to drug resistance, and is accompanied by many side effects which are related to a lack of specific target. Exosomes are nanoscale vesicles secreted by almost all cell types and can carry various bioactive substances which mediate cell communication and material transport. They are characterized by a low immunogenicity, low cytotoxicity, high penetration potential and homing capacity, and possess the potential of being used as advanced drug carriers. Therefore, it is a hot research topic to use drug-loaded exosomes for tumor therapy. They may alleviate chemotherapy resistance, reduce side effects, and enhance the curative effect. In recent years, exosome drug carriers have achieved considerable results in PC chemotherapy studies.

Caracterización clinicoepidemiológica de pacientes con cáncer de páncreas en un servicio de cirugía general / Clinical epidemiological characterization of patients with pancreas cancer in a general surgery service

Introducción: El cáncer de páncreas constituye una de las neoplasias de peor pronóstico debido a su diagnóstico tardío. Objetivo: Caracterizar a los pacientes con cáncer de páncreas según variables clinicoepidemiológicas y exámenes complementarios. Métodos: Se realizó un estudio observacional, descriptivo y transversal de 70 pacientes con cáncer de páncreas, egresados del Servicio de Cirugía General del Hospital Provincial Docente Saturnino Lora de Santiago de Cuba durante el periodo 2016-2020. Se estudiaron las variables: edad, sexo, factores de riesgo, enfermedades asociadas, manifestaciones clínicas y exámenes complementarios. Resultados: Predominaron el sexo masculino ( 54,2 %), las edades comprendidas de entre 51- 70 años, la ingestión de comidas grasas y los hábitos tabáquico y alcohólico como factores de riesgo; el alcoholismo crónico, la diabetes mellitus y la hipertensión arterial como enfermedades asociadas más comunes, así como el síndrome general, la ictericia y la coluria entre las manifestaciones clínicas más frecuentes. Por su parte, según los estudios imagenológicos, la mayoría de los afectados se diagnosticaron mediante tomografía computarizada y ecografía abdominal (94,3 y 70,0 %, respectivamente). Conclusiones: La tomografía computarizada multicorte es la técnica de imagen de elección recomendada por las guías de consenso internacional. Si bien el informe radiográfico es clave para la toma de decisiones posteriores, existen circunstancias del paciente que pueden afectarlas, tales como edad, factores de riesgo, manifestaciones clínicas y comorbilidad, entre otras.

Introduction: The pancreas cancer constitutes one of the neoplasms with worse prognosis due to its late diagnosis. Objective: To characterize patients with pancreas cancer according to clinical epidemiological variables and complementary exams. Methods: An observational, descriptive and cross-sectional study of 70 patients with pancreas cancer was carried out, who were discharged from the General Surgery Service of Saturnino Lora Teaching Provincial Hospital in Santiago de Cuba during 2016-2020. The variables studied were: age, sex, risk factors, associated diseases, signs and symptoms and complementary exams. Results: There was a prevalence of the male sex (54.2 %), the 51-70 age group, the ingestion of fatty foods and nicotine addiction and alcoholism as risk factors, the chronic alcoholism, diabetes mellitus and hypertension as more common associated diseases, as well as the general syndrome, jaundice and coluria among the most frequent signs and symptoms. On the other hand, according to the imaging studies, most of those affected were diagnosed by means of computerized axial tomography and abdominal echography (94.3 and 70.0 %, respectively). Conclusions: The multiscan computerized axial tomography is the image technique of election recommended by the guides of international consent. The radiographic report is the key for later decisions making but there are circumstances of the patient that can affect them, such as age, risk factors, signs and symptoms and comorbidity, among others.

Índice pronóstico nutricional en pacientes con cáncer de páncreas avanzado tratados con nimotuzumab combinado a quimioterapia / Nutritional prognostic index in patients with advanced pancreatic cancer treated with nimotuzumab combined with chemotherapy

Introducción: El índice pronóstico nutricional es un marcador inmuno-nutricional que puede ser útil como factor pronóstico en tumores gastrointestinales. Objetivo: Evaluar supervivencia de pacientes con adenocarcinoma pancreático avanzado tratados con quimioinmunoterapia según índice pronóstico nutricional, según parámetros clínico-patológicos y tratamiento. Métodos: Se realizó estudio retrospectivo y observacional en pacientes que recibieron quimioterapia gemcitabina-oxaliplatino combinado a nimotuzumab (n=118), en el Hospital Ameijeiras, entre 2014 y 2019. Se evaluó supervivencia por método Kaplan-Meier, y regresión de Cox, para determinar los factores pronósticos independientes de supervivencia. Resultados: El punto de corte seleccionado fue 40 (sensibilidad 52,9 por ciento y especificidad 85,7 por ciento (p = 0,019), con área bajo la curva de 0,693. Para pacientes con índice menor de 40, la supervivencia fue más baja respecto a los pacientes con índice ≥ 40 (11,4 meses frente a 16,0 meses; p=0,001), con un HR de 1,7 (1,13-2,60; p=0,011). Las variables mayormente asociadas con índice pronóstico nutricional altos son pacientes con sesenta años o menos; ECOG cero, índice de masa corporal ≥25 Kg/m2 y albúmina sérica >3,5g/dL (x² < 0,05). Los pacientes con índice ≥ 40 tienen medianas de supervivencia más altas que pacientes con índice < 40 en las variables seleccionadas con p < 0,05, excepto el índice de masa corporal. Conclusiones: Este trabajo constituye el primer reporte nacional de utilización del índice pronóstico nutricional como pronóstico de supervivencia en pacientes con cáncer de páncreas avanzado(AU)

Background: The nutritional prognostic index is an immuno-nutritional marker that can be useful as a prognostic factor in gastrointestinal tumors. Aim: To evaluate the survival of patients with advanced pancreatic adenocarcinoma treated with chemoimmunotherapy according to the nutritional prognostic index, according to clinical-pathological parameters and treatment. Methods: A retrospective and observational study was carried out in patients who received gemcitabine-oxaliplatin chemotherapy combined with nimotuzumab (n=118), at the Ameijeiras Hospital, between 2014 and 2019. Survival was evaluated by the Kaplan-Meier method, and Cox regression, for determine independent prognostic factors for survival. Results: The selected cut-off point was 40 (52.9 percent sensitivity and 85.7 percent specificity) (p=0,019), with an area under the curve of 0,693. For patients with an index less than 40, survival was lower compared to patients with index ≥ 40 (11, 4 months vs. 16, 0 months; p=0,001), with a HR of 1, 7 (1, 13-2, 60; p=0,011). The variables mostly associated with nutritional prognostic index patients with 60 years or less, ECOG 0, body mass index ≥ 25 kg/m2 and serum albumin >3,5g/dL (x2 < 0, 05). Patients with index ≥ 40 have higher median survival than patients with index < 40 in the selected variables with p < 0, 05, except body mass index. Conclusions: This work constitutes the first national report on the use of the nutritional prognostic index as a prognosis of survival in patients with advanced pancreatic cancer(AU)

Páncreas ectópico en antro gástrico asociado a síntomas de reflujo. Reporte de un caso / Ectopic pancreas in gastric antrum associated to reflux symptoms. Report of a case

RESUMEN El páncreas ectópico es una entidad poco común. Como tumor submucoso de origen congénito, frecuentemente presenta un curso asintomático, aunque con posibles complicaciones. Su diagnóstico de certeza se basa en la endoscopia, el ultrasonido endoscópico y la histología, que permiten adoptar una conducta expectante o quirúrgica. El paciente estudiado presentó un páncreas ectópico localizado en antro gástrico asociado a síntomas de reflujo gastroesofágico rebeldes a tratamiento, los cuales motivaron el estudio endoscópico, con el consecuente hallazgo de dicha entidad (AU).

ABSTRACT Ectopic pancreas is a little common entity. As congenital-originated sub mucous tumor, it frequently presents an asymptomatic course, though with possible complications. Its definitive diagnosis is based in the endoscopy, endoscopic ultrasound and histology, allowing to adopt an expectant or surgical behavior. The current patient presented an unresponsive-to-treatment ectopic pancreas located in the gastric antrum associated to gastro-esophageal reflux symptoms. This motivated the endoscopic study consequently leading to finding this entity (AU).

Carcinoma pseudopapilar sólido del páncreas / Solid pseudo-papillary carcinoma of the pancreas

El tumor sólido pseudopapilar del páncreas, conocido también como tumor de Frantz, es una enfermedad rara: neoplasia bien delimitada, de lento crecimiento, no agresiva pero maligna, habitualmente con pronóstico favorable. El tratamiento de elección es quirúrgico. Aunque algunos de ellos son agresivos a nivel local, la mayoría de los pacientes se curan con la resección completa del tumor. Se reportó el caso de una mujer de 30 años, ingresada en el Servicio de Cirugía General del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, con diagnóstico presuntivo clínico e imagenológico, de tumor pseudopapilar sólido del páncreas, con confirmación histológica tras la resección quirúrgica. Este infrecuente tumor debe ser considerado en el diagnóstico diferencial de los tumores pancreáticos, fundamentalmente en mujeres jóvenes(AU)

The solid pseudo-papillary carcinoma, also known as Frantz´s tumor, is a rare disease. It is a well-defined neoplasia, of low growth, non-aggressive but malignant, usually with a favorable prognosis. The elective treatment is the surgery. Although some of them are locally aggressive, most patients are healed with the complete tumor resection. The authors reported the case of a woman, aged 30 years who entered the Service of General Surgery of the University Hospital Comandante Faustino Pérez Hernández, with a presumptive clinical and imaging diagnosis of pancreas solid pseudo-papillary tumor, histologically confirmed after surgical resection. This infrequent tumor should be taken into account in the differential diagnosis of pancreatic tumors, mainly in young women(AU)

Análise da sobrevida de pacientes com câncer de pâncreas / Survival analysis of patients with pancreatic cancer

Objetivo: Estimar a taxa de sobrevida por câncer de pâncreas. Métodos: Trata-se de estudo com delineamento de coorte retrospectiva, realizado no período de 2007 a 2018, em um hospital terciário no Sul do Brasil. A amostra foi composta de 66 indivíduos que realizaram acompanhamento no Hospital Nossa Senhora da Conceição, em Tubarão (SC), cujo sítio primário da doença tenha sido o pâncreas. Resultados: Dos 66 prontuários avaliados, 35 pertenciam a pessoas do sexo masculino (53%), com média de idade de diagnóstico de 64,3 anos. O estádio mais prevalente foi o IV (46 pacientes, correspondente a 69,7%). O tempo médio de sobrevida global foi de 462,02 dias (desvio-padrão de 90,76), e a mediana foi de 320 dias. Conclusão: Identificou-se uma prevalência maior em pessoas do sexo masculino, idosos e caucasianos e em indivíduos no estadiamento IV.

Objective: To estimate the survival rate for pancreatic cancer. Methods: This is aretrospective cohort study conducted from 2007 to 2018 in a tertiary hospital in Southern Brazil. The sample consisted of 66 individuals followed up at Hospital Nossa Senhora da Conceição, in Tubarão (SC), whose primary site of the disease was the pancreas. Results: Of the 66 medical records assessed, 35 were of male (53%) individuals, with a mean age at diagnosis of 64.3 years. The most prevalent stage was IV (46 patients, corresponding to 69.7%). The mean overall survival time was 462.02 days (standard deviation of 90.76) and the median was 320 days. Conclusion: Higher prevalence of males, elderly people, and Caucasians was observed, as well as IV staging.

Non-inflammatory pancreatic cysts: from diagnosis to treatment (97 cases series) / Cistos não inflamatórios de pâncreas: do diagnóstico ao tratamento (série de 97 casos)

ABSTRACT Objective: to describe the implications of the diagnosis and treatment of non-inflammatory pancreatic cysts in a series of patients. Methods: we included patients with pancreatic cysts ≥1.0 cm, excluding those with a presumptive diagnosis of a pseudocyst. Imaging tests, echoendoscopy, and histopathology determined the diagnosis of the type of cyst. We applied the guidelines of the International Association of Pancreatology, with some modifications, in patients with mucinous or indeterminate lesions. Results: 97 adult patients participated in the study. A cystic neoplasm of the pancreas was diagnosed in 82.5% of cases. Diagnosis was mainly made by magnetic resonance (46% of cases). The two most common diagnoses were intraductal papillary mucinous neoplasm (43.3%) and serous cystadenoma (26%). Twenty-nine patients underwent surgery (33.3%). The most common surgical procedure was distal pancreatectomy associated with splenectomy in 19 cases (65.5%). Among the operated patients, 11 were diagnosed with cancer. None of the followed, non-operated patients had a diagnosis of cancer. Conclusions: magnetic resonance showed good accuracy, particularly in the diagnosis of intraductal papillary mucinous neoplasm. The guidelines of the International Association of Pancreatology, as applied in this study, showed a negative predictive value for cancer of 100%. A development of better diagnostic tests can reduce the number of unnecessary operations.

RESUMO Objetivo: descrever as implicações do diagnóstico e tratamento dos cistos não inflamatórios do pâncreas em série de pacientes. Metódos: foram incluídos pacientes com cisto de pâncreas ≥1,0cm excluindo aqueles com diagnóstico presuntivo de pseudocisto. Exames de imagem, ecoendoscopia e anatomia-patológica determinaram o diagnóstico do tipo de cisto. As diretrizes da Associação Internacional de Pancreatologia foram aplicadas, com algumas modificações, nos pacientes com lesões mucinosas ou indeterminadas. Resultados: noventa e sete pacientes adultos participaram do estudo. A neoplasia cística de pâncreas foi diagnosticada em 82,5% dos casos. O diagnóstico foi feito principalmente por ressonância magnética (46% dos casos). Os dois diagnósticos mais frequentes foram a neoplasia papilar intraductal mucinosa (43,3%), e o cistoadenoma seroso (26%). Vinte e nove pacientes foram submetidos a operação (33,3%). O procedimento cirúrgico mais comum foi a pancreatectomia corpo-caudal associada à esplenectomia em 19 casos (65,5%). Entre os pacientes operados, 11 tiveram o diagnóstico de câncer. Nenhum dos pacientes seguidos teve o diagnóstico de câncer. Conclusões: a ressonância magnética apresentou boa acurácia, particularmente no diagnóstico da neoplasia papilar intraductal mucinosa. As diretrizes da Associação Internacional de Pancreatologia da forma que foram aplicadas no presente estudo, mostraram valor preditivo negativo para o câncer de 100%. O desenvolvimento de estratégias diagnósticas com melhor acurácia podem reduzir o número de cirurgias desnecessárias.

Insulinoma simulando una epilepsia: reporte de caso / Insulinoma simulating epilepsy: case report

Insulinoma es un tumor neuroendocrino que surge de las células ß del páncreas y produce hiperinsulinemia endógena. Son neoplasias raras con una incidencia reportada de 4 casos por millón de habitantes por año. La presentación clínica típicamente cursa con síntomas adrenérgicos y neuroglucopénicos secundarios a hipoglicemia. Requiere estudios de niveles séricos de insulina, pro-insulina y péptido C, además de imágenes diagnosticas que confirmen los hallazgos. La mayoría de los insulinomas son benignos, su sitio primario más común es el páncreas y pueden extirparse quirúrgicamente. Se presenta el caso de un hombre de 36 años con déficit cognitivo leve y episodios de diaforesis con deterioro neurológico hasta convulsiones tónico clónicas generalizadas que curiosamente resolvían con uso doméstico de "panela molida". Se ingresó a urgencias por ataques recurrentes de hipoglicemia severa con requerimiento de altas dosis de dextrosa al 50% por acceso central, hasta confirmación diagnóstica, intervención y resección de tumor neuroendocrino pancreático bien diferenciado (G1 según clasificación OMS) tipo insulinoma en la cola del páncreas.

Insulinoma is a neuroendocrine tumor that arises from the ß cells of the pancreas and produces endogenous hyperinsulinemia. They are rare neoplasms with a reported incidence to 4 cases per million inhabitants per year. The clinical presentation typically presents with adrenergic and neuroglycopenic symptoms secondary to hypoglycemia. It requires studies of serum levels of insulin, pro-insulin and C-peptide, in addition to diagnostic images that confirm the findings. Most insulinomas are benign, their most common primary site is the pancreas, and they can be removed surgically. We present the case of a 36-year-old man with mild cognitive deficits and episodes of diaphoresis with neurological deterioration to generalized clonic tonic seizures that curiously resolved with domestic use of "ground brown sugar". He was admitted to the emergency department due to recurrent attacks of severe hypoglycemia with a high-dose requirement for 50% dextrose through central access, until diagnostic confirmation, intervention, and resection of a welldifferentiated pancreatic neuroendocrine tumor (G1 according to WHO classification) insulinoma in the tail of pancreas.

Hiperplasia de células neuroendocrinas que simula tumor sólido de páncreas / Neuroendocrine cell hyperplasia mimicking a solid pancreatic tumor

RESUMEN La hiperplasia de células neuroendocrinas pancreáticas es una patología donde se produce un aumen to en el número de células de los islotes de Langerhans y a veces puede simular un proceso tumoral. Caso clínico: presentamos el caso de un paciente con tumor sólido de cola de páncreas, sintomático, al que se le realizó esplenopancreatectomía corporocaudal laparoscópica. El resultado anatomopatoló gico posterior informó una hiperplasia neuroendocrina. Conclusión: la hiperplasia de células neuroen docrinas debería considerarse en el diagnóstico diferencial de tumores sólidos de páncreas. La alterna tiva quirúrgica laparoscópica es factible cuando no es posible establecer el diagnóstico prequirúrgico con estudios de imágenes o biopsia.

ABSTRACT Pancreatic endocrine cell hyperplasia is defined as an increase in the number of cells of Langerhans islets and can sometimes mimic a tumoral process. Case report: a male patient with a symptomatic solid tail of pancreas tumor underwent laparoscopic distal pancreatectomy and splenectomy. The pathological examination reported neuroendocrine cell hyperplasia. Conclusion: pancreatic endocrine cell hyperplasia should be considered in the differential diagnosis of solid pancreatic tumors. Laparoscopic surgery is feasible when the preoperative diagnosis with imaging tests of biopsy is not possible.

Differences in lipidomics may be potential biomarkers for early diagnosis of pancreatic cancer

Abstract Purpose To analyze the plasma lipid spectrum between healthy control and patients with pancreatic cancer and to select differentially expressed tumor markers for early diagnosis. Methods In total, 20 patents were divided into case group and healthy control group according to surgical pathology. Of almost 1206 plasma lipid molecules harvested from 20 patients were measured by HILIC using the normal phase LC/MS. Heat map presented the relative levels of metabolites and lipids in the healthy control group and patients with pancreatic cancer. The PCA model was constructed to find out the difference in lipid metabolites. The principal components were drawn in a score plot and any clustering tendency could be observed. PLS-DA were performed to distinguish the healthy control group and pancreatic cancer according to the identified lipid profiling datasets. The volcano plot was used to visualize all variables with VIP>1 and presented the important variables with P<0.01 and -FC->2. Results The upregulated lipid metabolites in patients with pancreatic cancer contained 9 lipids; however, the downregulated lipid metabolites contained 79 lipids. Conclusion There were lipid metabolomic differences in patients with pancreatic cancer, which could serve as potential tumor markers for pancreatic cancer.

Granuloma anular, pronóstico de diabetes mellitus. A propósito de un caso / Annular granuloma, prognosis of diabetes mellitus. On the purpose of a case

RESUMEN El granuloma anular es una dermatosis de relativa frecuencia en niños, jóvenes y adultos. Está caracterizado por lesiones cutáneas eritemato-pápulo-nodulares, que adoptan una disposición anular. Su etiopatogenia es desconocida, pero con numerosos factores predisponentes, desencadenantes o asociados a ella; como es la diabetes mellitus y/o procesos neoplásicos o paraneoplásicos. Resulta importante el estudio de pacientes con este diagnóstico por su asociación con entidades como las antes mencionadas. Se realizó el reporte de un caso en adulto mayor de 65 años, con diagnóstico de granuloma anular, diabetes mellitus y neoplasia de páncreas.

ABSTRACT Annular granuloma is a dermatosis relatively frequent in children, young and adult people. It is characterized by erythematous-papular-nodular skin lesions adopting annular disposition. Its etio-pathogenesis is unknown, but there are many predisposal, unleashing factors, or associated to this disease, like diabetes mellitus and/or neoplastic or paraneoplastic processes. It is important to study the patients diagnosed with the disease due to its association with entities like those before mentioned. The reported case is the case of a patient elder than 65 years, diagnosed with annular granuloma, diabetes mellitus and pancreas neoplasia.

Tumores sólidos pseudopapilares del páncreas en Costa Rica: serie de casos y revisión de tema / Solid pseudopapillary tumors of pancreas in Costa Rica: serie of cases and review of literature

Introducción: Los tumores sólidos pseudopapilares de páncreas son neoplasias poco frecuentes, más comunes en mujeres, con comportamiento incierto. Objetivo: La presente revisión tiene como meta la descripción de la experiencia en el manejo de estos tumores en nuestro centro y aportar a la casuística nacional. Materiales y métodos: Se revisó bases de datos del Servicio de Patología del Hospital Calderón Guardia y del Hospital México durante el periodo comprendido entre enero del 2013 a abril del 2018 y se encontró un total de 13 muestras compatibles con tumores sólidos pseudopapilares; se revisaron datos clínicos y epidemiológicos y se utilizó estadística descriptiva para el reporte de los datos encontrados. Resultados: Se encontró 13 casos compatibles con tumores sólidos pseudopapilares. La mayoría correspondía a mujeres con un promedio de edad de 32 años. La mayor cantidad se presentó como hallazgo incidental y la localización en cabeza fue la más frecuente. La mayor parte fue manejada de manera quirúrgica. Conclusión: Este es el primer estudio en Costa Rica que describe las características de los tumores sólidos pseudopapilares del páncreas, en el cual se documentó una similitud en las características de nuestros pacientes a las reportadas en series internacionales.

Introduction: Solid pseudopapillary tumors of pancreas are rare primary neoplasm of the pancreas, typically affects women. Objectives: We have to describe our experience in the management of this kind of tumors in our center. Material and Materials and methods: We reviewed database from the Pathology Service in Hospital Calderon Guardia and Mexico Hospital between January 2013 to April 2018. We found 13 cases of solid pseudopapillary tumors, reviewed their charts and describe their data. Results: We found 13 cases of solid pseudopapillary tumors of pancreas. The majority were women, and their middle age was 32 years old. The majority of cases were incidental findings, and the head of pancreas was the most common affected localization. Conclusion: This is the first report from Costa Rica that describe the characteristics of solid pseudopapillary tumors, our results were similar than international series.

Enfermedad por IgG4 multisistémica: a propósito de un caso: revisión de la literatura / Multisystemic IgG4 disease: a case report: literature review

We report a 63-year-old male patient who consulted for a 4-month history of xerophthalmia, xerostomia and cervicalgia, associated with jaundice, choluria, low weight and night sweats. Exams show an obstructive pattern and abdominal ultrasound describes a possible mass in the pancreatic head with secondary dilation of the bile duct. Colangio-MRI (magnetic resonance imaging) confirms a focal pancreatic head lesion that determines intrapancreatic bile duct stenosis, proximal dilation of the bile duct and stenosis of the main pancreatic duct. Pancreatic neoplasia versus autoimmune pancreatitis (PAI) is proposed, complementing a study with a count of IgG subclasses where IgG4 stands out at 1050 mg/dl (normal range: 3.9-86) and computed tomography (CT) of the thorax, abdomen and pelvis, that in addition to the biliary-pancreatic alterations, shows thickening of the vesicular wall, multiple bilateral lesions in the renal parenchyma and peri-aortic soft tissue. Salivary gland biopsy reports lymphoplasmacytic infiltrate characteristic of IgG4 disease. A disease related to IgG4 (ER-IgG4) is diagnosed with pancreatic, renal, biliary, vascular, lymphatic, salivary and lacrimal glands involvement. It is treated with corticoidal therapy, evolving favorably with resolution of the symptomatology and regression of imaging alterations.

Se reporta caso de paciente de sexo masculino de 63 años que consulta por cuadro de 4 meses de xeroftalmia, xerostomía y cervicalgia, asociado a ictericia, coluria, baja de peso y sudoración nocturna. En exámenes destaca pruebas hepáticas con un patrón obstructivo y ecografía abdominal que muestra una posible masa en la cabeza pancreática con dilatación secundaria de la vía biliar. Colangio-resonancia (resonancia magnética-RM) confirma una lesión focal en la cabeza pancreática que determina estenosis del colédoco intrapancreático, dilatación proximal de la vía biliar y estenosis del conducto pancreático principal. Se plantea neoplasia de páncreas versus pancreatitis autoinmune (PAI), complementando estudio con recuento de subclases de IgG donde destaca IgG4 de 1.050 mg/dl (rango normal: 3,9-86) y tomografía computada (TC) de tórax, abdomen y pelvis, que además de las alteraciones bilio-pancreáticas, demuestra engrosamiento de la pared vesicular, lesiones múltiples bilaterales en el parénquima renal y tejido de partes blandas peri-aórtico. Biopsia de las glándulas salivales informa sialoadenitis crónica e inespecífica. Se diagnostica una enfermedad relacionada a IgG4 (ER-IgG4) con compromiso pancreático, renal, biliar, vascular, linfático, de glándulas salivales y lagrimales. Se trata con terapia corticoidal, evolucionando favorablemente con resolución de la sintomatología y regresión de las alteraciones imagenológicas.

Difficultés diagnostiques et modalités thérapeutiques d'une rupture canalaire traumatique isolée du pancréas

Introduction : Les traumatismes du pancréas sont plus fréquents. Ils rentrent souvent dans un contexte de polytraumatisme, les traumatismes isolés étant beaucoup plus rares. La présentation clinique est variée, à l'origine de retard de consultation. La tomodensitométrie abdominale reste l'examen diagnostique de référence. La chirurgie intègre l'arsenal thérapeutique avec de nombreuses options. Les auteurs se proposent de rapporter ce cas opéré au CHU de Libreville afin de relever les difficultés diagnostiques et les modalités thérapeutiques de cette entité rare. Observation : Mr SM, 37 ans, consultait pour un traumatisme abdominal post-rixe. L'examen physique notait un état de choc, une sensibilité diffuse abdominale, sans défense ni contracture. La TDM abdominale objectivait un hématome rétro-péritonéal et un épanchement péritonéal associé. L'amylasémie était à 660 UI/mL, associée à une anémie normochrome normocytaire à 9 g/dL. L'exploration chirurgicale révélait un hématome de la tête du pancréas et du deuxième duodénum. L'évacuation de l'hématome avec pose d'un drain étaient réalisés. Les suites post-opératoires étaient compliquées d'une fistule pancréatique abondante. La seconde laparotomie objectivait une fistule pancréatique avec rupture canalaire à la jonction tête-corps. Une duodéno-pancréatectomie céphalique selon Whipple était réalisée. Le patient décédait à J3 post-opératoire. Conclusion : Les traumatismes pancréatiques isolés sont rares. Leur gravité est matérialisée par l'atteinte canalaire. Le diagnostic repose sur la TDM abdominale qui doit être est systématique en cas de traumatisme abdominal et la CPRE. La DPC est une option chirurgicale avec des complications lourdes

Insulinoma descubierto en paciente con aparente trastorno mental: reporte de un caso / Insulinoma found in patient with apparent mental disorder: a case report

El Insulinoma pancreático es un tumor neuroendocrino de las células beta de los islotes de Langerhans, tiene una incidencia de 4 casos por 1 000 000 habitantes. Se reporta el caso de una mujer de 36 años con alteración del comportamiento asociado a melancolía. Psiquiatría describe un examen mental anormal y diagnosticó depresión doble; sin embargo, la paciente tuvo la triada de Whipple y razón insulina/glucosa mayor a 0,3. El insulinoma fue localizado mediante resonancia magnética y tratado con cirugía. Los insulinomas pueden simular trastornos mentales, dificultando un diagnóstico temprano. Se compara los datos de la atención médica en nuestra localidad con otros obtenidos de la literatura a nivel mundial. Concluimos que a pesar de las limitaciones técnicas se debe incluir al insulinoma en el diagnóstico diferencial de trastornos mentales con hallazgo de hipoglucemia.

Pancreatic Insulinoma is a neuroendocrine tumor of the beta cells of the islets of Langerhans, has an incidence of 4 cases per 1 000 000 persons. We report the case of a 36-year-old woman with altered behavior associated with melancholy. Psychiatry describes an abnormal mental examination and diagnosed double depression; however, the patient had the Whipple triad and insulin/glucose ratio higher than 0.3. The insulinoma was localized by magnetic resonance imaging and treated with surgery. Insulinomas can mimic mental disorders, making early diagnosis difficult. We compare health care data in our locality with others obtained from the global literature. We conclude that despite the technical limitations, insulinoma should be included in the differential diagnosis of mental disorders with hypoglycemia.

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

Divertículo duodenal simulando neoplasia quística de páncreas / Duodenal diverticulum as a cystis neoplasm of pancreas

Resumen Objetivo: El divertículo duodenal se presenta con una frecuencia del 1 al 23% según series radiológicas y de autopsias. La localización más frecuente es la segunda porción duodenal cercana a la cabeza pancreática, por lo cual puede ser confundido con neoplasias pancreáticas quísticas. Material y Método: Presentamos un paciente con diagnóstico de sospecha radiológica, mediante ecoendoscopia y punción aspiración con aguja fina (PAAF), de neoplasia mucinosa de páncreas que fue intervenido, encontrándose un endurecimiento de la cabeza pancreática y un divertículo duodenal yuxtavateriano, realizándose extirpación en bloque ante la sospecha de malignidad. Resultado: El posoperatorio del paciente fue favorable y el resultado anatomopatológico del tejido pancreático informó de tejido pancreático sin anomalías y divertículo duodenal. Discusión: El diagnóstico diferencial preoperatorio del divertículo duodenal con la neoplasia mucinosa quística de páncreas es muy complejo, ya que la punción del líquido del interior del divertículo puede ser similar al de un proceso neoplásico mucinoso pancreático. Ante la sospecha diagnóstica y la presencia de clínica está indicado realizar laparotomía exploradora, para obtener un diagnóstico de certeza.

Objective: The duodenal diverticulum presents with a frequency of 1 to 23% according to radiological series and autopsies. The most frequent localization is the second duodenal portion near the pancreatic head so it may be confused with cystic pancreatic neoplasms. Material and Method: We present a patient with diagnosis of radiological suspicion by means of echoendoscopy and fine needle aspiration biopsy (FNAB) of a mucinous neoplasm of the pancreas that was intervened, being a hardening of the pancreatic head and a duodenal juxtavaterian diverticulum, being performed a block removal on suspicion of malignancy. Result: The patient's postoperative period was favorable and the anatomopathological result of the pancreatic tissue was of pancreatic tissue without anomalies and duodenal diverticulum. Discussion: The preoperative differential diagnosis of duodenal diverticulum with mucinous cystic neoplasia of the pancreas is very complex, since the puncture of the fluid inside the diverticulum may be similar to that of a neoplastic process of the pancreatic mucin. Before the suspected diagnosis and the presence of clinic is indicated to perform exploratory laparotomy, to obtain a diagnosis of certainty.

Intravascular large B-cell lymphoma with multi-organ failure presenting as a pancreatic mass: a case with atypical presentation and definite diagnosis postmortem

Intravascular large B-cell lymphoma (IVLBCL) is a very rare extra nodal lymphoma that tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules while sparing the organ parenchyma. The cause of its affinity for the vascular bed remains unknown. Because of its rarity and unremarkable clinical presentation, a timely diagnosis of IVLBCL is very challenging. Here, we describe a case of IVLBCL presenting as pancreatic mass that was ultimately diagnosed at autopsy. A 71-year-old Caucasian female presented with a 3-month history of fatigue, abdominal pain, and weight loss. She was referred to the emergency room with a new diagnosis of portal vein thrombosis and lactic acidosis. During her hospital course she was found to have a 1.9 × 1.8 cm lesion in the pancreatic tail on imaging; The cytologic specimen on the mass showed a high-grade lymphoma. A bone marrow biopsy showed no involvement. The patient's condition rapidly deteriorated and she, later, died due to multi-organ failure. An autopsy revealed diffuse intravascular invasion in multiple organs by the lymphoma cells. Based on our literature review­and to the best of our knowledge­there are virtually no reports describing the presentation of this lymphoma with a discernible tissue mass and associated multi-organ failure. The immunophenotypic studies performed revealed de novo CD5+ intravascular large B-cell lymphoma, which is known to be aggressive with very poor prognosis. Although it is a very rare lymphoma, it should be considered as a potential cause of multi-organ failure when no other cause has been identified. A prompt tissue diagnosis, appropriate high-dose chemotherapy and stem cell transplantation remain the only viable alternative to achieve some kind of remission.

Masa pancreática: una presentación inhabitual de nesidioblastosis en el adulto / Pancreatic mass: an unusual presentation of nesidioblastosis in adults

A 41-year-old woman, multiparous of 4, with personal or familiar history of diabetes, with a history of Nissen fundoplication due to pathological gastro-oesophageal reflux, is refer to an endocrinologjst during her post-operatiye follow up, 4 months after her surgery for a 14 kg weight loss in 10 months and symtomatic hypoglycemia to repetition. A positive prolonged fasting test for hypoglycemia was performed. In addition, abdominal computed axial tomography was performed, which resulted normal and endosonography, showing a lesion on the head of the pancreas. Octreoscan positive for pancreatic head focal lesion with positive somatostatin receptors compatible with insulinoma. Whipple surgery was performed where surgeon palpated pancreatic tumor, biopsy showed tissue compatible with diffuse nesidioblastosis. In the postoperative period, the patient decreased frequency and intensity of hypoglycemic episodes compared to their previous stage. Control prolonged fasting test and Octreoscan were within normal ranges. However, 4 months after surgery, the patient presented hypoglycemia of lower intensity and frequency than before surgery. Currently he remains in control with nutritionist and endocrinologist, mainly adjusting diet and with good control glycemias.