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El objetivo de este trabajo es analizar la presentación epidemiológica y la sobrevida de los pacientes con adenocarcinoma ductal de páncreas de acuerdo con su estadío clínico y al tipo de intervención realizada, en una cohorte de pacientes atendidos en una clínica en Lima, Perú. Estudio de cohortes retrospectivas que evaluó desde enero del 2015 a febrero del 2021 a pacientes con diagnóstico de adenocarcinoma ductal de páncreas considerando diversos factores epidemiológicos, radiológicos, estadiaje oncológico, haber recibido quimioterapia neoadyuvante o adyuvante, haber sido sometidos a cirugía y la sobrevida posterior a alguna de las intervenciones realizadas. De los 249 pacientes analizados, se encontró que 75 de ellos requerían cirugía resectiva. Entre los principales resultados obtenidos, se observó que aquellos con un nivel de CA 19-9 menor a 200 U/mL presentaban una media de sobrevida más alta en comparación con aquellos cuyo nivel de CA 19-9 era superior a 200 U/mL (HR: 1,96; IC95%: 0,18-0,53; p≤0,001). Asimismo, al comparar a los pacientes según su etapa, se encontró que aquellos con tumores resecables tenían una media de sobrevida de 37,72 meses, mientras que aquellos con tumores localmente avanzados tenían una media de sobrevida de 13,47 meses y aquellos con tumores metastásicos tenían una media de sobrevida de 7,69 meses (HR: 0,87; IC95%: 0,31-0,25; p≤0,001). Igualmente, se observó que recibir tratamiento neoadyuvante se asociaba con un mejor pronóstico de sobrevida para los pacientes (HR: 0,32; IC95%: 0,19-0,53; p≤0,001). Asimismo, se llevaron a cabo 5 pancreatectomías con resección metastásica en pacientes oligometastásicos tratados con quimioterapia de rescate, y se encontró que la media de sobrevida para estos pacientes fue de 22,51 meses. Conclusión: La cirugía resectiva en un estadío clínico temprano , presentar valores de CA 19-9 por debajo de 200 U/mL y haber recibido quimioterapia neoadyuvante se correlaciona estadísticamente con una mayor esperanza de sobrevida.

The objective of this study is to analyze the epidemiological presentation and survival of patients with pancreatic ductal adenocarcinoma according to their clinical stage and the type of intervention performed, in a cohort of patients treated at a clinic in Lima, Peru. A retrospective cohort study evaluated patients diagnosed with pancreatic ductal adenocarcinoma from January 2015 to February 2021, considering various epidemiological factors, radiological findings, oncological staging, receipt of neoadjuvant or adjuvant chemotherapy, undergoing surgery, and post-intervention survival. Out of the 249 patients analyzed, 75 of them required resective surgery. Among the main findings, it was observed that those with a CA 19-9 level below 200 U/mL had a higher median survival compared to those with a CA 19-9 level above 200 U/mL (HR: 1.96; 95% CI: 0.18-0.53; p≤0.001). Furthermore, when comparing patients according to their stage, those with resectable tumors had a median survival of 37.72 months, while those with locally advanced tumors had a median survival of 13.47 months, and those with metastatic tumors had a median survival of 7.69 months (HR: 0.87; 95% CI: 0.31-0.25; p≤0.001). Additionally, receiving neoadjuvant treatment was associated with a better prognosis of survival for patients (HR: 0.32; 95% CI: 0.19-0.53; p≤0.001). Furthermore, 5 pancreatectomies with metastatic resection were performed in oligometastatic patients treated with salvage chemotherapy, and the median survival for these patients was 22.51 months. Conclusion: Resective surgery at an early clinical stage, CA 19-9 levels below 200 U/mL, and receiving neoadjuvant chemotherapy are statistically correlated with a higher overall survival.

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Background: Despite being rare in domestic animals, pancreatic adenocarcinoma is the most common malignant tumor of the feline pancreas. Due non-specificity of clinical signs in cats and the late diagnosis of the neoplasm, it is necessary to understand this disease better, to contribute for the knowledge of its early recognition and treatment. Thus, this study aims to report a case of metastatic pancreatic ductal adenocarcinoma in a cat, focusing on the main clinical aspects, diagnosis, and prognosis of this disease, in addition to the description of the presentation of peritoneal carcinomatosis. Case: A 14-year-old male neutered mixed breed cat, was referred to the Feline Medicine Service (MedFel) of the Hospital de Clínicas Veterinárias (HCV) - Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, with a history of hyporexia, constipation and increased abdominal volume for 3 days, besides mild difficulty in locomotion and progressive weight loss in the last 6 months. On the physical examination, the patient was alert, with a body condition score of 6/9; muscle condition score 1/4 and moderate dehydration of 7%. Popliteal lymph nodes were enlarged, and abdominal distension was evident. Around 200 mL of a slightly cloudy, straw-yellow liquid were drained from the abdominal cavity. After draining the fluid, a new abdominal palpation was performed, and there were fecal retention and a palpable mass in the right hypogastric region. The result of the cytological analysis of the fluid was consistent with a protein-rich transudate, suggesting neoplastic effusion of epithelial origin. Hematological and biochemical changes included leukocytosis due to neutrophilia, monocytosis, lymphopenia, thrombocytosis and azotemia. On abdominal ultrasound, the patient had free fluid in the abdominal cavity, and the gallbladder had discreet of biliary sludge. The intestines showed some corrugated segments with other segments lacking definition of its layers, and without peristaltic movements, suggesting intestinal neoplasia. Pancreas and adrenals were not visualized. On the chest X-ray, moderate opacification of lung fields with a diffuse interstitial pattern was observed, suggesting lung metastasis. The patient presented an acute worsening of the clinical condition and the owner requested euthanasia. The patient was referred for necropsy and based on the macroscopic and microscopic changes, the post-mortem diagnosis was metastatic pancreatic ductal adenocarcinoma with peritoneal carcinomatosis. Discussion: The clinical presentation of cats with exocrine pancreatic neoplasia is nonspecific, as clinical signs are common to several diseases, such as anorexia, vomiting, abdominal pain, weight loss with normal appetite, jaundice, depression, and lethargy. Complementary blood tests also do not provide data that could lead to the suspicion of pancreatic neoplastic disease. In the present case, the diagnosis of metastatic pancreatic ductal adenocarcinoma with peritoneal carcinomatosis was only possible post mortem. The pancreas is a difficult organ to assess adequately using most diagnostic imaging methods, so histopathology is still the method of choice for differentiating pancreatic tissue comorbidities. Therefore, exploratory laparotomy should be instituted to provide tissue samples from the pancreas and its metastases for histopathological diagnosis, whenever ultrasound or other imaging methods indicate suspicious abdominal changes. The literature reports that less than 10% of affected cats treated with complete surgical removal of the mass and chemotherapy alone will survive more than a year, and the average time for untreated cats is only 6 days. The prognosis of this disease is bad and most cats are euthanized, due to rapid clinical worsening. Therefore, diagnosis is essential to determine an adequate prognosis in advanced cases and to support therapeutic decisions or euthanasia.

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El adenocarcinoma pancreático ductal (APD) es la cuarta causa de muerte por cáncer y se proyecta que para el 2030 ocupe el segundo lugar. El pronóstico es sombrío, siendo la sobrevida menor a 9% en 5 años. Se consideró durante mucho tiempo a la resección quirúrgica como el único tratamiento curativo, sin embargo, sólo el 15 a 20% de los pacientes pueden ser beneficiados con la misma. La clasificación pre terapéutica más utilizada es la del National Comprehensive Cáncer Network (NCCN), basada en la relación del tumor con estructuras vasculares, clasificándolos en tumores "resecables", de resección límite "Borderlines" y "localmente avanzados". Se presenta el primer caso registrado en Paraguay de APD con infiltración de la Vena Mesentérica Superior (VMS) tratado con duodenopancreatectomía cefálica (DPC) asociada a resección vascular mayor.

Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer death and is projected to rank second by 2030. The prognosis is bleak, with survival being less than 9% in 5 years. For a long time, surgical resection was considered the only curative treatment, however, only 15 to 20% of patients can benefit from it. The most widely used pre-therapeutic classification is that of the National Comprehensive Cancer Network (NCCN), based on the relationship of the tumor with vascular structures, classifying them into "resectable", "borderline" and "locally advanced" tumors. We present the first registered case in Paraguay of PDA with infiltration of the Superior Mesenteric Vein (SMV) treated with cephalic duodenopancreatectomy (CPD) associated with major vascular resection.

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Introducción: la diabetes mellitus (DM) se considera un factor de riesgo para el desarrollo de adenocarcinoma ductal de páncreas (ACDP). Objetivos: describir la prevalencia de DM y glucemia en ayuno alterada (GAA) al diagnóstico de ACDP en pacientes asistidos en un centro de referencia gastroenterológico; analizar las diferencias en las características personales y nutricionales en pacientes con ACDP y DM, ACDP y GAA, y ACDP sin DM ni GAA; establecer el tiempo transcurrido desde el diagnóstico de DM hasta diagnosticar ACDP. Materiales y métodos: de octubre de 2019 a marzo de 2020 se revisaron 465 historias clínicas de las Secciones Oncología y Nutrición de pacientes >18 años con diagnóstico de ACDP. Resultados: se registraron 171 historias clínicas (36,7%) con ACDP y DM, y 294 (63,2%) con ACDP sin DM. En el 45,1% de las primeras, el intervalo entre el diagnóstico de DM y el de ACDP fue <1 año, y en el 17,65%, 15,69% y 21,57% los lapsos correspondieron a 1 y 5 años, entre 5 y 10 años y >10 años respectivamente. Conclusiones: la prevalencia de DM en ACDP fue superior a la registrada en la población general (37% vs 12,7%), siendo del 45,10% cuando se presentó dentro del primer año del diagnóstico oncológico. Nuestros resultados concuerdan con la bibliografía internacional que relaciona la DM de reciente diagnóstico como factor asociado a la presencia de ACDP por factores de riesgo compartidos, variables fisiopatológicas de la DM o a consecuencia de la terapéutica farmacológica de la misma.

Introduction: diabetes mellitus (DM) is considered to be a risk factor for the development of pancreatic ductal adenocarcinoma (PDAC). Objectives: describe the prevalence of DM and of impaired fasting glucose (IFG) at the diagnosis of PDAC, among patients assisted in a gastroenterological reference center. Analyze differences in personal and nutritional characteristics in patients with both PDAC and DM; with both PDAC and IFG; and with PDAC but neither DM nor IFG. Determine the time lapse between the diagnosis of DM and the diagnosis of PDAC. Materials and methods: between October 2019 and March 2020, we analyzed 465 clinical records of PDAC-diagnosed patients over 18 years, from Oncology and Nutrition Sections. Results: 171 clinical records (36.7%) showed both PDAC and DM; 294 clinical records (63.2%) showed PDAC but not DM. In 45.1% of the former, the interval between the diagnosis of DM and that of PDAC was <1 year, and in 17.65%, 15.69% and 21.57%, the lapses corresponded to 1 and 5 years, between 5 and 10 years y >10 years, respectively. Conclusions: the prevalence of DM in PDAC patients (37%) is higher than that registered in the overall population (12.7%), reaching a 45.10% when detected during the first year of oncological diagnosis. Our results match the international literature relating recently-diagnosed DM with the presence of PDAC, as effect of shared risk factors between both diseases, or DM pathophysiology factors, or DM pharmacological therapeutic

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O adenocarcinoma ductal do pâncreas é a quarta causa associada a câncer mais comum de morte no mundo ocidental. A presença de células tumorais circulantes (CTCs) no sangue pode ser considerada como um potencial fator prognóstico. Assim, o estudo de componentes que contribuem para sua formação de metástases tem se mostrado promissor. CTCs representam, em tempo real, a progressão tumoral, permitindo o monitoramento da eficácia terapêutica. O presente projeto teve por objetivo detectar CTCs presentes no sangue periférico de pacientes com adenocarcinoma ductal de pâncreas, avaliar a expressão de proteínas relacionadas à transição epitélio-mesênquima (TEM) tais como a mesotelina, vimentina, Metaloproteinase de Matriz 2 (MMP2) e o Receptor Beta do Fator de Crescimento Transformador I (TGFß-RI) e correlacionar com a resposta ao tratamento e sobrevida livre de progressão. Ainda, tentamos correlacionar os níveis de CTCs e expressão dos miRNAs destas células com sobrevidas livre de progressão (SLP) e global (SG). Foram analisadas amostras de sangue de 9 pacientes com adenocarcinoma de pâncreas (10 ml de sangue periférico) antes do início do tratamento e após 60 e 120 dias. As CTCs foram detectadas pelo sistema ISET (Rarecells, France) e depois caracterizadas por imunocitoquímica . Para análise de miRNAS das CTCs, foram colhidos em paralelo, leucócitos periféricos dos mesmos pacientes e de indivíduos saudáveis, como controle. Para essa análise, utilizamos apenas o material da coleta baseline. A extração do material foi realizada com um kit comercial (Qiagen) e a avaliação da expressão dos microRNAs com TaqMan Low Density Array (TLDA) em pool. As análises das proteínas envolvidas na TEM na coleta baseline, indicam que as CTCs expressavam predominantemente MMP2 (77,77%), seguida de TGFß-RI (44,44%), vimentina (33,33%) e mesotelina (22,22%). No primeiro grupo de acompanhamento de 5 pacientes, as CTCs expressaram MMP2 e vimentina (80%), TGFß-RI (60%) e mesotelina (20%). Comparadas ao grupo de 8 pacientes do segundo seguimento, as CTCs expressaram MMP2 (50%), vimentina (25%) e TGF-RI (12,5%). Constatamos que 3/9 pacientes no presente estudo progrediram (33,33%). Em dois pacientes, foram encontrados microêmbolos tumorais circulantes (MTC) e ambos apresentaram Trombose Venosa Periférica (TVP), mostrando que talvez haja uma correlação entre MTC e TVP. Encontramos dois microRNAs altamente expressos nas CTCs dos pacientes aqui avaliados, ambos envolvidos na estimulação do processo de TEM: hsa-miR-203a-3p e hsa-324-5p. Não houve diferença estatisticamente significante no número de casos com presença de proteína ou correlação com outros fatores, embora a MMP2 tenha sido altamente expressa nas três coletas, seguida por TGFß-RI e vimentina. Também não encontramos qualquer correlação entre as variáveis analisadas e SLP e SG. Neste trabalho foi possível encontrar CTCs em todos os 9 pacientes com câncer de pâncreas. Devido ao baixo número de pacientes incluídos e curto tempo de follow-up, não conseguimos ver correlação entre níveis de CTCs e expressão de proteínas e SLPe SG, mas continuaremos acompanhando o pacientes. Encontramos correlação entre presença de MTC e TEP. E conforme esperávamos, encontramos microRNAs relacionados à TEM altamente expressos em CTCs de pacientes com câncer de pâncreas (AU)

Ductal adenocarcinoma of the pancreas is the fourth most common cancer-associated cause of death in the Western world. The presence of circulating tumor cells (CTCs) in the blood can be considered as a potential prognostic factor. Thus, the study of components that contribute to metastases formation has shown to be promising. CTCs represent, in real time, tumor progression, allowing monitoring of therapeutic efficacy. The aim of this project was to detect CTCs present in the peripheral blood of patients with pancreatic ductal adenocarcinoma, to evaluate the expression of proteins related to the epithelial-mesenchymal transition (TEM) such as mesothelin, vimentin, Matrix Metalloproteinase 2 (MMP2) and Transforming Growth Factor Beta Receptor I (TGFß-RI) and correlate with response to treatment, progression-free survival (PFS) and overall survival (OS). Still, we tried to correlate the levels of CTCs and expression of miRNAs of these cells with progression-free and global survival. Blood samples from 9 patients with pancreatic adenocarcinoma (10 ml of peripheral blood) were analyzed before the start of treatment and after 60 and 120 days. CTCs were detected by the ISET system (Rarecells, France) and then characterized by immunocytochemistry. For analysis of the CTCs miRNAs, peripheral leukocytes from the same patients and healthy individuals were collected in parallel as a control. For this analysis, we used only the material from the baseline collection. The extraction of the material was made with a commercial kit (Qiagen) and the evaluation of the expression of the microRNAs with TaqMan Low Density Array (TLDA) in pool. The analysis of proteins involved in TEM in the baseline collection, indicates that CTCs expressed predominantly MMP2 (77.77%), TGFß-RI (44.44%), vimentin (33.33%) and mesothelin (22.22%). In the first follow-up group of 5 patients, CTCs expressed MMP2 in (80%), vimentin and TGFß-RI in (60%) and mesothelin (20%). Compared to the group of 8 patients in the second follow-up, CTCs expressed MMP2 in (50%), vimentin (25%) and TGF-RI in (12.5%). We found that 3/9 patients in the present study progressed (33.33%). In two patients, circulating tumor microemboli (CTM) were found and both had Peripheral Venous Thrombosis (PVT), showing that there may be a correlation between CTM and PVT. We found two microRNAs highly expressed in the CTCs of the patients evaluated here, both involved in the stimulation of the TEM process: hsa-miR-203a-3p and hsa-324-5p. There was no statistically significant difference in the number of cases with protein or correlation with other factors, although MMP2 was highly expressed in the three collections, followed by TGFß-R1 and vimentin. We also found no correlation between the variables analyzed and PFS and OS. In this work, it was possible to find CTCs in all 9 pancreatic cancer patients. Due to the low number of patients included and short follow-up time, we were unable to see a correlation between CTC levels and protein expression and PFS and OS, but we will continue to monitor the patients. Here, we found a correlation between the presence of CTM and PVT. As we expected, we found TEM-related microRNAs highly expressed in CTCs of patients with pancreatic cancer (AU)

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Resumen El cáncer de páncreas es una enfermedad mortal, principalmente porque se descubre muy tarde y es muy resistente a la quimioterapia y radioterapia. El tipo más común de cáncer de páncreas (más del 90%) se desarrolla a partir de las células exocrinas del páncreas y se denomina adenocarcinoma ductal pancreático (ACDP). Se han reconocido tres lesiones precursoras de cáncer de páncreas ductal: neoplasia intraepitelial pancreática (PanIN), neoplasia papilar-mucinosa intraductal (NPMI) y neoplasia quística mucinosa (NCM). Uno de los primeros eventos genéticos implicados en la patogénesis de ACDP es una mutación en el punto de activación en el oncogén KRAS, una mutación conductora oncogénica que se encuentra en más del 90% de todos los cánceres de páncreas. Además, se ha informado que hasta un 10% de los cánceres de páncreas están asociados con el historial familiar. Aunque la causa es multifactorial, el tabaquismo y la historia familiar son dominantes. Existe heterogeneidad morfológica en muchos cánceres humanos, pero parece ser un hallazgo particularmente común en ACDP. La cirugía solo es posible en 15-20% de los casos: tumores confinados al páncreas con posible afectación ganglionar local no muy extensa y que no produce afectación vascular o está limitada.

Abstract Pancreatic cancer is a deadly disease, mainly because it is generally discovered very late and it is very resistant to chemotherapy and radiation therapy. The most common type of pancreatic cancer (over 90%) develops from the exocrine cells of the pancreas and is named pancreatic ductal adenocarcinoma (PDAC). Three precursor lesions of ductal pancreatic cancer have been recognized: pancreatic intraepithelial neoplasia (PanIN), intraductal papillary-mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). One of the earliest genetic events involved in PDAC pathogenesis is an activating point mutation in the KRAS oncogene, an oncogenic driver mutation found in more than 90% of all pancreatic cancer. In addition, it has been reported that up to 10% of pancreatic cancer is associated with family history. Although the cause is multifactorial, cigarette smoking and family history are dominant. Morphological heterogeneity exists in many human cancers, but seems to be a particularly common finding in PDAC. Surgery is only possible in 15-20% of cases: tumors confined to the pancreas with possible local nodal involvement not very extensive and that do not produce vascular involvement or is limited.

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Introdução: Este artigo revisa o conhecimento atual do adenocarcinoma pancreático, dissertando sobre a definição, a sintomatologia e os processos diagnóstico, terapêutico e prognóstico. Métodos: Revisão bibliográfica de artigos científicos, selecionados nas bases Medline e PubMed entre março e maio de 2018, e em sites epidemiológicos sobre neoplasias pancreáticas. Resultados: A doença maligna do pâncreas é uma das neoplasias mais letais na atualidade, uma vez que sua detecção normalmente ocorre em estágios avançados da doença, impossibilitando a ressecção cirúrgica, que é a única opção potencialmente curativa disponível. A maior parte dos casos, entretanto, não é candidata a cirurgia por presença de metástases à distância ou por comprometimento vascular local, notadamente dos vasos mesentéricos. Conclusão: O adenocarcinoma ductal pancreático é uma patologia incomum, mas que merece atenção por sua alta agressividade e prognóstico reservado, com baixos índices de cura e de sobrevida, situação que se mantém inalterada ao longo das últimas décadas.

Introduction: This article reviews the current knowledge about pancreatic adenocarcinoma, discussing definition, symptomatology and diagnostic, as well as therapeutic and prognostic processes. Methods: Bibliographic review of scientific articles, selected from Medline and PubMed databases between March and May 2018, and in epidemiological sites on pancreatic neoplasms. Results: Malignant disease of the pancreas is one of the most lethal neoplasms today, since its detection usually occurs in advanced stages of the disease, making surgical resection impossible, which is the only potentially curative option available. Most cases, however, are not candidates for surgery due to presence of distant metastases or local vascular impairment, notably mesenteric vessels. Conclusion: Pancreatic ductal adenocarcinoma is an uncommon pathology, but it deserves attention because of its high aggressiveness and reserved prognosis, with low rates of cure and survival, a situation that has remained unchanged over the last decades.

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O adenocarcinoma de pâncreas, constitui uma das neoplasias mais letais do trato gastrointestinal. Nos últimos anos, pouco avanço ocorreu, no que diz respeito a melhora da sobrevida dos pacientes tratados por essa doença. Dessa forma justifica-se o estudo de potenciais mecanismos de desenvolvimento e evolução dessa doença para possíveis alvos terapêuticos. Este estudo avaliou de forma retrospectiva 76 pacientes operados por adenocarcinoma de pâncreas com intuito curativo. Análise do impacto na sobrevida de dados clínicos, demográficos, e patológicos como: idade, sexo, CA19.9, estadiamento, invasão perineural e grau de diferenciação com sobrevida. Análise de expressão de VEGF, COX-2 e D2-40 por meio do método de tissue array, de forma automatizada, com o programa ACIS, e interpretação desses resultados com ênfase em sobrevida e impacto nas variáveis histopatológicas. A expressão de COX- 2 esteve relacionada de forma significativa com o grau de diferenciação tumoral (p=0,03). A expressão de COX-2 apresentou uma tendência a associação com prognóstico, porém sem atingir significância estatística. A VEGF não apresentou impacto na sobrevida, bem como não esteve relacionado a nenhuma das variáveis histopatológicas. Invasão perineural e nível de CA19.9, foram fatores independentes de impacto na sobrevivência.

Pancreatic adenocarcinoma, is one of the most lethal cancers of the gastrointestinal tract. In recent years, little progress has occurred, with respect to survival of patients treated for this disease. In order to achieve more information of the biology of this disease, this study is justified to evaluate potential mechanisms of the pancreatic cancer development. This might help in the future, to achieve new therapeutic targets. This study assessed retrospectively 76 patients operated with curative intent, with the diagnosis of adenocarcinoma of the pancreas. Analysis of the impact on survival of clinical data, incluiding: age, sex, CA19.9, staging, and pathological data, such as: vascular invasion, tumor size, perineural invasion and degree of differentiation. Analysis of expression of VEGF, COX-2 and D2-40 through the method of tissue array, trough an automated manner, with the ACIS program. And interpretation of these results with emphasis on survival and impact on histopathological variables. The expression of COX-2 was related to any significant degree of differentiation with the tumor (p = 0.03). Expression of COX-2 showed a trend association with the prognosis, but not reach statistical significance. VEGF did not show an impact on survival, and was not related to any of the histopathological variables. Perineural invasion and level of CA19.9 were independent of factors impact on survival.

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