Fístula pancreática: una complicación temida. Experiencia en una unidad de cirugía hepatobiliopancreática de cuarto nivel / Pancreatic fistula: A feared complication. Experience in a fourth level hepatobiliopancreatic surgery unit

Introducción. La fístula pancreática postoperatoria es una de las complicaciones más importantes en la cirugía hepatobiliopancreática. Su diagnóstico se hace mediante la presencia de un nivel de amilasa en el líquido de drenaje al menos tres veces por encima del valor de la amilasa en suero a partir del tercer día postoperatorio. El objetivo de este estudio fue caracterizar los pacientes con fístula pancreática postoperatoria en nuestra institución, evaluando la importancia de la detección temprana y el establecimiento de un manejo oportuno. Métodos. Estudio descriptivo, retrospectivo, que incluyó los pacientes sometidos a pancreatoduodenectomía, con diagnóstico de fístula pancreática postoperatoria como complicación de cirugía hepatobiliopancreática, en el Hospital Internacional de Colombia, en Piedecuesta, entre enero del 2017 y diciembre de 2020. Se excluyeron los pacientes con otro tipo procedimiento quirúrgico y aquellos que decidieron no participar en el estudio. Resultados. Se evaluaron 69 pacientes, con un predominio del sexo femenino (n=38; 55,1 %) y mediana de la edad de 57 años. El 33,3 % (n=24) de los pacientes intervenidos desarrollaron fístula pancreática postoperatoria, siendo el 23,2 % fuga bioquímica, grado B 8,7 % y grado C 2,9 %, para quienes se indicaron manejo expectante, control ecográfico y reintervención, respectivamente. Fallecieron 5 pacientes (7,2 %). Conclusiones. La fístula pancreáticapostoperatoria es una complicación para tener en cuenta en todos los pacientes sometidos a pancreatoduodenectomía. Existen estrategias que pueden permitir disminuir la incidencia de esta complicación, con el fin de mejorar el desenlace, el pronóstico y la morbilidad posquirúrgica.

Introduction. Postoperative pancreatic fistula is one of the most important complications in hepatobiliopancreatic surgery. Its diagnosis is made by the presence of an amylase level in the drainage fluid at least three times above the serum amylase value from the third postoperative day. The objective of this study was to characterize patients with postoperative pancreatic fistula at our institution, evaluating the importance of early detection and to establish a timely management. Methods. Descriptive, retrospective study that included patients who underwent pancreatoduodenectomy with a diagnosis of postoperative pancreatic fistula as a complication of hepatobiliopancreatic surgery at the Hospital Internacional Colombia, between January 2017 and December 2020. Patients with another type of procedure performed by this specialty and those who did not decide to participate in the study were excluded. Results. A total of 69 patients were included, the median age was 57 years with a predominance of females (n=38; 55.1%). 33.3% (n=24) of the operated patients developed postoperative pancreatic fistula, with 23.2% having a biochemical leak, grade B in 8.7% and grade C in 2.9%, for whom expectant management, ultrasound control and reintervention were indicated, respectively. Five patients died (7.2%). Conclusions. Pancreatic fistula is a complication to take into account in all patients undergoing pancreatoduodenectomy. There are strategies that can reduce the incidence of this complication and thus improve not only the outcome but also the prognosis and postoperative morbidity.

Tumor pseudopapilar sólido de páncreas, una neoplasia inusual / Solid Pseudopapillary Tumor of the Pancreas, an Unusual Neoplasm

Presentación del caso. Se trata de una mujer de 26 años que presentó dolor en epigastrio e hipocondrio izquierdo, con aumento del perímetro abdominal y pérdida de 5 kg de peso corporal. En el examen físico se detectó una masa de gran tamaño en el epigastrio, con bordes regulares, ligeramente dolorosa al tacto y no móvil. Los estudios de imagen revelaron una neoplasia mixta en el cuerpo y cola pancreática. Intervención terapéutica. Se practicó una esplenopancreatectomía corpo-caudal, con extirpación completa del tumor. Evolución clínica. La paciente recibió cuidados especializados y vigilancia estrecha posquirúrgica en la unidad de cuidados intensivos, sin presentar complicaciones relevantes. Tras el alta hospitalaria, la paciente refirió un buen estado general en los controles de seguimiento, que incluyeron una tomografía realizada a los 12 meses, donde no se evidenciaron restos o recidivas tumorales

Case presentation. A 26-year-old woman who presented with pain in the epigastrium and left hypochondrium, with increased abdominal perimeter and loss of 5 kg of body weight. Physical examination revealed a large mass in the epigastrium, with regular borders, slightly painful to the touch and non-mobile. Imaging studies revealed a mixed neoplasm in the pancreatic body and tail. Treatment. A corpo-caudal splenopancreatectomy was performed, with complete removal of the tumor. Outcome. The patient received specialized care and close postoperative surveillance in the intensive care unit, with no relevant complications. After hospital discharge, the patient reported a good general condition in the follow-up controls, which included a computed tomography scan performed after 12 months, where no tumor remnants or recurrences were evidenced

Complicaciones de cirugía de Whipple en un paciente pediátrico con tumor pseudopapilar de páncreas / Complications of Whipple procedure in a pediatric patient with pseudopapillary tumor of the pancreas

Las neoplasias de páncreas son una entidad poco frecuente en pediatría; el tumor pseudopapilar de páncreas (TSP) es el más comúnmente diagnosticado. Habitualmente, se localizan en la cabeza del páncreas. La cirugía de Whipple o pancreatoduodenectomía es la técnica elegida para el tratamiento de los tumores benignos o malignos de páncreas. Si bien la mortalidad conocida ha descendido en los últimos años, debido a la mayor experiencia de los cirujanos y al mejor cuidado pre- y posoperatorio, la morbilidad se ha mantenido elevada secundaria a las complicaciones asociadas. Dentro de estas se destacan retardo en el vaciamiento gástrico, colecciones intraabdominales, fístula pancreática, reestenosis del sitio quirúrgico y hemorragia pospancreatectomía. Se presenta el caso clínico de una niña de 13 años con diagnóstico de TSP que recibió tratamiento quirúrgico efectivo desde el punto de vista oncológico, pero que requirió una internación prolongada secundaria a las complicaciones quirúrgicas.

Pancreatic neoplasms are rare in pediatrics; the pseudopapillary tumor (PPT) of the pancreas is the most common. PPTs of the pancreas are usually located in the head of the pancreas. A pancreaticoduodenectomy or Whipple procedure is the technique of choice for the treatment of benign or malignant pancreatic tumors. Although mortality for this cause has decreased in recent years, due to the greater experience of surgeons and improved pre- and postoperative care, morbidity has remained high secondary to associated complications. These include delayed gastric emptying, intra-abdominal collections, pancreatic fistula, surgical site restenosis, and post-pancreatectomy hemorrhage. Here we describe the clinical case of a 13-year-old girl diagnosed with PPT of the pancreas who underwent an effective surgery in terms of cancer treatment, but who required a prolonged hospitalization secondary to surgical complications.

Sobrevida del adenocarcinoma ductal de páncreas

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.

Endoscopic ultrasound-guided celiac plexus neurolysis in pancreatic cancer-associated pain: different technical approaches in three challenging cases

Abdominal pain is severe in the vast majority of patients with pancreatic cancer. In some cases, chronic use of analgesics markedly reduces quality of life due to side effects. Endoscopic ultrasound-guided celiac plexus neurolysis is a procedure that controls cancerassociated pain in this population and consists of injecting a neurolytic agent around or within the celiac plexus. In this report, we present three cases with different technical approaches for celiac plexus neurolysis.

El cáncer de páncreas se puede presentar con dolor abdominal intenso, siendo necesario el uso de analgésicos a largo plazo en muchos de los pacientes. Sin embargo, estos medicamentos pueden tener efectos adversos que finalmente reducen la calidad de vida de los pacientes. La neurólisis del plexo celíaco guiada por ecoendoscopia es un procedimiento que controla el dolor asociado a este tipo de neoplasia y consiste en inyectar un agente neurolítico en o alrededor del plexo celíaco. Presentamos tres casos en los cuales se realizan diferentes técnicas de abordaje terapéutico.

Metástasis Pancreática Metacrónica de un Carcinoma de Células Renales. Reporte de un Caso / Metachronic Pancreatic Metastasis of a Renal Cell Carcinoma. Case Report

El carcinoma de células renales (CCR) a nivel mundial presenta una incidencia de 431.288 casos anuales, causando 179.368 muertes en 2020. Sin embargo, a pesar de su incidencia, el desarrollo de metástasis pancreática (MP) de un RCC es un hecho inusual. El objetivo de este manuscrito fue reportar el caso de una paciente con una MP metacrónica de un CCR. Se trata de una paciente de 56 años, sexo femenino, nefrectomizada derecha hace 132 meses por un CCR, en adyuvancia con inmunoterapia. En un control imagenológico de rutina, se le pesquisó una lesión de aspecto tumoral en el cuerpo y cola del páncreas. Se intervino quirúrgicamente, realizándose una pancreatectomía córporo-caudal con preservación esplénica. Evolucionó de forma satisfactoria, sin complicaciones, siendo dada de alta al 4º día de su cirugía. El informe del estudio de la pieza operatoria con estudio inmunohistoquímico concluyó que se trataba de una MP de CCR. La paciente se encuentra en buenas condiciones generales y reinició quimioterapia con anticuerpos monoclonales. El seguimiento frecuente y prolongado de pacientes con antecedentes de CCR, facilita un diagnóstico y tratamiento oportuno de MP facilitando el mejor pronóstico de los pacientes, con tasas más altas de supervivencia.

SUMMARY: Renal cell carcinoma (RCC) worldwide has an incidence of 431,288 cases per year, causing 179,368 deaths in 2020. However, despite its incidence, the development of pancreatic metastasis (MP) from RCC is unusual. The aim of this manuscript was to report the case of a patient with a PM of a RCC. This is a 56-year-old female patient, underwent right nephrectomy 132 months earlier for RCC. While she was in adjuvant immunotherapy, in a routine imaging control, it was found a tumor lesion in the body and the tail of the pancreas. So, she underwent surgery, performing a corpora-caudal pancreatectomy with splenic preservation. Postoperative evolution was correct, without complications, and she was discharged on the 4th day after surgery. The report of the study of the surgical piece with an immunohistochemical study included, conclusive of PM of RCC. Currently, the patient is in good general condition and restarted chemotherapy with monoclonal antibodies. Frequent and prolonged follow-up of patients with a history of RCC facilitates timely diag- nosis and treatment of PM, facilitating the best prognosis for patients, with higher survival rates.

Impacto da pandemia de COVID-19 nos procedimentos de ultrassonografia endoscópica em uma unidade de endoscopia de alto volume no Brasil / The impact of the covid-19 pandemic on endoscopic ultrasound procedures in a high-volume endoscopy unit in brazil

ABSTRACT Background: Reports of the impact of the 2020 COVID-19 pandemic period/2020 on endoscopic ultrasound (EUS) are scarce. Objective: We analyzed the impact of the pandemic period/2020 on the demographics, indications, and number of diagnostic EUS (D-EUS) and interventional EUS (I-EUS) procedures performed in a high-volume endoscopy unit compared with the previous non-pandemic period/2019. Methods: We retrospectively reviewed the medical records of all patients undergoing D-EUS or I-EUS from March 1, 2019, to February 29, 2020 (non-pandemic period/2019) and from March 1, 2020, to February 28, 2021 (pandemic period/2020). Data compared between the study periods included sex, age, comorbidities, EUS findings and diagnosis, need for interventional procedures during EUS, and adverse events (AEs). Results were significant at P<0.05. Results: EUS procedures decreased from 475 in the non-pandemic period/2019 to 289 in the pandemic period/2020, accounting for a 39% reduction. In non-pandemic period/2019, 388 (81.7%) D-EUS and 88 (18.5%) I-EUS were performed, against 206 (71.3%) D-EUS and 83 (28.7%) I-EUS in pandemic period/2020 (P=0.001). Only 5/289 (1.7%) patients had COVID-19. Fewer patients with comorbidities underwent EUS during pandemic period/2020 due to lockdown measures (P<0.001). D-EUS decreased, whereas I-EUS increased (P<0.001). EUS-guided tissue acquisition (EUS-TA) was the most common I-EUS, performed in 83/289 (28.7%) patients in pandemic period/2020, against 88/475 (18.5%) in non-pandemic period/2019 (P=0.001). AEs did not differ significantly between the study periods. Conclusion: Pandemic Period/2020 had a moderate impact on reducing EUS procedures due to the risks involved. Although I-EUS increased, EUS-related AEs did not. Solid and cystic pancreatic tumors remained a major indication for EUS-TA even during the pandemic period/2020.

RESUMO Contexto: Os dados sobre o impacto da pandemia de COVID-19 2020 na ultrassonografia endoscópica (EUS) são escassos. Objetivo: Analisamos o impacto do período pandêmico/2020 na demografia, indicações e número das EUS diagnósticas (D-EUS) e intervencionistas EUS (I-EUS) realizados em uma unidade de endoscopia de alto volume e os comparamos com o período imediatamente anterior não-pandêmico/2019. Métodos: Revisamos retrospectivamente os prontuários de todos os pacientes submetidos a D-EUS ou I-EUS de 1 de março de 2019 a 29 de fevereiro de 2020 (período não-pandêmico/2019) e de 1º de março de 2020 a 28 de fevereiro de 2021 (período da pandemia/2020). Comparamos os dados entre os períodos do estudo incluímos o sexo, idade, comorbidades, achados e diagnóstico da EUS, necessidade de procedimentos intervencionistas durante a EUS e a ocorrência de eventos adversos (EAs). Os resultados foram significativos com P<0,05. Resultados: O número de ecoendoscopias diminuíram de 475 no período não-pandêmico/2019 para 289 no período pandêmico/2020, representando uma redução de 39%. No período não-pandêmico/2019 e pandêmico/2020 foram realizados 388 (81,7%) D-EUS e 88 (18,5%) I-EUS, contra 206 (71,3%) D-EUS e 83 (28,7%) I-EUS, respectivamente (P=0,001). Apenas 5/289 (1,7%) pacientes tinham COVID-19. Menos pacientes com comorbidades realizaram EUS durante o período pandêmico/2020 devido as medidas de bloqueio (P<0,001). D-EUS diminuiu, enquanto I-EUS aumentou (P<0,001). A EUS associada a aquisição tecidual (EUS-AT) foi a I-EUS mais comum, realizada em 83/289 (28,7%) pacientes no período pandêmico/2020, versus 88/475 (18,5%) no período não-pandêmico/2019 (P=0,001). Os EAs não diferiram significativamente entre os períodos do estudo. Conclusão: O período da pandemia/2020 teve impacto moderado na redução da EUS devido aos riscos envolvidos. Embora o I-EUS tenha aumentado, os EAs relacionados ao EUS não aumentaram. Os tumores pancreáticos sólidos e císticos permaneceram como uma das principais indicações para EUS-AT mesmo durante o período pandêmico/2020.

Fases del desarrollo de biomarcadores para la detección temprana del cáncer / Phases of the development of biomarkers for early detection of cancer

Introducción. Un biomarcador se define como una alteración molecular presente en el desarrollo de la patogénesis del cáncer, que puede ser utilizada para el diagnóstico temprano de la enfermedad. La medición del biomarcador se hace por medio de diversas técnicas, como bioquímica, inmunohistoquímica o biología molecular, en diferentes tipos de muestras, como tejido, sangre periférica y orina. El biomarcador ideal será aquel que sea válido y específico a la vez, que sea no invasivo, barato y fácilmente detectable. El uso de biomarcadores para la detección temprana del cáncer debe seguir un desarrollo ordenado y sistemático antes de introducirlos en la práctica clínica. Métodos. Se realizó una búsqueda exhaustiva en las bases de datos de PubMed y Embase, seleccionando los artículos pertinentes para revisarlos acorde a la temática específica de interés. Resultados. Se propone la sistematización del desarrollo de biomarcadores en cinco grandes fases, las cuales tienen la característica de ser ordenadas desde las evidencias más tempranas hasta las fases finales de su estudio. Conclusiones. El correcto desarrollo de biomarcadores hace posible la introducción de intervenciones terapéuticas en el ámbito de la prevención secundaria del cáncer.

Introduction. A biomarker can be defined as a molecular alteration present in the development of cancer pathogenesis which can be used for early diagnosis of the disease. The measurement of the biomarker can be carried out through various techniques such as biochemistry, immunohistochemistry, molecular biology, in different types of samples such as tissue, peripheral blood, and urine. The ideal biomarker will be one that is valid and specific while is non-invasive, cheap, and easily detectable. The use of biomarkers for the early detection of cancer must follow an orderly and systematic development before introducing them into clinical practice. Methods. An exhaustive search was performed in PubMed and Embase databases, selecting the relevant articles according to the specific topic of interest. Results. Systematization of the development of biomarkers in five large phases is proposed, which has the characteristic of being ordered from the earliest evidence to the final phases of their study. Conclusions. The correct development of biomarkers makes possible the introduction of therapeutic interventions in the field of secondary prevention of cancer.

Síndrome colestásico como forma de presentación de linfoma no Hodgkin. Reporte de un caso pediátrico / Cholestatic syndrome as a presentation of non-Hodgkin lymphoma. A pediatric case report

La ictericia colestásica se debe a la alteración de la secreción de bilirrubina conjugada; es una de las posibles causas la alteración del flujo biliar por obstrucción de la vía biliar extrahepática. El linfoma es la tercera neoplasia más frecuente en pediatría, mientras que los tumores pancreáticos son poco frecuentes y, en su mayoría, lesiones benignas. Las manifestaciones clínicas de los tumores de localización retroperitoneal son poco específicas y suelen ser tardías, por lo que la sospecha clínica debe ser alta. El objetivo del siguiente trabajo es presentar el caso de un niño de 7 años con síndrome colestásico en el que se halló un tumor en la cabeza del páncreas que comprimía la vía biliar extrahepática. El diagnóstico del tumor fue linfoma no Hodgkin (LNH). Se destaca la infrecuencia de este tumor en esta localización en la edad pediátrica

Cholestatic jaundice is due to an alteration in conjugated bilirubin secretion; a possible cause is an altered bile flow resulting from an obstruction of the extrahepatic bile duct. A lymphoma is the third most common neoplasm in pediatrics, while pancreatic tumors are rare and mostly benign. The clinical manifestations of retroperitoneal tumors are not very specific and are usually late, so a high level of clinical suspicion is required. The objective of this study is to describe the case of a 7-year-old boy with cholestatic syndrome with a tumor in the head of the pancreas compressing the extrahepatic bile duct. The tumor diagnosis was non-Hodgkin lymphoma (NHL). It is worth noting that the presence of a tumor in this location in pediatric age is uncommon

Lower gastrointestinal bleeding due to pancreatic cancer: an unusual presentation

Pancreatic cancer is a malignant neoplasm with a poor prognosis. When it manifests clinically with cold jaundice, general repercussion or dyspepsia, it usually corresponds to a locally advanced tumor. Enterorrhagia as a form of presentation of pancreatic cancer is extremely infrequent; it corresponds to a severe form with an ominous prognosis. We present the case of a 61-year-old man who attended emergency service for enterorrhagia associated with organic abdominal pain and general repercussions, to whom a diagnosis of pancreatic tail cancer was diagnosed. Colonoscopy revealed mucosal infiltration with intense edema, erythema, necrosis, and spontaneous bleeding at the level of the splenic exure of the colon. Histology conrmed colonic infiltration by pancreatic neoplasm. Computed tomography allowed staging in stage IV. Palliative surgical treatment was performed, with a survival of 3 months.

El cáncer de páncreas corresponde a una neoplasia maligna con pobre pronóstico. Cuando se manifiesta clínicamente con ictericia fría, repercusión general o dispepsia, habitualmente corresponde a un tumor localmente avanzado. La enterorragia como forma de presentación del cáncer de páncreas es extremadamente infrecuente, corresponde a una forma grave y de pronóstico ominoso. Se presenta el caso de un hombre de 61 años que consultó por enterorragia asociada a dolor abdominal de características orgánicas y repercusión general, en el que se realizó diagnóstico de cáncer de cola de páncreas. La colonoscopía evidenció a nivel del ángulo esplénico del colon, infiltración mucosa con intenso edema, eritema, necrosis y sangrado espontáneo. La histología confirmó la infiltración colónica por neoplasma de páncreas. La tomografía computarizada permitió su estadificación en estadio IV. Se realizó tratamiento quirúrgico paliativo, con una sobrevida de 3 meses.

Papel da imagem na indicação da eletroporação irreversível no manejo terapêutico do adenocarcinoma de pâncreas / Role of imaging in the applicability of irreversible electroporation for the management of pancreatic adenocarcinoma

Resumo O adenocarcinoma ductal de pâncreas é uma das neoplasias malignas mais agressivas, com taxas de sobrevivência anuais inferiores a 20%. Os métodos axiais (tomografia computadorizada e ressonância magnética) têm papel fundamental no diagnóstico e estadiamento da doença, por fornecerem adequada resolução anatômica na avaliação de estruturas-chave, principalmente vasculares. O adenocarcinoma ductal de pâncreas é frequentemente descoberto em estágios avançados e sem viabilidade de ressecção cirúrgica, e nesse cenário o desenvolvimento de alternativas terapêuticas minimamente invasivas tem sido ainda mais importante para a mudança de sua história natural. A eletroporação irreversível, procedimento intervencionista que minimiza efeitos deletérios nos tecidos adjacentes, vem se destacando no tratamento de lesões tradicionalmente consideradas irressecáveis. Essa técnica, apesar de ganhar cada vez mais espaço no manejo terapêutico do adenocarcinoma ductal de pâncreas, ainda é pouco familiar aos radiologistas. Neste estudo, buscamos expor, de forma sucinta e didática, os fundamentos da técnica, as principais características de imagem e os critérios de elegibilidade que devem ser considerados para indicação da eletroporação irreversível nessa doença.

Abstract Pancreatic ductal adenocarcinoma is one of the most aggressive malignant neoplasms, with a one-year survival rate below 20%. Axial methods (computed tomography and magnetic resonance imaging) play a fundamental role in the diagnosis and staging of the disease, because they provide adequate anatomical resolution in the assessment of key structures, mainly vascular structures. Pancreatic ductal adenocarcinoma is most often discovered in advanced stages, when surgical resection is no longer feasible. In that scenario, minimally invasive treatment alternatives have been developed in attempts to change the natural history of the disease. Irreversible electroporation, an interventional procedure that minimizes deleterious effects on adjacent tissues, has proven useful for the treatment of tumors traditionally considered unresectable. Despite the growing acknowledgment of this technique as a tool for the management of pancreatic ductal adenocarcinoma, it is still relatively unknown among radiologists. In this study, we sought to provide an overview of the main characteristics and eligibility criteria that must be considered for the indication of irreversible electroporation in cases of pancreatic ductal adenocarcinoma.

Tendências de mortalidade por câncer de pâncreas correlacionadas com o índice de desenvolvimento humano (IDH) no Brasil em 40 anos / Pancreatic cancer mortality trends and correlation with human development index (hdi) in brazil over 40 years

ABSTRACT Background Pancreatic cancer mortality is greater in countries with a high Human Development Index (HDI). This study analyzed pancreatic cancer mortality rates trends, and their correlation with HDI in Brazil over 40 years. Methods: Data on pancreatic cancer mortality in Brazil between 1979 and 2019 were obtained from the Mortality Information System (SIM). Age-standardized mortality rates (ASMR) and Annual Average Percent Change (AAPC) were calculated. Pearson's correlation test was applied to compare mortality rates and HDI for three periods: 1986-1995 was correlated with HDI of 1991, 1996-2005 with HDI of 2000, and 2006-2015 with HDI of 2010; and to the correlation of AAPC versus the percentage change in HDI from 1991 to 2010. Results: A total of 209,425 deaths from pancreatic cancer were reported in Brazil, with an annual increase of 1.5% in men and 1.9% in women. There was an upward trend for mortality in most Brazilian states, with the highest trends observed in the North and Northeast states. A positive correlation between pancreatic mortality and HDI was observed over the three decades (r>0.80, P<0.05) and also between AAPC and HDI improvement by sex (r=0.75 for men and r=0.78 for women, P<0.05). Conclusion There was an upward trend in pancreatic cancer mortality in Brazil for both sexes, but rates among women were higher. Mortality trends were higher in states with a higher percentage improvement in HDI, such as the North and Northeast states.

RESUMO Contexto A mortalidade por câncer de pâncreas é maior em países com alto Índice de Desenvolvimento Humano (IDH). Este estudo analisou as taxas e tendências de mortalidade por câncer de pâncreas e correlacionou-as com o IDH no Brasil no período de 40 anos. Métodos: Os dados sobre mortalidade por câncer de pâncreas no Brasil, entre 1979 e 2019, foram extraídos do Sistema de Informações sobre Mortalidade (SIM). As taxas de mortalidade padronizadas por idade e variação percentual média anual (AAPC) foram calculadas. O teste de correlação de Pearson foi aplicado para comparar as taxas de mortalidade e IDH em três períodos: 1986-1995 foi correlacionado com o IDH de 1991, 1996-2005 com IDH 2000 e 2006-2015 com IDH 2010; e a correlação da AAPC versus o percentual de variação do IDH de 1991 a 2010. Resultados: Foram notificados 209.425 óbitos por câncer de pâncreas no Brasil no período de 1979 a 2019, com aumento de 1,5% ao ano em homens e de 1,9% em mulheres. Houve tendência de aumento da mortalidade na maioria dos estados brasileiros, com maiores tendências nos estados das regiões Norte e Nordeste. Foi observada uma correlação positiva na mortalidade por câncer de pâncreas e o IDH ao longo de três décadas (r>0,80, P<0,05); também, entre o AAPC e o incremento do IHD entre 1991 e 2010 (r=0,75 para homens e r=0,78 para mulheres, P<0,05). Conclusão: Houve tendência crescente da mortalidade por câncer de pâncreas no Brasil, em ambos os sexos, porém maior entre as mulheres. As tendências de mortalidade foram maiores nos estados com maior percentual de incremento do IDH, como estados das regiões Norte e Nordeste.

Cystic pancreatic lesions: imaging versus anatomopathological findings-how to improve diagnostic accuracy? / Lesões císticas do pâncreas: imagens versus achados anatomopatológicos. como melhorar a acurácia diagnóstica?

ABSTRACT BACKGROUND: Pancreatic cystic lesions are a group of pancreatic neoplasms with different behavior and risk of malignancy. Imaging diagnosis and differentiation of these lesions remain a challenge. AIMS: The aim of this study was to evaluate the agreement between computed tomography and/or magnetic resonance imaging and post-operative pathologic diagnoses of Pancreatic cystic lesions in a University Hospital of São Paulo State. METHODS: A total of 39 patients with surgically diagnosed Pancreatic cystic lesions were enrolled, as a study cohort from 2009 to 2019. Preoperative radiological and final pathological diagnosis was correlated to measure computed tomography and/or magnetic resonance imaging diagnostic. Pancreatic adenocarcinoma, choledochal pancreatic cyst, mucinous cystadenoma, serous cystadenoma, intraductal papillary mucinous neoplasms, and pancreatic pseudocyst were classified as neoplastic cysts. RESULTS: It was noted that 27 patients (69.23%) had preoperative computed tomography and magnetic resonance imaging, 11 patients (28.20%) had preoperative computed tomography only, and 1 patient had preoperative magnetic resonance imaging only. The values for diagnoses made only with computed tomography (p=0.47) and from the combination of computed tomography+magnetic resonance imaging (p=0.50) did also point to moderate agreement with the anatomopathological findings. The values pointed to a fair agreement for the diagnosis of mucinous cystadenoma (p=0.3), moderate agreement for intraductal papillary mucinous neoplasms (p= 0.41), good agreement for serous cystadenoma (p=0.79), and excellent agreement for choledochal pancreatic cyst (p=1), pancreatic pseudocyst (p=0.84), and Frantz tumor (p=1) (p<0.05). CONCLUSIONS: The findings of computed tomography and/or magnetic resonance imaging have an equivalent diagnostic agreement with an anatomopathological diagnosis for differentiating benign from malignant Pancreatic cystic lesions and in suggesting a specific diagnosis. There is no statistical difference between the use of computed tomography alone and computed tomography+magnetic resonance imaging in the improvement of diagnostic accuracy.

RESUMO RACIONAL: Lesões císticas pancreáticas são um grupo de neoplasias pancreáticas com diferentes comportamentos e riscos de malignidade. O diagnóstico por imagem e a diferenciação dessas lesões constituem um desafio. OBJETIVOS: Avaliar a concordância entre o diagnóstico de imagem pré operatório obtido através da tomografia computadorizada e/ou da ressonância nuclear magnética e o diagnóstico anátomopatológico das lesões císticas pancreáticas, no Hospital de Base de São José do Rio Preto - SP. MÉTODOS: Trinta e nove pacientes com lesões císticas pancreáticas, comprovados cirurgicamente, foram incluídos para o estudo, de 2009 a 2019. O diagnóstico radiológico pré-operatório e o diagnóstico anatomopatológico final foram correlacionadas para medir a acurácia da tomografia computadorizada e/ou da ressonância nuclear magnética. O adenocarcinoma pancreático, o cisto pancreato-coledociano, o cistoadenoma mucinoso, o cistoadenoma seroso, a neoplasia mucinosa papilar intraductal, e o pseudocisto pancreático foram classificados como cistos neoplásicos. As informações foram comparadas e estatisticamente analisadas. RESULTADOS: Vinte e sete pacientes fizeram tomografia computadorizada e ressonância nuclear magnética pré-operatórios (69,23%), 11 pacientes fizeram apenas tomografia computadorizada (28,20%), e 1 paciente fez apenas ressonância nuclear magnética (2,57%). Os achados de tomografia computadorizada para diagnóstico (p=0,47) e para a combinação tomografia computadorizada+RM (p=0,50) mostraram moderada concordância com os achados anatomopatológicos. Houve leve concordância para o diagnóstico de cistoadenoma mucinoso (p=0,3), moderada concordância para intraductal papillary mucinous neoplasms (p=0,41), boa concordância para cistoadenoma seroso (p=0,79) e excelente concordância para pseudocisto pancreático (p=0,84), cisto pancreato-coledociano (p=1) e tumor de Frantz (p=1) (p<0,05). CONCLUSÕES: Os achados de imagem da tomografia computadorizada e/ou ressonância nuclear magnética apresentaram concordância diagnóstica com os exames anatomopatológicos na diferenciação de lesões císticas pancreáticas benignas e malignas, porém a diferença entre o uso apenas da tomografia computadorizada e tomografia computadorizada+ressonância nuclear magnética na melhora da acurácia diagnóstica não apresentou relevância estatística tal como a literatura.

From left to right. para-aortic lymph nodes sampling during pancreatoduodenectomy for pancreatic cancer / Da esquerda para a direita. ressecção de linfonodos para-aórticos durante duodenopancreatectomia para câncer pancreático

ABSTRACT BACKGROUND: Para-aortic lymph nodes involvement in pancreatic head cancer has been described as an independent adverse prognostic factor. To avoid futile pancreatic resection, we systematically perform para-aortic lymphadenectomy as a first step. AIMS: To describe our technique for para-aortic lymphadenectomy. METHODS: A 77-year-old female patient, with jaundice and resectable pancreatic head adenocarcinoma, underwent pancreaticoduodenectomy associated with infracolic lymphadenectomy. RESULTS: The infracolic anterior technique has two main advantages. It is faster and prevents the formation of postoperative adhesions, which can make subsequent surgical interventions more difficult. CONCLUSIONS: We recommend systematic para-aortic lymphadenectomy as the first step of pancreaticoduodenectomy for pancreatic head adenocarcinoma by this approach.

RESUMO RACIONAL: O envolvimento dos gânglios linfáticos para-aórticos no câncer da cabeça do pâncreas tem sido descrito como um fator prognóstico adverso independente. Para evitar a ressecção pancreática inútil, realizamos sistematicamente linfadenectomia para-aórtica. OBJETIVOS: Descrever a técnica de linfadenectomia para-aórtica. MÉTODOS: Paciente do sexo feminino, 77 anos, com quadro de icterícia e adenocarcinoma da cabeça do pâncreas ressecável, submetida à duodenopancreatectomia associada à linfadenectomia infracólica. RESULTADOS: Esta técnica anterior infracólica tem duas vantagens principais: é mais rápida e evita a formação de aderências pós-operatórias, o que pode dificultar as intervenções cirúrgicas subsequentes. CONCLUSÕES: Recomendamos a linfadenectomia para-aórtica sistemática como o primeiro passo da duodenopancreatectomia para o adenocarcinoma da cabeça do pâncreas por esta abordagem.

Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells / 中华肿瘤杂志

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.

Long-term outcomes of definitive radiotherapy-based comprehensive treatment for inoperable stage I-III non-metastatic pancreatic cancer / 中华放射肿瘤学杂志

Objective:To analyze long-term outcomes of inoperable non-metastatic pancreatic cancer patients treated with definitive radiotherapy-based comprehensive treatment.Methods:Clinical data of 168 patients with medically unfit, refusal to surgery or inoperable non-metastatic pancreatic cancer treated with radiotherapy-based comprehensive treatment in PLA General Hospital between January 2016 and December 2020 were retrospectively analyzed. Survival outcomes,prognostic factors and patterns of treatment failure were analyzed in the radiotherapy ( n=95) and combined chemoradiotherapy ( n=73) groups. The survival analysis was conducted by Kaplan-Meier method. The survival curve was compared by log-rank test. Independent prognostic factors were identified by Cox proportional harzard model. Results:With a median follow-up of 20.2 months in the entire group, the median overall survival (OS) and median progression-free survival (PFS) were 18.0 and 12.3 months. The corresponding median OS and median PFS after receiving radiotherapy were 14.3 and 7.7 months. The 1-, 2-and 3-year OS rates were 72.1%, 36.6% and 21.5%, and the 1- and 2-year local control rates were 82.6% and 64.3%, respectively. The median OS for stage Ⅰ, stage Ⅱ and stage III were 27.1, 18.0 and 17.0 months, respectively. There was no significant difference in the median OS of patients with localized disease (stage Ⅰ-Ⅱ) between the radiotherapy and combined chemoradiotherapy groups (21.1 vs. 20.4 months, P=0.470). In patients with locally advanced disease (stage Ⅲ), combined chemoradiotherapy group showed better median OS compared with radiotherapy group (19.2 vs. 13.8 months, P=0.004). Clinical stage, CA19-9 before radiotherapy, comprehensive treatment and biological effective dose (BED 10) were identified as the independent prognostic factors for OS ( P=0.032, 0.011, 0.003 and 0.014). The cumulative 1- and 2-year actuarial rates of treatment failure, local-regional recurrence and distant metastasis were 48% and 74.4%, 15.0% and 27.4%, 23.6% and 33.1%, respectively. Liver metastasis (16.1%, 27/168) and local recurrence (11.9%, 20/168) were the primary patterns of treatment failure. Conclusions:Definitive radiotherapy-based comprehensive treatment effectively prolongs long-term survival in patients with inoperable non-metastatic pancreatic cancer. Definitive radiotherapy can be an alternative treatment option with curative intent for patients with localized pancreatic cancer who are medically unfit or refuse to undergo surgery. The combination of radiotherapy and chemotherapy remains an effective treatment choice for locally advanced unresectable pancreatic cancer.

Efficacy and safety of intraoperative radiotherapy for pancreatic cancer: a meta-analysis / 中华放射肿瘤学杂志

Objective:To compare and analyze the efficacy and safety of intraoperative radiotherapy (IORT) combined with conventional therapy (surgery combined with radiochemotherapy) and conventional therapy alone for pancreatic cancer.Methods:Literature review was conducted from PubMed, Cochrane Library, Web of Science, Embase, Chongqing VIP, CNKI, Wanfang Data and China Biomedical Literature Service System (SinoMed). The literatures that met the inclusion criteria were screened and the data were extracted. Meta-analysis was carried out by RevMan 5.4 software.Results:A total of 11 studies consisting of 813 patients were included. According to the combined results, compared with conventional therapy, IORT combined with conventional therapy could improve the overall survival rate of pancreatic cancer ( HR=0.66, 95% CI=0.54-0.81, Z=4.03, P<0.001), and did not increase the treatment-related side effects ( OR=1.00, 95% CI=0.69-1.46, Z=0.01, P=0.99), but failed to bring benefit to the local control rate ( HR=0.56, 95% CI=0.31-1.01, Z=1.93, P=0.05). Conclusions:The overall survival rate in the IORT combined with conventional therapy group is significantly better than that in the conventional therapy group. No significant difference is found in the treatment-related adverse reactions between two groups. IORT combined with conventional therapy is worthy of clinical application.

Analysis of influencing factors for breakthrough cancer pain in patients with advanced pancreatic cancer / 中华胰腺病杂志

Objective:To investigate the influencing factors of breakthrough cancer pain (BTcP) in patients with advanced pancreatic cancer.Methods:According to the inclusion and exclusion criteria, patients with advanced pancreatic cancer who were diagnosed and followed up by outpatient service in the 909th Hospital of the Joint Logistic Support Force from January 2019 to December 2020 were prospectively selected as the study subjects. According to whether breakthrough cancer pain occurred, all patients were divided into observation group (breakthrough cancer pain) and control group (no breakthrough cancer pain). The relevant clinical data of the included patients including age, gender, presence or absence of vomit, constipation, sleep disruption, frequency of basic pain every week, with or without regular medication, heavy physical labor, with or without vascular invasion, bone metastasis, abdominal metastasis and lung metastasis, as well as whether surgery, radiotherapy or chemotherapy were collected and the data of evaluation indicators during follow-up were recorded. Digital pain score (NRS) and visual analog score (VAS) were used as pain evaluation score. Univariate and logistic regression were used to analyze the related influencing factors of breakthrough cancer pain. Receiver operating characteristic curve (ROC) was drawn, and area under curve (AUC), sensitivity and specificity were calculated to analyze the predictive value for breakthrough cancer pain.Results:A total of 173 patients were included in the study, with 49 cases in the observation group and 124 cases in the control group. Univariate analysis showed that aged ≥50 years old, constipation, sleep disruption, frequency of basic pain ≥3 times, irregular medication, heavy physical labor, bone metastasis, lung metastasis, radiochemotherapy, high NRS score and high VAS score were the influencing factors for breakthrough cancer pain (all P value <0.05). Multivariate analysis showed that irregular medication ( OR=1.879, 95% CI 2.473-4.757, P=0.002), basal pain ≥3 times ( OR=2.067, 95% CI 1.364-6.825, P=0.004), bone metastasis ( OR=2.756, 95% CI 1.153-5.846, P<0.001), NRS score ( OR=3.787, 95% CI 2.647-5.958, P<0.001), VAS score ( OR=2.684, 95% CI 1.545-7.878, P<0.001), were the risk factors for breakthrough cancer pain. The AUC of NRS score for predicting the occurrence of breakthrough cancer pain was 0.665 (95% CI0.573-0.757, P=0.001), and the cut-off value was 2.5 score with a sensitivity of 61.2% and a specificity of 77.1%. The AUC for predicting breakthrough cancer pain by VAS score was 0.608 (95% CI0.515-0.701, P=0.028), and the cut-off value was 2.5 score with a sensitivity of 67.9% and a specificity of 63.7%. The AUC of NRS+ VAS score for predicting breakthrough cancer pain was 0.692 (95% CI0.604-0.780), and the cut-off value was 4.5 score with a sensitivity of 81.6% and a specificity of 79.8%. Conclusions:Patients with advanced pancreatic cancer have a high incidence of breakthrough cancer pain, which was related to a variety of factors. NRS combined with VAS score can effectively predict the occurrence of breakthrough cancer pain.

Regulatory effect of miR-210 in hypoxia-induced epithelial-mesenchymal transition of pancreatic cancer PANC1 cells / 中华胰腺病杂志

Objective:To explore the regulatory role of miR-210 in hypoxia-induced epithelial-mesenchymal transition (EMT) of pancreatic cancer PANC1 cells.Methods:PANC1 cells cultured in normoxia and hypoxia were established in normoxia group and hypoxia group. Recombinant plasmid carrrying miR-210 mimics and miR-210 antagomirs were constructed. The recombinant plasmids were transfected with PANC1 cells cultured in normoxia and hypoxia by liposome method to establish cell lines of miR-210 overexpression (miR-210 mimics normoxia group) and miR-210 expression inhibition (miR-210 antagomirs hypoxia group). The blank plasmids were transfected to establish blank plasmid normoxia group and blank plasmid hypoxia group. Relative expression levels of miR-210 for PANC1 cells were determined by qRT-PCR in each group. Western blot was used to measure the expressions of HIF-1α, NF-κB and EMT related protein such as E-cadherin, β-catenin, vimentin and N-cadherin. Cell relative viability under gemcitabine and in vitro cell invasion ability were detected by CCK8 and Transwell chamber experiments, respectively. Results:The relative expressions of miR-210 in hypoxia group and miR-210 mimics normoxia group were significantly higher than those in normoxia group and blank plasmid normoxia group. However, there were significantly lower in miR-210 antagomirs hypoxia group than those in blank plasmid hypoxia group. The expression levels of HIF-1α, NF-κB and mesenchymal cell markers such as vimentin and N-cadherin in hypoxia group were significantly higher than those in normoxia group (0.74±0.06 vs 0.40±0.05, 1.58±0.16 vs 1.09±0.13, 0.46±0.04 vs 0.17±0.02, 1.27±0.07 vs 0.40±0.03) and the epithelial cell markers such as E-cadherin and β-catenin were significantly lower (0.40±0.07 vs 0.77±0.10, 0.35±0.02 vs 0.94±0.08). The expression levels of HIF-1α, NF-κB, vimentin and N-cadherin in miR-210 mimics normoxia group were significantly higher than those in blank plasmid normoxia group (0.91±0.08 vs 0.40±0.06, 1.52±0.17 vs 1.05±0.14, 0.82±0.06 vs 0.66±0.07, 0.76±0.04 vs 0.46±0.03) and E-cadherin and β-catenin were significantly lower (0.38±0.07 vs 0.65±0.09, 0.50±0.03 vs 0.94±0.08). The expression levels of HIF-1α, NF-κB, vimentin and N-cadherin in miR-210 antagomirs hypoxia group were significantly lower than those in blank plasmid hypoxia group (0.31±0.05 vs 0.55±0.06, 0.68±0.05 vs 1.11±0.13, 0.41±0.03 vs 0.74±0.07, 0.69±0.06 vs 0.78±0.05), while E-cadherin and β-catenin were significantly higher (0.72±0.13 vs 0.50±0.07, 0.71±0.04 vs 0.54±0.05). All the differences among the groups were statistically significant (all P value <0.05). Under gemcitabine, the relative viability of PANC1 cells in hypoxia group and miR-210 mimics normoxia group were significantly higher than those in normoxia group and blank plasmid normoxia group at 48 h (1.10±0.10 vs 0.76±0.05, 1.46±0.11 vs 1.12±0.09) and 72 h (1.12±0.13 vs 0.76±0.05, 1.54±0.13 vs 1.12±0.09) accordingly. However, there were significantly lower in miR-210 antagomirs hypoxia group than those in blank plasmid hypoxia group at 48 and 72 h (0.75±0.09 vs 1.10±0.10, 1.19±0.12 vs 1.46±0.11). All the differences among the groups were statistically significant (all P value <0.05). The number of transmembrane cells in hypoxia group and miR-210 mimics normoxia group was significantly higher than those in normoxia group and blank plasmid normoxia group, respectively (417.50±81.22 vs 228.30±47.71, 371.30±72.81 vs 245.00±33.62 per high field), while those in miR-210 antagomirs hypoxia group was significantly lower than those in blank plasmid hypoxia group (228.30±54.01 vs 433.30±65.63 per high field). All the differences among the groups were statistically significant (all P value <0.05). Conclusions:miR-210 could weaken the sensitivity to gemcitabine and promote the invasion of PANC1 cells by regulating the occurrence of the hypoxia-induced epithelial-mesenchymal transition.

Differentiating pancreatic adenosquamous carcinoma from pancreatic ductal adenocarcinoma by CT radiomic and deep learning features / 中华胰腺病杂志

Objective:To develop and validate the models based on mixed enhanced computed tomography (CT) radiomics and deep learning features, and evaluate the efficacy for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC) before surgery.Methods:The clinical data of 201 patients with surgically resected and histopathologically confirmed PASC (PASC group) and 332 patients with surgically resected histopathologically confirmed PDAC (PDAC group) who underwent enhanced CT within 1 month before surgery in the First Affiliated Hospital of Naval Medical University from January 2011 to December 2020 were retrospectively collected. The patients were chronologically divided into a training set (treated between January 2011 and January 2018, 156 patients with PASC and 241 patients with PDAC) and a validation set (treated between February 2018 and December 2020, 45 patients with PASC and 91 patients with PDAC) according to the international consensus on the predictive model. The nnU-Net model was used for pancreatic tumor automatic segmentation, the clinical and CT images were evaluated, and radiomics features and deep learning features during portal vein phase were extracted; then the features were dimensionally reduced and screened. Binary logistic analysis was performed to develop the clinical, radiomics and deep learning models in the training set. The models' performances were determined by area under the ROC curve (AUC), sensitivity, specificity, accuracy, and decision curve analysis (DCA).Results:Significant differences were observed in tumor size, ring-enhancement, upstream pancreatic parenchymal atrophy and cystic degeneration of tumor both in PASC and PDAC group in the training and validation set (all P value <0.05). The multivariable logistic regression analysis showed the tumor size, ring-enhancement, dilation of the common bile duct and upstream pancreatic parenchymal atrophy were associated with PASC significantly in the clinical model. The ring-enhancement, dilation of the common bile duct, upstream pancreatic parenchymal atrophy and radiomics score were associated with PASC significantly in the radiomics model. The ring-enhancement, upstream pancreatic parenchymal atrophy and deep learning score were associated with PASC significantly in the deep learning model. The diagnostic efficacy of the deep learning model was highest, and the AUC, sensitivity, specificity, and accuracy of the deep learning model was 0.86 (95% CI 0.82-0.90), 75.00%, 84.23%, and 80.60% and those of clinical and radiomics models were 0.81 (95% CI 0.76-0.85), 62.18%, 85.89%, 76.57% and 0.84 (95% CI 0.80-0.88), 73.08%, 82.16%, 78.59% in the training set. In the validation set, the area AUC, sensitivity, specificity, and accuracy of deep learning model were 0.78 (95% CI 0.67-0.84), 68.89%, 78.02% and 75.00%, those of clinical and radiomics were 0.72 (95% CI 0.63-0.81), 77.78%, 59.34%, 65.44% and 0.75 (95% CI 0.66-0.84), 86.67%, 56.04%, 66.18%. The DCA in the training and validation sets showed that if the threshold probabilities were >0.05 and >0.1, respectively, using the deep learning model to distinguish PASC from PDAC was more beneficial for the patients than the treat-all-patients as having PDAC scheme or the treat-all-patients as having PASC scheme. Conclusions:The deep learning model based on CT automatic image segmentation of pancreatic neoplasm could effectively differentiate PASC from PDAC, and provide a new non-invasive method for confirming PASC before surgery.