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.

Evaluation of Fine Needle Biopsy (FNB) for Endoscopic Ultrasound (EUS)-guided tissue acquisition of pancreatic masses to negate the need for rapid on-site evaluation: A randomized control trial

Background and Objectives@#The benefits of rapid on-site evaluation (ROSE) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid masses have not been convincingly shown in large, randomized trials. New equipment using EUS-guided fine needle biopsy (FNB) allows for more material to be acquired that may obviate the need for ROSE. This study aimed to evaluate if EUS-FNB without ROSE was non-inferior to EUS-FNA with ROSE in solid pancreatic masses (SPMs). @*Methods@#Patients with SPMs requiring tissue sampling were randomly assigned to undergo either EUS-FNA with ROSE or EUS-FNB without ROSE. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy and secondary endpoints were specimen quality, complication rates, and procedure time. @*Results@#Seventy-eight patients were randomized and analyzed (39 EUS-FNA with ROSE and 39 EUS-FNB without ROSE). Non-significantly different diagnostic accuracies were noted in both groups (97% with ROSE and 100% without ROSE, P < 0.371). The bloodiness of histologic samples and complication rates were not significantly different between groups. A significantly shorter mean sampling procedural time was noted for EUS-FNB over EUS-FNA with ROSE (30.4 ± 10.4 vs 35.8 ± 9.8 minutes, P < .02). @*Conclusions@#EUS-FNB demonstrated equal diagnostic accuracy with shorter procedure times in evaluating SPMs compared to EUS-FNA with ROSE. These new-generation FNB needles may obviate the need for ROSE.

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.

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.

Evolução da mortalidade por neoplasias entre os anos de 2010 a 2020 no Brasil segundo sexo e localização primária do tumor / Evolution of mortality from neoplasms between the years 2010 to 2020 in Brazil according to gender and primary location of the tumour

Introdução: o câncer é um grave problema de saúde pública, considerado a segunda causa de óbitos no Brasil. Devido à sua relevância, é indispensável um controle eficiente dos casos através do acompanhamento da taxa de mortalidade. Dessa forma, o trabalho analisou a evolução da mortalidade por câncer para as localizações primárias mais frequentes, segundo sexo, durante o período de 2010 a 2020. Metodologia: trata-se de um estudo observacional descritivo, no qual os dados foram obtidos através do Atlas On-line de Mortalidade por Câncer. Os dados colhidos correspondem ao número de óbitos estratificados por tipo de câncer mais frequente, por ano estudado e por sexo, além das taxas de mortalidade específica bruta e a taxa de mortalidade ajustada por idade para o sexo masculino e feminino, para cada tipo de câncer em estudo, considerando a população padrão mundial, sendo avaliado por regressão linear a significância da tendência temporal. Resultados: no Brasil, no período de 2010 a 2020, as neoplasias mais frequentes em mulheres foram câncer de mama, câncer nos brônquios e pulmões, câncer no colo do útero, câncer no cólon e no pâncreas e em homens foram brônquios e pulmões, câncer de próstata, câncer de estômago, de esôfago e no fígado e vias biliares, sendo observado uma tendência crescente na taxa de mortalidade em mulheres e decrescente na taxa de mortalidade em homens. Conclusão: os resultados demonstram um possível comprometimento com a notificação durante o período de pandemia por Covid-19 e um possível rastreamento ainda deficiente de câncer na população masculina.

Introduction: cancer is a severe public health problem, considered the second cause of death in Brazil. Due to its relevance, efficient control of cases by monitoring the mortality rate is essential. Thus, the work analysed the evolution of cancer mortality for the most frequent primary locations, according to sex, from 2010 to 2020. Methodology: this is a descriptive observational study in which data were obtained through the Atlas Online Cancer Mortality Report. The data collected correspond to the number of deaths stratified by the most frequent type of cancer, by year studied and by sex, in addition to the crude specific mortality rates and the age-adjusted mortality rate for males and females, for each type of cancer. Understudy, considering the standard world population, the significance of the temporal trend is evaluated by linear regression. Results: in Brazil, from 2010 to 2020, the most frequent neoplasms in women were breast cancer, bronchial and lung cancer, cervical cancer, colon and pancreas cancer and in men, they were bronchial and lung cancer, cancer prostate, stomach, oesophagal and liver and biliary tract cancer, with an increasing trend in the mortality rate in women and a decreasing trend in the mortality rate in men. Conclusion: the results demonstrate a possible compromise with notification during the Covid-19 pandemic and a possible still poor screening of cancer in the male population.

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.

Hallazgos clínicos, epidemiológicos, histológicos y anatómicos en pacientes adultos con diagnóstico de cáncer de páncreas / Clinical, Epidemiological, Histological and Anatomical Findings in Adult Patients Diagnosed with Pancreatic Cancer

Introducción: El cáncer de páncreas constituye un problema de salud debido al diagnóstico tardío, su agresividad biológica y la ausencia de un tratamiento sistémico efectivo. Objetivo: Caracterizar clínica, epidemiológica, histológica y anatómicamente a pacientes con cáncer de páncreas. Métodos: Se realizó un estudio descriptivo de casos clínicos, en pacientes con cáncer de páncreas que acudieron al Hospital Oncológico Conrado Benítez; de Santiago de Cuba, en el período comprendido diciembre 2017 hasta diciembre 2018. El universo estuvo conformado por el total de los pacientes de ambos sexos, cuya cifra ascendió a 19 que cumplieron con los criterios de inclusión. Resultados: No existió predominio significativo según el sexo, prevaleció el grupo de edades entre 61-70 años en un 31,6 por ciento, el 84,2 por ciento de los pacientes presentó como factor de riesgo la dieta rica en grasas y pobre en verduras y el tabaquismo, en el 63,2 por ciento coexistió la hipertensión arterial, la pérdida de peso fue el signo que sobresalió en el 79,0 por ciento. El 47,4 por ciento se les diagnosticó adenocarcinoma poco diferenciado, siendo la localización más frecuente de los tumores (31,6 por ciento) la cabeza del páncreas. Conclusiones: El cáncer de páncreas es una enfermedad maligna que se relacionada con la edad y sus síntomas se manifiestan tardíamente, se asocia con la presencia de factores de riesgo por lo que es necesario identificarlos precozmente, modificarlos y/o atenuarlos(AU)

Introduction: Pancreatic cancer constitutes a health problem due to late diagnosis, its biological aggressiveness and the absence of effective systemic treatment. Objective: To clinically, epidemiologically, histologically and anatomically characterize patients with pancreatic cancer. Methods: A descriptive study of clinical cases was carried out in patients with pancreatic cancer who attended the Conrado Benítez; Oncological Hospital of Santiago de Cuba, in the period from December 2017 to December 2018. The universe was made up of the total number of patients of both genders, which amounted to 19 meeting the inclusion criteria. Results: There was no significant predominance according to gender, the age group between 61-70 years prevailed in 31.6 percent, 84.2 percent of patients presented as risk factor the diet rich in fat and poor in vegetables and smoking, in 63.2 percent coexisted arterial hypertension, weight loss was the sign that stood out in 79.0 percent. The 47.4 percent were diagnosed with poorly differentiated adenocarcinoma, being the pancreatic head the most frequent location of the tumors (31.6 percent). Conclusions: Pancreatic cancer is an age-related malignant disease and its symptoms manifest late that is associated with the presence of risk factors, so it is necessary to identify them early, modify and/or attenuate them(AU)

Epidemiologia do câncer de pâncreas na América Latina e no Brasil / Epidemiology of pancreatic cancer in Latin America and Brazil

Introdução: O câncer de pâncreas é um tumor de alta letalidade, é o décimo segundo tipo mais comum e a sétima causa de morte, em ambos os sexos, no mundo. Estima-se que o câncer de pâncreas terá um aumento contínuo de incidência e mortalidade nos próximos 20 anos e isso causará um enorme ônus econômico para as populações em todo o mundo. Para o monitoramento e vigilância epidemiológica em câncer, pode-se apoiar em dados secundários como no Sistema de Informação em Mortalidade e dos registros de câncer (de base populacional e hospitalares) e estimativas a partir destes dados; por essa razão, investigou-se a epidemiologia do câncer de pâncreas na América Latina e no Brasil. Métodos: A tese compreende três manuscritos: (i) tendências de incidência, mortalidade e anos de vida ajustados por incapacidade (DALYs), bem como a fração de mortes por câncer de pâncreas atribuíveis a fatores de risco comportamentais e metabólicos em países da América Latina e Caribe (LAC) entre 1990 e 2019 (Global Burden Disease, 2019); (ii) mortalidade por câncer de pâncreas no Brasil e unidades da federação entre 1979 e 2019, dados do Sistema de Informação em Mortalidade (SIM); (iii) comparabilidade, validade, completude e pontualidade para cinco tumores gastrointestinais, câncer de esôfago, estômago, colorretal, fígado e pâncreas, em Registros de Câncer de Base Populacional (RCBPs) brasileiros. Resultados: Observou-se um aumento na incidência, mortalidade e DALYs para o câncer de pâncreas em ambos os sexos na maioria dos países da América Latina e Caribe; as maiores taxas de incidência e mortalidade foram observadas no Uruguai e as menores no Haiti. Redução na fração de mortes atribuíveis ao tabagismo entre 1990 e 2019, para ambos os sexos nos países da LAC; entretanto, aumento dentre os fatores metabólicos. No Brasil, entre 1979 e 2019, foram notificados um total de 209.425 óbitos por câncer de pâncreas, com tendência de aumento de 1,5% ao ano em homens e 1,9% em mulheres. Houve tendência de aumento da mortalidade na maioria dos estados brasileiros, com maiores tendências nas regiões Norte e Nordeste, e correlação positiva entre o índice de desenvolvimento humano e a tendência de aumento da mortalidade por câncer de pâncreas. Dentre os dezesseis RCBPs brasileiros estudados, todos atenderam aos critérios de comparabilidade, porém metade apresentou índices abaixo do esperado para validade e completude para tumores de fígado e pâncreas. Para pontualidade, os dezesseis registros apresentaram mais de 48 meses de atraso na divulgação dos dados em relação ao ano calendário de 2023. Considerações finais: O câncer de pâncreas representa um desafio para a saúde pública nos países da América Latina e no Brasil, diante do desafio na redução da incidência e da mortalidade, assim como na vigilância epidemiológica em câncer através dos RCBPs brasileiros que necessitam de suporte para continuidade do monitoramento da incidência do câncer.

Introduction: Pancreatic cancer is a tumor of high lethality, is the twelfth most common type and the seventh cause of death, in both sexes, in the world. It is estimated that pancreatic cancer will have a continuous increase in incidence and mortality over the next 20 years and this will cause a huge economic burden for populations around the world. For epidemiological monitoring and surveillance in cancer, it is possible to use on secondary data such as the Mortality Information System and cancer registries (population-based and hospital) and estimates from these data, for this reason the epidemiology of pancreatic cancer in Latin America and Brazil was investigated. Methods: The thesis comprises three manuscripts: (i) trends in incidence, mortality and disability-adjusted life years (DALYs) as well as the fraction of pancreatic cancer deaths attributable to behavioral and metabolic risk factors in Latin American and Caribbean (LAC) countries between 1990 and 2019 (Global Burden Disease, GBD 2019); (ii) mortality from pancreatic cancer in Brazil and federal units between 1979 and 2019, data from the Mortality Information System (SIM); (iii) comparability, validity, completeness and timeless for five gastrointestinal tumors, esophageal, stomach, colorectal, liver and pancreatic cancers, in the Brazilian Population-Based Cancer Registries (PBCRs). Results: An increase in the incidence, mortality and DALYs of pancreatic cancer was observed in most countries in Latin America and the Caribbean, the highest incidence and mortality rates were observed in Uruguay and the lowest in Haiti. The fraction of pancreatic cancer deaths attributable to smoking reduced between 1990 and 2019 for both sexes in LAC countries, however, it increased for metabolic risk factors. In Brazil, between 1979 and 2019, a total of 209,425 deaths from pancreatic cancer were reported, with a trend of increase of 1.5% per year in men and 1.9% in women. There was an increase in mortality in most Brazilian states, higher in the North and Northeast regions with a positive correlation between the improvement of the human development index and the trend of increased mortality from pancreatic cancer. Among the sixteen Brazilian PBCRs studied, all agreement the criteria of comparability, but half have lower than expected indices for validity and completeness for liver and pancreatic tumors, and as for timeless the sixteen records are more than 48 months late in the release of data in relation to the calendar year 2023. Conclusions: Pancreatic cancer represents a challenge for public health in LAC and Brazil, given the challenge in reducing incidence and mortality, as well as in epidemiological surveillance in cancer through Brazilian PBCRs to ensure the activity and stability for continued monitoring of cancer incidence.

Neoplasia cística mucinosa do pâncreas / Mucinous cystic neoplasia of the pancreas

Introdução: Neoplasia cística mucinosa é tumor mucinoso benigno (cistoadenoma mucinoso) ou maligno (cistoadenocarcinoma mucinoso), que não se comunica com os ductos pancreáticos. Objetivo: Apresentar revisão da literatura sobre o tema. Método: Ênfase nas diretrizes das principais sociedades médicas mundiais na orientação do diagnóstico, tratamento e a vigilância da neoplasia cística mucinosa. Resultado: A quase totalidade dessas neoplasias ocorre no gênero feminino de 40-50 anos de idade. Como raras exceções, esta neoplasia é encontrada na cauda/corpo do pâncreas. Para estabelecer o diagnóstico é necessário a presença de estroma similar ao do ovário na parede do cisto no exame patológico. Exames de imagem de alta resolução, como tomografia, ressonância magnética e ecoendoscopia apresentam elevada precisão para identificar esta neoplasia. O tratamento cirúrgico consiste na pancreatectomia distal com linfadenectomia e esplenectomia. A via laparoscópica ou robótica é preferida para tumores <5-7 cm. Devido a possibilidade de rotura do tumor e disseminação da neoplasia, as lesões >5-7 cm devem ser submetidos à ressecção laparotômica. Conclusão: Não existe uniformidade internacional na conduta terapêutica. O tratamento cirúrgico deve ser indicado para todos os pacientes com condições cirúrgicas e que apresentam neoplasia ≥3-4 cm, dependendo do consenso.

Introduction: Mucinous cystic neoplasia is a benign mucinous tumor (mucinous cystadenoma) or malignant (mucinous cystadenocarcinoma), which does not communicate with the pancreatic ducts. Objective: To present a review of the literature on the topic. Method: Emphasis on the guidelines of the main global medical societies in guiding the diagnosis, treatment and surveillance of mucinous cystic neoplasia. Result: Almost all of these neoplasms occur in females aged 40-50 years. As a rare exception, this neoplasm is found in the tail/body of the pancreas. To establish the diagnosis, the presence of stroma similar to that of the ovary in the cyst wall is necessary on pathological examination. High-resolution imaging exams, such as tomography, magnetic resonance imaging and endoscopic ultrasound, are highly accurate in identifying this neoplasm. Surgical treatment consists of distal pancreatectomy with lymphadenectomy and splenectomy. The laparoscopic or robotic route is preferred for tumors <5-7 cm. Due to the possibility of tumor rupture and dissemination of the neoplasm, lesions >5-7 cm must undergo laparotomic resection. Conclusion: There is no international uniformity in therapeutic conduct. Surgical treatment should be indicated for all patients with surgical conditions and who have neoplasia ≥3-4 cm, depending on the consensus.

Aspectos anatomo-clínicos de un caso de neoplasia sólida seudopapilar de páncreas: (tumor de Frantz) / Solid pseudopapillary neoplasm of the pancreas: (Frantz´s tumor) anatomo-clinical aspects / Aspectos anátomo-clínicos de um caso de neoplasia sólida pseudopapilar do pâncreas: (tumor de Frantz)

El tumor pseudopapilar de páncreas, conocido como tumor de Frantz, es excepcional; comprende entre el 0.2 y 2.7 % de los carcinomas de páncreas. Su etiología es desconocida y predomina en mujeres jóvenes. Son tumores de bajo potencial maligno, que cursan asintomáticos y dan síntomas por compresión regional: dolor gravativo y/o masa abdominal palpable. La probabilidad de una forma definidamente maligna es de 15 %. Anatómicamente se localizan con mayor frecuencia en la cola del páncreas, seguido por la cabeza y el cuerpo. El tratamiento es la resección quirúrgica y su pronóstico es excelente, con sobrevida a 5 años de casi 100 %. El diagnóstico es anátomo-patológico, considerando el aspecto microscópico y el perfil inmunohistoquímico. Se presenta un caso de una mujer de 21 años, en la cual se realizó una cirugía de excéresis completa del tumor y que se mantiene a asintomática a 24 meses de operada.

Pseudo papillary tumor of the pancreas, also called Frantz´s tumor, is a very rare disease; between 0.2 and 2.7 % of pancreatic carcinomas. Ethiology is unknown; is observed in young women. It´s a tumors with low malignant potential, usually of asymptomatic evolution by long time and the symptoms are due to regional compression: pain or abdominal mass. The possibility of a malignant form is around 15 %. Anatomically, they are most frequently located in the tail of the pancreas, followed by the head and body. The treatment is the surgical resection; with an excellent prognosis and a 5-year survival almost 100 %. The diagnosis is with pathological study, considering the microscopic appearance and the immunohistochemical profile. Its perform an analysis of the literature and once case of a 21 years old, woman is reported. A complete resection surgery of the tumor was performed and remains asymptomatic at 24 months of follow-up.

O tumor pseudopapilar do pâncreas, conhecido como tumor de Frantz, é excepcional; compreende entre 0,2 e 2,7 % dos carcinomas pancreáticos. Sua etiologia é desconhecida e predomina em mulheres jovens. São tumores de baixo potencial maligno, que são assintomáticos e apresentam sintomas devido à compressão regional: dor intensa e/ou massa abdominal palpável. A probabilidade de uma forma definitivamente maligna é de 15 %. Anatomicamente, eles estão localizados com mais frequência na cauda do pâncreas, seguido pela cabeça e corpo. O tratamento é a ressecção cirúrgica e seu prognóstico é excelente, com sobrevida em 5 anos de quase 100 %. O diagnóstico é anátomo-patológico, considerando o aspecto microscópico e o perfil imuno-histoquímico. Apresenta-se o caso de uma mulher de 21 anos submetida a cirurgia de excisão completa do tumor e que permanece assintomática 24 meses após a cirurgia.

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.

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.

Progressin Tumor-Associated Macrophages in the Treatment of Pancreatic Cancer / 中国医学科学院学报

Pancreatic cancer is one of the digestive system tumors with a high degree of malignancy,and most of the patients are diagnosed in advanced stages.Because of limited available therapies,the mortality of this disease remains high.Tumor-associated macrophages(TAM),the main immune cells in the tumor microenvironment,are involved in the regulation of the occurrence and development of pancreatic cancer.Specifically,TAM are involved in the proliferation,invasion,immune escape,and chemoresistance of pancreatic cancer cells,demonstrating potential in the targeted therapy of pancreatic cancer.In this paper,we summarize the TAM-based therapies including consuming TAM,reprogramming TAM,dynamic imaging of TAM with nanoprobes,and regulating the phagocytic ability of TAM for pancreatic cancer,aiming to provide a theoretical basis for developing new therapies for pancreatic cancer.

The role of cholesterol metabolism reprogramming in pancreatic cancer and the application of cholesterol-targeted metabolism drugs / 生理学报

Pancreatic cancer has an insidious onset and lacks effective treatment methods, which is one of the tumors with the worst prognosis, so it is urgent to explore new treatment directions. Metabolic reprogramming is one of the important hallmarks of tumors. Pancreatic cancer cells in the harsh tumor microenvironment have comprehensively increased cholesterol metabolism in order to maintain strong metabolic needs, and cancer associated fibroblasts also provide cancer cells with a large amount of lipids. Cholesterol metabolism reprogramming involves the changes in the synthesis, uptake, esterification and metabolites of cholesterol, which are closely related to the proliferation, invasion, metastasis, drug resistance, and immunosuppression of pancreatic cancer. Inhibition of cholesterol metabolism has obvious anti-tumor effect. In this paper, the important effects and complexity of cholesterol metabolism in pancreatic cancer were comprehensively reviewed from perspectives of risk factors for pancreatic cancer, energy interaction between tumor-related cells, key targets of cholesterol metabolism and its targeted drugs. Cholesterol metabolism has a strict regulation and feedback mechanism, and the effect of single-target drugs in clinical application is not clear. Therefore, multi-target therapy of cholesterol metabolism is a new direction for pancreatic cancer treatment.

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.

Complete and sustained response after peptide receptor radionuclide therapy in a 66-year-old Filipino male with metastatic pancreatic neuroendocrine tumor: A case report

@#The introduction of peptide receptor radionuclide therapy (PRRT) to the Philippines has allowed for novel approaches in the management of neuroendocrine tumors (NETs). This case report details the management of a 66-year-old Filipino man diagnosed with metastatic pancreatic NET after biopsy and staging with Ga-68 DOTATATE PET-CT. After poor response to somatostatin analogue therapy, the patient was advised to undergo PRRT. Upon completing four cycles of PRRT with Lu-177 DOTATATE, the metastatic hepatic lesions showed resolution and the pancreatic tail tumor exhibited regression, allowing the patient to undergo surgical resection of the primary tumor. On follow-up, he was declared to be in remission with good quality of life and no imaging evidence of recurrence. The case underscores the diagnostic and therapeutic utility of radiolabeled somatostatin analogues along with the importance of a multidisciplinary approach in the management of an initially unresectable metastatic pancreatic NET

Advanced Faster RCNN: a non-contrast CT-based algorithm for detecting pancreatic lesions in multiple disease stages / 南方医科大学学报

OBJECTIVE@#To propose a non-contrast CT-based algorithm for automated and accurate detection of pancreatic lesions at a low cost.@*METHODS@#With Faster RCNN as the benchmark model, an advanced Faster RCNN (aFaster RCNN) model for pancreatic lesions detection based on plain CT was constructed. The model uses the residual connection network Resnet50 as the feature extraction module to extract the deep image features of pancreatic lesions. According to the morphology of pancreatic lesions, 9 anchor frame sizes were redesigned to construct the RPN module. A new Bounding Box regression loss function was proposed to constrain the training process of RPN module regression subnetwork by comprehensively considering the constraints of the lesion shape and anatomical structure. Finally, a detection frame was generated using the detector in the second stage. The data from a total of 728 cases of pancreatic diseases from 4 clinical centers in China were used for training (518 cases, 71.15%) and testing (210 cases, 28.85%) of the model. The performance of aFaster RCNN was verified through ablation experiments and comparison experiments with 3 classical target detection models SSD, YOLO and CenterNet.@*RESULTS@#The aFaster RCNN model for pancreatic lesion detection achieved recall rates of 73.64% at the image level and 92.38% at the patient level, with an average precision of 45.29% and 53.80% at the image and patient levels, respectively, which were higher than those of the 3 models for comparison.@*CONCLUSION@#The proposed method can effectively extract the imaging features of pancreatic lesions from non-contrast CT images to detect the pancreatic lesions.

Clinical value of lymph node dissection of No. 14cd during pancreaticoduodenectomy in patients with pancreatic head carcinoma / 中华外科杂志

Objectives: To evaluate the positive rate of left posterior lymph nodes of the superior mesenteric artery (14cd-LN) in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma,to analyze the impact of 14cd-LN dissection on lymph node staging and tumor TNM staging. Methods: The clinical and pathological data of 103 consecutive patients with pancreatic cancer who underwent pancreaticoduodenectomy at Pancreatic Center,the First Affiliated Hospital of Nanjing Medical University from January to December 2022 were analyzed,retrospectively. There were 69 males and 34 females,with an age(M (IQR))of 63.0 (14.0) years (range:48.0 to 86.0 years). The χ2 test and Fisher's exact probability method was used for comparison of the count data between the groups,respectively. The rank sum test was used for comparison of the measurement data between groups. Univariate and multivariate Logistic regression analyzes were used for the analysis of risk factors. Results: All 103 patients underwent pancreaticoduodenectomy successfully using the left-sided uncinate process and the artery first approach. Pathological examination showed pancreatic ductal adenocarcinoma in all cases. The location of the tumors was the pancreatic head in 40 cases,pancreatic head-uncinate in 45 cases,and pancreatic head-neck in 18 cases. Of the 103 patients,38 cases had moderately differentiated tumor and 65 cases had poorly differentiated tumor. The diameter of the lesions was 3.2 (0.8) cm (range:1.7 to 6.5 cm),the number of lymph nodes harvested was 25 (10) (range:11 to 53),and the number of positive lymph nodes was 1 (3) (range:0 to 40). The lymph node stage was stage N0 in 35 cases (34.0%),stage N1 in 43 cases (41.7%),and stage N2 in 25 cases (24.3%). TNM staging was stage ⅠA in 5 cases (4.9%),stage ⅠB in 19 cases (18.4%),stage ⅡA in 2 cases (1.9%),stage ⅡB in 38 cases (36.9%),stage Ⅲ in 38 cases (36.9%),and stage Ⅳ in 1 case (1.0%). In 103 patients with pancreatic head cancer,the overall positivity rate for 14cd-LN was 31.1% (32/103),and the positive rates for 14c-LN and 14d-LN were 21.4% (22/103) and 18.4% (19/103),respectively. 14cd-LN dissection increased the number of lymph nodes (P<0.01) and positive lymph nodes (P<0.01). As a result of the 14cd-LN dissection,the lymph node stage was changed in 6 patients,including 5 patients changed from N0 to N1 and 1 patient changed from N1 to N2. Similarly,the TNM stage was changed in 5 patients,including 2 patients changed from stage ⅠB to ⅡB,2 patients changed from stage ⅡA to ⅡB,and 1 patient changed from stage ⅡB to Ⅲ. Tumors located in the pancreatic head-uncinate (OR=3.43,95%CI:1.08 to 10.93,P=0.037) and the positivity of 7,8,9,12 LN (OR=5.45,95%CI:1.45 to 20.44,P=0.012) were independent risk factors for 14c-LN metastasis; while tumors with diameter >3 cm (OR=3.93,95%CI:1.08 to 14.33,P=0.038) and the positivity of 7,8,9,12 LN (OR=11.09,95%CI:2.69 to 45.80,P=0.001) were independent risk factors for 14d-LN metastasis. Conclusion: Due to its high positive rate in pancreatic head cancer,dissection of 14cd-LN during pancreaticoduodenectomy should be recommended,which can increase the number of lymph nodes harvested,provide a more accurate lymph node staging and TNM staging.

Surgical treatment strategies for pancreatic cancer with simultaneous liver metastasis / 中华外科杂志

Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.

Pay attention to whole cycle management of pancreatic cancer / 中华外科杂志

The prognosis for pancreatic cancer is extremely poor. To improve the prognosis of pancreatic cancer, it is urgently needed to improve early detection to advance treatment. And basically, it is also necessary to emphasise basic research to find novel therapies. By promoting the disease-centered multidisciplinary team model, researchers should achieve high-quality closed-loop process management of the entire life cycle which consists of prevention, screening, diagnosis, treatment, rehabilitation,and follow-up, with the objective of establishing a standard clinical process to improve the outcome in essence. This article summarized the progress of pancreatic cancer at different stages of the whole cycle management recently and shared the experience of pancreatic cancer treatment from the author's team in the past ten years.