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.

5HT2A modulation attenuates pancreatic cancer induced pain mouse model by inhibiting HDAC

Purpose Patients have been severely suffered from cancer associated pain, and pancreatic cancer is the most severe form of cancer associated with pain. There are very few options available to manage it. The present report evaluated the effect of 5HT2A on pancreatic cancer associated pain. Methods Pancreatic cancer was induced by injecting SW 1,990 cells (~3×106 in a 20 µL suspension) into the pancreas and formed a 2­3-mm vesicle using an inoculator fitted with a 26-gauge needle in BALB/c-nu mice. Survival rate and body weight of the mice were observed. Pain behaviour testing was performed at the end of each week (third and fourth week) after surgery. Inflammatory mediators and HDAC 2 proteins were determined in the spinal tissue using quantitative real-time polymerase chain reaction. Results There was improvement in the survival rate and body weight in 5HT2A antagonist treated group than pancreatic cancer group of mice. Moreover, 5HT2A antagonist ameliorated the alteration in pain behaviour of pancreatic cancer mice. mRNA expression of HDAC2 and level of inflammatory cytokines were reduced in the spinal tissue of 5HT 2A antagonist treated group than pancreatic cancer group of mice. Conclusions Data revealed that 5HT2A antagonist ameliorates pain associated with pancreatic cancer mice by HDAC inhibition and inflammatory cytokines. The result of investigation supports that modulation of 5HT2A receptor could be used clinically to protects neuropathic pain in pancreatic cancer.

Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Pancreatic ductal adenocarcinoma chemoresistance: From metabolism reprogramming to novel treatment / 中华医学杂志(英文版)

As pancreatic cancer (PC) is highly malignant, its patients tend to develop metastasis at an early stage and show a poor response to conventional chemotherapies. First-line chemotherapies for PC, according to current guidelines, include fluoropyrimidine- and gemcitabine-based regimens. Accumulating research on drug resistance has shown that biochemical metabolic aberrations in PC, especially those involving glycolysis and glutamine metabolism, are highly associated with chemoresistance. Additionally, lipid metabolism is a major factor in chemoresistance. However, emerging compounds that target these key metabolic pathways have the potential to overcome chemoresistance. This review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.

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.

Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor / 中国结合医学杂志

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

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)

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.

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.

Duodenopancreatectomía laparoscópica: evolución de los primeros casos en Venezuela / Laparoscopic duodenopancreatectomy: evolution of the first cases in Venezuela

La duodenopancreatectomía cefálica es la única opción con criterio curativo de los tumores periampulares y cabeza de páncreas. El abordaje mínimamente invasivo ha mostrado sus beneficios en la duodenopancreatectomía cefálica lo cual ha llevado a un mayor interés a nivel mundial por esta técnica. El objetivo es describir la técnica utilizada y analizar la evolución que presentaron los primeros casos realizados en Venezuela de duodenopancreatectomía laparoscópica y así dar a conocer nuestra experiencia, es un estudio retrospectivo, descriptivo, de corte transversal; se revisaron 106 historias clínicas, obteniendo 8 casos para este estudio: 5 femeninos y 3 masculinos, los promedios de edad y tiempo de evolución de la enfermedad fueron de 54,15 años y de 7 meses respectivamente, la indicación fue 4 tumores de cabeza de páncreas y 4 periampulares, el índice de masa corporal promedio fue de 23,44 kg/mt2, el tiempo quirúrgico osciló entre 315 ­ 475 min, la estancia hospitalaria de 4 ­ 24 días, las perdidas hemáticas fueron de 200cc ± 20cc, tres pacientes presentaron complicaciones post operatorias mediatas. En conclusión, los resultados que hemos observado en nuestro reporte inicial de casos de duodenopancreatectomía laparoscópica reúnen las características de otras publicaciones similares y se ratifica los beneficios de este abordaje, la clave para la duodenopancreatectomía laparoscópica de rutina es que sea realizada en centros especializados, con protocolos estandarizados, ejecutado por cirujanos hepatobiliar y pancreática con experiencia en laparoscopia avanzada(AU)

Duodenopancreatectomy is the only option with curative criteria of the periampullary tumors and pancreatic head. The minimally invasive approach has shown its benefits in cephalic duodenopancreatectomy which has led to greater interest worldwide in this technique. The objective is to describe the technique used and analyze the evolution presented by the first cases of laparoscopic duodenopancreatectomy and thus publicize our experience, it is a retrospective, descriptive, cross-sectional study; 106 medical records were reviewed, obtaining 8 cases for this study: 5 women and 3 men, the average age and the time of evolution of the disease were 54.15 years and 7 months, the indication was 4 pancreas head and 4 periampullary tumors, the average body mass index was 23, 44 kg/mt2, assisted surgery was performed in 4 patients and 4 totally laparoscopic, the surgical time ranged between 315 - 475 min, and the hospital stay was 4 - 24 days, the blood loss was 200cc ± 20cc, three patients presented mediated postoperative complications. In conclusion, the results we have observed in our initial case report of laparoscopic duodenopancreatectomy meet the characteristics of other similar publications and the benefits of this approach are ratified, the key to routine laparoscopic duodenopancreatectomy is that it is performed in specialized centers, with standardized protocols, executed by surgeons with experience in advanced laparoscopy in addition to hepatobiliary and pancreatic surgery(AU)

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.

Tumores neuroendócrinos pancreáticos: revisão histopatológica / Pancreatic neuroendocrine tumors: histopathological review

Introdução: Os tumores neuroendócrinos pancreáticos são considerados raros. Eles são classificados em funcionantes e não funcionantes. Objetivo: Definir e classificar tumores neuroendócrinos pancreáticos de acordo com sua avaliação histopatológica e imunoistoquímica, associado aos critérios diagnósticos. Método: Trata-se de revisão narrativa sobre publicações encontradas no PubMed, SciELO e Google Acadêmico. Resultados: Esses tumores podem ser bem ou pouco diferenciados e apresentam características microscópicas distintas. As células bem diferenciadas têm formato pequeno, núcleos uniformes redondos ou ovais, citoplasma finamente granular indicando forte capacidade secretória e mantêm a estrutura organoide. A presença de necrose tumoral, atividade mitótica aumentada e índice de Ki-67 elevado indicam alta probabilidade de neoplasia neuroendócrina. Cromogranina A e sinaptofisina favorecem o diagnóstico do bem diferenciado. Já a marcação positiva do BCL 10 em conjunto com a ausência de expressão da cromogranina A e da sinaptofisina mostram a precária diferenciação tumoral. A presença de marcação positiva para as expressões hormonais não define o tumor como funcionante. Conclusão: Houve aumento do diagnóstico de tumores neuroendócrinos pancreáticos com o uso de técnicas de imagem e a conscientização sobre a doença. A análise histopatológica com imunoistoquímica, especialmente quando há sintomas consumptivos, podem indicar o tipo do carcinoma e induzir ao mais adequado tratamento.

Introduction: Pancreatic neuroendocrine tumors are considered rare. They are classified into functioning and non-functioning. Objective: To define and classify pancreatic neuroendocrine tumors according to their histopathological and immunohistochemical evaluation, associated with diagnostic criteria. Method: This is a narrative review of publications found in PubMed, SciELO and Google Scholar. \Results: These tumors can be well or poorly differentiated and have distinct microscopic characteristics. Well-differentiated cells are small in shape, have uniform round or oval nuclei, finely granular cytoplasm indicating strong secretory capacity, and maintain the organoid structure. Presence of tumor necrosis, increased mitotic activity and high Ki-67 index indicate a high probability of neuroendocrine neoplasia. Chromogranin A and synaptophysin favor the diagnosis of well-differentiated. The positive staining of BCL 10 together with the absence of expression of chromogranin A and synaptophysin show poor tumor differentiation. The presence of positive staining for hormone expressions does not define the tumor as functioning. Conclusion: There was an increase in the diagnosis of pancreatic neuroendocrine tumors with the use of imaging techniques and awareness of the disease. Histopathological analysis with immunohistochemistry, especially when there are consuming symptoms, can indicate the type of carcinoma and lead to the most appropriate treatment.

Study of perioperative safety of laparoscopic pancreaticoduodenectomy in elderly patients / 中华危重病急救医学

OBJECTIVE@#To investigate the safety of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients and the related risk factors admitted to the intensive care unit (ICU) after LPD.@*METHODS@#The perioperative data of patients who underwent LPD in Tianjin Medical University General Hospital from February 2017 to June 2023 were retrospectively collected, including basic data, preoperative laboratory indicators, intraoperative and postoperative indicators, pathological results (tumor size, lymph node dissection and pathological type), postoperative complications, ICU postoperative management and prognosis. The patients were divided into the elderly group (≥ 65 years) and the non-elderly group (< 65 years) according to age. Perioperative data between two groups were compared. Kaplan-Meier survival curve was drawn to analyze the survival rate of the elderly group and the non-elderly group, and the pancreatic head carcinoma group and other type of tumors group after LPD. Logistic regression was used to analyze the risk factors of ICU stay (length of ICU stay > 1 day) after LPD in elderly patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of this risk factor for ICU stay after LPD in elderly patients.@*RESULTS@#A total of 160 patients were enrolled, including 57 cases in the elderly group (17 cases of vascular reconstruction) and 103 cases in the non-elderly group (40 cases of vascular reconstruction). All patients underwent R0 resection and were transferred to the comprehensive ICU for treatment. The follow-up time of patients with malignant tumors was 43 (6, 72) months. The elderly group had significantly longer surgery time, postoperative hospital stay and oral feeding time than the non-elderly group, and the incidence of delayed gastric emptying (DGE) was significantly higher than that in the non-elderly group. There were no significant differences in intraoperative blood transfusion rate, intraoperative blood loss, pathological results, short-term and severe postoperative complications, reoperation rate and 90-day mortality between the two groups. In patients with vascular resection reconstruction, the intraoperative blood loss in the elderly group was significantly higher than that in the non-elderly group, and the operation time and postoperative hospital stay were significantly longer. During ICU, the acute physiology and chronic health evaluation II [APACHE II: 12 (9, 14) vs. 8 (7, 10)], sequential organ failure assessment [SOFA: 6 (4, 8) vs. 3 (2, 5)] within 24 hours after admission to ICU were significantly increased in the elderly group (both P < 0.05), the time of mechanical ventilation [hours: 12 (10, 15) vs. 9 (5, 13)] and the length of ICU stay [days: 2 (1, 2) vs. 1 (1, 1)] were significantly increased in the elderly group (both P < 0.05), and the proportion of multi-disciplinary team (MDT) was also significantly increased in the elderly group (33.3% vs. 17.4%, P < 0.05), there were no significant differences in the levels of hemoglobin (Hb), albumin, and blood lactic acid between the two groups. Logistic regression analysis showed that the APACHE II score was an independent risk factor for ICU stay after LPD in elderly patients (β = 1.737, P = 0.028). ROC curve showed that the prediction performance was the best when the APACHE II score was 13, with the sensitivity of 72.41% and the specificity of 96.43%, and the area under the ROC curve (AUC) of 0.884. The Kaplan-Meier survival curve showed that there were no significant difference in median survival time (months: 24.1 vs. 24.7) and 5-year survival rate (19.01% vs. 19.02%) between the elderly group (52 cases) and the non-elderly group (92 cases) among the 144 patients with malignant tumors (both P > 0.05). The median survival time in the pancreatic head carcinoma group was significantly shorter than that in the other tumors group (63 cases; months: 20.2 vs. 40.1, P < 0.05), 5-year survival rate was significantly lower than that in the other tumors group (21.98% vs. 30.91%, P < 0.05).@*CONCLUSIONS@#LPD is a safe and feasible treatment for elderly patients. APACHE II score has a certain predictive value for ICU stay after LPD in elderly patients.

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges / 医学前沿

Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast / 医学前沿

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.