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)

Chinese expert consensus on minimally invasive radical surgery for pancreatic ductal adenocarcinoma (version 2022) / 中华外科杂志

Although there are still controversies over the efficiency and safety of minimally invasive radical surgery for pancreatic ductal adenocarcinoma (PDAC), most available studies have suggested a promising application of minimally invasive radical surgery. This consensus, referring to Chinese expert opinions and worldwide researches, aimed to discuss the related issues on minimally invasive radical surgery for PDAC to ensure the perioperative and oncological outcomes. Quality of evidence and strength of recommendations were evaluated based on the GRADE approach. The 15 recommendations covered 5 topics: oncological outcomes and patient safety of laparoscopic and robotic pancreatoduodenectomy, left-side pancreatectomy for PDAC, learning curve, safety of neoadjuvant therapy, and vascular resection in minimally invasive radical surgery for PDAC. This consensus gives reference and guidance to surgeons on the use of minimally invasive radical surgery for PDAC. Although this consensus is not sufficient to answer all the questions about minimally invasive radical surgery for PDAC, it represents the current consensus on the application of the techniques in the treatment of PDAC on the Chinese mainland.

Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miRNAs / 中华肿瘤杂志

Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.

O Uso do Sequenciamento Total do Exoma no Diagnóstico do Adenocarcinoma Ductal Pancreático / Using Whole Exome Sequencing on Diagnosis of Pancreatic Ductal Adenocarcinoma / El uso de la Secuenciación del Exoma Total en el Diagnóstico del Adenocarcinoma Ductal Pancreático

Introdução: O adenocarcinoma ductal pancreático (PDAC) é uma doença agressiva responsável no Brasil por 2% das neoplasias e 5% das mortes por câncer. A análise do exoma ­ parte do DNA que codifica as proteínas ­ permite identificar as variantes somáticas do tumor e as germinativas do paciente. Essa informação é necessária para implementar a terapia-alvo para o PDAC, pois fornece evidência para selecionar, ou excluir, tratamentos para a doença. Objetivo: Identificar as variantes de interesse clínico e farmacológico presentes no PDAC de quatro pacientes, por meio da técnica de sequenciamento total do exoma(WES). Método: Foram utilizados dados públicos de quatro amostras de pares tumor-normal de PDAC, localizados na cabeça do pâncreas de pacientes caucasianos, estádio T3N1M0, sequenciadas e publicizadas pelo Texas Cancer Research Biobank. Para identificar as variações somáticas e germinativas, utilizou-se o software GATK. As consequências clínicas e farmacológicas dessas variações foram anotadas por meio do software VEP e analisadas mediante o softwareestatístico R. Resultados: Dos quatro tumores, um possui variante estrutural com duplicação do gene AKT2; outro, variantes nos genes da via das ciclinas CDK14 e CDKN2C, o que altera o regime quimioterápico; na linhagem germinativa, um paciente tem variantes no gene XRCC1, que sugere aumento da resposta à platina. Conclusão: Embora a patologia classifique todos os tumores como PDAC, cada paciente ­ bem como o respectivo tumor ­ apresenta especificidades que afetam o diagnóstico e as possibilidades terapêuticas. O WES permite identificá-las a um custo baixo, o que amplia as possibilidades de tratamento do PDAC.

ntroduction: The prevalence of pancreatic ductal adenocarcinoma (PDAC) in Brazil is around two percent of all neoplasms. It is an aggressive disease responsible for five percent of all deaths by cancer. The analysis of exome ­ part of the DNA encoding the proteins ­ allows the identification of tumor-specific variants and the patient polymorphism. This information is necessary to implement target therapy for PDAC, as it provides evidence to select, or exclude, PDAC treatments. Objective: Identify the somatic and germinative variants of clinical and pharmacological interest in the PDAC for four patients through the whole-exome sequencing technique (WES). Method: Public sequencing exome data published by Texas Cancer Research Biobank were utilized, from four tumor-normal samples pair of PDAC located in the pancreas head of Caucasian patients, T3N1M0 stage. To identify somatic and germinative variations, the GATK software was adopted. Furthermore, these variants were noted with their clinical and pharmacological information through the VEP software and its consequences were analyzed through the statistical software R. Results: Of the four tumors, one has a structural variant with duplication of the AKT2 gene; another, changes in the pathway of cyclins CDK14 and CDKN2C. Both findings alter the chemotherapy regimen; in the germline, one patient has variants in the XRCC1 gene, which suggests increased response to platinum. Conclusion: Although the pathology classifies all tumours as PDAC, each patient ­ as well as their respective tumor ­ shows specificities that affect the diagnosis and therapeutic possibilities. WES allows to identify them at a low cost, expanding the treatment possibilities of PDAC.

Introducción: El adenocarcinoma ductal pancreático (PDAC) es una enfermedad agresiva que causa en Brasil 5% de las muertes por cáncer. El análisis del exoma ­ parte del ADN que codifica las proteínas ­ permite la identificación de mutaciones específicas del tumor, así como los polimorfismos del paciente. Esta información es necesaria para implementar la terapia dirigida para PDAC. Objetivo: Identificar las variaciones de interés clínico y farmacológico presentes en el PDAC de cuatro pacientes, mediante la técnica secuenciación del exoma completo (WES). Método: Se utilizaron datos públicos de cuatro muestras de pares de tumores normales (T-N) de PDAC, localizados en la cabeza del páncreas de pacientes caucásicos, estadio T3N1M0, secuenciadas y publicadas por Texas Cancer Research Biobank. Para identificar las variaciones somáticas y germinativas, se utilizó el softwareGATK. Se observaron las consecuencias clínicas y farmacológicas de estas variaciones a través del software VEP. Y analizadas sus consecuencias a través del software estadístico R. Resultados: De los cuatro tumores, uno tiene una variante estructural con duplicación del gen AKT2; otro, cambios en la vía de las ciclinas CDK14 y CDKN2C, que altera el régimen de quimioterapia; en el linaje germinal, un paciente tiene variantes en el gen XRCC1, lo que sugiere una mayor respuesta al platino. Conclusión: Aunque la patología clasifica todos los tumores como PDAC, cada paciente ­ así como el tumor respectivo ­ presenta especificidades que afectan el diagnóstico y las posibilidades terapéuticas. WES le permite identificarlos a un bajo costo, lo que amplía las posibilidades de tratamiento de PDAC

Schwannoma pancreático como tumor sincrónico. Reporte de caso / Pancreatic schwannoma as a synchronous tumor. Case report

Los Schwannomas son tumores derivados de las células de Schwann de las vainas de los nervios periféricos. Se pueden localizar en cualquier región anatómica que contenga tejido nervioso periférico, siendo más frecuentes en la región craneofacial y las extremidades. Los Schwannomas pancreáticos son entidades sumamente infrecuentes de las cuales solo se han descrito 68 casos a nivel mundial. En el presente trabajo se presenta el caso de un paciente con hallazgo incidental de tres tumores sincrónicos dentro de los cuales se encuentra un Schwannoma pancreático.Caso clínico : Paciente femenino de 66 años de edad con antecedente de diabetes mellitus tipo 1 y enfermedad diverticular pancolónica quien acude presentando cuadro clínico compatible con absceso lumbar izquierdo. Se realiza TC de abdomen y pelvis con doble contraste que evidencia extensa área de colección heterogénea en región retroperitoneal que diseca hacia región lumbar y glútea izquierda, además de la presencia de tumor hipodenso de bordes lobulados en mesogastrio. Se realiza colonoscopia que reporta lesión exofítica ulcerada en unión rectosigmoidea. El resto de paraclínicos y estudios de extensión se encontraban dentro de límites normales. Se decide resolución quirúrgica mediante drenaje percutáneo de absceso y laparotomía exploradora. Informe histopatológico: cistoadenoma seroso microquístico de cuerpo de páncreas, Schwannoma de cola de páncreas y adenocarcinoma moderadamente diferenciado de colon sigmoides.Conclusión : Los Schwannomas pancreáticos son entidades sumamente infrecuentes que pueden presentarse con una amplia variedad de manifestaciones clínicas, sin embargo, deben tenerse en cuenta como posible diagnóstico diferencial ante el hallazgo de un tumor pancreático(AU)

Schwannomas, also called Neurilemmomas or Neurinomas, are tumors derived from Schwann cells of the peripheral nerve sheaths. They can be located in any anatomical region that contains peripheral nervous tissue, being more frequent in the craniofacial region and the extremities. Pancreatic Schwannomas are extremely rare entities of which only 68 cases have been described worldwide. In the present study we present the case of a patient with an incidental finding of three synchronous tumors, including a pancreatic Schwannoma.Clinical case : A 66-year-old female patient with a history of type 1 diabetes mellitus and pancolonic diverticular disease who presented with symptoms compatible with left lumbar abscess. A double-contrast CT of the abdomen and pelvis was performed, which revealed a large area of heterogeneous collection in the retroperitoneal region that dissected towards the left lumbar and gluteal region, in addition to the presence of a hypodense tumor with lobulated borders in the mesogastrium. A colonoscopy was performed, which reported an ulcerated exophytic lesion at the rectosigmoid junction. The rest of the paraclinical and extension studies were within normal limits. Surgical resolution is decided by percutaneous abscess drainage and exploratory laparotomy. Histopathological report: microcystic serous cystadenoma of the body of the pancreas, Schwannoma of the pancreas tail, and moderately differentiated adenocarcinoma of the sigmoid colon.Conclusion : Pancreatic Schwannomas are extremely rare entities that can present with a wide variety of clinical manifestations, however, they should be taken into account as a possible differential diagnosis when a pancreatic tumor is found(AU)

Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma / 中华病理学杂志

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.

Supervivencia a largo plazo luego de pancreatectomía por cáncer de páncreas / Long-term survival after pancreatic cancer surgery

Resumen El adenocarcinoma ductal de páncreas es una enfermedad agresiva asociada con pobres resultados de supervivencia a largo plazo. La resección quirúrgica y los nuevos tratamientos oncológicos pe rioperatorios han logrado mejorar la supervivencia de estos pacientes en la experiencia internacional. En este estudio retrospectivo se analiza la supervivencia global y la libre de enfermedad de todos los pacientes operados por cáncer de páncreas en el Hospital Italiano de Buenos Aires de enero 2010 a enero 2020. Se identificaron 242 pacientes con resecciones pancreáticas por adenocarcinoma de páncreas o carcinoma indiferenciado. La supervivencia global mediana fue de 22.8 meses (IC 95%: 19.5-29) y la tasa de supervivencia global a 1, 3 y 5 años fue de 72%, 32.5% y 20.8% respectivamente. La supervivencia libre de enfermedad mediana fue de 13.8 meses (IC 95%: 12-17.6) y la tasa de supervivencia libre de enfermedad a 1, 3 y 5 años fueron de 56.1%, 21.8% y 19.4% respectivamente. El grupo de pacientes que logró completar el tratamiento adyuvante mostró una mayor supervivencia global (p<0.0001).

Abstract Pancreatic cancer is an aggressive disease associated with poor results regarding long term survival. Surgical treatment along with new onco logic treatments have improved the survival of these patients in international experience reports. The aim of this study was to describe overall survival and disease-free survival after pancreatectomy for pancreatic ductal adenocarcinoma. A retrospective study of consecutive patients undergoing pancreatic resection due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 in a single tertiary center was performed. Overall, 242 patients underwent complete pancreatic resections for pancreatic ductal adenocarcinoma or undifferentiated carcinoma. Median overall survival was 22.8 months (95% CI: 19.5-29) and survival at 1, 3 and 5 years were 72%, 32.5% and 20.8% respectively. The median disease-free survival was 13.8 months (95% CI: 12-17.6) and 1, 3- and 5-years disease-free survival were 56.1%, 21.8% and 19.4% respectively. The groups of patients that completed adjuvant treatment showed a better overall survival (p < 0.0001).

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

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

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

Whether early stage pancreatic ductal adenocarcinoma patients could benefit from the post-operation chemotherapy regimens: a SEER-based propensity score matching study / 浙江大学学报·医学版

To investigate whether chemotherapy could prolong the postoperative survival time in patients with early stages pancreatic ductal adenocarcinoma (PDAC). A total of 5280 stage ⅠA -ⅡB PDAC patients diagnosed from 2010 to 2015 were selected from surveillance，epidemiology，and end results (SEER) database. Propensity score matching (PSM) analysis was adopted to reduce the baseline differences between the groups. Univariate survival analysis was conducted with the Kaplan-Meier method. Multivariate survival analysis was performed with the Cox proportional hazards model. Univariate and multivariate survival analyses showed that age, differentiation, stage, chemotherapy were independent risk factors for the survival of PDAC patients. After PSM, it is found that adjuvant chemotherapy could prolong the median overall survival time (mOS) for stage ⅠB, ⅡA and ⅡB patients. However, for stage ⅠA patients, there were no significant differences in 3-year survival rate and mOS between patients with chemotherapy (=283) and without chemotherapy (=229) (57.4% vs 55.6%, vs all >0.05). Further analyses show that among 101 patients with well differentiated PDAC and 294 patients with moderately differentiated PDAC, there were no significant differences in survival rate and mOS between patients with and without chemotherapy (all >0.05). Among 117 patients with low-differentiated + undifferentiated PDAC, 3-year survival rate and mOS in patients with chemotherapy were significantly better than those without chemotherapy (48.5% vs 34.1%, vs all <0.05). Chemotherapy regimen used currently is not beneficial for patients with moderately and well differentiated stage ⅠA PDAC, but it is an independent prognostic factor for low-differentiated + undifferentiated PDAC patients.

Expression and Prognostic Value of Cripto-1 in Pancreatic Cancer / 中国医学科学院学报

Objective To investigate the expression of Cripto-1 in pancreatic cancer and to analyze its clinical significance. Methods Cripto-1 expression in normal pancreas,pancreatic cancer and adjacent non-tumor tissues,chronic pancreatitis tissues and other related tissues was evaluated using immunohistochemistry.The association of Cripto-1 expression with the clinicopathological characteristics and the prognostic value of Cripto-1 in patients with pancreatic cancer were analyzed. Results The expression of Cripto-1 was higher in chronic pancreatitis tissues,pancreatic cancer and its metastases than in normal pancreas(P=0.019,P=0.025,and P=0.018,respectively).Cripto-1 overexpression was correlated with poorly differentiated pancreatic cancer.The patients with Cripto-1 upregulation had shorter median survival time(8 months vs.16 months,χ

A pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) (NET and undifferentiated carcinoma of the pancreas with osteoclast-like giant cells) with metastatic neuroendocrine component to the liver

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGCs) is an extremely rare morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC), exhibiting a characteristic component of reactive osteoclast-like giant cells admixed with neoplastic mononuclear cells. Sommers and Meissner first described it in 1954 as an "unusual carcinoma of the pancreas". Later it acquired many different names. In 2010, the WHO classified these tumors as a variant of PDAC under the heading of "undifferentiated carcinoma with osteoclast-like giant cells". Here we describe the first case of pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) composed of UCOGC and pancreatic neuroendocrine tumor (NET), which occurred in a 78-year-old man with biliary colic and pancreatitis. The mass did not respond to the chemotherapy, and he soon developed liver metastasis from the NET component, and unfortunately, the patient passed away 10 months later. Since UCOGC is extremely rare, and its association with NET has not been reported yet, our case expands the knowledge regarding its unusual presentation and poor prognosis.

A expressão e relevância da proteína IMPACT no Adenocarcinoma de Pâncreas / Expression and relevance of IMPACT protein in Pancreatic Adenocarcinoma

Um dos principais pontos de controle da tradução de mRNAs ocorre através da fosforilação da subunidade alfa do fator de início de tradução eIF2 (eIF2α), o que leva à inibição da síntese geral de proteínas. GCN2 é uma das quinases de eIF2α que responde à carência de aminoácidos e radiação UV, fosforilando eIF2α e inibindo a tradução geral. Sua atividade depende da união com a proteína GCN1. A proteína IMPACT também interage com GCN1, competindo pela ligação GCN1-GCN2, inibindo a atividade de GCN2 e estimulando a tradução. Através de pesquisas em bancos de dados utilizando o cBioPortal, observamos que em adenocarcinomas de pâncreas, existem alterações nos genes que codificam IMPACT, GCN1 e GCN2 em uma porcentagem significativa de casos. No Brasil, este tumor é responsável por cerca de 2% de todos os tipos de câncer diagnosticados e por 4% do total de mortes por câncer. Devido à natureza agressiva da doença e ao diagnóstico tardio, a maioria dos pacientes apresenta o câncer localmente avançado ou metastático, possuindo uma alta taxa de mortalidade e sobrevida de 5 anos menor que 7%. Portanto, desvendar mecanismos moleculares associados a este tumor é de extrema importância para o desenvolvimento de novas abordagens terapêuticas. Utilizando um modelo celular de adenocarcinoma de pâncreas, nocaute para IMPACT, realizamos ensaios funcionais. eIF2 foi mais fosforilado pelas linhagens nocautes na avaliação por estresse a UV, mas não para privação de leucina. Além disso, células nocautes também apresentaram menor capacidade de formar colônias independentemente de ancoragem, e menos formação tumoral nos ensaios em vivo, além de apresentarem menor capacidade de formar e manter estruturas 3D avaliadas no ensaio de esferoides e adesão. A partir da avaliação dos Tissue Micro Arrays (TMAs), tumores primários apresentaram maior quantidade de IMPACT quando comparados com tumores metastáticos e tecido normal. Interessantemente, tanto no TMA quanto nas linhagens celulares foram observados grânulos de IMPACT tanto no núcleo quanto no citoplasma e associados a proteínas características de grânulos de estresse e proteínas do nucléolo. Diante dos resultados encontrados, podemos concluir que a proteína IMPACT pode ter atuação no ciclo celular além de fazer parte de grânulos de estresse. Além disso, levanta-se a hipótese que pode atuar em dois momentos na progressão tumoral: um primeiro momento onde a superexpressão favoreceria a sobrevivência do tumor e um segundo momento onde a diminuição de IMPACT facilitaria a metástase. Portanto o estudo dessa proteína pode melhorar o entendimento não só dos mecanismos envolvidos no desenvolvimento e progressão do Adenocarcinoma de Pâncreas, mas também de processos biológicos relacionados com outros tumores e até mesmo outras doenças.

Aspectos tomográficos e histológicos en pacientes con neoplasia exocrina de páncreas / Tomographic and histologic aspects in patients with pancreas exocrine neoplasm

Introducción: El cáncer de páncreas se origina en la glándula pancreática y es una de las neoplasias más invasivas debido a su rápida diseminación, la falta de síntomas específicos en sus inicios y su diagnóstico tardío. Objetivo: Caracterizar a pacientes con cáncer de páncreas según variables de interés. Métodos: Se efectuó un estudio observacional, descriptivo y transversal en el Servicio de Imagenología del Hospital Provincial Clinicoquirúrgico Docente Saturnino Lora de la provincia de Santiago de Cuba, desde enero de 2013 hasta diciembre de 2017, de 70 pacientes con diagnóstico tomográfico sugestivo de dicha neoplasia maligna. Resultados: En la serie el tumor exocrino pancreático primó en pacientes mayores de 60 años de edad (37,1 %), del sexo masculino (54,2 %) y de la raza mestiza (61,4 %). El diagnóstico histológico predominante fue el de adenocarcinoma ductal poco diferenciado (47,2 %), en tanto, los factores de riesgo mayormente asociados al proceso neoplásico fueron las comidas grasas (68,6 %), el tabaquismo (61,4 %) y el alcoholismo (50,0 %), y el antecedente patológico personal más frecuente, la diabetes mellitus (37,1 %). Conclusiones: La tomografía axial computarizada proporciona una descripción detallada de las neoplasias pancreáticas y su extensión, lo cual es de gran utilidad para la estadificación de estas y, además, determina la conducta terapéutica a seguir.

Introduction: The pancreas cancer originates in the pancreatic gland and it is one of the more invasive neoplasms due to its quick dissemination, lack of specific symptoms in its beginnings and its late diagnosis. Objective: To characterize patients with pancreas cancer according to variables of interest. Methods: An observational, descriptive and cross-sectional study was carried out in the Imaging Service of Saturnino Lora Teaching Provincial Clinical Surgical Hospital in Santiago de Cuba, from January, 2013 to December, 2017 to 70 patients with suggestive tomographic diagnosis of this malignancy. Results: In the series the pancreatic exocrine tumor prevailed in patients older than 60 years (37.1 %), the male sex (54.2 %) and mixed race (61.4 %). The predominant histologic diagnosis was the ductal adenocarcinoma hardly differentiated (47.2 %), as long as, the risk factors mostly associated with the neoplasm were fatty foods (68.6 %), nicotine addiction (61.4 %) and alcoholism (50.0 %), and the most frequent personal pathological history was diabetes mellitus (37.1 %). Conclusions: The computerized axial tomography provides a detailed description of the pancreatic neoplasms and their extension, which is very useful for the staging of these malignancies and, also, it determines the therapeutic behavior we should follow.

Arginine metabolism: a potential target in pancreatic cancer therapy / 中华医学杂志(英文版)

Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant disease, which has an extremely low survival rate of <9% in the United States. As a new hallmark of cancer, metabolism reprogramming exerts crucial impacts on PDAC development and progression. Notably, arginine metabolism is altered in PDAC cells and participates in vital signaling pathways. In addition, arginine and its metabolites including polyamine, creatine, agmatine, and nitric oxide regulate the proliferation, growth, autophagy, apoptosis, and metastasis of cancer cells. Due to the loss of argininosuccinate synthetase 1 (ASS1) expression, the key enzyme in arginine biosynthesis, arginine deprivation is regarded as a potential strategy for PDAC therapy. However, drug resistance develops during arginine depletion treatment, along with the re-expression of ASS1, metabolic dysfunction, and the appearance of anti-drug antibody. Additionally, arginase 1 exerts crucial roles in myeloid-derived suppressor cells, indicating its potential targeting by cancer immunotherapy. In this review, we introduce arginine metabolism and its impacts on PDAC cells. Also, we discuss the role of arginine metabolism in arginine deprivation therapy and immunotherapy for cancer.

Fatores prognósticos pré-operatórios em pacientes com adenocarcinoma ductal da cabeça do pâncreas / Preoperative prognostic factors in patients with ductal adenocarcinoma of the head of the pancreas

RESUMO Objetivos: Identificar fatores prognósticos pré-operatórios relacionados à sobrevida de pacientes com adenocarcinoma ductal da cabeça de pâncreas (ADCP) submetidos a tratamento cirúrgico com intenção curativa em uma única instituição brasileira. Método: No período de 2005 a 2018, dados clinicodemográficos e laboratoriais pré-operatórios foram prospectivamente coletados. A análise de sobrevida foi feita pelo método de Kaplan-Meier e a comparação entre as curvas pelo teste de log-rank. Para a análise multivariada utilizou-se o modelo de regressão de Cox. Resultados: Os fatores pré-operatórios com impacto significativo na sobrevida à análise univariada foram a idade maior ou igual a 70 anos (p=0,012) e história pessoal prévia positiva para câncer (p=0,026). A análise multivariada, pacientes com níveis séricos pré-operatórios de CA 19.9 de 38 a 554 U/ml apresentaram 3,15 vezes maior chance de óbito (HR 3,15; IC 95% 1,01 - 9,82; p=0,047), enquanto que os pacientes com o marcador acima de 554 U/ml evoluíram com chance 3,96 vezes maior de óbito que aqueles com a dosagem normal (HR 3,96; IC 95% 1,19 - 13,10; p=0,024). Pacientes com comorbidades prévias evoluíram com chance 2,90 vezes superior de óbito que doentes sem condições associadas (HR 2,90; IC 95% 1,10 - 7,67; p=0,032). Conclusão: O ADCP mostrou ser doença agressiva para a qual os fatores pré-operatórios de pior prognóstico foram idade avançada, presença de comorbidades, história prévia de câncer e nível sérico de CA 19.9 elevado no pré-operatório.

ABSTRACT Objective: To identify the preoperative prognostic factors influencing pancreatic cancer survival following curative resection in a single Brazilian institution. Methods: From 2005 to 2018, preoperative clinic, demographic and laboratory data were prospectively collected. Survival analysis was performed by the Kaplan-Meier method and the comparison between curves by the log-rank test. For multivariate analysis, the Cox regression model was used. Results: advanced age (p = 0.012) and previous history of cancer (p = 0.026) were the preoperative factors, according to the univariate analysis, that significantly impacted survival. Patients with preoperative serum levels of CA 19.9 from 38 to 554 U/mL had a 3.15 times higher chances of death (HR 3.15; 95% CI 1.01-9.82; p = 0.047), whereas patients with the marker above 554 U/mL were 3.96 times more likely than those with the normal level (HR 3.96; 95% CI 1.19-13.10; p = 0.024), by using the multivariate analysis. Patients with previous comorbidities had a 2.90 times higher chance of death than those without associated conditions (HR 2.90; 95% CI 1.10-7.67; p = 0.032). Conclusion: Preoperative factors related to the worst prognosis after pancreatic ductal adenocarcinoma resection were advanced age, presence of comorbidities, previous history of cancer and elevated preoperative serum CA 19.9.

Pancreatectomía corpo-caudal con resección en bloque de tronco celíaco: reporte de 2 casos / Corporal caudal pancreatectomy with celiac trunk block resection: report of 2 cases

INTRODUCCIÓN: El adenocarcinoma de cuerpo y cola de páncreas corresponde a cerca de un tercio del total de cánceres pancreáticos. Evoluciona en forma silenciosa hasta alcanzar estadios avanzados, llegando a comprometer muchas veces grandes vasos como tronco celíaco y sus ramas, y la arteria mesentérica superior. La resolución quirúrgica parece ser la única alternativa en estos casos. OBJETIVO: Presentar dos casos de adenocarcinoma de cuerpo y cola de páncreas tratados en nuestro hospital con pancreatectomía corpo-caudal y resección en bloque de tronco celíaco (procedimiento de Appleby modificado). DISCUSIÓN: Este procedimiento ha demostrado aumentar la sobrevida de estos pacientes, además de generar un alivio inmediato y duradero del dolor. Sin embargo, corresponde a una intervención con una alta morbilidad, siendo la fístula pancreática y la gastropatía isquémica las complicaciones más frecuentes. La evaluación del flujo de los vasos colaterales es un paso crítico para evitar las complicaciones isquémicas. CONCLUSIONES: La pancreatectomía corpo-caudal con resección en bloque de tronco celíaco, es una alternativa factible en adenocarcinoma de cuerpo y cola de páncreas localmente avanzado. Su indicación debe ser cuidadosa debido a que corresponde a un procedimiento con alta morbilidad.

INTRODUCTION: Adenocarcinoma of the body and tail of the pancreas corresponds to about one third of all pancreatic cancers. It evolves silently to reach advanced stages, often involving large vessels such as the celiac trunk and its branches, and the superior mesenteric artery. Surgical resolution seems to be the only alternative in these cases. AIM: To present two cases of adenocarcinoma of the body and tail of the pancreas treated in our hospital with distal pancreatectomy and celiac trunk en block resection (modified Appleby procedure). DISCUSSION: This procedure has been shown to increase the survival of these patients, in addition to generating immediate and lasting pain relief. However, it corresponds to an intervention with a high morbidity, being the pancreatic fistula and the ischemic gastropathy the most frequent complications. The evaluation of the flow of the collateral vessels is a critical step to avoid ischemic complications. CONCLUSIONS: Distal pancreatectomy with en bloc resection of the celiac trunk is a feasible alternative in locally advanced adenocarcinoma of the body and tail of the pancreas. Its indication must be careful since is a procedure with high morbidity.

Caso Clínico Tumor Mucinoso Papilar Intra Ductal del Páncreas / Clinical case Mucinous Papillary Intra Ductal Tumor of the Pancreas

Introducción: La aparición de nuevas técnicas de imagen y mayor conocimiento de esta entidad han contribuido para que el diagnóstico del Tumor Mucinoso Papilar Intraductal haya aumentado en la última década. En el presente artículo describimos un caso de un paciente con Tumor Mucinoso Papilar Intraductal de páncreas, hallazgo incidental en Tomografía computarizada de abdomen. Caso Clínico: Se trata de una mujer de 71 años de edad, con antecedentes de Diabetes tipo 2, Hipertensión Arterial Esencial, y cáncer de mama intervenida. En un estudio de control con tomografía computarizada de abdomen se observó un tumor pancreático de 3 x 1.1 cm. Se realizó una punción transagástrica, con lo que se obtuvo una muestra para estudio patológico, el cual reportó una neoplasia mucinosa papilar intraductal. Evolución: La paciente fue sometida a cirugía con la Técnica de Whipple, con duodenopancreatectomía, en donde se retiró la cabeza del páncreas con el tumor adyacente. El estudio de patología confirmó una neoplasia mucinosa papilar intraductal. La paciente no presentó complicaciones post-operatorias y continúa en revisión en consulta externa. Conclusión: Por tratarse de una lesión maligna, el diagnóstico oportuno y correcto fue importante en este caso, para la conducta terapéutica quirúrgica resolutiva.

Introduction: The appearance of new imaging techniques and greater knowledge of this entity have contributed to the diagnosis of the Mucinous Papular Intraductal Tumor has increased in the last decade. In the present article, we describe a case of a patient with pancreatic papillary intraductal mucosal tumor, incidental finding in abdominal CT scan. Clinical Case: This is a 71-year-old woman with a history of type 2 diabetes, essential arterial hypertension, and intervened breast cancer. In a control study with abdominal CT, a pancreatic tumor of 3 x 1.1 cm was observed. A transgastric puncture was performed, which obtained a sample for pathological study, which reported an intraductal papillary mucinous neoplasia. Evolution: The patient underwent surgery with the Whipple Technique, with pancreaticoduodenectomy, in which the head of the pancreas with the adjacent tumor was removed. The pathology study confirmed an intraductal papillary mucinous neoplasm. The patient did not present post-operative complications and continues in external consultation review. Conclusion: Because it is a malignant lesion, the opportune and correct diagnosis was important in this case, for the operative surgical therapeutic behavior.

MicroRNA-21 correlates TGF-β1 pathway of pancreatic ductal adenocarcinoma / 中南大学学报(医学版)

To conduct genetic analysis of pancreatic ductal adenocarcinoma tissues and analyze the correlation between targeted microRNA (miRNA) and pathways in pancreatic ductal adenocarcinoma.
 Methods: We collected 19 samples of peripheral venous blood serum from patients with pancreatic ductal adenocarcinoma in Hainan Provincial Hospital of Chinese Medicine, and also collected 21 blood serum samples as a control group of non-pancreatic ductal adenocarcinoma. We used the bioinformatics analysis of literature GCBI data platform for screening and analyzing the genetics of pancreatic ductal adenocarcinoma samples. Through GCBI data platform of hierarchy clustering analysis and the enrichment of gene function analysis, the relevant miRNA was screened as a research object in patients with pancreatic ductal adenocarcinoma. The miRNA was screened by literature analysis and pancreatic cancer gene analysis. Real-time PCR and Western blotting were carried out to study the relationship between the selected miRNA and TGF-β1 by overexpression and suppression of the gene in pancreatic ductal adenocarcinoma cells.
 Results: MiRNA-21 was screened as a gene associated with pancreatic ductal carcinoma via hierarchy clustering analysis and gene function analysis. MiRNA-21 was highly expressed in the pancreatic ductal carcinoma patients. Expressions of TGF-β1 were inhibired in miRNA-21 overexpressed PANC-1. While the expression of miRNA-21 was inhibited, TGF-β1 expression increased obviously.
 Conclusion: MiRNA-21 is highly expressed in patients with pancreatic ductal adenocarcinoma, can regulate the expression of TGF-β1, which may be a mechanism of miRNA-21 in pancreatic ductal adenocarcinoma.

Stage 1A Pancreatic Cancer Initially Manifesting as Clinical Acute Pancreatitis / 대한내과학회지

Pancreatic cancer has a poor prognosis due to the difficulty of early diagnosis. Observation is recommended for early diagnosis of pancreatic cancer in elderly patients with risk factors such as newly diagnosed diabetes and chronic pancreatitis. A 66-year-old male suffered from acute pancreatitis of uncertain etiology. Initial pancreatic imaging showed a main pancreatic duct stricture at the pancreas body/tail junction and minimal duct dilatation without a visible mass. Eight months later, however, pancreatic imaging revealed a pancreatic mass at the previous stricture site with progression of the upstream duct dilation. The patient underwent distal pancreatectomy, and a pathologic examination showed stage 1A pancreatic cancer with a predominantly intraductal spreading pattern. We report a case of stage 1A pancreatic cancer that initially manifested as acute obstructive pancreatitis, which enabled early diagnosis of pancreatic cancer.