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

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

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

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

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

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

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

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

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

Lower gastrointestinal bleeding due to pancreatic cancer: an unusual presentation

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

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

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

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

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

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

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

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

Expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances / 肿瘤研究与临床

Objective:To explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.Methods:The clinical data of 57 patients diagnosed as pancreatic ductal carcinoma (PDAC) at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed. The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues (within 3 cm from the edge of cancer tissues) were examined by using quantificational reverse transcription-polymerase chain reaction (qRT-PCR). The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry. The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared. The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis. Moreover, the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.Results:The positive expression of ISG15 protein in pancreatic cancer tissues was 40.4% (23/57), which was higher than that in paracancerous normal tissues [15.8% (9/57)] ( χ2 = 7.90, P = 0.004), and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36, which was lower than that in paracancerous normal tissues (1.26±0.41) ( t = 4.80, P < 0.001). For 23 (40.4%) ISG15-positive patients and 34 (59.7%) ISG15-negative patients, the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27 ( P < 0.001). Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions ( ρ = -0.429, P = 0.001). The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between LINC00673 expression and patients' age, tumor site, preoperative CA199 level, and TNM stage (all P > 0.05); ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor, TNM stage Ⅲ-Ⅳ, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between ISG15 protein expression and patients' gender, age, tumor site, and preoperative CA199 level (all P > 0.05). Conclusions:The expression of LINC00673 in pancreatic cancer is related to vascular invasion, tumor differentiation degree and lymph node metastasis, and the expression of ISG15 in pancreatic cancer is related to vascular invasion, tumor differentiation degree, lymph node metastasis and TNM stage. The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer. The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.

Correlation of the duration of preoperative biliary drainage and postoperative complications after pancreaticoduodenectomy / 肿瘤研究与临床

Objective:To investigate the effect of the duration of preoperative biliary drainage on postoperative complications after pancreaticoduodenectomy.Methods:The clinical data of 102 patients with benign and malignant hepatopancreatic ductal periampullary tumors who underwent pancreaticoduodenectomy and preoperative biliary drainage in Beijing Friendship Hospital, Capital Medical University from January 2016 to July 2020 were retrospectively analyzed. According to the median duration of preoperative biliary drainage, the patients were divided into short-term drainage group (≤ the median duration of biliary drainage) and long-term drainage group (> the median duration of biliary drainage). The general data, the effect of biliary drainage, inflammation-related indicators and postoperative complications were compared between the two groups. Multivariate logistic regression was used to screen the risk factors related to the postoperative severe complications.Results:Of the 102 patients, 68 (66.7%) were males and 34 (33.3%) were females, with a median age of 63 years (43-80 years). The median duration of preoperative biliary drainage was 14 d. There were 68 patients in short-term drainage group and 34 patients in long-term drainage group. There were no statistically significant differences in age, gender, body mass index (BMI), hypertension, diabetes mellitus, surgery history of upper abdominal, American Society of Anesthesiologists (ASA) grade, carcinoembryonic antigen, carbohydrate antigen 125, alpha-fetoprotein, prothrombin time, pancreaticojejunostomy method, operation time, and pathological type between the two groups (all P > 0.05). However, patients in long-term drainage group had higher conversion rate, more blood loss and longer hospital stay compared with those in short-term drainage group (all P < 0.05). Before biliary drainage, alanine aminotransferase (ALT) level in short-term drainage group was higher than that in long-term drainage group ( Z = -2.59, P = 0.009), and there were no statistically significant differences in aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TB) and direct bilirubin (DB) levels between the two groups before biliary drainage (all P > 0.05). After biliary drainage, DB in short-term drainage group was higher than that in long-term drainage group ( Z = -3.34, P = 0.001), and there was no statistically significant difference in ALT, AST, ALB, TB levels between the two groups (all P > 0.05). There were no statistically significant differences in the levels of white blood cells, neutrophils, lymphocytes and the ratio of neutrophils to lymphocytes between the two groups on the 1st and 3rd day after the operation (all P > 0.05). The total incidence of postoperative related complications in short-term drainage group and long-term drainage group was 63.2% (43/68), 70.6% (24/34), respectively, and the difference was statistically significant ( χ2 = 0.54, P = 0.461); the incidences of bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying, all grades of pancreatic leakage, grade B and C pancreatic leakage were not statistically different between the two groups (all P > 0.05); the incidence of severe postoperative related complications in short-term drainage group was higher than that in long-term drainage group [27.9% (19/68) vs. 8.8% (3/34), χ2 = 4.90, P = 0.027]. Multivariate logistic regression analysis showed that the long-term preoperative biliary drainage was an independent protective factor for postoperative severe complications (long-term drainage vs. short-term drainage: OR = 0.253, 95% CI 0.066-0.975, P = 0.046), while BMI ( OR = 1.174, 95% CI 0.986-1.398, P = 0.071) and pathological type (benign or borderline vs. malignant tumor: OR = 0.247, 95% CI 0.043-1.419, P = 0.117) were not independent influencing factors for postoperative severe complications. Conclusions:Short-term biliary drainage (≤14 d) is a risk factor for postoperative severe complications in patients with hepatopancreatic ductal periampullary tumor undergoing preoperative biliary drainage. Preoperative biliary drainage time is not associated with postoperative total complications, pancreatic leakage, bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying.

Expression and prognostic significance of cell division cycle associated protein 5 in pancreatic cancer tissues / 肿瘤研究与临床

Objective:To analyze the expression of cell division cycle associated protein 5 (CDCA5) in pancreatic cancer tissues and its correlation with prognosis based on the bioinformatics.Methods:The RNA sequencing data (HTSeq-FPKM) and corresponding clinical information of 168 pancreatic cancer samples from January to December 2021 were downloaded from the Cancer Genome Atlas (TCGA) database, and the data of 179 pancreatic patients from January to December 2021 were downloaded from the GEPIA2 database, and 171 normal pancreatic tissues from TCGA and GTEx databases were simultaneously integrated. The relative expression level of CDCA5 mRNA in pancreatic cancer patients in GEPIA2 database and its relationship with overall survival (OS) and disease-free survival (DFS) were explored. Combined with the clinical data of the patients, univariate and multivariate Cox regression model analysis was used to analyze the factors influencing the OS of pancreatic cancer patients. Gene set enrichment analysis (GSEA) was performed to investigate the possibly involved signal pathways of CDCA5 in pancreatic cancer.Results:In the GEPIA2 database, the relative expression level of CDCA5 mRNA in pancreatic cancer tissues was higher than that in normal pancreatic tissues, and the difference was statistically significant ( P < 0.05). The pancreatic cancer patients were divided into the high CDCA5 mRNA expression group (89 cases) and the low CDCA5 mRNA expression group (89 cases) according to the median of relative expression level of CDCA5 mRNA (the case equal to the median value was not subgrouped). Survival analysis showed that patients with high CDCA5 mRNA expression had shorter OS ( P = 0.024) and DFS ( P = 0.025) compared with those with low CDCA5 mRNA expression. Multivariate Cox analysis showed that in TCGA database, N staging ( HR = 2.15, 95% CI 1.24-3.72, P = 0.006) and CDCA5 expression ( HR = 1.71, 95% CI 1.23-2.38, P = 0.001) were independent influencing factors of OS for pancreatic cancer patients. The results of GSEA enrichment analysis indicated that high CDCA5 mRNA expression was enriched in 13 biological pathways [all P < 0.05, false discovery rate (FDR) < 0.005] including cell cycle, DNA replication, homologous recombination, pyrimidine metabolism, mismatch repair, pentose phosphate pathway, glycolysis gluconeogenesis and p53. The expression of CDCA5 mRNA was positively correlated with the expressions of HK2, PKM, PGK1, ALDOA, EN01 and LDHA (all P < 0.05). Conclusions:CDCA5 is highly expressed in pancreatic cancer tissues and is associated with poor prognosis of patients, and it can be used as a prognostic marker for pancreatic cancer.

Laparoscopic radical anterograde modular pancreatosplenectomy for pancreatic tail cancer / 中华普通外科杂志

Objective:To evaluate the safety and feasibility of laparoscopic radical anterograde modular pancreatosplenectomy (Lap-RAMPS).Methods:From Jan 2014 to Dec 2020, the clinical data of 83 patients who underwent laparoscopic radical resection for pancreatic tail cancer in LiHuili Hospital of Ningbo Medical Center were retrospectively analyzed.Results:Eighty-three cases were divided into Lap-RAMPS group (44 cases) and laparoscopic conventional distal pancreatectomy and splenectomy(Lap-CDP) group (39 cases). There were no significant differences in the duration of surgery [(245.34±70.30) min vs. (239.87±68.10) min], intraoperative blood lose [(159.32±115.60) ml vs. (208.97±161.70) ml] and intraoperative transfusions (2 cases vs. 3 cases) between the two groups ( P>0.05). There were no statistical significance in both groups in postoperative pancreatic fistula, postoperative bleeding grade, postoperative gastric emptying delay, Clavien-Dindo complication and postoperative hospital stay ( P>0.05). There were statistically significant differences in the negative margin rate (93.2% vs. 76.9%),lymph node harvest(12.91±8.24 vs. 8.49±6.85) and median survival time (25.0 months vs. 15.0 months) between the two groups ( P<0.05). Conclusion:Lap-RAMPS for pancreatic tail cancer is safe and feasible, increasing the negative rate of pancreatic margins, improving the lymph node harvest, and prolonging patients' survival time.

The value of superior mesenteric artery preferential approach in the treatment of borderline resectable pancreatic head cancer / 中华普通外科杂志

Objective:To evaluate superior mesenteric artery preferential approach in the borderline resectable pancreatic head cancer.Methods:The clinical and follow-up data of 90 patients with borderline resectable pancreatic head cancer who underwent radical pancreatoduodenectomy at Beijing Chaoyang Hospital,Capital Medical University from Jan 2015 to Dec 2021 were analyzed.Results:After exploring the superior mesenteric artery in the lower colon area to confirm the vascular invasion meet the resection criteria, the blood supply is cut off first, then the tumors were resected en bloc, with the invaded vessels resected and reconstructed or replaced. All 90 patients successfully completed the operation without perioperative death. Pathology established pancreatic ductal adenocarcinoma. The 1-year, 2-year, and 3-year disease-free survival rates of patients in the arterial priority approach group were 68.2%, 60.4%, and 54.3%, while the 1-year, 2-year, and 3-year disease-free survival rates of patients by conventional approach were 58.4%, 26.4%, and 11.7% ( P=0.001). Conclusion:The superior mesenteric artery preferential approach in the inferior colon region can prolong the survival time of patients after surgery, and reduce the recurrence.

Construction and validation of a nomogram prediction model for early recurrence of patients undergoing radical pancreaticoduodenectomy for pancreatic ductal adenocarcinoma / 中华肝胆外科杂志

Objective:To study the risk factors for early recurrence of patients undergoing radical pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) and construct a normogram model.Methods:Patients undergoing open radical PD for PDAC at Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from January 2014 to December 2021 were retrospectively screened. A total of 213 patients were enrolled, including 145 males and 68 females, aged (58.4±9.8) years. Patients were divided into the early recurrence group ( n=59, recurrence within 6 months after surgery) and a control group ( n=154, no recurrence within 6 months after surgery). Using minimum absolute value convergence and selection operator regression (LASSO) and multi-factor logistic regression analysis, we screened out the best predictor of early recurrence after PD for PDAC, and then established a nomogram model. The effectiveness of the model was validated by receiver operating characteristic (ROC) curve, calibration curves, and decision analysis curves. Results:Multivariate logistic regression analysis showed that patients with obstructive jaundice, vascular invasion, massive intraoperative bleeding, high-risk tumors (poorly differentiated or undifferentiated), high carbohydrate antigen 19-9 to total bilirubin ratio, and high fibrinogen and neutrophil to lymphocyte ratio scores had a higher risk of early postoperative recurrence. Based on the indexes above, a nomogram prediction model was constructed. The area under the ROC curve was 0.797 (95% CI: 0.726-0.854). Validation of the calibration curve exhibited good concordance between the predicted probability and ideal probability, decision curve analysis showed that the net benefits of the groupings established according to the model were all greater than 0 within the high risk threshold of 0.08 to 1.00. Conclusion:The nomogram for predicting early recurrence after PD for PDAC has a good efficiency, which could be helpful to screen out the high-risk patients for adjuvant or neoadjuvant therapy.

Thought and practice of long-term management for hepatobiliary and pancreatic malignant tumors / 中华肝胆外科杂志

Radical resection is the only measurement to cure patients of hepatobiliary and pancreatic tumors. The comprehensive application of endoscopy, interventional therapy, radiotherapy and systemic therapy can not only significantly improve the early diagnosis rate of the disease, and successfully transform some borderline resectable tumors into radical resectable states, but also reduce the recurrence rate of tumors after surgery, thus prolonging the survival time of patients. In recent years, the continuous emergence of new systemic therapeutic drugs has brought new opportunities for patients with hepatobiliary and pancreatic malignancies, but the number of doctors participating in diagnosis and treatment has also increased accordingly. Therefore, the contradiction between the division system based on treatment methods and the orderly and standardized treatment is becoming more and more prominent. According to the latest progress of hepatobiliary and pancreatic cancer research at home and abroad, and combined with our clinical experience, we proposed a long-term management concept based on hepatobiliary and pancreatic comprehensive multi-technical team. Based on this concept, we have carried out new thought and practice on the diagnosis and treatment of patients with hepatobiliary and pancreatic malignant tumors.

Research progress of stroma-targeted therapies for pancreatic ductal adenocarcinoma / 中华肝胆外科杂志

Desmoplastic stroma of pancreatic ductal adenocarcinoma plays an important role in tumor progression and treatment resistance. Stroma-targeted therapies are therefore promising for clinical application and extensive related researches are undergoing. In this article, recent advances in stromal targeting strategies were reviewed from three perspectives: cancer-associated fibroblasts, extracellular matrix and angiogenesis, and an outlook for the future of this strategy was also provided.

Value of the imaging features of extrapancreatic nerve plexus in predicting the early postoperative recurrence of ductal adenocarcinoma of pancreatic head / 中华肝胆外科杂志

Objective:To study the value of imaging features of extrapancreatic nerve plexus in predicting early postoperative recurrence of ductal adenocarcinoma of pancreatic head.Methods:The clinical, imaging and pathological data of patients with ductal adenocarcinoma of pancreatic head undergoing pancreati-coduodenectomy at the Hepatobiliary Pancreatic Center of Beijing Tsinghua Changgung Hospital, Tsinghua University from January 2014 to April 2022 were retrospectively analyzed. A total of 73 patients were included, including 51 males and 22 females, aged (66.1±9.0) years old. The patients were followed up by telephone or outpatient review, who were divided into two groups according to the recurrence within 6 months after surgery: the recurrence group ( n=26) and the non-recurrence group ( n=47). Streaks or soft-tissue densities in the distribution area of extrapancreatic nerve plexus, difference in CT values between the portal and arterial phases of the distribution area of extrapancreatic nerve plexus, maximum tumor diameter, and regional lymph node enlargement were compared between the two groups. Results:The incidences of streaks or soft-tissue densities showing in the distribution area of extrapancreatic nerve plexus were 80.8%(21/26) in the recurrence group and 51.1%(24/47) in the non-recurrence group, respectively. A CT value difference ≥15 HU between the portal and arterial phases of the distribution area of extrapancreatic nerve plexus occurred in 50.0%(13/26) patients of the recurrence group and 25.5%(27/47) of the non-recurrence group, respectively. Maximum tumor diameter ≥25 mm were found in 80.8% (21/26) patients of the recurrence group and 57.4% (27/47) of the non-recurrence group, respectively. ≥3 reginal lymph node enlargement showed in 65.4% (17/26) patients of the recurrence group and 31.9% (15/47) of the non-recurrence group, respectively (all P<0.05). The risk of early postoperative recurrence increased in patients with a CT value difference ≥15 HU between the portal and arterial phases of the distribution area of extrapancreatic nerve plexus ( OR=3.609, 95% CI: 1.099-11.855), and regional lymph node enlargement ≥ 3 ( OR=4.665, 95% CI: 1.400-15.545) (all P<0.05). And these two independent risk factors were combined to predict early postoperative recurrence of ductal adenocarcinoma of pancreatic head with an area under receiver operating characteristic curve of 0.748, sensitivity of 92.3%, and specificity of 48.9% ( P<0.001). Conclusion:≥ 15 HU CT value difference between the portal and arterial phases of the distribution area of extrapancreatic nerve plexus and ≥ 3 regional lymph node enlargement are independent risk factors for the early postoperative recurrence of pancreatic head ductal adenocarcinoma, which could provide more predictive information preoperatively.

Risk factors of the recurrences of solid pseudopapillary neoplasms of the pancreas: meta-analysis / 中华肝胆外科杂志

Objective:To investigate the risk factors of postoperative recurrence of solid pseudopapillary neoplasms of the pancreas (SPN).Methods:Case-control studies on risk factors for postoperative recurrence in patients with SPN were conducted by searching in China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Web of Science and Embase database from inception of these databases to November 2022. Two investigators screened the collected literatures independently according to the inclusion and exclusion criteria, extracted the data and evaluated the methodological quality, and then used Review Manager 5.4 for statistical analysis, odds ratio ( OR) was calculated with 95% confidence interval ( CI). Results:A total of 14 articles were included, including 1 409 patients with 67 cases in recurrence group and 1 342 cases in non-recurrence group. Twelve risk factors with predictive value for postoperative recurrence of SPN were extracted from the literatures. The analysis showed that the pooled OR and 95% CI of each risk factor were: gender ( OR=0.75, 95% CI: 0.35-1.59, P=0.450), age( OR=-2.08, 95% CI: -5.24-1.08, P=0.200), tumor diameter( OR=5.29, 95% CI: 4.71-5.87, P<0.001), tumor location( OR=0.56, 95% CI: 0.28-1.13, P=0.100), synchronous metastasis( OR=86.84, 95% CI: 22.64-333.05, P<0.001), lymph node metastasis ( OR=7.55, 95% CI: 2.58-22.06, P<0.001), perineural invasion ( OR=2.10, 95% CI: 0.98-4.48, P=0.060), positive margin( OR=7.00, 95% CI: 2.56-19.15, P<0.001), calcification( OR=0.49, 95% CI: 0.11-2.23, P=0.360), lymphovascular invasion( OR=11.22, 95% CI: 4.81-26.18, P<0.001), peripancreatic soft tissue invasion( OR=1.38, 95% CI: 0.48-4.00, P=0.550), capsular invasion( OR=1.72, 95% CI: 0.53-5.65, P=0.370). Conclusion:Large tumor diameter, synchronous metastasis, lymph node metastasis, positive margin, lymphovascular invasion increase the risk of recurrence of pancreatic SPN after resection, and patients with these characteristics should receive long-term follow-up.

Expression of Toll like receptor in pancreatic cancer cells / 中华肝胆外科杂志

Objective:To compare the expression difference of Toll like receptor (TLR) and inflammatory factors between pancreatic cancer and normal pancreatic epithelial cells, and explore the correlation between TLR and inflammatory microenvironment.Methods:Normal pancreatic duct epithelium cells (HPNE) and pancreatic cancer cells (Panc-1 and Mia-PACA-2) were cultured and proteins were obtained. The expression of TLR family protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and myeloid differentiation factor 88 (MyD88) were examined by western blot in HPNE, Panc-1 and Mia-PACA-2. The correlations between TLR and inflammation cytokines of pancreatic cancer were analyzed by Pearson correlation analysis.Results:Compared with HPNE, the TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 were highly expressed in Panc-1 and Mia-PACA-2 (all P<0.05). Compared with Panc-1, the expression of TLR2 and TLR4 in Mia-PACA-2 were increased obviously, while the TLR9 expression was mildly decreased (all P<0.05). The expression of IL-6 in HPNE was found less than that in Panc-1 (0.52±0.03 vs. 0.76±0.04) and Mia-PACA-2 (0.52±0.03 vs. 1.12±0.09) with statistical differences ( P<0.05). Similarly, the expression of TNF-α was found significantly less than that of Panc-1 cells (0.63±0.04 vs. 0.87±0.06) and Mia-PACA-2 cells (0.63±0.04 vs. 0.95±0.10) with statistical differences (all P<0.05). The expression of IL-6 was found positively correlated with expressions of TLR2 ( r=0.964), TLR4 ( r=0.968), TLR7 ( r=0.844), TLR8 ( r=0.668) (all P<0.05), and the expression of TNF-α was found positively correlated with expressions of TLR2 ( r=0.805), TLR4 ( r=0.893), TLR7 ( r=0.847), TLR8 ( r=0.780) (all P<0.05). In contrast with HPNE, the expression of MyD88 was found highly expressed in Panc-1 (0.91±0.10 vs. 0.33±0.03) and Mia-PACA-2 (1.14±0.10 vs. 0.33±0.03) (all P<0.001). Compared with Panc-1, the expression of MyD88 in Mia-PACA-2 was obviously increased (1.14±0.10 vs. 0.91±0.10) with statistical difference ( P=0.048). Conclusion:The TLR family may play a critical role in development of pancreatic cancer by regulating the immune microenvironment, and its mechanism may be through upregulating MyD88 which functions as key signal transduction.

Study of miR-506 in M2 macrophage polarization and immune intervention in pancreatic cancer mice / 中华肝胆外科杂志

Objective:To analyze the effect of microRNA-506 (miR-506) on M2 macrophages polarization and immune intervention in pancreatic cancer mice.Methods:Macrophages from peripheral blood of healthy volunteers were cultured in vitro, polarized into M1 or M2 type macrophages, and transfected with miR-506 or control sequence (miR-ctrl), respectively. Polarized macrophages from M1+ miR-ctrl group, M1+ miR-506 group, M2+ miR-ctrl group and M2+ miR-506 group were collected. The relative expression of marker genes of M1 and M2 type macrophages of four groups were analyzed by qRT-PCR. The characteristic functions of M1 and M2 type macrophages of four groups were also detected, such as phagocytosis and nitric oxide (NO) synthesis (characteristic function of M1 type macrophages), arginase 1 activity and the secretion of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), interleukin-10 (IL-10) (characteristic function of M2 type macrophages). Sixty healthy male C57BL/6 mice without specific pathogen, weighing 20-25 g, were randomly divided into miR-ctrl programmed death-1 (PD-1) group, miR-506 PD-1 group, miR-ctrl iso group, and miR-506 iso group. They were injected with miR-506, miR-ctrl, PD-1 antibodies, and isotype control antibodies, with 15 in each group. The tumor volume, tumor weight, Ki-67 and interferon γ expression were analyzed three weeks later. Results:Compared with M2+ miR-ctrl group, the relative expression of M1 type macrophage marker genes increased, and the relative expression of M2 type macrophage marker genes decreased in M2+ miR-506 group, with significant difference (all P<0.05). Compared with M2+ miR-ctrl group, the phagocytic function and NO synthesis of macrophages in M2+ miR-506 group increased, the activity of arginase 1 and the secretion of VEGF, TGF-β and IL-10 decreased, with significant difference (all P<0.05). There was no significant differences in tumor weight, volume, Ki-67, and interferon γ expression between miR-ctrl iso and miR-ctrl PD-1 group (all P>0.05). The tumor weight, tumor volume and Ki-67 in miR-506 PD-1 group were lower than those in miR-ctrl PD-1 group [(0.32±0.13) g vs (0.85±0.24) g; (0.72±0.23) cm 3 vs (2.03±0.21) cm 3; (25.9±10.3)% vs (55.6±12.5)%], while interferon-γ expression was significantly higher than that in miR-ctrl PD-1 group [(122.4±15.3) ng/g vs (82.4±22.2) ng/g] (all P<0.05). Conclusion:miR-506 inhibits the polarization of M2 macrophages and increases the anti PD-1 immunotherapy sensitivity in pancreatic cancer.

Clinical and pathological features of intraductal tubulopapillary neoplasms / 中华肝胆外科杂志

Objective:To investigate the clinical and pathological features and improve the acknowledgement of intraductal tubulopapillary neoplasm (ITPN) of pancreas.Methods:Six cases with ITPN in the Shandong Provincial Hospital Affiliated to Shandong First Medical University combined with 40 cases from PubMed and CNKI were retrospectively analyzed. There were 25 males and 21 females, aged (58.6±16.0) years. The clinical manifestations, pathological features, treatment and so on were analyzed.Results:All cases were treated with surgery. The main clinical symptoms were upper abdominal pain and discomfort (23 cases, 50.0%), followed by jaundice (9 cases, 19.6%). Seven cases (15.2%) had no clinical symptoms. Three cases (6.5%) had low back discomfort, chills and other rare symptoms, and 4 cases (8.7%) had no clinical symptoms mentioned in the literature. Tumors of 27 cases (58.7%) located in the head of the pancreas, 9 cases (19.6%) in the body and tail, 4 cases (8.7%) in the whole pancreas, 3 cases (6.5%) in the body, 2 cases (4.3%) in ampulla and 1 case (2.2%) in head and body. Most of the tumors located in the main pancreatic duct. Microscopically, back-to-back tubular glands were densely arranged, parts of them with papillary structure, with obvious cell atypia and many mitoses. Twenty-two cases (47.8%) of ITPN were completely confined to the pancreatic duct, and 24 cases (52.2%) were with associated invasive carcinoma. Tumor cells were positive for cytokeratin 7 and mucin 1, but negative for cytokeratin 20, synaptophysin, chromogranin and trypsin. Mucin 2, mucin 5AC and mucin 6 were negative in most cases. Ki-67 ranged from 10% to 70%.Conclusion:Pancreatic ITPNs were mostly located in the pancreatic head, confined to the main pancreatic duct, and were mostly manifested as pain and discomfort in the upper abdomen. Surgery was the main treatment. Tumors cells of ITPN were arranged in tubular and papillary, with severe epithelial atypia and special immunophenotype, parts of cases accompanied with associated invasive carcinoma.

Clinical application of modified pancreaticogastrostomy based on the concept of " Hong's one-stitch method" in digestive tract reconstruction in pancreaticoduodenectomy / 中华肝胆外科杂志

Objective:To study the safety and therapeutic effects of the modified pancreaticogastrostomy based on the concept of " Hong's one-stitch method" in digestive tract reconstruction in pancreatic surgery.Methods:The clinical data of 44 patients who underwent modified pancreaticogastresstomy at the Department of Hepatobiliary Surgery, the Second Hospital of Hebei Medical University from May 2022 to October 2022 were analyzed retrospectively. There were 23 males and 21 females , with a median age of 54 years old (range 18 to 70 years old). The operation time, intraoperative blood loss, postoperative condition and complications were analysed.Results:All the 44 patients completed the operation successfully. There were 29 patients who underwent laparoscopic pancreaticoduodenectomy, 11 patients laparoscopic duodenum-preserving pancreatic head resection, 1 patient laparoscopic central pancreatectomy, and 3 patients open pancreaticoduodenectomy. The time required for the pancreaticogastrostomy was (15.4±1.0) min in laparoscopic surgery, and (9.1±0.5) min in open surgery. There were 2 patients who developed grade A pancreatic fistula (4.55%, 2/44) and 7 patients gastric emptying disorder (15.91%, 7/44). There were no grade B or C pancreatic fistula, biliary fistula, gastrointestinal anastomotic fistula, abdominal infection, postoperative bleeding and perioperative death.Conclusion:The modified pancreaticogastrostomy for digestive tract reconstruction in pancreatic surgery was safe and reliable. It effectively reduced the incidence of postoperative pancreatic fistula and improved prognosis of patients.