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ObjectiveTo investigate the risk factors for early tumor recurrence after laparoscopic pancreaticoduodenectomy （LPD） in patients with pancreatic ductal adenocarcinoma （PDAC）， and to establish a predictive model. MethodsA retrospective analysis was performed for the clinical data of 240 PDAC patients who underwent LPD in The First Hospital of Jilin University from April 2016 to July 2022， with early postoperative tumor recurrence （time to recurrence ≤12 months） as the study outcome. The patients were randomly divided into training group with 168 patients and validation group with 72 patients at a ratio of 7∶3. In the training group， there were 70 patients （41.67%） with early postoperative recurrence and 98 （58.33%） without early recurrence， and in the validation group， there were 32 （44.44%） with early postoperative recurrence and 40 （55.56%） without early recurrence. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a logistic regression analysis was used to investigate the risk factors for early postoperative recurrence； the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to evaluate the discriminatory ability of the model， with AUC>0.75 indicating that the model had adequate discriminatory ability. The Bootstrap resampling method was used for validation after 1 000 times of random sampling， and the model was validated again in the validation group. The calibration curve and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the degree of calibration， and the decision curve analysis was used to evaluate clinical practicability. ResultsThe univariate and multivariate analyses showed that preoperative CA19-9 level≥37 U/mL （odds ratio ［OR］=6.265， 95% confidence interval ［CI］： 1.938 — 20.249， P<0.05）， maximum tumor diameter >3 cm （OR=10.878， 95%CI： 4.090 — 28.932， P<0.05）， poor tumor differentiation （OR=3.679， 95%CI： 1.435 — 9.433， P<0.05）， lymph node metastasis （OR=0.209， 95%CI： 0.080 — 0.551， P<0.05）， and absence of adjuvant chemotherapy after surgery （OR=0.167， 95%CI： 0.058 — 0.480， P<0.05）. A nomogram model was constructed based on these factors； the ROC curve analysis showed that the model had an AUC of 0.895 （95%CI： 0.846 — 0.943， P<0.001）， and the calibration curve and the Hosmer-Lemeshow test showed that the model had a good degree of calibration （P=0.173）. The decision curve analysis showed that the nomogram had a good clinical application value. ConclusionPreoperative CA19-9 level ≥37 U/mL， maximum tumor diameter >3 cm， poor tumor differentiation， lymph node metastasis， and absence of adjuvant chemotherapy after surgery are independent risk factors for the early recurrence of PDAC after LPD， and the nomogram model established based on these factors can effectively predict early postoperative recurrence.
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El objetivo de este trabajo es analizar la presentación epidemiológica y la sobrevida de los pacientes con adenocarcinoma ductal de páncreas de acuerdo con su estadío clínico y al tipo de intervención realizada, en una cohorte de pacientes atendidos en una clínica en Lima, Perú. Estudio de cohortes retrospectivas que evaluó desde enero del 2015 a febrero del 2021 a pacientes con diagnóstico de adenocarcinoma ductal de páncreas considerando diversos factores epidemiológicos, radiológicos, estadiaje oncológico, haber recibido quimioterapia neoadyuvante o adyuvante, haber sido sometidos a cirugía y la sobrevida posterior a alguna de las intervenciones realizadas. De los 249 pacientes analizados, se encontró que 75 de ellos requerían cirugía resectiva. Entre los principales resultados obtenidos, se observó que aquellos con un nivel de CA 19-9 menor a 200 U/mL presentaban una media de sobrevida más alta en comparación con aquellos cuyo nivel de CA 19-9 era superior a 200 U/mL (HR: 1,96; IC95%: 0,18-0,53; p≤0,001). Asimismo, al comparar a los pacientes según su etapa, se encontró que aquellos con tumores resecables tenían una media de sobrevida de 37,72 meses, mientras que aquellos con tumores localmente avanzados tenían una media de sobrevida de 13,47 meses y aquellos con tumores metastásicos tenían una media de sobrevida de 7,69 meses (HR: 0,87; IC95%: 0,31-0,25; p≤0,001). Igualmente, se observó que recibir tratamiento neoadyuvante se asociaba con un mejor pronóstico de sobrevida para los pacientes (HR: 0,32; IC95%: 0,19-0,53; p≤0,001). Asimismo, se llevaron a cabo 5 pancreatectomías con resección metastásica en pacientes oligometastásicos tratados con quimioterapia de rescate, y se encontró que la media de sobrevida para estos pacientes fue de 22,51 meses. Conclusión: La cirugía resectiva en un estadío clínico temprano , presentar valores de CA 19-9 por debajo de 200 U/mL y haber recibido quimioterapia neoadyuvante se correlaciona estadísticamente con una mayor esperanza de sobrevida.
The objective of this study is to analyze the epidemiological presentation and survival of patients with pancreatic ductal adenocarcinoma according to their clinical stage and the type of intervention performed, in a cohort of patients treated at a clinic in Lima, Peru. A retrospective cohort study evaluated patients diagnosed with pancreatic ductal adenocarcinoma from January 2015 to February 2021, considering various epidemiological factors, radiological findings, oncological staging, receipt of neoadjuvant or adjuvant chemotherapy, undergoing surgery, and post-intervention survival. Out of the 249 patients analyzed, 75 of them required resective surgery. Among the main findings, it was observed that those with a CA 19-9 level below 200 U/mL had a higher median survival compared to those with a CA 19-9 level above 200 U/mL (HR: 1.96; 95% CI: 0.18-0.53; p≤0.001). Furthermore, when comparing patients according to their stage, those with resectable tumors had a median survival of 37.72 months, while those with locally advanced tumors had a median survival of 13.47 months, and those with metastatic tumors had a median survival of 7.69 months (HR: 0.87; 95% CI: 0.31-0.25; p≤0.001). Additionally, receiving neoadjuvant treatment was associated with a better prognosis of survival for patients (HR: 0.32; 95% CI: 0.19-0.53; p≤0.001). Furthermore, 5 pancreatectomies with metastatic resection were performed in oligometastatic patients treated with salvage chemotherapy, and the median survival for these patients was 22.51 months. Conclusion: Resective surgery at an early clinical stage, CA 19-9 levels below 200 U/mL, and receiving neoadjuvant chemotherapy are statistically correlated with a higher overall survival.
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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.
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Objective To investigate the predictive value of preoperative fibrinogen/albumin ratio (FAR) and systemic immune inflammation index (SII) on the postoperative prognosis of patients with pancreatic ductal adenocarcinoma. Methods An ROC curve was used in determining the best cutoff values of FAR and SII and then grouped. The Cox proportional hazards model was used in analyzing the prognostic factors of radical pancreatic cancer surgery, and then a Nomogram prognostic model was established. C-index, AUC, and calibration curve were used in evaluating the discrimination and calibration ability of the Nomogram. DCA curves were used in assessing the clinical validity of the Nomograms. Results The optimal cutoff values for preoperative FAR and SII were 0.095 and 532.945, respectively. FAR≥ 0.095, SII≥ 532.945, CA199≥ 450.9 U/ml, maximum tumor diameter≥ 4 cm, and the absence of postoperative chemotherapy were independent risk factors for the poor prognosis of pancreatic cancer (P<0.05). The discrimination ability, calibration ability, and clinical effectiveness of Nomogram prognostic model were better than those of the TNM staging system. Conclusion The constructed Nomogram prognostic model has higher accuracy and level of discrimination and more clinical benefits than the TNM staging prognostic model.
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Objective To investigate the differential metabolites of lymph node metastasis in pancreatic ductal carcinoma (PDAC) and provide new ideas for the pathogenesis, early diagnosis and treatment of metastatic pancreatic cancer. Methods Forty serum specimens of patients with pancreatic ductal carcinoma were collected and divided into lymph node metastasis group (18 cases) and non-metastasis group (22 cases). Thirty-one serum specimens were also collected from the healthy control group. Liquid chromatographytandem mass spectrometry was used to analyze the differential metabolites and metabolic pathways between patients with PDAC and healthy controls as well as between lymph node metastasis and non-metastasis groups. Results Principal component analysis and partial least squares-discriminant analysis revealed statistically significant differences in metabolites and metabolic pathways between patients with PDAC and the healthy controls and between lymph node metastasis and non-metastasis groups. The differences in profiles were also statistically significant. Seventy-six different metabolites and 11 metabolic pathways were screened between patients with PDAC and the healthy controls, among which phenylalanine metabolism and histidine metabolism were the two most influential metabolic pathways. Four different metabolites were screened between lymph node metastasis and non-metastasis groups, and the expression of ethopropazine and phenylalanine were upregulated but the expression of tetrahydrodeoxycorticosterone and oxprenolol were downregulated. Conclusion Metabolites are significantly altered in the lymph node metastasis group of patients with PDAC compared with the non-metastasis group. Ethopropazine, phenylalanine, tetrahydrodeoxy corticosterone, and oxprenolol are potential biomarkers of lymph node metastasis in patients with PDAC.
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Objective:To investigate the value of enhanced MRI in evaluating the tissue permeability of pancreatic ductal adenocarcinoma (PDAC) animal model.Methods:The experimental animals were 27 female C57BL/6 mice. The mice were divided into 3 groups with 9 mice in each group by random number method. Murine pancreatic adenocarcinoma (Panc02) and embryonic fibroblasts (NIH/3T3) were implanted subcutaneously at the ratio of 2∶1 and 1∶1 to establish PDAC models with different tissue permeability, which were low fibroblast group and high fibroblast group, respectively, and simple Panc02 implantation model was control group. The positive expression rate of α-smooth muscle actin (α-SMA), the positive expression rate of fibroblast activating protein (FAP), the coverage rate of collagen fibers, number of blood vessels and the long/short diameter of tissue vessels were quantitatively evaluated by tissue staining, and the tissue permeation efficiency was quantified by the average optical density (AOD) of tissue sections stained by Evans blue (EB). Enhanced MRI was performed on mice, and the enhancement degree and the enhancement rate of 20 min were obtained. One-way ANOVA was used to compare the overall differences of tumor histological indexes and MRI enhancement parameters in each group, and the correlation between the indexes was analyzed by Pearson correlation analysis. Multiple linear stepwise regression analysis was conducted with 20 min enhancement rate as dependent variable, while α-SMA positive expression rate, collagen fiber coverage rate and vascular long/short diameter as independent variables.Results:There were significant differences in AOD value, α-SMA positive expression rate, FAP positive expression rate, collagen fiber coverage rate, vascular long/short diameter, 20 min enhancement degree and 20 min enhancement rate among the three groups ( P<0.001), but there was no significant difference in the number of blood vessels ( P=0.650). The AOD value was negatively correlated with the positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels in PDAC model, respectively ( r=-0.888, P=0.001; r=-0.813, P=0.008; r=-0.915, P<0.001). The 20 min enhancement degree was positively correlated with AOD value ( r=0.954, P<0.001). The positive expression rate of α-SMA, collagen fiber coverage and vascular long/short diameter were negatively correlated with 20 min enhancement rate ( r=-0.901, P<0.001; r=-0.837, P=0.005; r=-0.880, P=0.002). The results of multiple linear stepwise regression analysis showed that the positive expression rate of α-SMA was an important influencing factor for the 20 min enhancement rate (R 2=0.813, P=0.001). Conclusions:The increase of fibroblast implantation ratio significantly decreased the permeation efficiency of tumor tissue. The positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels were negatively correlated with the permeation efficiency of tumor tissue. The 20 min enhancement degree was positively correlated with tissue permeation efficiency.
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Objective:To develop and validate the models based on mixed enhanced computed tomography (CT) radiomics and deep learning features, and evaluate the efficacy for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC) before surgery.Methods:The clinical data of 201 patients with surgically resected and histopathologically confirmed PASC (PASC group) and 332 patients with surgically resected histopathologically confirmed PDAC (PDAC group) who underwent enhanced CT within 1 month before surgery in the First Affiliated Hospital of Naval Medical University from January 2011 to December 2020 were retrospectively collected. The patients were chronologically divided into a training set (treated between January 2011 and January 2018, 156 patients with PASC and 241 patients with PDAC) and a validation set (treated between February 2018 and December 2020, 45 patients with PASC and 91 patients with PDAC) according to the international consensus on the predictive model. The nnU-Net model was used for pancreatic tumor automatic segmentation, the clinical and CT images were evaluated, and radiomics features and deep learning features during portal vein phase were extracted; then the features were dimensionally reduced and screened. Binary logistic analysis was performed to develop the clinical, radiomics and deep learning models in the training set. The models' performances were determined by area under the ROC curve (AUC), sensitivity, specificity, accuracy, and decision curve analysis (DCA).Results:Significant differences were observed in tumor size, ring-enhancement, upstream pancreatic parenchymal atrophy and cystic degeneration of tumor both in PASC and PDAC group in the training and validation set (all P value <0.05). The multivariable logistic regression analysis showed the tumor size, ring-enhancement, dilation of the common bile duct and upstream pancreatic parenchymal atrophy were associated with PASC significantly in the clinical model. The ring-enhancement, dilation of the common bile duct, upstream pancreatic parenchymal atrophy and radiomics score were associated with PASC significantly in the radiomics model. The ring-enhancement, upstream pancreatic parenchymal atrophy and deep learning score were associated with PASC significantly in the deep learning model. The diagnostic efficacy of the deep learning model was highest, and the AUC, sensitivity, specificity, and accuracy of the deep learning model was 0.86 (95% CI 0.82-0.90), 75.00%, 84.23%, and 80.60% and those of clinical and radiomics models were 0.81 (95% CI 0.76-0.85), 62.18%, 85.89%, 76.57% and 0.84 (95% CI 0.80-0.88), 73.08%, 82.16%, 78.59% in the training set. In the validation set, the area AUC, sensitivity, specificity, and accuracy of deep learning model were 0.78 (95% CI 0.67-0.84), 68.89%, 78.02% and 75.00%, those of clinical and radiomics were 0.72 (95% CI 0.63-0.81), 77.78%, 59.34%, 65.44% and 0.75 (95% CI 0.66-0.84), 86.67%, 56.04%, 66.18%. The DCA in the training and validation sets showed that if the threshold probabilities were >0.05 and >0.1, respectively, using the deep learning model to distinguish PASC from PDAC was more beneficial for the patients than the treat-all-patients as having PDAC scheme or the treat-all-patients as having PASC scheme. Conclusions:The deep learning model based on CT automatic image segmentation of pancreatic neoplasm could effectively differentiate PASC from PDAC, and provide a new non-invasive method for confirming PASC before surgery.
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It is discovered that activated caspase-3 tends to induce apoptosis in gasdermin E (GSDME)-deficient cells, but pyroptosis in GSDME-sufficient cells. The high GSDME expression and apoptosis resistance of pancreatic ductal adenocarcinoma (PDAC) cells shed light on another attractive strategy for PDAC treatment by promoting pyroptosis. Here we report a hGLuc-hGSDME-PCA system for high-throughput screening of potential GSDME activators against PDAC. This screening system neatly quantifies the oligomerization of GSDME-N to characterize whether pyroptosis occurs under the stimulation of chemotherapy drugs. Based on this system, ponatinib and perifosine are screened out from the FDA-approved anti-cancer drug library containing 106 compounds. Concretely, they exhibit the most potent luminescent activity and cause drastic pyroptosis in PDAC cells. Further, we demonstrate that perifosine suppresses pancreatic cancer by promoting pyroptosis via caspase-3/GSDME pathway both in vitro and in vivo. Collectively, this study reveals the great significance of hGLuc-hGSDME-PCA in identifying compounds triggering GSDME-dependent pyroptosis and developing promising therapeutic agents for PDAC.
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Gelsolin (GSN) can sever actin filaments associated with autophagy. This study investigated how GSN-regulated actin filaments control autophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP). AP was produced in a rat model and PDECs using caerulein (CAE). Rat pancreatic duct tissue and HPDE6-C7 cells were extracted at 6, 12, 24, and 48 h after CAE treatment. HPDE6-C7 cells in the presence of CAE were treated with cytochalasin B (CB) or silenced for GSN for 24 h. Pancreatic histopathology and serum amylase levels were analyzed. Cellular ultrastructure and autophagy in PDECs were observed by transmission electron microscopy after 24 h of CAE treatment. The expression of GSN and autophagy markers LC3, P62, and LAMP2 was evaluated in PDECs by immunohistochemistry and western blotting. Actin filaments were observed microscopically. Amylase levels were highest at 6 h of AP, and pancreatic tissue damage increased over time. Mitochondrial vacuolization and autophagy were observed in PDECs. CAE increased GSN expression in these cells over time, increased the LC3-II/LC3-I ratio and LAMP2 expression at 24 and 6 h of treatment, respectively, and decreased P62 expression at all time points. CB treatment for 24 h decreased the LC3-II/LC3-I ratio and LAMP2 expression, increased P62 levels, but had no impact on GSN expression in CAE-treated PDECs. CAE induced actin depolymerization, and CB potentiated this effect. GSN silencing increased the LC3-II/LC3-I ratio and LAMP2 expression and reduced actin depolymerization in CAE-treated PDECs. GSN may inhibit autophagosome biogenesis and autophagosome-lysosome fusion by increasing actin depolymerization in PDECs in AP.
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El adenocarcinoma pancreático ductal (APD) es la cuarta causa de muerte por cáncer y se proyecta que para el 2030 ocupe el segundo lugar. El pronóstico es sombrío, siendo la sobrevida menor a 9% en 5 años. Se consideró durante mucho tiempo a la resección quirúrgica como el único tratamiento curativo, sin embargo, sólo el 15 a 20% de los pacientes pueden ser beneficiados con la misma. La clasificación pre terapéutica más utilizada es la del National Comprehensive Cáncer Network (NCCN), basada en la relación del tumor con estructuras vasculares, clasificándolos en tumores "resecables", de resección límite "Borderlines" y "localmente avanzados". Se presenta el primer caso registrado en Paraguay de APD con infiltración de la Vena Mesentérica Superior (VMS) tratado con duodenopancreatectomía cefálica (DPC) asociada a resección vascular mayor.
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer death and is projected to rank second by 2030. The prognosis is bleak, with survival being less than 9% in 5 years. For a long time, surgical resection was considered the only curative treatment, however, only 15 to 20% of patients can benefit from it. The most widely used pre-therapeutic classification is that of the National Comprehensive Cancer Network (NCCN), based on the relationship of the tumor with vascular structures, classifying them into "resectable", "borderline" and "locally advanced" tumors. We present the first registered case in Paraguay of PDA with infiltration of the Superior Mesenteric Vein (SMV) treated with cephalic duodenopancreatectomy (CPD) associated with major vascular resection.
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Adenocarcinoma , Pancreaticoduodenectomy , Proctectomy/methodsABSTRACT
Borderline resectable pancreatic ductal adenocarcinoma accounts for approximately 20% of newly diagnosed pancreatic cancer patients. This type of adenocarcinoma is between resectable and unresectable. It has a high degree of heterogeneity and features in anatomy, biology, and physical condition. The biological characteristics of invasiveness determine that, rather than direct surgery, neoadjuvant therapy should be primarily given to patients to achieve R0 resection and avoid early postoperative recurrence. However, this treatment model is still controversial. According to the latest research on this topic, the full text summarizes the definition of BR-PDAC, resectable evaluation, neoadjuvant treatment selection and evaluation, surgical results after neoadjuvant therapy, and the efficacy of adjuvant therapy after neoadjuvant therapy.
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Objective To establish a modified induction method for differentiation of rat pancreatic ductal stem cells (rPDSCs) to form islet-like cells. Methods All-trans retinic acid(ATRA) was added at 2, 4, 6 and 8 jjimol/L in the basal culture medium DMEM/F12 + 10% FBS + 1% penicillin/1% streptomycin to induce the differentiation of rPDSCs to form islet-like cells in vitro, and the optimal induction concentration of ATRA was screened. Based on the optimal ATRA induction concentration, rPDSCs were then induced to form islet-like cells in vitro by matrigel culture, suspension culture or hanging drop culture, respectively, to screen the optimal induction culture method . Cell morphology, dithizone(DTZ) staining, cell immunofluorescence staining, Real-time PCR and ELISA were used to detect the induced islet-like cells. Results Compared with the control group, 6 (jumol/L ATRA and matrigel culture were the best in the basic culture medium. After 28 days of induction, the cells enriched and differentiated to form islet-like spherical cell clusters; DTZ staining was positive; Pancreatic duodenal homeobox-1 (Pdxl) and insulin were expressed at gene and protein levels, respectively; Glucose stimulation, release insulin and C-peptide, showed glucose concentration dependent. Conclusion The in vitro differentiation of rPDSCs to form islet-like cells could be successfully induced by using 6 |xmol/L ATRA + DMEM/F12+10% FBS+1% double antibody under matrigel culture method in the present study.
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RESUMEN Objetivo: El objetivo de este trabajo es analizar retrospectivamente la resección en pacientes con adenocarcinoma de páncreas en estadio IV oligometastásicos, luego de quimioterapia de primera línea para cáncer de páncreas metastásico evaluando la sobrevida de estos casos. Materiales y métodos: Entre enero del 2005 hasta diciembre del 2019 se evaluó de manera retrospectiva a 5 pacientes con diagnóstico de cáncer de páncreas oligometastásico sometidos a quimioterapia de primera línea luego de la cual se les efectuó cirugía resectiva. Resultados: La cirugía resectiva realizadas en estos pacientes fueron: Tres pancreatectomias distales con esplenectomía, una duodenopancreatectomia y una pancreatectomia total. Todos recibieron tratamiento con quimioterapia; tres pacientes recibieron tratamiento con Folfurinox, uno recibió 5 fluoruracilo y otro recibió gemcitabina más capecitabina. Los pacientes recibieron en promedio 4 meses de quimioterapia (3-6 meses) y luego de estos se programó la cirugía resectiva. La sobrevida media en estos pacientes fue de 23 meses (11 a 39 meses), solamente un paciente presento recidiva de la enfermedad y falleció a los 28 meses, los 4 restantes se encuentran vivos. Conclusión: La cirugía resectiva en pacientes con estadio IV con cáncer de páncreas se puede hacer de forma segura. Esta se podría considerar en pacientes seleccionados con una buena respuesta radiológica y bioquímica luego de un periodo adecuado de quimioterapia en los cuales no exista enfermedad a distancia evidente.
ABSTRACT Objective: The objective of this work is to retrospectively analyze the resection in patients with oligometastatic stage IV pancreatic adenocarcinoma, after first-line chemotherapy for metastatic pancreatic cancer, evaluating the survival of these cases. Materials and methods: Between January 2005 and December 2019, 5 patients diagnosed with oligometastatic pancreatic cancer undergoing first-line chemotherapy were retrospectively evaluated, after which resective surgery was performed. Results: The resective surgery performed in these patients were: three distal pancreatectomies with splenectomy, one duodenopancreatectomy and one total pancreatectomy. All received chemotherapy treatment; three patients received treatment with Folfurinox, one received 5-fluorouracil, and one received gemcitabine plus capecitabine. The patients received an average of 4 months of chemotherapy (3-6 months) and after this, resective surgery was scheduled. The average survival in these patients was 23 months (11 to 39 months), only one patient presented recurrence of the disease and died at 28 months, the remaining 4 are alive. Conclusion: Resective surgery in patients with stage IV pancreatic cancer can be done safely. This could be considered in selected patients with a good radiological and biochemical response after an adequate period of chemotherapy in whom there is no obvious distant disease.
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Objective:To investigate the segmentation methods of pancreatic ductal adenocarcinoma (PDAC) tumor regions in 18F-fluorodeoxyglucose (FDG) PET/CT images, as well as their impact on radiomic features-based pathological grade prediction. Methods:A total of 72 patients (46 males, 26 females, age range: 25-87 years) with pathologically confirmed PDAC and a preoperative 18F-FDG PET/CT scan in Peking Union Medical College Hospital between September 2010 and January 2016 were enrolled retrospectively. The cohort of patients was classified as well differentiated group and non-well differentiated group based on the pathological grade of PDAC, and patients were divided into training set and validation set in the ratio of 3∶1 randomly. Two physicians performed manual contours in the tumor region (referred as region of interest (ROI)_M1 and ROI_M2) and semi-automatic ROIs based on standardized uptake value (SUV) gradient edge search (referred as ROI_G) and 40% threshold applied to the maximum SUV (SUV max; referred as ROI_S) were drawn. The four types of segmentation results were compared in terms of volume and Dice similarity coefficient (DSC). Shape, first-order, and texture features were extracted from PET/CT original and preprocessed images, and the interclass correlation coefficient (ICC) was used to assess each feature′s consistency across all segmentations. Kruskal-Wallis rank sum test, independent-sample t test or z test were used to analyze the data. The area under the receiver operating characteristic curve was used to assess model accuracy, and cross validation was used to assess generalization ability. Results:There were 55 patients in the training set (14 well differentiated cases and 41 non-well differentiated cases) and 17 patients in the validation set (4 well differentiated cases and 13 non-well differentiated cases). A total of 44 selected features were predictive of the pathological grade of PDAC among 20 feature groups. There was significant difference among the volumes of ROI_M1, ROI_M2, ROI_G and ROI_S (10.29(4.01, 19.43), 9.34(4.26, 17.27), 11.86(5.52, 19.74) and 15.08(9.62, 27.44) cm 3; H=18.641, P<0.05). The degree of contour coincidence and feature consistency between ROI_M1 and ROI_M2 were both higher (DSC=0.86 (0.76, 0.90), ICC=0.86 (0.74, 0.94)). Compared to manual contours, the degree of contour coincidence and feature consistency of ROI_G (DSC: 0.86(0.75, 0.91), 0.91(0.85, 0.96); ICC: 0.87(0.72, 0.94), 0.94(0.88, 0.98)) were better. There was no statistically significant difference in model accuracy or generalization ability between ROI_M1 and ROI_G ( z=1.052, t=0.712, both P>0.05). The accuracy of ROI_M2 was better than ROI_G ( z=3.031, P=0.002), but the generalization ability of ROI_M2 was insufficient ( t=3.086, P=0.012). Conclusions:Although the manual contour prediction models are highly accurate, their performance are unstable. Semi-automatic contouring based on gradient can achieve comparable accuracy to manual contouring, and the model′s generalization ability is stronger.
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Objective: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tract tumors with a poor prognosis and high recurrence rate. Recently, ferroptosis resistance has been found in PDAC. However, the underlying mechanism of ferroptosis resistance has not been fully elucidated. Cytochrome P4502J2 (CYP2J2) is the main enzyme which mediates arachidonic acid to produce epoxyeicosatrienoic acids (EETs) in human tissues. It has been reported that EETs involve in the development of cancer, while the roles of EETs in PDAC and ferroptosis remain unclear. This study aims to explore the effect of CYP2J2/EETs on ferroptosis of human pancreatic ductal adenocarcinoma cells PANC-1 cells and the underlying mechanisms.Methods: The tumor tissues and para-carcinoma tissues of 9 patients with PDAC were collected and the expression of CYP2J2 was detected with real-time PCR and Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET), and the degradation product of 8,9-epoxyeicosa-trienoic acid (8, 9-EET). PANC-1 cells were used in this study. The ferroptosis inducer erastin was used to induce ferroptosis. The intracellular long-chain acyl-CoA synthetase 4 (ACSL4) protein level, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) content, Fe2+concentration, and cell survival were detected. The 8, 9-EET was pretreated to observe its effect on erastin-induced ferroptosis in PANC-1 cells. Lentivirus was used to construct a CYP2J2 knockdown cell line to observe its effect on the ferroptosis of PANC-1 cells induced by erastin. A peroxisome proliferation-activated receptor γ (PPARγ) blocker was used to observe the effect of 8, 9-EET on erastin-induced glutathione peroxidase 4 (GPX4) and MDA content in PANC-1 cells.Results: High expression of CYP2J2 was found in PDAC, accompanied by an increased level of 8, 9-DHET. The 8, 9-EET pretreatment significantly attenuated the PANC-1 cell death induced by erastin. The 8, 9-EET reduced the Fe2+ concentration, LDH activity and MDA content, and ACSL4 protein expression in erastin-treated PANC-1 cells. The 8,9-EET also restored the ferroportin (FPN) and ferroptosis suppressor protein 1 (FSP1) mRNA expressions in erastin-treated PANC-1 cells. But CYP2J2 knockdown exacerbated the erastin-induced ferroptosis in PANC-1 cells. Besides, CYP2J2 knockdown furtherly down-regulated the gene expression of FPN and FSP1. The 8, 9-EET increased the expression of GPX4 in the erastin-treated PANC-1 cells, which was eliminated by a PPARγ blocker GW9662. And GW9662 abolished the anti-ferroptosis effects of 8,9-EET. Conclusion: CYP2J2/EETs are highly expressed in PDAC tissues. EETs inhibit the ferroptosis via up-regulation of GPX4 in a PPARγ-dependent manner, which contributes to the ferroptosis resistance of PDAC.
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Objective:To detect the expression of replication factor C4(RFC4) in pancreatic ductal adeno-carcinoma, and to explore the clinical prognosis of RFC4 and pancreatic ductal adenocarcinoma. To explore the possibility of RFC4 as a potential biomarker for pancreatic ductal adenocarcinoma.Methods:The mRNA level of RFC4 in pancreatic ductal adenocarcinoma and normal tissues adjacent to the cancer was analyzed by bioinformatics methods, and the relationship between its expression and the survival rate of patients with pancreatic ductal adenocarcinoma was analyzed. The clinicopathological data of 76 patients with pancreatic ductal adenocarcinoma who underwent surgical treatment were retrospectively analyzed. Immunohistochemical method was used to detect the expression level of RFC4 protein in pancreatic ductal adenocarcinoma tissue and normal tissues adjacent to the cancer, and to analyze its relationship with clinicopathological characteristics of patients with pancreatic ductal adenocarcinoma.Results:The results of bioinformatics analysis showed that RFC4 mRNA was significantly highly expressed in pancreatic ductal adenocarcinoma tissue, and was significantly correlated with the overall survival rate ( P=0.046) and disease-free survival rate ( P=0.042) of the patients. Immunohistochemical results showed that the expression of RFC4 in pancreatic ductal adenocarcinoma tissue was significantly higher than that in normal tissues adjacent to the cancer. The high expression of RFC4 in pancreatic ductal adenocarcinoma tissue was related to tumor size ( P=0.043), but not related to age, gender, and tumor grade (all P>0.05). Conclusions:RFC4 is highly expressed in pancreatic ductal adenocarcinoma tissues and indicates a poor prognosis, and its expression level is related to the tumor stage of pancreatic ductal adenocarcinoma. RFC4 may serve as a new prognostic predictor for pancreatic ductal adenocarcinoma.
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Pancreatic ductal adenocarcinoma is a highly invasive malignant tumor of the digestive system with an extremely poor prognosis. Leukemia inhibitory factor is an important member of the interleukin-6 family and can regulate multiple physiological processes such as cell differentiation, growth, and renewing. This article reviews the mechanism of action of leukemia inhibitory factor in pancreatic ductal adenocarcinoma and the research advances in leukocyte inhibitory factor-targeted therapy based on literature evidence, and the analysis shows that leukemia inhibitory factor plays an important role in the progression, immune escape, and chemotherapy resistance of pancreatic ductal adenocarcinoma and may gradually become a potential biomarker and therapeutic target for pancreatic ductal adenocarcinoma.
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Objective:To explore the differential diagnosis of pancreatic acinar cell carcinoma (PACC) and pancreatic ductal adenocarcinoma (PDAC) based on multidetector computed tomography (MDCT) features.Methods:The clinical, pathological and MDCT imaging data of 26 patients with pathologically confirmed PACC and 145 patients with pathologically confirmed PDAC who underwent MDCT from November 2013 to April 2021 were retrospectively studied. The differences of MDCT features including tumor location, tumor size, common pancreatic duct and bile duct dilatation, pancreatitis, lymph node metastasis, cyst, pancreatic parenchyma atrophy, duodenal involvement, bile ductal and vascular involvement between the two groups were compared. Univariate analysis and multivariate analysis by logistic regression models were performed to identify the independent predictive factors for PACC.Results:The tumor size, bile duct dilatation, lymph node metastasis, pancreatic parenchyma atrophy and vascular involvement were significantly different between PACC group and PDAC group (all P value<0.05). Multivariate analysis revealed that the tumor size ( OR=1.07, 95% CI 1.028-1.15, P=0.001), lymph node metastasis ( OR=0.23, 95% CI 0.065-0.800, P=0.02), pancreatic parenchyma atrophy ( OR=0.15, 95% CI 0.048-0.490, P=0.002) were closely associated with PACC. Conclusions:The tumor size, bile duct dilatation, lymph node metastasis, pancreatic parenchyma atrophy and vascular involvement evaluated by MDCT had a certain value in differentiating PACC from PDAC, and the tumor size, lymph node metastasis and pancreatic parenchyma atrophy were independent predictors for the diagnosis of PACC.
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Objective:To investigate the relationship between the perineural invasion score based on multidetector computed tomography (MDCT) and extrapancreatic perineural invasion (EPNI) in pancreatic ductal adenocarcinoma (PDAC).Methods:The clinical, radiological, and pathological data of 374 patients pathologically diagnosed as pancreatic cancer who underwent radical resection in the First Affiliated Hospital of Naval Medical University from March 2018 to May 2020 were analyzed retrospectively. Patients were divided into EPNI negative group ( n=111) and EPNI positive group (n=263) based on the pathological presence of EPNI. The perineural invasion score was performed for each patient based on radiological images. Univariate and multivariate logistic regression models were used to analyze the association between the perineural invasion score based on MDCT and EPNI in PDAC. Results:There were significant statistical differences between EPNI negative group and positive group on both pathological characteristics (T stage, N stage, invasion of common bile duct, and positive surgical margin) and radiological characteristics (tumor size, vascular invasion, lymph node metastasis, perineural invasion score based on MDCT, pancreatic border, parenchymal atrophy, invasion of duodenum, invasion of spleen and splenic vein and invasion of common bile duct) (all P value <0.05). Univariate analysis revealed that the tumor size, vascular invasion, lymph node metastasis, perineural invasion score based on MDCT, pancreatic border, pancreatic atrophy, invasion of duodenum, invasion of spleen and splenic vein and invasion of common bile duct were independently associated with EPNI. Multivariate analyses revealed that the perineural invasion based on MDCT was an independent risk factor for EPNI in pancreatic cancer (score=1, OR=2.93, 95% CI 1.61-5.32, P<0.001; score=2, OR=5.92, 95% CI 2.68-13.10, P<0.001). Conclusions:The perineural invasion score based on MDCT was an independent risk factor for EPNI in pancreatic cancer and can be used as an evaluation indicator for preoperative prediction of EPNI in PDAC.
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Pancreatic ductal adenocarcinoma (PDA) organoids are 3D cultured from patient-derived stem cells or progenitor cells in vitro. PDA organoids have a variety of cell types, can realize structural self-organization through cell self-renewal, and are similar to the cells in the body of the original organ function in vivo biological bank. PDA organoids can be derived from surgical or biopsy tissue. The ability to build organoids from biopsy will facilitate the sampling of a larger population of PDA patients. Repeated sampling of patients can track the entire progression of the disease longitudinally. Compared with the traditional 2D cell culture and patient-derived xenotransplantation models, the three-dimensional culture of PDA organoids has the characteristics of short time and high success rate, and can be cryopreserved and maintain the stability of genetic traits. Organoids that can simulate diseases can be used as an alternative drug testing system. Using it for drug testing can not only better reflect the patient's response to drugs, but also can reduce the number of animal experiments. Moreover, when using organoids for testing, there is no need to understand the underlying molecular mechanism a priori, and chemical sensitivity testing can be performed directly, thereby shortening the testing time. In this paper, the advantages and disadvantages of different PDA organoids 3D culture methods and the verification methods for the stability and invasiveness of PDA organoids were reviewed. The mechanism of PDA organoids used for tumor chemotherapy drug sensitivity screening was discussed, and the application prospects and challenges of tumor biology in patient individualized treatment and precision medical treatment were discussed.