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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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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 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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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: 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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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.
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Despite recent advances in treatment with multidrug chemotherapy regimens, outcomes of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remain very poor. Treatment with targeted therapies has shown marginal benefits due to intrinsic or acquired resistance. Actionable mutations, while detected infrequently in patients with PDAC, are becoming increasingly used in personalized medicine. Here, we describe an epidermal growth factor receptor (EGFR)-activating mutation (E746_T751>VP) to erlotinib, a first-generation tyrosine kinase inhibitor (TKI), in a patient with metastatic PDAC. After an initial partial response to erlotinib for 12 months, the patient's disease progressed with emergence of the EGFR A647T mutation. Certainly, the patient also progressed after switching therapy to a third-generation EGFR TKI (osimertinib). This case illustrates the posttreatment evolution of EGFR A647T-mediated resistance to the first- and third-generation TKIs. To our knowledge, this is the first case to report the aforementioned activating and resistance-mediated mutations. In summary, genomic analysis performed in this patient with PDAC on the tumor biopsy and peripheral blood provided tools to understand mechanisms of response and resistance to targeted therapy with EFGR TKIs
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We present a case of Robo1‑specific chimeric antigen receptor natural killer (CAR‑NK) cell therapy for pancreatic ductal adenocarcinomawith liver metastasis in a 46‑year‑old male. The patient was treated with Robo1‑specific CAR‑NK cell infusion. Liver metastasis wastreated with percutaneous Robo1‑specific CAR‑NK Cell injection. In the 1st month, the patient received Robo1‑CAR‑NK intravenousinjection on days 1 and 3 and percutaneous injection on days 2 and 4 every week, respectively, and the dosage administered was1×109 Robo1‑ specific CAR‑NK cell, respectively. The patient continuously received Robo1‑CAR‑NK intravenous injection once aweek. An evaluation was conducted every 2 weeks. The patient was safely applied the therapy with no substantial adverse effects.Pancreatic lesion was controlled within 5 months. Karnofsky Performance Score and child stage of the patient did not change greatlyduring the therapy, and the patient’s overall survival time was 8 months
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Objective: To analyze the clinical characteristics of adenosquamous carcinoma of the pancreas (ACP) and pancreatic ductal adenocarcinoma (PDA), and to explore the differences in prognosis between the two types. Methods: The clinical and pathological characteristics of 26 cases with ACP (Group A) and another 26 with PDA (Group B), both of whom underwent radical surgery at Tianjin Medical University Cancer Hospital from August 2014 to April 2019, were retrospectively analyzed, and were matched according to the ratio of one to one. In our study, the characteristics of each pair included preoperative ECOG score, age, gender, the location and size of the tumors, TNM staging, CA19-9, CEA. The prognostic differences between the two groups were compared and analyzed. Results: There were 7 females and 19 males in both groups, among which 12 had lesions in the head of the pancreas and 14 in the tail of the pancreas; TNM staging: 13 in stageb, 6 in stage Ⅱa, 6 in stage Ⅱb, and 1 in stage III. The average tumor size was 3.9 cm in the Group B, and 4.4 cm in the Group A. Radical surgery was performed in the patients of both groups, and among them 7 patients in Group A received combined organ resections. Survival analysis showed that the median survival time was 8.5 months in Group A and 19 moths in Group B (HR: 0.442; 95% CI: 0.224-0.872; P=0.019). Conclusions: ACP is more common in the males and its The prognosis is worse compared with PDA, but it has no specific clinical manifestations.
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Autoimmune pancreatitis (AIP) is a unique subtype of chronic pancreatitis, which shares many clinical presentations with pancreatic ductal adenocarcinoma (PDA). The misdiagnosis of AIP often leads to unnecessary pancreatic resection. F-FDG positron emission tomography/ computed tomography (PET/CT) could provide comprehensive information on the morphology, density, and functional metabolism of the pancreas at the same time. It has been proved to be a promising modality for noninvasive differentiation between AIP and PDA. However, there is a lack of clinical analysis of PET/CT image texture features. Difficulty still remains in differentiating AIP and PDA based on commonly used diagnostic methods. Therefore, this paper studied the differentiation of AIP and PDA based on multi-modality texture features. We utilized multiple feature extraction algorithms to extract the texture features from CT and PET images at first. Then, the Fisher criterion and sequence forward floating selection algorithm (SFFS) combined with support vector machine (SVM) was employed to select the optimal multi-modality feature subset. Finally, the SVM classifier was used to differentiate AIP from PDA. The results prove that texture analysis of lesions helps to achieve accurate differentiation of AIP and PDA.
Subject(s)
Humans , Adenocarcinoma , Diagnostic Imaging , Algorithms , Autoimmune Diseases , Diagnostic Imaging , Diagnosis, Differential , Fluorodeoxyglucose F18 , Pancreatic Neoplasms , Diagnostic Imaging , Pancreatitis , Diagnostic Imaging , Positron Emission Tomography Computed Tomography , Support Vector MachineABSTRACT
Objective@#Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the leading causes of cancer-related death worldwide. Hence, the development of effective anti-PDAC therapies is urgently required. Patient-derived xenograft (PDX) models are useful models for developing anti-cancer therapies and screening drugs for precision medicine. This review aimed to provide an updated summary of using PDX models in PDAC.@*Data sources@#The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms, including PDAC, pancreatic carcinoma, pancreatic cancer, patient-derived xenografts or PDX, and patient-derived tumor xenografts or PDTX.@*Study selection@#Original articles and review articles relevant to the review’s theme were selected.@*Results@#PDX models are better than cell line-derived xenograft and other models. PDX models consistently demonstrate retained tumor morphology and genetic stability, are beneficial in cancer research, could enhance drug discovery and oncologic mechanism development of PDAC, allow an improved understanding of human cancer cell biology, and help guide personalized treatment.@*Conclusions@#In this review, we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches. PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.
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@# Objective: To investigate the expression of ECT2 (epithelial Transforming sequence 2) gene in human pancreatic ductal adenocarcinoma (PDAC) and its effect on the proliferation and apoptosis of pancreatic cancer cells. Methods: Carcinoma tissues and corresponding para-carcinoma tissues from 35 PDAC patients at Changhai Hospital Affiliated to Naval Medical University from July 2018 to March 2019 were collected for this study. The differentially expressed genes in pancreatic cancer were screened out by using Gene Expression Omnibus (GEO) Database. Then, the related gene expression in PDAC and its relation with patients’survival were analyzed by The Cancer Genome Atlas (TCGA) database. QPCR and immunohistochemistry were used to verify the mRNAand protein expressions of ECT2 in human PDAC samples. To explore the effect of ECT2 on the biological behaviors of pancreatic cancer cells, si-RNA was used to silence the ECT2 gene in pancreatic cancer PANC-1 cells, and CCK-8 proliferation assay and Flow cytometry were used to detect the proliferation and apoptosis rate of PANC-1 cells after ECT2 silence. Finally, the expressions of apoptosis-related proteins were detected by WB. Results: The differentially expressed gene-ECT2, was screened out by analyzing the gene expression profiles of human pancreatic cancer in GEO database. TCGA database analysis showed that ECT2 was highly expressed in pancreatic cancer tissues (t=4.005, P<0.05) and significantly correlated with patients’survival (P< 0.01). Moreover, it is also verified that ECT2 was highly expressed in PDAC tissues at mRNA (1.01±0.06 vs 4.25±0.12; t=24.09， P<0.01) and protein level. After ECT2 silence in PANC-1 cells, the proliferation rate was decreased (P<0.01), while the Tamoxifeninduced apoptosis rate was increased (P<0.01), and the expressions of apoptosis-related proteins (BAX and Bcl-2) were also affected. Conclusion: ECT2 is highly expressed in human pancreatic ductal adenocarcinoma and is related with patients’survival. ECT2 promotes the proliferation and apoptosis resistance of pancreatic cancer cells, providing the basis for exploring ECT2 as a new target for the prognostic judgment and treatment of pancreatic cancer.
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Objective To investigate the feasibility of the CT texture analysis (CTTA)in differentiating autoimmune pancreatitis (AIP)from pancreatic ductal adenocarcinoma (PDAC).Methods 25 patients with AIP and 31 patients with PDAC who confirmed by pathological or clinical underwent pretreatment three-phase contrast-enhanced CT were enrolled.Histogram parameters (mean CT values,median CT values,25 th,75 th percentile CT values,skewness,kurtosis,entropy and uniformity)were derived from CT images through texture analysis.The differences of histogram parameters between AIP and PDAC groups were compared.ROC and AUC were used to evaluate the diagnostic efficacy of histogram parameters in differentiating AIP from PDAC.Results The values for mean CT values,median CT values,25 th,75 th percentile CT values and uniformity of AIP were significantly higher than those of PDAC group,while the values for entropy of AIP were significantly lower than those of PDAC group in arterial phase,portal phase,and delay phases (all P＜0.05). There were no significant differences in kurtosis and skewness between AIP and PDAC groups (all P＞0.05).The uniformity in portal phase achieved the optimal diagnostic accuracy in differentiating AIP from PDAC (AUC＝0.973 ),the cutoff value was 0.797,the corresponding sensitivity and specificity were 92% and 9 6.8%,respectively.Conclusion CTTA can be used as a quantitative analysis method for differential diagnosis between AIP and PDAC,providing a reference for clinicians to select therapeutic schedules.
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Objective To investigate the value of contrast‐enhanced ultrasound ( CEUS ) in the differential diagnosis of pancreatic neoplasia ( SPN ) before operation . Methods Forty‐six cases of SPN confirmed by operation and histopathological results from January 2012 to June 2018 were enrolled in the study . According to the European Ultrasound Association ( EFSUMB) guidelines for CEUS in 2018 ,the enhancement pattern of pancreatic lesion with normal surrounding pancreatic parenchyma was used for reference . T he enhancement pattern of SPN were observed during the arterial phase ,venous phase and delayed phase . CEUS pattern of 16 cases with pancreatic ductal adenocarcinoma ( PDAC ) with cystic changes proved by histopathology were observed and compared with SPN . Results T he mean size of 46 cases of SPN was ( 32 .72 ± 25 .51) mm . Fifteen SPN lesions located in the head of pancreas ,31 cases located in the body and tail of the pancreas . Most of SPN were solidcystic lesions with thin separation on conventional B mode ultrasoud ,without communication with the main pancreatic duct . Color flow signals could be detected in 78 .3% ( 36/46) SPN lesions . After the injection of 2 .4 ml ultrasound contrast agent , the substantial part of all SPN showed hyperenhancement ( n＝ 44 ,99 .7% ) or isoenhancement ( n ＝ 2 , 4 .3% ) during the arterial phase ,venous phase and late phase . However ,93 .8% ( 15/16 ) of the PDAC lesion with cystic changes showed consistent hypo enhancement throughout the arterial ,venous and late phase ( P ＜0 .05) . T he accuracy of preoperative diagnosis of CEUS was 95 .6% . Conclusions Depending on its unique advantages such as real‐time observation ,high‐resolution imaging ,and no radiation ,CEUS is helpful for early detection ,accurate localization and preoperative diagnosis of SPN . CEUS has potential role for clinical decision‐making before treatment .
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Objective To investigate the imaging anatomy and clinical significance of the inferior pancreaticoduodenal veins (IPDVs).Methods The retrospective and descriptive study was conducted.The clinicopathological data of 42 patients with pancreatic head ductal adenocarcinoma who were admitted to Peking Union Medical College Hospital from January to June 2018 were collected.There were 24 males and 18 females,aged from 41 to 78 years,with an average age of 61 years.Patients received preoperative contrast-enhanced computed tomography (CT) examination with 1 mm slice thickness,and underwent corresponding surgery according to the preoperative evaluation.Observation indicators:(1) results of preoperative CT examination;(2) surgical situations.Normality of measurement data was analyzed using Shapiro-Wilk test.Measurement data with skewed distribution were described as M (QR) or M (range),and comparison between groups was analyzed by the Mann-Whitney U test.Count data were described as absolute number or percentage,and comparison between groups was analyzed by the chi-square test.Results (1) Results of preoperative CT examination:42 patients received preoperative contrast-enhanced CT examination with 1 mm slice thickness.① The first jejunal venous trunk was identified in all the 42 patients.The first jejunal venous trunk crossed dorsal to the superior mesenteric artery (SMA) in 34 patients and ventral to the SMA in 8 patients.② Of 42 patients,2 showed no IPDV,and 40 showed IPDV including 23 with 1 IPDV,13 with 2 IPDVs,3 with 3 IPDVs,and 1 with 4 IPDVs.A total of 62 IPDVs were identified in the 42 patients,with an average IPDV number of 1 (range,0-4).There were 43 IPDVs drained into first or second jejunal venous trunks and 19 IPDVs drained into superior mesenteric vein (SMV).③ Of 42 patients,type Ⅰ IPDV was identified in 32 patients including 20 with 1 IPDV drained into jejunal venous trunk at dorsal side of SMA,7 with 2 IPDVs drained into jejunal venous trunk at dorsal side of SMA,2 with 3 IPDVs drained into jejunal venous trunk at dorsal side of SMA,and 3 with 1 IPDV drained into jejunal venous trunk at ventral side of SMA,and non-type Ⅰ IPDV was identified in 10 patients;type Ⅱ IPDV was identified in 18 patients including 17 with 1 IPDV drained into SMV and 1 with 2 IPDVs drained into SMV,and non-type Ⅱ IPDV was identified in 24 patients.Some patients can simultaneously had type Ⅰ and type Ⅱ IPDV.(2) Surgical situations:42 patients underwent pancreatoduodenectomy,14 of which underwent laparoscopic surgery and 28 underwent open surgery.There were 5 cases with SMV or portal vein reconstruction,and 18 with intraoperative blood transfusion.All the 42 patients were diagnosed as pancreatic ductal adenocarcinoma by postoperative pathological examination,including 30 of R0 resection and 12 of R1 resection.The volume of intraoperative blood loss,cases with intraoperative blood transfusion,cases with R0 and R1 resection (situation of surgical margin),cases with SMV or portal vein reconstruction were 650 mL(853 mL),15,20,12,4 in the 32 patients with type Ⅰ IPDV,aod 475 mL (480 mL),3,10,0,1 in the 10 patients with non-type Ⅰ IPDV;there were significant differences in the volume of intraoperative blood loss and situation of surgical margin (Z=94.000,x2=5.250,P＜ 0.05).There was no significant difference in the cases with intraoperative blood transfusion,cases with SMV or portal vein reconstruction between patients with type Ⅰ and non-type Ⅰ IPDV (x2 =0.045,0.886,P＞0.05).Conclusions IPDVs can be distinguished on the contrast-enhanced CT with slice thickness,and classified as IPDVs drained into SMV or jejunal venous trunk.It is necessary to carefully deal with IPDVs drained into jejunal venous trunk in the pancreaticoduodenectomy due to its more volume of intraoperative blood loss and lower R0 resection rate.