PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine tumors.However,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains uncertain.Methods:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were examined.Grade of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was evaluated.Results:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS.The GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic factors.The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions:Ki-67 is a valuable prognostic indicator for PDAC.Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Correlation of dynamic contrast-enhanced ultrasonography and the Ki-67 labelling index in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly malignant and aggressive tumor,and high Ki-67 expression indicates poor histological differentiation and prognosis.Therefore,one of the challenges in diagnosing preoperatively patients with PDAC is predicting the degree of malignancy.Dynamic contrast-enhanced ultrasonography(DCE-US)plays a crucial role in abdominal tumor diagnosis,and can adequately show the microvascular composition within the tumors.However,the relationship between DCE-US and the Ki-67 labelling index remains unclear at the present time.AIM To predict the correlation between Ki-67 expression and the parameters of DCEUS.METHODS Patients with PDAC who underwent DCE-US were retrospectively analyzed.Patients who had received any treatment(radiotherapy or chemotherapy)prior to DCE-US;had incomplete clinical,imaging,or pathologic information;and had poor-quality image analysis were excluded.Correlations between Ki-67 expression and the parameters of DCE-US in patients with PDAC were assessed using Spearman’s rank correlation analysis.The diagnostic performances of these parameters in high Ki-67 expression group were evaluated according to receiver operating characteristic curve.RESULTS Based on the Ki-67 labelling index,30 patients were divided into two groups,i.e.,the high expression group and the low expression group.Among the relative quantitative parameters between the two groups,relative half-decrease time(rHDT),relative peak enhancement,relative wash-in perfusion index and relative wash-in rate were significantly different between two groups(P=0.018,P=0.025,P=0.028,P=0.035,respectively).The DCE-US parameter rHDT was moderately correlated with Ki-67 expression,and rHDT≥1.07 was more helpful in accurately diagnosing high Ki-67 expression,exhibiting a sensitivity and specificity of 53.8%and 94.1%,respectively.CONCLUSION One parameter of DCE-US,rHDT,correlates with high Ki-67 expression.It demonstrates that parameters obtained noninvasively by DCE-US could better predict Ki-67 expression in PDAC preoperatively.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization

BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis.Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis.METHODS Cell culture and various experiments,including protein analysis,immunohisto-chemistry,and animal model experiments,were conducted.We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features.Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers.Finally,we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms.RESULTS Our research showed that there was a significant increase in FAM53B levels in PDAC tissues,which was linked to adverse tumor features.Experimental findings indicated that FAM53B can enhance macrophage M2 polarization,leading to increased anti-inflammatory factor release.The results from the mouse model further supported the role of FAM53B in PDAC metastasis,as blocking FAM53B prevented tumor cell invasion and metastasis.CONCLUSION FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization.This discovery could lead to the development of new strategies for treating PDAC.For example,interfering with the FAM53B signaling pathway may prevent cancer spread.Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.

Computed tomography-based radiomics diagnostic approach for differential diagnosis between early-and late-stage pancreatic ductal adenocarcinoma

BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late stages.There is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest stages.METHODS A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography(CT)within 30 d prior to surgery were included in the study.Tumor staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging system.Radiomics features were extracted from the region of interest(ROI)for each patient using Analysis Kit software.The most important and predictive radiomics features were selected using Mann-Whitney U test,univar-iate logistic regression analysis,and minimum redundancy maximum relevance(MRMR)method.Random forest(RF)method was used to construct the radiomics model,and 10-times leave group out cross-validation(LGOCV)method was used to validate the robustness and reproducibility of the model.RESULTS A total of 792 radiomics features(396 from late arterial phase and 396 from portal venous phase)were extracted from the ROI for each patient using Analysis Kit software.Nine most important and predictive features were selected using Mann-Whitney U test,univariate logistic regression analysis,and MRMR method.RF method was used to construct the radiomics model with the nine most predictive radiomics features,which showed a high discriminative ability with 97.7%accuracy,97.6%sensitivity,97.8%specificity,98.4%positive predictive value,and 96.8%negative predictive value.The radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built models.CONCLUSION The radiomics model based on CT could serve as a promising non-invasive method in differential diagnosis between early and late stage PDAC.

Comparison of prognosis and postoperative morbidities between standard pancreaticoduodenectomy and the TRIANGLE technique for resectable pancreatic ductal adenocarcinoma

BACKGROUND Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocar-cinoma(PDAC),although tumor recurrence,especially locally,still inhibits the treatment efficacy.The TRIANGLE technique was introduced as an extended dissection procedure to improve the R0 resection rate of borderline resectable or locally advanced PDAC.However,there was a lack of studies concerning postoperative complications and long-term outcomes of this procedure on patients with resectable PDAC.PDAC.METHODS Patients with resectable PDAC eligible for PD from our hospital between June 2018 and December 2021 were enrolled in this retrospective cohort study.All the patients were divided into PDstandard and PDTRIANGLE groups according to the surgical procedure.Baseline characteristics,surgical data,and postoperative morbidities were recorded.All of the patients were followed up,and the date and location of tumor recurrence,and death were recorded.The Kaplan-Meier method and log-rank test were used for the survival analysis.RESULTS There were 93 patients included in the study and 37 underwent the TRIANGLE technique.Duration of operation was longer in the PDTRIANGLE group compared with the PDstandard group[440(410-480)min vs 320(265-427)min](P=0.001).Intraoperative blood loss[700(500-1200)mL vs 500(300-800)mL](P=0.009)and blood transfusion[975(0-1250)mL vs 400(0-800)mL](P=0.009)were higher in the PDTRIANGLE group.There was a higher incidence of surgical site infection(43.2%vs 12.5%)(P=0.001)and postoperative diarrhea(54.1%vs 12.5%)(P=0.001)in the PDTRIANGLE group.The rates of R0 resection and local recurrence,overall survival,and disease-free survival did not differ significantly between the two groups.CONCLUSION The TRIANGLE technique is safe,with acceptable postoperative morbidities compared with standardized PD,but it does not improve prognosis for patients with resectable PDAC.

Recurrence scoring system predicting early recurrence for patients with pancreatic ductal adenocarcinoma undergoing pancreatectomy and portomesenteric vein resection

BACKGROUND Pancreatectomy with concomitant portomesenteric vein resection(PVR)enables patients with portomesenteric vein(PV)involvement to achieve radical resection of pancreatic ductal adenocarcinoma,however,early recurrence(ER)is frequently observed.AIM To predict ER and identify patients at high risk of ER for individualized therapy.METHODS Totally 238 patients undergoing pancreatectomy and PVR were retrospectively enrolled and were allocated to the training or validating cohort.Univariate Cox and LASSO regression analyses were performed to construct serum recurrence score(SRS)based on 26 serum-derived parameters.Uni-and multivariate Cox regression analyses of SRS and 18 clinicopathological variables were performed to establish a Nomogram.Receiver operating characteristic curve analysis was used to evaluate the predictive accuracy.Survival analysis was performed using Kaplan-Meier method and log-rank test.RESULTS Independent serum-derived recurrence-relevant factors of LASSO regression model,including postoperative carbohydrate antigen 19-9,postoperative carcinoembryonic antigen,postoperative carbohydrate antigen 125,preoperative albumin(ALB),preoperative platelet to ALB ratio,and postoperative platelets to lymphocytes ratio,were used to construct SRS[area under the curve(AUC):0.855,95%CI:0.786–0.924].Independent risk factors of recurrence,including SRS[hazard ratio(HR):1.688,95%CI:1.075-2.652],pain(HR:1.653,95%CI:1.052-2.598),perineural invasion(HR:2.070,95%CI:0.827-5.182),and PV invasion(HR:1.603,95%CI:1.063-2.417),were used to establish the recurrence nomogram(AUC:0.869,95%CI:0.803-0.934).Patients with either SRS>0.53 or recurrence nomogram score>4.23 were considered at high risk for ER,and had poor long-term outcomes.CONCLUSION The recurrence scoring system unique for pancreatectomy and PVR,will help clinicians in predicting recurrence efficiently and identifying patients at high risk of ER for individualized therapy.

Postoperative serum tumor markers-based nomogram predicting early recurrence for patients undergoing radical resections of pancreatic ductal adenocarcinoma

BACKGROUND Early recurrence(ER)is associated with dismal outcomes in patients undergoing radical resection for pancreatic ductal adenocarcinoma(PDAC).Approaches for predicting ER will help clinicians in implementing individualized adjuvant therapies.Postoperative serum tumor markers(STMs)are indicators of tumor progression and may improve current systems for predicting ER.AIM To establish an improved nomogram based on postoperative STMs to predict ER in PDAC.METHODS We retrospectively enrolled 282 patients who underwent radical resection for PDAC at our institute between 2019 and 2021.Univariate and multivariate Cox regression analyses of variables with or without postoperative STMs,were performed to identify independent risk factors for ER.A nomogram was constructed based on the independent postoperative STMs.Receiver operating characteristic curve analysis was used to evaluate the area under the curve(AUC)of the nomogram.Survival analysis was performed using Kaplan-Meier survival plot and log-rank test.RESULTS Postoperative carbohydrate antigen 19-9 and carcinoembryonic antigen levels,preoperative carbohydrate antigen 125 levels,perineural invasion,and pTNM stage III were independent risk factors for ER in PDAC.The postoperative STMs-based nomogram(AUC:0.774,95%CI:0.713-0.835)had superior accuracy in predicting ER compared with the nomogram without postoperative STMs(AUC:0.688,95%CI:0.625-0.750)(P=0.016).Patients with a recurrence nomogram score(RNS)>1.56 were at high risk for ER,and had significantly poorer recurrence-free survival[median:3.08 months,interquartile range(IQR):1.80-8.15]than those with RNS≤1.56(14.00 months,IQR:6.67-24.80),P<0.001).CONCLUSION The postoperative STMs-based nomogram improves the predictive accuracy of ER in PDAC,stratifies the risk of ER,and identifies patients at high risk of ER for tailored adjuvant therapies.

Cystic ductal adenocarcinoma of pancreas complicated with neuroendocrine tumor:A case report and review of literature

BACKGROUND Difficulties in making an accurate preoperative diagnosis of cystic pancreatic lesions pose a challenge for radiologists.It would be helpful to report rare cases and review the literature.CASE SUMMARY In the present report,a case of a patient with a pancreatic cystic lesion initially misdiagnosed as a pseudocyst by radiologist was documented,which was later pathologically confirmed as pancreatic ductal adenocarcinoma with neuroendocrine tumor.However,subsequent literature review yielded no previous reports of pancreatic ductal adenocarcinoma with neuroendocrine tumors and cystic lesions.Therefore,literature on the imaging diagnosis of pancreatic cystic lesions was instead reviewed and discussed.CONCLUSION Careful evaluation of the characteristics revealed by multimodal imaging techniques,medical history,laboratory examination data and follow-up observations,is critical to the diagnosis and treatment of pancreatic cystic disease.We provide valuable insights into the diagnosis of pancreatic cystic disease through a rare case report and literature review.

Comparison between solid pseudopapillary neoplasms of the pancreas and pancreatic ductal adenocarcinoma with cystic changes using computed tomography

BACKGROUND Solid pseudopapillary neoplasms of the pancreas(SPN)share similar imaging findings with pancreatic ductal adenocarcinoma with cystic changes(PDAC with cystic changes),which may result in unnecessary surgery.AIM To investigate the value of computed tomography(CT)in differentiation of SPN from PDAC with cystic changes.METHODS This study retrospectively analyzed the clinical and imaging findings of 32 patients diagnosed with SPN and 14 patients diagnosed with PDAC exhibiting cystic changes,confirmed through pathological diagnosis.Quantitative and qualitative analysis was performed,including assessment of age,sex,tumor size,shape,margin,density,enhancement pattern,CT values of tumors,CT contrast enhancement ratios,“floating cloud sign,”calcification,main pancreatic duct dilatation,pancreatic atrophy,and peripancreatic invasion or distal metastasis.Multivariate logistic regression analysis was used to identify relevant features to differentiate between SPN and PDAC with cystic changes,and receiver operating characteristic curves were obtained to evaluate the diagnostic performance of each variable and their combination.RESULTS When compared to PDAC with cystic changes,SPN had a lower age(32 years vs 64 years,P<0.05)and a slightly larger size(5.41 cm vs 3.90 cm,P<0.05).SPN had a higher frequency of“floating cloud sign”and peripancreatic invasion or distal metastasis than PDAC with cystic changes(both P<0.05).No significant difference was found with respect to sex,tumor location,shape,margin,density,main pancreatic duct dilatation,calcification,pancreatic atrophy,enhancement pattern,CT values of tumors,or CT contrast enhancement ratios between the two groups(all P>0.05).The area under the receiver operating characteristic curve of the combination was 0.833(95%confidence interval:0.708-0.957)with 78.6%sensitivity,81.3%specificity,and 80.4%accuracy in differentiation of SPN from PDAC with cystic changes.CONCLUSION A larger tumor size,“floating cloud sign,”and peripancreatic invasion or distal metastasis are useful CT imaging features that are more common in SPN and may help discriminate SPN from PDAC with cystic changes.

Robotic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: Analysis of surgical outcomes and long-term prognosis in a high-volume center

Background: Robotic pancreaticoduodenectomy(RPD) has been reported to be safe and feasible for patients with pancreatic ductal adenocarcinoma(PDAC) of the pancreatic head. This study aimed to analyze the surgical outcomes and risk factors for poor long-term prognosis of these patients. Methods: Data from patients who underwent RPD for PDAC of pancreatic head were retrospectively analyzed. Multivariate Cox regression analysis was used to seek the independent prognostic factors for overall survival(OS), and an online nomogram calculator was developed based on the independent prognostic factors. Results: Of the 273 patients who met the inclusion criteria, the median operative time was 280.0 minutes, the estimated blood loss was 100.0 m L, the median OS was 23.6 months, and the median recurrence-free survival(RFS) was 14.4 months. Multivariate analysis showed that preoperative carbohydrate antigen 19-9(CA19-9) [hazard ratio(HR) = 2.607, 95% confidence interval(CI): 1.560-4.354, P < 0.001], lymph node metastasis(HR = 1.429, 95% CI: 1.005-2.034, P = 0.047), tumor moderately(HR = 3.190, 95% CI: 1.813-5.614, P < 0.001) or poorly differentiated(HR = 5.114, 95% CI: 2.839-9.212, P < 0.001), and Clavien-Dindo grade ≥ Ⅲ(HR = 1.657, 95% CI: 1.079-2.546, P = 0.021) were independent prognostic factors for OS. The concordance index(C-index) of the nomogram constructed based on the above four independent prognostic factors was 0.685(95% CI: 0.640-0.729), which was significantly higher than that of the AJCC staging(8th edition): 0.541(95% CI: 0.493-0.589)( P < 0.001). Conclusions: This large-scale study indicated that RPD was feasible for PDAC of pancreatic head. Preoperative CA19-9, lymph node metastasis, tumor poorly differentiated, and Clavien-Dindo grade ≥ Ⅲ were independent prognostic factors for OS. The online nomogram calculator could predict the OS of these patients in a simple and convenient manner.

Robotic versus laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: A propensity score-matched analysis

Background: Minimally invasive surgery is becoming increasingly popular in the field of pancreatic surgery. However, there are few studies of robotic distal pancreatectomy(RDP) for pancreatic ductal adenocarcinoma(PDAC). This study aimed to investigate the efficacy and feasibility of RDP for PDAC. Methods: Patients who underwent RDP or laparoscopic distal pancreatectomy(LDP) for PDAC between January 2015 and September 2020 were reviewed. Propensity score matching analyses were performed. Results: Of the 335 patients included in the study, 24 underwent RDP and 311 underwent LDP. A total of 21 RDP patients were matched 1:1 with LDP patients. RDP was associated with longer operative time(209.7 vs. 163.2 min;P = 0.003), lower open conversion rate(0% vs. 4.8%;P < 0.001), higher cost(15 722 vs. 12 699 dollars;P = 0.003), and a higher rate of achievement of an R0 resection margin(90.5% vs. 61.9%;P = 0.042). However, postoperative pancreatic fistula grade B or C showed no significant intergroup difference(9.5% vs. 9.5%). The median disease-free survival(34.5 vs. 17.3 months;P = 0.588) and overall survival(37.7 vs. 21.9 months;P = 0.171) were comparable between the groups. Conclusions: RDP is associated with longer operative time, a higher cost of surgery, and a higher likelihood of achieving R0 margins than LDP.

Serum biomarkers for the differentiation of autoimmune pancreatitis from pancreatic ductal adenocarcinoma

Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).Serum biomarkers,substances that quantitatively change in sera during disease development,are a promising non-invasive tool with high utility for differentiating between these diseases.In this way,the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4(IgG4)antibody are elevated.However,this approach has some drawbacks.Notably,IgG4 antibody concentrations are also elevated in sera from some patients with PDAC.This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC,evaluating the usefulness of immunoglobulins,autoantibodies,chemokines,and cytokines.The proposed serum biomarkers have proven useful,although most studies had a small sample size,did not examine their presence in patients with PDAC,or did not test them in humans.In addition,current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity,either alone or in combination with clinical data and/or radiological images.

Establishment of organoid models for pancreatic ductal adenocarcinoma and screening of individualized therapy strategy

Background:Patients with pancreatic ductal adenocarcinoma(PDAC)who undergo surgical resection and receive effective chemotherapy have the best chance for longterm survival.Unfortunately,because of the heterogeneity of pancreatic cancer,it is difficult to find a personalized treatment strategy for patients.Organoids are ideal preclinical models for personalized medicine.Therefore,we explore the cultivation conditions and construction methods of PDAC organoid models to screen the individualized therapy strategy.Methods:Fresh PDAC tissues from surgical resection were collected and digested with digestive enzymes;then the tumor cells were embedded in Matrigel with a suitable medium to establish the PDAC organoid models.The genetic stability of the organoids was analyzed using whole exon sequencing;hematoxylin and eosin staining and immunohistochemistry of organoids were performed to analyze their consistency with the pathological morphology of the patient's tumor tissue;After 2 days of organoid culture,we selected four commonly used clinical chemotherapy drugs for single or combined treatment to analyze drug sensitivity.Results:Two cases of PDAC organoid models were successfully established,and the results of their pathological characteristics and exome sequencing were consistent with those of the patient's tumor tissue.Both PDAC organoids showed more sensitivity to gemcitabine and cisplatin,and the combined treatment was more effective than monotherapy.Conclusion:Both organoids better retained the pathological characteristics,genomic stability,and heterogeneity with the original tumor.Individual PDAC organoids exhibited different sensitivities to the same drugs.Thus,this study provided ideal experimental models for screening individualized therapy strategy for patients with PDAC.

Derivation and validation of a preoperative prognostic model for resectable pancreatic ductal adenocarcinoma

Background: The prognosis of patients with pancreatic ductal adenocarcinoma(PDAC) remains poor even after radical pancreaticoduodenectomy(PD). The study aimed to develop and validate a novel preoperative prognostic model to accurately predict the long-term survival of patients with PDAC.Methods: Patients with PDAC of pancreatic head from Chinese PLA General Hospital were included. The preoperative PDAC model with contour plots was developed using a non-linear model in the training cohort and then tested in the validation cohort.Results: Of 421 patients who met the inclusion criteria, 280 were in the training cohort and 141 in the validation cohort. Contour plots for preoperative PDAC model were established to visually predict the survival probabilities of these patients, based on preoperative carbohydrate antigen 19-9, preoperative fibrinogen to albumin ratio and pain symptoms. This model stratified patients into low-and high-risk groups with distinctly different long-term survival in the training cohort [median overall survival(OS)32.1 vs. 17.5 months;median recurrence-free survival(RFS) 19.3 vs. 10.0 months, both P < 0.001] and the validation cohort(median OS 28.3 vs. 19.0 months;median RFS 17.5 vs. 11.2 months, both P < 0.001).Time-dependent receiver operating characteristic and decision curve analyses revealed that the model provided higher diagnostic accuracy and superior net benefit compared to other staging systems.Conclusions: This study constructed and validated a novel preoperative prognostic model that can accurately and conveniently predict the long-term survival of patients with resectable PDAC of pancreatic head. Besides, the model can screen high-risk patients with poor prognosis, which may provide references for personal treatment strategies in the future.

Survival benefits and disparities in radiation therapy for elderly patients with pancreatic ductal adenocarcinoma

BACKGROUND Older patients represent a unique subgroup of the cancer patient population,for which the role of cancer therapy requires special consideration.However,the outcomes of radiation therapy(RT)in elderly patients with pancreatic ductal adenocarcinoma(PDAC)are not well-defined in the literature.AIM To explore the use and effectiveness of RT in the treatment of elderly patients with PDAC in clinical practice.METHODS Data from patients with PDAC aged≥65 years between 2004 and 2018 were collected from the Surveillance,Epidemiology,and End Results database.Multivariate logistic regression analysis was performed to determine factors associated with RT administration.Overall survival(OS)and cancer-specific survival(CSS)were evaluated using the Kaplan–Meier method with the log-rank test.Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors for OS.Propensity score matching(PSM)was applied to balance the baseline characteristics between the RT and non-RT groups.Subgroup analyses were performed based on clinical characteristics.RESULTS A total of 12245 patients met the inclusion criteria,of whom 2551(20.8%)were treated with RT and 9694(79.2%)were not.The odds of receiving RT increased with younger age,diagnosis in an earlier period,primary site in the head,localized disease,greater tumor size,and receiving chemotherapy(all P<0.05).Before PSM,the RT group had better outcomes than did the non-RT group[median OS,14.0 vs 6.0 mo;hazard ratio(HR)for OS:0.862,95%confidence interval(CI):0.819–0.908,P<0.001;and HR for CSS:0.867,95%CI:0.823–0.914,P<0.001].After PSM,the survival benefit associated with RT remained comparable(median OS:14.0 vs 11.0 mo;HR for OS:0.818,95%CI:0.768–0.872,P<0.001;and HR for CSS:0.816,95%CI:0.765–0.871,P<0.001).Subgroup analysis revealed that the survival benefits(OS and CSS)of RT were more significant in patients aged 65 to 80 years,in regional and distant stages,with no surgery,and receiving chemotherapy.CONCLUSION RT improved the outcome of elderly patients with PDAC,particularly those aged 65 to 80 years,in regional and distant stages,with no surgery,and who received chemotherapy.Further prospective studies are warranted to validate our results.

Current controversies and challenges for resection of pancreatic ductal adenocarcinoma in pancreatic head aiming at cure

Pancreatic ductal adenocarcinoma(PDAC) is a very common but a highly lethal malignancy due to its biological aggressive behavior. PDAC more commonly affects the head than other parts of the pancreas. As PDAC in the head of pancreas is located at an anatomical position with a lot of adjacent vital structures, and the cornerstone of treatment aiming at cure is pancreaticoduodenectomy(PD).

Roles of lncRNAs in pancreatic ductal adenocarcinoma: Diagnosis,treatment, and the development of drug resistance

Background: Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs(lnc RNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. Data sources: We carried out a systematic review on lnc RNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lnc RNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in Pub Med with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lnc RNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed. Results: Lnc RNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting mi RNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process. Conclusions: The functional lnc RNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC.

Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma

BACKGROUND Islet amyloid deposition and reducedβ-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects.To date,the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma(PDAC)have not been specifically addressed.AIM To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences(proximal vs distal residual pancreas)are associated with islet amyloid deposition.METHODS We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients,including 14 patients with normal glucose tolerance(NGT),16 patients with prediabetes and 15 new-onset diabetes(NOD)patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020.Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans.Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows:(1)Hematoxylin and eosin for general histological appearance;(2)hematoxylin and insulin for the determination of fractionalβ-cell area(immunohistochemistry);and(3)quadruple insulin,glucagon,thioflavin T and DAPI staining for the determination ofβ-cell area,α-cell area and amyloid deposits.RESULTS Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition,fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions,especially in the prediabetes and NOD groups.Consistent with this finding,the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group(37.35±12.16 cm^(3) vs 69.79±18.17 cm^(3),P<0.001).As expected,islets that stained positive for amyloid(islet amyloid density)were found in the majority of PDAC cases.The proportion of amyloid/islet area(severity of amyloid deposition)was significantly higher in both prediabetes and NOD patients than in NGT patients(P=0.002;P<0.0001,respectively).We further examined the regional differences in islet amyloid deposits.Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups(3.98%±3.39%vs 0.50%±0.72%,P=0.01;12.03%vs 1.51%,P=0.001,respectively).CONCLUSION In conclusion,these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation,which may be associated with the pathogenesis of NOD secondary to PDAC.