BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment opti...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.展开更多
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...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.展开更多
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)immunohistochemis...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.展开更多
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 i...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.展开更多
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 diagno...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.展开更多
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 r...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.展开更多
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...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.展开更多
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 identif...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.展开更多
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 l...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.展开更多
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 re...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.展开更多
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...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.展开更多
AIM:To investigate the expression of toll-like receptor(TLR) 4,nuclear factor-κB(NF-κB) p65 and hypoxiainducible transcription factor 1α(HIF-1α) in pancreatic ductal adenocarcinoma and their clinical significance....AIM:To investigate the expression of toll-like receptor(TLR) 4,nuclear factor-κB(NF-κB) p65 and hypoxiainducible transcription factor 1α(HIF-1α) in pancreatic ductal adenocarcinoma and their clinical significance.METHODS:The mRNA of TLR4 and HIF-1α were investigated by real-time polymerase chain reaction in 30 cases of pancreatic ductal adenocarcinoma and its adjacent tissues,and expression of TLR4,NF-κB p65 and HIF-1α protein were detected by immunohistochemistry in 65 cases of pancreatic ductal adenocarcinoma tissues and 38 cases of corresponding adjacent tissues.The relationship between TLR4 or HIF-1α and pathologic features,as well as the association between TLR4 and HIF-1α,were also analyzed.Kaplan-Meier method was used to assess the impact of expression of TLR4 and HIF-1α on survival of patients with pancreatic cancer.RESULTS:The relative quantif ication of TLR4 and HIF-1α mRNA in tumor tissues was 0.81±0.10 and 0.87±0.11,respectively,signif icantly higher than that in adjacent tissues(0.81±0.10 vs 0.70±0.16,P=0.002;0.87±0.11 vs 0.68±0.13,P=0.000).The protein expression of TLR4,NF-κB p65 and HIF-1α in tumor tissues was 69.20%,66.15% and 70.80%,respectively,being signif icantly higher than that in adjacent normal tissues(69.20% vs 39.50%,P=0.003;66.15% vs 31.58%,P=0.001;70.80% vs 36.80%,P=0.001).There was no signif icant correlation between TLR4 or HIF-1α expression and the age,gender,tumor location,the degree of tumor differentiation in the patients(P>0.05).However,there was signif icant correlation between the expression of TLR4 or HIF-1α and tumor size,lymph node metastasis,venous invasion and clinical staging(P<0.05).The expression of TLR4 and HIF-1α had a signif icant impact on survival of patients with pancreatic adenocarcinoma.CONCLUSION:TLR4,NF-κB p65 and HIF-1α are overexpressed in pancreatic adenocarcinoma,TLR4 may be partly involved in up-regulating HIF-1α,and both synergestically promote development of pancreatic adenocarcinoma.展开更多
Objective： To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma （PDAC）. Methods： Parasympathetic neurogene...Objective： To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma （PDAC）. Methods： Parasympathetic neurogenesis was defined as the distribution of abnormal parasympathetic nerves in the stroma tissue. Staining of vesicular acetylcholine transporter （VAChT）, as a marker for parasympathetic neurogenesis, was performed on a representative specimen of the tumor for 59 PDAC patients with available clinical, pathologic, and follow-up information. Three specimens containing normal pancreatic tissues were stained in parallel. The number of parasympathetic nerve fibers was counted in five high-power microscopic fields （5×0.785 mm2）. Cut-offvalues were calculated by receiver operating characteristic curve analysis. Results： VAChT-positive parasympathetic nerve fibers were not seen in the stroma of 3 cases of normal pancreatic tissues. In 59 PDAC cases, the range of parasympathetic neurogenesis was 4-38 fibers/（5×0.785） mm2, with a median of 18 fibers/（5×0.785） mm2. Patients with parasympathetic neurogenesis 〉 15 fibers/（5×0.785） mm2 were defined as the high-density group （39 patients, 66.1%）, and those with parasympathetic neurogenesis 〈15 fibers/（5×0.785） mm2 as the low-density group （20 patients, 33.9%）. The high-density group had a higher occurrence of tumor budding （P=0.001） and a higher rate of early recurrence （P=0.035）. Parasympathetic neurogenesis appeared to be an independent adverse prognostic factor [hazard ratio （HR）=2.45, 95% confidence interval （95% CI）： 1.25-4.81, P=0.009], in addition to American Joint Committee on Cancer （AJCC） stage （P=0.010） and tumor budding （P=0.009）. Conclusions： Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in PDAC.展开更多
Despite major improvements concerning its diagnosis and treatment,pancreatic ductal adenocarcinoma(PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology,as interface discipline between basic ...Despite major improvements concerning its diagnosis and treatment,pancreatic ductal adenocarcinoma(PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology,as interface discipline between basic and clinical medicine,has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition,by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC,a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC.This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results.Finally,recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response.The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.展开更多
BACKGROUND： Various scoring systems based on assessment of the systemic inflammatory response help assessing the prognosis of patients with pancreatic ductal adenocarcinoma.In the present systematic review we evaluat...BACKGROUND： Various scoring systems based on assessment of the systemic inflammatory response help assessing the prognosis of patients with pancreatic ductal adenocarcinoma.In the present systematic review we evaluated the validity of four pre-intervention scoring systems： Glasgow prognostic score（GPS） and its modified version（mGPS）, platelet lymphocyte ratio（PLR）, neutrophil lymphocyte ratio（NLR）, and prognostic nutrition index（PNI）.DATA SOURCES： MOOSE guidelines were followed and EMBASE and MEDLINE databases were searched for all published studies until September 2013 using comprehensive text word and MeSH terms. All identified studies were analyzed, and relevant studies were included in the systematic review.RESULTS： Six studies were identified for GPS/mGPS with3 reporting statistical significance for GPS/mGPS on both univariate analysis（UVA） and multivariate analysis（MVA）.Two studies suggested prognostic significance on UVA but not MVA, and in the final study UVA failed to show significance.Eleven studies evaluated the prognostic value of NLR. Six of them reported prognostic significance for NLR on UVA that persisted at MVA in 4 studies, and in the remaining 2 studies NLR was the only significant factor on UVA. In the remaining5 studies, all in patients undergoing resection, there was no significance on UVA. Seven studies evaluated PLR, with only one study demonstrated its prognostic significance on both UVAand MVA, the rest did not show the significance on UVA. Of the two studies identified for PNI, one demonstrated a statistically significant difference in survival on both UVA and MVA, and the other reported no significance for PNI on UVA.CONCLUSIONS： Both GPS/mGPS and NLR may be useful but further better-designed studies are required to confirm their value. PLR might be little useful, and there are at present inadequate data to assess the prognostic value of PNI. At present, no scoring system is reliable enough to be accepted into routine use for the prognosis of patients with pancreatic ductal adenocarcinoma.展开更多
AIM To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma(PDAC) and assess unresectability of synchronous liver metastasis.METHODS Retrospective records of PDAC patie...AIM To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma(PDAC) and assess unresectability of synchronous liver metastasis.METHODS Retrospective records of PDAC patients with synchronous liver metastasis who underwent simultaneous resections of primary PDAC and synchronous liver metastasis, or palliative surgical bypass, were collected from 2007 to 2015. A series of pre-operative clinical parameters, including tumor markers and inflammation-based indices, were analyzed by logistic regression to figure out predictive factors and assess unresectability of synchronous liver metastasis. Cox regression was used to identify prognostic factors in liver-metastasized PDAC patients after surgery, with intention to validate their conformance to the indications of simultaneous resections and palliative surgical bypass. Survival of patients from different groups were analyzed by the Kaplan-Meier method. Intra- and post-operative courses were compared, including complications. PDAC patients with no distant metastases who underwent curative resection served as the control group.RESULTS CA125 > 38 U/mL(OR = 12.397, 95%CI: 5.468-28.105, P < 0.001) and diabetes mellitus(OR = 3.343, 95%CI: 1.539-7.262, P = 0.002) independently predicted synchronous liver metastasis from resectable PDAC. CA125 > 62 U/mL(OR = 5.181, 95%CI: 1.612-16.665, P = 0.006) and age > 62 years(OR = 3.921, 95%CI: 1.217-12.632, P = 0.022) correlated with unresectability of synchronous liver metastasis, both of which also indicated a worse long-term outcome of liver-metastasized PDAC patients after surgery. After the simultaneous resections, patients with postoperatively elevated serum CA125 levels had shorter survival than those with post-operatively reduced serum CA125 levels(7.7 mo vs 16.3 mo, P = 0.013). The survival of liver-metastasized PDAC patients who underwent the simultaneous resections was similar to that of non-metastasized PDAC patients who underwent curative pancreatectomy alone(7.0 mo vs 16.9 mo, P < 0.001), with no higher rates of either pancreatic fistula(P = 0.072) or other complications(P = 0.230) and no greater impacts on length of hospital stay(P = 0.602) or post-operative diabetic control(P = 0.479).CONCLUSION The criterion set up by CA125 levels could facilitate careful diagnosis of synchronous liver metastases from PDAC, and prudent selection of appropriate patients for the simultaneous resections.展开更多
BACKGROUND Inflammation plays an important role in tumor progression,and growing evidence has confirmed that the fibrinogen-to-albumin ratio(FAR)is an important prognostic factor for overall survival in malignant tumo...BACKGROUND Inflammation plays an important role in tumor progression,and growing evidence has confirmed that the fibrinogen-to-albumin ratio(FAR)is an important prognostic factor for overall survival in malignant tumors.AIM To investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma(PDAC).METHODS We retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019.The surv_cutpoint function of the R package survminer via RStudio software(version 1.3.1073,http://www.rstudio.org)was used to determine the optimal cut-off values of biological markers,such as preoperative FAR.The Kaplan-Meier method and log-rank tests were used for univariate survival analysis,and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection.RESULTS The optimal cut-off value of FAR was 0.08 by the surv_cutpoint function.Higher preoperative FAR was significantly correlated with clinical symptoms(P=0.001),tumor location(P<0.001),surgical approaches(P<0.001),preoperative plasma fibrinogen concentration(P<0.001),and preoperative plasma albumin level(P<0.001).Multivariate analysis showed that degree of tumor differentiation(P<0.001),number of metastatic lymph nodes[hazard ratio(HR):0.678,95%confidence interval(CI):0.509-0.904,P=0.008],adjuvant therapy(HR:1.604,95%CI:1.214-2.118,P=0.001),preoperative cancer antigen 19-9 level(HR:1.740,95%CI:1.288-2.352,P<0.001),and preoperative FAR(HR:2.258,95%CI:1.720-2.963,P<0.001)were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection.CONCLUSION The increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC.Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.展开更多
Authors introduction： Qian Zhan, female, who was born in Sept, 1979. She studied in the Shanghai Second Medical University during 1998 to 2005. She majored in Clinical Medicine, and earned her master degree in 2005. ...Authors introduction： Qian Zhan, female, who was born in Sept, 1979. She studied in the Shanghai Second Medical University during 1998 to 2005. She majored in Clinical Medicine, and earned her master degree in 2005. In 2005, she went to the Beaujon Hospital of Paris 7th Universit3. in France, as a foreign intern. Later, she came to postgraduate work and residencies in the general surgery department of Shanghai Ruijin Hospital. Her clinical work is focused on multidisciplinary especially postoperative management for the patients with pancreatic cancer. In addition, she is a lead researcher in the pancreatic cancer group for nano based drug delivery, systems. Chenghong Peng, male, who was born in Apr, 1957. He worked in the 2nd Affiliated Hospital of Zhejiang University School of Medicine during 1989 to 2002. In 2002, Chenghong Peng came m Shanghai Ruiiin Hospital and began to take charge of general surgery department. As a pioneer in the hepatobifiopancreatic field, Chenghong Peng devoted himself in the basic and clinical research of pancreatic tmnors. He brings forth new ideas by creating ＂Pancreatic multiple treatment collaborating groups＂, which integrate the advantages of gasn＇oenterology, department, endoscopy department, radiology department, pathology deparnnent and SICU. He constantly strives for excellence in pancreatic surgery. In the previous five years, he performed more than 300 cases of pancreatectomy each year, and has accomplished more than 2,000 cases of pancreatectomy altogether, among which the resectable rate is 74%. Besides, he is also committed to laparoscopic surgery and robotic surgeD,. He has achieved more than 200 laparoscopic hepatectomies, 150 laparoscopic pancreatectomies and 500 robotic hepatobiliopancreatic surgeries （350 robotic pancreatic surgeries included）, which keeps leading position in China. In 2011, Chenghong Peng has won the first prize in 3rd international congress of CRSA, which marked that our achievement in robotic surgery was recognized by oversea peers.Background： To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma （PDAC）. Methods： The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed. Results： Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy （DP）, the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy （NIP）, the average operative time was 225 rain and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula （n=11）, bile leak （n=5）, anastomotic bleeding （n：2）, pancreatic fistula complicated with portal vein thrombosis （n=1）, and anastomotic bleeding complicated with acute renal failure （n=l）. Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 （15.6±5.8） months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis. Conclusions- Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and therefore can achieve the lymph node dissection scope and tumor resection margin required by the standards of radical resection for pancreatic cancer. Nevertheless, its long-term efficacy requires further validation.展开更多
Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer types.Its delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo...Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer types.Its delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo-and radiotherapy.Unfortunately,these strategies are insufficient to improve its poor prognosis.Despite the advances made in chemotherapy(e.g.nab-paclitaxel and gemcitabine),many patients with PDAC are unable to benefit from them due to the rapid development of drug resistance.Currently,more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins,mucins,NF-κB,RAS and CXCR4.Moreover,drug resistance in PDAC is thought to be mediated by the modulation of miRNAs(e.g.miRNA-21,miRNA-145 and miRNA-155),which regulate genes that participate in cell proliferation,invasion and metastasis.Finally,cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes-involved in drug transport-,and enzymes such as aldehyde dehydrogenases-implicated in cellular drug metabolism-and poly(ADP-ribose)polymerases-involved in drug-induced DNA damage repair.Understanding the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.展开更多
Objective:To validate the 8 th edition of the American Joint Committee on Cancer(AJCC)staging system for pancreatic ductal adenocarcinoma(PDAC)in a Chinese cohort of radically resected patients and to develop a refine...Objective:To validate the 8 th edition of the American Joint Committee on Cancer(AJCC)staging system for pancreatic ductal adenocarcinoma(PDAC)in a Chinese cohort of radically resected patients and to develop a refined staging system for PDAC.Methods:Data were collected from the China Pancreas Data Center(CPDC)for patients with resected PDAC in 2016 and 2017,and cancer-specific survival(CSS)was evaluated using the Kaplan-Meier method and log-rank test.Univariate and multivariate analyses based on Cox regression were performed to identify prognostic factors.The recursive partitioning analysis(RPA),Kaplan-Meier method,and log-rank test were performed on the training dataset to generate a proposed modification for the 8 th TNM staging system utilizing the preoperative carbohydrate antigen(CA)19-9 level.Validation was performed for both staging systems in the validation cohort.Results:A total of 1,676 PDAC patients were retrieved,and the median CSS was significantly different between the 8 th TNM groupings,with no significant difference in survival between stage IB and IIA.The analysis of T and N stages demonstrated a better prognostic value in the N category.Multivariate analysis showed that the preoperative serum CA19-9 level was the strongest prognostic indicator among all the independent risk factors.All patients with CA19-9>500 U/mL had similar survival,and we proposed a new staging system by combining IB and IIA and stratifying all patients with high CA19-9 into stage III.The modified staging system had a better performance for predicting CSS than the 8 th AJCC staging scheme.Conclusions:The 8 th AJCC staging system for PDAC is suitable for a Chinese cohort of resected patients,and the N category has a better prognostic value than the T category.Our modified staging system has superior accuracy in predicting survival than the 8 th AJCC TNM staging system.展开更多
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.
文摘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.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘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.
基金Supported by National Natural Science Foundation of China,No.82373012.
文摘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.
文摘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.
文摘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.
基金Natural Science Foundation of Chongqing,China,No.cstc2021jcyj-msxmX0501Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2022QNXM074.
文摘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.
基金Supported by the National Natural Science foundation of China,No.82202135,82371919,82372017,and 82171925China Postdoctoral Science Foundation,No.2023M741808+3 种基金Young Elite Scientists Sponsorship Program by Jiangsu Association for Science and Technology,No.JSTJ-2023-WJ027Foundation of Excellent Young Doctor of Jiangsu Province Hospital of Chinese Medicine,No.2023QB0112Nanjing Postdoctoral Science Foundation,Natural Science Foundation of Nanjing University of Chinese Medicine,No.XZR2023036 and XZR2021050Medical Imaging Artificial Intelligence Special Research Fund Project,Nanjing Medical Association Radiology Branch,Project of National Clinical Research Base of Traditional Chinese Medicine in Jiangsu Province,China,No.JD2023SZ16.
文摘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.
基金Supported by the National Natural Science Foundation of China,No.31971518.
文摘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.
基金Supported by National Natural Science Foundation of China,No.82373012.
文摘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.
基金Supported by the National Natural Science foundation of China,No.82202135,No.82371919,No.82372017 and No.82171925Project funded by China Postdoctoral Science Foundation,No.2023M741808+4 种基金Jiangsu Provincial Key research and development program,No.BE2023789Young Elite Scientists Sponsorship Program by Jiangsu Association for Science and Technology,No.JSTJ-2023-WJ027Foundation of Excellent Young Doctor of Jiangsu Province Hospital of Chinese Medicine,No.2023QB0112Project funded by Nanjing Postdoctoral Science Foundation,Natural Science Foundation of Nanjing University of Chinese Medicine,No.XZR2023036,No.XZR2021003 and No.XZR2021050Medical Imaging Artificial Intelligence Special Research Fund Project,Nanjing Medical Association Radiology Branch,Project of National Clinical Research Base of Traditional Chinese Medicine in Jiangsu Province,China,No.JD2023SZ16.
文摘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.
基金Supported by Grants from the National Natural Science Foundation of China, No 30972898
文摘AIM:To investigate the expression of toll-like receptor(TLR) 4,nuclear factor-κB(NF-κB) p65 and hypoxiainducible transcription factor 1α(HIF-1α) in pancreatic ductal adenocarcinoma and their clinical significance.METHODS:The mRNA of TLR4 and HIF-1α were investigated by real-time polymerase chain reaction in 30 cases of pancreatic ductal adenocarcinoma and its adjacent tissues,and expression of TLR4,NF-κB p65 and HIF-1α protein were detected by immunohistochemistry in 65 cases of pancreatic ductal adenocarcinoma tissues and 38 cases of corresponding adjacent tissues.The relationship between TLR4 or HIF-1α and pathologic features,as well as the association between TLR4 and HIF-1α,were also analyzed.Kaplan-Meier method was used to assess the impact of expression of TLR4 and HIF-1α on survival of patients with pancreatic cancer.RESULTS:The relative quantif ication of TLR4 and HIF-1α mRNA in tumor tissues was 0.81±0.10 and 0.87±0.11,respectively,signif icantly higher than that in adjacent tissues(0.81±0.10 vs 0.70±0.16,P=0.002;0.87±0.11 vs 0.68±0.13,P=0.000).The protein expression of TLR4,NF-κB p65 and HIF-1α in tumor tissues was 69.20%,66.15% and 70.80%,respectively,being signif icantly higher than that in adjacent normal tissues(69.20% vs 39.50%,P=0.003;66.15% vs 31.58%,P=0.001;70.80% vs 36.80%,P=0.001).There was no signif icant correlation between TLR4 or HIF-1α expression and the age,gender,tumor location,the degree of tumor differentiation in the patients(P>0.05).However,there was signif icant correlation between the expression of TLR4 or HIF-1α and tumor size,lymph node metastasis,venous invasion and clinical staging(P<0.05).The expression of TLR4 and HIF-1α had a signif icant impact on survival of patients with pancreatic adenocarcinoma.CONCLUSION:TLR4,NF-κB p65 and HIF-1α are overexpressed in pancreatic adenocarcinoma,TLR4 may be partly involved in up-regulating HIF-1α,and both synergestically promote development of pancreatic adenocarcinoma.
基金supported by grants from China Cancer Research Foundation Y-N2013-008the Doctoral Program of the Ministry of Education 20130001110089 to DR Xiu+1 种基金the National Natural Science Foundation of China 81272709 to W FuPeking University Third Hospital Grant Y81524-01 to LF Zhang
文摘Objective： To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma （PDAC）. Methods： Parasympathetic neurogenesis was defined as the distribution of abnormal parasympathetic nerves in the stroma tissue. Staining of vesicular acetylcholine transporter （VAChT）, as a marker for parasympathetic neurogenesis, was performed on a representative specimen of the tumor for 59 PDAC patients with available clinical, pathologic, and follow-up information. Three specimens containing normal pancreatic tissues were stained in parallel. The number of parasympathetic nerve fibers was counted in five high-power microscopic fields （5×0.785 mm2）. Cut-offvalues were calculated by receiver operating characteristic curve analysis. Results： VAChT-positive parasympathetic nerve fibers were not seen in the stroma of 3 cases of normal pancreatic tissues. In 59 PDAC cases, the range of parasympathetic neurogenesis was 4-38 fibers/（5×0.785） mm2, with a median of 18 fibers/（5×0.785） mm2. Patients with parasympathetic neurogenesis 〉 15 fibers/（5×0.785） mm2 were defined as the high-density group （39 patients, 66.1%）, and those with parasympathetic neurogenesis 〈15 fibers/（5×0.785） mm2 as the low-density group （20 patients, 33.9%）. The high-density group had a higher occurrence of tumor budding （P=0.001） and a higher rate of early recurrence （P=0.035）. Parasympathetic neurogenesis appeared to be an independent adverse prognostic factor [hazard ratio （HR）=2.45, 95% confidence interval （95% CI）： 1.25-4.81, P=0.009], in addition to American Joint Committee on Cancer （AJCC） stage （P=0.010） and tumor budding （P=0.009）. Conclusions： Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in PDAC.
基金Supported by EU COST Action BM1204 EUPancreas"An integrated european platform for pancreas cancer research:from basic science to cinical and public health interventions for a rare disease"
文摘Despite major improvements concerning its diagnosis and treatment,pancreatic ductal adenocarcinoma(PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology,as interface discipline between basic and clinical medicine,has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition,by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC,a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC.This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results.Finally,recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response.The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.
文摘BACKGROUND： Various scoring systems based on assessment of the systemic inflammatory response help assessing the prognosis of patients with pancreatic ductal adenocarcinoma.In the present systematic review we evaluated the validity of four pre-intervention scoring systems： Glasgow prognostic score（GPS） and its modified version（mGPS）, platelet lymphocyte ratio（PLR）, neutrophil lymphocyte ratio（NLR）, and prognostic nutrition index（PNI）.DATA SOURCES： MOOSE guidelines were followed and EMBASE and MEDLINE databases were searched for all published studies until September 2013 using comprehensive text word and MeSH terms. All identified studies were analyzed, and relevant studies were included in the systematic review.RESULTS： Six studies were identified for GPS/mGPS with3 reporting statistical significance for GPS/mGPS on both univariate analysis（UVA） and multivariate analysis（MVA）.Two studies suggested prognostic significance on UVA but not MVA, and in the final study UVA failed to show significance.Eleven studies evaluated the prognostic value of NLR. Six of them reported prognostic significance for NLR on UVA that persisted at MVA in 4 studies, and in the remaining 2 studies NLR was the only significant factor on UVA. In the remaining5 studies, all in patients undergoing resection, there was no significance on UVA. Seven studies evaluated PLR, with only one study demonstrated its prognostic significance on both UVAand MVA, the rest did not show the significance on UVA. Of the two studies identified for PNI, one demonstrated a statistically significant difference in survival on both UVA and MVA, and the other reported no significance for PNI on UVA.CONCLUSIONS： Both GPS/mGPS and NLR may be useful but further better-designed studies are required to confirm their value. PLR might be little useful, and there are at present inadequate data to assess the prognostic value of PNI. At present, no scoring system is reliable enough to be accepted into routine use for the prognosis of patients with pancreatic ductal adenocarcinoma.
基金Supported by the National Natural Science Foundation of China,No.81472221Clinical key projects of the National Health and Family Planning-Oncology 2013-2015
文摘AIM To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma(PDAC) and assess unresectability of synchronous liver metastasis.METHODS Retrospective records of PDAC patients with synchronous liver metastasis who underwent simultaneous resections of primary PDAC and synchronous liver metastasis, or palliative surgical bypass, were collected from 2007 to 2015. A series of pre-operative clinical parameters, including tumor markers and inflammation-based indices, were analyzed by logistic regression to figure out predictive factors and assess unresectability of synchronous liver metastasis. Cox regression was used to identify prognostic factors in liver-metastasized PDAC patients after surgery, with intention to validate their conformance to the indications of simultaneous resections and palliative surgical bypass. Survival of patients from different groups were analyzed by the Kaplan-Meier method. Intra- and post-operative courses were compared, including complications. PDAC patients with no distant metastases who underwent curative resection served as the control group.RESULTS CA125 > 38 U/mL(OR = 12.397, 95%CI: 5.468-28.105, P < 0.001) and diabetes mellitus(OR = 3.343, 95%CI: 1.539-7.262, P = 0.002) independently predicted synchronous liver metastasis from resectable PDAC. CA125 > 62 U/mL(OR = 5.181, 95%CI: 1.612-16.665, P = 0.006) and age > 62 years(OR = 3.921, 95%CI: 1.217-12.632, P = 0.022) correlated with unresectability of synchronous liver metastasis, both of which also indicated a worse long-term outcome of liver-metastasized PDAC patients after surgery. After the simultaneous resections, patients with postoperatively elevated serum CA125 levels had shorter survival than those with post-operatively reduced serum CA125 levels(7.7 mo vs 16.3 mo, P = 0.013). The survival of liver-metastasized PDAC patients who underwent the simultaneous resections was similar to that of non-metastasized PDAC patients who underwent curative pancreatectomy alone(7.0 mo vs 16.9 mo, P < 0.001), with no higher rates of either pancreatic fistula(P = 0.072) or other complications(P = 0.230) and no greater impacts on length of hospital stay(P = 0.602) or post-operative diabetic control(P = 0.479).CONCLUSION The criterion set up by CA125 levels could facilitate careful diagnosis of synchronous liver metastases from PDAC, and prudent selection of appropriate patients for the simultaneous resections.
基金National Natural Science Foundation of China,No.81972314Innovation Fund for Medical Sciences of Chinese Academy of Medical Sciences,No.2016-I2M-1-001.
文摘BACKGROUND Inflammation plays an important role in tumor progression,and growing evidence has confirmed that the fibrinogen-to-albumin ratio(FAR)is an important prognostic factor for overall survival in malignant tumors.AIM To investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma(PDAC).METHODS We retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019.The surv_cutpoint function of the R package survminer via RStudio software(version 1.3.1073,http://www.rstudio.org)was used to determine the optimal cut-off values of biological markers,such as preoperative FAR.The Kaplan-Meier method and log-rank tests were used for univariate survival analysis,and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection.RESULTS The optimal cut-off value of FAR was 0.08 by the surv_cutpoint function.Higher preoperative FAR was significantly correlated with clinical symptoms(P=0.001),tumor location(P<0.001),surgical approaches(P<0.001),preoperative plasma fibrinogen concentration(P<0.001),and preoperative plasma albumin level(P<0.001).Multivariate analysis showed that degree of tumor differentiation(P<0.001),number of metastatic lymph nodes[hazard ratio(HR):0.678,95%confidence interval(CI):0.509-0.904,P=0.008],adjuvant therapy(HR:1.604,95%CI:1.214-2.118,P=0.001),preoperative cancer antigen 19-9 level(HR:1.740,95%CI:1.288-2.352,P<0.001),and preoperative FAR(HR:2.258,95%CI:1.720-2.963,P<0.001)were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection.CONCLUSION The increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC.Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.
文摘Authors introduction： Qian Zhan, female, who was born in Sept, 1979. She studied in the Shanghai Second Medical University during 1998 to 2005. She majored in Clinical Medicine, and earned her master degree in 2005. In 2005, she went to the Beaujon Hospital of Paris 7th Universit3. in France, as a foreign intern. Later, she came to postgraduate work and residencies in the general surgery department of Shanghai Ruijin Hospital. Her clinical work is focused on multidisciplinary especially postoperative management for the patients with pancreatic cancer. In addition, she is a lead researcher in the pancreatic cancer group for nano based drug delivery, systems. Chenghong Peng, male, who was born in Apr, 1957. He worked in the 2nd Affiliated Hospital of Zhejiang University School of Medicine during 1989 to 2002. In 2002, Chenghong Peng came m Shanghai Ruiiin Hospital and began to take charge of general surgery department. As a pioneer in the hepatobifiopancreatic field, Chenghong Peng devoted himself in the basic and clinical research of pancreatic tmnors. He brings forth new ideas by creating ＂Pancreatic multiple treatment collaborating groups＂, which integrate the advantages of gasn＇oenterology, department, endoscopy department, radiology department, pathology deparnnent and SICU. He constantly strives for excellence in pancreatic surgery. In the previous five years, he performed more than 300 cases of pancreatectomy each year, and has accomplished more than 2,000 cases of pancreatectomy altogether, among which the resectable rate is 74%. Besides, he is also committed to laparoscopic surgery and robotic surgeD,. He has achieved more than 200 laparoscopic hepatectomies, 150 laparoscopic pancreatectomies and 500 robotic hepatobiliopancreatic surgeries （350 robotic pancreatic surgeries included）, which keeps leading position in China. In 2011, Chenghong Peng has won the first prize in 3rd international congress of CRSA, which marked that our achievement in robotic surgery was recognized by oversea peers.Background： To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma （PDAC）. Methods： The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed. Results： Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy （DP）, the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy （NIP）, the average operative time was 225 rain and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula （n=11）, bile leak （n=5）, anastomotic bleeding （n：2）, pancreatic fistula complicated with portal vein thrombosis （n=1）, and anastomotic bleeding complicated with acute renal failure （n=l）. Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 （15.6±5.8） months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis. Conclusions- Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and therefore can achieve the lymph node dissection scope and tumor resection margin required by the standards of radical resection for pancreatic cancer. Nevertheless, its long-term efficacy requires further validation.
基金funded by grants from Instituto de Salud Carlos III (Grant No. DTS15/00201 and DTS17/00081)Junta de Andalucía (Grant No. PIN-0474-2016)
文摘Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer types.Its delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo-and radiotherapy.Unfortunately,these strategies are insufficient to improve its poor prognosis.Despite the advances made in chemotherapy(e.g.nab-paclitaxel and gemcitabine),many patients with PDAC are unable to benefit from them due to the rapid development of drug resistance.Currently,more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins,mucins,NF-κB,RAS and CXCR4.Moreover,drug resistance in PDAC is thought to be mediated by the modulation of miRNAs(e.g.miRNA-21,miRNA-145 and miRNA-155),which regulate genes that participate in cell proliferation,invasion and metastasis.Finally,cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes-involved in drug transport-,and enzymes such as aldehyde dehydrogenases-implicated in cellular drug metabolism-and poly(ADP-ribose)polymerases-involved in drug-induced DNA damage repair.Understanding the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.
基金supported by grants from the National Natural Science Foundation of China(No.81672353 and 81871954)。
文摘Objective:To validate the 8 th edition of the American Joint Committee on Cancer(AJCC)staging system for pancreatic ductal adenocarcinoma(PDAC)in a Chinese cohort of radically resected patients and to develop a refined staging system for PDAC.Methods:Data were collected from the China Pancreas Data Center(CPDC)for patients with resected PDAC in 2016 and 2017,and cancer-specific survival(CSS)was evaluated using the Kaplan-Meier method and log-rank test.Univariate and multivariate analyses based on Cox regression were performed to identify prognostic factors.The recursive partitioning analysis(RPA),Kaplan-Meier method,and log-rank test were performed on the training dataset to generate a proposed modification for the 8 th TNM staging system utilizing the preoperative carbohydrate antigen(CA)19-9 level.Validation was performed for both staging systems in the validation cohort.Results:A total of 1,676 PDAC patients were retrieved,and the median CSS was significantly different between the 8 th TNM groupings,with no significant difference in survival between stage IB and IIA.The analysis of T and N stages demonstrated a better prognostic value in the N category.Multivariate analysis showed that the preoperative serum CA19-9 level was the strongest prognostic indicator among all the independent risk factors.All patients with CA19-9>500 U/mL had similar survival,and we proposed a new staging system by combining IB and IIA and stratifying all patients with high CA19-9 into stage III.The modified staging system had a better performance for predicting CSS than the 8 th AJCC staging scheme.Conclusions:The 8 th AJCC staging system for PDAC is suitable for a Chinese cohort of resected patients,and the N category has a better prognostic value than the T category.Our modified staging system has superior accuracy in predicting survival than the 8 th AJCC TNM staging system.
