Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis:What does the evidence say

Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.

Dysregulation of genes involved in the long-chain fatty acid transport in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.

Molecular mechanism of pancreatic ductal adenocarcinoma:The heterogeneity of cancer-associated fibroblasts and key signaling pathways

Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.

Programmed cell death 1 inhibitor sintilimab plus S-1 and gemcitabine for liver metastatic pancreatic ductal adenocarcinoma

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.

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.

Stereotactic body radiotherapy in pancreatic adenocarcinoma

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

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.

A comparison of laparoscopic to open pancreaticoduodenectomy for pancreatic adenocarcinoma by propensity score matching analysis

Objective:In previous studies,laparoscopic pancreaticoduodenectomy(LPD)has demonstrated safety and potential benefits over open pancreaticoduodenectomy(OPD)for pancreatic adenocarcinoma(PDAC).After performing both LPD and OPD procedures interchangeably in routine practice for a decade,the outcomes of LPD versus OPD for PDAC were analyzed and compared at a single institution.Our primary aim was to compare features of LPD and OPD in PDAC patients so that the suitable surgical approach may be chosen for each individual.Methods:From January 2010 through December 2020,all patients undergoing pancreaticoduodenectomy(PD)were identified,and information was collected prospectively.At a single institution,PD was performed on 589 patients,of whom 347 were OPD patients and 242 were LPD patients.After excluding those who underwent pancreatectomy for indications other than PDAC,total pancreatectomy,major vascular or concomitant organ resection,there were 237 patients(OPD¼157,LPD¼80).Then propensity score matching was completed to analyze 77 OPD patients versus 77 LPD patients to create a similar group of patients who underwent either LPD or OPD for PDAC.A comparison of perioperative data and 90-day outcomes with subsequent statistical analysis was performed.Results:Operative time(491 min vs.281 min,p<0.001)was longer for LPD than OPD.The rates of pancreatic fistula(11.7%vs.0.0%,p<0.001)and delayed gastric emptying(15.6%vs.3.9%,p¼0.027)were higher for LPD than OPD respectively but overall morbidity was similar.Blood loss,mortality and postpancreatectomy hemorrhage were also similar for both groups,but total costs($60,245 vs.$50,900,p¼0.002)were significantly higher for LPD than OPD.Recurrence and overall survival were similar for the two groups.Conclusion:In our experience,LPD does not offer any advantages over OPD for PDAC and is associated with a higher rate of complications and costs.

A Deep Learning Framework for Mass-Forming Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma Classification Based on Magnetic Resonance Imaging

Pancreatic diseases, including mass-forming chronic pancreatitis (MFCP) and pancreatic ductal adenocarcinoma(PDAC), present with similar imaging features, leading to diagnostic complexities. Deep Learning (DL) methodshave been shown to perform well on diagnostic tasks. Existing DL pancreatic lesion diagnosis studies basedon Magnetic Resonance Imaging (MRI) utilize the prior information to guide models to focus on the lesionregion. However, over-reliance on prior information may ignore the background information that is helpful fordiagnosis. This study verifies the diagnostic significance of the background information using a clinical dataset.Consequently, the Prior Difference Guidance Network (PDGNet) is proposed, merging decoupled lesion andbackground information via the Prior Normalization Fusion (PNF) strategy and the Feature Difference Guidance(FDG) module, to direct the model to concentrate on beneficial regions for diagnosis. Extensive experiments inthe clinical dataset demonstrate that the proposed method achieves promising diagnosis performance: PDGNetsbased on conventional networks record an ACC (Accuracy) and AUC (Area Under the Curve) of 87.50% and89.98%, marking improvements of 8.19% and 7.64% over the prior-free benchmark. Compared to lesion-focusedbenchmarks, the uplift is 6.14% and 6.02%. PDGNets based on advanced networks reach an ACC and AUC of89.77% and 92.80%. The study underscores the potential of harnessing background information in medical imagediagnosis, suggesting a more holistic view for future research.

Pancreatic panniculitis as the first presentation of pancreatic ductaladenocarcinoma

To the Editor:Pancreatic panniculitis,also known as pancreatic fat necrosis or enzymatic panniculitis,is a rare type of panniculitis that occurs in 0.3%−3%of patients with pancreatic disease such as acute or chronic pancreatitis and pancreatic carcinoma,especially acinar cell carcinoma[1,2].The clinical manifestations are nonspecific erythema tender nodules.

Nutritional Supplement Ocoxin® Combined with Gemcitabine-Based Chemotherapy in Patients with Advanced Pancreatic Adenocarcinoma

Background: the quality of life (QoL) of patients with pancreatic ductal adenocarcinoma (PDAC), with its limited survival, can be affected by chemotherapy-induced toxicity. The main objective was to evaluate the effect of introducing ocoxin oral solution (OOS) in combination with standard therapy on quality of life. Methods: Thirty patients were enrolled in an exploratory, prospective, single-centre clinical trial in the oncology department of “Hermanos Ameijeiras” University Hospital in Havana, Cuba. Quality of life was measured using the EORTC QLQ-C30 questionnaire and toxicity was assessed using the NCI-CTC-AE classification version 5.0. Results: There was stability in the scores over time for overall QoL and the functional scale criteria, while in terms of symptoms, fatigue, pain and loss of appetite were reduced. No grade 3 - 4 adverse events (AEs) were recorded, and only 14.9% of toxicities were classified as grade 2, and these were considered to be unrelated to OOS. Biochemical and nutritional parameters were normalised at 12 months compared to the baseline values. Conclusions: This clinical study is the first report of the use of OOS in patients with advanced pancreatic cancer, and demonstrates that it is able to maintain optimal quality of life with reduced severity of toxicity during and after combination treatment with gemcitabine-based chemotherapy.

Novel lactylation-related signature to predict prognosis for pancreatic adenocarcinoma

BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS RNA-seq and clinical data of pancreatic adenocarcinoma(PDAC)were obtained from the GTEx(Genotype-Tissue Expression)and TCGA(The Cancer Genome Atlas)databases via Xena Explorer,and GSE62452 datasets from GEO.Data on lactylation-related genes were obtained from publicly available sources.Differential expressed genes(DEGs)were acquired by using R package“DESeq2”in R.Univariate COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model.Further analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells.In vivo validation was performed using an established tumor model.RESULTS In this study,we successfully identified 10 differentially expressed lactylation-related genes(LRGs)with prognostic value.Subsequently,a lactylation-related signature was developed based on five OS-related lactylationrelated genes(SLC16A1,HLA-DRB1,KCNN4,KIF23,and HPDL)using Lasso Cox hazard regression analysis.Subsequently,we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma.A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups.Furthermore,we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport.Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression,indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.CONCLUSION We constructed a novel lactylation-related prognostic signature to predict OS,immune status,and treatment response of patients with pancreatic adenocarcinoma,providing new strategic directions and antitumor immunotherapies.

Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor:A case report

BACKGROUND Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms(MiNENs)are rare malignancies affecting the pancreas.The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components,each constituting 30%or more of the tumor volume.Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination.A well-differentiated neuroendocrine tumor(NET)component is rarely reported in MiNENs.CASE SUMMARY Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas.The two tumors show distinct histology and significant differentiation discrepancy(poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET),and also present as metastases in separate lymph nodes.Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma,but no genetic alterations in the NET,suggesting divergent origins for these two components.Although tumors like this meet the diagnostic criteria for MiNEN,clinicians often find the diagnosis and staging confusing and impractical for clinical management.CONCLUSION Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

Clinical outcomes of second-line chemotherapy in patients with advanced pancreatic adenocarcinoma:a real-world study

Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition,the optimal second-line chemotherapy regimen has not been determined.This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC.Methods:Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis.The primary and secondary endpoints were overall survival(OS)and progression-free survival(PFS),respectively.Results:Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment,respectively.Demographic and clinical features,except age and liver metastasis,were comparable between the two groups(P<0.05).The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy,respectively(HR=1.244,95%CI=1.090–1.419;P<0.001).The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care,respectively(HR=0.766,95%CI=0.677–0.867;P<0.001).The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy.Conclusions:A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

Identification of breath volatile organic compounds to distinguish pancreatic adenocarcinoma,pancreatic cystic neoplasm,and patients without pancreatic lesions

BACKGROUND Volatile organic compounds(VOCs)are a promising potential biomarker that may be able to identify the presence of cancers.AIM To identify exhaled breath VOCs that distinguish pancreatic ductal adenocar-cinoma(PDAC)from intraductal papillary mucinous neoplasm(IPMN)and healthy volunteers.METHODS We collected exhaled breath from histologically proven PDAC patients,radiological diagnosis IPMN,and healthy volunteers using the ReCIVA®device between 10/2021-11/2022.VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups.RESULTS A total of 156 participants(44%male,mean age 62.6±10.6)were enrolled(54 PDAC,42 IPMN,and 60 controls).Among the nine VOCs identified,two VOCs that showed differences between groups were dimethyl sulfide[0.73 vs 0.74 vs 0.94 arbitrary units(AU),respectively;P=0.008]and acetone dimers(3.95 vs 4.49 vs 5.19 AU,respectively;P<0.001).After adjusting for the imbalance parameters,PDAC showed higher dimethyl sulfide levels than the control and IPMN groups,with adjusted odds ratio(aOR)of 6.98(95%CI:1.15-42.17)and 4.56(1.03-20.20),respectively(P<0.05 both).Acetone dimer levels were also higher in PDAC compared to controls and IPMN(aOR:5.12(1.80-14.57)and aOR:3.35(1.47-7.63),respectively(P<0.05 both).Acetone dimer,but not dimethyl sulfide,performed better than CA19-9 in PDAC diagnosis(AUROC 0.910 vs 0.796).The AUROC of acetone dimer increased to 0.936 when combined with CA19-9,which was better than CA19-9 alone(P<0.05).CONCLUSION Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants.Additional prospective studies are required to validate these findings.

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.

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.

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.

Neoadjuvant treatment of pancreatic ductal adenocarcinoma:Whom,when and how

Pancreatic ductal adenocarcinoma(PDAC),which is notorious for its aggressiveness and poor prognosis,remains an area of great unmet medical need,with a 5-year survival rate of 10%-the lowest of all solid tumours.At diagnosis,only 20%of patients have resectable pancreatic cancer(RPC)or borderline RPC(BRPC)disease,while 80%of patients have unresectable tumours that are locally advanced pancreatic cancer(LAPC)or have distant metastases.Nearly 60%of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy(CHT)because of postoperative complications and early cancer recurrence.An important paradigm shift to achieve better outcomes has been the sequence of therapy,with neoadjuvant CHT preceding surgery.Three surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers:RPC,BRPC,and LAPC.The main goal of neoadjuvant treatment(NAT)is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT,reducing tumour volume before surgery to improve the rate of margin-negative resection(R0 resection,a microscopic margin-negative resection),reducing the rate of positive lymph node occurrence at surgery,providing early treatment of occult micrometastatic disease,and assessing tumour chemosensitivity and tolerance to treatment as potential surgical criteria.In this editorial,we summarize evidence concerning NAT of PDAC,providing insights into future practice and study design.Future research is needed to establish predictive biomarkers,measures of therapeutic response,and multidisciplinary stra tegies to improve patient-centered outcomes.