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Preoperative prediction of perineural invasion of rectal cancer based on a magnetic resonance imaging radiomics model:A dual-center study

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World Journal of Gastroenterology 2024年第16期30卷 2233-2248页

作者： Yan Liu Bai-Jin-Tao Sun Chuan Zhang Bing Li Xiao-Xuan Yu Yong Du Department of Radiology The Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina Department of Radiology The Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina.duyong@***

BACKGROUND perineural invasion(PNI)has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer(RC).Preoperative prediction of PNI status is helpful for individualized treatment of RC.Recently,several radiomics studies have been used to predict the PNI status in RC,demonstrating a good predictive effect,but the results lacked generalizability.The preoperative prediction of PNI status is still challenging and needs further study.AIM To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients.METHODS This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers.The patients underwent preoperative high-resolution magnetic resonance imaging(MRI)between May 2019 and August 2022.Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging(T2WI)and contrast-enhanced T1WI(T1CE)sequences.The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared(T2WI,T1CE and T2WI+T1CE fusion sequences).A clinical-radiomics(CR)model was established by combining the radiomics features and clinical risk factors.The internal and external validation groups were used to validate the proposed models.The area under the receiver operating characteristic curve(AUC),DeLong test,net reclassification improvement(NRI),integrated discrimination improvement(IDI),calibration curve,and decision curve analysis(DCA)were used to evaluate the model performance.RESULTS Among the radiomics models,the T2WI+T1CE fusion sequences model showed the best predictive performance,in the training and internal validation groups,the AUCs of the fusion sequence model were 0.839[95%confidence interval(CI):0.757-0.921]and 0.787(95%CI:0.650-0.923),which were higher than those of the T2WI and T1CE sequence models.The CR model constructed by combining clinical risk factors had the best predictive

关键词： Rectal cancer perineural invasion Magnetic resonance imaging Radiomics Nomogram

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Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning

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World Journal of Gastroenterology 2024年第6期30卷 542-555页

作者： Hui-Ting Ge Jian-Wu Chen Li-Li Wang Tian-Xiu Zou Bin Zheng Yuan-Fen Liu Yun-Jing Xue Wei-Wen Lin Department of Radiology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Digestive Hematological and Breast MalignanciesClinical Research Center for Radiology and Radiotherapy of Fujian ProvinceFuzhou 350001Fujian ProvinceChina Department of Radiation Oncology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Department of Diagnostic Radiology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina School of Electrical and Computer Engineering University of OklahomaOklahomaOK 73019United States

BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were ind

关键词： Spectral computed tomography Gastric cancer Lymphovascular invasion perineural invasion

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Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

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BIOCELL 2024年第6期48卷 923-934页

作者： BINGJIE LI WENBO CAO JINJING XIAO YIXIAO CHEN QIYING WEI MINGJIN YUE SAIJUN MO Department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhouChina Collaborative Innovation Center of Henan Province for Cancer Chemoprevention ZhengzhouChina State Key Laboratory of Esophageal Cancer Prevention and Treatment ZhengzhouChina Department of Research and Development Henan Tianxing Education and Media Company LimitedZhengzhouChina

perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,inﬁltrating distant regions devoid of lymphatic or vascular structures.PNI often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of cancers.Despite its clinical signiﬁcance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of speciﬁc and efﬁcacious diagnostic and therapeutic strategies.In the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-speciﬁc expression proﬁles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and treatment.Among the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as inﬂuential players in PNI.Their involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic resistance.Our study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in cancer.This comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

关键词： perineural invasion Non-coding RNA Diagnose and treatment Cancer Biomarker

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Prediction of the lymphatic,microvascular,and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging

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World Journal of Gastrointestinal Surgery 2023年第12期15卷 2809-2819页

作者： Yu-Liang Liu Hai-Bin Zhu Mai-Lin Chen Wei Sun Xiao-Ting Li Ying-Shi Sun Department of Radiology Peking University Cancer Hospital and InstituteBeijing 100142China Department of Pathology Peking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and LMPI.AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study.The patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were collected.In order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was constructed.Diagnostic performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy.RESULTS There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of NF-PNETs.The area under the receiver value for the predictive performance of combined predictive factors was 0.855.The sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,respectively.CONCLUSION Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.

关键词： Pancreatic neuroendocrine tumors Magnetic resonance imaging Lymphatic invasion Microvascular invasion perineural invasion

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perineural invasion status, Gleason score and number of positive cores in biopsy pathology are predictors of positive surgical margin following laparoscopic radical prostatectomy

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Asian Journal of Andrology 2017年第4期19卷 468-472页

作者： Rong Yang Kai Cao Tao Han Yi-Feng Zhang Gu-Tian Zhang Lin-Feng XU Hui-Bo Lian Xiao-Gong Li Hong-Qian Guo Department of Urology Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 China Department of Urology Nanjing Children's Hospital Nanjing 210008 China Department of Pathology Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 China

This study was designed to define possible preoperative predictors of positive surgical margin after laparoscopic radical prostatectomy. We retrospectively analyzed the records of 296 patients with prostate cancer diagnosed by prostate biopsy, and eventually treated with laparoscopic radical prostatectomy. The prognostic impact of age, prostate volume, preoperative prostate-specific antigen, biopsy Gleason score, maximum percentage tumor per core, number of positive cores, biopsy perineurat invasion, capsule invasion on imaging, and tumor laterality on surgical margin was assessed. The overall positive surgical margin rate was 29.1%. Gleason score, number of positive cores, perineural invasion, tumor laterality in the biopsy specimen, and prostate volume significantly correlated with risk of positive surgical margin by univariate analysis （P 〈 0.05）. Gleason score （odds ratio [OR] = 2.286, 95% confidence interval [95% CI] = 1.431-3.653, P= 0.001）, perineural invasion （OR = 4.961, 95% CI = 2.656-9.270, P〈 0.001）, and number of positive cores （OR = 4.403, 95% CI = 1.878-10.325, P = 0.001） were independent predictors of positive surgical margin at the multivariable logistic regression analysis. Patients with perineural invasion, higher biopsy Gleason scores and/or a large number of positive cores in biopsy pathology had more possibility of capsule invasion. The positive surgical margin rate in patients with capsule invasion （49.5%） was much higher than that with localized disease （17.8%）. In contrast, prostate volume showed a protective effect against positive surgical margin （OR = 0.572, 95% CI = 0.346-0.945, P = 0.029）. Gleason score, perineural invasion, and number of positive cores in the biopsy specimen were preoperative independent predictors of positive surgical margin after laparoscopic radical prostatectomy while prostate volume was a protective factor against positive surgical margin.

关键词： needle biopsy perineural invasion positive surgical margin prostatectomy prostatic neoplasms

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Continuous Low-dose-rate Irradiation of Iodine-125 Seeds Inhibiting perineural invasion in Pancreatic Cancer

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Chinese Medical Journal 2016年第20期129卷 2460-2468页

作者： Zheng Lu Teng-Hui Dong Pei-Ren Si Wei Shen Yi-Liang Bi Min Min Xin Chen Yan Liu Liver Cirrhosis Diagnosis and Therapy Center 302 Hospital of People's Liberation ArmyBeijing 100039China Department of Gastroenterology and Hepatology 307 Hospital of People's Liberation ArmyAcademy of Military Medical SciencesBeijing 100071China Department of Gastroenterology and Hepatology 107 Hospital of People's Liberation ArmyYantaiShandong 264002China Department of Bioengineering and Therapeutic Sciences University of CaliforniaSan FranciscoCA 94143-0912USA

Background：perineural invasion （PNI） is a histopathological characteristic of pancreatic cancer （PanCa）.The aim of this study was to observe the treatment effect of continuous low-dose-rate （CLDR） irradiation to PNI and assess the PNI-related pain relief caused by iodine-125 （125I） seed implantation.Methods：The in vitro PNI model established by co-culture with dorsal root ganglion （DRG） and cancer cells was interfered under 2 and 4 Gy of 125I seeds CLDR irradiation.The orthotopic models of PNI were established,and 125I seeds were implanted in tumor.The PNI-related molecules were analyzed.In 30 patients with panCa,the pain relief was assessed using a visual analog scale （VAS）.Pain intensity was measured before and 1 week,2 weeks,and 1,3,and 6 months after 125I seed implantation.Results：The co-culture of DRG and PanCa cells could promote the growth of PanCa cells and DRG neurites.In co-culture groups,the increased number of DRG neurites and pancreatic cells in radiation group was significantly less.In orthotopic models,the PNI-positive rate in radiation and control group was 3/11 and 7/11;meanwhile,the degrees of PNI between radiation and control groups was significant difference （P 〈 0.05）.At week 2,the mean VAS pain score in patients decreased by 50% and significantly improved than the score at baseline （P 〈 0.05）.The pain scores were lower in all patients,and the pain-relieving effect was retained about 3 months.Conclusions：The CLDR irradiation could inhibit PNI of PanCa with the value of further study.The CLDR irradiation could do great favor in preventing local recurrence and alleviating pain.

关键词： Continuous Low-dose-rate Irradiation Pancreatic Cancer perineural invasion Radioactive Seeds

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Radiomics for predicting perineural invasion status in rectal cancer

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World Journal of Gastroenterology 2021年第33期27卷 5610-5621页

作者： Mou Li Yu-Mei Jin Yong-Chang Zhang Ya-Li Zhao Chen-Cui Huang Sheng-Mei Liu Bin Song Department of Radiology West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Radiology Chengdu Seventh People’s HospitalChengdu 610213Sichuan ProvinceChina Department of Research Collaboration R&D CenterBeijing Deepwise&League of PHD Technology Co.LtdBeijing 100080China

BACKGROUND perineural invasion(PNI),as a key pathological feature of tumor spread,has emerged as an independent prognostic factor in patients with rectal cancer(RC).The preoperative stratification of RC patients according to PNI status is beneficial for individualized treatment and improved prognosis.However,the preoperative evaluation of PNI status is still challenging.AIM To establish a radiomics model for evaluating PNI status preoperatively in RC patients.METHODS This retrospective study enrolled 303 RC patients in a single institution from March 2018 to October 2019.These patients were classified as the training cohort(n=242)and validation cohort(n=61)at a ratio of 8:2.A large number of intraand peritumoral radiomics features were extracted from portal venous phase images of computed tomography(CT).After deleting redundant features,we tested different feature selection(n=6)and machine-learning(n=14)methods to form 84 classifiers.The best performing classifier was then selected to establish Rad-score.Finally,the clinicoradiological model(combined model)was developed by combining Rad-score with clinical factors.These models for predicting PNI were compared using receiver operating characteristic curve(ROC)analysis and area under the ROC curve(AUC).RESULTS One hundred and forty-four of the 303 patients were eventually found to be PNIpositive.Clinical factors including CT-reported T stage(cT),N stage(cN),and carcinoembryonic antigen(CEA)level were independent risk factors for predicting PNI preoperatively.We established Rad-score by logistic regression analysis after selecting features with the L1-based method.The combined model was developed by combining Rad-score with cT,cN,and CEA.The combined model showed good performance to predict PNI status,with an AUC of 0.828[95%confidence interval(CI):0.774-0.873]in the training cohort and 0.801(95%CI:0.679-0.892)in the validation cohort.For comparison of the models,the combined model achieved a higher AUC than the clinical model(cT+cN+CEA)achieved(P<0.001 in the train

关键词： Radiomics perineural invasion Rectal cancer Computed tomography Preoperative prediction Model building

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Relationship between autophagy and perineural invasion, clinicopathological features, and prognosis in pancreatic cancer

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World Journal of Gastroenterology 2017年第40期23卷 7232-7241页

作者： Yan-Hui Yang Jiang-Bo Liu Yang Gui Liang-Liang Lei Shui-Jun Zhang Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Zhengzhou University Department of Hepatobiliary Surgery First Affiliated Hospital College of Clinical Medicine Henan University of Science and Technology Department of General Surgery First Affiliated Hospital College of Clinical Medicine Henan University of Science and Technology Henan Key Laboratory of Digestive Organ Transplantation Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities Zhengzhou Key Laboratory of Hepatobiliary Pancreatic Diseases and Organ Transplantation

AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubuleassociated protein 1 A/1 B-light chain 3(LC3) and PNI marker ubiquitin carboxy-terminal hydrolase(UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS In 109 cases of pancreatic cancer, 68.8%(75/109) had evidence of PNI and 61.5%(67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels(P invasion(P invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients(P invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.

关键词： Pancreatic cancer perineural invasion Autophagy Clinical pathological features Prognosis

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Cellular and molecular mechanisms of perineural invasion of pancreatic ductal adenocarcinoma

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Cancer Communications 2021年第8期41卷 642-660页

作者： Jingbo Li Rui Kang Daolin Tang Department of Surgery UT Southwestern Medical CenterDallasTexas 75390USA

Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells.Recent works have revealed that the dynamic interaction between cancer cells and neuronal cells leads to perineural invasion(PNI),a clinical pathological feature of PDAC.The formation and function of PNI are dually regulated by molecular(e.g.,involving neurotrophins,cytokines,chemokines,and neurotransmitters),metabolic(e.g.,serine metabolism),and cellular mechanisms(e.g.,involving Schwann cells,stromal cells,T cells,and macrophages).Such integrated mechanisms of PNI not only support tumor development,growth,invasion,and metastasis but also mediate the formation of pain,all of which are closely related to poor disease prognosis in PDAC.This review details the modulation,signaling pathways,detection,and clinical relevance of PNI and highlights the opportunities for further exploration that may benefit PDAC patients.

关键词： neurotrophins pancreatic ductal adenocarcinoma perineural invasion schwann cells tumor microenvironment

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Muscarinic acetylcholine receptor M3 in proliferation and perineural invasion of cholangiocarcinoma cells

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Hepatobiliary & Pancreatic Diseases International 2012年第4期11卷 418-423页

作者： Yu-Jie Feng,Bing-Yuan Zhang,Ru-Yong Yao and Yun LuSecond Department of General Surgery and Central Laboratory of Molecular Biology,Affiliated Medical College Hospital,Qingdao University,Qingdao 266003,China Second Department of General Surgery Affiliated Medical College Hospital Qingdao University Qingdao 266003 China Second Department of General Surgery and Central Laboratory of Molecular Biology Affiliated Medical College Hospital Qingdao University Qingdao 266003 China

BACKGROUND:Cholangiocarcinoma,a type of malignant tumor,originates from epithelial cells of the bile duct.perineural invasion is common path for cholangiocarcinoma metastasis,and it is highly correlated with postoperative recurrence and poor prognosis.It has been reported that muscarinic acetylcholine receptor M3(mAChR M3) is widely expressed in digestive tract cancer,and may play an important role in the proliferation,differentiation,transformation and carcinogenesis of tumors.This study was to explore the effect of mAChR M3 on the growth of cholangiocarcinoma cells in vitro and provide a new approach to the pathogenesis and treatment of cholangiocarcinoma.METHODS:Streptavidin-biotin complex immunohistochemistry was carried out to assess the expression of mAChR M3 in surgical specimens of cholangiocarcinomas(40 cases) and normal bile duct tissues(9),as well as to investigate nerve infiltration.The cholangiocarcinoma cells were treated with different concentrations of selective M-receptor agonist pilocarpine and M-receptor blocker atropine sulfate to induce changes in cell proliferation.The experimental data were analyzed by the Chi-square test.RESULTS:The strongly-positive expression rate of mAChR M3 was much higher in poorly-differentiated(69%,9/13) than in well-and moderately-differentiated cholangiocarcinomas(30%,8/27)(χ 2 =5.631,P<0.05).The strongly-positive mAChR M3 expression rate in hilar cholangiocarcinoma(50%,14/28) was higher than that in cholangiocarcinomas from the middle and lower common bile duct(25%,3/12)(χ 2 =2.148,P<0.05).Cholangiocarcinomas with distant metastasis had a stronglypositive expression rate(75%,9/12),which was much higher than those without distant metastasis(29%,8/28)(χ 2 =7.410,P<0.01).The absorbance value in the pilocarpine+atropine group was significantly higher than the corresponding value in the pilocarpine group.CONCLUSIONS:The expression of mAChR M3 is influenced by the extent of differentiation,distant metastasis and the site of cholangiocarcinoma.It also plays a key role i

关键词： cholangiocarcinoma mAChR M3 immunohistochemistry perineural invasion proliferation

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