In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding ma...In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding markers.Although most rNETs patients have a favourable prognosis,the median survival period significantly decreases when high-risk factors,such as larger tumours,poorer differentiation,and lymph node metastasis exist,are present.Clinical prediction models play a vital role in guiding diagnosis and prognosis in health care,but their complex calculation formulae limit clinical use.Moreover,the prognostic models that have been developed for rNETs to date still have several limitations,such as insufficient sample sizes and the lack of external validation.A high-quality prognostic model for rNETs would guide treatment and follow-up,enabling the precise formulation of individual patient treatment and follow-up plans.The future development of models for rNETs should involve closer collab-oration with statistical experts,which would allow the construction of clinical prediction models to be standardized and robust,accurate,and highly general-izable prediction models to be created,ultimately achieving the goal of precision medicine.展开更多
AIM: To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma.METHODS: A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomograp...AIM: To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma.METHODS: A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to observe tumorgrowth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded.RESULTS: Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density loci of the tumor in the rectum wail, while enhanced CT scanning demonstrated a symmetrical intensification in tumor loci. MRI scanning showed alow signal of the tumor on T1-weighted imaging anda high signal of the tumor on T2-weighted imaging.Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could beobserved 6 wk after VX2 cell implantation, and a largearea of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation.CONCLUSION: The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma.展开更多
BACKGROUND Colorectal cancer is a common digestive cancer worldwide.As a comprehensive treatment for locally advanced rectal cancer(LARC),neoadjuvant therapy(NT)has been increasingly used as the standard treatment for...BACKGROUND Colorectal cancer is a common digestive cancer worldwide.As a comprehensive treatment for locally advanced rectal cancer(LARC),neoadjuvant therapy(NT)has been increasingly used as the standard treatment for clinical stage II/III rectal cancer.However,few patients achieve a complete pathological response,and most patients require surgical resection and adjuvant therapy.Therefore,identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance.AIM To establish effective prognostic nomograms and risk score prediction models to predict overall survival(OS)and disease-free survival(DFS)for LARC treated with NT.METHODS Nomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017.The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors,which were validated by the Cox regression method.Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves,and that of the two nomograms was conducted by calculating the concordance index(C-index)and calibration curves.The results were validated in a cohort of 65 patients from 2015 to 2017.RESULTS Seven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model:Vascular_tumors_bolt,cancer nodules,yN,body mass index,matchmouth distance from the edge,nerve aggression and postoperative carcinoembryonic antigen.The nomogram showed good predictive value for OS,with a C-index of 0.91(95%CI:0.85,0.97)and good calibration.In the validation cohort,the C-index was 0.69(95%CI:0.53,0.84).The risk factor prediction model showed good predictive value.The areas under the curve for 3-and 5-year survival were 0.811 and 0.782.The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77(95%CI:0.69,0.85).In the validation cohort,the C-index was 0.71(95%CI:0.61,0.81).The prediction model for DFS also had good predictive value,with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754.CONCLUSION We established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.展开更多
BACKGROUND Three-dimensional(3D)modelling technology translates the patient-specific anatomical information derived from two-dimensional radiological images into virtual or physical 3D models,which more closely resemb...BACKGROUND Three-dimensional(3D)modelling technology translates the patient-specific anatomical information derived from two-dimensional radiological images into virtual or physical 3D models,which more closely resemble the complex environment encountered during surgery.It has been successfully applied to surgical planning and navigation,as well as surgical training and patient education in several surgical specialties,but its uptake lags behind in colorectal surgery.Rectal cancer surgery poses specific challenges due to the complex anatomy of the pelvis,which is difficult to comprehend and visualise.AIM To review the current and emerging applications of the 3D models,both virtual and physical,in rectal cancer surgery。METHODS Medline/PubMed,Embase and Scopus databases were searched using the keywords“rectal surgery”,“colorectal surgery”,“three-dimensional”,“3D”,“modelling”,“3D printing”,“surgical planning”,“surgical navigation”,“surgical education”,“patient education”to identify the eligible full-text studies published in English between 2001 and 2020.Reference list from each article was manually reviewed to identify additional relevant papers.The conference abstracts,animal and cadaveric studies and studies describing 3D pelvimetry or radiotherapy planning were excluded.Data were extracted from the retrieved manuscripts and summarised in a descriptive way.The manuscript was prepared and revised in accordance with PRISMA 2009 checklist.RESULTS Sixteen studies,including 9 feasibility studies,were included in the systematic review.The studies were classified into four categories:feasibility of the use of 3D modelling technology in rectal cancer surgery,preoperative planning and intraoperative navigation,surgical education and surgical device design.Thirteen studies used virtual models,one 3D printed model and 2 both types of models.The construction of virtual and physical models depicting the normal pelvic anatomy and rectal cancer,was shown to be feasible.Within the clinical context,3D models were used to identify vascular anomalies,for surgical planning and navigation in lateral pelvic wall lymph node dissection and in management of recurrent rectal cancer.Both physical and virtual 3D models were found to be valuable in surgical education,with a preference for 3D printed models.The main limitations of the current technology identified in the studies were related to the restrictions of the segmentation process and the lack of 3D printing materials that could mimic the soft and deformable tissues.CONCLUSION 3D modelling technology has potential to be utilised in multiple aspects of rectal cancer surgery,however,it is still at the experimental stage of application in this setting.展开更多
BACKGROUND Multiple linear stapler firings during double stapling technique(DST)after laparoscopic low anterior resection(LAR)are associated with an increased risk of anastomotic leakage(AL).However,it is difficult to...BACKGROUND Multiple linear stapler firings during double stapling technique(DST)after laparoscopic low anterior resection(LAR)are associated with an increased risk of anastomotic leakage(AL).However,it is difficult to predict preoperatively the need for multiple linear stapler cartridges during DST anastomosis.AIM To develop a deep learning model to predict multiple firings during DST anastomosis based on pelvic magnetic resonance imaging(MRI).METHODS We collected 9476 MR images from 328 mid-low rectal cancer patients undergoing LAR with DST anastomosis,which were randomly divided into a training set(n=260)and testing set(n=68).Binary logistic regression was adopted to create a clinical model using six factors.The sequence of fast spin-echo T2-weighted MRI of the entire pelvis was segmented and analyzed.Pure-image and clinical-image integrated deep learning models were constructed using the mask region-based convolutional neural network segmentation tool and three-dimensional convolutional networks.Sensitivity,specificity,accuracy,positive predictive value(PPV),and area under the receiver operating characteristic curve(AUC)was calculated for each model.RESULTS The prevalence of≥3 linear stapler cartridges was 17.7%(58/328).The prevalence of AL was statistically significantly higher in patients with≥3 cartridges compared to those with≤2 cartridges(25.0%vs 11.8%,P=0.018).Preoperative carcinoembryonic antigen level>5 ng/mL(OR=2.11,95%CI 1.08-4.12,P=0.028)and tumor size≥5 cm(OR=3.57,95%CI 1.61-7.89,P=0.002)were recognized as independent risk factors for use of≥3 linear stapler cartridges.Diagnostic performance was better with the integrated model(accuracy=94.1%,PPV=87.5%,and AUC=0.88)compared with the clinical model(accuracy=86.7%,PPV=38.9%,and AUC=0.72)and the image model(accuracy=91.2%,PPV=83.3%,and AUC=0.81).CONCLUSION MRI-based deep learning model can predict the use of≥3 linear stapler cartridges during DST anastomosis in laparoscopic LAR surgery.This model might help determine the best anastomosis strategy by avoiding DST when there is a high probability of the need for≥3 linear stapler cartridges.展开更多
BACKGROUND Nomograms for prognosis prediction in colorectal cancer patients are few,and prognostic indicators differ with age.AIM To construct a new nomogram survival prediction tool for middle-aged and elderly patien...BACKGROUND Nomograms for prognosis prediction in colorectal cancer patients are few,and prognostic indicators differ with age.AIM To construct a new nomogram survival prediction tool for middle-aged and elderly patients with stage III rectal adenocarcinoma.METHODS A total of 2773 eligible patients were divided into the training cohort(70%)and the validation cohort(30%).Optimal cutoff values were calculated using the X-tile software for continuous variables.Univariate and multivariate Cox proportional hazards regression analyses were used to determine overall survival(OS)and cancer-specific survival(CSS)-related prognostic factors.Two nomograms were successfully constructed.The discriminant and predictive ability and clinical usefulness of the model were also assessed by multiple methods of analysis.RESULTS The 95%CI in the training group was 0.719(0.690-0.749)and 0.733(0.702-0.74),while that in the validation group was 0.739(0.696-0.782)and 0.750(0.701-0.800)for the OS and CSS nomogram prediction models,respectively.In the validation group,the AUC of the three-year survival rate was 0.762 and 0.770,while the AUC of the five-year survival rate was 0.722 and 0.744 for the OS and CSS nomograms,respectively.The nomogram distinguishes all-cause mortality from cancer-specific mortality in patients with different risk grades.The time-dependent AUC and decision curve analysis showed that the nomogram had good clinical predictive ability and decision efficacy and was significantly better than the tumor-node-metastases staging system.CONCLUSION The survival prediction model constructed in this study is helpful in evaluating the prognosis of patients and can aid physicians in clinical diagnosis and treatment.展开更多
Objective This study aimed to construct a prognostic model for rectal adenocarcinomas based on immune-related long noncoding RNAs(lncRNAs)and verify its prediction efficiency.Methods Transcript data and clinical data ...Objective This study aimed to construct a prognostic model for rectal adenocarcinomas based on immune-related long noncoding RNAs(lncRNAs)and verify its prediction efficiency.Methods Transcript data and clinical data of rectal adenocarcinomas were downloaded from The Cancer Genome Atlas(TCGA)database.Perl software(strawberry version)and R language(version 3.6.1)were used to analyze the immune-related genes and immune-related lncRNAs of rectal adenocarcinomas,and the differentially expressed immune-related lncRNAs were screened according to the criteria|log2FC|>1 and P<0.05.The key immune-related lncRNAs were screened using single-factor Cox regression analysis and lasso regression analysis.Multivariate Cox regression analysis was performed to construct an immune-related lncRNA prognostic model using the risk scores.Next,we evaluated the effectiveness of the model through Kaplan-Meier(K-M)survival analysis,ROC curve analysis,and independent prognostic analysis of clinical features.In addition,prognostic biomarkers of immune-related lncRNAs in the model were analyzed by K-M survival analysis.Results In this study,we obtained gene expression profile matrices of 89 rectal adenocarcinomas and 2 paracancerous specimens from TCGA database and applied immunologic signatures to these transcripts.Through R and Perl software analysis,we obtained 847 immune-related lncRNAs and 331 protein-encoded immune-related genes in rectal adenocarcinomas.Eight important immune-related lncRNAs related to the prognosis of rectal adenocarcinomas were identified using univariate Cox regression and lasso regression analysis.Furthermore,four immune-related lncRNAs were identified as prognostic markers of rectal adenocarcinomas via multivariate Cox regression analysis.The prognostic risk model was as follows:risk score=(-4.084)*expression LINC01871+(3.112)*expression AL158152.2+(7.616)*expression PXN-AS1+(-0.867)*expression HCP5.The independent prognostic effect of the rectal adenocarcinoma risk score model was revealed through K-M analysis,ROC curve analysis,and univariate,and multivariate Cox regression analysis(P=0.035).LINC01871(P=0.006),PXN-AS1(P=0.008),and AL158152.2(P=0.0386)were closely correlated with the prognosis of rectal adenocarcinomas through the K-M survival analysis.Conclusion We constructed a prognostic model of rectal adenocarcinomas based on four immune-related lncRNAs by analyzing the data based on TCGA database,with high prediction accuracy.We also identified two biomarkers with poor prognosis(PXN-AS1 and AL158152.2)and one biomarker with good prognosis(LINC01871).展开更多
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 accor...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 training cohort,and P=0.045 in the validation cohort).CONCLUSION The combined model incorporating Rad-score and clinical factors can provide an individualized evaluation of PNI status and help clinicians guide individualized treatment of RC patients.展开更多
AIM To establish patient-individual tumor models of rectal cancer for analyses of novel biomarkers, individual response prediction and individual therapy regimens.METHODS Establishment of cell lines was conducted by d...AIM To establish patient-individual tumor models of rectal cancer for analyses of novel biomarkers, individual response prediction and individual therapy regimens.METHODS Establishment of cell lines was conducted by direct in vitro culturing and in vivo xenografting with subsequent in vitro culturing. Cell lines were in-depth characterized concerning morphological features, invasive and migratory behavior, phenotype, molecular profile including mutational analysis, protein expression, and confirmation of origin by DNA fingerprint. Assessment of chemosensitivity towards an extensive range of current chemotherapeutic drugs and of radiosensitivity was performed including analysis of a combined radioand chemotherapeutic treatment. In addition, glucose metabolism was assessed with 18 F-fluorodeoxyglucose(FDG) and proliferation with 18 F-fluorothymidine.RESULTS We describe the establishment of ultra-low passage rectal cancer cell lines of three patients suffering from rectal cancer. Two cell lines(HROC126, HROC284 Met) were established directly from tumor specimens while HROC239 T0 M1 was established subsequent to xenografting of the tumor. Molecular analysis classified all three cell lines as CIMP-0/non-MSI-H(sporadic standard) type. Mutational analysis revealed following mutational profiles: HROC126: APC^(wt), TP53^(wt), KRAS^(wt), BRAF^(wt), PTEN^(wt); HROC239 T0 M1: APC^(mut), P53^(wt), KRAS^(mut), BRAF^(wt), PTEN^(mut) and HROC284 Met: APC^(wt), P53^(mut), KRAS^(mut), BRAF^(wt), PTEN^(mut). All cell lines could be characterized as epithelial(EpCAM+) tumor cells with equivalent morphologic features and comparable growth kinetics. The cell lines displayed a heterogeneous response toward chemotherapy, radiotherapy and their combined application. HROC126 showed a highly radio-resistant phenotype and HROC284 Met was more susceptible to a combined radiochemotherapy than HROC126 and HROC239 T0 M1. Analysis of 18 F-FDG uptake displayed a markedly reduced FDG uptake of all three cell lines after combined radiochemotherapy. CONCLUSION These newly established and in-depth characterized ultra-low passage rectal cancer cell lines provide a useful instrument for analysis of biological characteristics of rectal cancer.展开更多
目的筛选直肠癌新辅助放化疗(CRT)疗效预测长链非编码RNA(lncRNA)分子标志物,分析参与CRT疗效调控相关信号通路,建立CRT疗效预测模型。方法利用lncRNA芯片进行lncRNA差异表达检测,使用R软件Limma包在CRT反应组和CRT无反应组间对比筛选差...目的筛选直肠癌新辅助放化疗(CRT)疗效预测长链非编码RNA(lncRNA)分子标志物,分析参与CRT疗效调控相关信号通路,建立CRT疗效预测模型。方法利用lncRNA芯片进行lncRNA差异表达检测,使用R软件Limma包在CRT反应组和CRT无反应组间对比筛选差异lncRNA(P<0.05和|Log2FC|>1),进行分子标志物筛选。采用基因本体(GO)分析对差异表达基因进行功能分析,采用京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)对筛选的差异基因进行信号通路富集分析。进一步采用实时定量反转录聚合酶链式反应(qRT-PCR)检测98例样本。采用logistic回归构建CRT治疗预测模型。绘制受试者操作特征曲线(ROC)计算曲线下面积(AUC)以评价模型的判别区分能力。结果CRT反应组中,823个lncRNA表达上调,216个lncRNA表达下调,449个基因表达上调,81个基因表达下调。新辅助放化疗相关上调排名前10的差异表达lncRNA分别为LUCAT1、LINC02356、HIF1A-AS2、Lnc-ZNF644-1、Lnc-ADAMTS12-3、LINC02356、Lnc-CLIC4-1、Lnc-PTX3-4、DARS-AS1、MIR210HG。下调排名前10的分别为Lnc-COL6A3-2、Lnc-FBN1-2、Lnc-FOXA1-3、Lnc-KRTAP9-7-1、LINC00562、Lnc-NCS1-1、LINC00456、Lnc-FBLL1-2、USP2-AS1、Lnc-INPPL1-2。GO分析结果提示,差异基因主要富集在上皮细胞分化、中间丝、中间丝细胞骨架、突触后膜、颗粒分泌、细胞因子受体活性等分子生物学功能方面。KEGG富集分析提示,差异表达基因主要富集在HIF-1信号通路、Th17细胞分化、戊糖磷酸途径、精氨酸和脯氨酸代谢、果糖和甘露糖代谢、磷脂酶D信号通路、溶酶体等信号通路方面。logistic回归模型显示,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型具有较好的预测能力,AUC为0.887(95%CI 0.820~0.954)。模型回归方程logit(p)=1.582×LINC00562-1.969×LINC02356-0.798×LUCAT1+4.357。模型的灵敏度为81.3%,特异度为84.0%。结论直肠癌CRT反应良好和CRT无反应者间lncRNA分子存在明显的差异表达,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型对CRT疗效具有较好的预测能力。展开更多
基金Supported by the National Natural Science Foundation of China,No.82100599 and No.81960112the Jiangxi Provincial Department of Science and Technology,No.20242BAB26122+1 种基金the Science and Technology Plan of Jiangxi Provincial Administration of Traditional Chinese Medicine,No.2023Z021the Project of Jiangxi Provincial Academic and Technical Leaders Training Program for Major Disciplines,No.20243BCE51001.
文摘In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding markers.Although most rNETs patients have a favourable prognosis,the median survival period significantly decreases when high-risk factors,such as larger tumours,poorer differentiation,and lymph node metastasis exist,are present.Clinical prediction models play a vital role in guiding diagnosis and prognosis in health care,but their complex calculation formulae limit clinical use.Moreover,the prognostic models that have been developed for rNETs to date still have several limitations,such as insufficient sample sizes and the lack of external validation.A high-quality prognostic model for rNETs would guide treatment and follow-up,enabling the precise formulation of individual patient treatment and follow-up plans.The future development of models for rNETs should involve closer collab-oration with statistical experts,which would allow the construction of clinical prediction models to be standardized and robust,accurate,and highly general-izable prediction models to be created,ultimately achieving the goal of precision medicine.
文摘AIM: To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma.METHODS: A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to observe tumorgrowth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded.RESULTS: Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density loci of the tumor in the rectum wail, while enhanced CT scanning demonstrated a symmetrical intensification in tumor loci. MRI scanning showed alow signal of the tumor on T1-weighted imaging anda high signal of the tumor on T2-weighted imaging.Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could beobserved 6 wk after VX2 cell implantation, and a largearea of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation.CONCLUSION: The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma.
文摘BACKGROUND Colorectal cancer is a common digestive cancer worldwide.As a comprehensive treatment for locally advanced rectal cancer(LARC),neoadjuvant therapy(NT)has been increasingly used as the standard treatment for clinical stage II/III rectal cancer.However,few patients achieve a complete pathological response,and most patients require surgical resection and adjuvant therapy.Therefore,identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance.AIM To establish effective prognostic nomograms and risk score prediction models to predict overall survival(OS)and disease-free survival(DFS)for LARC treated with NT.METHODS Nomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017.The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors,which were validated by the Cox regression method.Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves,and that of the two nomograms was conducted by calculating the concordance index(C-index)and calibration curves.The results were validated in a cohort of 65 patients from 2015 to 2017.RESULTS Seven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model:Vascular_tumors_bolt,cancer nodules,yN,body mass index,matchmouth distance from the edge,nerve aggression and postoperative carcinoembryonic antigen.The nomogram showed good predictive value for OS,with a C-index of 0.91(95%CI:0.85,0.97)and good calibration.In the validation cohort,the C-index was 0.69(95%CI:0.53,0.84).The risk factor prediction model showed good predictive value.The areas under the curve for 3-and 5-year survival were 0.811 and 0.782.The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77(95%CI:0.69,0.85).In the validation cohort,the C-index was 0.71(95%CI:0.61,0.81).The prediction model for DFS also had good predictive value,with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754.CONCLUSION We established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.
文摘BACKGROUND Three-dimensional(3D)modelling technology translates the patient-specific anatomical information derived from two-dimensional radiological images into virtual or physical 3D models,which more closely resemble the complex environment encountered during surgery.It has been successfully applied to surgical planning and navigation,as well as surgical training and patient education in several surgical specialties,but its uptake lags behind in colorectal surgery.Rectal cancer surgery poses specific challenges due to the complex anatomy of the pelvis,which is difficult to comprehend and visualise.AIM To review the current and emerging applications of the 3D models,both virtual and physical,in rectal cancer surgery。METHODS Medline/PubMed,Embase and Scopus databases were searched using the keywords“rectal surgery”,“colorectal surgery”,“three-dimensional”,“3D”,“modelling”,“3D printing”,“surgical planning”,“surgical navigation”,“surgical education”,“patient education”to identify the eligible full-text studies published in English between 2001 and 2020.Reference list from each article was manually reviewed to identify additional relevant papers.The conference abstracts,animal and cadaveric studies and studies describing 3D pelvimetry or radiotherapy planning were excluded.Data were extracted from the retrieved manuscripts and summarised in a descriptive way.The manuscript was prepared and revised in accordance with PRISMA 2009 checklist.RESULTS Sixteen studies,including 9 feasibility studies,were included in the systematic review.The studies were classified into four categories:feasibility of the use of 3D modelling technology in rectal cancer surgery,preoperative planning and intraoperative navigation,surgical education and surgical device design.Thirteen studies used virtual models,one 3D printed model and 2 both types of models.The construction of virtual and physical models depicting the normal pelvic anatomy and rectal cancer,was shown to be feasible.Within the clinical context,3D models were used to identify vascular anomalies,for surgical planning and navigation in lateral pelvic wall lymph node dissection and in management of recurrent rectal cancer.Both physical and virtual 3D models were found to be valuable in surgical education,with a preference for 3D printed models.The main limitations of the current technology identified in the studies were related to the restrictions of the segmentation process and the lack of 3D printing materials that could mimic the soft and deformable tissues.CONCLUSION 3D modelling technology has potential to be utilised in multiple aspects of rectal cancer surgery,however,it is still at the experimental stage of application in this setting.
基金Shanghai Jiaotong University,No.YG2019QNB24This study was reviewed and approved by Ruijin Hospital Ethics Committee(Approval No.2019-82).
文摘BACKGROUND Multiple linear stapler firings during double stapling technique(DST)after laparoscopic low anterior resection(LAR)are associated with an increased risk of anastomotic leakage(AL).However,it is difficult to predict preoperatively the need for multiple linear stapler cartridges during DST anastomosis.AIM To develop a deep learning model to predict multiple firings during DST anastomosis based on pelvic magnetic resonance imaging(MRI).METHODS We collected 9476 MR images from 328 mid-low rectal cancer patients undergoing LAR with DST anastomosis,which were randomly divided into a training set(n=260)and testing set(n=68).Binary logistic regression was adopted to create a clinical model using six factors.The sequence of fast spin-echo T2-weighted MRI of the entire pelvis was segmented and analyzed.Pure-image and clinical-image integrated deep learning models were constructed using the mask region-based convolutional neural network segmentation tool and three-dimensional convolutional networks.Sensitivity,specificity,accuracy,positive predictive value(PPV),and area under the receiver operating characteristic curve(AUC)was calculated for each model.RESULTS The prevalence of≥3 linear stapler cartridges was 17.7%(58/328).The prevalence of AL was statistically significantly higher in patients with≥3 cartridges compared to those with≤2 cartridges(25.0%vs 11.8%,P=0.018).Preoperative carcinoembryonic antigen level>5 ng/mL(OR=2.11,95%CI 1.08-4.12,P=0.028)and tumor size≥5 cm(OR=3.57,95%CI 1.61-7.89,P=0.002)were recognized as independent risk factors for use of≥3 linear stapler cartridges.Diagnostic performance was better with the integrated model(accuracy=94.1%,PPV=87.5%,and AUC=0.88)compared with the clinical model(accuracy=86.7%,PPV=38.9%,and AUC=0.72)and the image model(accuracy=91.2%,PPV=83.3%,and AUC=0.81).CONCLUSION MRI-based deep learning model can predict the use of≥3 linear stapler cartridges during DST anastomosis in laparoscopic LAR surgery.This model might help determine the best anastomosis strategy by avoiding DST when there is a high probability of the need for≥3 linear stapler cartridges.
基金The National Natural Science Foundation of China,No.81770631.
文摘BACKGROUND Nomograms for prognosis prediction in colorectal cancer patients are few,and prognostic indicators differ with age.AIM To construct a new nomogram survival prediction tool for middle-aged and elderly patients with stage III rectal adenocarcinoma.METHODS A total of 2773 eligible patients were divided into the training cohort(70%)and the validation cohort(30%).Optimal cutoff values were calculated using the X-tile software for continuous variables.Univariate and multivariate Cox proportional hazards regression analyses were used to determine overall survival(OS)and cancer-specific survival(CSS)-related prognostic factors.Two nomograms were successfully constructed.The discriminant and predictive ability and clinical usefulness of the model were also assessed by multiple methods of analysis.RESULTS The 95%CI in the training group was 0.719(0.690-0.749)and 0.733(0.702-0.74),while that in the validation group was 0.739(0.696-0.782)and 0.750(0.701-0.800)for the OS and CSS nomogram prediction models,respectively.In the validation group,the AUC of the three-year survival rate was 0.762 and 0.770,while the AUC of the five-year survival rate was 0.722 and 0.744 for the OS and CSS nomograms,respectively.The nomogram distinguishes all-cause mortality from cancer-specific mortality in patients with different risk grades.The time-dependent AUC and decision curve analysis showed that the nomogram had good clinical predictive ability and decision efficacy and was significantly better than the tumor-node-metastases staging system.CONCLUSION The survival prediction model constructed in this study is helpful in evaluating the prognosis of patients and can aid physicians in clinical diagnosis and treatment.
基金Supported by a grant from the Health Commission of Hubei Province Scientific Research Project(No.WJ2019M118)。
文摘Objective This study aimed to construct a prognostic model for rectal adenocarcinomas based on immune-related long noncoding RNAs(lncRNAs)and verify its prediction efficiency.Methods Transcript data and clinical data of rectal adenocarcinomas were downloaded from The Cancer Genome Atlas(TCGA)database.Perl software(strawberry version)and R language(version 3.6.1)were used to analyze the immune-related genes and immune-related lncRNAs of rectal adenocarcinomas,and the differentially expressed immune-related lncRNAs were screened according to the criteria|log2FC|>1 and P<0.05.The key immune-related lncRNAs were screened using single-factor Cox regression analysis and lasso regression analysis.Multivariate Cox regression analysis was performed to construct an immune-related lncRNA prognostic model using the risk scores.Next,we evaluated the effectiveness of the model through Kaplan-Meier(K-M)survival analysis,ROC curve analysis,and independent prognostic analysis of clinical features.In addition,prognostic biomarkers of immune-related lncRNAs in the model were analyzed by K-M survival analysis.Results In this study,we obtained gene expression profile matrices of 89 rectal adenocarcinomas and 2 paracancerous specimens from TCGA database and applied immunologic signatures to these transcripts.Through R and Perl software analysis,we obtained 847 immune-related lncRNAs and 331 protein-encoded immune-related genes in rectal adenocarcinomas.Eight important immune-related lncRNAs related to the prognosis of rectal adenocarcinomas were identified using univariate Cox regression and lasso regression analysis.Furthermore,four immune-related lncRNAs were identified as prognostic markers of rectal adenocarcinomas via multivariate Cox regression analysis.The prognostic risk model was as follows:risk score=(-4.084)*expression LINC01871+(3.112)*expression AL158152.2+(7.616)*expression PXN-AS1+(-0.867)*expression HCP5.The independent prognostic effect of the rectal adenocarcinoma risk score model was revealed through K-M analysis,ROC curve analysis,and univariate,and multivariate Cox regression analysis(P=0.035).LINC01871(P=0.006),PXN-AS1(P=0.008),and AL158152.2(P=0.0386)were closely correlated with the prognosis of rectal adenocarcinomas through the K-M survival analysis.Conclusion We constructed a prognostic model of rectal adenocarcinomas based on four immune-related lncRNAs by analyzing the data based on TCGA database,with high prediction accuracy.We also identified two biomarkers with poor prognosis(PXN-AS1 and AL158152.2)and one biomarker with good prognosis(LINC01871).
基金This study was reviewed and approved by the Ethics Committee of West China Hospital of Sichuan University(Approved No.1159).
文摘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 training cohort,and P=0.045 in the validation cohort).CONCLUSION The combined model incorporating Rad-score and clinical factors can provide an individualized evaluation of PNI status and help clinicians guide individualized treatment of RC patients.
基金the German Cancer Foundation to Oliver H Kr?mer,No.KR 2291/7-1
文摘AIM To establish patient-individual tumor models of rectal cancer for analyses of novel biomarkers, individual response prediction and individual therapy regimens.METHODS Establishment of cell lines was conducted by direct in vitro culturing and in vivo xenografting with subsequent in vitro culturing. Cell lines were in-depth characterized concerning morphological features, invasive and migratory behavior, phenotype, molecular profile including mutational analysis, protein expression, and confirmation of origin by DNA fingerprint. Assessment of chemosensitivity towards an extensive range of current chemotherapeutic drugs and of radiosensitivity was performed including analysis of a combined radioand chemotherapeutic treatment. In addition, glucose metabolism was assessed with 18 F-fluorodeoxyglucose(FDG) and proliferation with 18 F-fluorothymidine.RESULTS We describe the establishment of ultra-low passage rectal cancer cell lines of three patients suffering from rectal cancer. Two cell lines(HROC126, HROC284 Met) were established directly from tumor specimens while HROC239 T0 M1 was established subsequent to xenografting of the tumor. Molecular analysis classified all three cell lines as CIMP-0/non-MSI-H(sporadic standard) type. Mutational analysis revealed following mutational profiles: HROC126: APC^(wt), TP53^(wt), KRAS^(wt), BRAF^(wt), PTEN^(wt); HROC239 T0 M1: APC^(mut), P53^(wt), KRAS^(mut), BRAF^(wt), PTEN^(mut) and HROC284 Met: APC^(wt), P53^(mut), KRAS^(mut), BRAF^(wt), PTEN^(mut). All cell lines could be characterized as epithelial(EpCAM+) tumor cells with equivalent morphologic features and comparable growth kinetics. The cell lines displayed a heterogeneous response toward chemotherapy, radiotherapy and their combined application. HROC126 showed a highly radio-resistant phenotype and HROC284 Met was more susceptible to a combined radiochemotherapy than HROC126 and HROC239 T0 M1. Analysis of 18 F-FDG uptake displayed a markedly reduced FDG uptake of all three cell lines after combined radiochemotherapy. CONCLUSION These newly established and in-depth characterized ultra-low passage rectal cancer cell lines provide a useful instrument for analysis of biological characteristics of rectal cancer.
文摘目的筛选直肠癌新辅助放化疗(CRT)疗效预测长链非编码RNA(lncRNA)分子标志物,分析参与CRT疗效调控相关信号通路,建立CRT疗效预测模型。方法利用lncRNA芯片进行lncRNA差异表达检测,使用R软件Limma包在CRT反应组和CRT无反应组间对比筛选差异lncRNA(P<0.05和|Log2FC|>1),进行分子标志物筛选。采用基因本体(GO)分析对差异表达基因进行功能分析,采用京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)对筛选的差异基因进行信号通路富集分析。进一步采用实时定量反转录聚合酶链式反应(qRT-PCR)检测98例样本。采用logistic回归构建CRT治疗预测模型。绘制受试者操作特征曲线(ROC)计算曲线下面积(AUC)以评价模型的判别区分能力。结果CRT反应组中,823个lncRNA表达上调,216个lncRNA表达下调,449个基因表达上调,81个基因表达下调。新辅助放化疗相关上调排名前10的差异表达lncRNA分别为LUCAT1、LINC02356、HIF1A-AS2、Lnc-ZNF644-1、Lnc-ADAMTS12-3、LINC02356、Lnc-CLIC4-1、Lnc-PTX3-4、DARS-AS1、MIR210HG。下调排名前10的分别为Lnc-COL6A3-2、Lnc-FBN1-2、Lnc-FOXA1-3、Lnc-KRTAP9-7-1、LINC00562、Lnc-NCS1-1、LINC00456、Lnc-FBLL1-2、USP2-AS1、Lnc-INPPL1-2。GO分析结果提示,差异基因主要富集在上皮细胞分化、中间丝、中间丝细胞骨架、突触后膜、颗粒分泌、细胞因子受体活性等分子生物学功能方面。KEGG富集分析提示,差异表达基因主要富集在HIF-1信号通路、Th17细胞分化、戊糖磷酸途径、精氨酸和脯氨酸代谢、果糖和甘露糖代谢、磷脂酶D信号通路、溶酶体等信号通路方面。logistic回归模型显示,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型具有较好的预测能力,AUC为0.887(95%CI 0.820~0.954)。模型回归方程logit(p)=1.582×LINC00562-1.969×LINC02356-0.798×LUCAT1+4.357。模型的灵敏度为81.3%,特异度为84.0%。结论直肠癌CRT反应良好和CRT无反应者间lncRNA分子存在明显的差异表达,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型对CRT疗效具有较好的预测能力。