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Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis

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Chinese Medical Journal 2024年第4期137卷 421-430页

作者： Ming Cai Ke Zhao Lin Wu Yanqi Huang Minning Zhao Qingru Hu Qicong Chen Su Yao Zhenhui Li xinjuan fan Zaiyi Liu Department of Radiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application GuangzhouGuangdong 510080China Guangdong Cardiovascular Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Medical Research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalYunnan Cancer CenterKunmingYunnan 650118China The Second School of Clinical Medicine Southern Medical UniversityGuangzhouGuangdong 510515China Institute of Computing Science and Technology Guangzhou UniversityGuangzhouGuangdong 510006China Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655China

Background:Artificial intelligence(AI)technology represented by deep learning has made remarkable achievements in digital pathology,enhancing the accuracy and reliability of diagnosis and prognosis *** spatial distribution of CD3^(+)and CD8^(+)T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer(CRC).This study aimed to investigate CD3_(CT)(CD3^(+)T cells density in the core of the tumor[CT])prognostic ability in patients with CRC by using AI ***:The study involved the enrollment of 492 patients from two distinct medical centers,with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation *** facilitate tissue segmentation and T-cells quantification in whole-slide images(WSIs),a fully automated workflow based on deep learning was *** the completion of tissue segmentation and subsequent cell segmentation,a comprehensive analysis was ***:The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3_(CT) and CD3-CD8(the combination of CD3^(+)and CD8^(+)T cells density within the CT and invasive margin)in predicting mortality(C-index in training cohort:0.65 vs.0.64;validation cohort:0.69 vs.0.69).The CD3_(CT) was confirmed as an independent prognostic factor,with high CD3_(CT) density associated with increased overall survival(OS)in the training cohort(hazard ratio[HR]=0.22,95%confidence interval[CI]:0.12–0.38,P<0.001)and validation cohort(HR=0.21,95%CI:0.05–0.92,P=0.037).Conclusions:We quantify the spatial distribution of CD3^(+)and CD8^(+)T cells within tissue regions in WSIs using AI *** CD3_(CT) confirmed as a stage-independent predictor for OS in CRC ***,CD3_(CT) shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

关键词： Colorectal cancer Artificial intelligence Deep learning Digital pathology Prognosis Immune cells CD3 CD8 TME

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Radiation-induced injury on surgical margins:a clue to anastomotic leakage after rectal-cancer resection with neoadjuvant chemoradiotherapy?

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Gastroenterology Report 2019年第2期7卷 98-106,I0001页

作者： Qiyuan Qin Yaxi Zhu Peihuang Wu xinjuan fan Yan Huang Binjie Huang Jianping Wang Lei Wang Department of Colorectal Surgery The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510655P.R.China Department of Pathology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510655P.R.China Guangdong Institute of Gastroenterology GuangzhouGuangdong 510655P.R.China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases GuangzhouGuangdong 510655P.R.China

Background:Few studies on anastomotic condition after rectal-cancer resection and its effect on anastomotic leakage(AL)are available up to *** study aimed to investigate potential radiation-induced injury left on surgical margins of anterior resection after neoadjuvant chemoradiotherapy(nCRT)and its association with ***:We retrospectively identified 161 consecutive patients who underwent anterior resection with nCRT,neoadjuvant chemotherapy without radiation(nCT)or no neoadjuvant therapy between 2014 and *** samples of resection margins were assessed using a specific histopathological score and microvessel density in *** score matching was used to balance the baseline *** between AL and histopathological features was ***:AL occurred in 13 of 54 patients undergoing nCRT,5 of 48 patients undergoing nCT and 7 of 59 patients without neoadjuvant *** after matching showed median(range)histopathological scores as follows:3(0–8)vs 0(0–3)vs 0(0–2)for the proximal margin(P<0.001);4(2–9)vs 0(0–4)vs 0(0–3)for the distal margin(P<0.001).Correspondingly,mean(SD)microvessel densities were as follows:21.7(7.9)vs 27.2(8.6)vs 27.3(9.4)for the proximal margin(P=0.003);18.1(9.3)vs 25.2(12.9)vs 24.9(7.4)for the distal margin(P<0.001).Among patients undergoing nCRT,AL was associated with increased histopathological score(P=0.003)and decreased microvessel density(P=0.004)on the proximal ***:Surgical margins of rectal-cancer resection are exposed to certain radiation-induced injury after *** is associated with aggravated radiation damage on the proximal margin.

关键词： Anastomotic leakage rectal cancer anterior resection neoadjuvant chemoradiotherapy radiation injury histopathology

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Density and distribution of lymphocytes in pretherapeutic rectal cancer and response to neoadjuvant therapy

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Gastroenterology Report 2020年第6期8卷 445-452,I0002页

作者： Sicong Lai Xiaoying Lou xinjuan fan Weipeng Sun Yanhong Deng Jianping Wang Yan Huang Ruoxu Dou Department of Colorectal Surgery The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Pathology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Colorectal Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Department of Medical Oncology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Lymphocytic density in rectal cancer has been reported to be associated with therapeutic response,but the role of the lymphocytic distribution pattern remains to be *** study aimed to evaluate the association between the distribution and density of lymphocytes in rectal-cancer tissue with tumor response to neoadjuvant ***:We retrospectively analysed 134 patients with rectal cancer receiving neoadjuvant therapy within a prospectively maintained *** biopsy samples were stained with immunohistochemistry(CD4 and CD8).Densities of intratumoral periglandular lymphocytes(IPLs)and tumor-infiltrating lymphocytes(TILs)were assessed ***-regression analysis was used to assess associations of lymphocyte densities with tumor regression grade(TRG),controlling for clinicopathological,molecular,and regimen ***:Compared with cases in the lowest quartile of CD8^(+)TILs,those in the highest quartile were significantly associated with better TRG(multivariate odds ratio,0.23;95%confidence interval,0.07 to 0.76;P<0.001).In contrast,CD8^(+)IPLs,CD4^(+)IPLs,and CD4^(+)TILswere not significantly associatedwith TRG(P=0.033,0.156,and 0.170,respectively).Sensitivity analyses detected no interaction between CD8^(+)TILs and regimen of neoadjuvant radiation(Pinteraction=0.831)or chemotherapy(Pinteraction=0.879)on ***:Our data suggest that CD8^(+)TILs,but not IPLs,are independently associated with response to neoadjuvant therapy,regardless of the regimen of radiation or chemotherapy.

关键词： neoadjuvant therapy tumor-infiltrating lymphocytes therapeutic response locally advanced rectal cancer

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Bone marrow metastasis from advanced gastric cancer complicated with disseminated intravascular coagulation:a highly aggressive but manageable disease subtype

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Cancer Communications 2022年第4期42卷 350-354页

作者： Xiaohui Zhai Caiqin Wang Shanshan Li Taiyuan Cao Ge Du Yan Zhang Dianke Chen xinjuan fan Yan Huang Ping Hu Jian Zheng Zuli Yang Lei Lian Junsheng Peng Ping Lan Jian Xiao Department of Medical Oncology The Sixth Affiliated Hospital of Sun-Yat Sen UniversityGuangzhouGuangdong 510655P.R.China Department of Pathology The Sixth Affiliated Hospital of Sun-Yat Sen UniversityGuangzhouGuangdong 510655P.R.China Department of Nuclear Medicine The Sixth Affiliated Hospital of Sun-Yat Sen UniversityGuangzhouGuangdong 510655P.R.China Department of Radiation Oncology The Sixth Affiliated Hospital of Sun-Yat Sen UniversityGuangzhouGuangdong 510655P.R.China Department of Gastrointestinal Surgery The Sixth Affiliated Hospital of Sun-Yat Sen UniversityGuangzhouGuangdong 510655P.R.China Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseasesthe Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655P.R.China Department of Colorectal Surgery The Sixth Affiliated Hospital of Sun-Yat Sen UniversityGuangzhouGuangdong 510655P.R.China

Dear Editor,Gastric cancer(GC)is the fifth most commonly diagnosed cancer and the fourth cause of cancer-related death worldwide[1,2].It has a greater prevalence in Eastern Asia,compared to other parts of the world,whereby more than two-thirds of the cases are diagnosed as advanced gastric cancer(AGC)[3].Disseminated intravascular coagulation(DIC)is a clinicopathologic syndrome characterized by laboratory evidence of platelets and clotting factors consumption,and proteolytic degradation.

关键词： intravascular cancer metastasis

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基于改进的全卷积网络模型预测局部进展期直肠癌新辅助放化疗疗效

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协和医学杂志 2022年第4期13卷 605-612页

作者：王方庞晓琳范新娟中山大学胃肠病学研究所广州510655 中山大学附属第六医院放射肿瘤科广州510655 中山大学附属第六医院病理科广州510655

目的建立基于MRI影像图像预测局部进展期直肠癌(locally advanced rectal cancer,LARC)新辅助放化疗(neoadjuvant chemoradiotherapy,nCRT)后病理学完全缓解(pathological complete response,pCR)模型,以辅助患者个性化治疗方案的制订。方法回顾性纳入2013年6月至2018年12月中山大学附属第六医院接受nCRT治疗且行全直肠系膜切除术组织病理对治疗效果进行评定的LARC患者。按1∶2的比例将患者依照住院时间先后顺序分为Data A与Data B 2个数据集。其中Data A数据集用于语义分割模型训练,Data B数据集按7∶3的比例随机分为训练集和验证集,分别用于pCR预测模型训练与评价。收集Data A数据集病例的T2加权MRI影像资料,采用改进的全卷积网络(fully convolutional networks,FCN)模型对肿瘤区域进行语义分割,建立语义分割模型并提取最终卷积层中的影像特征。采用最小绝对值收缩和选择算子(least absolute shrinkage and selection operator,LASSO)回归法对提取的影像特征进行筛选,构建可预测pCR状态的支持向量机(support vector machine,SVM)分类器(预测模型)。以Data B训练集数据为基础,对该预测模型的性能进行训练,进一步在Data B验证集中对其性能进行评价。结果共入选符合纳入和排除标准的LARC患者304例,nCRT治疗后82例判定为pCR,222例为非pCR。2013年6月至2015年11月的103例患者为Data A数据集,2015年12月至2018年12月的201例患者为Data B数据集。Data B数据集中,训练集140例、验证集61例。改进的FCN模型对Data B数据集图像分割的Dice值为0.79(95%CI:0.65~0.81),灵敏度为80%(95%CI:77%~83%),特异度为72%(95%CI:64%~85%)。语义分割模型共提取最终卷积层中512个影像特征,经LASSO回归筛选后保留7个,用于pCR状态预测。预测模型在Data B训练集中预测pCR的曲线下面积(area under the curve,AUC)为0.65(95%CI:0.61~0.71),在Data B验证集中的AUC为0.69(95%CI:0.59~0.74)。结论本研究提出的改进的FCN模型,对MRI图像进行语义分割具有较高的准确度。基于该方法构建的模型预测LARC患者接受nCRT治疗后pCR状态具有可行性。

关键词：局部进展期直肠癌新辅助治疗病理学完全缓解深度学习

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Preoperative Prediction of Lymph Node Metastasis in Colorectal Cancer with Deep Learning

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Biomedical Engineering Frontiers 2022年第1期3卷 93-104页

作者： Hailing Liu Yu Zhao fan Yang Xiaoying Lou Feng Wu Hang Li Xiaohan Xing Tingying Peng Bjoern Menze Junzhou Huang Shujun Zhang Anjia Han Jianhua Yao xinjuan fan Department of Pathology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510655China AI Lab TencentShenzhen 518057China Department of Computer Science Technical University of MunichMunich 85748Germany Department of Computer Science Xiamen UniversityXiamen 361005China Department of Electronic Engineering The Chinese University of Hong KongHong Kong 999077China Institute of Computational Biology Helmholtz Zentrum MünchenNeuherberg 85764Germany Helmholtz AI Helmholtz Zentrum MünchenNeuherberg 85764Germany Department of Quantitative Biomedicine University of ZurichZurich 8091Switzerland Department of Pathology The Fourth Hospital of Harbin Medical UniversityHarbin 150001China Department of Pathology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China

*** develop an artificial intelligence method predicting lymph node metastasis(LNM)for patients with colorectal cancer(CRC).Impact Statement.A novel interpretable multimodal AI-based method to predict LNM for CRC patients by integrating information of pathological images and serum tumor-specific *** diagnosis of LNM is essential in treatment planning for CRC *** radiology imaging and genomic tests approaches are either unreliable or too ***.A total of 1338 patients were recruited,where 1128 patients from one centre were included as the discovery cohort and 210 patients from other two centres were involved as the external validation *** developed a Multimodal Multiple Instance Learning(MMIL)model to learn latent features from pathological images and then jointly integrated the clinical biomarker features for predicting LNM *** heatmaps of the obtained MMIL model were generated for model *** MMIL model outperformed preoperative radiology-imaging diagnosis and yielded high area under the curve(AUCs)of 0.926,0.878,0.809,and 0.857 for patients with stage T1,T2,T3,and T4 CRC,on the discovery *** the external cohort,it obtained AUCs of 0.855,0.832,0.691,and 0.792,respectively(T1-T4),which indicates its prediction accuracy and potential adaptability among multiple *** MMIL model showed the potential in the early diagnosis of LNM by referring to pathological images and tumor-specific biomarkers,which is easily accessed in different *** revealed the histomorphologic features determining the LNM prediction indicating the model ability to learn informative latent features.

关键词： diagnosis centre latent

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溃疡性结肠炎与克罗恩病的病理鉴别诊断

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中华炎性肠病杂志（中英文） 2018年第3期2卷 191-194页

作者：范新娟田素芳李增山黄艳中山大学附属第六医院病理科广州510655 武汉大学中南医院病理科 430071 空军军医大学(第四军医大学)西京消化病医院病理科西安710032

炎症性肠病(inflammatory bowel disease,IBD)是病因尚不清楚的慢性非特异性肠道炎症性疾病,主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD).IBD的诊断缺乏金标准,确诊需要综合临床、内镜、影像及病理表现...

炎症性肠病(inflammatory bowel disease,IBD)是病因尚不清楚的慢性非特异性肠道炎症性疾病,主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD).IBD的诊断缺乏金标准,确诊需要综合临床、内镜、影像及病理表现,并且在排除感染性肠炎和其他非感染性肠炎后作出诊断.UC与CD的鉴别在手术标本中相对容易,但在内镜活检标本相对困难.本文主要从这两个方面进行概述,并简要介绍IBD的少见亚型.

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脑肿瘤术后患者植入输液港相关感染危险因素分析

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巴楚医学 2020年第4期3卷 34-38页

作者：熊丽娇范新娟神经外科&三峡大学神经病学研究所湖北宜昌443003 眼科湖北宜昌443003

目的:探讨脑肿瘤术后接受放化疗患者发生完全植入式输液港(TIAP)相关感染的危险因素。方法:纳入2017年10月~2019年11月期间脑肿瘤术后接受TIAP植入的患者,对患者一般临床资料、TIAP相关操作指标、输液港及外周血细菌培养结果进行分析。... 详细信息

目的:探讨脑肿瘤术后接受放化疗患者发生完全植入式输液港(TIAP)相关感染的危险因素。方法:纳入2017年10月~2019年11月期间脑肿瘤术后接受TIAP植入的患者,对患者一般临床资料、TIAP相关操作指标、输液港及外周血细菌培养结果进行分析。结果:255例脑肿瘤术后患者植入TIAP,24例发生TIAP相关性感染者。与非感染组相比,感染组年龄大,合并糖尿病、其他部位感染、发生上肢静脉血栓以及门诊随访的比例更高(均P0.05)。结论:患者高龄、合并糖尿病、发生上肢静脉血栓、门诊维护及管理是TIAP相关性感染发生的重要危险因素。

关键词：完全植入式输液港脑肿瘤感染

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Epidermal growth factor receptor stabilizes programmed death ligand 1 by glycosylation in colorectal cancer with microstatellite instability status

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Journal of Bio-X Research 2019年第1期2卷 1-8页

作者： Xinke Yin Yunlong Wang Shaomei Bai Weixing Feng Lili Feng Wanwen Zhao Mingbiao Wei Xiaolin Pang Shuai Liu Haiyang Chen fang He Yikan Cheng Junxiang Yin Dalu Zhang Jian Zheng Lei Wang xinjuan fan Xiangbo Wan Guangdong Institute of Gastroenterology Institute Sun Yat-sen University Department of Radiation Oncology the Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong Province Department of Pathology the Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong Province China National Center for Biotechnology Development BeijingChina

Programmed death ligand-1(PD-L1)is involved in inhibiting of T lymphocyte proliferation,producing cytokine,cytolytic activity,and suppressing of the immune *** with molecular alterations involved in DNA mismatch repair promote cancer initiation and tumor *** studies show that colorectal cancer(CRC)patients harboring microsatellite instability(MSI)have a higher anti-programmed cell death protein 1/PD-L1 immunotherapy response ratio compared with microsatellite stable subgroup *** underlying mechanism has however remained ***,we found that compared with microsatellite stable samples,PD-L1 was glycosylated and highly expressed both in MSI CRC cell lines and tissue ***,PD-L1 was Nglycosylated at its N35,N192,N200,and N219 sites,and the four glycosylation sites were all responsible for PD-L1 ***,non-glycosylated PD-L1 underwent rapid degradation compared with glycosylated PD-L1 through the 26S proteasome *** faster degradation of the non-glycosylated PD-L1 was ascribed to its binding to glycogen synthase kinase 3b via *** degradation phenotype was,however,not observed for glycosylated ***,glycosylated PD-L1 was up-regulated by activated epidermal growth factor receptor in MSI CRC ***,our results indicate that epidermal growth factor receptor stabilized PD-L1 via glycosylation in MSI CRC cells,uncovering a novel role of PD-L1 in MSI CRC immunosuppression and disease *** study was approved by the Clinical Ethics Review Committee at the Six Affiliated Hospital of Sun Yat-sen University,China(Approval No.2019ZSLYEC-005).

关键词： epidermal growth factor receptor glycogen synthase kinase 3b glycosylation microsatellite instability microsatellite stability programmed death ligand-1

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斯坦纳阐释学视角下的译者主体性微探——以《丰乳肥臀》为例

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安康学院学报 2015年第2期27卷 68-71,96页

作者：范新娟阮红梅西北工业大学外国语学院陕西西安710072

传统的译论以原文和作者为中心,译者处于边缘地位,依附于作者而存在。西方翻译研究的"文化转向"以来,译者在翻译中的作用得到了关注,译者的主体性成为译介的一个热门研究课题。本文借助译者主体性的研究和乔治·斯坦纳翻译四步骤,以《... 详细信息

传统的译论以原文和作者为中心,译者处于边缘地位,依附于作者而存在。西方翻译研究的"文化转向"以来,译者在翻译中的作用得到了关注,译者的主体性成为译介的一个热门研究课题。本文借助译者主体性的研究和乔治·斯坦纳翻译四步骤,以《丰乳肥臀》英译本为例,分析译本语言的翻译特色,并认为翻译过程中从译本的选择到作品的阐释、语言层面上的艺术再创造,都充分彰显了译者主体性。

关键词：乔治·斯坦纳阐释学译者主体性《丰乳肥臀》葛浩文

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