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Head-to-head comparison of the test performance of selfadministered qualitative vs. laboratory-based quantitative fecal immunochemical tests in detecting Colorectal neoplasm

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Chinese Medical Journal 2021年第11期134卷 1335-1344页

作者： Ming Lu Yu-Han Zhang Bin Lu Jie Cai Cheng-Cheng Liu Hong-Da Chen Min Dai Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Background:Fecal immunochemical tests(FITs)are the most widely used non-invasive tests in colorectal cancer(CRC)screening.However,evidence about the direct comparison of the test performance of the self-administered qualitative a laboratory-based quantitative FITs in a CRC screening setting is sparse.Methods:Based on a CRC screening trial(TARGET-C),we included 3144 pre-colonoscopy fecal samples,including 24 CRCs,230 advanced adenomas,622 non-advanced adenomas,and 2268 participants without significant findings at colonoscopy.Three selfadministered qualitative FITs(Pupu tube)with positivity thresholds of 8.0,14.4,or 20.8 mg hemoglobin(Hb)/g preset by the manufacturer and one laboratory-based quantitative FIT(OC-Sensor)with a positivity threshold of 20 mg Hb/g recommended by the manufacturer were tested by trained staff in the central laboratory.The diagnostic performance of the FITs for detecting Colorectal neoplasms was compared in the different scenarios using the preset and adjusted thresholds(for the quantitative FIT).Results:At the thresholds preset by the manufacturers,apart from the qualitative FIT-3,significantly higher sensitivities for detecting advanced adenoma were observed for the qualitative FIT-1(33.9%[95%CI:28.7–39.4%])and qualitative FIT-2(22.2%[95%CI:17.7–27.2%])compared to the quantitative FIT(11.7%[95%CI:8.4–15.8%]),while at a cost of significantly lower specificities.However,such difference was not observed for detecting CRC.For scenarios of adjusting the positivity thresholds of the quantitative FIT to yield comparable specificity or comparable positivity rate to the three qualitative FITs accordingly,there were no significant differences in terms of sensitivity,specificity,positive/negative predictive values and positive/negative likelihood ratios for detecting CRC or advanced adenoma between the two types of FITs,which was further evidenced in ROC analysis.Conclusions:Although the self-administered qualitative and the laboratory-based quantitative FITs had varied test performance at the posi

关键词： Fecal immunochemical test Test performance Colorectal neoplasm Screening

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The measurement and modification of hypoxia in colorectal cancer:overlooked but not forgotten

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Gastroenterology Report 2022年第1期10卷 132-144页

作者： Teddy Fletcher Alex J.Thompson Hutan Ashrafian Ara Darzi Department of Surgery and Cancer Queen Elizabeth the Queen Mother WingSt Mary’s HospitalImperial College LondonLondonUK The Hamlyn Centre Institute of Global Health InnovationImperial College LondonLondonUK

Tumour hypoxia is the inevitable consequence of a tumour’s rapid growth and disorganized,inefficient vasculature.The compensatorymechanisms employed by tumours,and indeed the absence of oxygen itself,hinder the ability of all treatmentmodalities.The clinical consequence is poorer overall survival,disease-free survival,and locoregional control.Recognizing this,clinicians have been attenuating the effect of hypoxia,primarily with hypoxicmodification or with hypoxia-activated prodrugs,and notable success has been demonstrated.However,in the case of colorectal cancer(CRC),there is a general paucity of knowledge and evidence surrounding themeasurement andmodification of hypoxia,and this is possibly due to the comparative inaccessibility of such tumours.We specifically review the role of hypoxia in CRC and focus on the current evidence for the existence of hypoxia in CRC,themajority of which originates from indirect positron emission topography imaging with hypoxia selective radiotracers;the evidence correlating CRC hypoxia with poorer oncological outcome,which is largely based on themeasurement of hypoxia inducible factor in correlation with clinical outcome;the evidence of hypoxicmodification in CRC,of which no direct evidence exists,but is reflected in a number of indirectmarkers;the prognostic andmonitoring implications of accurate CRC hypoxia quantification and its potential in the field of precision oncology;and the present and future imaging tools and technologies being developed for themeasurement of CRC hypoxia,including the use of blood-oxygenlevel-dependentmagnetic resonance imaging and diffuse reflectance spectroscopy.

关键词： hypoxia Colorectal neoplasm prognostication neoadjuvant chemoradiotherapy

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Establishment of organoid models based on a nested array chip for fast and reproducible drug testing in colorectal cancer therapy

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Bio-Design and Manufacturing 2022年第4期5卷 674-686页

作者： Yancheng Cui Rongrong Xiao Yushi Zhou Jianchuang Liu Yi Wang Xiaodong Yang Zhanlong Shen Bin Liang Kai Shen Yi Li Geng Xiong Yingjiang Ye Xiaoni Ai State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Gastrointestinal Surgery Peking University People’s HospitalBeijing 100044China Beijing Daxiang Biotech Co. Ltd.Beijing 100195China Merck Innovation Hub(Guangdong)Co. Ltd.Guangzhou 510005China

The conventional microwell-based platform for construction of organoid models exhibits limitations in precision oncology applications because of low-speed growth and high variability. Here, we established organoid models on a nested array chip for fast and reproducible drug testing using 50% matrigel. First, we constructed mouse small intestinal and colonic organoid models. Compared with the conventional microwell-based platform, the mouse organoids on the chip showed accelerated growth and improved reproducibility due to the nested design of the chip. The design of the chip provides miniaturized and uniform shaping of the matrigel that allows the organoid to grow in a concentrated and controlled manner. Next, a patient-derived organoid(PDO) model from colorectal cancer tissues was successfully generated and characterized on the chip. Finally, the PDO models on the chip, from three patients, were implemented for high-throughput drug screening using nine treatment regimens. The drug sensitivity testing on the PDO models showed good quality control with a coefficient of variation under 10% and a Z’ factor of more than 0.7. More importantly, the drug responses on the chip recapitulate the heterogeneous response of individual patients, as well as showing a potential correlation with clinical outcomes. Therefore,the organoid model coupled with the nested array chip platform provides a fast and reproducible means for predicting drug responses to accelerate precise oncology.

关键词： Organoid on chip Patient-derived organoids Precise oncology Colorectal neoplasm Drug screening

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Association between white opaque substance under magnifying colonoscopy and lipid droplets in colorectal epithelial neoplasms

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World Journal of Gastroenterology 2017年第47期23卷 8367-8375页

作者： Keisuke Kawasaki Makoto Eizuka Shotaro Nakamura Masaki Endo Shunichi Yanai Risaburo Akasaka Yosuke Toya Yasuko Fujita Noriyuki Uesugi Kazuyuki Ishida Tamotsu Sugai Takayuki Matsumoto Division of Gastroenterology Department of Internal MedicineIwate Medical University Department of Diagnostic Pathology Iwate Medical University Kaiunbashi Endoscopy Clinic

AIM To examine the association between white opaque substance(WOS) and histologically verified lipiddroplets in colorectal epithelial neoplasms.METHODS We reviewed colonoscopy records at our institution from 2014 to 2016 and identified cases of endoscopically or surgically resected colorectal epithelial neoplasms observed by magnifying narrow-band imaging(M-NBI) colonoscopy. Immunohistochemistry was used to stain tumors with a monoclonal antibody specific to adipophilin as a marker of lipids. The expression and distribution of adipophilin were compared between WOS-positive and WOS-negative lesions and among tumors classified by histologic type and depth of invasion.RESULTS Under M-NBI colonoscopy, 81 lesions were positive for WOS and 48 lesions were negative for WOS. The rate of adipophilin expression was significantly higher in WOS-positive lesions(95.1%) than in WOS-negative lesions(68.7%)(P = 0.0001). The incidence of deep adipophilin expression was higher in WOS-positive lesions(24.7%) than in WOS-negative lesions(4.2%)(P = 0.001). The incidence of deep expression was predominant among cancers with massive submucosal invasion(62.5%) compared to adenoma(7.2%) and high-grade dysplasia or cancers with slight submucosal invasion(12.7%)(P = 0.0001).CONCLUSION The distribution of lipid droplets may be closely associated with the visibility of WOS under M-NBI colonoscopy, and with histologic grade and depth of tumor invasion.

关键词： White opaque substance Adipophilin Magnifying narrow-band imaging Colorectal neoplasm Magnifying endoscopy

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Comparative yield and efficiency of strategies based on risk assessment and fecal immunochemical test in colorectal cancer screening:A cross-sectional population-based analysis

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Chinese Journal of Cancer Research 2021年第4期33卷 512-521页

作者： Hongda Chen Le Wang Ming Lu Chen Zhu Yunfeng Zhu Weihua Ma Xinmin Chen Lingbin Du Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Cancer Prevention Institute of Cancer and Basic MedicineChinese Academy of Sciences/Cancer Hospital of University of Chinese Academy of Sciences/Zhejiang Cancer HospitalHangzhou 310005China Haining Hospital of Traditional Chinese Medicine Haining 314499China

Objective:Integration of risk stratification into fecal immunochemical test(FIT)might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer(CRC)screening.A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment(QRA)and FIT,FIT-only and QRA-only strategies in a CRC screening program in China.Methods:The study included 29,626 individuals aged 40-74 years and invited to participate in a CRC screening program in China.Participants were first invited to undertake QRA and one-time FIT(OC-sensor).Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy.Participation,detection rate,and resource demand for colonoscopy were calculated and compared.Results:Of the 29,626 invitees,20,203 completed the parallel combination,8,592 completed the QRA-only,and11 completed the FIT-only strategy.For the parallel combination,FIT-only,and QRA-only strategies,the overall positivity rates were 10.2%(2,928/28,806),5.4%(1,096/20,214),and 6.8%(1,944/28,795),respectively;the yield of advanced neoplasm per 10,000 invitees were 46.9[95%confidence interval(95%CI):39.8-55.4],36.8(95%CI:30.5-44.4),and 12.2(95%CI:8.8-16.8),respectively;the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7%(95%CI:4.0%-5.6%),9.9%(95%CI:8.3%-11.9%),and 1.9%(95%CI:1.3%-2.6%),respectively;the number of colonoscopies required to detect one advanced neoplasm was 11.4(95%CI:9.8-13.4),5.7(95%CI:4.8-6.7),and 28.4(95%CI:20.7-39.2),respectively.Conclusions:The parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.

关键词： Colorectal neoplasm screening fecal immunochemical test risk stratification

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Topic highlight on texture and color enhancement imaging in gastrointestinal diseases

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World Journal of Gastroenterology 2024年第14期30卷 1934-1940页

作者： Osamu Toyoshima Toshihiro Nishizawa Keisuke Hata Department of Gastroenterology Toyoshima Endoscopy ClinicTokyo 157-0066Japan Department of Gastroenterology and Hepatology International University of Health and WelfareNarita HospitalNarita 286-8520Japan Department of Gastroenterology Nihonbashi Muromachi Mitsui Tower Midtown ClinicTokyo 103-0022Japan

Olympus Corporation developed texture and color enhancement imaging(TXI)as a novel image-enhancing endoscopic technique.This topic highlights a series of hot-topic articles that investigated the efficacy of TXI for gastrointestinal disease identification in the clinical setting.A randomized controlled trial demonstrated improvements in the colorectal adenoma detection rate(ADR)and the mean number of adenomas per procedure(MAP)of TXI compared with those of white-light imaging(WLI)observation(58.7%vs 42.7%,adjusted relative risk 1.35,95%CI:1.17-1.56;1.36 vs 0.89,adjusted incident risk ratio 1.48,95%CI:1.22-1.80,respectively).A cross-over study also showed that the colorectal MAP and ADR in TXI were higher than those in WLI(1.5 vs 1.0,adjusted odds ratio 1.4,95%CI:1.2-1.6;58.2%vs 46.8%,1.5,1.0-2.3,respectively).A randomized controlled trial demonstrated non-inferiority of TXI to narrow-band imaging in the colorectal mean number of adenomas and sessile serrated lesions per procedure(0.29 vs 0.30,difference for non-inferiority-0.01,95%CI:-0.10 to 0.08).A cohort study found that scoring for ulcerative colitis severity using TXI could predict relapse of ulcerative colitis.A cross-sectional study found that TXI improved the gastric cancer detection rate compared to WLI(0.71%vs 0.29%).A cross-sectional study revealed that the sensitivity and accuracy for active Helicobacter pylori gastritis in TXI were higher than those of WLI(69.2%vs 52.5%and 85.3%vs 78.7%,res-pectively).In conclusion,TXI can improve gastrointestinal lesion detection and qualitative diagnosis.Therefore,further studies on the efficacy of TXI in clinical practice are required.

关键词： Endoscopy Texture and color enhancement imaging White-light imaging Narrow-band imaging Colorectal neoplasm Gastric cancer Adenoma Ulcerative colitis Helicobacter infections Colonoscopy

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Organoid Culture of Isolated Cells from Patient-derived Tissues with colorectal Cancer

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Chinese Medical Journal 2016年第20期129卷 2469-2475页

作者： Bing-Ying Xie Ai-Wen Wu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Gastrointestinal SurgeryPeking University Cancer Hospital & InstituteBeijing100142China

Background：colorectal cancer （CRC） is a heterogeneous disease;current research relies on cancer cell lines and animal cancer models,which may not precisely imitate inner human tumors and guide clinical medicine.The purpose of our study was to explore and further improve the process of producing three-dimensional （3D） organoid model and impel the development of personalized therapy.Methods：We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts （PDXs）.Isolated cells from PDXs at appropriate tumor size were mingled with Matrigel,and then seeded in ultra-low attachment 96-well plates at four cell densities （500,1000,2000,and 4000 single cells/well）.Cells were cultured with advanced Dulbecco＇s Modified Eagle Mediurn/F 12 medium additional with various factors added to maintain tumor＇s biological traits and growth activity.The growth curves of the four cell densities were measured after 24 h of culture until 25 days.We evaluated the effects of four chemotherapeutic agents on organoid model by the CellTiter-Glo（R） Luminescent Cell Viability Assay.Hematoxylin and eosin （H and E） staining of 3D organoids was performed and compared with patient and CRC PDX tissues.Furthermore,immunohistochemistry was performed,in which the organoids were stained with the proliferation marker,Ki-67.During the experimental process,a phase-contrast microscope was used.Results：Phenotype experimental results showed that 3D organoids were tightly packed together and grew robustly over time.All four densities of cells formed organoids while that composed of 2000 cells/well provided an adequate cultivation system and grew approximately 8-fold at the 25th day.The chemosensitivity of the four conventional drugs was [s]-l 0-hydroxycamptothecin 〉 mitomycin C 〉 adriamycin 〉 paclitaxel,which can guide clinical treatment.Histological features of CRC patient＇s tumor tissues and mice tumor xenograft tissues were highly similar,with high-column-like epithelium and extracellular matri

关键词： Colorectal neoplasm Drug Therapy, neoplasm Transplantation Printing, Three-dimensional

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Colonoscopy plays an important role in detecting Colorectal neoplasms in patients with gastric neoplasms

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 133-143页

作者： Xu-Rui Liu Ze-Lin Wen Fei Liu Zi-Wei Li Xiao-Yu Liu Wei Zhang Dong Peng Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Gastrointestinal Surgery Yongchuan Hospital of Chongqing Medical UniversityChongqing 402160China

BACKGROUND Gastric cancer(GC)and colorectal cancer(CRC)are the fifth and third most common cancer worldwide,respectively.Nowadays,GC is reported to have a potential predictive value for CRC,especially for advanced CRC.AIM To evaluate the necessity of colonoscopy for gastric neoplasm(GN)patients.METHODS Four databases,including PubMed,EMBASE,the Cochrane Library,and Ovid,were used to perform the search strategy on May 2,2023.The prevalence of Colorectal neoplasms(CRN)and baseline characteristics were compared between the neoplasm group and the control group.Continuous variables are expressed as the mean difference and standard deviation.Relationships of categorical variables in the two groups are expressed as odds ratios(OR)and 95%confidence intervals(95%CIs).Subgroup analysis according to different kinds of GNs was conducted for more in-depth analysis.The results of this study are represented by forest plots.Publication bias was evaluated by a funnel plot.All data analyses were performed by STATA SE 16.0 software.RESULTS A total of 3018 patients with GNs and 3905 healthy controls(age and sex matched)were enrolled for analysis.After comparing the prevalence of CRNs between the two groups,CRNs were detected significantly more frequently in GN patients than in controls(OR=1.69,95%CI=1.28 to 2.23,I^(2)=85.12%,P=0.00),especially in patients with GC(OR=1.80,95%CI=1.49 to 2.18,I^(2)=25.55%,P<0.1).Moreover,other risk factors including age(OR=1.08,95%CI=1.00 to 1.17,I^(2)=90.13%,P=0.00)and male sex(OR=2.31,95%CI=1.26 to 4.22,I^(2)=87.35%,P=0.00),were related to the prevalence of CRNs.For patients in the GN group,body mass index(BMI,OR=0.88,95%CI=0.80 to 0.98,I^(2)=0.00%,P=0.92)and smoking(OR=1.03,95%CI=1.01 to 1.05,I^(2)=0.00%,P=0.57)were protective and risk factors for CRNs,respectively.CONCLUSION Patients are recommended to undergo colonoscopy when diagnosed with GNs,especially GC patients with a low BMI and a history of smoking.

关键词： Gastric neoplasm Gastric cancer Colorectal neoplasm Colonoscopy

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A systemic review of glutathione S-transferase P1 Ile105Val polymorphism and colorectal cancer risk

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Chinese Journal of Cancer Research 2014年第3期26卷 255-267页

作者： Qi-Bin Song Qi Wang Wei-Guo Hu Department of Oncology Renmin Hospital of Wuhan University

Objectives： To investigate the correlation between glutathione S-transferase P1 （GSTP1） Ilel05Val polymorphism and colorectal cancer （CRC） risk. Methods： Studies were identified to investigate the association between GSTP1 Ilel05Val polymorphism and CRC risk. Systematic computerized searches of the PubMed, Chinese National Knowledge Infrastructure, WANFANG and SinoMed were performed. Summary odds ratios （OR） and 95% confidence intervals （95 % CI） were used to measure GSTP 1 Ile 105Val polymorphisms and CRC risk. Results： A total of 23 retrospective studies were included in the meta-analysis. During all studies including 6,981 cases and 8,977 controls, sample sizes ranged from 146 to 2,144. Overall, the pooled results revealed that lie 105Val polymorphism was not associated with CRC risk and confused results were found in subgroup analyses. Further meta-analyses were conducted after excluding low-quality studies. GSTP1 Ilel05Val is associated with increased risk of CRC limited in studies with matched control. There was no significant heterogeneity in all genetic comparisons, but heterogeneity existed in subgroup analyses of heterozygous and dominant comparisons. The meta-regression analyses indicated that matched controls were the significant factor influencing between-study heterogeneity in all possible influential factors including published year, ethnicity, source of control, sample size, Hardy-Weinberg equilibrium （HWE） in control and matched controls. Sensitivity analysis revealed the pooled ORs were not changed before and after removal of each single study in all genetic comparisons, indicating the robustness of the results. Conclusions： GSTP1 Ilel05Val might be associated with increased risk of CRC. However, more high- quality case-control studies should be performed to confirm the authenticity of our conclusion.

关键词： Colorectal neoplasm glutathione S-transferase P 1 （GSTP 1） polymorphisms

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Recent advances and current challenges in endoscopic resection with the full-thickness resection device

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World Journal of Gastroenterology 2023年第25期29卷 4009-4020页

作者： Elijah J Mun Mihir S Wagh Division of Gastroenterology University of Colorado School of MedicineAuroraCO 80045United States Interventional Endoscopy Division of GastroenterologyUniversity of Colorado School of MedicineAuroraCO 80045United States

Endoscopic full-thickness resection(EFTR)has emerged as a viable technique in the management of mucosal and subepithelial lesions of the gastrointestinal tract(GIT)not amenable to conventional therapeutic approaches.While various devices and techniques have been described for EFTR,a single,combined fullthickness resection and closure device(full-thickness resection device,FTRD system,Ovesco Endoscopy AG,Tuebingen,Germany)has become commercially available in recent years.Initially,the FTRD system was limited to use in the colorectum only.Recently,a modified version of the FTRD has been released for EFTR in the upper GIT as well.This review provides a broad summary of the FTRD,highlighting recent advances and current challenges.

关键词： Endoscopic full-thickness resection Full-thickness resection device Colorectal neoplasm Subepithelial lesions Scarred non-lifting polyps

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