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Nomogram using F-18 fluorodeoxyglucose positron emission tomography/computed tomography for preoperative prediction of lymph node metastasis in gastric cancer

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World Journal of Gastrointestinal Oncology 2020年第4期12卷 447-456页

作者： Bong-Il Song Department of Nuclear Medicine Keimyung University Dongsan HospitalKeimyung University School of MedicineDaegu 42601South Korea

BACKGROUND Lymph node(LN)metastasis is an important prognostic factor in patients with gastric cancer(GC).However,the evaluation of LN metastasis status in the preoperative setting is not accurate.Therefore,precise preoperative prediction of LN metastasis status is crucial for optimal treatment in patients with GC.AIM To develop a preoperative nomogram for LN metastasis using F-18 fluorodeoxyglucose(F-18 FDG)positron emission tomography/computed tomography(PET/CT)and preoperative laboratory test findings in GC.METHODS In this study,the data of 566 GC patients who underwent preoperative F-18 FDG PET/CT and subsequent surgical resection were analyzed.The LN metastasis prediction model was developed in the training cohort and validated in the internal validation cohort.Routine preoperative laboratory tests,including albumin and carbohydrate antigen(CA)19-9 were performed in all patients.Univariate and multivariable logistic regression was performed to validate the preoperative predictive indicators for LN metastasis.RESULTS Of the 566 patients,232(41%)had confirmed histopathologic LN metastasis.Univariate logistic regression revealed that the tumor location,blood hemoglobin,serum albumin levels,neutrophil to lymphocyte ratio,platelet to lymphocyte ratio,CA 19-9,maximum standardized uptake value(SUVmax)of the primary tumor(T_SUVmax),and SUVmax of LN(N_SUVmax)were significantly associated with LN metastasis.In multivariate analysis,T_SUVmax(OR=1.08;95%CI:1.02–1.15;P=0.011)and N_SUVmax(OR=1.49;95%CI:1.19–1.97;P=0.002)were found to be significant predictive factors for LNmetastasis.The LN metastasis prediction model using T_SUVmax,N_SUVmax,serum albumin,and CA 19-9 yielded an area under the curve(AUC)of 0.733(95%CI:0.683–0.784,P=0.025)in the training cohort and AUC of 0.756(95%CI:0.678–0.833,P<0.001)in the test cohort.CONCLUSION T_SUVmax and N_SUVmax measured by preoperative F-18 FDG PET/CT are independent predictive factors for LN metastasis in GC.

关键词： Gastric cancer Lymph node metastasis Positron emission tomography/computed tomography Fluorodeoxyglucose Prognostication Standardized uptake value

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Critical size limit of biodegradable nanopartides for enhanced lymph node trafficking and paracortex penetration

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Nano Research 2019年第4期12卷 837-844页

作者： Gregory P. Howard Garima Verma Xiyu Ke Winter M. Thayer Timothy Hamerly Victoria K. Baxter John E. Lee Rhoel R. Dinglasan Hai-Quan Mao Department of Biomedical Engineering Johns Hopkins School of Medicine Baltimore MD 21218 USA Institute for NanoBioTechnology Johns Hopkins University Baltimore MD 2121 & USA W. Harry Feinstone Department of Molecular Microbiology & Immunology and the Malaria Research Institute Johns Hopkins Bloomberg School of Public Health Baltimore MD 21205 USA Emerging Pathogens Institute Department of Infectious Diseases & Immunology College of Veterinary Medicine University of Florida Gainesville FL 32611 USA Department of Materials Science and Engineering Whiting School of Engineering Johns Hopkins University Baltimore MD 21218 USA Johns Hopkins School of Nursing Baltimore MD 21205 USA Department of Molecular and Comparative Pathobiology Johns Hopkins School of Medicine Baltimore MD 21205 USA Department of Biomedical Engineering Yale University New Haven CT 06520 USA Translational Tissue Engineering Center Johns Hopkins University School of Medicine Baltimore MD 21231 USA

Lymph node (LN) targeti ng through interstitial drain age of nan oparticles (NPs) is an attractive strategy to stimulate a pote nt immune respo nse, as LNs are the primary site for lymphocyte priming by antigen presenting cells (APCs) and triggering of an adaptive immune response. NP size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable NPs are preferred as carrier for vaccine delivery. However, the selective "size gateM for effective LN-drainage, particularly the kinetics of LN trafficking, is less well defined. This is partly due to the challenge in generating size-controlled NPs from biodegradable polymers in the sub-100-nm range. Here, we report the preparation of three sets of poly(lactic-co-glycolic)-b-poly(ethylene-glycol)(PLGA-b-PEG) NPs with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanoprecipitation. Using NPs labeled with a near-infrared dye, we showed that 20-nm NPs drain rapidly across proximal and distal LNs following subcutaneous inoculation in mice and are retai ned in LNs more effectively than NPs with a nu mber average diameter of 40-nm. The drain age of 100-nm NPs was n egligible. Furthermore, the 20-nm NPs showed the highest degree of penetration around the paracortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled PLGA-b-PEG NPs at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and APC uptake after s.c. administration. This report could inform the design of LN-targeted NP carrier for the delivery of therapeutic or prophylactic vaccines.

关键词： biodegradable nano particle lymph node trafficking vaccine delivery nanoparticle size an tigen presenting cells in vivo imaging

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Diagnostic ability of multi-detector spiral computed tomography for pathological lymph node metastasis of advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2020年第4期12卷 435-446页

作者： Zhi-Yong Jiang Shinichi Kinami Naohiko Nakamura Takashi Miyata Hideto Fujita Hiroyuki Takamura Nobuhiko Ueda Takeo Kosaka Department of Surgical Oncology Kanazawa Medical University1-1 DaigakuUchinada-machiKahoku-gunIshikawa 920-0293Japan

BACKGROUND The reliability of preoperative nodal diagnosis of advanced gastric cancer by multi-detector spiral computed tomography(MDCT)is still unclear.AIM To examine the diagnostic ability of MDCT more precisely by using data on intranodal pathological metastatic patterns.METHODS A total of 108 patients with advanced gastric cancer who underwent MDCT and curative gastrectomy at Kanazawa Medical University Hospital were enrolled in this study.The nodal sizes measured on computed tomography(CT)images were compared with the pathology results.A receiver-operating characteristic curve was constructed,from which the critical value(CV)was calculated by using the data of the first 69 patients retrospectively.By using the CV,sensitivity and specificity were calculated with prospectively collected data from 39 consecutive patients.This enabled a more precise one-to-one correspondence of lymph nodes between CT and pathological examination by using the size data of lymph node mapping.The intranodal pathological metastatic patterns were classified into the following four types:Small nodular,peripheral,large nodular,and diffuse.RESULTS Although all the cases were clinically suspected as having metastasis,81 had lymph node metastasis and 27 had no metastasis.The number of dissected,detected on CT,and metastatic nodes were,4241,897,and 801,respectively.The CV obtained from the receiver-operating characteristic was 7.6 mm for the long axis.The sensitivity was 91.4%and the specificity was 47.3%in the prospective phase.The large nodular and diffuse metastases were easy to diagnose becausemetastatic nodes with a large axis often exhibit these forms.CONCLUSION The ability of MDCT to contribute to a nodal diagnosis of advanced gastric cancer was examined prospectively with precise size data from node mapping,using a CV of 7.6 mm for the long axis that was calculated from the retrospectively collected data.The sensitivity was as high as 91%,and would be improved when referring to the enhanced patterns.However,its specificity was as l

关键词： Advanced gastric cancer Lymph node metastasis Multi-detector spiral computed tomography Pathological diagnosis

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Feasibility of endoscopic treatment and predictors of lymph node metastasis in early gastric cancer

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World Journal of Gastroenterology 2019年第35期25卷 5344-5355页

作者： Yu-Ning Chu Ya-Nan Yu Xue Jing Tao Mao Yun-Qing Chen Xiao-Bin Zhou Wen Song Xian-Zhi Zhao Zi-Bin Tian Department of Gastroenterology the Affiliated Hospital of Qingdao University Qingdao 266003 Shandong Province China Department of Pathology the Affiliated Hospital of Qingdao University Qingdao 266003 Shandong Province China Department of Epidemiology and Health Statistics School of Public Health Qingdao University Qingdao 266021 Shandong Province China Endoscopy Center the Affiliated Hospital of Qingdao University Qingdao 266003 Shandong Province China

BACKGROUND Endoscopic submucosal dissection (ESD) has been routinely performed in applicable early gastric cancer (EGC) patients as an alternative to conventional surgical operations that involve lymph node dissection. The indications for ESD have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. The risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for EGC. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. In addition, whether patients who meet the expanded indications for ESD can be managed safely remains controversial. AIM To determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC. METHODS We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients’ clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses. RESULTS LNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren’s types. Multivariate analysis demonstrated SM1 invasi

关键词： Early gastric cancer Lymph node metastasis Predictors Endoscopic submucosal dissection Expanded indications

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Predictive factors for central lymph node metastases in papillary thyroid microcarcinoma

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World Journal of Clinical Cases 2020年第8期8卷 1350-1360页

作者： Xin Wu Bing-Lu Li Chao-Ji Zheng Xiao-Dong He Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Papillary thyroid microcarcinoma(PTMC)measures 1 cm or less in its longest dimension.The incidence of PTMC is increasing worldwide.Surgery is the primary treatment;however,prophylactic central lymph node dissection is controversial,and discrepancies between different guidelines have been noted.Routine prophylactic central lymph node dissection may result in hypoparathyroidism and recurrent laryngeal nerve injury in some patients without lymph node metastasis,while simple thyroidectomy may leave metastatic lymph nodes in high-risk patients.To selectively perform prophylactic lymph node dissections in high-risk patients,it is important to identify predictive factors for lymph node metastases in patients with PTMC.Several studies have reported on this,but their conclusions are not entirely consistent.Several clinicopathologic characteristics have been identified as risk factors for central lymph node metastases,and the most commonly reported factors include age,gender,tumor size and location,multifocality,bilaterality,extrathyroidal extension,and abnormal lymph node found using ultrasound.Here,we provide an overview of previous studies along with a favorable opinion on or against these factors,with the aim of increasing the understanding of this topic among the medical community.In addition,current opinions about prophylactic central lymph node dissection are reviewed and discussed.

关键词： Papillary thyroid carcinoma Papillary thyroid microcarcinoma Central lymph node dissection Prophylactic Risk factor Prognosis

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Radiomics-based predictive risk score: A scoring system for preoperatively predicting risk of lymph node metastasis in patients with resectable non-small cell lung cancer

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Chinese Journal of Cancer Research 2019年第4期31卷 641-652页

作者： Lan He Yanqi Huang Lixu Yan Junhui Zheng Changhong Liang Zaiyi Liu Department of Radiology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Pathology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China

Objective: To develop and validate a radiomics-based predictive risk score(RPRS) for preoperative prediction of lymph node(LN) metastasis in patients with resectable non-small cell lung cancer(NSCLC).Methods: We retrospectively analyzed 717 who underwent surgical resection for primary NSCLC with systematic mediastinal lymphadenectomy from October 2007 to July 2016. By using the method of radiomics analysis, 591 computed tomography(CT)-based radiomics features were extracted, and the radiomics-based classifier was constructed. Then, using multivariable logistic regression analysis, a weighted score RPRS was derived to identify LN metastasis. Apparent prediction performance of RPRS was assessed with its calibration,discrimination, and clinical usefulness.Results: The radiomics-based classifier was constructed, which consisted of 13 selected radiomics features.Multivariate models demonstrated that radiomics-based classifier, age group, tumor diameter, tumor location, and CT-based LN status were independent predictors. When we assigned the corresponding score to each variable,patients with RPRSs of 0-3, 4-5, 6, 7-8, and 9 had distinctly very low(0%-20%), low(21%-40%), intermediate(41%-60%), high(61%-80%), and very high(81%-100%) risks of LN involvement, respectively. The developed RPRS showed good discrimination and satisfactory calibration (C-index: 0.785, 95% confidence interval(95% CI):0.780-0.790)Additionally, RPRS outperformed the clinicopathologic-based characteristics model with net reclassification index(NRI) of 0.711(95% CI: 0.555-0.867).Conclusions: The novel clinical scoring system developed as RPRS can serve as an easy-to-use tool to facilitate the preoperatively individualized prediction of LN metastasis in patients with resectable NSCLC. This stratification of patients according to their LN status may provide a basis for individualized treatment.

关键词： Lymph node radiomics risk score CT non-small cell lung cancer

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Role of D2 gastrectomy in gastric cancer with clinical para-aortic lymph node metastasis

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World Journal of Gastroenterology 2019年第19期25卷 2338-2353页

作者： Xiao-Hao Zheng Wen Zhang Lin Yang Chun-Xia Du Ning Li Gu-Sheng Xing Yan-Tao Tian Yi-Bin Xie Department of Pancreatic and Gastric Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Diagnostic Radiology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

BACKGROUND Owing to the technical difficulty of pathological diagnosis, imaging is still the most commonly used method for clinical diagnosis of para-aortic lymph node metastasis(PALM) and evaluation of therapeutic effects in gastric cancer, which leads to inevitable false-positive findings in imaging. Patients with clinical PALM may have entirely different pathological stages(stage IV or not), which require completely different treatment strategies. There is no consensus on whether surgical intervention should be implemented for this group of patients. In particular, the value of D2 gastrectomy in a multidisciplinary treatment(MDT)approach for advanced gastric cancer with clinical PALM remains unknown.AIM To investigate the value of D2 gastrectomy in a MDT approach for gastric cancer patients with clinical PALM.METHODS In this real-world study, clinico-pathological data of all gastric cancer patients treated at the Cancer Hospital, Chinese Academy of Medical Sciences between 2011 and 2016 were reviewed to identify those with clinically enlarged PALM. All the clinico-pathological data were prospectively documented in the patient medical record. For all the gastric cancer patients with advanced stage disease,especially those with suspicious distant metastasis, the treatment methods were determined by a multidisciplinary team.RESULTS In total, 48 of 7077 primary gastric cancer patients were diagnosed as having clinical PALM without other distant metastases. All 48 patients received chemotherapy as the initial treatment. Complete or partial response was observed in 39.6%(19/48) of patients in overall and 52.1%(25/48) of patients in the primary tumor. Complete response of PALM was observed in 50.0%(24/48)of patients. After chemotherapy, 45.8%(22/48) of patients received D2 gastrectomy, and 12.5%(6/48) of patients received additional radiotherapy. The postoperative major complication rate and mortality were 27.3%(6/22) and 4.5%(1/22), respectively. The median overall survival and progression-free survival of all the p

关键词： Gastric cancer Para-aortic lymph node Multidisciplinary Gastrectomy Conversion Neoadjuvant

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Direct contacts of microglia on myelin sheath and Ranvier’s node in the corpus callosum in rats

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The Journal of Biomedical Research 2019年第3期33卷 192-200页

作者： Jingdong Zhang Xinglong Yang You Zhou Howard Fox Huangui Xiong Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Department of Clinical and Scientific Training Affiliated Hospital to Academy of Military Medicine Sciences Center for Biotechnology University of Nebraska at Lincoln School of Veterinary Medicine and Biomedical Sciences

Over the recent years, it has been found that microglia pseudopodia contact synapses, detect sick ones and prune them, even in adult animals. Myelinated nerves also carry out plasticity in which microglia remove myelin debris by phagocytosis. However, it remains unknown whether microglia explore structures on nerve fibers, such as Ranvier’s node(RN) or myelin sheath, before they become debris. By double or triple staining RNs or myelin sheathes and microglia in healthy rat corpus callosum, this study unveiled direct contacts of microglia pseudopodia with RNs and with para-and inter-nodal myelin sheathes, which was then verified by electron microscopic observations. Our data indicated that microglia also explore unmyelinated nerve fibers. Furthermore, we used the animals with matured white matter;therefore, microglia may be actively involved in plasticity of matured white matter tracts as it does for synapse pruning, instead of only passively phagocytize myelin debris.

关键词： Ranvier’s node myelin sheath microglia contact matured white matter tract

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Impact of the number of examined lymph nodes on outcomes in patients with lymph node-negative gallbladder carcinoma

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World Journal of Gastroenterology 2018年第26期24卷 2886-2892页

作者： Dong-Xu Fan Rong-Wei Xu Yong-Cheng Li Bing-Qing Zhao Ming-Yu Sun Department of Vascular surgery First Affiliated Hospital of Jiamusi University Department of Vascular Surgery Shandong Provincial Qianfoshan Hospital Shandong University Department of Medical Oncology Xuzhou Central Hospital The Affiliated Xuzhou Hospital of Medical College of Southeast University Department of Surgery Tianjin Second People's Hospital Department of Breast Surgery Xuzhou Central Hospital The Affiliated Xuzhou Hospital of Medical College of Southeast University

AIM To determine whether the number of examined lymph nodes(LNs) is correlated with the overall survival of gallbladder carcinoma(GBC) patients. METHODS Patients were collected from the Surveillance Epidemiology and End Results database(2004-2013) and categorized by the number of LNs into six groups: 1 LN, 2 LNs, 3 LNs, 4 LNs, 5 LNs, and ≥ 6 LNs. Survival curves for overall survival were plotted with a KaplanMeier analysis. The log-rank test was used for univariate comparisons.RESULTS In a cohort of 893 patients, the median number of examined LNs was two for the entire cohort. The survival for the 1 LN group was significantly poorer than those of the stage Ⅰ and Ⅱ disease groups and for the entire cohort. By dichotomizing the number of LNs from 1 to 6, we found that the minimum number of LNs that should be examined was four for stage Ⅰ, four or five for stage Ⅱ, and six for stage ⅢA disease. Therefore, for the entire cohort, the number of examined LNs should be at least six, which is exactly consistent with the American Joint Committee on Cancer criteria.CONCLUSION The examination of higher numbers of LNs is associated with improved survival after resection surgery for N0 GBC. The guidelines for GBC surgery, which recommend that six LNs be examined at least, are statistically valid and should be applied in clinical practice widely.

关键词： Gallbladder carcinoma Lymph node N0 stage Prognostic factor

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Lateral lymph node dissection for low rectal cancer: Is it necessary?

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World Journal of Gastroenterology 2019年第31期25卷 4294-4299页

作者： Niki Christou Jeremy Meyer Christian Toso Frédéric Ris Nicolas Christian Buchs Service de Chirurgie Digestive Endocrinienne et GénéraleCHU de LimogesLimoges Cedex 87042France Division of Digestive Surgery University Hospitals of GenevaGenève 1211Switzerland Unit of Surgical Research University of GenevaGenève 1206Switzerland

Rectal cancer constitutes a major public health issue.Total mesorectal excision has remained the gold standard treatment for mid and low rectal tumors since its introduction in the late 1980s.Removal of all lymph nodes located in the mesorectum has indeed improved pathological and oncological outcomes.However,when cancer spreads to the lateral lymph nodes(located along the iliac and obturator arteries)Western and Japanese practices differ.Where the Western guidelines consider this condition as an advanced form of the disease and use neoadjuvant radiochemotherapy liberally,the Japanese guidelines define it as a local disease and proceed to lateral lymph node dissection with or without neoadjuvant treatment.Herein,we review the current literature regarding both therapeutic strategies,with the aim of contributing to potential improvements in treatment and outcome for patients with low and mid rectal cancer.

关键词： Total mesorectum excision Mesorectal resection Lateral node metastasis Extended lymphadenectomy

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