1.Serological assessment of pepsinogens in patients with gastric mucosal lesions using latex enhanced immunoturbidimetry
Fan WANG ; Xiangyi LIU ; Haitong GU ; Li LI ; Xinxin LU
Chinese Journal of Laboratory Medicine 2016;39(10):771-775
Objective To evaluate serum level of pepsinogenⅠ( PGⅠ) ,PGⅡ, and PGⅠ/PGⅡ-ratio ( PGR ) using latex enhanced turbidimetric immunoassay in patients with different gastric mucosal lesions, and to investigate their changes and clinical significance.Methods Case-control study.Two hundred and seventy-five patients who had enteroscopy and pathological examination from the department of gastroenterology and surgery from Beijing Tongren Hospital between January 2015 and January 2016 were enrolled.Endoscopic and histopathological examination confirmed the normal control group (n=20), chronic non-atrophic gastritis group ( n=68 ) , chronic atrophic gastritis group ( n=76 ) , including antral atrophic gastritis ( n=30 ) , gastric body atrophic gastritis ( n=26 ) , and multifocal atrophic gastritis ( n=20 );intestinal metaplasia group ( n=28 ) , intraepithelial neoplasia group ( n=9 ) , benign gastric ulcer group ( n=46) and intestinal gastric cancer group ( n=28).Latex-enhanced immune turbidity method were used to detect the patients fasting serum PGⅠand PGⅡ.Then the PGR was calculated.The normally distributed data of each group were statistically analyzed by ANOVA, the data between groups were nalyzed using the Mann-Whitney U test and Kruskal-Wallis test.Results Serum PGⅠ[ ( 74.23 ±22.36 ) ] ng/ml and PGR (6.92 ±2.16) in chronic atrophic gastritis group were lower than those in normal controls[PGⅠ(98.94 ± 21.00) ng/ml, PGR 8.13 ±2.47],(FPGⅠ =18.297,PPGⅠ <0.01,FPGR =4.713,PPGR <0.01).The serum PGⅠ[(44.46 ±26.72) ng/ml] and PGR (3.09 ±0.83) in the intestinal type of gastric cancer group were lower than those in the chronic atrophic gastritis group[PGⅠ(74.23 ±22.36)ng/ml, PGR 6.92 ±2.16], (ZPGⅠ =-3.921,PPGⅠ <0.01,ZPGR =-6.662,PPGR <0.01).PGⅠ[(129.95 ±43.39) ng/ml].PGⅡ[(21.09 ±6.78) ng/ml]in the gastric benign ulcer group were higher than those in the normal controls[PGⅠ (98.94 ±21.00) ng/ml, PGⅡ(12.64 ±1.84) ng/ml], FPGⅠ =10.803,PPGⅠ <0.01;FPGⅡ =39.130,PPGⅡ <0.01. PGⅠ[(52.44 ±10.37) ng/ml and PGR (5.47 ±1.59) in the multifocal atrophic gastritis group were lower than those in the antral atrophic gastritis[PGⅠ(94.95 ±14.45)ng/ml, PGR 8.39 ±1.48],ZPGⅠ =-5.941,PPGⅠ <0.01,ZPGR =-4.911,PPGR <0.01.The AUC of PGⅠand PGR for diagnosis of chronic atrophic gastritis were 0.752 and 0.683 respectively.The sequence combined detection sensitivity was 72.37%(55/76), and the specificity was 70.85%(141/199).The AUC of PG I and PGR for diagnosis of intestinal type of gastric cancer were 0.852 and 0.895 respectively.The sequence combined detection sensitivity was 71.42% ( 20/28 ) and the specificity was 81.78% ( 202/247 ) . Conclusion The Latex-enhanced immune turbidity method of combined detection of serum PGⅠ, PGⅡlevels and PGR can be used in the clinic to monitor the status and function of gastric mucosa and are informative for gastric cancer and precancerous lesions of gastric mucosa.
2.Effect of Wamingfen on Eosinophil Apoptosis, Oxygen Free Radical and Serum Hydrocortisone Level in Asthma Guinea Pigs
Xiaodong BIE ; Haitong WAN ; Lanhua LOU ; Jianming WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2000;0(05):-
Objective: To explore the effect of Wamingfen on eosinophil apoptosis and oxygen free radicals and to study the influence of hydrocortisone on airway inflammation in asthma guinea pigs. Methods: Guinea pig models of asthma were induced by egg albumin. The effect of Wamingfen on plasma malonyl dialdehyde (MDA), blood glutathione peroxidase (GSH-Px),erythrocytic superoxide dismutase (SOD) activity , serum hydrocortisone level and the percentage of EOS apoptosis in bronchial-alveolar lavage fluid (BALF) were observed. Results: Wamingfen can apparently increase the content of GSH-Px ,SOD and serum hydrocortisone, promote the apoptosis of EOS and reduce the amount of MDA. Conclusion: Wamingfen can effectively increase serum hydrocortisone content, remove the oxygen free radical, promote eosinophil apoptosis and reduce the hyper-reactivity in the inflammatory airway.
3.Four novel sequence types in catheter-related MRSE isolates
Xinrong SHANG ; Junrui WANG ; Mei WANG ; Lijun WANG ; Yanfei HUANG ; Haitong GU ; Xianxi KONG ; Xinxin LU
Chinese Journal of Laboratory Medicine 2011;34(3):245-248
Objective To study the genotypic and biological characteristics of catheter-related MRSE isolates and to further provide information for the diagnosis and prevention of catheter-related bloodstream infection. Methods Thirty strains of catheter-related MRSE isolates were collected from venosus blood and whole blood of 30 inpatients including 20 males and 10 females from Beijing Tongren Hospital, Capital Medical University from January 2006 to December 2009. The genetic features of these strains were determined by MLST. PCR was used to detect the icoA gene (encoding the polysaccharide intercellular adhesion associated with pathogenicity), and the antimicrobial susceptibility test was detected by disc diffusion test. Results A total of 15 STs were obtained from 30 strains ST259, ST20, ST2 and ST235 were common clones obtained from 17 strains. Four novel STs were found and uploaded to the MLST database (http://www. mlst. net), including ST259 (6 strains), ST260 (1 strain), ST261 (1 strain) and ST262 (1 strain). The ST259 was the dominant clone of catheter-related MRSE isolates in this hospital, and 3 strains carrying icaA gene were detected in this study. Conclusion Some ST259 isolates express high pathogenesis among the four novel STs, which may make them as the pandemic strains in nosocomial infection, and this would increase the difficulty of the prevention and control of nosocomial infection.
4.Virulence characteristics and multilocus sequence type of Vibrio parahaemolyticus isolated from clinic
Yanyan FAN ; Min ZHU ; Xinrong SHANG ; Mei WANG ; Yanfei HUANG ; Haitong GU ; Xinxin LU
Chinese Journal of Laboratory Medicine 2013;(6):548-552
Objective To study on virulence characteristics and multilocus sequence type of Vibrio parahaemolyticus isolated from clinic in Beijing Tongren hospital.Methods Total 152 strains of Vibrio parahaemolyticus isolates were collected from diarrheal patients of outpatients in Beijing Tongren Hospital,Capital Medical University from 2009 to 2011.PCR was used to detect hemolysin gene thermo stable direct themolysin gene (tdh),TDH-related hemolysin gene (trh),type Ⅲ secretion system 2 (T3SS2α,T3SS2β)and systematic functional gene (toxRS/new,orf8) for pandemic 03∶ K6 clone and its derivatives.The genetic features of these strains were determined by multilocus sequence typing (MLST).Results 96% (146/152) VP harbored tdh gene,2% (3/152) VP harbored trh gene and 100% (152/152) VP harbored T3SS2 gene.In this study there were 107 pandemic strains (both tdh and toxRS/new positive and trh negative),38 pathogenic strains (tdh positive and/or trh positive) and 6 nonpathogenic strains (both tdh and trh negative).All nonpathogenic strains harbored systematic functional gene (toxRS/new,orf8).Only one pathogenic strains harbored orf8 gene.One clone harbored all virulence gene.In this study there were 16 sequence types,and ST3 is the pandemic sequence type,including 113 strains,and four new sequence types were found.Conclusions In this study more than 90% Vibrio haemolyticus harbored tdh gene and ST3 was the pandemic sequence type in Beijing.One can get bacterial pathogenic charateristic and population genetics information by virulence gene testing and MLST.
5.Permeability of blood-brain barrier oxygen-glucose deprivation induced by tetramethylpyrazine-puerarin in vitro.
Jinhui LI ; Lingyan CHE ; Yu WANG ; Yuyan ZHANG ; Haitong WAN ; Jiehong YANG
China Journal of Chinese Materia Medica 2010;35(20):2745-2748
OBJECTIVETo explore permeability of artificial blood-brain barrier (aBBB) by oxygen-glucose deprivation combined (OGD)-induced using tetramethylpyrazine combined with puerarin in vitro.
METHODRats were divided into normal control group, model group, tetramethylpyrazine group, puerarin group, tetramethylpyrazine-puerarin group and nimodipine group. Culture rat brain microvascular endothelial cells and astrocytes in vitro and build the OGD-induced aBBB damage model. Evaluate aBBB damage characteristics by TEER, gamma-GT, AKP and LDH. Determine contents of tetramethylpyrazine, puerarin, nimodipine and calculate drug permeating concentration of OGD-induced aBBB model by HPLC.
RESULTCompared with the model, the level of TEER was lower than the control group with significant difference (P < 0.01). The levels of gamma-GT, AKP in tetramethylpyrazine group, tetramethylpyrazine-puerarin group and nimodipine group were higher than the model group, the differences were significant (P < 0.01). Compared with tetramethylpyrazine group or puerarin group, the level of AKP of tetramethylpyrazine-puerarin group increased significantly (P < 0.01). The differences of levels of TEER, gamma-GT, AKP and LDH between tetramethylpyrazine-puerarin group and nimodipinthe group were significant (P < 0.05). Tetramethylpyrazine-puerarin group has a synergistic effect of increasing TEER, gamma-GT, AKP and reducing LDH. The permeating rate in tetramethylpyrazine-puerarin group was higher than tetramethylpyrazine group and puerarin group.
CONCLUSIONTetramethylpyrazine-puerarin can permeate aBBB more easily and protect aBBB. The cause may relate to reducing the permeability of the OGD-induced aBBB.
Animals ; Blood-Brain Barrier ; drug effects ; Drug Combinations ; Glucose ; physiology ; Isoflavones ; administration & dosage ; pharmacology ; Male ; Oxygen ; physiology ; Permeability ; Pyrazines ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley
6.A safety and effectiveness research of Yinhua Pinggan granule of Qingjie Xuantou lung defense prescription for treatment of patients with upper respiratory tract infection accompanied by syndrome of pathogen stagnated in lung-defense phase: a randomized double blinded, positive drug parallel controlled and multicentric clinical trial
Haitong WAN ; Yu HE ; Huifen ZHOU ; Jiehong YANG ; Jian LU ; Liling WAN ; Su ZHENG ; Wei WANG ; Li YU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2017;24(6):602-607
Objective To evaluate the safety and efficacy of Yinhua Pinggan granule of Qingjie Xuantou lung defense prescription in the treatment of patients with upper respiratory tract infection accompanied by traditional Chinese medicine (TCM) syndrome of pathogen stagnated in lung-defense phase and to explore the best effective dose.Methods A randomized double blinded, positive drug parallel controlled and multicentric clinical trial was conducted, 270 patients with upper respiratory infection were collected from the First Affiliated Hospital of Zhejiang Chinese Medical University, Affiliated Hospital of Jiangxi Medical University, the Second Affiliated Hospital of Tianjin University of TCM, Tongde Hospital of Zhejiang Province, and Fujian Province Institute of TCM, after screening only 242 cases were consistent with the criteria of enrollment into the Per-Protocol Set (PPS) population, and they were divided into three groups: high dose observation group (82 cases), low dose observation group (79 cases) and control group (81 cases). The high and low dose observation groups were treated with Yinhua Pinggan granule (5 g per bag), high dose means once 1 bag orally taken 3 times a day, low dose indicates once 1 bag taken twice a day; the control group was treated with Yinqiao Jiedu granule (5 g per bag) once 1 bag, 3 times a day; the curative effects of the above groups were all evaluated after consecutive oral administration of the drug respectively for 1 therapeutic course (3 days). The main efficacy evaluation indexes included the TCM syndrome total score and the total score of main symptoms of upper respiratory tract infection; the secondary efficacy evaluation indexes included the situations of patients with different scores of main symptoms of fever and chills, and of disappearance of TCM symptoms; the clinical comprehensive therapeutic effect and the changes of proportion of neutrophils were observed and the safety of drugs was evaluated.Results In PPS population, after treatment the TCM syndrome total score and the total score of main symptoms in the control group and the high and low dose observation groups were all significantly lower than those before treatment, on the 3rd day statistical significant differences were shown (4.4±3.9 vs. 15.5±4.6, 3.7±3.2 vs. 15.0±4.3, 3.0±2.7 vs. 15.2±3.9, 2.8±2.6 vs. 9.7±2.7, 2.3±2.1 vs. 9.5±2.5, 2.0±1.9 vs. 9.6±2.4, respectively, all P < 0.01). After treatment for 1 day, the numbers of patients with 6 score in the control group and the high and low dose observation groups were reduced significantly compared with those before treatment in main symptoms of fever with chills (7 vs. 32 cases, 6 vs. 31 cases, 4 vs. 28 cases, respectively); 3 days after treatment, compared with those before treatment, the numbers of patients with main symptoms of fever with chills score being 0 were significantly increased in the above three groups (65, 73, 77 cases vs. 0 cases, respectively), the numbers of patients with the score being 3 were significantly decreased (16 vs. 47 cases, 5 vs. 46 cases, 5 vs. 52 cases, respectively); the control and high dose observation group had no patients with the score being 6, there was only 1 case with the score being 6 in the low dose observation group. The results showed that the treatments of high and low dose observation groups and the control group all could alleviate the clinical symptoms, and the changes of numbers of patients with the scoresbeing 0 and 3 in high and low dose groups were more significant than those in the control group (respectively 73, 77 vs. 65 cases, 5, 5 vs. 16 cases, allP < 0.05), showing that the antipyretic effect of Yinhua Pinggan granule was superior to that of the Yinqiao Jiedu granule. The disappearance rates of fever with chills symptoms in high and low dose observation groups were significantly higher than that in the control group [respectively 93.9% (77/82), 92.4% (73/79) vs. 80.2% (65/81), allP < 0.05]. The TCM syndrome cure and obvious effect rate and effective rate in high and low dose observation groups were higher than those in the control group [respectively 87.80% (72/82), 79.75% (63/79) vs. 74.07% (60/81) and 98.78% (81/82), 96.20% (76/79) vs. 96.30% (78/81)]; the cure and marked effective rate and effective rate of controlling symptoms of upper respiratory tract infection in high and low dose observation groups were higher than those in the control group [respectively 78.05% (64/82), 74.68% (59/79) vs. 65.43% (78/81) and 98.78% (81/82), 96.20% (76/79) vs. 96.30% (78/81)], comparisons of efficacy among the three groups possessed clinical practical significance, but the differences were not statistically significant (allP > 0.05). The percentages of neutrophils in high and low dose observation groups and control group were significantly lower than those before treatment (respectively 0.61±0.08 vs. 0.63±0.08, 0.62±0.08 vs. 0.64±0.08, 0.61±0.09 vs. 0.64±0.09, allP < 0.05). Yinhua Pinggan granule was safe in the prescribed course of treatment and range of therapeutic dose.Conclusions Yinhua Pinggan granule is a safe and effective drug in the treatment of patients with upper respiratory tract infection accompanied by syndrome of pathogen stagnated in lung-defense phase.
7.Current status of surgical treatment for adenocarcinoma of esophagogastric junction
Chinese Journal of Digestive Surgery 2019;18(6):513-517
Adenocarcinoma of esophagogastric junction (AEG) refers to the tumor invading the esophagogastric junction and Siewert type is the most practical classification at present.There are many surgical controversies about AEG,mainly focusing on Siewert Ⅱ type.In this paper,definition and classification of AEG,epidemiological characteristics,pathological TNM staging,rules of lymph node metastasis and dissection,esophageal resection margin,gastric resection scope,surgical approach and other issues are investigated combined with recent highquality evidence.
8.Age-related change in mitochondrial DNA copy number and its correlation with intrinsic capacity and body composition
Tingting HUANG ; Danmei ZHANG ; Li QIN ; Shu CHEN ; Yan MAO ; Haitong BAO ; Xiao WANG ; Qianqian ZHU ; Qiangwei TONG ; Guoxian DING ; Juan LIU
Chinese Journal of Geriatrics 2023;42(1):1-6
Objective:To investigate the correlation of peripheral blood relative mitochondrial DNA copy number(mtDNAcn)with intrinsic capacity and body composition, and to identify potential biomarkers for healthy aging.Methods:Clinical data of 416 patients admitted to our hospital from September 2019 to June 2021 were consecutively collected.MtDNA was extracted from peripheral blood of these subjects, and mtDNAcn was determined by a real-time fluoresence quantitative reverse transcription-polymerase chain reaction(qRT-PCR). Intrinsic capacity assessment included 5 aspects that were exercise[Morse Fall Scale(MFS), Physiological Frailty Phenotype(PFP), Sarcopenia Questionnaire(SARC-CALF), Short Physical Performance Battery(SPPB), Time Up and Go Test(TUG)]; vitality[Mini Nutritional Assessment(MNA), Multidimensional Prognostic Index(MPI)]; cognition[Mini-Mental State Examination(MMSE)scale]; psychology[Geriatric Depression Scale(GDS), Self-rating Anxiety Scale(SAS)]; sensory capacities[Cumulative Illness Rating Scale-the Comorbidity Index(CIRS-CI)]. To assess body composition, dual-energy X-ray absorptiometry was used to measure body fat, including trunk fat, total body fat, fat in the abdominal region, fat in the buttock region, and then to calculate fat index(FMI)and limb skeletal muscle mass index(ASMI).Results:Spearman correlation analysis showed that mtDNAcn had a negatively correlation with age( r=-0.176, P<0.05). After adjustment for gender and body mass index, partial correlation analysis showed mtDNAcn were still negatively correlated with age( r=-0.144, P<0.05). Furthermore, mtDNAcn was significantly correlated with 4 m gait speed, the scores of SARC-CalF, MFS, MNA, MMSE, MPI and its sub-scale's Activities of Daily Living(ADL)and Short Portable Mental Status Questionnaire(SPMSQ)( r=0.171, -0.207, -0.163, 0.221, 0.184, -0.210, 0.241, -0.269, all P<0.05). After adjustment for age, gender and body mass index, partial correlation analysis showed mtDNAcn still had a significant correlation with gait speed, the scores of MFS, MNA, MPI and SPMSQ( r=0.170, -0.170, 0.148, -0.242, -0.188, all P<0.05). In addition, the Spearman correlation analysis showed that mtDNAcn was positively correlated with FMI, trunk fat, total body fat, abdominal fat and fat in the buttock region( r=0.168, 0.143, 0.175, 0.116, 0.199, all P<0.05). However, after adjustment for age and gender, mtDNAcn was only correlated with FMI, total body fat, fat in the buttock region( r=0.126, 0.131, 0.127, all P<0.05). On the other hand, multiple linear regression analysis showed that mtDNAcn was significantly correlated with age, gait speed, FMI, total body fat, fat in the buttock region, the scores of MFS, PFP, MNA and MPI( β=-0.191, 0.156, 0.126, 0.131, 0.125, -0.119, -0.145, 0.151, -0.171, all P<0.05). Conclusions:MtDNAcn is correlated with physical function, frailty, nutrition, falling, cognition and body composition, and may be considered as a biomarker for the evaluation of the locomotion and vitality of human intrinsic capacity.
9.The pattern of lymph node metastasis and prognostic factors analysis of Siewert type Ⅱ adenocarcinoma of esophagogastric junction
Haitong WANG ; Lei GONG ; Hongdian ZHANG ; Xianxian WU ; Yueyang YANG ; Kai ZHU ; Peng REN ; Zhentao YU
Chinese Journal of Digestive Surgery 2019;18(6):556-562
Objective To investigate the pattern of lymph node metastasis and analyze prognostic factors of Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods The retrospective case-control study was conducted.The clinicopathological data of 368 patients with Siewert type Ⅱ AEG who were admitted to Tianjin Medical University Cancer Institute and Hospital from June 2010 and November 2015 were collected.There were 323 males and 45 females,aged from 35 to 80 years,with an average age of 64 years.Of 368 patients,209 underwent left transthoracic surgery,1 12 underwent thoracoabdominal surgery,and 47 underwent Ivor-Lewis surgery.Observation indicators:(1) total lymph node metastasis and metastasis of various lymph node stations;(2) follow-up and survival;(3) prognostic factors analysis;(4) influencing factors affecting thoracic lymph node metastasis.Follow-up using outpatient examination and telephone interview was performed to detect survival of patients up to November 2018.Measurement data with skewed distribution were represented as M (range).Count data were represented as absolute number or percentage.The survival time and rate were calculated using the Kaplan-Meier method.The univariate and multivariate analyses were done by the COX proportional hazard model.Results (1) Total lymph node metastasis and metastasis of various lymph node stations:the total lymph node metastasis rate was 66.58% (245/368) in 368 patients.The metastasis rates of abdominal lymph nodes,thoracic lymph nodes,lower mediastinal lymph nodes,and upper mediastinal lymph nodes were 65.49% (241/368),12.77% (47/368),12.23% (45/368),and 1.09% (4/368),respectively.The order of metastasis rate of various lymph node stations from high to low was 51.99%(170/237) of No.7 left gastric artery,34.23%(89/260) of No.1 right paracardial region,33.88% (83/245) of No.2 left paracardial region,28.91% (85/294) of No.3 lesser curvature,27.10%(29/107) of No.1 1 splenic artery,19.75%(16/81) of No.9 celiac trunk,15.25%(36/236) of No.E8Lo lower paraesophageal region,11.94% (16/134) of No.4 greater curvature,11.76% (6/51) of No.E8M middle paraesophageal region,11.1 1%(10/90) of No.8 common hepatic artery,4.65%(4/86) of No.E9L left inferior pulmonary ligament and 3.39% (2/59) of No.E7 subcarinal region.(2) Follow-up and survival:of the 368 patients,309 were followed up for 1-103 months,with a median follow-up time of 38 months.The survival time of 309 patients was 0.7-101.9 months,and the median survival time was 35.9 months.During the followup,the postoperative l-,2-,3-year overall survival rates were 85.9%,68.6%,and 58.7%,respectively.(3) Prognostic factors analysis.Results of univariate analysis showed that tumor differentiation degree,presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,tumor diameter,and length of esophageal invasion were associated factors affecting prognosis of patients (x2 =8.776,26.582,46.057,18.679,22.460,9.158,P<0.05).Results of multivariate analysis showed that presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,and tumor diameter were independent influencing factors for prognosis of patients [odds ratio (OR) =1.699,1.271,1.422,1.238,95% confidence interval:1.102-2.621,1.019-1.481,1.090-1.856,0.971-1.481,P<0.05].(4) Influencing factors affecting thoracic lymph node metastasis:results of univariate analysis showed that tumor diameter,length of esophageal invasion,number of lymph lodes harvested in thorax were related factors for thoracic lymph node metastasis (x2 =5.129,43.140,10.605,P<0.05).Results of multivariate analysis showed that length of esophageal invasion ≥2 cm,number of lymph lodes harvested in thorax ≥ 4 were independent risk factors for thoracic lymph node metastasis (OR =6.321,1.097,95% confidence interval:2.982-13.398,1.026-1.173,P<0.05).Conclusion Lymph node metastasis of Siewert type Ⅱ AEG spreads two regions,mainly at abdominal lymph nodes,followed by the thoracic lymph nodes.Presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,and tumor diameter are independent influencing factors for prognosis of patients.Presence of thoracic lymph node metastasis indicates poor prognosis of patients.Length of esophageal invasion ≥ 2 cm and number of lymph lodes harvested in thorax ≥4 are independent risk factors for thoracic lymph node metastasis.
10.Value of number of negative lymph nodes in predicting the prognosis of patients with esophageal cancer after neoadjuvant therapy and the construction of nomogram prodiction model
Yueyang YANG ; Peng TANG ; Zhentao YU ; Haitong WANG ; Hongdian ZHANG ; Mingquan MA ; Yufeng QIAO ; Peng REN ; Xiangming LIU ; Lei GONG
Chinese Journal of Digestive Surgery 2023;22(3):371-382
Objective:To investigate the value of number of negative lymph nodes (NLNs) in predicting the prognosis of patients with esophageal cancer after neoadjuvant therapy and the construction of nomogram prodiction model.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 924 patients with esophageal cancer after neoadjuvant therapy uploaded to the Surveillance, Epidemiology, and End Results Database of the National Cancer Institute from 2004 to 2015 were collected. There were 1 624 males and 300 females, aged 63 (range, 23?85)years. All 1 924 patients were randomly divided into the training dataset of 1 348 cases and the validation dataset of 576 cases with a ratio of 7:3 based on random number method in the R software (3.6.2 version). The training dataset was used to constructed the nomogram predic-tion model, and the validation dataset was used to validate the performance of the nomogrram prediction model. The optimal cutoff values of number of NLNs and number of examined lymph nodes (ELNs) were 8, 14 and 10, 14, respectively, determined by the X-tile software (3.6.1 version), and then data of NLNs and ELNs were converted into classification variables. Observation indicators: (1) clinicopathological characteristics of patients in the training dataset and the validation dataset; (2) survival of patients in the training dataset and the validation dataset; (3) prognostic factors analysis of patients in the training dataset; (4) survival of patients in subgroup of the training dataset; (5) prognostic factors analysis in subgroup of the training dataset; (6) construction of nomogram prediction model and calibration curve. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and Log-Rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Based on the results of multivariate analysis, the nomogram prediction model was constructed. The prediction efficacy of nomogram prediction model was evaluated using the area under curve (AUC) of the receiver operating characteristic curve and the Harrell′s c index. Errors of the nomogram prediction model in predicting survival of patients for the training dataset and the validation dataset were evaluated using the calibration curve. Results:(1) Clinicopathological characteristics of patients in the training dataset and the validation dataset. There was no significant difference in clinicopatholo-gical characteristics between the 1 348 patients of the training dataset and the 576 patients of the validation dataset ( P>0.05). (2) Survival of patients in the training dataset and the validation dataset. All 1 924 patients were followed up for 50(range, 3?140)months, with 3-year and 5-year cumulative survival rate as 59.4% and 49.5%, respectively. The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the training dataset was 46.7%, 62.0% and 66.0%, respectively, and the 5-year cumulative survival rate was 38.1%, 52.1% and 59.7%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=33.70, P<0.05). The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the validation dataset was 51.1%, 54.9% and 71.2%, respectively, and the 5-year cumulative survival rate was 39.3%, 42.5% and 55.7%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=14.49, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the training dataset was 53.9%, 60.0% and 62.7%, respectively, and the 5-year cumulative survival rate was 44.7%, 49.1% and 56.9%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=9.88, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the validation dataset was 56.2%, 47.9% and 69.3%, respectively, and the 5-year cumula-tive survival rate was 44.9%, 38.4% and 51.9%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=9.30, P<0.05). (3) Prognostic factors analysis of patients in the training dataset. Results of multivariate analysis showed that gender, neoadjuvant pathological (yp) T staging, ypN staging (stage N1, stage N2, stage N3) and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=0.65, 1.44, 1.96, 2.41, 4.12, 0.69, 0.56, 95% confidence interval as 0.49?0.87, 1.17?1.78, 1.59?2.42, 1.84?3.14, 2.89?5.88, 0.56?0.86, 0.45?0.70, P<0.05). (4) Survival of patients in subgroup of the training dataset. Of the patients with NLNs in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 61.1%, 71.6% and 76.8%, respectively, and the 5-year cumulative survival rate was 50.7%, 59.9% and 70.1%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=12.66, P<0.05). Of the patients with positive lymph nodes in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 26.1%, 42.9% and 44.7%, respectively, and the 5-year cumulative survival rate was 20.0%, 36.5% and 39.3%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=20.39, P<0.05). (5) Prognostic factors analysis in subgroup of the training dataset. Results of multivariate analysis in patients with NLNs in the training dataset showed that gender, ypT staging and number of NLNs (>14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadju-vant therapy ( hazard ratio=0.67, 1.44, 0.56, 95% confidence interval as 0.47?0.96, 1.09?1.90, 0.41?0.77, P<0.05). Results of multi-variate analysis in patients with positive lymph nodes in the training dataset showed that race as others, histological grade as G2, ypN staging as stage N3 and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=2.73, 0.70, 2.08, 0.63, 0.59, 95% confidence interval as 1.43?5.21, 0.54?0.91, 1.44?3.02, 0.46?0.87, 0.44?0.78, P<0.05). (6) Construction of nomogram prediction model and calibration curve. Based on the multivariate analysis of prognosis in patients of the training dataset ,the nomogram prediction model for the prognosis of patients with esophageal cancer after neoadju-vant treatment was constructed based on the indicators of gender, ypT staging, ypN staging and number of NLNs. The AUC of nomogram prediction model in predicting the 3-, 5-year cumulative survival rate of patients in the training dataset and the validation dataset was 0.70, 0. 70 and 0.71, 0.71, respectively. The Harrell′s c index of nomogram prediction model of patients in the training dataset and the validation dataset was 0.66 and 0.63, respectively. Results of calibration curve showed that the predicted value of the nomogram prediction model of patients in the training dataset and the validation dataset was in good agreement with the actual observed value. Conclusion:The number of NLNs is an independent influencing factor for the prognosis of esophageal cancer patients after neoadjuvant therapy, and the nomogram prediction model based on number of NLNs can predict the prognosis of esophageal cancer patients after neoadjuvant therapy.