1.Reconstruction and analysis of K-Clip surgery process based on finite element method
Hao SHI ; Wenbin OUYANG ; Shiguo LI ; Qi LI ; Fengwen ZHANG ; Yao LIU ; Wenxin LU ; Chang LIU ; Shaojie ZHANG ; Xiangbin PAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):44-50
Objective To investigate the effects of different types of tricuspid regurgitation, implantation positions, and device models on the treatment outcomes of K-Clip for tricuspid regurgitation using numerical simulations. Methods Three-dimensional reconstruction of the heart model was performed based on CT images. Two different regurgitation orifices were obtained by modifying the standard parameterized tricuspid valve leaflets and chordae tendineae. The effects of different K-Clip models at different implantation positions (posterior leaflet midpoint, anterior-posterior commissure, anterior leaflet midpoint, posterior septal commissure) were simulated using commercial explicit dynamics software Ls-Dyna. Conclusion For the two types of regurgitation in this study, clipping at the posterior leaflet midpoint resulted in a better reduction of the regurgitation orifice (up to 75% reduction in area). Higher clamping forces were required for implantation at the anterior leaflet midpoint and posterior septal commissure, which was unfavorable for the smooth closure of the clipping components. There was no statistical difference in the treatment outcomes between the 18T and 16T K-Clip components, and the 16T component required less clamping force. Therefore, the use of the 16T K-Clip component is recommended.
2.Consistent analysis of the expression of different PD-L1 antibodies in gastric adenocarcinoma
Wenbin ZHOU ; Xue CHEN ; Yao FU ; Hongyan WU ; Chaoshan WANG ; Qi SUN
Chinese Journal of Clinical and Experimental Pathology 2024;40(6):597-602
Purpose The purpose of this study was to in-vestigate programmed death ligand-1(PD-L1)expression in gastric adenocarcinoma(GAC)patients and the consistency of immunohistochemical(IHC)detection of four different clones of PD-L1 antibodies,so as to provide reference for the gradual standardization of PD-L1 IHC detection in gastric adenocarcino-ma and subsequent clinical studies.Methods This study col-lected surgically resected and pathologically confirmed specimens from 286 gastric adenocarcinoma patients,and specimens were stained with four antibodies:PD-L1 22C3,SP263,E1L3N and SP142.The consistency of the antibodies was statistically ana-lyzed under different critical values using two scoring criteria:comprehensive positive score(CPS)and tumor proportion score(TPS).Results Regardless of the TPS and CPS cut-off val-ues,the positive rate of 22C3 was the highest among the four an-tibodies.Consistency analysis showed that E1L3N had good con-sistency with SP142(κ=0.612)and SP263(κ=0.660)only when the cut-off value of CPS positive was 1.In addition,the consistency between the other antibodies was only moderate or poor.Conclusion The four PD-L1 antibodies exhibited incon-sistent concordance across various TPS and CPS positive thresh-olds,so it is not recommended to exchange reagents during clini-cal testing of GAC and the test results shall be documented in accordance with the specification.
3.Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT)
Huiqiang HUANG ; Zhiming LI ; Lihong LIU ; Liang HUANG ; Jie JIN ; Hongyan TONG ; Hui ZHOU ; Zengjun LI ; Zhenqian HUANG ; Wenbin QIAN ; Kaiyang DING ; Quande LIN ; Ming HOU ; Yunhong HUANG ; Jingbo WANG ; Pengcheng HE ; Xiuhua SUN ; Xiaobo WANG ; Zunmin ZHU ; Yao LIU ; Jinhai REN ; Huijing WU ; Liling ZHANG ; Hao ZHANG ; Liangquan GENG ; Jian GE ; Ou BAI ; Liping SU ; Guangxun GAO ; Xin LI ; Yanli YANG ; Yijian CHEN ; Aichun LIU ; Xin WANG ; Yi WANG ; Liqun ZOU ; Xiaobing HUANG ; Dongping HUANG ; Shujuan WEN ; Donglu ZHAO ; Jun MA
Journal of Leukemia & Lymphoma 2023;32(8):457-464
Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.
4.Effects of hypoxia on the expression and function of P-gp in Caco-2 cells.
Anpeng ZHAO ; Hongfang MU ; Wanteng YAO ; Xiwen CHANG ; Wenbin LI ; Rong WANG
Journal of Central South University(Medical Sciences) 2023;48(4):491-498
OBJECTIVES:
Hypoxia can alter the oral bioavailability of drugs, including various substrates (drugs) of P-glycoprotein (P-gp), suggesting that hypoxia may affect the function of P-gp in intestinal epithelial cells. Currently, Caco-2 monolayer model is the classic model for studying the function of intestinal epithelial P-gp. This study combines the Caco-2 monolayer model with hypoxia to investigate the effects of hypoxia on the expression and function of P-gp in Caco-2 cells, which helps to elucidate the mechanism of changes in drug transport on intestinal epithelial cells in high-altitude hypoxia environment.
METHODS:
Normally cultured Caco-2 cells were cultured in 1% oxygen concentration for 24, 48, and 72 h, respectively. After the extraction of the membrane proteins, the levels of P-gp were measured by Western blotting. The hypoxia time, with the most significant change of P-gp expression, was selected as the subsequent study condition. After culturing Caco-2 cells in transwell cells for 21 days and establishing a Caco-2 monolayer model, they were divided into a normoxic control group and a hypoxic group. The normoxic control group was continuously cultured in normal condition for 72 h, while the hypoxic group was incubated for 72 h in 1% oxygen concentration. The integrity and polarability of Caco-2 cells monolayer were evaluated by transepithelial electrical resistance (TEER), apparent permeability (Papp) of lucifer yellow, the activity of alkaline phosphatase (AKP), and microvilli morphology and tight junction structure under transmission electron microscope. Then, the Papp of rhodamine 123 (Rh123), a kind of P-gp specific substrate, was detected and the efflux rate was calculated. The Caco-2 cell monolayer, culturing at plastic flasks, was incubated for 72 h in 1% oxygen concentration, the expression level of P-gp was detected.
RESULTS:
P-gp was decreased in Caco-2 cells with 1% oxygen concentration, especially the duration of 72 h (P<0.01). In hypoxic group, the TEER of monolayer was more than 400 Ω·cm2, the Papp of lucifer yellow was less than 5×10-7 cm/s, and the ratio of AKP activity between apical side and basal side was greater than 3. The establishment of Caco-2 monolayer model was successful, and hypoxia treatment did not affect the integrity and polarization state of the model. Compared with the normoxic control group, the efflux rate of Rh123 was significantly reduced in Caco-2 cell monolayer of the hypoxic group (P<0.01). Hypoxia reduced the expression of P-gp in Caco-2 cell monolayer (P<0.01).
CONCLUSIONS
Hypoxia inhibits P-gp function in Caco-2 cells, which may be related to the decreased P-gp level.
Humans
;
ATP Binding Cassette Transporter, Subfamily B, Member 1
;
Caco-2 Cells
;
ATP Binding Cassette Transporter, Subfamily B
;
Hypoxia
;
Oxygen
5.Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma.
Yingqiang LIU ; Zhengsheng ZHAN ; Zhuang KANG ; Mengyuan LI ; Yongcong LV ; Shenglan LI ; Linjiang TONG ; Fang FENG ; Yan LI ; Mengge ZHANG ; Yaping XUE ; Yi CHEN ; Tao ZHANG ; Peiran SONG ; Yi SU ; Yanyan SHEN ; Yiming SUN ; Xinying YANG ; Yi CHEN ; Shanyan YAO ; Hanyu YANG ; Caixia WANG ; Meiyu GENG ; Wenbin LI ; Wenhu DUAN ; Hua XIE ; Jian DING
Acta Pharmaceutica Sinica B 2023;13(12):4748-4764
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).
6.Effects of plateau hypoxia on pharmacokinetic parameters and cerebral-blood distribution of levetiracetam in rats
Anpeng ZHAO ; Lin HU ; Wanteng YAO ; Xiwen CHANG ; Rong WANG ; Wenbin LI
Journal of Central South University(Medical Sciences) 2023;48(10):1445-1452
Objective:Plateau hypoxia exposure causes changes in pharmacokinetic parameters and cerebral-blood distribution of drugs,including many substrates of P-glycoprotein(P-gp).Levetiracetam,a kind of antiepileptic drugs,is a substrate of P-gp.Whether plateau hypoxia exposure changes its pharmacokinetic characteristics and cerebral-blood distribution remains unclear.This study aims to investigate the effects of plateau hypoxia on the pharmacokinetics and cerebra-blood distribution of levetiracetam. Methods:Wistar rats were divided into a low-altitude control group,a high-altitude group,a solvent group,and a P-gp induction group.After 24 h of exposure at altitude of 4 010 m,rats in the high-altitude group were given levetiracetam orally or intravenously.The plasma was respectively collected at 0.083,0.25,0.5,0.83,1.25,2,4,6,8,10,12,and 24 h after oral administration of the drug,while both plasma and brain were respectively collected at 5,45,60,120 and 240 min after intravenous injection.After 3 days administration of dexamethasone,plasma and brain of rats in the P-gp induction group were collected at 120 min after intravenously giving levetiracetam.Plasma and brain concentrations of the drug were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The expression of P-gp in blood-brain barrier was detected by Western blotting. Results:Compared with the low-altitude control group,the area under the curve(AUC)and mean residence time(MRT)of levetiracetam were respectively decreased by 14.69%(P<0.01)and 15.42%(P<0.01),while the clearance(CL)was increased by 16.67%(P<0.01)in the high-altitude group.The ratio of brain/blood plasma drug concentration was decreased by 22.82%(P<0.05),12.42%(P<0.05),17.40%(P<0.01),and 13.22%(P<0.01)at 5,45,120,and 240 min after injection,respectively.The expression of P-gp on the blood-brain barrier was increased by 86.3%(P<0.05).Compared with the solvent control group,the expression of P-gp on the blood-brain barrier in the P-gp induction group was increased by 56.3%(P<0.05),the ratio of brain/blood plasma drug concentration was decreased by 19.3%(P<0.05). Conclusion:After acute plateau hypoxia exposure,the pharmacokinetic of levetiracetam in rats are altered,and the cerebral-blood distribution of the drug in rats is decreased,which may be related to the up-regulation of P-gp expression on the blood-brain barrier.
7. Protective effect of hypoxia inducible factor-1α on intestinal mucosal barrier in sepsis
Rui HE ; Wenbin TENG ; Shengmei ZHU ; Liuxu YAO ; Yue SHAN ; Yuhong LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(3):264-270
AIM: To investigate the effect and mechanism of hypoxia inducible factor-1α on intestinal mucosal barrier in sepsis. METHODS: SD rats were randomly divided into 4 groups: sham group, sepsis group, sepsis+HIF-1α stimulant (sepsis+DMOG group), sepsis+HIF-1α inhibitor (sepsis+Bay87-2243 group), 6 rats in each group. Sepsis model was established by cecal ligation and perforation (CLP). The levels of inflammatory markers IL-1β, IL-6, TNF-α, oxidative stress markers MDA and antioxidant factors SOD and CAT were detected by ELISA and the expression of HIF-1α in intestinal mucosa was detected by Western blot. The pathological damage of intestinal mucosa was detected by HE staining. RESULTS: Inflammatory factors, oxidative stress factors and HIF-1α were significantly up-regulated in septic rats (P<0.05). The contents of IL-1β, IL-6, TNF-α and MDA in plasma were significantly decreased by intraperitoneal injection of DMOG (P<0.05); the levels of SOD and CAT in plasma were increased (P<0.05), HIF-1α was up-regulated (P<0.05), and the pathological damage of intestinal mucosa was alleviated, with decreased Chiu's score (P<0.05). Oral administration of Bay87-2243 gave the opposite result. CONCLUSION: HIF-1α has a protective effect on intestinal mucosal injury in sepsis. The mechanism may be related to the alleviation of inflammatory response and inhibition of oxidative stress.
8.Establishment of an auxiliary diagnosis system of newborn screening for inherited metabolic diseases based on artificial intelligence technology and a clinical trial
Rulai YANG ; Yanling YANG ; Ting WANG ; Weize XU ; Gang YU ; Jianbin YANG ; Qiaoling SUN ; Maosheng GU ; Haibo LI ; Dehua ZHAO ; Juying PEI ; Tao JIANG ; Jun HE ; Hui ZOU ; Xinmei MAO ; Guoxing GENG ; Rong QIANG ; Guoli TIAN ; Yan WANG ; Hongwei WEI ; Xiaogang ZHANG ; Hua WANG ; Yaping TIAN ; Lin ZOU ; Yuanyuan KONG ; Yuxia ZHOU ; Mingcai OU ; Zerong YAO ; Yulin ZHOU ; Wenbin ZHU ; Yonglan HUANG ; Yuhong WANG ; Cidan HUANG ; Ying TAN ; Long LI ; Qing SHANG ; Hong ZHENG ; Shaolei LYU ; Wenjun WANG ; Yan YAO ; Jing LE ; Qiang SHU
Chinese Journal of Pediatrics 2021;59(4):286-293
Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.
9.Percutaneous transcatheter closure of atrial septal defect guided by transthoracic echocardiography in outpatients
DENG Rundi ; ZHANG Fengwen ; XIE Yongquan ; OUYANG Wenbin ; LIU Yao ; ZOU Mengxuan ; WEN Bin ; ZHANG Gejun ; YAN Chaowu ; PAN Xiangbin
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(01):10-13
Objective To assess the feasibility and safety of percutaneous transcatheter closure of atrial septal defect (ASD) guided by transthoracic echocardiography (TTE) in outpatients. Methods From December 2016 to June 2018, 50 simple ASD patients underwent TTE-guided transcatheter closure in the outpatient operating room of our hospital (a TTE group) including 22 males and 28 females at the age of 16-48 (27.40±6.95) years. Fifty patients with simple ASD treated with the guidance of conventional fluoroscopy during the same period were treated as a control group, including 22 males and 28 females at the age of 15-48 (28.58±6.96) years. Both groups were re-examined by TTE during follow-up at 1 month, 3 months, 6 months and 1 year. Results The mean age, body weight, the size of ASD and occluder and success rate had no statistical difference between the two groups (P>0.05). Compared with the control group, the TTE group had significantly lower mean operation time (P<0.01) and less cost (P<0.01) since patients need not to be hospitalized. No related complications were found in the TTE group during follow-up. Conclusion Percutaneous transcatheter closure of ASD guided by TTE appears safe and effective for outpatients, and can significantly reduce the cost.
10.A multicenter retrospective study on surgical indications of gallbladder polyps: a report of 2 272 cases
Dong ZHANG ; Qi LI ; Xiaodi ZHANG ; Pengbo JIA ; Xintuan WANG ; Xilin GENG ; Yu ZHANG ; Junhui LI ; Chunhe YAO ; Yimin LIU ; Zhihua GUO ; Rui YANG ; Da LEI ; Chenglin YANG ; Qiwei HAO ; Wenbin YANG ; Zhimin GENG
Chinese Journal of Digestive Surgery 2020;19(8):824-834
Objective:To investigate the surgical indications of gallbladder polyps.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 272 patients with gallbladder polyps who underwent cholecystectomy in 11 medical centers from January 2015 to December 2019 were collected, including 585 in the First Affiliated Hospital of Xi′an Jiaotong University, 352 in No. 215 Hospital of Shaanxi Nuclear Industry, 332 in the First People′s Hospital of Xianyang, 233 in Shaanxi Provincial People′s Hospital, 152 in the Second Affiliated Hospital of Xi′an Jiaotong University, 138 in Xianyang Hospital of Yan′an University, 137 in People′s Hospital of Baoji, 125 in Hanzhong Central Hospital, 95 in Baoji Central Hospital, 72 in Ankang Central Hospital, 51 in Yulin No.2 Hospital. There were 887 males and 1 385 females, aged (48±12)years, with a range from 12 to 86 years. Observation indicators: (1) surgical treatment, pathological examination and hospitalization; (2) follow-up and complications; (3) comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps; (4) comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis; (5) analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis; (6) construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Follow-up using outpatient examination or telephone interview was conducted to detect complications and survival of patients up to April 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the rank-sum test. Ordinal data was analyzed using the rank-sum test of multi-samples. Analysis of influence factors for the incidence of neoplastic polyps was conducted after excluding missing data of CEA and CA19-9. Univariate analysis was conducted using the chi-square test or rank-sum test of multi-samples, and multivariate analysis was conducted using Logistic regression model. Based on Logistic regression model multivariate analysis, the nomogram prediction model was constructed using the R 3.6.0 version software. Results:(1) Surgical treatment, pathological examination and hospitalization: of the 2 272 patients, 2 199 cases underwent laparoscopic cholecystectomy, 43 cases underwent open cholecystectomy, 28 cases underwent radical resection for gallbladder carcinoma, and 2 cases underwent laparoscopic gallbladder preservation and polypectomy. There were 1 050 of the 2 272 patients undergoing intraoperative frozen section examination. Results of pathological examination showed that 1 953 of the 2 272 patients had non-neoplastic polyps including 1 681 cases with cholesterol polyps and 272 cases with inflammatory polyps; 319 cases had neoplastic polyps including 274 with benign polyps (93 cases with adenoma, 66 cases with adenomyoma, 81 cases with adenoma-like hyperplasia, 34 cases with adenoma combined with intraepithelial neoplasia); and 45 cases had malignant polyps including 43 cases with adenocarcinoma, 1 case with adenosquamous carcinoma and 1 case with sarcomatoid carcinoma. The duration of postoperative hospital stay of 2 272 patients was 3 days(range, 1 to 27 days). (2) Follow-up and complications: of the 2 272 patients, 1 932 were followed up for 3.5 to 63.5 months, with a median follow-up time of 31.0 months. During the follow-up, 180 patients had short-term complications and 170 patients had long-term complications. (3) Comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps: cases with age ≤50 years or >50 years, cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, CA125, cases with single or multiple polyps in preoperative ultrasonography examination, cases with diameter of polyps in preoperative ultrasonography examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasono-graphy examination as nodular, papillary, globular or mulberry-like, cases undergoing or not undergoing intraoperative frozen section examination, cases with diameter of polyps in postoperative pathological examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with gallbladder wall thickness in postoperative pathological examination as ≤4 mm or >4 mm of the 1 953 patients with non-neoplastic polyps were 1 118, 835, 1 027, 422, 230, 274, 2.0 mg/L(range, 0.2-8.6 mg/L), 14.5 U/mL(range, 2.6-116.4 U/mL), 10.5 U/mL(range, 1.2-58.7 U/mL), 658, 1 295, 674, 741, 413, 125, 1 389, 564, 407, 1 119, 292, 135, 832, 1 121, 698, 774, 385, 96, 1 719, 234, respectively. The above indicators of the 319 patients with neoplastic polyps were 160, 159, 204, 55, 26, 34, 2.9 mg/L(range, 0.2-28.8 mg/L), 19.7 U/mL(range, 3.5-437.1 U/mL), 15.0 U/mL(range, 1.0-945.0 U/mL), 203, 116, 49, 59, 100, 111, 154, 165, 92, 153, 49, 25, 218, 101, 53, 85, 90, 91, 263, 56, respectively. There were significant differences in the above indicators between the non-neoplastic polyps and neoplastic polyps patients ( χ2=5.599, Z=-3.668, -2.407, -3.023, -3.403, χ2=104.474, Z=-13.367, χ2=65.676, 12.622, 73.075, Z=-11.874, χ2=7.649, P<0.05). (4) Comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis: after excluding 311 of the 2 272 patients with cholecystolithiasis, there were 706 cases with gallbladder polyp diameter of 7 to 9 mm, 459 cases with gallbladder polyp diameter of 10 to 12 mm, and 205 cases with gallbladder polyp diameter ≥13 mm, respectively. Cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, cases with single or multiple polyps in preoperative ultrasonography examination, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasonography examination as nodular, papillary, globular or mulberry-like, cases with echo intensity of preoperative ultrasonography examination as slightly strong, medium or weak, cases undergoing or not undergoing intraoperative frozen section examination, and cases with pathological types of polyps as non-neoplastic polyps, benign polyps or malignant polyps of the 706 patients with gallbladder polyp diameter of 7 to 9 mm were 291, 170, 107, 138, 2.2 mg/L(range, 0.5-8.6 mg/L), 21.0 U/mL(range, 2.8-116.4 U/mL), 207, 499, 620, 86, 118, 463, 75, 50, 252, 410, 44, 379, 327, 657, 49, 0, respectively. The above indicators of the 459 patients with gallbladder polyp diameter of 10 to 12 mm were 267, 85, 43, 64, 1.6 mg/L(range, 0.4-9.3 mg/L), 10.4 U/mL(range, 3.3-354.0 U/mL), 205, 254, 237, 222, 158, 223, 51, 27, 222, 213, 24, 263, 196, 373, 79, 7, respectively. The above indicators of the 205 patients with gallbladder polyp diameter ≥13 mm were 128, 38, 20, 19, 2.1 mg/L(range, 0.6-28.8 mg/L), 10.2 U/mL(range, 3.6-307.0 U/mL), 120, 85, 75, 130, 68, 97, 22, 18, 98, 95, 12, 148, 57, 113, 71, 21, respectively. There were significant differences in the above indicators among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥ 13 mm ( χ2=46.482, 8.093, 39.504, 66.971, 277.043, 60.945, 19.672, 22.340, 197.854, P<0.05). (5) Analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: of the 459 patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis, there were 373 cases with non-neoplastic polyps, and 86 cases with neoplastic polyps, respectively. Results of univariate analysis showed that CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( χ2=10.342, 5.616, 20.009, Z=-4.352, χ2=6.203, P<0.05). Results of multivariate analysis showed that CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( odds ratio=8.423, 0.082, 0.337, 3.694, 2.318, 95% confidence interval: 1.547-45.843, 0.015-0.443, 0.198-0.575, 1.987-6.866, 1.372-3.916, P<0.05). (6) Construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were imported into R 3.6.0 version software to establish the nomogram prediction model for neoplastic polyps. The results showed the score for CEA>5.0 mg/L, CA19-9>39.0 U/mL, cases with single polyp in preoperative ultrasonography examination, cases with polyp diameter of 10 mm in preoperative ultrasonography examination, cases with polyp diameter of 11 mm in preoperative ultrasonography examination, cases with polyp diameter of 12 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were 25, 27, 100, 0, 26, 72, 98 in the nomogram prediction model, respectively. The C-index of nomogram prediction model was 0.768. Result of nomogram prediction model showed that the incidence of tumor polyps was 0, 6% and 10% in patients with multiple and pedicled gallbladder polyps with diameter of 10, 11, 12 mm and with CEA ≤5.0 mg/L and CA19-9 ≤39.0 U/mL, the incidence of tumor polyps was 43%, 53% and 70% in patients with single and broad base gallbladder polyps with diameter of 10, 11, 12 mm. The calibration curve showed that the probability of the nomogram prediction model predicting neoplastic polyps was nearly consistent with the actual probability. Conclusions:CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination are independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Cholecystectomy should be performed in time for patients with single and broad based gallbladder polyps with diameter of 10, 11, 12 mm.

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