1.Study on prognostic factors of patients with upper urinary tract urothelial carcinoma treated with Gemcitabine and Cisplatin
Jing XIAO ; Jimeng RUAN ; Miaomiao WANG ; Xiangyu WANG ; Tiandong HAN ; Caixiang ZHANG ; Meiyuan CHEN ; Xin TONG ; Yichen ZHU ; Ye TIAN
International Journal of Surgery 2018;45(9):591-595
Objective To investigate the prognostic factors of patients with upper urinary tract urothelial carcinoma (UTUC) treated with gemcitabine plus cisplatin (GC).Methods The clinical and follow-up data of 80 patients with UTUC admitted to Beijing Friendship Hospital,Capital Medical University from January 2013 to July 2018 were retrospectively analyzed.All patients underwent UTUC radical surgery.All patients were treated with GC regimen:1,8,and 15 days,Gemcitabine 800 mg/m2,intravenous infusion over 30 min;day 2 Cisplatin 70 mg/m2,protected from light 2 h intravenous drip;28 d for 1 cycle.Adjuvant treatments such as acid suppression,hydration,and antiemetic were given before and after chemotherapy.Patients completed 1 to 5 cycles with an average of 2 cycles.The patient's age,gender,presence or absence of water,primary tumor site,tumor stage and grade,lymphatic vascular infiltration,tumor recurrence,lymph node metastasis,organ metastasis,chemotherapy cycle,total Survival,etc.are used as indicators ofobservation.Univariate analysis of the patient's overall survival,screening for clinical variables associated with prognosis,and then using the COX proportional hazards model for multivariate prognostic analysis to determine independent influencing factors.Results Eighty patients with UTUC were followed up for 2 to 72 months with a median follow-up of 27 months.Sixteen patients (20%) died of UTUC recurrence or metastasis,and 64 (80%) patients survived.The 1-year cumulative survival rate was 78.26% (18/23),and the 2-year cumulative survival rate was 54.18% (9/13 ×78.26%),the 3-year cumulative survival rate was 39.41% (8/1 1 × 54.18%),the 4-year cumulative survival rate was 31.53% (12/15 × 39.41%),and the 5-year cumulative survival rate was 28.66% (10/11 × 31.53%).Univariate analysis showed combined hydronephrosis (P =0.023),lymphatic vessel infiltration (LVI) (P =0.001),tumor TNM stage (P =0.002),tumor recurrence (P =0.008),simple lymph node metastasis (P =0.005),organ metastasis (P < 0.001) was related to survival rate.COX model multivariate analysis showed that the independent risk factors associated with survival of patients with UTUC receiving chemotherapy with GC regimen were hydronephrosis (HR =4.355,95%CI:1.232-15.390,P=0.022),LVI (HR =0.133,95% CI:0.035-0.509,P=0.003),TNM stage (HR=0.099,95%CI:0.010-0.929,P=0.043).Conclusion The presence or absence of hydronephrosis,LVI,and tumor TNM staging are independent factors influencing the prognosis of patients with UTUC who have adjuvant chemotherapy.
2.Safety and efficacy of individualized transperineal prostate biopsy based on the segmentation of PI-RADS version 2 for mpMRI
Hongliang SHEN ; Jing XIAO ; Zhu DING ; Shenglei ZOU ; Wenhui LIU ; Meiyuan CHEN ; Dongxing ZHANG ; Yinxiang PANG ; Ye TIAN
Chinese Journal of Urology 2022;43(6):436-440
Objective:To investigate the safety and efficacy of individualized transperineal prostate biopsy based on the segmentation of PI-RADS v2 for mpMRI.Method:The clinical data of patients undergoing prostate biopsy in Beijing Friendship Hospital from December 2018 to November 2021 were analyzed retrospectively . A total of 228 patients with a median age of 65(49-83)years underwent biopsy. There were 102(44.7%) with tPSA <10 ng / ml, 108(47.4%) with tPSA 10-20 ng /ml, and 18(7.9%) with tPSA >20 ng /ml, with the median tPSA of 9.87(4.1-89.0)ng /ml. There were 42(18.4%) cases without MRI results, and 32(14.0%)cases with PI-RADS score of 1-2, 47(20.6%)cases of PI-RADS 3, 66(28.9%)cases of PI-RADS 4 and 41(18.1%)cases of PI-RADS 5, respectively.Transrectal ultrasound-guided transperineal prostate targeted biopsy (TB) and systematic biopsy (SB) were performed under local anesthesia or intravenous anesthesia. SB was performed for those without MRI and PI-RADS score of 1-2 (SB group), and TB and SB were performed for those with PI-RADS score of 3-5 (TB+ SB group). Prostate image under ultrasound was cognitively fused according to PI-RADS v2. One needle per area was distributed in 10 areas of each layer(the transition zone anterior and posterior sectors, the peripheral zone anterior, lateral, and medial sectors or central zone in left and right lobe). For those whose prostate length was less than 3cm, 10 needles were punctured, and two needles were added to each lateral lobe of the apex with a total of 14 needles. For those whose prostate length was from 3 to 6 cm, selected two layers with a total of 20 needles. For those with a length greater than 6cm, selected three layers with a total of 30 needles. If there was a suspicious lesion with PI-RADS score of 3-5, two needles were targeted for each lesion.The detection rate and complication rate of prostate cancer and clinically significant prostate cancer (csPCa) in the overall samples were observed, and the difference of the detection rate of prostate cancer and csPCa between the two groups was compared.Results:Of the 228 cases, there were 46 cases undergoing biopsy of one layer, 148 cases of two layers, and 34 cases of three layers, detecting 131 prostate cancer (PCa) diagnosed by pathology, with a detection rate of 57.5%, including 40 cases (17.5%)of clinically insignificant PCa and 91 cases(39.9%)of csPCa. The detection rate of PCa in TB+ SB group was 61.0%(94/154), which was higher than that in SB group, but there was no significant difference ( P=0.114). However, the detection rate of csPCa in TB + SB group was higher than that in SB group, which was 46.8%(72/154)vs. 25.6%(19/74), respectively ( P=0.002). In the combined TB and SB group (TB + SB group), the detection rate of csPCa by TB was 44.8% (69/154), which was higher than that of 33.8%(52/154)by SB( P=0.047). In the TB+ SB group, 7(4.5%) PCa were missed by SB, which was less than 18 cases (11.7%) missed by TB( P=0.022), but csPCa were missed by SB more than that missed by TB( P<0.001). There were 37 cases suffered from complications, with Clavien Dindo classification grade 1 of 29 cases (12.7%), grade 2 of 7 cases (3.1%), and grade 3 of 1 case(0.4%). Conclusions:Individualized transperineal prostate biopsy based on the segmentation of PI-RADS v2 for mpMRI is safe and reliable. Target biopsy by cognitive fusion can improve the detection rate of significant PCa. Systematic biopsy is also an important and essential supplement, which can detect prostate cancer missed by TB. Combined TB and SB are the best choice.
3.Preliminary study on the effect of Echinococcus multilocaris on phenotypic transformations of glucose metabolism and polarization types in macrophages
Yinhong SHEN ; Tao ZHANG ; Zihan YANG ; Yaogang ZHANG ; Dengliang HUANG ; Jing HOU ; Meiyuan TIAN ; Yanyan MA
Chinese Journal of Schistosomiasis Control 2023;35(6):590-603
Objective To investigate the effects of Echinococcus multilocularis on the phenotypic transformations of glucose metabolism, polarization types and inflammatory responses in macrophages, so as to provide insights into elucidation of echinococcosis pathogenesis. Methods Bone marrow cells were isolated from C57BL/6J mice at ages of 6 to 8 weeks, and induced into bone marrow-derived macrophages (BMDMs) with mouse macrophage colony-stimulating factor (M-CSF), which served as controls (BMDMs-M0). BMDMs-M0 induced M2 macrophages by interleukin-4 for 24 hours served as the IL-4 induction group, and BMDMs-M0 co-cultured with 2.4 ng/mL E. multilocularis cystic fluid (CF) served as the BMDM-CF co-culture group, while BMDMs-M0 co-cultured with E. multilocularis protoscolex (PSC) at a ratio of 500:1 served as the BMDM-PSC co-culture group. The types of polarization of BMDMs co-cultured with E. multilocularis CF and PSC were analyzed using flow cytometry, and the expression of macrophage markers, inflammatory factors, and glucose metabolism-related enzymes was quantified using fluorescent quantitative real-time PCR (qPCR) and Western blotting assays. Results There were significant differences among the four groups in terms of Arginase-1 (Arg1) (F = 1 457.00, P < 0.000 1), macrophages-derived C-C motif chemokine 22 (Ccl22) (F = 22 203.00, P < 0.000 1), resistin-like α (Retnla) (F = 151.90, P < 0.000 1), inducible nitric oxide synthase (iNOS) (F = 107.80, P < 0.001), hexokinase (HK) (F = 9 389.00, P < 0.000 1), pyruvate kinase (PK) (F = 641.40, P < 0.001), phosphofructokinase 1 (PFK1) (F = 43.97, P < 0.01), glucokinase (GK) (F = 432.50, P < 0.000 1), pyruvate dehydrogenase kinases1 (PDK1) (F = 737.30, P < 0.000 1), lactic dehydrogenase (LDH) (F = 3 632.00, P < 0.000 1), glucose transporter 1 (GLUT1) (F = 532.40, P < 0.000 1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (F = 460.00, P < 0.000 1), citrate synthase (CS) (F = 5 642.00, P < 0.01), glycogen synthase1 (GYS1) (F = 273.30, P < 0.000 1), IL-6 (F = 1 823.00, P < 0.000 1), IL-10 (F = 291.70, P < 0.000 1), IL-1β (F = 986.60, P < 0.000 1), and tumor necrosis factor (TNF)-α (F = 334.80, P < 0.000 1) and transforming growth factor (TGF)-β mRNA expression (F = 163.30, P < 0.001). The proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-PSC co-culture group [(22.87% ±1.48%) vs. (1.70% ±0.17%); t = 24.61, P < 0.001], and the proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-CF co-culture group [(20.07% ±0.64%) vs. (1.93% ±0.25%); t = 45.73, P < 0.001]. The mRNA expression of M2 macrophages markers Arg1, Ccl22 and Retnla was significantly higher in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01), and no significant difference was seen in the mRNA expression of the M1 macrophage marker iNOS among the three groups (P > 0.05), while qPCR assay quantified higher mRNA expression of key glycolytic enzymes HK, PK and PFK, as well as inflammatory factors IL-10, IL-1β, TNF-α and TGF-β in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01). Western blotting assay determined higher HK, PK and PFK protein expression in the BMDM-PSC co-culture group than in the control group (all P values < 0.05), and qPCR quantified higher GLUT1, GAPDH and IL-6 mRNA expression in the BMDM-CF co-culture group than in the control group (all P values < 0.05), while higher HK, PK and PFK protein and mRNA expression (all P values < 0.01), as well as lower IL-6 and TNF-α and higher TGF-β mRNA expression (both P values < 0.05) was detected in the IL-4 induction group than in the control group. Glycolytic stress test showed no significant difference in the extracellular acidification rate (ECAR) of mouse BMDM among the control group, IL-4 induction group and BMDM-PSC co-culture group (F = 124.4, P < 0.05), and a higher ECAR was seen in the BMDM-PSC co-culture group and a lower ECAR was found in the IL-4 induction group than in the control group (both P values < 0.05). Conclusions Treatment of E. multilocularis CF or PSC mainly causes polarization of BMDM into M2 macrophages, and phenotypic transformation of glucose metabolism into high-energy and high-glycolytic metabolism, and affects inflammatory responses in BMDM.