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Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.
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Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.
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Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.
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OBJECTIVE To establish an modified model of osteonecrosis in the rat and observe the clinical, pathological and imaging manifestations dynamically. METHODS Healthy male SD rats were divided into 5 groups randomly, including the control group (N, 8 rats), and radiation groups (a, b, c and d, 6 rats each group). For radiation groups, the left mandible of each rat was irradiated at doses of 7.0 Gy for 5 fractions, other rats were sham irradiated, serving as control groups.7 days after irradiation, the left mandibular molars of all rats were extracted. The radiation groups rats were sacrificed at 7, 14, 21, 28 days after irradiation randomly, the 2 rats in control group were sacrificed respectively. All the rats' mandibles were taken and examined by clinical manifestation and Micro-CT and histology methods. The data was analyzed with SPSS 18.0 software package. RESULTS In clinical observation, ulcers were seen in the irradiated site at the 7th day, after then, alopecia, occlusion disorder, and pus discharged from buccal side were seen. Weight loss rightly after radiation and weight gain were seen at the 14th day. In pathological observation, marrow cavity changed first. Many adipose cell was first seen at the 7th day, and inflammations, necrosis, and fibrosis were found in medulla in the irradiated groups after that. Significant increment of empty lacunae and decrement of osteocytes were observed in all irradiated groups at the 7th day. Necrotic bone of the irradiated mandible was only found at the 28th day. Lack of new bone formation within the socket was seen in the Micro-CT three-dimensional at 28th day, and there are no more changes at the early-stage in this model. CONCLUSION An modified rat model of osteoradionecrosis was successfully established, which can shorten experimental period, and this model early stage and deserved to be further researched. Can be used to observe clinical, pathological and imaging magnification, which play a basic role in the protection in early stage and deserved to be further researched.
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Objective To discuss the efficacy of intravesical instillation of sodium hyaluronate for the treatment of cystitis glandularis after transurethral resection.Methods 85 patients (9 male and 76 female,age range 37-70 years,mean age 51) who were diagnosed as CG in China-Japan Union Hospital of Jilin University underwent transurethral resection.After the operation they were divided into three groups randomly according to different intravescal instillation:sodium hyaluronate for group A,epirubicin for group B and no medicine for group C.The group A started to instill with sodium hyaluronate 40mg once a week for four weeks,and then once a month for four months.The group B did the same way of intravesical instillation of epirubicin.All the patients were followed-up for 12 months.The cystoscopy was done every three months to detect recurrence and the clinical symptom score was evaluated at 1,3,6 and 12 months.Results No patients in group A treated by sodium hyaluronate relapsed but 6 cases and 9 cases in group B and group C respectively.Recurrence rate of group A is significant low compared with group B and C (P ＜ 0.05).The scores of clinical symptom score appendix after 1,3,6 and 12 months for group A were (3.18 ± 1.44),(1.29 ±0.66),(1.25 ±0.65) and (1.21 ±0.63),respectively.It was (3.37 ±1.62),(3.33 ±1.59),(1.37±0.74) and (1.30±0.61) for group B,and (3.47±1.81),(3.40±1.52),(3.27±1.41) and (3.23 ± 1.19) for group C.Compare the score of clinical symptom in the same group,there were significant differences for the score after 3 months compare with the score after 1 month in group A (P ＜ 0.05).But in group B,the significant differences showed after 6 months (P ＜ 0.05).There was no significant difference in group C (P ＞ 0.05) in the whole year.Conclusions Intravesical sodium hyaluronate therapy can effectively decline the recurrence rate of cystitis glandularis after transurethral resection.It could also significantly improve the urinary tract symptoms.
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Objective To evaluate the efficacy and safety of solifenacin in patients with overactive bladder (OAB). Methods A multicenter clinical trial was conduced. 216 patients with OAB were enrolled. All the patients received solifenacin(5 mg once daily). With 5 weeks'treatment, all the patients recorded the diary and the adverse events as well. The symptoms of urgency, frequency, nocturia, urine volume, incontinence were evaluated. The results of the efficacy and safety were analyzed by using SPSS 13. 0. Results After 5 week treatments, all the index obviously improved(P<0.05). 187 cases (86.7%)were cured and 43 cases recovered normal voiding, 29 cases improved obviously. 11cases(5.0 %)reported adverse effect as dry mouth, dry eye. Conclusion Solifenacin could be the safe and effective drug in the treatment of OAB patients.
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Objective:To study the levels of TNF ? in serum and in urine and IL 6 in serum of renal allograft recipients with acute rejection, infection and CsA induced nephrotoxicity.Methods:The sequential monitoring of TNF ? and IL 6 was conducted by ELISA technique in 106 patients before and after renal transplantation.Results:The levels of IL 6 and TNF ? increased in the first day posttransplant, decreased and stabilized after 1 to 2 weeks, and increased 1 to 3 days prior to the clinical diagnosis in acute rejection, then decreased with effective treatment. IL 6 and TNF ? increased in serum in infection and had no difference in urine. TNF ? in serum and in urine and IL 6 in serum had no significant difference in CsA induced nephrotoxicity.Conclusion:It suggests that the sequential monitoring of IL 6 and TNF ? of renal allograft recipients can be used to estimate the function of graft, as markers of the early diagnosis of acute rejection.