Objective:To summarize the experience of Bacillus Calmette-Guerin(BCG) in the treatment of bladder cancer secondary to renal transplantation.Methods:The clinical data of 5 patients who underwent BCG bladder irrigation after secondary bladder cancer after kidney transplantation in Tianjin First Central Hospital from January 2015 to December 2019 were analyzed. There were 1 male and 4 female cases. During the period of immunosuppression after transplantation, 1 case developed secondary high-level non-muscular invasive bladder cancer (NMIBC), 3 cases developed secondary low-grade NMIBC, and 1 case developed secondary glandular cystitis (4 cases). The mean age of the 5 patients with secondary bladder cancer was 59.7±4.0 years. Case one with high level NMIBC was treated with transurethral resection of bladder tumor (TURBT) and postoperative irrigation of epirubicin. Case 3 and 5 with low-level NMIBC accepted regular postoperative irrigation of gemcitabine. No irrigative therapy was performed in case 2. Bladder cancer recurred in case 1, 2, 3 and 5 after 20.1±9.7 months. TURBT was observed in all the 4 patients, among which 3 were of high grade NMIBC and 1 was of low grade NMIBC. Four patients were irrigated with BCG 2 weeks after operation. Postoperative pathology indicated low-level NMIBC in case 4, and BCG was irrigated 2 weeks after the operation. During perfusion therapy, immunosuppressive agents were continued.Results:During BCG perfusion, 4 of the 5 cases showed BCG related local inflammation, among which 2 cases presented symptoms of bladder irritation, 1 case presented hematuria, and 1 case presented hematuria with low fever. Patients with frequent urination, pain in urine, hematuria and other symptoms improved after drinking plenty of water, taking bed rest and taking levofloxacin (0.5g/ day ×7 days). Patients with low fever were treated with antipyretic treatment. No antituberculous agents were used prophylactically during BCG perfusion. There were no symptoms of tuberculosis infection or sepsis. The function of transplantated kidney was normal and no tendency of rejection. The 5 patients were followed up for 7-24 months, 1 patient was lost to follow-up after 7 months of BCG bladder perfusion, and no tumor recurrence or metastasis was found in 5 patients during the follow-up.Conclusions:The use of immunosuppressive agents does not reduce the biological activity of BCG, and BCG does not increase the risk of systemic toxicity or affect the function of transplanted kidneys in immunocompromised patients. BCG is a treatment option for bladder cancer secondary to renal transplantation.

Nephron sparing surgery ( NSS ) has become the standard treatment of small renal cancer . NSS have the similar curative effect compared with radical nephrectomy and preserve the kidney fuction. However, positive surgical margins after NSS is increasing and has attracted more and more attention. We will discuss positive surgical margins related factors and how to reduce the positive surgical margins in this review.

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.

Objective: Systematic assessment of the effect of positive margin on recurrence and metastasis in patients with renal cell carcinoma who underwent partial nephrectomy. Methods: The literature were searched on the rate of recurrence and metastasis in patients with positive margin and partial nephrectomy published in PubMed, Embase, Cochrane, China Biomedical Literature Database, China Knowledge Network, VIP Chinese Science and Technology Journal Database, and Wanfang Chinese Database up to December 2018. The quality of the literature included in this study was evaluated by two reviewers, and a meta-analysis was performed on the literature that met the inclusion criteria using the Revman 5.0 statistical software provided by Cochrane Collaboration. Results: A total of seven articles were included, six of which were case-control studies, and the other one was a cohort study. These seven articles consisted of 6 928 patients, including 407 positive margins and 6 521 negative margins. For recurrence and metastasis, 407 positive margins were composed of 25 recurrences and 21 distant metastases, while 6 521 negative margins consisted of 68 recurrence and 96 distant metastasis. The disease-free survival rate of patients with positive margins is lower than that with negative margins (OR=4.92, 95%CI 2.66-9.08, P<0.001). The results of subgroup analysis of patients with recurrence and metastasis based on positive margin exhibited that positive margin increased the risk of recurrence in patients undergoing partial nephrectomy (OR=5.05, 95%CI 2.06-12.37, P<0.001), as well as the risk of metastasis (OR=3.70, 95%CI 2.18-6.26, P<0.001). Since different studies consisted of patients with different tumor staging, a stratified analysis was conducted and the disease-free survival rate of patients with positive margins decreased compared with that of negative margins (OR=4.13, 95%CI 2.54-6.70, P<0.001), although there were differences in the staging of tumor patients included in different studies, which did not weaken the results. Conclusions Positive margins increase the risk of recurrence and metastasis in patients undergoing partial nephrectomy.

Objective To explore the potential role of BK virus (BKV) in urothelial carcinoma after renal transplantation .Methods From May 2013 to March 2017 , We collected 26 cases of urothelial carcinoma after renal transplantation (study group) and 30 cases of urothelial carcinoma of non-immunosuppressed patients (control group) .Tumor tissues were stained with SV40 T antigen by immunohistochemical assay .Urinary and peripheral blood samples were assayed for BKV-DNA levels by real-time fluorescent quantitative polymerase chain reaction (PCR) .Results There were 7 positive cases of SV40 T-Ag in study group and only 1 weakly positive case in control group .The positive rate of BKV-DNA was 38 .5％ in urinary samples in study group (10 /26 ) and it was significantly higher than that in control group by 10％ (3/30)(P< 0 .05) .And the positive rate of blood BKV-DNA was not different between two groups ( P > 0 .05 ) .Conclusions There is a relatively high prevalence of BKV infection in urothelial carcinoma after renal transplantation .And a ,high level of BKV infection may play a role in urothelial carcinoma after renal transplantation .

Objective To investigate the expression of human leucocyte antigen G (HLA-G) in urothelial carcinoma after renal transplantation,and to analyse the relationship between HLA-G expression and the various clinical and pathological parameters.Methods 29 patients with urothelium carcinoma after renal transplantation for the first time from January 2005 to June 2016 were selected as the experimental group,the age range was 32-70 years,with an average of (55.5 ± 8.1) years.29 non-transplanted patients with urothelial carcinoma as the control group 1,the age range was 36-74 years,with an average of (57.9 ± 8.2) years.15 cases of normal urinary tract epithelial were from cystoscopy biopsy as the control group 2.Immunohistochemical method was used to detect the difference of HLA-G expression between the three groups.The clinical and pathological data of patients with urothelial carcinoma after renal transplantation were analyzed.Results The expression rate of HLA-G was 79.3％ (23/32) in patients with urothelial carcinoma after renal transplantation,37.9％ (11/32) in non-transplanted group and 0 (0/15) in normal urinary tract epithelium group.The expression rate of HLA-G in non-transplanted group was significantly higher than that in normal urinary tract epithelium group (P ＜ 0.05).The expression rate of HLA-G in patients with urothelial carcinoma after renal transplantation was significantly higher than that in nontransplanted group and normal urinary tract epithelium group (P ＜ 0.05).Conclusions HLA-G is associated with the occurrence of urothelial carcinoma after renal transplantation.It may provide a new idea for the prevention and treatment of urinary tract epithelium after renal transplantation.

Objective To explore the clinical characteristic,treatment,and prognosis of urological de novo malignant tumor in kidney transplant recipients.Methods A retrospective analysis was performed on 11 patients with urothelial carcinoma admitted in our institute between 2008 and 2016.Three patients were male and 8 patients were female.The interval between tumorigenesis and transplantation ranged from 12 to 132 months with a mean time of 68.4 months.Of the 11 cases,5 had pelvic TCC,4 cases had ureter TCC,and the rest 2 cases had pelvic and ureter TCC.All patients were in the same side of transplanted kidney (right).Of the 11 cases,7 had a main clinical manifestation of gross hematuria,3 cases had abdomen pain of the right side,and 1 case had hydronephosis of the right side during physical examination.Surgical treatment was taken in all 11 cases,combined with chemotherapy and irnmunotherapy (decreased immunosuppressive agents)treatment.Results Surgical treatment in all 11 cases was successful,and the postoperative pathology results confirmed the diagnosis of urothelial carcinoma.One patient receiving palliative treatment died 4 months after diagnosis.One patient died of extensive metastatic disease at 36th month postoperatively,and one patient died of respiratory failure.The rest 8 cases were followed for 4-96 months.One patient was given sirolimus (SRL) but diarrhea,so cyclosporine A (CsA) was administered.The renal function in the remaining 8 patients was normal.Conclusion Laparoscopic surgery combined with middle and small incision in the treatment of autologous ipsilateral urothelial carcinoma after renal transplantation is safe and effective.

Objective To establish acute hepatotoxic model induced by Amanita exitialis and to study the characteristics of acute toxic liver failure induced by mushrooms containing peptide toxins,in hope for providing some help to experimental research on poisoning induced by mushrooms containing peptide toxins.Methods UPLC-MS/MS (Ultra performance liquid chromatography-tandem mass spectrometry) method was used to detect peptide toxins in Amanita exitialis.To establish acute toxic liver hepatic failure model,the beagles were fed with 60 mg/kg of lyophilized powder of Amanita exitialis fungus which encapsulated in starch capsules.Toxic sighs were observed,coagulation function,hepatic and renal function,liver histopathological morphology,peptide toxin concentration in plasma and urine were detected during the experiment.Results Total peptide toxins in Amanita exitialis was (3 482.6 ± 124.94) mg/ kg.All the beagles had toxic signs including vomiting and diarrhea in 12-48 h after ingestion.On 24 h after ingestion,the beagles' ALT,AST,TBIL,ALP,PT and APTT levels increased obviously.On 36 h after ingestion,the beagles' ALT,AST,PT and APTT values reached their peaks (ALT:283.2 ± 112.9 Kallmann unit;AST:223.9 ±93.8 Kallmann units;PT:132.9 ± 152.6 s;APTT:131.4 ± 153.9 s).On 48 h after ingestion,the beagles' TBIL and ALP levels reached their peaks (TBIL:23.3 ± 14.6 mol/L;ALP:274.5 ± 115.5 U/L).The beagles' TBIL,TP and APTT returned to normal 1 week after ingestion,their ALT,AST and ALP levels returned to normal 3 weeks after ingestion.Three dogs died during 24-72 h after ingestion.Liver histopathological morphology study showed hemorrhagic necrosis of hepatocytes.Peptide toxins can be detected in plasma within 24 h after ingestion.Peptide toxins can be detected in urine within 96 h after ingestion.Conclusion Amanita peptide toxins can cause hemorrhagic necrosis of liver cells and lead to acute liver failure.This model is consistent with clinical pathophysiological process of acute toxic liver failure induced by mushrooms containing peptide toxins,and it can be applied to the study of diagnosis and treatment of poisoning induced by mushrooms containing peptide toxins.

DEK protein is an abundant chromatin protein in metazoans with highly conserved nuclear factor. This protein is a unique member of its family and is preferentially expressed in actively proliferating and malignant cells. Recently, much attention has been paid to the role of DEK protein in the development of various cancers, which was originally discovered in a subset of acute my-elogenous leukemia. Oncogene DEK is overexpressed in several malignancies including hepatocellular carcinoma, glioblastoma, retino-blastoma, bladder cancer, malignant melanoma, and cervical cancer. Oncogene DEK is a chromatin remodeling protein that supports cancer cell proliferation and invasion. In this review, we summarized research advancements in the correlation between DEK protein and oncogenesis.

Objective To evaluate the therapeutic effect and toxicities of low dose Gemcitabine combined with Oxaliplatin in the treatment of advanced or metastatic uroedthelial carcinoma.Methods A total of 42 patients pathologically confirmed advanced or metastatic urothelial carcinoma (23 bladder cancer cases,11 ureteral carcinoma cases,and 8 renal pelvic carcinoma cases) were reviewed.Karnofsky score for each patient before treatment was more than 60.Combined treatment with Gemcitabine and Oxaliplatin regimen was as follows:Gemcitabine 700 mg/m2,iv infusion at day 1,8 and day 15,Oxaliplatin 100 mg/m2,iv infusion at day 2.The regimen was administered for more than 2 cycles (every 4 weeks) and the response rate was evaluated.The regimen was used in palliative chemotherapy and adjuvant chemotherapy,respectively.Results According to WHO evaluation criteria on therapeutic effectiveness,7 patients (16.7％) had complete response,13 patients (30.9％) had partial response,14 cases (33.3％) remained stable status,and 8 cases (19.1％) had progression.The overall response rate was 47.6％.The main side effects included thrombocytopenia,leucopenia,nausea,vomiting and alopecia,which were mild to moderate and disappeared when the chemotherapy was ceased.No chemotherapy related death occurred.Conclusions Combined treatment with low dose Gemcitabine and Oxaliplatin is effective for advanced or metastatic urothelial carcinoma,with mild and tolerable toxicities.