Efficacy and Adverse Reaction of Tislelizumab Combined with Chemotherapy on Urothelial Carcinoma / 肿瘤防治研究

Objective To evaluate the efficacy and safety of tislelizumab combined with chemotherapy in the treatment of urothelial carcinoma in the real word. Methods We enrolled 32 patients with urothelial carcinoma who were treated with tislelizumab and chemotherapy (gemcitabine/cisplatin or paclitaxel). The incidence of treatment-related adverse reactions during treatment and the efficacy evaluation were statistically analyzed. Results All patients were divided into two groups: 15 patients in the tislelizumab combined with paclitaxel group and 17 patients in the tislelizumab combined with GC group. Among 24 efficacy-evaluable patients, the ORR was 54.2% and the DCR was 83.3%. The ORR were 50.0% and 58.3%, and the DCR were 75.0% and 91.7% in the tislelizumab combined with paclitaxel group and the tislelizumab combined with GC group respectively. Common treatment-related adverse reactions included anemia (56.3%), loss of appetite (53.1%) and skin pruritus (50.0%). The grade 3-4 treatment-related adverse events occurred in 21.8% of patients. Common immune-related adverse reactions included skin toxicity (53.1%) and immune colitis (9.4%). Conclusion Tislelizumab combined with chemotherapy on urothelial cancer has significant curative effect, safety and controllability, but attention should be paid to immune-related adverse reactions.

Risk factors for bladder recurrence after radical resection of upper urothelial carcinoma / 中华泌尿外科杂志

Objective:To explore the risk factors of bladder recurrence in patients with upper urinary tract urothelial carcinoma (upper tract urothelial carcinoma, UTUC).Methods:We retrospectively analyzed the data of 815 patients underwent radical nephroureterectomy for upper tract urothelial carcinoma between June 2009 to June 2019.There were 519 males and 340 females, aged from 26-93 years old(average 66.5±9.6 years old). 396 patients were renal pelvic caicinoma.463 patients were ureteral caicinoma.675 patients were accompanied with hydronephrosis.664 patients were accompanied with preoperative gross hematuria. Preoperative diagnostic ureteroscopy was performed in 323 cases.283 patients had the history of smoking.48 patients were con-comitant with bladder carcinoma at the first diagnosis. Univariate analysis and logistic multivariate regression analysis were used to investigate the risk factors for bladder recurrence after UTUC radical surgery.Results:Among the 859 patients, 407 (47.4%) had low-stage tumor (T is/T a/T 1), 452 (52.6%) had high-stage tumor (T 2-T 4), 110 (12.8%) had low-stage tumor (G 1/G 2), and 749 (87.2%) had high-stage tumor (G 3). 126 (17.2%) of 859 patients had relapse during the follow-up period, the average follow-up time was 17 months, the median recurrence time was 12 months, 101(80.1%) of the relapse occurred within 2 years after operation. In univariate analysis, lower tumor stage ( P=0.047), higher tumor grade ( P=0.043), preoperative hematuria symptom ( P=0.023) and preoperative diagnostic ureteroscopy ( P=0.002) were closely related to bladder recurrence. Taking the above factors into the logistic multivariate regression analysis showed that tumor staging T is/T s/T 1 ( B=0.476, P=0.019), tumor grade G 3( B=0.848, P=0.024), preoperative hematuria symptom ( B=0.521, P=0.048), preoperative diagnostic ureteroscopy( B=0.521, P=0.002) were independent risk factors of postoperative recurrence of bladder. Conclusion:lower tumor stage, higher tumor grade, preoperative hematuria symptom and preoperative diagnostic ureteroscopy are the independent risk factors of postoperative bladder recurrence in patients with UTUC. Routine intravesical chemotherapy should be performed in patients with UTUC with the above risk factors, and routine diagnostic ureteroscopy is not recommended.

Effects of Aspirin, Nonsteroidal Anti-inflammatory Drugs, Statin, and COX2 Inhibitor on the Developments of Urological Malignancies: A Population-Based Study with 10-Year Follow-up Data in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to determine the impact of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), statin, and cyclooxygenase 2 (COX-2) inhibitor on the development of kidney, prostate, and urothelial cancers by analyzing the Korean National Health Insurance Service–National Sample Cohort (NHIS-NSC) database. MATERIALS AND METHODS: Among a representative sample cohort of 1,025,340 participants in NHIS-NSC database in 2002, we extracted data of 799,850 individuals who visited the hospital more than once, and finally included 321,122 individuals aged 40 and older. Following a 1-year washout period between 2002 and 2003, we analyzed 143,870 (male), 320,861 and 320,613 individuals for evaluating the risk of prostate cancer, kidney cancer and urothelial cancer developments, respectively, during 10-year follow-up periods between 2004 and 2013. The medication group consisted of patients prescribed these drugs more than 60% of the time in 2003. To adjustfor various parameters of the patients, a multivariate Cox regression model was adopted. RESULTS: During 10-year follow-up periods between 2004 and 2013, 9,627 (6.7%), 1,107 (0.4%), and 2,121 (0.7%) patients were diagnosed with prostate cancer, kidney cancer, and urothelial cancer, respectively. Notably, multivariate analyses revealed that NSAIDs significantly increased the risk of prostate cancer (hazard ratio [HR], 1.35). Also, it was found that aspirin (HR, 1.28) and statin (HR, 1.55) elevated the risk of kidney cancer. No drugs were associated with the risk of urothelial cancer. CONCLUSION: In sum, our study provides the valuable information for the impact of aspirin, NSAID, statin, and COX-2 inhibitor on the risk of prostate, kidney, and urothelial cancer development and its survival outcomes.

Progress in study of long non-coding RNA UCA1 in tumors / 医学研究生学报

Urothelial carcinoma associated 1 was initially discovered and confirmed that was specifically high expressed in bladder cancer.The aberrant expression of UCA1 was reported in various tumors,especially in tumors occurred in digestive system and urogenital system.Recently,more and more advances have indicated that UCA1-overexpressed in a larger number tumors to play oncongenic roles in tumor onset,progression,and metastasis.However,the molecular mechanism of UCA1 in cancer development,progression and metastasis remains to be further explored.In this review,we focus on structure and isoforms of UCA1,function and mechanism for UCA 1 tumor-promoting effect.We further discuss the potential clinical application of UCA1 as a promising diagnostic biomarker or therapeutic target for human tumors.

Evolution Of Classification Of Bladder (Urothelial) Cancer.

The classification of bladder tumors has undergone a change over the years but still has not achieved success in predicting the behavior. The correct cellular classification of a tumor helps initiate appropriate treatment. Recently functional, genomic and proteomic data have been of help in aiding prognosis and modifying the treatment in many cancers. However, this data is not routinely integrated into the classification, and treatment protocols in bladder carcinoma hinge on grade and depth of invasion. An in depth understanding of the implication of grade, stage, molecular features on survival is necessary to understand the behavior of the tumor. The classification of Urothelial cancer has undergone a lot of change in terminology over the past century but we have still not identified markers (both morphologic and molecular) for preventing recurrences. It is believed that the treatment protocols should be based on a combination of these and we still have to conduct large-scale follow-up studies to identify these parameters. We present here the changes in bladder cancer classifications over the past century and the implications thereof in this review.

Expression and Clinical Significance of PPARγ in Bladder Urothelial Cancer / 华中科技大学学报(医学版)

Objective To investigate the expression and clinical significance of peroxisome proliferator activated receptor γ(PPARγ)in bladder urothelial cancer tissues.Methods Parafflin‐embeded specimen of bladder urothelial cancer tissues from 50 cases and normal tissues near the bladder urothelial cancer from 5 cases were harvested from the Pathology Department of the Renmin Hospital of Wuhan University between 2006 and 2009.Those cases had complete pathological and clinical data.The ex‐pression of PPARγ was detected by immunohistochemical SP method.Quantitative analysis of the PPARγ was measured by high definition pathological graphics context report system (HPIAS‐1000).One‐way analysis of variance and SNK (q)tests were used to analyze the mean density and the positive area rate of the immunohistochemical results.All data were processed by SPSS 13.0.Results The expression of PPARγwas significantly higher in bladder urothelial cancer tissues than in para‐carcinoma tis‐sues(P<0.05).Correlation between expression of PPARγ with TNM stag of bladder urothelial cancer was as follows :Positive rate of PPARγin the tissues with primary tumor size ≥3 cm was 72.4% ,significantly higher than 33.3% in the tissues with tumor size <3 cm(P<0.05);positive rate of PPARγin the cases with lymph node metastasis was 72.7% ,significantly higher than 46.4% in the cases without lymph node metastasis(P<0.05);positive rate of PPARγin patients at stage T3‐4 group was 75.0% ,significantly higher than 41.9% and 45.5% in patients at clinical stage T1 and T2(P<0.05);positive rate of PPARγin patients with poor differentiation was 68.2% ,significantly higher than 42.9% in patients with high or middle differentiation group(P<0.05).Conclusion PPARγ plays an important regulating role in the onset and progress of bladder urothelial cancer ;PPARγexpression level was correlated with primary tumor size ,pathological types and differentiation degree ,lymph node me‐tastasis and clinical stage.This result suggested that PPARγ was closely correlated to metastasis of bladder urothelial cancer.

Expression of KAI1 in urothelial cancer tissues and its relationship with invasion and metastasis of urothelial cancer / 第二军医大学学报

Objective: To investigate the expression of KAI1 gene in the urothelial cancer tissues and its relationship with the invasion and metastasis of urothelial cancer. Methods: The expression of KAI1 mRNA was detected by real-time fluorescent quantitative(RFQ-PCR) in urothelial cancer tissues and normal mucosa of urinary tract. The KAI1 protein expression was detected by immunohistochemistry(IHC) method in bladder transitional cell carcinoma tissues and the paired normal mucosal tissues. Results: QRT-PCR showed that the average level of KAI1 mRNA in the urothelial cancer tissues was significantly lower than that in the normal bladder tissues (P<0.01); moreover, the increase of pathological grades and clinical stages and the development of lymphatic metastasis were associated with the decrease of KAI1 expression, with significant difference found between the different groups(P<0.05 or P<0.01). The protein expression of KAI1 in the urothelial cancer tissues was significantly lower than that in the normal bladder tissues(P<0.01). The protein expression of KAI1 was decreased with the increase of pathological grades (P<0.05 or P<0.01). We also found that higher expression of KAI1 was associated with superficial invasion (P<0.05) and the presence of lymphatic metastasis (P<0.05). Conclusion: The down-regulation of KAI1 gene is associated with differentiation, infiltration, and lymphatic metastasis of urothelial cancer, which might serve as an effective indicator for malignancy, metastasis and prognosis of urothelial cancer.

Clinical research on utility of fluorescence in situ hybridization assay in the diagnosis of urothelial cancer / 中国癌症杂志

Background and purpose: Urothelial cancer is the most common malignant neoplasm in the urinary system. Urine cytology is the standard morality to diagnose urothelial cancer. Although cytology has been shown to have a high specificity, the sensitivity is unacceptably low. The count of copies of chromosomes in interphase cells by fluorescence in situ hybridization (FISH) assays has been successfully used as a screening tool in genetic and cancer studies. In this study, we investigated the value of FISH assay for diagnosis of urothelial cancer. Methods:Voided urine samples from 100 patients with haematuria were analyzed by FISH and cytology; labeled probes for chromosomes 3, 7, 9 and 17 were used to assess chromosomal abnormalities. The gold standard was pathology diagnosis. The overall sensitivity and specificity of FISH were evaluated and compared with cytology. Results: The sensitivity of FISH and cytology in detection urothelial cancer were 74.7% and 46.0% respectively; the specificity was 92.3% and 100% respectively (different not significant). There was a significant difference between the sensitivity of FISH and cytology in detection. Conclusion. The FISH assay has a higher sensitivity than cytology and a similar specificity in the detection of urothelial cancer, and could be used as a new method for diagnosis of urothelial cancer.

Genetic Polymorphisms of \it{CYP2A6} and \it{CYP2E1} with Tobacco Smoking is not Associated with Risk of Urothelial Cancer

Objectives: To elucidate the association between genetic polymorphisms of CYP2A6 and CYP2E1 and urothelial cancer susceptibility. Methods: A total of 137 Japanese patients with urothelial cancer and 217 Japanese healthy controls, frequency-matched for age and gender, were selected. The polymorphisms of CYP2A6 and CYP2E1 were analyzed by PCR-RFLP, and cigarette smoking histories were obtained through interviews. Results: The frequency of CYP2A6 homozygote deletion genotype was 2.9% in the patients, compared with 3.2% in the controls (OR=0.84, 95% CI 0.24−2.96). The frequencies of CYP2E1 C1/c2 and C2/c2 were 27.7% and 4.4% in the patients, compared with 35.5% and 6.0% in the controls (OR=0.68, 95% CI 0.42 −1.09, OR=0.67, 95% CI 0.24−1.84, respectively). No statistically significant differences were observed when the CYP2A6 homozygote deletion genotype and the CYP2E1 genotypes were examined relative to smoking status. Conclusions: Our data indicate that neither a relationship between genetically impaired nitrosamine metabolism and tobacco-smoking consumption, nor urothelial cancer risk related to the CYP2A6 deletion genotype and CYP2E1 Rsa I genotype was found in Japanese population.

Genetic polymorphisms ofCYP2A6 andCYP2E1 with tobacco smoking is not associated with risk of urothelial cancer

<p><b>OBJECTIVES</b>To elucidate the association between genetic polymorphisms ofCYP2a6 andCYP2E1 and urothelial cancer susceptibility.</p><p><b>METHODS</b>A total of 137 Japanese patients with urothelial cancer and 217 Japanese healthy controls, frequency-matched for age and gender, were selected. The polymorphisms ofCYP2A6 andCYP2E1 were analyzed by PCR-RFLP, and cigarette smoking histories were obtained through interviews</p><p><b>RESULTS</b>The frequency ofCYP2A6 homozygote deletion genotype was 2.9% in the patients, compared with 3.2% in the controls (OR=0.84, 95% CI 0.24-2.96). The frequencies ofCYP2E1 C1/c2 andC2/c2 were 27.7% and 4.4% in the patients, compared with 35.5% and 6.0% in the controls (OR=0.68, 95% CI 0.42-1.09, OR=0.67, 95% CI 0.24-1.84, respectively). No statistically significant differences were observed when theCYP2A6 homozygote deletion genotype and theCYP2E1 genotypes were examined relative to smoking status.</p><p><b>CONCLUSIONS</b>Our data indicate that neither a relationship between genetically impaired nitrosamine metabolism and tobacco-smoking consumption, nor urothelial cancer risk related to theCYP2A6 deletion genotype andCYP2E1 Rsa I genotype was found in Japanese population.</p>

The Significance of Atypical Cell in Urinary Cytology / 대한비뇨기과학회지

PURPOSE: Atypical cells in urinary cytology are frequently observed in patients who have history of urothelial cancer A study was made to evaluate the significance of atypical cell in urinary cytology for the detection and surveillance of urothelial cancer. MATERIALS AND METHODS: We studied retrospectively 100 patients with atypical cell in urinary cytology. A bladder washing specimen was used for cytology Four groups of subjects were participated in this study. Group I - patients who showed gross hematuria, or lower urinary tract symptoms, but no history of the urothelial cancer. Group II - patients with urinary tract surgery for urothelial cancers. Group III - patients with intravesical therapy due to transitional cell carcinoma of the bladder. Group IV - patients with history of urothelial cancers, but no recurrence for l year or more. RESULTS: Mean follow up was 39 months. Cystoscopy and radiography showed urothelial cancer in 72 patients(72%) with atypical cytology. The bladder cancer was found in If of 27(63%) in group I, 26 of 26(100%) in group II, 4 of 5(80%) in group III and 13 of 14(93%) in group IV respectively. The interval from atypical cytology to the detection of urothelial cancer was 4 months. Upper tract tumors developed in 11 patients and prostatic urothelial recurrence in l patient. CONCLUSIONS: These data demonstrate the clinical importance of atypical cytology and emphasize the search for urothelial cancer. Patients with history of transitional cell carcinoma who showed atypical cells are likely to have a overt transitional cell carcinoma, and require further evaluation of intravesical and extravesical sites to detect the urothelial cancer.

The Role of nm23-H1 Gene in Urologic Cancer (II): Expression and Mutation of nm23-H1 Gene in Urothelial Cancer / 대한비뇨기과학회지

BACKGROUND AND PURPOSE: We had previously demonstrated by immunohistochemical study (IHS) that nm23-H1 gene may play an important role in disease prognosis as well as its participation in metastasis of urothelial cancer. The purpose of present study was 1) to reexamine the role of nm23-H1 gene in urothelial cancers at molecular level, 2) to identify the molecular mechanism of decreased immunoreactivity for nm23-H1 protein in metastatic urothelial cancers, and 3) to identify whether IHS is reliable in studying the expression of nm23-H1. MATERIALS AND METHODS: We studied expression level and mutation profiles of nm23-H1 gene in 25 fresh surgical specimens of urothelial cancer by reverse transcription polymerase chain reaction(RT-PCR)-Southern blotting analysis, and PCR of genomic DNA followed by single strand conformation polymorphism and sequencing analysis. The results of RT-PCR-Southern blotting were comparatively analyzed with those of IHS. RESULTS: mRNA transcript levels of nm23-H1 gene were significantly decreased in tumor tissues with metastasis as compared with those without metastasis. The transcript levels of nm23-H1 gene were also significantly decreased in metastatic tumor tissues as compared with primary tumor tissues. Point mutation of nm23-H1 gene was detected in only 1 of 13 urothelial cancer tissues with metastasis, whereas, mutation was observed in none of those without metastasis. The results of IHS corresponded with those of RT-PCR-Southern blotting analysis in 23 of 25 specimens. CONCLUSIONS: The nm23-H1 gene may play an important role in metastasis of urothelial cancer. Decreased transcription at mRNA level may be a major molecular mechanism of loss of immunoreactivity for nm23-H1 protein in urothelial cancer. IHS used in the present study may be a clinically useful method to study the expression of nm23-H1 and to predict metastasis potential and prognosis of urothelial cancers.

CLINICAL EVALUATION OF URINARY LEVEL OF NUCLEAR MATRIX PROTEIN 22(NMP22)IN DIAGNOSIS OF UROTHELIAL CANCER / 解放军医学杂志

To evaluate the clinical value of NMP22 for the diagnosis of urothelial cancer. Urinary NMP22 was determined with enzyme linked immunoaorbent assay (ELISA) in 50 patients in whom 24 patients were suffering from cancer of urothelium, and 20 cases of cancer of other origins, and 6 cases of artificial bladder after total cystectomy for cancer. The median NMP22 value of urothelial cancer was 37 49U/ml, which was significantly higher than those of other patients (4 33U/ml, P