1.Expert consensus of multi-disciplinary collaboration on bladder-preserving treatment for bladder cancer in China.
Chinese Journal of Oncology 2022;44(3):209-218
Objective: Bladder cancer is one of the most common malignant tumors in urology. Urothelial carcinoma accounts for about 90% of all bladder malignancies. According to whether the tumor invades the bladder muscle, it can be divided into non-muscle invasive bladder cancer and muscle invasive bladder cancer. Radical cystectomy is the standard treatment for muscle invasive bladder cancer patients and high-risk non-muscle invasive bladder cancer patients who have failed Bacillus Calmette-Guerin treatment. Due to the comorbidity of bladder cancer and the potential deterioration of the quality of life after surgery, many patients were not suitable or refused for radical cystectomy. Therefore, it is vital to find a bladder-preserving treatment that can achieve cure other than radical cystectomy. Bladder-preserving therapy that balances tumor control and quality of life serves as an alternative and supplement to radical cystectomy. This consensus is based on contemporary evidence-based medicine, combined with the native clinical practice of bladder preservation in a multidisciplinary treatment manner. To some extent, this consensus serves as a guidance for bladder-preservation therapy of bladder cancer in China. Several issues are extensively discussed here, including organizational structure and workflow of multidisciplinary treatment, the selection of patients for bladder-preserving therapy, treatment options and regimens, follow-up, as well as regimen choices of recurrence after bladder-preserving therapy.
Carcinoma, Transitional Cell/surgery*
;
Combined Modality Therapy
;
Consensus
;
Humans
;
Neoplasm Invasiveness/pathology*
;
Quality of Life
;
Urinary Bladder/surgery*
;
Urinary Bladder Neoplasms/surgery*
2.Correlation between adipokine and clinicopathological features and prognosis in upper tract urothelial carcinoma.
Xiang DAI ; Fei WANG ; Yi Qing DU ; Yu Xuan SONG ; Tao XU
Journal of Peking University(Health Sciences) 2022;54(4):605-614
OBJECTIVE:
To investigate the correlation between expression levels of adipokine and clinicopathological features and prognosis of patients with upper tract urothelial carcinoma (UTUC) based on immunohistochemical staining and bioinformatics analysis.
METHODS:
The 8 adipokines in this study included adiponectin (AdipoQ), leptin (LEP), interleukin (IL)-6, IL-10 and their receptors (AdipoR1, AdipoR2, LEPR, IL-6R, IL-10RA, IL-10RB). Tissue samples of patients with UTUC who underwent surgical treatment in Peking University People's Hospital from January 2014 to April 2021 were selected for immunohistochemical staining. Their quantitative gene expression data were calculated by H-Score, and relevant clinical and follow-up data were collected retrospectively. Transcription group sequencing data of UTUC patients in Gene Expression Omnibus database (GSE134292 dataset) were downloaded for comparison. Chi-square test or t-test was used to compare the expression level of adipokine between non-muscle invasive group and muscle invasive group. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival curve were utilized to analyze independent predictors of overall survival (OS), disease-free survival (DFS), intravesical recurrence-free survival (IVRFS) in the both cohorts. The P < 0.05 was considered statistically significant.
RESULTS:
In the study, 63 tissue samples of the patients with UTUC who underwent surgical treatment in Peking University People's Hospital and 57 UTUC patients in GSE134292 dataset were selected. In immunohistochemical cohort, the expressions of AdipoQ (P=0.003 6), AdipoR1 (P=0.006 5), LEP (P=0.007 7), IL-10 (P=0.006 9), and IL-10RA (P=0.008 9) were statistically higher in muscle invasive group. In GSE134292 cohort, the expressions of AdipoR1 (P=0.000 4), AdipoR2 (P=0.000 4), IL-6 (P=0.005 0), IL-10 (P=0.001 7), and IL-10RA (P=0.008 1) were statistically higher in muscle invasive group. Kaplan-Meier survival curve and multivariate Cox regression analysis showed that high IL-10RA expression was an independent predictive factor of IVRFS (P=0.044, HR=0.996, 95%CI: 0.992-0.998) in immunohistochemical cohort, which was confirmed in GSE134292 cohort (P=0.014, HR=0.515, 95%CI: 0.304-0.873).
CONCLUSION
The expression levels of AdipoQ, AdipoR1, IL-10, and IL-10RA were correlated with tumor stage, suggesting that these adipokines played important roles in tumor progression. IL-10RA was an independent predictor of IVRFS, suggesting that IL-10 and its receptor played a critical role in tumor recurrence.
Adipokines
;
Carcinoma, Transitional Cell/surgery*
;
Humans
;
Interleukin-10
;
Neoplasm Recurrence, Local
;
Prognosis
;
Retrospective Studies
;
Urinary Bladder Neoplasms/surgery*
;
Urologic Neoplasms/pathology*
3.Correlation between daily fluid intake behavioral habits and pathological characteristics of upper tract urothelial carcinoma.
Zhi Hua LI ; Chun Ru XU ; Ying LIU ; Hua GUAN ; Meng ZHANG ; Xin Yan CHE ; Qi TANG ; Yan Bo HUANG ; Xue Song LI ; Li Qun HOU
Journal of Peking University(Health Sciences) 2022;54(4):621-627
OBJECTIVE:
To investigate the correlation between drinking habits and pathological characteristics of patients with upper tract urothelial carcinoma (UTUC).
METHODS:
A preoperative questionnaire survey was conducted to understand the drinking habits of UTUC patients who were admitted to the Department of Urology, Peking University First Hospital for radical nephroureterectomy within one year from August 2020 to July 2021, and statistical analysis was performed in combination with their postoperative pathological characteristics. The statistical procedure was performed using SPSS 22.0 software, and firstly, the preliminary analysis was performed one by one using the columnar χ2 test on the pathological characteristics of UTUC tumors as the dependent variable and the factors related to patients' general information, past history and drinking habits as the independent variables, and the independent variables that met P < 0.2 between the case and control groups for each dependent variable were specified for screening. The screened variables were included in the binary Logistic regression analysis. A difference of P < 0.05 was used to indicate a statistically significant difference.
RESULTS:
A total of 239 patients, 134 males and 105 females, with a mean age of (68.1±9.98)years and a median disease duration of 4.8 months, were included in this study. Multifactorial Logistic regression results suggested that after adjusting for the effects of other variables, UTUC patients who had the habit of drinking at least once every hour during the daytime had a significantly increased risk of high grade (G3) tumors(OR=1.941, 95%CI: 0.352-1.029, P < 0.01); these patients also had a significantly decreased risk of multifocal UTUC tumors (OR=0.344, 95% CI: 1.18-5.582, P=0.004). The patients who had the habit of drinking over 100 mL water each time had a significantly decreased risk of mutifocal UTUC incidence (OR=0.477, 95%CI: 0.225-1.012, P=0.046). Patients who pay attention to daily water intakes had a significantly increased risk of renipelvic carcinoma (OR=2.530, 95%CI: 1.434-4.463, P=0.001) and a significantly decreased risk of ureteral carcinoma (OR=0.314, 95%CI: 0.172-0.573, P < 0.01). Other variables included in the regression model did not differ significantly in their effects on the occurrence of tumor pathological characteristics.
CONCLUSION
Having the awareness of drinking water every 1 h during the day, drinking over 100 mL water each time, having the awareness of daily drinking habits correlated significantly with pathological characteristics of UTUC such as the presence of G3 tumor, multifocal tumors and location of the tumor. This conclusion still needs to be verified by subsequent trials with higher levels of evidence.
Carcinoma, Transitional Cell/surgery*
;
Female
;
Habits
;
Humans
;
Male
;
Neoplasm Recurrence, Local/epidemiology*
;
Retrospective Studies
;
Ureteral Neoplasms/surgery*
;
Urinary Bladder Neoplasms/surgery*
;
Water
4.Clinical application of the needle electrode in transurethral plasmakinetic resection of bladder tumor around ureteral orifice: A report of 16 cases.
Tian WANG ; Xin HONG ; Xiao Feng WANG
Journal of Peking University(Health Sciences) 2020;52(4):632-636
OBJECTIVE:
To explore the clinical application value of using needle electrode in transurethral plasmakinetic resection of bladder tumor around ureteral orifice.
METHODS:
Retrospective analysis was performed on the clinical data of 16 cases who had bladder tumors around ureteral orifice and underwent transurethral resection using plasmakinetic needle electrode in Department of Urology, Peking University International Hospital from June 2015 to December 2019. There were nine cases with the tumor of one to two centimeters from the ureteral orifice. The rest of the seven cases had tumor that was within one centimeter from the ureteral orifice, including two cases whose ureteral orifice was invaded by the tumor. All the patients studied were diagnosed before surgery and contraindications were excluded. The plasmakinetic needle electrode was used to treat the tumor with en bloc resection, and all the excised tissue was sent for pathological examination. Intravesical chemotherapy and postoperative follow-ups were performed. Statistical analysis was performed on the operation time, the incidence of obturator nerve reflex, the peri-operative bleeding, the parameters of indwelling ureteral catheter or double-J stent, the incidence of postoperative hydronephrosis, the clinical stage of tumor, and the recurrence rate.
RESULTS:
The operation was successfully completed for all the sixteen cases. The operation time was 16 to 57 minutes, with an average of (32.6±11.8) minutes. No obvious obturator nerve reflex and perioperative bleeding occurred in all the patients. Ureteral catheters were indwelled prior to the operation of tumor resection in seven cases. Four of the seven cases had the ureteral catheters remained while the rest three were replaced by double-J stent after surgery. Postoperative pathological analysis showed that all the tumors were urothelial carcinoma, including 9 cases of low grade and 7 cases of high grade. Pathological staging: 10 cases were in Ta stage, 5 cases in T1 stage, and 1 case in T2a stage. All tumor bases and lateral margins were negative. All the patients received 3-56 months, with an average of (26.0±18.1) months of follow-up. There was no case of upper urinary tract hydronephrosis or tumor recurrence.
CONCLUSION
The transurethral plasmakinetic resection of bladder tumor using needle electrode can realize en bloc tumor resection without obturator nerve reflex and reduce the risk of ureteral orifice injury. It is a safe and effective surgical method for treating bladder tumors around the ureteral orifice.
Carcinoma, Transitional Cell
;
Electrodes
;
Humans
;
Neoplasm Recurrence, Local
;
Retrospective Studies
;
Urinary Bladder Neoplasms/surgery*
5.Pretreatment elevated fibrinogen level predicts worse oncologic outcomes in upper tract urothelial carcinoma.
Hang XU ; Jian-Zhong AI ; Ping TAN ; Tian-Hai LIN ; Xi JIN ; Li-Na GONG ; Hao-Ran LEI ; Lu YANG ; Qiang WEI
Asian Journal of Andrology 2020;22(2):177-183
This study aimed to further validate the prognostic role of fibrinogen in upper tract urothelial carcinoma (UTUC) in a large Chinese cohort. A total of 703 patients who underwent radical nephroureterectomy were retrospectively identified. Fibrinogen levels of ≥4.025 g l-1 were defined as elevated. Logistic regression analysis was performed to determine the association between fibrinogen and adverse pathological features. Kaplan-Meier analysis and Cox regression models were used to assess the associations of fibrinogen with cancer-specific survival (CSS), disease recurrence-free survival (RFS), and overall survival (OS). Harrell c-index and decision curve analysis were used to assess the clinical utility of multivariate models. The median follow-up duration was 42 (range: 1-168) months. Logistic regression analysis revealed that elevated fibrinogen was associated with higher tumor stage and grade, lymph node involvement, lymphovascular invasion, sessile carcinoma, concomitant variant histology, and positive surgical margins (all P < 0.05). Multivariate Cox regression analysis demonstrated that elevated fibrinogen was independently associated with decreased CSS (hazard ratio [HR]: 2.33; P < 0.001), RFS (HR: 2.09; P < 0.001), and OS (HR: 2.09; P < 0.001). The predictive accuracies of the multivariate models were improved by 3.2%, 2.0%, and 2.8% for CSS, RFS, and OS, respectively, when fibrinogen was added. Decision curve analysis showed an added benefit for CSS prediction when fibrinogen was added to the model. Preoperative fibrinogen may be a strong independent predictor of worse oncologic outcomes in UTUC; therefore, it may be valuable to apply this marker to the current risk stratification in UTUC.
Aged
;
Biomarkers, Tumor
;
Carcinoma, Transitional Cell/surgery*
;
China
;
Disease-Free Survival
;
Female
;
Fibrinogen/analysis*
;
Humans
;
Male
;
Middle Aged
;
Nephroureterectomy
;
Prognosis
;
Retrospective Studies
;
Survival Rate
;
Urologic Neoplasms/surgery*
6.Evaluating the impact of preoperative anemia on the prognosis of upper tract urothelial carcinoma following radical nephroureterectomy: A single-center retrospective study of 686 patients.
Bao GUAN ; Mai WENG ; Hang FAN ; Ding PENG ; Dong FANG ; Geng Yan XIONG ; Xue Song LI ; Li Qun ZHOU
Journal of Peking University(Health Sciences) 2019;51(6):1056-1061
OBJECTIVE:
To identify the effect of preoperative anemia on the prognosis of patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy.
METHODS:
Clinicopathological and prognosis data on 686 patients with UTUC who underwent RNU at Peking University First Hospital between January 2000 and December 2013 were retrospectively analyzed. Preoperative anemia was defined as hemoglobin <130 g/L in men and <120 g/L in women based on the World Health Organization classification. The Kaplan-Meier method with log-rank test was applied to estimate the effect of anemia on survival. The associations of clinicopathologic features with overall survival and cancer-specific survival were evaluated using univariate and multivariate Cox regression models.
RESULTS:
There were 303(44.2%, 303/686) male and 383(55.8%, 383/686) female patients, and the median age was 68 years (interquartile range: 60-74 years). In all, 320 (46.6%, 320/686) patients were anemic before surgery. The median follow-up duration was 47 months. In all, 160 (23.3%) patients died, 141 (20.6%) died of cancer and 19 (2.7%) died of other disease or accidents. Preoperative anemia was associated with gender (P=0.002), age (P<0.001), lymph node positive (P=0.026), increased tumor grade (P=0.018), concomitant carcinoma in situ (P=0.038), tumor necrosis (P=0.007) and poor renal function (P<0.001). In univariate analysis, overall mortality was correlated with pre-operative anemia (P<0.001), gender (P=0.009), hydronephrosis (P=0.024), tumor stage (P<0.001), lymph node positive (P<0.001), tumor grade (P<0.001), tumor architecture(P<0.001), sarcomatoid differentiation (P=0.013), history of ureteroscope (P=0.033) and tumor hemorrhage (P<0.001); cancer-specific mortality was correlated with preoperative anemia (P=0.001), gender (P=0.001), hydronephrosis (P=0.043), tumor stage (P<0.001), lymph node positive (P<0.001), tumor grade (P<0.001), tumor architecture (P<0.001), sarcomatoid differentiation (P=0.016), history of ureteroscope (P=0.028) and tumor hemorrhage (P=0.003). A multivariate Cox proportional hazards model indicated that preoperative anemia was an independent prognositic predictor for overall mortality (P<0.001, HR=1.861) and cancer-specific mortality (P=0.003, HR=1.688).
CONCLUSION
The preoperative anemia is an independent risk factor for cancer-specific survival and overall survival. Hemoglobin levels should be considered during patient counseling and in decision-making for further therapy.
Aged
;
Anemia
;
Carcinoma, Transitional Cell/surgery*
;
Female
;
Humans
;
Male
;
Middle Aged
;
Nephrectomy
;
Nephroureterectomy
;
Prognosis
;
Retrospective Studies
;
Urologic Neoplasms/surgery*
7.The preoperative serum cystatin-C as an independent prognostic factor for survival in upper tract urothelial carcinoma.
Ping TAN ; Ming SHI ; Jie CHEN ; Hang XU ; Nan XIE ; Huan XU ; Yong JIANG ; Jian-Zhong AI ; Liang-Ren LIU ; Lu YANG ; Qiang WEI
Asian Journal of Andrology 2019;21(2):163-169
Cystatin-C (Cys-C) has been reported as a valuable prognostic biomarker in various malignancies. However, its effect on upper tract urothelial carcinoma (UTUC) patients has not been investigated before. Thus, to explore the impact of Cys-C on survival outcomes in patients undergoing radical nephroureterectomy (RNU), a total of 538 patients with UTUC who underwent RNU between 2005 and 2014 in our center (West China Hospital, Chengdu, China) were included in this study. Kaplan-Meier method and Cox regression analyses were performed to assess the relationship between Cys-C and survival outcomes using SPSS version 22.0. The cutoff value of Cys-C was set as 1.4 mg l-1 using the receiver operating characteristic (ROC) curves and Youden index. The mean age of patients included was 66.1 ± 11.1 years, and the median follow-up duration was 38 (interquartile range: 19-56) months. Overall, 162 (30.1%) patients had elevated Cys-C, and they were much older and had worse renal function than those with Cys-C <1.4 mg l-1 (both P < 0.001). Meanwhile, Kaplan-Meier analysis revealed that the group with elevated Cys-C had worse cancer-specific survival (CSS, P = 0.001), disease recurrence-free survival (RFS, P = 0.003), and overall survival (OS, P < 0.001). Multivariable Cox analysis suggested that the elevated Cys-C was identified as an independent prognostic predictor of CSS (hazard ratio [HR]: 1.997, 95% confidential interval [CI]: 1.331-2.996), RFS (HR: 1.429, 95% CI: 1.009-2.023), and OS (HR: 1.989, 95% CI: 1.366-2.896). In conclusion, our result revealed that the elevated preoperative serum Cys-C was significantly associated with worse outcomes in UTUC patients undergoing RNU.
Age Factors
;
Aged
;
Biomarkers, Tumor/blood*
;
Carcinoma, Transitional Cell/surgery*
;
China
;
Cystatin C/blood*
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Female
;
Humans
;
Male
;
Middle Aged
;
Preoperative Period
;
Prognosis
;
Retrospective Studies
;
Survival Rate
;
Urologic Neoplasms/surgery*
8.Retrospective study of young bladder urothelial carcinoma from a single center within 16 years.
Xing Guo TANG ; Ye YAN ; Min QIU ; Jian LU ; Min LU ; Xiao Fei HOU ; Yi HUANG ; Lu Lin MA
Journal of Peking University(Health Sciences) 2018;50(4):630-633
OBJECTIVE:
To evaluate the clinical and pathological features, treatment and prognosis for bladder urothelial carcinoma in relative young patients under 40 years.
METHODS:
A retrospective study involved a total of 43 consecutive patients of bladder urothelial carcinoma, which were under 40 years old from January 2001 to December 2016.
RESULTS:
The incidence rate of bladder urothelial carcinoma in the patients under 40 years was 2.2%, and 35 males and 8 females were included. The average age was 33 years (ranging from 23 to 40 years). At initial visit, 62.8% of the patients presented with painless gross hematuria, 9 patients were discovered by routine examination, and 7 patients experienced lower urinary tract symptoms. Solitary tumor occurred in 34 cases whereas multiple carcinomas had been discovered in 9 cases,and all the 9 multiple cases were from 31-40-year-old subgroups. All the patients received proper surgical intervention according to their own clinical stages. Post-operative pathological results showed 29 low-grade urothelial carcinoma and 14 high-grade cases which included 31 Ta cases, with 7 cases of T1, 1 case of T3, and 3 cases of T4 and one case of T1 plus Tis. The total follow-up was from 5 to 165 months, 3 cases were lost. The overall recurrence rate was 12.5% (5 cases from 40). One patient developed distal metastasis, one died of metastasis after 13 months, and the other three received secondary trans-urethral resection of bladder tumors. The average recurrence time was 39 months (ranging from 3 to 105 months). The progression rate was 5% among all the followed-up patients (2 cases from 40). The recurrence rate in multiple lesions group (33%, 3/9) was significantly higher than that (5.9%, 2/34) in solitary lesion group (P=0.000 3).
CONCLUSION
The incidence rate of bladder urothelial carcinoma in young patients under 40 years becomes increasingly higher over years. The major initial presentation is painless gross hematuria among these young patients, but lower urinary tract symptoms should also be noticed for young patients to rule out tumor. Postoperative tumor recurrence might be associated with multiple lesions, which is not related to the tumor size or pathological features.
Adult
;
Carcinoma, Transitional Cell/surgery*
;
Female
;
Humans
;
Male
;
Neoplasm Recurrence, Local
;
Retrospective Studies
;
Urinary Bladder Neoplasms/surgery*
9.The prognostic impact of perioperative blood transfusion on survival in patients with bladder urothelial carcinoma treated with radical cystectomy.
Joong Sub LEE ; Hyung Suk KIM ; Chang Wook JEONG ; Cheol KWAK ; Hyeon Hoe KIM ; Ja Hyeon KU
Korean Journal of Urology 2015;56(4):295-304
PURPOSE: The aim of our study was to assess the influence of perioperative blood transfusion (PBT) on survival outcomes following radical cystectomy (RC) and pelvic lymph node dissection (PLND). MATERIALS AND METHODS: We reviewed and analyzed the clinical data of 432 patients who underwent RC for bladder cancer from 1991 to 2012. PBT was defined as the transfusion of allogeneic red blood cells during RC or postoperative hospitalization. RESULTS: Of all patients, 315 patients (72.9%) received PBT. On multivariate logistic regression analysis, female gender (p=0.015), a lower preoperative hemoglobin level (p=0.003), estimated blood loss>800 mL (p<0.001), and performance of neoadjuvant chemotherapy (p<0.001) were independent risk factors related to requiring perioperative transfusions. The receipt of PBT was associated with increased overall mortality (hazard ratio, 1.91; 95% confidence interval, 1.25-2.94; p=0.003) on univariate analysis, but its association was not confirmed by multivariate analysis (p=0.058). In transfused patients, a transfusion of >4 packed red blood cell units was an independent predictor of overall survival (p=0.007), but not in cancer specific survival. CONCLUSIONS: Our study was not conclusive to detect a clear association between PBT and survival after RC. However, the efforts should be made to continue limiting the overuse of transfusion especially in patients who are expected to have a high probability of PBT, such as females and those with a low preoperative hemoglobin level and history of neoadjuvant chemotherapy.
Aged
;
*Blood Transfusion/methods/mortality
;
*Carcinoma, Transitional Cell/mortality/pathology/surgery
;
Disease-Free Survival
;
Female
;
Humans
;
Kaplan-Meier Estimate
;
Lymph Node Excision/*methods
;
Male
;
Middle Aged
;
Pelvis/pathology/surgery
;
Perioperative Care/methods
;
Prognosis
;
Republic of Korea/epidemiology
;
Retrospective Studies
;
Risk Factors
;
Treatment Outcome
;
Urinary Bladder/pathology
;
*Urinary Bladder Neoplasms/mortality/pathology/surgery
10.New and contemporary markers of prognosis in nonmuscle invasive urothelial cancer.
Korean Journal of Urology 2015;56(8):553-564
Nonmuscle invasive (NMI) urothelial cancer (UC) is associated with varied biological potential. It is characterized by frequent recurrence and progression, which thus worsens the oncological outcome. Nearly three-quarters of NMI UCs recur within 5 years, whereas half can progress during follow-up. Progression is particularly seen in T1 and carcinoma in situ (CIS). Undoubtedly, NMI UC is one of the most expensive cancers to manage. The European Organisation for Research and Treatment of Cancer (EORTC) risk calculator is a commonly used tool for assessing the recurrence and progression potential of a newly diagnosed cancer. The parameters used in the assessment are tumor size and number, pathological stage and grade of the cancer, presence of CIS, and prior recurrence rate. The main advantages of the EORTC tool are its ease of use and the lack of need to run expensive molecular tests. However, reproducibility of pathologic stage and grade is modest, which is a concern to clinicians. Molecular markers have potential for predicting the clinical outcome of NMI UC, given that clinico-pathologic variables are not sufficient for prediction of prognosis in an individual. Significant work has been done in the past 2 decades in understanding the molecular biology of bladder cancer; however, the translational value of this knowledge remains poor. The role for molecular markers in predicting recurrence seems limited because multifocal disease and incomplete treatment are probably more important for recurrence than the molecular features of a resected tumor. Urinary markers have very limited value in prognostication of bladder cancer and are used (mainly as an adjunct to cytology) for detection and surveillance of urothelial cell cancer recurrence. Prediction of progression with molecular markers holds considerable promise. Nevertheless, the contemporary value of molecular markers over clinico-pathologic indexes is limited.
Age Factors
;
Biomarkers, Tumor/*metabolism
;
Carcinoma, Transitional Cell/*diagnosis/pathology/surgery
;
Disease Progression
;
Humans
;
Prognosis
;
Recurrence
;
Risk Assessment/methods
;
Urinary Bladder Neoplasms/*diagnosis/pathology/surgery

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