Novel Classification for Upper Tract Urothelial Carcinoma to Better Risk-stratify Patients Eligible for Kidney-sparing Strategies: An International Collaborative Study.

BACKGROUND: The European Association of Urology risk stratification dichotomizes patients with upper tract urothelial carcinoma (UTUC) into two risk categories. OBJECTIVE: To evaluate the predictive value of a new classification to better risk stratify patients eligible for kidney-sparing surgery (KSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study including 1214 patients from 21 centers who underwent ureterorenoscopy (URS) with biopsy followed by radical nephroureterectomy (RNU) for nonmetastatic UTUC between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariate logistic regression analysis identified predictors of muscle invasion (≥pT2) at RNU. The Youden index was used to identify cutoff points. RESULTS AND LIMITATIONS: A total of 811 patients (67%) were male and the median age was 71 yr (interquartile range 63-77). The presence of non-organ-confined disease on preoperative imaging (p < 0.0001), sessile tumor (p < 0.0001), hydronephrosis (p = 0.0003), high-grade cytology (p = 0.0043), or biopsy (p = 0.0174) and higher age at diagnosis (p = 0.029) were independently associated with ≥pT2 at RNU. Tumor size was significantly associated with ≥pT2 disease only in univariate analysis with a cutoff of 2 cm. Tumor size and all significant categorical variables defined the high-risk category. Tumor multifocality and a history of radical cystectomy help to dichotomize between low-risk and intermediate-risk categories. The odds ratio for muscle invasion were 5.5 (95% confidence interval [CI] 1.3-24.0; p = 0.023) for intermediate risk versus low risk, and 12.7 (95% CI 3.0-54.5; p = 0.0006) for high risk versus low risk. Limitations include the retrospective design and selection bias (all patients underwent RNU). CONCLUSIONS: Patients with low-risk UTUC represent ideal candidates for KSS, while some patients with intermediate-risk UTUC may also be considered. This classification needs further prospective validation and may help stratification in clinical trial design. PATIENT SUMMARY: We investigated factors predicting stage 2 or greater cancer of the upper urinary tract at the time of surgery for ureter and kidney removal and designed a new risk stratification. Patients with low or intermediate risk may be eligible for kidney-sparing surgery with close follow-up. Our classification scheme needs further validation based on cancer outcomes.

Pretreatment Risk Stratification for Endoscopic Kidney-sparing Surgery in Upper Tract Urothelial Carcinoma: An International Collaborative Study.

BACKGROUND: Several groups have proposed features to identify low-risk patients who may benefit from endoscopic kidney-sparing surgery in upper tract urothelial carcinoma (UTUC). OBJECTIVE: To evaluate standard risk stratification features, develop an optimal model to identify ≥pT2/N+ stage at radical nephroureterectomy (RNU), and compare it with the existing unvalidated models. DESIGN, SETTING, AND PARTICIPANTS: This was a collaborative retrospective study that included 1214 patients who underwent ureterorenoscopy with biopsy followed by RNU for nonmetastatic UTUC between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed multiple imputation of chained equations for missing data and multivariable logistic regression analysis with a stepwise selection algorithm to create the optimal predictive model. The area under the curve and a decision curve analysis were used to compare the models. RESULTS AND LIMITATIONS: Overall, 659 (54.3%) and 555 (45.7%) patients had ≤pT1N0/Nx and ≥pT2/N+ disease, respectively. In the multivariable logistic regression analysis of our model, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.0-1.03, p = 0.013), high-grade biopsy (OR 1.81, 95% CI 1.37-2.40, p < 0.001), biopsy cT1+ staging (OR 3.23, 95% CI 1.93-5.41, p < 0.001), preoperative hydronephrosis (OR 1.37 95% CI 1.04-1.80, p = 0.024), tumor size (OR 1.09, 95% CI 1.01-1.17, p = 0.029), invasion on imaging (OR 5.10, 95% CI 3.32-7.81, p < 0.001), and sessile architecture (OR 2.31, 95% CI 1.58-3.36, p < 0.001) were significantly associated with ≥pT2/pN+ disease. Compared with the existing models, our model had the highest performance accuracy (75% vs 66-71%) and an additional clinical net reduction (four per 100 patients). CONCLUSIONS: Our proposed risk-stratification model predicts the risk of harboring ≥pT2/N+ UTUC with reliable accuracy and a clinical net benefit outperforming the current risk-stratification models. PATIENT SUMMARY: We developed a risk stratification model to better identify patients for endoscopic kidney-sparing surgery in upper tract urothelial carcinoma.

Efficacy of Preoperative Chemotherapy for High Risk Upper Tract Urothelial Carcinoma.

PURPOSE: The impact of preoperative chemotherapy in patients with upper urinary tract urothelial carcinoma remains poorly investigated. We assessed the rates of pathological complete response (pT0N0/X) and downstaging (pT1N0/X or less) at radical nephroureterectomy after preoperative chemotherapy and evaluated their impact on survival. MATERIALS AND METHODS: This was an international observational study of patients who underwent preoperative chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma between 2005 and 2017. Multiple imputation of chained equations was applied to account for missing values. Logistic regression analyses were performed to identify predictors of pathological response. Cox proportional hazard regression models were used to estimate recurrence-free survival, cancer specific survival and overall survival. RESULTS: A total of 267 patients met our inclusion criteria. Among included patients 82 (31%) received methotrexate, vinblastine, doxorubicin and cisplatin; 123 (46%) gemcitabine and cisplatin; 25 (9%) gemcitabine and carboplatin; and 32 (12%) other regimens. The overall rates of pathological complete response and pathological downstaging were 10.1% and 44.9%, respectively. On multivariable analysis the use of gemcitabine and cisplatin, and gemcitabine and carboplatin was not statistically different from methotrexate, vinblastine, doxorubicin and cisplatin in achieving pathological complete response and pathological downstaging, respectively. The number of administered cycles did not appear to have an effect on pathological responses. Pathological downstaging was the strongest prognostic factor for recurrence-free survival (HR 0.2, p <0.001), cancer specific survival (HR 0.19, p <0.001) and overall survival (HR 0.40, p <0.001). CONCLUSIONS: Pathological downstaging after preoperative chemotherapy is a robust prognostic factor at radical nephroureterectomy and is associated with improved survival outcomes. Although preoperative chemotherapy appears to be effective, well designed prospective studies are still needed.

Influence of nutritional deficiency on prognosis of renal cell carcinoma (RCC).

OBJECTIVE: To evaluate the prognosis of patients with renal cell carcinoma (RCC) by nutritional status defined by body mass index (BMI), serum albumin and cholesterol. PATIENTS AND METHODS: This study retrospectively enrolled 1437 patients who underwent radical nephrectomy (932) or partial nephrectomy (505) for RCC. We assigned nutritional status according to the presence of none or one nutritional risk factor (control group) and two or all three of the following nutritional risk factors (nutritional deficiency group). The nutritional factors and thresholds were preoperative albumin level (<3.5 g/dL), preoperative cholesterol level (<220 mg/dL), and preoperative BMI (<23 kg/m(2) ) RESULTS: The patients' mean (sd) age was 55.23 (12.41) years and BMI was 24.36 (3.17) kg/m(2) . The mean (sd) serum cholesterol level was 180.07 (38.24) mg/dL, and the albumin level was 4.2 (0.45) g/dL. In all, 141 (9.8%) patients had none of the nutritional deficiency criteria, 802 (55.8%) had one, 429 (29.9%) had two, and 65 (4.5%) had all three. Clinicopathological variables, i.e. female gender, high tumour stage, positive lymph node metastasis, positive distant metastasis, high nuclear grade and non-clear cell type histopathology were associated with the nutritional deficiency group. In multivariate Cox analysis, nutritional deficiency was an independent predictor for RCC recurrence (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.05-1.83, P = 0.020) and RCC-related mortality (HR 2.06, 95% CI 1.39-3.03, P < 0.001). CONCLUSION: Nutritional deficiency defined by BMI, serum albumin and cholesterol is an important factor that predicts postoperative prognosis of patients with RCC who have undergone radical or partial nephrectomy.

Strategies to prevent progression of high-risk bladder cancer at initial diagnosis.

PURPOSE OF REVIEW: As high-risk nonmuscle invasive bladder cancer (NMIBC) has a high propensity to recur and progress, the primary therapeutic goal in patients with high-risk NMIBC is the prevention or delay of disease recurrence and progression. RECENT FINDINGS: For improving transurethral resection quality, new optical enhancement technology such as optical coherence tomography, photodynamic diagnosis and narrow band imaging might be considered because these emerging optical techniques may contribute to resection completeness and reduce the recurrence risk. Recent studies have confirmed that a second resection is associated with a lower risk of progression and cancer-related death. Although maintenance bacillus Calmette-Guérin (BCG) for at least 1 year has been recommended, some studies have shown no significant advantage to maintenance BCG. Although other options may be considered in early BCG failure, there are no large trials that have shown a long-term benefit in BCG-failure patients. SUMMARY: Current literature suggests that the best treatment for patients with high-risk NMIBC involves complete transurethral resection with intravesical BCG therapy. New approaches or therapeutic agents for preventing recurrence and progression are needed in this field.

Cytotoxicity and apoptosis by survivin small interfering RNA in bladder cancer cells.

OBJECTIVE: To investigate the effects of survivin gene RNA interference on cell growth and the cell cycle in the human bladder cancer cell line T24. MATERIALS AND METHODS: A small interfering RNA (siRNA) targeting survivin was transfected into T24 cells using a liposome approach. Reverse transcription-polymerase chain reaction and Western blot analysis were used to examine survivin gene expression in T24 cells. Cells densities were determined by haematocytometer counts and flow cytometry was used for cell cycle analysis. Caspase-3 activity was quantified. RESULTS: After treatment with survivin siRNA, the survivin gene expression in T24 cells was almost completely absent. The survivin siRNA treatment caused a profound decrease in survivin protein, which was correlated with a decrease in cell growth, G2/M arrest, and an increase in the fraction of cells undergoing apoptosis. The inhibition of survivin expression increased caspase-3 activity in T24 cells, which led to apoptosis. CONCLUSIONS: RNA interference can efficiently suppress survivin expression in T24 cells. Targeting survivin by siRNA may be a promising approach to block proliferation of bladder cancer cells and may provide a suitable adjuvant therapy for treatment of bladder cancer.

Influence of detrusor overactivity on storage symptoms following potassium-titanyl-phosphate photoselective vaporization of the prostate.

OBJECTIVES: To investigate whether the presence of detrusor overactivity (DO) influences storage symptoms after photoselective laser vaporization of the prostate (PVP) for benign prostatic hyperplasia (BPH). METHODS: A total of 149 patients who underwent PVP were included in this retrospective study. All patients underwent a preoperative evaluation including multichannel video urodynamics. The efficacy of the PVP was assessed at 1, 3, 6, and 12 months postoperatively using the International Prostate Symptom Score (IPSS), uroflowmetry, postvoid residual urine volume, and 3-day frequency-volume charts (FVC). The patients were stratified into 2 groups (DO group vs non-DO group). RESULTS: The IPSS and FVC showed that the storage symptoms were reduced significantly after the PVP in both groups (P<.05). Starting from 6 months after the PVP, the DO group (n=39) showed a significantly greater reduction in the subtotal storage symptom score than the non-DO group (n=110). When the improvement of storage symptoms was defined as a reduction of >or=50% in the subtotal storage symptom scores, the percentage of patients with improvement in the storage symptoms at 1, 3, 6, and 12 months after the PVP was 13.9%, 25.9%, 47.8%, and 52.9% in the DO group, and 22.2%, 24.4%, 33.3%, and 33.3% in the non-DO group, respectively. CONCLUSIONS: Our results show that storage and voiding symptoms significantly improved after the PVP. In addition, we found that men with DO might show more improvement of storage symptoms, after the PVP, than men without DO.

Laparoscopic resection of metastatic pelvic liposarcoma.

We report a pelvic liposarcoma originating from the left spermatic cord that recurred following inadequate excision. In our case, the tumor was resected without performing orchiectomy previously. The patient was managed by laparoscopic resection, before undergoing radical orchiectomy in the left inguinal region. To our knowledge, no case of laparoscopic resection for the recurrent liposarcoma has been described. In addition, the present case serves to demonstrate that radical orchiectomy with wide excision is needed for paratesticular tumor.

Laparoscopic resection of metastatic pelvic liposarcoma

We report a pelvic liposarcoma originating from the left spermatic cord that recurred following inadequate excision. In our case, the tumor was resected without performing orchiectomy previously. The patient was managed by laparoscopic resection, before undergoing radical orchiectomy in the left inguinal region. To our knowledge, no case of laparoscopic resection for the recurrent liposarcoma has been described. In addition, the present case serves to demonstrate that radical orchiectomy with wide excision is needed for paratesticular tumor.

Laparoscopic adrenalectomy for functioning and non-functioning adrenal tumors: analysis of surgical aspects based on histological types.

BACKGROUND: The aim of this study was to evaluate whether hormonal functions of the tumor influence the operative results of laparoscopic adrenalectomy, and to analyse the clinical outcomes in patients with various hormonally active adrenal tumors. METHODS: Clinical and pathological records of 68 patients were reviewed. The average age of patients was 40 years (range 20-75); 39 were women and 29 men. For the comparison, patients were divided into the non-functioning tumor group (n = 22) and the functioning tumor group (n = 46). RESULTS: All laparoscopic adrenalectomies were finished successfully, and no open surgery was necessary. The median operative time and blood loss in the two groups were similar; however, in subgroup analysis, operative time for pheochromocytoma was significantly longer than that for non-functioning tumor (P = 0.044). No difference was noted in intra- and postoperative data between the groups. Of the 22 patients with aldosteronoma, 18 (81.8%) became normotensive and no longer required postoperative blood pressure medications. Adrenalectomy led to an overall reduction in the median number of antihypertensive medications (P < 0.001). All patients with Cushing adenoma had resolution or improvement of the signs and symptoms during follow-up periods. There was no evidence of biochemical or clinical recurrence in any patient with pheochromocytoma. CONCLUSION: The results of this retrospective review document that laparoscopic adrenalectomy is a safe and effective treatment for functioning as well as non-functioning adrenal tumors, although endocrinologic features may play a significant role.