Outcomes of sorafenib treatment of advanced renal cell carcinoma according to IMDC risk criteria: analysis of Japanese real-world data from postmarketing all-patient surveillance of sorafenib.

Aim: To assess sorafenib survival outcomes in renal cell carcinoma patients using standard International Metastatic Renal Cell Carcinoma Data Consortium (IMDC) risk criteria. Patients & methods: The authors restratified a real-world cohort of 3255 advanced renal cell carcinoma patients, obtained from Japanese sorafenib postmarketing surveillance, to assess survival outcomes using IMDC criteria; intermediate risk was subdivided into intermediate 1 (Int-1) and imterdemiate 2 (Int-2; one and two risk factors, respectively). Results: Overall, 2225 (68%) IMDC-evaluable patients were reclassified as favorable (17%), intermediate (62%) and poor (21%) risk, with median progression-free survival of 10.4, 8.1 and 3.4 months, respectively. Int-1 (36%) and Int-2 (26%) subgroups had median progression-free survival of 10.1 and 6.0 months, respectively. Sorafenib had acceptable safety/tolerability. Conclusion: Sorafenib effectiveness was promising for IMDC intermediate risk, particularly Int-1, warranting further investigation.

Can bladder preservation therapy come to the center stage?

Decision-making in urological cancer care requires a multidisciplinary approach for refinement, but its impact on urothelial carcinoma of the bladder has not been fully addressed for the past three decades, except for the latest immunological checkpoint inhibitor approved by the U.S. Food and Drug Administration for metastatic muscle-invasive bladder cancer that is resistant to platinum-based chemotherapy. For the time being, radical cystectomy is the gold standard of curative therapy for muscle-invasive bladder cancer. Trimodal therapy that combines chemotherapy for the purpose of radiation sensitization, external beam radiotherapy and transurethral resection of bladder tumor has emerged as a potential alternative treatment option that preserves the bladder. In lack of randomized studies for bladder preservation therapy compared with surgery, the principles of management of urothelial carcinoma of the bladder have evolved in recent times, with an emphasis on bladder preservation. A number of bladder preservation techniques are available to the surgeon; however, appropriately selected patients with muscle-invasive bladder cancer should be offered the opportunity to discuss various treatment options, including organ-sparing trimodal therapy. The aim of the present study was to compare the primary outcomes of the available treatment methods and identify the sources of variance among studies. A review of various bladder preservation techniques in vogue for the management of urothelial carcinoma of the bladder is discussed.

Change in serum sodium level predicts clinical manifestations of transurethral resection syndrome: a retrospective review.

BACKGROUND: Patients undergoing transurethral resection (TUR) of the prostate are at risk of TUR syndrome, generally defined as having cardiovascular and/or neurological manifestations, along with serum sodium concentrations less than or equal to 125 mmol/l. As these symptoms can also occur in patients with serum sodium greater than 125 mmol/l, this study aimed to investigate the relationship between serum sodium concentrations and neurological manifestations of TUR syndrome. METHODS: Data on patients who underwent TUR of the prostate under local anesthesia over an 8-year period were retrospectively reviewed. Based on their cardiovascular and neurological manifestations, patients were divided into two groups: a symptomatic and an asymptomatic group. Logistic regression analysis was used to detect the risk factors for being symptomatic. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cutoff value of estimated change in serum sodium level that could predict the development of clinical manifestation of TUR syndrome. RESULTS: Of the 229 patients, 60 showed symptoms. Serum sodium level correlated with neurological score (Spearman's correlation coefficient > 0.5). Logistic regression detected that the risk factors for being symptomatic were serum sodium level variables, operation time longer than or equal 90 min, and presence of continuous drainage from the bladder. ROC curve analysis showed that a change in serum sodium level of 7.4 mmol/l was the optimal cutoff value, with a sensitivity of 0.72, a specificity of 0.87, and an area under the curve (AUC) of 0.87. ROC curve analysis also showed that a 7.0% change in serum sodium level was optimal for this parameter, with a sensitivity of 0.70, a specificity of 0.89, and an AUC of 0.87. CONCLUSIONS: Changes in serum sodium concentration of > 7 mmol/l and of > 7% could predict the development of cardiovascular and neurological manifestations, which were assumed to be symptoms of TUR syndrome.

Incidence of urethral stricture after bipolar transurethral resection of the prostate using TURis: results from a randomised trial.

OBJECTIVES: To assess whether bipolar transurethral resection of the prostate (B-TURP) using the TURis system has a similar level of efficacy and safety to that of the traditional monopolar transurethral resection of the prostate (M-TURP), and to evaluate the impact of the TURis system on postoperative urethral stricture rates over a 36-month follow-up period. PATIENTS AND METHODS: A total of 136 patients with benign prostatic obstruction were randomised to undergo either B-TURP using the TURis system or conventional M-TURP, and were regularly followed for 36 months after surgery. The primary endpoint was safety, which included the long-term complication rates of postoperative urethral stricture. The secondary endpoint was the follow-up measurement of efficacy. RESULTS: In peri-operative findings, no patient in either treatment group presented with transurethral resection syndrome, and the decline in levels of haemoglobin and hematocrit were similar. The mean operation time was significantly extended in the TURis treatment group compared with the M-TURP group (79.5 vs 68.6 min; P = 0.032) and postoperative clot retention was more likely to be seen after M-TURP (P = 0.044). Similar efficacy findings were maintained throughout 36 months, but a significant difference in postoperative urethral stricture rates between groups was detected (6.6% in M-TURP vs 19.0% in TURis; P = 0.022). After stratifying patients according to prostate volume, there was no significant difference between the two treatment groups with regard to urethral stricture rates in patients with a prostate volume ≤ 70 mL (3.8% in M-TURP vs 3.8% in TURis), but in the TURis group there was a significantly higher urethral stricture rate compared with the M-TURP group in patients with a prostate volume >70 mL (20% in TURis vs 2.2% in M-TURP; P = 0.012). Furthermore, the mean operation time for TURis was significantly longer than for M-TURP for the subgroup of patients with a prostate volume > 70 mL (99.6 vs 77.2 min; P = 0.011), but not for the subgroup of patients with a prostate volume ≤ 70 mL. CONCLUSION: The TURis system seems to be as efficacious and safe as conventional M-TURP except that there was a higher incidence of urethral stricture in patients with larger preoperative prostate volumes.

Prediction of clinical manifestations of transurethral resection syndrome by preoperative ultrasonographic estimation of prostate weight.

BACKGROUND: This study aimed to investigate the relationship between preoperative estimated prostate weight on ultrasonography and clinical manifestations of transurethral resection (TUR) syndrome. METHODS: The records of patients who underwent TUR of the prostate under regional anesthesia over a 6-year period were retrospectively reviewed. TUR syndrome is usually defined as a serum sodium level of < 125 mmol/l combined with clinical cardiovascular or neurological manifestations. This study focused on the clinical manifestations only, and recorded specific central nervous system and cardiovascular abnormalities according to the checklist proposed by Hahn. Patients with and without clinical manifestations of TUR syndrome were compared to determine the factors associated with TUR syndrome. Receiver operating characteristic curve analysis was used to determine the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome. RESULTS: This study included 167 patients, of which 42 developed clinical manifestations of TUR syndrome. There were significant differences in preoperative estimated prostate weight, operation time, resected prostate weight, intravenous fluid infusion volume, blood transfusion volume, and drainage of the suprapubic irrigation fluid between patients with and without clinical manifestations of TUR syndrome. The preoperative estimated prostate weight was correlated with the resected prostate weight (Spearman's correlation coefficient, 0.749). Receiver operator characteristic curve analysis showed that the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome was 75 g (sensitivity, 0.70; specificity, 0.69; area under the curve, 0.73). CONCLUSIONS: Preoperative estimation of prostate weight by ultrasonography can predict the development of clinical manifestations of TUR syndrome. Particular care should be taken when the estimated prostate weight is > 75 g.

Could transurethral resection of the prostate using the TURis system take over conventional monopolar transurethral resection of the prostate? A randomized controlled trial and midterm results.

OBJECTIVE: To assess whether bipolar transurethral resection of the prostate using the TURis (Olympus, Tokyo, Japan) system demonstrates comparable efficacy and safety reporting 36 months of follow-up findings. METHODS: The trial was registered at University hospital Medical Information Network Clinical Trials Registry in Japan (trial number UMIN 000010801). Patients were randomly selected to undergo transurethral resection of the prostate using either the TURis or the conventional monopolar technique. Primary end points were safety according to operation time, decline of sodium and hemoglobin levels, clot retention, and catheterization time. Secondary end points were efficacy findings for patients after 36 months of follow-up. RESULTS: A total of 136 patients were enrolled. Mean operation times were significantly prolonged in the TURis group (68.4 and 79.5 minutes for monopolar and TURis groups, respectively; P = .048). No significant differences in the decline of hemoglobin, hematocrit, and perioperative transfusion rates between groups were seen, whereas clot retention (grade 2) after the treatment seemed to occur more often in the monopolar group (7 of 62 [12.3%] in monopolar group vs 1 of 63 [1/8%] in TURis group; P = .061). No case presented symptomatic transurethral resection syndrome in either groups. CONCLUSION: Continued efficacy at 36 months after the treatment could be confirmed for the first time in TURis system, which also seems to be preferable as they produced more clinically favorable outcomes. Nevertheless, the TURis system required significantly more resection time, which might not entirely be a panacea for the treatment of benign prostatic obstruction, especially for patients having larger prostatic volumes.

Effect of Smad7 expression on metastasis of mouse mammary carcinoma JygMC(A) cells.

BACKGROUND: Transforming growth factor beta (TGF-beta) facilitates metastasis during the advanced stages of cancer. Smad6, Smad7, and c-Ski block signaling by the TGF-beta superfamily proteins through different modes of action. We used adenovirus-mediated gene transfer of these natural inhibitors in a mouse model of breast cancer to examine the roles of TGF-beta superfamily signaling in tumor growth and metastasis. METHODS: We systemically administered, by intravenous injection, adenoviruses (AdCMV) containing the mouse cDNAs for Smad7, Smad6, c-Ski, the c-Ski mutant c-Ski (ARPG), or LacZ (control) to nude mice (>19 mice/group) bearing tumors derived from mouse mammary carcinoma JygMC(A) cells, which spontaneously metastasize to lung and liver, and examined their effects on survival and metastasis. High-throughput western blotting analysis was used to examine the expression levels for 47 signal transduction proteins in JygMC(A) cells and primary tumors. We also investigated the proliferation, migration, and invasion of JygMC(A) cells that stably overexpressed Smad6 or Smad7. Nonparametric comparisons were done by Kruskal-Wallis H statistic and Wilcoxon's rank sum tests. Parametric comparisons were done by one-way analysis of variance or two-sided unpaired Student's t tests. All statistical tests were two-sided. RESULTS: Control mice bearing tumors derived from JygMC(A) cells showed many metastases to the lung and liver; all animals died by 50 days after cell inoculation. By contrast, mice treated with AdCMV-Smad7 or AdCMV-c-Ski demonstrated a dramatic decrease in metastasis and statistically significantly longer survival than control mice (Smad7 versus LacZ: medium survival = 55 days versus 41 days, difference = 14 days [95% confidence interval {CI} = 6 days to 22 days], P < .001), whereas mice treated with AdCMV-Smad6 or AdCMV-c-Ski (ARPG) did not. Expression of Smad7 in JygMC(A) cells was associated with increased expression of major components of adherens and tight junctions, including E-cadherin, decreased expression of N-cadherin, and decreases in the migratory and invasive abilities of the JygMC(A) cells. CONCLUSION: Smad7 inhibits metastasis, possibly by regulating cell-cell adhesion. Systemic expression of Smad7 may be a novel strategy for the prevention of metastasis of advanced cancers.