Kenji Omae

Template-based lymphadenectomy in urothelial carcinoma of the renal pelvis: A prospective study

Recent studies showed the therapeutic benefit of lymphadenectomy in advanced stage urothelial carcinoma of the upper urinary tract, but there is still a lack of prospective studies and standardization of the extent of lymphadenectomy. The aim of this multi‐institutional study was to examine the role of lymphadenectomy in urothelial carcinoma of the upper urinary tract.

Superior Tolerability of Altered Dosing Schedule of Sunitinib with 2-Weeks-on and 1-Week-off in Patients with Metastatic Renal Cell Carcinoma—Comparison to Standard Dosing Schedule of 4-Weeks-on and 2-Weeks-off

OBJECTIVE Poor tolerability to sunitinib with the standard dosing schedule has become an issue. We retrospectively analyzed the treatment efficacy and the profile of adverse events of 2 weeks of sunitinib treatment followed by 1-week-off (Schedule 2/1) and compared the results with the standard dosing schedule with 4 weeks of treatment followed by 2-weeks-off (Schedule 4/2). METHODS From January 2010 until December 2012, 48 patients with metastatic renal cell carcinoma who received at least two cycles of sunitinib as first-line therapy were the subjects of this study. After 2011, we switched to Schedule 2/1 for most patients. RESULTS Schedule 2/1 included 26 patients and Schedule 4/2 had 22. The incidence of most adverse events was not significantly different between the two groups except for hand-foot syndrome and diarrhoea, which were observed more frequently in Schedule 4/2 and reached statistical significance. A dose interruption due to adverse events in the first three cycles was significantly lower in Schedule 2/1 patients than in those on Schedule 4/2 (27 versus 53% P = 0.04). With respect to treatment efficacy, the objective response rate tended to be higher in Schedule 4/2 than in Schedule 2/1 (50 versus 32%), and median progression-free survival was longer in patients on Schedule 2/1 than those on Schedule 4/2 (18.4 versus 9.1 months). These differences, however, did not reach statistical significance (P = 0.14, P = 0.13). CONCLUSIONS Alteration in dosing schedule of sunitinib with 2-weeks-on and 1-week-off showed a lower incidence of dose interruption and a similar oncological outcome compared with the standard dosing schedule of 4-weeks-on and 2-weeks-off.

High preoperative C-reactive protein values predict poor survival in patients on chronic hemodialysis undergoing nephrectomy for renal cancer

OBJECTIVES Previous studies have reported that elevated pretreatment C-reactive protein (CRP) levels are associated with poor outcome in various malignancies, including renal cell carcinoma (RCC), in the general population. However, there is no evidence of such an association in dialysis patients. Therefore, the aim of this study is to evaluate the prognostic significance of preoperative serum CRP levels in patients with RCC related to end-stage renal disease (ESRD) requiring hemodialysis (HD). MATERIALS AND METHODS We evaluated 315 patients with ESRD requiring HD who underwent nephrectomy for RCC as the first-line treatment at our hospital from 1982 to 2013. Complete patient- and tumor-specific characteristics as well as preoperative CRP levels were assessed. We defined a serum CRP level >0.5mg/dl as elevated and divided these patients into 2 groups according to their preoperative CRP levels (CRP≤0.5 and >0.5mg/dl). The median follow-up was 51 months. RESULTS Preoperative CRP levels were elevated in 75 patients (23.8%). The Kaplan-Meier 5-year cancer-specific survival rates were 95.2% and 69.9% in patients with CRP levels≤0.5 and>0.5mg/dl, respectively (P<0.0001). Multivariate analysis identified preoperative CRP level as an independent predictor for cancer-specific survival, along with a pathological TNM stage and tumor grade (CRP>0.5: hazard ratio = 3.47; 95% CI: 1.35-9.18; P = 0.0098). The concordance index of multivariable base models increased after including the preoperative CRP levels. CONCLUSIONS Preoperative serum CRP level might be an independent predictor of postoperative survival in patients with RCC related to ESRD requiring HD. Its routine use, together with the TNM classification and tumor grade, could allow better risk stratification and risk-adjusted follow-up of these patients.

Early unclamping might reduce the risk of renal artery pseudoaneurysm after robot-assisted laparoscopic partial nephrectomy.

To determine the influence of the early unclamping technique on the risk of renal artery pseudoaneurysm during robot‐assisted laparoscopic partial nephrectomy.

Renal sinus exposure as an independent factor predicting asymptomatic unruptured pseudoaneurysm formation detected in the early postoperative period after minimally invasive partial nephrectomy

To investigate the incidence of asymptomatic unruptured renal artery pseudoaneurysm detected by 3‐D computed tomography arteriography in the early period after minimally invasive partial nephrectomy, including laparoscopic and robotic partial nephrectomy.

Mannitol has no impact on renal function after open partial nephrectomy in solitary kidneys

Mannitol has been administered during partial nephrectomy as a renal protective agent for ischemic damage. However, we do not have any high‐level clinical evidence of its effectiveness. The aim of the present study was to evaluate the effect of mannitol during open partial nephrectomy by comparing the postoperative renal function of patients who received it and those who did not. We retrospectively reviewed the records of 55 patients who underwent open partial nephrectomy for renal cancer in a solitary kidney from January 1990 to December 2012, and who were followed up postoperatively for at least 6 months. Of the 55 patients, mannitol was given to 20 patients (group M+) and not to the other 35 patients (group M−). We compared not only the postoperative estimated glomerular filtration rate, but also its decrease rate and the incidence of acute kidney injury requiring dialysis in the two groups. There were no significant differences in perioperative patient characteristics between the two groups. Mannitol made no significant difference in both the postoperative estimated glomerular filtration rate and its decrease rate at any point within 6 months of the postoperative period. The incidence of acute kidney injury requiring dialysis was one (5.0%) in group M+ and two (5.7%) in group M−. These findings suggest that there might be no advantage from the administration of mannitol during open partial nephrectomy.

Similar functional outcomes after partial nephrectomy for clinical T1b and T1a renal cell carcinoma.

Objectives:  To examine the medium‐term functional outcomes of partial nephrectomy for clinical T1b renal cell carcinoma, and to compare them with those of radical nephrectomy for clinical T1b and with those of partial nephrectomy for clinical T1a tumors.

Possible Role of Template-based Lymphadenectomy in Reducing the Risk of Regional Node Recurrence after Nephroureterectomy in Patients with Renal Pelvic Cancer

OBJECTIVE It remains unclear whether lymphadenectomy alters regional node recurrence after nephroureterectomy in patients with urothelial carcinoma of the renal pelvis. The predictive factors for regional node recurrence are still unclear. In this study, we retrospectively examined how the extent of lymphadenectomy influences regional node recurrence in patients with urothelial carcinoma of the renal pelvis. METHODS From January 1988 through July 2013, we performed nephroureterectomy in 180 patients with non-metastatic (cN0M0) urothelial carcinoma of the renal pelvis at two Japanese institutes. Regional nodes were determined according to our previous mapping study: complete lymphadenectomy designates that all regional sites were dissected; incomplete lymphadenectomy that all sites were not dissected. A third group included those without lymphadenectomy. RESULTS The 5-year cancer-specific and recurrence-free survival was significantly higher in the complete lymphadenectomy group than in the incomplete lymphadenectomy or without lymphadenectomy groups (P = 0.03). The incidence of regional node recurrence was significantly lower in the complete lymphadenectomy group at 2.9% (2/67) than in the incomplete lymphadenectomy at 18.1% (4/22) or without lymphadenectomy at 10.9% (10/91) groups (P = 0.03). In patients with incomplete lymphadenectomy, 75% of regional node recurrence occurred outside of the dissected sites. Complete lymphadenectomy is shown to be a likely predictive factor of reduced risk of recurrence at the regional nodes by multivariate analysis, after adjusting for patient age, pathological T stage, and pathological nodal metastases. CONCLUSIONS This study shows that template-based lymphadenectomy reduced the risk of regional node recurrence in patients with urothelial carcinoma of the renal pelvis and appears to result in improved survival.

Assessment of Surgical Outcomes of the Non-renorrhaphy Technique in Open Partial Nephrectomy for ≥T1b Renal Tumors.

OBJECTIVE To assess surgical outcomes between the non-renorrhaphy and renorrhaphy techniques in open partial nephrectomy for ≥T1b renal tumors using volumetric studies. METHODS We retrospectively analyzed the records of 91 patients with normal contralateral kidneys who underwent both open partial nephrectomy for ≥T1b renal tumors and pre- and postoperative enhanced computed tomography between 2010 and 2014. Volumetric studies to assess vascularized parenchymal volume of the operated kidney were performed within 2 months preoperatively and 6 months postoperatively. Using the non-renorrhaphy technique, we coagulated hemorrhagic areas on the surface of the renal parenchyma by monopolar soft coagulation, while a TachoSil tissue-sealing sheet was placed on the resected bed. RESULTS A total of 50 patients underwent renorrhaphy and 41 patients underwent non-renorrhaphy. Patient backgrounds and R.E.N.A.L. nephrometry scores were not significantly different between the two groups. Cold ischemia time was significantly longer in the renorrhaphy than that in the non-renorrhaphy (52 vs 42 minutes, P = .0162). However, significant differences were not observed in the preservation rate of the vascularized parenchymal mass in the operated kidney (renorrhaphy, 71%; non-renorrhaphy, 70%; P = .5054) and global kidney function (renorrhaphy, 88%; non-renorrhaphy, 90%; P = .3653) between the two groups. Renal artery pseudoaneurysm occurred in 2 cases in both groups. Urinary fistula tended to occur more frequently in non-renorrhaphy (2 cases) than in renorrhaphy (5 cases), though this difference was not statistically significant (P = .237). CONCLUSION The non-renorrhaphy technique failed to show a benefit in the preservation of vascularized parenchymal mass of the operated kidney and global renal function for ≥T1b renal tumors compared to the renorrhaphy technique.

Time to progression after first-line tyrosine kinase inhibitor predicts survival in patients with metastatic renal cell carcinoma receiving second-line molecular-targeted therapy

OBJECTIVES The effect of response to first-line tyrosine kinase inhibitor (TKI) therapy on second-line survival in patients with metastatic renal cell carcinoma who receive second-line molecular-targeted therapy (mTT) after first-line failure remains unclear. MATERIALS AND METHODS Sixty patients who developed disease progression after first-line TKI, without prior cytokine therapy, were enrolled. According to the median first-line time to progression (1L-TTP), patients were divided into 2 groups (i.e., short vs. long). Second-line progression-free survival (2L-PFS) and second-line overall survival (2L-OS) were defined as the time from second-line mTT initiation. Survival was calculated with the Kaplan-Meier method and compared using the log-rank test between patients with short and long 1L-PFS. Predictors for survivals were identified using Cox proportional hazards regression models. RESULTS The median 1L-TTP was 8.84 months. Thirty patients (50.0%) with short 1L-TTP (<8.84mo) had significantly shorter 2L-PFS and 2L-OS compared to patients with long 1L-TTP (2L-PFS: 4.96 vs. 10.2mo, P = 0.0002; 2L-OS: 9.6 vs. 28.0mo, P = 0.0036). Multivariable analyses for 2L-PFS and 2L-OS showed that 1L-TTP was an independent predictor both as a categorical classification (cutoff: 8.84mo) and as a continuous variable (both P<0.05). The median follow-up duration was 13.1 months (interquartile range: 6.56-24.7). CONCLUSIONS Patients who achieve a long-term response after first-line TKI therapy could have a favorable prognosis with second-line mTT.