Junya Furukawa

Interleukin-23 and Interleukin-27 Exert Quite Different Antitumor and Vaccine Effects on Poorly Immunogenic Melanoma

Recent studies revealed that two novel interleukin (IL)-12-related cytokines, IL-23 and IL-27, have potent antitumor activities. However, the antitumor effects were mainly evaluated in relatively highly immunogenic tumors and have not been fully evaluated against nonimmunogenic or poorly immunogenic tumors. In this study, we investigated the antitumor efficacies of IL-23 and IL-27 on poorly immunogenic B16F10 melanoma and found that the antitumor responses mediated by IL-23 and IL-27 were clearly different. In syngeneic mice, mouse single-chain (sc) IL-23-transfected B16F10 (B16/IL-23) tumors exhibited almost the same growth curve as B16F10 parental tumor about until day 20 after tumor injection and then showed growth inhibition or even regression. In contrast, scIL-27-transfected B16F10 (B16/IL-27) tumors exhibited significant retardation of tumor growth from the early stage. In vivo depletion assay revealed that the antitumor effect of B16/IL-23 was mainly mediated by CD8+ T cells and IFN-gamma whereas that of B16/IL-27 mainly involved natural killer cells and was independent of IFN-gamma. We also found that antitumor effects of B16/IL-23 and B16/IL-27 were synergistically enhanced by treatment with IL-18 and IL-12, respectively. Furthermore, B16/IL-23-vaccinated mice developed protective immunity against parental B16F10 tumors but B16/IL-27-vaccinated mice did not. When combined with prior in vivo depletion of CD25+ T cells, 80% of B16/IL-23-vaccinated mice completely rejected subsequent tumor challenge. Finally, we showed that the systemic administration of neither IL-23 nor IL-27 induced such intense toxicity as IL-12. Our data support that IL-23 and IL-27 might play a role in future cytokine-based immunotherapy against poorly immunogenic tumors.

Expression of urokinase-type plasminogen activator system in prostate cancer: Correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

The objective of this study was to evaluate the expression levels of urokinase-type plasminogen activator (uPA) system in radical prostatectomy (RP) specimens in order to clarify the significance of the uPA system in prostate cancer. Expression levels of uPA, uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and PAI-2 in RP specimens obtained from 153 patients with clinically organ-confined prostate cancer who had not received any neoadjuvant therapies were evaluated by immunohistochemical staining. Various expression levels of uPA, uPAR, PAI-1, and PAI-2 were noted in the majority of prostate cancer specimens. Expression levels of uPA and uPAR were significantly associated with major prognostic indicators, including pathological stage, Gleason score, lymphatic invasion, surgical margin status and lymph node metastasis. However, PAI-1 expression was related to only pathological stage and surgical margin status, and there was no significant association between the expression level of PAI-2 and several parameters examined. Despite the lack of prognostic significance in PAI-2 expression, biochemical recurrence-free survival of patients with strong uPA, uPAR, and PAI-1 expression was significantly lower than that of those with weak uPA, uPAR, and PAI-1 expression, respectively. Furthermore, strong expression of uPA in addition to a Gleason score, positive surgical margin, and lymph node metastasis could be independent predictors for biochemical recurrence after RP. These findings suggest that the uPA system may be involved in the progression of prostate cancer, and that the expression level of uPA in prostate cancer tissue could be used as a useful predictor of biochemical recurrence in patients undergoing RP.

Comparison of the Transperitoneal and Retroperitoneal Approach in Robot-Assisted Partial Nephrectomy in an Initial Case Series in Japan

PURPOSE To compare the results from the transperitoneal and retroperitoneal approaches in our initial case series of robot-assisted partial nephrectomy (RAPN) in terms of surgical time, renal artery clamping time, postoperative renal function, adverse events, and surgical margin status. PATIENTS AND METHODS The initial 26 consecutive RAPNs performed for solid renal tumors in our hospital were categorized by the approach used, transperitoneal or retroperitoneal, and compared for body mass index, tumor size, R.E.N.A.L. nephrometry score, PADUA score, tumor location, surgical time, renal artery clamping time, renal function change after surgery, operative blood loss, surgical margin status, and adverse events (AEs). RESULTS The median tumor size was 25 mm (range 15-50). A transperitoneal approach was used in 16 patients and a retroperitoneal approach was used in 10 patients. There was no significant difference in renal tumor and patient characteristics between the two groups except tumor location (anterior tumor was significantly more in the transperitoneal approach and posterior tumor was significantly more in retroperitoneal approach (P=0.0144 and P=0.0100, respectively)). Operative time (239 ± 63.0 minutes in the transperitoneal group vs. 193 ± 40.6 minutes in the retroperitoneal group), warm ischemic time (24.3 ± 9.07 minutes in the transperitoneal group vs. 24.7 ± 8.35 minutes in the retroperitoneal group) and AEs (1/16 in the transperitoneal group vs. 1/10 in the retroperitoneal group; both cases were Clavien-Dindo grade I) did not show any significant difference between the two approaches (P=0.0792, 0.5485, and 0.7270, respectively). CONCLUSIONS The retroperitoneal approach in RAPN appears to be a safe and technically feasible minimally invasive option for nephron-sparing surgery, based on our initial case series, and showed equivalent outcomes to those of the transperitoneal approach even though it was an initial robotic renal surgery series. Future studies, including a larger number of cases, are planned to draw more definitive conclusions.

Serum Level of Clusterin and Its Density in Men with Prostate Cancer as Novel Biomarkers Reflecting Disease Extension

OBJECTIVES To assess whether the serum level of clusterin and its density could be used as novel biomarkers of prostate cancer. METHODS Sera were obtained from 380 patients with prostate cancer and 120 with benign prostatic hyperplasia. Serum clusterin level was measured by a sandwich enzyme immunoassay, and clusterin density, which was determined by dividing the serum clusterin level by the prostate volume, was also calculated. These findings were analyzed with respect to several clinicopathologic factors. RESULTS The mean serum level of clusterin in prostate cancer patients was significantly higher than that in the benign prostatic hyperplasia group. Both the serum clusterin level and clusterin density in prostate cancer patients were significantly associated with major prognostic factors other than biopsy Gleason score. Of the 380 prostate cancer patients, 162 underwent radical prostatectomy and pelvic lymphadenectomy, and 104 and 58 were diagnosed as having organ-confined and extraprostatic diseases, respectively. The clusterin density in patients with organ-confined disease was significantly higher than that in patients with extraprostatic disease; however, there was no significant difference in the serum clusterin level between these 2 groups. Furthermore, biochemical recurrence-free survival in patients with elevated clusterin density was significantly lower than that in patients with normal density. CONCLUSIONS These findings suggest that serum clusterin level and its density could serve as a useful practical adjuncts to conventional parameters for estimating the extension of prostate cancer.

Console-integrated real-time three-dimensional image overlay navigation for robot-assisted partial nephrectomy with selective arterial clamping: early single-centre experience with 17 cases.

The objective of this study was to describe our early experience with robot‐assisted partial nephrectomy (RAPN) incorporating selective arterial clamping, using an image overlay navigation system.

Upper urinary tract recurrence following radical cystectomy for bladder cancer

Aim:  The objective of this study was to analyze the clinicopathological features of upper urinary tract recurrence following radical cystectomy for bladder cancer.

Prognostic significance of tumor extension into venous system in patients undergoing surgical treatment for renal cell carcinoma with venous tumor thrombus

AIMS The objective of this study was to evaluate the prognostic significance of the extent of a tumor thrombus in renal cell carcinoma (RCC) involving the venous system. METHODS This study included 135 consecutive RCC patients with a venous tumor thrombus undergoing radical nephrectomy and tumor thrombectomy between 1985 and 2009. These patients were classified based on the maximal level of the tumor thrombus extending into the venous system, as follows: group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic. RESULTS Of the 135 patients, 65, 49 and 21 were classified into groups 1, 2 and 3, respectively. The 1, 3 and 5-year cancer-specific survival (CSS) rates in these 135 patients were 89.2, 56.9 and 49.2%, respectively. Among several factors examined, tumor size, tumor grade, perirenal fat invasion and presence of metastasis, but not extent of tumor thrombus, were significantly associated with CSS on univariate analysis. Of these significant factors, only tumor size and presence of metastasis appeared to be independently related to CSS on multivariate analysis. When the patients without metastasis were analyzed separately, CSS in groups 2 and 3 was significantly poorer than that in group 1. CONCLUSIONS These findings suggest the absence of a significant prognostic impact of the level of the tumor thrombus in a complete cohort of RCC patients with a venous tumor thrombus; however, it is warranted to determine whether the level of the tumor thrombus has different effects on the prognosis according to the presence of metastatic diseases.

Long‐term functional outcomes in patients with various types of orthotopic intestinal neobladder

Objectives:  To evaluate the long‐term functional outcomes of various types of orthotopic neobladder (NB).

Persistent expression of Aurora-A after neoadjuvant hormonal therapy as a predictor of a poor clinical outcome in patients undergoing radical prostatectomy for prostate cancer

To characterize the changes in the expression of Aurora‐A protein in prostate cancer before and after androgen‐withdrawal therapy, and to assess the prognostic significance of the Aurora‐A expression in patients undergoing radical prostatectomy (RP) after neoadjuvant hormonal therapy (NHT).

Novel Telementoring System for Robot-assisted Radical Prostatectomy: Impact on the Learning Curve

OBJECTIVE To develop a Web-based audiovisual telementoring system for robot-assisted radical prostatectomy (RARP) and to assess the utility of this system. METHODS A telementoring system for RARP, consisting of a 3-dimensional high-definition view of the operating field, overview of the operating room, annotation function, and 2-channel audio feed with bidirectional connectivity between 2 institutions, was developed. The outcome of RARP performed for the initial 30 patients by 2 surgeons with telementoring was compared with that for 2 surgeons who received direct mentoring. RESULTS This system was shown to function properly with an acceptable latency. There were no significant differences in several parameters reflecting surgical outcomes, including the operating time, complication rate, early continence status, and positive margin rate between the telementoring and direct mentoring groups. CONCLUSION These findings suggest the usefulness of the telementoring system for promoting the spread of precise surgical techniques associated with RARP. To our knowledge, this is the first report concerning telementoring for robot-assisted surgery.