Nobutaka Furuya

Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer

BackgroundLymphovascular invasion (LVI) and lymph node metastasis are conventional pathological factors associated with an unfavorable prognosis of urothelial carcinoma of the upper urinary tract (UC-UUT), but little is known about the molecular mechanisms underlying LVI and nodal metastasis in this disease. Rac1 small GTPase (Rac1) is essential for tumor metastasis. Activated GTP-bound Rac1 (Rac1 activity) plays a key role in activating downstream effectors known as Pak (21-activated kinase), which are key regulators of cytoskeletal remolding, cell motility, and cell proliferation, and thus have a role in both carcinogenesis and tumor invasion.MethodsWe analyzed Rac1 activity and Pak1 protein expression in matched sets of tumor tissue, non-tumor tissue, and metastatic lymph node tissue obtained from the surgical specimens of 108 Japanese patients with UC-UUT.ResultsRac1 activity and Pak1 protein levels were higher in tumor tissue and metastatic lymph node tissue than in non-tumor tissue (both P < 0.0001). A high level of Rac1 activity and Pak1 protein expression in the primary tumor was related to poor differentiation (P < 0.05), muscle invasion (P < 0.01), LVI (P < 0.0001), and lymph node metastasis (P < 0.0001). Kaplan-Meier survival analysis showed that an increase of Rac1 activity and Pak1 protein was associated with a shorter disease-free survival time (P < 0.01) and shorter overall survival (P < 0.001). Cox proportional hazards analysis revealed that high Rac1 activity, Pak1 protein expression and LVI were independent prognostic factors for shorter overall and disease-free survival times (P < 0.01) on univariate analysis, although only Pak1 and LVI had an influence (P < 0.05) according to multivariate analysis.ConclusionsThese findings suggest that Rac1 activity and Pak1 are involved in LVI and lymph node metastasis of UC-UUT, and may be prognostic markers for this disease.

Single minimum incision endoscopic radical nephrectomy for renal tumors with preoperative virtual navigation using 3D-CT volume-rendering

BackgroundSingle minimum incision endoscopic surgery (MIES) involves the use of a flexible high-definition laparoscope to facilitate open surgery. We reviewed our method of radical nephrectomy for renal tumors, which is single MIES combined with preoperative virtual surgery employing three-dimensional CT images reconstructed by the volume rendering method (3D-CT images) in order to safely and appropriately approach the renal hilar vessels. We also assessed the usefulness of 3D-CT images.MethodsRadical nephrectomy was done by single MIES via the translumbar approach in 80 consecutive patients. We performed the initial 20 MIES nephrectomies without preoperative 3D-CT images and the subsequent 60 MIES nephrectomies with preoperative 3D-CT images for evaluation of the renal hilar vessels and the relation of each tumor to the surrounding structures. On the basis of the 3D information, preoperative virtual surgery was performed with a computer.ResultsSingle MIES nephrectomy was successful in all patients. In the 60 patients who underwent 3D-CT, the number of renal arteries and veins corresponded exactly with the preoperative 3D-CT data (100% sensitivity and 100% specificity). These 60 nephrectomies were completed with a shorter operating time and smaller blood loss than the initial 20 nephrectomies.ConclusionsSingle MIES radical nephrectomy combined with 3D-CT and virtual surgery achieved a shorter operating time and less blood loss, possibly due to safer and easier handling of the renal hilar vessels.

Ambulatory Urodynamics in Asymptomatic, Young, Healthy Male Volunteers

Objectives: To assess the incidence of detrusor overactivity and reproducibility of data from ambulatory urodynamic monitoring (AUM) in male volunteers.

Preoperative Virtual Navigation with 3D-CT Volume Rendering for Single Minimum Incision Endoscopic Nephron-Sparing Surgery on Renal Tumors

Thanks to various technical and imaging innovations, pure laparoscopic or hand-assisted laparoscopic surgery is now performed worldwide and is considered to be safe and effective, while also improving the quality of life for patients [1,2]. However, laparoscopy requires three to four incisions, each of which is about 1-2 cm long. Every incision is associated with the potential risk of bleeding, hernia, and/or damage to internal organs, and also incrementally worsens the cosmetic outcome [3,4]. Furthermore, several problems remain to be solved with regard to laparoscopy, including the use of CO2 pneumoperitoneum, the size of the incision required to retrieve the resected specimen, the need for trocar ports, and the high cost of equipment. Alternatives to conventional laparoscopy include single-site surgery, which is known as laparo-endoscopic single-site surgery (LESS), as well as natural orifice transluminal endoscopic surgery (NOTES). In 1998, Kihara et al. from Japan reported on minimum incision endoscopic surgery (MIES) performed via a single small incision, which was an attempt to solve the above-mentioned problems with conventional laparoscopic surgery and reduce technical difficulties (Figure 1) [5-9]. MIES is performed via a single small incision that is just large enough to allow extraction of the resected specimen, and is done without gas or trocar ports, making it a safe, reproducible, cost-effective, and minimally invasive treatment option [5-8]. Detection of small renal tumors has continued to increase as a result of improved imaging methods. In patients with a single, small (<4 cm), and localized renal cell carcinoma, nephron-sparing surgery (NSS) has become more common due to advances in renal imaging, improved surgical techniques, and the increasing number of incidentally discovered low-stage carcinomas. As a result, good tumor control and potentially better overall survival have been reported in patients undergoing NSS [10]. Therefore, radical nephrectomy is no longer the standard surgical procedure for such tumors and it has been