Kenji Seguchi

Successful Diagnosis Of Orthotopic Rat Superficial Bladder Tumor Model By Ultrathin Cystoscopy

PURPOSE In the orthotopic animal bladder tumor model noninvasive evaluation of the tumor establishment and the therapeutic effect has been difficult. To our knowledge we present the first diagnosis of orthotopic rat superficial bladder tumor model by ultrathin cystoscopy. MATERIALS AND METHODS The established AY-27 rat bladder carcinoma cell line was transplanted orthotopically into 22 female Fischer F344 rats. A cell suspension containing 4 x 10 AY-27 cells was instilled into the bladder, which had been conditioned with mild acid washing. To evaluate tumor growth serial cystoscopy was performed via the urethra with an ultrathin endoscope (diameter 0.75 mm.) 5 to 14 days after tumor cell inoculation. At intervals after cystoscopic tumor detection the rats were sacrificed for autopsy and histological examination. RESULTS In all 22 rats the orthotopic bladder tumor was established 7 to 10 days after tumor cell implantation and in most it was superficial. Cystoscopy permitted inspection of the urethra and whole bladder surface. We detected all tumors as broad based papillary mass (minimal lesion 1 mm. or less) and inspected its detailed appearance and accurate location. CONCLUSIONS The orthotopic rat superficial bladder tumor model and the diagnostic procedure by ultrathin cystoscopy would be ideal system for preclinical evaluation of new potential intravesical therapies.

Critical Parameters in the Cytotoxicity of Photodynamic Therapy Using a Pulsed Laser

Abstract.Photodynamic therapy (PDT) using a pulsed laser is becoming popular, but its cytotoxic effect is still not clear. We therefore studied the cytotoxicity of PDT using a pulsed laser by changing its irradiation parameters and compared the degrees of cytotoxicity with those of PDT using continuous-wave (CW) light sources. Mice renal cell carcinoma cells were incubated with PAD-S31, a water-soluble photosensitiser of which the excitation peak is 670 nm, and were then irradiated with either a tungsten lamp, a CW diode laser, or a nanosecond pulsed Nd:YAG laser-based optical parametric oscillator system. When the PAD-S31 concentration and total light dose were constant (12 µg/ml and 40 J/cm2, respectively), the CW laser caused fluence rate-dependent decrease in cellular proliferation until the fluence rate reached 90 mW/cm2, at which point inhibition of cellular proliferation was more than 80%. The cytotoxicity then became almost saturated at fluence rates of>90 mW/cm2. On the other hand, inhibition of cellular proliferation in samples irradiated with the pulsed laser reached 80% even at the fluence rate of 15 mW/cm2, and, interestingly, the cytotoxicity paradoxically decreased with increase in the fluence rate. Moreover, the cytotoxicity in the PDT using the pulsed laser depended on the repetition rate. The inhibition of cellular proliferation by PDT using 30-Hz irradiation was greater than that by PDT using 5-Hz irradiation when the same fluence rates were used. These results suggest that the efficacy of PDT using a pulsed laser depends considerably on fluence rate and repetition rate.

Prognostic factors for upper urinary tract urothelial carcinoma after nephroureterectomy.

Introduction: The purpose of this study was to evaluate prognostic factors for patients with upper urinary tract urothelial carcinoma (UUT-UC) after nephroureterectomy and to seek a better way of finding more favorable clinical results for these patients. Patients and Methods: We retrospectively reviewed the medical records of 121 UUT-UC patients who underwent a nephroureterectomy at our institution, and analyzed the prognostic significance of various clinicopathological parameters for progression-free and disease-specific survival rates by using univariate and multivariate analysis. Results: A Cox proportional hazards model showed that extravesical tumor recurrence after surgery was an independent prognostic factor for disease-specific survival (p < 0.0001). An additional model showed that lymphovascular invasion (LVI) was one of the independent predictors of lower extravesical-recurrence-free survival rates (p = 0.0004). Our final finding was that pathological tumor stage and positive surgical margin were significantly associated with the presence of LVI (p < 0.0001 and p = 0.0029, respectively). Conclusions: We conclude that there is a high possibility of LVI in patients with large tumors. Our findings should be helpful in terms of determining whether or not to perform neoadjuvant chemotherapy for patients with large tumors, given the fact that we frequently find a severe reduction in renal function after nephroureterectomy.

Incidentally discovered giant renal arteriovenous malformation

A case is presented of giant renal arteriovenous malformation (AVM). A 61‐year‐old woman was admitted to the National Defense Medical College Hospital for further evaluation of a renal cyst. Doppler ultrasonography and magnetic resonance imaging revealed a giant renal AVM, although the patient had no history nor clinical sign suggesting an AVM. Under the diagnosis of a right renal AVM, the patient underwent AVM resection.

Preoperative Risk Factors for Extraurothelial Recurrence in Patients with Ureteral Cancer Treated with Radical Nephroureterectomy

PURPOSE Recent studies have suggested that lymph node dissection may improve the prognosis in patients with upper tract urothelial carcinoma. Therefore, patients who will benefit from lymph node dissection need to be selected before surgery. Because patients who have extraurothelial recurrence theoretically include those whose prognoses are improved by lymph node dissection, we conducted this study to determine the preoperative predictors of extraurothelial recurrence in patients with ureteral cancer. MATERIALS AND METHODS Because it is not appropriate to categorize the preoperative radiologic findings of ureteral cancer and those of renal pelvic cancer using the same classification criteria, we focused on ureteral cancer. We reviewed preoperative factors in 70 patients with ureteral cancer treated with radical nephroureterectomy. Laboratory tests including inflammatory indices, tumor markers and estimated glomerular filtration rate, along with radiologic findings, were evaluated. Multivariate analyses were performed to determine independent factors predicting extraurothelial recurrence in patients with ureteral cancer. RESULTS Positive cytology, cT stage 3 or greater, length of ureteral cancer 3 cm or greater and estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 were independent predictors of extraurothelial recurrence on multivariate analysis. When patients were stratified into 3 groups according to the number of risk factors, the 3-year extraurothelial recurrence-free survival rates were 95.2% in the low risk group, 75.8% in the intermediate risk group and 25.1% in the high risk group. CONCLUSIONS Positive cytology, cT stage 3 or greater, length of ureteral cancer 3 cm or greater and estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 were preoperative predictive factors of extraurothelial recurrence in patients with ureteral cancer and lymph node dissection may be omitted for low risk patients.

Tumor necrosis is a strong predictor for recurrence in patients with pathological T1a renal cell carcinoma

Patients with pT1aN0M0 renal cell carcinoma (RCC) generally have good prognosis, and recurrence is rare. However, metastasis develops postoperatively in a small number of patients with pT1aN0M0 RCC. The present study was undertaken to identify predictors for recurrence in patients with pT1aN0M0 RCC. We reviewed the clinicopathological factors of 133 patients with pT1aN0M0 RCC who underwent radical or partial nephrectomy at the Department of Urology, National Defense Medical College (Saitama, Japan). Clinicopathological factors, including age, gender, tumor size, histological subtype, tumor grade, microvascular invasion, histological tumor necrosis, C-reactive protein levels and performance status were reviewed. These factors were compared between patients with and without postoperative recurrence. Recurrence-free survival (RFS) and cause-specific survival (CSS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to determine independent factors predicting recurrence in patients with pT1aN0M0 RCC. The 5-year RFS and CSS rates were 97.2 and 99.1%, respectively. When clinicopathological factors were compared between patients with and without recurrence, tumor size (P=0.0390) and percentage of tumor necrosis (P<0.0001) were significantly different between groups. All patients with recurrence had primary lesions ≥3 cm. By univariate analysis, tumor size (P=0.0379) and the presence of tumor necrosis (P=0.0319) were significant predictors for recurrence; tumor necrosis was also an independent predictor for recurrence (P=0.0143). In patients with pT1b tumors ≤5 cm (recurrence rate, 16.8%; n=48), the percentage of tumor necrosis was significantly higher in patients with recurrence compared with those without (P=0.0261). This suggests that tumor necrosis may be an important predictor for recurrence in small RCCs. Although recurrence is rare in pT1a RCC, the presence of tumor necrosis may be an important predictor for recurrence. Particularly, patients presenting with pT1a RCC with histological tumor necrosis should undergo careful follow-up.

Clinical significance of p21-activated kinase 1 expression level in patients with upper urinary tract urothelial carcinoma

OBJECTIVE The p21-activated kinase serine/threonine kinases have been outlined as the main cytoskeletal remolding regulators. The same holds true for cell proliferation and motility. They additionally have a part in cellular invasion and carcinogenesis, but the effect of p21-activated kinase 1 expression on the progression of upper urinary tract urothelial carcinoma remains unclear. Therefore, we assessed the relation of p21-activated kinase 1 positivity level to clinicopathological features in patients with upper urinary tract urothelial carcinoma. METHODS Immunohistochemical staining was performed using formalin-fixed and paraffin-embedded specimens, which were all from 124 patients with upper urinary tract urothelial carcinoma. The determination of staining level was based on the intensity of the staining along with portion of cells stained. Correlation of p21-activated kinase 1 positivity with clinicopathological parameters, including disease-specific or extravesical-recurrence-free survival, was evaluated. RESULTS Statistically significant association was observed between moderate or more than moderate p21-activated kinase 1 positivity and higher tumor grade, pathological T stage, lymphovascular invasion, history of adjuvant chemotherapy and extravesical recurrence. Positivity for p21-activated kinase 1 had a significant association with shortened disease-specific survival in a multivariate analysis among clinicopathological parameters. Strongly positive p21-activated kinase 1 expression was also one of the independent factors for shortened extravesical-recurrence-free survival time in N0M0 upper urinary tract urothelial carcinoma patients in another multivariate analysis as well as histology and lymphovascular invasion (P = 0.0304, hazard ratio = 4.425). CONCLUSIONS We conclude that our findings can help us continue a careful follow-up for upper urinary tract urothelial carcinoma patients with high p21-activated kinase 1 expression in surgical specimens.

Renal oncocytoma with intracytoplasmic lumina: a case report with ultrastructural findings of "oncoblasts".

The authors present a case of renal oncocytoma with numerous intracytoplasmic lumina in a 45-year-old woman, with an emphasis on the ultrastructural findings of so-called oncoblasts. The tumor was located in the upper pole of the left kidney, measuring about 3.3 cm in diameter. Histologically, it was composed of solid nests or acinar growths of so-called oncocytic tumor cells with numerous intracytoplasmic lumina and scattered foci of so-called oncoblasts. The luminal surface was positive for Hales colloidal iron stain. A very small number of glycogen-containing cells were found scattered in a few nests. Immunohistochemically, tumor cells were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and carcinoembryonic antigen. The Ki-67 labeling index was 1.2%. All of the Ki-67-positive cells were oncocytes. So-called oncoblasts were negative for Ki-67. Ultrastructural examination revealed that the predominant tumor cells had cytoplasm packed with round mitochondria and the mitochodria had lamellar long cristae. So-called oncoblasts showed scant cytoplasm with a moderate number of small mitochondria. Some of them showed pyknosis which can be regarded as mitochondrial involution. The authors believe that so-called oncoblasts are damaged or involuted oncocytes rather than precursors of oncocytes.The authors present a case of renal oncocytoma with numerous intracytoplasmic lumina in a 45-year-old woman, with an emphasis on the ultrastructural findings of so-called oncoblasts. The tumor was located in the upper pole of the left kidney, measuring about 3.3 cm in diameter. Histologically, it was composed of solid nests or acinar growths of so-called oncocytic tumor cells with numerous intracytoplasmic lumina and scattered foci of so-called oncoblasts. The luminal surface was positive for Halés colloidal iron stain. A very small number of glycogen-containing cells were found scattered in a few nests. Immunohistochemically, tumor cells were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and carcinoembryonic antigen. The Ki-67 labeling index was 1.2%. All of the Ki-67-positive cells were oncocytes. So-called oncoblasts were negative for Ki-67. Ultrastructural examination revealed that the predominant tumor cells had cytoplasm packed with round mitochondria and the mitochodria had lamellar long cristae. So-called oncoblasts showed scant cytoplasm with a moderate numberof small mitochondria. Someof themshowed pyknosis which can be regarded as mitochondrial involution. The authors believe that so-called oncoblasts are damaged or involuted oncocytes rather than precursors of oncocytes.

Clinical outcomes of percutaneous radiofrequency ablation for small renal cancer

Partial nephrectomy is the treatment of choice for small renal cell carcinoma (RCC) from the perspective of cancer management and renal function. However, when patients with RCC are of advanced age, exhibit severe comorbidities, including cardiovascular and pulmonary diseases, or have hereditary RCC, ablative therapies, including radiofrequency ablation (RFA) and cryoablation are useful treatment options. In the present study, the clinical outcomes of percutaneous RFA for treating small RCC were evaluated. Between December 2005 and March 2015, 40 patients (41 renal tumors in total) underwent RFA and a total of 50 sessions of RFA were performed. The average tumor size was 2.5 cm. A total of 18 tumors were exophytic and 23 were parenchymal. Of the 41 tumors, 85.4% were completely ablated by initial RFA and the rate of complete ablation following reablation for residual viable lesions was 95.1%. Local recurrence-free survival following complete ablation was 84.2% at 3 years. A patient with a 4.7 cm RCC tumor rapidly progressed following four RFA treatments until complete ablation was achieved. The metastasis-free survival rate following initial RFA was 95.7% at 3 years. The RCC-specific survival was 100% (mean follow-up, 38 months). Adverse events occurred in five sessions (10%); however, only 1 patient with arteriovenous fistula required intervention (transarterial embolization). The mean hospital stay following RFA was 3.2 days. The mean decrease in estimated glomerular filtration rate following RFA was 2.7%. The results of the present study indicate that percutaneous RFA was an effective treatment for small RCCs with respect to management of cancer, minimal invasiveness and minimal loss of renal function, particularly in patients for whom surgery would be a high risk and those at increased risk of deterioration of renal function.

A Case of Hemorrhagic Adrenal Pseudocyst Mimicking Solid Tumor

Patient: Female, 78 Final Diagnosis: Adrenal pseudocyst Symptoms: None Medication: — Clinical Procedure: Operation Specialty: Urology Objective: Mistake in diagnosis Background: Adrenal pseudocysts are often discovered incidentally on imaging, but the diagnosis and treatment can be challenging. A case of adrenal pseudocyst with hemorrhage is presented that mimicked a solid tumor on imaging, resulting in adrenalectomy. Case Report: A 78-year-old woman was found to have a right adrenal lesion on abdominal imaging. Enhanced computed tomography (CT) showed a heterogeneously enhanced mass, and magnetic resonance imaging (MRI) showed a high-intensity T1-weighted and T2-weighed image, with an irregular enhanced margin. The imaging findings were suggestive of a solid tumor of the adrenal gland. Although full endocrine serological studies were negative, the lesion increased in size at two-year follow-up. Right laparoscopic adrenalectomy was performed, and a benign hemorrhagic adrenal pseudocyst was diagnosed histologically. Conclusions: Adrenal pseudocyst can be associated with acute intracystic hemorrhage, and imaging will show contrast enhancement, suggesting malignancy. In such cases, surgical excision is both diagnostic and curative.