Rapid progression of mucinous tubular and spindle cell carcinoma of the kidney without sarcomatoid changes: A case report.

We report a case of unusually aggressive behavior of a mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney with no sarcomatoid changes. A 43-year-old man was referred to our hospital for a mass on his left kidney. Computed tomography revealed a tumor at the upper pole of the kidney and swollen lymph nodes. Left radical nephrectomy with lymph node dissection was performed and the tumor was diagnosed as MTSCC. Peritoneal dissemination was detected 4 months after the surgery. The patient received systemic treatments, which were not effective. He finally died of the disease 12 months after the surgery.

A Case of Hemorrhagic Adrenal Pseudocyst Mimicking Solid Tumor.

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.

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.

Increased nucleophosmin expression is a strong predictor of recurrence and prognosis in patients with N0M0 upper tract urothelial carcinoma undergoing radical nephroureterectomy.

PURPOSE: We aimed to evaluate whether increased nucleophosmin expression predicts recurrence and survival in upper tract urothelial carcinoma (UTUC). METHODS: Specimens from 101 patients with N0M0 UTUC undergoing radical nephroureterectomy were evaluated. Nucleophosmin expression was determined immunohistochemically and categorized into two groups according to nucleophosmin staining intensity. The association between nucleophosmin expression and various clinicopathological factors including Ki-67 expression was analyzed. Multivariate analyses were performed to identify the independent predictors of extraurothelial recurrence and cancer-specific survival. RESULTS: High nucleophosmin expression was significantly correlated with tumor location, pT ≥3, lymphovascular invasion, lymph node metastasis, and high Ki-67 expression. Patients whose tumors demonstrated high nucleophosmin expression had a significantly higher rate of extraurothelial recurrence and a lower survival rate than those with low nucleophosmin expression. Multivariate analysis showed that pT ≥3, lymph node metastasis, high nucleophosmin expression, and high Ki-67 expression were independent predictors of extraurothelial recurrence. When patients were stratified into three groups according to the number of risk factors, the 2-year extraurothelial recurrence-free survival rates were 92.9% in patients with 0 or 1 risk factor, 76.5% in patients with 2 risk factors, and 9.1% in patients with 3 or 4 risk factors. Regarding cancer-specific survival, lymphovascular invasion and high nucleophosmin expression were independent predictors. CONCLUSIONS: Increased nucleophosmin expression was a strong predictor of extraurothelial recurrence and cancer-specific survival in patients with N0M0 UTUC undergoing radical nephroureterectomy. Our risk stratification models integrating nucleophosmin expression may provide valuable information on disease recurrence and prognosis.

[CLINICAL ANALYSIS ABOUT PERCUTANEOUS NEEDLE BIOPSY FOR RENAL MASSES].

(Objective) We investigated the efficacy and safety of percutaneous renal mass biopsy retrospectively. (Methods) A retrospective review was performed of 44 patients (46 renal masses) who received ultrasound and/or computed tomography guided percutaneous biopsy of a solid renal mass between April 2004 and December 2012 in National Defense Medical College Hospital. (Results) The median renal mass size was 45 (range 15-140) mm with a median of 2 (1-5) cores taken. Thirteen masses were biopsied for differential diagnosis between RCC and other malignancies (or benign renal tumors), 11 were biopsied for differential diagnosis between RCC and renal pelvic urothelial carcinoma, 10 unresectable masses were biopsied to confirm the diagnosis pathologically before starting medication, and 12 small masses were biopsied before radio-frequency ablation. Of the initial 46 biopsies, 38 (82.6%) were diagnostic. The median lesion sizes in the diagnostic and nondiagnostic biopsy specimens were 45 (15-140) mm and 43 (17-128) mm. The median numbers of diagnostic and nondiagnostic cores were 2 (1-5) and 1.5 (1-4). These size and core number differences between the diagnostic and nondiagnostic biopsy specimens are not statistically significant. Of initial nondiagnostic 8 masses, 3 masses that were performed repeat biopsy resulted in determined diagnosis finally. There were mild postprocedural hematomas not requiring blood transfusion. There was no tumor dissemination after renal mass biopsy. (Conclusions) Percutaneous biopsy of renal masses is a safe procedure that provides diagnostic information.

Preoperative risk factors for extraurothelial recurrence in N0M0 patients with renal pelvic cancer treated by radical nephroureterectomy.

The prediction of extraurothelial recurrence (EUR) before radical nephroureterectomy (RNU) is difficult for patients with upper tract urothelial carcinoma. If EUR can be predicted preoperatively, it may be possible to determine the need for neoadjuvant chemotherapy or the surgical strategy. Our previous study identified preoperative risk factors for EUR in ureteral cancer, while the present study identified preoperative risk factors for EUR in renal pelvic cancer (RPC). The preoperative factors were reviewed in 71 N0M0 patients with RPC treated by RNU between 1999 and 2013. Preoperative clinical background data, laboratory test results, including inflammatory indices, lactate dehydrogenase (LDH), and estimated glomerular filtration rate, and radiological findings were subjected to multivariate analyses to identify independent predictive factors for EUR. The 3-year EUR-free survival (EURFS) rate was 81.9%, and univariate analysis showed that clinical T (cT) stage ≥3, white blood cell counts ≥7600/µl, neutrophil counts ≥4,500/µl, neutrophil-to-lymphocyte ratio ≥2.0, and LDH ≥210 IU/l were significantly associated with EURFS. Additionally, a cT stage ≥3 (P=0.0244) and LDH ≥210 IU/l (P=0.0322) were independent predictors for EUR. When patients were stratified into three groups according to the number of risk factors, the 3-year EURFS rates were 94.5, 76.3, and 33.3% for the low-, intermediate-, and high-risk patient groups, respectively. In conclusion, cT stage ≥3 and LDH ≥210 IU/l were preoperative predictive factors of EUR in patients with RPC. High-risk patients may be candidates for neoadjuvant chemotherapy and low-risk patients may be candidates for RNU without lymph node dissection.

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.

Clinical characteristics and prognosis of patients with renal cell carcinoma and liver metastasis.

The prognosis of patients with renal cell carcinoma (RCC) and liver metastasis (LM) is poor. We evaluated the clinical characteristics, prognosis and prognostic factors of RCC patients with LM. A total of 25 patients who underwent radical or partial nephrectomy (Nx) for RCC between November, 1980 and April, 2013 at the National Defense Medical College, Tokorozawa, Saitama, Japan, with LM at initial presentation or following Nx, were included in this study. The association between prognosis following development of LM and clinicopathological parameters was analyzed. The Cox proportional hazards regression model was used to identify prognostic predictors. The median cancer-specific survival (CSS) following LM diagnosis was 10.6 months. The presence of sarcomatoid differentiation, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, C-reactive protein ≥1.0 mg/dl, corrected calcium ≥10 mg/dl and presence of multiple organ metastases, were identified as CSS predictors. The multivariate analysis identified ECOG PS ≥2 as an independent CSS predictor. Nine patients survived for >20 months following LM diagnosis and 1 patient, who received treatment with tyrosine kinase inhibitors (TKIs) for LM, exhibited stable disease for 5 years. Nine patients underwent local LM treatment. Two patients, who underwent hepatic resection, survived for 55.1 and 22 months, respectively. In conclusion, RCC patients with LM may benefit from local LM treatment if they have a limited number of metastases in addition to LM and if their ECOG PS is satisfactory. Indeed, a proportion of RCC patients with LM benefit from TKI therapy. Furthermore, RCC patients with LM and ECOG PS ≥2 apparently have a poor prognosis, regardless of local or systemic therapies.

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.

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.

[Causes and salvage of failed urethroplasties for traumatic urethral injury].

OBJECTIVES: Salvage urethroplasty after failed repair of traumatic urethral injury is a urological challenge, and we herein describe our experience with it. METHODS: From October 2010 to January 2012, five patients underwent salvage repair of failed urethroplasties for traumatic urethral injuries: three bulbar straddle injuries and two pelvic fracture urethral injuries. One of the three failed urethroplasties for bulbar straddle injuries was a stricture excision and primary anastomosis, and its failure was due to periurethral abscess formation. Another was an augmented anastomotic urethroplasty using buccal mucosa, and its failure was due to periurethral abscess formation. The third was a tube graft urethroplasty using buccal mucosa, and its failure was due to a stricture at the anastomotic site. Two failed urethroplasties for pelvic fracture urethral injuries were perineal anastomotic repairs combined with corporal separation and inferior pubectomy, and the failures of both were due to ischemic bulbar necrosis. The urethral gap lengths estimated from urethrograms ranged from 12 to 45 mm (mean = 26 mm). RESULTS: Urethroplasties in all patients with bulbar straddle injuries were salvaged by stricture excision and primary anastomosis with corporal separation, and urethroplasties in both patients with pelvic fracture urethral injuries were salvaged by abdominal transpubic perineal urethroplasty. Although the patients who underwent transpubic urethroplasty had transient pelvic girdle pain, no severe complications were observed. All patients were for 10 to 25 months postoperatively (mean = 16 months) able to void satisfactorily without additional treatment. CONCLUSIONS: Failed urethroplasties for traumatic urethral injuries can be salvaged with a second reconstruction surgery. The procedure of choice for this salvage is anastomotic urethroplasty with techniques for tension-free anastomosis.

[Evaluation of clinical results in patients undergoing laparoscopic nephroureterectomy].

We evaluated the efficacy of laparoscopic radical nephroureterectomy (LNUx) by comparing the clinical results in 55 patients undergoing LNUx at the National Defense Medical College since 2001 with those in patients undergoing open radical nephroureterectomy (ONUx) there over the same period. LNUx was performed successfully in 54 of the patients, but one patient required conversion to ONUx. The mean operating time for LNUx was not significantly different from that for ONUx, and the mean estimated blood loss during LNUx was significantly lower than that during ONUx. Major complications occurring early in our laparoscopic series of cases were injury of the duodenum and bleeding from the inferior vena cava. Oncological outcomes were compared between LNUx (n＝50) and ONUx (n＝50) in patients with pathologically-confirmed urothelial carcinoma. The pT stage, histological grade, percentage of lymph node dissection and percentage of high grade hydronephrosis did not differ significantly between the two groups. Because the intravesical recurrence-free survival rates, extravesical recurrence-free survival rates, and disease specific survival rates were also similar in the two groups, we concluded that LNUx is an appropriate treatment for upper urinary tract urothelial carcinoma.

[The diagnostic value of pre-biopsy magnetic resonance imaging for precise detection of clinically localized prostate cancer compared to post-biopsy setting].

A total of 136 patients who underwent radical prostatectomy following histological diagnosis of prostate cancer by transrectal biopsy and 3-Tesla magnetic resonance imaging (MRI) were evaluated. MRI was performed on 26 patients before prostate biopsy (pre-biopsy group) and on 110 patients after prostate biopsy (post-biopsy group). We defined the largest tumor focus in a radical prostatectomy specimen as the index cancer. We compared the accuracy of MRI in detecting and localizing the index cancer in the groups. The sensitivity of detecting the index cancer by MRI was significantly (p = 0.012) higher in the pre-biopsy group (96.2%) than in the post-biopsy group (77. 3%). The negative predictive value of extracapsular invasion was 84.6% in the pre-biopsy group and 80.7% in the post-biopsy group. The average interval between biopsy and MRI was 42.8 days. Artifacts due to post-biopsy hemorrhage were observed in 32 (29.1%) of the patients in the post-biopsy group. The sensitivity of detecting the index cancer by MRI was significantly (p = 0.022) higher in 78 patients without artifacts due to hemorrhage (83.3%) than in the 32 patients with artifacts due to hemorrhage (62.5%). Even if MRI is delayed until after prostate biopsy,the artifact due to hemorrhage markedly interferes with the accuracy of MRI. Although pre-biopsy MRI is more accurate than post-biopsy MRI,there are some problems to be solved,such as cost effectiveness and the detectability of low-malignant and small cancers.

Prediction of biochemical recurrence after radical prostatectomy using peritumoral lymphatic vessel density in biopsy specimens in patients with localized prostate cancer.

INTRODUCTION: Lymphatic invasion has been associated with biochemical recurrence (BCR), and many patients with postoperative elevation of prostate-specific antigen (PSA) develop distant metastases within several years. We previously found peritumoral lymphatic vessel density (PTLD) in biopsy cores to be an independent predictor of lymphatic invasion in radical prostatectomy specimens, so we speculate that PTLD parameters in biopsy specimens could also be independent predictors of BCR after surgery. PATIENTS AND METHODS: We obtained positive biopsy cores from 110 patients who underwent radical prostatectomy at our institution. Biopsy cores were immunostained with the D2-40 monoclonal antibody, which specifically and selectively detects lymphatic endothelium. We evaluated differences between the BCR-free survival rates and used univariate and multivariate analyses to detect independent predictors of BCR. RESULTS: The results of a Cox proportional hazards model showed that lymphatic invasion in prostatectomy specimens was one of the independent postoperative prognostic factors for BCR (p = 0.0338). An additional model showed that one PTLD parameter, maximal PTLD, was among the independent preoperative predictors of lower BCR-free survival rates (p = 0.0200). CONCLUSIONS: Information about PTLD in prostate biopsy specimens could be helpful for selecting patients as radical prostatectomy candidates, and patients with high PTLD values should be carefully monitored after surgery.

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.

[The efficacy of direct vision internal urethrotomy for male urethral stricture].

OBJECTIVE: Direct vision internal urethrotomy (DVIU) has been considered to be a low invasive and widely used therapeutic modality for male urethral stricture. However, its efficacy is still controversial. We herein evaluated the efficacy of DVIU for male urethral stricture. PATIENTS AND METHODS: Nineteen patients 27 to 78 years old (median age = 59) underwent DVIU for urethral strictures at our hospital were included in this study. Strictures were at bulbar urethra in 17 patients, membranous urethra in 1 patient, and pendulous urethra in 1 patient. The stricture lengths estimated on retrograde urethrography were less than 1 cm in 13 patients, 1-2 cm in 2 patients, and more than 2 cm in 4 patients. The etiology of stricture was straddle injury in 7 patients, post transurethral surgery in 7 patients, pelvic fracture in 1 patient, and unknown in 4 patients. The operation was done by cold knife incision using guidewire. The duration of postoperative urethral catheterization was 5 to 35 days (mean 12.8 days). Follow up duration ranged from 1 month to 139 months (mean 48.2 months). The definition of postoperative re-stricture was the confirmation of re-stricture on retrograde urethrography or deterioration of symptom. RESULTS: While no severe complication was observed, postoperative re-stricture was seen in 13 patients. Stricture-free rates at 3 months, 6 months, and 5 years after the first DVIU were 44.4%, 38.1%, 20.3% respectively. Although second DVIU was done for 7 patients with re-stricture, six patients resulted in failure. Stricture-free rates at 3 months, 6 months, and 5 years after the second DVIU were 42.2%, 28.6%, 14.3% respectively. Though the third DVIU was done for two of them, they were unable to void just immediately after the removal of urethral catheters. Stricture-free rate in stricture less than 1 cm was higher than that in 1 cm or longer, though it did not reach significant difference (p = 0.1813). CONCLUSION: The efficacy of DVIU is lesser than we expected. DVIU seems to be excessively applied to male urethral strictures and should not be performed for long and recurrent urethral stricture.

Intravesical ultrasonography for tumor staging in an orthotopically implanted rat model of bladder cancer.

PURPOSE: Noninvasive and serial evaluation of tumor development and growth is important in an orthotopic animal bladder tumor model. However, to our knowledge a reliable method has not been established. We determined the usefulness of intravesical ultrasonography for tumor staging and volumetric assessment in an animal model. MATERIALS AND METHODS: Tumors with various stages were formed in 20 female Fischer F344 rats by implanting AY-27 rat bladder carcinoma cells. Cells were implanted by instilling a suspension (4x10 cells) into the bladder cavity after urothelial denudation using hydrochloric acid or by directly injecting the cell suspension into the bladder wall. Tumor volume and invasion depth were measured by intravesical ultrasonography using an ultrathin 2.5Fr intraluminal ultrasound catheter via the urethra 7 to 10 days after cancer cell implantation. The rats were then sacrificed for histopathological examination. RESULTS: All rats showed bladder tumors 7 to 10 days after cancer cell implantation, of which stages varied from superficial to advanced disease. Intravesical ultrasonography showed a clear cross-sectional view of all layers of the bladder wall and enabled visualization of bladder tumors (minimal 0.5 mm in diameter). This approach also provided an accurate diagnosis of tumor invasion into muscle layers and perivesical tissues with precise invasion depth and tumor size. The positive predictive ratio regarding tumor staging reached 85%. Repeat examinations were feasible without noticeable adverse effects. CONCLUSIONS: Intravesical ultrasonography is a reliable and appropriate noninvasive method for evaluating tumor stage and size in an orthotopic rat bladder tumor model.

Photodynamic therapy with PAD-S31, a new hydrophilic chlorin photosensitizer, in an orthotopic rat bladder tumor model.

PURPOSE: PAD-S31 (13,17-bis (1-carboxypropion) carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl-porphyrin sodium) (Photochemical Co., Ltd., Okayama, Japan), 1 of the latest second-generation photosensitizers, has hydrophilic characteristics and excitation wavelengths of around 670 nm. Using an orthotopic rat bladder tumor model we investigated the biodistribution of PAD-S31 and assessed the antitumor effects of photodynamic therapy (PDT) with PAD-S31. MATERIALS AND METHODS: An orthotopic rat bladder tumor was established by implanting AY-27 cells in the bladder wall. After intravenous PAD-S31 administration the accumulation of PAD-S31 in the tumor and normal bladder wall was investigated by a fluorometric technique. One or 3 hours after intravenous administration of PAD-S31 (5 mg/kg) bladder tumors in rats were transurethrally irradiated at 100 mW/cm with a light dose of 50 to 200 J/cm. The efficacy of PDT was evaluated 7 days later by observation with an ultrathin cystoscope and histopathological examination. RESULTS: The ratio of PAD-S31 concentration in tumor tissue to that in normal bladder wall was more than 1 at all time points and it achieved a maximum (more than 10) 150 to 240 minutes after PAD-S31 administration. All rats that were irradiated at 100 J/cm 3 hours after PAD-S31 administration showed more than 50% tumor destruction. When the light dose was more than 150 J/cm, more than half of the rats showed complete tumor eradication, of which the average size was 6 mm. CONCLUSIONS: We report that PDT using PAD-S31 is effective for destroying bladder tumors in an orthotopic rat model. These experimental results suggest that this therapy could be a clinically promising method for the treatment of patients with bladder cancer.

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.