[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to evaluate the clinical value of photodynamic diagnosis (PDD) with intravesical and oral instillation of 5-aminolevulinic acid (ALA) (ALA-PDD), and transurethral resection of bladder tumor (TURBT) guided by ALA-PDD (PDD-TURBT) for nonmuscle invasive bladder cancer.
Of all 210 cases, 75 underwent PDD with intravesically applied ALA, and 135 cases underwent PDD with orally applied ALA. Diagnostic accuracy was evaluated by comparing the level on images of ALA-induced fluorescence with the pathological result. PDD-TURBT was performed in 99 completely resectable cases corresponding to 210 ALA-PDD cases. To evaluate the abilities of PDD-TURBT, survival analysis regarding intravesical recurrence was retrospectively compared with the historical control cases that underwent conventional TURBT.
The diagnostic accuracy and capability of ALA-PDD were significantly superior to those of conventional endoscopic examination. Moreover, 72.1% of flat lesions, including dysplasia and carcinoma in situ, could be detected only by ALA-PDD. The recurrence-free survival rate in the cases that underwent PDD-TURBT was significantly higher than that of conventional TURBT. Moreover, multivariate analysis revealed that the only independent factor contributing to improving prognosis was PDD-TURBT (hazard ratio, 0.578; P = .012). Regardless of the ALA administration route, there was no significant difference in diagnostic accuracy, ability of PDD, or recurrence-free survival. All procedures were well tolerated by all patients without any severe adverse events.
This multicenter study is likely to be biased, because it is limited by the retrospective analysis. This study suggests that regardless of the ALA administration route, ALA-PDD and PDD-TURBT are remarkably helpful in detection and intraoperative navigation programs.
[Show abstract][Hide abstract] ABSTRACT: We performed a clinical evaluation of 151 patients with urosepsis at Chikamori Hospital from January 2006 through December 2009. The most common organism isolated from the patients was Escherichia coli (84 strains, 56%), followed by Proteus mirabilis (12%), Pseudomonas aeruginosa (7%), and MRSA (7%). The more frequent underlying diseases among the patients were cardiovascular disease (31%), endocrine disease (25%) and cerebrovascular disease (24%). Forty-seven patients (31.1%) had upper urolithiases. Twenty-nine patients (19.2%) had an indwelling urethral catheter. The hospital mortality rate was 13.2% (20/151) in this study. The current study confirmed the diversity of underlying diseases among patients with urosepsis. A further increase in the number of patients with urosepsis due to immune-deficiency condition is expected in the future as the elderly population increases, and the importance of primary intervention for emergency outpatients in the field of urology was profoundly recognized.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the false-positive findings in photodynamic diagnosis (PDD) with intravesical instillation of 5-aminolevulinic acid (5-ALA) for the treatment of bladder cancer. In 66 patients with bladder cancer, PDD using fluorescence cystoscopy was performed. Two to two and a half hours prior to transurethral biopsy 1.5g of 5-ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHC03) solution were instilled intravesically. The degree of red-fluorescence was compared with the pathological result of the biopsy specimens which were harvested from each 7 areas of the bladder. We analyzed pathologically the false-positive findings of PDD in each area. Among the 526 specimens obtained by transurethral biopsy, 180 specimens (34.2%) were pathologically diagnosed as malignant epithelium, including 36 specimens (6.8%) with carcinoma in situ and 40 specimens (7.6%) with dysplasia which were detected pathologically, with a sensitivity of 92.7% and a specificity of 68.2 %. It was found that the false-positive rate of all areas was 31.8%, while it was 51.0% in the neck of the urinary bladder, 52.3% in the trigone of the urinary bladder, and 67.7% in the prostatic urethra, these rates being markedly higher than in other areas. Moreover, there were pathologically more cases of benign tumor, mild dysplasia, squamous metaplasia and inflammatory findings in the samples which were false-positive for PDD compared to the samples which were true-negative for PDD in these areas. The false-positive finding of PDD for bladder cancer is caused by mild dysplasia, squamous metaplasia and inflammation. In the future, we will demonstrate more detailed analysis of porphyrin synthesis and genetic anomaly in these findings.
No preview · Article · Sep 2011 · Nishinihon Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: The authors report a case showing proliferation of KIT- and connexin 43-expressing mesenchymal cells of the urinary bladder. A 75-year-old woman had an ulcerated endophytic mass (size, approximately 2 × 2 cm) in the left posterolateral wall. She underwent transurethral resection and subsequent partial cystectomy. The suburothelial mass extended to the muscularis propria. The histopathological analysis revealed spindle-shaped mesenchymal cells that were loosely arranged with myxoid stroma and showed a focal compact fascicular arrangement. In the immunohistochemical analysis, these spindle cells were stained with specific antibodies to KIT and connexin 43. The patient is currently free of disease at 5 years after operation. The proliferating spindle cells in the present case might represent a phenotype of interstitial cells of the lamina propria.
Full-text · Article · Dec 2010 · Pathology Research International
[Show abstract][Hide abstract] ABSTRACT: To report our clinical experience regarding transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD) with intravesical instillations of 5-aminolevulinic acid (ALA) and to assess the usefulness of the therapeutic method.
TUR-Bt guided by PDD was performed in 57 patients of which 47 were men and 10 women with a median age of 74.3 years (range 45-90), 36 were primary cases and 21 were recurrent cases with non-muscle invasive bladder cancer. Two to two and half hours prior to endoscopy 1.5 g ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K.K.) was used. The tumorous lesions under white light guidance and the lesion with fluorescent excitation under blue (fluorescence) light guidance were taken by cold cup as a biopsy and also resected sequentially. To evaluate the accuracy of PDD, the levels in images of the ALA-induced fluorescence were compared with the pathological results. To evaluate the availability of TUR-Bt guided by PDD, survival Analysis regarding vesical recurrence was retrospectively examined compared to the cases underwent conventional TUR-Bt under white light guidance. Moreover, in these cases, multivariate analysis using Cox proportional-hazards model was performed to detect the clinico-pathological factor independently contribute to improving prognosis. (Results) In the 301 specimens obtained from 57 patients, the sensitivity and specificity of PDD were 92.5% and 60.1%, whereas the sensitivity and specificity of conventional endoscopic examination under white light guidance were 81.6% and 79.5%, respectively. Median follow-up period was 19.1 (range 8.6-49.9) months in 57 patients underwent TUR-Bt guided by PDD. Eight of 57 patients recurred and recurrence-free survival rate was 88.2 +/- 0.1% (at 12 months) and 76.2 +/- 0.1% (24-48 months). Median follow-up period was 49.9 (5.0-145.0) months in 149 patients underwent conventional TUR-Bt. Ninety-nine of 149 patients recurred and recurrence-free survival rate was 60.3 +/- 0.0% (12 months) and 31.6 +/- 0.0% (24-48 months). There was statistical significance in recurrence-free survival rate between these 2 therapeutic groups (p < 0.001). Moreover, multivariate analysis revealed the independent factor contribute to improving prognosis was only TUR-Bt guided by PDD (hazard ratio 0.279, p = 0.001).
It was suggested that TUR-Bt guided by PDD might reduce the risk of vesical recurrence in the early stage after operation of non-muscle invasive bladder cancer.
No preview · Article · Nov 2009 · Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology
[Show abstract][Hide abstract] ABSTRACT: Organ confined renal cell carcinoma can be cured in the majority of patients, whereas more extensive lesions have a poor prognosis. Therefore, the development of a useful biomarker for early diagnosis as well as postoperative metastatic status would contribute to the appropriate therapy for renal cell carcinoma. To diagnose renal cell carcinoma preoperatively we developed a novel urinary test and detected occult lymph node micrometastasis using a molecular approach.
Urine samples were obtained preoperatively from 27 patients with renal cell carcinoma and von Hippel-Lindau (VHL) gene mutations in the tumors, and were analyzed for VHL gene mutations using a nested single strand conformational polymorphism analysis. Lymph nodes without evidence of histological metastasis were obtained from 15 patients with renal cell carcinoma and VHL gene mutations, and analyzed for VHL gene mutations using mutation specific nested reverse transcription polymerase chain reaction method.
In urine samples 5 of 27 VHL gene mutations (18.5%) were found and each mutation pattern was the same as that detected in each renal cell carcinoma. One lymph node micrometastasis was found.
These data indicate the presence of detectable levels of tumor derived DNA in the urine of patients with renal cell carcinoma and suggest that nested single strand conformational polymorphism analysis of VHL gene of urine samples provides a possible tool for the early detection of renal cell carcinoma. Furthermore, mutation specific nested reverse transcription polymerase chain reaction is useful to detect occult lymph node micrometastasis and may predict patients at risk for local recurrence. These 2 combined approaches using VHL gene mutations may contribute to the total therapy for and prognosis of renal cell carcinoma.
No preview · Article · Jul 2003 · The Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: Our primary goal was to determine whether increased expression of the transmembrane carbonic anhydrase (CA) isozymes in renal cell carcinoma (RCC) is regulated by the von Hippel-Lindau (VHL) gene.
We studied mRNA expression of all three transmembrane CAs - CA IX, XII, and XIV - in 17 RCC cell lines, transformants of the wild-type VHL gene, and normal kidney tissue cultures, and then compared them with the mutation status in the VHL gene.
Northern blot analysis showed no detectable signal for CA XIV mRNA expression in normal and cancer cells. CA XII mRNA was ubiquitously expressed except in two cell lines. Although CA XII expression levels tended to be lower in RCC cell lines without the VHL mutation and in transformants of the wild-type VHL gene, the results were not conclusive. Significant expression of CA IX mRNA was seen in eight of 17 RCC cell lines. Among five cell lines which had no VHL mutation, four lines showed no detectable signal and one cell line showed a low amount of CA IX mRNA expression. In patients with RCC, VHL mutations and significant CA IX expression were seen in established tumor cell lines but not in primary tissue cultures from normal counterparts. Further study of methylation status showed that the 5' region in the CA9 gene was hypomethylated in all CA IX-positive cell lines and hypermethylated in all CA IX-negative cell lines. Especially, methylation status at -74 and -6 CpG sites perfectly correlated with CA IX expression.
These findings indicate that VHL suppresses CA IX expression but has no conclusive effect on CA XII and XIV expressions in RCC. CA IX expression is also driven by the methylation status of the CA9 gene.
No preview · Article · Nov 2002 · Journal of Cancer Research and Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Mutations of the von Hippel-Lindau (VHL) tumor suppressor gene have been detected in up to 60% of sporadic clear cell renal carcinomas (RCCs). Even patients with RCCs believed to be curable with radical nephrectomy sometimes develop distant metastasis 5-10 years after surgery, suggesting hematogenous circulation of cancer cells. Useful tumor markers have not yet been established for RCC. To detect patients at high risk of metastasis after surgery, we developed a highly sensitive and specific nested reverse transcription-PCR method using VHL gene mutation to detect circulating cancer cells. We screened 29 sporadic clear cell RCCs from patients for mutations of the VHL gene by direct sequencing. We next examined blood samples from patients with the VHL gene mutation using mutation-specific nested reverse transcription-PCR. Somatic mutations were detected in 20 of 29 (69.0%) sporadic clear cell RCCs. The VHL gene mutations were detected in peripheral and/or renal venous blood from 15 of 20 (75%) patients. The mutations were detected in the peripheral blood in 2 of 17 (11.8%) patients before surgery, 6 of 16 (37.5%) patients within 24 h after surgery, 3 of 16 (18.8%) patients on day 7 after surgery, and 2 of 11 (18.2%) patients on day 30 after surgery. In seven of nine (77.8%) patients, mutations were detected in renal venous blood during surgery. These findings indicate the presence of circulating cancer cells with VHL gene mutation. Although much larger studies are needed to determine the clinical significance, our study shows that this technique is feasible for detecting circulating RCC cells.
No preview · Article · Nov 2000 · Clinical Cancer Research
[Show abstract][Hide abstract] ABSTRACT: We report a case of AFBN. A 22-year-old woman consulted a local medical doctor with episodes of fever and back pain. Using ultrasonography (US) and computed tomography (CT), an abnormal mass lesion of the rt. kidney was detected and the patient was introduced to our clinic. An uneven hypoechoic and poorly marginated mass lesion was noted at the rt. kidney by US, while CT demonstrated a low density mass that was poorly enhanced. AFBN was diagnosed from these radiological and laboratory findings. The patient was treated with antibiotics, and her clinical symptoms improved following a reduction in the size of the mass which was confirmed by follow-up US and CT.
No preview · Article · Jul 1997 · Nishinihon Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: Two cases of yolk tumor of the infantile testis are reported. The patients were 23 months 27 months old, each with a painless swelling of the right scrotal contents and an elevated level of serum α Fetoprotein (AFP). Right high orchiectomies were performed in these cases. Histological examinations revealed yolk sac tumor (pT1) without any other elements or vascular invasion. After the operation, chest X-ray and abdominal CT scans were performed, but neither distant nor lymph node metastasis was seen. Their cases were diagnosed as stage I, and so adjuvant therapy was performed. Neither of these cases has shown any evidence of disease for more than 1 year, whilst showing normal physical growth. The initial treatment for stage 1 yolk sac tumor of the infantile testis must be decided strictly according to the results of pathological examinations, and as such, we believe that watchful waiting after the operation is the best modality for our cases.
[Show abstract][Hide abstract] ABSTRACT: An unusual case of intrascrotal extratesticular neurofibroma is reported. A 31-year-old man was hospitalized with the complaint of left scrotal swelling without pain. The resected tumor weighed 28 g and measured 11 x 2 x 2 cm. The cut surface of the tumor was greyish white without hemorrhage or necrosis. The histological diagnosis of the specimen was plexiform neurofibroma. This patient did not show any sign of von Recklinghausen disease and remains free of recurrence 2 years postoperatively.
No preview · Article · Jan 1997 · Nishinihon Journal of Urology