Development of a fully automated chemiluminescence immunoassay for urine monomeric laminin-γ2 as a promising diagnostic tool of non-muscle invasive bladder cancer.

BACKGROUND: Monomeric laminin-γ2 in urine is a potential biomarker for bladder cancer. However, the current detection system uses an antibody that cannot discriminate between monomeric laminin-γ2 and the heterotrimeric γ2 chain of laminin-332, which may cause false-positive reactions. The present study aimed to develop a fully automated chemiluminescence immunoassay system using a specific monoclonal antibody against monomeric laminin-γ2. METHODS: In total, 237 urine specimens (84 from patients with bladder cancer, 48 from patients with benign urological disease, and 105 from healthy donors) were collected, and monomeric laminin-γ2 values in the urine were measured using a fully automated chemiluminescence immunoassay. RESULTS: The results revealed that laminin-γ2 values in patients with benign urological disease were comparable to those of healthy donors and that the chemiluminescence immunoassay's lower limit of detection was 10 pg/mL (approximately 20-fold better than the sandwich enzyme-linked immunosorbent assay's limit of 200 pg/mL). Moreover, the chemiluminescence immunoassay demonstrated that patients with bladder cancer, including non-muscle invasive bladder cancer (≤pT1), had higher laminin-γ2 values than patients with benign urological disease or healthy donors. CONCLUSIONS: These results suggest that urine monomeric laminin-γ2 may be a promising biomarker to diagnose cases of non-muscle invasive bladder cancer using a fully automated chemiluminescence immunoassay system.

Urinary laminin-γ2 is a novel biomarker of non-muscle invasive urothelial carcinoma.

Lack of appropriate biomarkers has hampered early detection of urothelial cancer (UC), therefore, development of biomarkers for its diagnosis at earlier stages is of importance. Laminin-332 (Ln-332, formerly Ln-5), a component of basement membranes, consists of Ln-α3, Ln-ß3, and Ln-γ2 polypeptides. However, monomeric Ln-γ2 alone is frequently expressed in malignant neoplasms. If Ln-γ2 is also expressed in UC and secreted into the urine, its detection could be useful for UC diagnosis. Here, we evaluated Ln-γ2 levels from 60 patients with urinary diseases (including UC) by Western blotting, and detected it in approximately 53% of UC cases. Using immunohistochemistry, we confirmed Ln-γ2 expression in UC tissues that were positive for Ln-γ2, whereas Ln-α3 expression was absent. We next developed a sandwich enzyme-linked immunosorbent assay and applied it for screening 39 patients with non-muscle invasive UC and 61 patients with benign urologic diseases. The Ln-γ2 levels were higher in UC patients than in those with benign urologic diseases. Ln-γ2 was detected even in patients with earlier stages of UC, such as Ta, T1, or carcinoma in situ. The sensitivity of Ln-γ2 testing for UC was 97.4%, and the specificity was 45.9%, using a cut-off of 0.5 µg/g∙crn. Ln-γ2 had greater diagnostic value for detecting non-muscle invasive UC compared to conventional urine cytology and available biomarkers for UC, and may be useful as a urine biomarker for the diagnosis and monitoring of UC.

IgG4-related disease of the paratestis in a patient with Wells syndrome: a case report.

BACKGROUND: We report a case of a 33-year-old man who presented with immunoglobulin (Ig)G4-related disease (IgG4-RD) forming a pseudotumor in the left paratesticular region during oral administration of corticosteroid for Wells syndrome, which involves cellulitis with eosinophilia. CASE PRESENTATION: The patient was introduced to our institution from a private hospital with a 3-month history of asymptomatic left scrotal mass. A 5-cm diameter nodule was palpable in the left scrotum. Tumor lesion in the left paratestis involving the epididymis and spermatic cord was observed on computed tomography and magnetic resonance imaging. Blood testing showed no abnormalities other than a minimal increase in C-reactive protein levels. Urine examination likewise revealed no significant findings. Left radical orchidectomy was performed under a diagnosis of left paratesticular neoplasm suspected as malignant tumor. The tumor was pathologically identified as IgG4-RD of the left paratestis involving the epididymis and spermatic cord. CONCLUSIONS: We present a first description of IgG4-RD in a patient with Wells syndrome and the ninth case of IgG4-RD in a scrotal organ, and discuss this very rare entity with reference to the literature. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_225.

Novel combination therapy with imiquimod and sorafenib for renal cell carcinoma.

OBJECTIVES: To investigate whether the combination of the imidazoquinoline immune response modifier, imiquimod, and the multitargeted tyrosine-kinase inhibitor, sorafenib, inhibits the growth of renal cell carcinoma in mice. METHODS: Female BALB/c mice were implanted subcutaneously with 2 × 10(5) RENCA mouse kidney cancer cells, and were treated with transcutaneously applied cream containing imiquimod and oral administrations of sorafenib beginning 5 days after implantation of the cells. Tumor incidence and burden were determined at 28 days after initiation of therapy. T cell infiltration in the tumor was determined by immunofluorescence staining with anti-CD3-ε and CD8-α antibodies. RESULTS: Therapy with imiquimod, sorafenib or their combination was well tolerated. Combination therapy with imiquimod and sorafenib significantly inhibited tumor growth when compared with administration of control vehicle, imiquimod or sorafenib alone (P < 0.05). The CD3- and CD8-positive T cells infiltrated into tumors to a greater degree in response to the combination therapy when compared with tumors treated with control vehicle or sorafenib alone. CONCLUSIONS: Combination therapy with a tyrosine-kinase inhibitor and an imidazoquinoline could be a promising therapeutic strategy for patients with renal cell carcinoma.

[First experiences of laparoscopic radical cystectomy].

PURPOSE: We determined whether laparoscopic radical cystectomy (LRC) was useful for the patients with bladder cancer. MATERIALS AND METHODS: We investigated the surgical outcome of LRC in the initial 30 patients with bladder cancer. RESULTS: Mean patients age was 68 (54-81) years old. Twenty six male and 4 female were enrolled. Lymphnode dissection was variably performed under aeroperitoneum. Twenty six patients were undergone ileal conduit and 4 patients were undergone ileal neobladder as urinary diversion. The urinary diversion of all cases was undergone extra-corporeally. Seventeen patients were received platinum based neo and adjivant-chemotherapy. Mean surgical time was 684 (398-950) min, and mean aeroperitoneum time was 418 (235-660) min. Intraoperative major complications were ureter injury and blood loss. Mean blood loss was 1,063 (150-2,730) ml intraoperatively. Ileus and acute pyeronephritis were observed in the 3 patients postoperatively. Seven patients relapsed and 2 patients died with bladder cancer in 14.9 months of median follow-up period (0.7-35.9) after the surgery. Progression free survival rate and overall survival rate at a year after surgery were 75.2% and 100%, respectively. CONCLUSIONS: The surgical therapy with LRC was well tolerated and successful in the patients with bladder cancer.

Expression of angiogenesis-related gene profiles and development of resistance to tyrosine-kinase inhibitor in advanced renal cell carcinoma: characterization of sorafenib-resistant cells derived from a cutaneous metastasis.

OBJECTIVES: To investigate the potential mechanism of development of resistance to tyrosine kinase inhibitor in renal cell carcinoma. METHODS: A primary culture of renal cell carcinoma cells (KMRM-S2) was established from an advanced renal cell carcinoma patient with cutaneous metastasis, who had not responded to sorafenib. A total of 84 human angiogenesis-related genes were compared between cutaneous metastasis and the primary tumor by real time polymerase chain reaction. Spectral karyotyping and cell proliferation assay were carried out to determine the biological features of the cells. RESULTS: Primary tumor was histopathologically diagnosed as high-grade clear cell carcinoma with sarcomatoid change and rhabdoid features. The cutaneous metastasis also consisted of sarcomatoid components. Expression levels of many angiogenesis-related genes in the cutaneous metastasis were relatively higher than those of primary tumor. Chromosomal analysis of the KMRM-S2 showed cytogenetic abnormalities with hypertriploidy and translocation. In vitro proliferation assay showed the relatively higher resistance of KMRM-S2 against sorafenib. CONCLUSIONS: The sarcomatoid change and rhabdoid features of renal cell carcinoma with cytogenetic hyperploidy might be associated with elevated expression of angiogenesis-related genes, which leads to resistance against tyrosine kinase inhibitor. The present study might contribute to discovering novel therapeutic targets for the treatment of patients with advanced renal cell carcinoma resistant to tyrosine kinase inhibitor.

[The current clinical status of kidney cancers in patients with the VHL disease in Japan: a nationwide epidemiological survey].

PURPOSE: To understand the current clinical features of kidney cancers in patients with von Hippel-Lindau (VHL) disease in Japan. SUBJECT AND RESULT: We performed a nationwide epidemiological survey of patients with VHL disease using the epidemiology program for incurable disease by the Ministry of Health, Labour and Welfare. The content of the survey included age of onset of VHL disease, sex, residential area, treatment modalities, kidney function, ECOG performance status, and prognosis. Here, we report the results of kidney cancer. The incidence rate of kidney cancer in VHL disease in Japan is 50.3% (206/409). Males and females are equally affected. The mean age of onset is 37.8 + 0.92 years. The median age of onset is 35 years. The ages of onset are distributed between 15 and 75 years. The mostly affected age of onset is between 20 and 50 years. The incidence rate of patients with metastasis is 11.1% (23/206). The most common site for metastasis is the lung (60%, 14/23). Due to multiple numbers of tumors at initial diagnosis and the metachronous development of tumors, patients received treatment on multiple occasions (mean 1.6 times), including partial nephrectomy (46%), total nephrectomy (31%) or radiofrequency ablation (14%) up to 6 times. The multiple treatments resulted in deterioration of the kidney function, causing chronic dialyses in 7 cases (3%). The ECOG performance status was scored as more than 1 in 42% of patients. The ten-year survival rate in VHL patients with kidney cancer was 94%, which is relatively high compared with that survival rates in sporadic kidney cancers. CONCLUSION: The current study indicates that the age of onset of kidney cancers in VHL disease is relatively young, and kidney cancers have features of metachronous development. The clinical features of kidney cancer developed in VHL disease among Japanese population are very similar with those in European countries. Multiple treatments result in deterioration of the kidney function.

SNRPE is involved in cell proliferation and progression of high-grade prostate cancer through the regulation of androgen receptor expression.

Clinically high-grade prostate cancers (PC) with high Gleason scores of 8-10 exhibit rapid growth and are more likely to spread beyond the prostate. These cancer types demonstrate a poor response to androgen deprivation therapy and eventually acquire a castration-resistant phenotype. To identify novel molecular cancer drug targets, we previously analyzed the gene expression profiles of high-grade PC using a cDNA microarray combined with laser microbeam microdissection and found a number of genes that are transactivated in high-grade PC. Among these genes, we report the identification of a novel molecular target, small nuclear ribonucleoprotein polypeptide E (SNRPE). Semi-quantitative RT-PCR confirmed that SNRPE is overexpressed in high-grade PC cells compared with normal prostatic epithelial cells. Knockdown of SNRPE expression by short interfering RNA (siRNA) resulted in the marked suppression of PC cell proliferation. By contrast, SNRPE overexpression promoted PC cell proliferation, indicating its oncogenic effects. Furthermore, we demonstrated that SNRPE regulates androgen receptor (AR) mRNA expression in PC cells. Knockdown of SNRPE expression by siRNA resulted in the marked suppression of AR and its downstream target genes at the mRNA level. We suggest that the regulation of AR expression by SNRPE is essential for cell proliferation and progression of high-grade PC and that it may be a novel molecular target for cancer drugs.

Comparison between intravesical and oral administration of 5-aminolevulinic acid in the clinical benefit of photodynamic diagnosis for nonmuscle invasive bladder cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Granulocyte-colony stimulating factor producing squamous cell carcinoma of the renal pelvis: a case report].

We report a case of granulocyte-colony stimulating factor (G-CSF)-producing squamous cell carcinoma of the renal pelvis. A 71‒year-old woman presented with gross hematuria and leucocytosis of 21,300/mm3 (neutrophil : 86%) in the peripheral blood, but with no focus of infection. Right renal pelvic mass was found at a nearby hospital and she was referred to our hospital for examination and treatment. We performed right nephroureterectomy for a right renal pelvic tumor. Hematoxylin-eosin staining revealed squamous cell carcinoma of the renal pelvis and tumor cells stained strongly positive for G-CSF. According to these histopathological findings, we diagnosed this case as G-CSF-producing squamous cell carcinoma of the renal pelvis. She is presently alive without any new recurrent lesions for 12 months.

Pathobiological influence of a radiofrequency ablation system.

PURPOSE: The objective of this study was to optimize the least invasive technique of radiofrequency ablation (RFA) for the degenerated renal parenchyma and to develop a novel RFA system. MATERIALS AND METHODS: Tissue temperature and pathological degeneration were investigated at regular time intervals and distances from the RFA needle electrode in the renal parenchyma of the pig kidney. We also examined whether interruption of the renal artery or irrigation in the renal pelvis had an influence on the therapeutic effects. RESULTS: Pathological investigations showed a core necrotic area surrounded by an ischemic layer around the needle electrode. Interestingly, interruption of the renal artery and irrigation in the renal pelvis markedly enhanced the degeneration of the parenchyma. Especially the electric conductivity of irrigation solutions in the renal pelvis influenced the therapeutic effect. In this novel system which retains the flow of electricity between the 2 electrodes and maintains the electric power at a constant wattage, a marked therapeutic effect was observed between the 2 electrodes rather than on their outsides, and this was not influenced by renal artery interruption and/or renal parenchyma cooling. CONCLUSIONS: This novel RFA system may contribute to more effective and highly reproducible therapeutic results.

[Clinical experience with transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD)].

PURPOSE: 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. MATERIALS AND METHODS: 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). CONCLUSION: 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.

Regulation of 5-aminolevulinic acid-mediated protoporphyrin IX accumulation in human urothelial carcinomas.

PURPOSE: The purpose of this study was to clarify the regulatory mechanism of protoporphyrin IX (PpIX) synthesis mediated by 5-aminolevulinic acid (ALA) in human urothelial carcinoma (UC), leading to improved accuracy in photodynamic diagnosis and therapy using ALA. EXPERIMENTAL DESIGN: PpIX accumulation in cultured UC cells after incubation for 1-5 h with 0.5-5 mM ALA was analyzed by fluorescence analysis using fluorescence microscopy and flow cytometry technique. RESULTS: PpIX fluorescence mediated by ALA was increased, and the intensity of PpIX fluorescence was time-dependently increased in UC cells compared to noncancerous cells. The distribution of endogenous PpIX fluorescence primarily coincided with mitochondria, and then increased at a specific perinuclear region in the cells during the time of incubation. The ALA-mediated PpIX synthesis in UC cells was suppressed by beta-alanine, an inhibitor of beta-transporters of cell membrane, and carbonylcyanide p-trifluoromethoxyphenyl hydrazone, an uncoupler of mitochondrial oxidative phosphorylation. In contrast, the ALA-mediated PpIX accumulation was increased by deferoxamine, an iron chelator, manganese and nitric oxide, which is contributed to PpIX metabolism by inhibiting ferrochelatase activity, generated by a nitric oxide-generating reagent NOC-18. As observed above, ALA-mediated PpIX synthesis in human UC cells was regulated by the process of ALA uptake, ALA conversion to PpIX and metabolism of accumulated PpIX to heme. CONCLUSIONS: This shows that the suppression of ferrochelatase increased PpIX accumulation in UC cells using small amount of ALA, thus leading to an improved clinical practicability of photodynamic diagnosis and therapy.

[Successful response of reccurent adult wilms' tumor to multiagent chemotherapy].

We report a case of successful response of lung metastases of reccurent adult Wilms' tumor by multiagent chemotherapy. The patient was a 19-year-old woman who had undergone left radical nephrectomy and adjuvant chemotherapy (actinomycin D, vincristine) for stageadult Wilms' tumor when she was 16 years old. Coputed tomography (CT) revealed multiple lung metastases (right parietal pleura, left S10, right S10). We treated the patient with thoracoscopic partial resection of inferior lobe of lung. Then she received multiagent chemotherapy (vincristine, adriamycin, etoposide, cyclophosphamide). CT scan showed complete response of the lung metastases at 8 months.

[Experience in the treatment of eight cases of Fournier's gangrene].

Fournier's gangrene is a rare disease of rapidly progressive necrotising fasciitis of the genital, perineal and perianal regions and leads to sepsis and death. We report 8 cases of Fournier's gangrene treated at our hospital and affiliated hospitals from 1997 to 2007. There were seven males and one female in the series, and the age range was 23-89 years (mean age 56.6 years). Four patients among them had diabetes mellitus. We rescued all patients by broad-spectrum antibacterial chemotherapy and debridement. Good management should be based on broad-spectrum antibacterial chemotherapy, debridement and intensive care.

Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells.

Heat shock protein 27 (Hsp27) is a cytoprotective chaperone that is phosphoactivated during cell stress that prevents aggregation and/or regulate activity and degradation of certain client proteins. Recent evidence suggests that Hsp27 may be involved in tumor progression and the development of treatment resistance in various tumors, including bladder cancer. The purpose of this study was to examine, both in vitro and in vivo, the effects of overexpression of Hsp27 and, correspondingly, the down-regulation of Hsp27 using small interfering (si) RNA and OGX-427, a second-generation antisense oligonucleotide targeting Hsp27. Hsp27 overexpression increased UMUC-3 cell growth and resistance to paclitaxel. Both OGX-427 and Hsp27 siRNA decreased Hsp27 protein and mRNA levels by >90% in a dose- and sequence-specific manner in human bladder cancer UMUC-3 cells. OGX-427 or Hsp27 siRNA treatment induced apoptosis and enhanced sensitivity to paclitaxel in UMUC-3 cells. In vivo, OGX-427 significantly inhibited tumor growth in mice, enhanced sensitivity to paclitaxel, and induced significantly higher levels of apoptosis compared with xenografts treated with control oligonucleotides. Collectively, these findings suggest that Hsp27 knockdown with OGX-427 and combined therapy with paclitaxel could be a novel strategy to inhibit the progression of bladder cancer.

[Clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis using fluorescence cystoscopy for bladder cancer].

PURPOSE: To report our clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis of bladder cancer and to assess any side-effects of the diagnostic method. MATERIALS AND METHODS: Photodynamic diagnosis was performed in 18 patients of which 14 were men and 4 women with a median age of 71 years (range 44-84), 7 were primary cases and 11 were recurrent cases with bladder cancer. Two to two and half hours prior to endoscopy 1.5 g 5-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. Under white and fluorescence light guidance, tumor locations were recorded, cold cup biopsies were taken and tumors were resected. The levels in images of the 5-aminolevulinic acid-induced fluorescence were compared with the pathological results. The area under the receiver operative characteristic (ROC) curve (AUC) in blue light endoscopy was also compared with that in white light endoscopy. RESULTS: Among the 129 specimens obtained by transurethral biopsy 45 were obtained from polypoid lesion and 84 from non-polypoid lesion, and among the 76 malignant diseases 36 were obtained from polypoid lesion and 40 from non-polypoid lesion (including 19 carcinoma in situ), and 21 patients with dysplasia were detected pathologically, with a sensitivity of 89.5% and specificity of 58.5% with a predictive accuracy of 77.0%. The AUC in blue light endoscopy was more than that in white light endoscopy in not only all cases (p = 0.010) but also in cases with non-polypoid lesion (p = 0.007) and recurrent cases (p = 0.002). Duration of 5-ALA instillation with a median time of 80 (range 30-150) min. did not seem to affect the accuracy of photodynamic diagnosis. Procedures were well tolerated by all patients with mild bladder irritability but no systemic side effect. CONCLUSION: Photodynamic diagnosis with intravesically applied 5-ALA is more effective than observation by conventional cystoscopy in detecting bladder cancer without additional risk or complication, and is expected to become a golden standard in the detection program.

[Conservative therapy by percutaneous radiofrequency ablation of renal cell carcinomas--therapeutic experiments of four patients with seven renal tumors--].

We report 7 renal cell carcinomas in 4 patients treated by percutaneous image-guided radiofrequency ablation (RFA). The mean age of the patients was 59 years (male: 2, female: 2). All 4 were imperative cases. Two patients (5 tumor) had hereditary multiple renal cell carcinomas with von Hippel-Lindau (VHL) disease. The other two patients had sporadic renal cell carcinomas. RFA was performed guided by computed tomography under conscious sedation with local anesthetics. The mean size of the treated tumors was 4.5 (1.8-8.1) cm. Impedance-regulated RF energy from a generator at 94 (45-130) watts was applied at 11 (8-14) min intervals. The average procedure time was 91 (45-165) minutes. The maximum tissue temperature reached 82 (56-91) degrees C immediately after ablation. Three of the 7 lesions (42.9 %) were locally well controlled during the mean follow-up period of 6.3 (4-9) months. The two patients with VHL disease developed visceral metastasis after There were no major complications. Minor complications encountered included flank pain, nausea, perinephritic hematoma and fever. Although percutaneous image-guided RFA showed limited success in large or central renal tumors, the therapy against small exophytic renal tumors would be well tolerable and successful.

Genetic changes in localized prostate cancer of Japanese patients shown by comparative genomic hybridization.

To search for additional amplification and deletion sites that may serve as a starting point for the discovery of new oncogenes or tumor suppressor genes, 30 Japanese localized prostate cancers were analyzed by comparative genomic hybridization (CGH) in this study. CGH was used to search for changes in DNA sequence copy-number in a series of 30 primary prostate adenocarcinomas, consisting of 22 cases of pT2N0 (organ confined; without capsular invasion) and 8 cases of pT3N0 (with capsular invasion), removed by radical prostatectomy. CGH revealed that the shortest regions of overlap (SRO) of gains in pT2N0 were at 8q22.2 approximately q24.2, 11q13.1 approximately q14.1, and 12q23 approximately q24.2, whereas the SRO of losses were seen at 8p23.3 approximately p22, 13q21.2 approximately p22, and 18q21 approximately q22. The SRO of gains in pT3N0 were noted at 5q32 approximately q34, 8q22.3 approximately q24.1, 11q14.1 approximately q22.3, and 12q22 approximately q24.2, whereas the SRO of losses were seen at 18q21.2 approximately q23. These results suggest that gains or losses of DNA in these regions are important for prostate cancer progression. The detection of the SRO may serve as a starting point to discover novel oncogenes and tumor suppressor genes involved in prostate cancer progression.

Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma.

BACKGROUND: To identify organ-specific, metastasis-related factors that can be used to predict the development and location of metastasis of clear cell renal cell carcinoma (CRCC), the authors assessed the angiogenesis and the expression of angiogenesis-related genes in primary and metastatic tumors. METHODS: They evaluated intratumoral microvessel density (MVD) by immunohistochemical staining, assessed the expression of angiogenesis-related genes by mRNA in situ hybridization, and determined the clinicopathologic characteristics of 92 archival specimens of primary and metastatic CRCCs from 54 patients. All 38 metastatic tumor specimens were resected from 24 patients. RESULTS: The pathologic stage (P=0.026) of the primary tumor specimen was an important predictor for metastasis, as were MVD (P=0.000025) and the ratio of matrix metalloproteinases (MMPs) to E-cadherin (M/E ratio; P=0.000041). In addition, primary tumor specimens resected from patients with metastatic CRCCs had high MVD, high levels of MMP-2 expression, and a high M/E ratio (P <0.05). Relative to the primary tumors, the metastatic tumors also had high MVD, overexpression of basic fibroblast growth factor, vascular endothelial growth factor, interleukin-8, MMPs, and a high M/E ratio (P <0.05). Multivariate analysis revealed that MVD and the M/E ratio in the primary tumor were independent prognostic factors for metastasis (P=0.049 and P=0.001, respectively). Furthermore, the M/E ratio in metastatic tumor specimens resected from the lung and lymph node was an independent prognostic factor for metastasis (P=0.01823 and P=0.03950, respectively). CONCLUSIONS: The current study indicated that angiogenesis and M/E ratio were specific predictors for metastases of RCC, especially to the lung or lymph node. Therefore, MMPs and E-cadherin could be relevant targets for novel therapeutic strategies to control or prevent the metastasis of RCC.