[Show abstract][Hide abstract] ABSTRACT: Aquaporin 1 (AQP1) is a water channel expressed in many epithelial tissues and endothelium, including the proximal nephron of the kidney.
We measured AQP1 expression in primary renal cell carcinomas (RCCs) and evaluated its significance and prognostic utility.
We examined AQP1 expression in 559 sporadic renal tumors as well as in 43 normal kidney tissue samples and collected clinicopathologic and prognostic data.
AQP1 expression was measured by using real-time quantitative polymerase chain reaction (PCR).
All normal kidney samples presented substantial AQP1 expression. Among tumor subtypes, AQP1 expression was significantly higher in clear-cell and papillary RCCs, whereas it was lower in chromophobe RCCs, oncocytomas, and collecting-duct carcinomas. In clear-cell RCC, AQP1 was significantly higher in patients without symptomatic presentation or whose tumors were smaller, lower grade, or either lower stage or lacking in microvascular invasion. Von Hippel-Lindau (VHL) tumor suppressor gene mutational status did not affect expression level. Cox univariate and multivariate analyses strongly associated high AQP1 expression with better prognosis in cancer-specific and cancer-free survival tests in all patient cohorts, as well as in cancer-specific survival in a cohort of patients with advanced metastatic RCC. The time-dependent receiver operation characteristic (ROC) analyses, combined with logistic regression models, revealed that the addition of the AQP1 parameter to the University of California Los Angeles Integrated Staging System (UISS) prognostic score can improve the accuracy of predictions of both cancer death and recurrence for all patient cohorts as well as of cancer death for advanced cases within a 5-yr follow-up period in clear-cell RCC. High AQP1 expression was also associated with better outcome in a univariate cancer-specific survival test in papillary RCCs.
AQP1 shows RCC subtype-specific expression, and its expression level provides useful prognostic information for patients with clear-cell RCC.
European Urology 11/2008; 56(4):690-8. · 10.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Renal cell carcinomas (RCCs) are morphologically and genetically heterogeneous tumors and present diverse clinical courses. We developed a scoring system using levels of gene expression to predict the outcome for clear cell RCC patients. We selected differentially expressed genes from the DNA microarray data of 27 clear cell RCCs; 16 were metastasis phenotypes and 11 were not. We compared the selected gene set with previously published data and identified 33 overlapping genes closely associated with patient outcome. We selected the 12 top-ranked genes and confirmed the level of expression using quantitative reverse transcriptase PCR. Multivariate Cox analysis revealed that 3 genes-vascular cell adhesion molecule 1 (VCAM1), endothelin receptor type B (EDNRB), and regulator of G-protein signaling 5 (RGS5)-were the most tightly associated with cancer-specific survival and that higher expression of the 3 genes correlated with better outcome. A formula for an outcome predictor was generated from integration of the measurements of the expression levels of the 3 genes. Multivariate Cox models combined with a split-sample cross-validation method in a cohort of 386 clear cell RCC patients demonstrated that the derived score for outcome prediction was an independent predictor in cancer-specific survival tests. The accuracy of the prediction of cancer death after nephrectomy was improved by the inclusion of this score in receiver operating characteristic analysis from multivariate logistic regression models, suggesting that a scoring system based on the expression levels of these 3 genes is useful in the prediction of survival for patients with clear cell RCC.
International Journal of Cancer 10/2008; 123(5):1126-32. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The finding of an unexplainable persistent low level of serum human chorionic gonadotropin in the management of testicular cancer sometimes misleads physicians. To avoid unnecessary treatment we suggest a new classification and algorithm for testicular germ cell tumors to discriminate real human chorionic gonadotropin from false-positive results.
A total of 24 patients who seemed to have no cancer with an increased but low level of serum human chorionic gonadotropin were evaluated. They included 17 patients with testicular germ cell tumors and 7 with no evidence of germ cell tumor. In these cases parallel serum and urine human chorionic gonadotropin were measured with the same assay and serum human chorionic gonadotropin was measured with a different assay. False-positive cases were identified by critical criteria according to the classification of gestational trophoblastic disease.
Of 17 cases of testicular germ cell tumor 12 were classified as false-positive and 5 were classified as true-positive. All of the other 7 cases with no evidence of cancer were classified as phantom cases. Of the 7 patients with phantom human chorionic gonadotropin who had a history of germ cell tumor unnecessary treatments had been performed in 3. After the discrimination was implemented no unnecessary treatments or intensive examinations were performed.
Appropriate management is possible based on a good understanding of the causes of low human chorionic gonadotropin. Our algorithm for classifying low human chorionic gonadotropin may help avoid unnecessary treatment in these patients.
The Journal of urology 04/2008; 179(3):930-4; discussion 934-5. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: About 10-40% of testicular germ cell tumours (TGCTs) have been reported to have activating c-kit gene mutations. A European study group has reported that most bilateral TGCTs from European patients have c-kit mutations at codon 816, although few unilateral cases harbour the mutations. This implies that the presence of a c-kit mutation in a unilateral TGCT predicts the development of TGCT in the contralateral testis (bilateral disease). However, since little is known about on c-kit gene mutational frequencies in bilateral TGCTs from patients of Asian origin, we examined 12 bilateral TGCTs from seven Japanese patients, along with 39 unilateral TGCTs from Japanese patients, for the presence of c-kit mutations. We analyzed c-kit exons 11 and 17 by PCR followed by direct sequencing, and also analyzed the hotspot mutations at codon 816 by loop-hybrid mobility shift assay, a sensitive PCR-based method. We found c-kit mutations in seven of 39 (18%) unilateral TGCTs: two of the seven mutations were in exon 11 and the others, including four point mutations at codon 816, were in exon 17. No mutations, however, were observed in bilateral TGCTs. Thus, the presence of c-kit gene mutations in TGCTs may not be associated with bilateral diseases, at least in Japan.
Cancer Letters 02/2008; 259(1):119-26. · 5.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after treatment with the demethylating agent 5-azacytidine. This enabled us to identify HAI-2/SPINT2 as a novel epigenetically inactivated candidate RCC TSG. To identify further candidate TSGs, we undertook bioinformatic and molecular genetic evaluation of a further 60 genes differentially expressed after demethylation. In addition to HAI-2/SPINT2, four genes (PLAU, CDH1, IGFB3 and MT1G) had previously been shown to undergo promoter methylation in RCC. After bioinformatic prioritisation, expression and/or methylation analysis of RCC cell lines+/-primary tumours was performed for 34 genes. KRT19 and CXCL16 were methylated in RCC cell lines and primary RCC; however, 22 genes were differentially expressed after demethylation but did not show primary tumour-specific methylation (methylated in normal tissue (n=1); methylated only in RCC cell lines (n=9) and not methylated in RCC cell lines (n=12)). Re-expression of CXCL16 reduced growth of an RCC cell line in vitro. In a summary, a functional epigenomic analysis of four RCC cell lines using microarrays representing 11 000 human genes yielded both known and novel candidate TSGs epigenetically inactivated in RCC, suggesting that this is valid strategy for the identification of novel TSGs and biomarkers.
British Journal of Cancer 02/2008; 98(2):496-501. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 9-cm renal artery aneurysm near the primary bifurcation of the left main renal artery, which caused ischemic change and a small infarction in left renal anterior segment, was treated with staged coil packing of the aneurysm. Initial embolization with deployments of twelve 0.035-in. coils resulted in partial occlusion of the aneurysm and thickening aneurymal wall. Three months later after the initial embolization, packing of twenty-six 0.018-in. detachable coils achieved in occlusion of the aneurysm preserving contrast flow in near the neck and the posterior segmental artery. Both 3- and 1-year follow-up computed tomographic images, after the second session, confirmed no contrast flow in the aneurysm with restored contrast flow in the left kidney. This case indicates that staged coil embolization may be alternative to nephrectomy in patients with extraparenchymal giant renal artery aneurysms.
[Show abstract][Hide abstract] ABSTRACT: The toxicity of platinum-based chemotherapies is a common problem for patients with advanced urothelial carcinoma. We performed a prospective study to assess the efficacy and safety of the combination chemotherapy of methotrexate, epirubicin and nedaplatin (MEN) as first-line treatment in patients with advanced urothelial carcinoma. Eligible patients had pathologically proven measurable unresectable or metastatic urothelial carcinoma. Between February 2003 and February 2006, 11 patients with a mean age of 70 years were treated every 3 weeks with methotrexate (30 mg/m(2) on day 1) and epirubicin (50 mg/m(2) on day 1) and nedaplatin (80 mg/m(2) on day 2). A median of 2.6 cycles were administered. None of the 11 patients achieved a complete response (CR), but 6 patients (55%) achieved a partial response (PR) with a median duration of response of 10 months, and no responses occurred in 4 patients. The median survival time was 11 months. Grade 4 hematological toxicities included neutropenia in 1 case (9%), thrombocytopenia in 2 cases (19%) and anemia in 1 case (9%). None of the 11 patients had febrile neutropenic episodes, and no toxic death was observed. Our results suggest that the combination chemotherapy of methotrexate, epirubicin and nedaplatin (MEN) was effective and acceptable treatment in patients with advanced urothelial carcinoma.
Gan to kagaku ryoho. Cancer & chemotherapy 06/2007; 34(5):739-43.
[Show abstract][Hide abstract] ABSTRACT: The most frequent cause of familial clear cell renal cell carcinoma (RCC) is von Hippel-Lindau disease and the VHL tumor suppressor gene (TSG) is inactivated in most sporadic clear cell RCC. Although there is relatively little information on the mechanisms of tumorigenesis of clear cell RCC without VHL inactivation, a subset of familial cases harbors a balanced constitutional chromosome 3 translocation. To date nine different chromosome 3 translocations have been associated with familial or multicentric clear cell RCC; and in three cases chromosome 6 was also involved. To identify candidate genes for renal tumorigenesis we characterized a constitutional translocation, t(3;6)(q22;q16.1) associated with multicentric RCC without evidence of VHL target gene dysregulation. Analysis of breakpoint sequences revealed a 1.3-kb deletion on chromosome 6 within the intron of a 2 exon predicted gene (NT_007299.434). However, RT-PCR analysis failed to detect the expression of this gene in lymphoblast, fibroblast, or kidney tumor cell lines. No known genes were disrupted by the translocation breakpoints but several candidate TSGs (e.g., EPHB1, EPHA7, PPP2R3A RNF184, and STAG1) map within close proximity to the breakpoints.
Genes Chromosomes and Cancer 05/2007; 46(4):311-7. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Birt-Hogg-Dubé (BHD) gene is responsible for BHD syndrome, a rare autosomal dominant disease, characterized by benign hair follicle tumours, spontaneous pneumothorax and renal neoplasms with diverse histology. To elucidate its involvement in the development of renal neoplasms, we examined a total of 100 sporadic renal tumours with various histological subtypes for BHD mutation by SSCP-sequencing analyses. We found one germline insertion mutation in the C8 hotspot of exon 11 (c.1733insC), which is known to have a strong association with renal tumour occurrence. The germline-mutated patient suffered from solitary renal cell carcinoma (RCC) but did not have any other BHD manifestations or family history. The tumour revealed heterogeneous cytomorphology, mainly a mixture of eosinophilic and focally clear cells with tubulopapillary architecture. In this tumour, both BHD alleles were inactivated by germline mutation concomitant with loss of heterozygosity, and the amount of BHD mRNA detected by real-time quantitative PCR (RQ-PCR) was very low. Renal tumour subtype/nephron segment-specific gene expression detected by RQ-PCR demonstrated that the tumour expressed relatively high amounts of alpha-methylacyl-CoA racemase (AMACR) and the KIT oncogene, but relatively low amounts of carbonic anhydrase IX (CA9), aquaporin 1 (AQP1), claudin 7 (CLDN7), parvalbumin (PVALB), chloride channel Kb (CLCNKB) and 11-beta-hydroxysteroid dehydrogenase 2 (HSD11B2), suggesting diverse mRNA signatures. Further clustering analysis of 88 renal tumours based on expression of these eight genes sub-classified the tumour as close to oncocytomas and chromophobe RCCs, which are considered distal nephron-associated tumours. These data suggest that somatic mutation of BHD is relatively rare in Japanese patients. The BHD-mutated RCC identified in this study, which exhibits heterogeneous biological features in both morphology and gene expression signatures, seems to deviate from our current understanding of renal tumour classification.
The Journal of Pathology 05/2007; 211(5):524-31. · 7.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are three kind of assays related to human chorionic gonadotropin (hCG) : free beta hCG (fbetahCG), which is the standard assay for the management of testicular cancer in Japan, intact hCG (ihCG), which detects hCG only, and total hCG (thCG), which detects hCG free-betahCG and possibly other degradation products. We examined the efficacy of thCG assay for the management of testicular cancer.
The simultaneous determination of serum thCG (DPC IMMULYZE hCG), ihCG (hCG [SRL] or (ECLusys hCG STAT)) and fbetahCG (BALL ELSA F-betahCG) was performed in 21 patients with germ-cell tumor (18 gonadal tumors and 3 extra-gonadal tumors; 8 seminomatous germ-cell tumors [SGCTs] and 13 non-seminomatous germ-cell tumors [NSGCTs]) during treatment. We examined the correlation, diagnostic sensitivity and efficacy of management with three assays.
There was no correlation between fbetahCG and the other two assays in SGCTs, while there was good correlation among the three assays in NSGCTs. In SGCTs, diagnostic sensitivity was higher in thCG, whereas in NSGCTs diagnostic sensitivity was higher in thCG and ihCG. In 7 patients whose hCG assays were positive at diagnosis, serum fbetahCG became negative first during treatment in all patients, but serum thCG and ihCG became negative after about 4 weeks.
In this study, thCG assay was significant for the diagnosis and management of patients with testicular cancer especially NSGCTs compared with fbetahCG assay. This study revealed that thCG assay is appropriate as the standard assay in NSGCTs.
Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 02/2007; 98(1):23-9.
[Show abstract][Hide abstract] ABSTRACT: We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC). To further evaluate the correlation between ADFP expression levels and clinicopathologic characteristics and patient outcome, we retrospectively examined patients with clear cell RCC.
A series of 432 consecutive patients with sporadic clear cell RCC who underwent nephrectomy between March 1986 and June 2004 were enrolled in the study. ADFP expression levels in the primary tumors and in 18 metastases were measured by real-time quantitative PCR. The clinicopathologic and prognostic data were collected, as well as the von Hippel-Lindau disease (VHL) gene alteration status in selected cases.
ADFP expression was apparently high in cases without a symptomatic presentation, as well as in cases of low-stage, low-grade, or VHL alteration-positive clear cell RCC, whereas it was down-regulated in undifferentiated tumors with a spindle/pleomorphic component or metastatic lesions. Univariate analyses showed that high ADFP expression was associated with better cancer-specific survival and cancer-free survival. Further Cox multivariate analyses combined with the split-sample validation method showed that ADFP expression still remains an independent predictor for cancer-specific survival in all tumor stages and in advanced metastatic cases, whereas the predictive value of ADFP expression for cancer recurrence is rather weak.
The ADFP expression may represent the tumor differentiation status, and the detection of the expression levels provides useful prognostic information for cancer-specific survival in patients with clear cell RCC.
Clinical Cancer Research 02/2007; 13(1):152-60. · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vascular cell adhesion molecule 1 (VCAM1) is a cell surface glycoprotein implicated in various pathophysiologic conditions. We measured VCAM1 expression levels in tumor tissues and evaluated its significance and prognostic use in renal cell carcinoma (RCC).
We used real-time quantitative PCR to examine the VCAM1 expression levels of a total of 485 sporadic renal tumors, including 429 clear cell, 21 papillary, 17 chromophobe, 11 oncocytomas, and 7 collecting duct carcinomas. We retrospectively examined the relationship of this expression to various clinicopathologic variables and the von Hippel-Lindau alteration status. We evaluated its significance with respect to patient survival rates using the Cox regression model combined with the split-sample method.
Compared with normal kidney samples (n = 43), VCAM1 was significantly up-regulated in clear cell RCC and papillary RCC, whereas it was down-regulated in chromophobe RCC and oncocytoma. In clear cell RCC, VCAM1 expression levels were apparently high in patients asymptomatic at presentation and in patients with small tumor size, low-stage, low-grade, microvascular invasion-negative, and von Hippel-Lindau alteration-positive tumors. Univariate analyses showed that VCAM1 high expression is strongly associated with better outcomes in clear cell and papillary RCCs. Further, Cox multivariate analysis models combined with the split-sample method revealed that this association is significant only in cancer-free survival for patients with clear cell RCC after curative surgical resection.
VCAM1 expression levels were found to be histologically subtype specific in renal tumors. Determination of the VCAM1 expression level as a biomarker can provide useful prognostic information for patients with clear cell RCC.
Clinical Cancer Research 01/2007; 12(24):7339-46. · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 32-year-old male consulted a hospital with a complaint of left scrotal swelling. Serum hCGbeta and LDH levels were elevated and computed tomography demonstrated a suspicious small lymphadenopathy in the paraaortic region. Left inguinal orchiectomy was performed. Histological examination demonstrated seminoma. We diagnosed the disease as clinical stage 2A and the patient received 2 courses of chemotherapy with cisplatin, etoposide and bleomycin. After this therapy, the small lymphadenopathy in the paraaortic region did not decrease in size. We considered this lesion a vessel or connective tissue. Although he achieved clinical complete remission and serum LDH level was normalized, the serum hCGbeta level remained low level positive. Urinary hCGbeta level after chemotherapy was below the threshold of detectability. We measured the serum from this patient as well as control sera by two- and four-fold dilution with a diluent comprised of mouse serum as a heterophilic antibody-blocking agent. The serum hCGbeta level of this patient was obviously decreased; in contrast, control sera were decreased in parallel. The serum hCGbeta level of this patient remained low level positive without recurrence for 8 months after chemotherapy. These results strongly suggested that low level of positivity for serum hCGbea in this case was a false positive finding. We consider the measurement of urinary hCGbeta and dilution measurement using a heterophilic antibody-blocking agent to be useful methods of distinguishing false positive findings for serum hCGbeta.
Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 10/2006; 97(6):804-8.
[Show abstract][Hide abstract] ABSTRACT: Decrease in serum prostate specific antigen (PSA) concentration is inevitably associated with antiandrogen therapy for benign prostatic hyperplasia (BPH), and might mask the presence of prostate cancer or delay its diagnosis. To determine the appropriate timepoint for determination of correct PSA value, we sequentially measured serum PSA and testosterone levels after discontinuation of antiandrogen therapy for BPH. With informed consent, 12 patients (72.8 +/- 12.2* years old) with BPH were treated with allylestrenol 50 mg/day for 4 months. Serum testosterone and PSA concentrations were determined before and just after treatment, as well as every month after treatment up to 3 months. After treatment with allylestrenol for 4 months, mean serum testosterone and PSA levels were significantly decreased from 408 +/- 136* to 87.9 +/- 76.2* ng/dl, and from 2.81 +/- 0.87* to 2.04 +/- 0.82* ng/ml, respectively. The mean serum PSA level recovered to the pretreatment level within 2 months and mean serum testosterone concentration within one month after discontinuation of administration. In conclusion, during treatment of BPH with antiandrogen allylestrenol, a two-month washout is adequate for determination of correct PSA value (*: M +/- SD).
[Show abstract][Hide abstract] ABSTRACT: To investigate how urinary frequency and incontinence affect the patient's subjective quality of life (QOL) and whether an improvement in objective findings by medical treatment affects his/her subjective QOL, a voiding diary using the King's Health Questionnaire (KHQ) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was delivered to patients with urinary frequency and/or incontinence before and after treatment with propiverine hydrochloride for 8 weeks. Sixty-eight patients completed the diary and the questionnaires. Objective symptoms decreased significantly with respect to the mean frequency of urination and to the mean incidence of urinary incontinence. The KHQ and ICIQ-SF scores improved significantly with respect to all domains except personal relationships in the KHQ. In the KHQ, furthermore, a significant correlation was found between decreased incidence of urinary incontinence and improvement in role limitations and between decreased incidence of urinary incontinence and improvement in emotional problems. In the ICIQ-SF, a significant correlation was found between decreased incidence of urinary frequency and subjective improvement in quantity of leakage, between decreased incidence of urinary frequency and improvement in subjective QOL scores, between decreased incidence of urinary frequency and improvement in the total ICIQ-SF score, and between decreased incidence of urinary incontinence and improvement in subjective QOL scores. Thirty-two episodes of adverse reactions were observed. None of them were serious. These results suggest that an improvement in objective symptoms with propiverine hydrochloride favorably improves subjective QOL of the patient, and provide further evidence about the safety and efficacy of propiverine hydrochloride.
[Show abstract][Hide abstract] ABSTRACT: Germline mutations of the VHL gene are responsible for VHL. Approximately 70% of VHL families display small intragenic mutations detectable by sequencing, whereas partial- or whole-gene deletions have been described in the majority of the remaining families. For such large deletions, complex genetic techniques other than sequencing might have to be used. In this study, we describe an RQ-PCR assay with TaqMan fluorescent probes to detect germline VHL deletions. The RQ-PCR primer/probe sets were designed for the three VHL coding exons as well as for the 5' promoter and 3' untranslated regions. The RQ-PCR assay for 30 normal and 10 known VHL deletion control samples demonstrated high sensitivity and specificity. We then screened 29 individuals from 19 classical VHL families (16 type 1, 2 type 2A, and one type 2B) and one PHEO family, as well as four solitary suspected cases, none displaying any sequence changes, for VHL deletions by the RQ-PCR assay. We detected germline deletions in 17 (89%) classical families including 15 type 1, one type 2A, and one type 2B. We also identified two mutation carriers and two non-carriers in our family cohort. The one PHEO family and four solitary cases did not display any deletion patterns. These findings indicated that the TaqMan-based RQ-PCR assay is a simple and potent technique for the rapid, sensitive, and specific investigation of VHL genetic diagnoses that could be used profitably before more complex large-deletion detection techniques.
Cancer Science 06/2006; 97(5):400-5. · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is well known that inactivation of von Hippel-Lindau (VHL) gene predisposes for human clear cell renal carcinoma (CCRC). However, details about critical roles of VHL inactivation during tumorigenesis are still unknown. MET protein is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), which regulates cell growth, cell morphology, and cell motility. We showed that MET protein overexpressed in CCRC cells was phosphorylated without HGF/SF. This constitutive phosphorylation of MET protein in CCRC cells was inhibited by the rescue of exogenous wild-type VHL gene without a decrease in expression level of MET protein. Interestingly, wild-type VHL gene suppressed the phosphorylation of MET protein only under high cell density conditions. Additionally, MET protein activated by the inactivation of VHL gene modified cell adherence, including N-cadherin and beta-catenin. When activation of MET protein in CCRC cells was inhibited by the MET inhibitor K252a, the growth of CCRC cells in vitro and the tumorigenesis induced by CCRC cells in nude mice were suppressed. From these results, we concluded that inactivation of VHL gene induced constitutive phosphorylation of MET protein and modified intercellular adherence structure to trigger the cell growth released from contact inhibition, finally resulting in tumorigenesis. This is one of the mechanisms of CCRC oncogenesis, and MET protein has potential as a molecular target for novel CCRC therapies.
Cancer Research 05/2006; 66(7):3699-705. · 8.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pathological characteristics, patient outcome, and preoperative examinations of 16 cases (4.1%) of chromophobe renal cell carcinoma (RCC) observed among 389 patients with RCC treated at Yokohama City University Hospital and Yokohama City University Medical Center between 1991 and 2004 were analyzed. The age distribution was 16 to 74 years old (average age; 50.9 +/- 17.0). Pathologically, 14 patients had pure chromophobe RCC, and two patients had chromophobe RCC coexisting with aggressive pathological elements, that is, sarcomatoid change in one patient and collecting duct carcinoma in the other. The average tumor size was 7.1 +/- 4.1 cm. On preoperative imaging studies with enhanced computed tomography or angiography, all cases showed a hypovascular pattern. C-reactive protein (CRP) and immunosuppressive acidic protein (IAP) were increased specifically in the two cases coexisting with aggressive pathological elements. Fourteen cases showing pure chromophobe RCC did not metastases on preoperative examination. Thirteen cases were treated by nephrectomy, and another was treated by partial nephrectomy. To date there have been no recurrences during the 6 to 160 months postoperative follow-up. The patient with a mixture of chromophobe RCC and sarcomatoid change (pT3aN0M0) died of multiple lung metastases 18 months after nephrectomy. The patient showing a mixture of chromophobe RCC and collecting duct carcinoma demonstrated metastases to the paraaortic lymph nodes at preoperative examination (pT1bN2M0), and died of multiple lung and bone metastases and carcinomatous peritonitis 8 months after nephrectomy. The patients with pure chromophobe RCC had a favorable prognosis, but those with a mixed type including aggressive elements such as sarcomatoid change or collecting duct carcinoma, showed a poor clinical course. The increase in CRP or IAP could predict poor prognosis in such cases.
[Show abstract][Hide abstract] ABSTRACT: Although patients with prostate cancer with metastatic lesions initially respond to androgen ablation therapy, most patients ultimately develop a hormone-refractory state. Effective treatment for men with hormone-refractory prostate cancer (HRPC) has not been established. We performed a clinical study of docetaxel in HRPC patients, and evaluated its efficacy.
Nine patients with HRPC were administered 55 mg/m2 docetaxel, every 3 weeks, simultaneously with hormonal therapy, with a luteinizing hormone-releasing hormone analog, and daily oral dexamethasone. Change in serum prostate-specific antigen (PSA) was determined as the primary endpoint.
The mean age of the patients was 64 years (range, 49 to 76 years). Median follow-up time was 8.5 months (range, 5.3 to 16.7 months). In eight patients whose pretreatment serum PSA was elevated, six patients (75.0%) had a PSA decline of more than 50%, and four (50.0%) had a PSA decline of more than 75%. Median time to progression for all patients was 7.9 months (range, 0.0 to 11.6 months; 95% confidence interval [CI], 0.0 to 26.3). The median overall survival was 8.5 months (range, 5.3 to 16.7 months; 95% CI, 8.1 to 13.8). Four of six patients (66.7%) with pain before treatment obtained pain relief and were able to discontinue analgesic agents. This regimen was well tolerated. Grade 3 or 4 neutropenia or leukocytopenia without fever was seen in three patients (33.3%). Only one patient required administration of granulocyte-colony stimulating factor because of neutropenia. No other grade 3 or 4 toxicity was observed.
Docetaxel was an active agent in Japanese HRPC patients, and was well tolerated in this population. To establish its efficacy and safety in Japanese HRPC patients, a large-scale study in Japan is warranted.
International Journal of Clinical Oncology 07/2005; 10(3):182-6. · 1.73 Impact Factor