Androgen receptor expression is associated with adverse pathological features in ureteral but not in pelvicalyceal urothelial carcinomas of the upper urinary tract.

PURPOSE: This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC). METHODS: AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system (p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS. CONCLUSIONS: In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors.

Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids.

BACKGROUND: Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. METHODS: We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. RESULTS: HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. CONCLUSIONS: We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx.

Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma.

BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly elevated (⩾181.5 U l(-1)). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit. CONCLUSIONS: Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.

P16INK4A immunohistochemistry for detection of human papilloma virus-associated penile squamous cell carcinoma is superior to in-situ hybridization.

We evaluated p16INK4A as a reliable option to detect human papilloma virus (HPV) DNA in penile tumor specimens. Formalin-fixed paraffin embedded samples of 26 patients with penile cancer and another 18 cases with non-tumorigenic lesions were stained by three different widely used commercially available chromogenic in-situ hybridization assays high-risk HPV CISH Y1443 (Genpoint, DAKO), pan HPV CISH Y1404 (Genpoint, DAKO), INFORM HPV III (Ventana, Tucson, Arizona) and p16INK4A immunohistochemistry, then compared to the known gold standard polymerase chain reaction detecting HPV 16, 18, 31, and 33. Immunoreactivity for p16INK4A was evaluated by using a 4-tiered (0, 1, 2, and 3) pattern based system. 19 cases were positive for p16INK4A, 13 of which showed a continuous transepithelial staining (pattern 3). Pan HPV ISH showed positivity in 9 cases, high-risk HPV ISH in 7 cases and INFORM HPVIII ISH in 7 cases. p16INK4A IHC pattern 3 versus pattern 0, 1 and 2 exhibited a specificity and positive predictive value of 100 percent, with a sensitivity and negative predictive value of 72 and 62 percent, respectively, which was much better than all HPV in-situ hybridization methods referred to polymerase chain reaction. p16INK4A seems to be a superior marker for the detection of HPV-associated penile squamous cell carcinoma compared to CISH tests, but is not recommend for the detection of non-tumorigenic lesions, where PCR should be used for the initial assessment.

Serum 20S proteasome is elevated in patients with renal cell carcinoma and associated with poor prognosis.

BACKGROUND: To date, no reliable serum marker for clear cell renal cell carcinoma (CCRCC) is available. The aim of this study was to evaluate the putative significance of circulating 20S proteasome levels. METHODS: Preoperative 20S proteasome serum levels were determined in 113 CCRCC patients and 15 healthy controls by a sandwich enzyme-linked immunosorbent assay. Associations with CCRCC, pathological variables, disease-specific survival (DSS), and response to sunitinib were evaluated. RESULTS: Median 20S proteasome levels were higher in CCRCC patients than in healthy controls (4.66 vs 1.52 µg ml(-1), P<0.0001). The area under the receiver operating characteristics curve curve was 87.1%. The 20S proteasome levels were associated with symptoms (P=0.0008), distant metastases (P=0.0011), grade (P=0.0247), and necrosis (P=0.0462). The 20S proteasome levels were identified as a prognostic factor for DSS in both univariable (hazards ratio 1.21, P<0.001) and multivariable (hazards ratio 1.17, P=0.0015) survival analysis. In patients responding to sunitinib, 20S proteasome levels were lower than in patients with stable disease and progressive disease. CONCLUSION: This study demonstrates for the first time that increased 20S proteasome levels are associated with CCRCC, advanced disease, and poor prognosis. Routine use of this marker may allow better diagnosis, risk stratification, risk-adjusted follow-up, and identification of patients with a greater likelihood of response to targeted therapy.

Dual inhibition of EGFR and mTOR pathways in small cell lung cancer.

BACKGROUND: In this report we investigated the combination of epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) pathway inhibition as a possible new therapeutic strategy for small cell lung cancer (SCLC). METHODS: EGFR, p-AKT, p-ERK, p-mTOR and p-p70s6K protein expressions were studied by immunohistochemistry in 107 small cell lung carcinomas and correlated with clinicopathological parameters. Cells of SCLC were treated with erlotinib+/-RAD001 and analysed for cell viability, proliferation, autophagy, and pathway regulation. RESULTS: Epidermal growth factor receptor, p-AKT, p-ERK, p-mTOR, and p-p70s6K were expressed in 37, 24, 13, 55 and 91% of the tumour specimens of all SCLC patients, respectively, and were not associated with disease-free or overall survival. The expression of EGFR was lower in neoadjuvant-treated patients (P=0.038); mTOR pathway activation was higher in the early stages of disease (P=0.048). Coexpression of EGFR/p-mTOR/p-p70s6K was observed in 28% of all patients . EGFR immunoreactivity was associated with p-ERK and p-mTOR expression (P=0.02 and P=0.0001); p-mTOR immunoreactivity was associated with p-p70s6K expression (P=0.001). Tumour cells comprised a functional EGFR, no activating mutations in exons 18-21, and resistance to RAD001 monotherapy. We found synergistic effects of erlotinib and RAD001 combination therapy on the molecular level, cell viability, proliferation and autophagy. CONCLUSIONS: The combined inhibition of EGFR/mTOR pathways could be a promising approach to treat SCLC.

CD98hc (SLC3A2), a novel marker in renal cell cancer.

BACKGROUND: In a variety of malignant diseases, molecular targeting represents a therapeutic option, whereby, when compared with chemotherapy, fewer side effects are thought to be expected. Especially in renal cell cancer (RCC), tyrosine kinase-inhibitors have been established as useful and highly effective therapy. However, tyrosine kinase-inhibitors currently approved for RCC treatment lack single molecule specificity and bear a variety of side effects of the gastro-intestinal tract, skin, heart and haematopoietic system. Therefore, the identification of novel cell surface markers is sought, which might lead to novel diagnostic and therapeutic strategies in cancer. MATERIAL AND METHODS: Paraffin-embedded RCCs from a well characterized tissue bank were immunohistochemically quantified for embryonic transmembrane antigen CD98hc (SLC3A2) expression and semi-quantitative analyses were correlated with subtype or grade of differentiation. RESULTS: We found increased CD98hc expression in different types of malign RCCs, among them clear cell (cc)RCC, papillary (p)RCC and chromophobe (ch)RCC, but lack of expression in the benign renal oncocytoma. Thereby, the extent of CD98hc expression directly complies with grade of malignancy. Furthermore, the more malignant type II pRCC significantly higher expressed CD98hc than the less malignant and more differentiated type I pRCC (type II 83.34%, type I 4.76% CD98hc positive, P < 0.00001; n = 51). The established marker for type I pRCC, Cytokreatin 7, showed 95.24% expression in type I and 26.67% expression in type II pRCC (P < 0.00001, n = 51). CONCLUSIONS: From these data, we conclude that CD98hc is expressed in RCCs, whereby the extent of expression is likely to correlate directly with grade of malignancy. In pRCCs, CD98hc might represent a novel and reliable marker for type II pRCC.

mdm2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinicopathological parameters.

The present study was designed to analyze the expression of p53 and mdm2 in clear cell renal cell carcinoma with special emphasis on their association with tumor grade and clinical outcome. In particular, the value of individual protein overexpression as well as combined p53/mdm2 positivity was evaluated because both proteins are functionally connected, and their expression is controlled by an autoregulatory feedback loop. A cohort of 97 clear cell renal cell carcinomas was analyzed. The overexpression of mdm2 and p53 proteins was investigated on paraffin-embedded material by using monoclonal antibodies. Eighteen tumors showed mdm2 positivity, whereas 35 of the tumors overexpressed p53. Whereas p53 and mdm2 positivity correlated significantly (P = 0.00004), no correlation could be found between mdm2 protein overexpression and tumor stage, lymph node involvement, and presence of distant metastases. mdm2 positivity was found significantly more frequently in tumors of higher grade. In univariate analysis, there was a statistically significant correlation between p53 and mdm2 overexpression in the same tumor and poor survival (P = 0.00179). Multivariate analysis revealed that coincident mdm2/p53 overexpression, the presence of distant metastases, and tumor grade were independent predictors for tumor progression. Our results indicate that mdm2/p53 co-overexpression, nuclear grade, and preoperative presence of distant metastasis are independent predictors for poor survival.

Proliferating cell nuclear antigen and MIB-1. An alternative to classic prognostic indicators in renal cell carcinomas?

Tumor progression and clinical outcome for patients with renal cell carcinomas (RCCs) cannot be predicted based solely on tumor staging and grading. In a retrospective study we have therefore attempted to analyze the capacity of proliferation markers to provide additional prognostic information. One hundred seven cases of RCC were investigated by immunohistochemical analysis using two different monoclonal antibodies: PC10, which recognizes a proliferating cell nuclear antigen (PCNA), and MIB-1, which identifies the Ki-67 antigen in formalin-fixed, paraffin-embedded material. PCNA frequency ranged from 0% to 71% (mean, 17%), and MIB-1 expression, from 0% to 43% (mean, 11%). PCNA scores correlated significantly with MIB-1 immunoreactivity. PCNA and MIB-1 immunoreactivity showed a significant correlation with tumor grade. A strong correlation was also observed for T-component of stage and MIB-1 scores, but no correlation was found between PCNA and T-component of stage. In univariate analysis, PCNA immunoreactivity and MIB-1 scores were significant predictors of survival. Multivariate analysis, using a Cox proportional hazard model, showed PCNA index, N-component of stage, and tumor grade to be independent predictors of tumor progression, which is not the case for MIB-1 index.

Spontaneous nontraumatic rupture of a contracted kidney with subcapsular and perirenal hematoma in a patient receiving chronic hemodialysis.

Spontaneous renal bleeding with diversion of blood into the subcapsular and/or perinephric spaces in a patient on chronic hemodialysis is a very rare clinical entity. We describe a patient on chronic hemodialysis in whom a spontaneous renal subcapsular hematoma and perirenal hemorrhage developed in a contracted kidney.

Sperm analysis and serum follicle-stimulating hormone levels before and after adjuvant single-agent carboplatin therapy for clinical stage I seminoma.

OBJECTIVES: During the past 25 years, radiotherapy has been considered the standard adjuvant treatment for clinical Stage I seminoma after orchiectomy. However, the late effects of this treatment have prompted a re-examination of the alternatives, including surveillance and adjuvant administration of carboplatin. To our knowledge, the present clinical study is the first to report the effects of two adjuvant courses of single-agent carboplatin on the pituitary-testicular axis and on sperm analysis. METHODS: Twenty-two patients with clinical Stage I seminoma participated in a prospective investigation of gonadal function before and after carboplatin therapy. After orchiectomy but before chemotherapy, blood samples for determination of follicle-stimulating hormone (FSH) serum levels were obtained from all 22 patients. Seventeen patients provided a semen sample at the same time, but 5 were unable to do so. At the end of chemotherapy, all 22 patients provided repeated semen samples starting 1 year after the termination of treatment and continuing at intervals of 12 months. FSH serum levels were determined at the same time. The study period was 48 months. RESULTS: Before chemotherapy, 2 patients (12%) had azoospermia, 9 (53%) had oligospermia, and 6 (35%) had normospermia. During the study period, sperm counts continued to increase in all patients. After 4 years, 7 patients (32%) had oligospermia and 15 (68%) normospermia. The mean prechemotherapy FSH level (15.5 IU/L) was increased in accordance with subnormal spermatogenesis, but a constant trend toward normalization was observed thereafter. CONCLUSIONS: Our results show recovery of spermatogenesis after adjuvant single-agent carboplatin for clinical Stage I seminoma in a remarkably high percentage of patients.

Multifocality of transitional cell carcinoma results from genetic instability of entire transitional epithelium.

OBJECTIVES: Multifocality of transitional cell carcinoma (TCC) has been attributed to seeding of exfoliated tumor cells or to a general sensitivity of the entire urothelium to carcinogenic stimuli. By contrast, TCC has been shown to evolve as a consequence of genetic defects and chromosomal instability. We analyzed chromosomal patterns, total DNA content, and p53 and Ki67 expression in malignant and normal transitional cells to evaluate their relationship to the development of multifocal TCC. METHODS: Included in the study were 47 patients, 16 women and 31 men, with a mean age of 70.04 years (range 37 to 83). Of 47 patients, 45 had TCC of the urinary bladder and 7 of those had synchronous ureteral involvement. Two patients had ureteral TCC and a history of TCC of the bladder. Using fluorescence in situ hybridization, numerical aberrations of chromosomes 7, 9, and 17 were detected in imprint specimens of histologically verified tumor and "normal" urothelium and were compared with static ploidy and p53 and Ki67 expression. RESULTS: Chromosome 7 was altered in 93.6%, chromosome 9 in 63.8% (including monosomy), and chromosome 17 in 87.2% of the 47 analyzed tumor and normal imprints. Differences between tumor and normal epithelium were observed in aberrational frequencies (number of cells showing chromosomal aberrations calculated on 200 cells counted, given in percentages). DNA content was aneuploid in all tumor specimens, but diploid in 20 (42.5%) of 47 normal specimens, according to lower aberration frequencies in these patients. p53 detection was positive in 82.9% of the tumor specimens and 76.6% of the normal specimens. Ki67 was positive in 87.2% of the tumor imprints and in 72.3% of the normal specimens. CONCLUSIONS: These data suggest a general genetic instability as a reason for multifocality in the entire transitional epithelium.

Paclitaxel and carboplatin in patients with metastatic transitional cell cancer of the urinary tract.

OBJECTIVES: The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) is currently considered the most effective chemotherapy for metastatic transitional cell cancer (TCC) of the urinary tract, but because of its considerable toxicity, alternative regimens appear very interesting. We evaluated the efficacy and toxicity of a combination of paclitaxel and carboplatin as first-line therapy for metastatic TCC. METHODS: Thirty-two patients (8 women, 24 men; mean age 67.03 years, range 50 to 79) with metastatic TCC of the bladder or upper urinary tract were included in the study. Paclitaxel (175 mg/m2) was given as a 3-hour intravenous infusion, carboplatin was dosed to an area under the plasma concentration curve of 5 mg/m/min calculated according to the Calvert formula [(creatinine clearance + 25) x 5] as a 30-minute intravenous infusion immediately after paclitaxel. Response evaluation was performed after every 2 cycles and additional therapy depended on response. The maximum number of cycles was 6. RESULTS: With a mean follow-up of 13.1 months (range 2 to 28), 23 of 32 patients responded to treatment (response rate 71.9%), with 31.3% complete remission (CR) (10 of 32) and 40.6% partial remission (PR) (13 of 32). Four patients (12.5%) had stable disease, and 5 patients (15.6%) showed progression. These results compare well with the outcome after MVAC. Toxicity was mainly characterized by neurotoxicity grade 3 and 4 in 9.4%, grade 3 and 4 leukopenia in 37.5%, and grade 3 thrombocytopenia in 3.1% of the patients. No nephrotoxicity was observed, but all patients developed alopecia. Time to progression after CR was a mean of 7.0 months (range 4 to 13) and after PR a mean of 5.9 months (range 2 to 9). CONCLUSIONS: Paclitaxel/carboplatin is an effective therapy for metastatic TCC, with low toxicity.

Nephrogenic adenoma in renal transplant recipients: a truly benign lesion?

OBJECTIVES: Nephrogenic adenoma is a benign metaplastic lesion of the urinary bladder, reported to occur as a response to inflammation, trauma, intravesical therapies, and after renal transplantation. The aim of this study was to evaluate on the basis of chromosomal analysis whether nephrogenic adenoma really is benign. METHODS: Twelve renal transplant recipients with histologically verified nephrogenic adenoma were analyzed for numerical aberrations of chromosomes 7, 9, and 17. Results were related to total DNA content, p53 and Ki-67 positivity, and clinical outcome. Ten patients with superficial bladder cancer and 10 healthy renal transplant recipients formed the control groups. RESULTS: All 12 patients with nephrogenic adenoma had monosomy 9 in a mean of 24.3% (range 20% to 30%) of the evaluated cells; 3 patients had an additional trisomy 7 in a mean of 8% (range 6% to 10%) of the counted cells. Chromosome 1 7 was disomic in all patients. DNA histograms were diploid in 11 of the 12 patients and aneuploid in 1 patient. No p53 and Ki-67 positivity was present in this group. All patients with superficial bladder cancer had monosomy 9 in a mean of 79.8% (range 75% to 85%) of the counted cells. Two patients were found to have an additional trisomy 7 in 50% and 65% of the cells, respectively. The latter had an aneuploid histogram; the others had haploid/diploid histograms. p53 was negative in all specimens. Ki-67 positivity was present in 70% of these patients. All healthy transplant recipients had disomic chromosomal patterns according to diploid DNA histograms and negative immunocytochemical results. CONCLUSIONS: Even if in a lower percentage of cells, aberrations of chromosome 7 and 9 were detected in nephrogenic adenoma. It therefore cannot be excluded that nephrogenic adenomas in immunosuppressed renal transplant recipients may develop into malignant lesions.

Numerical chromosomal aberrations in muscle invasive squamous cell and transitional cell cancer of the urinary bladder: an alternative to classic prognostic indicators?

OBJECTIVES: To evaluate the prognostic value of chromosomal aberrations in muscle invasive bladder cancer, because they are of diagnostic and prognostic significance in superficial bladder cancer. METHODS: One hundred ninety patients, who underwent radical cystectomy because of squamous cell carcinoma (SCC) of the urinary bladder in 94 cases and transitional cell carcinoma (TCC) in 96 cases, were studied retrospectively. Numerical aberrations of chromosomes 7, 9, and 17, p53 positivity, histologic stage and grade, histologic tumor type, lymph node status, and the presence of bilharzial eggs were investigated as possible prognostic factors. RESULTS: Univariate analysis demonstrated the prognostic significance of all parameters analyzed, excluding chromosome 9. Multivariate analysis revealed only T category (P = 0.01095266), lymph node involvement (P = 0.00054877), and p53 positivity (P = 0.0316974) to be independent prognostic factors in muscle invasive SCC and TCC. CONCLUSIONS: Although chromosomal aberrations are associated with progression-free survival, they are not independent prognostic factors and give the clinician no additional information on patients with muscle invasive bladder cancer.

Primary adenocarcinoma of the ureter. Case report with immunohistochemical characterization.

Genuine adenocarcinomas of the ureter are rare tumors and have to be distinguished from other gland-forming malignancies arising from the transitional epithelium, due to the poor clinical outcome. The histopathological features of a tumor combined with intestinal metaplasia of the adjacent urothelium are described. The tumor has to be distinguished from transitional cell cancer with glandular metaplasia, muco-urothelial cancer, microcystic transitional cell cancer and transitional cell cancer with mucoid cytoplasmatic inclusions. Immunohistochemical analysis of the cancer shows positivity for carcinoembryonic antigen and a staining pattern characteristic for adenocarcinomas. The expression of keratin types 7 and 13, which is typically found in transitional cell carcinomas, is lost.

Expression of bcl-2, bcl-x, bax and bak in renal parenchyma, oncocytomas and renal cell carcinomas.

Proteins of the bcl-2 family are important regulators of programmed cell death. Alterations in the expression of these proteins may contribute to the progression of cancer. Expression of bcl-2, bcl-x, bax and bak was investigated by immunohistochemistry and Western-blotting of regular and alterated renal parenchyma as well as in 57 renal cell carcinomas. Bcl-2, bcl-x and in part bax were found to be overexpressed in inflammed renal parenchyma, whereas atrophic tubuli predominantly stained for bcl-2 and to a lesser degree for bcl-x and bax. Only little bak expression was detected in alterated tubuli. Moderate to strong expression for bcl-2, bcl-x, bax and bak was found in 24, 38, 2 and 13 of 57 carcinomas, respectively. Bcl-2, bcl-x, bax and bak expression were correlated to tumor type. Chromophilic carcinomas stained stronger for bcl-2, bcl-x and bax, whereas chromophobic carcinomas stained stronger for bcl-x, bax and bak compared to clear cell carcinomas. Expression of bak correlated with that of bcl-x and with an unfavorable histology as indicated by nuclear grading in these tumors. Our findings suggest that expression of bcl-2 and bcl-x may be important for cell survival only in a subset of renal cell carcinomas, and that the anti-apoptotic effect of these proteins appears to be frequently bypassed possibly by other factors impeding programmed cell death.

Technical Note: evaluation of the uncertainties in (choline + creatine)/citrate ratios measured by proton MR spectroscopic imaging in patients suspicious for prostate cancer.

The presented evaluation of the relative uncertainty (δ'CCC) of the (choline + creatine)/citrate (CC/C) ratios can provide objective information about the quality and diagnostic value of prostate MR spectroscopic imaging data. This information can be combined with the numeric values of CC/C ratios and provides metabolic-quality maps enabling accurate cancer detection and user-independent data evaluation. In addition, the prostate areas suffering most from the low precision of CC/C ratios (e. g., prostate base) were identified.

Prognostic factors in metastatic renal cell carcinoma: metastasectomy as independent prognostic variable.

Prognostic and predictive factors in patients with metastatic renal cell carcinoma (MRCC) have been evaluated from untreated patients or patients on several different treatment approaches. The aim of this analysis was to define prognostic and predictive factors in patients treated uniformly with a low-dose outpatient cytokine combination. The relationship between patient-, tumour-, and treatment-related factors was analysed in 99 patients with MRCC. These features were first examined in univariate analyses, then a stepwise modelling approach based on Cox regression was used to form a multivariate model. Nuclear grade, metastasectomy--even incomplete--C-reactive protein and lactate dehydrogenase were identified as independent prognostic factors for survival. Patients assigned to three different risk groups had statistically significant survival differences (30, 22 and 6 months, respectively). A total of 43.4% had undergone metastasectomy, mostly incomplete. Risk group affiliation was correlated with response to treatment. Our findings strongly suggest the consideration of metastasectomy in the management of patients with metastatic renal cell cancer undergoing either immunotherapy or targeted treatment.