DNA ploidy, nuclear size, proliferation index and DNA-hypomethylation in ovarian cancer.

OBJECTIVE: The present study was undertaken to analyze the impact of epigenetic alterations with a main focus on nuclear area, aneuploidy, hyperploidy, and proliferation in 70 ovarian cancer specimens. METHODS: Morphometric changes and somatic chromosomal ploidy status were assessed by Feulgen spectrophotometry. DNA-hypomethylation of LINE1 repeats was analyzed by means of MethyLight PCR, and methylation levels of satellite 2 (Sat2) and satellite alpha (Satα) DNA sequences in chromosome 1 were measured by Southern blot analysis. These parameters were analyzed with regard to correlations as well as to recurrence and survival. RESULTS: We identified a significant association between LINE1 DNA-hypomethylation and patient age (p=0.029). Furthermore, LINE1 DNA-hypomethylation was positively correlated with the nuclear area (r=0.47; p<0.001) and the proliferation index (r=0.36; p<0.001). Univariate survival analysis showed that the nuclear area and LINE1 DNA-hypomethylation were prognostic factors for overall (p=0.015 and =0.006, respectively) and progression-free survival (p=0.020 and p=0.001 respectively), the percentage of aneuploidy only for overall survival (p=0.031). Subgroup survival analyses revealed that the prognostic value of these factors is strictly confined to mucinous cancers. In serous cancers no prognostic value could be pointed out for any analyzed parameter. Multivariate analysis of the entire cohort showed that the percentage of hyperploidy was an independent prognostic parameter for overall survival (p=0.003) and LINE1 DNA-hypomethylation for progression-free survival (p=0.03). In mucinous cancers nuclear area and LINE1 DNA-hypomethylation were found to be independent predictors of progression-free and overall survival. CONCLUSIONS: In this study we identified the correlations between early cancer-associated genome DNA-hypomethylation, nuclear morphometric changes, somatic chromosomal ploidy status and the proliferation index. Prognostic relevance of nuclear area and LINE1 DNA-hypomethylation was revealed exclusively in mucinous ovarian cancers.

Ultrasound of the prostate.

Ultrasound is a widely used imaging modality for evaluation of the prostate. The main topic of diagnostic imaging is an improvement of prostate cancer diagnosis. The current available systematic prostate biopsy is performed only under ultrasound guidance, but new imaging techniques allow prostate cancer visualization and therefore improved detection. Evolving methods such as contrast-enhanced colour Doppler imaging, contrast-specific ultrasound techniques and elastography may dramatically change the role of ultrasound for prostate cancer diagnosis. The purpose of this review is to provide an overview of ultrasound and its different techniques for imaging of the prostate and to discuss current trends and future directions.

Treatment of recurrent platinum-resistant ovarian cancer with pegylated liposomal doxorubicin--an evaluation of the therapeutic index with special emphasis on cardiac toxicity.

BACKGROUND: To study the efficacy of pegylated liposomal doxorubicin (PLD) at a modified dose of 45 mg/m(2) every 4 weeks in platinum-resistant ovarian cancer and to evaluate toxicities and effects on quality of life (QoL) of this single-agent regimen. METHODS: Treatment response was evaluated by CT scan or CA 125 levels. Toxicity and QoL was recorded according to the common toxicity criteria of the National Cancer Institute and the EORTC QLQ-C30 questionnaire, respectively. RESULTS: Eighty-five patients entered this nationwide observational study (384 cycles administered) and 4 (4.7%) achieved complete and 22 (25.8%) partial remission, giving an objective response rate of 30.5%. Eight patients experienced therapy-limiting side effects prompting discontinuation of treatment. Palmoplantar erythrodysesthesia (PPE) and/or stomatitis were the main reasons for discontinuation. Grade 3-4 PPE and stomatitis occurred in 4.2 and 2.2% of the 384 cycles, respectively. Grade 3-4 cardiotoxicity was absent and overall QoL was not significantly decreased following PLD treatment. CONCLUSION: Single-agent PLD at a dose of 45 mg/m(2) is an efficient treatment in recurrent platinum-resistant ovarian cancer and exhibits an exceptionally favorable therapeutic index.

Ureteroiliac fistula: a case report review of the literature.

INTRODUCTION: Ureteroiliac fistulas are rare but potentially life-threatening. Risk factors to develop a fistula are chronic indwelling ureteral stents, previous pelvic surgery and radiotherapy. CASE PRESENTATION: We report a case of a patient with intermittent gross hematuria after previous abdominal surgery, radiotherapy and indwelling ureteric stents. After several diagnostic and therapeutic procedures an ureteroiliac fistula could be finally identified and treated by endovascular stenting. CONCLUSION: Ureteroiliac fistula should be considered in any patient with intermittent gross hematuria and any of the known risk factors.

Acute pyelonephritis: comparison of diagnosis with computed tomography and contrast-enhanced ultrasonography.

OBJECTIVE: To assess the value of contrast-enhanced ultrasonography (US) with the contrast pulse-sequence (CPS) technique for detecting renal parenchymal changes in acute pyelonephritis (APN), compared with contrast-enhanced computed tomography (CT) as the reference standard. PATIENTS AND METHODS: We examined 100 patients (82 women, 18 men; mean age 30.2 years, range 18-67); children (those aged <18 years) were excluded from the study. All patients had clinical symptoms suggestive of APN. For the US a Sequoia 512 (Acuson, Mountain View, CA, USA) unit including Cadence CPS technology, with a 6C2 probe, was used. A bolus of a 2.4-mL US contrast agent SonoVue (Bracco, Milan, Italy) was injected. For CT a multislice 16-row unit was used (Sensation 16, Siemens, Erlangen, Germany), at a table speed of 2.5 mm/s and a slice thickness of 3 mm; 100 mL of intravenous iodinated contrast agent (flow 3 mL/s) was injected. RESULTS: On contrast CT, 84 patients (84%) had renal parenchymal changes suggestive of APN; on contrast US, 82 of the 84 (98%) showed renal parenchymal changes, and APN was correctly diagnosed. Seventy-six patients (90%) had unilateral and eight (10%) had bilateral APN, and in two (2%) with APN the diagnosis could not be confirmed by US/CPS (false-negative). No false-positive findings were detected on US/CPS, which had a sensitivity of 98%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 89%. CONCLUSION: CPS/US is accurate for detecting parenchymal changes in APN; it is very sensitive and specific, and allows small renal parenchymal changes to be detected with no radiation exposure.

Soluble isoforms but not the transmembrane form of coxsackie-adenovirus receptor are of clinical relevance in epithelial ovarian cancer.

The coxsackie-adenovirus receptor (hCAR) has been extensively studied in context of adenoviral-based gene therapy for cancer. However, there is strong evidence that besides its decisive role in coxsackie and adenovirus cell-entry, hCAR is a component of epithelial tight junctions and involved in cell-cell adhesions in normal and cancer cells. Furthermore, this adhesion molecule behaves like a cell surface receptor endowed with tumor suppressive properties via signal transduction. Moreover, 3 truncated soluble isoforms of hCAR were recently identified. We investigated the quantitative expression of all known CAR isoforms in a training set of 140 ovarian cancer samples and 21 controls by RT-PCR. The expression levels of the various isoforms were compared with clinicopathologic parameters and their prognostic significance was assessed. Expression levels of all CAR isoforms were elevated in ovarian carcinomas as compared with those of non-malignant controls. mRNA-expression correlated with protein levels. Moreover, expression of the soluble isoforms CAR 3/7 and CAR 4/7 but not that of hCAR was significantly increased in advanced ovarian cancer as revealed by a highly significant correlation with FIGO stage and residual disease > 2 cm in diameter after debulking surgery. High expression of CAR 3/7 and 4/7 was shown to be of independent prognostic relevance for progression-free (CAR 4/7) and overall survival (CAR 3/7 and CAR 4/7). In conclusion, soluble CAR isoforms 3/7 and 4/7 may play a pivotal role in ovarian cancer biology, possibly by counteracting migration- and growth-inhibitory properties of the membranous hCAR and thus favoring cancer cell dissemination throughout the peritoneal cavity.