Prostate cancer treatment ascertained from several sources: analysis of disagreement and error.

BACKGROUND: Treatment data for prostate cancer can be obtained from a variety of sources. Each of these sources has its own strengths and weaknesses and is subject to error. MATERIALS AND METHODS: In a population-based cohort of 319 prostate cancer patients, data on treatment were obtained from five sources: two patient interviews at 6 and 12 months after diagnosis, primary caregiver interviews, physician questionnaires, and medical records. Inter-reporting agreement and accuracy of reporting (compared with medical records) were assessed. Multivariate analyses examined patient, caregiver, and physician characteristics as determinants of reporting error. RESULTS: The agreement among different reporting methods was generally good to excellent for prostatectomy and brachytherapy (kappa range 0.70-0.90) and fair to good (kappa range 0.35-0.75) for external beam radiation and hormonal treatment. Compared with medical records, the interview- and questionnaire-based data collection methods were more accurate for prostatectomy and brachytherapy than for external beam radiation and hormonal therapy. Using medical records as the 'gold standard', patient and caregiver interviews at 6 months after the diagnosis had higher sensitivity and specificity than other reporting sources. CONCLUSION: Interviews of prostate cancer patients and caregivers are useful alternatives to medical record abstraction, particularly if carried out during, or soon after, treatment.

Intratumor C-reactive protein as a biomarker of prognosis in localized renal cell carcinoma.

PURPOSE: Serum C-reactive protein has been shown to have prognostic value in localized and metastatic renal cell carcinoma. However, the prognostic value of intratumor C-reactive protein remains unknown. MATERIALS AND METHODS: A total of 95 patients with resected, clinically localized (T1-T4N0M0) clear cell renal cell carcinoma were followed postoperatively. Intratumor C-reactive protein expression was assessed in surgical specimens using immunohistochemical analysis. Patients were categorized by staining intensity into low risk (staining 0 to 1), intermediate risk (staining 2) and high risk (staining 3) groups. Kaplan-Meier and multivariate Cox regression analyses were used to examine overall survival across patient and disease characteristics. Variables examined in multivariate Cox regression analysis included T stage, Fuhrman nuclear grade, tumor size, preoperative serum C-reactive protein and intratumor C-reactive protein staining. RESULTS: Followup extended up to 46 months with a mean (SD) of 29.8 (11.0) months. Twelve patients (12.6%) died during followup. Of all tumors 49.5%, 25.3% and 25.3% were graded by intratumor C-reactive protein staining as low risk (0 to 1), intermediate risk (2) and high risk (3), respectively. After controlling for variables significant on univariate analysis, patients in the high risk (3) group experienced a 27-fold increased risk of overall mortality compared to those in the low risk (0-1) group (HR 27.767, 95% CI 1.488-518.182). After adjusting for tumor staining, preoperative serum C-reactive protein was not a significant predictor of overall survival (p = 0.741). CONCLUSIONS: Intratumor C-reactive protein may be a robust biomarker of prognosis in patients with localized renal cell carcinoma.

Postoperative better than preoperative C-reactive protein at predicting outcome after potentially curative nephrectomy for renal cell carcinoma.

OBJECTIVES: Preoperative C-reactive protein (CRP) predicts metastasis and mortality in localized renal cell carcinoma (RCC). However, the predictive potential of after resection of localized RCC remains unclear. Therefore, we assessed the absolute ability of postoperative CRP to predict metastases and mortality as a continuous variable. METHODS: Patients with clinically localized (T1-T3N0M0) clear-cell RCC were followed for 1 year postoperatively. Metastases were identified radiologically and mortality by death certificate. Univariate and multivariate binary logistic regression analyses examined 1 year relapse-free survival (RFS) and overall survival (OS) across patient and disease characteristics. RESULTS: Of the 110 patients in this study, 16.4% developed metastases and 6.4% died. Mean (SD) postoperative CRP for patients who did and did not develop metastases were 69.06 (73.55) mg/L and 5.27 (7.80), respectively. Mean (SD) postoperative CRP for patients who did and did not die were 89.31 (69.51) mg/L and 10.88 (30.32), respectively. In multivariate analysis, T-stage (OR: 12.452, 95% CI: 2.889-53.660) and postoperative CRP ((B: .080, SE: .025; P < .001) were significant predictors of RFS. T-Stage (OR: 11.715; 95% CI: 1.102-124.519) and postoperative CRP (B: .017; SE: .007; P < .001) were also significant predictors of OS. After adjusting for postoperative CRP, preoperative CRP was not predictive of these outcomes. CONCLUSIONS: Postoperative, not preoperative, CRP is the better predictor of metastasis and mortality following nephrectomy for localized RCC. Clinicians should consider absolute postoperative CRP to identify high-risk patients for closer surveillance or additional therapy. Predictive algorithms should consider incorporating postoperative CRP as a continuous variable to maximize predictive ability.

Absolute preoperative C-reactive protein predicts metastasis and mortality in the first year following potentially curative nephrectomy for clear cell renal cell carcinoma.

PURPOSE: C-reactive protein is an inflammatory biomarker associated with tumor burden and metastasis in renal cell carcinoma. Recent studies suggest that preoperative C-reactive protein predicts metastasis and mortality after nephrectomy for localized renal cell carcinoma. However, these studies dichotomized C-reactive protein (typically 10 mg/l or greater vs less than 10 mg/l). Considering the continuous range of C-reactive protein (less than 1 mg/l to greater than 100 mg/l) we assessed the ability of absolute preoperative C-reactive protein to predict metastases and mortality as a continuous variable. MATERIALS AND METHODS: Patients with clinically localized (T1-T3N0M0) clear cell renal cell carcinoma were followed for 1 year postoperatively. Metastases were identified radiologically and mortality was determined by death certificate. Univariate and multivariate binary logistic regression analyses examined 1-year relapse-free survival and overall relative survival across patient and disease characteristics. RESULTS: Of the 130 patients in this study metastases developed in 24.6% and 10.8% of the patients died. Mean (SD) preoperative C-reactive protein for patients in whom metastases did and did not develop was 89.17 (74.17) and 9.16 (30.62) mg/l, respectively. Mean preoperative C-reactive protein for patients who did and did not die was 102.61 (77.32) and 19.52 (46.10) mg/l, respectively. On multivariate analysis SSIGN score (p <0.001) and preoperative C-reactive protein (B 0.027, SE 0.003, p <0.001) were significant predictors of relapse-free survival, and preoperative platelets (p = 0.009) and preoperative C-reactive protein (B 0.011, SE 0.008, p <0.001) were significant predictors of overall relative survival. CONCLUSIONS: Absolute preoperative C-reactive protein is a robust predictor of metastasis and mortality after nephrectomy for localized renal cell carcinoma. Clinicians should consider absolute preoperative C-reactive protein to identify high risk patients for closer surveillance or additional therapy. In addition, predictive algorithms and models of metastasis should consider incorporating C-reactive protein as a continuous variable to maximize predictive ability.

Grade migration in prostate cancer: an analysis using the Surveillance, Epidemiology, and End Results registry.

To utilize the Surveillance, Epidemiology, and End Results (SEER) registry to examine trends in grade assignment. Data from 411 325 patients from 1984 to 2003 were analyzed for grade migration and for cause-specific survival (CSS) as a function of grade. There has been a significant grade migration during the study period (P<0.001), principally from well-differentiated (WD) to moderately differentiated (MD) disease. Five-year CSS of MD and WD patients have converged, suggesting a decreasing role of grade as a prognostic factor. A grade migration from WD to MD assignment has occurred, suggesting that prognostic categorizations based on grade across eras may be difficult to interpret.

Ejaculatory physiology and dysfunction.

The sequence of events encompassing ejaculation has been well described. Multiple disease processes can result in ejaculatory dysfunction. Evaluation and subsequent treatment of ejaculatory dysfunction is possible using behavioral, mechanical, and medical and surgical modalities. Further elucidation of ejaculation is now taking place at the molecular level.

Conserved anterior boundaries of Hox gene expression in the central nervous system of the leech Helobdella.

Molecular developmental studies of fly and mouse embryos have shown that the identity of individual body segments is controlled by a suite of homeobox-containing genes called the Hox cluster. To examine the conservation of this patterning mechanism in other segmented phyla, we here describe four Hox gene homologs isolated from glossiphoniid leeches of the genus Helobdella. Based on sequence similarity and phylogenetic analysis, the leech genes Lox7, Lox6, Lox20, and Lox5 are deemed to be orthologs of the Drosophila genes lab, Dfd, Scr, and Antp, respectively. Sequence similarities between Lox5 and Antp outside the homeodomain and phylogenetic reconstructions suggest that the Antennapedia family of Hox genes (as defined by Bürglin, 1994) had already expanded to include at least two discrete Antp and Ubx/abdA precursors prior to the annelid/arthropod divergence. In situ hybridization reveals that the four Lox genes described in this study are all expressed at high levels within the segmented portion of the central nervous system (CNS), with variable levels of expression in the segmental mesoderm. Little or no expression was seen in peripheral ectoderm or endoderm, or in the unsegmented head region (prostomium). Each Lox gene has a distinct anterior expression boundary within one of the four rostral segments, and the anterior-posterior (AP) order of these expression boundaries is identical to that reported for the orthologous Hox gene products in fly and mouse. This finding supports the idea that the process of AP axis differentiation is conserved among the higher metazoan phyla with respect to the regional expression of individual Hox genes along that axis. One unusual feature of leech Hox genes is the observation that some genes are only expressed during later development -- beginning at the time of terminal cell differentiation -- whereas others begin expression at a much earlier stage, and their RNA ceases to be detectable shortly after the onset of expression of the 'late' Hox genes. The functional significance of this temporal disparity is unknown, but it is noteworthy that only the two 'early' Hox genes display high levels of mesodermal expression.

Isolation, characterization, and expression of Le-msx, a maternally expressed member of the msx gene family from the glossiphoniid leech, Helobdella.

The msx gene family is one of the most highly conserved of the nonclustered homeobox-containing genes. We have isolated an msx homolog (Le-msx) from the glossiphoniid leech, Helobdella robusta, and characterized its pattern of expression by whole mount in situ hybridization. In situ expression and reverse transcription polymerase chain reaction (RT-PCR) data results show that Le-msx is a maternal transcript initially uniformly distributed in the cortex of immature oocytes that becomes asymmetrically localized to the polar regions of the uncleaved zygote. This is the earliest reported expression for the msx gene family and the first maternally expressed homeodomain-containing transcription factor reported in annelids. During embryonic development, Le-msx is expressed in all 10 embryonic stem cells and their segmental founder cell descendants. At midembryonic stages, Le-msx is expressed in the expanding germinal plate. Le-msx is confined to the central nervous system and nephridia at late (stage 9) stages and subsequently disappears from nephridia. In addition, we present a phylogenetic hypothesis for the evolution of the msx gene family, including the identification of a putative C. elegans msx homolog and the realignment of the sponge msx homolog to the NK class of homeodomain genes.

Homeobox genes in the Ctenophora: identification of paired-type and Hox homologues in the atentaculate ctenophore, Beroë ovata.

Homeobox-containing genes are a phylogenetically widespread family of transcription factors that can regulate cell fates during embryogenesis. Two distinct homeobox gene sequences are described for the atentaculate ctenophore Beroë, the first homeoboxes to be identified in this phylum. Beroë homeobox fragments were cloned in a survey of genomic DNA using polymerase chain reaction (PCR). Parsimony, neighbor-joining, and maximum likelihood methods were used to infer the orthology of the ctenophore sequences to specific homeoboxes from higher metazoans including Drosophila, Caenorhabditis elegans, and humans. Cteno-paired appears most closely related to paired-typed homeoboxes. This is the first evidence of a paired-type homeobox in one of the so-called diploblastic animals. Cteno-Hoxl appears most closely related to members of the Hox class, particularly Antennapedia.