Postprostatectomy cancer-free survival of African Americans is similar to non-African Americans after adjustment for baseline cancer severity

African American men with localized prostate cancer are less likely than White men to receive a radical prostatectomy. This disparity may exist because African American men have prostate cancers that are more biologically aggressive. We investigated if similar stage cancers of African American men and White men show differences in cancer control after radical prostatectomy. Men with localized prostate cancer who underwent radical prostatectomy during a 6-yr period were stratified by race, and time to prostate-specific antigen recurrence was measured. We used Chi-square and t-tests to compare baseline clinical and pathological factors based on race. Cox proportional hazards model was used to determine effects of race on cancer control while controlling for baseline measures of cancer severity. There were 1,228 cases evaluated. At baseline, African American men were treated at a significantly younger age than White men (P = 0.0027) but showed no significant difference in prostate-specific antigen PSA, Gleason score, pathology stage, maximum tumor dimension, and surgical margin status. Multivariable Cox proportional hazards analysis controlling for cancer severity at prostatectomy revealed that cancer-free survival was not worse among African Americans compared to other subjects (P = 0.16). The responsiveness of prostate cancers among African American men to radical prostatectomy was similar to White men of similar stage and grade. Early detection in African American men may facilitate diagnosis of cancer amenable to prostatectomy. Studies are needed to evaluate the possible interaction of prostate cancer stage and grade shift in African American men and the disease free survival in this population.     

Genome-wide scan for prostate cancer susceptibility genes using families from the University of Michigan prostate cancer genetics project finds evidence for linkage on chromosome 17 near BRCA1

BACKGROUND: Previous linkage studies have suggested prostate cancer susceptibility genes located on chromosomes 1, 20, and X. Several putative prostate cancer candidate genes have also been identified including RNASEL, MSR1, and ELAC2. Presently, these linkage regions and candidate genes appear to explain only a small proportion of hereditary prostate cancer cases suggesting the need for additional whole genome analyses. METHODS: A genome-wide mode-of-inheritance-free linkage scan, using 405 genetic markers, was conducted on 175 pedigrees, the majority containing three or more affected individuals diagnosed with prostate cancer. Stratified linkage analyses were performed based on previously established criteria. RESULTS: Results based on the entire set of 175 pedigrees showed strong suggestive evidence for linkage on chromosome 17q (LOD = 2.36), with strongest evidence coming from the subset of pedigrees with four or more affected individuals (LOD = 3.27). Race specific analyses revealed strong suggestive evidence for linkage in our African-American pedigrees on chromosome 22q (LOD = 2.35). CONCLUSIONS: Genome-wide analysis of a large set of prostate cancer families indicates new areas of the genome that may harbor prostate cancer susceptibility genes. Specifically, our linkage results suggest that there is a prostate cancer susceptibility gene on chromosome 17 that is independent of ELAC2. Further research including combined analyses of independent genome-wide scan data may clarify the most important regions for future investigation.     

CD44 enhances tumor formation and lung metastasis in experimental osteosarcoma and is an additional predictor for poor patient outcome

Formation of metastases in the lungs is the major cause of death in patients suffering from osteosarcoma (OS). Metastases at presentation and poor response to preoperative chemotherapy are strong predictors for poor patient outcome. The elucidation of molecular markers that promote metastasis formation and/or chemoresistance is therefore of importance. CD44 is a plasma membrane glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and has been shown to be involved in metastasis formation in a variety of other tumors. Here we investigated the role of CD44 expression on OS tumor formation and metastasis. High CD44 expression, evaluated with a tissue microarray including samples from 53 OS patients and stained with a pan‐CD44 antibody (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However, nonresponders and patients with lung metastases and high CD44 expression had significantly poorer prognosis than patients with low CD44 expression. Overexpression of the standard CD44 isoform (CD44s) and its HA‐binding defective mutant R41A in osteoblastic SaOS‐2 cells resulted in HA‐independent higher migration rates and increased chemoresistance, partially dependent on HA. In an orthotopic mouse model of OS, overexpression of CD44s in SaOS‐2 cells resulted in an HA‐dependent increased primary tumor formation and increased numbers of micrometastases and macrometastases in the lungs. In conclusion, although CD44 failed to be an independent predictor for patient outcome in this limited cohort of OS patients, increased CD44 expression was associated with even worse survival in patients with chemoresistance and with lung metastases. CD44‐associated chemoresistance was also observed in vitro, and increased formation of lung metastases was found in vivo in SCID mice. © 2013 American Society for Bone and Mineral Research.     

Optimizing dose and scheduling of filgrastim (granulocyte colony- stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers [see comments]

To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met- human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM- CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 micrograms/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 micrograms/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients.     

Resection of large inferior vena caval thrombi from renal cell carcinoma with the use of circulatory arrest

Removal of a large extension of renal cell carcinoma into the inferior vena cava can be a difficult operation. Circulatory arrest is an operative technique that recently has been used to assist in resection of tumors that extend into the vena cava above the level of the hepatic veins. At our clinic 18 patients were operated on with the intent of using circulatory arrest during radical nephrectomy and inferior vena caval thrombectomy. Of the 18 patients 13 ultimately underwent this procedure, since the remaining 5 had unresectable tumors. One patient died intraoperatively of an adverse reaction to protamine after technically successful removal of the tumor and thrombus. Resection was successful in 12 patients and 9 remained free of disease with short followup. We believe that the addition of circulatory arrest during resection of a large inferior vena caval thrombus allows for an opportunity to resect the tumor in a controlled situation that reduces the potential for sudden massive blood loss or a major vascular injury, and ultimately makes the operation safer.     

In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection: comparison with other imaging modalities

When infection of prosthetic orthopedic implants is suspected, optimal management requires accurate confirmation or exclusion of infection. The authors retrospectively studied 98 patients with possible infection who underwent scanning with indium-111-labeled white blood cells (WBCs) and subsequently underwent surgery within 14 days. At surgery, 50 patients had infections, as determined by means of culture or histologic results. The diagnostic accuracy of In-111 scanning was compared with that of plain radiography, arthrography, three-phase bone scanning, and various clinical and laboratory findings classically associated with infection. Positive findings on In-111 WBC scans and elevated erythrocyte sedimentation rates were found to be the most predictive variables in the diagnosis of septic prostheses (P less than or equal to .001 and P less than or equal to .002, respectively). Likelihood ratio analysis more clearly demonstrated the superiority of In-111 WBC scanning, with positive and negative scans yielding likelihood ratios of 5.0 and 0.16, respectively.     

原发性病原真菌和条件性真菌所致的甲真菌病

近40年间在易感或免疫受损个体中原发性和条件性真菌感染显著增多。其发病率的增加与艾滋病的流行和医疗技术的重大发展,尤其是器官移植、肿瘤及免疫性疾病新的治疗方法相关。在真菌性疾病中,尽管某些人群更易患甲真菌病,但每一个体均可能患该病。虽然甲真菌病呈慢性经过且并不威胁生命,但可严重影响患者的身心健康。甲真菌病的患病率在许多国家似乎呈上升趋势,范围在3%～15%。尽管临床表现可提示有真菌感染,但保证诊断正确和治疗合理仍依赖实验室检查。尽管酵母和霉菌也可成为单独或混合感染的病原菌,但大多数甲真菌病是由皮肤癣菌引起的。…