Citations

AbstractProperly performed clinical trials provide a foundation for evidence‐based medical practice. The surgeon plays a central role in the management of patients with malignant solid tumors, including thyroid cancer, because operative extirpation of the malignancy is the essential first step in effective therapy. This article discusses the role of the surgeon in the clinical research of thyroid cancer and also reviews the important clinical trials that have influenced the treatment of patients with thyroid cancer. Recent discoveries defining the genetic mutations underlying the various types of thyroid cancers have led to the development of targeted therapies. These chemical compounds, which are now being evaluated in clinical trials, hold great promise for the treatment of patients with locally advanced and distant metastatic disease. The surgical investigator also plays an important role in procuring tumor tissue from patients in clinical trials. The molecular analysis of these tissues is of critical importance in selecting specific therapies and predicting patient response and prognosis.

Abstract Background: Family-based linkage studies, association studies, and studies of tumors have highlighted human chromosome 8q as a genomic region of interest for prostate cancer susceptibility loci. Recently, a locus at 8q24, characterized by both a single nucleotide polymorphism (SNP) and a microsatellite marker, was shown to be associated with prostate cancer risk in Icelandic, Swedish, and U.S. samples. Although the data were provocative, the U.S. samples were not population based, which precludes assessment of the potential contribution of this locus to prostate cancer incidence in the United States. Methods: We analyzed both markers in a population-based, case-control study of middle-aged men from King County, Washington. Results: Overall, there was a significant positive association between the A allele of the SNP rs1447295 and prostate cancer risk [odds ratio, 1.4; 95% confidence interval (95% CI), 1.1-2.0] but no significant association with the microsatellite DG8S737. However, significant associations were observed for both markers in men with high Gleason scores. Adjusting for age, first-degree family history of prostate cancer, and prostate cancer screening history, the adjusted odds ratios were 1.4 (95% CI, 1.1-1.8) for the A allele of the SNP and 1.9 (95% CI, 1.2-2.8) for the −10 allele of the microsatellite. Conclusions: These data suggest that the locus on chromosome 8q24 harbors a genetic variant associated with prostate cancer and that the microsatellite marker is a stronger risk factor for aggressive prostate cancers defined by poorly differentiated tumor morphology. (Cancer Epidemiol Biomarkers Prev 2007;16(4):809–14)

Hip simulators are regularly used by researchers to assess total hip arthroplasty (THA) implants, range of motion, stability, and alignment of acetabular cup and stem. Previous papers have described three types of simulators: three-dimensional protractors, biaxial rocking motion (BRM) protractors, and single-axis prosthetic range-of-motion (PROM) devices. We have developed a new hip simulator in which the ROM device is completely automated in three independent axes (elevation, internal/external rotation, and plane of elevation). Coupled with the simulator, we used a FaroArm Gold Series coordinate measuring machine (CMM) to accurately align the implant components. The results show that the methodology and alignment setup are accurate and repeatable. With this simulator and digitizer, we are able to study the characteristics of numerous THA implants at various orientations of the pelvis, acetabular cup, stem, and femur.

Purpose There has been a significant increase in surgeon as well as patient interest in arthroscopic treatment of shoulder pathology. We hypothesize that patients have a strong preference for arthroscopic shoulder surgery. Currently, there are no data in the literature reporting on how people perceive open versus arthroscopic shoulder surgery. Methods Prospectively, a total of 202 patients were administered a questionnaire at the offices of 2 fellowship‐trained shoulder surgeons, 1 located at a tertiary referral center (center A) and 1 in private practice (center B). The questionnaire asked a series of questions about specific factors when choosing an orthopaedic surgeon and the preference for arthroscopic or open surgery. In addition, 7 short‐term and long‐term outcomes were listed, and the patient was asked to choose whether open or arthroscopic surgery would provide the best outcome or whether he or she felt that there was no difference. Results Among patients at center A, 88% would prefer arthroscopy if they were to have shoulder surgery, as would 96% of patients at center B. Among patients at center A, 14% would avoid shoulder surgery if the only option was open surgery, as would 25% at center B. The reputation of the surgeon and institution were the primary factors in choosing a surgeon. Recommendation of a former patient and years of surgeon experience were less important factors for patient selection of a shoulder surgeon. Conclusions The study shows that the vast majority of patients perceive multiple advantages of arthroscopic shoulder surgery despite a lack of published data to support many of these assumptions, particularly with regard to expected functional outcome of arthroscopic versus open shoulder surgery. Clinical Relevance Shoulder surgeons should be aware of these perceptions when discussing treatment options with patients. A continued effort should be made to emphasize known scientific data when considering the relative risks and benefits of arthroscopic and open shoulder surgery.

Purpose We tested the hypothesis that the preimplantation mechanical properties of BioCleanse‐treated bone–patellar tendon–bone (BPTB) allografts are not significantly different from those of untreated specimens. Methods For this controlled laboratory study, specimens were harvested as central third or hemi‐BPTB units from both knees of 17 cadaveric tissue donors (11 men and 6 women) aged 19 to 88 years. Donor‐matched specimens (20 per group) were randomly assigned to either BioCleanse‐treated or untreated control groups. Specimens were subjected to 25 minutes of pretensioning at 89 N and then cyclically loaded under longitudinal tension between 50 N and 250 N for 1,000 cycles at 1 Hz, followed by ramp to failure at 50 mm/min. Results No statistically significant difference was found between untreated and BioCleanse‐treated specimens in stiffness (235.3 ± 37.6 N/mm v 222.3 ± 53.4 N/mm, P = .37), cyclic creep (0.38 ± 0.42 mm v 0.40 ± 0.26 mm, P = .81), maximum force (1,685.7 ± 471.6 N v 1,807.0 ± 657.8 N, P = .47), or ultimate stress (29.0 ± 9.8 MPa v 29.0 ± 12.8 MPa, P = .98). Conclusions The preimplantation mechanical properties of BPTB allografts treated with BioCleanse are not significantly different from those of untreated controls. Clinical Relevance This laboratory study compares the biomechanical properties of chemically treated allografts, which are currently being used in anterior cruciate ligament reconstruction, with those of nontreated fresh‐frozen allografts.

Abstract Estrogen-induced Syrian hamster tumors in the kidney represent a useful model to gain insight into the role of estrogens in oncogenic processes. We provided evidence that early tumor foci in the kidney arise from interstitial ectopic uterine-like germinal stem cells, and that early tumor foci and well-established tumors are highly aneuploid (92–94%). The molecular mechanisms whereby estrogens mediate this process are unclear. Here, we report that estrogen treatment induced significant increases in Aurora A protein expression (8.7-fold), activity (2.6-fold), mRNA (6.0-fold), and Aurora B protein expression (4.6-fold) in tumors, compared with age-matched cholesterol-treated kidneys. Immunohistochemistry revealed that this increase in Aurora A and B protein expression was essentially confined to cells within early and large tumor foci at 3.5 and 6 months of estrogen treatment, respectively. Upon estrogen withdrawal or coadministration of tamoxifen for 10 days, a 78% to 79% and 81% to 64% reduction in Aurora A and B expression, respectively, were observed in primary tumors compared with tumors continuously exposed to estrogens. These data indicate that overexpressed Aurora A and B in these tumors are under estrogen control via estrogen receptor α. Aurora A coenriched with the centrosome fraction isolated from tumors in the kidney. Centrosome amplification (number and area/cell) was detected in early tumor foci and large tumors but not in adjacent uninvolved or age-matched control kidneys. Taken together, these data indicate that persistent overexpression of Aurora A and B is under estrogen control, and is coincident with centrosome amplification, chromosomal instability, and aneuploidy, and represent an important mechanism driving tumorigenesis. [Cancer Res 2007;67(7):2957–63]

Abstract Two variants (rs1447295/DG8S737) of chromosome 8q24 were recently reported to be associated with increased risk of prostate cancer (PC). To confirm this finding, we genotyped and compared the frequencies of these polymorphisms among 1,121 Caucasian men with PC (435 men with familial PC, 491 men with sporadic PC, and 195 men with aggressive PC) to 545 population-based controls. For the single nucleotide polymorphism marker rs1447295, frequencies of the minor allele (A) were 10.3% in controls, 11.9% in sporadic cases, 16.7% in familial cases, and 17.2% in aggressive cases. Compared with controls, the A allele was significantly more common in both familial PC [odds ratios (OR), 1.93; 95% confidence intervals (95% CI), 1.37–2.72; P = 0.0004] and aggressive PC (OR, 1.87; 95% CI, 1.28–2.74; P = 0.0005) but not for sporadic PC (OR, 1.16; 95% CI, 0.85–1.58; P = 0.25). Although the A allele was more frequent in aggressive PC cases when compared with controls, the allele frequencies were similar among cases with high- and low-grade PC (Gleason grades <7 and ≥7, respectively). For the microsatellite marker DG8S737, the −8 allele was significantly more frequent in familial PC (OR, 1.68; 95% CI, 1.09–2.60; P = 0.031), whereas the −10 allele was more frequent in aggressive PC (OR, 2.85; 95% CI, 1.52–5.36; P = 0.0004). Haplotype analysis showed significant differences in haplotype frequencies between the familial PC (P = 0.006) and aggressive PC (P = 0.005) cases versus controls. The −8/A haplotype showed the strongest association with familial PC (P = 0.008), whereas the −10/A haplotype was most strongly associated with aggressive PC (P = 0.00005). These results further confirm the importance of these two polymorphic variants (rs1447295 and DG8S737) as risk factors for PC. However, the mechanism explaining this increased risk has not yet been established. [Cancer Res 2007;67(7):2944–50]

Abstract Standard therapy for nonorgan confined prostate cancer aims to block the production or action of androgens. Although initially successful, antiandrogen therapy eventually fails and androgen depletion independent (ADI) disease emerges. Remarkably, ADI prostate cancers still rely on a functional androgen receptor (AR). Aberrant expression of coregulatory proteins required for the formation of productive AR transcriptional complexes is critical for ADI AR activation. Previously, we have shown that the transcriptional coactivator p300 is required for ADI activation of the AR and is up-regulated in prostate cancer, in which its expression is associated with cell proliferation and predicts aggressive tumor features. The mechanism responsible for the deregulated expression of p300, however, remains elusive. Here, we show that p300 expression in prostate cancer cells is subject to androgen regulation. In several prostate cancer model systems, addition of synthetic and natural androgens led to decreased expression of p300 in a time-dependent and dose-dependent manner. Experiments using AR antagonists or small interfering RNA targeting the AR revealed that down-regulation of p300 depends entirely on the presence of a functional AR. It is noteworthy that androgens down-regulated p300 protein expression while leaving messenger levels unaltered. Conversely, both short-term and long-term androgen deprivation resulted in marked up-regulation of p300 expression. The androgen deprivation–induced increase in p300 expression was not affected by the addition of cytokines or growth factors or by cotreatment with antiandrogens. Moreover, increased p300 expression upon androgen starvation is crucial for prostate cancer cell proliferation, as loss of p300 expression severely reduces expression of cyclins governing G1-S and G2-M cell cycle transition and decreases 5-bromo-2′-deoxyuridine incorporation. [Cancer Res 2007;67(7):3422–30]