FDG PET imaging for grading and prediction of outcome in chondrosarcoma patients

The aims of this study were to assess the potential of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) for tumor grading in chondrosarcoma patients and to evaluate the role of standardized uptake value (SUV) as a parameter for prediction of patient outcome. FDG PET imaging was performed in 31 patients with chondrosarcoma prior to therapy. SUV was calculated for each tumor and correlated to tumor grade and size, and to patient outcome in terms of local relapse or metastatic disease with a mean follow-up period of 48 months. Chondrosarcomas were detectable in all patients. Tumor SUV was 3.38±1.61 for grade I (n=15), 5.44±3.06 for grade II (n=13), and 7.10±2.61 for grade III (n=3). Significant differences were found between patients with and without disease progression: SUV was 6.42±2.70 (n=10) in patients developing recurrent or metastatic disease compared with 3.74±2.22 in patients without relapse (P=0.015). Using a cut-off of 4 for SUV, sensitivity, specificity, and positive and negative predictive values for a relapse were 90%, 76%, 64%, and 94%, respectively. Combining tumor grade and SUV, these parameters improved to 90%, 95%, 90%, and 95%, respectively. Pretherapeutic tumor SUV obtained by FDG PET imaging was a useful parameter for tumor grading and prediction of outcome in chondrosarcoma patients. The combination of SUV and histopathologic tumor grade further improved prediction of outcome substantially, allowing identification of patients at high risk for local relapse or metastatic disease.     

Hemodynamic status after the Norwood procedure: a comparison of right ventricle-to-pulmonary artery connection versus modified Blalock-Taussig shunt

Background

The aim of this study is to compare hemodynamic status, in particular systemic oxygen delivery, in patients undergoing a Norwood procedure with a right ventricle-to-pulmonary artery (RV-PA) versus a modified Blalock-Taussig (mBT) shunt.

Methods

From June 2000 to November 2003, 44 consecutive neonates with hypoplastic left heart syndrome underwent a Norwood procedure. The first 25 patients received an mBT shunt; the subsequent 19 an RV-PA shunt. Hemodynamic data, including mixed venous oxygen saturation, was determined during the first 48 hours after surgery.

Results

The mBT and RV-PA shunt patients had no significant differences in systemic oxygen saturation, mixed venous oxygen saturation, arteriovenous oxygen saturation difference, or oxygen excess factor during the first 48 hours. Mixed venous saturation declined to a nadir in both groups at 6 to 12 hours. The RV-PA patients had significantly higher diastolic and mean blood pressures, and lower systolic blood pressure. Mean heart rate, common atrial pressure, and inotrope score did not differ between the two groups. The RV-PA patients received higher fraction of inspired oxygen and minute ventilation to achieve partial pressures of arterial oxygen and carbon dioxide, and pH, similar to mBT patients. Durations of mechanical ventilation, intensive care unit stay, and hospital stay did not differ between mBT and RV-PA patients. Operative survival in the mBT versus RV-PA group was 20 of 25 (80%) versus 17 of 19 (89%; p = 0.7).

Conclusions

Indicators of postoperative systemic oxygen delivery are equivalent in neonates who have undergone a Norwood procedure with an mBT or RV-PA shunt. Both mBT and RV-PA patients undergo similar declines in hemodynamic status 6 to 12 hours after surgery. Any advantages of one approach over the other lie in areas other than systemic oxygen delivery, such as resistance to physiologic insults, or preservation of ventricular function.     

The mitosis-specific antibody anti-phosphohistone-H3 (PHH3) facilitates rapid reliable grading of meningiomas according to WHO 2000 criteria

Mitotic figure (MF) counting is the most objective criterion for grading of meningiomas according to the 2000 World Health Organization (WHO) classification. However, the search for the area(s) of highest mitotic activity is tedious, and there is high interobserver variability in differentiating MF from apoptotic cells. We tested the utility of the mitosis-specific marker phosphohistone-H3 (PHH3) to enhance rapid recognition of MFs and quick reliable grading of meningioma. Fifty-four archival meningiomas (26 benign, 20 atypical, 8 anaplastic) were reclassified according to current WHO criteria. PHH3-immunostained MFs were counted the same way as in hematoxylin and eosin-stained sections. Anti-PHH3-labeled MFs were easily seen and permitted quick identification of the area(s) of highest mitotic activity. Count results (mean) show a strong correlation between both methods: benign, hematoxylin and eosin 1.4, PHH3 2.2; atypical, hematoxylin and eosin 9.0, PHH3 15.9; anaplastic, hematoxylin and eosin 22.4, PHH3 34.1. PHH3 counting yielded greater sensitivity and in 12 cases (22.2%) suggested a change in grade (increased 9; lowered 3). All cases in which PHH3 lowered the grade were from older blocks, suggesting a loss of antigen preservation. PHH3 immunostaining facilitates the rapid reliable grading of meningiomas by focusing attention on the most mitotically active areas and by allowing easy and objective differentiation of MFs from apoptotic nuclei.     

Met160Val polymorphism in the TRMPSS2 gene and risk of prostate cancer in a population-based case-control study

BACKGROUND: Serine proteases play an important role in prostate cancer (PCa) invasion through the degradation of extracellular matrix proteins and interaction with growth modulating factors. The transmembrane serine protease 2 (TMPRSS2) gene encodes a type II transmembrane protein which, due to its cell surface localization, could be a potentially useful predictive marker for PCa. METHODS: We screened a population of 24 unrelated individuals for sequence variants in the TMPRSS2 gene, and found a Met160Val change in 33%. We then tested 559 cases and 523 controls from a population-based case-control study of middle-aged men from Washington State. RESULTS: Men with the GG genotype and a first-degree family history of PCa had a significantly higher risk for PCa relative to men without a family history (OR = 2.05; 95% CI = 1.3-3.2). However, the interaction between genotype and family history of PCa was not significant (P = 0.52). CONCLUSIONS: Larger, more detailed studies are needed to fully investigate the role of serine proteases in PCa.     

Vitamin D receptor gene polymorphisms and prostate cancer risk

BACKGROUND: Vitamin D is a steroid hormone that is thought to play a role in the etiology and progression of prostate cancer. Hormone activity requires binding to the vitamin D receptor (VDR), which contains several genetic polymorphisms that have been associated with risk of prostate cancer. To further evaluate this relationship, we conducted a population-based case-control study of the VDR BsmI, FokI, and Poly-A polymorphisms, and prostate cancer. METHODS: Germline DNA samples and survey data from incident prostate cancer cases (n = 559) and controls (n = 523) of similar age (40-64 years) without a history of the disease who resided in King County, Washington were analyzed. RESULTS: The frequency of the BsmI, FokI, and Poly-A genotypes were similar in cases and controls, and no overall association between any variants and prostate cancer risk were noted. Stratification by clinical features of disease revealed that among men with localized stage disease, the BsmI bb genotype was associated with a modest increase in risk (OR, 1.49; 95% CI, 1.02-2.17; P = 0.04) compared to the BB genotype. CONCLUSIONS: These results suggest that polymorphisms in the VDR gene are not strong predictors of prostate cancer risk among Caucasian men in the U.S.     

Arthrodesis of the knee

The most common indication for arthrodesis of the knee is an infection at the site of a total knee arthroplasty. Deficiencies in bone stock and poor bone apposition adversely affect the success of a knee arthrodesis. Arthrodesis of the knee can provide a stable, painless extremity for high-functioning patients who are able to walk. Patient function after arthrodesis of the knee is superior to that after above-the-knee amputation. Conversion of a solid knee fusion to a total knee arthroplasty has a substantial complication rate.