The prognostic significance of thrombocytosis in uterine papillary serous carcinomas

OBJECTIVES: We have shown that preoperative thrombocytosis (platelet counts >400 x 10(9)/l) is an independent poor prognostic factor in epithelial ovarian cancers (EOC) and is associated with worse survival. In light of the similarities between uterine papillary serous carcinomas (UPSC) and EOC, we sought to determine the incidence of thrombocytosis in UPSC and examine associations with clinico-pathologic features and survival. METHODS: 68 patients with UPSC were identified between 1996 and 2004 at 3 institutions. After IRB approval, records were retrospectively reviewed and data analyzed using Chi-squared and Cox proportional hazards model; survival was analyzed by the method of Kaplan and Meier. RESULTS: 8/68 (12%) patients had thrombocytosis at primary diagnosis. Patients with thrombocytosis were found to have more advanced stage disease (p=0.002) and ascites >1 L (p<0.0001). Of the 21 patients with stage IV disease, those with normal preoperative platelet counts demonstrated a greater likelihood of optimal tumor resection to less than 1 cm residual disease (13/15 versus 1/6 in patients with thrombocytosis, p<0.002). Patients with thrombocytosis had a shorter disease-free interval (17 months versus median survival not yet reached, p=0.0067) and overall survival (24 versus 45 months, p=0.0026). On multivariate analysis, thrombocytosis retained significance as a poor prognostic indicator in patients after controlling for age and stage (p=0.04). CONCLUSIONS: Thrombocytosis may be a marker of aggressive tumor biology in UPSC. Platelet-secreted growth factors may promote aggressive cancer phenotype through contribution to metastasis, invasion, and primary tumor growth.     

Health care M&A advisory alert: Delaware court decision illustrates importance of specialized due diligence on Medicare/Medicaid issues in health care acquisition

Lawyers and clients contemplating a health care transaction must have a strong working knowledge not only of the applicable law, but also of the provider's needs and culture. As illustrated by a recent Delaware court decision, Interim Healthcare, Inc. et al. v. Spherion Corporation, parties engaging in health care provider acquisitions are well advised to select a team of experienced business and legal advisors with specialized knowledge in health care practices that can find and address any suspicious activities before it is too late.     

Influence of bilateral skeletonized harvesting on occurrence of deep sternal wound infection in 1,000 consecutive patients undergoing bilateral internal thoracic artery grafting

OBJECTIVE: To evaluate the risk of deep sternal infection in a large patient cohort following bilateral internal thoracic artery (BITA) grafting using skeletonized BITA dissection. SUMMARY BACKGROUND DATA: Complete myocardial revascularization using BITAs improves long-term survival and lowers the rate of repeat operations. Harvesting of ITAs as skeletonized vessels preserves sternal collateral blood supply, thus enabling rapid sternal healing with less risk of deep sternal infection. METHODS: One thousand consecutive patients (763 men, 340 patients >70 years old, 304 diabetics) underwent skeletonized BITA grafting from April 1996 to July 1999. RESULTS: The 30-day mortality rate was 3.4%. There were 10 perioperative infarcts, 16 strokes, and 22 deep sternal infections. There was an increased risk of deep sternal infection in repeat coronary artery bypass grafting (CABG) operations (15%), chronic obstructive pulmonary disease (COPD) (6.2%), congestive heart failure (4.7%), left ventricular dysfunction (ejection fraction < 35%, 4.5%), and longer aortic cross-clamping time. After adjustment for other demographic, clinical, and surgical predictors, the only independent predictors of deep sternal infection were repeat operations, COPD, and duration of aortic cross-clamping. No patients in the reoperation subgroup died, but three of six COPD patients with deep sternal infection died, and COPD was an independent predictor of overall (early + late) mortality. CONCLUSIONS: Skeletonized BITA grafting carries an acceptable risk of deep sternal infection but is not recommended for repeat CABG or for patients with COPD.     

Arterial myocardial revascularization with in situ crossover right internal thoracic artery to left anterior descending artery

BACKGROUND: The extra length obtained by skeletonizing the internal thoracic arteries (ITAs) enables versatile use of in situ bilateral ITAs for coronary artery bypass grafting, as the longer skeletonized right ITA more easily reaches the anastomotic site on the left anterior descending coronary artery. METHODS: Between April 1996 and November 1999, 365 consecutive patients underwent revascularization with bilateral in situ ITAs (29% of 1,250 grafting procedures performed with both ITAs in our department during this period). The right ITA was routed anterior to the aorta to graft the left anterior descending coronary artery, and the in situ left ITA was used to graft circumflex branches. Right coronary artery branches were grafted with right gastroepiploic artery or saphenous vein graft. The right ITA crossed the midline above the aorta at the most cranial point to avoid damage in case of a repeat sternotomy in the future. RESULTS: The operative mortality rate was 2.2% (8 patients). Postoperative morbidity included seven strokes (1.9%), eight sternal wound infections (2.2%), and four perioperative myocardial infarctions (1.1%). Follow-up (6 to 49 months) of 97% of hospital survivors showed a return of angina in 3%. Postoperative coronary angiography (22 patients) revealed a 95% patency rate of both ITAs. One-year and 4-year survival rates (Kaplan-Meier) were 95% and 92.4%, respectively. Important predictors of an early unfavorable event were chronic obstructive pulmonary disease, old age (> or = 70 years), emergency operation, and diabetes. Chronic obstructive pulmonary disease was the only independent predictor of sternal wound infection (odds ratio, 15; 95% confidence interval, 2.8 to 80). It also predicted decreased late survival (hazard ratio, 8.3; 95% confidence interval, 3 to 21.5). CONCLUSIONS: With skeletonized dissection of ITAs, the right ITA easily reaches the left anterior descending coronary artery for left-sided arterial revascularization with in situ bilateral ITAs. This procedure is safe, but we recommend avoiding its use in patients with chronic obstructive pulmonary disease.     

Revealing targeted therapy for human cancer by gene module maps

A major goal of cancer research is to match specific therapies to molecular targets in cancer. Genome-scale expression profiling has identified new subtypes of cancer based on consistent patterns of variation in gene expression, leading to improved prognostic predictions. However, how these new genetic subtypes of cancers should be treated is unknown. Here, we show that a gene module map can guide the prospective identification of targeted therapies for genetic subtypes of cancer. By visualizing genome-scale gene expression in cancer as combinations of activated and deactivated functional modules, gene module maps can reveal specific functional pathways associated with each subtype that might be susceptible to targeted therapies. We show that in human breast cancers, activation of a poor-prognosis "wound signature" is strongly associated with induction of both a mitochondria gene module and a proteasome gene module. We found that 3-bromopyruvic acid, which inhibits glycolysis, selectively killed breast cells expressing the mitochondria and wound signatures. In addition, inhibition of proteasome activity by bortezomib, a drug approved for human use in multiple myeloma, abrogated wound signature expression and selectively killed breast cells expressing the wound signature. Thus, gene module maps may enable rapid translation of complex genomic signatures in human disease to targeted therapeutic strategies.     

Lemierre syndrome: a case report

Lemierre syndrome is a condition that can have high morbidity and mortality, but if it is diagnosed early in a patient's workup, that is, in the ED, the morbidity and mortality can be significantly decreased. First described by Dr Andre Lemierre in 1936, Lemierre syndrome is a clinical condition, which presents as septic emboli in the internal jugular vein after an untreated pharyngitis. This condition can have significant morbidity and mortality; therefore, although it is not common in today's era of antimicrobials, it should still be considered and thought of to prevent the significant consequences that may occur from it. In this article, we will present a child who was admitted for fever, neck pain, lymphadenopathy, and lung abscesses which was diagnosed as Lemierre syndrome. This syndrome will be discussed so as to heighten clinical awareness of it.     

Protamine-induced cardiotoxicity is prevented by anti-TNF-alpha antibodies and heparin.

BACKGROUND: We investigated the role of tumor necrosis factor alpha (TNF-alpha) in protamine-induced cardiotoxicity and the possibility of preventing or decreasing this effect by anti TNF-alpha antibodies and heparin. METHODS: Isolated rat hearts were perfused for 60 min with Krebs-Henseleit solution (KH). The control group was perfused with KH alone, the KH > protamine > KH group was treated from the 20th to the 40th minute with protamine, and the KH + anti-TNF > protamine + anti-TNF > KH + anti-TNF group was treated the same as the KH > protamine > KH group but with anti-TNF-alpha antibodies added throughout perfusion. The KH + heparin > protamine + heparin > KH + heparin group was treated the same as the KH > protamine > KH group but with heparin added to KH throughout perfusion. The KH > protamine > KH + heparin was perfused the same as the KH> protamine > KH group but with heparin added to KH for the last 20 min. Left ventricular (LV) function and coronary flow were measured every 10 min. TNF-alpha was measured in the coronary sinus effluent. Left ventricular TNF messenger RNA was determined in the control and KH > protamine > KH groups at baseline and after the 40-min perfusion. RESULTS: Protamine caused a significant decrease of peak systolic pressure and dP/dt (to 25% of baseline). Significant amounts of TNF-alpha in the effluent in the KH > protamine > KH group (102.3 +/- 15.5 pg/min) and TNF messenger RNA expression in left ventricular samples were detected. TNF-alpha was below detectable concentrations in the control, KH + anti-TNF > protamine + anti-TNF > KH + anti-TNF, and KH + heparin > protamine + heparin > KH + heparin groups. TNF-alpha concentrations correlated with depression of LV peak systolic pressure (r = 0.984; P = 0.01) and first derivate of the increase of LV pressure (r = 0.976; P = 0.001). Heparin improved LV recovery and decreased protamine-induced TNF-alpha release (KH > protamine > KH + heparin group). CONCLUSIONS: Anti-TNF-alpha antibodies and heparin prevent protamine-induced TNF-alpha release and depression of LV function. Heparin improves protamine-induced depression of cardiac function.