Steroid hormones stimulate human prostate cancer progression and metastasis

Tissue recombinants (TRs) composed of mouse urogenital mesenchyme (mUGM) plus an immortalized nontumorigenic human prostatic epithelial cell line (BPH-1) were grown under the kidney capsule of male athymic nude mice under different hormonal conditions. The objectives were to determine temporal plasma concentrations of testosterone (T) and estradiol-17beta (E2) that elicit progression of nontumorigenic human prostatic epithelial cells in vivo. Second, to determine whether mUGM+BPH-1 TRs in [T+E2]-treated hosts could progress to metastases. Control mouse hosts received no exogenous hormonal support, whereas treated mice received Silastic implants containing T and E2 for 1-4 months. Plasma from hormonally treated mice contained significantly higher (p < 0.01) concentrations of T at 1 month (11.7 vs. 0.9 ng/ml). Plasma levels of E2 in steroid implanted mice were significantly higher (p < 0.05) at 2 months (104.5 vs. 25.6 ng/l) and 4 months (122.8 vs. 19.2 pg/ml). Wet weights of mUGM+BPH-1 TRs from [T+E2]-implanted mice were significantly larger (p < 0.001) than those from untreated hosts. Untreated mUGM+BPH-1 TRs contained a well organized differentiated epithelium surrounded by smooth muscle stroma similar to developing prostate. In [T+E2]-implanted mice, mUGM+BPH-1 TRs formed carcinomas that contained a fibrous connective tissue stroma permeating the tumor; smooth muscle when present was associated with vasculature. Renal lymph nodes collected from [T+E2]-treated mice, but not untreated mice, contained metastatic carcinoma cells. Moreover, metastases could be observed at distant sites including lung and liver. Epithelial cells isolated from untreated mUGM+BPH-1 TRs exhibited benign histology and formed small nontumorigenic grafts when subsequently transplanted into athymic nude mice. In contrast, epithelial cells isolated from mUGM+BPH-1 tumors of [T+E2]-treated hosts formed large tumors that grew independent of stromal and hormonal support and developed lymph node metastases. We conclude that [T+E2]-treatment promotes prostatic cancer progression in mUGM+BPH-1 TRs. Use of mUGM in this system will allow future studies to utilize the power of mouse genetics to identify paracrine factors involved in human prostatic carcinogenesis.     

Prospective Study of Quality of Life in Adults with Newly Diagnosed High-grade Gliomas

Summary Objective To assess baseline quality of life (QOL) and its prognostic importance for adults with newly diagnosed high-grade gliomas, we analyzed QOL and outcome data prospectively collected in three phase II high-grade glioma protocols. Methods At study entry, patients completed five self-administered forms to assess overall QOL (linear analogue scale assessment [LASA] and Functional Assessment of Cancer Therapy-Brain [FACT-Br]); fatigue (Symptom Distress Scale [SDS]); excessive daytime somnolence (Epworth Sleepiness Scale [ESS]); and depression (POMS-SF). Folstein Mini-Mental State Examination (MMSE) and Eastern Cooperative Oncology Group (ECOG) performance scores (PS) were obtained by the health care provider. Results Baseline QOL data were available for 194 of 220 patients (88%) enrolled in the three protocols. Differences in baseline QOL among the three studies were not statistically significant. One-third of patients had clinically significant fatigue at baseline. Increased fatigue (P = 0.003), excessive daytime somnolence (P = 0.01), and lower overall QOL scores (LASA, P = 0.001; FACT-Br, P = 0.0001) correlated with worse ECOG PS. No relation was found between QOL and corticosteroid or anticonvulsant therapy, extent of resection, tumor grade, or sex. Multivariate analyses found worse ECOG PS (PS 2, P = 0.007) associated with increased fatigue. Worse ECOG PS (PS 2, P = 0.002) was also associated with worse overall QOL (LASA). On multivariate analyses of survival, increased fatigue (P = 0.003) predicted poorer overall survival. Conclusions Performance status is related to QOL in patients with newly diagnosed high-grade brain tumors. Increased fatigue is an independent predictor of overall survival. Interventional studies directed at improving QOL, especially fatigue, may have important benefits for these patients.     

Shelter-based convalescence for homeless adults

OBJECTIVES: Homelessness is associated with increased hospital costs and length of stay, and medical or surgical conditions are typically complicated by secondary diagnoses of substance abuse or mental illness. Convalescence care to provide timely treatment has not been analyzed. This is a retrospective study of diagnoses and utility of shelter-based convalescence in a cohort of homeless subjects. METHODS: A 20-bed shelter-based unit providing up to 3 months stay post hospital discharge, or for treatment of addictions or for those too ill to remain in the general shelter was studied. Charting was by the use of an electronic health record developed for the project. Demographics, reason for admission and outcomes are retrospectively described. RESULTS: 140 men had 181 admissions from July 2000-April 2003; 23.8% were post hospital discharge, 57.4% were from the general shelter. Average length of stay was 40 days. 83.4% were treated for a medical or surgical condition, 83.6% for psychiatric disease and 29.8% for addictions. Medication adherence was >80% in the majority. During admission, 20% obtained a new health card, 43.6% a new drug card, 89.3% received transportation to appointments, 60% applied for housing and 24.3% obtained housing. CONCLUSION: A shelter-based convalescence unit can provide health care to homeless persons, treat medical and mental illness, ensure adherence to treatment regimes, decrease substance abuse and assist with housing.     

Towards the development of a pediatric ventricular assist device

The very limited options available to treat ventricular failure in children with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device at the University of Pittsburgh (UoP) and University of Pittsburgh Medical Center (UPMC). Our effort involves a consortium consisting of UoP, Children's Hospital of Pittsburgh (CHP), Carnegie Mellon University, World Heart Corporation, and LaunchPoint Technologies, Inc. The overall aim of our program is to develop a highly reliable, biocompatible ventricular assist device (VAD) for chronic support (6 months) of the unique and high-risk population of children between 3 and 15 kg (patients from birth to 2 years of age). The innovative pediatric ventricular assist device we are developing is based on a miniature mixed flow turbodynamic pump featuring magnetic levitation, to assure minimal blood trauma and risk of thrombosis. This review article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.     

A salutary tale of mistaken identity in testicular cancer

This case report illustrates the importance of not relying on imaging alone. A 26-year-old patient underwent an orchidectomy for mature teratoma; however, as he had abdominal lymphadenopathy, he was treated with 2 cycles of chemotherapy followed by retroperitoneal lymph node dissection. The abdominal histology revealed mature teratoma and he remained on intense surveillance. Three years later, computerized tomography (CT) indicated he had lung lesions and left hilar lymphadenopathy and, despite normal tumor markers, he was thought to have relapsed. He was treated with 2 cycles of second-line chemotherapy but there was no change in the lung lesions. He underwent a CT-guided biopsy which diagnosed sarcoidosis. He was kept under observation by the respiratory physicians and remains well. Sarcoidosis is commonly associated with lymphoma among other malignancies. In the Mayo series, they concluded there was a strong association between sarcoidosis and teratoma but cautioned against a causal relationship as both diseases are rare and found in the same age group. This case report reminds us to always consider the differential diagnoses, particularly if the imaging does not fit the rest of the clinical picture, and when in doubt obtain histology prior to treatment.     

Intraoperative Peripherally Inserted Central Venous Catheter Central Venous Pressure Monitoring in Abdominal Aortic Aneurysm Reconstruction

Numerous studies have found no clinically significant benefit to the perioperative use of pulmonary artery catheters (PACs), and peripherally inserted central venous catheters (PICCs) have been reported to measure central venous pressure (CVP) accurately. The objective of this study was to determine whether the dynamic shifts in preload associated with elective reconstruction of abdominal aortic aneurysms (AAAs) are accurately reflected by CVP measurements from open-ended PICCs compared to CVP measurements from concomitant indwelling PACs. This is a retrospective review of prospectively collected data. PICCs and PACs were placed preoperatively in five patients undergoing elective AAA reconstruction. CVP measurements were recorded every 15 min during the operation. Bland-Altman statistical analysis was used to determine the degree of agreement in data collected by the two measurement devices. Seventy-three paired measurements of CVP from concomitant indwelling PICCs and PACs obtained from five patients undergoing elective AAA reconstruction revealed PICC measurements to be higher than PAC measurements by 0.6 mm Hg (overall correlation coefficient 0.92). The difference between the two measurement devices was expected to be <3.4 mm Hg at least 95% of the time. The findings of this pilot study indicate that PICCs are an effective method for CVP monitoring in situations of dynamic systemic compliance and preload, such as those observed during elective AAA reconstruction.