Assessing satisfaction of search in virtual mammograms for experienced and novice searchers.

Purpose: Satisfaction of search (SOS) is a phenomenon where searchers are more likely to miss a lesion/target after detecting a first lesion/target. Here, we investigated SOS for masses and calcifications in virtual mammograms with experienced and novice searchers to determine the extent to which: (1) SOS affects breast lesion detection, (2) similarity between lesions impacts detection, and (3) experience impacts SOS rates. Approach: The open virtual clinical trials framework was used to simulate the breast anatomy of patients, and up to two simulated masses and/or single-calcifications were inserted into the breast models. Experienced searchers (residents, fellows, and radiologists with breast imaging experience) and novice searchers (undergraduates who had no breast imaging experience) were instructed to search for up to two lesions (masses and calcifications) per image. Results: 2×2 mixed factors analysis of variances (ANOVAs) were run with: (1) single versus second lesion hit rates, (2) similar versus dissimilar second-lesion hit rates, and (3) similar versus dissimilar second-lesion response times as within-subject factors and experience as the between subject's factor. The ANOVAs demonstrated that: (1) experienced and novice searchers made a significant amount of SOS errors, (2) similarity had little impact on experienced searchers, but novice searchers were more likely to miss a dissimilar second lesion compared to when it was similar to a detected first lesion, (3) experienced and novice searchers were faster at finding similar compared to dissimilar second lesions. Conclusions: We demonstrated that SOS is a significant cause of lesion misses in virtual mammograms and that reader experience impacts detection rates for similar compared to dissimilar abnormalities. These results suggest that experience may impact strategy and/or recognition with theoretical implications for determining why SOS occurs.

The Effect of Asparagus Extract on Pancreatic Cancer: An Intriguing Surprise.

BACKGROUND: Pancreatic cancer is the most lethal digestive cancer and the fourth overall cause of cancer death in the US. Asparagus, a widely consumed savory vegetable, is a rich source of antioxidants, saponins, vitamins, and minerals. In recent years, it has been shown that components of asparagus have anticancer effects on endometrial adenocarcinoma, and in prostate, breast, and colon cancer. In pancreatic cancer, it has been shown to have an anticancer effect on the KLM1-R cell line. This study was designed to investigate if asparagus extract (AE) had any effect on the growth of a widely used pancreatic cancer cell line MDAPanc-28 and to elucidate possible molecular mechanisms behind it. MATERIALS AND METHODS: Clonogenic survival assay, proliferation, and caspase-3 activity kits were used to evaluate the effects of AE on cell survival, proliferation, and apoptosis pathway of MDAPanc-28 cells. We further investigated the possible molecular mechanisms by using reverse transcription-polymerase chain reaction. RESULTS: The colony numbers and proliferation of MDAPanc-28 cells were surprisingly increased when treated with AE. The relative caspase-3 activity in cancer cells decreased when they were treated with AE. The pro-proliferative effect of AE on MDAPanc-28 cells correlated with down-regulation of anti-proliferative molecules P21 and P53. The potential anti-apoptotic effect of AE correlated with down-regulation of the pro-apoptotic molecule Fas cell surface death receptor (FAS) and down-regulation of caspase-3 activity. CONCLUSION: AE exhibits a pro-tumor effect on MDAPanc-28 pancreatic cancer cells by down-regulation of P21, P53, and FAS.

Selective hydrosilylation of alkynes and ketones: contrasting reactivity between cationic 3-iminophosphine palladium and nickel complexes.

The catalytic hydrosilylation of alkynes and ketones has been explored utilizing palladium- and nickel(allyl) complexes supported by 3-iminophosphine ligands. Palladium and nickel demonstrated distinctly different reactivity profiles, with palladium proving very effective for the hydrosilylation of electron-deficient alkynes, while nickel excelled with ketones and internal alkynes. Additionally, in many cases, regioselective hydrosilylation was observed.

Cationic [(Iminophosphine)Nickel(Allyl)]+ Complexes as the First Example of Nickel Catalysts for Direct Hydroamination of Allenes.

The first example of nickel-catalyzed hydroamination of allenes is reported. The new cationic [(3-iminophosphine)nickel(allyl)]+ catalysts have been fully characterized and act regioselectively in the catalytic hydroamination of allenes with secondary amines at room temperature.

Targeting androgen receptor and JunD interaction for prevention of prostate cancer progression.

BACKGROUND: Multiple studies show that reactive oxygen species (ROS) play a major role in prostate cancer (PCa) development and progression. Previously, we reported an induction of Spermidine/Spermine N(1) -Acetyl Transferase (SSAT) by androgen-activated androgen receptor (AR)-JunD protein complex that leads to over-production of ROS in PCa cells. In our current research, we identify small molecules that specifically block AR-JunD in this ROS-generating metabolic pathway. METHODS: A high throughput assay based on Gaussia Luciferase reconstitution was used to identify inhibitors of the AR-JunD interaction. Selected hits were further screened using a fluorescence polarization competitor assay to eliminate those that bind to the AR Ligand Binding Domain (LBD), in order to identify molecules that specifically target events downstream to androgen activation of AR. Eleven molecules were selected for studies on their efficacy against ROS generation and growth of cultured human PCa cells by DCFH dye-oxidation assay and DNA fluorescence assay, respectively. In situ Proximity Ligation Assay (PLA), SSAT promoter-luciferase reporter assay, and western blotting of apoptosis and cell cycle markers were used to study mechanism of action of the lead compound. RESULTS: Selected lead compound GWARJD10 with EC(50) 10 µM against ROS production was shown to block AR-JunD interaction in situ as well as block androgen-induced SSAT gene expression at IC(50) 5 µM. This compound had no effect on apoptosis markers, but reduced cyclin D1 protein level. CONCLUSIONS: Inhibitor of AR-JunD interaction, GWARJD10 shows promise for prevention of progression of PCa at an early stage of the disease by blocking growth and ROS production.

Urinary bladder leiomyoma associated with pulmonary lymphangioleiomyomatosis.

Leiomyomas account for less than 0.43% of all bladder tumors. To date only about 250 cases have been reported in the literature. Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease featuring abnormal proliferation of atypical smooth muscle cells around bronchovascular structures. We describe a woman with LAM who presented with pelvic pain and was found to have a leiomyoma of the bladder wall. Although urologic manifestations of pulmonary LAM are uncommon, they should be considered in the differential diagnosis of a patient who presents with a pelvic mass and a history of LAM.

Isolated prostate cancer recurrence presenting as pelvic mass nine years after radical retropubic prostatectomy.

Pelvic seeding from radical retropubic prostatectomy for adenocarcinoma of the prostate is uncommon. We describe a patient who presented with a prostate-specific antigen recurrence and was found to have a solitary metastasis adjacent to his pubic bone 9 years after radical prostatectomy. Computed tomography scanning followed by surgery documented the pelvic recurrence.

Correlating metabolic and anatomic responses of primary lung cancers to radiotherapy by combined F-18 FDG PET-CT imaging.

BACKGROUND: To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy. METHODS: 36 patients were studied pre- and post-radiotherapy with18FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy. RESULTS: There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 +/- 32.7% vs 47.1 +/- 26.1% respectively, p = 0.03) CONCLUSION: Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.

Identifying problems faced by spouses and partners of patients with prostate cancer.

PURPOSE/OBJECTIVES: To describe problems chosen as targets of problem-solving therapy by spouses and partners of patients with prostate cancer. DESIGN: Descriptive, cross-sectional. SETTING: Spouses' and partners' homes. SAMPLE: Spouses and partners (N = 66) aged 32-79 years (mean = 60 years). The sample was predominantly Caucasian (82%) and African American (8%). METHODS: As part of a randomized clinical trial, women received problem-solving therapy to help manage issues related to their husbands' or partners' prostate cancer. The issues they chose to address during therapy and the categorization of the issues fell into four groups: treatment and side-effect issues, patient issues, family issues, and spouse issues. Scores on the Social Problem-Solving Inventory-Revised, which measures everyday problem-solving skills, and the Profile of Mood States, which measures mood disturbance, were contrasted with the problems women chose to address. MAIN RESEARCH VARIABLES: Problems faced by spouses and partners of patients with prostate cancer. FINDINGS: The most frequently reported categories were spouse issues (e.g., women's emotional wellness, balancing their medical concerns with their husbands' condition) and patient issues (e.g., men's lack of communication, fear, or depression). CONCLUSIONS: Findings of this study alert nurses to a variety of key problem areas for spouses and partners of patients with prostate cancer. IMPLICATIONS FOR NURSING: Spouses and partners play a critical role when their loved ones have cancer. Understanding the problems spouses and partners face can help nurses design optimal supportive care interventions.

Simple perineal prostatectomy: lessons learned from a modern series.

PURPOSE: Experience with simple perineal prostatectomy has not been well described in the recent literature. We describe our operative technique and compare objective demographic, preoperative, intraoperative and postoperative parameters in patients undergoing open prostatectomy for benign prostatic hyperplasia via 3 routes, namely perineal, retropubic, and suprapubic. MATERIALS AND METHODS: We retrospectively reviewed all cases of open prostatectomy at Veterans Affairs Medical Center, San Diego between August 2001 and September 2002. A total of 22 patients were identified. Objective parameters were recorded and compared, including patient age, history of urinary retention, ultrasound volume, prostate specific antigen, patient and specimen weight, operative time, estimated blood loss, transfusion requirement, days of hospitalization and postoperative analgesic requirement. RESULTS: In the 22 patients who underwent open prostatectomy the operative approach was perineal in 6, retropubic in 8 and suprapubic in 8. Operative time and hospital stay were significantly less in the perineal prostatectomy group. CONCLUSIONS: Simple perineal prostatectomy is a viable alternative for most patients considered candidates for open prostatectomy and it is our preferred approach for obese patients. With perineal prostatectomy patients may expect shorter hospitalization and less analgesic requirement but likely require a longer period of catheter drainage.

Urology practice patterns after residency training in radical perineal prostatectomy.

OBJECTIVES: To assess the impact of residency training in radical perineal prostatectomy (RPP) on subsequent use of RPP in urology practice. METHODS: Urologists who completed residency training at Tulane University and the University of California, San Diego, Medical Center from 1977 to 1999 were surveyed by anonymous questionnaire for their practice demographics, operative experience in RPP during residency, the role of RPP in their current practice, and the reasons they do or do not perform RPP. RESULTS: Of 91 former residents, 61 (67%) responded. RPP was in current use by 41% of the urologists trained in RPP during residency and by 13% of those with no residency RPP training. Those who had performed 10 or more RPPs during residency reported a higher rate of current RPP use (53%) than did those who had performed fewer than 10 RPPs during residency (21%). Urologists trained in RPP during residency cited partner preference (28%) and inadequate exposure (26%) as reasons they did not perform RPP; respondents with no residency RPP training cited inadequate exposure (25%), difficulty of the operation (25%), and time required to perform the operation (25%). CONCLUSIONS: A urologist with residency training in RPP is more likely to perform RPP in practice than is a urologist without such training. The intensity of training, in the form of greater operative experience during residency, had a positive impact on the future use of this specialized surgical technique.

Identification of a human telomerase reverse transcriptase peptide of low affinity for HLA A2.1 that induces cytotoxic T lymphocytes and mediates lysis of tumor cells.

Telomerase reverse transcriptase (TRT) is a tumor-associated antigen expressed in the vast majority of human tumors and is presently one of the most promising target candidates for a therapeutic cancer vaccine. TRT is also expressed at low level in selected tissues and should be considered a self antigen. In the present study we sought to develop cytotoxic T lymphocytes (CTL) responses directed against human (h)TRT peptides with low relative affinity for which the available repertoire is to be preferentially spared from tolerance. This was accomplished by using analogue peptides of hTRT whose relative affinity for the MHC was increased by a targeted (-->Tyr) substitution in position one. By immunizing HLA A2.1 transgenic mice with these analogue peptides, we identified one such low relative affinity peptide (p572) that is endogenously processed and presented by HLA A2.1 in tumor cells, and is recognized by specific CTL. We used the highly immunogenic analogue peptide to successfully induce TRT-specific CTL in cancer patients and normal donors. CTL against p572-lysed human and mouse tumor cells but not activated autologous B cells. This peptide represents, therefore, an important candidate component of a cancer vaccine based on a TRT substrate and validates the strategy of targeting peptides with low affinity for the MHC for cancer immunotherapy.

Problems associated with prostate cancer: differences of opinion among health care providers, patients, and spouses.

BACKGROUND: Problems accompany any experience with cancer. METHODS: Patients, spouses, and providers were asked to identify their perceptions of the problems associated with recently diagnosed prostate cancer. Their answers were compared across respondent categories (physician, nurse, patient, and spouse) and cross-informant variance was analyzed. RESULTS: Significant variation in responses was noted by respondent categories in spite of the relatively small sample. CONCLUSION: The response variance may contribute to communication problems among patients, spouses, and providers, as well as missed opportunities for medically appropriate referrals to psychological treatment and community support resources.

The long-term effect of specific type II 5alpha-reductase inhibition with finasteride on bone mineral density in men: results of a 4-year placebo controlled trial.

PURPOSE: We determine the effect of long-term suppression of dihydrotestosterone with finasteride, a specific type II 5alpha-reductase inhibitor, on bone mineral density. MATERIALS AND METHODS: As part of a large (3,040 cases) 4-year, double-blind, placebo controlled trial designed to assess the long-term effects of finasteride in men with benign prostatic hyperplasia, 157 men 46 to 76 years old who were randomized to receive either 5 mg. finasteride or placebo underwent dual energy x-ray absorptiometry of the lumbar spine at baseline and at years 2, 3 and 4. RESULTS: Of 117 patients who had a baseline measurement and at least 1 additional measurement during the study baseline mean plus or minus standard deviation bone mineral density values were 1.12 +/- 0.17 gm./cm.2 in the finasteride group (63) and 1.10 +/- 0.17 gm./cm.2 in the placebo group (54). After 4 years bone mineral density was not different between treatment groups (finasteride 1.14 +/- 0.17 gm./cm.2 and placebo 1.13 +/- 0.18 gm./cm.2). Similar results were obtained for the 33 finasteride and 25 placebo treated patients who completed the study with year 4 bone mineral density measurements. CONCLUSIONS: These data demonstrate that long-term inhibition of type II 5alpha-reductase with finasteride does not adversely affect bone mineral density.

Chemotherapy Programs of the National Prostatic Cancer Project (NPCP).

Results of the first nationally randomized trial of the National Prostatic Cancer Project revealed a demonstrable advantage for chemotherapy in the management of advanced disease (Stage D in relapse from endocrine therapy). Both cyclophosphamide and 5-Fluorouracil showed improved activity over standard therapy. A second trial for patients previously irradiated, with less tolerance to myelosuppressive agents, revealed an advantage for estramustine phosphate and streptozotocin over standard therapy. Subsequently completed trials have revealed activity for prednimustine and imidazole carboxamide (DTIC). Trials currently underway for newly-diagnosed Stage D and for Stage D disease clinically stable to diethylstilbestrol (DES) show promising activity for DES combined with cyclophosphamide. Current trials with single agents in advanced disease are comparing methyl-CCNU and hydroxyurea with cyclophosphamide; another is evaluating estramustine phosphate and vincristine alone and in combination. The use of chemotherapy in earlier staged patients as adjuvants to definitive surgery or irradiation is underway in two clinical trials, where the effect of cyclophosphamide and estramustine phosphate as long-term therapies is compared with no additional treatment.