New imaging techniques in prostate cancer

Correct staging of prostate cancer at initial diagnosis, as well as accurate staging and tumor localization with biochemical recurrence, remains generally inaccurate with current imaging techniques. Newer modalities are being investigated to accurately identify patients with prostate cancer at different stages of disease. Identification of locally recurrent disease or distant metastasis at the time of biochemical failure after local therapy will help guide treatment options and avoid potentially toxic salvage therapies in patients who will not benefit. A review of prostate cancer imaging literature over the past 12 months was performed to identify emerging imaging modalities that may be beneficial in the management of prostate cancer. Enhanced transrectal ultrasonography modalities, including ultrasound contrast agents, color and power Doppler, and elastrography, have demonstrated incremental benefit when combined with standard grayscale ultrasonography to accurately target and diagnose prostate cancer. Endorectal MRI, with contrast enhancement and spectroscopic imaging, shows promise in the initial staging of prostate cancer prior to local therapy. The use of positron-emission tomography scan for prostate cancer remains to be defined, but may help delineate the site of recurrence with biochemical failure after local therapy. Several new imaging modalities show promise for the evaluation of the patient with prostate cancer. Enhanced ultrasonography techniques may prove to be more accurate in diagnosing prostate cancer over standard gray-scale ultrasonography. Accumulating evidence supports the use of endorectal MRI and spectroscopy to help treatment planning with either surgical or radiotherapeutic approaches. Although intriguing, the available data for positron-emission tomography in prostate cancer remains too shallow to advocate routine use.     

Comparing food intake using the Dietary Risk Assessment with multiple 24-hour dietary recalls and the 7-Day Dietary Recall

The Dietary Risk Assessment (DRA) is a brief dietary assessment tool used to identify dietary behaviors associated with cardiovascular disease. Intended for use by physicians and other nondietitians, the DRA identifies healthful and problematic dietary behaviors and alerts the physician to patients who require further nutrition counseling. To determine the relative validity of this tool, we compared it to the 7-Day Dietary Recall (an instrument developed to assess intake of dietary fat) and to the average of 7 telephone-administered 24-hour dietary recalls. Forty-two free-living subjects were recruited into the study. The 7-Day Dietary Recall and DRA were administered to each subject twice, at the beginning and the end of the study period, and the 24-hour recalls were conducted during the intervening time period. Correlation coefficients were computed to compare the food scores derived from the 3 assessment methods. Correlations between the DRA and 7-Day Dietary Recall data were moderate (r = .47, on average, for postmeasures); correlations between the DRA and 24-hour recalls were lower. The ability of the DRA to assess dietary fat consumption and ease of administration make it a clinically useful screening instrument for the physician when counseling patients about dietary fat reduction.     

The optical properties of the anterior segment of the eye: implications for cortical cataract.

Epidemiological studies have correlated cortical cataract with exposure to light and have suggested that this is due primarily to relatively short wavelengths of ultraviolet radiation (UV-B). In addition, some cellular and animal models also implicate UV-B. In order to evaluate the likely role of different wavelengths of light in the etiology of cortical cataracts, the optical characteristics of several animal models were ascertained and compared to the primate. This study shows that the mouse model absorbs UV-B almost exclusively whereas other animal models such as the rabbit and the guinea pig also contain chromophores that absorb UV-A. The absorptive characteristics of the human lens varies drastically with age. The young lens absorbs primarily UV-A, whereas with age, there are increases in absorptions at 320 nm and out to wavelengths as long as 550 nm. By sectioning human lenses it was found that these changes in absorption properties increased toward the central and the nuclear regions.These absorptive characteristics were then compared to the amount of light reaching the surface of the lens. It was found that UV-B is a minor component of total energy reaching the surface of the human lens and old human lens proteins absorb 2 orders of magnitude more UV-A and visible light than UV-B. It is concluded that it is premature to exclude UV-A or even visible light in the etiology of human cortical cataracts.     

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.     

Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53.

Vascular endothelial growth factor (VEGF) expression and mutations of cancer-related genes increase with cancer progression. This correlation suggests the hypothesis that oncogenes and tumour suppressors regulate VEGF, and a significant correlation between p53 alteration and increased VEGF expression in human lung cancer was reported recently. To further examine this hypothesis, we analysed VEGF protein expression and mutations in p53 and K-ras in 27 non-small-cell lung cancers (NSCLC): 16 squamous cell, six adenocarcinomas, one large cell, two carcinoids and two undifferentiated tumours. VEGF was expressed in 50% of the squamous cell carcinomas (SCC) and carcinoids but none of the others. p53 mutations occurred in 14 tumours (52%), and K-ras mutations were found in two adenocarcinomas and one SCC; there was no correlation between the mutations and VEGF expression. As nitric oxide also regulates angiogenesis, we examined NOS expression in NSCLC. The Ca2+-dependent NOS activity, which indicates NOS1 and NOS3 expression, was significantly reduced in lung carcinomas compared with adjacent non-tumour tissue (P < 0.004). Although the Ca2+-independent NOS activity, which indicates NOS2 expression, was low or undetectable in non-tumour tissues and most carcinomas, significant activity occurred in three SCC. In summary, our data do not show a direct regulation of VEGF by p53 in NSCLC. Finally, we did not find the up-regulation of NOS isoforms during NSCLC progression that has been suggested for gynaecological and breast cancers.     

The effect of incisions for cataract on corneal curvature

PURPOSE: To determine the magnitude and duration of change on the horizontal and vertical meridians of the cornea after five different incisions for cataract. DESIGN: Retrospective comparative interventional study of five commonly used incisions for cataract surgery: extracapsular cataract extraction (ECCE), 6-mm superior scleral tunnel (6Sup), 3-mm superior scleral tunnel (3Sup), 3-mm temporal scleral tunnel (3Temp), and 3-mm temporal corneal incision (3Cor). PARTICIPANTS: A total of 662 cases with preoperative regular astigmatism, measured with keratometry. METHODS: The mean net change on each meridian was computed at 1 day, 1 week, 2 weeks, 1 month, 1.5 months, 2 months, 4 months, 6 months, and 12 months and at succeeding 6-month intervals after surgery. Best-fit parameters were calculated for the observed changes in the horizontal and vertical keratometry values after each incision. To determine when the cornea stabilized, average change on the horizontal and vertical meridians was compared with an estimate of the accuracy of keratometry measurement. MAIN OUTCOME MEASURES: The pattern of change on the horizontal and vertical meridians and time for the cornea to stabilize after each incision. RESULTS: The initial and final net changes after a superior incision decrease with length. A sigmoid equation describes the course of the changes on the horizontal and vertical meridians after the superior incisions. The changes after the temporal incisions depend linearly on time after surgery. Considering the uncertainty of keratometry, the corneal meridians stabilized 4.5 months after ECCE, 1.2 months after 6Sup, and 0.3 months after 3Sup. No significant change was detected on the horizontal and vertical meridians after 3Temp and 3Cor. CONCLUSIONS: The magnitude and the duration of keratometric change on the horizontal and vertical meridians of the cornea depend on the length and location of the incision. Within the limits of measurement error, no significant change in corneal curvature was detected after either small temporal incision.     

Comparative in vitro activities of GAR-936 against aerobic and anaerobic animal and human bite wound pathogens

GAR-936 is a new semisynthetic glycylcycline with a broad antibacterial spectrum, including tetracycline-resistant strains. The in vitro activities of GAR-936, minocycline, doxycycline, tetracycline, moxifloxacin, penicillin G, and erythromycin were determined by agar dilution methods against 268 aerobic and 148 anaerobic strains of bacteria (including Pasteurella, Eikenella, Moraxella, Bergeyella, Neisseria, EF-4, Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Staphylococcus, Streptococcus, Enterococcus, Corynebacterium, Propionibacterium, Peptostreptococcus, and Actinomyces) isolated from infected human and animal bite wounds in humans, including strains resistant to commonly used antimicrobials. GAR-936 was very active, with an MIC at which 90% of the strains are inhibited (MIC(90)) of < or =0.25 microg/ml, against all aerobic gram-positive and -negative strains, including tetracycline-resistant strains of Enterococcus, Streptococcus, and coagulase-negative staphylococci, except for Eikenella corrodens (MIC(90), < or =4 microg/ml). GAR-936 was also very active against all anaerobic species, including tetracycline-, doxycycline-, and minocycline-resistant strains of Prevotella spp., Porphyromonas spp., Bacteroides tectum, and Peptostreptococcus spp., with an MIC(90) of < or =0.25 microg/ml. Erythromycin- and moxifloxacin-resistant fusobacteria were susceptible to GAR-936, with an MIC(90) of 0.06 microg/ml.