Faculty Bibliography

PURPOSE: To compare thin-section multi-detector row computed tomographic (CT) colonography with conventional colonoscopy in the evaluation of colorectal polyps and cancer in asymptomatic average-risk patients. MATERIALS AND METHODS: Sixty-eight asymptomatic men (age > 50 years) scheduled to undergo screening colonoscopy were enrolled in this study. CT colonography was followed by conventional colonoscopy, performed on the same day. Supine and prone CT colonography were performed after colonic insufflation with room air. A gastroenterologist measured all polyps, which were categorized as 1-5, 6-9, or over 10 mm. Biopsy and histologic evaluation were performed of all polyps. CT colonography and colonoscopy results were compared for location, size, and morphology of detected lesions. Point estimates and 95% CIs were provided for specificity and sensitivity of CT by using results at conventional colonoscopy as the reference standard. RESULTS: At colonoscopy, 98 polyps were identified in 39 patients; 21 (21.4%) of 98 were detected at CT colonography. Sensitivity was 11.5% (nine of 78) for polyps 1-5 mm, 52.9% (nine of 17) for polyps 6-9 mm, and 100% (three of three) for polyps over 10 mm. Results at colonoscopy were normal in 29 (42.6%) of 68 patients; at CT colonography, results were correctly identified as normal in 26 of these 29 patients. In one of these patients, a lesion larger than 10 mm was detected at CT colonography. The per-patient specificity of CT was 89.7% (26 of 29; 95% CI: 72.7%, 97.8%). The mean time for CT image interpretation was 9 minutes. CONCLUSION: In patients at average risk for colorectal cancer, CT colonography is a sensitive and specific screening test for detecting polyps 10 mm or larger; the sensitivity for detecting smaller polyps is decreased. Examination findings can be interpreted in a clinically feasible amount of time

PURPOSE: Ionizing radiation can reduce tumor growth outside the field of radiation, known as the abscopal effect. Although it has been reported in multiple malignancies, the abscopal effect remains a rare and poorly understood event. Ionizing radiation generates inflammatory signals and, in principle, could provide both tumor-specific antigens from dying cells and maturation stimuli that are necessary for dendritic cells' activation of tumor-specific T cells. We therefore tested the hypothesis that the abscopal effect elicited by radiation is immune mediated. This was directly tested by enhancing the number of available dendritic cells using the growth factor Flt3-Ligand (Flt3-L). METHODS AND MATERIALS: Mice bearing a syngeneic mammary carcinoma, 67NR, in both flanks were treated with Flt3-L daily for 10 days after local radiation therapy (RT) to only 1 of the 2 tumors at a single dose of 2 or 6 Gy. The second nonirradiated tumor was used as indicator of the abscopal effect. Data were analyzed using repeated measures regression. RESULTS: RT alone led to growth delay exclusively of the irradiated 67NR tumor, as expected. Surprisingly, growth of the nonirradiated tumor was also impaired by the combination of RT and Flt3-L. As control, Flt3-L had no effect without RT. Importantly, the abscopal effect was shown to be tumor specific, because growth of a nonirradiated A20 lymphoma in the same mice containing a treated 67NR tumor was not affected. Moreover, no growth delay of nonirradiated 67NR tumors was observed when T cell deficient (nude) mice were treated with RT plus Flt3-L. CONCLUSIONS: These results demonstrate that the abscopal effect is in part immune mediated and that T cells are required to mediate distant tumor inhibition induced by radiation

PURPOSE: To prospectively determine hemodynamic changes in the normal-appearing white matter (NAWM) of patients with relapsing-remitting multiple sclerosis (RR-MS) by using dynamic susceptibility contrast material-enhanced perfusion magnetic resonance (MR) imaging. MATERIALS AND METHODS: Conventional MR imaging (which included acquisition of pre- and postcontrast transverse T1-weighted, fluid-attenuated inversion recovery, and T2-weighted images) and dynamic susceptibility contrast-enhanced T2*-weighted MR imaging were performed in 17 patients with RR-MS (five men and 12 women; median age, 38.4 years; age range, 27.6-56.9 years) and 17 control patients (seven men and 10 women; median age, 42.0 years; age range, 18.7-62.5 years). Absolute cerebral blood volume (CBV), absolute cerebral blood flow (CBF), and mean transit time (MTT) (referenced to an arterial input function by using an automated method) were determined in periventricular, intermediate, and subcortical regions of NAWM at the level of the lateral ventricles. Least-squares regression analysis (controlled for age and sex) was used to compare perfusion measures in each region between patients with RR-MS and control patients. Repeated-measures analysis of variance and the Tukey honestly significant difference test were used to perform pairwise comparison of brain regions in terms of each perfusion measure. RESULTS: Each region of NAWM in patients with RR-MS had significantly decreased CBF (P <.005) and prolonged MTT (P <.001) compared with the corresponding region in control patients. No significant differences in CBV were found between patients with RR-MS and control patients in any of the corresponding areas of NAWM examined. In control patients, periventricular NAWM regions had significantly higher CBF (P =.03) and CBV (P =.04) than did intermediate NAWM regions. No significant regional differences in CBF, CBV, or MTT were found in patients with RR-MS. CONCLUSION: The NAWM of patients with RR-MS shows decreased perfusion compared with that of controls

Global brain atrophy estimated using MRI and whole brain N-acetylaspartate (WBNAA) concentration measured with proton MR spectroscopy were obtained in 42 patients with relapsing-remitting multiple sclerosis and 41 matched control subjects. Patients exhibited cross-sectional atrophy (0.5%; p = 0.033) and WBNAA decline (1.8%/y; p = 0.005) vs disease duration. The 3.6-fold rate disparity between the two processes suggests that neuronal/axonal dysfunction (N-acetylaspartate decline) precedes parenchyma loss, not its consequence (i.e., is an earlier, more sensitive specific metric of the ongoing disease activity)

The metabolic changes in the deep gray matter (GM) nuclei, thalamus, and basal ganglia of patients with relapsing-remitting multiple sclerosis were investigated with quantitative, multivoxel, three-dimensional proton MR spectroscopy. This technique facilitated the study of several bilateral structures in a single session at sub-cubic centimeter spatial resolution. Compared with 9 matched control subjects, the deep GM nuclei of 11 patients showed 7% lower N-acetylaspartate and 14% higher choline levels (p = 0.02 for both)

BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) permit in vivo assessment of glioma microvasculature. We assessed the associations between rCBV and K(trans) derived from dynamic, susceptibility-weighted, contrast-enhanced (DSC) MR imaging and tumor grade and between rCBV and K(trans). METHODS: Seventy-three patients with primary gliomas underwent conventional and DSC MR imaging. rCBVs were obtained from regions of maximal abnormality for each lesion on rCBV color maps. K(trans) was derived from a pharmacokinetic modeling algorithm. Histopathologic grade was compared with rCBV and K(trans) (Tukey honestly significant difference). Spearman and Pearson correlation factors were determined between rCBV, K(trans), and tumor grade. The diagnostic utility of rCBV and K(trans) in discriminating grade II or III tumors from grade I tumors was assessed by logistic regression. RESULTS: rCBV was significantly different for all three grades (P </=.0005). K(trans) was significantly different between grade I and grade II or III (P =.027) but not between other grades or combinations of grades. Spearman rank and Pearson correlations, respectively, were as follows: rCBV and grade, r = 0.817 and r = 0.771; K(trans) and grade, r = 0.234 and r = 0.277; and rCBV and K(trans), r = 0.266 and r = 0.163. Only rCBV was significantly predictive of high-grade gliomas (P <.0001). CONCLUSION: rCBV with strongly correlated with tumor grade; the correlation between K(trans) and tumor grade was weaker. rCBV and K(trans) were positively but weakly correlated, suggesting that these parameters demonstrate different tumor characteristics. rCBV is a more significant predictor of high-grade glioma than K(trans)

PURPOSE: A patient-specific dose-escalation scheme using a Bayesian model of Escalation with Overdose Control (EWOC) was conducted to establish the maximum tolerated dose (MTD) of PNU-214936 in advanced non-small-cell lung cancer (NSCLC). PNU-214936 is a murine Fab fragment of the monoclonal antibody 5T4 fused to a mutated superantigen staphylococcal enterotoxin A (SEA). PATIENTS AND METHODS: Seventy-eight patients with NSCLC were treated with an individualized dose of PNU-214936 calculated using EWOC, based on their anti-SEA antibody level, and given as a 3-hour infusion on 4 consecutive days. RESULTS: Fever (82%; grade 3 to 4, 2.6%) and hypotension (57%; grade 3 to 4, 9%) were the most common toxicities. Eight dose-limiting toxicities occurred, as defined as any grade 4 toxicity occurring within the first 5 days. The MTD was defined as a function of pretreatment anti-SEA antibody level. MTD ranged from 103 ng/kg for patients with anti-SEA concentrations < or = 10 pmol/mL, to 601 ng/kg for patients with anti-SEA concentrations of 91 to 150 pmol/mL. A minor tumor response was demonstrated in five of 66 assessable patients. CONCLUSION: EWOC determined phase I doses of PNU-214936 that were adjusted for patient anti-SEA antibody level, while safeguarding against overdose. Furthermore, the method permitted the construction of a dosing algorithm that would allow patients in subsequent clinical investigations to be treated with a dose of PNU-214936 that is tailored to their specific tolerance for the agent, as reflected by their pretreatment anti-SEA

OBJECTIVE: The effects of a 6-week psychoeducational group intervention on the distress, coping, personal growth, and marital communication of wives of men diagnosed with prostate cancer were evaluated using a randomized clinical trial. METHODS: Sixty wives completed measures prior to random assignment to either the psychoeducational group intervention or a no-treatment control group, and 1 month after completion of the group. RESULTS: No differences with regard to wives' general distress or cancer-specific distress were noted. In comparison with the control group, participants receiving the intervention perceived that having a spouse with prostate cancer had made positive contributions to their lives, reported gains in the use of positive reappraisal coping and reductions in denial coping. CONCLUSION: Although the psychoeducational intervention did not result in changes in psychological distress, improvements in adaptive coping and indicators of psychological growth were found. The utility of group interventions for spouses of men with prostate cancer is discussed

The ovarian surface epithelium (OSE) is a single layer of flattened or cuboidal cells covering the ovary. Ninety percent of all human ovarian malignancies arise from this layer of cells. Incessant ovulation, hyperovulation induced by infertility treatment, and hormone replacement therapy have been suggested as risk factors for ovarian cancer. In this study, two groups of rats, with and without surgically induced injury to the ovary, were treated with 17beta-estradiol, pregnant mare's serum gonadotropin (PMSG), human chorionic gonadotropin (hCG), or the combination PMSG/hCG, and the proliferative response of the OSE cells was measured using bromodeoxyuridne (BrdU) and (3)H-thymidine. All hormones, alone or in combination with ovarian surgery, were found to increase significantly the rate of proliferation of the rat OSE. These data demonstrate that hormones associated with infertility treatments and hormone replacement therapy, as well as injury- or ovulation-induced rupture of the ovarian surface, stimulate the rat OSE, and hence could have a role in the development of ovarian cancer via proliferation-associated mutagenesis, or alternatively, by promoting the rapid selection of OSE cells with accumulated mutations

Dynamic, contrast-enhanced MRI (deMRI) is increasingly being used to evaluate cerebral microcirculation. There are two different approaches for analyzing deMRI data. Intravascular indicator dilution theory has been used to estimate blood volume (and perfusion), usually from T(2)- or T(2) (*)-weighted images of the first pass of the bolus. However, the theory assumes that the tracer (i.e., contrast agent) remains intravascular, which is often not the case when the blood-brain barrier (BBB) is damaged. Furthermore, the method provides no information on the vascular transfer constant. Pharmacokinetic modeling analyses of T(1)-weighted images after first pass do give values of the vascular transfer constant and the volume of the extravascular, extracellular space (EES), but they generally are unable to give estimates of blood volume. In this study we apply pharmacokinetic modeling to dynamic T(2) (*)-weighted imaging of the first pass of a tracer bolus. This method, which we call first-pass pharmacokinetic modeling (FPPM), gives an estimate of the blood volume, vascular transfer constant, and EES volume. The method was applied to a group of 26 patients with surgically proven tumors (10 glioblastomas multiforme (GBMs), six lymphomas, and 10 meningiomas). The measurements of the blood volume and transfer constant were consistent with the known physiology of these tumors