Faculty Bibliography

PURPOSE: To evaluate the effect of two-dimensional wavelet-based computed tomographic (CT) image compression according to the Joint Photographic Experts Group (JPEG) 2000 standard on computer-assisted assessment of nodule volume. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the research board at the authors' institution; patients' informed consent was not required. Fifty-one nodules in 23 patients (seven men, 16 women; mean age, 59 years; age range, 39-75 years) were selected on low-dose CT scans that were compressed to levels of 10:1, 20:1, 30:1, and 40:1 by using a two-dimensional JPEG 2000 wavelet-based image compression method. Nodules were classified according to size (< or = 5 mm or > 5 mm in diameter), location (central, peripheral, or abutting pleura or fissures), and attenuation (solid, calcified, or subsolid). Regions of interest were placed on the original images and transposed onto compressed images. Nodule volumes on original (noncompressed) and compressed images were measured by using a computer-assisted method. A mixed-model analysis of variance was conducted for statistical evaluation. RESULTS: Nodule volumes averaged 388.1 mm3 (range, 34-3474 mm3). There were three calcified, 33 solid noncalcified, and 15 subsolid nodules (13 with ground-glass attenuation). Average volume decreased with increasing compression level, to 383 mm3 (10:1), 370 mm3 (20:1), 360 mm3 (30:1), and 354 mm3 (40:1). No significant difference was identified between measurements obtained on original images and those compressed to a level of 10:1. Significant differences were noted, however, between original images and those compressed to a level of 20:1 or greater (P < .05). Compression level significantly interacted with nodule size, location, and attenuation (P < .001). The effect of compression was greater for nodules with ground-glass attenuation than for those with higher attenuation values. The difference in mean volumes between original images and those compressed to a level of 20:1 was 34.9 mm3 for nodules with ground-glass attenuation, compared with 8.3 mm3 for higher-attenuation nodules, a 4.2-fold difference. CONCLUSION: Nodule volumes measured on images compressed to a level of 20:1 differed significantly from those measured on noncompressed images, especially for nodules with ground-glass attenuation. This difference could affect the assessment of nodule change in size as measured with computer-assisted methods

OBJECTIVE: Our objective was to examine the degree and pattern of (18)F-FDG uptake within the shoulder as a potential marker of joint inflammation or injury. SUBJECTS AND METHODS: Twenty-four patients undergoing (18)F-FDG PET for clinical oncologic assessment completed questionnaires regarding history of shoulder disease, trauma, pain, and/or functional impairment. Thorough physical examination of the shoulder was performed. A clinical diagnosis of specific shoulder derangement or normal was established for each patient. PET scans were evaluated blindly by a nuclear medicine physician and a musculoskeletal radiologist qualitatively for location, distribution, and intensity of shoulder uptake. Standardized uptake values (SUV) were measured. RESULTS: Twenty-one patients had shoulder PET findings. Fourteen had clinical findings consistent with a specific diagnosis in the PET-positive shoulder. The remaining seven PET-positive patients were clinically normal. Three recognizable patterns of uptake were appreciable. Eight of 10 patients with diffuse uptake had findings of osteoarthritis (n = 7) or bursitis (n = 1). Two of four patients with focal greater tuberosity uptake had findings of rotator cuff injury. Two of four patients with focal glenoid uptake had findings of frozen shoulder. SUV showed a positive correlation with subject age (p < 0.01), but no association with clinical findings was identified. CONCLUSION: The pattern of FDG uptake within the shoulder may point to specific clinical entities. While focal uptake is less reliably related to clinical findings, diffuse uptake is associated with signs and symptoms of osteoarthritis or bursitis

BACKGROUND AND PURPOSE: Because of their invasive nature, high-grade glial tumors are uniformly fatal. The purpose of this study was to quantify MR imaging-occult, glial tumor infiltration beyond its radiologic margin through its consequent neuronal cell damage, assessed by the global concentration decline of the neuronal marker N-acetylaspartate (NAA). METHODS: Seventeen patients (10 men; median age, 39 years; age range, 23-79 years) with radiologically suspected (later pathologically confirmed) supratentorial glial neoplasms, and 17 age- and sex-matched controls were studied. Their whole-brain NAA (WBNAA) amounts were obtained with proton MR spectroscopy: for patients on the day of surgery (n = 17), 1 day postsurgery (n = 15), and once for each control. To convert into concentrations, suitable for intersubject comparison, patients' global NAA amounts were divided by their brain volumes segmented from MR imaging. Least squares regression was used to analyze the data. RESULTS: Pre- and postoperative WBNAA (mean +/- SD) of 9.2 +/- 2.1 and 9.7 +/- 1.8 mmol/L, respectively, in patients were indistinguishable (P = .369) but significantly lower than in controls (12.5 +/- 1.4 mmol/L). Mean resected tumor size (n = 15) was approximately 3% of total brain volume. CONCLUSION: The average 26% WBNAA deficit in the patients, which persisted following surgical resection, cannot be explained merely by depletion within the approximately 3% MR imaging-visible tumor volume or an age-dependent effect. Although there could be several possible causes of such widespread decline--perineuronal satellitosis, neuronal deafferentation, Wallerian and retrograde degeneration, vasogenic edema, functional diaschisis, secondary vascular changes--most are a direct or indirect reflection of extensive, MR imaging-occult, microscopic tumor cell infiltration, diffusely throughout the otherwise 'normal-appearing' brain

PURPOSE: To retrospectively assess the importance and imaging appearance of small (< or = 20 mm in diameter) hepatic arterial phase-enhancing (HAPE) lesions that are occult during portal and/or equilibrium phases and at unenhanced T1- and T2-weighted magnetic resonance (MR) imaging and to determine the gross pathologic diagnosis with whole-liver explant comparison. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and compliant with HIPPA. Forty-six patients with cirrhosis who underwent MR imaging and transplantation within 90 days were evaluated with breath-hold T2-weighted and volumetric three-dimensional gadolinium-enhanced gradient-echo MR imaging in the hepatic arterial, portal venous, and equilibrium phases at 1.5 T. Three readers, who were blinded to the pathologic results, retrospectively reviewed the MR images in consensus for small HAPE nodules that were occult at T2-weighted and portal and/or equilibrium phase MR imaging. Only patients with nodules that enhanced during the arterial phase were included in the final study group, which included 16 patients (12 men and four women) aged 18-66 years (median age, 51.5 years). Explanted livers were serially sliced into 5-8-mm-thick sections to evaluate dysplastic nodules and hepatocellular carcinomas (HCCs). The Fisher exact test was performed to determine whether there was a relationship between HCC and the presence of a neoplastic HAPE-only lesion. The Mann-Whitney test was used to determine if patients with at least one neoplastic HAPE-only lesion had a larger number of non-HAPE-only lesions. RESULTS: The 16 patients had 45 HAPE-only lesions; three (7%) of which were neoplastic, including one overt HCC, one HCC arising in a dysplastic nodule, and one dysplastic nodule. None of the remaining 42 HAPE-only lesions (93%) had correlative pathologic findings. All three neoplastic lesions seen only during the arterial phase were found in eight patients with concomitant HCC, who also had an additional 13 pathologically proved nonneoplastic HAPE-only lesions. In eight patients without HCC, none of the HAPE-only lesions were neoplastic. A concomitant non-HAPE-only neoplastic lesion was not a significant (P = .2) predictor for the presence of at least one neoplastic HAPE-only lesion. There was a preliminary but insignificant (P = .13) indication that the number of non-HAPE-only lesions tends to be higher in patients with neoplastic HAPE-only lesions. CONCLUSION: The majority (93%) of HAPE-only lesions that are occult at T2-weighted and portal and/or equilibrium phase MR imaging are nonneoplastic, even in patients with pathologically proved HCC

The purpose of the following study is to describe the localization of COX-2 protein and COX-2 mRNA during human colorectal tumorigenesis and to identify potential cellular targets for COX-2 inhibition in chemopreventive strategies. Immunohistochemistry with digital image analysis was used to determine COX-2 protein expression in histologic sections containing synchronous normal colorectal mucosa, adenomas and carcinomas, from 17 previously untreated patients. Epithelial and stromal COX-2 mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), on laser-capture microdissected samples from the same histologies. The stromal compartment in normal colorectal mucosa and adenomas showed higher levels of COX-2 protein expression compared to colorectal carcinomas (p < .0001). Conversely, epithelial COX-2 protein was significantly increased only after development of the invasive phenotype (p < .0001). RT-PCR demonstrated higher stromal COX-2 mRNA expression compared to that within the epithelium for colorectal adenomas and carcinomas. In conclusion, stromal COX-2 may be the target for chemopreventive agents in the early stages of colorectal carcinogenesis

We propose a new paradigm for the clinical evaluation of new cancer therapies. It entails adjusting the search for the optimal dose on the basis of measurable patient characteristics that may be predictive of adverse responses to treatment, and extending this search beyond phase I and into phases II and III. We provide examples of (a) how the fine-tuning of dose may involve utilization of patient-specific attributes to obtain a personalized treatment regimen, and (b) how novel methods for phase I design can be used to update the working dose for the conduct of phase II and III cancer clinical trials. These examples should be interpreted as an enticement for the development of new methods to implement the proposed new paradigm

We examine a large class of prior distributions to model the dose-response relationship in cancer phase I clinical trials. We parameterize the dose-toxicity model in terms of the maximum tolerated dose (MTD) gamma and the probability of dose limiting toxicity (DLT) at the initial dose rho(0). The MTD is estimated using the EWOC (escalation with overdose control) method of Babb et al. We show through simulations that a candidate joint prior for (rho0,gamma) with negative a priori correlation structure results in a safer trial than the one that assumes independent priors for these two parameters while keeping the efficiency of the estimate of the MTD essentially unchanged

OBJECTIVE: To pilot a worksite smoking intervention. METHODS: Following baseline assessment, participants (N=6378) received cancer risk feedback; 2 annual evaluations were conducted. RESULTS: Using all data, smoking dropped from 13.7% to 8.4% and 9.3%, and smoker's readiness to quit increased. Using complete data, smoking initially increased from 5.7% to 6.7%, but subsequently decreased to 5.3%; the increase in smoker's readiness to quit remained. Being male, younger, and with lower education and self-efficacy predicted smoking. Lower age and higher self-efficacy predicted readiness to quit smoking. CONCLUSIONS: These findings support a formal evaluation of a worksite smoking intervention using cancer risk feedback

BACKGROUND: Patients with local recurrences or new head and neck primary tumors in previously irradiated tissues have few options for salvage treatment. One option for select patients is to undergo reirradiation with concurrent chemotherapy. The purpose of this study is to report the initial clinical results of the Fox Chase phase I and II prospective reirradiation and chemotherapy studies. METHODS: Between July 1996 and January 2002, 38 patients with locally recurrent unresectable squamous cell carcinoma of the head and neck were treated with concurrent chemotherapy and reirradiation on two prospective trials. All patients had received prior radiation therapy to the head and neck region (median dose, 64.2 Gy). Patients received cisplatin and paclitaxel along with hyperfractionated external beam radiation therapy to the site of recurrence. RESULTS: The median follow-up was 10 months. The median survival was 12.4 months, with actuarial rates of overall survival of 50% and 35% at 1 and 2 years, respectively. During follow-up, 63% of patients experienced local progression of disease, all in the irradiated field. Actuarial progression-free survival at 1 year was 33%, with a median time to progression of 7.3 months. Acute grade 3 to 4 toxicity included neutropenia, nausea, emesis, and mucositis. CONCLUSIONS: Hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy demonstrates durable locoregional control in select patients, although late toxicity may occasionally be significant. Only sites of disease recurrence need to be covered in the reirradiation fields

PURPOSE: To investigate the feasibility of diffusion tensor imaging (DTI) assessment of microscopic fiber tract injury in the corpus callosum (CC) and other normal-appearing white matter (NAWM) in patients with early multiple sclerosis (MS). MATERIALS AND METHODS: DTI was performed in 12 healthy volunteers and 15 patients who have relatively short disease duration (mean = 2.7 years). Both fractional anisotropy (FA) and mean diffusivity (MD) were obtained in different regions of normal-appearing CC (NACC) and NAWM in frontal and occipital regions. RESULTS: The data showed significantly lower FA (P < 0.001) and higher MD (P < 0.04) for NACC regions, but not for frontal and occipital NAWM regions, in patients than in those in healthy volunteers after Bonferroni adjustment. The increase of MD in the entire NACC regions was correlated with the total cerebral lesion volume (r = 0.75, P = 0.001) in patients. CONCLUSION: The water diffusion changes indicate that in the early phase of disease there is a preferential occult injury of CC, which is likely due to the Wallerian degeneration from distant lesions