Purpose: Genetically altered cells could become widespread across the epithelium of patients with oral cancer, often in clinically and histologically normal tissue, and contribute to recurrent disease. Molecular approaches have begun to yield information on cancer/risk fields; tissue optics could further extend our understanding of alteration to phenotype as a result of molecular change. Experimental Design: We used a simple hand-held device in the operating room to directly visualize subclinical field changes around oral cancers, documenting alteration to fluorescence. A total of 122 oral mucosa biopsies were obtained from 20 surgical specimens with each biopsy being assessed for location, fluorescence visualization (FV) status, histology, and loss of heterozygosity (LOH; 10 markers on three regions: 3p14, 9p21, and 17p13). Results: All tumors showed FV loss (FVL). For 19 of the 20 tumors, the loss extended in at least one direction beyond the clinically visible tumor, with the extension varying from 4 to 25 mm. Thirty-two of 36 FVL biopsies showed histologic change (including 7 squamous cell carcinoma/carcinomas in situ, 10 severe dysplasias, and 15 mild/moderate dysplasias) compared with 1of the 66 FV retained (FVR) biopsies. Molecular analysis on margins with low-grade or no dysplasia showed a significant association of LOH in FVL biopsies, with LOH at 3p and/or 9p (previously associated with local tumor recurrence) present in 12 of 19 FVL biopsies compared with 3 of 13 FVR biopsies (P = 0.04). Conclusions: These data have, for the first time, shown that direct FV can identify subclinical high-risk fields with cancerous and precancerous changes in the operating room setting.

Purpose:To determine whether the combination of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI provides higher diagnostic sensitivity for prostate cancer than each technique alone. Materials and Methods:Fourteen patients with a clinical suspicion of prostate cancer underwent endorectal MRI on a 1.5T scanner prior to transrectal ultrasound (TRUS)-guided biopsies. The average values of the apparent diffusion coefficient (ADC, calculated from b-values of 0 and 600), K trans , v e , maximum gadolinium (Gd) concentration, onset time, mean gradient, and maximum enhancement were determined. Correlation with histology was based on biopsy (six patients) and prostatectomy specimen (eight patients) results. The Tukey-Kramer test was used for statistical analysis. Results:The average values of all MRI parameters, except v e and maximum Gd concentration, showed significant differences between tumor and normal prostate. The sensitivity and specificity values were respectively 54% (35-72%) and 100% (95-100%) for the ADC data, and 59% (39 -77%) and 74% (63-83%) for the DCE data. When both ADC and DCE results were combined, the sensitivity increased to 87% (68 -95%) and specificity decreased to 74% (62-83%). Conclusion:All but two DW-and DCE-MRI parameters showed significant differences between tumor and normal prostate. Combining both techniques provides better sensitivity, with a small decrease in specificity.

A major barrier to oral cancer prevention has been the lack of validated risk predictors for oral premalignant lesions (OPLs). In 2000, we proposed a loss of heterozygosity (LOH) risk model in a retrospective study. This paper validated the previously reported LOH profiles as risk predictors and developed refined models via the largest longitudinal study to date of low-grade OPLs from a population-based patient group. Analysis involved a prospective cohort of 296 patients with primary mild/moderate oral dysplasia enrolled in the Oral Cancer Prediction Longitudinal Study. LOH status was determined in these OPLs. Patients were classified into high-risk or low-risk profiles to validate the 2000 model. Risk models were refined using recursive partitioning and Cox regression analyses. The prospective cohort validated that the high-risk lesions (3p &/or 9p LOH) had a 22·6 - fold increase in risk (P = 0·002) compared to low-risk lesions (3p & 9p retention). Addition of another two markers (loci on 4q/17p) further improved the risk prediction, with five-year progression rates of 3·1%, 16·3%, and 63·1% for the low-, intermediate-, and high-risk lesions, respectively. Compared to the low-risk group, intermediate- and high-risk groups had 11·6-fold and 52·1-fold increase in risk (P < 0·001). LOH profiles as risk predictors in the refined model were validated in the retrospective cohort. Multi-covariate analysis with clinical features showed LOH models to be the most significant predictors of progression. LOH profiles can reliably differentiate progression risk for OPLs. Potential uses include increasing surveillance for patients with elevated risk, improving target intervention for high-risk patients while sparing a large number of low-risk patients from needless screening and treatment.