Faculty Bibliography

Laser interstitial thermal therapy (LITT) is a new therapeutic strategy being explored in prostate cancer (CaP), which involves focal ablation of organlocalized tumor via an interstitial laser fiber. While little is known about treatment-related changes following LITT, studying post-LITT changes via imaging is extremely significant for enabling early image-guided intervention and follow-up. In this work, we present the first attempt at examining focal treatment-related changes on a per-voxel basis via quantitative comparison of MRI features pre- and post-LITT, and hence identifying computerized MRI features that are highly sensitive as well as specific to post-LITT changes within the ablation zone in the prostate. A retrospective cohort of 5 patient datasets comprising both pre- and post-LITT T2-weighted (T2w) and diffusion-weighted (DWI) acquisitions was considered, where DWI MRI yielded an Apparent Diffusion Co-efficient (ADC) map. Our scheme involved (1) inter-protocol registration of T2w and ADC MRI, as well as inter-acquisition registration of pre- and post-LITT MRI, (2) quantitation of MRI parameters by correcting for intensity drift in order to examine tissuespecific response, and (3) quantification of the information captured by T2w MRI and ADC maps via texture and intensity features. Correction of parameter drift resulted in visually discernible improvements in highlighting tissue-specific response in different MRI features. Quantitative, voxel-wise comparison of the changes in different MRI features indicated that steerable and non-steerable gradient texture features, rather than the original T2w intensity and ADC values, were highly sensitive as well as specific in identifying changes within the ablation zone pre- and post-LITT. The highest ranked texture feature yielded a normalized percentage change of 186% within the ablation zone and 43% in a spatially distinct normal region, relative to its pre-LITT value. By comparison, both the original T2w intensity and ADC value demonstrated a markedly less sensitive and specific response to changes within the ablation zone. Qualitative as well as quantitative evaluation of co-occurrence texture features indicated the presence of LITT-related effects such as edema adjacent to the ablation zone, which were indiscernible on the original T2w and ADC images. Our preliminary results thus indicate great potential for non-invasive computerized MRI imaging features for determining focal treatment related changes, informing image-guided interventions, as well as predicting long- and short-term patient outcome.

Focal therapy of prostate cancer is an evolving treatment strategy that destroys a predefined region of the prostate gland that harbors clinically significant disease. Although long-term oncologic control has yet to be demonstrated, focal therapy is associated with a marked decrease in treatment-related morbidity. Focal laser ablation is an emerging modality that has several advantages, most notably real-time magnetic resonance imaging (MRI) compatibility. This review presents the principles of laser ablation, the role of multiparametric MRI for delineating the site of significant prostate cancer, a summary of published clinical studies, and our initial experience with 23 patients, criteria for selecting candidates for focal prostate ablation, and speculation regarding future directions.

Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.

PURPOSE: Optimization of prostate biopsy requires addressing the shortcomings of standard systematic transrectal ultrasound guided biopsy including false negative rates, incorrect risk stratification, detection of clinically insignificant disease, and the need for repetitive biopsy. MRI is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer (PCa) at the time of biopsy, thereby enhancing clinical risk assessment, and improving the ability to appropriately counsel patients regarding therapy. The purpose of this review is to 1) summarize the various sequences that comprise a prostate multiparametric MRI exam along with its performance characteristics in cancer detection, localization and reporting standards, 2) evaluate potential applications of MRI targeting in prostate biopsy among men with no previous biopsy, a negative previous biopsy, and those with low stage cancer and 3) describe the techniques of MRI-targeted biopsy and their comparative study outcomes MATERIALS AND METHODS: A bibliographic search covering the period up to October, 2013 was conducted using MEDLINE(R)/PubMed(R). Articles were reviewed and categorized based on which of the three objectives of this review was addressed. Data was extracted, analyzed, and summarized. RESULTS: Mp-MRI consists of anatomic T2-weighted imaging coupled with at least 2 functional imaging techniques and has demonstrated improved PCa detection sensitivity up to 80% in the peripheral zone and 81% in the transition zone. A PCa MRI suspicion score has been developed and is depicted using the Likert or PI-RADS scale for better standardization of MRI interpretation and reporting. Among men with no previous biopsy, MRI increases the frequency of significant cancer detection to 50% in low risk and 71% in high risk patients. In low risk men, the negative predictive valve of a combination of negative MRI with prostate volume parameters is nearly 98%, suggesting a potential role in avoiding a biopsy and reducing overdetection/overtreatment. Among men with previous negative biopsy, 72-87% of cancers detected by MRI guidance are clinically significant. Among men with known low risk cancer, repeat biopsy by MR-targeting demonstrates a high likelihood of confirming low risk disease in low suspicion score lesions and for upgrading in high suspicion score lesions. Techniques of MRI-targeted biopsy include visual estimation TRUS-guided biopsy, software co-registered MRI-US TRUS-guided biopsy, and in-bore MRI-guided biopsy. Although the improvement in accuracy and efficiency of visual estimation biopsy compared to systematic appears limited, both co-registered MRI-US biopsy and in-bore MRI-guided biopsy appears to increase cancer detection rates in conjunction with increasing suspicion score. CONCLUSIONS: Use of MRI for targeting prostate biopsies has potential to reduce the sampling error associate with conventional biopsy by providing better disease localization and sampling. More accurate risk stratification through improved cancer sampling may impact upon therapeutic decision-making. Optimal clinical application of MRI-targeted biopsy remains under investigation.

Autopsy studies of men without known prostate cancer suggest that a substantial reservoir of prostate cancer that does not cause symptoms or death exists within the population. The majority of these cancers are Gleason 6 tumors and are frequently detected by prostate-specific antigen-based prostate cancer screening.There is strong evidence from longitudinal cohort studies of men with both treated and untreated Gleason 6 prostate cancer to suggest that Gleason 6 disease, when not associated with higher-grade cancer, virtually never demonstrates the ability to metastasize and thus represents an indolent entity that does not require treatment. Whether Gleason 6 has a propensity to progress to higher-grade cancer is still under investigation. Because the term "cancer" has historically been used to represent a disease state that leads to progressive illness that is uniformly fatal without treatment, we believe Gleason 6 disease should not be labeled with this term. Our challenge now is to develop the technology to differentiate true Gleason 6 disease from the higher grades of dysplasia with which it can be associated.