Transarterial embolization of renal cell carcinoma as an adjunctive therapy prior to cryoablation: a propensity score matching analysis

PURPOSE:We aimed to assess the safety and effectiveness of transarterial embolization (TAE) prior to percutaneous cryoablation (PCA) in the management of renal cell carcinoma (RCC) compared with PCA alone using a propensity score matching analysis to minimize confounding factors.METHODS:A retrospective review of all PCAs performed for renal masses identified 9 patients who underwent TAE prior to PCA. These patients were matched in a 2:1 ratio with patients who underwent PCA only using age, gender, and tumor size to create the propensity score model for matching. Other demographic, clinical, and outcomes data were collected.RESULTS:The TAE+PCA group included 5 males and 4 females with a mean age of 67.9 years and mean tumor diameter of 51.7 mm. The PCA only group included 11 males and 7 females with a mean age of 66.8 years and mean tumor diameter of 46.2 mm. No significant differences in these propensity score matched characteristics were identified. Further, the groups had no significant differences in tumor geometry (P = 0.831), R.E.N.A.L. nephrometry scores (P = 0.144), or comorbidity indices (P = 0.392). TAE was technically successful and without complication in all cases. PCA was technically successful in 8 of 9 patients in the TAE+PCA group and in 14 of 18 patients in the PCA only group (P = 0.483). No significant differences in the rate of complications (P = 0.483), change in eGFR (P = 0.691), or change in hematocrit (P = 0.152) were identified between the two groups.CONCLUSION:TAE of RCC prior to PCA is safe and technically feasible; however, no objective benefits over PCA alone were identified by propensity score matching analysis. Due to small sample size and limitations of the study, no definite conclusions should be drawn. Larger, prospective studies of this therapeutic approach are warranted

Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity

Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies

Imaging as a Personalized Biomarker for Prostate Cancer Risk Stratification

Biomarkers provide objective data to guide clinicians in disease management. Prostate-specific antigen serves as a biomarker for screening of prostate cancer but has come under scrutiny for detection of clinically indolent disease. Multiple imaging techniques demonstrate promising results for diagnosing, staging, and determining definitive management of prostate cancer. One such modality, multiparametric magnetic resonance imaging (mpMRI), detects more clinically significant disease while missing lower volume and clinically insignificant disease. It also provides valuable information regarding tumor characteristics such as location and extraprostatic extension to guide surgical planning. Information from mpMRI may also help patients avoid unnecessary biopsies in the future. It can also be incorporated into targeted biopsies as well as following patients on active surveillance. Other novel techniques have also been developed to detect metastatic disease with advantages over traditional computer tomography and magnetic resonance imaging, which primarily rely on defined size criteria. These new techniques take advantage of underlying biological changes in prostate cancer tissue to identify metastatic disease. The purpose of this review is to present literature on imaging as a personalized biomarker for prostate cancer risk stratification

Intestinal metaplasia of the urinary tract harbors potentially oncogenic genetic variants

In the urinary tract, there is an uncertain relationship between intestinal metaplasia (IM), primary adenocarcinoma, and urothelial carcinoma. Although IM is usually found adjacent to concurrent urothelial carcinoma or adenocarcinoma, small retrospective series have shown that most bladder biopsies with only IM do not subsequently develop cancer. However, IM with dysplasia does seem to be associated with a higher risk of concurrent malignancy or progressing to cancer. Since the molecular landscape of these lesions has remained largely unexplored, there are significant uncertainties about the oncogenic potential of IM in the bladder and urethra. This study investigated the presence of potentially oncogenic genetic variants in cases of IM with and without dysplasia. Twenty-three (23) cases of IM (3 urethra, 20 bladder) were sequenced using a solid tumor next-generation sequencing panel. Of these, five contained IM with high-grade dysplasia (including a case with paired IM-adenocarcinoma and another with paired IM-urothelial carcinoma) and 18 lacked dysplasia. Oncogenic genetic variants were found in all cases of IM with high-grade dysplasia and in five non-dysplastic IM cases, including mutations and copy number variants commonly seen in primary adenocarcinoma of the bladder and urothelial carcinoma. This study demonstrates that IM can harbor potentially oncogenic genetic variants, suggesting that it might represent a cancer precursor or a marker of increased cancer risk in a subset of cases

Rare MDM2 amplification in a fat-predominant angiomyolipoma

Angiomyolipomas (AMLs) are triphasic tumors (smooth muscle, vascular and adipocytic components) with myomelanocytic differentiation, arising most commonly in the kidneys, which can show predominant epithelioid morphology and fat-predominant or fat-poor variants. Fat-predominant AMLs can show areas of hypercellularity and lipoblast-like cells, and these features can mimic well-differentiated liposarcoma (WDLS). To date, only one documented metastatic epithelioid AML showed unequivocal MDM2 amplification by fluorescence in situ hybridization. We describe our findings in a series of 35 AMLs including epithelioid, fat-poor, and fat-predominant variants, following interrogation of the MDM2 locus by FISH and CISH assays. MDM2 amplification was detected in 1 fat-predominant AML. Our findings demonstrate that rare MDM2 amplifications can occur in AMLs. We favor that this finding likely represents a "molecular bystander" event since these tumors are mainly driven by aberrations in the TSC1/TSC2 genes. Nevertheless, the presence of MDM2 amplification in a fat-predominant AML could present a potential diagnostic pitfall, particularly when confronted with the differential diagnosis of fat-predominant AML and WDLS in limited material from the retroperitoneum

Fusion prostate biopsy outperforms 12-core systematic prostate biopsy in patients with prior negative systematic biopsy: A multi-institutional analysis

© 2018 Elsevier Inc. Introduction and objectives: Patients with persistently elevated prostate specific antigen (PSA) and prior negative 12-core TRUS prostate biopsy (or biopsies) (systematic biopsy—SBx) are a diagnostic challenge. Repeat SBx or saturation biopsy in this cohort has been shown to have an even lower yield. The aim of our study is to compare the prostate cancer yield of magnetic resonance imaging (MRI) fusion biopsy (FBx) to SBx in a multi-institutional cohort comprised of patients with prior negative biopsies. Methods: A multi-institutional review was performed on patients with a history of one or more prior negative SBx who underwent multiparametric MRI (mpMRI), followed by FBx and SBx in the same session. Imaging protocol was standardized across institutions and institutional genitourinary radiologists and pathologists reviewed mpMRI and pathology, respectively. Gleason score (GS) distribution and risk classifications were recorded. Prostate cancer with GS ≥3 + 4 was defined as clinically significant (CS). Univariate and multivariable logistic regression was done to identify predictors of cancer detection on SBx and FBx. Results: Seven-hundred seventy-nine patients from four institutions were included in the study. Median age and prostate specific antigen (IQR) were 63.1 (58.5–68.0) years and 8.5 (5.9–13.1) ng/dl, respectively. Median number of prior negative biopsies (range) was 2.0 (1–16). The cancer detection rate (CDR) in the cohort was 346/779 patients (44.4%). Total CS CDR was 30.7% (239/779 patients), with FBx detecting 26.3% (205/779) of patients with CS disease and SBx diagnosing an additional 4.4% (34/779) of patients (P\u3c0.001). Furthermore, of all cancers detected by each modality, FBx detected a higher proportion of CS cancer compared to SBx (one negative biopsy: 75 vs. 50%, P\u3c0.001, 2–3 negative biopsy: 76 vs. 61%, P = 0.006, 4 or more negative biopsies: 84 vs. 52%, P = 0.006). As such, SBx added a relatively small diagnostic value to FBx for detecting CS disease (one negative biopsy 3.5%, 2–3 negative biopsies 5%, 4 or more negative biopsies: 1%). FBx also outperformed SBx for upgrading patients to an intermediate or high-risk cancer category (GS\u3e6) (one negative biopsy 11.5% vs. 3.6%, 2–3 negative biopsy 10.3% vs. 5.3%, 4 or more negative biopsies 19.1% vs. 1.1%). On multivariable analysis, the number of prior negative biopsies was a significant negative predictor of CS CDR on SBx (P = 0.006), but not on FBx (P = 0.151). Conclusions: Using a large multi-institutional cohort, we were able to demonstrate that FBx outperformed SBx in patients with prior negative systematic biopsy. This was due, in part, to the decreasing CS CDR by SBx with increased number of prior biopsies. The yield of FBx stayed constant and did not decrease with increased number of prior negative biopsies. Therefore, repeat SBx alone in patients with multiple prior negative biopsies will be hindered by lower yield and FBx should be utilized concurrently in these patients