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Purpose: Indeterminate renal masses are increasingly incidentally found on cross-sectional imaging. 99mTc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) scans can be used to identify oncocytomas and oncocytic renal neoplasms, including a subset of chromophobe renal cell carcinomas (chRCCs), which are viewed as false-positive. Procedure: Patients imaged with renal sestamibi scans between 2014 and 2023 were reviewed. Those patients with solitary tumors that were originally classified as chRCC were included in the analysis. Imaging with SPECT/CT from the liver dome down had been carried out 75 min after the administration of 925 MBq of 99mTc-sestamibi. All available H&E and immunostained slides were re-reviewed and classified according to WHO 2022 criteria. Confirmatory immunohistochemical stains were performed in tumors considered morphologically suspicious for non-chRCC entities. Result: A total of 18 patients with solitary tumors were included in the final analysis. 13/18 (72.2%) tumors in this cohort remained classified as chRCC, with 4/18 (22.2%) being eosinophilic-variant chRCC. The reclassified tumors (5/18 [27.8%]) included 2/18 (11.1%) low-grade oncocytic tumor (LOT), 1/18 (5.5%) eosinophilic vacuolated tumor (EVT), and 2/18 (11.1%) unclassified low-grade oncocytic neoplasms. As such, only 2/9 (22.2%) qualitatively "hot" tumors were chRCC other than eosinophilic-variant and only 1/9 (11.1%) "cold" tumors was a histology other than chRCC. Conclusion: Based on current histopathologic classification methods, it is likely that the "false-positive" rate of uptake on renal sestamibi scans with chRCC has been over-stated. Further study is warranted to better refine the optimal utility of renal sestamibi scans for non-invasive risk stratification of indeterminate renal masses. [ABSTRACT FROM AUTHOR]

Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations. [ABSTRACT FROM AUTHOR]

This letter discusses the issue of unspecific bone uptake (UBU) in prostate-specific membrane antigen (PSMA)-targeted PET scans. The authors commend a systematic review on UBUs and emphasize the complexity of interpreting these lesions. They highlight that different PSMA-targeted radiotracers exhibit varying rates of UBUs, suggesting that the scaffold, rather than the radionuclide, plays a more significant role in determining UBU rates. The authors also challenge the assertion that fluorine-18 has higher spatial resolution and sensitivity, arguing that all PSMA-targeted PET agents are considered equally effective. They advocate for the use of fluorine-18 as a radionuclide for diagnostic imaging. [Extracted from the article]

Objective: The aims of this study were to investigate the utility of [18F]F-Florastamin, a novel prostate-specific membrane antigen (PSMA)-targeted PET radiotracer with facile radiochemistry, relative to the conventional imaging for the detection of sties of disease and evaluate the effect of multi-timepoint imaging with [18F]F-Florastamin PET on lesion detectability. Methods: Eight prostate cancer patients with known or suspected recurrence who underwent [18F]F-Florastamin PET/CT at 1-h and 2-h imaging time-points were included in this prospective pilot study. [18F]F-Florastamin PET images were interpreted visually and quantitatively at both time points and compared with CIM. Results: [18F]F-Florastamin PET was superior to CT in the detection of active osseous metastases and small-sized metastatic lymph nodes that do not fall under the anatomic imaging size criteria for metastasis. Multi-timepoint imaging showed a significant reduction in the blood pool, bone marrow and muscular uptake, and increase in liver uptake over time. There is a significant improvement in tumor-to-background ratio (TBR) at the 2-h imaging time-point (P = 0.04). The mean percentage change in TBR at 2-h was 21% (SD = 0.31). Conclusions: [18F]F-Florastamin is a promising new radioligand for PSMA-targeted PET with suitable lesion detectability and high TBR at both time points. [ABSTRACT FROM AUTHOR]

Background: Accurate classification of sites of interest on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) images is an important diagnostic requirement for the differentiation of prostate cancer (PCa) from foci of physiologic uptake. We developed a deep learning and radiomics framework to perform lesion-level and patient-level classification on PSMA PET images of patients with PCa. Methods: This was an IRB-approved, HIPAA-compliant, retrospective study. Lesions on [18F]DCFPyL PET/CT scans were assigned to PSMA reporting and data system (PSMA-RADS) categories and randomly partitioned into training, validation, and test sets. The framework extracted image features, radiomic features, and tissue type information from a cropped PET image slice containing a lesion and performed PSMA-RADS and PCa classification. Performance was evaluated by assessing the area under the receiver operating characteristic curve (AUROC). A t-distributed stochastic neighbor embedding (t-SNE) analysis was performed. Confidence and probability scores were measured. Statistical significance was determined using a two-tailed t test. Results: PSMA PET scans from 267 men with PCa had 3794 lesions assigned to PSMA-RADS categories. The framework yielded AUROC values of 0.87 and 0.90 for lesion-level and patient-level PSMA-RADS classification, respectively, on the test set. The framework yielded AUROC values of 0.92 and 0.85 for lesion-level and patient-level PCa classification, respectively, on the test set. A t-SNE analysis revealed learned relationships between the PSMA-RADS categories and disease findings. Mean confidence scores reflected the expected accuracy and were significantly higher for correct predictions than for incorrect predictions (P < 0.05). Measured probability scores reflected the likelihood of PCa consistent with the PSMA-RADS framework. Conclusion: The framework provided lesion-level and patient-level PSMA-RADS and PCa classification on PSMA PET images. The framework was interpretable and provided confidence and probability scores that may assist physicians in making more informed clinical decisions. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer is a common neoplasm but conventional imaging methods such as CT and bone scan are often insensitive. A new class of PET agents have emerged to diagnose and manage prostate cancer. Methods: The relevant literature on PET imaging agents for prostate cancer was reviewed. Results: This review shows a broad range of PET imaging agents, the most successful of which is prostate specific membrane antigen (PSMA) PET. Other agents either lack the sensitivity or specificity of PSMA PET. Conclusion: Among the available PET agents for prostate cancer, PSMA PET has emerged as the leader. It is likely to have great impact on the diagnosis, staging and management of prostate cancer patients. [ABSTRACT FROM AUTHOR]

A number of positron emission tomography (PET) radiotracers have been developed to improve the sensitivity and specificity of imaging for prostate cancer. These radiotracers include the bone-seeking agent Na18F as well as more tumor-specific compounds such as 11C-choline and 18F-fluciclovine. In this review, we will discuss the advantages and disadvantages of these PET radiotracers for the imaging of men with prostate cancer across a range of clinical contexts. We will also touch upon radiotracers in late clinical development that have not gained regulatory approval, including those targeted against prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR). [ABSTRACT FROM AUTHOR]

Objective: To describe our technique and early results performing transperineal prostate biopsy using cognitive magnetic resonance imaging (MRI)/biplanar ultrasound fusion. Key components of this technique include use of the PrecisionPoint Transperineal Access System (Perineologic, Cumberland, MD) and simultaneous transrectal ultrasound guidance in the axial and sagittal planes. Patients and methods: In total, 95 patients (38 studied retrospectively and 57 studied prospectively) underwent a transperineal MRI-targeted prostate biopsy using the technique detailed in this manuscript. All biopsies were performed by a single urologist (MAG). Data were collected with respect to cancer detection rates, tolerability, and complications. The subset of patients who were studied prospectively was assessed for complications by telephone interviews performed at 4–6 days and 25–31 days following the prostate biopsy. Results: Between February 2018 and June 2019, 95 men underwent a transperineal prostate biopsy using MRI/biplanar ultrasound fusion guidance. Patients had a total of 124 PI-RADS 3–5 lesions that were targeted for biopsy. In total, 108 (87.1%) lesions were found to harbor prostate cancer of any grade. Grade group ≥ 2 prostate cancer was found in 81 (65.3%) of targeted lesions. The detection rates for grade group ≥ 1 and grade group ≥ 2 prostate cancer rose with increasing PI-RADS score. In 65 (68.4%) cases, the patient's highest grade prostate cancer was found within an MRI target. Additionally, 12 of 55 (21.8%) patients who were found to have no or grade group 1 prostate cancer on systematic biopsy were upgraded to grade group ≥ 2 prostate cancer with MRI targeting. Only 1 (1.1%) patient received periprocedural antibiotics and no patient experienced an infectious complication. Self-limited hematuria and hematospermia were commonly reported following the procedure (75.4% and 40.4%, respectively) and only 1 (1.1%) patient developed urinary retention. Conclusions: We demonstrate the safety and feasibility of performing transperineal prostate biopsy using cognitive MRI/biplanar ultrasound fusion guidance. The described technique affords the safety benefits of the transperineal approach as well as obviates the need for a formal fusion platform. Additionally, this method can conveniently be performed under local anesthesia with acceptable tolerability. [ABSTRACT FROM AUTHOR]

Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has impacted the management of patients with prostate cancer (PCa) in many parts of the world. PSMA-targeted endoradiotherapies are also being increasingly utilized and for these applications, the radiopharmaceutical distribution in normal organs is particularly important because it may limit the dose that can be delivered to tumors. In this study, we measured both interpatient and intrapatient variability of [18F]DCFPyL uptake in the most relevant normal organs.Procedures: Baseline and 6-month follow-up PSMA-targeted [18F]DCFPyL PET/computed tomography (CT) scans from 39 patients with PCa were reviewed. Volumes of interest were manually drawn using the best visual approximation of the organ edge for both lacrimal glands, all four major salivary glands, the liver, the spleen, and both kidneys for all patients. The average SUVmean, the COVs, and intraclass correlation coefficients (ICCs) across scans were calculated. Bland-Altman analyses were performed for all organs to derive repeatability coefficients (RCs).Results: The liver demonstrated the lowest interpatient variability (13.0 and 16.6 % at baseline and follow-up, respectively), while the spleen demonstrated the largest interpatient variability (44.6 and 51.0 % at baseline and follow-up, respectively). The lowest intrapatient variability was found in the spleen (ICC 0.86) while the highest intrapatient variability was in the kidneys (ICCs 0.40-0.50). Bland-Altman analyses showed 95 % repeatability coefficients for mean uptake > 40 % for multiple organs and were highest for the lacrimal glands, kidneys, and spleen.Conclusions: Normal organs demonstrate significant variability in uptake of the PSMA-targeted radiotracer [18F]DCFPyL. Depending on the organ, different contributions of interpatient and intrapatient factors affect the intrinsic variability. The RCs also vary significantly among the different organs were highest for the lacrimal glands, kidneys, and spleen. These findings may have important implications for the design of clinical protocols and personalized dosimetry for PSMA-targeted endoradiotherapies. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we aimed to quantitatively investigate the biodistribution of [18F]DCFPyL in patients with prostate cancer (PCa) and to determine whether uptake in normal organs correlates with an increase in tumor burden.Procedures: Fifty patients who had been imaged with [18F]DCFPyL positron emission tomography/computed tomography (PET/CT) were retrospectively included in this study. Forty of 50 (80 %) demonstrated radiotracer uptake on [18F]DCFPyL PET/CT compatible with sites of PCa. Volumes of interests (VOIs) were set on normal organs (lacrimal glands, parotid glands, submandibular glands, liver, spleen, and kidneys) and on tumor lesions. Mean standardized uptake values corrected to lean body mass (SULmean) and mean standardized uptake values corrected to body weight (SUVmean) for normal organs were assessed. For the entire tumor burden, SULmean/max, SUVmean, tumor volume (TV), and the total activity in the VOI were obtained using tumor segmentation. A Spearman's rank correlation coefficient was used to investigate correlations between normal organ uptake and tumor burden.Results: There was no significant correlation between TV with the vast majority of the investigated organs (lacrimal glands, parotid glands, submandibular glands, spleen, and liver). Only the kidney showed significant correlation: With an isocontour threshold at 50 %, left kidney uptake parameters correlated significantly with TV (SUVmean, ρ = - 0.214 and SULmean, ρ = - 0.176, p < 0.05, respectively).Conclusions: Only a minimal sink effect with high tumor burden in patients imaged with [18F]DCFPyL was observed. Other factors, such as a high intra-patient variability of normal organ uptake, may be a much more important consideration for personalized dosimetry with PSMA-targeted therapeutic agents structurally related to [18F]DCFPyL than the tumor burden. [ABSTRACT FROM AUTHOR]

Upper tract urothelial carcinoma (UTUC) is a relatively uncommon but aggressive genitourinary malignancy for which multi-phase contrast-enhanced computed tomography (CT) plays an important role in evaluation and staging. 3D imaging with maximum intensity projection (MIP) and volume-rendered (VR) images has been described as a useful means of evaluating UTUC. In this study, we describe the technique of a novel 3D methodology known as cinematic rendering (CR) and provide clinical examples of UTUC visualized with CR. CR utilizes a complex universal lighting model in order to create photorealistic images with improved detail and depth in comparison to MIP or VR images. In the case of UTUC, CR can be used in different contrast phases to show abnormally thickened and enhancing urothelium or filling defects in the renal collecting system or ureters in the excretory phase. CR images can also be manipulated in order to generate translucent views of the upper urinary tract in order to add conspicuity to intraluminal findings. [ABSTRACT FROM AUTHOR]

Objective: Complete surgical resection of metastatic sites has been shown to prolong survival in select patients with oligometastatic RCC. This treatment strategy is dependent upon the accurate characterization of a patient's extent of disease. The objective of this study was to explore the utility of PSMA-targeted 18F-DCFPyL PET/CT in patients with presumed oligometastatic clear cell RCC.Methods: This is a subset analysis of a prospective study in which patients with RCC were imaged with 18F-DCFPyL PET/CT (ClinicalTrials.gov identifier NCT02687139). In the present analysis, patients with oligometastatic clear cell RCC, defined as ≤ 3 metastatic lesions on conventional imaging, were evaluated. 18F-DCFPyL PET/CT scans were reviewed for sites of disease and compared to conventional imaging.Results: The final cohort included 14 patients with oligometastatic clear cell RCC. Conventional imaging revealed 21 metastatic lesions and 3 primary tumors. 18F-DCFPyL PET/CT detected 29 sites of metastatic disease and 3 primary tumors. Of the 21 metastatic lesions detected on conventional imaging, 17 (81.0%) had radiotracer uptake. Additionally, all 3 primary tumors had radiotracer uptake. In 4 (28.6%) patients a total of 12 more lesions were identified on 18F-DCFPyL PET/CT than conventional imaging. Notably, 3 (21.4%) patients were no longer considered oligometastatic. The detection rates of conventional imaging and 18F-DCFPyL PET/CT for identifying sites of disease were 66.7% and 88.9%, respectively.Conclusions: PSMA-targeted PET/CT appears to aid in the identification of patients with oligometastatic clear cell RCC. If borne out in future studies, this suggests that PSMA-targeted imaging has the potential to help select candidates for metastasis-directed therapy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the utility of prostate-specific membrane antigen (PSMA)-targeted [18F]DCFPyL positron emission tomography (PET)/X-ray computed tomography (CT) imaging for the detection of sites of disease in patients with metastatic non-clear cell renal cell carcinoma (RCC).Procedures: Eight patients with metastatic non-clear cell RCC underwent imaging with PSMA-targeted [18F]DCFPyL PET/CT. Imaged RCC histologic subtypes included papillary RCC (n = 3), chromophobe RCC (n = 2), unclassified RCC (n = 2), and Xp11 translocation RCC (n = 1). Using comparison to conventional CT and/or magnetic resonance imaging as reference, two radiologists with expertise in nuclear medicine identified putative sites of disease on [18F]DCFPyL PET/CT and classified each lesion as having no radiotracer uptake, equivocal uptake, or definitive uptake.Resuts: In total, 73 metastatic sites and 3 primary tumors compatible with sites of non-clear cell RCC were identified on conventional imaging. Metastatic sites of disease included lymph nodes (n = 40), venous thrombi (n = 3), pulmonary nodules (n = 10), bone lesions (n = 15), brain lesions (n = 3), and retroperitoneal masses (n = 2). Only 10 of the 73 lesions (13.7 %) were classified as having definitive radiotracer uptake (median SUVmax = 3.25, range = 1.2-9.5), 14 lesions (19.2 %) had equivocal uptake (median SUVmax = 2.85, range = 0.5-6.5), and 49 lesions (67.1 %) had no definitive uptake above background (median SUVmax = 1.7, range = 0.2-3.0). The three primary renal tumors demonstrated lower radiotracer avidity relative to surrounding normal renal parenchyma.Conclusions: A small proportion of sites of non-clear cell RCC showed uptake of the PSMA-targeted radiotracer [18F]DCFPyL. Unlike for clear cell RCC, the results of this study indicate that PSMA-based PET is not appropriate for imaging other RCC subtypes. [ABSTRACT FROM AUTHOR]

3D computed tomography (CT) visualizations of volumetric data have become an important aspect of diagnostic imaging. The utility of 3D CT has been well described for the imaging of a number of renal pathologies. Recently, a new 3D visualization technique known as cinematic rendering (CR) has become available and provides photorealistic images derived from standard CT acquisitions by use of a complex global lighting model. Herein, we describe a number of normal variant and pathologic conditions of the kidney visualized with CR. We provide comparisons of findings with CR to traditional methods of 3D imaging and comment on the potential applications of this new method of 3D CT rendering. [ABSTRACT FROM AUTHOR]

Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET)-based imaging agents for prostate carcinoma and neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e., if the reader is familiar with one system, the other system can readily be applied, as well. In the present review, we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a potential future role of the umbrella framework MI-RADS compared to other classification systems. [ABSTRACT FROM AUTHOR]

Objective: Technetium-99m (99mTc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has previously been shown to allow for the accurate differentiation of benign renal oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) apart from other malignant renal tumor histologies, with oncocytomas/HOCTs showing high uptake and renal cell carcinoma (RCC) showing low uptake based on uptake ratios from non-quantitative single-photon emission computed tomography (SPECT) reconstructions. However, in this study, several tumors fell close to the uptake ratio cutoff, likely due to limitations in conventional SPECT/CT reconstruction methods. We hypothesized that application of quantitative SPECT/CT (QSPECT) reconstruction methods developed by our group would provide more robust separation of hot and cold lesions, serving as an imaging framework on which quantitative biomarkers can be validated for evaluation of renal masses with 99mTc-sestamibi.Methods: Single-photon emission computed tomography data were reconstructed using the clinical Flash 3D reconstruction and QSPECT methods. Two blinded readers then characterized each tumor as hot or cold. Semi-quantitative uptake ratios were calculated by dividing lesion activity by background renal activity for both Flash 3D and QSPECT reconstructions.Results: The difference between median (mean) hot and cold tumor uptake ratios measured 0.655 (0.73) with the QSPECT method and 0.624 (0.67) with the conventional method, resulting in increased separation between hot and cold tumors. Sub-analysis of 7 lesions near the separation point showed a higher absolute difference (0.16) between QPSECT and Flash 3D mean uptake ratios compared to the remaining lesions.Conclusions: Our finding of improved separation between uptake ratios of hot and cold lesions using QSPECT reconstruction lays the foundation for additional quantitative SPECT techniques such as SPECT-UV in the setting of renal 99mTc-sestamibi and other SPECT/CT exams. With robust quantitative image reconstruction and biomarker analysis, there may be an expanded role for SPECT/CT imaging in renal masses and other pathologic conditions. [ABSTRACT FROM AUTHOR]

Objective: Molecular imaging with positron emission tomography (PET) provides a powerful means of identifying and characterizing cancerous processes, as well as providing a quantitative framework within which response to therapy can be ascertained. Unfortunately, the most commonly used PET radiotracer, ¹⁸F-fluorodeoxyglucose (FDG), has not demonstrated a definitive role in determining response to therapy in metastatic renal cell carcinoma (RCC). As a result, new radiotracers able to reliably image RCC could be of tremendous value for this purpose.Methods: Five patients with known metastatic RCC were imaged with the low-molecular weight radiotracer ¹⁸F-DCFPyL, an inhibitor of the prostate-specific membrane antigen at 60 min post injection. ¹⁸F-DCFPyL PET/CT and conventional images (either contrast-enhanced computed tomography or magnetic resonance imaging) were centrally reviewed for suspected sites of disease.Results: In all five patients imaged, sites of putative metastatic disease were readily identifiable by abnormal ¹⁸F-DCFPyL uptake, with overall more lesions detected than on conventional imaging. These PET-detected sites included lymph nodes, pancreatic parenchymal lesions, lung parenchymal lesions, a brain parenchymal lesion, and other soft tissue sites. ¹⁸F-DCFPyL uptake ranged from subtle to intense with maximum standardized uptake values (SUVmax) for the identified lesions of 1.6-19.3. Based upon this small patient series, limited pathology and imaging follow-up of these patients suggests a higher sensitivity for ¹⁸F-DCFPyL compared to conventional imaging in the detection of metastatic RCC (94.7 versus 78.9%).Conclusions: PSMA expression in the tumor neovasculature of RCC has been previously established and is believed to provide the basis for the imaging findings presented here. PSMA-based PET/CT with radiotracers such as ¹⁸F-DCFPyL may allow more accurate staging of patients with RCC and conceivably the ability to predict and follow therapy in patients treated with agents targeting the neovasculature. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical utility of PSMA-targeted 18F-DCFPyL PET/CT in patients with metastatic urothelial carcinoma.Methods: Three patients with metastatic urothelial carcinoma were imaged with 18F-DCFPyL PET/CT. All lesions with perceptible radiotracer uptake above background were considered positive. Maximum standardized uptake values were recorded for each detected lesion and findings on 18F-DCFPyL PET/CT were compared to those on conventional imaging studies. To further explore PSMA as a molecular target of urothelial carcinoma, RNA-sequencing data from The Cancer Genome Atlas were used to compare the relative expression of PSMA among cases of bladder cancer, prostate cancer, and clear cell renal cell carcinoma. Additionally, immunohistochemical staining for PSMA was performed on a biopsy specimen from one of the imaged patients.Results: 18F-DCFPyL PET/CT allowed for the detection of sites of urothelial carcinoma, albeit with low levels of radiotracer uptake. Analysis of RNA-sequencing data revealed that bladder cancer had significantly lower levels of PSMA expression than both prostate cancer and clear cell renal cell carcinoma. Consistent with this observation, immunohistochemical staining of tissue from one of the imaged patients demonstrated a low level of neovascularization and nearly absent PSMA expression.Conclusion: The relatively scant expression of PSMA by urothelial carcinoma likely limits the utility of PSMA-targeted PET imaging of this malignancy. Future research efforts should focus on the development of other molecularly targeted imaging agents for urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Objective: Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent 18F-DCFPyL.Methods: A total of 98 patients who underwent 18F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUVmax), and maximum standardized uptake value corrected to lean body mass (SULmax) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUVmax and SULmax values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean).Results: Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated 18F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts.Conclusion: As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients' cancers must be understood. This is the first systematic evaluation of the uptake of 18F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research. [ABSTRACT FROM AUTHOR]

Background: Tc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has recently been explored for the characterization of indeterminate renal masses. As judged by increased intra-tumoral radiotracer uptake, we have previously reported the excellent diagnostic performance characteristics of this test for identifying benign/indolent oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs). In this study, we investigated potential molecular mechanisms underlying the discriminatory ability of Tc-sestamibi SPECT/CT for renal masses. Fifty renal masses imaged with Tc-sestamibi SPECT/CT prior to surgical resection were evaluated by immunohistochemistry for mitochondrial content and expression of the multi-drug resistance pump 1 (MDR1/P-gp). Immunohistochemical staining was scored semi-quantitatively, and results were compared across renal tumor histologies and correlated with Tc-sestamibi uptake. Results: In total, 6/6 (100%) and 2/2 (100%) HOCTs demonstrated strong mitochondrial content staining combined with low MDR1 staining. Clear cell renal cell carcinoma showed an opposite pattern with the majority having low mitochondrial (14/26, 54%) and high MDR1 staining (18/26, 69%). Other tumor types were more variable in staining pattern, although the staining pattern reliably predicted Tc-sestamibi uptake in almost all tumors except chromophobe renal cell carcinoma. Conclusions: Our findings confirm that renal tumors with high mitochondrial content and relatively low MDR pump expression activity accumulate Tc-sestamibi and allow for the accurate diagnosis of the benign/indolent tumor class that includes oncocytomas and HOCTs. For masses in which MDR activity outweighs the presence of mitochondria, the tumors appear cold on Tc-sestamibi SPECT/CT, allowing for high confidence in the diagnosis of renal cell carcinoma. [ABSTRACT FROM AUTHOR]

The cancer community continues to search for an efficient and cost-effective technique to isolate and characterize circulating cells (CTCs) as a 'real-time liquid biopsy'. Existing methods to isolate and analyze CTCs require various transfer, wash, and staining steps that can be time consuming, expensive, and led to the loss of rare cells. To overcome the limitations of existing CTC isolation strategies, we have developed an inexpensive 'lab on a chip' device for the enrichment, staining, and analysis of rare cell populations. This device utilizes immunomagnetic positive selection of antibody-bound cells, isolation of cells through an immiscible interface, and filtration. The isolated cells can then be stained utilizing immunofluorescence or used for other downstream detection methods. We describe the construction and initial preclinical testing of the device. Initial tests suggest that the device may be well suited for the isolation of CTCs and could allow the monitoring of cancer progression and the response to therapy over time. [ABSTRACT FROM AUTHOR]

To ensure the early detection of recurrent disease, all patients should undergo routine surveillance following partial nephrectomy for renal cell carcinoma. In order to optimize resource allocation and avoid unnecessary radiation exposure, the frequency and duration of surveillance should be tailored to the individual patient’s risk of cancer recurrence. The evidence for surveillance after partial nephrectomy is presented reviewing the current literature on prognostic models and proposed surveillance protocols based on the timing and patterns of renal cell carcinoma recurrence. In addition, we review recent guidelines on post partial nephrectomy surveillance as well as the literature on novel imaging techniques thatmay aid in early disease discovery. [ABSTRACT FROM AUTHOR]

Purpose: To describe the frequency and severity of atherosclerosis contained within the non-neoplastic tissue of partial nephrectomy (PN) specimens. Methods: Archived open PN specimens were evaluated for histological evidence of atherosclerosis. Clinically significant atherosclerosis was defined as arterial luminal narrowing of >25 % due to fibrointimal thickening. Histological findings were correlated with clinical data including history of major medical comorbidities and preoperative statin use. Results: The study cohort was comprised of 114 patients (71 men and 43 women). The mean age at the time of surgery was 59.3 years, and 69 (60.5 %) patients had a history of at least one major medical comorbidity including hypertension (54.5 %), diabetes (16.7 %) and coronary artery disease (12.3 %). Clinically significant atherosclerosis was observed in 29 (25.4 %) patients. These individuals were older ( p = 0.001), and three times more likely to have greater than one major medical comorbidity ( p = 0.002). In addition, only 17 (58.6 %) were prescribed a statin at the time of surgery. Conclusions: Atherosclerosis is frequently observed in the non-neoplastic tissue of PN specimens. Patients found to have atherosclerosis can potentially benefit from intensive lifestyle modification and medical therapy with lipid-lowering medications. These measures would likely have the greatest clinical impact on those patients without an existing history of major medical comorbidities. [ABSTRACT FROM AUTHOR]

Purpose: To identify preoperative factors associated with surgical complications and successful diagnostic renal biopsy in both laparoscopic and percutaneous radiofrequency ablation (RFA) of renal masses in order to help aid in preoperative patient counseling for renal RFA. Methods: We reviewed our Institutional Review Board approved database from November 2001 to January 2011, containing 335 tumors treated with either laparoscopic (LRFA) or percutaneous RFA (CTRFA). Preoperative patient demographics, tumor characteristics, and intraoperative surgical data were collected along with biopsy results and clinicopathologic outcomes. Results: RFA was performed on 335 renal tumors (124 LRFA, 211 CTRFA). Non-diagnostic biopsy occurred in 18 (5.5%) tumors. Of the 317 procedures performed, 121 complications occurred in 103 (30.7%) procedures. Multivariate analysis only showed CTRFA (vs LRFA) to increase the likelihood of non-diagnostic biopsy (OR 5.1, 95% CI 1.2-22, p = 0.032). Increased tumor size ( p = 0.007) and synchronous ablations ( p = 0.019) increased the risk for major complications, while decreased surgeon experience ( p = 0.003) and tumors close to the collecting system ( p = 0.005) increased the risk of any complication. Conclusions: Preoperative recommendations can be made to patients in the future. We suggest counseling patients that when undergoing RFA, percutaneous approach increases the risk of non-diagnostic biopsy, increased tumor size increases the risk of major complications, having more than 1 tumor ablated increases the risk of a major complication, and tumors close to the collecting system may increase the risk of complications. [ABSTRACT FROM AUTHOR]

Lymphadenectomy is utilized in both pelvic and retroperitoneal oncological surgery as a means to eradicate locoregional disease, improve staging accuracy and guide adjuvant therapy. However, pelvic and retroperitoneal lymphadenectomy have the potential for morbidity including lymphatic injury, vascular injury, thromboembolic events and neurologic injury. Across the spectrum of urologic malignancies, the evidence supporting both the necessity and the extent of lymphadenectomy varies considerably. Awareness of the potential for injury and ways to avoid and manage the most common complications is necessary to decrease the morbidity associated with these procedures. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify non-neoplastic pathologic changes in partial nephrectomy specimens of patients without a known history of medical comorbidities. Routine analysis of this tissue may allow the clinician to identify subclinical renal disease. Methods: We retrospectively reviewed our database of patients who underwent open partial nephrectomy for a small renal mass. Non-neoplastic tissue of partial nephrectomy specimens of patients without a known history of chronic kidney disease, diabetes mellitus, hypertension, or coronary artery disease was evaluated for glomerular, interstitial, and vascular pathologic changes. Results: A rim of non-neoplastic tissue was adequate for pathologic evaluation in 91.8% of specimens. A total of 45 patients were studied with a median age of 52.0 years. Atherosclerosis was the most commonly identified pathologic finding in 9 (20%) patients, followed by mesangial expansion and interstitial fibrosis, each found in 8 (17.8%) patients. Linear regression found interstitial fibrosis to be the only pathologic lesion associated with preoperative serum creatinine (coefficient = 0.697, P = 0.001). Male gender was also associated with a higher preoperative creatinine (coefficient = 0.270, P = 0.034). Postoperative serum creatinine was not associated with any of the examined lesions. Conclusions: Current surgical techniques provide adequate non-neoplastic tissue for pathologic evaluation. We observed a striking degree of pathologic disease in patients without a known history of medical comorbidities. Routine inspection of the non-neoplastic parenchyma of partial nephrectomy specimens should be performed as it can alert the clinician to presence subclinical renal disease allowing for medical intervention. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate oncologic outcomes following the use of intraoperative cell salvage (IOCS) as a blood loss management strategy during open radical prostatectomy (RP). Methods: We retrospectively reviewed all open retropubic RP cases performed by a single surgeon. Patients were identified who received IOCS blood and evaluated for an increased risk of biochemical recurrence (BCR) and overall mortality. Results: The study cohort consisted of 1,862 men, 395 (21.2%) of whom received IOCS blood. At a median follow-up of 47.0 months, men who received IOCS blood were not at an increased risk of BCR ( P = 0.323) or all-cause mortality ( P = 0.892). IOCS use did not confer an increased risk of BCR within any D'Amico preoperative risk category (low risk, P = 0.592; intermediate risk, P = 0.107; and high risk, P = 0.697). Conclusions: IOCS is safe for the management of blood loss during RP. At long-term follow-up, IOCS use was not associated with an increased risk of BCR or death. While it remains preferable to avoid any form of blood transfusion, we advocate for the use of IOCS in place of allogeneic blood. These conclusions are drawn from our study of the largest and longest followed cohort patients who received IOCS blood during RP. [ABSTRACT FROM AUTHOR]

In an effort to preserve renal function, nephron-sparing approaches such as partial nephrectomy are now routinely performed for the treatment of small renal masses (SRMs). To date, several groups have studied the utility of examining the renal parenchyma contained beyond the tumor margin of partial nephrectomy specimens for histopathologic evidence of non-neoplastic disease processes. The diagnosis of progressive renal disease through the study of this tissue allows for early medical intervention with possible further preservation of renal function. In this review, we discuss the management of SRMs with an emphasis on the emerging role of evaluating tumor specimens for non-neoplastic pathologic abnormalities. We believe that the thorough study of tissue contained beyond the tumor margin of partial nephrectomy specimens is the next step in preserving renal function and improving survival for patients with SRMs. [ABSTRACT FROM AUTHOR]

As part of an attempt to locate the von Hippel-Lindau locus (VHL) on chromosome 3, we evaluated 41 families with von Hippel-Lindau disease from the United States and Canada. One large family was identified whose disease phenotype was distinct from typical VHL. The most common disease manifestation was pheochromocytoma occuring in 57% (27/47) of affected family members. Few (4/47) affected family members had symptomatic spinal or cerebellar hemangioblastomas; no affected family member had renal cell carcinoma (0/47) or pancreatic cysts (0/24). Previously, genetic analysis demonstrated that the disease manifestations in this family were linked to RAF1 and D3S18, markers shown to be linked to typical VHL. These results suggest that there are mutant alleles at the VHL locus associated with distinct tissue specificities. [ABSTRACT FROM AUTHOR]

Retinal cavernous hemangiomas are rare vascular anomalies, and can be associated with cerebral cavernous malformations (CCM). Distinct mutations have been reported in patients who have both CCMs and retinal cavernous hemangiomas. Fluorescein angiography, spectral domain optical coherence tomography, and genetic testing were performed on a patient with a retinal cavernous hemangioma and a CCM. Our patient was heterozygous in the KRIT1/CCM1 gene for a frameshift mutation, c.1088delC. This would be predicted to result in premature protein termination. We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. We hypothesize that the occurrence of retinal cavernous hemangiomas and CCMs is underlaid by a common mechanism present in the KRIT1/CCM1 gene. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the developed world. While treatment is effective for the neovascular or "wet" form of AMD, no therapy is successful for the non-neovascular or "dry" form. Here we discuss the current knowledge on dry AMD pathobiology and propose future research directions that would expedite the development of new treatments. In our view, these should emphasize system biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy. No effective therapies exist for dry age-related macular degeneration. In this perspective, the authors propose that research should emphasize system biology approaches that integrate various 'omics' data into mathematical models to establish pathogenic mechanisms on which to design novel treatments, and identify biomarkers that predict disease progression and therapeutic response. [ABSTRACT FROM AUTHOR]

Purpose of Review: Determining the metastatic viability of suspicious retroperitoneal nodes in testicular cancer with conventional imaging is challenging. The aim of this report is to review recent evidence in the utilization of novel imaging modalities to assess viable testicular cancer nodal metastases.Recent Evidence: Testicular germ cell tumors (TCGTs) follow a predictable lymphatic metastatic spread to the retroperitoneum. Accordingly, retroperitoneal imaging is critical in staging, assessing treatment response, and evaluating for recurrence. Conventional computed tomography (CT) imaging is effective in diagnosing pathologically enlarged lymph nodes but lacks the molecular information to determine if suspicious nodes harbor viable tumor. Positron emission tomography (PET) with the metabolic radiotracer 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG or FDG) has been shown to be useful in determining the presence of or absence of viable tumor after chemotherapy for seminoma, but its role with non-seminomatous germ cell tumors (NSGCTs) and other clinical scenarios is limited. Patients with residual masses after chemotherapy for NSGCT present a difficult challenge because surgical resection carries a high degree of morbidity despite many patients only harboring fibrosis on final pathology. Current imaging modalities are unable to effectively differentiate fibrosis from viable tumor on preoperative imaging. Novel molecular imaging techniques present promising opportunities to improve diagnosis in these patients.Summary: Novel imaging platforms have potential to improve the ability to determine viable nodal metastases regardless of size and structure but confirmatory studies are currently lacking. [ABSTRACT FROM AUTHOR]

The article provides information about age-related macular degeneration. In this context, it informs about a study, which shows the evidence of a strong association of the Tyr402His polymorphism in the complement H factor gene with the development of a disease that is the leading cause of untreatable blindness in the elderly. Age-related macular degeneration (AMD) affects nearly 1.75 million individuals in the United States alone. With a prevalence of advanced AMD features in 1.4% of the population over the age of 40 years, which is prevalence raising to more than 15% for white women over the age of 80 years, it is estimated that by 2020, the number of individuals in the US with AMD will rise to nearly 3 million individuals.