Diagnostic Performance of Prostate-specific Antigen Density for Detecting Clinically Significant Prostate Cancer in the Era of Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

CONTEXT: There has been a dramatic increase in the use of prostate magnetic resonance imaging (MRI) in the diagnostic workup. With prostate volume calculated from MRI, prostate-specific antigen density (PSAD) now is a ready-to-use parameter for prostate cancer (PCa) risk stratification before prostate biopsy, especially among patients with negative MRI or equivocal lesions. OBJECTIVE: In this review, we aimed to evaluate the diagnostic performance of PSAD for clinically significant prostate cancer (CSPCa) among patients who received MRI before prostate biopsy. EVIDENCE ACQUISITION: Two investigators performed a systematic review according of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. Studies (published between January 1, 2012, and December 31, 2021) reporting the diagnostic performance (outcomes) of PSAD (intervention) for CSPCa among men who received prebiopsy prostate MRI and subsequent prostate biopsy (patients), using biopsy pathology as the gold standard (comparison), were eligible for inclusion. EVIDENCE SYNTHESIS: A total of 1536 papers were identified in PubMed, Scopus, and Embase. Of these, 248 studies were reviewed in detail and 39 were qualified. The pooled sensitivity (SENS) and specificity (SPEC) for diagnosing CSPCa among patients with positive MRI were, respectively, 0.87 and 0.35 for PSAD of 0.1 ng/ml/ml, 0.74 and 0.61 for PSAD of 0.15 ng/ml/ml, and 0.51 and 0.81 for PSAD of 0.2 ng/ml/ml. The pooled SENS and SPEC for diagnosing CSPCa among patients with negative MRI were, respectively, 0.85 and 0.36 for PSAD of 0.1 ng/ml/ml, 0.60 and 0.66 for PSAD of 0.15 ng/ml/ml, and 0.33 and 0.84 for PSAD of 0.2 ng/ml/ml. The pooled SENS and SPEC among patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 or Likert 3 lesions were, respectively, 0.87 and 0.39 for PSAD of 0.1 ng/ml/ml, 0.61 and 0.69 for PSAD of 0.15 ng/ml/ml, and 0.42 and 0.82 for PSAD of 0.2 ng/ml/ml. The post-test probability for CSPCa among patients with negative MRI was 6% if PSAD was <0.15 ng/ml/ml and dropped to 4% if PSAD was <0.10 ng/ml/ml. CONCLUSIONS: In this systematic review, we quantitatively evaluated the diagnosis performance of PSAD for CSPCa in combination with prostate MRI. It demonstrated a complementary performance and predictive value, especially among patients with negative MRI and PI-RADS 3 or Likert 3 lesions. Integration of PSAD into decision-making for prostate biopsy may facilitate improved risk-adjusted care. PATIENT SUMMARY: Prostate-specific antigen density is a ready-to-use parameter in the era of increased magnetic resonance imaging (MRI) use in clinically significant prostate cancer (CSPCa) diagnosis. Findings suggest that the chance of having CSPCa was very low (4% or 6% for those with negative prebiopsy MRI or Prostate Imaging Reporting and Data System (Likert) score 3 lesion, respectively, if the PSAD was <0.10 ng/ml/ml), which may lower the need for biopsy in these patients.

Real-Time Ultrasound-Computed Tomography Fusion with Volume Navigation to Assess Pancreatic Cystic Lesions.

Transabdominal ultrasound is a promising imaging modality for pancreatic cystic lesions. This study aims to determine if transabdominal ultrasonography with CT fusion (TAUS-f) using volume navigation can be used to measure pancreatic cystic lesions (PCLs) compared to CT alone. We evaluated 33 patients prospectively with known PCLs. The readers evaluated each PCL's size and imaging characteristics on TAUS-f and CT alone. These were compared to endoscopic ultrasonography reports. A total of 43 PCLs from 32 patients were evaluated. The detection rate by TAUS-f was 93%. Two of the three undetected PCLs were in the tail of the pancreas. Inter-reader variabilities for TAUS-f and CT were 0.005 cm and 0.03 cm, respectively. Subgroup analysis by size and location demonstrated that inter-modality variability between TAUS-f and CT was smallest for lesions < 1.5 cm with a size difference of -0.13 cm for each reader and smallest in the pancreatic head with a size difference of -0.16 cm and -0.17 cm for readers 1 and 2. We found that TAUS-f effectively evaluates PCLs compared to CT alone, thus suggesting that it should be considered part of the surveillance algorithm for a subset of patients.

Indocyanine Green (ICG) Fluorescence Is Dependent on Monomer with Planar and Twisted Structures and Inhibited by H-Aggregation.

The optical properties of indocyanine green (ICG) as a near-infrared (NIR) fluorescence dye depend on the nature of the solvent medium and the dye concentration. In the ICG absorption spectra of water, at high concentrations, there were absorption maxima at 700 nm, implying H-aggregates. With ICG dilution, the main absorption peak was at 780 nm, implying monomers. However, in ethanol, the absorption maximum was 780 nm, and the shapes of the absorption spectra were identical regardless of the ICG concentration, indicating that ICG in ethanol exists only as a monomer without H-aggregates. We found that emission was due to the monomer form and decreased with H-aggregate formation. In the fluorescence spectra, the 820 nm emission band was dominant at low concentrations, whereas at high concentrations, we found that the emission peaks were converted to 880 nm, suggesting a new form via the twisted intramolecular charge transfer (TICT) process of ICG. The NIR fluorescence intensity of ICG in ethanol was approximately 12- and 9-times brighter than in water in the NIR-I and -II regions, respectively. We propose an energy diagram of ICG to describe absorptive and emissive transitions through the ICG structures such as the monomer, H-aggregated, and TICT monomer forms.

Abdominal visceral tuberculosis: a malignancy mimic.

The purpose is to discuss abdominal tuberculosis mimicking malignancy involving the abdominal viscera. TB of the abdominal viscera is common, especially in countries where tuberculosis is endemic and in pockets of non-endemic countries. Diagnosis is challenging as clinical presentations are often non-specific. Tissue sampling may be necessary for definitive diagnosis. Awareness of the early and late disease imaging appearances of abdominal tuberculosis involving the viscera that can mimic malignancy can aid detecting TB, providing a differential diagnosis, assessing extent of spread, guiding biopsy, and evaluating response.

Hybrid magnetic resonance and PET imaging for prostate cancer recurrence.

PURPOSE OF REVIEW: Recurrence post definitive local therapy by prostatectomy or radiation therapy is often detected via rise in serum prostate-specific antigen (PSA) levels; however, PSA rise does not localize the disease. Distinguishing local versus distant recurrence guides whether to choose subsequent local versus systemic therapy. The purpose of this article is to review imaging for prostate cancer recurrence post local therapy. RECENT FINDINGS: Among imaging modalities, multiparametric MRI (mpMRI) is commonly used to assess for local recurrence. New radiopharmaceuticals target prostate cancer cells and enable whole-body imaging. These tend to be more sensitive for lymph node metastases than MRI or computed tomography (CT) and for bone lesions than bone scan at lower PSA levels but can be limited for local prostate cancer recurrence. Given greater soft tissue contrast, similar criteria for lymph nodes, and greater sensitivity for prostate bone metastases, MRI is advantageous to CT. MRI of the whole body and mpMRI are now feasible within a reasonable time frame and complementary to PET imaging, enabling whole-body and pelvis-focused PET-MRI, which should be advantageous in the setting of recurrent prostate cancer. SUMMARY: Hybrid PET-MRI with prostate cancer targeted radiopharmaceuticals and whole body with local multiparametric MRI can be complementary for detecting local and distant recurrence to guide treatment planning.

Prostate cancer grade downgrading at time of prostatectomy provides risk-stratification insight into future tumor behavior after prostatectomy.

BACKGROUND: Prostate biopsy (Bx) sampling-based diagnosis of prostate cancer (PCa) has well-described inaccuracy when compared against whole gland analysis upon prostatectomy. Although upgrading of PCa Grade Group (GG) is often described, the occurrence and prognostic implications of downgrading PCa GG at the time of radical prostatectomy (RP) is less understood. Our objective was to evaluate whether downgrading PCa GG at the time of RP was associated with future tumor behavior. METHODS: The SEER database was searched from 2010 to 2017 and patients were included if they were assigned pathological grades on both Bx and RP specimen. Patients were stratified into Bx GG > RP GG and Bx GG ≤ RP GG groups, and tumor behavior after treatment was examined. Cox regression was used for the survival analysis. RESULTS: Here, 99,835 patients were included in this study. A total of 18,516 (18.5%) patients encountered downgrading from Bx GG to RP GG. A downgrading of 1 grade occurred in 13,969 (75.4%) of these patients and of 2 or more grades occurred in 4547 (24.6%) patients. A history of higher Bx GG compared with RP GG increased the risk of cancer-specific mortality (CSM) for each given RP GG controlling for age, race, preop prostate-specific antigen level, percentage of positive biopsy cores, and pathologic TNM stages. Specifically, a history of high Bx GG conferred a 45% increased risk of CSM for any given RP GG (hazard ratio = 1.45 95% confidence interval = 1.16-1.82, p < 0.001). CONCLUSION: A history of higher Bx GG, and hence downgrading at the time of RP, demonstrates some value as a risk-stratification tool for future cancer outcomes after prostatectomy.

Prospective evaluation of PI-RADS v2 and quantitative MRI for clinically significant prostate cancer detection in Indian men - East meets West.

Purpose: To validate the detection of clinically significant prostate cancer (Gleason's score ≥7) by PI-RADS v2 and to assess the ability of quantitative MRI parameters to detect clinically significant prostate cancer (CSPCa) in Indian men. Methods: Adult men (n = 95) with serum PSA >4 ng/ml were prospectively evaluated with multiparametric MRI (mpMRI) followed by histopathological evaluation using systematic 12-core prostate biopsy in 69 patients and prostatectomy specimens in 26 patients, performed within six weeks of mpMRI. The imaging and the pathology were divided into 12 sectors per prostate. For the validation of PI-RADS v2, a cut-off of PI-RADS v2 score ≥ 3 and PI-RADS v2 score ≥ 4 were compared to histopathology as a reference standard. Further, quantitative parameters, apparent diffusion coefficient (ADC), Ktrans, and Kep were correlated with the Gleason score and evaluated for their ability to distinguish between sectors with CSPCa and sectors without CSPCa. Results: PI-RADS score ≥ 4 showed higher specificity (89%) than PI-RADS score ≥ 3 (72.2%) at the cost of mild but not significant reduction of sensitivity (sensitivity-87.6% vs 91.9), (n = 1,140 sectors, 95 patients). PI-RADS v2 and quantitative parameters demonstrated the ability to discriminate sectors positive vs negative for CSPCa: AUC (area under the curve) for ADC was 0.928, PI-RADS v2 was 0.903, Ktrans was 0.897 and Kep was 0.695. Gleason score correlated well with PI-RADS (r = 0.74), ADC (r = -0.73) and Ktrans (r = 0.69). Conclusion: PI-RADS v2 is a reliable method for the detection and localization of clinically significant prostate cancer in Indian men, suggesting applicability beyond European or American demographics. Quantitative mpMRI parameters can detect clinically significant prostate cancer with similar test characteristics as PI-RADS v2.

Performance of Multidetector Computed Tomography and Negative Versus Positive Enteric Contrast for Evaluation of Gastrointestinal Neuroendocrine Neoplasms.

BACKGROUND: Routine computed tomography (CT) scans are thought to have poor performance for detection of gastrointestinal (GI) neuroendocrine neoplasms (NENs), which leads to delayed workup. Detection of even 1 bowel tumor can guide diagnostic workup and management. The purposes of this study were to assess the accuracy of multidetector computed tomography (MDCT) and to compare negative versus positive enteric contrast in detecting at least 1 GI tumor per patient with suspected or confirmed diagnosis of a NEN. METHODS: This retrospective study included 107 patients with intravenous and oral contrast (65 positive, 40 negative, and 2 no oral contrast) abdominopelvic MDCT. Two abdominal radiologists independently analyzed the CTs for detection and localization of bowel NENs. Surgical pathology was considered the reference standard. Analyses included κ and summary statistics, McNemar test, Pearson χ2 test, and Fisher exact test. RESULTS: Among the 107 CT scans, there were 30 pathology negative studies and 77 studies with positive pathology for GI NEN. Interreader agreement for CT evaluation was substantial (κ = 0.61). At least 1 GI NEN per patient was detected with 51% to 53% sensitivity, 87% to 93% specificity, 91% to 95% positive predictive value (PPV), 42% negative predictive value, and 63% accuracy for each reader, and 57% accuracy when only the concordant (ie, matching) results of the 2 readers were considered. Computed tomography scans with negative enteric contrast had significantly higher sensitivity for concordant results than CTs with positive enteric contrast (58% vs 30%, P = 0.01). Specificity (100% vs 95%, P = 0.5), PPV (100% vs 93%, P = 0.49), negative predictive value (39% vs 39%, P = 0.99), and accuracy (67% vs 51%, P = 0.10) were not significantly different for negative versus positive enteric contrast for the concordant results. There was no significant difference in GI NEN localization between the readers. CONCLUSIONS: Routine MDCT with either positive or negative enteric contrast can detect at least 1 GI tumor per patient with more than 90% PPV and more than 50% accuracy in patients suspected of GI NEN. Using negative enteric contrast improves sensitivity for GI NEN versus positive enteric contrast. In addition, there is high accuracy in localizing the bowel tumor with positive or negative enteric contrast, which may guide surgery. Radiologists should have heightened awareness that evaluating such scans closely may lead to detection of primary bowel NENs at a higher rate than previously reported.

Tuberculosis of abdominal lymph nodes, peritoneum, and GI tract: a malignancy mimic.

OBJECTIVE: The purpose is to discuss abdominal tuberculosis mimicking malignancy involving the lymph nodes, peritoneum, and the GI tract. CONCLUSION: Awareness of the pathophysiology and imaging appearance on various modalities of abdominal tuberculosis involving the lymph nodes, peritoneum, and the GI tract that may simulate malignancy can aid differentiation, diagnosis, and therapy, particularly in areas where tuberculosis is endemic.

Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer.

BACKGROUND: No curative therapy is currently available for metastatic prostate cancer (PCa). The diverse mechanisms of progression include fibroblast growth factor (FGF) axis activation. OBJECTIVE: To investigate the molecular and clinical implications of fibroblast growth factor receptor 1 (FGFR1) and its isoforms (α/ß) in the pathogenesis of PCa bone metastases. DESIGN, SETTING, AND PARTICIPANTS: In silico, in vitro, and in vivo preclinical approaches were used. RNA-sequencing and immunohistochemical (IHC) studies in human samples were conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In mice, bone metastases (chi-square/Fisher's test) and survival (Mantel-Cox) were assessed. In human samples, FGFR1 and ladinin 1 (LAD1) analysis associated with PCa progression were evaluated (IHC studies, Fisher's test). RESULTS AND LIMITATIONS: FGFR1 isoform expression varied among PCa subtypes. Intracardiac injection of mice with FGFR1-expressing PC3 cells reduced mouse survival (α, p < 0.0001; ß, p = 0.032) and increased the incidence of bone metastases (α, p < 0.0001; ß, p = 0.02). Accordingly, IHC studies of human castration-resistant PCa (CRPC) bone metastases revealed significant enrichment of FGFR1 expression compared with treatment-naïve, nonmetastatic primary tumors (p = 0.0007). Expression of anchoring filament protein LAD1 increased in FGFR1-expressing PC3 cells and was enriched in human CRPC bone metastases (p = 0.005). CONCLUSIONS: FGFR1 expression induces bone metastases experimentally and is significantly enriched in human CRPC bone metastases, supporting its prometastatic effect in PCa. LAD1 expression, found in the prometastatic PCa cells expressing FGFR1, was also enriched in CRPC bone metastases. Our studies support and provide a roadmap for the development of FGFR blockade for advanced PCa. PATIENT SUMMARY: We studied the role of fibroblast growth factor receptor 1 (FGFR1) in prostate cancer (PCa) progression. We found that PCa cells with high FGFR1 expression increase metastases and that FGFR1 expression is increased in human PCa bone metastases, and identified genes that could participate in the metastases induced by FGFR1. These studies will help pinpoint PCa patients who use fibroblast growth factor to progress and will benefit by the inhibition of this pathway.

Tuberous Sclerosis Complex (TSC): Renal and Extrarenal Imaging.

Tuberous sclerosis complex is a multiorgan syndrome manifesting with several benign and malignant tumors. Complications arising from renal abnormalities are a leading cause of death in patients with tuberous sclerosis complex. Renal cell carcinoma is relatively uncommon, occurring in 2%-4% of patients with tuberous sclerosis complex syndrome, but nonetheless can significantly contribute to morbidity and mortality. Extrarenal manifestations of tuberous sclerosis complex, including within the chest, abdomen and central nervous system, aid in diagnosis. Pathogenesis and management are also discussed, including the importance of the types of renal masses found in these patients.

CD63-mediated cloaking of VEGF in small extracellular vesicles contributes to anti-VEGF therapy resistance.

Despite wide use of anti-vascular endothelial growth factor (VEGF) therapy for many solid cancers, most individuals become resistant to this therapy, leading to disease progression. Therefore, new biomarkers and strategies for blocking adaptive resistance of cancer to anti-VEGF therapy are needed. As described here, we demonstrate that cancer-derived small extracellular vesicles package increasing quantities of VEGF and other factors in response to anti-VEGF therapy. The packaging process of VEGF into small extracellular vesicles (EVs) is mediated by the tetraspanin CD63. Furthermore, small EV-VEGF (eVEGF) is not accessible to anti-VEGF antibodies and can trigger intracrine VEGF signaling in endothelial cells. eVEGF promotes angiogenesis and enhances tumor growth despite bevacizumab treatment. These data demonstrate a mechanism where VEGF is partitioned into small EVs and promotes tumor angiogenesis and progression. These findings have clinical implications for biomarkers and therapeutic strategies for ovarian cancer.

Imaging of Kaposi sarcoma.

Kaposi sarcoma (KS) is a form of cancer that primarily appears on the skin but can potentially involve internal organs. There are several types of KS. The purpose of this article is to discuss the manifestations of KS and their appearance on imaging, the differential diagnoses associated with these findings, and molecular markers associated with KS that can aid appropriate diagnosis and therapy.

Near Infrared Fluorescence Imaging of Intraperitoneal Ovarian Tumors in Mice Using Erythrocyte-Derived Optical Nanoparticles and Spatially-Modulated Illumination.

Ovarian cancer is the deadliest gynecological cancer. Cytoreductive surgery to remove primary and intraperitoneal tumor deposits remains as the standard therapeutic approach. However, lack of an intraoperative image-guided approach to enable the visualization of all tumors can result in incomplete cytoreduction and recurrence. We engineered nano-sized particles derived from erythrocytes that encapsulate the near infrared (NIR) fluorochrome, indocyanine green, as potential imaging probes for tumor visualization during cytoreductive surgery. Herein, we present the first demonstration of the use of these nanoparticles in conjunction with spatially-modulated illumination (SMI), at spatial frequencies in the range of 0-0.5 mm-1, to fluorescently image intraperitoneal ovarian tumors in mice. Results of our animal studies suggest that the nanoparticles accumulated at higher levels within tumors 24 h post-intraperitoneal injection as compared to various other organs. We demonstrate that, under the imaging specifications reported here, use of these nanoparticles in conjunction with SMI enhances the fluorescence image contrast between intraperitoneal tumors and liver, and between intraperitoneal tumors and spleen by nearly 2.1, and 3.0 times, respectively, at the spatial frequency of 0.2 mm-1 as compared to the contrast values at spatially-uniform (non-modulated) illumination. These results suggest that the combination of erythrocyte-derived NIR nanoparticles and structured illumination provides a promising approach for intraoperative fluorescence imaging of ovarian tumor nodules at enhanced contrast.

Advanced Imaging in Musculoskeletal Oncology: Moving Away From RECIST and Embracing Advanced Bone and Soft Tissue Tumor Imaging (ABASTI) - Part I - Tumor Response Criteria and Established Functional Imaging Techniques.

According to the Revised Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the majority of bone metastases are considered to be nonmeasurable disease. Traditional response criteria rely on physical measurements. New criteria would be valuable if they incorporated newly developed imaging features in order to provide a more comprehensive assessment of oncological status. Advanced magnetic resonance imaging (MRI) sequences such as diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) with dynamic contrast-enhanced (DCE) perfusion imaging are reviewed in the context of the initial and post-therapeutic assessment of musculoskeletal tumors. Particular attention is directed to the pseudoprogression phenomenon in which a successfully treated tumor enlarges from the pretherapeutic baseline, followed by regression without a change in therapy.

Advanced Imaging in Musculoskeletal Oncology: Moving Away From RECIST and Embracing Advanced Bone and Soft Tissue Tumor Imaging (ABASTI)-Part II-Novel Functional Imaging Techniques.

Functional imaging can add valuable information to conventional imaging in the settings of tumor characterization and treatment response assessment. Traditional response criteria rely primarily on physical measurements, while functional imaging can potentially give a more comprehensive evaluation of oncological status. The second part of this review article discusses advanced imaging techniques such as susceptibility-weighted imaging, tumor-associated macrophage imaging, diffusion-weighted imaging, perfusion-weighted imaging, Dixon imaging, whole-body magnetic resonance imaging, whole-body low-dose dual energy computed tomography with virtual noncalcium technique, and ultrasound elastography.