Purpose To determine the prostate cancer detection rate of multi-parametric (MP) MRI at 3T. Precise one to one histopathologic correlation with MRI was possible using prostate MRI based custom-printed specimen molds following radical prostatectomy. Materials and methods This IRB approved prospective study included forty-five patients (mean age 60.2 years, range 49–75 years) with a mean PSA of 6.37ng/mL (range 2.3–23.7ng/mL), who had biopsy proven prostate cancer (mean Gleason score of 6.7; range 6 to 9). Prior to prostatectomy, all patients underwent prostate MRI on a 3T scanner which included tri-plane T2 weighted MRI, apparent diffusion coefficient maps of diffusion weighted MRI, dynamic contrast enhanced MRI, and spectroscopy.. The prostate specimen was whole mount sectioned in the mold allowing geometric alignment to MRI. Tumors were mapped on MRI and histopathology.. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI for cancer detection were calculated. Additionally, the effects of tumor size and Gleason score on sensitivity of MP-MRI were evaluated. Results PPV of MP-MRI to detect prostate cancer was 98%, 98%, and 100% in overall prostate, peripheral zone, and central gland, respectively. Sensitivities of MRI sequences were higher for tumors >5mm in diameter, as well as for tumors with higher Gleason scores (>7) (p<0.05). Conclusion Prostate MRI at 3T allows for the detection of prostate cancer. A multi-parametric approach increases the predictive power of MRI for diagnosis. In this study, accurate correlation between MP-MRI and histopathology was obtained by the patient specific MRI-based mold technique.
Purpose A novel platform was developed that fuses pre-biopsy magnetic resonance imaging with real-time transrectal ultrasound imaging to identify and biopsy lesions suspicious for prostate cancer. The cancer detection rates for the first 101 patients are reported. Materials and Methods This prospective, single institution study was approved by the institutional review board. Patients underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil, which included T2-weighted, spectroscopic, dynamic contrast enhanced and diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for cancer were graded according to the number of sequences suspicious for cancer as low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard 12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging lesions. Chi-square and within cluster resampling analyses were used to correlate suspicion on magnetic resonance imaging and the incidence of cancer detected on biopsy. Results Mean patient age was 63 years old. Median prostate specific antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital rectal examination. Of patients with low, moderate and high suspicion on magnetic resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively (p <0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected more cancer per core than standard 12-core transrectal ultrasound biopsy for all levels of suspicion on magnetic resonance imaging. Conclusions Prostate cancer localized on magnetic resonance imaging may be targeted using this novel magnetic resonance imaging/ultrasound fusion guided biopsy platform. Further research is needed to determine the role of this platform in cancer detection, active surveillance and focal therapy, and to determine which patients may benefit.
BACKGROUND Pheochromocytomas are rare catecholamine–producing tumors derived in at least 30% of cases from mutations in 9 tumor-susceptibility genes identified to date. Testing of multiple genes at considerable expense is often undertaken before a mutation is detected. This study assessed whether measurements of plasma metanephrine, normetanephrine and methoxytyramine, the O-methylated metabolites of catecholamines, might help distinguish different hereditary forms of the tumor. METHODS Plasma concentrations of O-methylated metabolites were measured by liquid chromatography with electrochemical detection in 173 patients with pheochromocytoma, including 38 with multiple endocrine neoplasia type 2 (MEN 2), 10 with neurofibromatosis type 1 (NF1), 66 with von Hippel-Lindau (VHL) syndrome and 59 with mutations of succinate dehydrogenase (SDH) type B or D genes. RESULTS In contrast to patients with VHL and SDH mutations, all patients with MEN 2 and NF1 presented with tumors characterized by increased plasma concentrations of metanephrine (indicating epinephrine production). VHL patients usually showed solitary increases in normetanephrine (indicating norepinephrine production), whereas additional or solitary increases in methoxytyramine (indicating dopamine production) characterized 70% of patients with SDH mutations. Patients with NF1 and MEN 2 could be discriminated from those with VHL and SDH mutations in 99% of cases by the combination of normetanephrine and metanephrine. Measurements of plasma methoxytyramine discriminated patients with SDH mutations from those with VHL mutations in a further 78% of cases. CONCLUSIONS The distinct patterns of plasma catecholamine O-methylated metabolites in patients with hereditary pheochromocytoma provide an easily utilized tool to guide cost-effective genotyping of underlying disease-causing mutations.
Purpose Recently, a new renal cell cancer (RCC) syndrome has been linked to germline mutation of multiple subunits (SDHB/C/D) of the Krebs cycle enzyme, succinate dehydrogenase. We report our experience with diagnosis, evaluation and treatment of this novel form of hereditary kidney cancer. Materials and Methods Patients with suspected hereditary kidney cancer were enrolled on an NCI-IRB approved protocol to study inherited forms of kidney cancer. Individuals from families with germline SDHB, SDHC and SDHD mutations and kidney cancer underwent comprehensive clinical and genetic evaluation. Results Fourteen patients from twelve SDHB mutation families were evaluated. Patients presented with RCC at an early age, 33 yrs (range 15–62 yrs), four developed metastatic kidney cancer and some families were found to have no manifestations other than kidney tumors. An additional family with six individuals found to have clear cell RCC that presented at a young average age, 47 yrs (range 40–53yrs), was identified with a germline SDHC mutation (R133X), two of which developed metastatic disease. A patient with a history of carotid body paragangliomas and a very aggressive form of kidney cancer was evaluated from a family with germline SDHD mutation. Conclusions SDH-RCC can be an aggressive type of kidney cancer, especially in younger individuals. Although detection and management of early tumors is most often associated with good outcome, based on our initial experience with these patients and our long term experience with HLRCC, we recommend careful surveillance of patients at risk for SDH-RCC and wide surgical excision of renal tumors.
Summary Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting in decreased levels of AMP-activated kinase (AMPK) and p53 tumor suppressor, and activation of the anabolic factors, acetyl-CoA carboxylase and ribosomal protein S6. Reduced AMPK levels leads to diminished expression of the DMT1 iron transporter, and the resulting cytosolic iron deficiency activates the iron regulatory proteins, IRP1 and IRP2, and increases expression of the hypoxia inducible factor HIF-1α, but not HIF-2α. Silencing of HIF-1α or activation of AMPK diminishes invasive activities, indicating that alterations of HIF-1α and AMPK contribute to the oncogenic growth of FH-deficient cells.
Energy deregulation and abnormalities of tumor cell metabolism are critical issues in our understanding of cancer. Hereditary leiomyomatosis renal cell carcinoma (HLRCC) is an aggressive form of RCC characterized by germline mutation of the Krebs cycle enzyme, fumarate hydratase (FH), and is known to be highly metastatic and unusually lethal. There is significant utility in establishing preclinical cell and xenograft models for study of disorder of energy metabolism as well as development of new therapeutic approaches targeting of tricarboxylic acid (TCA) cycle deficient human cancers. Here we report the first immortal cell line derived from a patient having aggressive HLRCC-associated recurring kidney cancer, designated as UOK 262. We investigated gene expression, chromosome profiles, efflux bioenergetic analysis, mitochondrial ultrastructure, FH catabolic activity, invasiveness, and optimal glucose requirements for in vitro growth. UOK 262 cells have isochromosome 1q [i(1)(q10)] as recurring chromosome abnormality; demonstrate compromised oxidative phosphorylation and in vitro dependence on anaerobic glycolysis consistent with the clinical manifestation of HLRCC. Furthermore the cells display glucose-dependent growth, an elevated rate of lactate efflux, over-expression of the glucose transporter Glut 1 and lactate dehydrogenase (LDH) 5. Mutant FH protein was primarily present in edematous mitochondria, but its catalytic activity was nearly undetectable. UOK 262 xenografts retain the characteristics of HLRCC histopathology. Our findings indicate that the severe compromise of oxidative phosphorylation and rapid glycolytic flux in UOK 262 are an essential feature of this TCA cycle enzyme deficient form of kidney cancer. This tumor model is the embodiment of the "Warburg effect". UOK 262 provides a unique in vitro and in vivo preclinical mode to study the bioenergetics of the Warburg effect in human cancer.
After completing this course, the reader will be able to:1. Describe histologic features associated with sarcomatoid renal cell carcinoma.2. Outline current surgical approaches to treating sarcomatoid renal cell carcinoma.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTRecent advancements in the molecular characterization of renal cell carcinoma altered the classification system and now kidney cancer is divided into several distinct histologic subtypes. Although once a separate histologic category, sarcomatoid renal cell carcinoma is no longer considered a separate tumor type because it can occur with all histologic subtypes. Limited research on tumors with sarcomatoid change has led to minimal progress in the understanding and treatment of these tumors. Because the sarcomatoid variant of renal cell carcinoma can account for approximately one in six cases of advanced kidney cancer, we hope to familiarize clinicians with these tumors by describing the historic background, histologic features, molecular characterization, diagnosis, prognosis, treatment strategies, and active clinical trials of this aggressive type of tumor. The Oncologist 2012;17:46 -54
Phaeochromocytomas and paragangliomas (PPGLs) are highly heterogeneous tumours with variable catecholamine biochemical phenotypes and diverse hereditary backgrounds. This analysis of 18 catecholamine-related plasma and urinary biomarkers in 365 patients with and 846 subjects without PPGLs examined how catecholamine metabolomic profiles are impacted by hereditary background and relate to variable hormone secretion. Catecholamine secretion was assessed in a subgroup of 156 patients from whom tumour tissue was available for measurements of catecholamine contents. Among all analytes, the free catecholamine O-methylated metabolites measured in plasma showed the largest tumour-related increases relative to the reference group. Patients with tumours due to multiple endocrine neoplasia type 2 and neurofibromatosis type 1 (NF1) showed similar catecholamine metabolite and secretory profiles to patients with adrenaline-producing tumours and no evident hereditary background. Tumours from these three groups of patients contained higher contents of catecholamines, but secreted the hormones at lower rates compared to tumours that did not produce appreciable adrenaline, the latter including PPGLs due to von Hippel-Lindau and succinate dehydrogenase gene mutations. Large increases of plasma dopamine and its metabolites additionally characterized patients with PPGLs due to the latter mutations, whereas patients with NF1 were characterized by large increases in plasma dihydroxyphenylglycol and dihydroxyphenylacetic acid, the deaminated metabolites of noradrenaline and dopamine. This analysis establishes the utility of comprehensive catecholamine metabolite profiling for characterizing the distinct and highly diverse catecholamine metabolomic and secretory signatures among different groups of patients with PPGLs. The data further suggest developmental origins of PPGLs from different populations of chromaffin cell progenitors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.