To evaluate proton fat-water chemical shift fast low-angle shot magnetic resonance (MR) imaging for differentiation of fat-containing hyperechoic liver nodules from hyperechoic liver nodules without ...a fatty component.
T1-weighted fast low-angle shot fat-water chemical shift gradient-echo MR imaging was performed in 96 patients without cirrhosis with 138 hyperechoic liver nodules. In-phase and opposed-phase breath-hold images were acquired. The percentage of signal intensity variation between in-phase and opposed-phase images and the spleen-to-lesion contrast ratio were used to differentiate liver nodules.
Chemical shift MR images showed fat in 15 (11%) hyperechoic nodules (two angiomyolipomas and 13 nodular fatty infiltrations of the liver). The mean percentage of signal intensity variation between in-phase and opposed-phase images was 156% (standard error, 43.5%) in nodules with fat and -0.16% (standard error, 0.96%) in nodules without fat (P = .003). Spleen-to-lesion contrast was similar on in- and opposed-phase images in lesions without fat (mean difference, -0.0107; standard error, 0.012), whereas the mean difference in fat-containing nodules was 0.805 (standard error, 0.225; P = .003). The area under the receiver operating characteristic curve was 0.97 for signal intensity variation.
Hyperechogenicity in certain liver nodules is caused by fat. Chemical shift MR imaging allows accurate differentiation between these and other hyperechoic lesions with no fat component.
BACKGROUND: A major problem in cancer chemotherapy is the existence of primary resistance and/or the acquisition of secondary resistance. Many cellular defects contribute to chemoresistance, but ...epigenetic changes can also be a cause. METHODS: A DNA methylation microarray was used to identify epigenetic differences in oxaliplatin-sensitive and -resistant colorectal cancer cells. The candidate gene SRBC was validated by single-locus DNA methylation and expression techniques. Transfection and short hairpin experiments were used to assess oxaliplatin sensitivity. Progression-free survival (PFS) and overall survival (OS) in metastasic colorectal cancer patients were explored with Kaplan-Meier and Cox regression analyses. All statistical tests were two-sided. RESULTS: We found that oxaliplatin resistance in colorectal cancer cells depends on the DNA methylation-associated inactivation of the BRCA1 interactor SRBC gene. SRBC overexpression or depletion gives rise to sensitivity or resistance to oxaliplatin, respectively. SRBC epigenetic inactivation occurred in primary tumors from a discovery cohort of colorectal cancer patients (29.8%; n = 39 of 131), where it predicted shorter PFS (hazard ratio HR = 1.83; 95% confidence interval CI = 1.15 to 2.92; log-rank P = .01), particularly in oxaliplatin-treated case subjects for which metastasis surgery was not indicated (HR = 1.96; 95% CI = 1.13 to 3.40; log-rank P = .01). In a validation cohort of unresectable colorectal tumors treated with oxaliplatin (n = 58), SRBC hypermethylation was also associated with shorter PFS (HR = 1.90; 95% CI = 1.01 to 3.60; log-rank P = .045). CONCLUSIONS: These results provide a basis for future clinical studies to validate SRBC hypermethylation as a predictive marker for oxaliplatin resistance in colorectal cancer.
Brown tumors (BT) are benign focal bone lesions that may appear in the context of primary and secondary hyperparathyroidism (HPT). Involvement of the spine is exceedingly rare. We present a case of ...brown tumor involving the cervical spine, the third reported in the literature. In the literature review (until August 2010), we found nine cases of spinal BT in primary HPT and 14 cases in secondary HPT. Fifteen patients (65%) had evidence of spinal cord compression. A 34-year-old woman on long-term hemodialysis, with secondary HPT, presented with a 9-month history of persistent neck pain. Radiographs of the cervical spine revealed an expansive osteolytic lesion in the posterior arch of the second cervical vertebra. MR imaging revealed an expansive mass on C2 affecting the vertebral body, odontoid process, right pedicle, laminas, and spinous process; there were no signs of spinal edema. A CT-guided needle biopsy of the lesion showed destruction of trabecular bone, infiltration of the fibroblastic cells, and abundant osteoclast-like multinucleated giant cells with hemorrhage and hemosiderin pigment, and the diagnosis of brown tumor was made. Cervical pain disappeared within a few days of parathyroidectomy, and rapid remineralization of C2 was evident within a few months. BT must always be considered in the context of hyperparathyroidism and osteolytic lesions. Vertebral BT can be particularly devastating due to medullar compression symptoms. Regression or complete disappearance of these lesions after parathyroidectomy is common, but prompt surgical decompression is necessary in case of medullar compression symptoms.
Introduction
Methylation of the promoter of the
MGMT
gene and MGMT protein expression are recognized as predictive markers for response to alkylating chemotherapy in glioblastoma (GB).
Material and ...methods
We have assessed
MGMT
methylation with the methylation-specific polymerase chain reaction (MSP) in tumor samples from 70 GB patients and in serum samples from 37 of these patients. We have also assessed
MGMT
protein expression by immunohistochemical (IHC) analysis in tissue samples from 63 of these patients.
Results
We found concordance between
MGMT
methylation status in tissue and serum (Cohen’s Kappa = 0.586;
p
<0.0001). MSP for detection of non-methylated
MGMT
promoter in serum showed a sensitivity of 95.4% and a specificity of 60%, while the IHC methylation test showed a low specificity (8.9%). Patients whose
MGMT
promoter was methylated in tissue attained longer progression-free and overall survival. In the multivariate analysis, serum
MGMT
promoter methylation emerged as an independent factor for longer progression-free and overall survival.
Conclusion
Serum-based
MGMT
methylation analysis offers a promising alternative to tumor-based
MGMT
analysis in cases where tissue samples are unavailable.
This work addresses the detection of Helicobacter pylori a bacterium classified since 1994 as class 1 carcinogen to humans. By its highest specificity and sensitivity, the preferred diagnosis ...technique is the analysis of histological images with immunohistochemical staining, a process in which certain stained antibodies bind to antigens of the biological element of interest. This analysis is a time demanding task, which is currently done by an expert pathologist that visually inspects the digitized samples. We propose to use autoencoders to learn latent patterns of healthy tissue and detect H. pylori as an anomaly in image staining. Unlike existing classification approaches, an autoencoder is able to learn patterns in an unsupervised manner (without the need of image annotations) with high performance. In particular, our model has an overall 91% of accuracy with 86\% sensitivity, 96% specificity and 0.97 AUC in the detection of H. pylori.
To assess the putative prognostic value of K-ras mutations in nonmucinous ovarian tumors, the authors looked for K-ras point mutations at codons 12 and 13 in 144 nonmucinous ovarian tumors.
A series ...of 144 consecutive, unselected, archival, nonmucinous ovarian tumors (35 benign, 12 borderline, and 97 malignant) were studied. K-ras mutations at codons 12 and 13 were determined by polymerase chain reaction using the restriction fragment length polymorphism method with mismatched nested primers. Extensive clinicopathologic and follow-up data on all patients were evaluated.
The overall prevalence of K-ras mutations at codons 12 and 13 was 30.5% (44/144). In benign tumors, it was 20% (7/35); in borderline tumors, 25% (3/12); and in carcinomas, 35% (34/97). The presence of K-ras point mutations did not correlate with survival. Among the benign tumors, K-ras mutations were detected in three Brenner tumors with a mucinous component.
These results indicate that K-ras mutations are not initial events in the pathogenesis of nonmucinous ovarian tumors and do not appear to be related to survival.
Fibrous benign proliferations of the testis and paratesticular tissues are an uncommon and heterogeneous group of lesions that can mimic true neoplasms. Among them, those considered to be reactive ...proliferations have been included in the category of fibrous pseudotumors and are often associated with trauma, hydrocele, or infection. We report 2 cases of nodular and diffuse fibrous proliferation. This condition is part of the spectrum of reactive benign fibrous lesions and has previously been described in the testicular tunics and paratesticular region only. One of our 2 cases had the peculiarity of being located in the penile shaft, whereas the other involved the tunica vaginalis. To the best of our knowledge, this is the first report of a diffuse and nodular fibrous tumor involving the penis.
Mouse has been extensively used as a model organism in many studies to characterize biological pathways and drug effects and to mimic human diseases. Similar DNA sequences between both species ...facilitate these types of experiments. However, much less is known about the mouse epigenome, particularly for DNA methylation. Progress in delivering mouse DNA methylomes has been slow due to the currently available time-consuming and expensive methodologies. Following the great acceptance of the human DNA methylation microarrays, we have herein validated a newly developed DNA methylation microarray (Infinium Mouse Methylation BeadChip) that interrogates 280,754 unique CpG sites within the mouse genome. The CpGs included in the platform cover CpG Islands, shores, shelves and open sea sequences, and loci surrounding transcription start sites and gene bodies. From a functional standpoint, mouse ENCODE representative DNase hypersensitivity sites (rDHSs) and candidate cis-Regulatory Elements (cCREs) are also included. Herein, we show that the profiled mouse DNA methylation microarray provides reliable values among technical replicates; matched results from fresh frozen versus formalin-fixed samples; detects hemimethylated X-chromosome and imprinted CpG sites; and is able to determine CpG methylation changes in mouse cell lines treated with a DNA demethylating agent or upon genetic disruption of a DNA methyltransferase. Most important, using unsupervised hierarchical clustering and t-SNE approaches, the platform is able to classify all types of normal mouse tissues and organs. These data underscore the great features of the assessed microarray to obtain comprehensive DNA methylation profiles of the mouse genome.
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