Intrinsic contrast for characterization of acute radiofrequency ablation lesions.

BACKGROUND: Both intrinsic contrast (T1 and T2 relaxation and the equilibrium magnetization) and contrast agent (gadolinium)-enhanced MRI are used to visualize and evaluate acute radiofrequency ablation lesions. However, current methods are imprecise in delineating lesion extent shortly after the ablation. METHODS AND RESULTS: Fifteen lesions were created in the endocardium of 13 pigs. A multicontrast inversion recovery steady state free precession imaging method was used to delineate the acute ablation lesions, exploiting T1-weighted contrast. T2 and Mo(*) maps were also created from fast spin echo data in a subset of pigs (n=5) to help characterize the change in intrinsic contrast in the lesions. Gross pathology was used as reference for the lesion size comparison, and the lesion structures were confirmed with histological data. In addition, a colorimetric iron assay was used to measure ferric and ferrous iron content in the lesions and the healthy myocardium in a subset of pigs (n=2). The lesion sizes measured in inversion recovery steady state free precession images were highly correlated with the extent of lesion core identified in gross pathology. Magnetic resonance relaxometry showed that the radiofrequency ablation procedure changes the intrinsic T1 value in the lesion core and the intrinsic T2 in the edematous region. Furthermore, the T1 shortening appeared to be correlated with the presence of ferric iron, which may have been associated with metmyoglobin and methemoglobin in the lesions. CONCLUSIONS: The study suggests that T1 contrast may be able to separate necrotic cores from the surrounding edematous rims in acute radiofrequency ablation lesions.

Value of exercise tolerance testing in evaluation of diabetic patients presented with atypical chest discomfort.

BACKGROUND: Coronary artery disease is the single most important cause of mortality and morbidity in diabetic patients. Electrocardiographic stress test is a non-invasive modality to screen significant coronary involvement in minimally symptomatic diabetics. OBJECTIVES: We investigated the Positive Predictive Value (PPV) of this test in comparison with coronary angiography. MATERIALS AND METHODS: 130 diabetic patients with atypical chest discomfort were studied and tested using Exercise Tolerance Test (ETT) among which 100 cases showed positive results that further were studied invasively by selective coronary angiography. RESULTS: The positive predictive value of ETT for diagnosis of Coronary Artery Disease (CAD)among diabetic patients presented with atypical chest discomfort was 77%. CONCLUSION: We conclude that electrocardiographic stress test is a valuable inexpensive non-invasive screening test in diabetic patients with atypical chest discomfort.

Biomarkers of parathyroid carcinoma.

The diagnosis of parathyroid carcinoma can be challenging, and adjuvant therapies such as radiotherapy and chemotherapy are not particularly beneficial in the management of this disease, creating a challenge when dealing with unresectable recurrent and metastatic malignancy. We investigated the expression profile of biomarkers that represent potential markers of malignancy or targets for novel therapies in this disease. We constructed a tissue microarray of parathyroid carcinomas from 10 patients as well as parathyroid adenomas from 25 patients and stained the slides for 34 proteins involved in angiogenesis (platelet-derived growth factor receptor (PDGFR)-α, PDGFR-ß, vascular endothelial growth factor receptor-2 (VEGFR-2), and epidermal growth factor receptor (EGFR)), inflammation (cyclooxygenase (COX)-1 and COX-2), cell adhesion (matrix metalloproteinase (MMP)-1, CD9, and keratin 7), cell cycle (Cdc2p34, cyclin D1, retinoblastoma (Rb), p27, p21, parafibromin, Bmi-1, 14-3-3σ, and p53), and apoptosis (Bcl-2a, Mcl-1, Bcl-xL, and glutathione-S-transferase-isoenzyme π (Gst-π)) along with some markers of the sonic hedgehog (Smo, SHH, Gli-1, Gli-2, Gli-3, and patched), mTOR (AKT, mammalian target of rapamycin (mTOR), and Forkhead box O (FoxO)-1), and WNT (Wisp-1, Wisp-2, and ß-catenin) signal transduction pathways. Protein expression was determined using computerized image analysis software (Spectrum Plus©, Aperio). Bcl-2a, parafibromin, Rb, and p27 were significantly decreased to variable degrees in all parathyroid carcinomas. COX-1/2, CD9, MMP-1, FoxO-1, VEGFR-2, PDGFR-α/ß, Gst-π, Gli-1, Gli-2, Gli-3, and patched were expressed in the majority of benign and malignant tumor cells. These results indicate that the use of a panel that includes Bcl-2a, parafibromin, Rb, and p27 may be helpful in the assessment of atypical parathyroid neoplasms. Although the majority of other markers studied are also expressed in both benign and malignant parathyroid neoplasms, we have identified several potentially important target proteins related to angiogenesis and cell proliferation along with COX-1/2, Gst-π and members of sonic hedgehog pathway that may be therapeutic targets in parathyroid carcinoma. While these results are preliminary, a successful outcome of a clinical trial directed against these novel targets would provide much needed systemic adjuvant treatment for patients with metastatic parathyroid carcinoma.

Predicting prognosis in gastroentero-pancreatic neuroendocrine tumors: an overview and the value of Ki-67 immunostaining.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETS) are unusual and rare neoplasms for which prognostic assessment and the diagnosis of malignancy, on the basis of histology alone, represent considerable challenges for the pathologist. To date, many molecular markers have been identified with a view to providing accurate and timely prediction of response to treatment and long-term survival. Proliferation remains a key feature of tumor progression, which has been widely estimated by the immunohistochemical use of the Ki-67 nuclear antigen. Given the continued difficulties inherent in prediction of malignancy in pancreatic neuroendocrine tumors (PETs) in particular, it has become unclear whether Ki-67 is truly a reliable prognostication marker. This review seeks to better establish what the consensus is on the role of the Ki-67 proliferation index as a prognostic indicator of long-term outcome in pancreatic neuroendocrine tumors. We conclude that most studies favor the utility of the Ki-67 proliferation index despite different critical percentages and in concert with other pathological parameters in the routine work-up of PETs.

Adenosquamous carcinoma of the pancreas with clear cell and rhabdoid components. A case report.

CONTEXT: In as much as no such variant of this pancreatic tumour has been previously reported in the literature, we report an unusual case of an adenosquamous carcinoma of the pancreas characterized by clear cells and rhabdoid cells. CASE REPORT: A 75-year-old man presented with upper abdominal distention, dyspepsia, jaundice, and significant weight loss over a period of 3 months. Imaging of the abdomen showed a solid mass with cystic components in the region of the uncinate process of the pancreas. Endoscopic retrograde pancreatography showed mild to moderate dilatation of the intrapancreatic biliary tract and of the pancreatic duct, and a biliary stent was placed. The patient subsequently underwent a Whipple's procedure with curative intent. Histological evaluation of the pancreatic mass revealed an adenosquamous carcinoma displaying both clear cell and rhabdoid components. CONCLUSIONS: Assessing the predominant histology of pancreatic adenosquamous carcinoma variants such as those characterized by clear cells and rhabdoid cells may help select and improve upon therapies in this aggressive lesion.

The C-terminus of myogenin, but not MyoD, targets upregulation of MEF2C expression.

The myogenic regulatory family of basic helix-loop-helix transcription factors, including MyoD and myogenin, functions cooperatively with the myocyte-specific enhancer binding factor 2 (MEF2) family during skeletal myogenesis. Previously, using aggregated P19 cells, we have shown that myogenin upregulates MEF2C expression while MyoD does not [Ridgeway et al., J. Biol. Chem. 275 (2000) 41-46]. In order to identify the domain of myogenin responsible for activating MEF2C expression, a series of chimeras of MyoD and myogenin were generated. Only chimeras containing the C-terminal region of myogenin were able to activate MEF2C in aggregated P19 cells, suggesting that the C-terminus of myogenin is responsible for the regulation of specific target genes.