Prognostic Factors and Analysis of S100a4 Protein in Resected Pulmonary Metastases from Renal Cell Carcinoma

Background  This study analyzes our experience with pulmonary resection for metastases from renal cell carcinoma. The goals were to search for factors influencing prognosis and to investigate the presence and the prognostic value of S100A4 protein in lung metastases and corresponding primary renal tumors. Methods  Sixty-five patients underwent surgical resection for renal and pulmonary lesions between 1992 and 2007. S100A4 protein expression was immunohistochemically examined in the peritumoral infiltrate of 64 lesions (32 metastases and the 32 corresponding primary carcinomas). Results  Overall 3-, 5-, and 10-year survival rates were 58, 46, and 25%, respectively. Univariate analysis revealed that surgical radicality (p = 0.0039) and stratification into groups according to the International Registry of Lung Metastases classification (p = 0.0137) were prognostic factors. Multivariate analysis confirmed that this classification was a significant prognostic factor (p = 0.01). All metastases and the corresponding primary carcinomas expressed S100A4 protein. Twenty-one metastases (66%) had weak expression and 11 (34%) had strong expression. Twelve (37.5%) primary lesions had weak expression and 20 (62.5%) had strong expression. The 5-year survival rate for patients with strong expression in primary carcinoma was 41%, significantly lower than that of patients with weak expression (78%; p = 0.05). Conclusions  Pulmonary resection in metastatic renal cell carcinoma results in long-term survival. Complete resection and stratification into groups according to the International Registry of Lung Metastases classification were prognostic factors. Overexpression of S100A4 protein in primary tumors was correlated with a poor prognosis. If confirmed in larger studies this finding could be used to schedule adjuvant treatments in patients undergoing nephrectomy for renal cell carcinoma.     

Differential cerebro spinal fluid proteome investigation of Leber hereditary optic neuropathy (LHON) and multiple sclerosis

Leber's hereditary optic neuropathy (LHON) is a genetic disease leading to the loss of central vision and optic nerve atrophy. The existence of occasional cases of LHON patients developing a Multiple Sclerosis (MS)-like illness and the hypothesis that mtDNA variants may be involved in MS suggest the possibility of some common molecular mechanisms linking the two diseases. We have pursued a comparative proteomics approach on cerebrospinal fluid (CSF) samples from LHON and MS patients, as well as healthy donors by employing 2-DE gel separations coupled to MALDI-TOF-MS and nLC-MS/MS investigations. 7 protein spots showed significant differential distribution among the three groups. Both CSF of LHON or MS patients are characterized by lower level of transthyretin dimer adduct while a specific up regulation of Apo A-IV was detected in LHON CSF.     

An overview of current microarray-based human globin gene mutation detection methods

The panoply of human globin gene mutation detection methods could become significantly enriched with the advent of microarray-based genotyping platforms. The aim of this article is to provide an overview of the current medium and high-throughput microarray-based globin gene mutation detection platforms, namely the microelectronic array, the "thalassochip" arrayed primer extension (APEX) technology and the single base extension methods. This article also outlines an emerging method based on multiple ligation probe amplification (MLPA) and discusses the implications of customized solutions for resequencing of genomic loci in relation to molecular genetic testing of hemoglobinopathies.     

Impact of hepatitis C virus infection on lifestyle

AIM: To evaluate the impact of the diagnosis of hepatitis C infection on lifestyle habits such as smoking, drinking, sports activity and diet.METHODS: A self-administered, anonymous question-naire was offered to out-patients with HCV infection consecutively attending three clinical centres in Italy.RESULTS: Of the 275 respondents, 62.2% (171) were male. Mean age was 51 (range 20-80) years. Overall, after the diagnosis of hepatitis C, 74.5% of drinkers had modified (giving up or reducing) alcohol consumption, 21.3% of smokers had modifi ed their habits and 32.3% of subjects who reported sports activity had either stopped or reduced frequency of activity or chose a less fatiguing sport. Sixty-four percent of the respondents reported having modified their diet, most of them on physician's advice. CONCLUSION: After the diagnosis of hepatitis C many patients correctly modif ied their alcohol consumption and a minority their smoking habits. The reason for reported changes in diet and physical activity needs further investigations.     

Clinical application of CT angiography in acute ischemic stroke

OBJECTIVE: To evaluate the contribution of CT angiography (CTA) in predicting clinical outcome in a broad spectrum of patients presenting with acute neurological deficits suggestive of brain ischemia, to assess its strengths and limitations in this setting, and examine its influence on selection of patients for thrombolytic treatment. PATIENTS AND METHODS: Prospective, observational outcome study of 54 consecutive patients with acute neurological deficits suggestive of brain ischemia who received immediate CTA. Clinical outcome was compared for patients presenting with and without arterial occlusion on CTA. Treatment decisions made by a vascular neurologist blinded to CTA results were compared to CTA cognizant treatment. RESULTS: For patients presenting with slight to moderate neurological deficits, the sensitivity and specificity for predicting good clinical outcome was 0.62 and 0.79, respectively, using the initial NIH Stroke Scale (NIHSS) score alone, and 0.38 and 0.92 if additionally, CTA showed no occlusion. For patients presenting with more severe deficits, the sensitivity and specificity for predicting poor clinical outcome using the NIHSS score alone was 0.79 and 0.60, compared to 0.67 and 0.92 if CTA showed vessel obstruction. CTA correctly identified six stroke mimickers. Selection of patients for thrombolysis made with knowledge of CTA results were more often conservative, and corresponded to CTA blinded decisions in 42/50 cases (84%, r=0.72). CONCLUSIONS: Combining CTA results with the neurological exam allows increased specificity for predicting clinical outcome as compared to predictions based on admission NIH Stroke Scale score alone. Awareness of CTA results was occasionally associated with less aggressive treatment and testing decisions.     

Improving lesion detection and visualization: implications for neurosurgical planning and follow-up

Contrast-enhanced magnetic resonance (MR) imaging is considered the most sensitive method for detecting tumors in the central nervous system (CNS). The primary objective is to improve lesion detection, delineation, and characterization (benign or malignant) in order to more accurately define the location, extent, and type of disease and the appropriate treatment option for improved patient outcome (surgical intervention, radiation therapy or cytotoxic chemotherapy). This article reviews the various types of tumor occurring in the brain and the specific role of contrast-enhanced MR imaging for the evaluation of these tumors. Emphasis is placed on the value of contrast-enhanced MR imaging in the evaluation of primary intra-axial brain lesions and how high relaxivity contrast agents such as MultiHance (Bracco Imaging, Milan, Italy) might improve detection, treatment planning, and follow-up.     

O6-methylguanine-DNA methyltransferase promoter hypermethylation in colorectal carcinogenesis

Epigenetic alterations have been reported in colorectal neoplasia which can either complement or in some cases be predisposed to genetic alterations such as K-ras mutations. We examined the promoter methylation status of the CDKN2A and O6-methylguanine-DNA methyltransferase (MGMT) genes, after sodium bisulfite conversion and DNA amplification with methylation specific PCR. Moreover, we searched for G to A transitions in codons 12 and 13 of the K-ras oncogene in normal colorectal mucosae, aberrant crypt foci (ACF, early premalignant lesions) and carcinomas. CDKN2A hypermethylation was an infrequent event in ACF (2 of 26, 7.7%). On the contrary, MGMT hypermethylation was found in the normal mucosae (3 of the 12 samples, 25%), in 14 of the 26 ACF (53.8%) and in 7 of the 9 (77.8%) carcinomas examined. K-ras mutations were evident in 6 ACF (23%) and in 3 carcinomas (33.3%), mostly associated with MGMT promoter hypermethylation. These findings strongly support the hypothesis that epigenetic mechanisms play an important role in the early steps of colorectal carcinogenesis.