Search for Neuro-Endocrine Markers (Chromogranin A,Synaptophysin and VGF) in Breast Cancers. An integrated Approach Using Immunohistochemistry and Gene Expression Profiling

Discordant data are reported in the literature on the definition, incidence and clinical features of neuroendocrine (NE) carcinomas of the breast. This tumour entity is currently assessed by immunohistochemistry (IHC) detecting “general” NE markers such as chromogranin A (CHGA) and synaptophysin (SYP), but other markers have been considered as well. In the present study, in addition to CHGA and SYP, we investigated the expression of VGF, a neurotrophin-inducible gene, which is emerging as a new specific NE marker. In order to evaluate the differential expression of these neuro-endocrine markers in breast cancers, we conducted parallel immunohistochemical and gene expression analyses, using PCR, gene array and real-time quantitative PCR procedures. Data obtained in 28 cases were further validated with a meta-analysis of published datasets of 103 breast cancer cases. The value of IHC positivity (irrespective of the percentage of positive cells) was confirmed by over-expression of the related gene. However, the genetic approach emerged as more sensitive, showing over-expression of NE markers in a subset of IHC-negative carcinomas. In conclusion, the present study confirms, by a novel approach, the occurrence of NE differentiation in breast cancers. Over-expression of one or more NE marker (CHGA and/or SYP and/or VGF) characterizes a significant fraction (approximately 10 %) of infiltrative breast cancers.     

Hood Colonoscopy in Trainees: A Useful Adjunct to Improve the Performance

Background

The use of a transparent hood to improve colonoscopic performance has recently been proposed.

Aims

The purpose of this study was to evaluate whether using the hood might improve the cecal intubation rate, cecal intubation time, number of attempts needed to intubate the ileo-cecal valve, and polyp detection rate in trainees.

Methods

Patients undergoing colonoscopy (n = 378) were randomized in two groups, one studied with hood colonoscopy (n = 179) and the other (n = 199) with standard examination.

Results

No differences were found between hood and standard colonoscopy with respect to cecal intubation rate (95 vs 92 %), whereas hood colonoscopy significantly shortened the cecal intubation time, the number of attempts needed to intubate the ileo-cecal valve, and the overall polyp detection rate (p < 0.01 for all these variables).

Conclusions

Hood colonoscopy might represent a useful adjunct to standard colonoscopy, especially improving the performance of endoscopic trainees.     

Hypothyroidism in the elderly: diagnostic pitfalls illustrated by a case report

A diagnosis of hypothyroidism in the elderly can easily be overlooked if we rely exclusively on its clinical presentation because this may be highly non-specific, since the signs and symptoms of the disease are common to other diseases typical of old age, and even to the normal aging process. Imaging diagnostics (ultrasound or CT), when considered alone, are also of little use for the purpose of clarifying thyroid gland function. We report here on a case of primary hypothyroidism that was diagnosed late because the correlated signs and symptoms (asthenia, bradycardia, pleural effusions, hyponatremia, worsening renal and respiratory insufficiency, hoarseness) had previously been attributed to the normal aging process and to the patient's other health conditions (Parkinson's disease, PD; chronic obstructive pulmonary disease, COPD). After a couple of weeks of treatment with levothyroxine and liothyronine, there were clinical and laboratory evidences of an improvement in the patient's condition. She became more reactive, with a shriller voice. The pleural effusion disappeared, and so did the bradycardia. Laboratory tests showed normal sodium levels, and the renal insufficiency had improved. The lack of specificity of the clinical presentation of hypothyroidism in the elderly might justify the routine measurement of thyroid-stimulating hormone in these patients.     

Sperm DNA damage in patients with chronic viral C hepatitis

Introduction

The aim of this study was to evaluate the conventional and biofunctional parameters of sperm in young infertile patients with Hepatitis C (HCV) infection.

Methods

Forty HCV patients with primary infertility, aged 27 to 42 years (mean 36.4 years) and twenty HCV patients with secondary infertility aged 28 to 45 years (mean 35.0 ± 2.8 years), underwent hormonal and sperm analysis in addition to the determination of reactive oxygen species (ROS) concentrations in the sperm and flow-cytometric evaluation. The following biofunctional sperm parameters were evaluated by flow cytometry: DNA fragmentation, mitochondrial membrane potential, chromatin condensation, and the rate of early apoptosis.

Results

Overall, patients with HCV showed significantly worse median values of conventional and biofunctional sperm parameters than control subjects, including sperm density (31.7 vs. 80.4 million/ml), forward motility (9.4 vs. 25%), normal forms (15.4 vs. 24.8%), DNA fragmentation (6.6 vs. 2.2%), low MMP (45.5 vs. 8%), an early apoptosis rate (5 vs. 2.7%), and abnormal chromatin (18.9 vs. 13.9%). Finally, HCV patients had significantly higher basal (250 vs. 75 × 10³/cpm) and stimulated (550 vs. 120 × 10³/cpm) ROS levels in semen compared to control subjects. None of the examined parameters (sperm, hormonal, biofunctional and assessment of oxidative status in the semen) was significantly different between HCV patients with primary and secondary infertilities.

Discussion

These results confirm that HCV infection has a negative impact on sperm parameters. The overlap of the results observed in the two groups of HCV patients supports the hypothesis that HCV infection may cause to alterations in sperm parameters.