Breast cancer in reproductive age. The new plaque or just myth?

It is interesting to assess the hitherto knowledge, on breast cancer in reproductive and young females, aged <35. Even if breast cancer is rare in this group, it is, also physically and emotionally devastating. It is characterized by worse prognosis and outcome, in a stage of life, which is delicate for the female patients. This rare subgroup of breast cancer patients is ought to be the center of investigation in future studies. This paper's mail goal is to elucidate this entity, by presenting several aspects of the disease including risk factors, therapy, natural history and major differences between the groups of breast cancer patients and last but not least, the psychosocial features of this clinical entity, by reviewing the current and past medical literature till April 2011.

Aortoenteric fistulae: present-day management.

An aortoenteric fistula (AEF) is a communication between the aorta and an adjacent loop of the bowel. The three most useful diagnostic modalities for detecting AEF are abdominal computed tomography scan with intravenous contrast, esophagogastroduodenoscopy, and arteriography. The treatment of AEFs has improved in recent years, but despite the multiple surgical techniques reported, many of the patients do not survive or are left debilitated after treatment. Endovascular repair is an efficient and safe method to stabilize patients with life-threatening AEFs. The aim of this study is to provide a comprehensive and synthetic review of the latest advantages on the diagnosis and management of primary and secondary AEF.

Cell cyclins: triggering elements of cancer or not?

Cyclins are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation. Recent studies have also revealed more mechanisms through which cyclins can express their oncogenic potential. This review focuses on the aberrant expression of G1/S cyclins and especially cyclin D and cyclin E; the pathways through which they lead to tumour formation and their involvement in different types of cancer. These elements indicate the mechanisms that could act as targets for cancer therapy.

Endogenous estrogen levels are associated with endothelial function in males independently of lipid levels.

Estrogens and androgens may play an important role in vascular health in both sexes. The aim of this study was to examine the relation of endogenous sex hormone levels with early markers of atherosclerosis in a cohort of apparently healthy males. 124 males (age 46.25 ± 9.56) attending a preventive medicine program were examined for unrecognised features of the metabolic syndrome. Flow-mediated dilatation (FMD) and intima-media thickness (IMT) of the common carotid artery were evaluated. Obesity parameters were recorded; estradiol, testosterone, SHBG, free testosterone, insulin, as well as glucose and lipid levels were measured. FMD was positively correlated with estradiol (r = 0.201, P = 0.041) and negatively with total cholesterol (r = -0.205, P = 0.022), low density lipoproteins (r = -0.232, P = 0.009), and triglyceride levels (r = -0.179, P = 0.046). In multivariate analysis, the association of FMD with estrogen was independent of BMI and lipid levels. No significant association between FMD and testosterone levels was found. Subjects with an increased mean IMT (> 0.73 mm, i.e., > 3rd tertile) had lower levels of free (P = 0.021) and bioavailable (P = 0.016) testosterone. In multivariate logistic regression analysis, this association was no longer significant when age or cholesterol levels were considered. Endogenous estrogen levels are associated with FMD, independently of age and lipid levels, showing a protective effect in middle-age male subjects. Circulating androgens are associated, although not independently, with structural changes such as the IMT of carotid artery; this effect is possibly influenced by lipid levels and age.

Iron metabolism gene expression in human skeletal muscle.

Little is known about iron metabolism in skeletal muscle while hepatic iron metabolism is well understood. The aim of this study is to compare the iron metabolism gene expression profile in skeletal muscle and the liver in humans. Muscle and hepatic biopsies from six normal individuals were acquired. Twelve genes involved in iron metabolism( import, storage, export) were selected to be studied. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed in order to determine the expression profile in skeletal muscle and compare it to the one from the liver. Semi-quantification of the gene expression in the studied tissues was performed by densitometric analysis (DA). The results were expressed relative to the percentage of the ß-actin gene. Fine analysis was performed by real-time PCR (q-PCR) quantification for the genes that their expression presented a difference of more than 20% in the 2 tissues in the first applied densitometric analysis. Most of the studied genes, HJV, TFR1, HFE, DMT1, DMT1nonIRE, NGAL, HEPH, IREG1, FTH1 were well expressed (>70% of ß-actin) in skeletal muscle . HAMP, CP, and TFR2 were absent or minimally expressed (<10% of ß-actin) in skeletal muscle while they were well expressed in liver. HJV and Heph were found to have higher expression in skeletal muscle (SM) compared to liver (L) (SM/L=2.65 ± 1.1(p<0.05) and SM/L=1.5 ± 0.06(p<0.05 respectively in q-PCR). The relative expressions of the studied genes in both tissues and their relative contribution in iron homeostasis in different pathways are discussed.

Arterial stiffness but not intima-media thickness is increased in euthyroid patients with Hashimoto's thyroiditis: The effect of menopausal status.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disorder associated with increased cardiovascular risk, mainly as a result of accelerated atherosclerosis. The aim of this study was to determine the effect of HT on carotid atherosclerosis and arterial stiffness, as possible mediators of this vascular impairment. Menopausal status was also considered in this setting since HT is mainly prevalent in women. METHODS: Fifty-four women with HT and normal thyroid function (thyrotropin [TSH] < 4.5 mU/L) and 72 healthy controls with comparable age and risk factor prevalence were examined in this cross-sectional study. Intima-media thickness (IMT) in the carotid arteries averaged from six sites and carotid-femoral pulse wave velocity (PWV) were measured. RESULTS: Although both groups had TSH levels within normal limits, TSH was higher in HT patients (2.1 +/- 1.16 vs. 1.5 +/- 0.8 mU/L, p = 0.001). PWV (7.95 +/- 2.02 vs. 7.21 +/- 1.24 m/s, p = 0.021), but not IMT (0.644 +/- 0.144 vs. 0.651 +/- 0.169 mm, p = 0.798), was significantly higher in HT patients compared to controls. When the women were divided according to menopausal status, only premenopausal women without HT had significantly lower PWV when compared with the three other subgroups (6.51 +/- 1.09 m/s premenopausal controls vs. 7.64 +/- 2.05 m/s premenopausal HT vs. 7.69 +/- 1.11 m/s postmenopausal controls vs. 8.3 +/- 1.97 m/s postmenopausal HT, p < 0.001). By multivariate analysis PWV independently correlated with age (p = 0.042), the presence of HT (p = 0.002), TSH (p = 0.003), and menopause (p < 0.001) in the whole population while HT was an independent determinant of PWV only in premenopausal women. CONCLUSIONS: HT is associated with increased PWV independent of arterial atheromatosis, indicating a direct impact of this disorder on arterial stiffening. This effect may be masked in postmenopausal women possibly due to their heavier cardiovascular risk profile.

Complete abdominal aortic aneurysm thrombosis and obstruction of both common iliac arteries with intrathrombotic pressures demonstrating a continuing risk of rupture: a case report and review of the literature.

INTRODUCTION: Although mural thrombus in an abdominal aortic aneurysm is frequent and its role has been studied extensively, complete thrombosis of an abdominal aneurysm is extremely rare and its natural history in relation to the risk of rupture is not known. The case of a patient with a completely thrombosed infrarenal aneurysm is presented along with a literature review. CASE PRESENTATION: We report the case of a 56-year-old Caucasian man with an infrarenal abdominal aortic aneurysm, presenting at our hospital due to critical ischemia of his right lower limb. Computed tomography and angiography demonstrated complete aneurysm thrombosis and obstruction of both common iliac arteries. CONCLUSION: During the operation, systolic and mean intrathrombotic pressures, measured in different levels, constituted 74.5-90.2% and 77.5-92.5% of systolic and mean intraluminal pressure and 73-88.4% and 76.5-91.3% of systemic pressure, respectively. Our findings show that there may be a continuing risk of rupture in cases of a thrombosed abdominal aortic aneurysm.

VEGF and ki 67 expression in squamous cell carcinoma of the tongue: An immunohistochemical and computerized image analysis study.

Over-expression of ki 67 and vascular endothelial growth factor (VEGF) is a frequent finding in squamous cell carcinoma (SCC) of the oral mucosa. The expression of VEGF and ki 67 proteins was studied in a cohort of 87 patients with primary, previously untreated SCC of the tongue, using computerized image analysis (CIA) in order to determine the potential prognostic significance of these factors. Immunohistochemical analysis was performed with monoclonal anti-ki 67 (MIB 1) and anti-VEGF antibodies. A digital image analysis assay was applied for the evaluation of the results. Using CIA, VEGF over-expression was observed in 24/87 (27.5%) of the examined cases and this finding correlated to the stage of the disease (p=0.05). ki 67 was over-expressed in 49/87 (56.3%) of the cases and correlated to the size of the tumors (p=0.05). Cox regression analysis showed that there was no prognostic significance associating VEGF protein expression to survival status of the examined patients (p=0.77), whereas ki 67 over-expression was strongly correlated to poor prognosis (p=0.017). The size of the primary tumors was also strongly correlated to survival status of the patients (p=0.024), whereas stage of disease showed a borderline statistical significance (p=0.091).

CD56 as a useful marker in the regenerative process of the histological progression of primary biliary cirrhosis.

OBJECTIVE: Owing to recent contradicting results in the study of the regenerative process after hepatic injury in primary biliary cirrhosis, we investigated the use of CD56 in tissue repair during the histological progression of primary biliary cirrhosis. METHODS: Fifty-three specimens were classified into Ludwig's stages (1-4) as follows: 14 specimens as stage 1, 23 as stage 2, 14 as stage 3, and two as stage 4. Immunohistochemical stain was performed for CD56. The cell types expressing the marker were morphologically analyzed to determine their origin. RESULTS: In normal liver biliary epithelial cells (including the epithelium of terminal bile ducts and bile ductules), hepatocytes, and intermediate cells (features between hepatocytes and biliary cells, distributed in interface between hepatic parenchyma and portal tract) were CD56. In primary biliary cirrhosis specimens, biliary epithelial cells, hepatocytes, and intermediate cells were CD56 distributed as 10 out of 14 cases as stage 1 (71.43%), 18 out of 23 as stage 2 (78.26%), nine out of 14 as stage 3 (64.28%), and two out of two as stage 4 (100%). The total positive cases were 39 of 53 (73.58%). CD56 was expressed equally in all three types of cells. CONCLUSION: These findings indicate that the consistent and uniform expression of CD56 in biliary epithelial cells, hepatocytes, and intermediate cells during hepatic injury in primary biliary cirrhosis is probably related to cellular damage and may be important in tissue regeneration. Furthermore, we cannot distinguish a specific cell type from the three above mentioned ones (biliary epithelial cells, hepatocytes, intermediate cells) as a putative stem cell in primary biliary cirrhosis.

Expression of nuclear factor-kappaB in human astrocytomas: relation to pI kappa Ba, vascular endothelial growth factor, Cox-2, microvascular characteristics, and survival.

Although NF-kappaB has been reported to be constitutively activated in various neoplasms, little information is available about its clinical significance in astrocytomas. In this study, we investigated the association of NF kappa B1/p50 and pI kappa Ba immunohistochemical expression with clinicopathologic features, vascular endothelial growth factor, Cox-2, and microvascular parameters in paraffin-embedded tissue from 82 patients with astrocytomas. pI kappa Ba expression was positively correlated with nuclear (P = .0010) and negatively with cytoplasmic (P = .0008) NF kappa B1/p50 expression. Nuclear NF kappa B1/p50 and pI kappa Ba expression increased with tumor grade (P = .0001 and P < .0001). Nuclear NF kappa B1/p50 was associated with vascular endothelial growth factor (P = .0079), Cox-2 (P = .0500), and total vascular surface area (P = .0430), although the latter was significant only in grades II and III. pI kappa Ba was also positively correlated with microvessel caliber (pI kappa Ba/area; P = .0087). Multivariate analysis selected NF kappa B/p50 expression as an independent prognosticator not only for the entire cohort (P = .0220), but also for grades II and III (P = .0029) and grade IV cases (P = .0310). Our results suggest that nuclear NF kappa B1/p50 expression is dictated by its interaction with I kappa Ba in astrocytomas and is associated with tumor grade and angiogenic factors, denoting the importance of nuclear NF kappa B/p50 expression in patients' prognosis.

Clinical significance of nuclear factor (NF)-kappaB levels in urothelial carcinoma of the urinary bladder.

Nuclear factor (NF)-kappaB has been reported to be constitutively activated in various human neoplasms. However, its clinical significance in bladder urothelial carcinoma (UC) remains an unresolved issue. We conducted this study trying to elucidate the role of NFkappaB in bladder UC and its potential prognostic significance, by quantifying immunohistochemically the levels of p65/RelA expression in paraffin-embedded tissue from 116 patients. Some of the cases had previously been stained for cellular FLICE-like inhibitory protein (c-FLIP) and bcl-2. Seventy-four cases displayed concurrent cytoplasmic and nuclear immunoreactivity, whereas 18 only nuclear immunoexpression and 21 only cytoplasmic immunoexpression, and the remaining three cases were negative for p65/RelA. Nuclear p65/RelA expression was positively associated with tumour grade and T-category (p=0.0001 in both cases). In addition, cytoplasmic p65/RelA expression was lower in advanced T-category (p=0.0030). Moreover, p65/RelA nuclear expression was positively correlated with c-FLIP (p=0.0109) and bcl-2 (p=0.0452). p65/RelA nuclear expression adversely affected survival in both univariate and multivariate analysis in superficial (Ta-T1; p=0.0010 and p=0.0008) as well as in muscle-invasive carcinomas (T2-T4; p=0.0004 and p=0.0003). Our results demonstrate that NF-kappaB nuclear expression is correlated with histologic grade and T category in bladder UC. Moreover, NF-kappaB nuclear expression emerges as an independent prognosticator of adverse significance, conveying information beyond that obtained by standard clinicopathological prognosticators.

High rates of comorbid conditions in patients with type 2 diabetes and foot ulcers.

UNLABELLED:   Background/Aim. Foot ulceration is one of the most important diabetic complications that results in major medical, social, and economic consequences for patients, their families, and society as a whole. Previous studies have shown increased mortality in patients with diabetes with foot ulcers; however, the reason for the high mortality in this group of patients is not known. The aim of this cross-sectional study was to investigate prevalence rates of comorbid conditions in patients with diabetes and foot ulcers. METHODS: A total of 742 patients with type 2 diabetes (234 with foot ulcers and 508 without ulcers), consecutively attending the outpatient diabetes and diabetic foot clinics of the authors' hospital were reviewed. Clinical examination was performed to classify ulcers as neuropathic or neuroischemic, microvascular and macrovascular complications, as well as laboratory tests that were reviewed from medical records. RESULTS: Patients with diabetes with and without foot ulcers did not differ significantly in terms of age, sex, smoking habits, glycemic control, and prevalence rates of hypertension, dyslipidemia, and cerebrovascular disease. Known duration of diabetes was longer (P < 0.001), while the values of body mass index (P = 0.03) and creatinine clearance (P = 0.003) were lower in the patients with foot ulcers than in those without ulcers. In addition, prevalence rates of coronary artery disease (P = 0.005), lower extremity arterial disease (P < 0.001), retinopathy (P < 0.001), and nephropathy (P = 0.04), were higher in the patients with foot ulcers compared to those without ulcers. Additionally, duration of diabetes was longer and the prevalence rates of microvascular and macrovascular complications as well as hypertension, dyslipidemia, and smoking were much higher in the patients with neuroischemic ulcers in comparison to those with neuropathic ulcers. CONCLUSION: The high mortality rates in patients with diabetes and foot ulcers may be due to the high prevalence rates of comorbid conditions, especially coronary artery disease and nephropathy.