Invasive Lobular Breast Cancer Presenting an Unusual Metastatic Pattern in the Form of Peritoneal and Rectal Metastases: A Case Report

Gastrointestinal metastases from invasive lobular breast cancer are uncommon with the stomach and small intestines being the most common metastatic sites. Peritoneal and rectal metastases are very rare and only rarely occur as the first manifestation of disease. We herein report the case of a 47-year-old woman who presented with abdominal carcinomatosis as a first sign of invasive lobular breast carcinoma (ILC). Identifying the most important immunohistochemical markers for ILC: gross cystic disease fluid protein 15, estrogen and progesterone receptors enabled a correct diagnosis. After a six year disease-free period, relapse occurred with severe obstruction due to rectal metastasis from lobular breast carcinoma. Since there was no widespread metastatic disease, surgery with concomitant hormonal therapy was performed.     

Association of MMP-3 5A/6A gene polymorphism with susceptibility to carotid atherosclerosis

ObjectivesStromelysin-1 (MMP-3) as a key member of metalloproteinase family could have an important role in atherogenesis. The 5A/6A polymorphism in the promoter of MMP-3 gene affects the level of MMP-3 gene expression. We assessed whether the MMP-3 promoter low- and high-activity genotypes are related to susceptibility for carotid atherosclerosis (CA) in Serbian population.Design and methodsThe study group of case-control design consisted of 515 participants. The 265 patients with ultrasonographic evidence of carotid plaque presence were recruited for the study. The 5A/6A polymorphism was typed by RFLP-PCR.ResultsThere was significantly higher prevalence of genotypes containing 6A allele in the patients with CA compared to controls (p < 0.05). The model of inheritance with the dominant effect of 6A allele gave elevated and significant OR for carotid atherosclerosis (adjusted OR 2.35, CI = 1.0–5.5, p = 0.048).ConclusionsSubjects carrying genotypes with 6A allele had significantly higher susceptibility to carotid atherosclerosis.     

Association of the MMP-3 5A/6A gene polymorphism with multiple sclerosis in patients from Serbia

Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in remodeling of the extracellular matrix. MMPs are suggested to play a role in the influx of inflammatory cells into the CNS, disruption of the blood brain barrier, and to degrade myelin in vitro. In this study, we have investigated the possible association of MMP-3 5A/6A gene polymorphism with MS susceptibility and/or severity in patients from Serbia. A total of 184 MS patients (150 RR, 34 SP) and 236 controls have been studied. Results show that the distribution of MMP-3 5A/6A genotype frequencies between MS patients and controls were not significantly different. In bout onset patients, carriers of MMP-3 6A/6A genotype had significantly higher mean MSSS values compared to the carriers of 5A allele (6.29+/-1.89 vs. 5.29+/-2.62, respectively, ANCOVA, p=0.01 Scheffe post-hoc test). In conclusion, our results indicate association of MMP-3 6A/6A genotype with significantly higher mean MSSS values. Thus, the obtained results suggest that it should be carefully considered during follow up of patients with MS. Further genetic and functional studies are needed to resolve the complex role of MMPs and their tissue inhibitors in MS pathology and/or regeneration.     

Pancreaticoduodenal artery pseudoaneurysm embolization

We report a case of successful transcatheter arterial embolization of a pancreaticoduodenal artery pseudoaneurysm (PSA) caused by erosion of the pancreatic pseudocyst content near pancreaticoduodenal arteries. A 55-year-old man was admitted to a local hospital for investigation of severe, stabbing epigastric pain confined to the upper abdomen. He had a history of previous alcohol abuse, chronic pancreatitis, and a duodenal ulcer. Upper gastrointestinal endoscopy revealed narrowing in the pyloric channel along with an ulcer located at the first and second portions of the duodenum with oozing beneath an adherent cloth and duodenal distortion. Computed tomography additionally revealed an enlarged head of the pancreas with numerous spot calcifications and round cystic formation inside, with a diameter of 30 x 25 mm. Following two surgical procedures for duodenal ulcers, selective angiography revealed a PSA located inside the pancreas head and high-grade stenosis > 90% of the celiac trunk and hepatic artery that rose separately from the aorta. Fiber coil embolization was used to occlude the PSA sac successfully. There was no complication after completion of the last embolic procedure. The patient was doing well after 26 months.     

Influence of haemodialysis on early markers of atherosclerosis

Introduction: End-stage renal disease (ESRD) patients treated by haemodialysis (HD) have impaired endothelium-dependent vasodilatation and increased intima-media thickness (IMT) of the carotid artery The aim of the study was to analyse the relationships between parameters of chronic HD treatment and non-invasive assessments of preclinical atherosclerosis (endothelial dysfunction and carotid IMT) in ESRD patients on HD. Methods: Fifty-two (19 females, 33 males) adult patients on chronic maintenance (4.65 ± 3.29 years) HD aged 59.88 ± 15.49 years were investigated. Ultrasonographic studies were performed with a 7.5 MHz high-resolution probe. The common carotid artery IMT was measured. Brachial artery diameter was analysed to the rest. In order to assess flow-mediated dilatation (FMD), hyperaemia was induced by a pneumatic cuff, and an analysis of the diameter was performed 1, 2, 3 and 4 min after cuff deflation. Results: Significant differences were found in the average carotid IMT value between subjects with delivered dialysis dose (Kt/V) ≥1.2 and <1.2 (0.89 ± 0.21 vs 1.04 ± 0.11, P = 0.0045). A correlation between Kt/V and IMT (r = 0.366, P = 0.004) was demonstrated. FMD values of the brachial artery did not correlate with Kt/V. A correlation between low molecular weight heparin per kg of body mass and maximal percent of FMD was demonstrated (r = −0.242, P = 0.049). The maximal percent of brachial FMD was correlated with absolute difference between pre- and postdialysis pulse pressure values (r = −0.265, P = 0.033). In a partial correlation with haemoglobin as control, a variable significant correlation between total erythropoietin dose and maximal carotid IMT (r = −0.262, P = 0.036) was found. In a multiple linear regression model, Kt/V was independently correlated with carotid IMT values (β = −0.227, P = 0.0335). Conclusion: This study has demonstrated the association between HD procedure and early atherosclerosis markers. HD treatment has to be considered as potential modifying factor in atherosclerosis development.     

The role of poly(ADP-ribose) polymerase (PARP) in the autonomous proliferative response of endothelial cells to hypoxia

OBJECTIVE: The autonomous proliferative response of endothelial cells to hypoxia has been shown to be dependent on activation of NAD(P)H oxidase, on the cytosolic Ca2+ load, and, consequently, on nuclear translocation of extracellular signal-regulated kinase (ERK)1/2 during transient hypoxia. The aim of the present study was to investigate whether poly(ADP-ribose) polymerase (PARP) is a downstream signal of NAD(P)H oxidase, mediating cytosolic Ca2+ load and hence nuclear translocation of ERK1/2 and endothelial cell proliferation. METHODS: Porcine aortic endothelial cells were incubated under hypoxic conditions for 40 min. Cytosolic [Ca2+] and reactive oxygen species (ROS) formation were measured in fura-2- and DCF-loaded cells, respectively. PARP activation was detected by immunocytochemistry, and endothelial cell proliferation was determined 24 h after 60 min of transient hypoxia. RESULTS: Inhibition of NAD(P)H oxidase with antisense oligonucleotide against the p22(phox) subunit, MEK/ERK signalling with UO 126 (30 microM), or PARP with PJ 34 (10 microM) leads to a marked reduction in hypoxia-induced cytosolic Ca2+ load and activation of PARP. Hypoxia-induced translocation of ERK1/2 and endothelial cell proliferation were also prevented when NAD(P)H oxidase or PARP were inhibited; however, hypoxic ROS formation was not affected in the presence of PARP inhibitor. CONCLUSION: PARP represents a downstream effector of NADP(H) oxidase and acts as a necessary intermediate step for the hypoxic proliferative response of endothelial cells.     

Current state of screening for bladder cancer

Bladder cancer is the fourth most commonly diagnosed cancer in men and the eighth most common cancer in women in the USA. Efforts to reduce mortality from bladder cancer must focus on three areas: prevention, development of effective therapies for muscle-invasive and metastatic disease, and early detection of potentially invasive lesions while they are still superficial and amenable to less morbid, but still effective, treatments. As more effective therapies for metastatic transitional cell carcinoma are not on the immediate horizon and preventive measures (except for smoking cessation) have been disappointing, if we are to reduce this disease's morbidity and mortality rates significantly, early detection strategies need to be improved and implemented. The goal of screening for any type of cancer is to detect the disease in its early stages in order to increase the chances for cure or prolongation of life (before micro or gross metastases occur). Since all patients who die of bladder cancer do so from metastases and since almost all patients with metastases have muscle-invading cancers appearing as the first bladder cancer event, diagnosing cancers destined to become muscle invading before they actually are should reduce bladder cancer mortality. This special report reviews the current state of bladder cancer screening in the USA.     

Prevalence of posttraumatic stress disorder in alcohol dependent patients in Poland

The present study investigates the prevalence of comorbid posttraumatic stress disorder (PTSD) in a sample of Polish alcohol dependent patients and examines the relationship between comorbid PTSD and alcohol use-related problems. Patients (n=458) were recruited from randomly chosen clinical settings and were administered self-report measures of trauma exposure, PTSD symptomatology, and alcohol use-related problems. From this sample, 67% of the patients reported having experienced at least one criterion A traumatic event, and 60% of them reported multiple traumas. Approximately 25% of them met the criteria for current PTSD. The only significant difference between the PTSD and non-PTSD groups was abuse/dependence of other psychoactive substances. However, patients reporting physical assaults committed by a non-stranger reported more frequent PTSD diagnosis, more extensive symptomatology, more conflicts with the law and more physical injuries due to drinking. The findings of the study confirm the importance of assessing trauma and PTSD in alcohol dependent patients.     

Protective effects of nebivolol and reversal of endothelial dysfunction in diabetes associated with hypertension

This study aims to decipher the potential effects of nebivolol in prevention and/or regression of renal artery dysfunction in diabetes associated with hypertension. Renal arteries were isolated from 80 male mice divided into four experimental groups: (i) group D: diabetics, at 2 months since streptozotocin injection; (ii) group Din: mice that at the initiation of streptozotocin diabetes were treated with 10 mg/kg b.w./day nebivolol for 2 months, to test for the potential prevention of vascular dysfunction; (iii) group Dfin: mice that after 2 months of diabetes were treated daily with 10 mg/kg b.w./day nebivolol for additional 2 months, in order to follow the possible regression of the dysfunction, and (iv) controls (C), age-matched healthy animals. The following measurements were performed: arterial blood pressure, plasma glucose concentration, and the vascular reactivity of the renal arteries in response to noradrenaline (10(-4) M), acetylcholine (10(-4) M) and sodium nitroprusside (10(-4) M). To assess the molecular mechanisms involved in the reactivity of the renal artery, the contribution of mitogen-activated protein kinase (MAP kinase) pathway and of L-type voltage gated Ca(2+) channels (in the contractile response to noradrenaline), of nitric oxide (NO) and Ca(2+) activated K(+) channels (in the endothelium-dependent vasodilator response), and of cGMP (in the endothelium-independent vasodilator response) was examined by exposing the arteries to corresponding inhibitors, and by using myograph and patch-clamp techniques, immunoblotting and NO assays. Results showed that, group D was characterized by hyperglycemia (blood glucose concentration: 136.66 +/- 4.96 mg/dl, a value approximately 65% increased compared to group C) and hypertension (systolic blood pressure: 145.66 +/- 5.96 mm Hg, a value approximately 34% increased compared to group C). Compared to group D, group Din was characterized by diminished blood glucose concentration ( approximately 1.6 fold), reduced systolic and diastolic blood pressure ( approximately 1.3 fold) and heart rate ( approximately 1.6 fold), as well as by increased contractile response of the renal artery to noradrenaline ( approximately 1.84 fold) and of the impeded vasodilator response to acetylcholine ( approximately 1.81 fold) and sodium nitroprusside ( approximately 1.42 fold). Together, these effects demonstrate that administration of 10 mg/kg b.w./day nebivolol at the moment of diabetes induction has preventive effects, ameliorating diabetes dysfunctions. Compared to group D, group Dfin was characterized by diminished glucose concentration ( approximately 1.3 fold), reduced systolic and diastolic blood pressure and heart rate (both approximately 1.2 fold), and by augmentation of contractile response of the renal artery to noradrenaline ( approximately 1.62 fold) and of vasodilator response to acetylcholine ( approximately 1.13 fold) and sodium nitroprusside ( approximately 1.19 fold). These effects assess that administration of 10 mg/kg b.w./day nebivolol after 2 months of diabetes contributes to regression of diabetes-associated dysfunctionalies. Nebivolol influenced the molecular mechanisms involved in renal artery reactivity in diabetic and hypertensive mice: it increased the NO production and endothelial NO synthase (eNOS) protein expression, decreased the expression of proportional, variant protein in L-type calcium channels and Ca(2+) activated K(+) channels, and diminished the MAP kinase activity. The reported data suggest that nebivolol may offer additional vascular protection for treating diabetes associated with hypertension.