Wnt (canonical and non canonical) pathways in breast carcinoma with extensive vascular invasion and inflammatory breast carcinoma.

BACKGROUND: Breast carcinoma with extensive peritumoral vascular invasion (ePVI-BC) is a cancer with massive vascular invasion (>10) detected in more than one slide. This neoplasm shows clinic-pathological affinity with inflammatory breast carcinoma (IBC). In this paper we evaluate their biological relationship through the study of surrogate markers (ß-catenin and NFAT5) of Canonical (cWnt) and non-canonical (nWnt) Wnt pathways activation. METHODS: By immunoistochemistry, we investigate ß-catenin and NFAT5 in 39 IBC, 74 ePVI-BC and 84 control cases (CG-BC). RESULTS: cWnt was activated in 100 % of ePVI-BC, in 64 % of IBC and 10 % of CG-BC. nWnt was activated in 20 % of ePVI-BC, 50 % of IBC and 1% of CG-BC. The prognosis of carcinomas with nWnt activated was poor similar to IBC. The statistical analysis evidences as both the pathways are synergistic in malignant progression and survival time. ß-catenin show an important association with prognostic factors and NFAT5 shows a relevant prognostic role on OS (p = 1.5*10-6) and DFS (P = 1,2*10-4). nWnt is associated with a worse prognosis independently of cWnt. cWnt is associated with adverse prognosis (DFS p = 0.0469; OS p = 0.004891) but its prognostic role is indifferent in carcinoma with nWnt activated. CONCLUSIONS: Canonical Wnt pathway is involved in malignant progression with dominant role for vascular invasion whereas non canonical Wnt pathway plays an important role on survival time including the capacity to identify carcinomas with IBC-like prognosis. Furthermore ePVI may represent a "prodromal form of IBC" as demonstrated by its clinicopathological and biological similarity with IBC.

A clinical-biological risk stratification model for resected gastric cancer: prognostic impact of Her2, Fhit, and APC expression status.

BACKGROUND: To obtain a prognostic stratification model for resected gastric cancer patients. PATIENTS AND METHODS: Clinicopathological and molecular data (expression of Cdx2, Apc, ß-catenin, E-cadherin, Fhit, p53, and human epidermal growth factor receptor-2 (Her2); HER2 and TOPO2A gene copy number; PIK3CA mutations; microsatellite instability) were correlated to cancer-specific/overall survival (CSS/OS) using a Cox model. Individual patient probability (IPP) was estimated by logistic equation. A continuous score to identify risk-classes was derived according to the model ratios. RESULTS: Two-hundred eight patients were studied (median follow-up 20 months). At multivariate analysis, sex, stage, margins, location, nodes, Apc, and Fhit were independent predictors for CSS; the same factors (and age and Her2, except Fhit) predicted OS. Multivariate model predicted IPP with high prognostic accuracy (0.90 for CSS; 0.91 for OS). A two-class model significantly separated low- and high-risk patients for CSS (23.4% and 85.6%, P < 0.0001) and OS (21.4% and 82.0%, P < 0.0001). A three-class model differentiated low-, intermediate-, and high-risk patients for CSS (6.3%, 35.3%, and 88.0%, P < 0.0001) and OS (6.1%, 34.6%, and 86.5%, P < 0.0001). CONCLUSIONS: A risk classification system comprising the immunohistochemical expression of three proteins (Apc, Fhit, and Her2) and five clinicopathological parameters (stage, resected nodes, margins, location, and sex) accurately separates the resected gastric cancer patients into three classes of risk.

Perioperative management of face-to-face craniopagus twins separation.

Craniopagus conjoining represents a complex and challenging issue for neurosurgeons as well as for anesthesiologists. A rare face-to-face case of conjoined twins underwent surgical separation and presented peculiar differences compared with those already reported in the literature. Even in cases lacking large cerebrovascular sinus connections, the impending risk of large blood loss and hemorrhagic shock in the infant requires a high level of surveillance and the institution of invasive monitoring.

Iron-ovotransferrin preparation does not interfere with ciprofloxacin absorption.

Iron supplements can interfere with the bioavailability of a number of drugs, including thyroxine, tetracycline derivatives, penicillamine, methyldopa, levodopa, carbidopa, ciprofloxacin, and the newer fluoroquinolones. A new iron formulation was tested in which iron ions are bound to ovotransferrin, a protein that shares more than an 80% similarity with the sequence of human transferrin and apparently is less likely than the commonly used iron salts to reduce drug absorption. Ciprofloxacin was taken as a model drug, of wide use and restricted range of therapeutic levels, and its absorption was evaluated after the administration of the iron-ovotransferrin complex versus an iron-gluconate formulation in healthy volunteers. At variance with the iron gluconate formulation, which led to a reduction of about 50% of peak serum ciprofloxacin levels (Cmax; 1.0 +/- 0.2 versus 2.4 +/- 0.3 micrograms/ml; p < 0.01) and of the area under the serum concentration-time curve from time 0 to infinity [AUC(0 - infinity); 10.1 +/- 1.1 versus 18.3 +/- 1.0 mg.L-1.hr; p < 0.01], the iron-ovotransferrin complex caused only modest, non significant changes in absorption with a minimal reduction of the AUC[0 - infinity) (17.3 +/- 1.0 versus 18.3 +/- 1.0 mg.L-1.hr; difference not significant) and a nonsignificant decrease in the Cmax (2.2 +/- 0.3 versus 2.4 +/- 0.3 microgram/ml; difference not significant). Iron was also well absorbed from the formulation in the presence of a fatty meal. The very common drug interactions with oral iron preparations can be effectively prevented by the use of the iron-ovotransferrin complex interacting to a minimal extent with a sensitive drug with a reduced margin of efficacy, such as ciprofloxacin.

Cost effective prophylaxys of postoperative nausea and vomiting by anesthetic premedication.

Postoperative emesis is a common daily problem in anesthetic practice. Authors report their experience about prevention of PONV (postoperative nausea and vomiting) with the association of different drugs in premedication, and suggest Promethazine as an effective and inexpensive medication to prevent PONV in orthopedic surgery.

Intravenous premedication with atropine and postanesthetic delirium. Report of two cases.

The authors report two cases of postanesthetic delirium in patients receiving intravenous atropine sulphate before surgery. In the first case the diagnosis of atropinic syndrome has been suggested by a cause effect relationship; in the second case the diagnosis has been supported by the prompt resolution after intravenous physostigmine salycilate administration. Since such syndrome was never observed in patients receiving atropine sulphate as i.m. premedicant, authors are prone to consider the i.m. route a safer approach to premedication with this drug.

The amino acid cerebral pool after toxic doses of lidocaine and mexiletine. An experimental study on guinea pigs.

Lidocaine and Mexiletine are two anti-arrhythmic drugs which when administered in toxic doses cause alterations in the central nervous system (convulsions, tremors, coma). An experimental study was carried out to clarify some neurological side-effects caused by these two drugs, by studying the variations of the brain amino acid pool. With Lidocaine one can observe an increase of phenyl-alanine and tyrosine, a decrease of glycine, GABA, alanine, aspartate and glutamate, while taurine and ammonia showed no significant changes. After Mexiletine one can observe an increase of ammonia, a decrease of GABA, glutamine, glycine and alanine, while glutamate, taurine, phenyl-alanine and tyrosine remain within normal values. In conclusion, on the basis of the data obtained by comparing the two drugs, one could say that Lidocaine has a greater interference on the catecholaminic precursors which are little influenced by Mexiletine. For the rest, the data obtained are practically super- imposable .

The brain amino acid pattern in experimental coma due to phenytoin in guinea pigs.

An experimental study was carried out on 50 guinea pigs to evaluate the amino acid pattern in the whole brain after a toxic dose of phenytoin (1 g . kg-1 body wt). One group of 25 guinea pigs was treated with the drug which made them comatose, and their brains removed by craniotomy and frozen in liquid nitrogen; 25 guinea pigs were used as a control group. The brain amino acid pattern was determined by ion-exchange chromatography. All the amino acids, except threonine and methionine, decreased. Hypotheses about the particular cerebral metabolic pathways involved are discussed.

The effect of five drugs in coma doses on neurotransmitter amino acids in the brains of guinea pigs.

The study has been carried out in order to investigate the effects of some drugs in coma doses on the concentration in brain of some amino acids involved in brain function. Six groups of 25 guinea pigs each were utilized. In each of the five groups a subcutaneous dose of diazepam, flunitrazepam, phenobarbital, phenytoin or alfaxalone, was injected and one group was utilized as control. Some neurotransmitter amino acids (glutamate, aspartate, glycine and taurine) and precursors of neurotransmitters (phenylalanine and tyrosine) were determined in brain preparations. The results are discussed.

Cerebral and systemic amino acid metabolism in experimental acute amphetamine poisoning in guinea pigs.

Protein catabolism, as measured by plasma amino acids is increased by amphetamine injection (15 mg/kg body wt) administered to 10 adult male guinea pigs. Changes in the cerebrospinal fluid were less marked than those in the plasma. The amphetamine seemed to inhibit the enzymes of the metabolic pathways that use amino acids.

Amino acid distribution in guinea pig plasma, cerebrospinal fluid and brain tissue in acute experimental hypoxia.

An experimental study of 150 guinea pigs has been carried out to analyze the amino acid pattern in plasma, cerebrospinal fluid and brain tissue in acute hypoxia. The distribution of these compounds changed, and hypotheses about particular cerebral metabolic pathways involved are presented.