Role of thrombolestagrophy in monitoring perioperative coagulation status and effect of thromboprophylaxis in bariatric surgery.

BACKGROUND: Thromboelastography is a technique that surveys the properties of viscoelastic blood clot. The purpose of this paper was to evaluate the hypercoagulability state and the effect of antithrombotic prophylaxis on thromboelastogram (TEG) results in bariatric surgery. METHODS: Twenty-five patients enrolled received 0.8 ml of nodraparin starting on the day before surgery and continuing postoperatively. TEG profile was collected before induction of anesthesia, on the first and third postoperative days. Each sample was run also in a cup added with heparinase to eliminate the interference of antithrombotic prophylaxis. RESULTS: TEG analysis with heparinase showed a tendency to reduce the r-time (rate of initial fibrin formation) and k-time (time to clot firmness) and increase the alpha angle (rate of clot growth), while an increase of maximal amplitude (MA, a measure of maximal stiffness of the clot; p = 0.01) and GI or shear elastic modules strength (p = 0.03)was observed from basal to postoperative day 3 (POD3). TEG without heparinase evidenced and increase of r-time (p = 0.02) and k-time (p = 0.05), a reduction of the alpha angle (p = 0.03), and an increase of MA (p = 0.01) and GI (p = 0.03) from basal to POD3. The comparison of TEG techniques showed that normal TEGs had lower values of r-time and k-time and higher values of alpha angles and MA than TEG with heparinase. No differences were evident for basal and POD1 samples and the G values comparing the two TEG technique. No correlation was observed between the variation of normal TEG parameters and dosage of anticoagulant used in each patient. CONCLUSIONS: Our patients presented a tendency to hypercoagulability determined most by MA and GI. Comparison between TEGs indicates that low-molecular-weight heparin not titrated on weight is able to determine a reduction of hypercoabulable tendency in the early postoperative period with few effects on increasing MA and GI.

ErbB-receptors expression and survival in breast carcinoma: a 15-year follow-up study.

Aberrant expression of the epidermal growth factor receptor family has been implicated in the pathogenesis and progression of breast cancer and associated with poor prognosis. To evaluate the prognostic impact of the ErbB receptors expression profile, we analyzed a well-characterized series of 145 primary breast carcinomas for the simultaneous expression of epidermal growth factor receptor (EGFR/HER-1), ErbB-2 (HER-2), ErbB-3 (HER-3), and ErbB-4 (HER-4), using immunohistochemistry. Tumors were considered negative or positive for each marker when less than or more than 25% of the cancer cells were immunopositive. Expression of EGFR, ErbB-2, ErbB-3, and ErbB-4 was observed in 31 (21.4%), 65 (44.8%), 72 (49.7%), and 81 (55.9%) of the cases, respectively. There were significant associations between EGFR expression and pT status (P = 0.01), and between ErbB-3 expression and pN (P = 0.003), menopausal (P = 0.01) and PR (P < 0.001) status. The majority of the cases co-expressed two or more receptors. ErbB-3 resulted positive in 51/81 (63.0%) of the ErbB-4 positive cases and ErbB-3/ErbB-4 co-expression was statistically significant (P = 0.0003). As expected, ErbB-2 expression was associated with reduced overall survival at 15 years of follow-up (P = 0.04), even after adjusting for a series of other prognostic factors (P = 0.05). Moreover, cumulative analysis of ErbB-2/3/4 expression showed a strong positive association between higher total ErbB-2/3/4 expression score and worse prognosis (P = 0.002). The simultaneous expression in cancer cells of more than one ErbB receptor identifies a subset of breast cancer patients at high risk for poor survival.

BRCA1 and BRCA2 mutation status and tumor characteristics in male breast cancer: a population-based study in Italy.

To investigate at the population level the impact of BRCA1/BRCA2 gene alterations in male breast cancer, we analyzed a population-based series of 25 male breast cancer cases from Florence, Central Italy. We combined mutational screening with the study of germ-line allele transcript levels and of tumor-associated losses of heterozygosity. Screening by protein truncation test and single-strand conformational polymorphism assay, followed by sequencing, revealed 4 pathogenetic mutations (4 of 25 = 16%; 95% confidence interval, 5-37%), 1 in BRCA1 and 3 in BRCA2, including mutations recurring in Central Italy (BRCA1 3345delAG and BRCA2 6696delTC). The a priori probability of carrying a mutation, estimated using BRCAPRO software, showed a good agreement between expected and observed mutations (14% versus 16%). A 7-fold association between germ-line mutations and family history of breast-ovarian cancer emerged. To investigate associations between BRCA1/BRCA2 status and clinicopathological characteristics, we analyzed the histopathological and immunophenotypic parameters of the tumors. A significant association emerged between mutation carrier status and high histological grade (P = 0.02). Furthermore, one BRCA2 carrier was affected with Paget's disease, an extremely rare male breast cancer histotype. Overall, BRCA1/2 mutations were observed to be strongly associated with positive c-erbB-2 immunostaining (P = 0.004). To evaluate germ-line allele expression, we used primer extension assays targeting frequent BRCA1 and BRCA2 polymorphisms. A BRCA2 allele transcript imbalance was found in one of four heterozygotes tested, all of them negative for germ-line mutations. BRCA1 transcript imbalances were not detected in nine heterozygotes analyzed. Losses of heterozygosity at one or more of nine loci in the BRCA2 region were found in 8 of 22 tumors tested. Interestingly, a case that was negative for BRCA1/BRCA2 germ-line mutations and that had a priori mutation probability <10% showed loss of heterozygosity at all three of the intragenic BRCA2 markers analyzed, which could be related to a somatic involvement of BRCA2. No losses of heterozygosity were detected at BRCA1. In conclusion, constitutional BRCA1/BRCA2 mutations accounted for 16% of the male breast cancer cases in this area of Central Italy. The detection of a BRCA2 germ-line transcript imbalance and of a somatic loss of BRCA2 among the cases that resulted negative for germ-line mutations suggests a role of this gene more relevant than indicated by conventional mutational analysis. A distinct pattern of characteristics indicative of aggressive behavior, including high-grade and c-erbB-2 expression, was evident in tumors from germ-line BRCA2 mutation carriers. This suggests that phenotypic characteristics may contribute to the identification of hereditary BRCA2-related male breast cancers and that these tumors might share a unique molecular pathway of cancer progression.