Morphometric analysis of cryofixed muscular tissue for intraoperative consultation.

For diagnostic purposes, cryofixation of tissues is a daily routine technique to investigate rapidly about the presence of tumours during a surgical procedure in patients. We performed morphometric analysis of cryofixed muscular tissues according to different techniques. About 1,000 muscle fibers and 1,493 nuclei, were automatically examined. After freezing, ice tissue interfaces shrinkage of the cells were present. Liquid isopentane or liquid nitrogen produced a statistical increase of fractal dimension, D, of the ice-tissue interfaces, P < 0.001 respect to the formalin-fixed samples, cryofixation performed inside the cryostat chamber at t = -20°C produced a D value close to the formalin-fixed samples. Shrinkage of the muscle fibers was higher in the samples cryofixed inside the cryostat chamber (P < 0.001). Cryofixation inside cryostat or by liquid nitrogen caused decreases of the nuclei dimensions and altered nuclear morphology (P < 0.01), liquid isopentane appeared not affecting the nuclei of the fibers. Cryofixation inside the cryostat chamber produced the highest shrinkage but it was reduced performing cryofixation in liquid nitrogen or isopentane. Freezing damage inside the muscle cells was absent in the samples cryofixed inside the cryostat, it was present after cryofixation by liquid nitrogen or isopentane. Subcellular components like the nuclei were preserved by isopentane. This paper present, for the first time, an objective method able to quantify and characterize the damages produced by cryofixation in biological sample for intraoperative consultation.

RV Longitudinal Deformation Correlates With Myocardial Fibrosis in Patients With End-Stage Heart Failure.

OBJECTIVES: This study was performed to determine the accuracy of right ventricular (RV) longitudinal strain (LS) in predicting myocardial fibrosis in patients with severe heart failure (HF) undergoing heart transplantation. BACKGROUND: RVLS plays a key role in the evaluation of its systolic performance and clinical outcome in patients with refractory HF. METHODS: We studied 27 patients with severe systolic HF (ejection fraction ≤25% and New York Heart Association functional class III to IV, despite full medical therapy and cardiac resynchronization therapy) using echocardiography before heart transplantation. RV free wall LS, right atrial LS, sphericity index (SI), and tricuspid annular plane systolic excursion (TAPSE) were all measured. Upon removal of the heart, from the myocardial histologic analysis, the ratio of the fibrotic to the total sample area determined the extent of fibrosis (%). RESULTS: RV myocardial fibrosis correlated with RV free wall LS (r = 0.80; p < 0.0001), SI (r = 0.42; p = 0.01) and VO2 max (r = -0.41; p = 0.03), with a poor correlation with TAPSE (r = -0.34; p = 0.05) and right atrial LS (r = -0.37; p = 0.03). Stepwise multivariate analysis showed that RV free wall LS (ß = 0.701, p < 0.0001) was independently associated with RV fibrosis (overall model R(2) = 0.64, p < 0.0001). RV free wall LS was the main determinant of myocardial fibrosis. In the subgroup of patients with severe RV fibrosis, RV free wall LS had the highest diagnostic accuracy for detecting severe myocardial fibrosis (area under the curve = 0.87; 95% confidence interval: 0.80 to 0.94). CONCLUSIONS: In late-stage HF patients, the right ventricle is enlarged, with reduced systolic function due to significant myocardial fibrosis. RV free wall myocardial deformation is the most accurate functional measure that correlates with the extent of RV myocardial fibrosis and functional capacity.

Unusual clear cell, lymphoplasmacyte-rich, dural-based tumor with divergent differentiation: a tricky case mimicking a meningioma.

We describe an unusual case of a recurrent dural neoplasm, previously diagnosed as meningioma. Histopathologically, the tumor is characterized by aggregates of divergently differentiated clear cells embedded in an abundant lymphoplasmacyte-rich stroma, mimicking a lymphoplasmacyte-rich meningioma. This study focuses on the histologic and immunohistochemical characterization of a unique dural-based tumor and provides useful guidelines for differentiating meningioma from other uncommon dural-based neoplasms. We propose that this recurrent dural neoplasm is a distinctive entity and, therefore, enlarges the spectrum of dural-based neoplasms that enter the differential diagnosis with meningiomas. Awareness of this tumor entity could prove useful for appropriate patient management.

"Clinical significance of multifocal and multicentric breast cancers and choice of surgical treatment: a retrospective study on a series of 1158 cases".

BACKGROUND: The biological and clinical significance of multifocal and multicentric (MF/MC) breast cancers and the choice of appropriate surgical treatment for these tumors are still debated. METHODS: 1158 women operated on for a stage I-III breast cancer were included in this retrospective study; clinical and pathological data were obtained from the institutional database of the Department of Oncology of the University of Siena, Italy. The impact of MF/MC breast cancers on patterns of recurrence and breast cancer specific survival (BCSS) was investigated in relation to the type of surgical treatment. RESULTS: MF and MC cancers were present in 131 cases (11.3%) and 60 cases (5.2%) respectively and were more frequently treated with mastectomy (55 MF and 60 MC cancers, 81.2%) than with breast conserving surgery (36 MF cancers, 18.9%; p < 0.001). MF and MC breast cancers were associated with a worse prognosis with a BCSS of 154 months compared to 204 months of unicentric cancers (p < 0.001). In multivariate analysis, MF/MC cancers were independent prognostic factors for BCSS together with higher number of metastatic axillary nodes, absence of estrogen receptors and high proliferative activity. MF and MC cancers were related to a significantly shorter BCSS in patients submitted to mastectomy as well as those submitted to breast conserving surgery. Relapse at any site was higher in the subgroup of MF and MC cancers but the incidence of loco-regional and distant recurrences did not differ between patients treated with mastectomy or breast conserving surgery. CONCLUSIONS: Our results indicate that MF/MC cancers have a negative impact on prognosis and are related to higher loregional and distant relapse independently from the type of surgery performed. Adjuvant therapies did not modify the poorer outcome, but in patients receiving adjuvant anthacyclines, the differences with unicentric tumors were reduced. Our data support the hypothesis that MF/MC tumors may have a worse biological behavior and that the presence of multiple foci should be considered in planning adjuvant treatments.

Epithelial cyst of the superior oblique muscle trochlea.

Most of the congenital orbital cysts are choristomas such as dermoid or epidermoid and only in a few cases they are epithelial. Clinically, they manifest as cystic movable formations mostly localized in the upper temporal quadrant of the orbit. We describe here the case of a 49-year-old man with an orbital cyst localized in the upper-nasal quadrant of the orbit and which was showing signs of a gradual enlargement and progression over the past weeks. Computed tomography revealed a cyst of 1.9 × 1.6 cm in size and located within the trochlea of the upper oblique muscle. The cyst was completely extirpated after orbitotomy performed by superciliary approach. Histopathology revealed a cyst with nonkeratinized cuboidal epithelium. Postoperative course was uneventful, without inflammation signs, and after 5 weeks excellent functional and aesthetic effects were achieved with no iatrogenic alteration of the ocular motility.

Usefulness of atrial deformation analysis to predict left atrial fibrosis and endocardial thickness in patients undergoing mitral valve operations for severe mitral regurgitation secondary to mitral valve prolapse.

In patients with severe mitral regurgitation (MR) referred for cardiac surgery, left atrial (LA) remodeling and enlargement are accompanied by mechanical stress, mediated cellular hypertrophy, and interstitial fibrosis that finally lead to LA failure. Speckle tracking echocardiography is a novel non-Doppler-based method that allows an objective quantification of LA myocardial deformation, becoming useful for LA functional analysis. We conducted a study to evaluate the relation between the traditional and novel atrial indexes and the extent of ultrastructural alterations, obtained from patients with severe MR who were undergoing surgical correction of the valvular disease. The study population included 46 patients with severe MR, referred to our echocardiographic laboratory for a diagnostic examination before cardiac surgery. The global peak atrial longitudinal strain (PALS) was measured in all subjects by averaging all atrial segments. LA tissue samples were obtained from all patients. Masson's trichrome staining was performed to assess the extent of the fibrosis. The LA endocardial thickness was measured. A close negative correlation between the global PALS and grade of LA myocardial fibrosis was found (r = -0.82, p <0.0001), with poorer correlations for the LA indexed volume (r = 0.51, p = 0.01), LA ejection fraction (r = 0.61, p = 0.005), and E/E' ratio (0.14, p = NS). Of these indexes, global PALS showed the best diagnostic accuracy to detect LA fibrosis (area under the curve 0.89), and it appears to be a strong and independent predictor of LA fibrosis. Furthermore, we also demonstrated an inverse correlation between the global PALS and LA endocardial thickness (r = -0.66, p = 0.0001). In conclusion, in patients with severe MR referred for cardiac surgery, impairment of LA longitudinal deformation, as assessed by the global PALS, correlated strongly with the extent of LA fibrosis and remodeling.

Is tissue inhibitor of metalloproteinase-1 a new prognosticator for breast cancer? An analysis of 266 cases.

Overexpression of tissue inhibitor of metalloproteinase-1 at either the messenger RNA or protein level has been related to a poorer prognosis in breast cancer. We investigated the role of tissue inhibitor of metalloproteinase-1 tissue expression, which was evaluated by immunohistochemistry staining of paraffin-embedded samples, as a possible prognostic indicator in breast cancer. The study included 266 patients treated by primary surgery. Tumors were scored tissue inhibitor of metalloproteinase-1 positive when at least 10% of the cells showed moderate or strong staining. Staining was observed in 76 (28.6%) patients; by multivariate analysis, factors independently associated with tissue inhibitor of metalloproteinase-1 positivity included more than 9 metastatic axillary nodes, high Mib-1 expression, and positivity for plasminogen activator inhibitor and CD44. With a median follow-up of 125 months, tissue inhibitor of metalloproteinase-1 expression showed a significant prognostic role in disease-free and overall survival by univariate analysis. Multivariate analysis confirmed an independent negative prognostic impact of tissue inhibitor of metalloproteinase-1 on overall but not disease-free together with high values of Mib-1. The number of involved axillary nodes, and triple negativity were independent predictors of either poorer disease-free or overall survival. In our study, tissue inhibitor of metalloproteinase-1 expression was significantly related to markers of tumor aggressiveness and was a powerful indicator of poorer prognosis, with a difference in 10-year disease-free and overall survival of 14% and 28%, respectively, between tissue inhibitor of metalloproteinase-1-negative and tissue inhibitor of metalloproteinase-1-positive cases. Expression of tissue inhibitor of metalloproteinase-1 also was an independent prognostic factor in node-positive cases, indicating a possible role of tissue inhibitor of metalloproteinase-1 as a marker of reduced chemosensitivity. Thus, tissue inhibitor of metalloproteinase-1 may have a role in clinical practice as a prognostic and predictive factor and a possible target for future therapies.

Two-dimensional speckle tracking echocardiography of acute cardiac transplant rejection following pregnancy.

A 44-year-old woman, who had undergone orthotopic cardiac transplantation in 1999, presented acute allograft rejection 4 months after childbirth. Analysis of myocardial deformation by speckle tracking echocardiography showed, in contrast with traditional markers of systolic function, a strong reduction of left ventricular strain, which recovered, together with rejection, under pharmacological treatment. This case documents the potential advantages of speckle tracking echocardiography in the noninvasive management of transplant recipients.