Initial panel of immunocytochemical markers for identification of primary carcinoma site for effusions and peritoneal washings from women

Introduction: In women, most malignant effusions are from breast and ovary primary carcinomas that have metastasized to body cavity fluids (pleural, peritoneal and pericardial). When carcinoma is diagnosed in effusions, it is not possible to identify its site of origin solely by cytology (morphology); therefore, immunocytochemistry is used as a complementary method. There are no immunocytochemical markers with 100% sensitivity and specificity for identifying carcinoma primary site. The markers most used are TTF-1 for the lung, GATA-3 for the breast, and PAX-8 for the ovary. The aim of this study was to evaluate the sensitivity and specificity of a panel including these markers for detecting the primary site of carcinoma in effusions. Methods: Samples of pleural, pericardial, and peritoneal effusions and peritoneal washings with carcinoma of known primary site from women (n = 60) and men (n = 18) were prepared by using the cell block method, and immunocytochemistry was performed to evaluate the expression of primary site markers (TTF-1, PAX-8, and GATA-3). Results: In women, the breast was the most frequent primary site of metastatic carcinoma to both pleural and pericardial cavities, followed by the lung, whereas the ovary was the most frequent primary site of carcinoma within peritoneal effusions and washings, followed by the gastrointestinal tract (stomach or intestine). The expected profiles for carcinomas of the most common primary sites were: breast (GATA-3 (+), PAX-8 (-), TTF-1 (-)), ovary (PAX-8 (+), GATA-3 (-), TTF-1 (-)), lung (TTF-1 (+), PAX-8 (-) GATA-3 (-)) and gastrointestinal tract (PAX-8 (-), GATA-3 (-), TTF-1 (-)). These were observed in 88.23% (45/51) of women’s samples with carcinoma from these primary sites. By using TTF-1 as the sole primary site marker, 6.25% of carcinomas of primary site other than the lung would have been misdiagnosed. Conclusion: An initial panel of markers including GATA-3, PAX-8, and TTF-1 allows, with high sensitivity and specificity, the identification or exclusion of frequent primary sites of carcinoma in effusions from women. Our results highlight the importance of using a panel of markers to avoid misidentification of the primary site of tumor.     

Ventricular remodeling and mitral valve modifications in dilated cardiomyopathy: new insights from anatomic study

OBJECTIVE: The purpose of this study was to analyze the behavior of the mitral valve ring and the left ventricle in dilated cardiomyopathy. METHODS: We analyzed 68 fixed adult human hearts, divided into 48 hearts with dilated cardiomyopathy of ischemic or idiopathic origin and 20 hearts free of pathologic heart conditions. Digital images of the mitral ring perimeter, attachment of the anterior and posterior leaflets, and fibrous and muscular portions were collected. We also measured the internal perimeter of the left ventricle, the distance from the septum to the anterior and posterior papillary muscles, the distance between the papillary muscles, and the extension of interventricular septum. RESULTS: The analysis of the results showed proportional distribution of the ring's fibrous portion (r2 = 0.98) and muscular portion (r2 = 0.99) according to the degree of mitral valve dilation. Linear regression revealed that the perimeters of anterior and posterior leaflet attachments (r2 = 0.96 and r2 = 0.98, respectively) also had a proportional relation. We did not observe proportionality between the degree of dilation of the mitral ring and the left ventricle. It was observed that dilation of the left ventricle takes place globally in its segments. CONCLUSION: Differently from what was thought, in ischemic or idiopathic dilated cardiomyopathy, dilation of mitral ring is proportional and does not exclusively affect the posterior portion. The degree of left ventricular dilation does not determine the degree of dilation of the mitral ring because they are independent processes. These observations shed new light on the techniques used to correct mitral valve insufficiency in dilated cardiomyopathy.     

Leiomyosarcoma of the inferior vena cava--a case report

This paper presents a patient successfully treated for leiomyosarcoma of the vena cava, with no recurrence or symptoms on an 8-year follow-up. A 56-year-old woman presented with chronic and progressive periumbilical and right upper abdominal pain. Physical examination and laboratory tests revealed no abnormalities. Computed tomography showed a high-density image inside the vena cava. Cavography showed a filling defect with complete occlusion of the vena cava involving the renal veins and greatly developed collateral circulation through lumbar veins. Laparotomy was performed and a large caval mass involving the renal veins was dissected and resected. Venous reconstruction was undertaken using a 19-mm bovine pericardium prosthesis (Labcor, MG-Brazil) interposed as a substitute to the vena cava, and the renal veins were anastomosed to the side of the graft. Pathologic examination confirmed a leiomyosarcoma with free surgical margins. The postoperative course was uneventful and the patient was discharged on postoperative day 8. The venous flow through the inferior vena became normal, as confirmed by later cavography. This paper presents a case of successfully managed leiomyosarcoma of the vena cava with a thorough review of the literature. The treatment of such patients and the use of bovine pericardium are also discussed.     

Implication of breast cancer phenotype for patients with leptomeningeal carcinomatosis

BackgroundWe aimed to study the implications of breast cancer (BC) subtypes for the development and prognosis of leptomeningeal carcinomatosis (LC).Patients and methodsData from the breast cancer patients diagnosed with LC between 2005 and 2010 were retrieved. Patients were classified in luminal A, B, HER2 positive and triple negative (TN) and their BC diagnosis, treatment, and outcome were analyzed according to each subtype. Pearson's chi-square and Fisher's exact test were used for categorical variables. Survival analyses were performed by Kaplan–Meier method and compared with the log-rank test.ResultsA total of 38 BC patients were identified, with a median age of 54.8 years (range 36–79). The proportion of luminal A, B, HER2 positive and TN was 18.4%, 31.6%, 26.3% and 23.7%, respectively. LC was the first evidence of metastatic disease in 5 BC patients. Twenty patients received the systemic chemotherapy, with 16 (80%) whole brain radiotherapy (WBRT). Nine patients received only WBRT. TN patients had the shorter interval between metastatic breast cancer diagnosis and the development of LC. Median survival after the diagnosis of LC (OSLC) was 2.6 months (range 1.2–6.4), and did not differ across breast cancer subtypes. In univariate analysis, performance status (ECOG = 0–2) and chemotherapy were prognostic for OSLC, but only the treatment stood as an independent prognostic factor in multivariate analysis.ConclusionsBreast cancer subtype influences the timing of LC appearance, but not OSLC. Patients with LC from breast cancer should be offered systemic treatment, as it appears to associate with the improved outcome. New therapeutic strategy, including, targeted and intrathecal therapy are deserved for BC patients with LC.     

Bone repair following bone grafting hydroxyapatite guided bone regeneration and infra-red laser photobiomodulation: a histological study in a rodent model

The aim of the investigation was to assess histologically the effect of laser photobiomodulation (LPBM) on a repair of defects surgically created in the femurs of rats. Forty-five Wistar rats were divided into four groups: group I (control); group II (LPBM); group III (hydroxyapatite guided bone regeneration; HA GBR); group IV (HA GBR LPBM). The animals in the irradiated groups were subjected to the first irradiation immediately after surgery, and it was repeated every day for 2 weeks. The animals were killed 15 days, 21 days and 30 days after surgery. When the groups irradiated with implant and membrane were compared, it was observed that the repair of the defects submitted to LPBM was also processed faster, starting from the 15th day. At the 30th day, the level of repair of the defects was similar in the irradiated groups and those not irradiated. New bone formation was seen inside the cavity, probably by the osteoconduction of the implant, and, in the irradiated groups, this new bone formation was incremental. The present preliminary data seem to suggest that LPMB therapy might have a positive effect upon early wound healing of bone defects treated with a combination of HA and GBR.     

Liver regeneration following partial hepatectomy is improved by enhancing the HGF/Met axis and Akt and Erk pathways after low-power laser irradiation in rats

A simple, easy, and safe procedure aiming to improve liver regeneration could be of great clinical benefit in critical situations such as major hepatectomy, trauma, or hemorrhage. Low-power laser irradiation (LPLI) has come into a wide range of use in clinical practice by inducing regeneration in healthy and injured tissues. However, the effect of LPLI on the process of liver regeneration, especially those related to the molecular mechanisms, is not fully understood. Thus, the aim of the present study was to investigate the main molecular mechanisms involved in liver regeneration of partially hepatectomized rats exposed to LPLI. We used Wistar male rats, which had their remaining liver irradiated or not with LPLI (wavelength of 632.8 nm and fluence of 65 mW/cm²) for 15 min after a 70 % hepatectomy. We subsequently investigated hepatocyte growth factor (HGF), Met, Akt, and Erk 1/2 signaling pathways through protein expression and phosphorylation analyses along with cell proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67) using immunoblotting and histological studies. Our results show that LPLI can improve liver regeneration as shown by increased HGF protein expression and the phosphorylation levels of Met, Akt, and Erk 1/2 accompanied by higher levels of the PCNA and Ki-67 protein in the remnant livers. In summary, our results suggest that LPLI may play a clinical role as a simple, fast, and easy-to-perform strategy in order to enhance the liver regenerative capacity of a small liver remnant after hepatectomy.     

Relative localizing value of amygdalo-hippocampal MR biometry in temporal lobe epilepsy

OBJECTIVES: The aims of the study were (i) to examine the localizing value of three MRI quantitative modalities (qMRI) currently used for the analysis of the hippocampus and amygdala in the context of pre-surgical screening and (ii) to propose a step-by-step protocol based on the sensitivity and performance of the different MR techniques. METHODS: Ninety-two adults with chronic mesial temporal lobe epilepsy (TLE) of which 28 underwent amygdalo-hippocampal resection, and 34 age-matched controls were included in the study. High-resolution qMRI was performed at 1.5 T, including a tilted T1-weighted 3D-dataset for volumetry and four-echoes T2 relaxometry (both for hippocampus and amygdala quantifications) and multi-voxel spectroscopy [NAA/(Cho+Cre)] (exclusively in the hippocampus). Individual qMRI data were compared with electroencephalography regarding the localization of the epileptogenic area, with the neuropathological data and with postoperative outcome. MRI pathology was defined based on 99% confidence ellipses. Ten controls were used to assess the quantitative MRI intra- and inter-observer variability for all variables. RESULTS: Volumetric measurements revealed unilateral damage in 77% of the patients, T2-relaxometry in 64% and spectroscopy in 53%. Additional measurements of the amygdalae (T2-relaxometry) allowed us to localize pathology that coexists with that of the hippocampus in 34%, and isolated unilateral amygdala damage in 8% of patients. Volumetry and T2-relaxometry (not spectroscopy) were associated with postoperative outcome, but accurate predictive models were computed based on hippocampal measures only. At least at 1-year follow-up, volumetry predicts outcome correctly in 100% of the cases, whilst T2-relaxometry classified 96.4% (27/28) of these patients. All operated patients had hippocampal sclerosis. CONCLUSIONS: Hippocampal structural damage is equivocally depicted by spectroscopy. For diagnostic and pre-operative evaluation, hippocampal volumetry and T2-relaxometry provide maximal accuracy. Amygdala quantifications are irrelevant in the pre-operative evaluation but may be useful for diagnostic purposes. Of the three qMRI modalities tested, T2-relaxometry provided the best balance between diagnosis accuracy and time-efficiency to lateralize a sclerotic lesion on the majority of the patients. Cases that remain undecided after T2-relaxometry may benefit from additional measurements based on hippocampal volumetry.