Lymphatic Vessel Density and VEGF-C Expression are Significantly Different Among Benign and Malignant Thyroid Lesions

Thyroid cancer is the most frequent endocrine neoplasia worldwide. The route for metastasis and loco-regional invasion preferentially occurs by lymphatic vessels. For this reason, the assessment of lymphatic vessel density (LVD) is supposed to represent both a prognostic parameter and also a potential therapeutic target. In order to evaluate the value of LVD in benign and malignant thyroid lesions, we analyzed 110 thyroidectomy specimens using D2-40, a specific marker for lymphatic vessels and vascular endothelial growth factor C (VEGF-C), the most potent molecule of lymphatic proliferation. LVD was significantly different between papillary and follicular carcinomas in total (p = 0.045) and peritumoral area (p = 0.042). Follicular adenoma and follicular carcinoma showed an important difference of intra- (p = 0.019) and peritumoral (p = 0.033) LVD. VEGF-C was more markedly expressed in malignancies than in benignant lesions (p = 0.0001). Almost all cancers with high positive VEGF-C expression also exhibited increased peritumoral LVD (p = 0.049) when compared with the benignant lesions. Indeed, the high peritumoral LVD of malignant thyroid lesions is an important finding for surgery planning and supports the practice of total thyroidectomy in malignant thyroid neoplasm`s since the lymphatic peritumoral vessels definitely are an escape path for tumor cells.

Oral lesions in lupus erythematosus-cytokines profiles of inflammatory infiltrate

Background: Lupus erythematosus (LE) is a chronic inflammatory disease. Presence of type 1 cytokines in cutaneous discoid lesions suggests that they may be critical for induction, development and maintenance of these manifestations. Type 2 cytokines in combination with local interferon gamma (INF-gamma) are thought to be related to the physiopathology of cutaneous LE. Cytokines profiles are still unknown in oral LE lesions. Materials and Methods: Expression of Th1 and Th2 cytokines (including IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor alpha (TNF-alpha) and INF-gamma was investigated and compared in 29 biopsies of intra-oral (sun-protected) and labial lesions (sun-exposed) of LE using immunohistochemistry. Results: Inflammatory infiltrate of LE lesions was strongly positive for IFN-gamma (97%) and TNF-alpha (90%), both Th1 type cytokines. Interleukin-10, a Th2 cytokine was also strongly expressed. Other cytokines were only mildly positive. Cytokines patterns were similar in intra-oral (sun-covered) and labial (sun-exposed) LE lesions. Conclusions: Oral LE lesions are associated with both type 1 and type 2 cytokines, characterized by stronger expression of INF-gamma, TNF-alpha and IL-10. These findings suggest that although ultraviolet (UV) light is involved in the induction of LE lesions, mechanisms of lesions formation may be similar in sun-exposed as well as sun-covered areas.

Estrogen receptor-positive breast carcinomas in younger women are different from those of older women: A pathological and immunohistochemical study

The higher frequency of triple-negative and HER-2-positive tumors detected in younger patients has been suggested as an explanation for the more aggressive tumor types observed in this age group. However, estrogen receptor (ER)-positive tumors are the most frequent subtype of breast carcinomas identified, even in younger patients. In this retrospective study, the morphological and immunohistochemical profiles of ER-positive breast carcinomas from women 35 yrs and younger that were diagnosed between 1997 and 2007 were evaluated. From these cases, 213 were selected based on the availability of pathology reports and paraffin blocks. For comparison, 117 consecutive cases of breast carcinomas diagnosed in patients >60 yrs from 2006 were included. Paraffin-embedded tumors were stained for expression of ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2). Ki-67 antigen, epidermal growth factor receptor (EGFR), cytokeratin 5/6, p53, vimentin, CD117, and p63 using tissue microarrays. ER-positive carcinomas were diagnosed in 120 (56.1%) samples of the younger patient group and in 92 (78.6%) samples of the older patient group. Of these ER-positive carcinomas, 48 (40%) from the younger patient group presented the subtype luminal A, compared with 53 (57.6%) from the older patient group (p=0.01). Tumors from the younger patient group were also associated with increased vascular involvement, co-expression of HER-2, and decreased expression of CD117. These results highlight differences in expression markers and the pathology of ER-positive tumors detected in younger women, with a notable characteristic being co-expression of HER-2. (C) 2010 Elsevier Ltd. All rights reserved.

Lichen planus sialadenitis: a mucosal analog of lichen planopilaris and lichen planoporitis

Lichen planus (LP) is the most prevalent dermatological disorder with oral manifestation. Oral lesions comprise a broad spectrum of clinical presentations. We report the case of a 56-year-old woman who presented erosive LP on the buccal and lower lip mucosae. Besides typical erosions, small white keratotic papules on an erythematosus background on the lower lip mucosa were observed. Biopsy of lower lip lesions showed an unusual histopathological presentation consisting of a lichenoid inflammation targeted to salivary gland ducts. This is probably a salivary gland analog of lichen planopilaris and lichen planoporitis.

E-cadherin and beta-catenin Loss of Expression Related to Bone Metastasis in Prostate Cancer

Objectives: E-cadherin and beta-catenin are adhesion molecules responsible for the maintenance of normal epithelial cell phenotype. A disturbance in epithelial cell adhesion, which leads to a more invasive and metastatic phenotype, is a hallmark of tumor progression. Several immunohistochemical studies have reported a strong correlation between loss of their expression to higher stage and grade in prostate carcinoma, but their influence in metastatic process is not yet known. The aim of this study is to verify the role of adhesion molecules in the progression of prostate cancer (PC), assessing the expression of E-cadherin and beta-catenin in bone metastasis. Materials and Methods: Twenty-eight bone metastases of prostate carcinoma were submitted to immunohistochemistry analysis for E-cadherin and beta-catenin expression. In 6 patients, we were able to assess the expression of the adhesion molecules in the primary tumors and their respective metastases. The definition of normal expression for both antibodies was strong and diffuse expression in more than 70% of tumor cells. Results: In bone metastases, there was loss of expression of E-cadherin and beta-catenin in 86% and 82%, respectively. Among the primary tumors, E-cadherin and beta-catenin expression was normal in 83% and 50% cases, respectively. Considering the 6 patients with paired primary and bone metastasis, we found loss of expression for both E-cadherin and beta-catenin in most of the cases. Conclusions: Comparing primary PC and its metastasis, we showed persistent loss of E-cadherin and beta-catenin expression. This phenomenon may be related to metastatic potential in PC, because we have shown underexpression for E-cadherin and beta-catenin in 86% and 82% of bone metastases.

Maternal alcohol consumption may influence cord blood ascorbic acid concentration: findings from a study of Brazilian mothers and their newborns

Studies that have investigated ascorbic acid (AA) concentrations in cord blood have pointed to significant associations with maternal blood AA concentrations. smoking, age, diet, type of delivery, duration of gestation, fetal distress and birth weight. The aim of the present study was to determine the relationship between cord blood AA concentrations in newborns and maternal characteristics. A total of 117 Brazilian healthy parturients were included in this cross-sectional study. The concentrations of AA in blood were determined by the HPLC method. Data concerning socio-economic, demographic, obstetric, nutritional and health characteristics of the parturients, including alcohol consumption and smoking habit, were assessed by a standardised questionnaire. A FFQ was used to investigate the intake of foods rich in vitamin C. Cord blood AA concentration was significantly correlated with per capita income (r 0.26; P=0.005), maternal blood AA concentration (r 0.48; P<0.001) and maternal vitamin C-rich food intake score (r 0.36; P<0.001). The linear regression model including maternal AA concentration, alcohol consumption, smoking, parity, vitamin C-rich food intake score and per capita income explained 31.13% of the variation in cord blood AA concentrations in newborns. We recommend further experimental studies to assess the effects of ethanol on placental AA uptake, and epidemiological cohort studies to evaluate in detail the influence of maternal alcohol consumption on cord blood AA concentrations.

Brain abscess due to viridans streptococci in a severely immunosuppressed HIV-infected patient

We report a case of viriclans streptococcus brain abscess in a severely immunosuppressed HIV-infected patient with a history of chronic sinusitis. A 39-year-old homosexual man showed mental confusion and worsening of a frontal brain lesion after two weeks with antitoxoplasma therapy. Empiric treatment for central nervous system tuberculosis and pyogenic brain abscess was started. He underwent surgical drainage and the diagnosis of brain abscess due to viriclans streptococci was confirmed. All empiric treatments were stopped and ceftriaxone was used for eight weeks, showing complete clinical and radiological resolution. Although infrequent, viriclans streptococci, a common pyogenic aetiology of brain abscess in immunocompetent patients, should be considered in the differential diagnosis of brain lesions in AIDS patients.

An MRI-based approach for the measurement of the dorsolateral prefrontal cortex in humans

The dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of mental disorders. Previous region-of-interest MRI studies that attempted to delineate this region adopted various landmarks and measurement techniques, with inconsistent results. We developed a new region-of-interest measurement method to obtain morphometric data of this region from structural MRI scans, taking into account knowledge from cytoarchitectonic postmortem studies and the large inter-individual variability of this region. MRI scans of 10 subjects were obtained, and DLPFC tracing was performed in the coronal plane by two independent raters using the semi-automated software Brains2. The intra-class correlation coefficients between two independent raters were 0.94 for the left DLPFC and 0.93 for the right DLPFC. The mean +/- S.D. DLPFC volumes were 9.23 +/- 2.35 ml for the left hemisphere and 8.20 +/- 2.08 ml for the right hemisphere. Our proposed method has high inter-rater reliability and is easy to implement, permitting the standardized measurement of this region for clinical research applications. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Apoptosis, cell proliferation and modulation of cyclin-dependent kinase inhibitor p21(cip1) in vascular remodelling during vein arterialization in the rat

Neo-intima development and atherosclerosis limit long-term vein graft use for revascularization of ischaemic tissues. Using a rat model, which is technically less challenging than smaller rodents, we provide evidence that the temporal morphological, cellular, and key molecular events during vein arterialization resemble the human vein graft adaptation. Right jugular vein was surgically connected to carotid artery and observed up to 90 days. Morphometry demonstrated gradual thickening of the medial layer and important formation of neo-intima with deposition of smooth muscle cells (SMC) in the subendothelial layer from day 7 onwards. Transmission electron microscopy showed that SMCs switch from the contractile to synthetic phenotype on day 3 and new elastic lamellae formation occurs from day 7 onwards. Apoptosis markedly increased on day 1, while alpha-actin immunostaining for SMC almost disappeared by day 3. On day 7, cell proliferation reached the highest level and cellular density gradually increased until day 90. The relative magnitude of cellular changes was higher in the intima vs. the media layer (100 vs. 2 times respectively). Cyclin-dependent kinase inhibitors (CDKIs) p27(Kip1) and p16(INKA) remained unchanged, whereas p21(Cip1) was gradually downregulated, reaching the lowest levels by day 7 until day 90. Taken together, these data indicate for the first time that p21(Cip1) is the main CDKI protein modulated during the arterialization process the rat model of vein arterialization that may be useful to identify and validate new targets and interventions to improve the long-term patency of vein grafts.

Laparoscopic resection of uncinate process of the pancreas

Solid pseudopapillary neoplasm of the pancreas is an uncommon but distinctive pancreatic neoplasm with low metastatic potential [1]. Therefore, whenever feasible, an organ-preserving operation should be performed. As previously reported, women with solid pseudopapillary neoplasm of the pancreas may be best treated by more conservative procedures [2]. Recently, laparoscopic pancreatic resections became more common and are being performed in highly specialized centers. There are only six cases of laparoscopic resection for solid pseudopapillary neoplasm of pancreas published in the English literature and, to our knowledge, laparoscopic resection of uncinate process of the pancreas has never been reported [3-6]. This video demonstrates the technical aspects of a totally laparoscopic resection of the uncinate process of the pancreas in a patient with solid pseudopapillary neoplasm. A 26-year-old woman with a 4-cm solid pseudopapillary pancreatic neoplasm was referred for surgical treatment. According to preoperative echoendoscopy, there was a safe margin between neoplasm and main pancreatic duct. The patient was placed in supine position with the surgeon standing between her legs. Four trocars, one 10-mm and three 5-mm, were used. At inspection, the inferior vena cava, transverse colon, duodenum, and pancreas are clearly identified. A Kocher maneuver was performed with complete exposure of pancreatic head and uncinate process. The uncinate process was dissected from the superior mesenteric vein and venous branches were divided between metallic clips or by use of laparoscopic coagulation shears (LCS; Ethicon Endo Surgery Industries, Cincinnati, OH, USA). Blood supply of the duodenum was preserved by ligature of small pancreatic branches from inferior pancreatoduodenal artery. Transection of pancreatic parenchyma was performed using laparoscopic coagulation shears, which is an effective tool for cutting the pancreas [7, 8]. Surgical specimen was removed through a suprapubic incision inside a retrieval bag. A hemostatic absorbable tissue (Surgicel; Ethicon Inc., Cincinnati, OH) was placed in the cutting pancreatic surface, and one round 19F Blake abdominal drain (Ethicon) was left in place. Operative time was 180 minutes and blood loss estimated in 40 ml with no blood transfusion. Hospital stay was 4 days. The patient did not have postoperative pancreatitis or pancreatic leakage, and the abdominal drain was removed on the tenth postoperative day. Final pathology confirmed the diagnosis of solid pseudopapillary neoplasm of pancreas with free surgical margins. The patient was well and asymptomatic 2 months after the procedure. Laparoscopic resection of uncinate process of the pancreas is safe and feasible and should be considered for patients suffering from pancreatic neoplasms.

Clear cell sarcoma of the mediastinum

A 59-year-old woman presented with a large mediastinal mass. At thoracotomy, the mass was found tightly adherent to the esophageal wall and right lower lobe of the lung. Histological examination showed a solid tumor composed of closely packed nests of cells with clear and eosinophilic cytoplasm, which were strongly and diffusely positive for S 100 protein but negative for HMB45 and Melan-A. The diagnosis of clear cell sarcoma was supported by demonstrating the presence of an EWS gene rearrangement by fluorescence in situ hybridization. There was no evidence that this lesion represented metastatic disease. To the best of our knowledge, primary mediastinal clear cell sarcoma has not been previously reported in the literature. We present the case and discuss the differential diagnosis. (C) 2009 Elsevier Inc. All rights reserved.

Effects of Chronic Exposure to Crack Cocaine on the Respiratory Tract of Mice

Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronchiolar and alveolar macrophage cell density, alveolar hemosiderin content, and in addition determined the vasoconstriction index and the wall thickness of pulmonary arteries. The serum cocaine level was 212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium increased in crack-exposed animals, and the nasal and bronchial epithelium thickness decreased significantly. The alveolar hemosiderin content and the alveolar and bronchiolar macrophage cell density increased in animals exposed to crack. The vasoconstriction index increased in the pulmonary arteries of the exposed group. Chronic crack cocaine inhalation causes extensive histological changes along the entire respiratory tract.

Cardiopulmonary Manifestations of Hepatosplenic Schistosomiasis

Background -Schistosomiasis is a highly prevalent disease with >200 million infected people. Pulmonary hypertension is one of the pulmonary manifestations in this disease, particularly in its hepatosplenic presentation. The aim of this study was to determine the prevalence of pulmonary hypertension in schistosomiasis patients with the hepatosplenic form of the disease. Methods and Results -All patients with hepatosplenic schistosomiasis followed up at the gastroenterology department of our university hospital underwent echocardiographic evaluation to search for pulmonary hypertension. Patients presenting with systolic pulmonary artery pressure >40 mm Hg were further evaluated through right heart catheterization. Our study showed an 18.5% prevalence of patients with elevated systolic pulmonary artery pressure at echocardiography. Invasive hemodynamics confirmed the presence of pulmonary hypertension in 7.7% (95% confidence interval, 3.3 to 16.7) of patients, with a prevalence of precapillary (arterial) pulmonary hypertension of 4.6% (95% confidence interval, 1.5 to 12.7). Conclusions -Our study reinforces the role of echocardiography as a screening tool in the investigation of pulmonary hypertension, together with the need for invasive monitoring for a proper diagnosis. We conclude that hepatosplenic schistosomiasis may account for one of the most prevalent forms of pulmonary hypertension worldwide, justifying the development of further studies to evaluate the effect of specific pulmonary hypertension treatment in this particular form of the disease. (Circulation. 2009; 119: 1518-1523.)

Toll-like receptor activity in Recurrent Aphthous Ulceration

Toll-like receptors (TLR) are membrane proteins that recognize conserved molecules derived from bacterial, virus, fungal or host tissues. Activation of TLRs causes the production of cytokines that mediate inflammatory responses and drive T helper (Th) 1 and 2 cell development. As an exaggerated Th1 immune response is supposed to be involved in pathogenesis of Recurrent Aphthous Ulceration (RAU), we suggest that RAU patients may have an imbalance in TLR pathways. To study the function of TLR activation ex vivo, peripheral blood mononuclear cells (PBMCs) from RAU patients (n = 17) and controls (n = 17) were exposed to TLR2 [lipoteichoic acid (LTA), heat-killed Listeria monocytogenes (HKLM) and PamC3CSK4], TLR3 [Poly(I:C)], TLR4 [lipopolysaccharide (LPS)], TLR5 (flagellin) and TLR7 (imiquimod) ligands, and the time course of supernatant tumor necrosis factor-alpha (TNF-alpha) levels was quantified by enzyme-linked immunosorbent assay. In addition, serological and salivary TNF-alpha and soluble CD14 levels were quantified. The TNF-alpha produced by PBMCs in contact with each TLR ligand and autologous serum or saliva at the same time was also investigated. The data were analyzed by statistical multivariate tests. The control group had a higher response to LTA, whereas RAU had a higher response to HKLM. LTA and LPS interfered with the salivary stimulation of the RAU PBMC and HKLM with the stimulation of the control. Autologous serum was capable of inhibiting TLR2 responsiveness to LTA and enhancing LPS stimulation. Salivary and serological levels of sCD14 and TNF-alpha were not significantly different. Recurrent Aphthous Ulceration patients have an anomalous activity of the TLR2 pathway that probably influences the stimulation of an abnormal Th1 immune response.

UPGRADING THE GLEASON SCORE IN EXTENDED PROSTATE BIOPSY: IMPLICATIONS FOR TREATMENT CHOICE

Purpose: To determine the incidence of overestimation of Gleason score (GS) in extended prostate biopsy, and consequently circumventing unnecessary aggressive treatment. Methods and Materials: This is a retrospective study of 464 patients who underwent prostate biopsy and radical prostatectomy between January 2001 and November 2007. The GS from biopsy and radical prostatectomy were compared. The incidence of overestimation of GS in biopsies and tumor volume were studied. Multivariate analysis was applied to find parameters that predict upgrading the GS in prostate biopsy. Results: The exact agreement of GS between prostate biopsy and radical prostatectomy occurred in 56.9% of cases. In 29.1% cases it was underestimated, and it was overestimated in 14%. One hundred and six (22.8%) patients received a diagnosis of high GS (8, 9, or 10) in a prostate biopsy. In 29.2% of cases, the definitive Gleason Score was 7 or lower. In cases in which GS was overestimated in the biopsy, tumors were significantly smaller. In multivariate analysis, the total percentage of tumor was the only independent factor in overestimation of GS. Tumors occupying less than 33% of cores had a 5.6-fold greater chance of being overestimated. Conclusion: In the extended biopsy era and after the International Society of Urological Pathology consensus on G, almost one third of tumors considered to have high GS at the biopsy may be intermediate-risk cancers. In that condition, tumors are smaller in biopsy. This should be remembered by professionals involved with prostate cancer to avoid overtreatment and undesirable side effects. (c) 2009 Elsevier Inc.