BUBR1 expression in benign oral lesions and squamous cell carcinomas: Correlation with human papillomavirus

Oral squamous Cell carcinoma (OSCC) is the most common head and neck cancer. Only in Brazil, the estimate is for 14,160 new cases in 2009. HPV is associated with increasing risk of oral cancer, but its role in carcinogenesis is still controversial. BUBR1, all important protein in the mitotic spindle assembly checkpoint (SAC), has been associated with some virus-encoded proteins and cancer. The aim of the present study was to evaluate the expression of BUBR1 in non-malignant oral lesions and OSCC with and without metastasis associated with HPV infection. We performed immunohistochemistry for BUBR1 in 70 OSCC biopsies divided into three groups (in situ tumors, invasive tumors without metastasis and invasive tumors with metastasis) with their respective lymph nodes from samples with metastasis and in 16 non-malignant oral lesions. PCR was performed in order to detect HPV DNA. Significantly higher BUBR1 expression associated with shorter survival (p=0.0479) was observed in malignant lesions. There was also it significant correlation (r=1.000) with BUBR1 expression in lesions with metastasis and their lymph nodes. Ninety percent of OSCC and 100% of benign lesions were HPV positive. HPV16 and HVP18 were present in 13 and 24% of HPV-positive OSCC samples, respectively. HPV was more prevalent (76%) in samples with a high BUBR1 expression and the absence of viral DNA had no influence oil BUBR1 expression. These findings suggest that HPV could be associated with overexpression of BUBR1 in OSCC. but not in benign oral lesions.

Expression of cell adhesion proteins and proteins related to angiogenesis and fatty acid metabolism in benign, atypical, and anaplastic meningiomas

Most meningiomas are benign tumours of arachnoidal origin, although a small number have high proliferative rates and invasive properties which complicate complete surgical resection and are associated with increased recurrence rates. Few prognostic indicators exist for meningiomas and further research is necessary to identify factors that influence tumour invasion, oedema and recurrence. Paraffin sections from 25 intracranial meningiomas were analysed for expression of the proteins vascular endothelial growth factor (VEGF), VEGF receptors Flt1 and Flk1, E-cadherin, metalloproteinases 2 and 9 (MMP2, MMP9), CD44, receptor for hyaluronic acid-mediated motility (RHAMM), hyaluronic acid (HA), CD45, cyclooxygenase 2 (COX2), brain fatty acid binding protein (BFABP), Ki67, and proliferating cell nuclear antigen (PCNA). Correlations among protein expression were found for several markers of proliferation (Ki67, PCNA, MI) and microvessel density (MVD). COX2 expression increased with increasing with tumour grade and correlated with Ki67, PCNA, MI, MVD, and BFABP. BFABP expression also correlated with Ki67 and PCNA expression. Relationships were also identified among angiogenic factors (VEGF, Flt1, Flk1) and proliferation markers. Oedema was found to correlate with MMP9 expression and MMP9 also correlated with proliferation markers. No correlations were found for MMP2, E-cadherin, or CD44 in meningiomas. In conclusion Ki67, PCNA, MI, MVD, BFABP, and COX2 were significantly correlated with meningioma tumour grade and with each other. These findings, by correlating both intracellular fatty acid transport and eicosanoid metabolism with tumour proliferation, as determined by Ki67 labelling and mitotic index, suggest fatty acids are involved in the progression of meningiomas.

Warthin Tumor of the Upper Lip: An Unusual Location of a Benign Salivary Gland Tumor

Warthin tumor (papillary cystadenoma lymphomatosum) is a benign salivary gland tumor involving almost exclusively the parotid gland. The lip is a very unusual location for this type of tumor, which develops only rarely in minor salivary glands. The case of 42-year-old woman with Warthin tumor arising in minor salivary glands of the upper lip is reported.

Simpson's paradox: A logically benign, empirically treacherous hydra

This article examines Simpson's paradox as applied to the theory of probabilites and percentages. The author discusses possible flaws in the paradox and compares it to the Sure Thing Principle, statistical inference, causal inference and probabilistic analyses of causation.

Pathologic features of breast cancers in women with previous benign breast disease

To compare pathologic features of the cancers arising after different types of benign breast disease (BBD), we reviewed the invasive breast cancer slides of 169 women with a previous benign biopsy result. Lesions were categorized previously as nonproliferative, proliferative without atypia, or atypical hyperplasia. Pathologic features of the cancers were evaluated without knowledge of the previous BBD category. Estrogen and progesterone receptor immunohistochemistry was performed on available tissue blocks. The median times between a benign result and cancer were 100, 124, and 92 months for women with nonproliferative lesions, proliferative lesions without atypia, and atypical hyperplasia, respectively. Cancers in the 3 groups did not differ significantly in tumor size, axillary lymph node status, or histologic grade, and there was no significant difference in the distribution of histologic types of breast cancer. Lymphatic vessel invasion, extensive intraductal component, and hormone receptor status did not differ among BBD categories. The pathologic features of breast cancers that develop in women with a previous benign biopsy result do not vary according to the histologic category of the previous BBD.

Expression of MUC1 splice variants in benign and malignant ovarian tumours

MUC1 is expressed on the surface of ovarian cancer cells. Nine different splice variants of MUC1 have been described, but no study has reported on the expression of MUC1 iso-forms in human ovarian cancer. Our study compares patterns of expression of MUC1 splice variants of malignant and benign ovarian tumours. Ovarian tissue samples were taken from patients with benign ovarian tumours (n = 34) and from patients who had surgery for primary (n = 47) or recurrent (n = 8) ovarian cancer. RT-PCR for MUC1 splice variants A, B, C, D, X, Y, Z, REP and SEC was performed and their expression compared to clinical and histopathologic parameters. Variants A, D, X, Y and Z were more frequently expressed in malignant than in benign tumours. All primary ovarian cancer cases were positive for variant REP but negative for variant SEC. No significant association of the expression of MUC1 splice variants with the response to chemotherapy or patient survival could be demonstrated. Expression of MUC1 splice variants A, D, X, Y, Z and REP is associated with the presence of malignancy, whereas expression of MUC1/SEC is associated with the absence of malignancy. (C) 2002 Wiley-Liss, Inc.

Present and future pharmacotherapy for benign prostatic hyperplasia

Around 50% of men 51-60 years of age have pathological benign prostatic hyperplasia (BPH). Pharmacotherapy for BPH includes the 5alpha-reductase inhibitor finasteride, and alpha(1)-adrenoceptor antagonists. Finasteride reduces prostate volume and symptom scores, while increasing peak urinary flow rates. The main problem with finasteride treatment is that it increases the incidence of ejaculation disorders. All of the alpha(1)-adrenoceptor antagonists have been shown to reduce symptom scores and increase peak urinary flow rates in BPH. The nonselective alpha(1)-adrenoceptor antagonists (prazosin, terazosin and doxazosin) were developed as antihypertensives, and hypotensive-related side effects are the main problem with these agents in BPH. These side effects can be diminished by reducing peak concentrations of the drugs, as with once-daily alfuzosin, or by using the uroselective antagonist tamsulosin. Phytopharmaceuticals are commonly used in the treatment of BPH, such as saw palmetto berry which has been shown to improve the symptoms and peak urinary flow rate. Androgen receptor antagonists are not used in BPH because of their adverse effects. Newer drugs under development for the treatment of BPH include alpha(1)-adrenoceptor antagonists that show more selectivity for alpha(1A)-adrenoceptors than tamsulosin, combined 5alpha-reductase/alpha(1)-adrenoceptor inhibitors and combined type 1/type 2 5alpha-reductase inhibitors. New targets for the drug treatment of BPH include indothelin, growth factors, estrogens and the phosphodiesterase isoenzymes.

Auditory event-related potentials in children with benign epilepsy with centro-temporal spikes

Benign focal epilepsy in childhood with centro-temporal spikes (BECTS) is one of the most common forms of idiopathic epilepsy, with onset from age 3 to 14 years. Although the prognosis for children with BECTS is excellent, some studies have revealed neuropsychological deficits in many domains, including language. Auditory event-related potentials (AERPs) reflect activation of different neuronal populations and are suggested to contribute to the evaluation of auditory discrimination (N1), attention allocation and phonological categorization (N2), and echoic memory (mismatch negativity – MMN). The scarce existing literature about this theme motivated the present study, which aims to investigate and document the existing AERP changes in a group of children with BECTS. AERPs were recorded, during the day, to pure and vocal tones and in a conventional auditory oddball paradigm in five children with BECTS (aged 8–12; mean = 10 years; male = 5) and in six gender and age-matched controls. Results revealed high amplitude of AERPs for the group of children with BECTS with a slight latency delay more pronounced in fronto-central electrodes. Children with BECTS may have abnormal central auditory processing, reflected by electrophysiological measures such as AERPs. In advance, AERPs seem a good tool to detect and reliably reveal cortical excitability in children with typical BECTS.

Prostatic Artery Embolization in the Treatment of Benign Prostatic Hyperplasia: Short and Medium Follow-Up

To evaluate the short and mid-term results of prostatic artery embolization in patients with benign prostatic embolization. Retrospective study between March 2009 and June 2011 with 103 patients (mean age 66.8 years, 50-85) that met our inclusion criteria with symptomatic benign prostatic hyperplasia. The clinical outcome was evaluated by the International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function, prostate volume (PV), prostate-specific antigen (PSA), peak urinary flow (Q(max)), and post-void residual volume (PVR) measurements at 3 and 6 months, 1 year, 18 months, and 2 years after PAE and comparison with baseline values was made. Technical and clinical successes, as well as poor clinical outcome definitions, were previously defined. In this review, we evaluate the short and mid-term clinical outcomes and morbidity of patients treated only with non-spherical polyvinyl alcohol. Six months after the procedure, the PV decreased about 23%, IPSS changed to a mean value of 11.95 (almost 50% reduction), the QoL improved slightly more than 2 points, the Q(max) changed to a mean value of 12.63mL/s, the PVR underwent a change of almost half of the baseline value, and the PSA decreased about 2.3ng/mL. In the mid-term follow-up and comparing to the baseline values, we still assisted to a reduction in PV, IPSS, QoL, PVR, and PSA, and an increase in Q(max). Prostatic Artery Embolization is a safe procedure with low morbidity that shows good short- and mid-term clinical outcome in our institution.

Embolisation of Prostatic Arteries as Treatment of Moderate to Severe Lower Urinary Symptoms (LUTS) Secondary to Benign Hyperplasia: Results of Short- and Mid-Term Follow-Up

OBJECTIVES: To evaluate the short- and medium-term results of prostatic arterial embolisation (PAE) for benign prostatic hyperplasia (BPH). METHODS: This was a prospective non-randomised study including 255 patients diagnosed with BPH and moderate to severe lower urinary tract symptoms after failure of medical treatment for at least 6 months. The patients underwent PAE between March 2009 and April 2012. Technical success is when selective prostatic arterial embolisation is completed in at least one pelvic side. Clinical success was defined as improving symptoms and quality of life. Evaluation was performed before PAE and at 1, 3, 6 and every 6 months thereafter with the International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF), uroflowmetry, prostatic specific antigen (PSA) and volume. Non-spherical polyvinyl alcohol particles were used. RESULTS: PAE was technically successful in 250 patients (97.9 %). Mean follow-up, in 238 patients, was 10 months (range 1-36). Cumulative rates of clinical success were 81.9 %, 80.7 %, 77.9 %, 75.2 %, 72.0 %, 72.0 %, 72.0 % and 72.0 % at 1, 3, 6, 12, 18, 24, 30 and 36 months, respectively. There was one major complication. CONCLUSIONS: PAE is a procedure with good results for BPH patients with moderate to severe LUTS after failure of medical therapy. KEY POINTS: • Prostatic artery embolisation offers minimally invasive therapy for benign prostatic hyperplasia. • Prostatic artery embolisation is a challenging procedure because of vascular anatomical variations. • PAE is a promising new technique that has shown good results.

Prostatic Arterial Embolization to Treat Benign Prostatic Hyperplasia

PURPOSE: To evaluate whether prostatic arterial embolization (PAE) might be a feasible procedure to treat lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Fifteen patients (age range, 62-82 years; mean age, 74.1 y) with symptomatic BPH after failure of medical treatment were selected for PAE with nonspherical 200-μm polyvinyl alcohol particles. The procedure was performed by a single femoral approach. Technical success was considered when selective prostatic arterial catheterization and embolization was achieved on at least one pelvic side. RESULTS: PAE was technically successful in 14 of the 15 patients (93.3%). There was a mean follow-up of 7.9 months (range, 3-12 months). International Prostate Symptom Score decreased a mean of 6.5 points (P = .005), quality of life improved 1.14 points (P = .065), International Index of Erectile Function increased 1.7 points (P = .063), and peak urinary flow increased 3.85 mL/sec (P = .015). There was a mean prostate-specific antigen reduction of 2.27 ng/mL (P = .072) and a mean prostate volume decrease of 26.5 mL (P = .0001) by ultrasound and 28.9 mL (P = .008) by magnetic resonance imaging. There was one major complication (a 1.5-cm(2) ischemic area of the bladder wall) and four clinical failures (28.6%). CONCLUSIONS: In this small group of patients, PAE was a feasible procedure, with preliminary results and short-term follow-up suggesting good symptom control without sexual dysfunction in suitable candidates, associated with a reduction in prostate volume.

Benign and malignant neoplasias in 261 necropsies for HIV-positive patients in the period of 1989 to 2008

Considering that there are some studies with autopsies from AIDS describing only malignant neoplasias and that changes can occur after the introduction of Highly Active Antiretroviral Therapy (HAART), our objectives were to analyze the frequency of benign and malignant neoplasms in AIDS patients in the periods of both pre- and post-HAART. This is a retrospective study with 261 autopsies of HIV-positive patients between 1989 and 2008 in Uberaba, Brazil. Sixty-six neoplasms were found (39 benign, 21 malignant and six premalignant) in 58 patients. The most frequent malignant neoplasms were lymphoid, in 2.7% (four Non-Hodgkin lymphoma, one Hodgkin, one multiple myeloma and one plasmablastic plasmacytoma), and Kaposi's Sarcoma, in 2.3% (six cases). The most frequent benign neoplasms were hepatic hemangiomas in 11 (4.2%) of 261 cases and uterine leiomyoma in 11 (15.7%) of 70 woman. In the pre-HAART period eight (9.8%) benign neoplasias and four (4.9%) malignant occurred in 82 patients; in the post-HAART period, 29 (16.2%) benign and 17 (9.5%) malignant were present; however, the differences were not significant. We conclude that the introduction of HAART in our region doesn't look to have modified the frequency of neoplasms occurring in patients with HIV.

Analysis of the Generators of Epileptic Activity in Early-Onset Childhood Benign Occipital Lobe Epilepsy

Objective: The Panayiotopoulos type of idiopathic occipital epilepsy has peculiar and easily recognizable ictal symptoms, which are associated with complex and variable spike activity over the posterior scalp areas. These characteristics of spikes have prevented localization of the particular brain regions originating clinical manifestations. We studied spike activity in this epilepsy to determine their brain generators. Methods: The EEG of 5 patients (ages 7–9) was recorded, spikes were submitted to blind decomposition in independent components (ICs) and those to source analysis (sLORETA), revealing the spike generators. Coherence analysis evaluated the dynamics of the components. Results: Several ICs were recovered for posterior spikes in contrast to central spikes which originated a single one. Coherence analysis supports a model with epileptic activity originating near lateral occipital area and spreading to cortical temporal or parietal areas. Conclusions: Posterior spikes demonstrate rapid spread of epileptic activity to nearby lobes, starting in the lateral occipital area. In contrast, central spikes remain localized in the rolandic fissure. Significance: Rapid spread of posterior epileptic activity in the Panayitopoulos type of occipital lobe epilepsy is responsible for the variable and poorly localized spike EEG. The lateral occipital cortex is the primary generator of the epileptic activity.

Origin of Frontal Lobe Spikes in the Early Onset Benign Occipital Lobe Epilepsy (Panayiotopoulos Syndrome)

Objective: Early onset benign occipital lobe epilepsy (Panayiotopoulos syndrome [PS]) is a common and easily recognizable epilepsy. Interictal EEG spike activity is often multifocal but most frequently localized in the occipital lobes. The origin and clinical significance of the extra-occipital spikes remain poorly understood. Methods: Three patients with the PS and interictal EEG spikes with frontal lobe topography were studied using high-resolution EEG. Independent component analysis (ICA) was used to decompose the spikes in components with distinct temporal dynamics. The components were mapped in the scalp with a spline-laplacian algorithm. Results: The change in scalp potential topography from spike onset to peak, suggests the contribution of several intracranial generators, with different kinetics of activation and significant overlap. ICA was able to separate the major contributors to frontal spikes and consistently revealed an early activating group of components over the occipital areas in all the patients. The local origin of these early potentials was established by the spline-laplacian montage. Conclusions: Frontal spikes in PS are consistently associated with early and unilateral occipital lobe activation, suggesting a posteroanterior spike propagation. Significance: Frontal spikes in the PS represent a secondary activation triggered by occipital interictal discharges and do not represent an independent focus.