Synchronous Bilateral Breast Carcinoma in a Patient with Cowden Syndrome: A Case Report with Morphologic,Immunohistochemical and Genetic Analysis

Abstract: Synchronous bilateral breast carcinoma (SBBC) and early onset are important characteristics of hereditary cases. The lifetime risk for breast carcinoma in Cowden syndrome (CS) is estimated to be 25–50%. We reported a 44‐year‐old woman presenting SBBC and characteristic mucocutaneous lesions of CS, confirmed by PTEN gene mutation analysis. Bilateral modified mastectomy and axillary dissection were performed. Histopathologic examination revealed a moderate‐differentiated invasive ductal carcinoma with mixed features of luminal A immunophenotype (Estrogen and/or Progesterone Receptors >50% and/or Ki67 < 30% of positive cells). The skin lesions showed the characteristic findings of tricholemmoma. Lack of PTEN expression was observed in all specimens. Sequencing analysis confirmed the presence of PTEN splice‐acceptor site mutation in intron 8 (c.1027‐2A>G), a germline mutation which had not been previously reported in CS. The patient received adjuvant chemotherapy and tamoxifen for 5 years. After 5 years of follow‐up, she persists recurrence‐free. SBBC with early onset suggests a hereditary predisposition. Thus, analysis of PTEN expression abnormality, easily assessed by immunohistochemistry, may be of clinical value to screen those patients with CS.     

Use of 201Tl SPECT Imaging to Assess the Response to Therapy in Patients with High Grade Gliomas

Purpose. To assess the potential role of ²⁰¹Tl single photon emission tomography (201-Thallium SPECT) when compared to other imaging modalities in the evaluation of the response to therapy in high grade gliomas. Materials and methods. Twenty patients with histologically proved high grade glioma have been included: 15 with glioblastoma (GBM), 3 with anaplastic astrocytoma (AA) and 2 with anaplastic oligoastrocytoma (AOA). Patients were assessed by ²⁰¹Tl SPECT, computed tomography (CT) and magnetic resonance imaging (MRI) at (a) either at the moment of maximum response to first line chemotherapy, or after the completion of radiotherapy and chemotherapy if post-surgical residual disease was present, and (b) after the completion of second line chemotherapy if disease persisted, or either a relapse or disease progression was confirmed. Final response was evaluated according to the McDonald criteria, and by comparing SPECT, CT and MRI results. Results. According to the McDonald criteria, clinical response after first line chemotherapy was 5 partial response, 7 stable disease and 8 progressive disease. Evaluation by ²⁰¹Tl SPECT was in agreement with such criteria in nearly all patients (90%). MRI findings closely agreed with the clinical follow-up. CT findings clearly differed from those observed by SPECT and MRI. After second line therapy, 10 patients progressed, 3 had stable disease and 7 had partial response. ²⁰¹Tl SPECT agreed with the clinical status in 89% cases, whereas MRI and, specially CT, fared significantly lower. Conclusion. Compared to conventional neuroimaging, ²⁰¹Tl SPECT added valuable information in the assessment of the response to therapy in our patient population; whenever findings were not conclusive and in the case of disagreement between CT and MRI findings.     

Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy

The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4,745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. 111In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the following week. These preliminary results indicate the feasibility of targeting activated lymphocytes with somatostatin receptor imaging in the detection of cardiac allograft rejection. Somatostatin receptor imaging may predict impending rejection at least 1 week before the endomyocardial biopsy becomes positive. The late appearance of diagnostic endomyocardial biopsy probably reflects a lag-time between lymphocytic activation and induction of myocyte damage. Furthermore, somatostatin receptor imaging at 4 h may in any case allow earlier intervention in the event of rejection, given the time required for histological processing of endomyocardial biopsy.     

Is avoidance of surgery possible in patients with perimenopausal ovarian tumors using transvaginal ultrasound and duplex color Doppler sonography?

A total of 108 cases of small perimenopausal ovarian tumors (largest diameter, less than 7 cm) were evaluated by transvaginal sonography and duplex color Doppler sonography; 101 had criteria for benignity and 7 for malignancy. All cysts were punctured and aspirated to avoid unnecessary surgery (benign cases) and establish the cytologic diagnosis as well as to avoid the risk of leakage (malignant cases). Recurrence rate of benign punctured cysts was 25% within 1 year of follow up. No difference in recurrent rate was seen between pre- and postmenopausal patients (19 of 56 cases in the premenopausal group, and five of 28 cases in the postmenopausal group). The larger the cyst, the greater the risk of recurrence. Puncture and aspiration of seven sonographically established malignant tumors allowed cytologic diagnosis before surgery, and no evidence of leakage was noted at the time of surgery. No significant differences were observed between cytologic and histopathologic findings in cases that went to surgery. Puncture and aspiration of small endometriomas (17 cases) was found to be inefficient for therapeutic purposes. Finally, owing to the high percentage of unsatisfactory cytologic results (20%) with cyst aspiration, vaginal and color Doppler sonography seemed more efficient in distinguishing between benignity and malignancy.     

Seroprevalence of varicella among children and adolescents in Valencia, Spain. Reliability of the parent's reported history and the medical file for identification of potential candidates for vaccination

This study assessed the seroprevalence of varicella antibodies in children and adolescents in Spain and evaluated the reliability of two methods for detecting susceptible individuals: (1) parental-reported history of varicella and (2) medically-documented histories maintained by the pediatrician. A total of 186 children (6 to 15 years of age) were recruited in 13 pediatric offices of Valencia, Spain. A brief case report form was completed including previous history of varicella referred by the parents, and a 5 mL blood sample was obtained. The pediatrician medical file was reviewed for antecedent of varicella. The overall prevalence of varicella antibodies was 84% and 88% in the 6-9 years and 10-15 years age brackets, respectively. The predictive value of a negative history of varicella disease was 48% by parental recall (52% "false negative"), and only 26% by medical record (74% "false negative"). However, the positive predictive value of a positive parental reported history or a positive medically-documented history was 95%. The most effective strategy for varicella vaccination of older children and adolescents in Spain will be to immunize those individuals with a lack of positive (unknown or negative) history of disease.     

Treatment of chronic anal fissure

Current treatment of chronic anal fissure continues to be based on conventional conservative measures in a high percentage of cases. What is known as chemical sphincterotomy aims to achieve a temporary decrease of anal pressures that allows fissures to heal. There are various alternatives such as nitroglycerine or diltiazem ointment and botulinum toxin injections. However, because of collateral effects and recurrences in the medium term, the definitive role of these treatments remains to be elucidated. Nevertheless, chemical sphincterotomy should be the first option in patients with a high risk of incontinence. "Open" or "closed" lateral internal sphincterotomy performed in the ambulatory setting with local anesthesia can currently be considered the ideal treatment of chronic anal fissure refractory to conservative measures so long as the patient is informed about the risk of minor incontinence. This procedure provides rapid and permanent recovery in more than 95% of patients. There is evidence demonstrating that the incontinence rate is related to the extent of the lateral internal sphincterotomy and consequently the extent of this procedure should be reduced to the length of the fissure.     

Health impact evaluation of particle air pollution in five Spanish cities. European APHEIS project

BACKGROUND: The health effects of air pollution have been analyzed in numerous studies over recent years, thus having made it possible to quantify the relationship between the two. This study is aimed at analyzing the theoretical benefits which would be achieved by meeting the air quality objectives set forth under EC Directive 1999/30/EC with regard to suspended particles. METHODS: The exposure measurement was taken for Black Smoke (Barcelona, Bilbao, Valencia) and suspended particles under 10 microm (PM10) (Bilbao, Madrid y Sevilla). The health indicators calculated were the mortality due to all causes and respiratory and cardiovascular causes, and emergency hospital admissions and mortality due to respiratory and cardiovascular causes. In the case of PM10 the impact has been calculated because its effects to short-term, within a period of up to 40 days following exposure, and to long-term. For Black Smoke the effects only has been calculated to short-term. RESULTS: The daily levels of PM10 from exceeding 50 microg/m3 in Bilbao, Madrid and Sevilla cause the earlier death of 1.4/100,000 individuals per year because its effects. The effect within a period of up to 40 days following exposure is of 2.8 deaths/100,000. The total number of deaths per year which may be later due to long-term exposure if the yearly average is lowered to 20 microg/m3 is 68/100,000. CONCLUSIONS: The health impact of the current air pollution levels is quantifiable and is not insignificant. APHEIS and the impact evaluations may be of aid in healthcare planning and environmental policies.     

trans-Resveratrol, a natural antioxidant from grapes, increases sperm output in healthy rats

trans-Resveratrol was reported to have health benefits including anticarcinogenic effects and protection against cardiovascular disease. One of the mechanisms by which it exerts its action is through modulating the estrogen response systems. Because estrogen is involved in male reproductive biology, we investigated the effect of trans-resveratrol on testis and spermatogenesis. Adult male rats were divided into 2 groups. The treated group was administered by gavage 20 mg/(kg . d) of trans-resveratrol suspended in 10 g/L of carboxymethylcellulose for 90 d, whereas the control group received only carboxymethylcellulose during the same period. The relative weight of testes did not differ between the groups. However, the diameter of the seminiferous tubules was significantly reduced from 437.5 +/- 0.1 mum in the controls to 310.9 +/- 0.1 mum in the resveratrol-treated rats. This decrease was accompanied by a significant increase in tubular density, from 3.20 +/- 0.18 in controls to 6.58 +/- 0.18 tubules/mm(2) in the treated group. Moreover, sperm counts were significantly greater in the resveratrol-treated rats (24.8 +/- 3.30 x 10(7)) than in the control group (14.1 +/- 0.80 x 10(7)), but sperm quality did not differ. Serum concentrations of gonadotrophins and testosterone were significantly higher in the resveratrol-treated group. We identified a novel activity of trans-resveratrol. The daily oral administration of this phytochemical to adult male rats enhanced sperm production by stimulating the hypothalamic-pituitary-gonadal axis, without inducing adverse effects.