Discordant expression of hormone receptors and HER2 in breast cancer. A retrospective comparison of primary tumors with paired metachronous recurrences or metastases.

PURPOSE: Expression of biomarkers in breast cancer, such as the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), can impact therapeutic decisions; however, it has been reported that their expression may change with disease progression. The aim of this retrospective study was to investigate the expression of these biomarkers in primary breast cancer and in its metachronous recurrences or metastases, and to estimate the percentage of cases with discordant expression. METHODS: Paired primary and metastatic tumor samples were collected from patients with primary breast cancer and subsequent metachronous distant metastases, diagnosed at the Metaxa Cancer Hospital, Piraeus, Greece, from 1988 to 2008. Two cases of local recurrence were also included. ER, PR and HER2 expression were assessed by immunohistochemistry (IHC) according to ASCO-CAP 2007 guidelines. Statistical comparisons were made using McNemar's exact test and Bowker's test for symmetry. RESULTS: Tumor samples from 110 patients were analysed. In the primary tumor, ER, PR and HER2 were positively expressed in 64.5%, 58.2% and 32.7% of cases, respectively, and expression of these biomarkers was lost in 18.2%, 21.8% and 10.9% of the corresponding metastases, respectively. Overall, a change of ER, PR and HER2 expression from positive to negative and vice versa occurred in 27.3% (p = 0.0987), 25.5% (p < 0.001) and 18.2% (p = 0.5034) of the cases, respectively. CONCLUSION: The expression of ER, PR and HER2 in metachronous recurrences or metastases can be discordant from that observed in the primary tumor. As such changes can occur during disease progression, the evaluation of biomarkers in metastatic sites should be mandatory, whenever possible, to ensure that patients are receiving the most effective treatment at all times.

Analysis of 7 immunohistochemical markers in male germ cell tumors demonstrates the prognostic significance of p53 and MIB-1.

BACKGROUND: Various prognostic factors have been investigated in order to predict the minority of male germ cell tumor (GCT) patients who will develop resistant disease. However, no prognostic system has been proven accurate. MATERIALS AND METHODS: Paraffin-embedded tissue specimens, obtained from primary lesions during the initial diagnosis of 83 advanced chemotherapy-treated GCT male patients, were stained for 7 immunohistochemical markers: p53, bax, bcl-2, MIB-1, topoisomerase IIa, c-kit and COX-2. The percentage of positive cells for each marker was measured for each patient. Cox regression was used for the prognostic factor analysis. RESULTS: All patients were followed for a median of 4 years. Nineteen patients had seminoma and 64 non-seminomatous GCT. In univariate analysis, only p53 (hazard ratio (HR) = 4.01, 95% confidence interval (CI) = 1.25-12.84, p = 0.019) and MIB-1 (HR = 3.16, 95% CI = 1.06-9.45, p = 0.039) were found to be prognostic for disease-specific survival. The best prognostic cut-off values of p53 and MIB-1 were 10% and 30% respectively. In multivariate analysis, these two markers obtained independent significance only when considered in combination (HR = 6.63, 95% CI = 1.40-31.41, p = 0.017, for patients with one or both markers above their cut-off), while the International Germ Cell Consensus Cancer Group (IGCCCG) risk was the most significant (HR = 7.99, 95% CI = 1.96-32.52, p = 0.004, for the high-risk group). However, the expression of these markers seemed to be significantly correlated with known prognostic factors. Nevertheless, we identified 34 patients of low IGCCCG risk expressing both markers below their cut-off with excellent survival. CONCLUSION: Among 7 immunohistochemical markers, p53 and MIB-1 demonstrated prognostic significance. Their combination may contribute to improvement of the accuracy of the currently approved prognostic system (IGCCCG).

The histological outcome of glandular dyskaryosis--AGUS--reported in Papanicolaou smears.

PURPOSE: The objective of this study was to investigate the prognostic significance of glandular dyskaryosis/AGUS, reported in Papanicolaou (Pap) smears. MATERIALS AND METHODS: During a 4-year period 26,408 smears were assessed at the Department of Cytology of our hospital. Thirty (0.11%) smears were reported as having glandular dyskaryosis. The studied material was taken by colposcopy, fractional curettage and/or cone biopsy. RESULTS: The final diagnosis included 2 cases of invasive cervical carcinoma (1 squamous cell and 1 adenocarcinoma), 1 case with ovarian cancer, 8 cases with high grade squamous intraepithelial lesion (HGSIL) and 10 cases with other nonmalignant pathology (polyps, hyperplasia) of endometrial origin. These findings reflect a 36.7% positive predictive value for significant squamous and glandular pathology. CONCLUSION: Patients with glandular dyskaryosis require further evaluation because it may hide serious pathology from all internal genital organs. Colposcopy in combination with fractional curettage and/or cone biopsy are proposed as the appropriate diagnostic tools in women with such cytological abnormality.

Late struma ovarii diagnosis many years after total thyroidectomy. A rare entity.

We present the case of a 53-year-old lady with incidental diagnosis of struma ovarii 10 years after total thyroidectomy due to papillary thyroid carcinoma. The disease was diagnosed owing to high levels of serum thyroglobulin. The patient underwent exploratory laparotomy with total hysterectomy and bilateral salpingo-oophorectomy. Close follow-up was proposed and her prognosis is excellent.

Kit expression in male germ cell tumors.

OBJECTIVE: KIT functions as the receptor for stem cell factor (SCF) and this interaction is essential for regulation of proliferation and survival, particularly for germ cells since it regulates oogenesis, folliculogenesis and spermatogenesis. Up-regulation of KIT signalling has been associated with oncogenic transformation in cells expressing the molecule. Our objective was to investigate the expression of KIT in germ cell tumor patients and correlate it with the patients' clinical characteristics. PATIENTS AND METHODS: One hundred and seventy-three archival blocks of formalin fixed, paraffin-embedded tumor samples from histologically confirmed germ cell tumor (GCT) patients were included in the study. Immunohistochemical staining for KIT was performed and the percentage of positive cells was calculated by an independent pathologist. KIT expression was considered as positive if > 10% of tumor cells displayed membranous or cytoplasmic staining. RESULTS: Sixty-one patients with seminomatous (49 pure, 11 anaplastic, 1 spermocytic) and 112 with non-seminomatous GCTs (36 malignant teratoma undifferentiated (MTU), 15 malignant teratoma trophoblastic (MTT), 20 malignant teratoma intermediate (MTI), 35 malignant teratoma combined (MTC) and six others) were identified. Among pure seminoma patients, 38 (77.5%) revealed a positive staining for KIT, while only two out of eleven (18.2%) anaplastic seminoma patients were identified as positive. This difference was statistically significant (p < 0.001). Among 35 patients with an MTC, 48.6% had a positive KIT staining while only two of the remaining patients with a non-seminomatous GCT had a positive staining. Although KIT was strongly correlated with seminomatous histology (p < 0.001), it failed to correlate with stage (p = 0.19) or treatment response (p = 0.11) in these patients. Overall, four (one seminoma, three MTC) out of 22 chemoresistant patients showed a positive staining for KIT. CONCLUSION: KIT is expressed in the majority of seminomas and in seminomatous components of the combined tumors, but only in a minority of anaplastic seminomas and rarely in non-seminomatous GCTs. The recent development of tyrosine kinase inhibitors may offer a possibility of cure in chemoresistant patients overexpressing KIT.

SENSATION remote monitoring system for enabling the "anytime, anywhere" monitoring of patients with selected sleep disorders.

The SENSATION Integrated Project aims at promoting the health, safety and quality of life of people and protect the environment by reducing relevant accidents and thus the impact on environment through the application of novel micro and nano sensors and related technologies, of low-cost and high-efficiency, for physiological state monitoring. The focus of the work will be the brain activity, including the sleep and wakefulness states and their boundaries, stress, inattention and hypovigilance states, for hypovigilance detection, prediction and management as well as diagnosis, treatment and remote monitoring of sleep disorders. In this paper, a presentation of the application scenarios of the integrated medical system will be made.

Continuous home care monitoring services through INTERLIFE.

INTERLIFE is a revolutionary product that can radically change the way healthcare services are offered by introducing new means for quality health care management by the healthcare providers, and by improving the patients', health providers' and citizens' quality of life. INTERLIFE is a technological and medical knowledge management and processing infrastructure able to support an early discharge and a continuous home monitoring service thus leading to reduction hospitalisation rates and to the increased efficacy of healthcare service delivery of patients suffering from chronic diseases such as CHF, COPD and Diabetes as well as a special category of acute health care related patients. Six test sites are participating in the validation trials, more specifically EAP Sardenya and MUTUAM in Spain, Hippokrateion Hospital and AHEPA Hospital in Greece, RAMIT in Belgium and University of Regensburg Medical Centre in Germany.

Giant solid abdominal mass with cystic lesions: a case report and diaphorodiagnostic approach.

A peri-menopausal woman presented with abdominal distention, pelvic discomfort and problems of constipation for the last 4 months. All clinical and radiological examinations were in favor of a giant solid mass with cystic lesions arised from the left ovary. These findings raised suspicion of a primary malignant ovarian tumor or a preudomyxoma peritonei. Surgery revealed a giant mass arised from the uterine fundus. An abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy were preformed. The histological examination verified a degenerated myoma with cystic lesions with no evidence of malignancy. The patient made an uneventful recovery. A gynecologist should always be prepared to perform a different surgery than planned according to operational findings (Fig. 2, Ref. 11).

Effectiveness of home-centered care through telemedicine applications for overweight and obese patients: a randomized controlled trial.

OBJECTIVE: To determine if home-centered monitoring through telemedicine has an impact on clinical characteristics, metabolic profile and quality of life in overweight and obese patients. DESIGN: Randomized controlled trial, 6-month duration. SETTING: Tertiary care academic hospital. SUBJECTS: A total of 122 patients were eligible to participate as they met the inclusion criteria of increased body mass index (BMI>25 kg/m(2)), age>18 and <70 y and ability to operate electronic microdevices. INTERVENTIONS: All patients in the control group (n=77) received standard hospital care. Patients in the intervention group (n=45), additionally, measured three times a week, for 6 months, their blood pressure and body weight and transmitted them to an automated call center. These values were not shared with the patients' physician or dietician. MAIN OUTCOME MEASURES: Clinical (body weight, BMI, blood pressure), laboratory (fasting plasma glucose, triglycerides, HDL-cholesterol, total cholesterol) and quality of life parameters (SF-36((R)), Visual Analog Scale of European Quality-5 Dimensions, Obesity Assessment Survey). Data were analyzed in an intention-to-treat-way (last observation carried forward). RESULTS: Drop-out rate was similar in the control and intervention groups: 12 vs 11 percent, respectively, P=NS. There were no significant differences at baseline between intervention and control groups in all main outcome parameters. There were significant decreases for patients in the intervention group in body weight (from 101.6+/-22.4 to 89.2+/-14.7 kg, P=0.002, P=0.05 vs controls at 6 months), total cholesterol (from 247.6+/-42.0 to 220.7+/-42.6 mg/dl, P=0.002, P=0.05 vs controls at 6 months) and triglycerides (from 148.4+/-35.0 to 122.3+/-31.4 mg/dl, P=0.001, P=0.01 vs controls at 6 months). Intervention group patients made a total of 1997 phone contacts. The number of phone contacts was correlated positively with Social Functioning (SF), Vitality (VT) and Mental Health (MH) scores of SF-36((R)) at baseline (r=0.48, r=0.41, r=0.41, respectively, P=0.05) but not with weight loss. CONCLUSIONS: Home-centered, intense treatment through the use of telemedicine can be effective in improving short-term obesity outcomes.

Citizen centered health and lifestyle management via interactive TV: The PANACEIA-ITV health system.

In the context of an IST European project with acronym PANACEIA-ITV, a home care service provisioning system is described, based on interactive TV technology. The purpose of PANACEIA-ITV is to facilitate essential lifestyle changes and to promote compliance with scientifically sound self-care recommendations, through the application of interactive digital television for family health maintenance. The means to achieve these goals are based on technological, health services and business models. PANACEIA-ITV is looking for communication of monitoring micro-devices with I-TV set-top-boxes using infrared technology, and embodiment of analogous H/W and S/W in the I-TV set-top-boxes. Intelligent agents are used to regulate data flow, user queries as well as service provisions from and to the household through the satellite digital platform, the portal and the back-end decision support mechanisms, using predominantly the Active Service Provision (ASP) model. Moreover, interactive digital TV services are developed for the delivery of health care in the home care environment.

Communication infrastructure in a contact center for home care monitoring of chronic disease patients.

The Citizen Health System (CHS) is a European Commission (EC) funded project in the field of IST for Health. Its main goal is to develop a generic contact center which in its pilot stage can be used in the monitoring, treatment and management of chronically ill patients at home in Greece, Spain and Germany. Such contact centers, which can use any type of communication technology, and can provide timely and preventive prompting to the patients are envisaged in the future to evolve into well-being contact centers providing services to all citizens. In this paper, we present the structure of such a generic contact center and in particular the telecommunication infrastructure, the communication protocols and procedures, and finally the educational modules that are integrated into this contact center. We discuss the procedures followed for two target groups of patients where two randomized control clinical trials are under way, namely diabetic patients with obesity problems, and congestive heart failure patients. We present examples of the communication means between the contact center medical personnel and these patients, and elaborate on the educational issues involved.

Intrasellar chordomas mimicking pituitary adenoma.

OBJECT: Whereas chordomas involving the sellar region are uncommon, largely or entirely intrasellar examples are rare. The goal in this study was to present examples of these rare tumors as a guide to their proper diagnosis and treatment. METHODS: The authors report three cases in which the chordomas filled the pituitary fossa and presented as nonfunctioning pituitary adenomas. All lesions exhibited the typical histological patterns and immunophenotype of chordoma. One tumor, studied ultrastructurally and subjected to DNA analysis, was shown to have a diploid histogram. The authors present a clinicopathological study of these three cases and review the literature on intrasellar chordomas. CONCLUSIONS: Although these tumors are easily misdiagnosed and therefore may not receive optimal treatment, aggressive surgical resection can yield a favorable prognosis in lesions with a limited extent.