High-intensity focused ultrasound in the treatment of breast fibroadenomata (HIFU-F trial).

BACKGROUND: High-intensity focussed ultrasound (HIFU) is a non-invasive ablative technique utilising the application of high frequency ultrasound (US) pressure waves to cause tissue necrosis. This emerging technology is currently limited by prolonged treatment times. The aim of the HIFU-F trial was to perform circumferential HIFU treatment as a means of shortening treatment times. METHODS: A prospective trial was set up to treat 50 consecutive patients ≥18 years of age. Eligible patients possessed symptomatic fibroadenomata, visible on US. Patients ≥25 years of age required histological confirmation of the diagnosis. Primary outcome measures were reduction in treatment time, reduction in volume on US after 12 months and complication rates. RESULTS: HIFU treatment was performed in 51 patients (53 treatments) with a mean age of 29.8 years (SD 7.2 years) and a diameter of 2.6 cm (SD 1.4 cm). Circumferential ablation reduced treatment times by an estimated 19.9 min (SD 25.1 min), which is a 29.4% (SD 15.2%) reduction compared with whole lesion ablation. Volume reduction of 43.2% (SD 35.4%; p < 0.005, paired t-test) was observed on US at 12 months post-treatment. Local complications completely resolved at 1 month apart from skin hyper-pigmentation, which persisted in nine cases at three months, six cases at 6 months and six at 12 months. CONCLUSION: Circumferential HIFU treatment for breast fibroadenomata is feasible to reduce both lesion size and treatment time. HIFU is a non-invasive alternative technique for the treatment of breast fibroadenomata. ISRCTN registration: 76622747.

Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: A study combining quantitative immunohistochemistry with digital slide image analysis.

BACKGROUND: In breast cancer, hormonal receptors hold promise for developing novel targeted therapies. The thyroid exerts its actions via the thyroid hormone receptors alpha and beta. The clinical significance of the expression of thyroid hormone receptors in breast cancer is unclear. MATERIAL AND METHODS: We studied thyroid hormone receptor alpha (TRa) expression in 82 samples from 41 women with ductal invasive breast cancer and no thyroid disease. We performed quantitative immunohistochemistry with digital image analysis and correlated TRa expression with clinicopathological parameters. RESULTS: TRa was expressed in both normal breast epithelium and breast cancer, but expression in breast cancer was significantly lower. TRa was expressed significantly less in larger and grade III tumors. Conversely, breast cancers with lymphovascular invasion showed increased TRa expression compared to cancers without lymphovascular invasion. TRa expression was not significantly different between node-positive and node-negative breast cancers, or among different hormonal profiles and intrinsic subtypes. DISCUSSION: This is the first-in-human study to combine quantitative immunohistochemistry with image analysis to study TRa expression in women with ductal invasive breast cancer and no clinical or biochemical evidence of thyroid dysfunction. We confirm that TRa is expressed in both normal and malignant breast epithelium and suggest that TRa expression is downregulated during breast carcinogenesis. Larger and higher grade breast cancers demonstrate partial loss in TRa expression. Alterations in TRa expression take place even in the absence of clinical or biochemical thyroid disease. The underlying mechanism of these findings and their potential significance in survival and relapse mandate further research.

Incidence of inactive allele CYP2D6*4 among Greek women suffering from hormone-sensitive breast cancer.

BACKGROUND: The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning (null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The aim of the present study is to estimate the incidence of CYP2D6*4, in the Greek population and more precisely among females suffering from breast cancer. MATERIALS AND METHODS: Eighty unrelated mainland Greek female volunteers suffering from hormone-sensitive breast cancer were recruited during their primary handling or follow-up examination in order to provide samples for purification and polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) of genomic DNA derived from buccal swabs. RESULTS: The incidence of individuals with at least one present allele*4 within the Hellenic population was estimated to be as high as 30% (n = 24/80), with a 95% confidence interval of 20% to 40%. From the statistical point of view, it can be securely stated that incidence of *4 among Greek women is over 20%. The incidence of homozygous carriers of *4 in the present sample occurred in 8.75%, while the incidence of allele*4 haplo-type occurred in 19.4% (n=160). CONCLUSION: Although the outcoming results for Greek women are actually in line with existing data for other European nations, it should be noted, that a routine CYP2D6 testing of women suffering from breast cancer is formally not recommended, as the clinical significance of CYP2D6 phenotype in treatment and outcome of breast cancer remains unclear.

Platelet indices and netrophil to lymphocyte ratio in adults with acute appendicitis.

BACKGROUND: A study was performed in adults with acute appendicitis and matched controls to assess the utility of the platelet indices and neutrophil to lymphocyte ratio, as a diagnostic adjunct. METHOD: Data were retrospectively collected from a complete blood count test of 155 adult patients (72 men and 83 women) with histologically proven acute appendicitis upon admission, and of 50 healthy adults (20 men and 30 women). The parameters for white blood cells and platelets were compared between the two groups, and for each gender separately. RESULTS: A higher white blood cell count, neutrophil count, neutrophil percentage, neutrophil to lymphocyte ratio and lower lymphocyte percentage was reported in patients with acute appendicitis than that in the healthy controls, with high areas under the curve (AUC), sensitivities, specifi cities, positive predictive values (PPVs) and moderate negative predictive values (NPVs). The lymphocyte count was lower in patients than it was in the healthy controls. The platletcrit was lower in the female patients than that in the female controls, whereas a difference was not detected in the male participants. Differences were not detected with regard to platelet count, mean platelet volume and platelet distribution width for both genders. CONCLUSION: The neutrophil to lymphocyte ratio increases and lymphocyte percentage decreases in acute appendicitis, and can be used as an additional diagnostic marker. Plateletcrit, and therefore total platelet mass, is reduced in women with acute appendicitis, indicating the involvement of platelets in its pathophysiology. However, it is neither a reliable predictor or excluder of the disease.

Nonfunctioning symptomatic paraganglioma: Is there an optimal follow-up for patients with extra-adrenal benign paragangliomas.

Paragangliomas are rare neuroendocrine neoplasms originating from the embryological neural crest. In most cases, they exhibit a benign behavior. Here we report a case of a small symptomatic para-aortic paraganglioma, which was completely removed surgically and a review of the available literature regarding the optimal follow-up of a benign paraganglioma, since no guidelines are currently available for this rare entity.

Management of cystic and solid pancreatic incidentalomas: a review analysis.

Incidentally discovered pancreatic lesions that are asymptomatic have become much more common in recent years. It is important to characterize these lesions and to determine which patients can be safely observed and which should undergo an operation, as a substantial proportion of them might be malignant or premalignant. This review focus on the diagnostic approach and management of the different types of cystic and solid incidental pancreatic lesions based on appropriate clinical input, imaging screening and histological criteria. The task of developing guidelines to deal with an incidentally found pancreatic lesion, however, is much more complex and controversial than with other organs incidentalomas. In most series, pancreatic incidentalomas (PIs) <2 cm and of cystic appearance are likely to be benign, whereas those >2 cm are usually premalignant or malignant. Serous cystadenomas can reach very large size and are usually benign lesions. The presence of a solid mass or a mural nodule in a cystic lesion along with main pancreatic duct dilatation, thick septations and biliary obstruction are considered features suspicious of malignancy. Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are malignant or lesions of malignant potential and need surgical exploration. Solid lesions are much more likely to be premalignant or malignant and most of patients will undergo resection. The decision to operate rather than follow a solid lesion is a matter of tumor size and of clinical judgment based on the age and patient comorbidities. The present study should serve as a general guide and not applied as strict principles. Key words: cystic pancreatic incidentalomas, diagnostic approach, management, solid pancreatic incidentalomas.

Focal nodular hyperplasia and hepatocellular adenoma: current views.

Focal Nodular Hyperplasia (FNH) is a rare benign hepatic lesion believed to generate upon a hyperplastic response of the hepatocyte. Hepatocellular Adenoma (HA) occurs predominantly in young women receiving oral contraceptive medication. These two lesions have drawn significant attention throughout the recent years due to their specific clinical and pathological features as well as their challenging management. Although Focal Nodular Hyperplasia is managed conservatively in the majority of cases, it can albeit pose a difficult diagnostic dilemma. On the other hand, Hepatocellular Adenoma can be complicated with catastrophic hemorrhage or malignant transformation and therefore mandates surgical excision in many cases. The aim of this work is to review the current literature pertaining to these two clinical entities regarding their pathogenesis, diagnostic approach and genetics, as well as to shed light on specific differential diagnostic issues arising in many cases these lesions are encountered.

Carotid endarterectomy in a low volume vascular centre.

BACKGROUND: Carotid endarterectomy (CEA) is considered the golden standard of treatment for carotid artery disease in selected patients. METHODS: We studied retrospectively 246 CEAs performed in our centre from 2000-2008, and assessed the complications occurring during the first 30 days postoperatively. Surgical indications included symptomatic carotid stenosis > or = 60% and asymptomatic carotid stenosis > or = 75%. All patients underwent CEA with systematic use of a shunt, under general anesthesia. All arteriotomies were patched. All patients were transferred to ICU for 24 hours postoperatively. Mean hospital stay was 4.2 +/- 0.9 days. Ultrasound was performed 1 month postoperatively. RESULTS: Death, stroke, myocardial infarction (MI) and transient ischemic attack (TIA) were considered as major postoperative complications during the first 30 days after surgery. One death (0.4%), one nonfatal MI (0.4%) and two TIAs (0.81%) were recorded, while no stroke was present. CONCLUSIONS: We demonstrated that carotid endarterectomy can be safely performed in our low volume vascular centre. (246 CEAs in a nine year period).