Role of cytological and ultrasonographic features in predicting the risk of malignancy in thyroid nodules with indeterminate cytology.

AIM: The aim of this paper was to examine the diagnostic value of several cytological and ultrasonographic features in predicting malignancy in thyroid follicular neoplasms. METHODS: The sample of the study consisted of 145 patients, who have had the diagnosis of follicular neoplasm on US guided fine-needle aspiration (FNA), and had undergone thyroidectomy. The cytological slides and the ultrasonographic images were reviewed, and several ultrasonographic and cytological features were evaluated and correlated with final histology. RESULTS: Histological diagnosis of malignancy was obtained in 14.5% of the patients, papillary carcinoma being the most frequent (66% of malignancies). The cytological and ultrasonographic features that have been associated with malignancy were: micro-fragments (P<0.00001), overlapping (P<0.005), hypercellularity (P<0.009), micronucleoli (P<0.013), atypical features (P<0.027), nodule size larger than 2 cm (P<0.029) and micro-calcifications (P<0.0002). Using the features that were statistically independent ones, which included two cytological features: micro-fragments and micronuclei, and one ultrasonographic feature: micro-calcifications, a statistical model for predicting malignancy was constructed. According to this model, it was found that the risk for malignancy is 2.65% in the absence of the three parameters, and amounts to 93.93% in the presence of all three of them. CONCLUSION: In a thyroid follicular neoplasm, the cytological and ultrasonographic features that were associated with malignancy were: micro-fragments, overlapping, hypercellularity, micronucleoli, atypical features, nodule size larger than 2 cm and micro-calcifications. In an attempt to predict malignancy, we proposed a simple statistical model using only three features derived from cytological and ultrasonographic tests.

B cell-activating factor enhances interleukin-6 and interleukin-10 production by ODN-activated human B cells.

We aim to investigate the additive value of B cell-activating factor (BAFF) when added to oligodeoxynucleotides (ODN)-activated B cells with respect to TLR-9, CD69, MHC-II expression, IL-6 and IL-10 secretion and B cell cycling. Therefore, B cells from healthy individuals were incubated under the following conditions: (1) B cells with medium, (2) B cells with ODN 0.5 µm, (3) B cells with BAFF 20 µm and (4) B cells with both ODN 0.5 µm and BAFF 20 µm. We found that addition of BAFF did not enhance the expression of TLR-9, CD69 and MHC-II in ODN-activated B cells. Incubation of B cells with BAFF and ODN together leads to a marked elevation of IL-6 and IL-10 levels compared to ODN alone. Synthesis and mitosis were higher in B cells stimulated by BAFF than in B cells stimulated by ODN. These findings suggest that both BAFF and TLR-9 contribute independently to B cell function.

Wwox inactivation enhances mammary tumorigenesis.

Breast cancer is the leading cause of cancer-related death in women worldwide. Expression of the WWOX tumor suppressor is absent or reduced in a large proportion of breast tumors suggesting that loss of WWOX may contribute to breast tumorigenesis. Wwox-deficient mice die by 3-4 weeks of age precluding adult tumor analysis. To evaluate the effect of WWOX-altered expression on mammary tumor formation, the Wwox-heterozygous allele was back crossed onto the C3H mammary tumor-susceptible genetic background (Wwox(C3H)+/-) and incidence of mammary tumor formation was evaluated. Although 50% of the female Wwox(C3H)+/- mice developed mammary carcinomas, only 7% of Wwox(C3H)+/+ mice did. Intriguingly, mammary tumors in Wwox(C3H)+/- mice frequently lost WWOX protein expression suggesting a genetic predisposition toward mammary tumorigenesis. Immunohistochemical staining of hormone receptors revealed loss of estrogen receptor-α (ER) and progesterone receptor in the majority of these tumors. In vitro, depletion of WWOX in MCF7 ER-positive cells led to reduced ER expression and reduced sensitivity to tamoxifen and estrogen treatment and was associated with enhanced survival and anchorage-independent growth. Finally, cDNA array analyses of murine normal mammary epithelial cells and mammary tumors identified 163 significantly downreguated and 129 upregulated genes in the tumors. The majority of differentially expressed genes were part of pathways involved in cellular movement, cell-to-cell signaling and interaction, cellular development, cellular growth and proliferation and cell death. These changes in gene expression of mouse mammary tumors in Wwox(C3H)+/- mice resemble, at least in part, human breast cancer development. Our findings demonstrate the critical role that the WWOX tumor suppressor gene has in preventing tumorigenesis in breast cancer.

Diagnosis and treatment of lymph node metastases of a rectal carcinoid tumor using In111-octreotide-scintigraphy and intraoperative gamma probe detection.

Carcinoids represent 1-2% of the rectal cancer. We report the case of a woman with a rectal carcinoid and a hypogastric node metastasis. We propose a less invasive treatment of the metastase using In11-octreotide-scintigraphy and intraoperative gamma-probe detector.

Normal fetal salivary glands at 14-16 weeks of gestation as observed by transvaginal ultrasound imaging.

OBJECTIVES: Absence or congenital anomalies of the parotid glands are associated with significant long-term morbidity. To date there are no published data on ultrasonographic detection of these defects in early pregnancy. We set out to demonstrate and measure the fetal parotid and submandibular salivary glands at 14-16 weeks using transvaginal ultrasound imaging. METHODS: During a routine fetal anomaly detection scan in 30 consecutive patients, an attempt was made to examine the fetal parotid and submandibular glands. The fetal head was scanned in transverse sections just below the fetal ears, and the area of the parotid and submandibular glands was inspected. The examination time was not prolonged for the purpose of measuring the salivary glands. The fetal biparietal diameter and the femur length were also documented. RESULTS: The median gestational age was 15.4 (range, 14.4-16.5) weeks. In all 30 patients examined, at least one pair of parotid and submandibular glands was clearly visualized and measured. In seven patients the parotid and submandibular glands were visualized on both sides. The median length of the parotid gland was 7.5 (range, 5.5-11.5) mm and that of the submandibular gland was 5.4 (range, 3.7-8.5) mm. CONCLUSIONS: The fetal salivary glands can be demonstrated by transvaginal ultrasound imaging at 14-16 weeks of gestation. This is the first reported study presenting the normal values of salivary gland measurements, which may be important in detecting fetuses with congenital absence or other malformations of the glands.

Liver transplantation exceeding UCSF criteria: case report of a late recurrence treated by surgery and review of the literature.

INTRODUCTION: Treatment of a recurrence of hepatocellular carcinoma (HCC) after liver transplantation. Surgery has seldom been considered in such a situation because HCC recurrences are generally considered as a systemic disease. PATIENT AND METHODS: We describe a 47-year-old male patient who underwent liver transplantation in October 1999 for HCC exceeding the Milan and University of California, San Francisco (UCSF), criteria. RESULTS: In 2007 (8 years after liver transplantation), the patient developed a cervical bone metastasis treated by surgery. In April 2008, HCC had disseminated to hepatic pedicle lymph nodes. An extended hepatic pedicle lymphadenectomy was then performed. Today, our patient is doing well, without signs of recurrence. DISCUSSION: The risk of developing a tumor recurrence is the main argument against expanding the UCSF criteria. In case of an HCC recurrence, various treatments ranging from a change in the immunosuppression regimen to chemotherapy have been proposed. Surgical treatment has rarely been envisaged in the treatment of HCC recurrences because of the technical difficulties and the frequent dissemination of cancer.

Acute abdomen from chylous peritonitis: a surgical diagnosis. Case report and literature review.

Acute accumulation of chyle in the peritoneal cavity is a rare event (less than 100 cases are described in the literature) and is to be distinguished from chylous ascites, which is characteristically chronic. It is frequently idiopathic, and diagnosis is usually made at laparotomy, whenever signs of acute peritonitis impose it. Peritoneal toilette and drainage are the only treatment required, and the prognosis is excellent. We describe the case of a 69-year-old man who underwent emergency surgery for acute peritonitis. Approximately 0.5 liters of chyle were found free in the peritoneal cavity at laparoscopic exploration, without any important underlying pathological condition apart from a blood vessel congestion in the bowel resembling angiomatosis. Laparotomic conversion, peritoneal toilette and drainage, with postoperative low-fat diet, were the pursued treatments. Two years after discharge, chemistry and clinics are normal, without evidence of associated disease or recurrence.

MammoGrid--a prototype distributed mammographic database for Europe.

This paper describes the prototype for a Europe-wide distributed database of mammograms entitled MammoGrid, which was developed as part of an EU-funded project. The MammoGrid database appears to the user to be a single database, but the mammograms that comprise it are in fact retained and curated in the centres that generated them. Linked to each image is a potentially large and expandable set of patient information, known as metadata. Transmission of mammograms and metadata is secure, and a data acquisition system has been developed to upload and download mammograms from the distributed database, and then annotate them, rewriting the annotations to the database. The user can be anywhere in the world, but access rights can be applied. The paper aims to raise awareness among radiologists of the potential of emerging "grid" technology ("the second-generation Internet").

A comparison of some anthropometric parameters between an Italian and a UK population: "proof of principle" of a European project using MammoGrid.

AIM: To demonstrate the use of grid technology to produce a database of mammograms and supporting patient data, specifically using breast density as a biomarker of risk for breast cancer, for epidemiological purposes. METHOD: The cohort comprised 1737 women from the UK and Italy, aged 28-87 years, mean 54.7 years, who underwent mammography after giving consent to the use of their data in the project. Information regarding height, weight, and exposure data (mAs and kV) was recorded. The computer program Generate-SMF was applied to all films in the database to measure breast volume, dense breast volume, and thereby percentage density. Visual readings of density using a six-category classification system were also available for 596 women. RESULTS: The UK and Italian participants were similar in height, but the UK women were significantly heavier with a slightly higher body mass index (BMI), despite being younger. Both absolute and percentage breast density were significantly higher in the Udine cohort. Images from the medio-lateral projection (MLO) give a significantly lower percentage density than cranio-caudal (CC) images (p<0.0001). Total breast volume is negatively associated with percentage density, as are BMI and age (p<0.0001 for all), although 80% of the variability in percentage density remains unexplained. CONCLUSION: The study offers proof of principle that confederated databases generated using Grid technology provide a useful and adaptable environment for large quantities of image, numerical, and qualitative data suitable for epidemiological research using the example of mammographic density as a biomarker of risk for breast cancer.

Effect of genioglossus contraction on pharyngeal lumen and airflow in sleep apnoea patients.

The purpose of the present study was to quantify the mechanical effect of genioglossus stimulation on flow mechanics and pharyngeal cross-sectional area in patients with obstructive sleep apnoea, and to identify variables that determine the magnitude of the respiratory effect of tongue protrusion. The pressure/flow and pressure/cross-sectional area relationships of the velo- and oropharynx were assessed in spontaneously breathing propofol-anaesthetised subjects before and during genioglossus stimulation. Genioglossus contraction decreased the critical pressure significantly from 1.2+/-3.3 to -0.7+/-3.8 cmH(2)O, with individual decreases ranging -0.6-5.9 cmH(2)O. Pharyngeal compliance was not affected by genioglossus contraction. The pharyngeal response to genioglossus stimulation was related to the magnitude of advancement of the posterior side of the tongue, but not to the severity of sleep apnoea, critical pressure, compliance or the shape and other characteristics of the velopharynx. Genioglossus contraction enlarges both the velo- and the oropharynx and lowers the critical pressure without affecting pharyngeal stiffness. The response to genioglossus stimulation depends upon the magnitude of tongue protrusion achieved rather than on inherent characteristics of the patient and their airway.

Three-dimensional endometrial volume and 3-dimensional power Doppler analysis in predicting endometrial carcinoma and hyperplasia.

OBJECTIVE: To evaluate the accuracy of endometrial volume measurement and 3-dimensional power Doppler analysis (3D-PDA) in the diagnosis of endometrial carcinoma and endometrial hyperplasia in women with post- and peri-menopausal bleeding. METHODS: 56 women with post-menopausal and 89 with peri-menopausal bleeding were enrolled. All were scheduled for hysteroscopy, dilatation and curettage, endometrial sampling or hysterectomy, and the ultrasound was performed within 24 h before the procedure. Endometrial thickness, endometrial volume, vascularity index (VI), flow index (FI) and vascularity flow index (VFI) were measured. These parameters were compared between the group of women with normal histology (including endometrial polyps) and the pathologic group (carcinoma and hyperplasia with or without atypia). RESULTS: Ninety women (62%) had normal histology, 26 (17.9%) had an endometrial polyp, 18 (12.5%) hyperplasia and 11 (7.6%) had endometrial carcinoma. Mean endometrial thickness was 11 mm and 15.5 mm in the normal and pathologic groups respectively (p<0.005). The mean endometrial volume was 6.87 cc and 15.5 cc in the two groups respectively (p<0.001). The VI was 2.27% and 2.95% in the two groups respectively (p=0.022). The FI was 18.6 and 23.6 in the two groups respectively (p=0.014). The VFI was 0.68 and 0.89 in the two groups respectively (p=0.018). Using ROC the area under the curve was 0.698, 0.728, 0.621, 0.631, and 0.625 for endometrial thickness, endometrial volume, VI, FI and VFI respectively. The best predictor of endometrial carcinoma was an endometrial volume of 3.56 cc or more (sensitivity 93.1%, specificity 36.2%). CONCLUSIONS: Endometrial volume and 3D-PDA are good diagnostic tools in predicting endometrial carcinoma and hyperplasia in women with post- and peri-menopausal bleeding.

Pathogenesis of hepatic encephalopathy: the tumour necrosis factor-alpha theory.

Hepatic encephalopathy (HE) is a major complication for acute and chronic liver failure. Despite several decades of intensive clinical and basic research, the pathogenesis of HE is still incompletely understood, and the precise mechanisms causing brain dysfunction in liver failure are still not fully established. Several theories concerning the pathogenesis of HE have been previously suggested, including the ammonia theory, which received the most attention. These theories are not mutually exclusive and the validity of none of them has been definitely proved experimentally. In this review article, an attractive theory concerning the pathogenesis of HE, the tumour necrosis factor-alpha (TNF) theory, is presented and comprehensively discussed after accumulation of sufficient data which indicate that the pro-inflammatory cytokine, TNF, is strongly involved in the pathogenesis of HE associated with both acute and chronic liver failure. This theory seems to be superior to all other previous theories in the pathogenesis of HE, and may induce development of other beneficial therapeutical modalities for HE directed towards inhibition of TNF production and/or action, and towards enhancement of its degradation.

Experiences of engineering Grid-based medical software.

OBJECTIVES: Grid-based technologies are emerging as potential solutions for managing and collaborating distributed resources in the biomedical domain. Few examples exist, however, of successful implementations of Grid-enabled medical systems and even fewer have been deployed for evaluation in practice. The objective of this paper is to evaluate the use in clinical practice of a Grid-based imaging prototype and to establish directions for engineering future medical Grid developments and their subsequent deployment. METHOD: The MammoGrid project has deployed a prototype system for clinicians using the Grid as its information infrastructure. To assist in the specification of the system requirements (and for the first time in healthgrid applications), use-case modelling has been carried out in close collaboration with clinicians and radiologists who had no prior experience of this modelling technique. A critical qualitative and, where possible, quantitative analysis of the MammoGrid prototype is presented leading to a set of recommendations from the delivery of the first deployed Grid-based medical imaging application. RESULTS: We report critically on the application of software engineering techniques in the specification and implementation of the MammoGrid project and show that use-case modelling is a suitable vehicle for representing medical requirements and for communicating effectively with the clinical community. This paper also discusses the practical advantages and limitations of applying the Grid to real-life clinical applications and presents the consequent lessons learned. CONCLUSIONS: The work presented in this paper demonstrates that given suitable commitment from collaborating radiologists it is practical to deploy in practice medical imaging analysis applications using the Grid but that standardization in and stability of the Grid software is a necessary pre-requisite for successful healthgrids. The MammoGrid prototype has therefore paved the way for further advanced Grid-based deployments in the medical and biomedical domains.

Effect of positional changes of anatomic structures on upper airway dilating muscle shortening during electro- and chemostimulation.

Positional changes of anatomic structures surrounding the upper airway are known to affect pharyngeal mechanics and collapsibility. We hypothesized that these alterations also affect the ability of the upper airway dilator muscles to enlarge the pharynx by altering their ability to shorten when activated. Using sonomicrometry, we evaluated in seven anesthetized dogs the effects of changes in tracheal and head position on the length of the genioglossus (GG) and the geniohyoid (GH) and the effects of these positional changes on the magnitude of shortening of the two muscles in response to electro- (ES) and chemostimulation (CS). Caudal traction of the trachea lengthened the GG and GH in all dogs, whereas cranial displacement of the trachea and flexion of the head to a vertical position shortened the muscles. Compared with the magnitude of ES-induced shortening in the neutral position, ES-induced shortening of the GG was 144.7 +/- 14.6, 49.3 +/- 4.3, and 33.5 +/- 11.6% during caudal and cranial displacement of the trachea and during head flexion, respectively. Similar effects of the positional changes were found for the GH, as well as for both muscles during respiratory stimulation with P(CO2) of 90 Torr at the end of CO(2) rebreathing, although inspiratory muscle shortening during CS reached only one-quarter to one-third of the magnitude observed during ES. We conclude that positional alterations of anatomic structures in the neck have a dramatic effect on the magnitude of shortening of the activated GG and GH, which may reduce substantially their ability to protect pharyngeal patency.

Resolving clinicians' queries across a Grid's infrastructure.

OBJECTIVES: The past decade has witnessed order of magnitude increases in computing power, data storage capacity and network speed, giving birth to applications which may handle large data volumes of increased complexity, distributed over the internet. METHODS: Medical image analysis is one of the areas for which this unique opportunity likely brings revolutionary advances both for the scientist's research study and the clinician's everyday work. Grids [1] computing promises to resolve many of the difficulties in facilitating medical image analysis to allow radiologists to collaborate without having to co-locate. RESULTS: The EU-funded MammoGrid project [2] aims to investigate the feasibility of developing a Grid-enabled European database of mammograms and provide an information infrastructure which federates multiple mammogram databases. This will enable clinicians to develop new common, collaborative and co-operative approaches to the analysis of mammographic data. CONCLUSION: This paper focuses on one of the key requirements for large-scale distributed mammogram analysis: resolving queries across a grid-connected federation of images.

The role of pleural fluid-serum gradient of tumor necrosis factor-alpha concentration in discrimination between complicated and uncomplicated parapneumonic effusion.

In a previous preliminary study an excess of tumor necrosis factor-alpha (TNF) was found in pleural fluid of patients with complicated parapneumonic effusion (CPPE), and its levels in pleural fluid of these patients were shown to be significantly higher than those in patients with uncomplicated parapneumonic effusion (UCPPE). This larger population study was undertaken to investigate, for the first time, the role of pleural fluid-serum gradient of TNF (TNFgradient) in discrimination between UCPPE and CPPE. Using a commercially available high sensitivity ELISA kit, levels of TNF were measured in serum and pleural fluid of 51 patients with UCPPE and 30 patients with nonempyemic CPPE. The mean +/- SEM values of serum TNF (TNFserum), pleural fluid TNF (TNFpf), and TNFgradient in the UCPPE group were 6.65 +/- 0.48 pg/mL, 10.85 +/- 0.74 pg/mL, and 4.2 +/- 0.38 pg/mL respectively, and in the CPPE group they were 7.59 +/- 0.87 pg/mL, 54.02 +/- 5.43 pg/mL, and 46.43 +/- 5.34 pg/mL, respectively. While no significant difference was found between the two groups regarding levels of TNFserum (p = 0.31), a highly significant difference between these two groups was found regarding levels of TNFpf and TNFgradient (p < 0.0001 for both variables). A significant correlation was found between levels of TNFserum and levels of TNFpf in the UCPPE group (r = 0.89, p < 0.0001), but not in the CPPE group (r = 0.18, p < 0.33). TNFgradient at an optimal cut-off level of 9.0 pg/mL was found to be a good marker for discrimination between UCPPE and CPPE (sensitivity, 96.7%, specificity, 98%, accuracy, 97.5%, and p < 0.0001). In conclusion, levels of TNFpf but not TNFserum are significantly higher in CPPEs than those in UCPPEs where TNFgradient at an optimal cut-off level of 9.0 pg/mL is a good marker for discrimination between UCPPE and CPPE.

Correlation between levels of tumour necrosis factor-alpha and levels of pH, glucose, and lactate dehydrogenase in parapneumonic effusions.

OBJECTIVES: This study was undertaken to investigate the correlation, which has not been previously investigated, between levels of tumour necrosis factor-alpha (TNF) and levels of pH, glucose, and lactate dehydrogenase (LDH) in pleural fluid of patients with uncomplicated parapneumonic effusion (UCPPE), and patients with complicated parapneumonic effusion (CPPE). METHODS: Using a commercially-available high sensitivity ELISA kit, levels of TNF were measured in pleural fluid of patients with UCPPE (n = 23), and CPPE (n = 15), and were compared with levels of pH, glucose, and LDH in these two groups. RESULTS: The mean +/- SD values of pleural fluid TNF, pH, glucose, and LDH in the UCPPE group were 11.05 +/- 7.65 pg/ml, 7.41 +/- 0.08, 125 +/- 48 mg/dl, and 306 +/- 182 IU/l, respectively. In the CPPE group the values were 56.07 +/- 28.5 pg/ml, 6.82 +/- 0.25, 42 +/- 36 mg/dl, and 2096 +/- 1916 IU/l, respectively. The only significant correlation, which was negative, was found between levels of TNF and pH in the CPPE group (r = -0.62, P = 0.01). Levels of pleural fluid TNF and LDH were significantly higher, and levels of glucose were significantly lower in the CPPE group than in the UCPPE group (P < 0.0001). CONCLUSIONS: This study demonstrates, for the first time that TNF levels correlate inversely with levels of pH in pleural fluid of patients with CPPE but not of patients with UCPPE. This correlation may, in part, explain the pathophysiology of the pleural complications which occur in the presence of CPPE.

Uterine artery embolization for management of interstitial twin ectopic pregnancy: case report.

Interstitial pregnancy is rare and dangerous variation of ectopic pregnancy. We describe a case of unilateral interstitial viable twin pregnancy treated by selective uterine artery embolization. A 23-year-old women with clinical and ultrasonic diagnosis of viable twin interstitial pregnancy was treated by selective uterine artery embolization after failure of systemic methotrexate treatment. Her serum beta-HCG was undetectable 2 months after the procedure and the ultrasound scan 70 days after embolization showed only multiple echogenic spots in the right uterine cornua. This therapeutic modality seems to be effective for conservative management of interstitial ectopic pregnancy, and as a prophylactic measure before surgical intervention to prevent major bleeding.