Digital mammography: physical principles and future applications

Mammography is currently considered the best tool for the detection of breast cancer, pathology with a rate of incidence in constant increase. To produce the radiological picture a screen film combination is conventionally used. One of the inherent limitations of screen- film combination is the fact that the detection, display and storage processes are one and the same, making it impossible to separately optimize each stage. These limitations can be overcome with digital systems. In this work we evaluate the main characteristics of digital detectors available on the market and we compare the performance of digital and conventional systems. Digital mammography, due to the possibility to process images, offers many potential advantages, among these the possibility to introduce the dual-energy technique which employs the composition of two digital images obtained with two different energies to enhance the inherent contrast of pathologies by removing the uniform background. This technique was previously tested by using synchrotron monochromatic beam and a digital detector, and then the Senographe 2000D full-field digital system manufactured by GE Medical Systems. In this work we present preliminary results and the future applications of this technique.     

Magnetic Resonance enteroclysis imaging in Crohn's disease

PURPOSE: To assess the role of magnetic resonance enteroclysis (MRE) in patients with Crohn's disease, in order to identify involved segments, define the extension and evaluate transmural alterations. MATERIALS AND METHODS: Eighteen patients with known Crohn's disease were studied with MR (1.5 T), with breath-hold T2-weighted TSE, T2-weighted TSE SPIR and 3D T1-weighted sequences before and after gadolinium injection (0.2 mmol/kg) in the coronal and axial planes. The small bowel was distended by the administration of 2 l of methylcellulose through a nasojejunal tube and drug induced hypotony. Typical patterns of Crohn's disease, such as mucosal abnormalities, parietal thickening and narrowing of the bowel, prestenotic dilation, fibrofatty proliferation and enlarged lymph nodes were analysed on radiological and MRE images. MRE was performed within 30 days from conventional radiological studies (conventional enteroclysis and small bowel follow-through). RESULTS: Good distension of the bowel wall was obtained in all cases. MRE assessed the presence of parietal thickening and narrowing of the bowel wall (14/18 cases) and the presence of prestenotic dilatation (12/18 cases). Vascular enhancement (14/18 cases), transmural abnormalities (8/18 cases), fibrofatty proliferation (3/18 cases), abscess formation (2/18 cases) and enlarged mesenteric lymph nodes (6/18 cases) were also observed. MRE missed small fistulas which were visible in radiological studies in two patients. CONCLUSIONS: MRE appears to be a promising technique in patients with Crohn's disease. Due to limited spatial resolution MRE could be a useful adjunct to radiological studies and in following up selected groups of patients with prior known disease.     

Prevalence of patent foramen ovale in subjects with obstructive sleep apnea: a transcranial Doppler ultrasound study

BACKGROUND: Under particular conditions a patent foramen ovale (PFO) can potentially give rise to ischemic stroke by means of paradoxic embolization. In obstructive sleep apnea syndrome (OSAS) right to left shunting (RLSh) can occur through PFO during periods of nocturnal apnea. Our study aimed to evaluate the prevalence of PFO diagnosed by means of transcranial Doppler (TcD) in subjects with OSAS. METHODS: Seventy-eight consecutive subjects with OSAS (mean age 53+/-12 years) and 89 normal controls (mean age 48+/-9 years) underwent TcD with intravenous application of agitated physiological saline solution. The test was performed on patients at rest and during Valsalva maneuver. RESULTS: PFO was present in 21 out of 78 patients with OSA (27%) and in 13 out of 89 control patients (15%). Seventeen out of 21 patients with OSA showed PFO only during Valsalva maneuver (85%) with respect to 12 out of 13 subjects of the control group (92%). Prevalence of PFO in OSAS was statistically different with respect to the control group (P<0.05). However, no statistically significant differences could be found for the prevalence of provocative-only shunting PFO with respect to already at rest shunting PFO in patients with OSAS with respect to the control group. CONCLUSIONS: Prevalence of PFO in subjects with OSA is significantly higher than in normal controls. The shunt is frequently present only during Valsalva maneuver.     

Split-liver transplantation eliminates the need for living-donor liver transplantation in children with end-stage cholestatic liver disease

BACKGROUND: End-stage cholestatic liver disease (ESCLD) is the main indication for liver replacement in children. Pediatric cadaver-organ-donor shortage has prompted the most important evolutions in the technique of liver transplantation, in particular living-donor liver transplantation (LDLT) and split-liver transplantation (SLT). METHODS: Between November 1997 and June 2001, 127 children with ESCLD were evaluated for liver transplantation, and 124 underwent 138 liver transplantations after a median time of 40 days. Causes of liver disease were congenital biliary atresia (n=96), Alagille's syndrome (n=12), Byler's disease (n=8), and other cholestatic diseases (n=8). RESULTS: Ninety (73%) patients received a split-liver graft, 28 (23%) a whole liver, and 6 (4%) a reduced-size liver. Overall 2- and 4-year patient survival rates were 93% and 91%, respectively; the 2- and 4-year graft-survival rates were 84% and 80%, respectively. In split-liver recipients, 4-year patient and graft-survival rates were 91% and 83%, respectively; these were 93% and 78%, respectively, in whole-liver recipients and 67% and 63%, respectively, in reduced-size liver recipients. Retransplantation rate was 11%, whereas mortality rate was 8%. Overall incidence of vascular and biliary complication were 16% and 27%, respectively. CONCLUSIONS: SLT can provide liver grafts for children with ESCLD with an outcome similar to the one reported following LDLT, eliminating mortality while they are on a transplantation wait list. The need for pediatric LDLT should be reevaluated and programs of SLT strongly encouraged and supported at a national and international level.     

Rapamycin impairs antigen uptake of human dendritic cells

BACKGROUND: Rapamycin is a recently introduced immunosuppressive agent. Its effect on lymphocytes has been extensively studied. Whether it can also modulate dendritic cell (DC) function is unknown. METHODS: The effect of rapamycin on differentiation, antigen uptake, and the immunostimulatory capacity of human DC was examined. DC were derived from monocytes upon culture with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor in the presence or absence of rapamycin (0.1-100 ng/mL). Surface phenotype and antigen uptake capacity of DC were assessed by flow cytometry. Immunostimulatory capacity was measured by mixed lymphocyte culture. RESULTS: Rapamycin reduced DC recovery and increased DC apoptosis. DC differentiated in the presence of rapamycin (rapa-DC) had increased expression of CD1a, CD1b, and CD1c and decreased expression of MHC I, MHC II, CD80, CD86, and CD40. Antigen uptake receptor expression (mannose receptor, CD32, CD91, CD46) was decreased, and receptor-mediated endocytosis of fluorescein isothiocyanate-dextran was markedly impaired in rapa-DC, as were fluid phase endocytosis of Lucipher Yellow and phagocytic activity of bacteria and dead or apoptotic cells. CD40 ligand-induced production of both IL-12 and IL-10 was reduced in rapa-DC, and allogeneic T lymphocyte responses were moderately impaired when rapa-DC were used as stimulator cells. Neither cyclosporine nor FK506 affected DC function. However, the effects of rapamycin on DC could be completely inhibited by a 10-fold excess of FK506 but not by up to 100-fold excess of cyclosporine. CONCLUSION: Rapamycin has a unique and profound inhibitory effect on DC function, which seems to be at least in part mediated by the FKBP immunophilins.     

Mutations of the D310 mitochondrial mononucleotide repeat in primary tumors and cytological specimens

A mononucleotide repeat (D310) in mitochondrial DNA has been recently identified as a mutational hot spot in primary tumors. We analyzed 56 tumors for insertion/deletion mutations in the D310 repeat. A total of 13 mutations were detected. The highest frequency of mutations was found for cervical cancer, followed by bladder tumors, breast cancer and endometrial neoplasia. No alterations were observed in four patients suspected of malignancy but without evidence of malignant tumor. We detected identical changes in four of four urine sediments from patients with bladder cancer and in three of three fine needle aspirates of patients with breast cancer. Our results indicate that D310 abnormalities are detectable in cytology specimens from patients with cancer and support the notion that D310 analysis may represent a new molecular tool for cancer detection.     

Critical role of cyclin D3 in TSH-dependent growth of thyrocytes and in hyperproliferative diseases of the thyroid gland

We report that cyclin D3 is rate limiting for G1 progression in thyroid follicular cells and that its constitutive upregulation by chronic stimulation of the TSH/cAMP pathway plays a role in human and experimental hyperproliferative diseases of the thyroid gland. These conclusions are supported by in vitro and in vivo studies. In rat thyrocytes (PC Cl 3 cells), cyclin D3 expression is enhanced in response to activation of the TSH/cAMP pathway. Interference with the expression of G1 cyclins (in particular cyclin D3) by the antisense methodology strongly reduced TSH-dependent proliferation of PC Cl 3 cells, indicating that proper progression through G1 requires cyclin D3. Accordingly, PC Cl 3 cells engineered to overexpress cyclin D3 (PC-D3 cells) show enhanced growth rate and elude hormone-dependence and contact inhibition. Using an animal experimental model of thyroid stimulation, we demonstrate that cyclin D3 is a key mediator of TSH-dependent proliferation of thyroid follicular cells also in vivo. Cyclin D3 protein levels were higher in the thyrocytes from glands of propylthiouracil-treated rats compared with control animals. The increase in cyclin D3 expression occurred after the propylthiouracil-induced increase in TSH levels and preceded the burst of cell proliferation. Finally, we found that cyclin D3 protein is expressed in a fraction of human goiters but it is strongly overexpressed in most follicular adenomas.     

Lonidamine: efficacy and safety in clinical trials for the treatment of solid tumors

Lonidamine, a derivate of indazole-3-carboxylic acid, is an antineoplastic drug with a typical mechanism of action. Lonidamine has no function on cellular nucleic acids or protein synthesis, whereas it exerts a powerful inhibitory effect on oxygen consumption, aerobic glycolysis and lactate transport and accumulation of neoplastic cells. Nevertheless, its proven ability to modify the permeability of membranes is consistent with the possible increase of drug uptake, reverse of drug resistance and triggering of apoptotic pathway. Lonidamine has been experimentally shown to potentiate the cytotoxic effects of anthracyclines in human breast cancer cell lines and cisplatin activity in both platinum-sensitive and platinum-resistant human ovarian carcinoma cell lines. Since the specific mechanism of action and side effects are not overlapping with those of standard antineoplastic agents, combination of lonidamine with standard chemotherapy has been widely investigated for the treatment of solid tumors. Additionally, the enhancement of radiotherapy activity by lonidamine has been considered for palliative therapy of lesions from metastatic cancers. The encouraging results of phase II-III trials for the treatment of advanced breast, ovarian and lung cancer must be confirmed by larger studies. Specifically designed studies to address the role of lonidamine in the adjuvant setting are warranted. Lonidamine, a dechlorinate derivative of indazole-3-carboxylic acid, has proved to exert a powerful antiproliferative effect and to impair the energy metabolism of neoplastic cells. Herein we review the current experience on combining lonidamine and chemotherapy and/or radiation therapy in the treatment of solid tumors. Several studies have been published on this topic. The total number of trials reported in literature and length of follow-up are still insufficient to draw a firm conclusion. However, the available data demonstrate a significant role of lonidamine in modulating anthracycline and platinum compound activity.