Association between gastroesophageal reflux and endobronchial carcinoid: a case report.

Children with neurological disorders may suffer from gastroesophageal reflux disease (GERD). Typical symptoms are vomiting, regurgitation and hematemesis. Patients present with respiratory symptoms only in cases with swallowing disorders causing chronic airway aspiration. We report the case of a patient affected by chromosome 8 p deletion syndrome with mental retardation, referred to our unit for suspected GERD. Chest X-ray, performed at admission for coexisting respiratory complaints, showed left lower lobe pneumonia; esophageal pH monitoring and upper endoscopy were normal for GERD. To rule out chronic airway aspiration, gastroesophageal 99 mTc scintigraphy with lung scan 18 to 24 h after a test meal and video fluoroscopy swallowing study were performed, both negative. Two months later, a second episode of left lower lobe pneumonia occurred. A chest CT scan was performed and showed an endobronchial mass; the biopsy taken during the broncoscopy was not conclusive. Surgical excision resulted in a diagnosis of pulmonary carcinoid. Bronchial carcinoids, although rare, should be taken into consideration as a potential cause of recurrent pneumonia even in the presence of demonstrated GERD where severe respiratory infections only occur with coexisting chronic pulmonary aspiration, even in neurologically impaired people.

Unusual bladder mass in a 14-year-old boy: bladder paraganglioma.

A 14-year-old boy presenting headache crisis, sweating and palpitation was observed. On ultrasound scan, a 3 × 2.5 cm hypoechoic mass, highly vascularized, was observed arising from the left bladder wall. Magnetic resonance imaging confirmed the mass situated close to the ureteral orifice, with intense peripheral enhancement and a central non-enhanced portion. Left partial cystectomy was performed. Large clear cells, presenting cytoplasmatic granules positive for S100 and chromogranin, were observed at histology. Bladder paraganglioma derives from chromaffin tissue of the sympathic system and it is uncommon in children. The estimated prevalence is very low (0.06% of bladder tumors). Symptomatology is related to the catecholamine production. In pediatrics, prognosis is usually good but long-term follow-up is required.

Diffusion-weighted imaging in breast lesion evaluation.

PURPOSE: The purpose of this study was to investigate the ability of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) in the detection and characterisation of breast lesions. MATERIALS AND METHODS: From September 2005 to September 2007, 86 patients with breast lesions who underwent magnetic resonance imaging (MRI) in our department were included in our study. MRI was performed with a 1.5-T unit using a standard protocol including DWI sequence. For each breast lesion, the ADC value was calculated and compared with that of normal breast tissue and to the definitive pathological diagnosis. Mann-Whitney U and Kruskal-Wallis tests were used for statistical analysis. RESULTS: A total of 126 breast lesions were detected. Pathology results revealed 100 malignant and 26 benign lesions. Mean diameter of lesions was 26.02 mm (range 4-90 mm), including 52 lesions

MRI accuracy in residual disease evaluation in breast cancer patients treated with neoadjuvant chemotherapy.

AIM: To assess the accuracy of magnetic resonance imaging (MRI) in evaluating residual disease after neoadjuvant chemotherapy in patients with large breast cancers. MATERIALS AND METHODS: Forty-five women with large breast cancers underwent MRI mammography before and after neoadjuvant chemotherapy (three or six cycles). Dynamic MRI was performed using a 1.5 T unit using three-dimensional FSPGR sequences. For each patient tumour size, tumour volume and dynamic curve were obtained before and after neoadjuvant treatment. Residual tumour sizes obtained using MRI were compared with pathological findings to assess the accuracy of MRI in detecting and in measuring residual tumour. RESULTS: The sensitivity, specificity and accuracy of MRI in detecting residual disease was 90.5, 100, and 91.3%, respectively. The mean of largest diameters measured at histology and at MRI were 26 and 28.2mm, respectively. The tumour size correlation coefficient between MRI and pathology measurements was very high: r(2)=0.9657 (p<0.0001). The interclass correlation coefficient between preoperative imaging measurements and pathological measurements of residual disease was 0.944 (95% CI: 0.906-0.982). CONCLUSION: The presence and size of residual disease in breast patients treated with neoadjuvant chemotherapy could be accurately evaluated using MRI.

Peripheral benzodiazepine receptor ligands in rat liver mitochondria: effect on cholesterol translocation.

Peripheral benzodiazepine receptors mediate cholesterol translocation between the outer and inner mitochondrial membranes in steroidogenic tissues. They are found in many other tissues too, including liver. We studied the effect of the peripheral benzodiazepine receptor ligands PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxa mid e], Ro 5-4864 (4-chlorodiazepam), hemin, protoporphyrin IX and N-methyl protoporphyrin IX on cholesterol mitochondrial intermembrane transport of cholesterol in vitro in rat liver. Endogenous cholesterol translocation from outer to inner mitochondrial membranes was significantly increased by PK11195 and N-methyl protoporphyrin IX (140% and 150% increase, respectively, at 1 microM, P<0.01). 5 microM protoporphyrin IX, 1 microM Ro 5-4864 and 5 microM hemin was ineffective. When mitochondria were labeled with exogenous [4-14C]cholesterol, PK11195 and N-methyl protoporphyrin IX were the most effective in increasing total cholesterol incorporation and cholesterol translocation into inner membranes, and their effect was dose-dependent. These data suggest that in liver the binding to peripheral benzodiazepine receptors is related to cholesterol translocation and the interaction of ligands with these receptors may play a role in the complex mechanism of regulation of cholesterol traffic between liver mitochondrial membranes.

Fate of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET18-OME) in malignant cells, normal cells, and isolated and perfused rat liver.

Ether lipids show high specific cytotoxicity in vitro on a wide variety of experimental tumors, but only moderate activity in vivo. One reason for this lack of activity in the whole animal might be a high degree of metabolic degradation. We therefore studied the biotransformation of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine ([3H]ET18-OMe) labeled in position 9-10 of the 1-alkyl chain, in rat plasma and erythrocytes, HL60 and K562 leukemic cells, HT29 adenocarcinoma cells, and cultured hepatocytes at 37 degrees C, and in a system of isolated and perfused rat liver. ET18-OMe and its metabolites were identified and quantified after lipid extraction and TLC separation. In tumor cells, 98% of ET18-OMe remained almost unmodified in vitro after 24-hr incubation. Plasma and erythrocytes from rats metabolized only 4-5% of the original compound in 3 hr. In cultured hepatocytes, 35% and 58.3%, respectively, of ET18-OMe was present after 6 and 24 hr as the metabolites 1-O-alkyl-2-O-methylglycerol (AMG), 1-O-alkyl-2-O-methylphosphatidic acid (AMPA), and stearyl alcohol (SA) (products of direct hydrolysis by phospholipases C and D and alkylhydrolase); phospholipids (phosphatidylcholine and phosphatidylethanolamine); and neutral lipids (products of secondary metabolism). In perfused rat liver, approximately 15% of the total radioactivity incorporated after 3 hr was distributed in metabolites as follows: 5.9% of AMPA, 5.0% of AMG, and 3.1% of SA. We conclude that the metabolism of ET18-OMe in normal tissues occurring through the same enzymes that metabolize natural lipids may partly explain the lack of effect in vivo.

Effect of cell density on cytotoxicity of ether lipid analogues in variants of B16 murine melanoma.

Ether lipids are defined here as analogues of naturally occurring lysophosphatidylcholines with cytotoxic activity against neoplastic cells. The activity of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET18OMe) and 3-hexadecylmercapto-2-methoxymethyl-propyl-1-phosphocholine (Ilmofosine) (BM 41.440) was tested in variants of B16 murine melanoma, grown in adhesion cultures (B16F1 with low metastatic potential; B16F10 and B16BL6 with high metastatic potential). Cytotoxicity was evaluated by counting the cells that survived after 24 h of drug exposure. Cholesterol, sphingomyelin, total phospholipid and phosphatidylcholine levels were determined. After 24 h of drug exposure, cultures of the B16BL6 variant contained a larger number of cells, especially when high drug concentrations (100-250 microM) were used, than cultures of the B16F1 and B16F10 variants. The sensitivity to ET18OMe of the three variants was evaluated at different cell densities (at each density the dose was equalized per number of cells/well; 0.1 mumol/10(6) cells/well). In B16F1 and B16F10 cultures the dose-response curve was not affected by the number of cells/well, while in B16BL6 no more than 20% of the cells were killed at all cell densities measured. A linear relationship was noted between cell density and cholesterol/phospholipid and sphingomyelin/phosphatidylcholine ratios in the resistant variant B16BL6, confirming that lipid composition modulates the cytotoxic activity of ether lipids.

Phospholipid composition, phosphoinositide metabolism and metastatic capacity in murine melanoma B16 variants at different stages of growth.

Experimental efforts to identify characteristic features of metastatic subpopulations have led to the selection of strains of specialized cells with high and low metastatic potential in the hope that by studying their biochemical and biophysical properties we might start to clarify how tumour cells metastasize. We report data on the phospholipid composition of three variants of murine melanoma B16: F1, with low metastatic potential; F10, highly metastatic when injected i.v.; and BL6, highly metastatic, spontaneous metastases developing from a primary s.c. tumour. Cells were studied at different stages of growth: subconfluent cultures (40-70 x 10(3) cells/cm2) or dense cultures (140-170 x 10(3) cells/cm2). Total phospholipid content decreased as cell density increased in all variants; these changes can probably be related to the reduction in cell volume with increasing cell numbers in the well. As a consequence of this reduction, the amounts of individual phospholipids also decreased in dense cultures. Phosphatidylinositol behaved differently in the highly metastatic variants. In the F1 strain it was three times lower than would be expected from the total phospholipid reduction, while in F10 and BL6 levels increased when cell density increased. Differences in phosphatidylinositol level were also found between variants within each density, suggesting that phosphoinositide synthesis may be related to the metastatic potential of the variants. Incorporation of ([3H] myo)-inositol incorporation into phospholipids over a period of 4 h was greater in F1 cells than in F10 and BL6 at both cell densities.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of cell cholesterol in modulating antineoplastic ether lipid uptake, membrane effects and cytotoxicity.

Membrane-interactive ether lipids (EL) exert toxic and antiproliferative effects on cancer cells in vitro. They appear to be selectively more toxic to cancer cells than to normal cells and thus they are ideal candidates for bone-marrow purging procedures. However, no conclusive explanation has yet been provided for this property. We now present some data indicating that the cholesterol concentration in the incubation medium modulates EL toxicity against the HL60 leukemic cell line in vitro. Furthermore, model membranes richer in cholesterol take up EL more slowly, and cell cholesterol enrichment of HL60 cells counteracts EL biophysical membrane interaction, but not toxicity, in our experimental model. However, the K562 cell line, a leukemia line less sensitive to EL toxic action, has higher levels of cell cholesterol. Our data provide evidence to explain differences in sensitivity to EL among different cell types and contribute to the understanding of the mechanism of action of EL.