Phase II study of tamoxifen and high-dose retinyl acetate in patients with advanced breast cancer.

Retinoids have shown a tumor growth inhibition and a synergistic activity with hormonal manipulations in human breast cancer cell lines and rat mammary carcinoma. To investigate the potential usefulness of this synergistic activity in human breast cancer, 33 postmenopausal patients with advanced disease were treated with the combination of tamoxifen (10 mg p.o. three times a day) and retinyl acetate (300,000 IU p.o. daily). Out of 31 evaluable patients, 3 achieved complete response, 9 partial response (overall response rate: 38.5%, 95% confidence interval = 21%-56%) and 16 (52%) showed no change. The median duration of response was 11.5 months (range: 3-19+ months), while the 2-year overall survival rate for the entire group of patients was 63%. Toxicity was generally mild, hot flushes, nausea (and/or vomiting), headache and cutaneous itching being the most frequent side-effects. Only 1 patient discontinued treatment for severe toxicity. These preliminary results suggest that the combination of tamoxifen and high-dose retinyl acetate is a safe and effective regimen for breast cancer patients. However, the study design does not allow us to establish whether the very low rate of early disease progression we observed might be related to a possible synergistic effect between retinoids and antiestrogens or rather to the quite indolent disease of the patients who have been selected for entry into this trial.

Plasma retinol levels and side effects following high-dose retinyl acetate in breast cancer patients.

Plasma retinol levels and toxicity were evaluated in thirteen metastatic breast cancer patients treated orally with high-dose (300,000 I.U./day) retinyl acetate in combination with oral tamoxifen. Following the first dose of the drug, there was a drop of plasma retinol concentrations followed by a recovery to the pre-treatment levels and by a further increase to reach a plateau six to eight hours after drug administration. During the first two months of treatment cumulative increase of plasma retinol was seen, and long-term systemic concentrations in the +50-60% range level were maintained by the treatment. The toxicity observed was acceptable and included gastrointestinal symptoms, skin toxicity and headache. These toxicities could be related to the long-term increase of retinol systemic concentrations. We concluded that the daily dose of 300,000 I.U. retinyl acetate can be administered to cancer patients over a period of several months, is well tolerated and yields a substantial increase of systemic retinol.

[Postoperative evaluation of vascular bifurcation prostheses by means of helical CT]. / Valutazione postoperatoria delle protesi vascolari biforcate mediante TC spiroidea.

The dilatation of the vascular grafts is a well known phenomenon. It is usually evaluated by means of ultrasounds or, in selected cases, by CT scans or MRI; nevertheless its characteristics are far beyond to be fully recognized. Following our promising preliminary experience with helical CT as sole preoperative imaging for AAA, we have evaluated its reliability in the postoperative follow-up. We have studied 12 patients with aorto-iliac and 11 with aorto-femoral bypass for AAA, with a follow-up ranging between 1 and 3 years. A helical CT acquisition was performed during a single breath-holding with a 5-mm slice thickness, thus resulting in a 30 cm z-axis coverage. Axial images were reconstructed at 2-mm increments and used to generate high quality multiplanar reformatted (MPR) and three-dimensional (3D) surface rendered images. For each patient we evaluated the characteristics of the graft, the maximal diameters and the wall modifications. The average expansion was 28% at 1 year, stable at 2 years and then increased up to 44% at 3 years. Considering the different types of Dacron grafts, the dilatation was ranging between 22% and 46% (21 cases). The mean expansion was 31.3% and 29.5% for the trunk and for the branches of the graft respectively. No perigraft seroma nor anastomotic aneurysms were detected. A peculiar observation, both with and without contrast medium injection, was that all the grafts made on Dacron were not anymore depictable from the aortic wall after 1 year; the contrary was observed for the ePTFE grafts.

[Preoperative imaging of aneurysms of the abdominal aorta. Role of CT scan]. / Imaging preoperatorio degli aneurismi dell'aorta addominale. Ruolo della TC spiroidea.

The reliability of helical CT as sole preoperative diagnostic technique for abdominal aortic aneurysms (AAA) and its accuracy in detecting vascular anomalies in the abdominal region was evaluated retrospectively in 42 patients with asymptomatic AAA > 40 mm. A single breath-holding helical scan was performed with 5 mm slice thickness, during a single injection of contrast medium, resulting in a 20 cm z-axis coverage. Axial images were reconstructed and used to generate high quality multiplanar reformatted images. Digital subtraction angiography (DSA) was performed in the first 18 patients and then in case of associated peripheral vascular disease (6 patients). Helical CT exactly showed, in all cases, the proximal and distal extent of the AAA. The visceral vessels as well as the inferior vena cava and renal veins were always clearly depicted, showing anatomical variants or pathological involvement in 19 patients. DSA gave sufficient details on the distal run-off but did not allow a reliable visualization of the visceral branches, venous anomalies and true extent of AAA. In our experience helical CT should be considered as the sole method for preoperative imaging of AAA. It allows a complete and precise evaluation; it is fast, with low doses of radiations and does not require hospitalization.

Evidence for Ca(2+)-permeable AMPA receptors in the olfactory bulb.

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs), a subtype of glutamate receptor, contribute to olfactory processing in the olfactory bulb (OB). These ion channels consist of various combinations of the subunits GluR1-GluR4, which bestow certain properties. For example, AMPARs that lack GluR2 are highly permeable to Ca(2+) and generate inwardly rectifying currents. Because increased intracellular Ca(2+) could trigger a host of Ca(2+)-dependent odor-encoding processes, we used whole cell recording as well as histological and immunocytochemical (ICC) techniques to investigate whether AMPARs on rat OB neurons flux Ca(2+). Application of 1-naphthylacetyl spermine (NAS), a selective antagonist of Ca(2+)-permeable AMPARs (CP-AMPARs), inhibited AMPAR-mediated currents in subsets of interneurons and principal cells in cultures and slices. The addition of spermine to the electrode yielded inwardly rectifying current-voltage plots in some cells. In OB slices, olfactory nerve stimulation elicited excitatory responses in juxtaglomerular and mitral cells. Bath application of NAS with d,l-2-amino-5-phosphonovaleric acid (AP5) to isolate AMPARs suppressed the amplitudes of these synaptic responses compared with responses obtained using AP5 alone. Co(2+) staining, which involves the kainate-stimulated influx of Co(2+) through CP-AMPARs, produced diverse patterns of labeling in cultures and slices as did ICC techniques used with a GluR2-selective antibody. These results suggest that subsets of OB neurons express CP-AMPARs, including functional CP-AMPARs at synapses. Ca(2+) entry into cells via these receptors could influence odor encoding by modulating K(+) channels, N-methyl-d-aspartate receptors, and Ca(2+)-binding proteins, or it could facilitate synaptic vesicle fusion.

Role of blood groups as prognostic factors in primary breast cancer.

The role of blood groups as risk factors for breast cancer and their predictive value after radical surgery have been retrospectively evaluated in 315 breast cancer patients. The AB0 group distribution in these breast cancer patients was not significantly different from that of control women. Patients with blood group 0 showed a significantly lower risk of death than those with groups A, B and AB. Moreover, by using Cox's multivariate analysis, blood groups were shown to possess a predictive value independent of other known prognostic factors. These results suggest that also genetic factors could be involved in the pathophysiology of breast cancer growth and need to be further investigated.

[Defecography by spiral computed tomography]. / La defecografia con Tomografia Computerizzata spirale.

PURPOSE: We investigated the possible role of helical CT defecography in pelvic floor disorders by comparing our results with those of conventional defecography. MATERIAL AND METHODS: Our series consisted of 90 patients, namely 62 women and 28 men, ranging in age 24-82 years. They were all submitted to conventional defecography, and 18 questionable cases were also studied with helical CT defecography. The conventional examination was performed during the 4 standard phases of resting, squeezing, Valsalva and straining; we used a remote-control unit. The parameters for helical CT defecography were: 5 mm beam collimation, pitch 2, 120 KV, 250 mAs and 18-20 degrees gantry inclination to acquire coronal images of the pelvic floor. The rectal ampulla was distended with a bolus of 300 mL nonionic iodinated contrast agent (dilution: 3 g/cc). The patient wore a napkin and was seated on the table, except for those who could not hold the position and were thus examined supine. Twenty-second helical scans were performed at rest and during evacuation; multiplanar reconstructions were obtained especially on the sagittal plane for comparison with conventional defecographic images. RESULTS: An unquestionable diagnosis could be made in all the 18 patients submitted to helical CT defecography. The diagnosis was in agreement with proctology results and added new information in all cases. Sixteen patients had constipation and 2 fecal incontinence--one from rectal prolapse and the other from a rectovaginal fistula. In this latter case helical CT defecography permitted to confirm the fistula and suggest its course. One patient had a previously undetected ovarian cancer metastatic to the anterior rectal wall. DISCUSSION AND CONCLUSIONS: Coronal helical CT defecography images permitted to map the perineal floor muscles, while sagittal reconstructions provided information on the ampulla and the levator ani. To conclude, helical CT defecography performed well in the study of pelvic floor disorders and can follow conventional defecography especially in questionable cases.