Prognostic evaluation of patients submitted to surgery for malignant pleural mesothelioma

The role of surgical resection remains controversial in malignant pleural mesothelioma. The assessment of its impact on prognosis is complicated by a poor understanding of the prognostic factors in the disease. We therefore evaluated, through univariate and multivariate analysis, the role on prognosis of 24 variables in 57 patients submitted to surgery from 1985 to 1993. Sixteen patients had only exploratory thoracotomy and 12 minimal residual disease after surgery (no nodules >1 cm in diameter). Thirty-four cases had epithelial histotype, 6 sarcomatous and 17 mixed. Median survival for the whole group was 15.7 months. Multivariate analysis showed a highly significant influence on survival for minimal residual disease after surgery (p=0.0006), followed by TNM stage (p=0.01). Median survival for patients with TNM stage I disease was 36.3 months and for patients with minimal residual disease 33 months. In conclusion, these data suggest that patients with limited disease have a longer survival after surgery than those with extensive disease. At the same time, our results indicate that the achievement of significant disease reduction with surgery has a critical impact on the prognosis of pleural mesothelioma.     

Feasibility of intra-arterial chemotherapy followed by chemoembolization, every 28 days, in unresectable hepatocellular carcinoma

Encouraging response rates and survival have been reported with intra-arterial (i.a.) chemotherapy and chemoembolization, but limited data are available on the association of the two treatment modalities. We therefore started a feasibility study of i.a. chemotherapy plus chemoembolization, performed every 28 days for 3 cycles, according to the following schedule: L-leucovorin (100 mg/m(2) i.v.), fluorouracil (800 mg/m(2) i.a.), and carboplatin (250 mg/m(2) i.a.). Chemoembolization with mitoxantrone (10 mg/m(2)) plus ethiodized oil was performed immediately after this treatment, followed by gelatin powder. Fourteen patients entered the study and were evaluable for side effects. Main patient characteristics were: males 13, females 1; median age 65 yr (range 45-75); stage TNM II-III 10, IVA 4; Childs' A 8, Childs' B 6; elevated baseline alpha-fetoprotein, 11; cirrhosis 14. No drug-related deaths have been observed. Ten patients were able to complete the program. The reasons for discontinuing treatment were worsening of liver functions in 3 cases and grade IV neutropenia in 1 patient. Eight patients had grade I-II pain and 10 patients had grade I-II fever. In conclusion the study demonstrated that chemoembolization plus i.a. chemotherapy is feasible in patients with hepatocellular carcinoma in cirrhosis and deserves further investigation.     

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

The neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP or allopregnanolone) is a positive modulator of GABA_A receptors synthesized in the brain, adrenal glands, and gonads. In rats, ethanol activates the hypothalamic–pituitary–adrenal axis and elevates 3α,5α-THP in plasma, cerebral cortex, and hippocampus. In vivo, these effects are dependent on both the pituitary and adrenal glands. In vitro, however, ethanol locally increases 3α,5α-THP in hippocampal slices, in the absence of adrenal influence. Therefore, it is not known whether ethanol can change local brain levels of 3α,5α-THP in vivo, independent of the adrenals. To directly address this controversy, we administered ethanol (2 g/kg) or saline to rats that underwent adrenalectomy (ADX) or received sham surgery and performed immunohistochemistry for 3α,5α-THP. In the medial prefrontal cortex (mPFC), ethanol increased 3α,5α-THP after sham surgery, compared with saline controls, with no ethanol-induced change in 3α,5α-THP following ADX. In subcortical regions, 3α,5α-THP was increased independent of adrenals in the CA1 pyramidal cell layer, dentate gyrus polymorphic layer, bed nucleus of the stria terminalis, and paraventricular nucleus of the hypothalamus. Furthermore, ethanol decreased 3α,5α-THP labeling in the nucleus accumbens shore and central nucleus of the amygdala, independent of the adrenal glands. These data indicate that ethanol dynamically regulates local 3α,5α-THP levels in several subcortical regions; however, the adrenal glands contribute to 3α,5α-THP elevations in the mPFC. Using double immunofluorescent labeling we determined that adrenal dependence of 3α,5α-THP induction by ethanol is not due to a lack of colocalization of 3α,5α-THP with the cholesterol transporters steroidogenic acute regulatory protein (StAR) or translocator protein (TSPO).     

Enhanced Expression of Sodium Hydrogen Exchanger (NHE)-1, 2 and 4 in the Cervix of Ovariectomised Rats by Phytoestrogen Genistein

Restoring the pH of cervicovaginal fluid is important for the cervicovaginal health after menopause. Genistein, which is a widely consumed dietary health supplement to overcome the post-menopausal complications could help to restore the cervicovaginal fluid pH. We hypothesized that genistien effect involves changes in expression of NHE-1, 2 and 4 proteins and mRNAs in the cervix. This study investigated effect of genistein on NHE-1, 2 and 4 protein and mRNA expression in the cervix in order to elucidate the mechanisms underlying possible effect of this compound on cervicovaginal fluid pH after menopause. Methods: Ovariectomised adult female rats received 25, 50 and 100 mg/kg/day genistein for seven consecutive days. At the end of the treatment, animals were sacrificed and cervix was harvested. Expression of Nhe-1, 2 and 4 mRNA were analyzed by Real-time PCR while distribution of NHE-1, 2 and 4 protein were observed by immunohistochemistry. Results: Treatment with 50 and 100 mg/kg/day genistein caused marked increase in the levels of expression and distribution of NHE-1, 2 and 4 proteins in the endocervical epithelia. Levels of Nhe-1, 2 and 4 mRNA in the cervix were also increased. Coadministration of ICI 182 780 and genistein reduced the expression levels of NHE-1, 2 and 4 proteins and mRNAs in the cervix. Conclusions: Enhanced expression of NHE-1, 2 and 4 proteins and mRNAs expression in cervix under genistein influence could help to restore the cervicovaginal fluid pH that might help to prevent cervicovaginal complications related to menopause.     

Ecliptic method for the determination of backscatter into the beam monitor chambers in photon beams of medical accelerators

A new method to measure the effect of the backscatter into the beam monitor chambers in linear accelerators is introduced from first principles. The technique, applicable to high-energy photon beams, is similar to the well-known telescopic method although here the heavy blocks are replaced by a very small, centred block on the shadow tray, thus the name 'ecliptic method'. This effect, caused mainly by backscattering from the secondary collimators, is known to be an output factor constituent and must be accounted for when detailed calculations involving the machine's head are required. Since its magnitude is generally small, experimental errors might obscure the behaviour of the phenomenon. Consequently, the procedure introduced goes along with an uncertainty assessment. Our theory was confirmed via measurements in cobalt-60 beams, where the studied effect does not contribute to the output factor. Measurements were also performed on our Saturne 41 linear accelerator and the results were qualitatively similar to those described elsewhere. The collimation systems were studied separately by varying one jaw setting while keeping the other at its maximum value. In the light of these results, we deduced an algorithm that can correlate the former data with the effect of backscattering to the beam monitor chambers for any rectangular field within 0.5%, which is of the order of the experimental uncertainty (0.6%). As we show, the experimental procedure is safe, simple, not invasive for the linac and requires only basic dosimetry equipment.