Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study.

PURPOSE: To appraise the performance of Comprehensive Geriatric Assessment (CGA) in elderly cancer patients (> or = 65 years) and to evaluate whether it could add further information with respect to the Eastern Cooperative Oncology Group performance status (PS). PATIENTS AND METHODS: We studied 363 elderly cancer patients (195 males, 168 females; median age, 72 years) with solid (n = 271) or hematologic (n = 92) tumors. In addition to PS, their physical function was assessed by means of the activity of daily living (ADL) and instrumental activities of daily living (IADL) scales. Comorbidities were categorized according to Satariano's index. The association between PS, comorbidity, and the items of the CGA was assessed by means of logistic regression analysis. RESULTS: These 363 elderly cancer patients had a good functional and mental status: 74% had a good PS (ie, lower than 2), 86% were ADL-independent, and 52% were IADL-independent. Forty-one percent of patients had one or more comorbid conditions. Of the patients with a good PS, 13.0% had two or more comorbidities; 9.3% and 37.7% had ADL or IADL limitations, respectively. By multivariate analysis, elderly cancer patients who were ADL-dependent or IADL-dependent had a nearly two-fold higher probability of having an elevated Satariano's index than independent patients. A strong association emerged between PS and CGA, with a nearly five-fold increased probability of having a poor PS (ie, > or = 2) recorded in patients dependent for ADL or IADL. CONCLUSION: The CGA adds substantial information on the functional assessment of elderly cancer patients, including patients with a good PS. The role of PS as unique marker of functional status needs to be reappraised among elderly cancer patients.     

Overexpression of vascular endothelial growth factor-A165 enhances tumor angiogenesis but not metastasis during beta-cell carcinogenesis.

The pivotal role of vascular endothelial growth factor (VEGF-A) in the regulation of angiogenesis, in particular in the onset and maintenance of tumor angiogenesis, has been demonstrated repeatedly in experimental model systems and, more recently, in clinical trials. Experimental evidence has also suggested that up-regulated expression of VEGF-A may cooperate with other genetic or epigenetic changes to induce or accelerate tumor progression to invasive and metastatic cancers. Here we report the generation of transgenic mouse lines that express human VEGF-A165 under the control of the rat insulin promoter in the beta cells of pancreatic islets of Langerhans (Rip1VEGF-A). These mice do not exhibit detectable changes in islet development, vascularization, or physiology. Intercrosses of these mice with a transgenic mouse model of pancreatic beta cell carcinogenesis (Rip1Tag2) result in an earlier onset of tumor angiogenesis and with it accelerated tumor growth and mortality. The transition from benign tumors (adenoma) to malignant tumors (carcinoma) is modestly accelerated; however, tumor metastases are not observed. Our findings indicate that in beta-cell tumorigenesis, overexpression of VEGF-A165 accelerates the onset of tumor angiogenesis and with it tumor progression but is not sufficient to induce tumor metastasis.     

Chronic liver herniation through a right Bochdalek hernia with acute onset in adulthood

Congenital right diaphragmatic hernia of Bochdalek rarely occurs in adults and usually is asymptomatic. We report a right Bochdalek hernia with chronic liver herniation and intestinal malrotation in a 55-year old woman who presented with acute intestinal occlusion. The diagnosis required definitive confirmation by CT scan. With impending strangulation, emergency surgery through a thoracoabdominal approach resulted in an easy hernia repair and reduced the technical difficulties due to the intestinal malrotation.     

Dopamine and morphine stimulate nitric oxide release in human endometrial glandular epithelial cells

OBJECTIVE: Previous studies have shown that human endometrial glandular epithelial cells contain endothelial nitric oxide synthase indicating that the endometrium might produce nitric oxide (NO). We conducted this study to identify stimuli that can activate a transient NO release from endometrial glandular epithelial cells because NO is an important intracellular and intercellular signal transduction pathway in reproductive cycle. METHODS: Endometrial glandular epithelial cells, free of endothelial cells, were isolated from human endometrial specimens and maintained viable in RPMI 1640 medium with 2% fetal bovine serum for 2-4 days. Nitric oxide release from the glandular cells in response to stimuli was monitored continuously amperometrically. RESULTS: Among the substances examined, we found that dopamine and morphine stimulated a transient surge of NO production that was dose-dependent, whereas estrogen, progesterone, or relaxin (RLX) had no short-term effect on NO release. Cells treated with RLX or dopamine for 4 days enhanced the dopamine-induced NO release fourfold to sixfold, with the peak of the NO surge shifting from 35 to 15 seconds. CONCLUSION: Endometrial glandular cells were capable of producing NO. Dopamine and morphine were potent stimuli for a transient surge of NO release from endometrial glandular cells. Furthermore, prolonged exposure to dopamine or RLX enhanced the sensitivity of NO release in endometrial glands.     

Recurrent antiphospholipid-related deep vein thrombosis as presenting manifestation of systemic lupus erythematosus

Antiphospholipid antibodies (aPL) are frequently associated with thrombotic disorders in the so-called antiphospholipid syndrome. Together with anticardiolipin antibodies (aCL), lupus anticoagulant (LA) is the main diagnostic tool for aPL detection. Since LA determination is based on the finding of prolonged clotting time in vitro, concomitant anticoagulant therapy may significantly interfere with its detection. We report a case of a boy in whom recurrent aPL-related thrombosis heralded for several months the onset of systemic lupus erythematosus (SLE). Abnormally increased in vitro clotting times at the time of the second thrombotic event led to the suspicion of the presence of LA activity. However, this latter finding was difficult to interpret since the patient was already on heparin treatment at the time of our first observation. Thus, LA was assayed using a commercial kit in which a heparin neutralizer is included (Staclot LA). Two consecutive samples from the patient were compared with eight patients on anticoagulant therapy for non-aPL-related thrombotic events and 20 healthy controls. The study showed that, taking into account the concomitant anticoagulant treatment, Staclot LA was positive only in the propositus, raising the suspicion of a possible aPL-related origin of the thrombotic event. This issue was definitively confirmed in a subsequent follow-up. Conclusion The present report shows that aPL-related deep vein thrombosis can be the earliest clinical manifestation of pediatric SLE, and that Staclot LA may have a role in LA detection during the course of anticoagulant treatment. Received: 6 October 1998 / Accepted: 15 September 1999     

Alcohol reduces MMP-2 in humans and isolated smooth muscle cells

Alcoholic beverages are known to exert a protective effect on atherosclerotic disease. This study aimed to assess the in vivo and in vitro effects of alcohol on matrix metalloproteinase (MMP) -2 and -9, known to determine atherosclerosis progression. Eighteen healthy volunteers, regular drinkers (two standard alcohol servings/day, on average) at first examination (baseline) were asked to abstain from any alcoholic beverage for one week (abstention), and then to assume two standard alcohol servings of beer daily for 1 week (re-exposure). Activity of MMP-2 and -9, total antioxidant activity (AOA), glutathione (GSH) plasma levels were carried out at baseline, at the end of abstention, and after 1 week of re-exposure. To validate the in vivo results, MMP-2 activity and expression, AOA, and GSH, were determined in human smooth muscle cells treated for 96 h with increasing concentrations (12.5-100 mM) of ethanol. MMP-2, but not MMP-9 plasma activity was higher at abstention than at baseline or re-exposure (P<.001 and P< or =.005, respectively). Changes in AOA and GSH throughout the study were not significant. No correlation was found between MMPs and antioxidant activity. In vitro, ethanol at 25 mM reduced by around 10% MMP-2 activity (P=.003) in smooth muscle cells, whereas MMP-2 expression, AOA, and GSH were unaffected. Alcohol reduces MMP-2 plasma activity in healthy humans and in isolated vascular smooth muscle cells. This in vitro reduction is unrelated to MMP-2 expression in vascular cells or to antioxidant levels changes.     

Expression of HER-2/neu oncoprotein, DNA-ploidy and S-phase fraction in advanced ovarian cancer

The immunohistochemical expression of HER-2/neu and cytofluorimetric data were retrospectively analyzed in a group of primary advanced ovarian cancers. Thirty-three out of 94 (35%) cases showed a specific p185/neu immunoreaction. No correlation between p185/neu expression and any of the clinico-pathologic parameters examined was observed. As far as cytofluorimetric data are concerned, 38 out of 69 (55%) of the tumors were diploid (DNA index = 1) while 31 (45%) were aneuploid (DNA index from 1.10 to 2.50 with a median value of 1.50). Ovarian tumors were defined as of low and high S-phase fraction in 68% and 32% of the cases, respectively. Tumor ploidy and S-phase fraction did not correlate with the clinico-pathologic characteristics or p185/neu oncoprotein expression. Aneuploid tumors had a higher S-phase fraction (mean: 15.81 ± 13.44) than diploid tumors (mean: 8.89 ± 7.98) ( P < 0.01). p185/neu expression failed to affect significantly both overall and progression free survival. On the other hand tumor ploidy was found to be related to the prognosis of advanced ovarian cancer patients although the difference was not statistically significant. As far as progression free survival is concerned, the median time to recurrence was not reached for diploid cases whereas it was 21 months for aneuploid cases ( P < 0.05). The 5-year survival for patients with a low S-phase fraction (58%) was significantly higher than for patients with high S-phase fraction tumors (28%) ( P < 0.01). Median time to recurrence was 48 and 17 months for low and high S-phase fraction tumor patients, respectively ( P < 0.05). However, in a multivariate analysis both tumor ploidy and S-phase fraction did not retain their prognostic value. The assessment of the role of the parameters examined in improving the prognostic characterization of ovarian cancer patients should be investigated in large multicenter clinical trials.