Insulin-like growth factor-II is a useful marker to detect hepatocellular carcinoma?

BACKGROUND: Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. The utility of serum alpha-fetoprotein (α-FP) in its detection is questionable. Over-expression and high circulating levels of insulin-like growth factor-II (IGF-II) were reported in tissue and in serum of patients with HCC. We investigated the diagnostic application of IGF-II in the diagnosis of HCC. METHODS: Serum IGF-II and α-FP levels were measured in 178 patients (82 with HCC and 96 with liver cirrhosis) and in 30 healthy controls. Spearman test, non parametric combination test and confidence interval analysis were used for statistical evaluation of data. RESULTS: The best cut-off values selected by ROC curves were 796 ng/ml for IGF-II and 132 ng/ml for α-FP. IGF-II mean values were higher in patients with HCC than in those with liver cirrhosis (LC) (p=0.0001) but lower in LC than in controls (p=0.0001). Serum IGF-II levels above cut-off were found in 22% of patients with HCC, in 9.3% of those with cirrhosis and in 20% of controls. α-FP serum levels >132 ng/ml were observed in 48% of HCC, in 3.1% of LC and in none of control group. By correlation study, serum IGF-II levels were significantly correlated with serum α-FP levels (r=0.427, p=0.0001) and with nodules' diameter (r=0.252, p=0.0130) but not with nodules' number (p>0.050). Finally, IGF-II showed lower sensitivity, specificity and predictive values than α-FP. CONCLUSION: Circulating IGF-II is not a useful marker for HCC. Further researches are however needed to evaluate its diagnostic accuracy before and after nutritional adjustment.

Reduction mammaplasty and related impact on psychosexual function.

INTRODUCTION: Reduction mammaplasty brings an effective improvement, both from the physical and psychological points of view. However, psychosexual consequences are as yet poorly studied, although scars, impairment of sensibility, change in shape and asymmetry can have a negative effect on sexual life. AIM: These authors retrospectively reviewed 55 patients to verify the existence of a close relationship between this popular surgical procedure and psychosexual function. MATERIAL AND METHODS: All patients were compared to a group (51 healthy women) chosen from the hospital personnel. Both groups answered four psychological questionnaires (Short Form (SF)-36, Hamilton Anxiety Rating Scale (Ham-A), Hamilton Rating Scale for Depression (Ham-D), Female Sexual Function Index (FSFI)) anonymously, in addition to the scar-assessment test as a single physical test. Psychological tests aim to evaluate self-esteem, quality of life (SF-36) and sexual function in women (FSFI, a test based on Erectile Function Index of Male). High levels of anxiety and depression were used as exclusion criteria in our study (Ham-D and Ham-A). Statistical analysis was based on non-parametric correlation test adjusted for small groups and Spearman's rho test to verify the associations among sub-items scales. RESULTS: Almost all patients (98%) fulfilled the inclusion criteria for our study. Sexual function index was equal in both groups, but it still showed a higher quality of life in the control group. Nevertheless, the SF-36 value of the patients' group is still enough to allow for acceptable self-esteem. CONCLUSIONS: We can confirm that reduction mammaplasty does not impair sexual satisfaction or quality of life; moreover, we believe that this procedure can improve such indices. Further investigation will compare patient's values prior to and following surgery to put in evidence a stronger relationship between mammary reduction and sexual function.

Acute intoxication with orphenadrine and clozapine.

This report describes a fatal intoxication with two different drugs: clozapine and orphenadrine. A 38-year-old man was found dead in the bedroom of his residence. Near the body were found various empty pharmaceutical boxes, employed in schizophrenic therapy, two of them containing clozapine and orphenadrine. High concentrations of clozapine and orphenadrine detected in blood, urine and gastric content were related to death. These compounds were identified and quantitated by liquid-liquid extraction followed by gas chromatographic/mass spectrometry (GC/MS) analysis.

-SH groups and glutathione in cancer patient's blood.

As reported in previous investigations, erythrocytes are the elements of peripheral blood most affected by free radical activity in the pathogenesis of cancer. In these studies, the level of sulphydrilic groups and reduced glutathione were assayed in the erythrocytes and plasma, while their successful scavenger activity against cell membrane oxidation and peroxidation has already been established. In subjects with cancer, the levels of -SH groups (p < 0.002) and reduced glutathione in both plasma and erythrocytes (p < 0.0001) were shown be a statistically significantly decreased compared to healthy controls. These differences were related to the defence of the hematic tissue against free radical activity. A similar pattern has also been reported when studying vitamin A and E content in the peripheral blood of cancer patients. The role of oxido-reduction phenomena in this disease is discussed, as well as the importance of reducing the oxido-peroxidation involvement of tissues and cell elements. The study of the GSH/GSSG ratio in order to determine the stage of the disease would be useful and might represent a systemic marker for cancerous lesions.

Free radical erythrocyte damage in tumoral disease assessed by He-Ne laser and optical microscope through "Heinz Bodies" method.

Results obtained from blood sample readings by optical microscopy and He-Ne laser (lambda = 630.1 mW), have confirmed the reduction in Heinz Bodies (HB) formation time and the Transmittance Reduction Degree (TRD), in malignancies. The results of spectrometric readings in colorectum polyposis, (TRD = 0.07) and fibrocystic mastopathy (TRD = 0.08) gave results overlapping with controls (TRD = 0.08). In neoplasias, the early HB formation in erythrocytes observed by optical microscope corresponded to TRD increase = 0.17 (P < 0.01). TRD increase was statistically significant (P < 0.01), as well as the reduction in the time of HB appearance (< 0.01). The relationship between optical and laser readings was exponential in tumors, while it was linear in controls, in polyposis and mastopathies. The values of the correlation coefficients obtained by both methods were significant (P < 0.01) for all the studied groups. Moreover, these research data further support the existence, even in the earlier stages of the disease, of the labile state of the red cell membrane due to strong lipid peroxidation by FRs.

Vitamins A and E in neoplastic disease.

Vitamins A and E play an important role against 'free radicals' (FRs). Their antioxidant action is evident in neoplastic disease (ND) that is known to have a FRs pathology. This finding has been supported by previous research showing increased lipid peroxidation of the erythrocyte membrane with increased permeability and higher hemoglobin susceptibility to oxidative stress. Connections exist between the two vitamins and FRs lipid peroxidation of the membranes. In order to study A and E vitamin behaviour in ND, they were assayed in the sera of 88 cancer patients versus 94 healthy subjects. In the 88 cancer cases, without considering variables such as age, sex and smoking habits, the average amount of vitamin A was 47.44+/-19.60 mu g/dl versus 71.77+/-18.30 in controls (P<0.0001). The average amount of vitamin E was 1144.42+/-507.45 in ND versus 1497.45+/-397.74 in controls (P<0.0001). The two vitamins were simultaneously assayed in the same serum by high pressure liquid chromatography. The method is rapid and gave exact and repeatable results. Reasons for vitamin decrease are discussed.

Anti free radical action of calcium antagonists and H1 and H2 receptors antagonists in neoplastic disease.

The blood of the subjects suffering from Neoplastic Disease (ND) shows phenomena of membrane peroxidation due to the presence of Free Radicals (FRs), in a quantity much greater than the one observed in the blood of healthy subjects. This can be detected either by calculating the time necessary for the formation of "Heinz bodies" (Hbs), (p < 0.00001) after oxidative stress of the blood in vitro with acetylphenylidrazine (APH), or by calculating the methemoglobin (metHb) quantity that forms after the same treatment (P < 0.00001). The statistical analyses we carried out showed that metHb formation was not affected by age, sex, smoking habits, red blood cell number, Hb, Ht or tumor staging. In this study, by using equal parameters of investigation, we noted that the blood of the subjects with ND who were previously treated with calcium-antagonists drugs and with antagonists of H1 and H2 receptors, gave results completely superimposable on the results obtained from healthy subjects, implying that the treatment had avoided the increase of FRs. Therefore we concluded that calcium-antagonists and the antagonists of the H1 and H2 receptors behave as antioxidant substances, having decreased the FRs damaging activity on the cellular membranes, thus controlling, although to a limited degree, the pejorative evolution of the disease. It is also important to remember that investigations into the ND, even possible screenings, must take into account the above said data, submitting the subjects under investigation to a pharmacological wash out, particularly with those substances which, are considered to be scavengers of FRs. Some of these substances are investigated in this work.

Hemoglobin oxidative stress in cancer.

The role played by free radicals in carcinogenesis and their relationships with antioxidant pool and cancer have already been shown. Free radicals induce increased membrane permeability through membrane lipid peroxidation, protein oxidation and histamine release from mast cells. Free radicals also cause oxyhemoglobin oxidative stress which increases methemoglobin and hemichromes. For this reason, we studied the in vitro formation of methemoglobin at 0' and 90', dosed following the HPLC method, after oxidative stress of blood by means of acetylphenylhydrazine in 40 subjects with cancer and 40 healthy donors. The results showed that methemoglobin formation was highly significant in tumors as compared to controls (P < 0.0001). The statistical analyses we carried out showed that metHb formation is not affected by age, sex, smoking habit, red blood cell number, Hb, Ht or tumor staging. This makes us believe that free radicals alter erythrocyte membrane permeability and predenaturate oxyhemoglobin so that erythrocyte membrane becomes more susceptible to new oxidative stress. This caused the abnormal response we found. Our results clearly underline the role played by free radicals in tumorous disease and provide a successful and easy method to detect early, even in a pre-clinical stage, the presence of tumorous alterations in the human body.