Impact of erythropoietin treatment on the quality of life of oncologic patients.

Anaemia has a high incidence in cancer patients, especially when it is a consequence of myelosuppressive treatments. The incidence and prevalence of this condition is influenced by the type and extension of the tumour, type and intensity of the myelosuppressive treatment that patients receive, and previous surgery or intercurrent infections. Clinical manifestations of anaemia, overlapped by tumour symptomatology, depend on haemoglobin (Hb) levels; these manifestations cause impairment of the functional capacity, as well as a negative impact on the quality of life (QOL) of cancer patients as a consequence. Erythropoietin treatment for anaemia has been established as optimal for correcting Hb levels. Its impact on patients' QOL has been evaluated in numerous randomised prospective studies by the use of diverse types of erythropoietin and administration modes. The three types of erythropoietin, alpha, beta and darbepoetin alpha, have shown a clear efficacy in all haematological parameters. This positive effect is related with significant improvements in the QOL of patients, especially those patients undergoing myelosuppressive treatments, and with regard to specific scales of fatigue and anaemia.

Impact of erythropoietin treatment on the quality of life of oncologic patients

Anaemia has a high incidence in cancer patients, especially when it is a consequence of myelosuppressive treatments. The incidence and prevalence of this condition is influenced by the type and extension of the tumour, type and intensity of the myelosuppressive treatment that patients receive, and previous surgery or intercurrent infections. Clinical manifestations of anaemia, overlapped by tumour symptomatology, depend on haemoglobin (Hb) levels; these manifestations cause impairment of the functional capacity, as well as a negative impact on the quality of life (QOL) of cancer patients as a consequence. Erythropoietin treatment for anaemia has been established as optimal for correcting Hb levels. Its impact on patients' QOL has been evaluated in numerous randomised prospective studies by the use of diverse types of erythropoietin and administration modes. The three types of erythropoietin, alpha, beta and darbepoetin alpha, have shown a clear efficacy in all haematological parameters. This positive effect is related with significant improvements in the QOL of patients, especially those patients undergoing myelosuppressive treatments, and with regard to specific scales of fatigue and anaemia (AU)

Caspase-3 and caspase-6 in ductal breast carcinoma: a descriptive study.

Caspases are the main point in the apoptotic process. We have collected some information from 210 cases of Ductal breast cancer (pT1 - pT2) such as tumour size, histological differentiation degree, lymph node status and tumor necrosis in the infiltrating component and we have evaluated the number of apoptotic cells or bodies by TUNEL technique as well as immunohistochemical studies to evaluate the expression of caspase 3 and caspase 6, and proliferation index. Our results show that lymph node status and cell atypism are independent prognostic factors for recurrence and mortality and only tumour size is an independent prognostic factor for recurrence. However, the apoptotic index and the immunohistochemical expression of caspases and cell proliferation index have not turned out to be independent prognostic factors neither for recurrence nor mortality. These results show that classic prognostic factors known until now are the most important factors to predict the evolution of the illness.

Prognostic value of apoptosis in breast cancer (pT1-pT2). A TUNEL, p53, bcl-2, bag-1 and Bax immunohistochemical study.

Apoptosis or programmed cell death produces cells breaking into several fragments of nuclei, cytoplasm or both nuclei and cytoplasm, known as apoptotic bodies which can be visualized in haematoxylin-eosin staining. Some genes (promoters and suppressors) control this process and certain mutations may induce the expression of abnormal proteins, which can be detected by immunohistochemical staining. Apoptosis can be detected by the TUNEL method either identifying apoptotic bodies or cells at the initial stages of the fragmentation process. We have studied 186 cases of infiltrating ductal breast carcinoma, stages pT1-pT2, and analysed the prognostic significance of tumour recurrence and overall survival of apoptotic index (AI) through univariate and multivariate analysis. We have also studied the immunohistochemical protein expression of apoptosis promoter and suppressors gene (p53, nuclear expression; bcl-2 and Bax, cytoplasm expression; BAG-1, nuclear and cytoplasm expression). The results indicate prognostic significance of p53 and bcl-2 related to patient death and bcl-2 and tumour size to tumour recurrence, bcl-2 acting as a protector factor (apoptotic suppressor) in both situations. On the other hand, we have not found useful prognostic information of AI either to tumour recurrence or overall survival in univariate or multivariate studies. In this study, Bax expression does not provide a new prognostic role in breast carcinoma, although it contrasts to the bcl-2 action and accelerates death.

Epirubicin-cyclophosphamide adjuvant chemotherapy plus tamoxifen administered concurrently versus sequentially: randomized phase III trial in postmenopausal node-positive breast cancer patients. A GEICAM 9401 study.

BACKGROUND: A prospective randomized clinical trial was implemented to assess whether the concomitant or the sequential addition of tamoxifen to chemotherapy provides improved clinical benefit in the adjuvant treatment of breast cancer in postmenopausal patients. PATIENTS AND METHODS: Four-hundred and eighty-five patients with node-positive operable disease were randomized to receive tamoxifen (20 mg/day) concomitantly (CON) or sequentially (SEQ) to EC chemotherapy (epirubicin 75 mg/m(2) + cyclophosphamide 600 mg/m(2) on day 1, every 21 days for four cycles). RESULTS: In the 474 fully evaluable patients there were 96 events; eight being second neoplasms and 88 being related to the breast cancer. Of these, 48 of 88 occurred in the CON arm and 40 of 88 in the SEQ arm. The Kaplan-Meier estimation of disease-free survival (DFS) at 5 years was 70% in the CON and 75% in the SEQ group (log-rank test, P = 0.43). Adjusted hazard ratio for treatment was 1.11 (95% confidence interval 0.71-1.73; P = 0.64). CONCLUSION: This study fails to show an advantage of one treatment arm over the other, but a trend, albeit non-significant, appears to favor the sequential addition of tamoxifen to epirubicin + cyclophosphamide and, as such, warrants further investigation.

Sequential doxorubicin and docetaxel as first-line treatment in metastatic breast cancer: a GEICAM-9801 phase II study.

PURPOSE: To evaluate the efficacy and the toxicity profile of the sequential administration of doxorubicin and docetaxel as first-line chemotherapy in metastatic breast cancer (MBC). PATIENTS AND METHODS: Eighty-one patients received a total of 436 cycles of chemotherapy: 236 of doxorubicin (75 mg/m2) and 200 of docetaxel (100 mg/m2 every 21 days). The first 35 patients received doxorubicin every 14 days with G-CSF support, and in the other 46 cases doxorubicin was administered every 21 days without G-CSF. RESULTS: After entire treatment the overall response rate was 65% (18 complete responses). With a median follow-up of 19 months (range, 1-48 months), the median time to progression was 11.3 months and the median survival time was 31 months. As expected, febrile neutropenia was the most important toxicity and it appeared in 26 cycles (6%) and 19 patients (23%). In the patients that received doxorubicin every 14 days, the febrile neutropenia incidence was higher during docetaxel treatment, especially after its first administration. CONCLUSIONS: The dose and schedule of doxorubicin and docetaxel used in this trial seems to be active in first-line treatment of patients with MBC. The toxicity profile appears to be better than observed with concomitant schedules.

When to treat dyslipidaemia of patients with chronic renal failure on haemodialysis? A need to define specific guidelines.

BACKGROUND: There are no specific recommendations for management of dyslipidaemia in patients with chronic renal failure (CRF) on haemodialysis, in which atherosclerosis is a common cause of morbidity and mortality. The aim of the present study was to analyse different approaches based on low-density lipoprotein (LDL) cholesterol (measured and calculated with a formula), non-high-density lipoprotein (HDL) cholesterol, and HDL cholesterol levels in the clinical management of dyslipidaemia in haemodialysis patients. METHODS: Calculated LDL cholesterol by the Friedewald formula was compared with measured LDL cholesterol after separation by ultracentrifugation in 101 male patients with CRF on haemodialysis and in 101 healthy control subjects. RESULTS: Calculated LDL cholesterol coincided with measured LDL cholesterol, with less than 10% error, in 54 patients (53.4%) and in 75 controls (74.2%). Calculated LDL cholesterol was overestimated, with an error of 10% or more with respect to measured LDL cholesterol, in 37.6% of patients and in 23.7% of controls, and underestimated in 8.9% and 1. 9% respectively. Despite a good correlation between calculated and measured LDL cholesterol, the intraclass correlation coefficients demonstrate a poor concordance between calculated and measured LDL cholesterol, both in patients and controls. Only 17 patients were at non-HDL cholesterol level risk defined as higher than 4.28 mmol/l. HDL cholesterol levels lower than 0.9 mmol/l were found in 70% of patients and in 23% of controls. CONCLUSIONS: LDL or non-HDL cholesterol levels may not be appropriate for management of lipoprotein abnormalities in CRF patients. Further studies must clarify whether HDL cholesterol may be the best lipoprotein parameter for evaluating cardiovascular risk in these patients.

Glomerulocystic kidney disease: a single entity?

A case of glomerulocystic disease in a young adult with no family history or presence of other extrarenal malformations is described. Histological study revealed the presence of numerous cortical cysts corresponding to dilatations of Bowman's space. The patient had mild stable chronic renal failure for 5 years. In our patient, the disease corresponded to a sporadic adult form of glomerulocystic disease.

Serum lipoprotein(a) concentration in patients with chronic renal failure receiving haemodialysis: influence of apolipoprotein (a) genetic polymorphism.

Serum lipoprotein(a) (Lp(a)) was measured in 101 men with end-stage chronic renal failure (CRF) receiving haemodialysis and in 101 age-matched male controls. Apolipoprotein(a) genetic polymorphism was determined by immunoblotting in 100 patients and in 92 controls. Patients with CRF on haemodialysis had significantly greater serum Lp(a) than controls. Apolipoprotein(a) phenotype frequencies in patients with CRF did not differ from those of the control group. Both patients and controls with phenotype S2 had greater serum Lp(a) than those with phenotype S4. It should be emphasized that serum Lp(a) was significantly greater in patients on haemodialysis than controls, both for those with phenotype S2 and those with S4. Increased serum Lp(a) together with other lipoprotein abnormalities in patients with CRF on haemodialysis imply an increased cardiovascular risk. Genetic polymorphism clearly influences serum Lp(a) both in controls and patients. In the latter group CRF itself, dialysis, or both, also play a role in increasing Lp(a).

Lipoprotein abnormalities in hyperlipidemic and normolipidemic men on hemodialysis with chronic renal failure.

Lipids, lipoproteins, apolipoproteins (apo) and apo E polymorphism were determined in 101 men with chronic renal failure (CRF) were were on hemodialysis and 101 healthy controls matched for age and sex. Patients with CRF on hemodialysis had significantly higher levels of serum triglycerides, very-low-density lipoprotein (VLDL) cholesterol, intermediate-density lipoproteins (IDL), and lower levels of low- and high-density lipoproteins (LDL and HDL, respectively) than controls. Regarding apolipoproteins, serum apo B concentrations were decreased. Apo C-III concentrations in sera and in VLDL and HDL fractions were significantly increased in 35 hemodialysis patients compared with 32 controls. Seventy-eight of the 101 CRF patients had normal serum cholesterol and triglycerides (less than 5.2 mmol/liter and less than 2.3 mmol/liter, respectively). However, this subgroup also showed a significant increase in VLDL-triglycerides and serum apo E concentration in addition to changes observed in the group as a whole. Apo E polymorphism in our study population did not differ from that reported for other European populations. According to the different apo E phenotypes, lipids and lipoprotein composition showed no significant differences in controls or patients. We conclude that accumulation of triglyceride-rich lipoproteins in patients with CRF on hemodialysis may thus be at least in part related to the enrichment of apo C-III in VLDL and HDL fractions. Lipoprotein profile in hemodialysis patients, including those with normal serum cholesterol and triglyceride levels, is consistent with high cardiovascular risk.

Effect of bezafibrate on lipoprotein (a) and triglyceride-rich lipoproteins, including intermediate-density lipoproteins, in patients with chronic renal failure receiving haemodialysis.

The effect of bezafibrate, at doses of 200 mg three times weekly throughout a period of 10 weeks, on lipoprotein (a) and triglyceride-rich lipoproteins including intermediate-density lipoproteins (IDL) has been studied in 12 patients with chronic renal failure receiving haemodialysis. No side-effects were observed, and serum creatine phosphate kinase values remained within normal limits throughout the duration of the study. Serum cholesterol, triglycerides and apoprotein (apo) B significantly decreased after bezafibrate, whereas apo A-I increased significantly. Serum lipoprotein (a) decreased after bezafibrate, although differences reached no statistical significance. The very-low-density lipoproteins (VLDL) cholesterol and the VLDL triglycerides decreased from 0.93 +/- 0.45 mmol/l (Mean +/- SD) to 0.54 +/- 0.27 mmol/l (P less than 0.05) and from 1.50 +/- 0.58 mmol/l to 0.91 +/- 0.35 mmol/l (P less than 0.01) respectively. The IDL cholesterol and IDL triglycerides decreased from 0.44 +/- 0.35 mmol/l to 0.20 +/- 0.18 mmol/l (P = NS) and from 0.46 +/- 0.35 mmol/l to 0.17 +/- 0.12 mmol/l (P less than 0.05) respectively. These data, with a substantial improvement of the lipoprotein profile in patients with chronic renal failure on haemodialysis after treatment with bezafibrate, suggest a decrease in the coronary heart disease risk.

[Pulmonary hemorrhage and glomerulonephritis associated with essential mixed cryoglobulinemia]. / Hemorragia pulmonar y glomerulonefritis asociados a crioglobulinemia mixta esencial.

A 49-year-old male with essential mixed cryoglobulinemia IgM kappa-IgG of 4-years duration was treated with corticosteroids and immunosuppressive drugs during the repeated episodes. Finally, he developed a new episode with severe renal involvement and pulmonary hemorrhage without other associated etiological factors. The optical and immunofluorescent histological findings in lung and kidney are described. This is the second case of pulmonary hemorrhage and cryoglobulinemia associated with essential mixed cryoglobulinemia reported in the literature. A relation between essential mixed cryoglobulinemia and glomerulonephritis and pulmonary hemorrhage is suggested.

Non-resectable phaeochromocytoma: long term follow-up.

A forty-two year old woman presented with hypertension, trembling, sweating, visual impairment, headache and weight loss. A right adrenal phaeochromocytoma was diagnosed. The tumour could not be resected because it encircled the inferior vena cava. She was treated at first with phenoxybenzamine and propranolol and later with phenoxybenzamine and labetalol. She has remained normo-tensive and free of signs of adrenergic hyperactivity for 11 years. We suggest that pharmacological treatment alone is a valid alternative in cases of phaeochromocytoma who are at high surgical risk or where the tumour is not resectable.

[Orofaciodigital syndrome]. / Síndrome oro-facial-digital.

The OFDS and kidney polycystic disease is a rare association. Only 7 cases we have been able to find in several references. A new female case with hypertension is reported.