Clinical evaluation of the simultaneous determination of tumor markers in fluid and serum and their ratio in the differential diagnosis of serous effusions.

We evaluated the diagnostic utility of simultaneous determination of 5 tumor markers, CEA, CA 125, CA 15-3, CA 19-9 and cytokeratin 19 (CYFRA 21-1), in fluid and serum from 101 patients, 52 with pleural effusion (22 malignant) and 49 patients with ascites (14 malignant). Tumor marker concentrations in fluid from patients with malignant effusions were significantly higher than those obtained in benign fluids or serum. However, there are two types of tumor markers: those released/secreted by normal mesothelia such as CA 125 and cytokeratin 19 (higher levels in benign fluids than in serum) and non-released/secreted tumor markers (low concentrations in benign fluids) such as CEA, CA 19-9 and CA 15-3. The fluid/serum (F/S) ratio showed better sensitivity with maximum specificity than a single determination in fluid for CEA, CA 15-3 and CA 19-9, but not for CA 125 and CYFRA. The combination of a F/S ratio greater than 1.2 and a cut-off of 5 ng/ml for CEA, 30 U/ml for CA 15-3 and 37 U/ml for CA 19-9 showed sensitivities of 58, 57 and 44%, respectively, and a specificity of 100%, with a combined sensitivity of 82% for overall effusions and 79% for fluids with negative cytology with a specificity of 100%. In conclusion, the use of the F/S ratio in nonsecreted tumor markers such as CEA, CA 19-9 and CA 15-3 improve the sensitivity and specificity and allow standardization of the cut-off.     

Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up.

PURPOSE: To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. PATIENTS AND METHODS: Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. RESULTS: All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. CONCLUSION: UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.     

Abnormalities in the serum insulin-like growth factor-1 axis in women with hyperandrogenism

Objective: To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women.

Design: Controlled clinical study.

Setting: Tertiary care institutional hospital.

Patient(s): Forty hirsute women and 17 women with normal menstrual cycles.

Intervention(s): Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons.

Main Outcome Measure(s): Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E₂, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured.

Result(s): Patients with idiopathic hirsutism were identified by normal serum androgen levels (n = 17). Those with functional ovarian hyperandrogenism (n = 15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n = 8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal IGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for.

Conclusion(s): The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.     

Treatment of osteoarthritis of the knee with valgus deformity by means of varus osteotomy

Nineteen cases of osteoarthritis of the knee with valgus deformity in 17 patients were treated by femoral supracondylar varus osteotomy (17 cases) or by high tibial varus osteotomy (2 cases) over the last 15 years. Fixation was performed using a 95 degrees AO blade-plate in 13 of the femoral osteotomies and a straight plate in the other four. The mean follow-up time was 6.5 years. The valgus deformity was idiopathic in 14 cases, secondary to rheumatoid arthritis in 2 cases and to tibial valgus in one case. The Hospital for Special Surgery (HSS) score was used to evaluate the clinical results: nearly 75% were excellent or good. The causes related to poor results are analyzed regarding indication and surgical technique. It appears that varus osteotomy is an effective procedure for the treatment of osteoarthritis of the knee with valgus deformity, above all in order to alleviate pain, although the operation requires precision, and correct selection of patients is of prime importance.     

Altered 5-HT(2A) binding sites and second messenger inositol trisphosphate (IP(3)) levels in hippocampus but not in frontal cortex from depressed suicide victims

The binding parameters of 5-HT(2A) and levels of its second messenger, 1,4,5-trisphosphate (IP(3)), were simultaneously studied in frontal cortex and hippocampus from the brains of 18 control subjects and 18 depressed suicide victims. All suicides met DSM-III-R criteria for depressive symptoms, suffered a violent death and had not taken any antidepressant drugs for at least 6 months prior to death. A significant decrease in the number of 5-HT(2A) binding sites (154+/-22 vs. 254+/-36 fmol/mg), together with a significantly lower apparent affinity constant (1.02+/- 0.08 vs. 1. 36+/-0.09 nM), was detected in hippocampus but not in frontal cortex from the depressed suicides compared to the control subjects. Furthermore, IP(3) concentrations were significantly increased in hippocampus (3.2+/-0.3 vs. 2.1+/-0.3 pmol/g) but not in frontal cortex (1.3+/-0.3 vs. 2.7+/-0.5 pmol/g) from the suicide victims. The reported results may indicate a significant hypersensitivity of the 5-HT(2A) postsynaptic receptor located in the hippocampus from depressed suicide victims, giving rise to an enhancement of its intracellular signaling system with higher IP(3) production.     

Análisis de la concentración sérica del ADN tumoral en el cáncer de pulmón no microcítico y avanzado: ¿es útil como factor pronóstico?

INTRODUCTION: Presence of circulating DNA in the serum of patients with cancer makes detection of tumour-specific genetic alterations feasible. OBJECTIVE: To study serum DNA concentration in patients diagnosed as having advanced Non-Small Cell Lung Cancer (NSCLC) and to evaluate its relationship with age, histology, stage, response, time-to-progression (TTP), and survival. METHODS: Serum DNA from 78 patients was purified and spectrophotometrically quantified. RESULTS: No significant correlations were found between serum DNA concentration and age, histology, response and survival. There was a significant correlation with respect to stage (IIIB = 408.75 ng/ml; IV = 478.74 ng/ml; p = 0.02). When patients were grouped according to DNA concentration, significant correlation with TTP was found; establishing a cut-off point at 500 ng/ml ([DNA] < 500 ng/ml TTP = 7.25 months, 95%CI: 3.5-5.25; [DNA ] > or = 500 ng/ml TTP = 4.25 months, 95%CI: 2-6.5; p = 0.05). CONCLUSIONS: Using the present method, DNA concentration quantification appears to be simple, but with certain deficiencies due to inter-sample variability and low specificity. This is because total DNA concentration is measured without distinguishing as to whether it is tumour-related. We suggest that there is a correlation between DNA concentration and prognosis which enables an analysis of the natural history of the disease.