Prognostic value of circulating KRAS2 gene mutations in colorectal cancer with distant metastases.

While tissue KRAS2 mutations have been extensively investigated, the role of circulating mutant KRAS2 gene in patients with colorectal carcinoma remains obscure. The aim of the present study was to explore the prognostic significance of circulating KRAS2 gene mutational status in subjects undergoing primary treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA samples extracted from the serum of 86 patients with colorectal cancer and were compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2 status was compared with other clinicopathological variables (including CEA and CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate analysis, cancer-related survival was associated with Dukes' stage (p<0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients with serum KRAS2 mutations died of the disease within 24 months of primary treatment; cancer-related survival was significantly better in 9 stage D patients without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1 patient (13%) alive after 44 months. Residual disease after surgery was evident in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage D patients without serum mutations. Serum KRAS2 status may impact substantially on the management of stage D colorectal carcinoma, since it appears to cor-relate with prognosis in this patient subgroup.

Long and short-term effect of prednisolone in hospitalized infants with acute bronchiolitis.

OBJECTIVE: To assess long and short-term effect of prednisolone in hospitalized infants with bronchiolitis. METHODOLOGY: A randomized and controlled trial was carried out at the Federal University of Rio Grande, Rio Grande-RS, Brazil. Twenty-eight patients were randomly allocated prednisolone (1 mg/kg/day for 5 days) plus standard care, and 24 patients allocated standard care alone. The primary endpoint was the prevalence of post-bronchiolitis wheezing at 1, 3, 6 and 12 months after hospital discharge. The secondary endpoints were: length of hospital stay, duration of oxygen therapy and time to clinical improvement during the hospitalization. RESULTS: There were no significant differences between the prednisolone and control group in the prevalence of post-bronchioltis wheezing at 1 month (73.1 vs 83.3%, P = 0.5), 3 months (73.1 vs 79.2%, P = 0.7), 6 months (65.4 vs 66.7%, P = 0.9) and 12 months (50.0 vs 58.3%, P = 0.5) after hospital discharge. No reduction was observed in the prednisolone group, compared with the control group, in terms of length of hospital stay (6.0 vs 5.0 days, P = 0.7), duration of oxygen therapy (24.0 vs 24.0 h, P = 0.4) and time to clinical resolution (4.0 vs 4.0 days, P = 0.8). CONCLUSIONS: Prednisolone has no significant effect on reducing the prevalence of post-bronchiolitis wheezing and on improving the acute course of illness in hospitalized infants with bronchiolitis.

Blood glutathione as a surrogate marker of cancer tissue glutathione S-transferase activity in non-small cell lung cancer and squamous cell carcinoma of the head and neck.

The identification of markers predicting the response to therapy is of the utmost importance in oncology. Several authors have suggested that increased levels of glutathione (GSH) and glutathione S-transferase (GST) activity might be meaningful predictors of poor responsiveness to chemotherapy in several human cancers, but the biological assays have not been standardised and published studies show conflicting evidence. The aim of the present study was to select a validated panel of tests to assess the GST/GSH system in a clinical setting. Matched blood and tissue samples (normal and malignant) from 52 cancer patients with either non-small cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (SCCHN) were investigated. GSH levels and GST activity were higher in cancer tissues than in matched normal tissues in both malignancies. The difference was statistically significant in NSCLC (P=0.0004 and P=0.0002, for GSH and GST, respectively) and borderline in SCCHN (P=0.03 and P=0.02, for GSH and GST, respectively). Moreover a strong correlation was found between the GSH level in whole blood and GST activity in cancer tissue in both malignancies (P=0.003, r=0.53 in NSCLC, P<0.0001, r=0.89 in SCCHN). In conclusion, reliable and robust methods for routine use in tissue extracts and in whole blood have been validated. Our finding regarding the GSH level in blood indicates that circulating GSH could have a clinical relevance as a surrogate marker of GST activity in tumour tissue.

Molecular detection of codon 12 K-RAS mutations in circulating DNA from serum of colorectal cancer patients.

Point mutations of the K-RAS gene at codon 12 are found in about 40% of cases with colorectal cancer. The diagnostic implications of the detection of these mutations and their clinical utility are still unclear. The aim of this study was to test both the feasibility of the detection of the mutated K-RAS gene in serum and its potential role in colorectal cancer detection and monitoring. Codon 12 K-RAS mutations were examined in DNA extracted from the serum of 35 patients with colorectal cancer and were compared with the K-RAS status in the corresponding primary tumor. Molecular detection was performed by the mutant-enriched PCR (ME-PCR) assay, a sensitive method capable of distinguishing a small quantity of mutated DNA in the presence of abundant wild-type DNA. The occurrence of mutations was compared with clinicopathological parameters as well as CEA and CA19.9 serum levels. We found codon 12 K-RAS mutations in the tissue of 13/35 (37%) patients. Serum mutations were detected in 5/13 (38.5%) patients with mutated K-RAS in the tissue. 26/35 (74%) patients showed an identical K-RAS pattern in tissue and serum. No codon 12 K-RAS alterations were found in serum samples of 22 patients with benign gastrointestinal diseases. Elevated serum CEA levels were detected in 16 patients, four of whom also presented serum RAS mutations. Our results confirm that K-RAS mutations can be found in circulating DNA extracted from serum samples of patients with colorectal cancer and show that there is a correspondence between serum and tissue K-RAS patterns.

[Trends in hospital admissions for pediatric asthma in childrenduring a period of eighteen years] / A tendência das hospitalizações por crises de asma em crianças em um período de dezoito anos.

OBJECTIVE: To study trends in hospital admissions for acute pediatric asthma in the Hospital da Santa Casa do Rio Grande during the period of 1979 to 1996. METHODS: This is a study of a series of cases. We reviewed all the discharge records of pediatric patients with diagnosis of acute asthma, pneumonia, and bronchiolitis within the period mentioned above. The main variable in this study was the percentage of admissions for acute asthma in relation to the total amount of hospital admissions. The percentages of admissions for bronchiolitis and pneumonia in relation to the total amount of hospital admissions were also calculated as reference values. RESULTS: There were 3,493 admissions for acute asthma in 3,122 patients during the studied period, with an average of 194 admissions per year. The percentage of admissions for acute asthma to total hospital admissions increased from 5,5% to 14,7% between 1983/84 and 1991/92. Half of this increase occurred during the period 1987-1992 in which hospitalizations for bronchiolitis and pneumonia were stable. This percentage decreased from 14,7% to 10,6% in the period of 1991/92 - 1995/96. CONCLUSIONS: There was a significant increase in hospital admissions for acute pediatric asthma in the Hospital da Santa Casa do Rio Grande during the period of 1983 - 1992. From then on, hospital admissions for asthma showed downward trends.

Hyperprolactinemia and pregnancy. Clinical series.

We report 15 cases of pregnancy in 11 patients with hyperprolactinemia. These patients initially went to our Gynecologic Endocrinology Center for various menstrual troubles. They were all treated with bromocriptine, except one whose hyperprolactinemia was diagnosed when she had already started a gonadotropin therapy, since HPRL assays performed elsewhere had given normal results. In 6 patients we diagnosed prolactin-secreting pituitary adenoma. Only two patients underwent adenomectomy. All patients gave up bromocryptine as soon as their pregnancy was detected. Two patients had two subsequent pregnancies, another one had three. All pregnancies were single. The only twin pregnancy followed a gonadotropin therapy. One of the 15 pregnancies ended with abortion at the 12th week; another one (twin) with spontaneous delivery at the 37th week; 13 with term-delivery. They all had physiologic courses, except for one case of threatened abortion and one case of diabetes insipidus at the 9th month. None of the 15 newborns (7 SGA and 8 AGA) showed malformations. No sign or symptom of tumour growth was detected in the patients affected by pituitary adenoma.