Improved local control and survival with the “sandwich” technique of pelvic radiotherapy for resectable rectal cancer A retrospective, multivariate analysis

PURPOSE: The following study was done to evaluate the therapeutic value of radiotherapy as an adjunct to surgery for rectal cancer patients. METHODS: One-hundred twenty-four patients underwent curative resection by one surgeon (RC) from 1982 to 1991. Forty patients received combined preoperative and postoperative (sandwich) radiotherapy, 30 patients received postoperative radiotherapy, and 54 patients were treated by surgery alone. During the study period sandwich radiotherapy was primarily offered as a free treatment option for patients with tumors which were believed to be transmurally invasive, whereas postoperative radiotherapy was an alternative therapeutic option offered to patients with tumor classified as Dukes B and C at histopathologic examination. RESULTS: Operative mortality was 2 percent in the sandwich radiotherapy group vs. 7 percent in the surgery alone group. After a median follow-up of 60 months, the actuarial locoregional recurrence rate at five years was 3 percent for the sandwich radiotherapy group compared with 18 and 30 percent for the postoperative radiotherapy and surgery alone groups, respectively (P =0.019). A multivariate analysis using the Cox model confirmed the favorable independent influence of sandwich radiotherapy on local tumor control, especially in distal tumors. The therapeutic benefit of sandwich radiotherapy translated into increased survival in the low-rectum Dukes B subgroup of patients. The actuarial five-year survival rates were 86 percent, 50 percent, and 28 percent in the sandwich radiotherapy, postoperative radiotherapy and surgery alone groups, respectively (P =0.05). CONCLUSIONS: Preoperative radiotherapy has a significant effect on the prognosis of rectal cancer patients.     

Effect of recombinant human growth hormone (GH) replacement on the hypothalamic-pituitary-adrenal axis in adult GH-deficient patients

The aim of the study was to evaluate the hypothalamus-pituitary-adrenal (HPA) axis in patients (nine males, three females; mean age +/- sem 51 +/- 2 yr) with adult-onset GH deficiency (GHD) due to surgically treated pituitary tumors with preserved HPA function and without evidence of tumor recurrence before and during recombinant human (rh) GH replacement therapy (duration 31 +/- 6 months). HPA function was assessed by urinary free cortisol and morning serum cortisol levels as well as cortisol responses to 1 mug ACTH test (n = 7 patients) or insulin tolerance test (n = 5 patients) before and during rhGH therapy, the cut-off for the diagnosis of hypoadrenalism being a cortisol peak less than 18 microg/dl (<500 nmol/liter) after stimulatory tests. Serum cortisol and urinary free cortisol levels were significantly lower on therapy than before [7.6 +/- 0.8 vs. 11.5 +/- 0.9 microg/dl (208 +/- 22 vs. 317 +/- 24 nmol/liter), P < 0.01, and 19.6 +/- 2.5 vs. 32.2 +/- 3.2 microg per 24 h (54 +/- 7 vs. 89 +/- 9 nmol per 24 h), P < 0.05, respectively], whereas no change in cortisol-binding globulin levels was observed. Cortisol peak after either ACTH test or insulin tolerance test was lower on rhGH therapy than before [15.9 +/- 1.5 vs. 20.2 +/- 1.1 microg/dl (437 +/- 43 vs. 557 +/- 31), P = 0.01, and 13.1 +/- 2.6 vs. 20.4 +/- 1.4 microg/dl (362 +/- 71 vs. 564 +/- 37 nmol/liter), P = 0.03, respectively]. Accordingly, central hypoadrenalism was detected in nine of 11 patients. In conclusion, low GH and IGF-I levels, likely enhancing the conversion of cortisone to cortisol, may mask a condition of central hypoadrenalism. Therefore, the reassessment of HPA function in GHD patients during rhGH therapy is mandatory.     

BRAF and NRAS Mutations Are Frequent in Nodular Melanoma but Are not Associated with Tumor Cell Proliferation or Patient Survival

Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.     

Bioelectrical impedance vector analysis evaluates cellularity and hydration in cirrhotic patients

BACKGROUNDMalnutrition in cirrhotic patients is correlated with mortality and a better response to liver transplantation. However, recovery of the nutritional status in these patients is a challenge due to the difficulty in establishing a reliable nutritional diagnosis. The bioelectrical impedance vector analysis (BIVA) method appears as a feasible tool in clinical practice to define the physiological state of cirrhotic patients by assessing hydration and body cellularity.AIMTo evaluate body composition in cirrhotic patients using BIVA.METHODSThis retrospective cross-sectional study was carried out by following cirrhotic outpatients at a hospital in Porto Alegre, Brazil. A tetrapolar bioelectrical impedance analysis device was used to evaluate cellularity and hydration and to perform the BIVA. The BIVA graphic was elaborated by software and for statistical analysis a significance level of 5% (P ≤ 0.05) was considered.RESULTSOne hundred and ninety patients, 61.1% males, with a mean age of 56.6 ± 11.0 years, were evaluated. Of these, 56.3% had Child-Turcotte-Pugh (CTP) A score, and the prevalent etiology was hepatitis C virus (47.4%). The patients were classified according to cellularity and hydration by the quadrants and ellipses of the BIVA method, quadrant 1 (47.9%); quadrant 2 (18.9%); quadrant 3 (14.2%); and quadrant 4 (18.9%). Those classified in quadrant 1 and 2 had a higher phase angle compared to those in quadrants 3 and 4 (P < 0.001). Quadrant 2 patients had a lower average age than the other groups. The association with CTP score showed that patients in quadrant 2 had a higher proportion of CTP A, and those in quadrant 4 had a higher proportion of CTP C (P < 0.052).CONCLUSIONThe BIVA method allows identification of the cellularity and hydration status of cirrhotic patients, and its association with clinical factors determines the disease severity, age and prognostic index.     

Daily Physical Activity,Functional Capacity and Quality of Life in Patients with COPD

Introduction: In the therapy of chronic obstructive pulmonary disease (COPD), it is a major goal to improve health-related quality of life (HRQOL). Patients with COPD often suffer from exertional dyspnea and adopt a sedentary lifestyle, which could be associated with poorer HRQOL. The aim of this study was to investigate the independent association of objectively measured daily physical activity and functional capacity with HRQOL in patients with COPD. Methods: In this cross-sectional study conducted at the University Hospital Basel, Switzerland, 87 stable patients (58.6% male, mean age: 67.3 ± 9.6 yrs) with COPD in GOLD grades I (n = 23), II (n = 46), III (n = 12) and IV (n = 6) were investigated. To assess HRQOL, the COPD assessment test (CAT) was completed. Patients performed spirometry and 6-min walk test. Physical activity was measured by the SenseWear Mini Armband on 7 consecutive days. By performing a multiple linear regression analysis, independent predictors of CAT score were identified. Results: Age (β = ?0.39, p = 0.001), average daily steps (β = ?0.31, p = 0.033) and 6-min walk distance (β = ?0.32, p = 0.019) were found to be independent predictors of CAT score, whereas physical activity duration above 3 METs (p = 0.498) and forced expiratory volume in 1 s in% of predicted (p = 0.364) showed no significant association. Conclusions: This study showed that average daily steps and functional capacity are independent determinants of HRQOL in patients with COPD. This emphasizes the importance to remain active and mobile, which is associated with better HRQOL.