DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach.

BACKGROUND: Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer. METHODS: DNA hypermethylation of RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities. RESULTS: In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set. CONCLUSIONS: Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer.

Resection of secondary pulmonary malignancies in head and neck cancer patients.

BACKGROUND: This study aimed to evaluate a single institute's experience with resection of metachronous pulmonary malignancy in patients treated for squamous cell carcinoma of the head and neck. METHODS: Sixty-three consecutive patients treated curatively for head and neck squamous cell carcinoma underwent surgical resection of malignant lung lesions. Survival was estimated and potential prognostic factors investigated. RESULTS: The median overall survival for the total group was 22.2 months. Fifty-one patients (81 per cent) had one lung lesion, while the remainder had multiple lesions (range, two to seven). In the 63 patients, 35 lobectomies, 4 pneumonectomies and 24 wedge resections were performed. For patients with pulmonary squamous cell carcinoma (n = 52), the three-year survival rate was 35 per cent (95 per cent confidence interval, 22-48); for patients with resected adenocarcinoma (n = 10), it was 50 per cent (95 per cent confidence interval, 18-75). The overall five-year survival rate was 30 per cent (95 per cent confidence interval, 19-42). CONCLUSION: In patients treated curatively for head and neck squamous cell carcinoma, resection of secondary pulmonary cancer is associated with favourable long term overall survival, especially for patients with adenocarcinoma lesions.

A CT-assisted method of dosimetry in brachytherapy of lung cancer. Rotterdam Oncological Thoracic Study Group.

BACKGROUND: The toxicity of endobronchial brachytherapy (EB), in particular fatal haemoptysis and bronchial wall necrosis, has been correlated with the total dose, fraction size, volume encompassed by the 100% isodose, and a proximal tumor location. We describe a CT-based planning method which, by improving target volume definition and volumetric dose information, can improve the therapeutic ratio of EB. MATERIALS AND METHODS: Sixteen CT-assisted EB procedures were performed in patients who were treated with palliative high-dose rate EB. The CT data were used to analyze applicator position in relation to anatomy. An example of a three-dimensional optimized treatment plan was generated and analyzed using different types of dose-volume histograms. RESULTS: The procedure was well tolerated by patients and no post-procedure complications were observed. The bronchial applicator was eccentrically positioned at the level of the carina/mainstem bronchus in 12 (of 14) CT scans. A planning CT prior to EB was not found to be useful as the final target volume and/or the final applicator position were not reliably predicted before the therapeutic bronchoscopy. CT-scans performed with the applicator in situ allowed the bronchial segments in the target volume to be identified and enabled dose prescription to the bronchial mucosa. CONCLUSIONS: CT-assisted EB is feasible and underlines the need for using centered applicators for proximally located tumors. By enabling accurate mucosal dose prescription, CT-assisted EB may reduce the toxicity of fractionated EB in the curative setting. However, faster on-line EB treatment planning is needed for the routine clinical application of this technique.

[Findings in children with psoriasis]. / Bevindingen bij kinderen met psoriasis.

OBJECTIVE: To describe the clinical characteristics and treatments of children with psoriasis. DESIGN: Retrospective, descriptive. METHODS: The medical records were studied of all 38 children with psoriasis who visited the outpatient clinic for Dermatology of the University Hospital/Wilhelmina Children's Hospital Utrecht, the Netherlands, for the first time between 1 January 1995 and 31 December 1997. RESULTS: The 38 children accounted for 3.6% of all children in whom a diagnosis was made. There were 19 boys and 19 girls. 79% had psoriasis vulgaris and 11% psoriasis guttata. Average age of onset was 6.8 years for girls and 9.3 years for boys. Family history was positive in 42%. The limbs were affected most. Nail changes were seen in 11%. Provoking factors were stress, infections, summertime and injuries of the skin. In almost all patients in the outpatient department local mono- and/or combination therapy of corticosteroids in cream or ointment with salicylic acid and tar was given.

Hymenoptera sting challenge of 348 patients: relation to subsequent field stings.

BACKGROUND: Patients with a history of a serious anaphylactic reaction after a Hymenoptera sting are usually given venom immunotherapy. Because the natural history of Hymenoptera sting anaphylaxis is often of a declining severity, there is a chance of overtreatment. OBJECTIVE: Identification of patients at risk for a future anaphylactic reaction may reduce the number of patients who need venom immunotherapy. METHODS: We investigated the relation between the grade of hypersensitivity to an in-hospital sting challenge and the reaction to a subsequent accidental field sting. From 1982 through 1992, 348 patients with mild or no symptoms after a sting challenge were not given venom immunotherapy. All patients were asked by letter whether they had experienced a subsequent field sting. In case of a sting, the severity of the reaction was further evaluated. RESULTS: Information could be obtained from 327 patients: 129 had been re-stung, and 110 of them had only had a local reaction. Thirteen patients had experienced mild systemic symptoms, and six patients had experienced serious manifestations. In two of the latter group hypotension was observed. CONCLUSION: In 95% of patients with a previous anaphylactic reaction, the result of the in-hospital sting challenge provided a good prediction of tolerance to a subsequent Hymenoptera field sting.