Prevalence and significance of MEFV gene mutations in patients with sarcoidosis.

OBJECTIVES: Sarcoidosis is a chronic granulomatous disease. Pyrin has anti-inflammatory activity in the regulation of inflammasomes and is encoded by the Mediterranean fever (MEFV) gene. MEFV gene mutations trigger the inflammatory cascade and cause familial Mediterranean fever (FMF). A relationship between various rheumatic diseases and MEFV gene mutations has been demonstrated. The aim of this study was to determine the prevalence of the MEFV gene mutation in Turkish patients with sarcoidosis and to detect any possible correlation with disease phenotype. METHOD: The study included 78 sarcoidosis patients and 85 healthy subjects matched for age, gender, and ethnicity. MEFV gene mutations were investigated with the FMF strip assay, which is based on reverse hybridization of biotinylated polymerase chain reaction (PCR) products. RESULTS: Of the 78 patients with sarcoidosis, nine (11.5%) were found to be carriers of MEFV gene mutations. The distribution of these nine mutations were: three (3.8%) V726A, two (2.5%) E148Q, two (2.5%) M680I, one (1.3%) A744S, and one (1.3%) K695R. Carriers of M694V, M694I, R761H, and P369S were not detected in any of the sarcoidosis patients. None of the sarcoidosis patients were found to be compound heterozygous carriers. The prevalence of the MEFV gene mutation carrier detected in the healthy control group was 22.4%. The distribution of the 19 MEFV gene mutations found in the healthy controls was: nine (10.6%) E148Q, two (2.3%) M694V, one (1.2%) M694I, one (1.2%) M680I, two (2.3%) V726A, one (1.2%) A744S, two (2.3%) K695R, and one (1.2%) P369S. When compared with the control group, a lower prevalence of the MEFV gene mutation carrier was found in sarcoidosis patients but this was not statistically significant (p = 0.067). In nine patients found to be MEFV gene mutation carriers, higher serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels and higher numbers patients with arthritis, enthesitis, and ankle arthritis were found (p = 0.01, p = 0.04, p = 0.028, p = 0.05, p = 0.05, respectively). CONCLUSIONS: When we compared Turkish sarcoidosis patients with the healthy control group, we found a lower prevalence of MEFV gene mutations. In sarcoidosis patients, the MEFV gene mutation carrier was found to be related to high acute-phase responses, arthritis, and enthesitis. The existence of MEFV gene mutations may have a preventive role with regard to the development of sarcoidosis. Prospective studies that include larger patient populations are needed.

The effect of blood vessel invasion on prognosis of operated stage I non-small cell lung cancer patients.

OBJECTIVE: A retrospective study was conducted to identify the effect of blood vessel invasion on prognosis in surgically treated stage I non-small cell lung cancer patients. METHODS: A total of 71 consecutive patients who had undergone complete resection for stage I primary non-small cell lung cancer (NSCLC) between 1998 and 2007 were evaluated. All pathological specimens were examined for evidence of blood vessel invasion. The follow-up period was 5-118 months. Survival data were analyzed for all patients using the Kaplan-Meier test. RESULTS: There were 63 men and 8 women (mean age 59.2, age range 35-86). The most common tumor types were adenocarcinoma (35 patients, 49 %) and squamous cell carcinoma (26 patients, 37 %). Twenty-five patients (35 %) had stage IA disease, and 46 had (65 %) stage IB disease. In 13 cases (18 %) blood vessel invasion was demonstrated, whereas in the remaining 58 cases there was no evidence of vascular invasion. Minimum and maximum follow-up periods were 5 and 118 months respectively, with a mean of 41.76 +/- 27 months (median 33.5 months). Overall disease-free survival was 79.6 +/- 6.4 months: 38.3 +/- 12.0 months for the group with blood vessel invasion and 87.5 +/- 6.7 months for the remaining group. The difference between the two groups was statistically significant ( P < 0.003). Overall survival rate was 86.7 +/- 6.7 months: 44.5 +/- 11.3 months for blood vessel invasion group and 98.2 +/- 6.2 months for the remaining group. The difference between the two groups was statistically significant ( P < 0.001). CONCLUSION: Vascular invasion can be an important factor for predicting unfavorable prognosis in stage I NSCLC patients.

The European Organization for Research and Treatment of Cancer QLQ-C30: an examination into the cultural validity and reliability of the Turkish version of the EORTC QLQ-C30.

The Turkish version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire version 2.0 (EORTC QLQ-C30 v.2.0) has started to be used in clinical trials recently. The objective of the study was to evaluate the validity and reliability of the Turkish version of the EORTC QLQ-C30 v.2.0 and the correlation between the Karnofsky Performance Scale (KPS) and the EORTC QLQ-C30. Two hundred and two lung cancer patients were included in the study between January and March 2000. All the subscales met the minimal standards of reliability (Cronbach's alpha > or = 0.70). Only the role functioning scale differed among the three disease stages of patients (local, locoregional and metastatic). There was no statistically significant difference among therapy types. All interscale correlations were statistically significant (P < 0.01). The strongest correlations were found among the physical functioning, role functioning and fatigue scales. Social functioning was closely related with physical, role, emotional and cognitive functioning. The weakest correlations were between nausea/vomiting and the other scales. Global quality of life (QOL) was substantially correlated with most of the scales except cognitive functioning. The coefficients for the correlation between the items differed between 0.12 and 0.97 and all the subscales were strongly correlated with the scales which they formed. The highest correlation between the EORTC QLQ-C30 and KPS was for physical functioning (r = 0.62, P < 0.05). The Turkish version of the EORTC QLQ-C30 is a valid (by means of interscales validity) and reliable instrument for Turkish lung cancer patients and can be used in clinical studies but needs supporting by the reference data on the QOL of the Turkish population.

High dose rate endobronchial brachytherapy in combination with external beam radiotherapy for stage III non-small cell lung cancer.

INTRODUCTION: A phase-II study was planned to test the effect of external beam radiotherapy in combination with endobronchial brachytherapy on the local control and survival of stage-III non-small cell lung cancer patients. MATERIALS AND METHODS: Thirty patients with stage-III non-small cell lung cancer have been treated with 60 Gy external beam radiotherapy and 3 x 5 Gy HDR endobronchial brachytherapy to control tumor and to prolong survival. RESULTS: Therapy regimen was found to be very effective for the palliation of major symptoms, palliation rates were 42.8% for cough, 95.2% for hemoptysis, 88.2% for chest pain and 80.0% for dyspnea. There was a 76.7% tumor response (53.3% complete, 23.3% partial) verified by chest CT scans and bronchoscopy. However, median locoregional disease free survival was 9+/-4 months (95% CI: 1-17) and it was only 9.6% at 5 years. Major side effects were radiation bronchitis (70.0%), esophagitis (6.6%) in the acute period and bronchial fibrosis (25%), esophagial fibrosis (12.5%) and fatal hemoptysis (10.5%) in the late period. Median survival was 11+/-4 months (95% CI: 4-18),and 5-year actuarial survival was 10%. Locoregional disease free survival (P=0.008) and the overall survival was longer (P<0.001) in the patients younger than 60, survival was also improved in the patients with complete response (P=0.019). There were no major complications during catheterisation; early side effects were quite tolerable but severe late complications were around 10%. CONCLUSIONS: It is concluded that endobronchial brachytherapy in combination with external irradiation provides a good rate of response, however does not eradicate locoregional disease and does not prolong survival except for some subgroups such as younger patients.