Mitsuru Miyazaki

Pattern of Lung Cancer in Turkey, 1994–1998

Background: Lung cancer is the most common neoplasm in Turkey, but there is not enough data on the characteristics of this mortal illness in our country. Objectives and Methods: The Turkish Thoracic Society, Lung and Pleural Malignancies Study Group (TTS-LPMSG) conducted a national retrospective hospital-based study to determine the pattern of lung cancer in Turkey. Results: A total of 11,849 lung cancer patients were studied between 1994 and 1998, 90.4% were male and 9.6% were female. The majority of patients were smokers (77.9%) or ex-smokers (10.8%). The mean age at the time of diagnosis was 58.4 years (20–84) and 56.7% of the patients were aged between 46 and 65 years. The most common histological types were squamous cell (45.4%), small cell (SCLC; 20.5%) and adenocarcinoma (20.2%). The majority of patients with non-small-cell lung cancer were diagnosed with metastatic disease (40.4%). Of the patients with SCLC patients, 37.9% had limited stage disease and 62.7% extensive stage disease at diagnosis. Conclusion: The results of the largest data so far collected in Turkey show that the vast majority of patients with lung cancer are male, squamous cell is the most common histological type, and only a small proportion of patients are diagnosed at an early stage.

Induction of λ-glutamylcysteine synthetase gene expression by platinum drugs in peripheral mononuclear cells of lung cancer patients

Summary Background: To investigate in vivo the roles of Y-glutamyl- cysteine synthetase (y-GCS), multidrug resistance-associated protein (MRP), human canalicular multispecific organic anion transporter (cMOAT) and DNA topoisomerase I (topo I) in relation to platinum drug resistance, we monitored the changes of the steady-state levels of the mRNAs for these factors in peripheral mononuclear cells (PMN) after completing plati- num drug administration. Patients and methods PMN from 46 subjects were studied. We obtained PMN from 14 previously untreated lung cancer patients and 14 normal volunteers to measure the baseline gene expression levels. We then obtained PMN from 18 patients with previously untreated advanced lung cancer before and after they received platinum drug treatment. We analyzed the gene expression levels by using the quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: There were no differences in the baseline expres- sion levels between normal volunteers and lung cancer patients in any of the genes. After platinum drug administration, the heavy subunit of y-GCS (y-GCSh) expression level increased 2.5-fold within 24 hours and the increase persisted for a month, whereas the light subunit of y-GCS (y-GCSl) expres- sion level did not show an early response but had increased after a month. By contrast, the MRP, cMOAT and topo I expression levels were similar before, during and after chemo- therapy. Conclusions: These results suggest that the gene expression levels of both subunits of y-GCS play an important in vivo role in platinum drug resistance.

A Case of Micronodular Pneumocyte Hyperplasia Diagnosed through Lung Biopsy Using Thoracoscopy

We present a case of a 39-year-old woman with sporadic tuberous sclerosis (TSC), whose chest radiograph demonstrated bilateral diffuse nodular shadowing. A transbronchial lung biopsy specimen revealed the possibility of multiple atypical adenomatous hyperplasia (AAH), which had not been reported in TSC. Thoracoscopic lung biopsy was, therefore, performed. The specimens revealed the characteristic histological and immunohistochemical features of micronodular pneumocyte hyperplasia, which has been reported as an extremely rare pulmonary manifestation of TSC. In addition, no evidence of AAH or any other pulmonary involvements of TSC including lymphangioleiomyomatosis were detected in biopsy specimens obtained at thoracoscopy.

Clinical pharmacological profile of etoposide in elderly patients with lung cancer

To clarify the clinical pharmacological profile of etoposide in the elderly, we carried out prospective therapeutic drug monitoring in 14 patients with advanced lung cancer aged 75 or more years. The patients received 50u2003mg etoposide as oral capsules for 21 consecutive days during the first course, and intravenous etoposide for 3u2003days during the second course of palliative treatment. Plasma and urine samples were collected on days 1 and 21 of the first course and day 1 of the second course, and etoposide concentrations were measured using high‐performance liquid chromatography. We compared these data with those obtained from 17 adult patients under 75 years old who participated in our previous study of combined oral etoposide/carboplatin chemotherapy. Within the elderly group, no significant differences in the area under the concentration‐versus‐time curve, elimination half‐life, plasma clearance, urinary excretion or bioavailability of oral etoposide were observed between day 1 and day 21. However, the mean (±SD) elimination half‐lives for elderly and adult patients were 10.3u2003±u20031.9u2003h and 5.8u2003±u20032.5u2003h, respectively, while the mean (±SD) bioavailabilities were 62.8u2003±u200327.5% and 37.4u2003±u200315.4%; both were significantly increased in the elderly patients. Our previously proposed limited sampling model was validated using the elderly data set and proved to be unbiased and precise. In conclusion, although no accumulation of oral etoposide was observed in elderly patients, there were age‐dependent changes in its pharmacokinetics, especially in bioavailability.