Methotrexate and gemcitabine combination chemotherapy for the treatment of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive tumor of serosal surfaces with a poor prognosis. Methotrexate and gemcitabine have exhibited single-agent activity in MPM. We evaluated the feasibility of sequential administration of these agents in the treatment of MPM. A total of 21 patients with MPM received a 30-min infusion of 100 mg/m2 methotrexate and, 30 min later, a 30-min infusion of 800 mg/m2 gemcitabine. Twenty-four hours following the administration of methotrexate, leucovorin rescue therapy was initiated (10 mg/m2 leucovorin administered 4 times at 6-h intervals). These treatments were administered weekly, with 4 weekly administrations constituting a cycle of therapy. A total of 88 cycles were administered to the 21 patients, with each patient receiving 1-10 cycles (median, 4.2 cycles). Eight patients (38.1%) exhibited a partial response, 10 patients (47.6%) had stable disease and 3 patients (14.3%) had progressive disease. The median overall survival was 19.4 months (range, 02-41 months). One-year and 2-year survival rates were 61.9 and 38.1%, respectively. Hematological toxicity was considered acceptable, with grade 3-4 toxicities occurring in 3 (14.3%) patients. Non-hematologic toxicity was generally mild. There was no treatment-related mortality. Our results suggest that methotrexate and gemcitabine combination therapy is feasible and effective in the treatment of MPM. This regimen may offer an alternative to platinum-based chemotherapy and a prospective trial including a larger cohort of patients is recommended to confirm these results.

[Expression of mesothelin as a potential diagnostic marker in mesothelioma].

Histological discrimination of mesothelioma from adenocarcinoma is often difficult, therefore, many investigators have tried immunohistochemical, ultrastructual, and molecular methods. Economically, immunohistological studies are more excellent, compared with ultrastractual and molecular biological methods. Immunohistologically, many well known markers are divided into two category; adenocarcinoma-related markers, which expressed by adenocarcinoma, and mesothelioma-related makers, which are positive for mesothelioma. CEA, TTF-1, and Ber-Ep4 are well known adenocarcinoma-related markers, mesothelin, TM, HBME-1 and calretinin, have been used as mesothelioma-related markers. Most previous reports associated with discrimination of adenocarcinoma and mesothelioma mentioned that a diagnosis of epithelioid mesothelioma would be excluded by the presence of adenocarcinoma-related antibody. The positive ratio of mesothelioma-related antibodies is lower than that of adenocarcinoma-related antibodies. Only a single mesothelioma-related marker cannot lead to a diagnosis of epithelioid mesothelioma and a correct diagnosis can be made by combination of several makers, which contain both mesothelioma-related markers and adenocarcinoma-related markers. We immunohistologically examined 41 cases of mesothelioma and 16 cases of adenocarcinoma of the lung, and re-evaluated the use of immunohistochemical markers, compared with previous reports. Reactivity for mesothelin was obtained in 19 (73%) of the epithelioid mesotheliomas, but none (0%) of the lung adenocarcinomas. None of the sarcomatoid mesotheliomas exhibited positivity for this marker, nor was any reactivity seen in the spindle cell component of the biphasic mesotheliomas. These findings indicate that, in some instances, mesothelin immunostaining can assist in the diagnosis of mesothelioma.

[A case of primary lung cancer with cervical tuberculous lymphadenitis].

A 66-year-old woman was admitted due to right cervical lymphadenopathy and an abnormal chest radiograph. Acid-fast bacilli smear of fine needle aspiration from a right cervical lymph node was positive. Histopathological examination of the specimen obtained by percutaneous right cervical lymph node biopsy showed necrotizing epithelioid granulomas and no malignant cells. Therefore, right cervical tuberculous lymphadenitis was diagnosed. Partial lung resection of the right S4 was carried out by video-assisted thoracoscopic surgery and primary lung cancer was diagnosed. To our knowledge, there has been no previous report of both primary lung cancer and cervical tuberculous lymphadenitis being present at the time of the first examination. We report this very rare case.

[A case of pulmonary eosinophilic granuloma that remitted after cessation of smoking].

A 43-year-old man was admitted to our hospital because of productive cough and an abnormal chest radiograph. He had smoked one pack of cigarettes per day for 23 years. Chest radiograph on admission showed diffuse reticulo-linear infiltrates, most prominent in both upper lung fields. Chest HRCT scan showed multiple micronodules, cavitated nodules, and thick-walled cysts with ground-glass attenuation. These radiographic findings suggested pulmonary eosinophilic granuloma (PEG). Histological findings of the biopsy specimen obtained from video-assisted thoracoscopy demonstrated granulomatous lesions consisting of S-100 protein-positive Langerhans cells with infiltration of eosinophils and fibrous lesions (starfish-like fibrosis). A definitive diagnosis of PEG was made, and he immediately ceased smoking. The symptoms and radiographic findings markedly improved within 3 months after cessation of smoking. Chest HRCT on the final scan revealed that nodules and almost all cystic lesions vanished. He resumed smoking without any sign of recurrence.