Impact of inherited polymorphisms in glutathione S-transferase M1, microsomal epoxide hydrolase, cytochrome P450 enzymes on DNA, and blood protein adducts of benzo(a)pyrene-diolepoxide.

The benzo(a)pyrene (BaP) metabolite benzo(a)pyrenediolepoxide (BPDE) is strongly implicated as a causative agent of lung cancer. To assess the risk of exposure to BaP, we made a combined analysis of levels of BPDE adducts to hemoglobin (Hb), serum albumin (SA), and lymphocyte DNA in 44 patients with incident lung cancer, as a prototype of a population mainly exposed to tobacco-derived BaP. We also investigated whether genetic polymorphisms of cytochrome P450IA1 (CYPIA1), microsomal epoxide hydrolase (mEH), and glutathione S-transferase M1 (GSTM1), which are involved in BaP metabolism, can be determinants of adduct formation. BPDE-Hb, BPDE-SA, and BPDE-DNA adducts were quantified as BaP tetrols released from hydrolysis of macromolecules and measured by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry to achieve high specificity and sensitivity. Individuals with detectable Hb adducts were positive for SA adducts but not vice versa, suggesting that BPDE-Hb adducts are less informative indicators of BaP exposure. Using PCR methods on DNA, we characterized GSTM1 deletion, CYPIA1 MspI and exon 7 valine variants, and mEH polymorphisms at amino acid positions 113 (EH3) and 139 (EH4). Levels of BPDE adducts were no different among CYPIA1, mEH, and GSTM1 genotypes. However, individuals with measurable BPDE-SA adducts were CYPIA1 variant carriers more frequently (P = 0.03). There was a slightly higher percentage of DNA detectable adducts in subjects with CYPIA1 exon 7 valine polymorphism. When subjects were classified by both polymorphisms on the mEH gene, those with two slow alleles (EH3 homozygous mutated) and no fast alleles (EH4 homozygous wild type) had a lower frequency of BPDE-SA adducts and no DNA adducts (P = 0.06). These results are based on a small number of observations thus far, but this exploratory study suggests that CYPIA1 and mEH variants might have an impact on BPDE exposure markers such as BPDE-SA adducts. Chemical specificity in adduct measurements is important to identify the biomarkers that reflect BaP exposure more accurately.

Video-assisted thoracoscopic resection of pulmonary sequestration in an infant.

Pulmonary sequestration is a congenital anomaly of lung parenchyma that can be definitively treated only with surgical resection. We report a case of an intralobar sequestration of the right lower pulmonary lobe in an infant successfully treated with video-thoracoscopic surgical removal of the involved lobe at 6 months of age.

Unusual clear cell variant of epithelioid mesothelioma.

Clear cell mesothelioma is an extremely rare neoplasm of the pleura, which can easily be mistaken for a metastasis of clear cell carcinoma to the pleura. We report here the histochemical, immunohistochemical, and ultrastructural aspects of a new case of clear cell pleural mesothelioma in a 52-year-old man with no known asbestos exposure. He was admitted to the hospital for recurrent pleural effusion, which was negative for neoplastic cells at the cytologic examination. A partial decortication of the right pleura was performed. The morphologic, immunohistochemical, and ultrastructural features reported for this case are consistent with the diagnosis of clear cell mesothelioma. The differential diagnosis and immunohistochemical features in comparison with other clear cell neoplasms are discussed.

[Prognostic influence of neoplastic involvement of bronchial stump after anatomical lung resection for NSCLC]. / Influenza prognostica della colonizzazione neoplastica del moncone bronchiale dopo resezione polmonare anatomica per NSCLC.

BACKGROUND: The problem of unexpected neoplastic residual at the bronchial stump after surgery is discussed. Even if the prognostic impact of a macroscopic neoplastic residual at the bronchial stump is well known, the microscopic residual is still uncertain as well as the better therapeutic strategy to face this problem. METHODS: 43 out of 2350 patients operated on for lung cancer in our Institute from 1976 to 1998 had a neoplastic residual bronchial stump; 16 patients underwent a second surgery and are no more included in this study. 27 patients with a mean follow-up of three years were treated without another operation. Radiotherapy was proposed to all these patients and performed only in 20, while 4 patients were treated with polychemotherapy alone. Postoperative stage was IIIa in 17 patients, IIb in 8 and IIa in 2. RESULTS: The three year survival rate is 29% (8 patients still alive, 7 of which disease free); 7 received radiotherapy (35% of the whole patients treated with radiotherapy), only 5 complicated by radiation pneumonia without stopping the treatment, and one only chemotherapy. The survival rate after therapy is the same of patients operated on in the same stage without neoplastic bronchial residual. CONCLUSIONS: The authors are favorable to perform a second look surgery to enlarge bronchial resection in the initial stages and to perform in all cases adjuvant therapy. Attention is given to the meaning of mucosal or extramucosal involvement, to the effectiveness of frozen section examination and the authors' therapeutic suggestions in relationship to stage and histotype are discussed.