Daisuke Matsuzoe

p53 mutations predict non-small cell lung carcinoma response to radiotherapy

In vitro and animal studies, the effect of loss of p53 function on radiosensitivity is controversial. p21Waf1/Cip1 is a potent inhibitor of cyclin-dependent kinases and p21 gene polymorphisms are associated with some human cancers. We sought to determine whether p53 mutations or p21 polymorphisms affect response to radiotherapy in patients with recurrent non-small cell lung carcinoma (NSCLC). Thirty-four patients with NSCLC who underwent radiotherapy for recurrent tumors after potentially curative resection were studied. Gene alterations or polymorphisms were analyzed in DNA from the primary tumor tissue, and the response to radiotherapy was based on the metastatic lesion. Mutations in exons 5-8 of the p53 gene were detected by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. p21 gene polymorphisms were identified by restriction digestion (BsmAI or PstI) of PCR products. Mutations in p53 were found in 13 of 34 patients (38.2%). The response rates (complete plus partial) were 15.4% for patients with tumors having p53 mutations and 61.9% for patients with wild-type p53 (P = 0.013). There was no significant difference between p21 polymorphisms and response to radiation. p53 gene mutations predict response to radiotherapy in NSCLC. Our results provide clinical support for the in vitro model that loss of p53 function decreases radiosensitivity.

Postoperative chylothorax following partial resection of mediastinal lymphangioma : report of a case

We report herein the rare case of a 20-year-old man in whom a mediastinal lymphangioma was incidentally detected by a chest roentgenogram taken during a routine health examination. Both computed tomography and magnetic resonance imaging confirmed a mass measuring 3×7 cm in diameter in the left anterior mediastinum. A thoracoscopic exploration was done, which confirmed a diagnosis of mediastinal lymphangioma, and 3 days later a sternotomy was performed. However, the tumor could not be completely extirpated due to partial invasion. Following the thoracoscopic procedure, a chylous discharge developed which was difficult to treat conservatively and he continued to drain 700–1,000 ml of chyle daily 2 weeks following the tumor extirpation. Therefore, a right thoracotomy with ligation of the thoracic duct was performed which resolved the chylothorax. The patient remains well without any regrowth of the regional tumor 9 months after his operation.

Synchronous multicentric thymona: report of a case.

We report a case of multiple thymoma with different histological subtypes, not associated with myasthenia gravis. We describe the histological findings, especially the results of immunohistochemical staining, which support the possibility of multicentric thymoma. The validity of extended thymectomy is also discussed.

Lymph node metastasis and prognosis in small peripheral non-small-cell lung cancers.

OBJECTIVE The lymph node dissection and curative resection for small peripheral non-small-cell lung cancers, it is essential to know the incidence and distribution of lymph node metastasis to confirm the pathological stage. METHODS Between January 1984 and August 1996, lobectomy with systemic mediastinal dissection (standard lobectomy) was conducted in 49 patients with small peripheral non-small-cell lung cancers (2.0 cm or less in diameter), and limited resection was conducted in 15 with cardiopulmonary insufficiency. RESULTS Lymph node metastasis was confirmed histologically in 14 patients undergoing standard lobectomy (28.6%). The incidence of lymph node metastasis was high in tumors with pleural (p2) or subpleural (p1) involvement (63.6%) (7/14). The 5-year survival between standard lobectomy and limited resection patients (83% vs. 71%) was not statistically significant. In patients undergoing standard lobectomy, survival in those with node-negative disease was better than in those with node-positive disease (94% vs. 44%, p < 0.01). CONCLUSIONS Lymph node involvement, especially in tumors with pleural involvement, is not uncommon, even when tumors are 2.0 cm or less in diameter. Systemic hilar and mediastinal dissection is therefore required for disease staging and treatment.

K-ras gene mutation in non-small cell lung cancer in Japanese

To evaluate the association of mutations in the K-ras gene with the incidence of non-small cell lung cancer (NSCLC) in Japanese patients, 410 patients treated surgically were studied. DNA was extracted from frozen specimens, and polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) hybridization assay was used to examine K-ras mutations in codons 12, 13 and 61. K-ras mutations were found in 33 patients (8.0%), and all were smokers or ex-smokers. There were no significant differences in clinical or pathological stage between wild-type cases and mutant cases. The most frequently identified mutation was a G-->T transversion (25/33, 75.8%) that resulted in the substitution of a glycine for a cysteine or a valine. Previous studies have shown that the majority of K-ras mutations among smokers are G-->T transversion. In our study, K-ras mutations were found only in smokers, and there was a high frequency of G-->T transversions. A clear correlation exists between smoking and K-ras gene mutations.

Analysis of Factors Influencing Operative Death or Long Hospital Stay Following Surgery for Lung Cancer

[目的] 肺癌手術例における術死症例 (術後30日以内)・術後長期入院症例 (術後30日以上) を抽出し, これに関与する患者背景因子・手術関連因子を多変量解析を用い検討した.[対象] 過去6年間に原発性肺癌に対し肺部分切除以上の肺切除手術を受けた534例.[結果] 術死は12例 (2.3%), 長期入院は60例 (1L6%) であった.多変量解析の結果, 術死要因は中枢気道再建, 主肺動脈再建, T因子, 術後長期入院要因は胸壁再建, 慢性閉塞性肺疾患の合併, 肺全摘, 気管支形成が指摘された.[考察] 多変量解析の結果, 患者自身の背景因子として意味を持つものは長期入院に対する閉塞性肺障害のみで, 他の併発症に関しては術前に良好に管理されている限り重大な問題とはならない可能性が示された.術式上問題となる因子は, 胸壁合併切除, 気道再建, 肺動脈再建, 肺全摘等であった.しかし, 手術侵襲を左右する因子として通常考えられているリンパ節郭清の程度は, 術死・長期入院双方に関してその因子とは認められなかった.