低度恶性腹膜囊性间皮瘤19例临床病理学观察

目的：观察低度恶性腹膜囊性间皮瘤的临床与病理特点。方法：采用HE染色，组织化学，免疫组化技术对19例低度恶性腹膜囊性间皮瘤进行观察，其中9例标本做了电镜检查，结果：本组以中年女性多见，主要症状为腹部疼痛或不适，6例为局限单发性囊性肿块型，7例为多发性囊性结节型，6例为弥漫性囊性结节型，其中8例肿瘤复发，19例肿瘤细胞CI均（＋），而HCI均（－），肿瘤细胞胞浆内keratin,vimentin及EMA等均（＋），结论：低度恶性腹膜囊性间皮瘤是一种具有临床和病理特征的原发性瘤，手术治疗预后好。     

The relationship between malignant mesothelioma and an asbestos cement plant environmental risk: a spatial case–control study in the city of Bari (Italy)

Objectives  To estimate the mesothelioma risk and environmental asbestos exposure (EAE) due to an asbestos-cement plant. Methods  A spatial case–control study including 48 malignant mesothelioma (MM) cases occurred in the period 1993–2003 selected from the regional mesothelioma register (RMR) and 273 controls. The disease risk was estimated by means of a logistic-regression model, in which the probability of disease-occurrence is expressed as a function of the classes of distances. A non-parametric method was applied to estimate the full relative risk surface. Results  Significant MM odds ratio of 5.29 (95 CI: 1.18–23.74) was found for people living within a range up to 500 m centered on the plant. The non-parametric estimation of relative risk surface unveiled a marked peak near the plant not paralleled by the spatial distribution of controls. Conclusion  Evidence of an association between mesothelioma risk and EAE is highlighted. The role played by the RMR in increasing the public health local authorities awareness is stressed.     

Inhibition of survivin and aurora B kinase sensitizes mesothelioma cells by enhancing mitotic arrests

PURPOSE: Survivin, a member of the inhibitor of apoptosis gene family, has also been shown to regulate mitosis. It binds Aurora B kinase and the inner centromere protein to form the chromosome passenger complex. Both Aurora B and survivin are overexpressed in many tumors. In this study, we examined whether irradiation affected survivin and Aurora B expression in mesothelioma cells, and how inhibition of these molecules affected radiosensitivity. METHODS AND MATERIALS: ZM447439 and survivin antisense oligonucleotides were used to inhibit survivin and Aurora B kinase respectively. Western blot was performed to determine the expression of survivin, Aurora B, phosphorylated-histone H3 (Ser 10), and caspase cleavage. Multinucleated cells were counted using flow cytometry, and cell survival after treatment was determined using clonogenic assay. RESULTS: At 3-Gy irradiation an increase was observed in levels of survivin and Aurora B as well as the kinase activity of Aurora B, with an increase in G2/M phase. The radiation-induced upregulation of these molecules was effectively attenuated by antisense oligonucleotides against survivin and a small-molecule inhibitor of Aurora B, ZM447439. Dual inhibition of survivin and Aurora B synergistically radiosensitized mesothelioma cells with a dose enhancement ratio of 2.55. This treatment resulted in increased formation of multinucleated cells after irradiation but did not increase levels of cleaved caspase 3. CONCLUSION: Inhibition of survivin and Aurora B induces mitotic cell arrest in mesothelioma cells after irradiation. These two proteins may be potential therapeutic targets for the enhancement of radiotherapy in malignant pleural mesothelioma.     

Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma

PURPOSE: To determine the incidence of fatal pulmonary events after extrapleural pneumonectomy and hemithoracic intensity-modulated radiotherapy (IMRT) for malignant pleural mesothelioma. METHODS AND MATERIALS: We retrospectively reviewed the records of 63 consecutive patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy and IMRT at the University of Texas M. D. Anderson Cancer Center. The endpoints studied were pulmonary-related death (PRD) and non-cancer-related death within 6 months of IMRT. RESULTS: Of the 63 patients, 23 (37%) had died within 6 months of IMRT (10 of recurrent cancer, 6 of pulmonary causes [pneumonia in 4 and pneumonitis in 2], and 7 of other noncancer causes [pulmonary embolus in 2, sepsis after bronchopleural fistula in 1, and cause unknown but without pulmonary symptoms or recurrent disease in 4]). On univariate analysis, the factors that predicted for PRD were a lower preoperative ejection fraction (p = 0.021), absolute volume of lung spared at 10 Gy (p = 0.025), percentage of lung volume receiving >or=20 Gy (V(20); p = 0.002), and mean lung dose (p = 0.013). On multivariate analysis, only V20 was predictive of PRD (p = 0.017; odds ratio, 1.50; 95% confidence interval, 1.08-2.08) or non-cancer-related death (p = 0.033; odds ratio, 1.21; 95% confidence interval, 1.02-1.45). CONCLUSION: The results of our study have shown that fatal pulmonary toxicities were associated with radiation to the contralateral lung. V20 was the only independent determinant for risk of PRD or non-cancer-related death. The mean V20 of the non-PRD patients was considerably lower than that accepted during standard thoracic radiotherapy, implying that the V20 should be kept as low as possible after extrapleural pneumonectomy.     

Late-onset chylothorax following extrapleural pneumonectomy for mesothelioma

We report a 64-year-old woman treated with surgical intervention for late-onset chylothorax following a pleuropneumonectomy. The patient underwent an extrapleural pneumonectomy for diffuse malignant mesothelioma and was uneventfully discharged on postoperative day 29. Pleural effusion aspirated on postoperative day 9 was dark red. A chest roentgenogram taken at our outpatient clinic revealed a mediastinal shift on postoperative day 56. No bacterial infection was found in the milky effusion. We made a diagnosis of postoperative late-onset chylothorax based on the laboratory data obtained from tests of the pleural fluid. A repeat thoracotomy to ligate the lymphatic duct was performed because conservative management with chest tube drainage and no oral feeding was unsuccessful. The patient was discharged after the operation with a good clinical course.     

Overview of Asbestos Issues in Korea

Asbestos is a carcinogen that causes diseases such as mesothelioma and lung cancer in humans. There was a sharp increase in the use of asbestos in Korea in the 1970s as Korea''s economy developed rapidly, and asbestos was only recently banned from use. Despite the ban of its use, previously applied asbestos still causes many problems. A series of asbestos-related events that recently occurred in Korea have caused the general public to become concerned about asbestos. Therefore, it is necessary to take proper action to deal with asbestos-related events, such as mass outbreaks of mesothelioma among residents who lived near asbestos textile factories or asbestos mines. Although there have been no rapid increases in asbestos-related illnesses in Korea to date, such illnesses are expected to increase greatly due to the amount of asbestos used and long latency period. Decreasing the asbestos exposure level to levels as low as possible is the most important step in preventing asbestos-related illnesses in the next few decades. However, there is a lack of specialized facilities for the analysis of asbestos and experts to diagnose and treat asbestos-related illnesses in Korea; therefore, national-level concern and support are required.     

Laparoscopy: An important tool in the staging of malignant pleural mesothelioma

Background: The current standard for the noninvasive staging of patients with malignant pleural mesothelioma is computed tomography (CT). However, CT often cannot determine whether a tumor is unresectable because of direct extension through the diaphragm to the peritoneal cavity. The aim of this prospective study was to determine whether laparoscopy detected transdiaphragmatic tumor extension when CT findings were equivocal. Methods: From June 1993 to July 1994, 12 of 36 patients considered for possible thoracotomy and surgical resection had equivocal CT findings of diaphragmatic invasion. All underwent laparoscopy using a multiport technique with diaphragmatic and peritoneal biopsies. Results: The mean operative time was 83 min. There were no perioperative complications. The median hospital stay was 1 day. Six patients had biopsy-proven transdiaphragmatic extension, or peritoneal studding of tumor. The other six patients subsequently underwent thoracotomy: three had a complete resection, and three had unresectable tumor due to chest wall (N=2) or mediastinal (N=1) invasion. In no case was transdiaphragmatic extension of a tumor seen. Conclusions: This preliminary experience demonstrates that laparoscopy is a safe and accurate method for detecting transdiaphragmatic tumor extension when CT fails to do so. Laparoscopy should be considered a standard part of prethoracotomy staging in this subset of patients. Results of this study were presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

A phase II trial investigating primary immunochemotherapy for malignant pleural mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal cytoreduction

Background: The treatment of malignant pleural mesothelioma (MPM) continues to be inadequate with the use of standard techniques, including surgery, radiotherapy and chemotherapy. We initiated a phase II trial of immunochemotherapy with cisplatinum (25 mg/m² four times weekly), interferon-α (5 mU/m² s.c. three times weekly), and tamoxifen (20 mg orally twice a day for 35 days) (CIT) based on in vitro and in vivo data suggesting interrelating efficacy of this combination. Methods: Since July 1991, 36 patients have been evaluable for response after receiving one to five cycles of CIT. Ten additional patients had debulking surgery followed by two cycles of postoperative adjuvant CIT commencing a mean of 6 weeks after surgery. Results: Toxicity was acceptable (4% grade III/IV). One treatment-related death (2%) occurred, from myocardial infarction. A 19% partial response rate, objectively quantified using three-dimensional computerized tomographic (CT) measurement of solid disease volume, was recorded. The median survival for the seven responders was 14.7 months, whereas that of the nonresponders was 8 months (p2=0.2). Median survival for the entire group was 8.7 months. Preoperative size, platelet count >360,000/ml, and nonepithelial histology were associated with shortened survival. Conclusions: The CIT regimen has some activity in MPM and can be delivered after debulking resection. In good-risk patients, as defined by favorable prognostic factors, a randomized trial using this combination may be warranted. Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.