Multimodality therapy for diffuse malignant pleural mesothelioma

Despite the rising incidence of diffuse malignant pleural mesothelioma (MPM), there is still no standard treatment for this disease, and the prognosis for patients remains poor. Recently, long-term survival has been reported when multimodality therapy is used, combining extrapleural pneumonectomy with perioperative chemotherapy and/or radiotherapy in highly selected patients. We report a case of a patient who presented with MPM, accompanied by a large malignant pleural effusion and pneumothorax, who was successfully treated with combination therapy. After being diagnosed with epithelial type MPM using thoracoscopic surgery, the patient underwent extrapleural pneumonectomy. Examination of the surgical specimen revealed invasion of the chest wall muscle and fat, as well as several positive mediastinal lymph nodes. The patient received 2 courses of postoperative chemotherapy using cisplatin and gemcitabine. He is currently alive and has been disease-free for 2 years.     

Trimodality management of malignant pleural mesothelioma.

OBJECTIVE: We reviewed our experience with trimodality management of malignant pleural mesothelioma (MPM). METHODS: From September 1998 to August 2000, 32 consecutive patients with histological diagnosis of MPM underwent trimodality therapy, including surgery followed by adjuvant chemotherapy and radiation therapy. Surgery consisted of pleurectomy/decortication (P/D) or pleural-pericardial-pneumonectomy and diaphragm (PPPD). Pre-operative staging according to the Brigham Staging System was accomplished using computed tomography (CT) and magnetic resonance imaging (MRI); patients with evident extrapleural spread were excluded. RESULTS: Our series included 21 men and 11 women with a median age of 53.5 years (range 40-69). Histologically, there were 26 epithelial, four mixed and two sarcomatous MPM. Post-surgical staging was as follows: six patients were at Stage I; of these, two received a P/D and four a PPPD. Ten patients were at Stage II and all received a PPPD; 16 patients were at Stage III (under-staged pre-operatively): of these, nine patients presented extrapleural lymph node metastases (N2) and all received a PPPD, seven patients presented with chest wall or mediastinal invasion (T4) with macroscopic residual tumour, and all received a de-bulking P/D. We observed major complications in ten patients: six bleeding, two respiratory insufficiency and two nerve paralysis. There were two perioperative deaths (6.25% mortality). Twenty-seven patients out of 30 surviving surgery had a follow-up greater than 6 months; 21 patients out of 27 are alive with a median follow-up of 12.5 months. CONCLUSIONS: (1) Trimodality therapy is feasible in selected patients with MPM and has an acceptable operative mortality rate. (2) Our current pre-operative staging based on CT/MRI looks rather inaccurate and needs to be improved. (3) The high rate of post-surgical N2 patients or with diffusion to the inferior surface of the diaphragm may suggest the use of routine mediastinoscopy and laparoscopy for a more appropriate patient selection.     

Radiation associated malignant pleural mesothelioma.

Malignant pleural mesothelioma of epithelial type developed in a 24 year old woman, 20 years after radiotherapy for Hodgkin's disease. This case and a review of published cases indicate that radiation may induce malignant mesothelioma.     

Diffuse malignant pleural mesothelioma

Malignant pleural mesothelioma is an uncommon neoplasm that caused 647 deaths in Japan in 2004. The incidence of the disease is increasing and is estimated to reach its peak in 2025. We reviewed the clinical features in 11 consecutive patients with pathologically confirmed diffuse malignant pleural mesothelioma in our institution from January 1997 to December 2002. Of the 11 patients, 9 were male and 2 were female with a mean age of 66 (range, 55 to 90) years. Symptoms included dyspnea in 4 patients, chest pain in 3, dyspnea plus chest pain in 2, and cough in 2. Median period between symptom onset and presentation was 1 (range, 0 to 6) month. A history of asbestos exposure was identified in 3 patients and suspected in 5. A definitive diagnosis was made by closed pleural biopsy in 8 patients, pleural fluid cytology in 2, and autopsy in 1. Histological subtypes included epithelioid in 6 patients, sarcomatoid in 2, biphasic in 1, and unknown in 2. International Mesothelioma Interest Group (IMIG) staging included stage II in 6 patients, stage III in 3, and stage IV in 2. Median period between presentation and diagnosis was 1 (range, 0 to 22) month. Treatment included intrapleural chemotherapy in 4 patients, extrapleural pneumonectomy in 3, pleural drainage in 2, and best supportive care in 2. During the follow-up period, 9 patients died and 2 survived. Median survival time after diagnosis was 3 (range, 0 to 51) months. Of the 11 patients, 7 (64%) died within 6 months after the first presentation, and only 1 (9%) lived longer than 2 years after diagnosis.     

Intradural pleural malignant mesothelioma

Summary Pleural malignant mesothelioma is a rare tumour of the pleural epithelium, which progresses by infiltration into the lung parenchyma, the chest wall, and the mediastinum. Haematogenous spreading may occur in the late stages of the disease. Spinal involvement is exceptional and usually occurs in the vertebral body or epidural space, and intradural location of a mesothelioma is even more uncommon. In this article, a MEDLINE literature review on intradural mesothelioma was conducted and four intradural mesothelioma cases in the English literature were retrieved: one in the intradural extramedullary location and three with intramedullary growth. Additionally, we report a 50-year-old patient with a pleural malignant mesothelioma that spreads across the dura into the spinal cord at T5.     

Localized malignant pleural mesothelioma

Localized malignant pleural mesothelioma (LMPM) is a rare tumor; previously only 52 cases have been reported in the English literature. This type of tumor should be distinguished from diffuse malignant pleural mesothelioma, because a good outcome may be obtained by surgical resection. We report a case of LMPM which grew rapidly within 1 year. Surgical resection was performed, and at present, 6 months since the operation, the patient remains free of the disease.     

Localized malignant lymphohistiocytoid pleural mesothelioma

We report a case of a 42-year-old man with a right pleural mesothelioma. This neoplasm has 3 rare features. Firstly, it was a localized form: suspected by imaging, visualized by video-assisted thoracoscopy, at the time of the curative-thoracotomy and confirmed by the pathological analysis. The second characteristic is its histological type: "malignant lymphohistiocytoid mesothelioma". This rare subtype has been reported in only 4 papers. Third, after pleuro-pneumonectomy, our patient is alive after 6 years and 5 months postoperatively without any sign of recurrence. Only one case with a long follow-up has been reported but with recurrence at 5 years postoperatively.     

The management of malignant pleural mesothelioma; single centre experience in 10 years.

BACKGROUND AND OBJECTIVES: Malignant pleural mesothelioma (MPM) is an asbestos-related disease of the pleura with a survival time without treatment ranging from 4 to 12 months. The objective of this study is to review our experience in selection of MPM patients for various modalities of treatment. METHODS: Between 1989 and 1998, 302 patients with MPM have been referred to our Centre for assessment. Majority (191 patients, 61%) of them received no specific treatment. Forty-seven patients were treated by decortication/pleurectomy and 64 had a radical extra-pleural pneumonectomy (EPP). Intrapleural chemotherapy and systemic post-operative chemotherapy was employed only in the last 51 patients following radical surgery. RESULTS: The average survival was 8.9 months for those treated by palliative care only. The average survival was 13 and 14 months for patients treated by radical surgery only or by decortication/pleurectomy, respectively. However, survival has improved to a mean of 35 months for patients treated by radical surgery followed by systemic post-operative chemotherapy. In this group, the survival prevalence was 90 and 70% for T1 patients and 85 and 36% for T2 patients at 1 and 3 years, respectively (P=0.002). Survival was surprisingly, not affected by lymph node involvement (P=0.08) or pathological type of MPM (P=0.07). The operative mortality was 9% for EPP and 0% for decortication/pleurectomy. CONCLUSION: In selected patients with MPM, complete surgical resection by EPP represents an important initial step in their management. Systemic chemotherapy improves survival in surgically treated patients. Further trials are needed to improve on the adjuvant treatment regimes.     

Histopathologic diagnosis of malignant pleural mesothelioma

Diffuse malignant mesothelioma is a malignant tumor arising in the pleura from mesothelial cells. It has extremely polymorphous varieties of morphological patterns. Thus, confirming histopathologic diagnosis as mesothelioma, it should need not only histological examination but several methods such as special stain, immunohistochemical study, cytology of pleural effusion and electromicroscopy.     

Treatment of malignant pleural mesothelioma]

BACKGROUND: In this study all patients observed between January 1993 and October 1997 with malignant pleural mesothelioma (MPM) have been analyzed in order to describe the impact of treatment modality on survival. METHODS: Medical records of 56 patients with MPM (44 male, 12 female, median age = 59 yrs) were reviewed. In 34 cases the histotype was epithelial, in 4 sarcomatoid, in 4 mixed, in 3 desmoplastic, and in 11 not specified. Four treatment modalities were identified: 1) Surgery (subtotal pleurectomy) = 20 patients; 2) Chemotherapy = 19 patients; 3) Surgery+Chemo-therapy = 8 patients; 4) Supportive care = 9 patients. RESULTS: The median survival was: 1) Surgery = 12.4 months; 2) Chemotherapy = 7.5 months; 3) Surgery+Chemotherapy = 12 months; 4) Supportive care = 11.4 months. Using univariate analysis, 8 prognostic factors were studied (age, sex, asbestos exposure, side, histotype, performance status, stage, treatment). Among these, only the stage and the performance status had shown a prognostic value on survival (p<0.05), while the treatment modality had not significantly influenced the prognosis. Using multivariate analysis only performance status showed to be significatively associated with survival (p=0.01 and odds ratio = 1.9, I.C. 1.2-3.2). CONCLUSIONS: Despite the limits of a retrospective study, personal experience confirms the ineffectiveness of current therapeutical approaches to MPM. A better understanding of MPM is required to develop new therapeutical approaches and alter the dismal prognosis of this disease.     

恶性胸膜间皮瘤治疗新进展

恶性胸膜间皮瘤是一种与石棉接触密切的肿瘤,其侵袭性很强,起病隐匿,发现时已在中晚期,目前的治疗方案尚未能有很好的治疗效果.采用溶瘤细胞性单纯性疱疹病毒和顺铂诱导溶瘤细胞性单纯性疱疹病毒产生GADD34蛋白增量调节方案能对间皮瘤癌细胞有相对的特异性,是一种有前景的治疗方案.     

Clinical diagnosis of malignant pleural mesothelioma

Accurate and rapid diagnosis of malignant pleural mesothelioma is important because of its rapid progress. But diagnosis of this disease is often difficult. We reviewed 64 cases with a pathological diagnosis of malignant pleural mesothelioma in the past 14 years in our hospital. We made diagnosis of this disease by cytologic study of pleural fluid (11 cases), percutaneous needle biopsy (16), thoracoscopic biopsy (34), or surgery (2). When cytologic findings are inconclusive, thoracoscopic biopsy is the most effective method for diagnosis and should be done without delay.     

Extrapleural pneumonectomy of malignant pleural mesothelioma

We analyzed 7 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy. Six men and a woman had a mean age of 65 years old. The postoperative mortality rate was 14% (1 death) and morbidity, 43% (3 cases). According to staging of International Mesothelioma Interest Group, 2 patients had stage I disease, 1 did stage II, 3 did stage III and 1 did stage IV. Local recurrences were found in 3 patients and metastasis in 2. In patients with local recurrences, 2 had irradiation with chemotherapy and 1, irradiation. In patients with recurrences of metastasis, 1 had chemotherapy and 1, supportive care. Seven patients with extrapleural pneumonectomy and 10 without surgery had median survivals of 16 months and 10 months, 1-year survival rates of 71% and 40% and 2-year survival rates of 57% and 0% respectively (p=0.071). Extrapleural pneumonectomy with adjuvant therapy could be effective treatment for malignant pleural mesothelioma.     

恶性胸膜间皮瘤的实验模型

恶性胸膜间皮瘤(malignant pleural mesothelioma，MPM)是一种少见的肿瘤，近年来发病率逐渐上升，由于诊断和治疗均较困难，所以迫切需要建立实验模型进行研究。通过对模型的种类、制作方法和各种模型的特点进行综述，归纳出其用途。MPM动物模型是临床研究最常用的实验模型，多用大鼠或裸鼠，以诱发性动物模型和异种移植模型较成熟。目前各种模型均存在一些缺点，或周期长、出瘤率低或与人差异较大等，离理想的模型仍有一定的距离。但随着分子生物学和分子遗传学的发展，利用基因或其它途径减少或消除大动物的个体差异，同时提高实验动物产量；研究裸鼠的繁殖、饲养规律，寻找廉价、饲养方便、体大、生命力强的裸鼠，以及对MPM转基因动物模型的研究，将有希望获得多种满足不同需要的理想MPM实验模型。     

Extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma.

A technique for extrapleural pneumonectomy in diffuse, malignant, pleural mesothelioma is described. The technique used in a protocol at Brigham and Women's Hospital has resulted in improved operative mortality figures and length of hospital stay. The right-sided procedure is presented followed by differences in technique required by the left-sided approach.     

Extrapleural pneumonectomy for malignant pleural mesothelioma

We analyzed 14 patients with malignant pleural mesothelioma (MPM) who underwent extrapleural pneumonectomy (EPP). 14 men had a mean age of 58.5 years. Preoperarive histological diagnosis was as follows: epithelial 12, biphasic 1, sarcomatous 1. Postoperative diagnosis was: 8, 5, 1, respectively. According to staging of International Mesothelioma Interest Group (IMIG), 3 patients had stage 11 disease, 8 did stage Ill and 3 did stage IV, postoperatively. The operative mortality rate was 7% (1 death), and morbidity rate was 50% (7 cases). The median survival time and 2- and 5-year survival rate were 20.2 months, 33. 8.3%, respectively. EPP for strictly selected patients has been successful in improving survival of patients with negative-node, epithelial type and negative residual tumors.     

Extrapleural pneumonectomy for malignant pleural mesothelioma

Standard treatment for malignant pleural mesothelioma (MPM) has not been proved yet. However, it has been recognized that extrapleural pneumonectomy (EPP) is a treatment of choice for epithelial MPM when combined with adjuvant therapies though EPP may frequently cause fetal complications. We report 5 cases of MPM with EPP, including 1 with good prognosis. Sixteen patients with MPM were admitted to our hospital between 1988 and 2003. Five patients underwent EPP, among which 4 were male and 1 female with ages from 46 to 61 years old. Histologically, 3 of them were epithelial and 2 were biphasic. Those with biphasic experienced acute respiratory failure and empyema, and died 81 days and 8 months after the surgery respectively. Among those with epithelial MPM, 2 are alive with no recurrence at 129 and 29 months after the surgery, and the other, followed by postoperative radiotherapy, died at 12 months. More cases with EPP or randomized controlled trials regarding EPP are necessary to evaluate efficacy of EPP for MPM.     

Outcome after extrapleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma is a mainly asbestos-related neoplasm that occurs with increasing frequency and is associated with a poor prognosis. Extrapleural pneumonectomy which was initially performed as a stand-alone treatment in patients with resectable disease is now currently almost uniformly applied as part of a multi-modal approach. Its value and advantage over other therapeutic strategies remain points of discussion. We therefore analysed our experience with extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. METHODS: We retrospectively reviewed our institutional experience with all consecutive patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma from 1994 to 2005. Patients were analysed with regard to hospital mortality and morbidity and long-term outcome. RESULTS: Forty-nine patients (10 female/39 male, mean age 58+12 years) underwent extrapleural pneumonectomy during the observation period. Median ICU stay was 1 day, median postoperative length of hospital stay was 13 days. After a mean follow-up of 2573 days, median survival was 376 days (mean 672+121 days, range 9-3384). One-year survival was 53%, 3-year survival 27% and 5-year survival 19%. CONCLUSION: Extrapleural pneumonectomy as part of a multi-modality treatment regimen is a good treatment option for selected patients with malignant pleural mesothelioma. The long-term results of this limited series compare favourably to non-surgical treatment regimens. Larger randomised prospective multi-centre trials are warranted to establish clear guidelines.