Multimodality approach in management of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a solid, locally aggressive tumor, which has been closely linked to asbestos exposure. The survival rate without treatment ranges from 4 to 12 months. Response to chemotherapy and radiation is poor, and surgery is the most effective therapy. There are currently 3000 new MPM cases per year in the United States, with the peak incidence in the United States and Europe expected to occur in the year 2020. The prognosis depends on the stage of the tumor at the time of diagnosis, its histological type, lymph node status, and resection margins. While the diagnosis is often delayed, earlier intervention may improve life expectancy. Single-modality therapy has not been effective in changing the natural history of MPM. As a result, multimodality regimens involving surgery with radiation, chemotherapy, or immunotherapy have been initiated. Multiple modality approach has demonstrated favorable outcome, particularly in patients with epithelial histology, negative resection margins and presence of no metastases to extrapleural lymph nodes. Cisplatin and mitomycin have demonstrated modest efficacy in management of distant tumor recurrence. Cisplatin and gemcitabine regimen as well as cisplatin/pemetrexed followed by 54 Gy of adjuvant hemithorax radiation have been reported to improve the outcome.     

Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma: techniques and complications

Innovative therapeutic agents and strategies are being investigated to improve survival with this lethal disease. New chemotherapy agents, including gemcitabine (Eli Lilly and Company; Indianapolis, Indiana) and pemtrexed (Eli Lilly and Company) show promise against mesothelioma. Kaiser has reported using novel therapies, such as cytokines and suicide gene therapy, to target mesothelioma. Pass et al , Moskal et al , Schouwink et al , and Friedberg et al have applied photodynamic therapy to the hemithorax after surgical resection. Because recurrence of mesothelioma after surgical resections tends be locoregional rather than distant , strategies to improve local control may be beneficial. Several groups, including our Brigham and Women's Hospital Thoracic Surgery Division and Dana Farber Thoracic Oncology Program, are investigating intraoperative intracavitary lavage of hyperthermic chemotherapy immediately after EP (discussed elsewhere in this issue). Although mesothelioma remains a difficult disease to treat, the techniques of surgical resection for mesothelioma have improved dramatically. Currently, EPP can be performed with acceptable morbidity and mortality at experienced centers.     

Multimodal therapy for malignant pleural mesothelioma including extrapleural pneumonectomy

Multimodal therapy including neoadjuvant chemotherapy with subsequent extrapleural pneumonectomy and postoperative radiotherapy has been shown to improve the survival of patients with malignant pleural mesothelioma (MPM) if they are selected carefully. Careful patient selection is required in order to administer aggressive multimodal therapy only to patients who will benefit from such a treatment. To achieve an accurate staging (相似文献   

Experimental photodynamic therapy for malignant pleural mesothelioma with pegylated mTHPC

BACKGROUND AND OBJECTIVES: Experimental assessment of photodynamic therapy (PDT) for malignant pleural mesothelioma using a polyethylene glycol conjugate of meta-tetrahydroxyphenylchlorin (PEG-mTHPC). STUDY DESIGN/MATERIALS AND METHODS: (a) PDT was tested on H-meso-1 xenografts (652 nm laser light; fluence 10 J/cm(2); 0.93, 9.3, or 27.8 mg/kg of PEG-mTHPC; drug-light intervals 3-8 days). (b) Intraoperative PDT with similar treatment conditions was performed in the chest cavity of minipigs (n = 18) following extrapleural pneumonectomy (EPP) using an optical integrating balloon device combined with in situ light dosimetry. RESULTS: (a) PDT using PEG-mTHPC resulted in larger extent of tumor necrosis than in untreated tumors (P < or = 0.01) without causing damage to normal tissue. (b) Intraoperative PDT following EPP was well tolerated in 17 of 18 animals. Mean fluence and fluence rates measured at four sites of the chest cavity ranged from 10.2 +/- 0.2 to 13.2 +/- 2.3 J/cm(2) and 5.5 +/- 1.2 to 7.9 +/- 1.7 mW/cm(2) (mean +/- SD). Histology 3 months after light delivery revealed no PDT related tissue injury in all but one animal. CONCLUSIONS: PEG-mTHPC mediated PDT showed selective destruction of mesothelioma xenografts without causing damage to intrathoracic organs in pigs at similar treatment conditions. The light delivery system afforded regular light distribution to different parts of the chest cavity.     

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.     

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.     

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.     

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.     

Survival and relapse pattern after trimodality therapy for malignant pleural mesothelioma

Purpose  

Multimodality therapy has been applied to resectable malignant pleural mesothelioma, but the tolerability of the treatment and relapse pattern in detail remain unknown. We reviewed our experience of trimodality therapy as a single-institution study in Japan.     

A case of panpleuropneumonectomy for diffuse pleural mesothelioma

A 58-year-old man was admitted to our hospital because of chest pain and dyspnea on July 15, 1999. A chest X-ray showed left pleural effusion, and a chest CT revealed left pleural effusion and diffuse pleural thickening. Because pleural fluid cytology and percutaneous needle pleural biopsy were negative for malignancy, thoracoscopic biopsy was performed on July 28. The biopsied specimen revealed malignant pleural mesothelioma (epithelial type). An operation was performed on August 16. First, mediastinal lymph node dissection was performed and we identified that there was no lymph node metastasis by frozen section diagnosis. Then panpleuropneumonectomy with combined resection of the diaphragm and pericardium was performed.     

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.     

Interleukin-4 receptor cytotoxin as therapy for human malignant pleural mesothelioma xenografts

Background

Malignant pleural mesothelioma (MPM) is an uncommon but highly fatal neoplasm for which only limited treatment is available.

Methods

Immunohistochemical analysis was used to determine the expression of interleukin-4 receptors (IL-4R) on mesothelioma cell lines and resected mesothelioma tumors. Radioreceptor binding assays were used to show that these IL-4R were high-affinity receptors. Previously, we had shown that a chimeric protein composed of a circularly permuted IL-4 molecule fused to a truncated form of Pseudomonas exotoxin A, IL-4(38-37)-PE38KDEL, could be used to kill IL-4R-bearing tumor cells in vitro. The toxicity of this molecule to mesothelioma cell lines was tested using a protein synthesis inhibition assay. A human mesothelioma xenograft model was then developed to assess the efficacy of this molecule in vivo.

Results

All MPM cell lines tested were found to express high-affinity cell-surface IL-4R. Immunohistochemical analysis of resected mesothelioma tumor specimens from 13 patients revealed that all tumors expressed moderate-to-high levels of IL-4R. Coculture of malignant mesothelioma cell lines with IL-4(38-37)-PE38KDEL resulted in a dose-dependent inhibition of tumor cell protein synthesis through an interaction with cell-surface IL-4R. In a nude mouse xenograft model of human MPM, intratumoral administration of IL-4(38-37)-PE38KDEL mediated a dose-dependent decrease in tumor volume and a dose-dependent increase in survival.

Conclusions

The chimeric protein, IL-4(38-37)-PE38KDEL, has potent antitumor effects against MPM both in vitro and in vivo.