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Mesothelioma Clinical Presentation^*

^* From the Division of Thoracic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

Correspondence to: Raphael Bueno, MD, FCCP, Division of Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115; e-mail: rbueno{at}bics.bwh.harvard.edu

	Abstract

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Objectives: Clinical teaching of treatment for mesothelioma

Design: Case presentation

Setting: Postgraduate course

Patient: A 52-year-old man with chest pain

Interventions: Multimodality therapy consisted of surgery, intrapleural chemotherapy, chemotherapy, and radiation therapy.

Results: Patient is alive and well 2 years after surgery.

Conclusions: Aggressive trimodality therapy for mesothelioma is presented as a successful treatment option.

Key Words: Mesothelioma • case report • multimodality therapy

	Case Presentation

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The patient, a 52-year-old man, was in his usual state of good health until 2 weeks before presentation when he noticed pain in his right chest and back. The pain was not positional or associated with a trauma. This man has had a past medical history significant only for hypertension and hypercholesterolemia. His father had coronary artery disease. He was a former 15-pack-year smoker who had quit 22 years before presentation. He also had a questionable history of asbestos exposure as a contractor and an architect. He denied any other ailments or symptoms. The only positive physical finding on examination was decreased breath sounds on the right side. A radiograph of his chest demonstrated multiple pleural-based masses involving his right chest. These masses were better seen on chest computed tomography scan and were found to be limited to the right side of the chest. His pulmonary function tests revealed an FEV₁ of 2.9 liters, which was 90% of the predicted measure for his age and body surface area.

The most likely diagnosis at this point of the evaluation was either lung cancer or malignant pleural mesothelioma. Tissue diagnosis was necessary to establish either diagnosis, and so the patient underwent a video thoracoscopic exploration and biopsy. This approach was chosen because it was the method most likely to yield sufficient tissue to make the diagnosis of mesothelioma. Needle biopsy or cytological analysis are often insufficient to make a correct diagnosis when mesothelioma is in the differential diagnosis.

When performing the procedure, it is important to make the incision(s) for diagnostic thoracoscopy or pleuroscopy in the line of a future thoracotomy, so that any tumor cells that are seeded in the biopsy incision may be excised in a future operation.

On thoracoscopic examination, multiple pleural-based masses were found and biopsied. Histological analysis revealed that the patient had the epithelial subtype of malignant pleural mesothelioma (MPM).

	Discussion

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MPM is a mesodermally derived neoplastic disease that arises in the pleura and grows relentlessly into adjacent structures (namely the lungs and the heart), until it ultimately results in the death of the patient.^{1 2} Asbestos is a major factor in the pathogenesis of this malignancy, with up to 80% of patients with MPM noting a history of asbestos exposure.^{1 2 3 4} Approximately 3,000 patients are diagnosed with MPM in the United States every year. The incidence of this disease worldwide is rising and is expected to peak in the next two decades.² Despite extensive research, there is little understanding of the pathogenesis of the disease. There are three histologic variants: epithelial, mixed, and sarcomatoid. Patients with the epithelial type do somewhat better than those with mixed or sarcomatoid type with respect to survival. There is no effective treatment for most patients who present with MPM. Without any treatment, the median survival of patients presenting with MPM is between 4 and 12 months. Chemotherapy or radiation therapy, alone or in combination, are not significantly effective, and the majority of patients will die within 2 years regardless of treatment.^{5 6 7} Patients who present with early disease demonstrate a survival benefit from a multimodality therapeutic approach. This treatment strategy includes a radical surgical resection (an extrapleural pneumonectomy and en bloc resection of all involved pleura, including the diaphragm and pericardium), followed by chemotherapy with paclitaxel and carboplatin as well as radiation therapy to the chest wall. However, in spite of an improved 5-year survival rate, the majority of these patients will eventually succumb to locally recurrent disease.^{8 9 10}

This particular patient presented with early disease and had good functional status. As part of his evaluation, he underwent an echocardiogram, which demonstrated a normal ejection fraction, no pulmonary hypertension, and no wall motion abnormalities. There was also no evidence of a pericardial effusion or tumor invasion through the pericardium. A chest MRI demonstrated disease confined to the right chest with no transdiaphragmatic involvement and no invasion into the chest wall. These criteria are consistent with Stage I mesothelioma, based on the Brigham Staging System. Patients with good functional status and early stage epithelial subtype mesothelioma, who undergo extrapleural pneumonectomy with adjuvant chemoradiation, have achieved a 5-year survival rate of 40%. For this reason, this patient underwent an exploratory right thoracotomy with the intent of proceeding with an extrapleural pneumonectomy. On exploration, the right lung was relatively free of tumor, but some of the tumor penetrated deep into the chest wall. The procedure was therefore modified to a pleurectomy with pericardial resection. All gross tumor was removed, and the sites of chest wall involvement were marked for radiation therapy boost doses.

The patient recovered promptly and received intrapleural infusion of cisplatin postoperatively. He then underwent two cycles of paclitaxel/carboplatin followed by thoracic irradiation, with localized boosts and concurrent paclitaxel. An additional two cycles of paclitaxel and carboplatin were administered to complete the standard adjuvant chemoradiation. The patient is currently alive, with no evidence of disease 2 years after surgery.

	Footnotes

 
Abbreviation: MPM = malignant pleural mesothelioma

	References

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1. Bignon, J, Brochard, P, Pairon, JC (1996) Mesothelioma: causes and fiber-related mechanisms. Aisner, J Arriagada, R Green, MRet al eds. Comprehensive textbook of thoracic oncology ,735-756 Williams & Wilkins Baltimore.
2. Sugarbaker, DJ, Norberto, JJ, Bueno, R (1997) Current therapy for mesothelioma. Cancer Control 4,326-334[Medline]
3. Corson, JM, Renshaw, AA (1996) Pathology of mesothelioma. Aisner, J Arriagada, R Green, MRet al eds. Comprehensive textbook of thoracic oncology ,757-778 Williams & Wilkins Baltimore.
4. DeLuca, A, Baldi, A, Esposito, V, et al (1997) The retinoblastoma gene family pRb/p105, p107, pRb2/p130, and simian virus-40 large T-antigen in human mesotheliomas. Nat Med 3,913-916[CrossRef][ISI][Medline]
5. Huncharek, M (1995) Genetic factors in the aetiology of malignant mesothelioma. Eur J Cancer 31,1741-1747[CrossRef]
6. Aisner, J (1996) Diagnosis, staging, and natural history of pleural mesothelioma. Aisner, J Arriagada, R Green, MRet al eds. Comprehensive textbook of thoracic oncology ,779-785 Williams & Wilkins Baltimore.
7. Ong, ST, Vogelzang, NJ (1996) Current therapeutic approaches to unresectable (primary and recurrent) disease. Aisner, J Arriagada, R Green, MRet al eds. Comprehensive textbook of thoracic oncology ,799-812 Williams & Wilkins Baltimore.
8. Sugarbaker, DJ, Liptay, MJ (1996) Therapeutic approaches for malignant pleural mesothelioma. Aisner, J Arriagada, R Green, MRet al eds. Comprehensive textbook of thoracic oncology ,786-779 William & Wilkins Baltimore.
9. Sugarbaker, DJ, Flores, RM, Jaklitsch, MT, et al (1999) Resection margins, extrapleural nodal status, and cell type determine post-surgical long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 117,54-65[Abstract/Free Full Text]
10. Sugarbaker, DJ, Mentzer, SJ, Strauss, G (1992) Extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. Ann Thorac Surg 54,941-946[Abstract]

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