Diffuse malignant peritoneal mesothelioma – An update on treatment

Abstract

Mesotheliomas are aggressive and lethal neoplasms arising from mesothelial cells lining the pleura, peritoneum, tunica vaginalis testis and pericardium. Malignant peritoneal mesothelioma accounts for about 30% of all mesotheliomas. Asbestos is the main known cause of the disease. Presenting symptoms in these patients include: ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and vomiting. Electron microscopy, immunohistochemistry, computed tomography scan, echotomography, magnetic resonance imaging, positron emission tomography and laparoscopy are used in diagnosis and follow-up. Chemotherapy alone is considered as a palliative treatment for these patients who are not eligible for radical surgery. The most promising non-surgical approach today in the management of peritoneal mesothelioma is the use of the combination chemotherapy regime of an antifolate (pemetrexed and raltitrexed) and a platinum based (cisplatin) agent with a median survival of about 12–14 months. Due to peritoneal confinement of malignant mesothelioma and low occurrence of metastasis, a locoregional approach consisting of cytoreductive surgery and perioperative intraperitoneal chemotherapy has been introduced as a curative treatment option over the last decade with an overall 5-year survival rate of 29–63%. In this locoregional approach, surgery can separate the adhesions and remove the bulky tumor, leaving microscopic residual tumors much more susceptible to the killing effect of chemotherapeutic drugs. Here in St. George hospital, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (using cisplatin and doxorubicin) resulted in significant survival advantage. This article describes how the prognosis of the disease has changed over the last decade.

Introduction

Peritoneal mesothelioma was first described by Miller and Wynn in 1908.¹ Mesothelioma is an aggressive lethal neoplasm arising from mesothelial cells lining the pleura, peritoneum, tunica vaginalis testis and pericardium.² Primary diffuse malignant peritoneal mesothelioma (DMPM) is a rare clinical entity, accounting for about 30% of all mesothelioma,[2], [3], [4] in which variable history of pleural plaques and asbestos exposure may be present.⁴ The lifetime probability of peritoneal mesothelioma has been reported as 1 per 10,000 women and between 1 and 1.5 per 10,000 in men.⁵ In developed countries, malignant mesothelioma is the most frequent malignant neoplasm of the peritoneum.⁶ Age-standardized incidence rates range from 0.5 to about 3 cases per million among men and from 0.2 to about 2 cases per million for women.⁶ The overall annual incidence of mesothelioma encompassing pleural, peritoneal, and retroperitoneal variants in Australia is 15.8 per million.⁷ Annual incidence of DMPM in USA is 300–400 cases.⁸ Women with DMPM have had better survival which may be related to the favourable clinical and histopathological features associated with the tumors in women.⁸ Associated tumors with DMPM are colorectal cancer, cheek basocellular carcinoma, papillary thyroid carcinoma, tongue carcinoma, bladder carcinoma, testicular seminoma, lung non-small-cell carcinoma and ileus neuroendocrine carcinoma.⁹ Both localized and DMPM form solid masses, but cystic and mucoid regions within the tumor may occur and create a heterogeneous consistency on the cut surface of the tumor.¹⁰ Recurrence rates continue to be very high with significant morbidity.⁴ The life expectancy of untreated patients and patients treated with conventional means is 4–12 months.[11], [12] However, with the introduction of radical debulking surgery combined with heated intraperitoneal chemotherapy, as described by Sugarbaker group, patients survival has improved.¹¹