Info about Mesothelioma

The treatment of peritoneal surface malignancy mainly focuses on diffuse malignant peritoneal mesothelioma, pseudomyxoma peritonei from appendiceal cancer, and peritoneal dissemination from gastrointestinal and ovarian cancers. Cancer progression causes peritoneal implants to be distributed throughout the abdominopelvic cavity. These nodules plus the ascitic fluid result in abdominal distension. As the disease progresses, these tumors cause intestinal obstruction leading to debilitating symptoms and a greatly impaired quality of life. In the past, the prognosis of patients with peritoneal surface malignancy was regarded dismal and cure was not an option. Recently, cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has shown an improved survival in selected patients with this disease. To date, multiple different treatment regimens of perioperative intraperitoneal chemotherapy have been used. This review focuses on the perioperative intraperitoneal chemotherapy currently in use in conjunction with cytoreductive surgery for the treatment of peritoneal surface malignancy at the Washington Cancer Institute.

 Journal of Translational Medicine 2006, 4:17     doi:10.1186/1479-5876-4-17

Background

Malignant pleural mesothelioma is a rare malignancy. The outcome remains poor despite complete surgical resection.

Patients and methods

Eleven patients with histologicaly proven epithelial type malignant pleural mesothelioma undergoing extrapleural pneumonectomy with systemic chemotherapy and/or radiotherapy before and after surgical resection were retrospectively reviewed.

Results

Ten out of 11 patients underwent complete surgical resection, of these 7 patients had stage I disease. Of these 7 patients, 5 are alive without any recurrence, a 2-year survival rate of 80% was observed in this group. There was no operative mortality or morbidity.

Conclusion

Extrapleural pneumonectomy with perioperative adjuvant treatment is safe and effective procedure for epithelial type malignant pleural mesothelioma.

Introduction

Malignant pleural mesothelioma (MPM) is a relatively rare entity among intrathoracic malignancies, as compared with lung cancer, although its prevalence has shown an increase in recent years [1]. Extrapleural pneumonectomy (EPP) is the surgical treatment of choice for MPM that do not extend in to the mediastinum or on to the chest wall, although its survival benefit is still not clear [2]. In a retrospective study of 189 Japanese cases [3], there were no significant differences in survival at 2-years between palliative surgery, such as decortication, and EPP (26% and 30%, respectively). EPP with adjuvant chemotherapy and/or radiotherapy has been reported to be effective against the MPM in its early stages [4,5]. Jaklitsch et al., [6] advocated that EPP plus postoperative chemotherapy using paclitaxel and carboplatin with radiotherapy is effective for MPM if it’s of epithelial histology, negative surgical margin, and if extrapleural lymph nodes are negative for metastasis. This study reports on resectable epithelial type MPM with perioperative treatment consisting of radiation and/or chemotherapy.

Patients and methods

Between 1995 and 2002, 10 patients with epithelial type MPM underwent EPP with postoperative or preoperative chemotherapy and/or radiotherapy. The clinical profiles of these patients are detailed in Table 1. The lesions were staged by computed tomographic (CT) scan using International Mesothelioma Interest Group (IMIG) classification. There were 6 stage III, 3 stage II and 1 stage I patient. A bone scan and Magnetic Resonance Imaging (MRI) of the brain were performed if metastasis was suspected. Using the Brigham and Womens Hospital (BWH) staging system of Sugarbakeret al. [4], after the surgical resection 6 patients were stage I, in terms of having completely resected primary tumors including chest wall invasion at the biopsy site.

A standard EPP was performed as described earlier [7]. Following a posterolateral incision, extrapleural space was entered from the 5^th or 6^th rib bed, and dissection was carried superiorly toward the apex, antero- and postero-laterally, and inferiorly toward the diaphragm. During the dissection, port site disease at the chest wall was resecteden block . Following an antero-medial pericardiotomy, hilar vessels were resected using a mechanical stapler, followed by resection of the main bronchus. The diaphragm was divided from the peritoneum, and EPP was completed. The defects of pericardium and diaphragm were reconstructed with prosthetic patches. A complete mediastinal lymph node dissection was performed in all cases.

In a preoperative adjuvant setting, one course of concurrent chemoradiotherapy using cisplatin (CDDP) (80 mg/m², on days 1 and 29) with 40 Gy external beam radiotherapy to the hemithorax [5], was performed in 4 patients (Case 1, 2, 3 and 5) and 2 or 3 courses of chemotherapy using CDDP (40 mg/m² on days 1 and , gemcitabine (GEM) (800 mg/m², on days 1 and , and vinorelbine (VNR) (20 mg/m², on days 1 and were given at intervals of 3 to 4 weeks in 4 patients (Case 6, 7, 8 and 11) (Table 1). Three patients received 2 courses of postoperative chemotherapy using CDDP (80 mg/m², on day 1 and , GEM (800 mg/m² on days 8 and 15) and UFT (tegafur/uracil) (400 mg/m² postoperative on days 1–15) with 3 to 4 weeks interval (Case 4, 9 and 10) (Table 1). One patient received 50 Gy postoperative radiation to the previous thoracic drainage site (Case 10).

Results

Postoperative course of the patients were uneventful, and no morbidity or mortality was experienced. Six patients experienced a relapse in the thorax. One patient underwent resection of the chest wall for recurrence at 12 months after EPP. Other 5 patients (Case 5, 6, 8, 9 and 11) are surviving without any disease. All the survivors had BWH stage I disease, which showed an 80%, 2-year survival. The survival in 4 patients with BWH stage II-III disease was 37% at 2-year. Postoperative chemotherapy was started 2 to 3 months after surgery, and grade 4 neutropenia was observed in all 3 cases, while grade 3 loss of appetite was observed in one. Of the 3 patients who underwent preoperative chemotherapy, a reduction in size of the tumors by 18 to 74% was seen following chemotherapy (Figure 1). Pathological examination of the resected specimens in all 3 cases showed extensive fibrosis with only a small focus of tumor cells (Figure 2). In Case 10, an exploratory thoracotomy was done for suspected recurrence, however, the intrathoracic lesion was found to be a herniated liver from the defect of the reconstructed diaphragm.

Discussion

Early stage MPM, especially of the epithelial type, is a disease localized to the hemithorax. Therefore, EPP with or without perioperative adjuvant therapy should be effective, as is shown previously. Sugarbakeret al., [4] reported that the treatment with EPP and adjuvant chemotherapy and hemithorax radiotherapy is effective for select patients with MPM. Nearly 50% of the cases who undergo complete resection of epithelial type MPM survive at 5 years. Ruschet al., [5] showed favorable results with EPP followed by radiation. Survival rate at 5-years for patients with stage I/II IMIG classification was 40% [5].

The aim of the perioperative adjuvant therapy is to control tumor cells located at the front line and the lymphatic system and to sterilize the margin of EPP. However, a therapeutically active modality must be considered from the standpoint of patient benefit and safety. The mortality rates for EPP reported in literature are 3.8% by Sugarbakeret al., [4] and 7.9% by Rusch et al., [5]. In our series, all patients returned to active social life following their treatment, indicating that EPP with perioperative adjuvant therapy is well tolerated. Complete resection of capsulated MPM was achieved in 6 cases that had been designated as BWH stage I. Interestingly, as shown in table 1, BWH stage predicted the prognosis well however IMIG stage failed to do so. This indicated that local therapy for epithelial type MPM might be crucial for staging and prognosis as well.

Sugarbaker et al., [4] started chemotherapy using carboplatin and paclitaxel within 4 weeks after EPP. In our series, chemotherapy was started 2 months after EPP in 4 patients who received CDDP/GEM/UFT. Of the 3 patients receiving preoperative chemotherapy using CDDP/GEM/VNR, 2 patients received 2 courses and the other received 3 courses. EPP was performed within 5 weeks after cessation of chemotherapy. The clinical and pathological effects were remarkable. Among chemotherapeutic agents, GEM [8] and VNR [9] are reported to be active and the combination of them with CDDP was used in our study. Neutropenia was the main adverse effect of this regimen observed, which reversed with G-CSF. We therefore suggest that preoperative chemotherapy using such active agents followed by EPP is effective and safe procedure. However, this needs to be tested in a randomized controlled trial.

References

World Journal of Surgical Oncology 2004, 2:11     doi:10.1186/1477-7819-2-11

Mesothelioma is an uncommon form of cancer, usually associated with previous exposure to asbestos. In this disease, malignant (cancerous) cells develop in the mesothelium, a protective lining that covers most of the body’s internal organs. Its most common site is the pleura (outer lining of the lungs and chest cavity), but it may also occur in the peritoneum (the lining of the abdominal cavity) or the pericardium (a sac that surrounds the heart).

Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or have been exposed to asbestos dust and fibre in other ways, such as by washing the clothes of a family member who worked with asbestos, or by home renovation using asbestos cement products. in wikipedia

Background

Malignant pleural mesothelioma (MPM) is a tumor known to be resistant to conventional therapies. Thus, an in vivo model can represent an important tool for assessing the efficacy of novel approaches in the treatment of MPM. Presently, human MPM cells have been grown orthotopically in mice upon transplantation of tumor masses or tumor cell suspensions following surgery. In these models however, surgery can interfere with the tumor growth and the early stages of tumor development cannot be easily explored. Finally, results may not be so accurate due to implantation of potentially different tumor samples in different experimental groups. Our work aimed at establishing a nude mouse model xenotransplanted with human MPM cell lines in which tumor progression exhibits some features of the human disease.

Methods

Three distinct human MPM cell lines previously established from MPM patients displaying two different phenotypes, biphasic (MM-B1 and IST-Mes3) and epithelioid (IST-Mes2), were directly injected into the pleural cavity of nude mice. At different times, mice were sacrificed for autopsy, tumor nodules were counted and then removed for histology. Presence of metastases in visceral organs was also monitored.

Results

IST-Mes2 cells were unable to grow in nude mice. MM-B1 and IST-Mes3 cells were capable of growing in nude mice and formed tumor nodules in the pleura. Post-mortem examination showed that MPM cells progressively colonized the parietal and visceral pleura, the diaphragm, the mediastinum and, lastly the lung parenchyma. No pneumo-thorax was evidenced in the mice. Pleural effusions as well as lymph node metastases were observed only at later times.

Conclusions

This model mimics the progression of human malignant mesothelioma and it is easy to perform and reproducible; therefore it can be useful to study human MPM biology and evaluate the efficacy of novel therapies.

BMC Cancer 2006, 6:130     doi:10.1186/1471-2407-6-130