Mesothelioma and Histological Evidence of Extra Pleural Lymph Node Metastases

Another interesting study is called, "The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural Mesothelioma" by J.E. Pillinga, D.J. Stewarta, A.E. Martin-Ucara, S. Mullerb, K.J. O'Byrnec, D.A. Wallera - Eur J Cardiothorac Surg 2004;25:497-501.  Here is an excerpt: "Objectives: To assess whether cervical mediastinoscopy is necessary before radical resection of malignant pleural mesothelioma (MPM). Methods: Patients who underwent radical excision of MPM in a 48-month period were prospectively followed for evidence of disease recurrence and death. Histological evidence of extra pleural lymph node metastases was correlated with survival. Lymph node size at intraoperative lymphadenectomy was correlated with the presence of metastatic tumour. Results: The 55 patients who underwent radical resection (51 extra pleural pneumonectomies and 4 radical pleurectomies) comprised 50 men and 5 women with a median age of 58 years, range 41–70. Histological examination revealed 50 epithelioid, four biphasic and one sarcomatoid histology. Postoperative IMIG T stage was stage I 4, II 11, III 30 and IV 10. Postoperatively the 17 patients with metastases to the extra pleural lymph nodes had significantly shorter survival (median 4.4 months, 95% CI 3.2–5.4) than those without (median survival 16.3 months, 95% CI 11.6–21.0) P=0.012 Kaplan–Meier analysis. Seventy-seven extra pleural lymph nodes without metastases were measured with a mean long axis diameter of 16.9 mm (range 4–55); 22 positive nodes had a mean long axis diameter of 15.2 mm (range 6–30). In 15 of the 17 patients with positive extra pleural nodes, the nodes could have been biopsied at cervical mediastinoscopy. Conclusions: This study confirms that extra pleural nodal metastases are related to poor survival. Pathological nodal involvement cannot be predicted from nodal dimensions. These data suggest that all patients being considered for radical resection of MPM should preferentially undergo preoperative cervical mediastinoscopy irrespective of radiological findings."

Another interesting study is called, "Induction chemotherapy, extrapleural pneumonectomy, and radiotherapy in the treatment of malignant pleural mesothelioma: The Memorial Sloan-Kettering experience" - Volume 49, Supplement 1, Pages S71-S74 (July 2005) by Raja M. Flores.  Here is an excerpt: "Summary - Approximately 25% of patients with malignant pleural mesothelioma (MPM) prove unresectable at surgery and the median survival of stage III MPM is <12 months even after complete resection by extrapleural pneumonectomy. From 1939–2004, a series of sequential clinical trials has been performed at our institution. The surgical procedure has been modified and improved upon, and adjuvant hemithoracic radiation (RT) standardized. The evolution of our current standard of care for MPM is discussed. Improving chemotherapy for MPM led us to test induction chemotherapy followed by EPP and adjuvant RT for locally advanced MPM to assess feasibility. Patients with T3–4 or N2 MPM by CT and PET scans were enrolled on a phase II study. Induction therapy was: gemcitabine (1250mg/m2days 1, 8) and cisplatin (75mg/m2day 8)×2–4 cycles. Patients underwent EPP 3–5 weeks after induction therapy, then 54 Gy RT 4–6 weeks postop. At surgery, 8/9 had complete resection by EPP with no postoperative deaths. All received planned adjuvant RT. This combined modality approach is feasible for locally advanced MPM, and initial analysis suggests improved resectability. This experience supports additional studies of induction and multimodality therapy, especially with regimens such as cisplatin and pemetrexed which may be better tolerated and more effective."

Another interesting study is called, "EGFR overexpression in malignant pleural mesothelioma: An immunohistochemical and molecular study with clinico-pathological correlations" by Destroa, G.L. Ceresolib, M. Fallenic, P.A. Zucalib, E. Morenghid, P. Bianchia, C. Pellegrinic, N. Cordanic, V. Vairac, M. Alloisioe, A. Rizzif, S. Bosaric, M. Roncallig - Volume 51, Issue 2, Pages 207-215 (February 2006).  Here is an excerpt: "Summary - The epidermal growth factor receptor (EGFR) is overexpressed in many epithelial malignancies, against which some antitumoral drugs have been developed. There is a lack of information as to EGFR expression in malignant pleural mesothelioma (MPM), an aggressive and fatal cancer poorly responsive to current oncological treatments. Our aim was to: (a) compare EGFR immunohistochemical expression with mRNA levels measured by real time PCR; (b) assess the relationships between EGFR expression and clinico-pathological data including survival; (c) analyze the EGFR mutations.

We developed an immunohistochemical method of EGFR evaluation based on the number of immunoreactive cells and staining intensity in 61 MPMs. EGFR immunoreactivity was documented in 34/61 (55.7%) cases. A significant correlation between EGFR protein and mRNA levels (p=0.0077) was found, demonstrating the reliability of our quantification method of EGFR membrane expression. Radically resected patients (p=0.005) and those with epithelial histotype (p=0.048) showed an increased survival. No statistical correlation between EGFR immunoreactivity and patients survival was observed. No EGFR mutation was documented.

This study documents EGFR overexpression in MPM at the protein and the transcriptional levels; it proposes a reliable method for EGFR expression evaluation in MPM. EGFR levels are not associated with clinico-pathological features of patients, including survival."

We all owe a debt of gratitude to these fine researchers.  If you found any of these excerpts interesting, please read the studies in their entirety.