Archive for the ‘Diffuse Malignant Peritoneal Mesothelioma’ Category

Mesothelioma Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion

Mesothelioma Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion

One interesting study is called, “Prognostic Analysis of Clinicopathologic Factors in 49 Patients With Diffuse Malignant Peritoneal Mesothelioma Treated With Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion” – by Marcello Deraco, Daisuke Nonaka, Dario Baratti, Paolo Casali, Juan Rosai, Rami Younan, Andreola Salvatore, Antonello D. Cabras AD and Shigeki Kusamura – Annals of Surgical Oncology Volume 13, Number 2, 229-237.  Here is an excerpt: “Abstract – Background Diffuse malignant peritoneal mesothelioma (DMPM) is a subset of peritoneal mesothelioma with a poor clinical outcome. We performed a prognostic analysis in a cohort of DMPM patients treated homogeneously by cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP). Methods – Forty-nine DMPM patients who underwent 52 consecutive procedures were enrolled onto the study. Cytoreductive surgery was performed according to the peritonectomy technique, and the IPHP was performed with cisplatin plus doxorubicin or cisplatin plus mitomycin C. We assessed the correlation of the clinicopathologic variables (previous surgical score, age, sex, performance status, previous systemic chemotherapy, carcinomatosis extension, completeness of cytoreduction, IPHP drug schedule, mitotic count [MC], nuclear grade, and biological markers [epidermal growth factor receptor, p16, matrix metalloproteinase 2 and matrix metalloproteinase 9]) with overall and progression-free survival.

Results – The mean age was 52 years (range, 22–74 years). The mean follow-up was 20.3 months (range, 1–89 months). Regarding the biological markers, the rates of immunoreactivity of epidermal growth factor receptor, p16, matrix metalloproteinase 2, and matrix metalloproteinase 9 were 94%, 60%, 100%, and 85%, respectively. The strongest factors influencing overall survival were completeness of cytoreduction and MC, whereas those for progression-free survival were performance status and MC. No biological markers were shown to be of prognostic value.

Conclusions – Completeness of cytoreduction, performance status, and MC seem to be the best determinants of outcome. These data warrant confirmation by a further prospective formal trial. No biological markers presented a significant correlation with the outcome. The overexpression of epidermal growth factor receptor, matrix metalloproteinase 2, and matrix metalloproteinase 9 and absent or reduced expression of p16 might be related to the underlining tumor kinetics of DMPM and warrant further investigation with other methods.

Another interesting study is called, “A randomised controlled trial of intervention site radiotherapy in malignant pleural mesothelioma.” By O’Rourke N, Garcia JC, Paul J, Lawless C, McMenemin R, Hill J. – Radiother Oncol. 2007 Jul;84(1):18-22. Epub 2007 Jun 22.  Here is an excerpt: “Abstract – BACKGROUND AND PURPOSE: To assess the effectiveness of radiotherapy in preventing tumour seeding after chest drain or pleural biopsy in patients with malignant mesothelioma and to determine, if tract metastases appear, whether they are tender or troublesome to patients.

PATIENTS AND METHODS: Patients with a histological diagnosis of pleural mesothelioma and an invasive procedure within the preceding 21 days were stratified by age, performance status and treatment centre. Randomisation was performed between immediate drain site radiotherapy 21Gy in three fractions (XRT arm) or best supportive care (BSC) with follow-up to 12 months. Patients were asked to complete questionnaires on treatment toxicity and on symptoms from any tract metastases detected.

RESULTS: Sixty-one patients were recruited from two centres between 1998 and 2004; 56 men, 5 women, median age 70. 31 were allocated to drain site radiotherapy. Seven patients developed tract metastases associated with the drain site (four XRT arm, three BSC) and four developed metastases associated with subsequent procedures at other sites (three XRT, one BSC). Two patients each developed two tract metastases. Of the 12 metastases, nine overlay the previous drain site but three were adjacent to the site. No statistically significant difference was found in the risk of tract metastasis associated with the drain site between the arms (p=0.748).

CONCLUSIONS: Prophylactic drain site radiotherapy in malignant pleural mesothelioma does not reduce the incidence of tumour seeding by the margin indicated by previous studies.

Another interesting study is called, “The value of chest computer tomography and cervical mediastinoscopy in the preoperative assessment of patients with malignant pleural Mesothelioma” by J. Hugo Schouwink, MD, Leo Schultze Kool, MD, PhD, Emiel J. Rutgers, MD, PhD, Frans A. N. Zoetmulder, MD, PhD, Nico van Zandwijk, MD, PhD, Marc J. v.d. Vijver, MD, PhDd, Paul Baas, MD, PhD – Ann Thorac Surg 2003;75:1715-1718.  Here is an excerpt: “BACKGROUND: Patients with localized malignant pleural mesothelioma (MPM) can be considered for surgical resection with or without additional treatment. For this approach it is imperative to select patients without mediastinal lymph node involvement. In this study cervical mediastinoscopy (CM) is compared with computer tomography (CT) scanning for its diagnostic accuracy in assessing mediastinal lymph nodes during preoperative workup.

METHODS: Computer tomography scans of the chest and CM were performed in 43 patients with proven unilateral MPM. The CT scans were reviewed by one radiologist and two chest physicians. At CM the lymph node samples were taken from stations Naruke 2, 3, 4, and 7. Computer tomography and CM results were compared with final histopathologic findings obtained at thoracotomy or, if this was not performed, at CM.

RESULTS: Computer tomography scanning revealed pathologic enlarged lymph nodes with a shortest diameter of at least 10 mm in 17 of 43 patients (39%). There was histopathologic evidence of lymph node metastases at CM in 11 of these patients (26%). This resulted in a sensitivity of 60% and 80%, a specificity of 71% and 100%, and a diagnostic accuracy of 67% and 93% for CT and CM, respectively.

CONCLUSIONS: Cervical mediastinoscopy is a valuable diagnostic procedure for patients with MPM who are considered candidates for surgical-based therapy. Results of CM are more reliable than those obtained by CT scanning. Our data confirm results of previous studies reporting that mediastinal lymph node involvement is a frequent event in MPM.”

Monty Wrobleski is the author of this article.  For more information please click on the following links

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Malignant Mesothelioma

 


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Radiological and Histopathological Parameters and Mesothelioma Analysis

Radiological and Histopathological Parameters and Mesothelioma Analysis

Another interesting study is called, “Prognostic Indicators for Patients Undergoing Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma” by Tristan D. Yan, Erwin A. Brun, Carlos A. Cerruto, Namik Haveric, David Chang and Paul H. Sugarbaker – Annals of Surgical Oncology Volume 14, Number 1, 41-49 – Here is an excerpt: “Background – This study evaluates clinical, radiological and histopathological prognostic indicators for survival of patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma (DMPM).

Methods – Sixty-two consecutive patients with DMPM underwent cytoreduction and perioperative intraperitoneal chemotherapy at the Washington Cancer Institute. Twenty-six clinical, radiological and histopathological parameters were analyzed in univariate and multivariate analyses using overall survival as an endpoint.  Results – The overall survival was 79 months (range 1–143 months), with 1-, 3- and 5-year survival rates of 84%, 58% and 50%, respectively. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (P = .045), peritoneal cancer index (P = .038), completeness of cytoreduction score (P = .010), interpretive CT findings of the small bowel and mesentery (P = .001), mesothelioma cell type (P < .001), mesothelioma nuclear size (P < .001), nuclear/cytoplasmic ratio (P < .001), mitotic count (P < .001), atypical mitosis (P < .001), chromatin pattern (P < .001), cellular necrosis (P < .001), perineural invasion (P = .037), stroma pattern (P < .001) and depth of invasion (P = .014). In the multivariate analysis, the only factor that was independently associated with an improved survival after cytoreduction and perioperative intraperitoneal chemotherapy was mesothelioma nuclear size.

Conclusions – Mesothelioma nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed.

Another interesting study is called, “HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of pleura.” By A D Kennedy, G King, K M Kerr
J Clin Pathol 1997;50:859-862.  Here is an excerpt: “Abstract – AIMS: To determine the usefulness of antibodies HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of the pleura. METHODS: Using microwave antigen retrieval and streptavidin-biotin complex horseradish peroxidase immunohistochemistry the above antibodies were used to stain sections of 57 malignant mesotheliomas, 17 reactive pleural hyperplasias, 23 cases of carcinoma metastatic in pleura, 20 primary ovarian cell carcinomas, and 20 primary renal cell carcinomas. RESULTS: Eighty six per cent of mesotheliomas and 82% of reactive mesothelial hyperplasias stained strongly with HBME-1. However, 48% of carcinomas metastatic to pleura also stained, as did all serous ovarian carcinomas. Seventy two per cent of mesotheliomas and 24% of reactive mesothelial hyperplasias stained strongly with the antithrombomodulin antibody; 86% and 88%, respectively, of these cases showed staining of any type. While 26% of metastatic carcinomas showed some staining with antithrombomodulin, only one third of these (9%) showed strong, yet focal, staining. Of 40 ovarian and renal carcinomas only two (5%) showed any staining with antithrombomodulin. CONCLUSIONS: HBME-1, although a sensitive mesothelial marker, is not sufficiently specific to be useful diagnostically, as almost half of carcinomas metastatic to pleura also stained positive. Antithrombomodulin is also a sensitive mesothelial marker and is sufficiently specific to be a useful discriminator, positively identifying, in appropriate circumstances, the mesothelial nature of a cell population.”

Another interesting study is called, “Malignant Pleural Mesothelioma: Surgical Roles and Novel Therapies” – Clinical Lung Cancer – Volume 3, Number 2 / November 2001.  Here is an excerpt: “Abstract – Malignant pleural mesothelioma (MPM) is a uniformly fatal disease that has been recalcitrant to curative therapies. Median survivals of 8-18 months have, for the most part, led to a sense of frustration and nihilism in the medical and surgical community with regard to management of the disease, and the relatively small numbers of patients with mesothelioma have made it an orphan among other cancers with regard to research efforts and funding. This review will comment on the clinical presentation of the disease and therapeutic options that are available at this time. The role, timing, degree, and availability of cytoreductive surgery in the context of a multimodality approach for MPM will be highlighted, and various strategies that incorporate adjunctive therapies before, during, or after the operation will be discussed. Newer cytotoxic chemotherapies, either alone or in combination, are reviewed, with an emphasis on the increasing number of options with increased response rates that are becoming available for MPM patients. The results of protocols at selected centers that offer gene therapy, photodynamic therapy, hyperthermic chemotherapeutic perfusion, and intrapleural chemokines will be discussed, as well as newer preclinical approaches that base targeted therapies on novel molecular findings. In considering the newest approaches to the disease, one is encouraged to seek specialty consultation at centers that concentrate programmatic efforts on mesothelioma in order to design translational-based approaches on preclinical findings. By using such an approach, the patient and physician will find that there are considerably more options in the new century for mesothelioma.”

Monty Wrobleski is the author of this article.  For more information please click on the following links

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