Pleural malignant mesothelioma causing cord infiltration through the nerve root. Case report.

Neurol Med Chir (Tokyo). 2009 Apr;49(4):167-71

Authors: Okura H, Suga Y, Akiyama O, Kudo K, Tsutsumi S, Abe Y, Yasumoto Y, Ito M, Izumi H,

Shiomi K A 61-year-old man presented with a rare pleural malignant mesothelioma of the spine manifesting as progressive weakness of the bilateral lower extremities, numbness in the body and both legs, and dysfunction of the bladder and bowel. He had previous occupational exposure to asbestos while working at a car repair shop and had undergone right panpleuropneumonectomy under a diagnosis of sarcomatous type mesothelioma in the right pleural space. Magnetic resonance imaging of the spine with gadolinium showed an enhanced intramedullary tumor at the T4 level. Operative findings disclosed the clouded and swollen right posterior nerve root, and the pial surface was covered by clouded arachnoid-like membrane. The removed part of the T4 posterior nerve root and intramedullary tumor revealed malignant mesothelioma with invasion spreading along the posterior nerve root. He died of respiratory failure 3 months after the diagnosis. This case shows that spinal metastasis must be considered if a patient with pleural malignant mesothelioma shows neurological worsening and neuroimaging shows an abnormal lesion in the thoracic spinal cord. However, the patient's neurological condition is very difficult to improve in the presence of spinal cord infiltration.

PMID: 19398862 [PubMed - indexed for MEDLINE]

Read Full Article pubmed: mesothelioma

Certified causes of death in patients with mesothelioma in South East England.

BMC Cancer. 2009;9:28 Authors: Okello C, Treasure T, Nicholson AG, Peto J, Møller H

BACKGROUND: Mesothelioma is a highly fatal cancer that is caused by exposure to asbestos fibres. In many populations, the occurrence of mesothelioma is monitored with the use of mortality data from death certification. We examine certified causes of death of patients who have been diagnosed with mesothelioma, and assess the validity of death certification data as a proxy for mesothelioma incidence.

Does video-assisted thoracoscopic decortication in advanced malignant mesothelioma improve prognosis?

Interact Cardiovasc Thorac Surg. 2009 Apr;8(4):454-6

Authors: Srivastava V, Dunning J,

Au J A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: Does video-assisted thoracoscopic (VATS) decortication in advanced malignant mesothelioma improve prognosis?

Malignant mesothelioma mortality--United States, 1999-2005.

MMWR Morb Mortal Wkly Rep. 2009 Apr 24;58(15):393-6

Malignant mesothelioma is a fatal cancer primarily associated with exposure to asbestos. The latency period between first exposure to asbestos and clinical disease usually is 20--40 years. Although asbestos is no longer mined in the United States, the mineral is still imported, and a substantial amount of asbestos remaining in buildings eventually will be removed, either during remediation or demolition. Currently, an estimated 1.3 million construction and general industry workers potentially are being exposed to asbestos. To characterize mortality attributed to mesothelioma, CDC's National Institute for Occupational Safety and Health (NIOSH) analyzed annual multiple-cause-of-death records for 1999--2005, the most recent years for which complete data are available. For those years, a total of 18,068 deaths of persons with malignant mesothelioma were reported, increasing from 2,482 deaths in 1999 to 2,704 in 2005, but the annual death rate was stable (14.1 per million in 1999 and 14.0 in 2005). Maintenance, renovation, or demolition activities that might disturb asbestos should be performed with precautions that sufficiently prevent exposures for workers and the public. In addition, physicians should document the occupational history of all suspected and confirmed mesothelioma cases.

PMID: 19390506 [PubMed - indexed for MEDLINE]

Read Full Article pubmed: mesothelioma

Malignant mesothelioma of the tunica vaginalis testis: a case report and literature review.

Kaohsiung J Med Sci. 2009 Feb;25(2):77-81

Authors: Chen JL, Hsu YH

Malignant mesothelioma of the tunica vaginalis testis is a rare but often fatal malignancy.

Malignant mesothelioma.

Orphanet J Rare Dis. 2008;3:34

Authors: Moore AJ, Parker RJ, Wiggins J

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10-20 years.

Malignant pleural mesothelioma: medical treatment update.

Clin Lung Cancer. 2009 Mar;10(2):112-7

Authors: Vorobiof DA, Mafafo K

Malignant pleural mesothelioma (MPM) is a disease usually unaffected by current therapeutic strategies, but for the majority of patients, the use of systemic chemotherapeutic drugs remains the only therapeutic option available.

Mesothelioma cells escape heat stress by upregulating Hsp40/Hsp70 expression via mitogen-activated protein kinases.

J Biomed Biotechnol. 2009;2009:451084

Authors: Roth M, Zhong J, Tamm M, Szilard J Therapy with hyperthermal chemotherapy in pleural diffuse malignant mesothelioma had limited benefits for patients. Here we investigated the effect of heat stress on heat shock proteins (HSP), which rescue tumour cells from apoptosis. In human mesothelioma and mesothelial cells heat stress (39-42 degrees C) induced the phosphorylation of two mitogen activated kinases (MAPK) Erk1/2 and p38, and increased Hsp40, and Hsp70 expression. Mesothelioma cells expressed more Hsp40 and were less sensitive to heat stress compared to mesothelial cells. Inhibition of Erk1/2 MAPK by PD98059 or by Erk1 siRNA down-regulated heat stress-induced Hsp40 and Hsp70 expression and reduced mesothelioma cell survival. Inhibition of p38MAPK by SB203580 or siRNA reduced Hsp40, but not Hsp70, expression and also increased mesothelioma cell death. Thus hyperthermia combined with suppression of p38 MAPK or Hsp40 may represent a novel approach to improve mesothelioma therapy.

PMID: 19551156 [PubMed - indexed for MEDLINE]

Read Full Article pubmed: mesothelioma

BMJ. 2009;339:b2862

Authors: Sweeney K, Toy L,Cornwell J

Professor Kieran Sweeney was diagnosed with malignant mesothelioma at age 57. He describes here his thoughts on his interactions with the health professionals who care for him.

PMID: 19684101 [PubMed - in process]

Read Full Article pubmed: mesothelioma and ((e...

Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P.

Clin Cancer Res. 2009 Aug 15;15(16):5274-9

Authors: Kreitman RJ, Hassan R, Fitzgerald DJ, Pastan I

PURPOSE: To conduct a phase I trial of recombinant immunotoxin SS1P given by continuous infusion in chemoresistant solid tumors expressing mesothelin.

EXPERIMENTAL DESIGN: Eligible patients had mesothelioma, ovarian, or pancreatic cancer, which was recurrent or unresectable despite standard therapy, and were mesothelin positive by immunohistochemistry. SS1P was given by continuous infusion for 10 days, and cycles could be repeated at 4-week intervals in the absence of neutralizing antibodies or progressive disease.

RESULTS: Twenty-four patients, five with peritoneal mesothelioma, nine with pleural mesothelioma, two with pleural peritoneal mesothelioma, seven with ovarian carcinoma, and one with pancreatic carcinoma, received 4, 8, 12, 18, and 25 microg/kg/d x10. The maximum tolerated dose was 25 microg/kg/d x10, where one of six patients had dose-limiting toxicity due to reversible vascular leak syndrome. Immunogenicity was observed in 18 (75%) of 24 patients, and five (21%) received a second cycle. Constant plasma levels of SS1P were maintained for most of the 10-day infusion time, with median peak levels of up to 153 ng/mL. One patient had a partial response. Nonmajor responses included cessation of ascites and independence from paracentesis, resolution of masses by positron emission tomography, and improved pain and range of motion.

CONCLUSIONS: As a single agent by continuous infusion, recombinant immunotoxin SS1P was well tolerated up to 25 microg/kg/d x10 and showed evidence of modest clinical activity. Continuous infusion showed no significant advantage over bolus dosing, and further clinical development of SS1P is proceeding by bolus dosing in combination with chemotherapy.

PMID: 19671873 [PubMed - in process]

Read Full Article Clin Cancer Res

Phenotype-dependent apoptosis signalling in mesothelioma cells after selenite exposure.

J Exp Clin Cancer Res. 2009;28:92

Authors: Nilsonne G, Olm E, Szulkin A, Mundt F, Stein A, Kocic B, Rundlöf AK, Fernandes AP, Björnstedt M, Dobra K

BACKGROUND: Selenite is a promising anticancer agent which has been shown to induce apoptosis in malignant mesothelioma cells in a phenotype-dependent manner, where cells of the chemoresistant sarcomatoid phenotype are more sensitive.

METHODS: In this paper, we investigate the apoptosis signalling mechanisms in sarcomatoid and epithelioid mesothelioma cells after selenite treatment. Apoptosis was measured with the Annexin-PI assay. The mitochondrial membrane potential, the expression of Bax, Bcl-XL, and the activation of caspase-3 were assayed with flow cytometry and a cytokeratin 18 cleavage assay. Signalling through JNK, p38, p53, and cathepsins B, D, and E was investigated with chemical inhibitors. Furthermore, the expression, nuclear translocation and DNA-binding activity of p53 was investigated using ICC, EMSA and the monitoring of p21 expression as a downstream event. Levels of thioredoxin (Trx) were measured by ELISA.

RESULTS: In both cell lines, 10 microM selenite caused apoptosis and a marked loss of mitochondrial membrane potential. Bax was up-regulated only in the sarcomatoid cell line, while the epithelioid cell line down-regulated Bcl-XL and showed greater caspase-3 activation. Nuclear translocation of p53 was seen in both cell lines, but very little p21 expression was induced. Chemical inhibition of p53 did not protect the cells from apoptosis. p53 lost its DNA binding ability after selenite treatment and was enriched in an inactive form. Levels of thioredoxin decreased after selenite treatment. Chemical inhibition of MAP kinases and cathepsins showed that p38 and cathepsin B had some mediatory effect while JNK had an anti-apoptotic role.

CONCLUSION: We delineate pathways of apoptosis signalling in response to selenite, showing differences between epithelioid and sarcomatoid mesothelioma cells. These differences may partly explain why sarcomatoid cells are more sensitive to selenite.

PMID: 19563663 [PubMed - indexed for MEDLINE]

Read Full Article pubmed: mesothelioma

Placenta growth factor expression has prognostic value in malignant pleural mesothelioma. Ann Thorac Surg. 2009 Aug;88(2):426-31 Authors: Pompeo E, Albonici L, Doldo E, Orlandi A, Manzari V, Modesti A, Mineo TC BACKGROUND: Malignant pleural mesothelioma is highly aggressive and recurs rapidly despite radical multimodality treatment. Progression of mesothelioma is thought to be governed by various growth factors, including vascular endothelial growth factor (VEGF). Placenta growth factor (PlGF) belongs to the VEGF family, although no study has yet investigated its expression in mesothelioma. We hypothesized that PlGF is overexpressed in mesothelioma and could have prognostic value in patients treated by extrapleural pneumonectomy. METHODS: We assessed by immunohistochemistry with semiquantitative classification (0 = no staining; 3 = strong staining), the expression levels of PlGF and its cognate receptors VEGF receptor 1, neuropilin-1, and neuropilin-2 in 27 patients with malignant pleural mesothelioma undergoing extrapleural pneumonectomy, in 14 patients with reactive mesothelium, and in 10 patients with normal mesothelium. RESULTS: Whereas PlGF was not expressed in normal mesothelium, it was overexpressed (grade 3) more frequently in mesothelioma than in reactive mesothelium specimens (11 or 41% versus 1 or 7%, respectively, p = 0.03). Furthermore, in mesothelioma, VEGF receptor 1 and neuropilin-1 and -2 were overexpressed in 18 specimens (67%), 8 specimens (30%), and 9 specimens (33%), respectively. Mean survival after extrapleural pneumonectomy was 17 months. An inverse relationship was found between the degree of PlGF expression and survival in months (R = -0.45, p = 0.01). No correlation was found between tumor stage and survival (R = -0.33) and between tumor stage and PlGF expression (R = 0.07). CONCLUSIONS: We have shown that PlGF can be overexpressed in malignant pleural mesothelioma. In addition, the finding of an inverse relationship between PlGF expression levels and survival suggests a pivotal role of this factor in the recurrence and progression of mesothelioma after extrapleural pneumonectomy. PMID: 19632388 [PubMed - indexed for MEDLINE]

Read Full Article pubmed: mesothelioma and ((e...

Primary localized malignant biphasic mesothelioma of the liver in a patient with asbestosis.

World J Gastroenterol. 2009 Feb 7;15(5):615-21

Authors: Sasaki M, Araki I, Yasui T, Kinoshita M, Itatsu K, Nojima T, Nakanuma Y

We report a case of primary localized malignant biphasic mesothelioma of the liver in a 66-year-old man associated with asbestosis. The tumor was detected as a hepatic nodule, 4 cm in diameter, in the right lobe (S8 segment) on CT scan. Histopathological examination demonstrated an intrahepatic tumor with central necrosis consisting of a papillary epithelioid pattern on the surface of the liver, microcystic (microglandular or adenomatoid) pattern mainly in the subcapsular area and sarcomatoid pattern intermingled with microcystic pattern in the major part of the hepatic nodular tumor. Tumor cells, especially of epithelioid type, showed distinct immunoreactivity for mesothelial markers (WT-1, calretinin, D2-40, CK5/6, mesothelin, thrombomodulin) and no immunoreactivity for epithelial (adenocarcinoma) markers (CEA, CD15, BerEP4, BG8, MOC31). P53 immunoreactivity was detected focally in papillary epithelioid tumor cells and extensively in microcystic and sarcomatoid components, suggesting that the papillary epithelioid mesothelioma arose on the surface of the liver, and tumor cells showing microcystic and sarcomatoid patterns invaded and grew into the liver. To date, this is the first case of primary localized malignant biphasic mesothelioma of the liver, since all three primary hepatic mesotheliomas reported so far were epithelioid type.

PMID: 19195066 [PubMed - indexed for MEDLINE]

Read Full Article pubmed: mesothelioma

Primary malignant pericardial mesothelioma presenting as pericardial constriction.

Ann Thorac Cardiovasc Surg. 2008 Dec;14(6):396-8

Authors: Kainuma S, Masai T, Yamauchi T, Takeda K, Ito H,

Sawa Y A 55-year-old man with a history of pericardiocentesis for massive pericardial effusion of unknown etiology was admitted to our hospital because of shortness of breath and systemic edema in September 2005. Transthoracic echocardiography demonstrated the massive PE 2 cm in diameter and with several areas of thick hyperrefractile echoes arising from the pericardium.

Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management.

Can J Surg. 2009 Feb;52(1):59-64 Authors: Chua TC, Yan TD, Morris DL

Mesothelioma is an asbestos-related tumour. Mesothelioma in the thorax occurs on the pleura and is known as pleural mesothelioma. It is the more common form of mesothelioma, accounting for 70% of cases.