Mesothelioma, peritoneal [keywords]
- Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study. [JOURNAL ARTICLE]
- Eur J Cancer 2016 Jul 26.:69-79.
Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network.From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC).All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033).This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.
- Updated mortality study of a cohort of asbestos textile workers. [JOURNAL ARTICLE]
- Cancer Med 2016 Jul 25.
Limited information is available on risk of peritoneal mesothelioma after asbestos exposure, and in general on the risk of cancer after cessation of asbestos exposure. We updated to 2013 the follow-up of a cohort of 1083 female and 894 male textile workers with heavy asbestos exposure (up to 100 fb/mL), often for short periods. A total of 1019 deaths were observed, corresponding to a standardized mortality ratio (SMR) of 1.68 (95% confidence interval [CI]: 1.57-1.78). SMRs were 29.1 (95% CI: 21.5-38.6) for peritoneal cancer, 2.96 (95% CI: 2.50-3.49) for lung cancer, 33.7 (95% CI: 25.7-43.4) for pleural cancer, and 3.03 (95% CI: 1.69-4.99) for ovarian cancer. For pleural and peritoneal cancer, there was no consistent pattern of risk in relation to time since last exposure, whereas for lung cancer there was an indication of a decline in risk after 25 years since last exposure. The findings of this unique cohort provide novel data for peritoneal cancer, indicating that - as for pleural cancer - the excess risk does not decline up to several decades after cessation of exposure.
- A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype. [JOURNAL ARTICLE]
- Am J Surg Pathol 2016 Jul 19.
Diffuse malignant peritoneal mesothelioma (MPeM) is rare and arises from peritoneal serosal surfaces. Although it shares similar histomorphology with its counterpart, malignant pleural mesothelioma, etiologies, clinical courses, and therapies differ. Nuclear grading and level of mitoses have been correlated with prognosis in malignant pleural mesothelioma with epithelioid subtype. Whether nuclear grading and level of mitoses correlate with prognosis in MPeM is still unknown. Our study utilizes a 2 tier system incorporating nuclear features and level of the mitoses to stratify cases of MPeM with epithelioid subtype. Fifty-one cases of MPeM with clinical follow-up underwent retrospective microscopic review. From that subset, 46 cases were of epithelioid subtype, which were then stratified into a low-grade or high-grade tier. Survival times were calculated on the basis of Kaplan-Meier analysis. The low-grade tier had higher overall survival with a median of 11.9 years and 57% at 5 years when compared with the high-grade tier with a median of 3.3 years and 21% at 5 years (P=0.002). Although not statistically significant, the low-grade tier had higher progression-free survival with a median of 4.7 years and 65% at 5 years when compared with the high-grade tier with a median of 1.9 years and 35% at 5 years (P=0.089). Our study is first to specifically evaluate and correlate nuclear features and level of mitoses with overall survival in MPeM with epithelioid subtype.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0/.
- PRECLINICAL ACTIVITY OF NEW [1,2]OXAZOLO[5,4-e]ISOINDOLE DERIVATIVES IN DIFFUSE MALIGNANT PERITONEAL MESOTHELIOMA. [JOURNAL ARTICLE]
- J Med Chem 2016 Jul 18.
A series of 22 derivatives of the [1,2]oxazolo[5,4-e]isoindole system were synthesized through an efficient and versatile procedure that involves the annelation of the [1,2]oxazole moiety to the isoindole ring producing derivatives with a wide substitution pattern. The structure-activity relationship indicates that the N-4-methoxybenzyl group appears crucial for potent activity. In addition, the presence of a 6-phenyl moiety is important and the best activity is reached with a 3,4,5-trimethoxy substituent. The most active compound, bearing both the structural features, was able to inhibit tumor cell proliferation at nanomolar concentrations when tested against the full NCI human tumor cell line panel. Interestingly, this compound was effective in reducing in vitro and in vivo cell growth, impairing cell cycle progression and inducing apoptosis, as a consequence of the inhibition of tubulin polymerization, in experimental models of diffuse malignant peritoneal mesothelioma (DMPM), a rapidly lethal disease, poorly responsive to conventional therapeutic strategies.
- Pleural effusions from mesothelioma patients induce recruitment of monocytes and their differentiation into M2 macrophages. [JOURNAL ARTICLE]
- J Thorac Oncol 2016 Jul 11.
Mesothelioma is a rare and aggressive cancer related to asbestos exposure. We recently showed that pleural effusions (PE) from mesothelioma patients contained high levels of the CCL2 inflammatory chemokine. In the present work, we studied the effect of CCL2 contained in mesothelioma samples particularly on monocyte recruitment. Then, we studied the fate of these monocytes in MPM PE and their impact on tumor cell properties.The implication of CCL2 in monocyte recruitment was evaluated using transmigration assays and a CCL2 blocking antibody. The phenotype of macrophages was determined by flow cytometry and ELISA. Immunohistochemistry was used to support the results. Co-cultures of macrophages with mesothelioma cells were performed to study cancer cell proliferation and resistance to treatment.We showed that CCL2 is a major factor of monocyte recruitment induced by MPM samples. Macrophages obtained in MPM samples were M2 macrophages (High CD14, high CD163 and IL-10 secretion following activation). CSF-1R/M-CSF pathway is implicated in M2 polarization and high levels of M-CSF were measured in MPM samples compared to benign PE (4.17 ± 2.75 ng/ml and 1.94 ± 1.47 ng/ml, respectively). Immunohistochemistry analysis confirmed the presence of M2 macrophages in pleural and peritoneal mesothelioma. Finally, we showed that M2 macrophages increased mesothelioma cell proliferation and resistance to treatment.These results demonstrate the implication of CCL2 in MPM pathogenesis and designate M-CSF as a new potential biomarker of MPM. This study also identifies CCL2 and CSF1-R/M-CSF as interesting new targets to modulate pro-tumorigenic properties of the tumor microenvironment.
- Benign Cystic Mesothelioma Misdiagnosed as Peritoneal Carcinomatosis. [Journal Article]
- Case Rep Gastroenterol 2016 Jan-Apr; 10(1):115-20.
Benign cystic mesothelioma (BCM) is a rare benign disease that forms multicystic masses in the abdomen, pelvis, and retroperitoneum. It occurs predominantly in young to middle-aged women. The majority of cases were associated with a history of abdominal or pelvic operation, a history of endometriosis, and pelvic inflammatory disease. We present a unique case of BCM which is different to the previous cases. The patient was a 52-year-old man showing features of peritoneal carcinomatosis accompanied by ascites on abdominal computed tomography scans. We herein report a case of BCM misdiagnosed with peritoneal carcinomatosis.
- Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas. [Journal Article]
- Int J Mol Sci 2016; 17(7)
BACKGROUND:Malignant mesothelioma (MM) is an aggressive tumour of the serosal membranes, associated with exposure to asbestos. Survival is generally poor, but prognostication for individual patients is difficult. We recently described Aquaporin 1 (AQP1) as independent prognostic factor in two separate retrospective cohorts of MM patients. Here we assess the usefulness of AQP1 prospectively, and determine the inter-observer agreement in assessing AQP1 scores; (2)
METHODS:A total of 104 consecutive cases of MM were included. Sufficient tissue for immunohistochemistry was available for 100 cases, and these cases were labelled for AQP1. Labelling was assessed by two pathologists. Complete clinical information and follow up was available for 91 cases; (3)
RESULTS:Labelling of ≥50% of tumour cells for AQP indicated improved prognosis in a univariate model (median survival 13 versus 8 months, p = 0.008), but the significance was decreased in a multivariate analysis. Scoring for AQP1 was robust, with an inter-observer kappa value of 0.722, indicating substantial agreement between observers; (4)
CONCLUSION:AQP1 is a useful prognostic marker that can be easily incorporated in existing diagnostic immunohistochemical panels and which can be reliably interpreted by different pathologists.
- A case of mesothelioma masquerading pre-operatively as ovarian cancer and brief review of the literature. [Journal Article]
- Gynecol Oncol Rep 2016 Aug.:26-8.
Malignant peritoneal mesothelioma (MPM) can masquerade as an ovarian epithelial neoplasm, with very similar presenting clinical symptoms and imaging findings. The gold standard in differentiating between these two diagnoses lies in tissue pathology.This is a case of MPM that was initially misdiagnosed as ovarian cancer based on family history, imaging, and surgical findings. Tissue diagnosis preoperatively would have changed the planned procedure. Retrospectively, after the diagnosis of MPM, the patient was found to have had an indirect exposure to asbestos through her father.This case highlights the importance of keeping a broad differential when diagnosing ovarian malignancies, collecting both family and social histories (including screening for exposure to asbestos), and the benefit of obtaining tissue diagnosis when MPM is suspected.
- Positive response of a primary malignant pericardial mesothelioma to pemetrexed plus cisplatin followed by pemetrexed maintenance chemotherapy: A case report. [JOURNAL ARTICLE]
- Oncol Lett 2016 Jul; 12(1):213-216.
Primary malignant pericardial mesothelioma (PMPM) is a rare tumor with poor prognosis. Surgery is the treatment of choice, but numerous cases are inoperable. For the treatment of inoperable or metastatic cases, systemic chemotherapy is required. However, a standard chemotherapeutic regimen for the treatment of pericardial mesothelioma has not yet been established. Chemotherapy involving pemetrexed and cisplatin has been actively used in the treatment of pleural or peritoneal mesothelioma, and may be considered for the treatment of PMPM. The present study reports the case of a patient with PMPM with lung metastasis who demonstrated a positive response to treatment with pemetrexed and cisplatin followed by pemetrexed maintenance chemotherapy, leading to prolonged progression-free survival for 21 months.
- Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma. [Journal Article]
- Biomaterials 2016 Sep.:175-86.
The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles.