Mesothelioma, peritoneal [keywords]
- Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies. [Journal Article, Review]
- World J Gastroenterol 2016 Aug 14; 22(30):6906-16.
Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis (PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases I, II and III clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.
- Mesothelioma response to carbon nanotubes is associated with an early and selective accumulation of immunosuppressive monocytic cells. [Journal Article]
- Part Fibre Toxicol 2016; 13(1):46.
The asbestos-like toxicity of some engineered carbon nanotubes (CNT), notably their capacity to induce mesothelioma, is a serious cause of concern for public health. Here we show that carcinogenic CNT induce an early and sustained immunosuppressive response characterized by the accumulation of monocytic Myeloid Derived Suppressor Cells (M-MDSC) that counteract effective immune surveillance of tumor cells.Wistar rats and C57BL/6 mice were intraperitoneally injected with carcinogenic multi-walled Mitsui-7 CNT (CNT-7) or crocidolite asbestos. Peritoneal mesothelioma development and immune cell accumulation were assessed until 12 months. Leukocyte sub-populations were identified by recording expression of CD11b/c and His48 by flow cytometry. The immunosuppressive activity on T lymphocytes of purified peritoneal leukocytes was assessed in a co-culture assay with activated spleen cells.We demonstrate that long and short mesotheliomagenic CNT-7 injected in the peritoneal cavity of rats induced, like asbestos, an early and selective accumulation of monocytic cells (CD11b/c(int) and His48(hi)) which possess the ability to suppress polyclonal activation of T lymphocytes and correspond to M-MDSC. Peritoneal M-MDSC persisted during the development of peritoneal mesothelioma in CNT-7-treated rats but were only transiently recruited after non-carcinogenic CNT (CNT-M, CNT-T) injection. Peritoneal M-MDSC did not accumulate in mice which are resistant to mesothelioma development.Our data provide new insights into the initial pathogenic events induced by CNT, adding a new component to the adverse outcome pathway leading to mesothelioma development. The specificity of the M-MDSC response after carcinogenic CNT exposure highlights the interest of this response for detecting the ability of new nanomaterials to cause cancer.
- Malignant mesothelioma effusions are infiltrated by CD3(+) T cells highly expressing PD-L1 and the PD-L1(+) tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab. [JOURNAL ARTICLE]
- J Thorac Oncol 2016 Aug 17.
The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied.Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1(+) and PD-L1(+) infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells.Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3(+) T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14(+)PD-1(+) cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells.The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3(+) T cells that highly express PD-L1. In addition, mesothelioma tumor cells are susceptible to ADCC by anti-PD-L1 antibody avelumab.
- Co-existing tuberculosis and malignant mesothelioma with multiple sites venous thrombosis: a case report. [Journal Article]
- BMC Res Notes 2016; 9(1):409.
Tuberculosis is endemic in India and almost 40 % of the Indian population is infected with tubercle bacilli. Tuberculosis being a great mimicker of infectious as well as non infectious diseases and recent rise of multi drug resistant and extended drug resistant cases have made diagnosis and management more difficult. To the best of our knowledge there have been no reported cases of tuberculosis coexisting with malignant peritoneal mesothelioma leading to multiple site venous thrombosis.Forty five year old male, belonging to Indian/Aryan ethnicity presented with cough, breathlessness and fever for 7 months with past history of pulmonary tuberculosis. On examination he was found to have pleural effusion for which he received anti-tuberculosis therapy empirically. Later his condition deteriorated and on further examination he was found to have ascites, multiple site venous thrombosis and pyothorax which was found positive for acid fast bacilli. Despite anti-tuberculosis therapy he did not improve and was suspected to be a multidrug resistant case. Later on computed tomography peritoneal nodule was detected and on biopsy revealed malignant mesothelioma.In a diagnosed case of tuberculosis with clinical findings compatible with it but not responding to anti tubercular therapy, underlying secondary co-existing pathology should be explored.
- Asbestos Fiber Preparation Methods Affect Fiber Toxicity. [JOURNAL ARTICLE]
- Environ Sci Technol Lett 2016 Jul 12; 3(7):270-274.
To measure the toxic potential of asbestos fibers-a known cause of asbestosis, lung cancer, and malignant mesothelioma-asbestos minerals are generally first ground down to small fibers, but it is unknown whether the grinding condition itself changes the fiber toxicity. To evaluate this, we ground chrysotile ore with or without water for 5-30 min and quantified asbestos-induced reactive oxygen species generation in elicited murine peritoneal macrophages as an indicator of fiber toxicity. The toxicity of dry-ground fibers was higher than the toxicity of wet-ground fibers. Grinding with or without water did not materially alter the mineralogical properties. However, dry-ground fibers contained at least 7 times more iron than wet-ground fibers. These results indicate that grinding methods significantly affect the surface concentration of iron, resulting in changes in fiber-induced reactive oxygen species generation or toxicity. Therefore, fiber preparation conditions should be accounted for when comparing the toxicity of asbestos fibers between reported studies.
- Evolution of management in peritoneal surface malignancies. [Journal Article, Review]
- Ulus Cerrahi Derg 2016; 32(3):203-7.
Management of peritoneal surface malignancies has gradually evolved by the introduction of cytoreductive surgery in combination with intraperitoneal chemotherapy applications. Recently, peritoneal metastases of intraabdominal solid organ tumors and primary peritoneal malignancies such as peritoneal mesothelioma are being treated with this new approach. Selection criteria are important to reduce morbidity and mortality rates of patients who will experience minimal or no benefit from these combined treatment modalities. Management of peritoneal surface malignancies with this current trend is presented in this review.
- Quercetin and Cisplatin combined treatment altered cell cycle and mitogen activated protein kinase expressions in malignant mesotelioma cells. [Journal Article]
- BMC Complement Altern Med 2016; 16(1):281.
Malignant mesothelioma is a locally aggressive and highly lethal neoplasm of pleural, peritoneal and pericardial mesothelial cells without successful therapy. Previously, we reported that Quercetin in combination with Cisplatin inhibits cell proliferation and activates caspase-9 and -3 enzymes in different malignant mesothelioma cell lines. Moreover, Quercetin + Cisplatin lead to accumulation of both SPC111 and SPC212 cell lines in S phase.In present work, 84 genes involved in cell growth and proliferation have analysed by using RT(2)-PCR array system and protein profile of mitogen activated protein kinase (MAPK) family proteins investigated by western blots.Our results showed that Quercetin and Quercetin + Cisplatin modulated gene expression of cyclins, cyclin dependent kinases and cyclin dependent kinases inhibitors. In addition genes involved in JNK, p38 and MAPK/ERK pathways were up regulated. Moreover, while p38 and JNK phosphorylations were increased, ERK phosphorylations were decreased after using Quercetin + Cisplatin.This research has clarified our previous results and detailed mechanism of anti-carcinogenic potential of Quercetin alone and incombination with Cisplatin on malignant mesothelioma cells.
- Genomic Landscape of Malignant Mesotheliomas. [JOURNAL ARTICLE]
- Mol Cancer Ther 2016 Aug 9.
Understanding the genomic landscape of malignant mesothelioma may identify novel molecular drivers of this ultra-rare disease, which can lead to an expanded roster of targeted therapies and clinical trial options for patients with mesothelioma. We examined the molecular profiles of 42 patients with malignant mesothelioma (including pleural, peritoneal, and pericardial) that were referred by clinicians to be tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory using next-generation sequencing (NGS) (182 or 236 genes). Among 42 patients, there were 116 alterations, with 92 being distinct. The number of genomic alterations per patient ranged from 1 to 5 (median = 3). No two patients had identical molecular portfolios. The most common aberrations were in BAP1 (BRCA1-associated protein 1) (47.6% [20/42]), NF2 (38.1% [16/42]), and CDKN2A/B (loss) (35.7% [15/42]). BAP1 alterations and CDKN2A/B loss were associated with pleural mesothelioma (odds ratio [OR]: 3.4, p = 0.059 [BAP1] [trend]; OR: 5.8, p = 0.01 [CDKN2A/B]). All 42 patients had a molecular abnormality that was potentially actionable (median = 3 actionable alterations per patient, range, 1 to 5), and, in 40 patients (95.2%), a drug approved by the Food and Drug Administration (FDA) was applicable. In conclusion, each individual with malignant mesothelioma harbored a unique set of genomic aberrations, suggesting that NGS-based profiling of patients will be needed if patients are to be optimally matched to cognate treatments. All 42 patients had at least one alteration that was, in theory, pharmacologically tractable.
- [Management of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy]. [English Abstract, Journal Article]
- Rev Med Suisse 2016 Jun 15; 12(523):1190-4.
In 2016, peritoneal carcinomatosis can be considered as a chronic disease that can be treated and sometimes cured. Hyperthermic Intra PEritoneal Chemotherapy (HIPEC) is a procedure developed in the eighties. Combined with CytoReductive (CR) surgery, this protocol underwent a considerable expansion in Washington Cancer Institute. CR combined with HIPEC was demonstrated to be the only curative treatment for PseudoMyxoma Peritonei syndrome (PMP). It is actually approved in the management of peritoneal carcinomatosis of ovarian, colorectal, or peritoneal primitive (mesothelioma) origin but is still studied for gastric cancer. CR/HIPEC is associated with an important mortality and morbidity. This article takes stock of indications to CR/HIPEC.
- Preventing recurrence of diffuse malignant peritoneal mesothelioma. [JOURNAL ARTICLE]
- Expert Rev Anticancer Ther 2016 Aug 3.
Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignancy with a poor prognosis when treated with systemic therapy. Cytoreductive surgery (CRS) with intraperitoneal chemotherapy (IPC) is considered the best therapy in DMPM, but a high risk of locoregional recurrence remains.This review describes patient selection and operative goals with CRS and IPC, the reported outcomes with this approach, and the data supporting platinum-based IPC. We assess the pharmacokinetics supporting the use of dwell IPC. We outline clinical, imaging and laboratory surveillance for recurrence. In addition, we highlight the role of re-operation, both as a planned second procedure and in the context of disease recurrence. Literature review was performed via Medline search. Expert commentary: CRS/IPC offers survival benefit in selected patients with DMPM, but given the high rate of recurrence, close surveillance is needed post-operatively. Strategies to prevent and treat recurrent disease include dwell IPC and second CRS/IPC.