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Mesothelioma, peritoneal [keywords]
- Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma. [JOURNAL ARTICLE]
- Cancer Sci 2014 Nov 25.
Malignant pleural mesothelioma (MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial or peritoneal lining. Although surgery, chemotherapy, radiotherapy and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there is currently no literature regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti-GM2 antibody BIW-8962 as an anti-MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. BIW-8962 showed a significant ADCC activity against the GM2-expressing MPM cell line MSTO-211H, the effect of which depended on the antibody concentration and effector/target ratio. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients This article is protected by copyright. All rights reserved.
- The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats. [JOURNAL ARTICLE]
- Part Fibre Toxicol 2014 Nov 20; 11(1):59.
BackgroundBiological effects of tailor-made multi-walled carbon nanotubes (MWCNTs) without functionalization were investigated in vivo in a two-year carcinogenicity study. In the past, intraperitoneal carcinogenicity studies in rats using biopersistent granular dusts had always been negative, whereas a number of such studies with different asbestos fibers had shown tumor induction. The aim of this study was to identify possible carcinogenic effects of MWCNTs. We compared induced tumors with asbestos-induced mesotheliomas and evaluated their relevance for humans by immunohistochemical methods.MethodsA total of 500 male Wistar rats (50 per group) were treated once by intraperitoneal injection with 109 or 5¿×¿109 WHO carbon nanotubes of one of four different MWCNTs suspended in artificial lung medium, which was also used as negative control. Amosite asbestos (108 WHO fibers) served as positive control. Morbid rats were sacrificed and necropsy comprising all organs was performed. Histopathological classification of tumors and, additionally, immunohistochemistry were conducted for podoplanin, pan-cytokeratin, and vimentin to compare induced tumors with malignant mesotheliomas occurring in humans.ResultsTreatments induced tumors in all dose groups, but incidences and times to tumor differed between groups. Most tumors were histologically and immunohistochemically classified as malignant mesotheliomas, revealing a predominantly superficial spread on the serosal surface of the abdominal cavity. Furthermore, most tumors showed invasion of peritoneal organs, especially the diaphragm. All tested MWCNT types caused mesotheliomas. We observed highest frequencies and earliest appearances after treatment with the rather straight MWCNT types A and B. In the MWCNT C groups, first appearances of morbid mesothelioma-bearing rats were only slightly later. Later during the two-year study, we found mesotheliomas also in rats treated with MWCNT D ¿ the most curved type of nanotubes. Malignant mesotheliomas induced by intraperitoneal injection of different MWCNTs and of asbestos were histopathologically and immunohistochemically similar, also compared with mesotheliomas in man, suggesting similar pathogenesis.ConclusionWe showed a carcinogenic effect for all tested MWCNTs. Besides aspect ratio, curvature seems to be an important parameter influencing the carcinogenicity of MWCNTs.
- Mesothelioma of the tunica vaginalis testis with prominent adenomatoid features: a case report. [Journal Article]
- Int J Clin Exp Pathol 2014; 7(10):7082-7.
Malignant mesotheliomas of the testis arise from the tunica vaginalis, formed from the evagination of the abdominal peritoneum into the scrotum. It is an extremely rare tumor representing 0.3% to 5% of all malignant mesotheliomas. We presented an interesting case of 68-year-old male with swelling and slightly painful in the right scrotum. Histologically, the lesion were composed of small tubular, microcystic, gland lined by flattened epithelioid cells and vague signet ring cells set in a myxofibrous stroma, which is resemblance to adenomatoid tumor. But the tumor cells showed significant atypical cytologic morphology and invaded into spermatic cord tissue, which indicated the diagnosis of malignant tumor. Immunohistochemistry study showed positive expression of CK, CK5/6, CK7, Calretinin, D2-40 and Vimentin which indicated the diagnosis of malignant mesothelioma. This case of mesothelioma should be classified as epithelial in type. To our knowledge, the mesothelioma of the tunica vaginalis testis with adenomatoid tumor-like microscopic features is very rare.
- Diffuse mesothelioma of the peritoneum: correlation between histological and clinical parameters and survival in 73 patients. [Journal Article]
- Pathology 2014 Dec; 46(7):604-9.
There are few studies addressing survival of diffuse peritoneal mesotheliomas (DPM).In this study, survival data were obtained retrospectively from 73 patients treated with intended cytoreductive surgery for DPM, with a mean follow-up of 42 months. Mesotheliomas were classified as well differentiated papillary (WDPM, n = 2), multicystic (MCM, n = 4), and epithelioid mesotheliomas were subclassified as tubulopapillary (TPM, n = 27), solid/deciduoid (S/DM, n = 34), and or biphasic mesothelioma (BPM, n = 6). Invasion was characterised as absent (grade 0), into stroma (grade 1), into fat (grade 2), and into adjacent structures (grade 3). Peritoneal cancer index (PCI) and completeness of cytoreduction (CCR) were assessed surgically.There were no deaths in the WDPM, MCM, and epithelioid DPM with ≤ grade 1 invasion. There was a stepwise decrease in overall survival from invasive TPM, S/DM, and BPM (p < 0.0001). By univariate analysis, advanced age (p = 0.01), incomplete CCR (p < 0.001), PCI (p = 0.004), mitotic count (p < 0.001), nuclear grade (p < 0.0001), stromal inflammation (p = 0.013), depth of invasion (p < 0.0001), necrosis (p = 0.002), and sarcomatoid growth (p < 0.0001) were associated with decreased overall survival. By multivariate analysis, only sarcomatoid growth (p = 0.0006), depth of invasion (p = 0.02), elevated CCR (CCR 2-3) (p = 0.02), and presence of inflammatory stroma (p = 0.04) were significant variables associated with decreased overall survival.DPM form a spectrum of indolent to highly aggressive tumours. Solid epithelioid/deciduoid tumours have a prognosis intermediate between biphasic mesotheliomas and invasive TPM. The presence and degree of invasion, sarcomatoid features, and inflammatory stroma are poor prognostic indicators.
- Scrotal Peritoneal Mesothelioma on PET/CT. [Journal Article]
- Clin Nucl Med 2014 Dec; 39(12):1045-6.
Although malignant mesothelioma originating from the tunica vaginalis has been reported in the literature, direct invasion of malignant peritoneal mesothelioma to the scrotal cavity has not been described yet. Herein, we presented a diffuse malignant peritoneal mesothelioma extending inferiorly to the scrotum via inguinal canal detected on FDG PET/CT.
- Mesothelioma Patients with Germline BAP1 Mutations Have Seven-Fold Improved Long-term Survival. [JOURNAL ARTICLE]
- Carcinogenesis 2014 Nov 7.
BAP1 mutations cause a new cancer syndrome, with a high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM associated with germline BAP1 mutations has a better prognosis compared to sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the US SEER data from 1973 to 2010. We identified 23 MM patients -11 alive- with germline BAP1 mutations and available data on survival. Ten patients had peritoneal MM, ten pleural MM, and three MM in both locations. Thirteen patients had one or more malignancies in addition to MM. Actuarial median survival for the MM patients with germline BAP1 mutations was five years, as compared with less than one year for the median survival in the US SEER MM group. Five-year survival was 47%, 95%CI [24-67%], as compared with 6.7% [6.2-7.3%] in the control SEER group. Analysis of the pooled cohort of germline BAP1 mutation MM showed that patients with peritoneal MM (median survival of 10 years, P=0.0571), or with a second malignancy in addition to MM (median survival of 10 years, P=0.0716), survived for a longer time compared to patients who only had pleural MM, or MM patients without a second malignancy, respectively. In conclusion, we found that MM patients with germline BAP1 mutations have an overall seven-fold increased long-term survival, independently of sex and age. Appropriate genetic counseling and clinical management should be considered for MM patients who are also BAP1 mutation carriers.
- Institutional Learning Curve of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Peritoneal Malignancies. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Nov 7.
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemoperfusion (HIPEC) is routinely used to treat certain peritoneal carcinomatoses (PC), but it can be associated with relatively high complication rates, prolonged hospital length of stay, and potential mortality. Our objective was to determine the learning curve (LC) of CRS/HIPEC in our high-volume institution.A total of 370 patients with PC from mucinous appendiceal neoplasms (MAN = 282), malignant peritoneal mesothelioma (MPM = 60), and gastric cancer (GC = 24) were studied. Outcomes analyzed included incomplete cytoreduction (IC), severe morbidity (SM), 60-day mortality, progression-free survival (PFS), and overall survival (OS). Risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of CRS/HIPEC for IC and SM using prespecified odds ratio (OR) boundaries derived from previously published data. Risk adjusted-cumulative average probability (RA-CAP) was used to analyze 1-year PFS and 2-year OS.Complete cytoreduction, severe morbidity, and 60-day mortality were 84.2, 30, and 1.9 % respectively. Higher simplified peritoneal cancer index was the major independent risk factor for IC, whereas high-grade histology, IC, and diagnosis of MPM and GC (compared with MAN) were predictors of SM after CRS/HIPEC (p < 0.05). RA-SPRT showed that approximately 180 cases are needed to achieve the lowest risk of IC and SM. Ninety cases were needed to achieve a steady 1-year PFS and 2-year OS in RA-CAP plots.The completeness of cytoreduction, morbidity, and mortality rates for CRS/HIPEC at our institution are comparable to previously reported data. Approximately 180 and 90 procedures are required to improve operative and oncologic outcomes respectively.
- Advances in malignant peritoneal mesothelioma. [JOURNAL ARTICLE]
- Int J Colorectal Dis 2014 Oct 21.
Malignant mesothelioma is a rare, insidious, and aggressive tumor arising from the mesothelial surface of pleural and peritoneal cavities, the pericardium, or the tunica vaginalis, with an increasing incidence worldwide, high misdiagnosis rate, and overall negative prognosis. A total of 20 % of all cases is peritoneum in origin.The present study is a review of literatures focusing on the advances in epidemiology, clinical presentations, radiological features, diagnosis, misdiagnosis, management, and prognostic factors of malignant peritoneal mesothelioma (MPM) occurred in the past decades.Asbestos, SV40, and radiation exposures have been demonstrated to be correlated with the pathogenesis of MPM. The main presentations are abdominal distension and pain. Computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) play an important role in the preoperative imaging and staging. Definitive diagnosis is made on the basis of immunohistochemistry. Prognostic factors have been identified and verified. Negative indicators include advanced age, male gender, poor performance status, non-epithelial histology, and absence of surgery. The management of MPM has evolved from single chemotherapy to multimodality treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), chemotherapy, radiotherapy, and immunotherapy. Promising results have been achieved after a combined treatment of CRS and HIPEC, with an elevated median survival time of 29.5-92 months and a 5-year survival rate of 39-63 %.CRS and HIPEC represent the standard treatment strategy for selected patients with MPM, and patients with unresectable tumors can benefit from the combined treatment of chemotherapy, radiotherapy, and immunotherapy.
- Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC). [JOURNAL ARTICLE]
- Langenbecks Arch Surg 2014 Oct 16.
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a novel curative treatment option for selected patients with peritoneal carcinomatosis (PC). We aimed to report the mortality rate and the most frequent grade III-IV adverse events and to identify associated prognostic markers. We report oncological outcomes and major prognostic factors influencing overall survival (OS) and disease-free survival.A total of 401 CRS plus HIPEC procedures were performed on 356 patients. Mortality, grade III-IV adverse events, OS, disease-free survival, and prognostic factors were studied.Based on Common Terminology Criteria for Adverse Events (CTCAE of the National Cancer Institute 2006), mortality rate was 1 % and overall rate of morbidity grade III-IV was 12.5 %. In multivariate analysis, only the number of digestive anastomoses (>1) significantly correlated with adverse events with an odds ratio of 2.8 (p = 0.032). OS was related to histological type of PC, with a median survival reaching 47.6 months for PC of ovarian cancer origin, 45.8 months for that of colorectal origin, 64.2 months for peritoneal mesothelioma, and 8.1 months for PC of gastric cancer origin. Over half the patients with pseudomyxoma are still alive. Major prognostic factors influencing survival were histological type, World Health Organization performance status (WHO PS) (hazard ratio (HR) = 3.56), operating time (HR = 0.45), previous chemotherapy (HR = 2.04), number of peritonectomies (HR = 2.03), and completeness of cytoreduction score (HR = 3.12). Disease-free survival across all groups was 16.8 months.The low mortality rate and 12.5 % grade III-IV morbidity of CRS and HIPEC are acceptable when weighed against overall oncologic survival. This multimodal treatment appears feasible for selected patients and trained centers.