恶性胸膜间皮瘤治疗新进展

恶性胸膜间皮瘤是一种胸膜恶性肿瘤,已发现其发生与石棉暴露有关.目前治疗恶性胸膜间皮瘤的方法有手术治疗、化疗和放疗,但效果均不理想.外科手术由于缺乏随机对照研究,其效果仍不确切.放疗因为恶性间皮瘤细胞的放射敏感性一般.故也存在争议.化疗对恶性胸膜间皮瘤的治疗效果相对较差.联合应用培美曲唑与顺铂能达到较好效果.多模式治疗方案被认为是目前治疗恶性胸膜间皮瘤的首选.     

Pathogenesis of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) results from neoplastic transformation of mesothelial cells. Past asbestos exposure represents the major risk factor for MPM, as the link between asbestos fibres and MPM has been largely proved by epidemiological and experimental studies. Asbestos fibres induce DNA and chromosome damage linked to oxidative stress following phagocytosis. Recently, simian virus 40 (SV40) has been implicated in the aetiology of MPM. The origin of human infection has been associated with SV40-contaminated polio vaccines, although to date, no epidemiological data supports this hypothesis. SV40 may act as a coactivator of asbestos in mesothelial oncogenesis. The transforming potency of SV40 results from the activity of two viral proteins, large T and small t antigens. SV40 infection stimulates production of growth factors elsewhere implicated in autocrine growth of mesothelioma cells and inactivates RASSF1, a gene silenced in MPM. Roles for ionising radiation, chemicals or genetic factors have also been suggested from the observation of sporadic MPM cases or animal studies. Genetic alterations in the tumour suppressor genes, P16/CDKN2A and neurofibromatosis 2 (NF2), are found both in human MPM and in asbestos-exposed Nf2-deficient mice. MPM is still of great international concern. Despite a ban on asbestos use in Western countries, the incidence of MPM is increasing, due to the long delay between asbestos exposure and diagnosis. Moreover, asbestos is still used in developing countries. The implication of other risk factors, especially SV40, supports a need for further research into MPM.     

A case of malignant pleural mesothelioma following exposure to atomic radiation in Nagasaki

Abstract We report the case of a 75-year-old Japanese man who developed malignant mesothelioma in the left hemithorax 50 years after the dropping of the atomic bomb on Nagasaki in 1945. This may be the first reported case of malignant mesothelioma following exposure to atomic radiation. Asbestos is the leading cause of malignant mesothelioma, but radiation therapy is the primary non-asbestos-related cause. In the case of radiation therapy, the interval between exposure and the occurrence of malignant mesothelioma tends to be many years. This patient was at a high risk of malignant mesothelioma as he had been exposed to radiation from the atomic bomb and may also have had a history of asbestos exposure at the munitions factory where he was employed as a shipbuilder for 2 years. It has been suggested that combined exposure to atomic radiation and asbestos is associated with an increased incidence of malignant mesothelioma. If thickening of the pleura or pleural effusion is found in atomic bomb survivors, malignant mesothelioma should be considered as one of the options in the differential diagnosis, even although the atomic bomb attacks occurred several decades ago.     

恶性胸膜间皮瘤的诊治进展

恶性间皮瘤（MM）是一种很少见的但恶性程度又很高的肿瘤,主要发生于胸膜（MPM）,也可在心包膜及腹膜,其发病的很大原因与石棉接触有关。当发现时已属晚期,对该病的诊断尤其是早期诊断很困难,近几年分子生物学、影像学的进展帮助我们更好地了解了该病。其治疗方面虽有很多的治疗方法但效果都不很理想,近年来倍美曲塞和雷替曲塞与顺铂结合治疗,以及基因、免疫和一些生物制剂给治疗该病提供了较好的前景。     

A narrative review of the health disparities associated with malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a cancer of the mesothelial lining of the pleura that has traditionally been associated with asbestos exposure in an industrial setting. Asbestos usage has fortunately been banned or phased out in most industrialized countries resulting in its decline in countries such as the United States. Despite this, MPM continues to place significant burden on its affected patients resulting in overall poor prognosis and survival. Questions arise as to what factors, especially what health disparities, contribute to the disease’s dismal prognosis. This article will present a narrative review of recent literature that identifies the impact age, sex, race, access to medical centers, and economics have on the diagnosis, treatment, and prognosis of MPM. As will be discussed, research has shown that factors including younger age, female sex, non-white race, private insurance, Medicare, and higher income have been associated with better survival in MPM. Whereas older age, male sex, white race, lack of insurance, and lower income are associated with worse survival. The identification of these and other health disparities related to MPM may allow for future research, clinical guidelines, and policies to be implemented to decrease the burden health disparities create in the diagnosis, treatment, and prognosis of patients with MPM.     

Recent discovery of an old disease: malignant pleural mesothelioma in a village in south-east Turkey

BACKGROUND AND OBJECTIVE: Environmental asbestos exposure is reportedly common in some districts of Turkey. The aim of this study was to investigate the presence and effect of environmental asbestos exposure in a village in Gaziantep, Turkey, with reported cases of mesothelioma. METHODS: All villagers > or =14 years old were subject to an interview rediagnosis and a detailed questionnaire. Chest microfilms were performed in all cases, and additional standard CXRs were obtained when necessary. Samples collected from the natural mantle, and whitewash from the houses were analysed for the presence of asbestos. RESULTS: In total, 269 villagers took part in the study. The incidence of histopathologically diagnosed malignant pleural mesothelioma was 0.32% relative to the total village population in the year 2000. The verbal autopsy revealed eight possible cases of malignant pleural mesothelioma, all of whom had died within the past 12 years. Of these eight, there was a first-degree kinship between three, and additionally, these patients had a third-degree relationship with a biopsy proven case. Radiological evaluation showed pleural calcification and/or thickness in 3.3%, and pleural effusion in 0.4% of patients undergoing CXR. All houses in the village were constructed using adobe soil, and the interior whitewash was made from soil containing asbestos. Analysis of soil samples revealed tremolite and/or actinolyte asbestos. CONCLUSION: The current findings suggest that environmental asbestos exposure continue to be a serious health concern in the Gaziantep region of Turkey.     

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

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.     

恶性胸膜间皮瘤合并肺结核/结核性胸腔积液的临床特征分析

目的:分析恶性胸膜间皮瘤(MPM)合并肺结核/结核性胸腔积液(TPE)患者的临床特征,以加强对该类疾病的认识,减少误诊误治。方法:收集首都医科大学附属北京胸科医院2012年2月至2020年2月MPM并肺结核/TPE患者病例资料14例,回顾性分析其临床症状、体征、实验室检查,胸部影像特征等,以总结其特点。结果:剧烈且进行...     

Malignant mesothelioma

Malignant mesothelioma (MM) is an aggressive tumour that commonly affects the mesothelial surfaces of the pleural and peritoneal cavities, and occasionally, the tunica vaginalis and the pericardium. Formerly a rare tumour, MM is increasing in incidence in Australia due to the heavy nationwide use of asbestos from 1940 until the 1980s. The incidence is expected to peak in Australia in the next decade, mirroring the long latency period between asbestos exposure and development of MM. Diagnosis of MM can be difficult. Definitive pathological diagnosis is required and it often requires an experienced pathologist to differentiate MM from other benign or malignant processes. Treatment of MM requires a multidisciplinary approach, regardless of palliative or curative intent. Treatment options, such as surgery, chemotherapy, radiotherapy and active symptom control or a combination of these, may be used. Further research is needed to advance the therapeutic options for MM, and strategies to realize personalisation of therapy through discovery of predictive markers. In the Australian society where asbestos contamination of the built environment is very high, education and stringent public health measures are required to prevent a second wave of increased MM incidence.     

Epidemiology of pleural mesothelioma in a population with non-occupational asbestos exposure

Background and objective:   This study describes the epidemiology of malignant pleural mesothelioma (MPM) in a rural population with environmental asbestos exposure.
Methods:   Patients with diagnosed MPM were recruited and their relevant demographic and exposure data were analysed.
Results:   A total of 131 patients with MPM (59 men, 72 women) were studied. The patients' mean age was 57.8 years and the mean exposure duration was 28.9 years. The cumulative fibre count of the villagers ranged from 0.19 to 14.61 fibre/mL-years. Of the 131 patients, 85 had epithelial cell type, 20 had mixed, and eight had sarcomatous pleural mesothelioma. No significant relationship was found between asbestos fibre type and age, exposure period, or cellular type of MPM; similarly, no significant relationship could be found between the cellular type and age or exposure period. Patients with sarcomatous mesotheliomas were considerably older. Only five of 131 (3.8%) patients had a family history of mesothelioma.
Conclusions:   Environmental exposure to asbestos begins at birth and this may be important in the age of disease onset, if a threshold model for cancer initiation is operative. Both men and women had an excess risk of mesothelioma. Given that a family history of MPM was not common in this relatively homogenous patient group, a genetic predisposition to mesothelioma appears unlikely.     

Epidemiology,diagnosis and treatment of the malignant pleural mesothelioma,a narrative review of literature

The malignant pleural mesothelioma is a very aggressive tumor which is arising from mesothelial cells and is associated with asbestos exposure. It is a heterogeneous cancer that shows a complex pattern of molecular changes, including genetic, chromosomic, and epigenetic abnormalities. The malignant pleural mesothelioma is characterized by a silent and slow clinical progression with an average period of 20–40 years from the asbestos exposure phase to the start of the symptoms. Unfortunately, to date, the therapeutic options are very limited, especially if the tumor is detected late. This narrative review provides an extended overview of the present evidence in the literature regarding the epidemiology, diagnostic pathways and treatment approaches of the malignant pleural mesothelioma. The treatment of mesothelioma has evolved slowly over the last 20 years not only from a surgical point of view but also radiotherapy, chemotherapy and immunotherapy play nowadays a key role. Several surgical strategies are available ranging from extrapleural pneumonectomy to cytoreductive surgery but a multidisciplinary approach seems to be mandatory because a single approach has not proved to date to be resolutive. New non-surgical treatment options appear to be promising but the results have to be taken in account with caution because clear evidence with high-quality studies is still lacking     

Advances in the diagnosis, evaluation, and management of malignant pleural mesothelioma

Malignant mesothelioma is an insidious neoplasm arising from the mesothelial surfaces of the pleural and peritoneal cavities, the pericardium, or the tunica vaginalis. A total of 80% of all cases are pleural in origin. The predominant cause of malignant mesothelioma is inhalational exposure to asbestos, although evidence is increasing to support the hypothesis that simian virus-40 virus plays a role in cocarcinogenesis. Immunohistochemical markers such as calretinin, WT-1, and cytokeratin 5/6 are becoming established diagnostic markers. Preliminary data suggests that a soluble form of mesothelin could serve as a serum marker for established and early cases of mesothelioma. Positron emission tomography with 18-fluorodeoxyglucose in conjunction with computed tomograhy scanning has improved preoperative imaging and staging. Prognostic factors have been identified and verified. Negative indicators include thrombocytosis, high leukocyte counts, poor performance status, and nonepithelial histology. For the first time, there is now evidence that some treatments are increasing the quality and quantity of life for patients with mesothelioma. Chemotherapy, with the new multi-targeted antifolate drug Pemetrexed, combined with cisplatin, has shown superior survival rates in a large phase III trial when compared to cisplatin alone. High-dose intensity-modulated radiotherapy when administered after extrapleural pneumonectomy has resulted in excellent local control. Multimodality treatment programs that combine surgical cytoreduction with novel forms of radiation therapy and more effective chemotherapy combinations may offer significant increases in survival for certain subgroups of mesothelioma patients. Innovative palliative approaches have proved successful in alleviation of the significant symptoms experienced by many mesothelioma patients. Experimental treatments such as immunotherapy and gene therapy present a window of hope for all mesothelioma patients, and in the future, may be combined with 'standard therapy' in multimodality protocols. Patients with adequate performance status should be enrolled into clinical trials where possible. Over the past decade, significant advances have been made on several fronts that have improved the ability to diagnose a stage, define prognosis, and treat malignant pleural mesothelioma.     

Diffuse malignant peritoneal mesothelioma

Mesothelioma often originates in the pleura and less frequently in the peritoneum. This article describes a rare case of diffuse malignant peritoneal mesothelioma in a 54-year-old male construction worker who was admitted to our hospital with a 2-month history of progressive abdominal distention. Abdominal computed tomography revealed extensive peritoneal nodularity and omental cake along with massive ascites. Imaging findings initially suggested peritoneal carcinomatosis, primary peritoneal carcinoma, and tuberculous peritonitis. Laparoscopic biopsy of the omentum and peritoneum confirmed the diagnosis of malignant peritoneal mesothelioma of epitheloid type. Although systemic chemotherapy was administered, no tumor regression was found. The patient finally died of nosocomial infection.     

Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients

BackgroundCisplatin plus pemetrexed is a standard front-line chemotherapeutic regimen for inoperable malignant pleural mesothelioma (MPM). However, no clinical trials have compared the efficacy of cisplatin plus pemetrexed and cisplatin plus gemcitabine, which may be comparable based on previous phase II study results. This study aimed at evaluating the efficacy of cisplatin plus pemetrexed and comparing it with that of cisplatin plus gemcitabine in Japanese MPM patients.MethodsFrom July 2002 to December 2011, 13 and 17 consecutive patients with inoperable MPM were treated with cisplatin plus gemcitabine and cisplatin plus pemetrexed, respectively, at the Shizuoka Cancer Center. We reviewed the medical charts of these patients and evaluated their characteristics as well as data regarding drug toxicity and antitumor efficacy.ResultsThe response rates were 15% and 35% in the cisplatin plus gemcitabine and cisplatin plus pemetrexed groups, respectively (P=0.4069), while disease control rates were 77%, and 82%, respectively (P=0.9999). Progression-free survival was significantly higher with cisplatin plus pemetrexed (median, 215.5 days) than with cisplatin plus gemcitabine (median, 142.5 days) (P=0.0146; hazard ratio [HR], 0.3552). Overall survival showed a tendency towards being superior with cisplatin plus pemetrexed (median, 597.5 days) compared with cisplatin plus gemcitabine (median, 306.5 days) (P=0.1725, HR, 0.5516). Hematological toxicities, especially thrombocytopenia and neutropenia, tended to be more frequent and severe in the cisplatin plus gemcitabine group.ConclusionsCisplatin plus pemetrexed may be superior and should continue to be the standard front-line chemotherapeutic regimen for inoperable MPM.     

Epidermal growth factor receptor gene mutation,amplification and protein expression in malignant pleural mesothelioma

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies. In lung cancer cases, EGFR gene mutation at the kinase domain and EGFR gene amplification are reported to be predictors of the response to EGFR tyrosine kinase inhibitors. In malignant pleural mesothelioma (MPM), the role of EGFR is less clear. We studied EGFR gene mutation, amplification and protein expression in 25 Japanese patients with MPM. None had previously reported EGFR mutations detected by the TaqMan PCR assay. Using immunohistochemistry, 8/25 (32%) cases were positive for the EGFR protein. The cases of sarcomatous type and desmoplastic type were all negative. Fluorescence in situ hybridization analysis revealed three low polysomy cases and one high polysomy case. The low polysomy cases included one biphasic type and two epithelial types, and the high polysomy case was epithelial type. These four cases expressed EGFR protein. In MPM, EGFR seems to play a role in a limited subset of patients. To identify possible candidates for EGFR tyrosine kinase in inhibitor therapy, the information on the EGFR gene status may be valuable.     

一例恶性腹膜间皮瘤误诊为结肠癌报道及文献复习

恶性腹膜间皮瘤是一种起源于腹膜腔上皮或间皮组织的少见恶性肿瘤,起病隐匿,几乎无特异性临床表现、敏感性实验室指标及影像学明显特征,早期诊断困难,极易误诊,病理学及免疫组化诊断是其金标准。该病目前尚无标准治疗方案推荐,确诊时多为晚期,病死率高,预后极差。本文报道一例54岁男性,初始误诊为结肠癌合并腹腔积液,后在腹腔镜下探查及活检,方得以明确诊断,采用多种药物灌注而腹腔积液仍不能控制,胸腹腔积液引流总量达7万余毫升,如此大量腹腔积液在临床上较少见,其生存期15个月。本文加以报道与文献回顾,旨在提高对该病之认识。     

Improving outcomes in malignant pleural mesothelioma in an integrated health care system

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive tumor that should be managed by an experienced surgical and multidisciplinary group. Our objective was to determine the impact of proficient surgeons and MPM bi-disciplinary review on outcomes of patients with MPM.MethodsThrough this cohort study, electronic medical records of 368 adult patients with MPM from 1/1/2009 to 12/31/2020 were reviewed and compared before and after MPM surgeries were regionalized to specialized surgeons and bi-disciplinary review of MPM patient treatment options. We used the Kaplan-Meier method and log-rank tests to compare survival rates by period, by treatment type, and by stage. Patients were followed from cancer diagnosis date until they died or end of study follow-up, whichever occurred first. We also conducted Cox proportional hazards regression model to examine the overall survival (OS) with adjustments for age, histology, stage, and Charlson comorbidity index (CCI).ResultsDespite similar staging, more patients received any MPM directed treatment from 2015–2020 compared with those patients from 2009–2014. Specifically, there was an increase in patients who received pleurectomy/decortication (PD) from 2015–2020 compared to those who received PD in 2009–2014. Patients with similar age, CCI, stage, and histology had an increase in OS of 12 months with multimodality therapy (surgery, systemic therapy, +/− radiation) compared to those patients who received no treatment.ConclusionsConsolidating mesothelioma surgery to a specialized surgical team and regular bi-disciplinary review of MPM cases to determine appropriate multimodality therapy, increases the incorporation of surgical treatments in the management of patients with MPM.