Epidemiology and trend analysis on malignant mesothelioma in China

Objective： Population-based cancer registration data were used to analyze the epidemiology and trend of malignant mesothelioma in China, and the result would provide basic data for its prevention and control. Methods： Malignant mesothelioma data in 2013 were retrieved from the database of National Cancer Registry. Malignant mesothelioma incidence and mortality were estimated using age-specific rate by urban/rural and gender according to the national population in 2013. Malignant mesothelioma data from 22 cancer registries were used for trend analysis during 2000-2013. Results： It is estimated that there were 2,041 new malignant mesothelioma cases and 1,659 malignant mesothelioma deaths occurred in 2013. The crude incidence rate in China were 1.50/106 （males 1.67/106, females 1.32/106）, age-standardized incidence rates by Chinese standard population （ASIRC） and by world standard population （ASIRW） were 1.03/106 and 1.02/106, respectively. The crude mortality rate in China was 1.22/106 （males 1.67/106, females 1.32/106）, age-standardized mortality rates by Chinese standard population （ASMRC） and by world standard population （ASMRW） were 0.83/106 and 0.81/106, respectively. There was an increasing trend of incidence rate for malignant mesothelioma in registration areas of China during 2000-2013 with annual percentage change （APC） of 2.5% [95% confidence interval （95% CI）： 0.6%--4.5%]. After age standardization, no significant differences were observed. No matter for crude mortality rates or age-standardized mortality rates, no significant differences were observed during 2000-2013. Conclusions： Malignant mesothelioma is the major occupational and environmental neoplasm associated with asbestos exposure. The increasing incidence trend suggests that more attention should be paid on this disease.

Malignant pleural mesothelioma mimics thoracic empyema: A case report

BACKGROUND Thoracic empyema and malignant pleural mesothelioma(MPM)are distinct medical conditions with similar symptoms,including cough,chest pain,and breathing difficulty.We present a rare MPM case mimicking thoracic empyema.Physicians must consider MPM risks for patients exposed to building material who exhibit lobulated pleural effusions,indicating thoracic empyema.CASE SUMMARY A 68-year-old retired male construction worker suffered from shortness of breath and chest tightness over 10 d,particularly during physical activity.A poor appetite and 4 kg weight loss over the past 3 wk were also reported.Chest images and laboratory data concluded a tentative impression of empyema thoracis(right).Video-assisted thoracic surgery with decortication and delobulation(right)was conducted.The pathological report yielded an MPM diagnosis.Refractory pleural bilateral effusions and respiratory failure developed postoperatively,and the patient died three weeks after the operation.CONCLUSION Thoracic empyema and MPM are distinct medical conditions that can present similar symptoms,and video-assisted thoracic surgery facilitates an accurate diagnosis.Empyema-mimicking presentations and postoperative refractory pleural effusion may indicate a poor MPM outcome.

Zimberelimab plus chemotherapy as the first-line treatment of malignant peritoneal mesothelioma:A case report and review of literature

BACKGROUND Malignant peritoneal mesothelioma(MPeM)is a rare cancer with a poor prognosis at advanced stage,and the standard first-line treatment for inoperable patients is chemotherapy.Although combining programmed cell death 1(PD-1)inhibitors with chemotherapy is generally considered safe and effective in several malignant solid tumors,there are few reports regarding initial immunochemotherapy in advanced MPeM.CASE SUMMARY Here,to our knowledge,we present the first case of a patient with epithelioid subtype MPeM,who was treatment-naïve and benefited from initial PD-1 inhibitor plus standard chemotherapy with a prolonged progression-free survival(PFS)and good tolerance.A 49-year-old man was admitted to our hospital for a persistent burning sensation in the abdomen.Computed tomography revealed a solid mass in the lower abdomen,which was subsequently diagnosed histologically as epithelioid subtype MPeM by core needle biopsy.The patient received eight cycles of pemetrexed 800 mg(day 1),cisplatin 60/50 mg(day 1–2),and zimberelimab(PD-1 inhibitor)240 mg(day 1)every 3 wk.He achieved significant reduction of peritoneal tumors with remarkable improvement in symptoms.The best tumor response was partial remission with a final PFS of 7 mo.No immunerelated adverse event occurred during the combination treatment.CONCLUSION The outcome of the present case demonstrates the promising anti-tumor activity of immunochemotherapy to treat inoperable MPeM in the future.

Immunophenotypings of Malignant Epithelial Mesothelioma and Their Roles in the Differential Diagnosis

To investigate the immunophenotypings of malignant epithelial mesothelioma (MEM), and to seek the valuable markers in distinguishing peritoneal MEM from peritoneal metastatic ovarian adenocarcinoma (OA) and colorectal adenocarcinoma (CA), immunohistochemical SP method was used to detect expressions of HBME-1, E-cadherin, CA19-9, MOC-31 and CK7 in paraffin-embedded tissues of 18 cases of MEM, 20 OA and 20 CA. The results showed that there was a significant difference in the expressions of E-cadherin, CA19-9 and MOC-31 between MEM and OA group (P<0.05). Similarly, the difference in the expression of HBME-1, E-cadherin, CA19-9, MOC-31 and CK7 between MEM and CA groups is significant (P<0.05). These results indicate that HBME-1 could be used as a positive marker in distinguishing MEM from CA. E-cadherin, CA19-9 and MOC-31 are considered to be useful negative markers in diagnostic distinction between MEM and metastatic adenocarcinomas, including OA and CA. CK7 is the best positive marker in distinguishing MEM from CA, but this marker appears to be valueless in discriminating MEM from OA.

Reactive oxygen species in the progression and treatment of malignant mesothelioma

Malignant mesothelioma(MM)is an aggressive cancer that affects the pleural and peritoneal mesothelial lining of the lungs and abdomen.Survival rates for patients with MM remain extremely low and effective treatments are limited.MM tumors harbor both genotypic and phenotypic features that indicate MM tumor cells are under increased oxidative stress,similar to other aggressive cancers.This increased oxidative stress in MM cells supports aggressive growth while providing a therapeutic vulnerability exploitable by redox-modulating compounds.MM tumor cells also exhibit altered mitochondrial structure and function that contribute to the disease through perturbations in metabolism and reactive oxygen species(ROS)production and metabolism.Targeting the altered redox status in cancer through increasing cellular ROS levels directly or inhibiting cellular antioxidant pathways and disrupting ROS scavenging mechanisms has become an exciting area for therapeutic intervention.This review discusses ROS sources and signaling,mitochondrial structure and function and targeting mitochondria ROS as a therapeutic approach for the treatment of MM.

GOECP/SEOR clinical guidelines on radiotherapy for malignant pleural mesothelioma

Malignant pleural mesothelioma(MPM)is a rare tumor with poor prognosis and rising incidence.Palliative care is common in MPM as radical treatment with curative intent is often not possible due to metastasis or extensive locoregional involvement.Numerous therapeutic advances have been made in recent years,including the use of less aggressive surgical techniques associated with lower morbidity and mortality(e.g.,pleurectomy/decortication),technological advancements in the field of radiotherapy(intensity-modulated radiotherapy,image-guided radiotherapy,stereotactic body radiotherapy,proton therapy),and developments in systemic therapies(chemotherapy and immunotherapy).These improvements have had as yet only a modest effect on local control and survival.Advances in the management of MPM and standardization of care are hampered by the evidence to date,limited by high heterogeneity among studies and small sample sizes.In this clinical guideline prepared by the oncological group for the study of lung cancer of the Spanish Society of Radiation Oncology,we review clinical,histologic,and therapeutic aspects of MPM,with a particular focus on all aspects relating to radiotherapy,including the current evidence base,associations with chemotherapy and surgery,treatment volumes and planning,technological advances,and reradiation.

Concurrent alcoholic cirrhosis and malignant peritoneal mesothelioma in a patient:A case report

BACKGROUND Malignant peritoneal mesothelioma(MPM)originates from the mesothelial and subcutaneous cells of the abdominal cavity.Its diagnose is difficult due to its nonspecific and vague symptoms,and it should be differentiated from alcoholic cirrhosis and liver and pancreatic cancers.Misdiagnosis and missed diagnosis can easily occur when MPM presents with other diseases.To the best of our knowledge,no case of MPM concurrent with alcoholic cirrhosis has been reported.CASE SUMMARY A 63-year-old man presented to our hospital with abdominal distension for 20days.He had a history of alcohol consumption for nearly 30 years and no history of special drug use or toxic exposure.After treatment for alcoholic cirrhosis in a community hospital,his symptoms did not improve significantly.The patient underwent exploratory laparotomy and surgical resection.Pathologic examination showed an epithelioid MPM.He was treated with chemotherapy and intraperitoneal hyperthermic perfusion after surgery.Currently,he is in a stable condition and tumor recurrence has not occurred.CONCLUSION Misdiagnosis and missed diagnosis of MPM can easily occur because of its insidious onset.Therefore,there is a need to understand.MPM in clinical practice,make the correct diagnosis,and provide timely and effective treatment.

Multiple bowel intussusceptions from metastatic localized malignant pleural mesothelioma:A case report

Localized malignant pleural mesothelioma (LMPM) is a rare occurrence, and gastrointestinal intra-luminal metastases have not previously been reported. Herein, we report a patient with LMPM who presented with a local recurrence 10 mo after initial en bloc surgical resection. Abdominal computed tomography was performed for intractable, vague abdominal pain with episodic vomiting, which showed a "target sign" over the left lower quadrant. Laparotomy revealed several intra-luminal metastatic tumors in the small intestine and colon and a segmental resection of metastatic lesions was performed. Unfortunately, the patient died of sepsis despite successful surgical intervention. Though local recurrence is more frequent in LMPM, the possibility of distant metastasis should not be ignored in patients with non-specifi c abdominal pain.

Malignant peritoneal mesothelioma with massive ascites as the first symptom:A case report

BACKGROUND Malignant peritoneal mesothelioma(MPM) is an extremely rare tumor with nonspecific clinical manifestations,which is extremely difficult to diagnose.Herein,we reported a case of MPM in the abdominal cavity with massive shortterm ascites as the first symptom.CASE SUMMARY A 65-year-old woman presented to the hospital with abdominal pain,distention,and shortness of breath that persisted for 15 d.The serum CA-125 level was 1075 U/m L.The abdominal computed tomography showed massive ascites and no obvious tumor lesions.The pathological examination of the ascitic fluid showed numerous heterotypic cells with some papillary structures.The immunohistochemistry and fluorescence in situ hybridization showed the deletion of CDX2(-),WT-1(-),Ki-67(about 10% +),CEA(-),Glut-1(+++),desmin(-),PD-L1(-),and CDKN2A(P16).The final diagnosis was MPM.The patient refused tumor cytoreductive surgery and received two cycles of cisplatin plus pemetrexed bidirectional chemotherapy.In the second cycle,she received an additional cycle of hyperthermic intraperitoneal chemotherapy and immune checkpoint inhibitor therapy due to massive recalcitrant ascites.She died of disease progression 2 mo after diagnosis.CONCLUSION In case of massive unexplained ascites,the possibility of MPM should not be excluded to avoid misdiagnosis and delay in treatment.

Primary malignant pericardial mesothelioma with difficult antemortem diagnosis:A case report

BACKGROUND Primary malignant pericardial mesothelioma(PMPM)is an extremely rare malignant tumor,and it is difficult to diagnose definitively before death.We present a case in which PMPM was diagnosed at autopsy.We consider this case to be highly suggestive and report it here.CASE SUMMARY A 78-year-old male presented with transient loss of consciousness and falls.The transient loss of consciousness was considered to result from complications of diastolic dysfunction due to pericardial disease,fever with dehydration,and paroxysmal atrial fibrillation.Ultrasound cardiography(UCG)and computed tomography showed cardiac enlargement and high-density pericardial effusion.We considered pericardial disease to be the main pathogenesis of this case.Cardiac magnetic resonance imaging and gadolinium contrast-enhanced T1-weighted images showed thick staining inside and outside the pericardium.Pericardial biopsy was considered to establish a definitive diagnosis,but the patient and his family refused further treatment and examinations,and the patient was followed conservatively.We noticed a thickening of the pericardium and massive changes in the pericardium on UCG over time.We performed an autopsy 60 h after the patient died of pneumonia.Giemsa staining of the autopsy tissue showed an epithelial-like arrangement in the pericardial tumor,and immunostaining showed positive and negative factors for the diagnosis of PMPM.Based on these findings,the final diagnosis of PMPM was made.CONCLUSION PMPM has a poor prognosis,and early diagnosis and treatment are important.The temporal echocardiographic findings may provide a clue for the diagnosis of PMPM.

Complex Target Volume Delineation and Treatment Planning in Radiotherapy for Malignant Pleural Mesothelioma (MPM)

Introduction: Radiotherapy alone or combined with surgery and/or chemotherapy is being investigated in the treatment of malignant pleural mesothelioma (MPM). This study aimed to simulate a Volumetric Modulated Arc Therapy (VMAT) treatment of a patient with MPM. Materials and Methods: CT images from a patient with intact lungs were imported via DICOM into the Pinnacle3 treatment planning (TP) system (TPS) and used as a model for MPM to delineate organs at risk (OAR) and both clinical and planning target volumes (CTV and PTV) with a margin of 5 mm. Elekta Synergy with 6 MV photons and 80 leafs MLCi2 was employed. VMAT plans were generated using two coplanar arcs with gantry rotation angles of 178° - 182°, the collimator angles of each arc were set to 90°, Octavius® 4D 729 was employed for quality assurance while the calculated and measured doses were compared using VeriSoft. Results: A TP was achieved. The Gamma volume analysis with criteria of 3 mm distance to agreement and 3% dose difference yielded the gamma passing rate = 99.9%. The reference isodose was 42.75 Gy with the coverage constraints for the PTV D95 and V95 = 95.0% of 45 Gy. The remaining dosimetric parameters met the recommendations from the clinically acceptable guidelines for the radiotherapy of MPM. Conclusion: Using well-defined TV and VMAT, a consistent TP compared to similar ones from publications was achieved. We obtained a high agreement between the 3D dose reconstructed and the dose calculated.

Extra-pleural pneumonectomy in the setting of tri-modality therapy for patients with malignant pleural mesothelioma

Although declining in the US due to restrictions of asbestos exposure, malignant pleura/mesothelioma （MPP） remains a very serious thoracic malignancy that is rising in incidence worldwide （1）. Trirnodality therapy with chemotherapy and radiotherapy combined with extrapleural pneumonectomy （EPP） has gained acceptance given the acceptable mortality rate （〈5%） and long term survival reported in patients with epithelial histology, negative margins, and no extrapleural lymph node involvement after trimodalitv treatment （2）.

Tsunami of immunotherapy reaches mesothelioma

Malignant pleural mesothelioma(MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase Ⅲ clinical trials published results positioning immunotherapy as a promising option for the first-and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte–associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase Ⅲ trials. In the Check Mate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naive patients and patients with progressive disease after chemotherapy.

THE CLINICOPATHOLOGICAL AND PROGNOSTIC STUDY ON 42 CASES WITH CARDIAC TUMOR

Objective: To analyze the relation between the pathological changes and the clinical manifestations and the prognosis of cardiac tumors through the pathological study on 42 cases with cardiac tumor, in order to improve the knowledge of the tumors, to make early diagnosis and to raise the curative ratio.Materials and Methods: 42 confirmed cardiac tumors of our department were selected, among whick 41was surgical specimen and 1 was autopsy. The study was Pcrformed by using the common and special histochemical staining.Results: 41 is Primary and 1 is secondary which is a metastazed hepatocelular carcinoma. In the Primary ones,39 (95.1%) is benign, including myxoma, fibroma,rhabdomyoma and Pericardial cyst, while 2 (4. 9%) is malignant, including neuroleminafibrosarcoma and malignant mesothelioma. In the myxomas, female patients occupy 75%, 91.7% exists in the left atrium and every one has got a peduncle adbesive to the fossa ovalis or adjacency of the atrial septum.Conclusions: The results of the pathological and prognostic study sbowes cardiac tuinors are quite different from the tumors in other sites, i.e., cven benign ones could cause fatal hemodynamic disturbance. Hence early diagnosis and early operation are necessary and if in such instance, the Prognosis of inost of the benign oncs would be good. But the prognosis of the malignant tumors is worst. The myxomas are different from the organized thrombi in heart cavity. And also the criteria of diagnosis and differential diagnosis are discussed.

Case Report:Malignant peritoneal mesothelioma presenting with persistent high fever

Malignant peritoneal mesothelioma(MPM) is a rare tumor that develops in the peritoneum.In this paper,we describe an extremely rare case of MPM metastasizing to the appendix in a 48-year-old female who initially presented with a persistent high fever.The woman reported a slight lower abdominal discomfort which had been relieved by urination for four months.She had lost 5 kg of weight.There was no nausea,vomiting,diarrhea,ab-dominal pain,or abdominal distension.Many broad spectrum antibiotics were given without relief of fever.Computed tomography(CT) scans revealed a thickened omentum majus and diffused multiple omental nodules.An omentec-tomy,appendectomy,and adnexectomy were carried out.A gross pathologic specimen of omentum tissue revealed a firm gray-white mass.Microscopic and immunohistochemical examinations confirmed the diagnosis of appendiceal and bilateral adnexal metastases of an MPM.These results suggest that MPM should be considered in the differential diagnosis of unexplained persistent high fever.Awareness of such atypical presentations of mesothelioma may help to make a correct diagnosis.

mprovement of Malignant Pleural Mesothelioma Prognosis： Early Diagnosis and Multimodality Treatment

Malignant pleural mesothelioma （MPM） is the most common primary malignancy of the pleura. The occurrence of malignant mesothelioma is typically related to exposure to mineral fibers such as asbestos and erionite.Reports suggest that genetic factors may also play a role in MPM.141 Moreover, latency periods that are the period of time between the first exposure to asbestos and a disease diagnosis range from 20 to 50 years. The mortality burden from asbestos-related diseases （ARD） is heavy andARD accounts for 92,250 deaths per year globally. To improve survival of MPM patients, effective strategy of early diagnosis and effective treatment strategies are highly needed.

Cancer-directed surgery in malignant pleural mesothelioma: extrapleural pneumonectomy and pleurectomy/decortication

Malignant pleural mesothelioma(MPM)is a primary solid malignancy related to inhalational asbestos exposure.Despite advances in therapy,MPM remains challenging to treat with a post-treatment survival of only 15%at 5-year.In recent years,extra-pleural pneumonectomy has decreased in popularity due to a high morbidity rate and mortality compared to pleurectomy/decortication and other therapeutic alternatives.In this review,we will discuss both procedures,outcomes,ongoing studies,and the roles of surgery in the future treatment of this disease.

Sarcomatoid malignant pleural mesothelioma confirmed by full-thickness biopsy

Diffuse malignant pleural mesothelioma （DMPM） is a rare thoracic malignancy, but its incidence isdramatically increasing worldwide as a result ot widespread use of asbestos. The World Health Organization classifies DMPM into three types： epithelioid, sarcomatoid, and biphasic types. DMPM remains suffering poor prognosis and the diagnosis should always be based on adequate, representative tissue samples. There still remains a considerable number of patients with DMPM who are misdiagnosed after a complete investigation including thoracoscopic biopsies.

Promising therapeutic potential of tumor suppressor microRNAs for malignant pleural mesothelioma

Malignant pleural mesothelioma(MPM)is an aggressive and recalcitrant surface neoplasm that defies current multimodality treatments.MicroRNAs(miRNAs)are small noncoding RNAs that epigenetically regulate multiple gene networks and cellular processes.In cancer,miRNA dysregulation is associated with tumorigenesis,with tumor suppressor miRNAs underexpressed or lost,while oncogenic miRNAs are overexpressed.Consequently,miRNAs have emerged as potential therapeutic candidates.Because loss of tumor suppressors predominates the pathophysiology of MPM,re-expressing tumor suppressor miRNAs could be an effective therapeutic strategy.This review highlights the most promising MPM-specific tumor suppressor miRNAs that could be developed into novel therapeutics,the supporting data,and what is known about their molecular mechanism(s).

Immunotherapy in malignant pleural mesothelioma:a long story ended in success

Malignant pleural mesothelioma(MPM)is an aggressive and rare disease,mainly due to asbestos exposure,characterized by a poor prognosis.For almost two decades,platinum-based chemotherapy has been the only approved therapeutic regimen for first-line MPM,with an overall survival of 12 months.In the last years,the therapeutic scenario of different tumor types,including MPM,has dramatically changed due to immune checkpoint inhibition.The promising results of this approach have promoted new efforts into clinical research,and many trials investigating novel therapeutic combinations are currently ongoing.The aim of the present review is to provide a comprehensive overview of the most promising immunotherapeutic-based strategies currently under investigation for advanced MPM.