Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sis...Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sistance and immunosuppressive tumor microenvironment.This review reports the latest studies on combination therapies for mesothelioma,focusing on the potential of integrating chemotherapeutic agents,molecularly targeted agents,vaccines and natural bioactive compounds such as polyphenols.Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients.Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments.Moreover,natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance.While several combination strategies are under clinical investigation,further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.展开更多
BACKGROUND Malignant pleural mesothelioma(MPM),a rare aggressive malignancy,is primarily caused by asbestos exposure.MPM typically affects older adults(median age,76 years),is uncommon in those under age 50 years and ...BACKGROUND Malignant pleural mesothelioma(MPM),a rare aggressive malignancy,is primarily caused by asbestos exposure.MPM typically affects older adults(median age,76 years),is uncommon in those under age 50 years and shows male predominance.Based on the American Society of Clinical Oncology guidelines,F-18 fluorodeoxyglucose positron emission tomography/computed tomography(F-18 FDG PET/CT)is essential for initial MPM staging.Integrating quantitative FDG metabolic data with computed tomography(CT)anatomy optimizes biopsy accuracy and staging.CASE SUMMARY A 21-year-old female college student presented with fever(peak 38.4°C),cough,and white mucoid sputum after cold exposure.Initial evaluation revealed elevated C-reactive protein[C-reactive protein(CRP);65.52 mg/L]and Mycoplasma pneumoniae IgM.Despite resolution of fever following a 14-day moxifloxacin regimen,persistent cough prompted chest CT,which demonstrated left pleural mass-like thickenings.Levofloxacin therapy for 2 weeks failed to alleviate symptoms,accompanied by 2.5-kg weight loss over 1 month.Re-evaluation showed rising CRP(88.87 mg/L)with stable CT lesions,and negative T-cell spot test for tuberculosis and tumor markers.Contrast-enhanced CT revealed heterogeneously enhancing masses,while PET/CT detected two broad-based pleural lesions with intense FDG avidity.CT-guided biopsy confirmed epithelioid MPM.Thoracoscopy exposed diffuse fragile,hemorrhagic nodules implanting on diaphragmatic and parietal pleura,confirming metastatic MPM with partial resection performed.This presentation challenges conventional imaging paradigms of MPM,underscoring its diagnostic complexity.CONCLUSION MPM should still be considered an important differential diagnosis in young patients presenting with solitary pleural masses and no history of typical asbestos exposure.F-18 FDG PET/CT,while serving as an essential component of initial staging for MPM,has some inherent limitations.展开更多
Malignant peritoneal mesothelioma(PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long latency period and non-specific symptomatology, a diagnosis of PM can be sugg...Malignant peritoneal mesothelioma(PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long latency period and non-specific symptomatology, a diagnosis of PM can be suggested by occupational exposure history, but ultimately relies heavily on imaging and diagnostic biopsy. Early treatment options including palliative operative debulking, intraperitoneal chemotherapy, and systemic chemotherapy have marginally improved the natural course of the disease with median survival being approximately one year. The advent of cytoreduction(CRS) with hyperthermic intraperitoneal chemotherapy(HIPEC) has dramatically improved survival outcomes with wide median survival estimates between 2.5 to 9 years; these studies however remain largely heterogeneous, with differing study populations, tumor biology, and specific treatment regimens. More recent investigations have explored extent of cytoreduction, repeated operative intervention, and choice of chemotherapy but have been unable to offer definitive conclusions. CRS and HIPEC remain morbid procedures with complication rates ranging between 30% to 46% in larger series. Ac-cordingly, an increasing interest in identifying molecular targets and developing targeted therapies is emerging. Among such novel targets is sphingosine kinase 1(SphK1) which regulates the production of sphingosine-1-phosphate, a biologically active lipid implicated in various cancers including malignant mesothelioma. The known action of specific SphK inhibitors may warrant further exploration in peritoneal disease.展开更多
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 advance...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.展开更多
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...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.展开更多
Malignant mesothelioma is a highly aggressive neoplasm.The incidence of malignant mesothelioma is increasing worldwide.Diffuse malignant peritoneal mesothelioma(DMPM) represents one-fourth of all mesotheliomas.Associa...Malignant mesothelioma is a highly aggressive neoplasm.The incidence of malignant mesothelioma is increasing worldwide.Diffuse malignant peritoneal mesothelioma(DMPM) represents one-fourth of all mesotheliomas.Association of asbestos exposure with DMPM has been observed,especially in males.The great majority of patients present with abdominal pain and distension,caused by accumulation of tumors and ascitic ? uid.In the past,DMPM was considered a pre-terminal condition;therefore attracted little attention.Patients invariably died from their disease within a year.Recently,several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy.This remarkable improvement in survival has prompted new search into the medical science related to DMPM,a disease previously ignored as uninteresting.This review article focuses on the key advances in the epidemiology,diagnosis,staging,treatments and prognosis of DMPM that have occurred in the past decade.展开更多
Benign multicystic peritoneal mesothelioma(BMPM)is a rare cystic mesothelial lesion that occurs predominantly in reproductive aged women.A 56-year-old Caucasian male was admitted to our surgical department with a chie...Benign multicystic peritoneal mesothelioma(BMPM)is a rare cystic mesothelial lesion that occurs predominantly in reproductive aged women.A 56-year-old Caucasian male was admitted to our surgical department with a chief complaint of a painful mass in his right lower abdomen for almost 2 years.The physical examination revealed a palpable painful mass.Computed tomography demonstrated an irregular,cystic tumor in his right lower abdomen.There was no obvious capsule or internal septations.No enhancement after intravenous administration of contrast was noted.An exploratory laparotomy was performed,and a multicystic tumor and adherent to the caecum was noted.The walls of the cysts were thin and smooth,filled with clear fluid,and very friable.An en bloc resection of the tumor,including appendix and caecum,was performed.Histological examination revealed multiple cysts lined with flattened simple epithelial cells,and the capsule walls of the cysts were composed of fibrous tissue.Immunohistochemical analysis documented positive expression of mesothelial cells and calretinin.The final diagnosis was BMPM.The patient was well at 6-mo follow-up.BMPM is exceedingly rare lesion.A complete resection of the tumor is required.The diagnosis of BMPM is based on pathological analysis.展开更多
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 presen...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.展开更多
Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon and rapidly fatal tumor.Therapeutic options have traditionally been limited and ineffective.The biologic and molecular events correlated with poor respon...Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon and rapidly fatal tumor.Therapeutic options have traditionally been limited and ineffective.The biologic and molecular events correlated with poor responsiveness to therapy are still poorly understood.In recent years,an innovative treatment approach involving aggressive cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has reportedly resulted in improved outcome,as compared to historical controls.Since 1995,at the National Cancer Institute (NCI) of Milan (Italy),patients with DMPM have been treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC).In the present paper,clinical experiences and basic science investigations on DMPM at Milan NCI are reviewed.Perioperative and long-term outcome results with CRS and HIPEC are presented.Clinico-pathological prognostic factors were investigated by multivariate analysis.The pathologic features and immunohistochemical markers related to DMPM biologic behavior were assessed in a large case-series uniformly treated at our institution.The prevalence and prognostic role of telomere maintenance mechanisms,which account for the limitless cell replicative potential of many malignancies,were studied.The dysregulation of the apoptotic pathways may play a role in the relative chemo-resistance of DMPM and a better understanding of apoptosis-related mechanisms could result in novel targeted therapeutic strategies.On this basis,the expression of survivin and other IAP family members (IAP-1,IAP-2,and X-IAP),the pro-apoptotic protein Smac/DIABLO,and antigens associated with cell proliferation (Ki-67) and apoptosis (caspase-cleaved cytokeratin-18) were analyzed.Finally,analyses of EGFR,PDGFRA and PDGFRB were performed to ascertain if deregulation of RTK could offer useful alternative therapeutic targets.展开更多
Mesothelioma develops most commonly in the pleura, and less frequently in the peritoneum. Usually, it manifests as diffuse peritoneal thickening and multiple nodules, and rarely as a solitary mass. We report a rare ca...Mesothelioma develops most commonly in the pleura, and less frequently in the peritoneum. Usually, it manifests as diffuse peritoneal thickening and multiple nodules, and rarely as a solitary mass. We report a rare case of primary malignant mesothelioma of the greater omentum, which mimicked omental infarct. A 54-year-old Korean man was admitted because of severe abdominal pain of sudden onset. A tender mass with indistinct margins was palpated in the upper abdomen. Abdominal ultrasound and computed tomography showed an ill- def ined mass in the greater omentum and little ascites in the peri-hepatic space, and neutrophil-dominant exudates were documented on paracentesis. Intravenous antibiotics and analgesics were given for omental infarction with superimposed infection, which resulted in symptomatic improvement. The imaging studies after a week revealed a growing mass and ascites. Laparoscopic surgery was performed and an 8 cm×3.3 cm greater omental mass was found, with multiple small nodules on the peritoneum, diaphragm, and pelvic cavity wall. Histological examination showed proliferating malignant epithelioid cells that stained strongly for calretinin, which was compatible with malignant mesothelioma. We recommend that primary omental mesothelioma should be included in the differential diagnosis of patients with omental infarction, despite its rarity.展开更多
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 s...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.展开更多
Malignant peritoneal mesothelioma is a rare aggres-sive tumor of the peritoneum. An increasing number of malignant mesothelioma cases have been reported in recent years. We report here a very rare case of malignant pe...Malignant peritoneal mesothelioma is a rare aggres-sive tumor of the peritoneum. An increasing number of malignant mesothelioma cases have been reported in recent years. We report here a very rare case of malignant peritoneal mesothelioma with both umbilical hernia and umbilical metastasis which is also called Sister Mary Joseph's nodule. We performed laparoscopy which showed specific laparoscopic findings, and the pathological findings of the biopsy specimen led to the diagnosis. This case was associated with umbilical her-nia which could be induced by massive ascites. A newly developed abdominal hernia should be noted as a primary symptom of malignant peritoneal mesothelioma, as shown in the present case.展开更多
Benign multicystic peritoneal mesothelioma （BMPM） is a rare tumor that occurs mainly in women in their reproductive age. The pathogenesis of BMPM is unclear and a controversy regarding its neoplastic and reactive na...Benign multicystic peritoneal mesothelioma （BMPM） is a rare tumor that occurs mainly in women in their reproductive age. The pathogenesis of BMPM is unclear and a controversy regarding its neoplastic and reactive nature exists. The biological behavior of BMPM is characterized by its slowly progressive process and high rate of recurrence after surgical resection. In addition this lesion does not present a strong tendency to transform into malignancy. Today approximately 130 cases have been reported. We here report a 62-year-old woman who had diffuse abdominal pain, nausea and vomiting. Physical examination revealed a painful mass in her upper abdomen. She reported a mild dehydration, but the vital signs were normal. Peristaltic rushes, gurgles and highpitched tinkles were audible. Upright plain abdominal film revealed small bowel loops with air-fluid levels. She was diagnosed having an incarcerated incisional hernia that resulted in intestinal obstruction. The patient underwent surgery during which a cystic mass of the right ovary measuring 6 cm × 5 cm × 4 cm, four small cysts of the small bowel （1 cm in diameter） and a cyst at the retroperitoneum measuring 11 cm× 10 cm × 3 cm were found. Complete resection of the lesion was performed. The patient had an uneventful recovery and had no recurrence two years after surgery.展开更多
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 extensi...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.展开更多
Malignant pleural mesothelioma is a rare primary tumor rising from the pleura and is associated with exposure to asbestos fibers. Mesothelioma is a locally aggressive disease that usually presents at an advanced stage...Malignant pleural mesothelioma is a rare primary tumor rising from the pleura and is associated with exposure to asbestos fibers. Mesothelioma is a locally aggressive disease that usually presents at an advanced stage and has a median overall survival of 1 year. Treatment options rarely result in cure of disease and range from trimodality treatment, including chemotherapy, radiation, and surgery, to supportive care. In patients with limited local disease and good functional status, trimodality treatment with extra-pleural pneumonectomy, chemotherapy, and radiation is frequently employed. Best supportive care should be instituted for patients with metastatic disease and poor functional status. Palliative therapy focuses on control of pleural effusions with drainage techniques and pain with radiation therapy. Novel therapies are showing promise, including photodynamic therapy, immunotherapy, and molecular targeted therapy.展开更多
The copper(Ⅱ)diethyldithiocarbamate(Cu(DDC)2)complex exhibited excellent inhibition to cancer cells.The usual administration is intravenous injection for disulfram and oral for copper.A new strategy was reported to i...The copper(Ⅱ)diethyldithiocarbamate(Cu(DDC)2)complex exhibited excellent inhibition to cancer cells.The usual administration is intravenous injection for disulfram and oral for copper.A new strategy was reported to improve the administration efficiency of the Cu(DDC)2 drug.Poly(lactide-co-glycolide)(PLGA)nanoparticles were used to trap disulfram and copper gluconate separately,the two types of drug loaded nanoparticles were injected in mesothelioma-bearing nude mice via intraperitoneal injection.The in vivo formation of Cu(DDC)2 complex was induced by disulfiram and Cu^2+ released from PLGA nanoparticles.This stra tegy avoided many obstacles in the use of Cu(DDC)2 complex as chemothe rapeutic and exhibited excellent anticancer activity to mesothelioma.展开更多
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 diff...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.展开更多
Background: Malignant pleural mesothelioma is a lethal disease and hence the strong need for identifying new prognostic factors. Methods: This is a retrospective study including all eligible patients with advanced mal...Background: Malignant pleural mesothelioma is a lethal disease and hence the strong need for identifying new prognostic factors. Methods: This is a retrospective study including all eligible patients with advanced malignant pleural mesothelioma (MPM) presenting to National Cancer Institute, Cairo University. Neutrophil lymphocyte (N/L) ratio was assessed before second line chemotherapy. 2.5 was used as the cutoff point. Endpoints were the assessment of correlation between N/L ratio and clinical response (CR), progression free survival (PFS) and overall survival (OS). Results: 52 patients (19 stage III and 33 stage IV) MPM were included and followed up during the period from July 2009 till November 2012 with a median follow-up period of 2.6 months. 87.5% of patients with N/L ratio > 2.5 showed progressive disease versus 91.7% in patients with N/L ratio < 2.5 (P-value = 0.66). 6-month PFS was 11% for patients with N/L ratio > 2.5 versus 14% for patients with N/L ratio < 2.5 (P-value = 0.001). 6-month OS was 72% for patients with N/L ratio > 2.5 versus 66% for patients with N/L ratio < 2.5 (P-value = 0.4). Conclusion: N/L ratio is a potential prognostic marker for advanced MPM treated with second line chemotherapy.展开更多
Crocidolite was found to be ubiquitous in a county in southwestern China. It had been widely used in the making of road pavement, stoves, wall paint, etc. The environmental levels of the asbestos fibers were determine...Crocidolite was found to be ubiquitous in a county in southwestern China. It had been widely used in the making of road pavement, stoves, wall paint, etc. The environmental levels of the asbestos fibers were determined. Of the 2175 local residents examined. 16 had asbestosis and 232 had pleural plaques. These clinical manifestations were noted mainly in patients over 50 years of age. (c)1990 Academic Press. Inc.展开更多
BACKGROUND We report the first case,to the best of our knowledge,of massive ascites due to recurrent malignant pleural mesothelioma that was controlled using KM-cell-free and concentrated ascites reinfusion therapy(KM...BACKGROUND We report the first case,to the best of our knowledge,of massive ascites due to recurrent malignant pleural mesothelioma that was controlled using KM-cell-free and concentrated ascites reinfusion therapy(KM-CART).The tumor cells derived via KM-CART were utilized secondarily in an in vitro cell growth assay using the collagen gel droplet-embedded culture drug sensitivity test(CD-DST)to investigate anticancer drug susceptibility.CASE SUMMARY A 56-year-old man presented with recurrent malignant mesothelioma with massive ascites;more than 4000 mL of ascitic fluid was removed,filtered,and concentrated using KM-CART,and the cell-free ascitic fluid was reinfused into the patient to improve quality of life.Cancer cells isolated secondarily in an in vitro proliferation assay using CD-DST exhibited low sensitivity to pemetrexed and high sensitivity to gemcitabine.Treatment with gemcitabine maintained stable disease for 4 mo.CONCLUSION The combination of KM-CART and CD-DST may be a promising treatment option for malignant ascites associated with malignant mesothelioma.展开更多
基金funded by a grant fromtheMinistero dell’Universita e della Ricerca,PRIN 2022 PNRR grant(Prot.P2022LZXNWto R.B.).
文摘Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sistance and immunosuppressive tumor microenvironment.This review reports the latest studies on combination therapies for mesothelioma,focusing on the potential of integrating chemotherapeutic agents,molecularly targeted agents,vaccines and natural bioactive compounds such as polyphenols.Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients.Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments.Moreover,natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance.While several combination strategies are under clinical investigation,further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.
基金Supported by the Tianjin Science and Technology Project,No.TJWJ2025RC008。
文摘BACKGROUND Malignant pleural mesothelioma(MPM),a rare aggressive malignancy,is primarily caused by asbestos exposure.MPM typically affects older adults(median age,76 years),is uncommon in those under age 50 years and shows male predominance.Based on the American Society of Clinical Oncology guidelines,F-18 fluorodeoxyglucose positron emission tomography/computed tomography(F-18 FDG PET/CT)is essential for initial MPM staging.Integrating quantitative FDG metabolic data with computed tomography(CT)anatomy optimizes biopsy accuracy and staging.CASE SUMMARY A 21-year-old female college student presented with fever(peak 38.4°C),cough,and white mucoid sputum after cold exposure.Initial evaluation revealed elevated C-reactive protein[C-reactive protein(CRP);65.52 mg/L]and Mycoplasma pneumoniae IgM.Despite resolution of fever following a 14-day moxifloxacin regimen,persistent cough prompted chest CT,which demonstrated left pleural mass-like thickenings.Levofloxacin therapy for 2 weeks failed to alleviate symptoms,accompanied by 2.5-kg weight loss over 1 month.Re-evaluation showed rising CRP(88.87 mg/L)with stable CT lesions,and negative T-cell spot test for tuberculosis and tumor markers.Contrast-enhanced CT revealed heterogeneously enhancing masses,while PET/CT detected two broad-based pleural lesions with intense FDG avidity.CT-guided biopsy confirmed epithelioid MPM.Thoracoscopy exposed diffuse fragile,hemorrhagic nodules implanting on diaphragmatic and parietal pleura,confirming metastatic MPM with partial resection performed.This presentation challenges conventional imaging paradigms of MPM,underscoring its diagnostic complexity.CONCLUSION MPM should still be considered an important differential diagnosis in young patients presenting with solitary pleural masses and no history of typical asbestos exposure.F-18 FDG PET/CT,while serving as an essential component of initial staging for MPM,has some inherent limitations.
基金Supported by United States National Institute of Health(to Kazuaki Takabe),No.R01CA160688Investigator Initiated Research Grant(to Susan G Komen),No.IIR12222224
文摘Malignant peritoneal mesothelioma(PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long latency period and non-specific symptomatology, a diagnosis of PM can be suggested by occupational exposure history, but ultimately relies heavily on imaging and diagnostic biopsy. Early treatment options including palliative operative debulking, intraperitoneal chemotherapy, and systemic chemotherapy have marginally improved the natural course of the disease with median survival being approximately one year. The advent of cytoreduction(CRS) with hyperthermic intraperitoneal chemotherapy(HIPEC) has dramatically improved survival outcomes with wide median survival estimates between 2.5 to 9 years; these studies however remain largely heterogeneous, with differing study populations, tumor biology, and specific treatment regimens. More recent investigations have explored extent of cytoreduction, repeated operative intervention, and choice of chemotherapy but have been unable to offer definitive conclusions. CRS and HIPEC remain morbid procedures with complication rates ranging between 30% to 46% in larger series. Ac-cordingly, an increasing interest in identifying molecular targets and developing targeted therapies is emerging. Among such novel targets is sphingosine kinase 1(SphK1) which regulates the production of sphingosine-1-phosphate, a biologically active lipid implicated in various cancers including malignant mesothelioma. The known action of specific SphK inhibitors may warrant further exploration in peritoneal disease.
文摘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.
文摘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.
文摘Malignant mesothelioma is a highly aggressive neoplasm.The incidence of malignant mesothelioma is increasing worldwide.Diffuse malignant peritoneal mesothelioma(DMPM) represents one-fourth of all mesotheliomas.Association of asbestos exposure with DMPM has been observed,especially in males.The great majority of patients present with abdominal pain and distension,caused by accumulation of tumors and ascitic ? uid.In the past,DMPM was considered a pre-terminal condition;therefore attracted little attention.Patients invariably died from their disease within a year.Recently,several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy.This remarkable improvement in survival has prompted new search into the medical science related to DMPM,a disease previously ignored as uninteresting.This review article focuses on the key advances in the epidemiology,diagnosis,staging,treatments and prognosis of DMPM that have occurred in the past decade.
文摘Benign multicystic peritoneal mesothelioma(BMPM)is a rare cystic mesothelial lesion that occurs predominantly in reproductive aged women.A 56-year-old Caucasian male was admitted to our surgical department with a chief complaint of a painful mass in his right lower abdomen for almost 2 years.The physical examination revealed a palpable painful mass.Computed tomography demonstrated an irregular,cystic tumor in his right lower abdomen.There was no obvious capsule or internal septations.No enhancement after intravenous administration of contrast was noted.An exploratory laparotomy was performed,and a multicystic tumor and adherent to the caecum was noted.The walls of the cysts were thin and smooth,filled with clear fluid,and very friable.An en bloc resection of the tumor,including appendix and caecum,was performed.Histological examination revealed multiple cysts lined with flattened simple epithelial cells,and the capsule walls of the cysts were composed of fibrous tissue.Immunohistochemical analysis documented positive expression of mesothelial cells and calretinin.The final diagnosis was BMPM.The patient was well at 6-mo follow-up.BMPM is exceedingly rare lesion.A complete resection of the tumor is required.The diagnosis of BMPM is based on pathological analysis.
文摘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.
文摘Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon and rapidly fatal tumor.Therapeutic options have traditionally been limited and ineffective.The biologic and molecular events correlated with poor responsiveness to therapy are still poorly understood.In recent years,an innovative treatment approach involving aggressive cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has reportedly resulted in improved outcome,as compared to historical controls.Since 1995,at the National Cancer Institute (NCI) of Milan (Italy),patients with DMPM have been treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC).In the present paper,clinical experiences and basic science investigations on DMPM at Milan NCI are reviewed.Perioperative and long-term outcome results with CRS and HIPEC are presented.Clinico-pathological prognostic factors were investigated by multivariate analysis.The pathologic features and immunohistochemical markers related to DMPM biologic behavior were assessed in a large case-series uniformly treated at our institution.The prevalence and prognostic role of telomere maintenance mechanisms,which account for the limitless cell replicative potential of many malignancies,were studied.The dysregulation of the apoptotic pathways may play a role in the relative chemo-resistance of DMPM and a better understanding of apoptosis-related mechanisms could result in novel targeted therapeutic strategies.On this basis,the expression of survivin and other IAP family members (IAP-1,IAP-2,and X-IAP),the pro-apoptotic protein Smac/DIABLO,and antigens associated with cell proliferation (Ki-67) and apoptosis (caspase-cleaved cytokeratin-18) were analyzed.Finally,analyses of EGFR,PDGFRA and PDGFRB were performed to ascertain if deregulation of RTK could offer useful alternative therapeutic targets.
文摘Mesothelioma develops most commonly in the pleura, and less frequently in the peritoneum. Usually, it manifests as diffuse peritoneal thickening and multiple nodules, and rarely as a solitary mass. We report a rare case of primary malignant mesothelioma of the greater omentum, which mimicked omental infarct. A 54-year-old Korean man was admitted because of severe abdominal pain of sudden onset. A tender mass with indistinct margins was palpated in the upper abdomen. Abdominal ultrasound and computed tomography showed an ill- def ined mass in the greater omentum and little ascites in the peri-hepatic space, and neutrophil-dominant exudates were documented on paracentesis. Intravenous antibiotics and analgesics were given for omental infarction with superimposed infection, which resulted in symptomatic improvement. The imaging studies after a week revealed a growing mass and ascites. Laparoscopic surgery was performed and an 8 cm×3.3 cm greater omental mass was found, with multiple small nodules on the peritoneum, diaphragm, and pelvic cavity wall. Histological examination showed proliferating malignant epithelioid cells that stained strongly for calretinin, which was compatible with malignant mesothelioma. We recommend that primary omental mesothelioma should be included in the differential diagnosis of patients with omental infarction, despite its rarity.
文摘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.
文摘Malignant peritoneal mesothelioma is a rare aggres-sive tumor of the peritoneum. An increasing number of malignant mesothelioma cases have been reported in recent years. We report here a very rare case of malignant peritoneal mesothelioma with both umbilical hernia and umbilical metastasis which is also called Sister Mary Joseph's nodule. We performed laparoscopy which showed specific laparoscopic findings, and the pathological findings of the biopsy specimen led to the diagnosis. This case was associated with umbilical her-nia which could be induced by massive ascites. A newly developed abdominal hernia should be noted as a primary symptom of malignant peritoneal mesothelioma, as shown in the present case.
文摘Benign multicystic peritoneal mesothelioma （BMPM） is a rare tumor that occurs mainly in women in their reproductive age. The pathogenesis of BMPM is unclear and a controversy regarding its neoplastic and reactive nature exists. The biological behavior of BMPM is characterized by its slowly progressive process and high rate of recurrence after surgical resection. In addition this lesion does not present a strong tendency to transform into malignancy. Today approximately 130 cases have been reported. We here report a 62-year-old woman who had diffuse abdominal pain, nausea and vomiting. Physical examination revealed a painful mass in her upper abdomen. She reported a mild dehydration, but the vital signs were normal. Peristaltic rushes, gurgles and highpitched tinkles were audible. Upright plain abdominal film revealed small bowel loops with air-fluid levels. She was diagnosed having an incarcerated incisional hernia that resulted in intestinal obstruction. The patient underwent surgery during which a cystic mass of the right ovary measuring 6 cm × 5 cm × 4 cm, four small cysts of the small bowel （1 cm in diameter） and a cyst at the retroperitoneum measuring 11 cm× 10 cm × 3 cm were found. Complete resection of the lesion was performed. The patient had an uneventful recovery and had no recurrence two years after surgery.
文摘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.
文摘Malignant pleural mesothelioma is a rare primary tumor rising from the pleura and is associated with exposure to asbestos fibers. Mesothelioma is a locally aggressive disease that usually presents at an advanced stage and has a median overall survival of 1 year. Treatment options rarely result in cure of disease and range from trimodality treatment, including chemotherapy, radiation, and surgery, to supportive care. In patients with limited local disease and good functional status, trimodality treatment with extra-pleural pneumonectomy, chemotherapy, and radiation is frequently employed. Best supportive care should be instituted for patients with metastatic disease and poor functional status. Palliative therapy focuses on control of pleural effusions with drainage techniques and pain with radiation therapy. Novel therapies are showing promise, including photodynamic therapy, immunotherapy, and molecular targeted therapy.
基金the National Natural Science Foundation of China(No.51773130)Natural Science Foundation of Shandong Province(No.ZR2017MC072)。
文摘The copper(Ⅱ)diethyldithiocarbamate(Cu(DDC)2)complex exhibited excellent inhibition to cancer cells.The usual administration is intravenous injection for disulfram and oral for copper.A new strategy was reported to improve the administration efficiency of the Cu(DDC)2 drug.Poly(lactide-co-glycolide)(PLGA)nanoparticles were used to trap disulfram and copper gluconate separately,the two types of drug loaded nanoparticles were injected in mesothelioma-bearing nude mice via intraperitoneal injection.The in vivo formation of Cu(DDC)2 complex was induced by disulfiram and Cu^2+ released from PLGA nanoparticles.This stra tegy avoided many obstacles in the use of Cu(DDC)2 complex as chemothe rapeutic and exhibited excellent anticancer activity to mesothelioma.
基金Shandong Province Medical and Health Science and Technology Development Plan,No.202003030878.
文摘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.
文摘Background: Malignant pleural mesothelioma is a lethal disease and hence the strong need for identifying new prognostic factors. Methods: This is a retrospective study including all eligible patients with advanced malignant pleural mesothelioma (MPM) presenting to National Cancer Institute, Cairo University. Neutrophil lymphocyte (N/L) ratio was assessed before second line chemotherapy. 2.5 was used as the cutoff point. Endpoints were the assessment of correlation between N/L ratio and clinical response (CR), progression free survival (PFS) and overall survival (OS). Results: 52 patients (19 stage III and 33 stage IV) MPM were included and followed up during the period from July 2009 till November 2012 with a median follow-up period of 2.6 months. 87.5% of patients with N/L ratio > 2.5 showed progressive disease versus 91.7% in patients with N/L ratio < 2.5 (P-value = 0.66). 6-month PFS was 11% for patients with N/L ratio > 2.5 versus 14% for patients with N/L ratio < 2.5 (P-value = 0.001). 6-month OS was 72% for patients with N/L ratio > 2.5 versus 66% for patients with N/L ratio < 2.5 (P-value = 0.4). Conclusion: N/L ratio is a potential prognostic marker for advanced MPM treated with second line chemotherapy.
文摘Crocidolite was found to be ubiquitous in a county in southwestern China. It had been widely used in the making of road pavement, stoves, wall paint, etc. The environmental levels of the asbestos fibers were determined. Of the 2175 local residents examined. 16 had asbestosis and 232 had pleural plaques. These clinical manifestations were noted mainly in patients over 50 years of age. (c)1990 Academic Press. Inc.
文摘BACKGROUND We report the first case,to the best of our knowledge,of massive ascites due to recurrent malignant pleural mesothelioma that was controlled using KM-cell-free and concentrated ascites reinfusion therapy(KM-CART).The tumor cells derived via KM-CART were utilized secondarily in an in vitro cell growth assay using the collagen gel droplet-embedded culture drug sensitivity test(CD-DST)to investigate anticancer drug susceptibility.CASE SUMMARY A 56-year-old man presented with recurrent malignant mesothelioma with massive ascites;more than 4000 mL of ascitic fluid was removed,filtered,and concentrated using KM-CART,and the cell-free ascitic fluid was reinfused into the patient to improve quality of life.Cancer cells isolated secondarily in an in vitro proliferation assay using CD-DST exhibited low sensitivity to pemetrexed and high sensitivity to gemcitabine.Treatment with gemcitabine maintained stable disease for 4 mo.CONCLUSION The combination of KM-CART and CD-DST may be a promising treatment option for malignant ascites associated with malignant mesothelioma.
