Assuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Mesotelioma Maligno/terapia , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Neoplasias Peritoneais/patologia , Procedimentos Cirúrgicos de Citorredução , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Estudos RetrospectivosRESUMO
Malignant pleural mesothelioma (MPM) is a severe form of cancer that originates from mesothelium cells. Around 54-90% of mesotheliomas are associated with pleural effusions. Brucea Javanica Oil Emulsion (BJOE) is the processed oil derived from the seeds of Brucea javanica, which has shown potential as a treatment option for several types of cancer. Here, we present a case study of a MPM patient with malignant pleural effusion who received intrapleural injection of BJOE. The treatment resulted in the complete response of pleural effusion and chest tightness. While the precise mechanisms underlying the therapeutic effects of BJOE for pleural effusion are not yet fully understood, it has demonstrated a satisfactory clinical response without significant adverse effects.
Assuntos
Brucea , Mesotelioma Maligno , Mesotelioma , Derrame Pleural Maligno , Humanos , Brucea javanica , Emulsões/uso terapêutico , Mesotelioma/complicações , Mesotelioma/tratamento farmacológico , Óleos de Plantas/uso terapêutico , Derrame Pleural Maligno/tratamento farmacológico , Derrame Pleural Maligno/patologiaRESUMO
BACKGROUND Malignant mesotheliomas are rare, yet highly malignant tumors. Mesotheliomas are tumors that develop from mesothelial surfaces, with the pleura being the most common, followed by the peritoneum. The diagnosis of malignant peritoneal mesothelioma (MPM) is usually established when the disease is advanced, owing to the nonspecific clinical appearance and abdominal symptoms. Initially, MPM was treated with palliative systemic chemotherapy, with or without palliative surgery. However, cytoreductive surgery (CRS) combined with bidirectional intraoperative chemotherapy (BDIC) has recently emerged as a treatment option for MPM. BDIC creates a bidirectional chemotherapy gradient in the peritoneal tumor cells through the simultaneous use of intraperitoneal and intravenous chemotherapy. CRS, combined with BDIC (CRS-BDIC), allows the complete elimination of residual tiny tumor cells after complete removal of the visible tumor nodules. CASE REPORT Herein, we present a case of a 51-year-old woman with MPM and chronic kidney disease (CKD) stage 3b. Her treatment consisted of neoadjuvant chemotherapy and immunotherapy, followed by CRS-BDIC using intraperitoneal cisplatin and doxorubicin, and intravenous ifosfamide. The surgery was successful, with no immediate complications or decline in the patient's kidney function. On follow up 2 months later, the patient denies suffering any chemotherapy-related adverse effects, and her kidney profile remains stable. CONCLUSIONS In conclusion, nephrotoxicity, a known adverse effect of cisplatin and ifosfamide, might not be a contraindication for the use of these potentially nephrotoxic drugs in CRS-BDIC in patients with renal impairment.
Assuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Insuficiência Renal Crônica , Insuficiência Renal , Feminino , Humanos , Pessoa de Meia-Idade , Mesotelioma Maligno/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Ifosfamida/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Terapia Combinada , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Insuficiência Renal/tratamento farmacológicoRESUMO
INTRODUCTION: Hyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high-dose magnesium attenuates cisplatin-induced AKI (CP-AKI) in animal models but has not been rigorously examined in humans. METHODS: We tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36-h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B. RESULTS: In Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium. CONCLUSIONS: A 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC-associated AKI.
Assuntos
Injúria Renal Aguda , Mesotelioma Maligno , Mesotelioma , Humanos , Cisplatino/efeitos adversos , Projetos Piloto , Magnésio/uso terapêutico , Bradicardia/induzido quimicamente , Bradicardia/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Mesotelioma Maligno/induzido quimicamente , Mesotelioma Maligno/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológicoAssuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Procedimentos Cirúrgicos de Citorredução , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia CombinadaRESUMO
BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an aggressive malignancy with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes, but recurrence rates remain high. Dendritic cell-based immunotherapy (DCBI) showed promising results in patients with pleural mesothelioma. The primary aim of this trial was to determine feasibility of adjuvant DCBI after CRS-HIPEC. METHODS: This open-label, single-center, phase II clinical trial, performed in the Erasmus MC Cancer Institute Rotterdam, the Netherlands, included patients with epithelioid MPM. 4-6 weeks before CRS-HIPEC leukapheresis was performed. 8-10 weeks after surgery, DCBI was administered three times biweekly. Feasibility was defined as administration of at least three adjuvant vaccinations in 75% of patients. Comprehensive immune cell profiling was performed on peripheral blood samples prior to and during treatment. RESULTS: All patients who received CRS-HIPEC (n=16) were successfully treated with adjuvant DCBI. No severe toxicity related to DCBI was observed. Median progression-free survival (PFS) was 12 months (IQR 5-23) and median overall survival was not reached. DCBI was associated with increased proliferation of circulating natural killer cells and CD4+ T-helper (Th) cells. Co-stimulatory molecules, including ICOS, HLA-DR, and CD28 were upregulated predominantly on memory or proliferating Th-cells and minimally on CD8+ cytotoxic T-lymphocytes (CTLs) after treatment. However, an increase in CD8+ terminally differentiated effector memory (Temra) cells positively correlated with PFS, whereas co-expression of ICOS and Ki67 on CTLs trended towards a positive correlation. CONCLUSIONS: Adjuvant DCBI after CRS-HIPEC in patients with MPM was feasible and safe, and showed promising survival outcomes. DCBI had an immune modulatory effect on lymphoid cells and induced memory T-cell activation. Moreover, an increase of CD8+ Temra cells was more pronounced in patients with longer PFS. These data provide rationale for future combination treatment strategies. TRIAL REGISTRATION NUMBER: NTR7060; Dutch Trial Register (NTR).
Assuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hipertermia Induzida/métodos , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Imunoterapia , Células Dendríticas/patologiaAssuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Terapia Combinada , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5-68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17-92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.
Assuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Mitomicina/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Mesotelioma/tratamento farmacológico , Mesotelioma Maligno/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Perfusão , Organoides/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos RetrospectivosRESUMO
OBJECTIVES: To establish a Bayesian network (BN) model to predict the survival of patients with malignant peritoneal mesothelioma (MPM) treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: The clinicopathological data of 154 MPM patients treated with CRS + HIPEC at our hospital from April 2015 to November 2022 were retrospectively analyzed. They were randomly divided into two groups in a 7:3 ratio. Survival analysis was conducted on the training set and a BN model was established. The accuracy of the model was validated using a confusion matrix of the testing set. The receiver operating characteristic (ROC) curve and area under the curve were used to evaluate the overall performance of the BN model. RESULTS: Survival analysis of 107 patients (69.5%) in the training set found ten factors affecting patient prognosis: age, Karnofsky performance score, surgical history, ascites volume, peritoneal cancer index, organ resections, red blood cell transfusion, pathological types, lymphatic metastasis, and Ki-67 index (all p < 0.05). The BN model was successfully established after the above factors were included, and the BN model structure was adjusted according to previous research and clinical experience. The results of confusion matrix obtained by internal validation of 47 cases in the testing set showed that the accuracy of BN model was 72.7%, and the area under ROC was 0.74. CONCLUSIONS: The BN model was established successfully with good overall performance and can be used as a clinical decision reference.
Assuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Teorema de Bayes , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Quimioterapia Intraperitoneal Hipertérmica , Mesotelioma/tratamento farmacológico , Mesotelioma/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVES: The aim of this study is to evaluate the results of treatment of diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) at a single center. METHODS: We conducted a retrospective single-center observational cohort study of consecutive patients with DMPM treated by CRS-HIPEC at the Department of Surgery I of the University Hospital in Olomouc, Czech Republic. RESULTS: Data on a total of 16 patients were processed. The study group of 16 patients had six (37.5 %) women. The mean age was approximately 62 years. Complete cytoreduction was achieved in all patients (100 %) (CC0: 75 %, CC1: 25 %). All patients underwent a closed form of HIPEC with cisplatin and doxorubicin for 90 min. The mean hospital stay was 13.5 days, including 4.38 days in the ICU (13.5 ± 5.07 and 4.38 ± 1.49, respectively). Major postoperative complications (CD grades 3-4) occurred in four patients (25 %). In-hospital mortality was 6.25 %. In the study group, the median overall survival was 20 months, and the median disease-free survival was 10.3 months. CONCLUSIONS: Also under the conditions at our specialized center, CRS-HIPEC is considered as an effective, affordable, and safe therapy with OS, DFS, morbidity, and mortality rates comparable to those reported in the literature (Tab. 5, Fig. 2, Ref. 28). Text in PDF www.elis.sk Keywords: cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, malignant mesothelioma, cisplatin, doxorubicin.
Assuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Mesotelioma Maligno/tratamento farmacológico , Quimioterapia Intraperitoneal Hipertérmica , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Cisplatino , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hipertermia Induzida/métodos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , DoxorrubicinaRESUMO
BACKGROUND Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm with a poor prognosis. Bidirectional intraoperative chemotherapy (BDIC) using concurrent intraperitoneal and intravenous chemotherapy in combination with cytoreductive surgery (CRS) is an emerging treatment option for selected cases of MPM. It is a locoregional treatment that involves intraoperative chemoperfusion of heated chemotherapy. The administration of systemic along with intraperitoneal chemotherapy allows for a bidirectional chemotherapy gradient in peritoneal tumor cells. The aim of this treatment is eradication of microscopic residual cancer cells after major removal of macroscopic tumor nodules. To date, there is no consensus on the chemotherapeutic regimen that can be used in BDIC to manage MPM in patients with severe renal impairment. Administering intravenous ifosfamide with hyperthermic intraperitoneal cisplatin and doxorubicin is a promising regimen in treating peritoneal mesothelioma. Nephrotoxicity is a dose-limiting adverse effect of cisplatin and ifosfamide. Therefore, dose adjustment is required in patients with renal impairment. CASE REPORT In this report, we describe a 46-year-old female patient with recurrent MPM and severe renal impairment. Her treatment was managed with hyperthermic intraperitoneal cisplatin and doxorubicin along with intravenous ifosfamide following CRS. The cisplatin dose was reduced to 50% and the ifosfamide dose was reduced by 25%. The patient tolerated the procedure well, without deterioration in her renal function. At her 9-month follow-up, she did not report experiencing chemotherapy-related adverse effects, and her kidney function remained stable. CONCLUSIONS Severe renal impairment might not be a contraindication to using potentially nephrotoxic chemotherapeutic agents in CRS-BDIC.
Assuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Feminino , Humanos , Pessoa de Meia-Idade , Cisplatino/uso terapêutico , Ifosfamida/uso terapêutico , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Doxorrubicina/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVES: The management of patients with extensive appendiceal mucinous neoplasms and mesothelioma is controversial. Our aims were to analyze overall survival (OS), disease-free survival (DFS) and independent prognostic factors associated with high peritoneal cancer index (PCI) status in patients who underwent cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). METHODS: A prospectively-maintained database for patients with appendiceal neoplasms and mesothelioma undergoing CRS/PIC from year 1996 to 2018 was retrospectively analyzed. Patients who achieved complete cytoreduction were stratified into limited (PCI < 30) and extensive (PCI ≥ 30) disease groups. RESULTS: 260 female and 235 male patients were identified. The 5-year survival for low-grade appendiceal mucinous neoplasms (LAMN) was significantly higher in the low PCI group (96.2% vs. 63.5%, p < 0.001). There was no difference in the OS across both groups in high-grade appendiceal mucinous neoplasms (HAMN) (63 vs. 69 months; p = 0.942) and mesothelioma (72 vs. 42 months; p = 0.058). Overall mortality was 2%. Grade III/IV complications were significantly higher in extensive disease (68% vs. 36.6%, p < 0.001). On multivariate analysis, use of EPIC and blood transfusion (>8 units) were independent positive and negative prognostic factors, respectively, associated with OS. Meanwhile, use of EPIC conferred benefit in DFS while increased blood transfusion (>8 units) and elevated preoperative CA125 were predictive of a poor DFS. CONCLUSION: Long-term survivals following CRS/PIC are achievable with acceptable mortality and higher morbidity rates in extensive appendiceal mucinous neoplasms and mesothelioma. High PCI status does not preclude treatment with CRS/PIC.
Assuntos
Neoplasias do Apêndice , Hipertermia Induzida , Mesotelioma , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Apêndice/tratamento farmacológico , Neoplasias do Apêndice/cirurgia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Masculino , Mesotelioma/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Malignant pleural mesothelioma (MPM) is one of the most aggressive tumors with few effective treatments worldwide. It has been suggested that alternative splicing at the transcriptome level plays an indispensable role in MPM. METHODS: We analyzed the splicing profile of 84 MPM patients from the TCGA cohort by using seven typical splicing types. We classified MPM patients based on their splicing status and conducted a comprehensive analysis of the correlation between the splicing classification and clinical characteristics, genetic variation, pathway changes, immune heterogeneity, and potential therapeutic targets. RESULTS: The expression of the alternative splicing regulator SRPK1 is significantly higher in MPM tissues than in normal tissues, and correlates with poor survival. SRPK1 deficiency promotes MPM cell apoptosis and inhibits cell migration in vitro. We divided the MPM patients into four clusters based on their splicing profile and identified two clusters associated with the shortest (cluster 3) and longest (cluster 4) survival time. We present the different gene signatures of each cluster that are related to survival and splicing. Comprehensive analysis of data from the GDSC and TCGA databases revealed that cluster 3 MPM patients could respond well to the small-molecule inhibitor CHIR-99021, a small-molecule inhibitor of GSK-3. CONCLUSION: We performed unsupervised clustering of alternative splicing data from 84 MPM patients from the TCGA database and identified a cluster associated with the worst prognosis that was sensitive to a GSK-3 inhibitor.
Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Processamento Alternativo , Linhagem Celular Tumoral , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/patologia , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Mesotelioma/patologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Proteínas Serina-Treonina QuinasesAssuntos
Criocirurgia , Neoplasias Pulmonares , Mesotelioma , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias Pulmonares/cirurgia , Medicina Tradicional Chinesa , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Mesotelioma/cirurgia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgiaRESUMO
PURPOSE: This single-center study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). METHODS: Prospectively collected data from a single institution data registry was retrospectively investigated. Eighty-four patients with primary malignant peritoneal mesothelioma underwent CRS and HIPEC with cisplatin and doxorubicin either for 60 min or 90 min of duration from 2011 to 2021. The primary endpoint was overall survival. The secondary endpoint was the evaluation of prognostic factors for overall survival. The tertiary endpoint was to assess the effect of neoadjuvant chemotherapy on survival. RESULTS: The median follow-up was 5.0 years (95%-CI 4.6-5.5). The median age was 59.2 years (IQR: 47-66). Eighty-two patients (97.6%) had epithelioid tumors. The median peritoneal cancer index was 18.0 (IQR: 13-27). Sixty-six patients (78.6%) had complete or near-complete cytoreduction (CCR 0 or CCR 1). Seventy patients (83.3%) received HIPEC for 60 min and 14 patients (16.7%) received it for 90 min. Twenty-two patients (26.2%) had grade 3 to 4 complications. Acute kidney injury (AKI) stage I-III occurred in 30 (35.7%) patients. Three patients (3.6%) died perioperatively. The overall median survival was 38.4 months (95%-CI 23.6-54.3), and the 5-year survival rate was 42%. Survival was independently associated with age, female gender, and thrombocytosis. Preoperative chemotherapy did not emerge as an adverse prognostic factor. CONCLUSION: In well-selected patients with DMPM, prolonged survival is achievable with CRS and HIPEC in specialized centers.
Assuntos
Hipertermia Induzida , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Neoplasias Peritoneais/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Taxa de SobrevidaRESUMO
OBJECTIVES: To investigate independent factors for the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of diffuse malignant peritoneal mesothelioma (DMPM). METHODS: The clinical database of 110 DMPM patients treated with CRS + HIPEC at our hospital was retrospectively analyzed. Independent prognostic factors were screened using univariate and multivariate analyses and the safety of the perioperative period was evaluated based on adverse events. RESULTS: Among the 110 patients with DMPM, 34 (30.9%) had a peritoneal cancer index (PCI) < 20 and 76 (69.1%) had PCI ≥20; 59 (53.6%) patients achieved completeness of cytoreduction (CC) 0/1 and 51 (46.4%) cases achieved CC 2/3. At the median follow-up of 43.3 (95%CI: 37.3-49.4) months, 48 (43.6%) patients were still alive and 62 (56.4%) patients died. The median overall survival was 32.6 months. Serious adverse events (SAEs) occurred in 41 patients (37.3%) and the perioperative mortality rate was 2.7%. Univariate analysis identified nine prognostic factors: Karnofsky performance status score, perioperative tumor markers, PCI, red blood cell infusion, pathological type, vascular tumor emboli, lymphatic metastasis, Ki-67 index, and perioperative SAEs (all p < 0.05). Multivariate analysis identified four independent prognostic factors: pathological type (p = 0.007), vascular tumor emboli (p = 0.044), Ki-67 index (p = 0.044), and SAEs (p = 0.004). CONCLUSIONS: CRS + HIPEC for DMPM treatment resulted in prolonged survival with acceptable safety. Tumor pathology and SAEs are key factors for successful CRS + HIPEC.
Assuntos
Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Neoplasias Vasculares , China , Procedimentos Cirúrgicos de Citorredução/métodos , Humanos , Hipertermia Induzida/métodos , Quimioterapia Intraperitoneal Hipertérmica , Antígeno Ki-67 , Mesotelioma/tratamento farmacológico , Mesotelioma/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Estudos Retrospectivos , Neoplasias Vasculares/tratamento farmacológicoRESUMO
Malignant pleural mesothelioma (MPM) is a kind of invasive malignant tumor originated from pleural tissue. The incidence of MPM is not high in the population, but the prognosis is very poor. The median survival time is only about 12 months. Pemetrexed combined with platinum is the first-line chemotherapy regimen recommended by the current guidelines. The use of bevacizumab will further prolong the survival of chemotherapy. Once resistance happened, no anti-tumor treatment has been confirmed to achieve survival benefits. Therefore, there is no recommended standard second-line MPM regimen in international and domestic guidelines, including National Comprehensive Cancer Network (NCCN) guidelines. Vinorelbine, gemcitabine and other monotherapy regimens are commonly used in clinical practice, but the median progression free survival (PFS) is only about 3 months. Immune checkpoint inhibitors (ICIS) have been proved to have a significant inhibitory effect on tumor growth in a variety of malignant tumors, and their efficacy is related to the expression of programmed death-ligand 1(PD-L1). In unresectable MPM, programmed death 1 (PD-1)/PD-L1 inhibitors have been used in a series of clinical studies in the first-line, second-line and above treatment. Some of the results have been cited and recommended by international guidelines, but the overall efficacy improvement is still limited. This review summarizes the latest clinical studies and researches in the field of MPM treatment and predicts the directions and prospect of improving the therapeutic effect in the future.
Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Pemetrexede/uso terapêutico , Pleura , Neoplasias Pleurais/tratamento farmacológico , PrognósticoRESUMO
BACKGROUND: Malignant peritoneal mesothelioma is a rare disease with poor outcomes. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is the cornerstone of therapy. We aim to compare outcomes of malignant peritoneal mesothelioma treated at academic versus community hospitals. METHODS: This was a retrospective cohort study using the National Cancer Database to identify patients with malignant peritoneal mesothelioma from 2004 to 2016. Patients were divided according to treating facility type: academic or community. Outcomes were assessed using log-rank tests, Cox proportional-hazard modeling, and Kaplan-Meier survival statistics. RESULTS: In total, 2682 patients with malignant peritoneal mesothelioma were identified. A total of 1272 (47.4%) were treated at an academic facility and 1410 (52.6%) were treated at a community facility. Five hundred forty-six (42.9%) of patients at academic facilities underwent debulking or radical surgery compared to 286 (20.2%) at community facilities. Three hundred sixty-six (28.8%) of patients at academic facilities received chemotherapy on the same day as surgery compared to 147 (10.4%) of patients at community facilities. Unadjusted 5-year survival was 29.7% (95% CI 26.7-32.7) for academic centers compared to 18.3% (95% CI 16.0-20.7) for community centers. In multivariable analysis, community facility was an independent predictor of increased risk of death (HR: 1.19, 95% CI 1.08-1.32, p = 0.001). CONCLUSIONS: We demonstrate better survival outcomes for malignant peritoneal mesothelioma treated at academic compared to community facilities. Patients at academic centers underwent surgery and received chemotherapy on the same day as surgery more frequently than those at community centers, suggesting that malignant peritoneal mesothelioma patients may be better served at experienced academic centers.
Assuntos
Hipertermia Induzida , Mesotelioma , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Hospitais Comunitários , Humanos , Mesotelioma/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
This study aimed to identify the proteomic changes produced by curcumin treatment following stimulation of the host immune system in a rat model of malignant mesothelioma. We analyzed the proteomes of secondary lymphoid organs from four normal rats, four untreated tumor-bearing rats, and four tumor-bearing rats receiving repeated intraperitoneal administrations of curcumin. Cross-comparing proteome analyses of histological sections of the spleen from the three groups first identified a list of eighty-three biomarkers of interest, thirteen of which corresponded to proteins already reported in the literature and involved in the anticancer therapeutic effects of curcumin. In a second step, comparing these data with proteomic analyses of histological sections of mesenteric lymph nodes revealed eight common biomarkers showing a similar pattern of changes in both lymphoid organs. Additional findings included a partial reduction of the increase in spleen-circulating biomarkers, a decrease in C-reactive protein and complement C3 in the spleen and lymph nodes, and an increase in lymph node purine nucleoside phosphorylase previously associated with liver immunodeficiency. Our results suggest some protein abundance changes could be related to the systemic, distant non-target antitumor effects produced by this phytochemical.
Assuntos
Biomarcadores Tumorais/metabolismo , Curcumina/farmacologia , Linfonodos/metabolismo , Mesotelioma , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentais , Neoplasias Peritoneais , Proteoma/metabolismo , Animais , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma/metabolismo , Mesotelioma/patologia , Invasividade Neoplásica , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Ratos , Ratos Endogâmicos F344RESUMO
BACKGROUND: Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections. METHODS: The RENAPE database (French expert centers network) was analyzed over a 1999-2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed. RESULTS: Overall 60 patients (50 women) were included with a median PCI of 10 (4-14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7-95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12-1.42, p = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC). CONCLUSION: MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.