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2.
Explore (NY) ; 20(1): 126-129, 2024.
Article in English | MEDLINE | ID: mdl-37286465

ABSTRACT

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.


Subject(s)
Brucea , Mesothelioma, Malignant , Mesothelioma , Pleural Effusion, Malignant , Humans , Brucea javanica , Emulsions/therapeutic use , Mesothelioma/complications , Mesothelioma/drug therapy , Plant Oils/therapeutic use , Pleural Effusion, Malignant/drug therapy , Pleural Effusion, Malignant/pathology
3.
Ann Surg Oncol ; 31(1): 556-566, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37940804

ABSTRACT

BACKGROUND: The available data on the role of perioperative systemic chemotherapy (SC) for diffuse malignant peritoneal mesothelioma (DMPM) patients undergoing (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is heterogeneous and unstandardized. This study aimed to evaluate the impact of SC on the survival outcomes of DMPM patients undergoing CRS-HIPEC and to identify prognostic factors that affect the decision to administer SC. METHODS: Patients who underwent CRS-HIPEC in the National Cancer Institute Milan (1995-2020) were retrospectively analyzed using propensity score-matching of known covariates. The patients were grouped into three groups: group A (neoadjuvant chemotherapy [NACT] and no-SC), group B (no-SC and adjuvant chemotherapy [ACT]), and group C (NACT and ACT). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meir method, and prognostic factors were calculated using the Cox-regression method. RESULTS: After a median follow-up period of 45 months (95% confidence interval [CI], 6.348-83.652 months) for group A, 115 months (95% CI, 44.379-185.621 months) for group B, and 88 months (95% CI, 3.296-172.704 months) for group C, the study analyzed 154 DMPM patients consisting of matched group A (NACT: 60 + no-SC: 52 = 112), group B (ACT: 38 + no-SC: 38 = 76), and group C (NACT: 31 + ACT: 31 = 62). The patients undergoing ACT had better 5-year OS and PFS than the patients undergoing NACT. In the multivariate analysis, ACT was significantly associated with improved OS by 48% (hazard ratio [HR], 0.52; 95% CI, 0.280-0.965, p = 0.038). For PFS, the association of ACT did not reach statistical significance (HR, 0.531; 95% CI, 0.266-1.058; p = 0.072). CONCLUSION: The optimum treatment sequence for DMPM is CRS-HIPEC followed by adjuvant chemotherapy for high-risk patients. Upfront surgery appears preferable to NACT for patients amenable to complete CRS.


Subject(s)
Hyperthermia, Induced , Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Peritoneal Neoplasms , Humans , Mesothelioma/pathology , Hyperthermic Intraperitoneal Chemotherapy , Retrospective Studies , Lung Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced/methods , Mesothelioma, Malignant/drug therapy , Peritoneal Neoplasms/surgery , Cytoreduction Surgical Procedures/methods , Survival Rate , Combined Modality Therapy
4.
Am J Case Rep ; 24: e941726, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38093612

ABSTRACT

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.


Subject(s)
Hyperthermia, Induced , Mesothelioma, Malignant , Mesothelioma , Peritoneal Neoplasms , Renal Insufficiency, Chronic , Renal Insufficiency , Female , Humans , Middle Aged , Mesothelioma, Malignant/drug therapy , Cisplatin/therapeutic use , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/pathology , Ifosfamide/therapeutic use , Cytoreduction Surgical Procedures , Combined Modality Therapy , Mesothelioma/drug therapy , Mesothelioma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Renal Insufficiency/drug therapy
5.
J Surg Oncol ; 128(7): 1141-1149, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37702402

ABSTRACT

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.


Subject(s)
Acute Kidney Injury , Mesothelioma, Malignant , Mesothelioma , Humans , Cisplatin/adverse effects , Pilot Projects , Magnesium/therapeutic use , Bradycardia/chemically induced , Bradycardia/drug therapy , Mesothelioma/drug therapy , Mesothelioma, Malignant/chemically induced , Mesothelioma, Malignant/drug therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/drug therapy
8.
J Immunother Cancer ; 11(8)2023 08.
Article in English | MEDLINE | ID: mdl-37536940

ABSTRACT

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).


Subject(s)
Hyperthermia, Induced , Mesothelioma, Malignant , Mesothelioma , Peritoneal Neoplasms , Humans , Hyperthermic Intraperitoneal Chemotherapy , Cytoreduction Surgical Procedures/adverse effects , Cytoreduction Surgical Procedures/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced/methods , Mesothelioma, Malignant/drug therapy , Mesothelioma/drug therapy , Peritoneal Neoplasms/drug therapy , Adjuvants, Immunologic/therapeutic use , Immunotherapy , Dendritic Cells/pathology
9.
Ann Surg Oncol ; 30(12): 7803-7813, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37481492

ABSTRACT

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and aggressive primary peritoneal disease, with recommended treatment, in eligible patients, of a combination of complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). As treatment is multimodal, there is a wide heterogeneity of HIPEC protocols precluding clear comparisons. Standardization at an international level is required. METHODS: The Peritoneal Surface Oncology Group International (PSOGI) designated a steering committee to produce consensus recommendations for HIPEC regimens, adapted to each etiology. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology was used, based on a systematic review focused on main outcomes related to HIPEC regimens in DMPM patients and on the patient, intervention, comparator, and outcome (PICO) method to elaborate main questions. An opinion survey was added. Furthermore, a Delphi process was performed with voting from a panel of international experts. RESULTS: Eleven questions were elaborated, including two for future research requirements and three to assess the HIPEC regimen preference of the panel. The level of evidence underlying questions was globally low. Overall, 75 (86%) and 67 (77%) of the 87 invited experts completed the vote at the first and second round, respectively. HIPEC following complete CRS was strongly supported by 88% of voters with no need to plan comparative studies with CRS alone for 61.2% of voters. Bi-drug regimens appeared to be preferred to mono-drug ones and cisplatin was globally favored. The opinion survey confirmed the combination of cisplatin and doxorubicin as the recommended regimen. CONCLUSION: International consensus confirmed the indication of HIPEC following complete CRS in DMPM patients and recommended cisplatin-doxorubicin as the first-line HIPEC regimen.


Subject(s)
Hyperthermia, Induced , Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Peritoneal Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin , Combined Modality Therapy , Consensus , Cytoreduction Surgical Procedures/methods , Doxorubicin , Hyperthermia, Induced/methods , Hyperthermic Intraperitoneal Chemotherapy , Lung Neoplasms/pathology , Mesothelioma/pathology , Mesothelioma, Malignant/drug therapy , Peritoneal Neoplasms/pathology , Retrospective Studies , Practice Guidelines as Topic
10.
Sci Rep ; 13(1): 11640, 2023 07 19.
Article in English | MEDLINE | ID: mdl-37468581

ABSTRACT

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.


Subject(s)
Hyperthermia, Induced , Mesothelioma, Malignant , Mesothelioma , Peritoneal Neoplasms , Humans , Mitomycin/therapeutic use , Cisplatin/pharmacology , Cisplatin/therapeutic use , Hyperthermic Intraperitoneal Chemotherapy , Combined Modality Therapy , Mesothelioma/drug therapy , Mesothelioma, Malignant/drug therapy , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/pathology , Perfusion , Organoids/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies
11.
J Surg Oncol ; 128(4): 604-611, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37409778

ABSTRACT

OBJECTIVES: Pleural metastasis has extremely poor prognosis. Resection of pleural implants with infusion of intrathoracic hyperthermic chemotherapy may offer a survival advantage in selected patients. We evaluated the safety and efficacy of hyperthermic intrathoracic extracorporeal chemotherapy (HITEC) in patients who underwent pleurectomy/decortication (P/D) for secondary malignant pleural disease (SPD). METHODS: A total of 101 patients were evaluated over 72 months, with 35 patients electing to proceed with P/D and 60 minutes of HITEC with cisplatin at 42°C. Inclusion criteria were adults 18-79 years with unilateral pleural dissemination. Exclusion criteria were patients without control of primary site, extrathoracic metastatic disease, significant comorbidities, and a history of adverse reaction to cisplatin. RESULTS: Median age was 56 years (36-73); 60% were women. SPD was thymoma in 13, breast cancer in 9, lung cancer in 6, colon cancer in 2, renal cell in 2, and esophageal, anal, and thymic cancers in one each. There was no operative mortality. Postoperative complications occurred in 18 patients (51%). No patient developed renal failure. Median follow-up was 24 months (4-60). The overall survival rate was 61%; 17 patients (49%) developed recurrent disease at a median of 12 months (6-36). There were no recurrences after 36 months Eleven patients (31%) died of metastatic disease at a median of 17 months (7-25). CONCLUSIONS: Surgical cytoreduction of SPD followed by HITEC with cisplatin was well tolerated. No patient developed cisplatin-related toxicities. Long-term follow-up is warranted to determine survival advantage and refinement of inclusion criteria.


Subject(s)
Hyperthermia, Induced , Mesothelioma , Pleural Diseases , Pleural Neoplasms , Thymus Neoplasms , Adult , Humans , Female , Middle Aged , Male , Cisplatin , Combined Modality Therapy , Pleural Neoplasms/drug therapy , Pleural Neoplasms/pathology , Mesothelioma/therapy , Thymus Neoplasms/pathology
12.
Int J Hyperthermia ; 40(1): 2223374, 2023.
Article in English | MEDLINE | ID: mdl-37348853

ABSTRACT

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.


Subject(s)
Hyperthermia, Induced , Mesothelioma, Malignant , Mesothelioma , Peritoneal Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bayes Theorem , Combined Modality Therapy , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Hyperthermic Intraperitoneal Chemotherapy , Mesothelioma/drug therapy , Mesothelioma/surgery , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Prognosis , Retrospective Studies , Survival Rate
14.
J Surg Oncol ; 128(4): 595-603, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37249154

ABSTRACT

INTRODUCTION: Peritoneal mesothelioma (PM) is a rare malignancy originating from the peritoneal lining. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is the standard-of-care for patients with isolated PM. Due to a paucity of prospective data there are several different HIPEC protocols. The aims of this study are to describe the CRS and HIPEC protocols for PM and patient outcomes across Canada. METHODS: A multicenter retrospective study was performed on patients diagnosed and treated for PM with CRS and HIPEC in four major peritoneal disease centers in Canada between 2000 and 2021. Data on patient characteristics, treatment patterns, postoperative morbidity, recurrence, and survival were collected. RESULTS: A total of 72 patients were identified. Mean age was 52 years (17-75) and 37.5% were male. Epithelioid (70.1%) and multicystic (13%) mesothelioma were the most common subtypes. Twenty-one patients (30%) were treated with neoadjuvant chemotherapy. CRS and HIPEC was performed in 64 patients (91.4%). Of these, the mean PCI was 22 (2-39) and cisplatin+doxorubicin was the most common HIPEC regimen (n = 33, 51.6%). A semi-closed coliseum technique was used in 68.8% of HIPECs and the mean duration of surgery was 486 min (90-1052). Clavien-Dindo III or IV complications occurred in 12 patients (16.9%). With a median follow-up of 24 months (0.2-104.4), we found a 5-year overall survival of 61% and a 5-year recurrence-free survival of 35%. CONCLUSION: CRS and HIPEC is a safe and effective treatment modality for well-selected patients with PM, with some achieving prolonged survival.


Subject(s)
Hyperthermia, Induced , Mesothelioma, Malignant , Mesothelioma , Percutaneous Coronary Intervention , Peritoneal Neoplasms , Humans , Male , Middle Aged , Female , Retrospective Studies , Prospective Studies , Cytoreduction Surgical Procedures/methods , Hyperthermic Intraperitoneal Chemotherapy , Hyperthermia, Induced/methods , Canada/epidemiology , Mesothelioma, Malignant/drug therapy , Mesothelioma/pathology , Peritoneal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Survival Rate
15.
Ann Surg Oncol ; 30(8): 5119-5129, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37140748

ABSTRACT

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignancy with a historically poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an effective therapy for patients with peritoneal malignancies. A contemporary analysis of trends in management of and survival from MPM is warranted. METHODS: Patients with MPM were identified from the National Cancer Database (2004-2018). Patients were categorized by treatment (CRS-HIPEC, CRS-chemotherapy, CRS only, chemotherapy only, no treatment), and joinpoint regression was employed to compute the annual percent change (APC) in treatment over time. Multivariable Cox proportional hazards models were used to analyze factors associated with survival. RESULTS: Of 2683 patients with MPM, 19.1% underwent CRS-HIPEC, and 21.1% received no treatment. Joinpoint regression revealed a statistically significant increase in the proportion of patients undergoing CRS-HIPEC over time (APC 3.21, p = 0.01), and a concurrent decrease in the proportion of patients who underwent no treatment (APC - 2.21, p = 0.02). Median overall survival was 19.5 months. Factors independently associated with survival included CRS-HIPEC, CRS, histology, sex, age, race, Charlson Comorbidity Index, insurance, and hospital type. Although there was a strong association between year of diagnosis and survival on univariate analysis (2016-2018 HR 0.67, p < 0.001), this association was attenuated after adjustment for treatment. CONCLUSIONS: CRS-HIPEC is increasingly employed as a treatment for MPM. In parallel, there has been a decrease in patients receiving no treatment with an increase in overall survival. These findings suggest that patients with MPM may be receiving more appropriate therapy; however, a substantial proportion of patients may remain undertreated.


Subject(s)
Hyperthermia, Induced , Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Peritoneal Neoplasms , Humans , Mesothelioma/pathology , Peritoneal Neoplasms/pathology , Lung Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis , Combined Modality Therapy , Cytoreduction Surgical Procedures , Survival Rate , Retrospective Studies
16.
Bratisl Lek Listy ; 124(5): 345-350, 2023.
Article in English | MEDLINE | ID: mdl-36876363

ABSTRACT

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.


Subject(s)
Hyperthermia, Induced , Mesothelioma, Malignant , Mesothelioma , Peritoneal Neoplasms , Humans , Female , Middle Aged , Male , Mesothelioma, Malignant/drug therapy , Hyperthermic Intraperitoneal Chemotherapy , Mesothelioma/drug therapy , Mesothelioma/pathology , Cytoreduction Surgical Procedures/methods , Cisplatin , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced/methods , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Doxorubicin
17.
Am J Case Rep ; 24: e938192, 2023 Mar 25.
Article in English | MEDLINE | ID: mdl-36964641

ABSTRACT

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.


Subject(s)
Hyperthermia, Induced , Mesothelioma, Malignant , Mesothelioma , Female , Humans , Middle Aged , Cisplatin/therapeutic use , Ifosfamide/therapeutic use , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Mesothelioma, Malignant/drug therapy , Mesothelioma/drug therapy , Mesothelioma/pathology , Doxorubicin/therapeutic use
18.
Environ Res ; 230: 115607, 2023 08 01.
Article in English | MEDLINE | ID: mdl-36965793

ABSTRACT

This paper summarizes recent insights into causal biological mechanisms underlying the carcinogenicity of asbestos. It addresses their implications for the shapes of exposure-response curves and considers recent epidemiologic trends in malignant mesotheliomas (MMs) and lung fiber burden studies. Since the commercial amphiboles crocidolite and amosite pose the highest risk of MMs and contain high levels of iron, endogenous and exogenous pathways of iron injury and repair are discussed. Some practical implications of recent developments are that: (1) Asbestos-cancer exposure-response relationships should be expected to have non-zero background rates; (2) Evidence from inflammation biology and other sources suggests that there are exposure concentration thresholds below which exposures do not increase inflammasome-mediated inflammation or resulting inflammation-mediated cancer risks above background risk rates; and (3) The size of the suggested exposure concentration threshold depends on both the detailed time patterns of exposure on a time scale of hours to days and also on the composition of asbestos fibers in terms of their physiochemical properties. These conclusions are supported by complementary strands of evidence including biomathematical modeling, cell biology and biochemistry of asbestos-cell interactions in vitro and in vivo, lung fiber burden analyses and epidemiology showing trends in human exposures and MM rates.


Subject(s)
Asbestos , Lung Neoplasms , Mesothelioma , Humans , Asbestos/toxicity , Mesothelioma/chemically induced , Mesothelioma/epidemiology , Lung Neoplasms/chemically induced , Lung Neoplasms/epidemiology , Lung/pathology , Asbestos, Amphibole/toxicity , Inflammation/metabolism
19.
Article in English | MEDLINE | ID: mdl-36833533

ABSTRACT

Background: This article provides an overview of the current status and research progress of mesothelioma. Methods: A total of 2638 documents published from 1 January 2004 to 30 November 2022 were retrieved from the Web of Science Core Collection and analyzed via Microsoft Office Excel 2019, VOSviewer 1.6.18, and Tableau 2022.2. Results: There was an obvious increase in the number of publications regarding mesothelioma in the last 18 years, with the United States dominating the research field with 715 publications and 23,882 citations, while the University of Turin contributed the most (118). Occupational & Environmental Medicine was the most popular journal (80), with Corrado Magnani being the most prolific author (52) and Michele Carbone obtaining the most citations (4472). "Oncology" and "Health Science of Environment & Occupation" were the two main subjects, while the keywords "asbestos", "lung cancer", "gene expression", "apoptosis", "survival", and "cisplatin" were the most popular. Conclusions: The containment of mesothelioma calls for more participation from low- and middle-income countries, and further attention needs to be paid to clinical research.


Subject(s)
Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Humans , Workplace , Bibliometrics
20.
Ann Surg Oncol ; 30(5): 2666-2675, 2023 May.
Article in English | MEDLINE | ID: mdl-36754945

ABSTRACT

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. METHODS: Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. RESULTS: The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, and the perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection status at first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. CONCLUSIONS: This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.


Subject(s)
Hyperthermia, Induced , Mesothelioma, Malignant , Mesothelioma , Percutaneous Coronary Intervention , Peritoneal Neoplasms , Humans , Male , Middle Aged , Female , Cytoreduction Surgical Procedures , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Mesothelioma, Malignant/drug therapy , Mesothelioma/pathology , Peritoneal Neoplasms/pathology , Combined Modality Therapy , Chemotherapy, Cancer, Regional Perfusion , Survival Rate , Retrospective Studies
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