Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment. METHODS: MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients. RESULTS: We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients. CONCLUSION: This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.

Perfusion Strategies for Cytoreductive Surgery With Heated Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma.

Cytoreductive surgery (CRS) with heated intraoperative intraperitoneal chemotherapy (HIPEC) has been shown to improve survival for patients with malignant peritoneal mesothelioma (MPM). Presently, there is no standardized HIPEC protocol with respect to chemotherapeutic agent, dose, administration temperature, or duration and limited literature comparing outcomes in different regimens. In this study, we analyze common practices and outcomes of published HIPEC regimens to gain insight into current practice to inform future directions of study. We conducted a literature search for investigational studies of CRS and HIPEC for MPM treatment in adults and identified 35 such articles. These studies were analyzed for institution type and location, drug regimens, perfusion temperatures and time, and study outcomes including median survival, complication rates, and perioperative mortality rates. On review, there is significant heterogeneity in HIPEC regimens and outcome reporting metrics, suggesting a need for multi-institutional standardized study protocols to better determine the safest and most efficacious treatment regimen.

Research progress of malignant peritoneal mesothelioma with paraneoplastic syndrome: A review.

Malignant peritoneal mesothelioma (MPM) is a rare and invasive tumor, and some patients will develop paraneoplastic syndrome (PS) during the course of the disease. This review summarizes PS associated with MPM, focusing on the clinical characteristics and treatment progress in hematological, endocrine, rheumatic, neurological, urinary, and other systems to decrease missed diagnosis and misdiagnosis, help early diagnosis and prompt treatment, and provide guidance for the clinical decision-making of this kind of patients.

Drug sensitivity tumor cell clusters in malignant peritoneal mesothelioma.

BACKGROUND: To explore the most effective adjuvant chemotherapy regimen for malignant peritoneal mesothelioma (MPM) through patient derived tumor-like cell clusters (PTC) drug sensitivity test. METHODS: PTC were cultured in vitro with intraoperative specimens, and drug sensitivity test was performed to calculate the most effective chemotherapy regimen for MPM. The patients were divided into conventional and individualized chemotherapy group according to whether they received PTC drug testing. Univariate and multivariate analyses were conducted to identify independent prognostic factors. RESULTS: Among 186 MPM patients included, 63 underwent PTC culture and drug sensitivity test. The results showed that the most effective chemotherapy regimen was oxaliplatin + gemcitabine. After propensity score matching, a total of 64 patients were enrolled in the following study, including 32 patients receiving individualized chemotherapy guided by PTC drug results as group 1 and 32 patients receiving conventional chemotherapy as group 2. Survival analysis showed that the median OS of group 1 was not reached, significantly longer than that of group 2 (23.5 months) (p < 0.05). CONCLUSIONS: Compared with conventional chemotherapy, individualized chemotherapy guided by PTC drug sensitivity tests can prolong patient survival, and oxaliplatin + gemcitabine + apatinib could be the optimal adjuvant treatment regimen for MPM.

Risk factors and prognosis of malignant peritoneal mesothelioma with paraneoplastic syndrome.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare and highly aggressive tumor. Its clinical manifestations are diverse, and the symptoms are not specific. Some patients will develop paraneoplastic syndrome (PS) during the disease course. This study aims to analyze the risk factors of PS in patients with MPM and their impacts on prognosis. METHODS: The clinical data of MPM patients who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) at our center from June 2015 to May 2023 were retrospectively analyzed. MPM patients were divided into PS group and non-PS group according to the diagnostic criteria. Univariate and multivariate analyses were performed to explore the risk factors of PS in MPM patients, and to analyze the impact of PS on prognosis. RESULTS: There were 146 MPM patients in this study, including 60 patients (41.1%) with PS and 86 patients (58.9%) without PS. The highest incidence of PS was thrombocytosis (33.6%), followed by neoplastic fever (9.6%). Univariate analysis revealed 8 factors (P < 0.05) with statistically significant differences between the two groups: prior surgical scores, targeted therapy history, Karnofsky performance status score, preoperative carbohydrate antigen (CA) 125 level, vascular tumor embolus, peritoneal cancer index, completeness of cytoreduction (CC) score and intraoperative ascites. Multivariate analysis identified 3 independent factors associated with PS: preoperative CA 125 level, vascular tumor embolus, and CC score. Survival analysis demonstrated that MPM patients with PS had worse prognosis, although PS was not an independent prognostic factor. CONCLUSIONS: PS is not rare in patients with MPM, and is independently associated with preoperative CA 125 level, vascular tumor embolus and CC score. PS often indicates advanced disease and poor prognosis.

Prognostic role of CD74, CD10 and Ki-67 immunohistochemical expression in patients with diffuse malignant peritoneal mesothelioma: a retrospective study.

BACKGROUND: Diagnosis and treatment of diffuse malignant peritoneal mesothelioma (DMPM) are still challenging. The aim of the present study was to explore the correlation between CD74, CD10, Ki-67 and clinicopathological parameters, and identify independent prognostic factors of DMPM. METHODS: Seventy patients with pathologically proven DMPM were retrospectively reviewed. The expression of CD74, CD10 and Ki-67 in peritoneal tissues was detected by immunohistochemical analysis using standard avidin biotin complex (ABC) immunostaining technique. Kaplan-Meier survival analysis and multivariate Cox regression analyses were performed to assess prognostic factors. The nomogram based on the Cox hazards regression model was established. C-index and calibration curve were performed to evaluate the accuracy of nomogram models. RESULTS: The median age of DMPM was 62.34 years, and the male-to-female ratio was 1: 1.80. CD74 expression was identified in 52 (74.29%) of 70 specimens, CD10 in 34 (48.57%) specimens, and higher Ki-67 in 33(47.14%) specimens. CD74 was negatively associated with asbestos exposure(r = -0.278), Ki-67(r = -0.251) and TNM stage(r = -0.313). All patients were effectively followed up in the survival analysis. Univariate analysis revealed that PCI, TNM stage, treatment, Ki-67, CD74 and ECOG PS were associated with DMPM prognosis. CD74 (HR = 0.65, 95%Cl:0.46-0.91, P = 0.014), Ki-67(HR = 2.09, 95%Cl:1.18-3.73, P = 0.012),TNM stage (HR = 1.89, 95%Cl:1.16-3.09, P = 0.011), ECOG PS(HR = 2.12, 95%Cl:1.06-4.25, P = 0.034), systemic chemotherapy (HR = 0.41, 95%Cl:0.21-0.82, P = 0.011) and intraperitoneal chemotherapy (HR = 0.34, 95%Cl:0.16-0.71, P = 0.004) were independent predictors by multivariate Cox analysis. The C­index of the nomogram for predicting overall survival (OS) was 0.81. The OS calibration curve showed good agreement between nomogram-predicted and observed survival. CONCLUSIONS: CD74, Ki-67, TNM stage, ECOG PS and treatment were independent factors affecting prognosis of DMPM. Reasonable chemotherapy treatment might improve the prognosis of patients. The proposed nomogram was a visual tool to effectively predict the OS of DMPM patients.

Establishment of a Bayesian network model to predict the survival of malignant peritoneal mesothelioma patients after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

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.

Correlation of serum-soluble mesothelin-related protein, HMGB1 and CA125 in diffuse malignant peritoneal mesothelioma and their combined measurement for prognosis.

Diagnosis of diffuse malignant peritoneal mesothelioma (DMPM) is challenging due to the lack of efficient biomarkers for early-stage DMPM. This study was designed to characterize three serum-soluble mesothelium-related proteins, including soluble mesothelin-related protein (SMRP), high mobility group box 1 (HMGB1), and cancer antigen 125 (CA125) in diagnosing DMPM. Serum samples of DMPM patients and healthy controls were collected and an enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of HMGB1, CA125, and SMRP. Correlations between these three serum proteins were examined and the diagnostic values of the biomarkers were assessed by receiver operating curve (ROC) analysis. The combined expression levels of the three markers were also analyzed in terms of predicting patient survival. Higher levels of CA125, SMRP, and HMGB1 was found to be a prominent characteristic of DMPM patients (with > two-fold higher for all levels in DMPM patients compared to control patients, all p < .001), particularly for those with higher-stage DMPM (stage III-IV) compared with lower-stage DMPM (stage I-II) (all p < .05). HMGB1, CA125, and SMRP were all significantly inter-correlated with each other (all p < .05), the combination of the three serum markers had high sensitivity and specificity for diagnosing DMPM. Combined values of the three markers demonstrated a high AUC of 0.85, sensitivity of 78.95%, specificity of 82.75% for identifying DMPM. The combined level of the three markers also demonstrated a significant positive correlation with poor survival of DMPM patients (p = .022). CA125, SMRP, and HMGB1 are potentially valuable diagnostic biomarkers to facilitate the diagnosis of DMPM.

The clinicopathological significance of TOP2A expression in malignant peritoneal mesothelioma.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. TOP2A expression is associated with cell proliferation and cell cycle progression. We aimed to demonstrate the expression profile of TOP2A in MPM and its correlation with clinicopathological features. METHODS: Clinicopathological information from 100 MPM cases was collected at Beijing Shijitan Hospital, Capital Medical University. Immunohistochemistry (IHC) was performed to evaluate TOP2A levels. The associations between TOP2A levels and clinicopathological features or prognosis were analyzed. Clinical follow-up data were reviewed to determine correlations among the pathological prognostic factors using the Kaplan-Meier estimator and univariate/multivariate Cox proportional hazards regression models. RESULTS: Among the 100 MPM patients, there were 48 males and 52 females, with a median age of 54 years (range: 24-72 years). The cutoff curve was used to find the boundary value of the TOP2A-positive rate. TOP2A positive rate ≥ 11.97 % accounted for 48 % in tumor tissue. The TOP2A-positive rate was not associated with sex, age, asbestos exposure, peritoneal carcinomatosis index (PCI) score, or completeness of cytoreduction (CC) score in MPM. Univariate analysis revealed survival-related pathological parameters, including asbestos exposure, CA125, histological type, PCI score, CC score, Ki-67 index, and TOP2A positive rate. Multivariate analysis identified that asbestos exposure history, PCI score, Ki-67 proliferation index and TOP2A positive rate in tissue are independent prognostic factors. CONCLUSIONS: High expression of TOP2A is linked to better prognosis of MPM.

[Pathological classification of malignant peritoneal mesothelioma and comparative analysis with peritoneal carcinomatosis].

Objective: To analyze the pathological classification of malignant peritoneal mesothelioma (MPeM) and screen the immunohistochemical markers that can distinguish MPeM from peritoneal metastatic carcinoma (PC) . Methods: In June 2020, the pathological results of peritoneal biopsy of 158 MPeM and 138 PC patients from Cangzhou Central Hospital, Cangzhou People's Hospital, and Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2011 to July 2019 were retrospectively analyzed, and the pathological classifications of MPeM in Cangzhou were summarized. Immunohistochemical markers of MPeM and PC patients were analyzed, and receiver operating characteristic curve (ROC curve) was drawn for differential diagnosis of MPeM and PC. Results: There were 55 male and 103 female MPeM patients in Cangzhou, with an average age of 57.1 years old. The asbestos exposure rate was 91.14% (144/158). The most common pathological classifications were cutaneous type, accounting for 90.51% (143/158). There were significant differences in the expression of calreticulum protein, CK5/6, vimentin, D2-40, carcinoembryonic antigen (CEA) and tail type homologous nuclear gene transcription factor 2 (CDX-2) between MPeM and PC (P<0.05). Among the 6 positive markers, the sensitivity of calreticulum protein was the highest (0.905) and CEA was the lowest (0.428) . Conclusion: Calreticulum protein, CK5/6, vimentin, D2-40, CEA and CDX-2 may be used as specific markers to distinguish the diagnosis of MPeM from PC.

DNA repair and damage pathways in mesothelioma development and therapy.

Malignant mesothelioma (MMe) is an aggressive neoplasm that occurs through the transformation of mesothelial cells. Asbestos exposure is the main risk factor for MMe carcinogenesis. Other important etiologies for MMe development include DNA damage, over-activation of survival signaling pathways, and failure of DNA damage response (DDR). In this review article, first, we will describe the most important signaling pathways that contribute to MMe development and their interaction with DDR. Then, the contribution of DDR failure in MMe progression will be discussed. Finally, we will review the latest MMe therapeutic strategies that target the DDR pathway.

Expression of PD-L1 in Patients With Malignant Peritoneal Mesothelioma: A Pilot Study.

INTRODUCTION: Frequency of PD-L1 expression and the role of immunotherapy in malignant peritoneal mesothelioma (MPM) have not been well characterized. The purpose of this study was to determine PD-L1 expression in patients with MPM and perform an exploratory analysis for associations between PD-L1 and its biological behavior in MPM. METHODS: Tumor samples were collected from patients undergoing surgical interventions between January 2018 and June 2020. Specimens were stained with anti-PD-L1 antibodies (Dako 22c3) and positivity was determined by tumor proportion score (TPS) or combined positive score (CPS) being ≥1%. RESULTS: Twenty one samples were obtained from 21 patients. Sixteen of 21 (76%) samples were CPS positive and 9 of 21 (43%) were TPS positive. Three samples had more aggressive biphasic/sarcomatoid histology and a high CPS and TPS (CPS: 3, 75, 95%; TPS: 2, 60, 90%). On an exploratory analysis, as the CPS or TPS threshold increased, there was a trend towards worse survival. CONCLUSIONS: MPM has a high frequency of PD-L1 expression, which may be associated with more aggressive tumor biology. These data provide the foundation for continued evaluation of checkpoint inhibition in patients with MPM.

Clinical-pathological characteristics and prognostic factors for malignant peritoneal mesothelioma in the elderly.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare disease characterized by atypical symptoms, difficult diagnosis, variable course and poor prognosis, and it develops mainly in elderly individuals. The authors aimed to identify the clinical-pathological characteristics, prognosis, and prognostic factors in elderly MPM patients. METHODS: From the National Cancer Institute Surveillance Epidemiology End Results (SEER) database, 1492 patients with MPM from 1975 to 2016 were selected and divided into the elderly group (≥ 65) and the adult group (< 65). We compared the clinical-pathological characteristics and treatment methods of the elderly group (N = 665) and the adult group (N = 827). At the same time, we analysed specific selected clinicopathological parameters and prognostic factors for elderly MPM patients. RESULTS: Compared with the adult group, the elderly group had higher percentages of male patients (P = 0.017) and white patients (P = 0.043) and lower proportions of insured patients (P < 0.001) married patients (P < 0.001), patients with peritoneal tumours (P = 0.006) and patients who underwent surgery (P < 0.001) and chemotherapy (P < 0.001). There was a significant difference in the differentiation grade between the two groups (P = 0.003). Elderly patients had a shorter median survival time than adult patients (6 months vs. 19 months). Uninsured (hazard ratio (HR): 5.187, P = 0.005), sarcomatoid type (HR 3.913, P < 0.001), poorly differentiated (HR 3.900, P < 0.001), distant metastasis (HR 1.735, P = 0.001), no cancer-directed surgery (HR 1.733, P < 0.001), and no chemotherapy (HR 1.532, P < 0.001) were independently associated with poorer prognosis in elderly MPM patients. CONCLUSION: Compared with adult patients, elderly MPM patients had a higher male ratio, poor differentiation and relatively conservative treatment. The cancer-specific survival (CSS) rate of elderly MPM patients was significantly lower than that of adult patients. Insurance status, histology type, differentiation grade, stage, surgery status, and chemotherapy status were all independent prognostic factors for elderly MPM patients.

Key factors for successful cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy to treat diffuse malignant peritoneal mesothelioma: results from specialized peritoneal cancer center in China.

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.

Ten-year single-center experience with treatment of primary diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

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.

NPM2 in malignant peritoneal mesothelioma: from basic tumor biology to clinical medicine.

BACKGROUND: This review systematically summarizes gene biology features and protein structure of nucleoplasmin2 (NPM2) and the relationship between NPM2 and malignant peritoneal mesothelioma (MPM), in order to explore the molecular pathological mechanism of MPM and explore new therapeutic targets. METHODS: NCBI PubMed database was used for the literature search. NCBI Gene and Protein databases, Ensembl Genome Browser, UniProt, and RCSB PDB database were used for gene and protein review. Three online tools (Consurf, DoGSiteScorer, and ZdockServer), the GEPIA database, and the Cancer Genome Atlas were used to analyze bioinformatics characteristics for NPM2 protein. RESULTS: The main structural domains of NPM2 protein include the N-terminal core region, acidic region, and motif and disordered region. The N-terminal core region, involved in histone binding, is the most conserved domain in the nucleoplasmin (NPM) family. NPM2 with a large acidic tract in its C-terminal tail (NPM2-A2) is able to bind histones and form large complexes. Bioinformatics results indicated that NPM2 expression was correlated with the pathology of multiple tumors. Among mesothelioma patients, 5-year survival of patients with low-NPM2-expression was significantly higher than that of the high-NPM2-expression patients. NPM2 can facilitate the formation of histone deacetylation. NPM2 may promote histone deacetylation and inhibit the related-gene transcription, thus leading to abnormal proliferation, invasion, and metastasis of MPM. CONCLUSION: NPM2 may play a key role in the development and progression of MPM.

Desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma: a case report of two rare diseases.

BACKGROUND: Desmoid-type fibromatosis (DTF) is a rare benign lesion that usually arises from the abdominal wall or extremities and rarely from the mesentery or intrabdominal organs. Malignant peritoneal mesothelioma is also a rare, yet aggressive disease. To our knowledge, this is the first case report of desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma. CASE PRESENTATION: An early 30-year-old female was referred to our center for large intra-abdominal mass concerning for recurrent malignant peritoneal mesothelioma after previous cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and adjuvant chemotherapy. Further investigation revealed a large mesenteric mass, which was resected en bloc with the cecum and terminal ileum. Pathologic findings confirmed a surprising diagnosis of desmoid-type fibromatosis. CONCLUSIONS: No adjuvant therapy was offered to this patient due to negative tumor margins; however, close follow-up will be provided for recurrence of both malignant peritoneal mesothelioma and desmoid-type fibromatosis, which can be differentiated in the future via biopsy in this patient.

Loss of NPM2 expression is a potential immunohistochemical marker for malignant peritoneal mesothelioma: a single-center study of 92 cases.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. In-depth pathological analysis is essential to assess tumor biological behaviors and explore potential therapeutic targets of MPM. Nucleoplasmin 2 (NPM2) is a molecular chaperone that binds histones and may play a key role in the development and progression of tumors. This study aimed to analyze the correlation between the expression level of NPM2 and the main clinicopathological characteristics and prognosis of MPM. METHODS: Ninety-two postoperative specimens from MPM patients following cytoreductive surgery were collected. Postoperative specimens were stained with immunohistochemistry. The expression level of NPM2 was quantitatively analyzed by QuPath-0.3.2 software. Univariate and multivariate analyses were conducted to investigate the correlation between NPM2 expression and other conventional clinicopathological characteristics. RESULTS: Among the 92 MPM patients, there were 47 males (48.9%) and 45 females (51.1%), with a median age of 56 (range: 24-73). There were 70 (76.0%) cases with loss of NPM2 protein expression, 11 (12.0%) cases with low expression, and 11 (12.0%) cases with high expression. Univariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was negatively correlated with the following three clinicopathological factors: completeness of cytoreduction (CC) score, vascular tumor emboli, and serious adverse events (SAEs) (all P < 0.05). Multivariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was independently negatively correlated with the following two clinicopathological factors: CC score [odds ratio (OR) = 0.317, 95% CI: 0.317-0.959, P = 0.042] and vascular tumor emboli (OR = 0.092, 95% CI = 0.011-0.770, P = 0.028). Survival analysis showed that loss of NPM2 protein expression (negative vs. positive) was associated with poor prognosis of MPM. CONCLUSIONS: Loss of NPM2 expression is a potential immunohistochemical marker for MPM.

Prognostic factors of malignant peritoneal mesothelioma: a retrospective study of 52 female patients.

BACKGROUND: Prognosis in malignant peritoneal mesothelioma (MPM) remains poor, and the associated factors are unclear. Therefore, this study aimed to investigate the prognostic factors of MPM. METHODS: A total of 52 female MPM patients treated in 2012-2017 were retrospectively analyzed. Kaplan-Meier survival curves were generated for survival analysis by the log-rank test. The Cox regression model was used for univariate and multivariate analyses. RESULTS: Univariate analysis showed that median survival time (MST) was longer in the epithelioid type compared with the sarcomatoid type (12 months vs 5 months); cumulative survival rates at 12 months were 45.7% and 0%, respectively (P=0.005). MST was longer in patients with proliferating cell nuclear antigen (Ki67) ≤ 10% compared with those with Ki67 > 10% (15 months vs 11 months). Cumulative survival rates at 12 months were 60.0% and 28.1%, respectively (P=0.036). MSTs in patients administered peritoneal biopsy or adnexectomy + paclitaxel + platinum perfusion, peritoneal biopsy (or adnexectomy) + pemetrexed + platinum perfusion, cytoreductive surgery + paclitaxel + platinum perfusion, and cytoreductive surgery + pemetrexed + platinum perfusion were 6, 11, 12, and 24 months, respectively, with cumulative survival rates at 12 months of 0%, 35.7%, 45.5%, and 73.3%, respectively. Survival time after cytoreductive surgery combined with pemetrexed + platinum was the longest. In multivariate analysis, pathological type, T staging, and therapeutic regimen were independent prognostic factors of MPM (P < 0.05). CONCLUSIONS: Prognosis in MPM is associated with pathological subtype, clinical staging, cytoreductive surgery, and subsequent pemetrexed use. Radical cytoreductive surgery and postoperative use of pemetrexed prolong survival.

Substance GP-2250 as a New Therapeutic Agent for Malignant Peritoneal Mesothelioma-A 3-D In Vitro Study.

Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options.