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AbstractObjectives 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

AbstractObjective To investigate the effects of standardized fluid management (SFM) on cardiac function in patients with pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).Method Patients with PMP who underwent CRS + HIPEC at our center were retrospectively analyzed. The patients were divided into control and study groups according to whether SFM was applied after CRS + HIPEC. We compared the preoperative and postoperative cardiac and renal function parameters, daily fluid volume three days after CRS, and cardiovascular-related adverse events. Univariate and multivariate analyses were performed to identify the indicators affecting clinical prognosis.Result Among the 104 patients, 42 (40.4%) were in the control group and 62 (59.6%) in the study group. There were no statistically significant differences between the two groups in the main clinicopathological characteristics, preoperative cardiac and renal function parameters, and CRS + HIPEC-related indicators. The incidences of cardiac troponin I (CTNI) > upper limit of normal (ULN), >2 × ULN, >3 × ULN, serum creatinine > ULN, and blood urea nitrogen > ULN were higher in the control group than in the study group (p 2 × ULN was an independent risk factor for serious circulatory adverse events. Survival analysis revealed pathological grading, completeness of cytoreduction score, and postoperative CTNI > ULN as independent prognostic factors.Conclusions SFM after CRS + HIPEC in patients with PMP may reduce cardiovascular adverse events risk and improve clinical outcomes.

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

Abstract 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.

Abstract 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.

ObjectiveTo investigate the clinical efficacy and adverse events (AEs) of apatinib salvage treatment for diffuse malignant peritoneal mesothelioma (DMPM) that has failed to respond to the recommended treatments.Methods27 patients with refractory DMPM were treated with apatinib at our center from April 2014 to October 2020, at the initial dose of 250 mg/d. The dose was reduced to 125 mg/d when serious adverse events (SAEs) occurred. 28-day was set as a treatment cycle. The frequency of follow up was once every 28 days. The efficacy evaluation was conducted according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and the serum tumor markers before and after apatinib treatment. The safety assessment was performed with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the secondary endpoints were AEs.ResultsThe 27 patients completed a median treatment-cycle of 15.0, ranging from 5.1 to 39.4 cycles. At the median follow-up of 14.3 (4.8-51.8) months, median overall survival (OS) was 59.4 months, median apatinib-treatment-related survival (ATRS) was 14.0 (4.8-36.8) months. Complete response (CR) was observed in 0 case (0.0%), partial response (PR) in 4 cases (14.8%), stable disease (SD) in 12 cases (44.4%), and progression disease (PD) in 11 cases (40.7%). The ORR was 14.8%, and DCR was 59.3%. The median serum CA125 values before and after apatinib treatment were 32.9 (7.0-4592.4) U/mL and 29.7 (6.1-4327.4) U/mL, respectively (P=0.009). The common AEs were hypertension (6/27; 22.2%), hand-foot syndrome (5/27; 18.5%), albuminuria (4/27; 14.8%), anemia (4/27; 14.8%), leukopenia (4/27; 14.8%), rash (2/27; 7.4%), fatigue (2/27; 7.4%), oral ulcers (2/27; 7.4%), hoarseness (2/27; 7.4%), nausea/vomiting (2/27; 7.4%), diarrhea (2/27; 7.4%), headache (1/27; 3.7%), and fever (1/27; 3.7%). The incidence rate of grade III/IV AEs was 16.2%.ConclusionsApatinib is effective in treating refractory DMPM, with promising efficacy and acceptable safety.

Abstract Background Pseudomyxoma peritonei (PMP) is an indolent malignancy and insensitive to systemic chemotherapy. The authors established patient‐derived xenograft (PDX) model of PMP, and evaluated the efficacy and toxicity of intraperitoneal (i.p.) administration of 5‐fluorouracil (5‐FU) in this model. Methods Human PMP sample was collected to establish subcutaneous (s.c.) and i.p. model. In vivo study of i.p. injection of 5‐FU was performed in i.p. model, with experimental peritoneal cancer index (ePCI) score and pathological examinations for evaluating the efficacy and toxicity. Results Both s.c. and i.p. models were constructed. The average passage interval of s.c. model was 44.2 ± 5.2 days, and the i.p. model was characterized by disseminated solid tumor nodules in abdominal‐pelvic cavity. Both models were diagnosed as peritoneal mucinous carcinomatosis with signet ring cells (PMCA‐S). Immunohistochemical characteristics was similar to human. GNAS mutation was detected in both model and patient. In the in vivo study, average ePCI of treatment group was lower than control and vehicle group (P = .004). Histopathology revealed obvious tumor necrosis in treatment group, and decreased Ki67 positive rate (P = .010). In toxicity study, 5‐FU significantly influenced body weight (P = .010) and 1 animal from treatment group died on day 14. Congestive splenomegaly was observed (88.9%). Hepatotoxicity presented as acidophilic body (55.6%), cholestasis (100%), bile canaliculus hyperplasia and obstruction (22.2%), and lymphocyte accumulation (77.8%). Conclusions PDX model of PMCA‐S was established successfully, and i.p. 5‐FU could inhibit tumor proliferation and progression, with decreased Ki67 positive rate and ePCI score. Hepatotoxicity was the main side effect.

ObjectiveMalignant peritoneal mesothelioma (MPM) is a rare malignancy with few effective molecular therapies. In this study, we evaluated the anti-tumor activity and safety of apatinib, a vascular endothelial growth factor receptor 2 inhibitor, in MPM in vitro and in vivo.MethodsWe established several patient-derived xenograft (PDX) models and primary cell lines of MPM. The cell lines were used to study the effects of apatinib on proliferation, cell cycle, migration, and apoptosis by CCK8, flow cytometry, wound-healing, Transwell, DAPI staining, and caspase-3 assays, respectively. For in vivo study, apatinib was delivered by gastric gavage into PDX models, and then efficacy and toxicity were determined by experimental peritoneal cancer index (ePCI) score and pathological examinations.ResultsOur results showed that apatinib significantly inhibited the proliferation and migration of MPM cells in vitro and induced cell cycle arrest. Studies on PDX models concurred that apatinib effectively suppressed subphrenic and liver invasions of nude mice. Moreover, histopathological analysis found that lymphocyte infiltration, coagulation necrosis and eosinophilic cell fragments were detected in tumor tissues after apatinib treatment. Apatinib showed no obvious effects on body mass of models and did not affect function of important organs, except for occasional focal lymphoid infiltration of liver (16.7%) and cardiac muscle (16.7%).ConclusionsWe successfully established MPM PDX models and primary cell lines, and confirmed that apatinib effectively inhibited proliferation and metastasis of MPM in vitro and in vivo study.