Peritoneal Mesothelioma Patients Research Articles

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for fourweeks postoperatively. Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p=0.21). Most events were symptomatic (n=16, 62%) and were attributable to pulmonary emboli (n=16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p=0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p=0.98). A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

Cisplatin exhibits superiority over MMC as a perfusion agent in a peritoneal mesothelioma patient specific organoid HIPEC platform

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.

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.

Surgical phenotype of patients with peritoneal mesothelioma and a germline mutation.

This study aimed to investigate if peritoneal mesothelioma (PM) patients with germline mutations (GM) have distinct surgical characteristics when compared to those without GM. PM patients were selected from an ongoing prospective study that conducts germline testing of 82 susceptibility genes. Germline status was correlated with surgical data obtained from a prospectively collected database using univariate, multivariate, and receiver operating characteristic (ROC) analyses. Out of 88 PM patients enrolled between 2009 and 2019, 18GMs (20.5%) were identified in BRCA1-associated protein 1 (BAP1) (n=11, 12.5% of all patients), SDHA (n=2) and WT1, CDKN2A, CHEK2, ATM, and BRCA2 (n=1 patient each). Surgical procedures were performed in 71 patients, the most common of which were cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy (n=61). Patients with GM presented with a higher prevalence of other prior cancers (61.1% vs. 31.4%, p=.02) and lower platelet count (251 [160-413] vs. 367 [196-780] K/µL, p=.005) compared to those without GM (n=70). Survival outcomes did not differ significantly between the groups. Patients with BAP1 GMs were more likely to develop bicavitary disease and to present with lower platelet count and mitotic count score, and higher peritoneal cancer index (PCI, all p≤.04) compared with those without GM. On ROC analysis, the combination of PCI, platelet count and mitotic score yielded an area under the curve of 0.96 (95% CI, 0.91-1.0) for BAP1 GM detection among operated PM patients. Higher intraoperative tumor burden and lower platelet count and mitotic score are suggestive of BAP1 GMs in surgical PM patients and should prompt germline testing.

CT Differentiation of Diffuse Malignant Peritoneal Mesothelioma, Tuberculous Peritonitis, and Peritoneal Carcinomatosis

Objective: To investigate the significance of computed tomography findings in diffuse malignant peritoneal mesothelioma (DMPeM), tuberculous peritonitis (TBP), and peritoneal carcinomatosis (PC) to differentiate the three diseases. Methods: The clinical manifestation and computed tomography scans of 147 patients with diffuse malignant peritoneal mesothelioma (n = 60), tuberculous peritonitis (n = 32), and peritoneal carcinomatosis (n = 55) were retrospectively reviewed, while taking into account of ascites, pleural plaques, viscera infiltration; abnormalities in the peritoneum; involvement of the mesentery and omentum; as well as the presence and location of enlarged lymph nodes. Results: There was no significant difference among all three groups in terms of clinical manifestation, peritoneum, omentum, and mesentery involvement, ascites, as well as the presence and location of enlarged lymph nodes. The study found that 95% of DMPeM patients had been exposed to asbestos in the past. The patients showed significant differences in the following aspects: (1) irregular peritoneum thickening, caked omentum thickening, pleural plaques, visceral infiltration, and asbestos exposure were more common in peritoneal mesothelioma patients; (2) nodular peritoneum thickening and visceral metastasis were more common in patients with peritoneal carcinomatosis; (3) smooth peritoneal thickening, pleural effusion, and extraperitoneal tuberculosis were more common in patients with tuberculous peritonitis. Conclusion: A combination of computed tomography findings could improve our ability in differentiating the three diseases.

Survival Outcomes for Malignant Peritoneal Mesothelioma at Academic Versus Community Hospitals

BackgroundMalignant 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. MethodsThis 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. ResultsIn 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). ConclusionsWe 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.

Loss of BAP1 as a candidate predictive biomarker for immunotherapy of mesothelioma

As trials of immune checkpoint inhibitor (ICI) therapies demonstrate responses in only a minority of pleural mesotheliomas (PlMs) and largely exclude patients with the related peritoneal mesothelioma (PeM), clinicians need predictive biomarkers of response and inclusion of PeM patients in future trials. A new study finds that loss of the deubiquitinase BAP1 in PeM correlates with an inflammatory tumor microenvironment, suggesting that BAP1 status might identify PeM, and possibly PlM, patients who would benefit from ICI therapy.

BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma

BackgroundMalignant peritoneal mesothelioma (PeM) is a rare and fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM exist. Some immune checkpoint inhibitor studies of mesothelioma have found positivity to be associated with a worse prognosis.MethodsTo search for novel therapeutic targets for PeM, we performed a comprehensive integrative multi-omics analysis of the genome, transcriptome, and proteome of 19 treatment-naïve PeM, and in particular, we examined BAP1 mutation and copy number status and its relationship to immune checkpoint inhibitor activation.ResultsWe found that PeM could be divided into tumors with an inflammatory tumor microenvironment and those without and that this distinction correlated with haploinsufficiency of BAP1. To further investigate the role of BAP1, we used our recently developed cancer driver gene prioritization algorithm, HIT’nDRIVE, and observed that PeM with BAP1 haploinsufficiency form a distinct molecular subtype characterized by distinct gene expression patterns of chromatin remodeling, DNA repair pathways, and immune checkpoint receptor activation. We demonstrate that this subtype is correlated with an inflammatory tumor microenvironment and thus is a candidate for immune checkpoint blockade therapies.ConclusionsOur findings reveal BAP1 to be a potential, easily trackable prognostic and predictive biomarker for PeM immunotherapy that refines PeM disease classification. BAP1 stratification may improve drug response rates in ongoing phases I and II clinical trials exploring the use of immune checkpoint blockade therapies in PeM in which BAP1 status is not considered. This integrated molecular characterization provides a comprehensive foundation for improved management of a subset of PeM patients.

Overall survival of pseudomyxoma peritonei and peritoneal mesothelioma patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy can be predicted by computed tomography quantified sarcopenia

BackgroundMalnutrition is associated with increased postoperative morbidity in abdominal surgery. This study aimed to determine if sarcopenia and/or abdominal fat composition could predict postoperative outcomes for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for pseudomyxoma peritonei (PMP) and peritoneal mesothelioma (PM). MethodsAll patients who underwent a complete CRS-HIPEC for PMP and PM, between January 2009 and September 2017, were retrospectively studied. Preoperative computed tomography (CT) was used to measure the cross-sectional surface of skeletal muscle mass and adipose tissue (visceral and subcutaneous), at the level of the third lumbar vertebrae, to assess for sarcopenia and abdominal fat composition. ResultsAmong 115 patients, 82 were treated for PMP and 33 for PM. 64 patients (55.7%) were sarcopenic on the preoperative imagery. Major postoperative complications occurred in 63 patients (54.8%), without observable difference between sarcopenic and non-sarcopenic patients (56.2% vs. 52.9%; p = 0.723). The median overall survival (OS) was 73.3 for the patients with a normal muscle mass and 57.2 months for the sarcopenic patients (p = 0.05). ConclusionCT measured sarcopenia is an independent predictive factor for overall survival in patients treated for PMP and PM with CRS-HIPEC, but cannot predict postoperative morbidity.

Current status of malignant mesothelioma with liver involvement in China: A brief report and review of the literature.

Primary and secondary intrahepatic malignant mesothelioma (PIHMM & SIHMM) caused by Peritoneal mesothelioma (PM) are extremely rare tumors and their clinicopathological characteristics remain unclear. The current study presented a case of a 63-year-old female with PIHMM and a literature review of Chinese case reports of SIHMM and PIHMM was performed. The patient received curative left hemihepatectomy because of a 5.5 × 5.0 × 4.0 cm mass occupying the II, III and the lateral portion of the IV segments and meanwhile tightly infiltrating the diaphragm (yellow arrow) was also observed. The pathological diagnosis was epithelial type PIHMM. Immunohistochemistry revealed that the tumor was positive for Calretinin, CK5/6, WT-1 and D2-40(N). The literature review included 11 studies and 6 case reports with a total of 293 PM patients accompanied with 31 SIHMM cases and then 3 case reports of PIHMM. SIHMM and PIHMM are extremely rare, easy to misdiagnose malignant tumors. Immunohistochemistry should be performed strictly in accordance with guidelines, which is crucial for pathological diagnosis. Comprehensive treatment of surgery combined with chemotherapy are mainstream methods for SIHMM and PIHMM. Also, exact survival data should be carefully explored so that objective evaluation of the efficacy of the treatment could be achieved.

Malignant peritoneal mesothelioma: Clinicopathological features, prognostic factors, and survival outcomes.

650 Background: Peritoneal mesothelioma (PeM) is an orphan disease with approximately 300-400 cases diagnosed in the United States each year. Due to its rarity, data on its presentation and prognostic factors is limited. The purpose of this study was to investigate the clinicopathological profile and outcome of Malignant PeM (MPeM). Methods: We retrospectively reviewed 128 PeM patients (pts) seen at UTMDACC (2011 - 2017) comprised of 111 MPeM and 17 variants (VPeM) [9 well-differentiated papillary and 8 multicystic]. Kaplan-Meier method was used to estimate median overall survival (mOS) and compared with log-rank tests. Results: Median age at diagnosis was 57 yrs. with a higher proportion of women (61%). The mOS for MPeM was significantly shorter than VPeM (HR 3.7, 95% CI: 1.6 – 8.4, P = 0.002). Among pts with MPeM, median age at diagnosis was 56 yrs. and 58% were women. Only 22% had prior exposure to asbestos. Epithelioid subtype was seen in 94 (85%) pts. Calretinin and WT-1 IHC were positive in 98% and 96% of cases. BerEP4 and MOC-31 IHC were negative in 90% and 84% of cases. After median follow-up of 31 months (m), the mOS for MPeM cohort was 78 m. In univariate analysis, age, prior asbestos exposure, ECOG PS, histologic subtype, CA125, neutrophil-lymphocyte ratio (NLR) and cytoreductive surgery (CRS) were found to be associated with OS. In multivariate analyses, age ≥ 65 years (HR 4.5, 95% CI: 1.3 - 15.2, P = 0.02), prior asbestos exposure (HR 4.1, 95% CI: 1.1 – 15.6, P = 0.04), poor PS (ECOG 2/3) (HR 8.9, 95% CI: 1.7 – 47.7, P = 0.01), elevated CA125 ( &gt; 3X upper limit of normal) (HR 4.5, 95% CI: 1.3 – 15.5, P = 0.02), and high NLR (HR 3.8, 95% CI: 1.1 – 12.6, P = 0.03) were found to be independently associated with poor OS. A total of 50 (45%) pts underwent CRS and among these the completion of cytoreduction score (CCS) was strongly associated with OS (mOS: 201 m, 53 m and 36 m for CCS 0, 1, 2/3, respectively, P = 0.005). Conclusions: MPeM is associated with poor survival outcomes. Prognostic factors include age, history of asbestos exposure, CA-125 level, NLR, and PS. CRS with CCS 0 results in favorable survival. Further understanding of molecular genetics is warranted to improve prognostication and outcomes.

The role of 18F-FDG-PET/ceCT in peritoneal mesothelioma.

The aim of this study was to assess glucose metabolism of multicystic peritoneal mesothelioma and epithelioid peritoneal mesothelioma by fluorine-18 fluorodeoxyglucose (F-FDG)-PET/contrast-enhanced computed tomography (ceCT) and to assess its prognostic impact. Twenty-three (14 women) patients, without previous treatment, underwent F-FDG-PET/ceCT before peritoneal mesothelioma cytoreductive surgery and intraperitoneal chemotherapy. F-FDG-PET/ceCT was interpreted prospectively as positive or negative. Maximum standardized uptake value (SUVmax) of each lesion was measured retrospectively on the basis of postsurgery data. At laparotomy, disease extension was estimated with the Peritoneal Cancer Index. The median follow-up was 27 months (95% confidence interval: 12.9-37.8); progression-free survival (PFS) was recorded. Nine patients were affected by multicystic and 14 were affected by epithelioid peritoneal mesothelioma. PET showed mild focal uptake in one case of multicystic peritoneal mesothelioma, whereas in eight patients, no abnormal uptake was observed. PET was positive in 12/14 patients with epithelioid peritoneal mesothelioma. Sensitivity, specificity and accuracy were respectively 86, 89 and 87%; the qualitative assessment was statistically different (P=0.0020, χ). Multicystic peritoneal mesothelioma histology was significantly associated with lower SUVmaxlesion (P=0.0061), SUVmaxlesion/liver (P=0.0025), Peritoneal Cancer Index, younger age, and it was observed only in women.Recurrence was observed on nine patients affected by epithelioid peritoneal mesothelioma, whereas no recurrences were observed among multicystic peritoneal mesothelioma patients. SUVmaxlesion (P=0.0278) and age (P=0.0241) were significantly associated with PFS in patients with epithelioid peritoneal mesothelioma. F-FDG-PET/ceCT showed significant differences between multicystic and epithelioid peritoneal mesothelioma, whereas SUVmaxlesion was associated with PFS in the latter. Although multicentre prospective studies are necessary, F-FDG-PET/ceCT appears to be a promising tool in patients affected by peritoneal mesothelioma.

Serum β-human chorionic gonadotropin as a tumor marker for malignant mesothelioma

Peritoneal mesotheliomas are aggressive tumors arising from the peritoneal mesothelium. Tumor markers are biochemical substances produced by tumor cells due to the effect of malignant process. They can be used for screening, diagnosis, and predicting the prognosis. β-human chorionic β-human chorionic gonadotrophin (β-hCG), is a marker of germ cell tumors and trophoblastic diseases. In some reports, a relationship between β-hCG and other malignant diseases has been described. Hereby, we present a case of malignant peritoneal mesothelioma associated with elevated serum β-hCG levels. A 49-year-old man was admitted to the hospital with ascites. Peritoneal mesothelioma was diagnosed with peritoneal biopsy. During the treatment period, serum β-hCG levels were elevated together with disease progression and tissue samples stained positive for β-hCG. Rising levels of serum β-hCG due to disease progression can predict the response to treatment. If these levels were elevated at the beginning of the treatment, it may be a prognostic marker for peritoneal mesothelioma. Thus, β-hCG may be an important marker for prognosis or prediction of treatment for peritoneal mesothelioma patients. Keywords: Mesothelioma, Human chorionic gonadotrophin, Tumor marker

Survival and fertility in women with malignant peritoneal mesothelioma.

111 Background: The prognosis of malignant peritoneal mesothelioma (MPM) has improved over the past decade in patients undergoing operative extirpation and intraperitoneal chemotherapy (IC). This study investigates the time from diagnosis to treatment intervention in premenopausal women and its impact on fertility and childbearing options. Methods: A retrospective analysis of 195 patients diagnosed with peritoneal mesothelioma between 1995 and 2015. Patients with unresectable or bicavity disease were not excluded. Kaplan-Meier curves and univariate cox proportional hazards model were used to estimate survival and significant treatment and prognosis factors. Results: The median survival time of all peritoneal mesothelioma patients (n = 195) was 3.21 years with (95% CI: 2.38- 5.53), with median follow-up of 3.44 years (SD = 3.4, minimum = 0.014 and maximum = 16.752) years from first operation. Patient set included 111 men (57%) and 84 women (43.1%) with female sex having favorable survival [HR: 0.442 95% CI: 0.296-0.659), p &lt; 0.001] of 110.1 months with (95% CI: lower bond: 48.3). Of these women, their mean age at diagnosis was 52 years, (SD = 14.5, minimum = 14.7 – maximum = 79.9), with a mean time of 8.20 months from diagnosis to the start of treatment (SD = 18.6, minimum = 0 and maximum = 128.6 months). Overall survival of premenopausal women (N = 23) during follow-up was 72.2% (SE = 27.8%). Mean age at time of diagnosis was 34.7 years, (SD = 9.26, minimum = 14.7, maximum = 48.1), with a mean time of 10.6 months from diagnosis to treatment (SD = 17.9, minimum = 0.63, maximum = 86.7). Of the 195 patients who received a full treatment course, 66 (33.8% CI: 95%) were still alive at the median follow-up, of those alive 37 are female: 7 are premenopausal and have presented with gynecological symptoms, and 17 are premenopausal and have presented with abdominal discomfort. Conclusions: This data suggests that women preparing for treatment of MPM should not be precluded from exploring fertility options. With a mean time of 10.6 months from diagnosis to treatment, it is possible for premenopausal women to take advantage of fertility preservation before starting treatment.

Quantitative X-ray Computed Tomography Peritoneography in Malignant Peritoneal Mesothelioma Patients Receiving Intraperitoneal Chemotherapy

BackgroundIntraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients.MethodsThirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR.ResultsDecreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167).DiscussionComputed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment’s surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.

The Role of Perioperative Systemic Chemotherapy in Diffuse Malignant Peritoneal Mesothelioma Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

The aim of this study was to evaluate the effects of perioperative systemic chemotherapy (CT) on short-term surgical and long-term oncologic results in diffuse malignant peritoneal mesothelioma (DMPM) patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We retrospectively analyzed data obtained from an institutional prospective database at NCI of Milan. The study group comprised 116 DMPM patients treated with CRS+HIPEC from August 1995 to October 2011. A total of 60 cases underwent preoperative CT (PRECT), 30 underwent postoperative CT (POSTCT), and 26 did not undergo any CT (NOCT). Also, 55 cases used the perioperative combination of platinum and pemetrexed. We tested whether covariates related to clinical, histologic, PRECT, and surgical treatment were correlated with completeness of cytoreduction (CC), postoperative G3-5 morbidity, and progression-free survival and overall survival (OS). Univariate and multivariate analyses were performed. Factors independently associated with CC were ECOG performance status (PF) of 0, and PCI <20. Factors independently associated with postoperative G3-5 morbidity were ECOG >1, bowel anastomosis, and number of peritonectomy procedures. Preoperative platelet count >400×103/mm(3), histological subtype (biphasic and sarcomatoid vs epithelial), CC, and G3-5 morbidity were independent prognostic factors. PRECT was not associated with CC or G3-5 morbidity. There was no significant difference in terms of survival between the PRECT, POSTCT, and NOCT groups. The CC, G3-5, and OS were not influenced by aspects related to perioperative CT. The present data warrants confirmation reconducting the comparative analysis in a larger multi-institutional series preferably using matching control techniques.

Genome-Wide Single Nucleotide Polymorphism Arrays as a Diagnostic Tool in Patients With Synchronous Endometrial and Ovarian Cancer

Synchronous carcinomas in the endometrium and ovaries can be a single primary tumor with metastasis (SPM) or dual primary tumors (DP). Although the prognosis of DP without any metastases is significantly better than that of SPM, pathological diagnosis is difficult in tumors with similar histological features. In 10 tumors from 5 patients with synchronous endometrial and ovarian carcinomas, 250K single nucleotide polymorphism arrays were performed. The patients were genetically diagnosed according to the pattern of copy number alterations (CNAs), in addition to microsatellite status and mutational analysis of PIK3CA, PTEN, K-Ras, and CTNNB1. Of the 5 patients, 3 exhibited identical CNA patterns, including type, loci, and degree of each alteration in the endometrial and ovarian carcinomas. The other 2 exhibited CNAs only in either endometrial or ovarian carcinoma. All 5 tumors had 1 or more genetic mutations in the genes examined. One patient exhibited mutations both in PIK3CA and PTEN at discordant sites between endometrial and ovarian carcinomas, whereas the other 4 exhibited concordant mutations. Overall, 4 of the 5 patients were genetically diagnosed with SPM, and the remaining 1 with DP. The pathological diagnosis was not in agreement with the genetic diagnosis in 4 of the 5 patients. Genome-wide genotyping diagnosis may represent a useful approach for distinguishing between SPM and DP in synchronous endometrial and ovarian carcinomas.

An Unusual Case of Primary Peritoneal Mesothelioma

Peritoneal mesothelioma is a rare disease, but it is increasing in frequency. Because of its unusual nature, the disease has not been clearly defined either in terms of its natural history, diagnosis, or management. Peritoneal mesothelioma patients generally present with two types of symptoms and signs; those with abdominal pain, usually localized and related to a dominant tumor mass with little or no ascites and those without abdominal pain, but with ascites and abdominal distention. Prognosis as determined by clinical presentation, the completeness of cytoreduction, and gender (females survive longer than males) appears to be improved by the use of intraperitoneal chemotherapy. We would like to report a case where our patient primarily presented with peritoneal mesothelioma without pleural involvement that responded well to standard wide surgical excision and postoperative chemotherapy.

A proposed staging system for diffuse malignant peritoneal mesothelioma patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy

4150 Background: There is no staging system available for diffuse malignant peritoneal mesothelioma (DMPM). This study evaluated seven clinical, seven radiological and twelve histopathologic prognostic parameters for survival of patients with DMPM. Methods: Between September 1989 and September 2005, sixty-two DMPM patients who were treated in a uniform fashion utilizing cytoreductive surgery combined with heated intraoperative intraperitoneal chemotherapy, with cisplatin and doxorubicin, followed by early postoperative intraperitoneal paclitaxel from postoperative day 1 to day 5 were included in this study. All prognostic parameters were analyzed in univariate and multivariate analyses using overall survival as the endpoint. The clinical and radiological data were obtained prospectively. A review of the histopathological features of DMPM was performed by two experienced pathologists, who individually evaluated each case. The mean number of specimens taken from separate anatomic sites was 11 ± 4 per patient. The mean number of slides studied was 20 ± 8 per patient. Results: The median follow-up was 37 months (range 8 to 143 months). The overall survival was 79 months (range 1 to 143 months) and 5-year survival was 50%. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (p = 0.045), peritoneal cancer index (p = 0.038), completeness of cytoreduction score (p = 0.010), interpretive CT findings of the small bowel (p = 0.001), histologic type (p &lt; 0.001), nuclear size (p &lt; 0.001), nuclear/cytoplasmic ratio (p &lt; 0.001), mitotic count (p &lt; 0.001), atypical mitosis (p &lt; 0.001), chromatin pattern (p &lt; 0.001), cellular necrosis (p &lt; 0.001), perineural invasion (p = 0.037), stroma pattern (p &lt; 0.001) and depth of invasion (p = 0.014). In the multivariate analysis, the only factor that was independently associated with an improved survival was nuclear size. The 3-year survival rates with nuclear size of 10–20 μm, 21–30 μm, 31–40 μm and &gt; 40 μm were 100%, 87%, 27% and 0%, respectively. Conclusions: Nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed. No significant financial relationships to disclose.

Peritoneal mesothelioma treated by cytoreductive surgery and intra peritoneal hyperthermic perfusion: Clinical and translational study

9729 Background: to report the NCI of Milan experience on treating Peritoneal Mesothelioma (PM) with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Secondary endpoints: 1) assessment of potential prognostic factors; 2) test of in vitro PM sensitivity to chemotherapies; 3) development of a gene therapy approach. Methods: Thirty eight PM patients underwent 40 consecutive procedures. Mean follow-up was 18,7 mths. 34 (89%) cases had malignant epithelioid disease. Twenty one (53%) cases received preoperative chemotherapy. The IPHP was performed with closed abdomen technique with cisplatin+mitomycin-C or cisplatin+doxorubicin through a heart-lung pump for 60 or 90 minutes at 42.5° C. Potential prognostic biological markers were evaluated on surgical 19 PM specimens. PM in vitro drug sensitivity was evaluated on primary cultures derived from surgical specimens. We established new PM cell lines for the development of a gene therapy approach, which aimed at the inhibition of cell survival factors. Results: 5-year overall and progression free survivals were 70% and 49%, respectively. The operative morbidity GIII, mortality and toxicity GIII/IV rates were 20%, 0% and 10%, respectively. PM cells largely expressed anti-apototic proteins belonging to bcl-2 and IAP family; most of the cases were negative for the expression of the pro-apototic factor SMAC/diablo. Reactivation of telomerase was found in 17/19 cases, which were positive for the expression of the hTERT catalytic subunit of the enzyme. The assessment of sensitivity profile of 7 PM primary cultures to a panel of drugs found a variable response rate for the different compounds. Conclusions: CRS+IPHP seems consistent with a potentially effective treatment for selected PM patients. Apoptosis related markers presented an apparent correlation with PM tumor cell biology, but the their prognostic significance is still undefined. Further definition of drug sensitivity profile and the development gene therapies will provide a possible biological rationale for the design of new clinical treatments. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AIRC (Italian Association of Cancer Research)