Multi-institutional experience of diffuse intra-abdominal multicystic peritoneal mesothelioma
ABSTRACT This study was undertaken to measure survival of patients with multicystic peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy through a multi-institutional collaboration.
A multi-institutional data registry, established by the Peritoneal Surface Oncology Group, was used to identify patients with peritoneal mesothelioma and the subgroup with multicystic tumours, treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Outcomes for this subgroup are reported. The primary endpoint was overall survival. A secondary endpoint was the incidence of treatment-related complications.
Of 405 patients with peritoneal mesothelioma, 26 (6·4 per cent) had multicystic tumours. There were 20 women and six men with a mean(s.d.) age of 42(12) years. The median peritoneal carcinomatosis index (PCI) was 14 (range 6-39). There was no perioperative mortality. Six patients developed grade III or IV complications. After a median follow-up of 54 (range 5-129) months, all 26 patients were still alive.
Multicystic peritoneal mesothelioma appears to be a distinct subtype of peritoneal mesothelioma, where long-term survival may be achieved through cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
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ABSTRACT: Peritoneal dissemination of abdominal malignancy (carcinomatosis) has a clinical course marked by bowel obstruction and death; it traditionally does not respond well to systemic therapy and has been approached with nihilism. To treat carcinomatosis, we use cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC). A prospective database of patients has been maintained since 1992. Patients with biopsy-proven peritoneal surface disease were uniformly evaluated for, and treated with, CS and HIPEC. Patient demographics, performance status (Eastern Cooperative Oncology Group), resection status, and peritoneal surface disease were classified according to primary site. Univariate and multivariate analyses were performed. The experience was divided into quintiles and outcomes compared. Between 1991 and 2013, a total of 1,000 patients underwent 1,097 HIPEC procedures. Mean age was 52.9 years and 53.1% were female. Primary tumor site was appendix in 472 (47.2%), colorectal in 248 (24.8%), mesothelioma in 72 (7.2%), ovary in 69 (6.9%), gastric in 46 (4.6%), and other in 97 (9.7%). Thirty-day mortality rate was 3.8% and median hospital stay was 8 days. Median overall survival was 29.4 months, with a 5-year survival rate of 32.5%. Factors correlating with improved survival on univariate and multivariate analysis (p ≤ 0.0001 for each) were preoperative performance status, primary tumor type, resection status, and experience quintile (p = 0.04). For the 5 quintiles, the 1- and 5-year survival rates, as well as the complete cytoreduction score (R0, R1, R2a) have increased, and transfusions, stoma creations, and complications have all decreased significantly (p < .001 for all). This largest reported single-center experience with CS and HIPEC demonstrates that prognostic factors include primary site, performance status, completeness of resection, and institutional experience. The data show that outcomes have improved over time, with more complete cytoreduction and fewer serious complications, transfusions, and stomas. This was due to better patient selection and increased operative experience. Cytoreductive surgery with HIPEC represents a substantial improvement in outcomes compared with historical series, and shows that meaningful long-term survival is possible for selected carcinomatosis patients. Multi-institutional cooperative trials are needed to refine the use of CS and HIPEC.Journal of the American College of Surgeons 12/2013; 218(4). DOI:10.1016/j.jamcollsurg.2013.12.013 · 4.45 Impact Factor
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ABSTRACT: Multicystic mesothelioma is a rare disease of unknown etiology and pathogenesis. Nothing has been known about the cytogenetic and molecular genetic features of these tumors. Here we present the first cytogenetically analyzed multicystic mesothelioma with the karyotype 46,XX,t(7;17)(p13;q23),t(8;11)(q23;p13). RNA-sequencing showed that the t(7;17)(p13;q23) generated a chimeric TNS3-MAP3K3 gene, which codes for a chimeric protein kinase, as well as the reciprocal MAP3K3-TNS3 in which the region of TNS3 coding for the SH2_Tensin_like region and the tensin phosphotyrosine-binding domain is under the control of the MAP3K3 promoter. The other translocation, t(8;11)(q23;p13), generated a chimeric ZFPM2-ELF5 gene which codes for a chimeric transcription factor in which the first 40 amino acids of ELF5 are replaced by the first 100 amino acid of ZFPM2. RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcripts. The finding of acquired clonal chromosome abnormalities in cells cultured from the lesion and the presence of the TNS3-MAP3K3 chimeric protein kinase and the ZFPM2-ELF5 chimeric transcription factor confirm the neoplastic nature of multicystic mesothelioma. Copyright © 2014. Published by Elsevier Ireland Ltd.Cancer Letters 12/2014; 357(2). DOI:10.1016/j.canlet.2014.12.002 · 5.02 Impact Factor
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ABSTRACT: BackgroundCytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option for selected patients with peritoneal carcinomatosis. There are limited data available on anaesthesia management and its impact on patients’ outcome. Our aim was to retrospectively analyze and evaluate perioperative management and the clinical course of patients undergoing CRS/HIPEC within a three-year period.MethodsAfter ethic committee approval, patient charts were retrospectively reviewed for patient characteristics, interventions, perioperative management, postoperative course, and complications. Analysis was intervention based. Data are presented as median (range).ResultsBetween 2009 and 2011, 54 consecutive patients underwent 57 interventions; median anaesthesia time was 715 (range 370 to 1135) minutes. HIPEC induced hyperthermia with an overall median peak temperature of 38.1 (35.7-40.2)°C with active cooling. Bleeding, expressed as median blood loss was 0.8 (0 to 6) litre and large fluid shifts occurred, requiring a total fluid input of 8.4 (4.2 to 29.4) litres per patient. Postoperative renal function was dependent on preoperative function and the type of fluids used. Administration of hydroxyethyl starch colloid solution had a significant negative impact on renal function, especially in younger patients. Major complications occurred after 12 procedures leading to death in 2 patients. Procedure time and need for blood transfusion were associated with a significantly higher risk for major complications.ConclusionsCytoreductive surgery with HIPEC is a high-risk surgical procedure associated with major hemodynamic and metabolic changes. As well as primary disease and complexity of surgery, we have shown that anaesthesia management, the type and amount of fluids used, and blood transfusions may also have a significant effect on patients’ outcome.World Journal of Surgical Oncology 05/2014; 12(1):136. DOI:10.1186/1477-7819-12-136 · 1.20 Impact Factor