Tatiana Beresnev

Analysis of Factors Associated With Outcome in Patients With Malignant Peritoneal Mesothelioma Undergoing Surgical Debulking and Intraperitoneal Chemotherapy

PURPOSE Malignant mesothelioma (MM) arising in the peritoneal cavity is a rare neoplasm characterized by peritoneal progression and for which there are limited therapeutic options. We evaluated the peritoneal progression-free and overall survival (PFS and OS, respectively) for patients with peritoneal MM after surgical resection and regional chemotherapy. PATIENTS AND METHODS Forty-nine patients (28 males, 21 females; median age, 47 years; range, 16 to 76 years) with MM underwent laparotomy, tumor resection, continuous hyperthermic peritoneal perfusion with cisplatin (median dose 250 mg/m2), and a single postoperative intraperitoneal dwell of fluorouracil and paclitaxel (n = 35) on protocols approved by the Institutional Review Board. Standard techniques for actuarial analyses of potential prognostic variables (Kaplan-Meier method with two-tailed log-rank test and Cox proportional hazards model) were performed. RESULTS At a median potential follow-up of 28.3 months, median actuarial PFS is 17 months and actuarial OS is 92 months. Factors associated with improved PFS and OS by the Cox proportional hazards model were a history of previous debulking surgery, absence of deep tissue invasion, minimal residual disease after surgical resection (OS only), and age younger than 60 years (OS only). CONCLUSION Surgical resection and regional chemotherapy for MM results in durable PFS and OS. Favorable outcome is associated with age, tumor biology (selection of patients with a history of previous debulking), lack of invasive tumor growth, and minimal residual disease after tumor resection.

Impact of Maximal Cytoreductive Surgery Plus Regional Heated Intraperitoneal Chemotherapy (HIPEC) on Outcome of Patients With Peritoneal Carcinomatosis of Gastric Origin: Results of the GYMSSA Trial

A prospective randomized trial was conducted to compare the impact of systemic chemotherapy versus multi‐modality therapy (complete cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and systemic chemotherapy) on overall survival (OS) in patients with gastric carcinomatosis.

Site-Specific Gene Expression Profiles and Novel Molecular Prognostic Factors in Patients with Lower Gastrointestinal Adenocarcinoma Diffusely Metastatic to Liver or Peritoneum

BackgroundGenerally, colorectal and high-grade appendiceal cancers are treated similarly; treatment approach is primarily based on tumor histology and stage of disease. Patients with adenocarcinoma of the lower gastrointestinal tract frequently experience diffuse metastases isolated to liver or peritoneum and have a poor survival. Identification of novel molecular pathways in metastases from these patients may identify novel targets and prognostic factors.MethodsMicroarray analyses of 20 metastatic tumors from patients with colorectal adenocarcinoma isolated to liver or peritoneum and eight high-grade appendiceal adenocarcinoma metastatic to peritoneum were performed using oligonucleotide microarray.ResultsIn an unsupervised hierarchical cluster analysis of 2-fold upregulated or downregulated genes, there was a clear site-specific segregation of liver versus peritoneal metastases. Genes primarily involved in metastasis, angiogenesis, cell cycle regulation, cell proliferation, and cell adhesion were distinctly altered between these two metastatic sites. Among the metastasis genes, the average expression levels of LI-cadherin, ALCAM, CD2, and CD14 were significantly higher in both metastatic sites. TIMP1 was overexpressed in both sites where as TIMP-2, IGF-1, and HIF-1α were upregulated only in peritoneal metastases demonstrating the potential benefit of metastasis site-specific treatments. Subsets of genes significantly associated with poor survival were defined, a RET proto-oncogene interacting gene, GOLGA5, was highly predictive for survival in patients with colorectal adenocarcinoma.ConclusionsThese results demonstrate that liver and peritoneal metastases of lower GI adenocarcinoma have distinct gene expression patterns; these distinctions may help in the development of therapies based on site of metastases.

Hepatic vascular isolation and perfusion for patients with progressive unresectable liver metastases from colorectal carcinoma refractory to previous systemic and regional chemotherapy

Many patients with colorectal carcinoma develop unresectable metastases confined to the liver that remain the life‐limiting component of disease despite best available systemic or regional chemotherapy. In the current study, the authors present their results using vascular isolation and perfusion of the liver for individuals with progressive, unresectable liver metastases from colorectal carcinoma that were refractory to both previous systemic and regional chemotherapy.