Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients With Malignant Ascites Secondary to Unresectable Gastric Cancer.

BACKGROUND: To compare the efficacy of 3 chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC). MATERIALS AND METHODS: From January 2010 to December 2013, 38 GC patients were randomly divided into 3 groups and treated by laparoscopic HIPPC with 1 of the 3 following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin (L-OHP), Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the 3 groups. RESULTS: The intraoperative course was successful in all patients, and no perioperative death or complication related to laparoscopic HIPPC was documented. The median follow-up period was 9 months and the median survival was 7.5 months for all patients. Patients in the Ra/L-OHP group had a median survival of 8.7 months, the Ra/DDP group had a median survival of 5.6 months, and the Ra/MMC group had a median survival of 7.5 months. Patients' median survival in the Ra/L-OHP group and Ra/MMC group is significantly longer than Ra/DDP group (P<0.05). No significant difference was found in total remission rate of ascites, increase in the Karnofsky performance scale, and incidence rate of port-site metastases among the 3 groups. CONCLUSIONS: Laparoscopy-assisted HIPPC provide modest yet encouraging efficacy for malignant ascites secondary to disseminated GC. Our preliminary data indicate that the chemotherapeutical combination of Ra/L-OHP and Ra/MMC might be more beneficial compared with Ra/DDP in terms of patients' survival.

Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Predictor of Sorafenib Benefit in Patients with Hepatocellular Carcinoma.

Sorafenib is the most recommended first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Yet there is no clinically applied biomarker for predicting sorafenib response. We have demonstrated that a vascular pattern, named VETC (Vessels that Encapsulate Tumor Clusters), facilitates the release of whole tumor clusters into the bloodstream; VETC-mediated metastasis relies on vascular pattern, but not on migration and invasion of cancer cells. In this study, we aimed to explore whether vascular pattern could predict sorafenib benefit. Two cohorts of patients were recruited from four academic hospitals. The survival benefit of sorafenib treatment for patients with or without the VETC pattern (VETC+ /VETC- ) was investigated. Kaplan-Meier analyses revealed that sorafenib treatment significantly reduced death risk and prolonged overall survival (OS; in cohort 1/2, P = 0.004/0.005; hazard ratio [HR] = 0.567/0.408) and postrecurrence survival (PRS; in cohort 1/2, P = 0.001/0.002; HR = 0.506/0.384) in VETC+ patients. However, sorafenib therapy was not beneficial for VETC- patients (OS in cohort 1/2, P = 0.204/0.549; HR = 0.761/1.221; PRS in cohort 1/2, P = 0.121/0.644; HR = 0.728/1.161). Univariate and multivariate analyses confirmed that sorafenib treatment significantly improved OS/PRS in VETC+ , but not VETC- , patients. Further mechanistic investigations showed that VETC+ and VETC- HCCs displayed similar levels of light chain 3 (LC3) and phosphorylated extracellular signal-regulated kinase (ERK) in tumor tissues (pERK) or endothelial cells (EC-pERK), and greater sorafenib benefit was consistently observed in VETC+ HCC patients than VETC- irrespective of levels of pERK/EC-pERK/LC3, suggesting that the different sorafenib benefit between VETC+ and VETC- HCCs may not result from activation of Raf/mitogen-activated protein kinase kinase (MEK)/ERK and vascular endothelial growth factor (VEGF)A/VEGF receptor 2 (VEGFR2)/ERK signaling or induction of autophagy. Conclusion: Sorafenib is effective in prolonging the survival of VETC+ , but not VETC- , patients. VETC pattern may act as a predictor of sorafenib benefit for HCC.

Port-Site Metastases and Chimney Effect of B-Ultrasound-Guided and Laparoscopically-Assisted Hyperthermic Intraperitoneal Perfusion Chemotherapy.

PURPOSE: CO2 leakage along the trocar (chimney effect) has been proposed to be an important factor underlying port-site metastasis after laparoscopic surgery. This study aimed to test this hypothesis by comparing the incidence of port-site metastasis between B-ultrasound-guided and laparoscopically-assisted hyperthermic intraperitoneal perfusion chemotherapy (HIPPC). MATERIALS AND METHODS: Sixty-two patients with malignant ascites induced by gastrointestinal or ovarian cancer were divided into two groups to receive either B-ultrasound-guided or laparoscopically-assisted HIPPC. Clinical efficacy was assessed from the objective remission rate (ORR), the Karnofsky Performance Status (KPS) score, and overall survival. The incidence of port-site metastasis was compared between the two groups. RESULTS: Patients in the B-ultrasound (n=32) and laparoscopy (n=30) groups were comparable in terms of age, sex, primary disease type, volume of ascites, and free cancer cell (FCC)-positive ascites. After HIPPC, there were no significant differences between the B-ultrasound and laparoscopy groups in the KPS score change, ORR, and median survival time. The incidence of port-site metastasis after HIPPC was not significantly different between the B-ultrasound (3 of 32, 9.36%) and laparoscopy (3 of 30, 10%) groups, but significantly different among pancreatic, gastric, ovarian, and colorectal cancer (33.33, 15.79, 10.00, and 0.00%, p<0.001). CONCLUSION: The chimney effect may not be the key reason for port-site metastasis after laparoscopy. Other factors may play a role, including the local microenvironment at the trocar site and the delivery of viable FCCs (from the tumor or malignant ascites) to the trauma site during laparoscopic surgery.

Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients with Malignant Ascites Secondary to Unresectable Gastric Cancer.

BACKGROUND: To compare the efficacy of three chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC). MATERIALS AND METHODS: From January 2010 to December 2013, 38 GC patients were randomly divided into three groups and treated by laparoscopic HIPPC with one of the three following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin [trans-(±)-diaminocyclohexane oxalatoplatinum (l-OHP)], Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the three groups. RESULTS: The intraoperative course was successful in all patients, and no perioperative death or complication related to laparoscopic HIPPC was documented. The median follow-up period was 9 months, and the median survival was 7.5 months for all patients. Patients in the Ra/l-OHP group had a median survival of 8.7 months, the Ra/DDP group had a median survival of 5.6 months, and the Ra/MMC group had a median survival of 7.5 months. Patients' median survival in the Ra/l-OHP group and Ra/MMC group was significantly longer than in the Ra/DDP group (P < .05). No significant difference was found in total remission rate of ascites, increase in the Karnofsky Performance Scale, and incidence rate of port-site metastases among the three groups. CONCLUSIONS: Laparoscopy-assisted HIPPC provides modest yet encouraging efficacy for malignant ascites secondary to disseminated GC. Our preliminary data indicate that the chemotherapeutic combination of Ra/l-OHP and Ra/MMC might be more beneficial compared with Ra/DDP in terms of patients' survival.

Multivariate comparison of B-ultrasound guided and laparoscopic continuous circulatory hyperthermic intraperitoneal perfusion chemotherapy for malignant ascites.

OBJECTIVE: Clinical efficacy of B-ultrasound-guided and laparoscopy-assisted continuous hyperthermic intraperitoneal perfusion chemotherapy (CHIPC) for treatment of malignant ascites was investigated. METHODS: Sixty-two patients with malignant ascites induced by ovarian or gastrointestinal cancers were randomly treated with B-ultrasound-guided CHIPC (therapeutic group) or laparoscopy-assisted CHIPC (control group) performed at the same center. Hospitalization costs and surgical duration were evaluated. Follow-up was conducted for 21 months with B-ultrasound or computed tomography at least once per month for assessment of ascites amount and tumor progression. Clinical efficacy was assessed by modified World Health Organization criteria. Survival time, Karnofsky performance score (KPS) of quality of life (QOL), and complications were recorded for all patients. RESULTS: Overall condition, primary disease type, and ascites amounts were comparable between groups. Significantly shorter mean duration of perfusion catheter placement (35 vs. 85 min) and mean hospitalization cost (36,000 vs. 55,000 ¥/patient) were observed in the therapeutic group than the control group (P < 0.01). Significantly different KPS scores were not observed before or after CHIPC (23.13 vs. 22.64 %) in both groups (P > 0.05). No significant differences in objective remission rates of malignant ascites (93.75 vs. 93.34 %), median survival times (9 vs. 8 months), or stamp hole metastasis rates (18.75 vs. 18.15 %) were observed between groups (P > 0.05). CONCLUSIONS: B-ultrasound-guided and laparoscopy-assisted CHIPC have similar clinical efficacy for improving QOL and prolonging patient survival. B-ultrasound-guided CHIPC may, however, shorten operation times and reduce hospitalization costs, making the treatment available to a broader patient population, although port hole metastasis remains an issue.