A Retrospective Case Series Of High-Intensity Focused Ultrasound (HIFU) In Combination With Gemcitabine And Oxaliplatin (Gemox) On Treating Elderly Middle And Advanced Pancreatic Cancer.

PURPOSE: This retrospective study was conducted to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) ablation combined with Gemcitabine and Oxaliplatin (Gemox) for the treatment of middle and advanced pancreatic cancer in elderly patients. METHODS: Forty-seven patients with pancreatic cancer treated with HIFU and Gemox were evaluated for inclusion, and 38 cases were finally included. The primary endpoint was safety. Secondary endpoints included the response rate, the clinical benefit response (CBR), overall survival (OS), progression-free survival (PFS). RESULTS: After combination therapy of HIFU and Gemox, severe complications were rarely reported, and no treatment-related death occurred. The rate of three or four-degree myelosuppression was low, and no obvious impairment of hepatorenal function was observed. Pancreatitis and gastrointestinal injury did not occurred. The disease control rate (DCR) was estimated to be 76.3%, including complete remission (CR), partial remission (PR), stable disease (SD) in 1, 6, 22 cases, respectively. And the objective response rate (ORR) was 18.4%. The clinical benefit rate (CBR) was 68.4%, with the pain significantly relieved (P<0.01). The serum level of CA19-9 showed significant changes after HIFU treatment. The median overall survival (OS) was 12.5 months, with a 6-month and 12-month OS rate of 82.13% and 59.34%, respectively. Stratified analyses did not reveal any significant difference between patients in different stages. CONCLUSION: Elderly patients (≥ 60 years old) with pancreatic cancer would experience tolerable toxicity and obtain good clinical benefits from the combination therapy of HIFU ablation and Gemox.

Transient increased expression of VEGF and MMP-1 in a rat liver tumor model after hepatic arterial occlusion.

BACKGROUND/AIMS: This study investigates the influence of hepatic arterial occlusion (HAO) on blood perfusion of transplanted cancer in rat's liver, and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1) and explores the mechanisms involved in transcatheter arterial embolization (TAE)-induced metastasis of liver cancer preliminarily. METHODOLOGY: Walker 256 carcinosarcoma was transplanted into rat's liver to create the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Rats bearing tumor were divided into three groups: control, laparotomy control, and HAL groups. Blood perfusion of tumor was analyzed by a Hoechst 33342 labeling assay. The level of serum VEGF was assayed by ELISA; and the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization. RESULTS: Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion of the tumor directly and hypoxia of tumor indirectly in the HAL group decreased significantly compared with that in the control group (329.1+/-29.3 vs. 383.6+/-19.2, P<0.01). The level of serum VEGF in the HAL group increased significantly compared with that of the control group (92.5+/-43.9 pg/mL vs. 54.9+/-19.3 pg/mL, P<0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups (P<0.05). The blood perfusion data of the tumor, represented by number of Hoechst 33342 labeled cells, showed an inverse correlation with the expression of VEGF mRNA in tumor tissue (P<0.05). While 6 days after HAL, the blood perfusion of tumor in HAL group decreased and the expression of VEGF and MMP-1 increased only slightly, not significantly, compared with that in the control group. CONCLUSIONS: In conclusion, blockage of hepatic arterial blood supply results in transient decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be the major reason for up-regulated expression of VEGF. Better understanding of the mechanisms involved with TAE-induced metastasis may lead to the enhancement of the long-term effects of TAE for liver cancer.

Influence of hepatic arterial blockage on blood perfusion and VEGF, MMP-1 expression of implanted liver cancer in rats.

AIM: To investigate the influence of hepatic arterial blockage on blood perfusion of transplanted cancer in rat liver and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1), and to explore the mechanisms involved in transarterial embolization (TAE)-induced metastasis of liver cancer preliminarily. METHODS: Walker 256 carcinosarcoma was transplanted into rat liver to establish the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Blood perfusion of tumor in control, laparotomy control, and HAL group was analyzed by Hoechst 33342 labeling assay, the serum VEGF level was assayed by ELISA, the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization. RESULTS: Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion of tumor directly and hypoxia of tumor indirectly in HAL group decreased significantly compared with that in control group (329+/-29 vs 384+/-19, P<0.01). The serum VEGF level in the HAL group increased significantly as against that of the control group (93 ng.L(-1)+/-44 ng.L(-1) vs 55 ng.L(-1)+/-19 ng.L(-1), P<0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups (P<0.05). The blood perfusion data of the tumor, represented by the number of Hoechst 33342 labeled cells, showed a good linear inverse correlation with the serum VEGF level (r=-0.606, P<0.05) and the expression of VEGF mRNA in the tumor tissue ( r =-0.338, P<0.01). CONCLUSION: Blockage of hepatic arterial blood supply results in decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be the major cause of up-regulated expression of VEGF.