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6
260
Journal of Gastrointestinal Surgery
Abstracts
6 The Number of Colorectal Liver Metastases Treated by Cryotherapy Does Not Predict Survival. Randall S Zuckerman, D.B Yan, David L Morris, aThe Mary Imogene Bassett Hospital, Cooperstown, NY; University of New South Wales, St. George Hospital, Kogarah, Australia Nearly 50 percent of patients with colorectal cancer will develop hepatic metastases. Cryoablation of metastases when used alone or in conjunction with hepatic resection is an effective treatment for patients with disease confined to the liver. The effect of the number of hepatic lesions on patient survival remains controversial. The purpose of this study was to determine the prognostic effect of the number of colorectal liver metastases treated by hepatic cryotherapy. There are 2241 patients in our Liver Unit Database. Of these, 1261 patients had CRC. 240 patients have been treated with cryotherapy from 1990-2002. 172 patients had cryotherapy alone or in conjunction with resection. Extra-hepatic disease and lesions greater than 6 cm were considered contraindications for cryotherapy. 146 patients had resections with cryoablation that resulted in complete destruction of all tumors Ro procedure. The number of lesions was determined by IUS. 77 patients or 44.8% had 1-3 lesions, 78 or 45.3% had 4-7 lesions and 17 or 2.9% had more than 8 lesions. There was a single mortality 0.47% and 27.9% morbidity. Median survival in this group was 29 months p0.0004. 1,2,3,4 and 5-year survival rates were 89%, 65%, 41%, 24% and 19% respectively. Median survival in months by number of lesions was as follows: 1, 32m; 2, 29m; 3, 30m; 4, 31m; 5, 27m; 6-7 37m; 8-12 21m. These differences were not significant. This paper suggests that the number of hepatic lesions is not prognostic of survival. If all disease can be treated Ro procedures, than a combination of resection and cryoablation should be used for multiple liver metastasis. The upper limit of number of metastases that should be treated remains unclear.
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zones of destruction in the liver as deep as 2cm. This tool should be helpful in extending resection margins and treating superficial tumors. A human study has been started.
8 Focal Adhesion Kinase (FAK) Inhibition Prevents Growth of Hepatocellular Carcinoma (HCC) Tumors in a Xenograft Model Carol P Bowen, Joshua Rovin, Wayne Ledinh, Kevin Thorne, Reid B Adams, University of Virginia Health System, Charlottesville, VA; Eastern Virginia Medical School, Norfolk, VA FAK is a critical regulator of adhesion signals, and therefore, cellular processes such as motility, proliferation, and apoptosis. FAK is upregulated in human tumors, but its role in HCC is unknown. Inhibition of FAK leads to apoptosis, a process regulated by the C-terminal domain of FAK (called FRNK, a negative regulator of adhesion signaling). We hypothesized that inhibition of these aberrant signals in HCC cells would prevent tumor growth in an in vivo mouse model. Adenoviral vectors expressing green fluorescent protein (GFP, control) or the fusion protein GFP-FRNK were generated. Human HCC cells were infected with GFP or GFP-FRNK (MOI 4) and 24 hours later 2106 cells were injected into the flanks of nude mice. Tumor development and volume were evaluated and data analyzed by ANOVA and ChiSquare. Tumor growth was significantly inhibited in GFP-FRNK treated groups (p0.01). Interruption of adhesion signals by inhibiting FAK prevented HCC tumor implantation and growth. This confirms a pivotal role for adhesion signaling in HCC tumorigenesis and suggests that FAK may be a potential therapeutic target.
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Saline-Linked Surface Radiofrequency Ablation: Factors Affecting Steam Popping and Depth of Tissue Injury in Pig Liver Stefan Topp, Michael Mcclurken, Aravinda Upadhya, Steven M Strasberg, Washington University in Saint Louis, Saint Louis, MO; TissueLink Medical Inc, Dover, NH Saline linked surface coagulation (TissueLink Medical Inc, Dover NH) is a new technology for hepatic division that has potential for ablation of superficial hepatic tumors and extension of hepatic resection margins. However, RF ablation on the liver surface may result in undesirable steam formation under the capsule, leading to tissue disruption, called steam popping. Also, no studies have been done to optimize tissue destruction by determining the controlling variables. This study was performed to determine how to prevent steam popping while maximizing the zone of tissue destruction. 12 pigs were studied. RF lesions were created from the liver surface using the Floating Ball FB3.0, varying treatment diameter, duration, power and inflow occlusion. After determining the threshold power for steam popping in 90 lesions, another 90 lesions were created with constant power at a particular treatment diameter (1cm/10W, 2cm/15W, 4cm/60W - subthreshold for popping) to assess the effect of time, power and inflow occlusion on depth of destruction. Lesions were sectioned, photographed and measured, followed by histological evaluation of tissue viability by NADH staining. Inflow occlusion, decreasing treatment diameter and increasing power, significantly raised the risk of steam popping, and the thresholds for popping were defined. Working below these thresholds we found that RF ablation using 1cm and 2cm diameters resulted in superficial lesions of 3-5mm depth. However depth could increased to 10mm by using a 4cm diameter. Using inflow occlusion plus 4cm/60W, depth of destruction doubled and was more predictable reaching 20mm. Histology showed that cell destruction in the RF zone was complete. Saline linked RF surface ablation is safe and highly effective in creating
WITHDRAWN
Journal of Gastrointestinal Surgery
Abstracts
6 The Number of Colorectal Liver Metastases Treated by Cryotherapy Does Not Predict Survival. Randall S Zuckerman, D.B Yan, David L Morris, aThe Mary Imogene Bassett Hospital, Cooperstown, NY; University of New South Wales, St. George Hospital, Kogarah, Australia Nearly 50 percent of patients with colorectal cancer will develop hepatic metastases. Cryoablation of metastases when used alone or in conjunction with hepatic resection is an effective treatment for patients with disease confined to the liver. The effect of the number of hepatic lesions on patient survival remains controversial. The purpose of this study was to determine the prognostic effect of the number of colorectal liver metastases treated by hepatic cryotherapy. There are 2241 patients in our Liver Unit Database. Of these, 1261 patients had CRC. 240 patients have been treated with cryotherapy from 1990-2002. 172 patients had cryotherapy alone or in conjunction with resection. Extra-hepatic disease and lesions greater than 6 cm were considered contraindications for cryotherapy. 146 patients had resections with cryoablation that resulted in complete destruction of all tumors Ro procedure. The number of lesions was determined by IUS. 77 patients or 44.8% had 1-3 lesions, 78 or 45.3% had 4-7 lesions and 17 or 2.9% had more than 8 lesions. There was a single mortality 0.47% and 27.9% morbidity. Median survival in this group was 29 months p0.0004. 1,2,3,4 and 5-year survival rates were 89%, 65%, 41%, 24% and 19% respectively. Median survival in months by number of lesions was as follows: 1, 32m; 2, 29m; 3, 30m; 4, 31m; 5, 27m; 6-7 37m; 8-12 21m. These differences were not significant. This paper suggests that the number of hepatic lesions is not prognostic of survival. If all disease can be treated Ro procedures, than a combination of resection and cryoablation should be used for multiple liver metastasis. The upper limit of number of metastases that should be treated remains unclear.
7
zones of destruction in the liver as deep as 2cm. This tool should be helpful in extending resection margins and treating superficial tumors. A human study has been started.
8 Focal Adhesion Kinase (FAK) Inhibition Prevents Growth of Hepatocellular Carcinoma (HCC) Tumors in a Xenograft Model Carol P Bowen, Joshua Rovin, Wayne Ledinh, Kevin Thorne, Reid B Adams, University of Virginia Health System, Charlottesville, VA; Eastern Virginia Medical School, Norfolk, VA FAK is a critical regulator of adhesion signals, and therefore, cellular processes such as motility, proliferation, and apoptosis. FAK is upregulated in human tumors, but its role in HCC is unknown. Inhibition of FAK leads to apoptosis, a process regulated by the C-terminal domain of FAK (called FRNK, a negative regulator of adhesion signaling). We hypothesized that inhibition of these aberrant signals in HCC cells would prevent tumor growth in an in vivo mouse model. Adenoviral vectors expressing green fluorescent protein (GFP, control) or the fusion protein GFP-FRNK were generated. Human HCC cells were infected with GFP or GFP-FRNK (MOI 4) and 24 hours later 2106 cells were injected into the flanks of nude mice. Tumor development and volume were evaluated and data analyzed by ANOVA and ChiSquare. Tumor growth was significantly inhibited in GFP-FRNK treated groups (p0.01). Interruption of adhesion signals by inhibiting FAK prevented HCC tumor implantation and growth. This confirms a pivotal role for adhesion signaling in HCC tumorigenesis and suggests that FAK may be a potential therapeutic target.
9
Saline-Linked Surface Radiofrequency Ablation: Factors Affecting Steam Popping and Depth of Tissue Injury in Pig Liver Stefan Topp, Michael Mcclurken, Aravinda Upadhya, Steven M Strasberg, Washington University in Saint Louis, Saint Louis, MO; TissueLink Medical Inc, Dover, NH Saline linked surface coagulation (TissueLink Medical Inc, Dover NH) is a new technology for hepatic division that has potential for ablation of superficial hepatic tumors and extension of hepatic resection margins. However, RF ablation on the liver surface may result in undesirable steam formation under the capsule, leading to tissue disruption, called steam popping. Also, no studies have been done to optimize tissue destruction by determining the controlling variables. This study was performed to determine how to prevent steam popping while maximizing the zone of tissue destruction. 12 pigs were studied. RF lesions were created from the liver surface using the Floating Ball FB3.0, varying treatment diameter, duration, power and inflow occlusion. After determining the threshold power for steam popping in 90 lesions, another 90 lesions were created with constant power at a particular treatment diameter (1cm/10W, 2cm/15W, 4cm/60W - subthreshold for popping) to assess the effect of time, power and inflow occlusion on depth of destruction. Lesions were sectioned, photographed and measured, followed by histological evaluation of tissue viability by NADH staining. Inflow occlusion, decreasing treatment diameter and increasing power, significantly raised the risk of steam popping, and the thresholds for popping were defined. Working below these thresholds we found that RF ablation using 1cm and 2cm diameters resulted in superficial lesions of 3-5mm depth. However depth could increased to 10mm by using a 4cm diameter. Using inflow occlusion plus 4cm/60W, depth of destruction doubled and was more predictable reaching 20mm. Histology showed that cell destruction in the RF zone was complete. Saline linked RF surface ablation is safe and highly effective in creating
WITHDRAWN