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Liver transplantation for hepatocellular carcinoma: Evaluation of selection criteria
570
Journal of Gastrointestinal Surgery
Abstracts
165 PROINFLAMMATORY CYTOKINE INDUCTION FOLLOWING LARGE VOLUME HEPATIC CRYOTHERAPY, RADIOFREQUENCY ABLATION, MICROWAVE TISSUE ABLATION, AND STANDARD HEPATIC RESECTION Fateh Ahmad, MD, MBBS, Andrew D. Strickland, MD, MBBS, Rizwan Basit, MBBS, Ian J. Beckingham, MD, MBBS, David M. Lloyd, MD, MBBS, Leicester Royal Infirmary, Leicester, United Kingdom; Queens Medical Centre, Nottingham, United Kingdom. Several local ablative techniques have been developed for the treatment of liver tumors. Cryoablation has been complicated by cryoshock, a variant of an exaggerated systemic inflammatory response syndrome (SIRS). Proinflammatory cytokines such as TNF-α, IL-1β, and IL6 have been implicated as important mediators of this response. This study investigates the inflammatory response following liver ablation by different modalities and conventional surgical resection using markers of systemic inflammation. Following laparotomy, adult rats underwent cryoablation, radiofrequency ablation (RFA), microwave tissue ablation (MTA) or resection of 15%, 33%, or 66% of the total liver volume. Control rats underwent a sham laparotomy. Blood samples were taken preoperatively, and at 1, 3, 6, 24, and 48 hours postprocedure. The levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were measured using standard enzyme-linked immunosorbent assay techniques. Following 15% and 33% ablation or resection, the animals in all treatment groups tolerated the procedures well. All animals undergoing 66% hepatic resection or MTA survived to the 48-hour timepoint. However, there was a 100% mortality rate at 6 hours following 66% cryoablation and 66% RFA. No significant difference in cytokine levels was observed in any group following 15% ablation or resection, compared to controls. Following 33% resection or ablation using MTA and RFA, cytokine levels peaked at 6 hours and dropped to baseline levels within 24 hours. Significantly raised cytokine levels were noted in the 33% and 66% cryoablation groups, the 66% RFA group and the 66% resection group. These elevated cytokine levels remained high for at least 24 hours. The 66% MTA group did not show a significantly elevated cytokine response. Large volume hepatic ablation using cryotherapy and RFA results in a significant proinflammatory cytokine response and high mortality. Microwave ablation, however, did not induce a similar cytokine response and was less than that observed following surgical resection.
166 DOES HEPATIC MICROWAVE TISSUE ABLATION INDUCE A SYSTEMIC INFLAMMATORY RESPONSE? AN INVESTIGATION WITH A NOVEL MICROWAVE SYSTEM Fateh Ahmad, MD, MBBS, Andrew D. Strickland, MD, MBBS, Rizwan Basit, MBBS, Gavin S. Robertson, MD, MBBS, David M. Lloyd, MD, MBBS, Leicester Royal Infirmary, Leicester, United Kingdom Several ablative techniques have been developed for the treatment of liver tumors. Cryoablation has been complicated by cryoshock, a variant of an exaggerated systemic inflammatory response syndrome (SIRS). A novel microwave tissue ablation (MTA) system has been developed at our institution capable of producing large volume ablations (⬎8-cm diameter) within a few minutes with a single insertion of the applicator. This study examined the SIRS response to MTA by assessing systemic and organ-specific markers of inflammation. Following laparotomy, adult rats underwent ablation or resection of 15%, 33%, or 66% of the total liver volume. Control rats underwent a sham laparotomy. Blood samples were taken at 0, 1, 3, 6, 24, and 48 hours postprocedure and the levels of the proinflammatory cytokines
TNF-α, IL-1β, and IL-6 were measured. At 48 hours the animals were culled and the left lung removed to assess the wet/dry lung ratio. Bronchoalveolar lavage (BAL) was performed to quantify the protein content and the presence of neutrophils in pulmonary oedema fluid as indicators of acute lung injury. Urine was collected to assess the presence of retinol binding protein (RBP), a urinary marker of renal damage. Lung, liver, and kidney sections were also examined histologically using routine and electron microscopic techniques. All animals survived to 48 hours. No significant elevation in proinflammatory cytokines was found following any of the MTA treatments. Protein content in BAL was not elevated, and no inflammatory cells were observed on cytology. There was no significant difference in the wet/ dry lung ratio, compared to controls. Urinary RBP was also not significantly raised. There was no evidence of acute inflammation in the lungs or kidneys following any of the MTA treatments. Systemic and organ-specific markers of inflammation are not raised as a result of MTA, suggesting that MTA is a safe procedure for liver ablation, even when large volumes of ablation are performed.
167 LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA: EVALUATION OF SELECTION CRITERIA Amer Q. Aldouri, K. Riyad, A. Almukhtar, S. Asthana, S. White, J. Wyatt, SG Pollard, J.P.A. Lodge, G.J. Toogood, K.R. Prasad., St James’s University Hospital, Leeds, United Kingdom Hepatocellular carcinoma (HCC) is a well-established indication for orthotopic liver transplantation (OLT). Patient selection is often based on Milan criteria. Since Mazzaferro et al’s report there have been conflicting reports questioning these criteria based on patient survival. The aim of this study was to compare the authors’ experience of 81 consecutive patients having OLT for HCC based on different criteria for transplantation. These included Milan, UCSF and the Pittsburgh modified TNM criteria. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression methods. During a seven-year period 852 OLT were performed; 81 patients (9.5%) underwent OLT for HCC. Preoperatively all patients were assessed by radiological cross-sectional imaging, to evaluate the number, size and presence of vascular invasion. The explanted specimens were histologically evaluated in terms of size, number, distribution, pathological grade, and vascular invasion (macro and micro). There was no significant difference in 5-year survival rates between patients with HCC exceeding Milan criteria (n ⫽ 30) versus those meeting Milan criteria (n ⫽ 51), 52% versus 58.6%, respectively. In comparison 5-year survival according to the UCSF criteria (n ⫽ 59) was 59% versus 47% for those outside UCSF criteria (n ⫽ 22) (P ⫽ 0.7). However patients with stage I & II Pittsburgh criteria had significantly higher 5-year survival compared to patients with stage III&IV disease (69% versus 34%; P ⫽ 0.01). In conclusion this study demonstrates that the Pittsburgh modified TNM criteria is a more useful predictor of long-term survival for patients with HCC treated by OLT.
168 CASES OF COLORECTAL CANCER AND GASTRIC CANCER WITH LIVER INVOLVEMENT—IS RESECTION OF LIVER METASTASIS AN EFFECTIVE APPROACH? Koji Asai, MD, Yoshinobu Sumiyama, MD, PhD, Manabu Watanabe, MD, PhD, Hidenori Tanaka, MD, Toshiyuki Enomoto, MD, Akihiro Ohsawa, MD, Ryota Kanai, MD, Hiroshi Matsukiyo, MD, Toho University School of Medicine, Tokyo, Japan The cases of colorectal cancer and gastric cancer with liver involvement that were detected for the past 14 years were reviewed. The subjects were 74 patients with colorectal cancer with liver involvement
Journal of Gastrointestinal Surgery
Abstracts
165 PROINFLAMMATORY CYTOKINE INDUCTION FOLLOWING LARGE VOLUME HEPATIC CRYOTHERAPY, RADIOFREQUENCY ABLATION, MICROWAVE TISSUE ABLATION, AND STANDARD HEPATIC RESECTION Fateh Ahmad, MD, MBBS, Andrew D. Strickland, MD, MBBS, Rizwan Basit, MBBS, Ian J. Beckingham, MD, MBBS, David M. Lloyd, MD, MBBS, Leicester Royal Infirmary, Leicester, United Kingdom; Queens Medical Centre, Nottingham, United Kingdom. Several local ablative techniques have been developed for the treatment of liver tumors. Cryoablation has been complicated by cryoshock, a variant of an exaggerated systemic inflammatory response syndrome (SIRS). Proinflammatory cytokines such as TNF-α, IL-1β, and IL6 have been implicated as important mediators of this response. This study investigates the inflammatory response following liver ablation by different modalities and conventional surgical resection using markers of systemic inflammation. Following laparotomy, adult rats underwent cryoablation, radiofrequency ablation (RFA), microwave tissue ablation (MTA) or resection of 15%, 33%, or 66% of the total liver volume. Control rats underwent a sham laparotomy. Blood samples were taken preoperatively, and at 1, 3, 6, 24, and 48 hours postprocedure. The levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were measured using standard enzyme-linked immunosorbent assay techniques. Following 15% and 33% ablation or resection, the animals in all treatment groups tolerated the procedures well. All animals undergoing 66% hepatic resection or MTA survived to the 48-hour timepoint. However, there was a 100% mortality rate at 6 hours following 66% cryoablation and 66% RFA. No significant difference in cytokine levels was observed in any group following 15% ablation or resection, compared to controls. Following 33% resection or ablation using MTA and RFA, cytokine levels peaked at 6 hours and dropped to baseline levels within 24 hours. Significantly raised cytokine levels were noted in the 33% and 66% cryoablation groups, the 66% RFA group and the 66% resection group. These elevated cytokine levels remained high for at least 24 hours. The 66% MTA group did not show a significantly elevated cytokine response. Large volume hepatic ablation using cryotherapy and RFA results in a significant proinflammatory cytokine response and high mortality. Microwave ablation, however, did not induce a similar cytokine response and was less than that observed following surgical resection.
166 DOES HEPATIC MICROWAVE TISSUE ABLATION INDUCE A SYSTEMIC INFLAMMATORY RESPONSE? AN INVESTIGATION WITH A NOVEL MICROWAVE SYSTEM Fateh Ahmad, MD, MBBS, Andrew D. Strickland, MD, MBBS, Rizwan Basit, MBBS, Gavin S. Robertson, MD, MBBS, David M. Lloyd, MD, MBBS, Leicester Royal Infirmary, Leicester, United Kingdom Several ablative techniques have been developed for the treatment of liver tumors. Cryoablation has been complicated by cryoshock, a variant of an exaggerated systemic inflammatory response syndrome (SIRS). A novel microwave tissue ablation (MTA) system has been developed at our institution capable of producing large volume ablations (⬎8-cm diameter) within a few minutes with a single insertion of the applicator. This study examined the SIRS response to MTA by assessing systemic and organ-specific markers of inflammation. Following laparotomy, adult rats underwent ablation or resection of 15%, 33%, or 66% of the total liver volume. Control rats underwent a sham laparotomy. Blood samples were taken at 0, 1, 3, 6, 24, and 48 hours postprocedure and the levels of the proinflammatory cytokines
TNF-α, IL-1β, and IL-6 were measured. At 48 hours the animals were culled and the left lung removed to assess the wet/dry lung ratio. Bronchoalveolar lavage (BAL) was performed to quantify the protein content and the presence of neutrophils in pulmonary oedema fluid as indicators of acute lung injury. Urine was collected to assess the presence of retinol binding protein (RBP), a urinary marker of renal damage. Lung, liver, and kidney sections were also examined histologically using routine and electron microscopic techniques. All animals survived to 48 hours. No significant elevation in proinflammatory cytokines was found following any of the MTA treatments. Protein content in BAL was not elevated, and no inflammatory cells were observed on cytology. There was no significant difference in the wet/ dry lung ratio, compared to controls. Urinary RBP was also not significantly raised. There was no evidence of acute inflammation in the lungs or kidneys following any of the MTA treatments. Systemic and organ-specific markers of inflammation are not raised as a result of MTA, suggesting that MTA is a safe procedure for liver ablation, even when large volumes of ablation are performed.
167 LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA: EVALUATION OF SELECTION CRITERIA Amer Q. Aldouri, K. Riyad, A. Almukhtar, S. Asthana, S. White, J. Wyatt, SG Pollard, J.P.A. Lodge, G.J. Toogood, K.R. Prasad., St James’s University Hospital, Leeds, United Kingdom Hepatocellular carcinoma (HCC) is a well-established indication for orthotopic liver transplantation (OLT). Patient selection is often based on Milan criteria. Since Mazzaferro et al’s report there have been conflicting reports questioning these criteria based on patient survival. The aim of this study was to compare the authors’ experience of 81 consecutive patients having OLT for HCC based on different criteria for transplantation. These included Milan, UCSF and the Pittsburgh modified TNM criteria. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression methods. During a seven-year period 852 OLT were performed; 81 patients (9.5%) underwent OLT for HCC. Preoperatively all patients were assessed by radiological cross-sectional imaging, to evaluate the number, size and presence of vascular invasion. The explanted specimens were histologically evaluated in terms of size, number, distribution, pathological grade, and vascular invasion (macro and micro). There was no significant difference in 5-year survival rates between patients with HCC exceeding Milan criteria (n ⫽ 30) versus those meeting Milan criteria (n ⫽ 51), 52% versus 58.6%, respectively. In comparison 5-year survival according to the UCSF criteria (n ⫽ 59) was 59% versus 47% for those outside UCSF criteria (n ⫽ 22) (P ⫽ 0.7). However patients with stage I & II Pittsburgh criteria had significantly higher 5-year survival compared to patients with stage III&IV disease (69% versus 34%; P ⫽ 0.01). In conclusion this study demonstrates that the Pittsburgh modified TNM criteria is a more useful predictor of long-term survival for patients with HCC treated by OLT.
168 CASES OF COLORECTAL CANCER AND GASTRIC CANCER WITH LIVER INVOLVEMENT—IS RESECTION OF LIVER METASTASIS AN EFFECTIVE APPROACH? Koji Asai, MD, Yoshinobu Sumiyama, MD, PhD, Manabu Watanabe, MD, PhD, Hidenori Tanaka, MD, Toshiyuki Enomoto, MD, Akihiro Ohsawa, MD, Ryota Kanai, MD, Hiroshi Matsukiyo, MD, Toho University School of Medicine, Tokyo, Japan The cases of colorectal cancer and gastric cancer with liver involvement that were detected for the past 14 years were reviewed. The subjects were 74 patients with colorectal cancer with liver involvement