633 TUMOUR SIZE OF HCC AND ITS RELATIONSHIP TO OUTCOME AFTER LIVER TRANSPLANTATION

633 TUMOUR SIZE OF HCC AND ITS RELATIONSHIP TO OUTCOME AFTER LIVER TRANSPLANTATION

POSTERS 631 OUTCOME OF LIVER TRANSPLANTATION (LT) FOR HEPATOCELLULAR CARCINOMA (HCC) ACCORDING TO DIFFERENT TRANSPLANT CRITERIA: A META-ANALYSIS G. Ge...

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POSTERS 631 OUTCOME OF LIVER TRANSPLANTATION (LT) FOR HEPATOCELLULAR CARCINOMA (HCC) ACCORDING TO DIFFERENT TRANSPLANT CRITERIA: A META-ANALYSIS G. Germani1 , M. Garcovich1 , K. Gurusamy2 , C. Toso3 , G. Fede1 , E. Tsochatzis1 , A.K. Burroughs1 . 1 The Royal Free Sheila Sherlock Liver Centre and Division of Surgery, University College London, 2 Hepato-Pancreatico-Biliary and Liver Transplant Unit, University Department of Surgery, Royal Free Campus, UCL Medical School, London, UK; 3 Services de Chirurgie Viscerale et Transplantation Hopitaux Universites de Geneve, Geneva, Switzerland E-mail: [email protected] Background and Aim: LT for HCC and cirrhosis is complicated by the prognosis of both diseases. Milan criteria are derived from explanted specimens, and when used based on pre-transplant imaging, results in a recurrence rate of ≤15%. There has been some evidence that extending selection criteria results in similar, but not increased recurrence rates. The most used extension criteria have been those termed “San Francisco criteria”. However it is not clear when UCSF criteria are extended from Milan, whether the size of the largest nodule or the number or both, is the critical permissive feature. The aim of this meta-analysis was to assessed the impact of different transplant criteria on overall survival (OS), disease-free survival (DFS) and recurrence after LT for HCC. Material and methods: MEDLINE, Cochrane Controlled trial Register (CENTRAL), EMBASE and Science Citation Index databases were searched until April 2010. Results: Fifty studies evaluating overall survival (OS), disease-free survival (DFS) and recurrence according to different criteria for LT in patients with HCC were included: 39 studies (8981 patients) evaluated the impact of Milan criteria (HR for OS 1.63; 95% CI 1.31–2.03, HR for DFS 3.27; 95% CI 2.12–5.05, HR for recurrence 2.79; 95% CI 1.71–4.54 vs. within Milan criteria), 13 studies (1987 patients) evaluated the impact of UCSF criteria (HR for OS 1.79; 95% CI 1–3.21, HR for DFS 3.41; 95% CI 1.21–9.60, HR for recurrence 6.11; 95% CI 2.45–15.23 vs. within UCSF). Two studies (6946 patients) evaluated the impact of outside Milan criteria, but within UCSF criteria (HR for OS 1.39; 95% CI 0.98–1.95 vs. within Milan criteria). Conclusion: Overall, Milan criteria seem to clearly influence the OS and DFS and recurrence after LT. UCSF criteria seem to clearly influence the DFS and recurrence after LT, whereas the impact on OS was borderline with the lower range of HR of 1. It appears that patients transplanted outside Milan criteria, but within UCSF have a non-statistical difference in risk of death compared with patients transplanted within Milan criteria, but this is only based on 2 studies. The results in the literature do not conclusively resolve which selection system better predicts recurrence and survival. 632 DOES THE NUMBER OF HCC NODULES IN CIRRHOSIS IMPACT ON OUTCOME AFTER LIVER TRANSPLANTATION? G. Germani1 , M. Garcovich1 , K. Gurusamy2 , C. Toso3 , G. Fede1 , E. Tsochatzis1 , A.K. Burroughs1 . 1 The Royal Free Sheila Sherlock Liver Centre and Division of Surgery, University College London, 2 Hepato-Pancreatico-Biliary and Liver Transplant Unit, University Department of Surgery, Royal Free Campus, UCL Medical School, London, UK; 3 Services de Chirurgie Viscerale et Transplantation Hopitaux Universites de Geneve, Geneva, Switzerland E-mail: [email protected] Background and Aim: In patients with cirrhosis imaging technique has not altered for the detection of nodules of 2 cm diameter or more, but has improved for the detection of smaller (0.5–1.5 cm size) nodules. Assuming these may have been missed on pretransplant imaging in the past (but only found on explant), then there may already be a case that the number of nodules particularly S256

if small (1–2 cm) may be less important for recurrence. Moreover these small nodules are known to be far less likely to be associated with microvascular invasion. The aim of this meta-analysis was to assessed the impact of tumour number on overall survival (OS), disease-free survival (DFS) and recurrence after LT for HCC. Material and methods: MEDLINE, Cochrane Controlled trial Register (CENTRAL), EMBASE and Science Citation Index databases were searched until April 2010. Results: Fifteen studies (4575 patients) evaluating the impact of tumour nodule number on OS, DFS and recurrence after LT were included: 5 studies (719 patients) reporting nodule number it as a continuous variable (HR for OS 1.09; 95% CI 0.88–1.34, HR for recurrence 1.07; 95% CI 0.93–1.23); 3 studies (468 patients) reporting multiple versus single nodules (HR for OS 1.23; 95% CI 1– 1.53); 7 studies (3289 patients) reporting it as cut-offs (3 nodules) (HR for OS 1.29; 95% CI 1.14–1.46, HR for DFS 1.24; 95% CI 0.77–2.01, HR for recurrence 1.02; 95% CI 0.25–4.24). Conclusions: The number of tumours evaluated as a continuous variable does not appear to have a clear impact on overall survival nor on recurrence. Multiple tumours double the risk of recurrence after LT compared to single tumour, but the impact of multiple tumours on OS is borderline. Patients with ≥3 tumours have an increased risk of death compared to those with <3 tumours. The best data based on a precise evaluation of the number of nodules suggests the relationship to recurrence and survival is not statistically significant suggesting that expansion of selection criteria can include an increased number of nodules, but the cut-off for maximum nodule size cannot be derived. 633 TUMOUR SIZE OF HCC AND ITS RELATIONSHIP TO OUTCOME AFTER LIVER TRANSPLANTATION G. Germani1 , M. Garcovich1 , K. Gurusamy2 , C. Toso3 , G. Fede1 , E. Tsochatzis1 , A.K. Burroughs1 . 1 The Royal Free Sheila Sherlock Liver Centre and Division of Surgery, University College London, 2 Hepato-Pancreatico-Biliary and Liver Transplant Unit, University Department of Surgery, Royal Free Campus, UCL Medical School, London, UK; 3 Services de Chirurgie Viscerale et Transplantation Hopitaux Universites de Geneve, Geneva, Switzerland E-mail: [email protected] Background and Aim: The aim of this meta-analysis was to assessed the impact of tumour size on overall survival (OS), diseasefree survival (DFS) and recurrence after LT for HCC. Material and methods: MEDLINE, Cochrane Controlled trial Register (CENTRAL), EMBASE and Science Citation Index databases were searched until April 2010. Results: Thirty-two studies evaluating the impact of tumour size on overall survival (OS), disease-free survival (DFS) and recurrence after LT were included. Total tumour size was evaluated in 7 studies (1502 patients): as continuous variable in 2 studies (HR for recurrence 1.19, 95% CI 0.95–1.49), as a cut-off of 10 cm in 3 studies (HR for OS 4.59, 95% CI 1.26–16.79), and as a cut-off of 9 cm in 2 studies (HR for DFS 1.98; 95% CI 1.49–2.64). The diameter of the largest tumour was evaluated in 9 studies (2743 patients): as a continuous variable in 3 studies (HR for recurrence 1.03; 95% CI 0.99–1.07), as a cut-off of 3 cm in 6 studies (HR for OS ≥3 cm 1.55; 95% CI 1.29–1.86, HR for recurrence 6.69; 95% CI 2.34–19.12). Tumour size without any other specification was assessed in 19 studies (2497 patients): as a continuous variable in 4 studies (HR for OS 1.14; 95% CI 1–1.30), as a cut-off (5 cm) in 16 studies (HR for OS 1.92; 95% CI 1.48–2.50, HR for DFS 4.30; 95% CI 2.48–7.49, HR for recurrence 2.56; 95% CI 1.53–3.34). Conclusions: Considering total tumour size OS is nearly 5 times lower in patients with a total tumour size ≥10 cm, and DFS is nearly 2 times lower with a total tumour size ≥9 cm. Based on diameter of the largest tumour nodule the probability of recurrence after LT nearly 6 times higher in patients with diameter of the largest

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POSTERS tumour ≥3 cm. Tumour size without other specification when ≥5 cm has a probability of DFS after LT nearly 4 lower and a probability of recurrence nearly 4 higher. The impact on OS is not as large as for the DFS. These data suggest caution in expanding HCC selection criteria for transplantation based on increasing size of largest nodule, or total tumour size. 634 BALLOON-OCCLUDED PERCUTANEOUS RADIO-FREQUENCY THERMAL ABLATION (RFA) PLUS TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE): A NEW COMBINED SINGLE-STEP THERAPY FOR TREATMENT OF MULTINODULAR UNRESECTABLE HEPATOCELLULAR CARCINOMA R. Iezzi1 , V. Cesario1 , F.R. Ponziani1 , G. Gigante1 , G. Caracciolo1 , E. Rinninella1 , M.A. Zocco1 , A.M. de Gaetano1 , M. Siciliano1 , A. Milani1 , L. Miele1 , G. Gasbarrini1,2 , S. Agnes1 , G. Bombardieri1 , F. Giuliante1 , A. Grieco1 , G. Nuzzo1 , M. Pompili1 , M. Basso1 , G.L. Rapaccini1 , E. di Stasio1 , L. Bonomo1 , A. Gasbarrini1 , HEPATOCAT Group for the Multidisciplinary Management of HCC. 1 Catholic University of Rome, 2 Fondazione Ricerca in Medicina, Roma, Italy E-mail: [email protected] Purpose: To evaluate the feasibility and safety of combined single-step therapy with balloon-occluded RFA followed by TACE in patients with multi-nodular unresectable hepatocellular carcinoma. Materials and methods: 10 consecutive patients with multinodular (2–6 nodules) unilobar unresectable HCC and with a target main lesion larger than 3 cm (range: 3.5–6 cm) were enrolled in our single-center multidisciplinary pilot study. The schedule consisted of: percutaneous RFA (single 3-cm monopolar needle insertion) of the target lesion during occlusion of the hepatic artery supplying the tumor followed by lobar TACE (450 mg carboplatin and lipiodol plus temporary embolization with spongostan). Adverse events as well as intra/periprocedural complications were clinically assessed. Early local efficacy was evaluated on 1-month follow-up multiphasic CT based on RECIST criteria. A separated evaluation of target lesions in terms of enhancement, necrotic diameter, presence and distribution of lipiodol uptake was also performed. Results: No major complications occurred. Overall technical success, defined as complete devascularization during the arterial phase of all nodules, was achivied in 7/10 patients with 3 partial response (persistence of hypervascular small nodules). When considering only target lesions, technical success was obtained in all patients, with a nonenhancing area corresponding in shape to the previously identified HCC (necrotic diameter: 3.5–5 cm) always obtained, and with a circonferential peripheral lipiodol uptake, as safety margin of lesion, of at least 0.5 cm (0.5–1.3 cm). Conclusions: Balloon-occluded-RFA plus TACE seems to be a safe and effective combined therapy for the treatment of advanced unresectable HCC lesions, allowing to obtain a high complete local response rate also in large lesions. 635 SIGNIFICANCE OF INTRAHEPATIC TUMOR CONTROL IN THE PROGNOSIS OF PATIENTS WITH HEPATOCELLULAR CARCINOMA AND EXTRAHEPATIC METASTASES S.M. Jung1 , J.W. Jang1 , C.R. You1 , S.H. Yoo1 , J.H. Kwon1 , K.W. Chung1 , C.S. Kay2 , H.S. Jung3 . 1 Internal Medicine, 2 Radiation Oncology, 3 Radiology, The Catholic University of Korea, Seoul, Republic of Korea E-mail: [email protected] Background and Aims: There has been little information about the long-term outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) and extrahepatic metastases. The purpose of this study was to investigate the clinical factors affecting survival after extrahepatic metastasis and to determine the survival benefit of controlling intrahepatic HCC.

Methods: Between 2004 and 2009, a total of 240 consecutive patients with HCC and extrahepatic metastasis were recruited. Based on tumor extent, performance, and hepatic function, the patients underwent locoregional and/or systemic treatments. After 2 months of anti-cancer therapy, the treatment response of the intrahepatic tumor after extrahepatic metastasis was assessed by modified RECIST. Other prognostic parameters were also analyzed. Results: During the mean follow-up of 276 days, 222 patients died; the median survival time was 146 days. Multivariate analysis revealed that Child–Pugh class A (P = 0.018), smaller hepatic tumor size (P = 0.025), absence of portal venous invasion (P = 0.002), single metastatic organ involvement (P = 0.001), and objective treatment response of the intrahepatic tumor (P < 0.001) were the favorable prognostic factors for survival. Of the 183 evaluable patients, 24 achieved complete or partial response for intrahepatic tumors after treatment. The overall survival for the 24 responders was significantly improved, with a median of 521 days, as compared to 170 days for the remaining 159 patients without objective tumor response. The leading cause of death was progressive intrahepatic tumor. Conclusions: Intrahepatic tumor status and hepatic reserve are among the significant predictors of survival in patients with HCC and extrahepatic metastases. This study indicates that even in patients with metastases from advanced HCC, therapeutic approaches to control intrahepatic tumor are important in improving patient survival. 636 OBSERVATION OF BUBBLES AND DETECTION OF HEPATOCYTES IN THE PORTAL VEIN DURING RADIOFREQUENCY ABLATION C. Kawamoto1 , K.-I. Manaka2 , A. Yamauchi3 , K. Kaneko1 , R. Miyamoto1 , H. Shimizu1 , K. Mizuno1 . 1 Department of Medicine, Division of Cardiology, Hepatology, Geriatrics and Integrated Medicine, Nippon Medical School, Tokyo, 2 Institute of International Education and Research, Dokkyo Medical University, Tochigi, 3 Department of Internal Medicine, Yorii Hospital, Saitama, Japan E-mail: [email protected] Background and Aims: Radiofrequency ablation (RFA) for hepatocellular carcinoma is considered as a less-invasive therapeutic technique associated with favorable local control. Although RFA was initially expected to decrease the incidence of local recurrence, sporadic cases of unexpected recurrence, such as intrahepatic dissemination, have been described following RFA. Some of these recurrences may be caused by increased intratumoral pressure. During RFA, high echoic areas can be observed by ultrasound in the vessels. Such high echoic areas are thought to represent steam (bubbles) generated by increased intrahepatic pressure in rapidly heated tissue. Therefore, we used an angioscope to observe the bubbles generated during RFA, and examined hepatocytes in the portal vein. Subjects and methods: Under general anesthesia, laparotomy was performed on 4 pigs. Bubbles in the portal vein were observed by angioscope using a 16-Fr sheath inserted into the portal vein. The 16-Fr sheath was directly inserted into the portal vein. After inserting a 3.8-mm angioscope into the sheath, a guidewire was used to guide the angioscope to the portal vein, and RFA was performed. A 20-mm LeVeen needle electrode and a cooledtip RF needle electrode were used for RFA. The down-streaming blood in the vessel attached to the irradiated part was collected and separated by using Ficoll-gradient method, and cultured for 15 hours to examine the existence of intact hepatocytes. Results: The outflow of bubbles from the RFA site was observed by angioscope at the same time as high echoic areas were observed on ultrasonography. In the fraction of the blood separated by using Ficoll-gradient method, albumin-positive cell clusters were found and were assumedly intact hepatocyte in their morphology.

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