Ruiz, R; Randall, H; Goldstein, R; Klintmalm, G; Levy, M; McKenna, G; Onaca, N; Jennings, L; Sanchez, E; Chinnakotla, S Author Information

The management of patients with hepatocellular carcinoma and cirrhosis awaiting liver transplant is a dilemma due to organ shortage and long wait times. We report the acute toxicity and evaluate the explant pathology in patients receiving stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation. From November 2005 to June 2007, 5 patients with six hepatomas were treated with SBRT as a bridge to liver transplantation. The median tumor size was 3.2 cm (range, 2.9-5.5 cm). The median radiation dose was 48 Gy (range, 33-54 Gy) given in three consecutive daily fractions with a median dose of 16 Gy each (range, 11-18 Gy). The median prescription isodose line was 62% (range, 50-66%). Toxicity was graded according to the Common Terminology Criteria for Adverse Events v3.0. The mean time on the liver transplant wait list was 394 days and the mean time from SBRT to transplant was 67 days (range, 8-185 days). Mean post-transplant follow-up was 112 days (3.7 months). Following SBRT only 1 patient had acute toxicity, Grade 1 abdominal discomfort. Overall, 4 of 5 (80%) patients had no acute toxicity following SBRT. Following SBRT and liver transplantation, examination of the explant pathology revealed two of six tumors had no evidence of viable tumor for a complete respose rate of 33%. Three of six tumors decreased in size following SBRT for a partial response rate of 50%. Only one tumor increased in size, from 3.3 cm to 3.7 cm in 48 days from SBRT to transplant. Overall local control was achieved in five of six (83%) hepatomas and in these patients the median time from SBRT to transplant was 90 days. All patients are alive and there are no post-transplant hepatoma recurrences. Stereotactic body radiation therapy as a bridge to liver transplant in patients with hepatoma is safe and well tolerated. Staining to evaluate molecular damage may be helpful in assessing response to therapy in patients with short interval between treatment and transplant. As a treatment alone or as part of multimodality approach, SBRT offers promise as a bridge during the long wait to liver transplant in patients with hepatocelluar carcinoma.

Ruiz, R1; Fischbach, B2; Onaca, N1; McKenna, G1; Randall, H1; Klintmalm, G1; Goldstein, R1; Levy, M1; Chinnakotla, S1; Sanchez, E1 Author Information

BACKGROUND:Radio-frequency ablation (RFA) is an increasingly used treatment modality for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation (OLTX). The current study evaluates the effectiveness of RFA in this setting based on evaluation of total cell death in explanted native livers. DESIGN:We evaluated 36 tumors from 35 patients with RFA-treated HCC who underwent OLTX at our center between 1998 and 2002. Native livers from OLTX were extensively sampled for histologic evaluation. For each HCC, an estimate ratio of necrotic tumor areas was calculated based on hematoxylin and eosin (H&E) sections. In tumors with 10% or more residual viable areas, Tdt-mediated UTP nick-end labeling (TUNEL) was further performed to assess apoptosis in the morphologically 'viable' areas. A final 'tumor cell death' (TCD) ratio was recalculated for each HCC to include areas of apoptosis identified by TUNEL. RESULTS:Based on H&E evaluation, 22/36 (61.1%) HCC revealed > or = 90% necrosis including 12/36 HCC (33.3%) showing no evidence of residual viable tumor. The overall median tumor necrosis was 79%. When TUNEL findings were added, 26/36 (72.2%) HCC revealed > or = 90% TCD including 14/36 HCC (38.8%) showing complete TCD (median TCD of 88.4%). None of our patients died of HCC while awaiting OLTX. Longer RFA-to-transplant time appears to be associated with a higher TCD rate (median of 154.5 days in patients with less than 90% TCD vs 326 days for patients with > or = 90% TCD; P = 0.019). There was no significant correlation between tumor grade or pre-RFA size of the tumors and TCD rate in RFA-treated HCC (P = 0.11). CONCLUSION:Extensive TCD (88.4% median) can be obtained using RFA for HCC in patients awaiting OLTX. Our TUNEL findings suggest that RFA-induced cell injury could be associated with apoptosis.

This is in response to the letter entitled: “Renal Replacement Therapy after Liver Transplantation.” I hope this sufficiently answers the questions raised by Drs. Morrissey and Fan. How many patients who received pretransplant renal replacement therapy (RRT) required permanent dialysis or renal transplantation after successful orthotopic liver transplantation (OLT)? There were 22 patients that required pretransplant RRT in this study population. The number of patients that required posttransplant continuous veno-venous hemodialysis or hemodialysis within the acute period after liver transplantation was 100%. Only one patient at 3 months required RRT, with the rest showing recovery. These same questions that you have raised have provided impetus for us to continue investigation into this patient population. We subsequently will be able to answer the questions brought forth, and we look to publish the data as it becomes available. With regards to patients in this subgroup requiring renal transplantation, our data did not show any patients that subsequently underwent renal transplantation at our center. What percent of patients, including those on pretransplant RRT, developed end-stage renal disease (ESRD) after liver transplantation? We defined the criteria of ESRD to still require HD at three months after liver transplant. The study population that consisted of 724 patients (the three groups combined) demonstrated only a total of 10 patients that fit the criteria for ESRD. Additionally, the 22 excluded patients that required pretransplant RRT only added one more patient to the total of ESRD patients. Therefore, 11 of 746 patients (1.47%) developed ESRD post liver transplant. Did any factors predict the development of ESRD? Unfortunately, the numbers of ESRD patients in this study group were small and therefore any meaningful analysis would be difficult to perform. Clinically, all the usual suspects do play a role (sepsis, multiple operations, massive transfusion requirements, need for retransplant, etc.). However, based on our patients we cannot determine significance at this time. What was the survival rate for combined liver kidney transplantation? The Baylor group previously reported 48% 5-year survival in 29 patients? The current 5-year patient survival rate is 78% in our 20 liver-kidney transplant recipients in this study. Edmund Sanchez Baylor Regional Transplant Institute Dallas, TX

P458 Aims: Advanced donor age has been shown to be an independent risk factor for rapid HCV recurrence after liver transplant. We reviewed our data to evaluate the effect of donor age and to identify potential immunosuppressive factors that may obviate recurrence. Methods: Retrospective database review of patients transplanted for HCV. Study population was divided into two chronologic eras: Group I (pts transplanted 1994-1998 pre MMF use) and Group II (1999-2001). Additionally, immunosuppression protocols were either CyA or tacrolimus based with steroid. Statistical analysis these populations was performed and comparisons between the groups were made. Recurrence was based only on biopsy diagnosis. Results: There were no significant differences in donor and recipient ages in both groups. Additionally, the use of tacrolimus and cyclosporine was not different in both groups, nor did they demonstrate a difference in recurrence rates. Univariate analysis of the data was performed and is included in the table below.Figure* p = 0.01, ** p < 0.001 Group I vs. Group II, *** p = 0.0009 Group I vs. Group II Conclusions: Donors over 50 yrs. did not alter the incidence of overall HCV recurrence in either group. This is unlike what is reported by other institutions. Increased use of MMF in Group II was seen. Therefore, its use may suggest a role in negating the increase in HCV recurrence after liver transplantation seen in other centers. Further detailed studies are necessary to correctly identify other factors that may be involved.

Sanchez, Edmund1; Marubashi, Shigeru1; Jung, Gbap1; Levy, Marlon F.1; Goldstein, Robert M.1; Molmenti, Ernesto P.1; Fasola, Carlos G.1; Gonwa, Thomas A.1; Jennings, Linda W.1; Conkey, Amy C.1; Brooks, Barbara K.1; Klintmalm, Goran B.1 Author Information