Salvage Living-Donor Liver Transplantation for Liver Failure Following Definitive Radiation Therapy for Recurrent Hepatocellular Carcinoma: A Case Report T. Kitajimaa,*, Y. Fujimotoa, E. Hatanoa, H. Nishidaa, K. Ogawaa, A. Moria, H. Okajimaa, T. Kaidoa, A. Nakamurab, H. Nagamatsuc, and S. Uemotoa a Department of Surgery, Graduate School of Medicine, Kyoto University, Japan; bDepartment of Radiation Oncology and ImageApplied Therapy, Graduate School of Medicine, Kyoto University, Japan; and cDepartment of Medicine, Yame General Hospital, Japan
ABSTRACT A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases.
L
IVER TRANSPLANTATION (LT) now plays an important role in the treatment of patients with hepatocellular carcinoma (HCC), and the safety and feasibility of LT after liver resection with favorable outcomes has now become accepted even in East Asia, where living-donor LT (LDLT) is the predominant treatment option [1]. On the other hand, the safety and efficacy of some forms of radiation therapy (RT) as a bridge to deceased-donor LT (DDLT), including stereotactic body radiotherapy (SBRT) [2,3] and conformal external-beam radiotherapy (cEBRT), have been reported, mainly from Western countries [4,5]. However, the impact of definitive RT on the transplantation procedure, owing to such problems as radiation-induced injury of the anastomotic vessels, remains to be elucidated, especially in cases of LDLT. We herein report a rare case of salvage LDLT 0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.02.011
804
for liver failure after definitive RT as a multidisciplinary treatment for recurrent HCC. We also provide a review of the pertinent literature. CASE REPORT A 57-year-old Japanese man with a history of chronic hepatitis B virus infection who developed liver failure after multidisciplinary treatment for recurrent HCC was referred to our hospital to undergo LDLT. Five years earlier, contrast-enhanced computerized
*Address correspondence to Toshihiro Kitajima, MD, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: [email protected] ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 804e808 (2015)
SALVAGE LDLT AFTER RT FOR RECURRENT HCC
Fig 1. Contrast enhanced computed tomography detected a 15-mm enhanced lesion at the cut surface in segment 4 in the arterial early phase (yellow arrow) that was consistent with recurrent hepatocellular carcinoma.
tomography (CT) detected the presence of solitary HCC, which measured 20 mm in size, with bile duct tumor thrombus in segments 5 and 6 in the liver, and right lobectomy was therefore performed. Two years later, transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) were performed for recurrent HCC in segment 2. Two years after those local therapies, contrastenhanced CT detected a 15-mm early-enhanced lesion at the cut surface in segment 4 that was compatible with recurrent HCC (Fig 1). Performing either resection or RFA of the lesion would have been difficult because it was adjacent to the main trunk of the portal vein (PV), so it was treated with transhepatic arterial infusion chemotherapy with cisplatin (CDDP-TAI) and conventional
805 radiation therapy (RT) with a cumulative dose of 60 Gy administered in 20 fractions (Fig 2). Irradiation planning revealed that both the retrohepatic inferior vena cava (IVC) and the hilar hepatic artery (HA), which are commonly engaged in vascular reconstruction, had likely been included in the fields and therefore had been irradiated with >50 Gy and w40 Gy, respectively (Fig 2). One month later aftter the start of CDDP-TAI and RT, multiple liver abscesses and intrahepatic bile duct (IHBD) dilation were detected. Although a persistent systemic infection was successfully controlled by the continuous administration of antibiotics and percutaneous transhepatic cholangiodrainage was performed to treat the dilation of the IHBD, and the serum level of total bilirubin gradually increased to 20 mg/dL within one-half year. Thereafter, various symptoms due to liver failure, including refractory massive ascites, jaundice, and malnutrition, developed and the patient repeatedly suffered from multiple episodes of severe infection despite the use of antibiotics. Therefore, the patient was listed as an LDLT candidate owing to severe liver failure following multidisciplinary treatment for metachronous recurrent HCC. When the patient was transferred to our hospital, the laboratory data were as follows: white blood cells, 9.6 109/L; platelets, 146 109/L; serum total bilirubin, 17.4 mg/dL; serum direct bilirubin, 11.6 mg/dL; aspartate aminotransferase, 93 IU/L; alanine aminotransferase, 27 IU/L; albumin, 1.4 g/dL; prothrombin time, 73%; g-glutamyltranspeptidase, 268 IU/L; total bile acid, 45 mmol/L; ammonia, 48 mg/dL, and C-reactive protein was 13.0 mg/dL. The serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels were within the normal limits (AFP, 2.5 ng/mL; DCP, 20 mAU/mL). Preoperative enhanced CT detected significant atrophy of the whole liver, multiple liver abscesses in the whole liver, and massive ascites (Fig 3A). There were no apparent lesions that were compatible with HCC. In addition, CT revealed an engorged left gastric vein and a thrombus in the main trunk of the extrahepatic portal vein (Fig 3B). At the time of transplantation, the Child-Pugh score of the patient was C and the Model for EndStage Liver Disease score 19.
Fig 2. The radiotherapy plan for the treatment of recurrent hepatocellular carcinoma. Four photon beams were selected to cover the treatment volume at a prescribed dose of 60 Gy in 20 fractions. Inferior vena cava, portal vein, and hepatic artery are shown in green, blue, and red, respectively.
806
KITAJIMA, FUJIMOTO, HATANO ET AL
Fig 3. Pre-transplantation enhanced computerized tomographic findings. (A) Significant atrophy of the whole liver, multiple liver abscesses in the whole liver, and massive ascites were detected. (B) An engorged left gastric vein (red circle) and a thrombus in the main trunk of the extrahepatic portal vein (yellow arrow) were detected.
LDLT was performed with the use of a right lobe graft without the middle hepatic vein from his wife, who had an identical blood type. The graft-to-recipient weight ratio was 1.27%. Regarding the intraoperative findings, severe adhesion was found between colon/ duodenum and liver. Although there was a serious concern about the quality of the vessels because of earlier RT, vascular reconstruction was nevertheless performed in the usual manner (Fig 4), because the anastomotic vessels had not been macroscopically injured. Hepatic vein reconstruction was performed in an end-toside (new orifice of IVC) fashion with an anterior patch using the donor’s left ovarian vein. PV reconstruction was therefore performed in an end-to-end fashion between the graft’s right PV and the recipient’s main trunk of the PV after performing thrombectomy, and hepatic artery reconstruction was performed in an endto-end fashion between the graft’s right HA and the recipient’s right HA. Grossly, no residual tumor was seen, and biliary necrosis was detected in the explanted liver (Fig 5). The patient recovered uneventfully and was discharged from our hospital on postoperative day 59. Eighteen months after the LDLT, 3-dimensional reconstruction imaging based on dynamic enhanced CT revealed sufficient patency of the anastomotic vessels (Fig 6). At the time of writing, the patient
Fig 4. Schematic drawing of the vessel anastomosis procedures in this case. Abbreviations: IVC, inferior vena cava; LHA, left hepatic artery; LHV, left hepatic vein; MHA, middle hepatic artery; MHV, middle hepatic vein; PV, portal vein; RHA, right hepatic artery; RHV, right hepatic vein.
had been doing well for 34 months, with no evidence of either vascular complications or a recurrence of HCC.
DISCUSSION
LT is now theoretically the optimal curative treatment for patients with HCC, because it removes the tumor radically as well as the underlying oncogenic liver disease [6]. However, a shortage of donor organs and dropping out from the waiting list because of tumor progression are still the biggest problems associated with DDLT for HCC. In an effort to reduce the number of patients who drop out during the waiting period, various strategies have evolved over the past 2 decades as bridging therapies, such as TACE, RFA, and liver resection. In 2000, Majno et al first proposed the use of salvage liver transplantation (SLT), which was defined as LT performed after HCC recurrence or a deterioration of the liver function after primary liver resection [7]. Regarding DDLT after earlier liver resection, Belghiti et al and Adam et al reported the short- and long-term outcomes in SLT
SALVAGE LDLT AFTER RT FOR RECURRENT HCC
Fig 5. Gross findings of the explanted liver: No residual tumor was seen, and biliary necrosis (yellow arrow) was detected.
patients compared with primary LT patients [8,9]. More recent studies have reported the safety and feasibility of SLT for recurrent HCC without impairing the long-term survival compared with PLT [10e12]. However, the role of pre-transplantation therapies differs somewhat between East Asian countries, where LDLT predominates, and Western countries where it does not. Because LDLT is regarded to be a 2nd- or 3rd-line option in Asian countries, such therapies are usually performed with a curative intent rather than as a bridging therapy. Our previous report demonstrated the safety and feasibility of salvage LDLT for recurrent HCC with favorable outcomes [1]. In the present case, although no recurrent HCC due to a multidisciplinary treatment with a curative intent was observed at the time of LDLT, salvage LDLT was considered to be the only treatment option to treat severe liver failure. Regarding the use of RT before LT, most reports have described it as a bridge to LT for advanced HCC to both prevent tumor progression and to down-stage tumors to meet the transplant criteria [2e5], or as a neoadjuvant therapy for hilar cholangiocarcinoma [13]. Regarding its use a bridge to LT for HCC, there have been several reports on the safety and efficacy of SBRT [2,3] and proton beams [14], and a few studies have demonstrated the use of cEBRT [4,5]. However, in the present case, pre-transplantation RT had been performed not as a bridge treatment, but as a
807
definitive therapy for recurrent HCC. To the best of our knowledge, this is the 1st case report of LDLT after definitive RT. It is necessary to consider the adverse effects that pre-transplantation RT might have on the transplantation procedures and postoperative patency of the anastomotic vessels. Vascular endothelial cells are highly radiosensitive and smaller vessels are especially sensitive to radiation injury [15]. Regarding larger vessels, some reports have demonstrated the presence of carotid and iliac artery injuries after radiotherapy for head, neck, and pelvic malignancies [16e18]. Furthermore, radiation-induced vessel injury typically develops as a late complication. Popovtzer et al noted that 40% of patients developed significant stenosis (>50%) of the carotid artery 10 years after the completion of RT [19]. In the present case, we did not observe any injuries in the anastomotic vessels and therefore successfully performed LDLT. We could not draw any firm conclusions, but we did speculate that the duration since the completion of RT had been relatively short for the onset of any late toxicities, and the irradiation field had been small, optimized with multiple beams to the recurrent tumor so that the pivotal vessels were not fully irradiated with high doses. Additionally, respiratory movement during RT might have blurred the high doses to the vessels. In light of our speculation and based on earlier reports regarding radiation-induced vascular damage, a close and long-term follow-up is necessary to confirm the patency of the anastomotic vessels in cases of LT after RT. Mantel et al reported that LDLT/DDLT with neoadjuvant chemoradiotherapy is associated with far higher rates of late (2e11 mo) arterial and PV complications [13]. However, transluminal boost of radiation with a high target dose of 2,000e3,000 cGy in addition to EBRT was delivered in the neoadjuvant protocol, which might be the cause of the high rate of vascular complications. According to several reports on RT as a bridge to DDLT for HCC, no vascular complications were observed in almost all cases [3,4]. In the present case, the dose per fraction was lower than that described in those reports, where a high dose per fraction, in principle, increases vascular damage. However, meticulous anastomotic procedures in more peripheral small vessels are usually needed in LDLT cases, compared with DDLT cases.
Fig 6. Three-dimensional reconstruction imaging based on dynamic enhanced computerized tomography revealed sufficient patency of the anastomotic vessels 18 months after the LDLT (arrows: anastomotic sites). Abbreviations: PV, portal vein; HA, hepatic artery; HV, hepatic vein.
808
Therefore, it is necessary to pay more attention to radiationinduced vascular complications in LDLT patients than in DDLT patients. In conclusion, a rare case of salvage LDLT after definitive RT as a multidisciplinary treatment for recurrent HCC was herein described. Although taking radiationinduced vessel injury as a late complication into careful consideration is considered to be essential, especially in the case of LDLT patients, the strategy of salvage LDLT was demonstrated to be effective even after multidisciplinary treatment. REFERENCES [1] Kaido T, Mori A, Ogura Y, Hata K, Yoshizawa A, Iida T, et al. Living donor liver transplantation for recurrent hepatocellular carcinoma after liver resection. Surgery 2012;151:55e60. [2] Andolino DL, Johnson CS, Maluccio M, Kwo P, Tector AJ, Zook J, et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2011;81:e447e53. [3] O’Connor JK, Trotter J, Davis GL, Dempster J, Klintmalm GB, Goldstein RM. Long-term outcomes of stereotactic body radiation therapy in the treatment of hepatocellular cancer as a bridge to transplantation. Liver Transpl 2012;18:949e54. [4] Sandroussi C, Dawson LA, Lee M, Guindi M, Fischer S, Ghanekar A, et al. Radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma. Transpl Int 2010;23:299e306. [5] Wigg A, Hon K, Mosel L, Sladden N, Palumbo K. Downstaging of hepatocellular carcinoma via external-beam radiotherapy with subsequent liver transplantation: a case report. Liver Transpl 2013;19:1119e24. [6] Hwang S, Lee SG, Joh JW, Suh KS, Kim DG. Liver transplantation for adult patients with hepatocellular carcinoma in Korea: comparison between cadaveric donor and living donor liver transplantations. Liver Transpl 2005;11:1265e72. [7] Majno PE, Sarasin FP, Mentha G, Hadengue A. Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma
KITAJIMA, FUJIMOTO, HATANO ET AL and preserved liver function: an outcome-oriented decision analysis. Hepatology 2000;31:899e906. [8] Belghiti J, Cortes A, Abdalla EK, Régimbeau JM, Prakash K, Durand F, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg 2003;238:885e92. [9] Adam R, Azoulay D, Castaing D, Eshkenazy R, Pascal G, Hashizume K, et al. Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy? Ann Surg 2003;238:508e18. [10] Zhu Y, Dong J, Wang WL, Li MX, Lu Y. Short- and longterm outcomes after salvage liver transplantation versus primary liver transplantation for hepatocellular carcinoma: a meta-analysis. Transplant Proc 2013;45:3329e42. [11] Guerrini GP, Gerunda GE, Montalti R, Ballarin R, Cautero N, De Ruvo N, et al. Results of salvage liver transplantation. Liver Int 2014;34:e96e104. [12] Qu W, Zhu ZJ, Sun LY, Wei L, Liu Y, Zeng ZG. Salvage liver transplantation for hepatocellular carcinoma recurrence after primary liver resection. Clin Res Hepatol Gastroenterol 2015;39:93e7. [13] Mantel HT, Rosen CB, Heimbach JK, Nyberg SL, Ishitani MB, Andrews JC, et al. Vascular complications after orthotopic liver transplantation after neoadjuvant therapy for hilar cholangiocarcinoma. Liver Transpl 2007;13:1372e81. [14] Bush DA, Kayali Z, Grove R, Slater JD. The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer 2011;117:3053e9. [15] Fajardo LF, Berthrong M. Vascular lesions following radiation. Pathol Annu 1988;23(Pt 1):297e330. [16] Friedlander AH, Federico M, Yueh R, Norman KM, Chin EE. Radiation-associated carotid artery atherosclerosis: case report and review of contemporaneous literature. Spec Care Dentist 2009;29:75e9. [17] Patel DA, Kochanski J, Suen AW, Fajardo LF, Hancock SL, Knox SJ. Clinical manifestations of noncoronary atherosclerotic vascular disease after moderate dose irradiation. Cancer 2006;106: 718e25. [18] Mellière D, Becquemin JP, Berrahal D, Desgranges P, Cavillon A. Management of radiation-induced occlusive arterial disease: a reassessment. J Cardiovasc Surg (Torino) 1997;38:261e9. [19] Popovtzer A, Eisbruch A. Advances in radiation therapy of head and neck cancer. Expert Rev Anticancer Ther 2008;8:633e44.
ABSTRACT A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases.
L
IVER TRANSPLANTATION (LT) now plays an important role in the treatment of patients with hepatocellular carcinoma (HCC), and the safety and feasibility of LT after liver resection with favorable outcomes has now become accepted even in East Asia, where living-donor LT (LDLT) is the predominant treatment option [1]. On the other hand, the safety and efficacy of some forms of radiation therapy (RT) as a bridge to deceased-donor LT (DDLT), including stereotactic body radiotherapy (SBRT) [2,3] and conformal external-beam radiotherapy (cEBRT), have been reported, mainly from Western countries [4,5]. However, the impact of definitive RT on the transplantation procedure, owing to such problems as radiation-induced injury of the anastomotic vessels, remains to be elucidated, especially in cases of LDLT. We herein report a rare case of salvage LDLT 0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.02.011
804
for liver failure after definitive RT as a multidisciplinary treatment for recurrent HCC. We also provide a review of the pertinent literature. CASE REPORT A 57-year-old Japanese man with a history of chronic hepatitis B virus infection who developed liver failure after multidisciplinary treatment for recurrent HCC was referred to our hospital to undergo LDLT. Five years earlier, contrast-enhanced computerized
*Address correspondence to Toshihiro Kitajima, MD, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: [email protected] ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 804e808 (2015)
SALVAGE LDLT AFTER RT FOR RECURRENT HCC
Fig 1. Contrast enhanced computed tomography detected a 15-mm enhanced lesion at the cut surface in segment 4 in the arterial early phase (yellow arrow) that was consistent with recurrent hepatocellular carcinoma.
tomography (CT) detected the presence of solitary HCC, which measured 20 mm in size, with bile duct tumor thrombus in segments 5 and 6 in the liver, and right lobectomy was therefore performed. Two years later, transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) were performed for recurrent HCC in segment 2. Two years after those local therapies, contrastenhanced CT detected a 15-mm early-enhanced lesion at the cut surface in segment 4 that was compatible with recurrent HCC (Fig 1). Performing either resection or RFA of the lesion would have been difficult because it was adjacent to the main trunk of the portal vein (PV), so it was treated with transhepatic arterial infusion chemotherapy with cisplatin (CDDP-TAI) and conventional
805 radiation therapy (RT) with a cumulative dose of 60 Gy administered in 20 fractions (Fig 2). Irradiation planning revealed that both the retrohepatic inferior vena cava (IVC) and the hilar hepatic artery (HA), which are commonly engaged in vascular reconstruction, had likely been included in the fields and therefore had been irradiated with >50 Gy and w40 Gy, respectively (Fig 2). One month later aftter the start of CDDP-TAI and RT, multiple liver abscesses and intrahepatic bile duct (IHBD) dilation were detected. Although a persistent systemic infection was successfully controlled by the continuous administration of antibiotics and percutaneous transhepatic cholangiodrainage was performed to treat the dilation of the IHBD, and the serum level of total bilirubin gradually increased to 20 mg/dL within one-half year. Thereafter, various symptoms due to liver failure, including refractory massive ascites, jaundice, and malnutrition, developed and the patient repeatedly suffered from multiple episodes of severe infection despite the use of antibiotics. Therefore, the patient was listed as an LDLT candidate owing to severe liver failure following multidisciplinary treatment for metachronous recurrent HCC. When the patient was transferred to our hospital, the laboratory data were as follows: white blood cells, 9.6 109/L; platelets, 146 109/L; serum total bilirubin, 17.4 mg/dL; serum direct bilirubin, 11.6 mg/dL; aspartate aminotransferase, 93 IU/L; alanine aminotransferase, 27 IU/L; albumin, 1.4 g/dL; prothrombin time, 73%; g-glutamyltranspeptidase, 268 IU/L; total bile acid, 45 mmol/L; ammonia, 48 mg/dL, and C-reactive protein was 13.0 mg/dL. The serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels were within the normal limits (AFP, 2.5 ng/mL; DCP, 20 mAU/mL). Preoperative enhanced CT detected significant atrophy of the whole liver, multiple liver abscesses in the whole liver, and massive ascites (Fig 3A). There were no apparent lesions that were compatible with HCC. In addition, CT revealed an engorged left gastric vein and a thrombus in the main trunk of the extrahepatic portal vein (Fig 3B). At the time of transplantation, the Child-Pugh score of the patient was C and the Model for EndStage Liver Disease score 19.
Fig 2. The radiotherapy plan for the treatment of recurrent hepatocellular carcinoma. Four photon beams were selected to cover the treatment volume at a prescribed dose of 60 Gy in 20 fractions. Inferior vena cava, portal vein, and hepatic artery are shown in green, blue, and red, respectively.
806
KITAJIMA, FUJIMOTO, HATANO ET AL
Fig 3. Pre-transplantation enhanced computerized tomographic findings. (A) Significant atrophy of the whole liver, multiple liver abscesses in the whole liver, and massive ascites were detected. (B) An engorged left gastric vein (red circle) and a thrombus in the main trunk of the extrahepatic portal vein (yellow arrow) were detected.
LDLT was performed with the use of a right lobe graft without the middle hepatic vein from his wife, who had an identical blood type. The graft-to-recipient weight ratio was 1.27%. Regarding the intraoperative findings, severe adhesion was found between colon/ duodenum and liver. Although there was a serious concern about the quality of the vessels because of earlier RT, vascular reconstruction was nevertheless performed in the usual manner (Fig 4), because the anastomotic vessels had not been macroscopically injured. Hepatic vein reconstruction was performed in an end-toside (new orifice of IVC) fashion with an anterior patch using the donor’s left ovarian vein. PV reconstruction was therefore performed in an end-to-end fashion between the graft’s right PV and the recipient’s main trunk of the PV after performing thrombectomy, and hepatic artery reconstruction was performed in an endto-end fashion between the graft’s right HA and the recipient’s right HA. Grossly, no residual tumor was seen, and biliary necrosis was detected in the explanted liver (Fig 5). The patient recovered uneventfully and was discharged from our hospital on postoperative day 59. Eighteen months after the LDLT, 3-dimensional reconstruction imaging based on dynamic enhanced CT revealed sufficient patency of the anastomotic vessels (Fig 6). At the time of writing, the patient
Fig 4. Schematic drawing of the vessel anastomosis procedures in this case. Abbreviations: IVC, inferior vena cava; LHA, left hepatic artery; LHV, left hepatic vein; MHA, middle hepatic artery; MHV, middle hepatic vein; PV, portal vein; RHA, right hepatic artery; RHV, right hepatic vein.
had been doing well for 34 months, with no evidence of either vascular complications or a recurrence of HCC.
DISCUSSION
LT is now theoretically the optimal curative treatment for patients with HCC, because it removes the tumor radically as well as the underlying oncogenic liver disease [6]. However, a shortage of donor organs and dropping out from the waiting list because of tumor progression are still the biggest problems associated with DDLT for HCC. In an effort to reduce the number of patients who drop out during the waiting period, various strategies have evolved over the past 2 decades as bridging therapies, such as TACE, RFA, and liver resection. In 2000, Majno et al first proposed the use of salvage liver transplantation (SLT), which was defined as LT performed after HCC recurrence or a deterioration of the liver function after primary liver resection [7]. Regarding DDLT after earlier liver resection, Belghiti et al and Adam et al reported the short- and long-term outcomes in SLT
SALVAGE LDLT AFTER RT FOR RECURRENT HCC
Fig 5. Gross findings of the explanted liver: No residual tumor was seen, and biliary necrosis (yellow arrow) was detected.
patients compared with primary LT patients [8,9]. More recent studies have reported the safety and feasibility of SLT for recurrent HCC without impairing the long-term survival compared with PLT [10e12]. However, the role of pre-transplantation therapies differs somewhat between East Asian countries, where LDLT predominates, and Western countries where it does not. Because LDLT is regarded to be a 2nd- or 3rd-line option in Asian countries, such therapies are usually performed with a curative intent rather than as a bridging therapy. Our previous report demonstrated the safety and feasibility of salvage LDLT for recurrent HCC with favorable outcomes [1]. In the present case, although no recurrent HCC due to a multidisciplinary treatment with a curative intent was observed at the time of LDLT, salvage LDLT was considered to be the only treatment option to treat severe liver failure. Regarding the use of RT before LT, most reports have described it as a bridge to LT for advanced HCC to both prevent tumor progression and to down-stage tumors to meet the transplant criteria [2e5], or as a neoadjuvant therapy for hilar cholangiocarcinoma [13]. Regarding its use a bridge to LT for HCC, there have been several reports on the safety and efficacy of SBRT [2,3] and proton beams [14], and a few studies have demonstrated the use of cEBRT [4,5]. However, in the present case, pre-transplantation RT had been performed not as a bridge treatment, but as a
807
definitive therapy for recurrent HCC. To the best of our knowledge, this is the 1st case report of LDLT after definitive RT. It is necessary to consider the adverse effects that pre-transplantation RT might have on the transplantation procedures and postoperative patency of the anastomotic vessels. Vascular endothelial cells are highly radiosensitive and smaller vessels are especially sensitive to radiation injury [15]. Regarding larger vessels, some reports have demonstrated the presence of carotid and iliac artery injuries after radiotherapy for head, neck, and pelvic malignancies [16e18]. Furthermore, radiation-induced vessel injury typically develops as a late complication. Popovtzer et al noted that 40% of patients developed significant stenosis (>50%) of the carotid artery 10 years after the completion of RT [19]. In the present case, we did not observe any injuries in the anastomotic vessels and therefore successfully performed LDLT. We could not draw any firm conclusions, but we did speculate that the duration since the completion of RT had been relatively short for the onset of any late toxicities, and the irradiation field had been small, optimized with multiple beams to the recurrent tumor so that the pivotal vessels were not fully irradiated with high doses. Additionally, respiratory movement during RT might have blurred the high doses to the vessels. In light of our speculation and based on earlier reports regarding radiation-induced vascular damage, a close and long-term follow-up is necessary to confirm the patency of the anastomotic vessels in cases of LT after RT. Mantel et al reported that LDLT/DDLT with neoadjuvant chemoradiotherapy is associated with far higher rates of late (2e11 mo) arterial and PV complications [13]. However, transluminal boost of radiation with a high target dose of 2,000e3,000 cGy in addition to EBRT was delivered in the neoadjuvant protocol, which might be the cause of the high rate of vascular complications. According to several reports on RT as a bridge to DDLT for HCC, no vascular complications were observed in almost all cases [3,4]. In the present case, the dose per fraction was lower than that described in those reports, where a high dose per fraction, in principle, increases vascular damage. However, meticulous anastomotic procedures in more peripheral small vessels are usually needed in LDLT cases, compared with DDLT cases.
Fig 6. Three-dimensional reconstruction imaging based on dynamic enhanced computerized tomography revealed sufficient patency of the anastomotic vessels 18 months after the LDLT (arrows: anastomotic sites). Abbreviations: PV, portal vein; HA, hepatic artery; HV, hepatic vein.
808
Therefore, it is necessary to pay more attention to radiationinduced vascular complications in LDLT patients than in DDLT patients. In conclusion, a rare case of salvage LDLT after definitive RT as a multidisciplinary treatment for recurrent HCC was herein described. Although taking radiationinduced vessel injury as a late complication into careful consideration is considered to be essential, especially in the case of LDLT patients, the strategy of salvage LDLT was demonstrated to be effective even after multidisciplinary treatment. REFERENCES [1] Kaido T, Mori A, Ogura Y, Hata K, Yoshizawa A, Iida T, et al. Living donor liver transplantation for recurrent hepatocellular carcinoma after liver resection. Surgery 2012;151:55e60. [2] Andolino DL, Johnson CS, Maluccio M, Kwo P, Tector AJ, Zook J, et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2011;81:e447e53. [3] O’Connor JK, Trotter J, Davis GL, Dempster J, Klintmalm GB, Goldstein RM. Long-term outcomes of stereotactic body radiation therapy in the treatment of hepatocellular cancer as a bridge to transplantation. Liver Transpl 2012;18:949e54. [4] Sandroussi C, Dawson LA, Lee M, Guindi M, Fischer S, Ghanekar A, et al. Radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma. Transpl Int 2010;23:299e306. [5] Wigg A, Hon K, Mosel L, Sladden N, Palumbo K. Downstaging of hepatocellular carcinoma via external-beam radiotherapy with subsequent liver transplantation: a case report. Liver Transpl 2013;19:1119e24. [6] Hwang S, Lee SG, Joh JW, Suh KS, Kim DG. Liver transplantation for adult patients with hepatocellular carcinoma in Korea: comparison between cadaveric donor and living donor liver transplantations. Liver Transpl 2005;11:1265e72. [7] Majno PE, Sarasin FP, Mentha G, Hadengue A. Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma
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