Orthotopic liver transplantation for unresectable hepatoblastoma

BACKGROUND: The outcome of treatment for advanced hepatoblastoma has recently improved after the introduction of preoperative or pre- and postoperative cisplatin-containing chemotherapy combined with complete surgical excision. The role of liver transplantation in a population of patients who have received this regimen has not been clearly defined. METHODS: Orthotopic liver transplantation (OLT) was performed in 13 children, aged 5 months to 11 years (median 27 months), who were assessed with unresectable hepatoblastoma, and whose pretreatment extent-of-disease was based on radiologic findings of group III (n=11) and group IV (n=2). One child with a multifocal tumor showed pulmonary metastases at presentation, but, according to radiologic studies, the deposits resolved with chemotherapy before liver transplantation. One other child showed exophytic extension of the primary tumor infiltrating the porta hepatis and body of the pancreas. All 13 patients received preoperative chemotherapy to reduce the size of the primary tumor(s) and to treat metastatic spread. RESULTS: Twelve children underwent elective OLT; all are alive and show normal graft function at a mean follow-up of 33 months (range 1-108). One child shows evidence of recurrent disease in the form of pulmonary metastases. One child underwent emergency OLT for acute liver failure after (incomplete) extended right hepatectomy and died from respiratory failure, with no evidence of recurrent tumor 3 weeks posttransplant. CONCLUSIONS: Liver transplantation is an effective treatment for unresectable unifocal or multifocal hepatoblastoma confined to the liver. A multidisciplinary approach to the management of hepatoblastoma, with thoughtful collaboration between pediatric oncologists, hepatologists, and liver surgeons, is essential.     

Pediatric liver transplantation for hepatoblastoma: a single center experience

The objective of this study was to review our experience with liver transplantation (OLT) for hepatoblastoma (HB) patients. We evaluated retrospectively clinical features of seven pediatric patients with HB who underwent OLT at our institute from 2007 to February 2011. We investigated pretreatment extent of disease (PRETEXT) stage at diagnosis, type of procedure, complications, changes in serum alpha-fetoprotein (AFP) level, recurrences and metastases. The median age at surgery was 47 months (range, 11 months to 10.3 years). OLT was performed for PRETEXT stage III with a central location (n = 2) and for PRETEXT stage IV cases (n = 5). Five children underwent live donor OLT (LDLT) and two deceased donor OLT including one split deceased donor OLT. One patient received a hepatic vein stent insertion due to stenosis and another experienced biliary leakage which was treated with percutaneous drainage and conservative management. Postoperative serum AFP level remained below 20 ng/mL during follow-up period in six patients who were free of recurrences or metastases. Postoperative serum AFP levels in one patient with pulmonary metastasis were never below 20 ng/mL and increased gradually thereafter. A Pulmonary metastasis was discovered in the 2^nd month post-operative. The other 6 patients are free of tumor recurrences with 29.9 month median follow-up.Although the number of cases is small without long term follow-up data, OLT for unresectable HB confined to the liver following chemotherapy seemed to show good clinical results. The role of post transplantation serum AFP levels needs further investigation.     

Liver transplantation for the management of hepatoblastoma

INTRODUCTION: Hepatoblastoma (HEP) is the most frequent liver malignancy occurring in childhood. Surgical resection currently represents the gold standard for treatment. In patients with initially unresectable tumors, chemotherapy may induce remarkable reductions in size. In nonresponder patients, liver transplantation (OLTx) may offer a chance of cure. MATERIALS AND METHODS: From 1990 to 2003, a total of 400 OLTx (31 pediatric transplants) have been performed at Padua University. Seven patients (4 males and 3 females) underwent OLTx for hepatoblastoma. All patients presented with bilobar liver involvement and had received chemotherapy according to the SIOPEL-1. In all patients preoperative staging was negative for extrahepatic involvement. RESULTS: The mean age of the pts was 8.2 years (range 6.4 months to 34 years). Mean follow-up after OLTx was 41.4 months (median 36, range 3 to 108 months). Actuarial patient survival rates after OLTx for hepatoblastoma are 83.3%, 83.3%, and 56% at 1, 3, and 5 years, respectively. Five of seven subjects with HEP are alive after transplant at 3, 12, 36, 65, and 108 months. Two patients died owing to recurrent disease after 6 and 60 months, respectively, from transplantation. Another subject, primarily treated with surgical resection, shows HEP recurrence at 40 months after OLTx. The remaining 4 patients are alive and well at a mean follow-up of 28 months (median 24, range 3 to 65 months). CONCLUSIONS: Liver transplantation may represent a valid therapeutic option for patients with unresectable HEP, but it is contraindicated in cases of recurrence following previous resection surgery. Neo-adjuvant chemotherapy is of paramount importance to obtain good long-term results.     

Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma

Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without extrahepatic or extrahepatic metastases were eligible. Patients initially received external-beam irradiation plus bolus fluorouracil (5-FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5-FU. 5-FU was then administered continuously through an ambulatory infusion pump until OLT After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n = 6), subsequent development of malignant ascites (n = 1), or death from intrahepatic biliary sepsis (n = 1). Eleven patients completed the protocol with successful OLT Except for 1 patient, all had early-stage disease (stages I and 11) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow-up of 44 months (range, 17 to 83 months; 7 of 9 patients > 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemother apy is associated with prolonged disease-free and overall survival in highly selected patients with early-stage cholangiocarcinoma.     

Treatment of Unresectable Hepatoblastoma with Liver Transplantation in the Pediatric Population

The purpose of our study was to evaluate the outcome of children who underwent liver transplantation as treatment for unresectable hepatoblastoma. We prospectively collected data on 311 consecutive liver transplants performed at Children's Medical Center of Dallas between October 1984 and November 2000. There were nine recipients (five boys, four girls) with a diagnosis of unresectable hepatoblastoma. Postoperative survival of those currently alive ranged from 6 months to 16 years (mean 6.4 years, median 7.7 years). All recipients received preoperative chemotherapy: 67% received postoperative chemotherapy. Mean AFP level prior to transplantation was 1 448000 ng/mL. Mean age at diagnosis was 0.81 years. Mean age at transplantation was 1.87 years. Only two patients experienced acute cellular rejection in the postoperative period. There was a total of three deaths and one recurrence. The only instance in which AFP levels did not decrease to low or undetectable levels post-transplantation was in the patient with recurrent tumor. Liver transplantation has an established role in the treatment of hepatoblastoma. It accounted for 3% of pediatric liver transplants, and provided the only opportunity for survival in otherwise incurable patients. Early diagnosis and treatment were found to be associated with better results. Response to chemotherapy may be an important factor influencing survival. Rising AFP levels after transplantation are associated with recurrence.     

Successful Surgical Resection and Chemotherapy for Unresectable Hepatoblastoma With Pulmonary Metastases and for Lung Recurrence After Liver Transplantation: A Case Report

BackgroundLiver transplantation (LTx) is indicated for unresectable hepatoblastoma (HB) without distal metastasis. However, to our knowledge, there is no consensus on the management of unresectable HB with pulmonary metastases, or on the treatment of recurrent HB. We report a successful case of metastatic HB treated with repeated lung resection, chemotherapy, and LTx. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor source.Case ReportOur case was a 1-year-old boy who developed pre-treatment extent of disease (PRETEXT) Ⅲ HB with multiple pulmonary metastases. The liver tumor was unresectable because it involved all hepatic veins. After 3 cycles of chemotherapy (cisplatin/carboplatin plus doxorubicin), the remaining 2 pulmonary metastases were resected and living donor liver transplantation (LDLT) was performed. Five months after LDLT, a tumor recurrence was detected in the right lung. Repeat lung resection was performed followed by 1 cycle of chemotherapy (carboplatin plus doxorubicin). There has been no recurrence for 18 months since the last lung resection.DiscussionPrevious reports revealed that 14 patients, including the present case, underwent LTx after resection of metastatic HB pulmonary lesions. Of these patients, the 2-year survival rate after LTx was 91%. Recurrence was reported in 5 patients, 2 of whom were successfully treated with repeated resection of the metastatic lesions. LTx after resection of lung recurrence may be a potential treatment for unresectable HB with pulmonary metastases.     

Chemotherapy can convert unresectable hepatoblastoma.

The surgical evaluation and management of children with hepatoblastoma has changed with recent advances in imaging modalities and preoperative chemotherapy. Pediatric Oncology Group (POG) Study no. 8697 has followed 63 patients with hepatoblastoma from 1986 to 1991. Twenty-six patients underwent primary tumor resection followed by chemotherapy consisting of cisplatin, vincristine, and 5-fluorouracil (group I). Thirty-seven patients with "unresectable" tumors received preoperative chemotherapy. Twenty-nine of these patients responded to chemotherapy and 26 underwent delayed surgical resection (group II). Eight patients had an inadequate response to chemotherapy; two have had successful liver transplantation and six are dead of disease progression. "Unresectable tumor" involved both liver lobes (25 patients), encased the inferior vena cava (2), involved adjacent tissues (1), involved the hepatic veins (2), or was deemed too large for safe resection (7). Two patients had distant metastases. The reason for an unresectable designation was not reported in five patients. The determination for an unresectable designation included exploratory laparotomy in 14 patients, angiogram in 7, computed tomography scan in 20, and magnetic resonance imaging in 3 patients. Operative times and transfusion requirements were similar in both groups. Perioperative complications were higher in patients in group II. There was no mortality and only minor morbidity associated with chemotherapy in each group. In both groups 77% of the patients are in complete remission after 13 to 54 months. Preoperative chemotherapy can allow successful resection of initially "unresectable" hepatoblastoma. Primary resection that may result in exsanguination should be postponed and chemotherapy given.     

Liver transplantation using donors older than 80 years: a single-center experience

AIM: The shortage of organs for orthotopic liver transplantation (OLT) has forced transplantation centers to expand the donor pool by using donors traditionally labeled as "extended criteria donors." One such example is OLT using a donor with advanced age. MATERIALS AND METHODS: We retrospectively evaluated 10 patients who received a liver graft from cadaveric donors older than 80 years. We analyzed pretransplantation donor and recipient characteristics, as well as the evolution of the recipients. RESULTS: All 10 donors were older than 80 years (median age, 83.5; range, 80-93). No steatosis (>30%) was accepted in the older donor group. Medium follow-up was 19.5 months. The most frequent cause for OLT was hepatitis C virus (HCV) cirrhosis (8/10 patients). We had 1 case of primary nonfunction, 1 patient died immediately after surgery because of extrahepatic complications (cardiac arrest), and 2 other patients had a severe HCV recurrence and died after 1 and 2 years from OLT, respectively. Five patients had HCV recurrence and biliary complications were present in 60% of the patients. No cases of acute or chronic rejection were described. Overall survival rates after 1 and 3 years were 80% and 40%, respectively. CONCLUSIONS: Old donor age is not an absolute contraindication to OLT. Liver grafts from donors older than 80 years can be used knowing that there is a high risk of postoperative complications. Furthermore, the increased risk of developing severe HCV recurrence, related to older donor age, suggests that such livers should be used in HCV-negative recipients.     

Survival after liver transplantation for hepatoblastoma: a 2-center experience

Purpose

Complete resection with adjuvant chemotherapy is the accepted treatment for hepatoblastoma. The aim of this study is to evaluate our results of liver transplantation (LT) for tumors still unresectable after adequate chemotherapy.

Methods

All patients transplanted for hepatoblastoma from 2 institutions between 1990 and 2004 were included. Variables reviewed to determine impact on survival included the following: previous tumor resection, metastatic disease at diagnosis, microscopic vascular invasion, α-fetoprotein (AFP) levels at diagnosis and at transplant, tumor histology, and administration of posttransplantation chemotherapy. Effectiveness of pretransplantation chemotherapy was defined as a drop of more than 99% in peak AFP levels.

Results

Fourteen patients were transplanted: 9 boys and 5 girls (age range, 18 months-13 years; mean age, 57 ± 48 months). Patients were transplanted a mean of 4 ± 1 months after diagnosis. Overall survival was 71% (10/14) with a mean follow-up of 46 months. All deaths were secondary to recurrent tumor. Of 10 patients who underwent a primary LT, 9 survived compared to only 1 of 4 transplanted for unresectable tumor recurrence after primary resection (90% vs 25%; P = .02). Decline in peak AFP of more than 99% was also associated with better survival (100% vs 56%; P = .08). Similarly, patients who received posttransplantation chemotherapy had 100% survival compared with 56% without chemotherapy (P = .08). Other variables had little effect on survival.

Conclusions

Liver transplantation is a successful treatment option for children with unresectable hepatoblastoma with a 90% survival rate for primary transplantation. Rescue LT for recurrent hepatoblastoma after previous resection has a poor survival outcome and should be considered a relative contraindication. Posttransplantation chemotherapy improves survival. A prospective multicenter collaboration to validate these findings with a larger patient population is necessary. Until that time, patients who receive rescue transplants should receive posttransplantation chemotherapy.     

Recurrence of Langerhans cell histiocytosis in the graft after pediatric liver transplantation

Two girls were diagnosed with Langerhans cell histiocytosis (LCH) at the age of 16 and 7 months and developed end stage chronic liver disease related to LCH-induced sclerosing cholangitis at 28 and 8 months, respectively. They received liver transplants at 34 and 14 months of age. Five months post-orthotopic liver transplantation (OLT) one of the patients developed posttransplant lymphoproliferative disease, successfully treated with a combination of surgery and reduction of immunosuppression. Fourteen months post-OLT she developed diabetes insipidus, bilateral ear discharge, and new osteolytic lesions. After transplantation both girls had mild skin reactivations of LCH, requiring minimal steroid increments. At 60 and 5 months post-OLT intrahepatic LCH recurrence was diagnosed on the basis of abnormal biliary enzymes and presence of Langerhans cells in the grafts. Initial cholangiography in both patients was unremarkable. LCH activity was controlled by maintenance chemotherapy with vinblastine, etoposide, and prednisolone. Ten months after reappearance of LCH in the liver graft a follow-up cholangiography in one of the girls demonstrated a low grade cholangiopathy. Residual elevation of liver enzymes probably represents an ongoing pathogenic process.     

Resection, including transplantation, for hepatoblastoma and hepatocellular carcinoma: impact on survival.

Long-term survival in children with primary hepatic malignancies can not be expected without complete tumor resection. In the last ten years we have treated 21 children with hepatocellular carcinoma (HCC) and 21 children with hepatoblastoma (HEP), with tumor extirpation our surgical goal. Operative treatment included partial hepatectomy ([PH] 20), either primary (10) or delayed (following chemotherapy) (10), total hepatectomy and orthotopic liver transplantation ([OLT] 13), or upper abdominal exenteration and multiple organ transplantation (2). Two patients had both PH and subsequent total hepatectomy and OLT. Overall survival was 48% (20/42), with 9 patients dying of progressive disease prior to removal of their tumor. HEP patient survival was 67% (14/21), including 2 of 6 who underwent primary PH, 7 of 8 who had delayed PH, and 5 of 6 who underwent OLT. Survival for the children with HCC was 29% (6/21), including 1 of 4 after primary PH, 1 of 2 following delayed PH, 3 of 7 following OLT, and 1 of 2 after exenteration and multiple organ transplantation. Preoperative chemotherapy facilitated removal of 10 initially unresectable tumors (8 HEP, 2 HCC) at a second-look procedure. Total hepatectomy and OLT markedly improved survival in patients with disease unresectable by standard methods. Partial hepatectomy, either primary or delayed, should be attempted in all children with hepatic malignancies. Total hepatectomy and OLT appears to be a viable adjunct in the treatment of childhood malignancies, and should be used for otherwise unresectable tumors as part of a carefully planned protocol.     

Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to evaluate the effect of postoperative adjuvant chemotherapy on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Historically, liver transplantation for HCC has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics. METHODS: Twenty-five patients were placed on 6 months of intravenous fluorouracil, doxorubicin, and cisplatin after OLT. Risk factors, recurrence rates, and survival rates were analyzed and compared with historic controls. RESULTS: Overall long-term survival in the protocol patients was 46% at 3 years, improved over our historic controls of 5.8% at 3 years (p = 0.0001). Overall recurrence rate was 20% (n = 4). Possible risk factors, such as tumor size, vascular invasion, multifocality, capsular invasion, and tumor differentiation, were not found to be significantly predictive of survival. Three patients with long-term, disease-free survival had tumors > 5 cm. Side effects from chemotherapy were common, but rarely severe. CONCLUSIONS: This study suggests that adjuvant chemotherapy after transplantation for HCC can provide long-term cure and may improve survival, even in patients with stage III and IV disease.     

Liver transplantation for biliary atresia

Biliary atresia is the most common indication for liver transplantation (OLT) in children. We present our experience with OLT as a treatment for end-stage liver disease in children with biliary atresia. We performed a retrospective review of 20 biliary atresia patients (11 male, 9 female patients; mean age, 21.4 months; range, 6 to 84 months) who had undergone OLT. Mean preoperative weight and height were 10.1 +/- 5.8 kg and 72.5 cm, respectively. Thirteen recipients were younger than 1 year of age, and 15 weighed less than 10 kg at the time of OLT. Fourteen recipients had undergone a Kasai operation prior to the OLT. The mean serum total bilirubin level was 22.56 mg/dL before OLT. Eighteen left lateral segment grafts and two whole grafts were transplanted. The mean recipient operative time was 9.25 hours. The mean recipient intraoperative blood loss was 1.81 U. Two hepatic arterial thromboses and one biliary leak occurred soon after surgery. Portal vein stenoses developed in two recipients at 10 and 12 months after OLT; both were treated with balloon dilatation. Two biliary stenoses, which occurred at 10 months and 3.5 years after surgery, were treated with balloon dilatation. Two recipients died at 2 and 12 days after OLT because of respiratory distress syndrome and sepsis, respectively. The remaining 18 (90%) recipients are alive with good graft function. The overall rejection rate was 31.25%. OLT is an effective treatment for children with biliary atresia and a failed Kasai procedure. Living related liver grafts represented an excellent organ supply for these patients.     

Expanded criteria for liver transplantation in patients with hepatocellular carcinoma

INTRODUCTION: Liver transplantation is the only curative treatment for patients with cirrhosis and unresectable hepatocellular carcinoma (HCC) without extrahepatic dissemination. Since criteria for transplantation in HCC are controversial, we evaluated our early results of liver transplantation for unresectable HCC. MATERIALS AND METHODS: Three women and 14 men (age range, 1.1 to 64 years) with preoperatively diagnosed or incidentally discovered HCC underwent liver transplantation. Six grafts were obtained from cadaveric donors, and each of the remaining 11 grafts from a living related donor. Criteria for participation, independent of tumor size and number of tumor nodules, were no invasion of major vascular structure and no evidence of extrahepatic disease. In nine patients, tumors were beyond the Milan criteria. Twelve patients (86.7%) received tacrolimus and 2 (13.30%), rapamycin monotherapy with early withdrawal of corticosteroid therapy. Two patients underwent neoadjuvant chemoembolization before transplantation; none received adjuvant chemotherapy. Seven patients with hepatitis B virus infection underwent antiviral prophylaxis with antibody to hepatitis B surface antigens and lamivudine. RESULTS: During follow-up (range, 1 to 17 months), all patients exhibited excellent graft function. Imaging studies revealed no evidence of tumor recurrence and no elevation of alpha fetoprotein or carcinoembryonic antigen levels. DISCUSSION: Low-dose immunosuppressive therapy and expanded criteria for liver transplantation in patients with HCC, especially when donation from a living related donor is possible, appear to inhibit disease recurrence and improve outcomes.     

Low risk of hepatitis B virus recurrence after withdrawal of long-term hepatitis B immunoglobulin in patients receiving maintenance nucleos(t)ide analogue therapy.

Hepatitis B virus (HBV) recurrence rates of 0-16% had been reported in patients maintained on nucleoside analogues (NA) after hepatitis B immunoglobulin (HBIG) discontinuation after orthotopic liver transplantation (OLT). However, follow-up in most studies was short. We aimed to determine the long-term risk of HBV recurrence using this strategy. All HBV patients who received > or =7 doses of intravenous HBIG after OLT, with no HBV recurrence while receiving HBIG, and who eventually discontinued HBIG and were maintained on NA, were included. HBV recurrence was defined as HBsAg-positive or HBV DNA > or =5 log copies/mL on 2 consecutive occasions. Twenty-one patients met the inclusion criteria. Immediate post-OLT prophylaxis was combination HBIG and NA in 15 patients, whereas 6 patients received HBIG monotherapy for 62-109 months before NA was added. HBIG was discontinued a median of 26 (range, 0.2-121) months after OLT. Median follow-up post-HBIG discontinuation was 40 (range, 5-51) months. Only 1 patient, who had 12 months of HBIG and was noncompliant to NA therapy, had HBV recurrence, 34 months after HBIG discontinuation. One patient had HBV DNA of 3.3 log copies/mL 47 and 48 months after HBIG discontinuation but remained HBsAg-negative. Lamivudine-resistant mutations were detected in both patients. Probability of HBV recurrence was 0% and 9% at 2 and 4 years after HBIG discontinuation. Three patients had 1-2 episodes of transiently detectable HBV DNA. All were HBV DNA and HBsAg negative on repeated tests over a period of 2-36 months. Maintenance therapy with NA after discontinuation of long-term HBIG therapy is associated with a low risk of HBV recurrence after OLT in compliant HBV patients.     

Living-Donor Liver Transplantation for Hepatoblastoma

Hepatoblastoma is the most common malignant liver tumor in children. Recently, liver transplantation has been indicated for unresectable hepatoblastoma. We retrospectively reviewed 14 children with a diagnosis of hepatoblastoma who had undergone living-donor liver transplantation (LDLT) at Kyoto University Hospital. During the period from June 1990 to December 2004, 607 children underwent LDLT. Of these interventions, 2.3% were performed for hepatoblastoma. Based on radiological findings, the pre-treatment extent of disease (PRETEXT) grouping was used for pre-treatment staging of the tumor. There were grade III in seven patients and grade IV in seven patients. Thirteen patients received chemotherapy, and seven underwent hepatectomy 11 times. Immunosuppressive treatment consisted of tacrolimus monotherapy in 11 patients. Actuarial 1- and 5-year graft and patient survival rates were 78.6% and 65.5%. The poor prognostic factors were macroscopic venous invasion and extrahepatic involvement with 1-year and 5-year survival rates of 33.0% and 0%. Pediatric patients without these factors showed an acceptable 5-year survival rate of 90.9%. LDLT provides a valuable alternative with excellent results in children with hepatoblastoma because it allows optimal timing of the liver transplantation, given the absence of delay between the completion of chemotherapy and planned liver transplantation.     

Strategy for the treatment of unresectable hepatoblastoma: neoadjuvant chemotherapy followed by delayed primary operation or liver transplantation

We present our experience in using neoadjuvant regional and systemic chemotherapy together with surgical resection as a strategy for the treatment of unresectable hepatoblastoma. Neoadjuvant chemotherapy was given prior to surgical treatment in six children with unresectable hepatoblastoma. Furthermore, the neoadjuvant chemotherapy was intensified according to response to the initial treatment. Surgical resection was performed when the tumor was judged to be resectable. The adjuvant chemotherapy was given after delayed primary operation. Five of six children receiving neoadjuvant chemotherapy responded to the treatment and subsequently received delayed primary operation or living donor liver transplantation. All five children who had successful surgery have completed treatment and show no evidence of disease to date (27-115 months after surgery). It is concluded that neoadjuvant chemotherapy given as a combination of regional and systemic chemotherapy was effective for tumor reduction in cases with early stage or stage III disease. Also, to increase the cure rate of children with localized disease that was still unresectable after chemotherapy, living donor liver transplantation, which offers some advantage in timing of transplant compared with cadaveric liver transplantation, seems to be a possible procedure.     

Liver transplantation in patients with hepatocellular carcinoma: one center's experience

Hepatocellular carcinoma (HCC), which worldwide is the fifth most common malignancy in men and the ninth most common malignancy in women, accounts for 6% of all malignant lesions. We evaluated our results of liver transplantation for patients with HCC. Between January 2004 and April 2007, 31 patients (5 females, 26 males; age range, 1.1-65 years) with preoperatively or incidentally diagnosed HCC underwent orthotopic liver transplantation (OLT) at our center. Eleven grafts were from deceased donors, and 20 from living-related donors. Inclusion criteria were no invasion of a major vascular structure and no evidence of extrahepatic disease. In 17 patients, tumors exceeded the Milan criteria. According to the tumor-node-metastasis staging system, 6 patients had stage 1, 8 had stage II, 2 had stage III, and 15 had stage 4A carcinoma. Three complications occurred in 31 patients: hepatic arterial thrombosis in 1 patient and biliary leakage in 2. At a mean follow-up of 24.3 +/- 12.5 months, 29 patients are well with excellent graft function. Two patients died at 23 and 17 months after OLT respectively. The longest graft survival is 43 months. There have been 4 tumor recurrences, namely, at 4, 26, 24, and 29 months after OLT, respectively. Patient and disease-free survival rates are 93.5% and 90%, respectively. In conclusion, OLT provided long-term disease-free survival for patients with HCC, even those with locally advanced tumors who had no effective alternative treatment than transplantation.     

Long-term outcome of liver resection and transplantation for Caroli disease and syndrome

OBJECTIVE: To assess the preoperative disease characteristics as well as the rate of postoperative complications, patient survival, and course of symptoms after liver resection or orthotopic liver transplantation (OLT) for Caroli disease (CD) or syndrome (CS). SUMMARY BACKGROUND DATA: The clinical course of monolobar or diffuse CD or CS is often characterized by multiple conservative treatment attempts and interventions with recurrent episodes of cholangitis and a serious reduction in quality of life. The role and effectiveness of surgical treatment is still not well defined. PATIENTS AND METHODS: Between June 1989 and December 2002, we treated 44 consecutive patients with CD or CS who had failure of conservative treatment before and were referred for surgical intervention. Demographic and clinical data, operative procedures and related morbidity, course of symptoms, and long-term follow-up were reviewed. Four patients with palliative resection for cholangiocarcinoma and incidental diagnosis of CD were excluded from the analysis. RESULTS: Twenty-two women and 18 men had a median period of 26.5 months from onset of symptoms to surgical therapy. Their median age at therapy was 49 years and 80% of the patients had monolobar disease with a left-right ratio of 2.6 to 1. Thirty-three (82.5%) patients underwent liver resection, while 4 (10%) patients received OLT for diffuse disease. Biliodigestive anastomosis alone was performed in 3 (7.5%) patients with contraindications to OLT. Patients (37.5%) had minor postoperative complications, which were treated conservatively, while 2 (5%) transplanted patients had a reoperation due to intraperitoneal bleeding. After a median follow-up of 86.5 months, we observed a favorable patient and graft survival. Three deaths during follow-up were not related to treatment or disease complications. Follow-up of disease-related symptoms, biliary complications, and antibiotic treatment revealed a significant improvement. CONCLUSION: Our data show that liver resection for monolobar CD or CS and OLT for diffuse manifestations can achieve excellent long-term patient survival with marked symptom relief. Because of life-threatening long-term complications such as biliary sepsis and development of cholangiocarcinoma, timely indication for surgical treatment is crucial.     

Long-term follow-up after recurrence of primary biliary cirrhosis after liver transplantation in 100 patients

Orthotopic liver transplantation (OLT) is the only effective curative therapy for end-stage primary biliary cirrhosis (PBC). Survival after OLT is excellent, although recent data have shown a recurrence rate of PBC of up to 32% after transplantation. The aim of this study is to investigate the course after disease recurrence, particularly with regard to liver function and survival in a long-term follow-up. Between April 1989 and April 2003, 1,553 liver transplantations were performed in 1,415 patients at the Charité, Virchow Clinic. Protocol liver biopsies were taken after one, three, five, seven, 10 and 13 yr. One hundred (7%) patients suffered from histologically proven PBC. Primary immunosuppression consisted of cyclosporine (n = 54) or tacrolimus (Tac) (n = 46). Immediately after OLT, all patients received ursodeoxycholic acid. Corticosteroids were withdrawn three to six months after OLT. The median age of the 85 women and 15 men was 55 yr (range 25-66 yr). The median follow-up after liver transplantation was 118 months (range 16-187 months) and after recurrence 30 months (range 4-79 months). Actuarial patient survival after five, 10 and 15 yr was 87, 84 and 82% respectively. Ten patients (10%) died after a median survival time of 32 months. Two of these patients developed organ dysfunction owing to recurrence of PBC. Histological recurrence was found in 14 patients (14%) after a median time of 61 months (range 36-122 months). Patients with Tac immunosuppression developed PBC recurrence more often (p < 0.05) and also earlier (p < 0.05). Fifty-seven patients developed an acute rejection and two patients a chronic rejection episode. Liver function did not alter within the first five yr after histologically proven PBC recurrence. Multivariate analysis of the investigated patients showed that the recipient's age and Tac immunosuppression were significant risk factors for PBC recurrence. Long-term follow-up of up to 15 yr after liver transplantation, owing to PBC, in addition to maintenance of liver function, shows excellent organ and patient survival rates. Although protocol liver biopsies revealed histological recurrence in 14 (14%) patients, only two patients developed graft dysfunction. Tac-treated patients showed more frequently and also earlier histologically proven PBC recurrence; however, in our population we could not observe an impact on graft dysfunction and patient's survival.