sábado, 29 de junio de 2019

Childhood Liver Cancer Treatment (PDQ®) 4/5 —Health Professional Version - National Cancer Institute

Childhood Liver Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

National Cancer Institute



Childhood Liver Cancer Treatment (PDQ®)–Health Professional Version



Hepatocellular Carcinoma

Incidence

The annual incidence of hepatocellular carcinoma in the United States is 0.8 cases per 1 million children between the ages of 0 and 14 years and 1.5 cases per 1 million adolescents aged 15 to 19 years.[1] Although the incidence of hepatocellular carcinoma in adults in the United States has steadily increased since the 1970s, possibly because of the increased frequency of chronic hepatitis C infection,[2] the incidence in children has not increased. In several Asian countries, the incidence of hepatocellular carcinoma in children is 10 times higher than the incidence in children in North America. The high incidence appears to be related to the incidence of perinatally acquired hepatitis B, which can be prevented in most cases by vaccination and administration of hepatitis B immune globulin to the newborn child.[3]
Fibrolamellar hepatocellular carcinoma, a subtype of hepatocellular carcinoma that is unrelated to cirrhosis, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection, generally occurs in adolescents and young adults, but has been reported in infants.[4]

Risk Factors

Conditions associated with hepatocellular carcinoma are described in Table 7.
Table 7. Conditions Associated With Hepatocellular Carcinoma
Associated DisorderClinical Findings
Alagille syndrome [5]Broad prominent forehead, deep set eyes, and small prominent chin. Abnormality of bile ducts leads to intrahepatic scarring.
Glycogen storage diseases I–IV [6]Symptoms vary by individual disorder.
Hepatitis B and C [7-9]Refer to the Hepatitis B and hepatitis C infection section of this summary for more information.
Progressive familial intrahepatic cholestasis [10,11]Symptoms of jaundice, pruritus, and failure to thrive begin in infancy and progress to portal hypertension and liver failure.
Tyrosinemia [12]First few months of life: failure to thrive, vomiting, jaundice.

Alagille syndrome

Alagille syndrome is an autosomal dominant genetic syndrome that is usually caused by a mutation in or deletion of the JAG1 gene. It involves the bile ducts of the liver, as well as the heart and blood vessels in the brain and kidney. Patients develop a characteristic facies.[5]

Hepatitis B and hepatitis C infection

In children, hepatocellular carcinoma is associated with perinatally acquired HBV, whereas in adults, it is associated with chronic HBV and HCV infection.[7-9] Widespread hepatitis B immunization has decreased the incidence of hepatocellular carcinoma in Asia.[3] Compared with adults, the incubation period from hepatitis virus infection to the genesis of hepatocellular carcinoma is extremely short in a small subset of children with perinatally acquired virus. Mutations in the met/hepatocyte growth factor receptor gene could be one mechanism that results in a shortened incubation period.[13]
Hepatitis C infection is associated with development of cirrhosis and hepatocellular carcinoma that takes decades to develop and is generally not seen in children.[9] Cirrhosis in children, compared with cirrhosis in adults, is much less commonly involved in the development of hepatocellular carcinoma, and is found in only 20% to 35% of children with hepatocellular carcinoma tumors.

Nonviral liver injury

Specific types of nonviral liver injury and cirrhosis that are associated with hepatocellular carcinoma in children include the following:
  • Tyrosinemia. Tyrosinemia patients are regularly screened for hepatocellular carcinoma, even if they are treated with nitisinone.[12] Nitisinone can prevent cirrhosis and decrease the incidence of hepatocellular carcinoma, especially when administered during infancy, after neonatal screening is used to diagnose tyrosinemia.[14] As of 2014, only a minority of state screening programs had adopted a highly recommended, new, more predictive newborn screen that is much more effective in newborn children aged 24 to 48 hours.[15]
    In an Iranian study, 36 children underwent liver transplant for tyrosinemia.[16] Twenty-two children had liver nodules greater than 10 cm, and in 20 children, the nodules were cirrhotic. Median age at transplant was 3.9 years. Five of 19 children older than 2 years had hepatocellular carcinoma, and no children younger than 2 years had hepatocellular carcinoma in the resected liver.
  • Aggressive familial intrahepatic cholestasis. Hepatocellular carcinoma may also arise in very young children with mutations in the bile salt export pump ABCB11, which causes progressive familial intrahepatic cholestasis.[10]

Genomics of Hepatocellular Carcinoma

Genomic abnormalities related to hepatocellular carcinoma include the following:
  • A first case of pediatric hepatocellular carcinoma was analyzed by whole-exome sequencing, which showed a higher mutation rate (53 variants) and the coexistence of CTNNB1 and NFE2L2 mutations.[17]
  • Fibrolamellar hepatocellular carcinoma is a rare subtype of hepatocellular carcinoma observed in older children. It is characterized by an approximately 400 kB deletion on chromosome 19 that results in production of a chimeric RNA coding for a protein containing the amino-terminal domain of DNAJB1, a homolog of the molecular chaperone DNAJ, fused in frame with PRKACA, the catalytic domain of protein kinase A.[18]
  • A rare, more aggressive subtype of childhood liver cancer (hepatocellular neoplasm, not otherwise specified, also termed transitional liver cell tumor) occurs in older children, and it has clinical and histopathological findings of both hepatoblastoma and hepatocellular carcinoma.
    TERT mutations were observed in two of four cases tested.[19] TERT mutations are also commonly observed in adults with hepatocellular carcinoma.[20]
To date, these genetic mutations have not been used to select therapeutic agents for investigation in clinical trials.

Diagnosis

Refer to the Diagnosis subsection in the Hepatoblastoma section of this summary for more information.

Prognosis and Prognostic Factors

The 5-year overall survival (OS) rate is 42% for children and adolescents with hepatocellular carcinoma.[1] The 5-year survival for hepatocellular carcinoma may be dependent on stage; in an intergroup chemotherapy study conducted in the 1990s, seven of eight stage I patients survived and less than 10% of stage III and IV patients survived.[1,21] An analysis of Surveillance, Epidemiology, and End Results (SEER) data found a 5-year OS rate of 24%, a 10-year rate of 23%, and a 20-year rate of 8% in patients aged 19 years and younger, suggesting improved outcome related to more recent treatment. In a multivariate analysis of the SEER data, surgical resection, localized tumor, and non-Hispanic ethnicity were all associated with improved outcome. Patients who had a complete surgical resection had an OS rate of 60%, compared with an OS rate of 0% for patients who had an incomplete resection.[22][Level of evidence: 3iiiA]
Factors affecting prognosis include the following:
  • Treatment-related factors:
    Cure of hepatocellular carcinoma requires gross tumor resection. However, hepatocellular carcinoma is often extensively invasive or multicentric, and less than 30% of tumors are resectable. Orthotopic liver transplant has been successful in selected children with hepatocellular carcinoma.[23,24]
  • PRE-Treatment EXTent of disease (PRETEXT) group (resectability) is also a prognostic factor (refer to the Risk Stratification section of this summary for more information).
  • Tumor histology:
    Refer to the Histology section of this summary for more information.

Histology

The cells of hepatocellular carcinoma are epithelial in appearance. Hepatocellular carcinoma commonly arises in the right lobe of the liver.

Fibrolamellar carcinoma

A distinctive histologic variant of hepatocellular carcinoma, termed fibrolamellar carcinoma, has been described in the livers of older children and young adults and, rarely, in infants.[4,25] This histology is characterized by a fusion transcript created by deletion of a 400 kb section of chromosome 19, which was found in 15 of 15 tumors that were tested.[18]
Fibrolamellar carcinoma is not associated with cirrhosis and was previously thought to be associated with an improved prognosis.[2,25,26] Unlike nonfibrolamellar hepatocellular carcinoma in adults, fibrolamellar hepatocellular carcinoma in older children and adults is not clearly increasing in incidence over time.[2,25] The improved outcomes of patients with fibrolamellar carcinoma in older studies may be related to a higher proportion of tumors being less invasive and more resectable in the absence of cirrhosis. However, the outcomes of patients with fibrolamellar carcinoma in recent prospective studies, when compared stage for stage and PRETEXT group to PRETEXT group, is not different from the outcomes of patients with conventional hepatocellular carcinomas.[27,28]; [29][Level of evidence: 3iiA]

Hepatocellular neoplasm, not otherwise specified (NOS)

Hepatocellular neoplasm, NOS is also known as transitional liver cell tumor. This tumor, with characteristics of both hepatoblastoma and hepatocellular carcinoma, is a rare neoplasm that is found in older children and adolescents, and has a putative intermediate position between hepatoblasts and more mature hepatocyte-like tumor cells. The tumor cells may vary in regions of the tumor between classical hepatoblastoma and obvious hepatocellular carcinoma. In the international consensus classification, these tumors are referred to as hepatocellular neoplasm, NOS.[30] The tumors are usually unifocal and may have central necrosis at presentation. Response to chemotherapy has not been rigorously studied but is felt to be much like that of hepatocellular carcinoma.[31]

Treatment of Hepatocellular Carcinoma

Treatment options for newly diagnosed hepatocellular carcinoma depend on the following:
  1. Whether the cancer is resectable at diagnosis.
  2. How the cancer responds to chemotherapy.
  3. Whether the cancer has metastasized.
  4. Whether the cancer is HBV related.

Treatment options for hepatocellular carcinoma that is resectable at diagnosis

Treatment options for hepatocellular carcinoma that is resectable at diagnosis include the following:
  1. Complete surgical resection of the primary tumor followed by chemotherapy.
  2. Chemotherapy followed by complete surgical resection of the primary tumor.[27]
  3. Complete surgical resection without chemotherapy.
Surgical resection and chemotherapy are the mainstays of treatment for resectable hepatocellular carcinoma.
Evidence (complete surgical resection followed by chemotherapy):
  1. Seven of eight patients with stage I hepatocellular carcinoma who were given adjuvant cisplatin-based chemotherapy survived disease free.[21]
  2. In a survey of childhood liver tumors treated before the consistent use of chemotherapy, only 12 of 33 patients with hepatocellular carcinoma who had complete excision of the tumor survived.[32] This suggests that treatment with adjuvant chemotherapy may benefit children with completely resected hepatocellular carcinoma.
  3. Cisplatin and doxorubicin may be administered as adjuvant therapy because these agents are active in the treatment of hepatocellular carcinoma.[27]
  4. In an analysis of SEER data for children and adolescents younger than 20 years diagnosed between 1976 and 2009, patients who underwent a complete resection had a 60% 5-year OS and those who did not have a complete resection had a 0% 5-year OS.[22][Level of evidence: 3iiiA]
Evidence (complete surgical resection without chemotherapy):
  1. In a single-institution retrospective report, 12 patients with stage I hepatocellular carcinoma were treated with surgery. Ten patients received no chemotherapy and two patients received a short course of chemotherapy based on oncologist preference.[33][Level of evidence: 3iiA]
    • All 12 patients are alive without evidence of disease at a median of 54 months.
Despite improvements in surgical techniques, chemotherapy delivery, and patient supportive care in the past 20 years, clinical trials of cancer chemotherapy have not shown improved survival rates for pediatric patients with hepatocellular carcinoma.[27] The International Childhood Liver Tumors Strategy Group (SIOPEL) studies in Europe have observed no improvement in 5-year OS since 1990. The only long-term survivors were patients whose tumors were resectable at diagnosis, which was less than 30% of children entered in the study.[34] However, some liver transplant studies (complete resection with transplant with or without neoadjuvant chemotherapy) have shown OS rates that are superior to the SIOPEL studies.[24,35-38]

Treatment options for nonmetastatic hepatocellular carcinoma that is not resectable at diagnosis

The use of neoadjuvant chemotherapy or transarterial chemoembolization (TACE) to enhance resectability or liver transplant, which may result in complete resection of tumor, is necessary for cure.
Treatment options for nonmetastatic hepatocellular carcinoma that is not resectable at diagnosis include the following:
  1. Chemotherapy followed by reassessment of surgical resectability. If the primary tumor is resectable, complete surgical resection.
  2. Chemotherapy followed by reassessment of surgical resectability. If the primary tumor remains unresectable:
    • Orthotopic liver transplant.
    • Temporizing TACE followed by complete resection or liver transplant.
    • TACE alone.
Evidence (chemotherapy followed by reassessment of surgical resectability and complete surgical resection of the primary tumor):
  1. In a prospective study of 41 patients who received preoperative cisplatin/doxorubicin chemotherapy, treatment resulted in some degree of decrease in tumor size, with a decrease in alpha-fetoprotein (AFP) levels in about 50% of patients. The responders had a superior tumor resectability and survival, although the OS was 28% and only those undergoing complete resection survived.[27]
Evidence (chemotherapy or TACE followed by reassessment of surgical resectability; treatment options for unresectable primary tumor after chemotherapy or TACE):
  1. Patients whose primary tumor remains unresectable after chemotherapy should be considered for orthotopic liver transplant. Liver transplant has been a successful therapy for children with unresectable hepatocellular carcinoma; survival is about 60%, with most deaths resulting from tumor recurrence.[23,38-41]
  2. A review of treatment for hepatocellular carcinoma in patients younger than 20 years reported to SEER revealed that 75% of patients underwent resection and 25% underwent liver transplant. The 5-year OS was 53.4% with resection and 85.3% with transplant, suggesting that the criteria for transplantation in hepatocellular carcinoma might be liberalized for overall patient benefit. This approach would benefit from prospective testing.[42]
  3. TACE followed by complete surgical resection of primary tumor may be an alternative to the use of chemotherapy followed by surgical resection.
    • Studies in adults in China suggest that repeated hepatic TACE before surgery may improve the outcome of subsequent hepatectomy.[43]
    • A meta-analysis found seven randomized trials that compared resection alone versus TACE followed by resection. There was no difference in 3-year event-free survival (EFS) and OS between the two groups, but the 5-year EFS and OS favored TACE followed by resection.[44]
If the primary tumor is not resectable after chemotherapy and the patient is not a transplant candidate, alternative treatment approaches used in adults include the following:
  • Sorafenib.
  • TACE.
  • Cryosurgery.
  • Intratumoral injection of alcohol.
  • Radiation therapy.
There are limited data on the use of these alternative treatment approaches in children.
Limited data from a European pilot study suggest that sorafenib was well tolerated in 12 newly diagnosed children and adolescents with advanced hepatocellular carcinoma when given in combination with standard chemotherapy of cisplatin and doxorubicin.[45] Additional study is needed to define its role in the treatment of children with hepatocellular carcinoma.
Cryosurgery, intratumoral injection of alcohol, and radiofrequency ablation can successfully treat small (<5 cm) tumors in adults with cirrhotic livers.[43,46,47] Some local approaches such as cryosurgery, radiofrequency ablation, and TACE that suppress hepatocellular carcinoma tumor progression are used as bridging therapy in adults to delay tumor growth while on a waiting list for cadaveric liver transplant.[48] In a pediatric study of eight patients with hepatocellular carcinoma, two patients died of progressive disease without transplant. Treatment with TACE stabilized disease in six patients, for a mean of 141 days to reach transplant.[49][Level of evidence: 3iiA] Five patients were alive at the end of the observation period, and one patient died of disease.(Refer to the PDQ summary on Adult Primary Liver Cancer Treatment for more information.)

Treatment options for hepatocellular carcinoma with metastases at diagnosis

No specific treatment has proven effective for metastatic hepatocellular carcinoma in the pediatric age group.
In two prospective trials, cisplatin plus either vincristine/fluorouracil or continuous-infusion doxorubicin was ineffective in adequately treating 25 patients with metastatic hepatocellular carcinoma.[21,27] Occasional patients may transiently benefit from treatment with cisplatin/doxorubicin therapy, especially if the localized hepatic tumor shrinks adequately enough to allow resection of disease and the metastatic disease disappears or becomes resectable.

Treatment options for hepatitis B virus (HBV)–related hepatocellular carcinoma

Although HBV-related hepatocellular carcinoma is not common in children in the United States, nucleotide/nucleoside analog HBV inhibitor treatment improves postoperative prognosis in children and adults treated in China.[50]
Treatment options for HBV-related hepatocellular carcinoma include the following:
  1. Antiviral therapy.
Evidence (antiviral therapy):
  1. In a randomized controlled trial, 163 patients post–radical hepatectomy were evaluated for response to one of three antiviral treatments.[50]
    • Antiviral treatment significantly decreased hepatocellular carcinoma recurrence, with a hazard ratio (HR) of 0.48 (95% confidence interval [CI], 0.32–0.70), and hepatocellular carcinoma–related death, with an HR of 0.26 (95% CI, 0.14–0.50), in multivariate Cox analyses.
    • Patients who received antiviral treatment had significantly decreased early recurrence (HR, 0.41; 95% CI, 0.27–0.62) and improved liver function 6 months after surgery than did the control patients (P < .001).

Treatment options for progressive or recurrent hepatocellular carcinoma

The prognosis for a patient with recurrent or progressive hepatocellular carcinoma is extremely poor.[51]
Treatment options for progressive or recurrent hepatocellular carcinoma include the following:
  1. Chemoembolization temporization before transplant or immediate liver transplant, for those with isolated recurrence in the liver.[23,38,39,52]
  2. Phase I and phase II clinical trials may be appropriate and should be considered.
    • Treatment with sorafenib has resulted in improved progression-free survival in adults with advanced hepatocellular carcinoma. For adult patients who received sorafenib, the median survival and time to radiologic progression were about 3 months longer than for patients who received a placebo.[53] A phase II COG trial of single-agent sorafenib has been completed in children and the study results are pending.

Treatment options under clinical evaluation for hepatocellular carcinoma

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
  • AHEP1531 (NCT03533582) (Cisplatin and Combination Chemotherapy in Treating Children and Young Adults with Hepatoblastoma or Liver Cancer After Surgery):
    This is the COG's participation in a large international trial (Pediatric Hepatic Malignancy International Therapeutic Trial [PHITT]) of treatment of all stages of hepatoblastoma and hepatocellular carcinoma in children.
    • Very low-risk hepatoblastoma is defined as either: 1) a well differentiated fetal mass completely resected at diagnosis, and these patients are treated with no chemotherapy; or 2) a non–well differentiated fetal mass or incompletely resected well differentiated fetal mass, and these patients are treated with two cycles of cisplatin chemotherapy.
    • Low-risk hepatoblastoma is defined as a PRETEXT I to III tumor without any positive VPEFR annotation factors (venous involvement, portal involvement, extrahepatic spread, multifocality, and tumor rupture). These patients are treated with two cycles of cisplatin chemotherapy and then undergo resection (if possible) followed by randomization between two and four more cycles of cisplatin. If the tumor is unresectable, the patient receives two more cycles of cisplatin chemotherapy, and the tumor's resectability is reassessed. If it is still unresectable, patients undergo liver transplant.
    • Intermediate-risk hepatoblastoma is defined as a PRETEXT I to III primary tumor with a positive VPEFR annotation factor but without metastasis. Patients are randomly assigned to either four 14-day cycles of cisplatin or four 21-day cycles of C5VD (cisplatin, fluorouracil, vincristine, and doxorubicin). Transplant teams are consulted early as needed. Patients in both arms then undergo resection and receive two more cycles of their assigned chemotherapy.
    • High-risk hepatoblastoma is defined as presence of distant metastasis or AFP less than 100 or age 8 years and older. All patients are treated with three cycles of induction chemotherapy per the SIOPEL-4 trial (dose-intensive cisplatin, doxorubicin, and carboplatin). The patients aged 8 years and older or with AFP less than 100 and those whose metastases have cleared receive three cycles of carboplatin and doxorubicin. Patients with metastases that have not cleared by end of induction are randomly assigned to receive either carboplatin/doxorubicin cycles alternating with carboplatin/etoposide for six cycles or carboplatin/doxorubicin alternating with vincristine/irinotecan for six cycles.
    • Hepatocellular carcinoma that is potentially resectable is treated with complete resection without any chemotherapy if the mass appears to derive from underlying liver disease. If the hepatocellular carcinoma appears to be de novo without underlying disease, it is treated with resection followed by four cycles of cisplatin/doxorubicin.
    • Patients with hepatocellular carcinoma that is metastatic or appears unresectable at diagnosis undergo consultation with interventional radiology and liver transplant services. Patients are then randomly assigned to receive either cisplatin/doxorubicin/sorafenib for three 21-day cycles or cisplatin/doxorubicin/sorafenib alternating with gemcitabine/oxaliplatin/sorafenib for four 14-day cycles. Responding patients continue chemotherapy for the same number of cycles (3 or 4); they receive the same chemotherapy regimen to which they were originally assigned.
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 4,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
References
  1. Childhood cancer by the ICCC. In: Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). Bethesda, Md: National Cancer Institute, 2012, Section 29. Also available online. Last accessed April 11, 2019.
  2. El-Serag HB, Davila JA, Petersen NJ, et al.: The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 139 (10): 817-23, 2003. [PUBMED Abstract]
  3. Chang MH, Chen TH, Hsu HM, et al.: Prevention of hepatocellular carcinoma by universal vaccination against hepatitis B virus: the effect and problems. Clin Cancer Res 11 (21): 7953-7, 2005. [PUBMED Abstract]
  4. Cruz O, Laguna A, Vancells M, et al.: Fibrolamellar hepatocellular carcinoma in an infant and literature review. J Pediatr Hematol Oncol 30 (12): 968-71, 2008. [PUBMED Abstract]
  5. Keeffe EB, Pinson CW, Ragsdale J, et al.: Hepatocellular carcinoma in arteriohepatic dysplasia. Am J Gastroenterol 88 (9): 1446-9, 1993. [PUBMED Abstract]
  6. Siciliano M, De Candia E, Ballarin S, et al.: Hepatocellular carcinoma complicating liver cirrhosis in type IIIa glycogen storage disease. J Clin Gastroenterol 31 (1): 80-2, 2000. [PUBMED Abstract]
  7. Ni YH, Chang MH, Hsu HY, et al.: Hepatocellular carcinoma in childhood. Clinical manifestations and prognosis. Cancer 68 (8): 1737-41, 1991. [PUBMED Abstract]
  8. Tsukuma H, Hiyama T, Tanaka S, et al.: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328 (25): 1797-801, 1993. [PUBMED Abstract]
  9. González-Peralta RP, Langham MR Jr, Andres JM, et al.: Hepatocellular carcinoma in 2 young adolescents with chronic hepatitis C. J Pediatr Gastroenterol Nutr 48 (5): 630-5, 2009. [PUBMED Abstract]
  10. Knisely AS, Strautnieks SS, Meier Y, et al.: Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency. Hepatology 44 (2): 478-86, 2006. [PUBMED Abstract]
  11. Alonso EM, Snover DC, Montag A, et al.: Histologic pathology of the liver in progressive familial intrahepatic cholestasis. J Pediatr Gastroenterol Nutr 18 (2): 128-33, 1994. [PUBMED Abstract]
  12. van Spronsen FJ, Bijleveld CM, van Maldegem BT, et al.: Hepatocellular carcinoma in hereditary tyrosinemia type I despite 2-(2 nitro-4-3 trifluoro- methylbenzoyl)-1, 3-cyclohexanedione treatment. J Pediatr Gastroenterol Nutr 40 (1): 90-3, 2005. [PUBMED Abstract]
  13. Park WS, Dong SM, Kim SY, et al.: Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res 59 (2): 307-10, 1999. [PUBMED Abstract]
  14. de Laet C, Dionisi-Vici C, Leonard JV, et al.: Recommendations for the management of tyrosinaemia type 1. Orphanet J Rare Dis 8: 8, 2013. [PUBMED Abstract]
  15. De Jesús VR, Adam BW, Mandel D, et al.: Succinylacetone as primary marker to detect tyrosinemia type I in newborns and its measurement by newborn screening programs. Mol Genet Metab 113 (1-2): 67-75, 2014 Sep-Oct. [PUBMED Abstract]
  16. Bahador A, Dehghani SM, Geramizadeh B, et al.: Liver Transplant for Children With Hepatocellular Carcinoma and Hereditary Tyrosinemia Type 1. Exp Clin Transplant 13 (4): 329-32, 2015. [PUBMED Abstract]
  17. Vilarinho S, Erson-Omay EZ, Harmanci AS, et al.: Paediatric hepatocellular carcinoma due to somatic CTNNB1 and NFE2L2 mutations in the setting of inherited bi-allelic ABCB11 mutations. J Hepatol 61 (5): 1178-83, 2014. [PUBMED Abstract]
  18. Honeyman JN, Simon EP, Robine N, et al.: Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma. Science 343 (6174): 1010-4, 2014. [PUBMED Abstract]
  19. Eichenmüller M, Trippel F, Kreuder M, et al.: The genomic landscape of hepatoblastoma and their progenies with HCC-like features. J Hepatol 61 (6): 1312-20, 2014. [PUBMED Abstract]
  20. Nault JC, Mallet M, Pilati C, et al.: High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions. Nat Commun 4: 2218, 2013. [PUBMED Abstract]
  21. Katzenstein HM, Krailo MD, Malogolowkin MH, et al.: Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study. J Clin Oncol 20 (12): 2789-97, 2002. [PUBMED Abstract]
  22. Allan BJ, Wang B, Davis JS, et al.: A review of 218 pediatric cases of hepatocellular carcinoma. J Pediatr Surg 49 (1): 166-71; discussion 171, 2014. [PUBMED Abstract]
  23. Austin MT, Leys CM, Feurer ID, et al.: Liver transplantation for childhood hepatic malignancy: a review of the United Network for Organ Sharing (UNOS) database. J Pediatr Surg 41 (1): 182-6, 2006. [PUBMED Abstract]
  24. Vinayak R, Cruz RJ Jr, Ranganathan S, et al.: Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multicenter and single-center experience (1981-2015). Liver Transpl 23 (12): 1577-1588, 2017. [PUBMED Abstract]
  25. Eggert T, McGlynn KA, Duffy A, et al.: Fibrolamellar hepatocellular carcinoma in the USA, 2000-2010: A detailed report on frequency, treatment and outcome based on the Surveillance, Epidemiology, and End Results database. United European Gastroenterol J 1 (5): 351-7, 2013. [PUBMED Abstract]
  26. Mayo SC, Mavros MN, Nathan H, et al.: Treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma: a national perspective. J Am Coll Surg 218 (2): 196-205, 2014. [PUBMED Abstract]
  27. Czauderna P, Mackinlay G, Perilongo G, et al.: Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group. J Clin Oncol 20 (12): 2798-804, 2002. [PUBMED Abstract]
  28. Katzenstein HM, Krailo MD, Malogolowkin MH, et al.: Fibrolamellar hepatocellular carcinoma in children and adolescents. Cancer 97 (8): 2006-12, 2003. [PUBMED Abstract]
  29. Weeda VB, Murawski M, McCabe AJ, et al.: Fibrolamellar variant of hepatocellular carcinoma does not have a better survival than conventional hepatocellular carcinoma--results and treatment recommendations from the Childhood Liver Tumour Strategy Group (SIOPEL) experience. Eur J Cancer 49 (12): 2698-704, 2013. [PUBMED Abstract]
  30. López-Terrada D, Alaggio R, de Dávila MT, et al.: Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium. Mod Pathol 27 (3): 472-91, 2014. [PUBMED Abstract]
  31. Prokurat A, Kluge P, Kościesza A, et al.: Transitional liver cell tumors (TLCT) in older children and adolescents: a novel group of aggressive hepatic tumors expressing beta-catenin. Med Pediatr Oncol 39 (5): 510-8, 2002. [PUBMED Abstract]
  32. Exelby PR, Filler RM, Grosfeld JL: Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey--1974. J Pediatr Surg 10 (3): 329-37, 1975. [PUBMED Abstract]
  33. D'Souza AM, Shah R, Gupta A, et al.: Surgical management of children and adolescents with upfront completely resected hepatocellular carcinoma. Pediatr Blood Cancer : e27293, 2018. [PUBMED Abstract]
  34. Murawski M, Weeda VB, Maibach R, et al.: Hepatocellular Carcinoma in Children: Does Modified Platinum- and Doxorubicin-Based Chemotherapy Increase Tumor Resectability and Change Outcome? Lessons Learned From the SIOPEL 2 and 3 Studies. J Clin Oncol 34 (10): 1050-6, 2016. [PUBMED Abstract]
  35. Kelly D, Sharif K, Brown RM, et al.: Hepatocellular carcinoma in children. Clin Liver Dis 19 (2): 433-47, 2015. [PUBMED Abstract]
  36. Malek MM, Shah SR, Atri P, et al.: Review of outcomes of primary liver cancers in children: our institutional experience with resection and transplantation. Surgery 148 (4): 778-82; discussion 782-4, 2010. [PUBMED Abstract]
  37. Ismail H, Broniszczak D, Kaliciński P, et al.: Liver transplantation in children with hepatocellular carcinoma. Do Milan criteria apply to pediatric patients? Pediatr Transplant 13 (6): 682-92, 2009. [PUBMED Abstract]
  38. Pham TA, Gallo AM, Concepcion W, et al.: Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer. JAMA Surg 150 (12): 1150-8, 2015. [PUBMED Abstract]
  39. Reyes JD, Carr B, Dvorchik I, et al.: Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence. J Pediatr 136 (6): 795-804, 2000. [PUBMED Abstract]
  40. Bilik R, Superina R: Transplantation for unresectable liver tumors in children. Transplant Proc 29 (7): 2834-5, 1997. [PUBMED Abstract]
  41. Romano F, Stroppa P, Bravi M, et al.: Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma. Pediatr Transplant 15 (6): 573-9, 2011. [PUBMED Abstract]
  42. McAteer JP, Goldin AB, Healey PJ, et al.: Surgical treatment of primary liver tumors in children: outcomes analysis of resection and transplantation in the SEER database. Pediatr Transplant 17 (8): 744-50, 2013. [PUBMED Abstract]
  43. Zhang Z, Liu Q, He J, et al.: The effect of preoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for hepatocellular carcinoma. Cancer 89 (12): 2606-12, 2000. [PUBMED Abstract]
  44. Yu T, Xu X, Chen B: TACE combined with liver resection versus liver resection alone in the treatment of resectable HCC: a meta-analysis. Chinese-German J Clin Oncol 12 (11): 532-6, 2013.
  45. Schmid I, Häberle B, Albert MH, et al.: Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma. Pediatr Blood Cancer 58 (4): 539-44, 2012. [PUBMED Abstract]
  46. Zhou XD, Tang ZY: Cryotherapy for primary liver cancer. Semin Surg Oncol 14 (2): 171-4, 1998. [PUBMED Abstract]
  47. Lencioni RA, Allgaier HP, Cioni D, et al.: Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228 (1): 235-40, 2003. [PUBMED Abstract]
  48. Lubienski A: Hepatocellular carcinoma: interventional bridging to liver transplantation. Transplantation 80 (1 Suppl): S113-9, 2005. [PUBMED Abstract]
  49. Weiss KE, Sze DY, Rangaswami AA, et al.: Transarterial chemoembolization in children to treat unresectable hepatocellular carcinoma. Pediatr Transplant 22 (4): e13187, 2018. [PUBMED Abstract]
  50. Yin J, Li N, Han Y, et al.: Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study. J Clin Oncol 31 (29): 3647-55, 2013. [PUBMED Abstract]
  51. Malogolowkin MH, Stanley P, Steele DA, et al.: Feasibility and toxicity of chemoembolization for children with liver tumors. J Clin Oncol 18 (6): 1279-84, 2000. [PUBMED Abstract]
  52. Otte JB, Pritchard J, Aronson DC, et al.: Liver transplantation for hepatoblastoma: results from the International Society of Pediatric Oncology (SIOP) study SIOPEL-1 and review of the world experience. Pediatr Blood Cancer 42 (1): 74-83, 2004. [PUBMED Abstract]
  53. Llovet JM, Ricci S, Mazzaferro V, et al.: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359 (4): 378-90, 2008. [PUBMED Abstract]
Publicado por en

No hay comentarios:

Publicar un comentario

Suscribirse a: Enviar comentarios (Atom)