Fibrolamellar Hepatocellular Carcinomas Research Articles

Interventional Radiology Management of Pediatric Liver Tumors

AbstractPediatric liver tumors are not only rare, they are also different from the adult liver tumors. Hepatoblastomas and hepatocellular carcinomas (HCCs) are the most common primary malignant tumors seen in children. Fibrolamellar HCC, sarcomas, cholangiocarcinoma, germ cell tumor, and rhabdoid tumor and metastatic tumors comprise the remainder of liver malignancies. Hepatic infantile hemangiomas, mesenchymal hamartoma, regenerative nodules, adenomas, and focal nodular hyperplasia are the common benign liver tumors of childhood. The Pediatric Hepatic International Tumour Trial (PHITT) is an international trial with the goal of evaluating new and existing treatments for pediatric liver tumors. Chemotherapy, surgery, and liver transplantation are well-established in the management of pediatric liver tumors. In the background of increasing incidence of pediatric tumors, and availability of newer, less invasive modalities to treat tumors, it is vital to understand the role of interventional radiology in the management of pediatric liver tumors.

Morphomolecular Classification Update on Hepatocellular Adenoma, Hepatocellular Carcinoma, and Intrahepatic Cholangiocarcinoma

Hepatocellular adenomas (HCAs), hepatocellular carcinomas (HCCs), and intrahepatic cholangiocarcinomas (iCCAs) are a highly heterogeneous group of liver tumors with diverse pathomolecular features and prognoses. High-throughput gene sequencing techniques have allowed discovery of distinct genetic and molecular underpinnings of these tumors and identified distinct subtypes that demonstrate varied clinicobiologic behaviors, imaging findings, and complications. The combination of histopathologic findings and molecular profiling form the basis for the morphomolecular classification of liver tumors. Distinct HCA subtypes with characteristic imaging findings and complications include HNF1A-inactivated, inflammatory, β-catenin-activated, β-catenin-activated inflammatory, and sonic hedgehog HCAs. HCCs can be grouped into proliferative and nonproliferative subtypes. Proliferative HCCs include macrotrabecular-massive, TP53-mutated, scirrhous, clear cell, fibrolamellar, and sarcomatoid HCCs and combined HCC-cholangiocarcinoma. Steatohepatitic and β-catenin-mutated HCCs constitute the nonproliferative subtypes. iCCAs are classified as small-duct and large-duct types on the basis of the level of bile duct involvement, with significant differences in pathogenesis, molecular signatures, imaging findings, and biologic behaviors. Cross-sectional imaging modalities, including multiphase CT and multiparametric MRI, play an essential role in diagnosis, staging, treatment response assessment, and surveillance. Select imaging phenotypes can be correlated with genetic abnormalities, and identification of surrogate imaging markers may help avoid genetic testing. Improved understanding of morphomolecular features of liver tumors has opened new areas of research in the targeted therapeutics and management guidelines. The purpose of this article is to review imaging findings of select morphomolecular subtypes of HCAs, HCCs, and iCCAs and discuss therapeutic and prognostic implications. Online supplemental material is available for this article. ©RSNA, 2022.

Variant Hepatocellular Carcinoma Subtypes According to the 2019 WHO Classification: An Imaging-Focused Review.

The 2019 5th edition of the WHO classification of digestive system tumors estimates that up to 35% of hepatocellular carcinomas (HCCs) can be classified as one of eight subtypes defined by molecular characteristics: steatohepatitic, clear cell, macrotrabecular-massive, scirrhous, chromophobe, fibrolamellar, neutrophil-rich, and lymphocyte-rich HCCs. Due to their distinct cellular and architectural characteristics, these subtypes may not display arterial phase hyperenhancement and washout appearance, which are the classic MRI features of HCC, creating challenges in noninvasively diagnosing such lesions as HCC. Moreover, certain subtypes with atypical imaging features have a worse prognosis than other HCCs. A range of distinguishing imaging features may help raise suspicion that a liver lesion represents one of these HCC subtypes. In this review, we describe the MRI features that have been reported in association with various HCC subtypes according to the 2019 WHO classification, with attention given to the current understanding of these subtypes' pathologic and molecular bases and relevance to clinical practice. Imaging findings that differentiate the subtypes from benign liver lesions and non-HCC malignancies are highlighted. Familiarity with these sub-types and their imaging features may allow the radiologist to suggest their presence, though histologic analysis remains needed to establish the diagnosis.

Comprehensive genomic profiling (CGP) of fibrolamellar oncocytic hepatoma (FLO) and conventional hepatocellular carcinomas (HCC): An observational study.

474 Background: FLO is a rare variant of liver cancer that disproportionately affects young adults and is frequently progressive and fatal as it is often detected in a clinically advanced stage. It is seldom associated with cirrhosis of liver, viral hepatitis or other risk factors associated with conventional HCC. Treatment options are largely limited to surgical resection, and there is dearth of effective targeted therapies for FLO. Methods: Comprehensive genomic profiling (CGP) was performed using the Foundation Medicine Inc. (FMI) data base on 63 FLO and 1,793 HCC clinically advanced cases between 6/2013-12/2020 using a hybrid capture-based assay of up to 324 genes a to detect genomic alterations (GA), tumor mutational burden (TMB) and microsatellite instability (MSI). PD-L1 expression in tumor cells (Dako 22C3) was measured by IHC and scored using the tumor proportion score (TPS) method. Results: The FLO patients (pts) were significantly younger than HCC pts (median age 20 vs. 64, respectively) and the male preponderance was similar. The HCC group featured significantly more GA/tumor than FLO group (3.74 vs 1.31 p<.0001). In the currently untargetable GA group, CTNNB1, TERT and TP53 GA were significantly more frequent in HCC than FLO. GA in potentially targetable genes were extremely uncommon in both FLO and HCC with HCC featuring slightly more MTOR pathway targets ( PTEN, TSC2, NF1). GA in DNA damage and repair (DDR) pathway including BRCA2 were infrequent in both groups. GA in targetable kinases including EGFR, ERBB2, ALK, RET and PIK3CA were extremely uncommon in both groups. GA associated with intrahepatic cholangiocarcinoma (IDH1, FGFR2) were extremely uncommon in these tumors. Although the mean TMB was significantly higher in HCC than FLO, overall TMB was low with very few cases having TMB > 10 mutations/Mb. PD-L1 expression was relatively low in both groups. GA in genes associated with immune checkpoint inhibitors (ICPI) drug response like PBRM1, CD274, MDM2, STK11 were rarely identified in both groups. Additional details are illustrated in the table. Conclusions: Comparison of CGP of FLO with HCC illustrates the multifarious nature of these cancers. In HCC, there is a high prevalence of GA in TERT, CTNNB1 and TP53. CGP identified certain targetable GA in the MTOR and DDR pathways and TMB was higher in HCC. These findings warrant further evaluation of clinically advanced FLO and HCC pts by CGP to identify possible targetable genomic pathways. [Table: see text]

Mixed fibrolamellar hepatocellular carcinoma.

Pure and mixed fibrolamellar hepatocellular carcinomas display distinct clinical presentations and epigenetic backgrounds leading to different prognoses and as such may be regarded as separate clinical entities.

Imaging findings of fibrolamellar hepatocellular carcinomas on ultrasonography: A comparison with conventional hepatocellular carcinomas.

Fibrolamellar hepatocellular carcinoma (FLHCC) is an unusual variant of hepatocellular carcinoma (HCC). Revealing the imaging features is important to the diagnosis of FLHCC. The aim of this study was to investigate the imaging characteristics of FLHCCs. This retrospective study included 29 patients with histopathologically proved FLHCC and 96 patients proved HCC. All patients underwent an ultrasound examination pre-operation. The average maximum diameters of the FLHCC and HCC lesions were 7.4±4.1 cm and 4.1±3.0 cm, respectively. On the ultrasound, 79.3% of the FLHCCs and 12.3% of the HCCs showed the internal hyperechoic area; 48.3% of the FLHCCs and 3.3% of the HCCs displayed a strip-like attenuation. Calcification was noted in 20.7% of the FLHCCs, while none in HCCs. On the contrast-enhanced ultrasound (CEUS), all FLHCC lesions and 87.7% of the HCCs displayed hyperenhancement in the arterial phase. An internal, unenhanced central scar appeared in all FLHCCs, while none in HCCs. The ultrasonographic features of FLHCC lesions indicate that they are relatively large masses showing the internal hyperechoic area or strip-like attenuation or calcification on the US and hypervascularity with an unenhanced central scar on the CEUS as compared with conventional HCC lesions.

Neurotensin as a source of cyclic AMP and co-mitogen in fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinomas (FL-HCCs) possess a unique mutation that encodes a chimeric form of protein kinase A (DNAJ-PKAc), which includes a chaperonin binding domain. DNAJ-PKAc retains most of the biochemical properties of the native enzyme, however, and activity remains dependent on cAMP. We thus speculated that a persistent source of cAMP is necessary to promote FL-HCC carcinogenesis, and that neurotensin (NTS) may drive cAMP production in this setting, given that NS serum and tumor levels are elevated in many patients with FL-HCC.We examined expression of NTS pathway components in human FL-HCCs and paired normal livers, and determined the role of NTS in driving proliferation in tumor slice cultures. Cultured hepatocytes were used to determine interactions between NTS and other proliferative pathways, and to determine the effects of NTS on cAMP production and PKA activity.We found that the NTS pathway is up-regulated in human FL-HCCs, and that NTS activates cAMP and PKA in hepatocytes. NTS increases proliferation in the presence of epidermal growth factor (EGF), and NTS-induced proliferation is dependent on NTSR1 and the EGFR/MEK pathway.We conclude that NTS serves as a co-mitogen in FL-HCC, and provides a source of cAMP to facilitate ongoing activation of DNAJ-PKAc.

Fibrolamellar hepatocellular carcinoma: multiphasic CT features of the primary tumor on pre-therapy CT and pattern of distant metastases.

The aim of our study is to describe the multiphasic CT features of fibrolamellar hepatocellular carcinomas (FLHCCs) and pattern of distant metastases. 33 patients (mean age 28years: 17M/16F) with pathologically confirmed FLHCC and pre-treatment multiphasic CT were included in the study. Two abdominal radiologists evaluated the multiphasic CT imaging features of these 33 FLHCC patients in consensus. Solitary hepatic mass was seen in 67% (22/33). Mean tumor size was 11.3cm (range 4.6-22cm). Tumor was well-defined in 64% (21/33). In the pre-contrast CT, 91% (30/33) were hypoattenuating. Central stellate scar was present in 73% (24/33). In FLHCC having central stellate scar, calcification within the central scar was seen in 88% (21/24). In the hepatic arterial phase, 82% (27/33) were hyperattenuating relative to liver. In the portal venous phase, 36% (12/33) were hyperattenuating, 46% (15/33) were isoattenuating, and 18% (6/33) were hypoattenuating. In the delayed phase images, 24% (8/23) were hyperattenuating, 67% (22/33) were isoattenuating, and 9% (3/33) were hypoattenuating. Delayed enhancement of the central stellate scar was seen in 12% (4/33). Distant metastases were seen in 54% (18/33). The most common site of metastases was lungs and was seen in 89% (16/18) of the patients with metastatic disease. FLHCC typically manifests as a large, solitary mass demonstrating heterogeneous hypervascular enhancement in the arterial phase. Most tend to be isoattenuating in delayed phase. Central stellate scar with internal calcification is a useful imaging feature that can help in the diagnosis of FLHCC. Lungs are the most common site of distant metastases in FLHCC.

Patent highlights December 2016-January 2017.

Patent highlights December 2016-January 2017.

Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells

The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA) characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for cancer stem cells as indicated by limited dilution tumourigenicity assays, spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model, with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for expression of endodermal stem cell traits. Transcriptomic analyses of the tumour line and of multiple, normal hepatic lineage stages reveal a gene signature for hFL-HCCs closely resembling that of biliary tree stem cells—newly discovered precursors for liver and pancreas. This model offers unprecedented opportunities to investigate mechanisms underlying hFL-HCCs pathogenesis and potential therapies.

Quantification of glypican 3, β-catenin and claudin-1 protein expression in hepatoblastoma and paediatric hepatocellular carcinoma by colour deconvolution.

To identify an immunohistochemical panel for paediatric malignant epithelial liver tumours. Forty-five hepatoblastomas (HBs), 13 paediatric hepatocellular carcinomas (HCCs) and two hepatocellular malignant neoplasms not otherwise specified (NOS) were chosen for immunohistochemical staining of glypican 3 (GPC3), β-catenin, claudin-1, delta-like protein (DLK), and forkhead box protein G1 (FOXG1). Immunostaining was quantitatively analysed with NIH imagej software coupled with colour deconvolution. Different subtypes of HB and HCC showed distinct staining patterns ofGPC3, β-catenin, and claudin-1. Moreover, GPC3, β-catenin and claudin-1 all showed higher expression in classic HCC and embryonal HB than in fetal HB; GPC3 showed complete negativity in small-cell undifferentiated (SCU) HB and fibrolamellar HCC (FLC); β-catenin showed the strongest expression in SCU HB but the weakest expression in FLC. A panel of these three immunomarkers was useful for the diagnosis of hepatocellular malignant neoplasms NOS. The expression of DLK and FOXG1 was inconstant among fetal and embryonal HB and classic HCC. A panel of GPC3, β-catenin and claudin-1 is helpful for differentiating HB subtypes and distinguishing HB from HCC.

Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells

Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells

Sal-like protein 4 (SALL4), a stem cell biomarker in liver cancers

Liver cancers, including hepatocellular carcinomas (HCCs), cholangiocarcinomas (CCs), and fibrolamellar HCCs (FL-HCCs) are among the most common cancers worldwide and are associated with a poor prognosis. Investigations of genes important in liver cancers have focused on Sal-like protein 4 (SALL4), a member of a family of zinc finger transcription factors. It is a regulator of embryogenesis, organogenesis, pluripotency, can elicit reprogramming of somatic cells, and is a marker of stem cells. We found it expressed in normal murine hepatoblasts, normal human hepatic stem cells, hepatoblasts and biliary tree stem cells, but not in mature parenchymal cells of liver or biliary tree. It was strongly expressed in surgical specimens of human HCCs, CCs, a combined hepatocellular and cholangiocarcinoma, a FL-HCC, and in derivative, transplantable tumor lines in immune-compromised hosts. Bioinformatics analyses indicated that elevated expression of SALL4 in tumors is associated with poor survival of HCC patients. Experimental manipulation of SALL4's expression results in changes in proliferation versus differentiation in human HCC cell lines in vitro and in vivo in immune-compromised hosts. Virus-mediated gene transfer of SALL4 was used for gain- and loss-of-function analyses in the cell lines. Significant growth inhibition in vitro and in vivo, accompanied by an increase in differentiation occurred with down-regulation of SALL4. Overexpression of SALL4 resulted in increased cell proliferation in vitro, correlating with an increase in expression of cytokeratin19 (CK19), epithelial cell adhesion molecules (EpCAM), and adenosine triphosphate (ATP)-binding cassette-G2 (ABCG2). SALL4's expression is an indicator of stem cells, a prognostic marker in liver cancers, correlates with cell and tumor growth, with resistance to 5-FU, and its suppression results in differentiation and slowed tumor growth. SALL4 is a novel therapeutic target for liver cancers.

High mobility group AT-hook 2 is overexpressed in hepatoblastoma

Hepatoblastoma is the most frequent malignant hepatic tumor in children. Expression of high mobility group AT-hook 2, an architectural nuclear factor and marker for hepatic progenitor cells, has not been studied in detail in hepatocellular neoplasms. Immunohistochemical stains using antibodies against high mobility group AT-hook 2, β-catenin, glypican-3, p53, and Ki-67 were performed in 15 hepatoblastomas, 15 fibrolamellar hepatocellular carcinomas, 34 hepatocellular carcinomas (12, ≤30 years old; 22, >30 years old), and 22 hepatic adenomas. High mobility group AT-hook 2 was expressed in all 15 hepatoblastomas, including all fetal and embryonal components, significantly higher than in 41.7% (5/12) of hepatocellular carcinomas of 30 years or younger (P = .001) and in 9% (2/22) of hepatocellular carcinomas of older than 30 years (P < .001). Aberrant β-catenin expression was detected in 80% (12/15) of hepatoblastomas, 41.6% (5/12) of hepatocellular carcinomas of 30 years or younger, and 18.2% (4/22) of hepatocellular carcinomas of older than 30 years. All 15 fibrolamellar hepatocellular carcinomas and 22 hepatic adenomas were negative for high mobility group AT-hook 2 or β-catenin. High mobility group AT-hook 2 and β-catenin expression correlated positively (P = .017; τ = 0.522) in 34 hepatocellular carcinomas. β-Catenin and glypican-3 exhibited a distinct spatial distribution within hepatoblastomas; glypican-3 was more frequently expressed in fetal components (P = .007), whereas β-catenin tended to be more frequently expressed in embryonal components (P = .062). In conclusion, high mobility group AT-hook 2 is expressed in all hepatoblastomas and could be used as a sensitive marker in their diagnosis. High mobility group AT-hook 2 was also expressed in a subset of hepatocellular carcinomas in association with β-catenin expression; this might represent a subtype of hepatocellular carcinoma with hepatic progenitor cell differentiation.

Focal hepatic lesions in Gd-EOB-DTPA enhanced MRI: the atlas

ObjectiveThis article reviews the different technical aspects and pitfalls of gadolinium (Gd)-ethoxibenzyl (EOB)-diethylenetriamine pentaacetic acid (DTPA) and the advantages of the hepatocellular phase (HCP) and defines its specific imaging features of liver lesions.BackgroundGd-EOB-DTPA is a contrast agent with combined properties of a conventional non-specific extracellular and a hepatocyte-specific contrast agent. Benign cirrhosis-associated nodules are characterised by isointensity in dynamic imaging and the HCP. Hepatocellular carcinomas (HCCs) usually show hyperenhancement in the arterial phase, with washout in the portal vein pressure (PVP) and hypointensity in the HCP. Among other characteristic findings, we have the mosaic pattern, a capsule, the “nodule-in-nodule” appearance and the satellite nodules. The fibrolamellar HCC is a large enhancing heterogeneous lesion, on a non-cirrhotic liver, with a hypointense scar in every sequence. THIDs (transient hepatic intensity differences) are perfusional alterations, characterised by hyperintensity in the arterial phase, with no alterations in the rest of the sequences including the HCP. Adenoma and focal nodular hyperplasia (FNH) are lesions, occurring more frequently in young women, with brisk arterial enhancement, differentiated by the scar and the uptake of Gd-EOB-DTPA in the HCP. Focal eosinophilic infiltration is a difficult diagnosis, with characteristics such as a non-spherical shape and irregular borders suggesting it. Besides these lesions, in which Gd-EOB-DTPA has a clear advantage, there are a few where the specificities of this agent can be troublesome: haemangiomas, focal fat/sparing, foreign body reaction, cholangiocarcinoma and metastases.ConclusionGd-EOB-DTPA is comparable to extracellular agents, and uptake by functioning hepatocytes in the delayed phase provides additional information that further improves detection and characterisation of many hepatic lesions.Main Messages Gd-EOB-DTPA offers advantages for the imaging of many liver lesions including HCC, fibrolamellar HCC, FNH and adenoma. The properties of Gd-EOB-DTPA can pose problems when dealing with haemangiomas, cholangiocarcinoma and metastases among others. The uptake of Gd-EOB-DTPA by functioning hepatocytes in the delayed phase provides additional information that further improves detection and characterisation of many hepatic lesions.

Pure and mixed fibrolamellar hepatocellular carcinomas differ in natural history and prognosis after complete surgical resection

The purpose of the current study was to describe pure and mixed fibrolamellar hepatocellular carcinoma (FL-HCC). Consecutive patients with pure and mixed FL-HCC were identified from a central pathological review using Edmondson's criteria. Clinical, pathological, and epigenetic characteristics of patients who underwent curative surgery were evaluated. Overall and disease-free survival as well as patterns of disease recurrence were examined. Methylation levels of L1 retrotransposon (LINE-1) repetitive elements and Ras association domain family 1A gene (RASSF1) promoter were also assessed using pyrosequencing. Forty of 53 patients with a median age of 22 years (range, 9 years-;65 years) met the criteria for analysis. Central pathological review found that 30 patients (75%) had pure and 10 patients (25%) had mixed FL-HCC. Pure FL-HCC typically occurred in patients aged < 30 years. These patients often presented with lymph node metastasis at the time of diagnosis and frequently experienced extrahepatic recurrences (n = 16). Conversely, mixed FL-HCC appeared to resemble to classic HCC, occurring in patients aged > 40 years and frequently involving the liver as the primary site of disease recurrence. With a median follow-up of 7.8 years, the median overall survival from the time of diagnosis in all patients was 6.4 years (range, 3.2 years-12 years). Multivariate analysis found that the risk of death was increased in patients with higher American Joint Committee on Cancer disease stages (P = .003) and those with mixed FL-HCC (P = .03). Methylation analysis of LINE-1 repetitive elements and RASSF1 promoter revealed different methylation levels between pure and mixed FL-HCC, suggesting a different epigenetic background. Pure and mixed FL-HCC display distinct clinical presentations and epigenetic backgrounds leading to different prognoses and as such may be regarded as separate clinical entities.

Claudins and tricellulin in fibrolamellar hepatocellular carcinoma

Fibrolamellar hepatocellular carcinoma is a subtype of hepatocellular carcinoma occurring in non-cirrhotic liver at a younger age. The tumor expresses both hepatocellular and cholangiocellular markers. Previously, our group described overexpression of tight junction protein claudin 4 in cholangiocellular carcinoma in contrast to hepatocellular carcinoma. In the present study, tight junction protein expressions were studied to possibly clarify bipotential lineage of fibrolamellar hepatocellular carcinoma. Eleven fibrolamellar hepatocellular carcinomas were compared with seven "conventional" hepatocellular carcinomas, seven cholangiocellular carcinomas, and five normal liver samples. By immunohistochemistry, all fibrolamellar hepatocellular carcinomas were positive for HepPar1 and cytokeratins 7, 8, and 18, but negative for cytokeratin 19. Glypican-3 gave weak staining in two cases. Expression of claudin 1 was lower, while that of claudin 2 was higher in fibrolamellar hepatocellular carcinomas than in other tumors. Claudins 3, 4, and 7 were not detectable in fibrolamellar hepatocellular carcinomas as in the majority of "conventional" hepatocellular carcinomas, contrary to high expression observed in cholangiocellular carcinomas. Focal or diffuse claudin 5 expression was detected in nine of 11 fibrolamellar hepatocellular carcinomas contrary to other tumors. Tricellulin was significantly downregulated in all tumors compared with normal liver. Our findings showed claudins to exhibit specific expression patterns in fibrolamellar hepatocellular carcinomas not observed in other primary liver tumors, with unique claudin 5 expression and pattern features similar to common hepatocellular carcinoma, but different from cholangiocellular carcinoma. This is the first report describing the loss of tricellulin expression in human hepatic tumors.

Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation

Purpose Hepatectomy remains a complex operation even in experienced hands. The objective of the present study was to describe our experience in liver resections, in the light of liver transplantation, emphasizing the indications for surgery, surgical techniques, complications, and results. Methods The medical records of 53 children who underwent liver resection for primary or metastatic hepatic tumors were reviewed. Ultrasonography, computed tomographic (CT) scan, and needle biopsy were the initial methods used to diagnose malignant tumors. After neoadjuvant chemotherapy, tumor resectability was evaluated by another CT scan. Surgery was performed by surgeons competent in liver transplantation. As in liver living donor operation, vascular anomalies were investigated. The main arterial anomalies found were the right hepatic artery emerging from the superior mesenteric artery and left hepatic artery from left gastric artery. Hilar structures were dissected very close to liver parenchyma. The hepatic artery and portal vein were dissected and ligated near their entrance to the liver parenchyma to avoid damaging the hilar vessels of the other lobe. During dissection of the suprahepatic veins, the venous infusion was decreased to reduce central venous pressure and potential bleeding from hepatic veins and the vena cava. Results Fifty-three children with hepatic tumors underwent surgical treatment, 47 patients underwent liver resections, and in 6 cases, liver transplantation was performed because the tumor was considered unresectable. There were 31 cases of hepatoblastoma, with a 9.6% mortality rate. Ten children presented with other malignant tumors—3 undifferentiated sarcomas, 2 hepatocellular carcinomas, 2 fibrolamellar hepatocellular carcinomas, a rhabdomyosarcoma, an immature ovarian teratoma, and a single neuroblastoma. These cases had a 50% mortality rate. Six children had benign tumors—4 mesenchymal hamartoma, 1 focal nodular hyperplasia, and a mucinous cystadenoma. All of these children had a favorable outcome. Hepatic resections included 22 right lobectomies, 9 right trisegmentectomies, 8 left lobectomies, 5 left trisegmentectomies, 2 left segmentectomies, and 1 case of monosegment (segment IV) resection. The overall mortality rate was 14.9%, and all deaths were related to recurrence of malignant disease. The mortality rate of hepatoblastoma patients was less than other malignant tumors ( P = .04). Conclusion The resection of hepatic tumors in children requires expertise in pediatric surgical practice, and many lessons learned from liver transplantation can be applied to hepatectomies. The present series showed no mortality directly related to the surgery and a low complication rate.

Pre-operative diagnostic biopsy and surgery in paediatric liver tumours—the Amsterdam experience

Aim To report 24 years of pre-treatment biopsy and surgical experience in primary liver tumours in children. Methods Between 1979 and 2003, 53 children presented with a primary liver tumour of whom 48 who underwent surgical resection were evaluated (two died, two were unresectable, and one was transplanted). Biopsy data, per- and post-operative complications, mortality, and survival were retrospectively reviewed. Results Benign tumours were diagnosed in eight patients. Surgical resection for a malignant tumour was performed in 40 patients (26 hepatoblastomas (HB), eight hepatocellular carcinomas (HCC) (four had fibrolamellar HCC), three rhabdomyosarcomas (RMS), one neuroblastoma, one non-hodgkin lymphoma (NHL), and one teratoma). Primary resection was performed in one HB, and four HCCs. The cumulative survival without evidence of disease was 73% for HB (median 7 years) and 88% for HCC (median 3.5 years). Conclusion The treatment results are comparable with those of larger international series except for HCC. The existing diagnostic pitfalls in differentiating between the various liver malignancies justify the use of a diagnostic biopsy.

Living donor liver transplant for fibrolamellar hepatocellular carcinoma using a deceased donor graft to reconstruct inferior vena cava

Liver transplantation is now an acceptable treatment for small hepatocellular carcinomas in the setting of cirrhosis. Larger tumors in cirrhotic livers and unresectable tumors in noncirrhotic livers (including fibrolamellar hepatocellular carcinomas) may also be indications for transplantation. With the limited number of cadaver grafts available, living donor liver transplant is becoming an option for some of these patients. We describe a method of reconstruction of the recipient inferior vena cava with deceased donor graft in right lobe living donation for fibrolamellar hepatocellular carcinoma.