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Hepatocellular Carcinoma

This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Fibrolamellar hepatocarcinoma is an infrequent liver tumor, currently considered to be a variant different from hepatocarcinoma. The differences lie in genomic alterations, a greater prevalence of fibrolamellar hepatocarcinoma in young patients, and its lack of association with underlying liver disease.

The clinical presentation is unspecific, with symptoms ranging from abdominal pain, malaise, and weight loss to atypical manifestation which include hyperammonemic encephalopathy. We present the case of a year-old woman with no prior medical history who presented with a coma and a diagnosis of inoperable fibrolamellar hepatocarcinoma requiring a cadaver donor transplant. While she was on the waiting list, she received hemofiltration and ammonium benzoate treatment, with progressive improvement in her state of consciousness.

Fibrolamellar hepatocellular carcinoma FHCC is a rare primary liver tumor which was described by Edmondson in [ 1 ].

Multidisciplinary management of hepatocellular carcinoma — MD Anderson Cancer Center

It was initially thought to be a variant of hepatocellular carcinoma HCC , but today it is considered to be a completely different entity. It is associated with few chromosomal changes and genomic heterogeneity, compared with HCC [ 2 ]. It occurs in the absence of cirrhosis or viral hepatitis [ 3 ]. Fibrolamellar hepatocellular carcinoma is a rare disease which infrequently requires transplantation [ 4 ].

However, some studies have found two incidence peaks at 10 to 30 years and 70 to 79 years of age [ 8 ]. Neuroendocrine-regulating genes are found in all three types of tumors [ 9 ]; this genomic print suggests that these tumors may have a different origin than that of hepatocarcinomas, which could produce directed treatments in the future [ 10 ]. A year-old female patient consulted due to a two-week history of disorientation and somnolence which progressed to stupor, requiring invasive mechanical ventilation.

The patient had a history of a Cesarean section four months prior to her admission to the emergency room, without complications during pregnancy or delivery, and no known medical, pharmacological, allergic, or family history. The physical exam was remarkable for the presence of jaundice and hepatomegaly, without clinical signs suggesting cirrhosis. The admission laboratory tests registered an altered liver profile Table 1 with elevated ammonia Therefore, an abdominal tomography was performed, reporting a focal liver lesion which was interpreted to be a hepatic adenoma.

Abdominal magnetic resonance imaging was then carried out Figure 1 which showed results compatible with fibrolamellar hepatocarcinoma, with no signs of cirrhosis or portal hypertension. In light of her neurological deterioration, a simple head tomography was performed which showed unspecific periventricular lesions. A lumbar puncture ruled out infectious involvement, and telemetry reported moderate encephalopathy without seizure activity. Operating under the diagnostic impression of hyperammonemic encephalopathy, urea metabolism disorders were studied, including urinary orotic acid levels, serum amino acids, and serum citrulline levels, all of which were normal Table 2.

Given the lack of an etiology of the hyperammonemic encephalopathy and findings suggestive of fibrolamellar hepatocellular carcinoma, a liver biopsy was performed which confirmed the diagnosis through immunohistochemistry Figure 2 which reports diffuse and intense expression for cytokeratin 7Y CD68, with marked sinusoidal capillarization with CD34 and expression for CD68 there is weak but diffuse expression for glutamine synthetase, and glypican 3 and amyloid A are negative. The expression for B-catenin is membrane, without aberrant expression. This morphological and phenotypic pattern favors a fibrolamellar variant hepatocellular carcinoma.

Extension studies ruled out metastatic bone or chest involvement, and neoplastic lesions elsewhere. The hyperammonemic encephalopathy was associated with intrahepatic shunts secondary to the tumor. Management was begun with continuous veno-venous hemofiltration and ammonium benzoate treatment, which led to a progressive improvement in her state of consciousness. On surgical evaluation, resection of the lesion was contraindicated due to extrinsic vascular and bile duct compression. Therefore, cadaveric donor liver transplantation was performed, with no postoperative complications.

The explant study evidences the presence of a single lesion confined to the liver corresponding to the FHCC, with borders of hepatic hilum and suprahepatic section free of tumor, not identifying vascular invasion, perineural, lymphatic, nor lymph node, so resection of regional lymph nodes was not necessary. The patient is currently being followed by the hepatology department, with no signs of neurological alterations or tumor relapse, and a normalized liver profile Figure 1.

The presenting symptoms include abdominal pain, weight loss, and malaise, and hepatomegaly may be found on physical exam [ 3 , 11 ]. The following have been described as atypical manifestations: vascular abnormalities such as compression of the vena cava [ 12 ] or Budd—Chiari syndrome [ 13 ]; amyloid deposition [ 14 ]; biliary obstruction due to bile duct invasion [ 15 ]; and presentations such as bone [ 16 ], pancreas [ 17 ], and ovarian [ 18 ] metastases.

Transaminases and alkaline phosphatase are normal or slightly elevated. If the patient should present with markedly elevated alkaline phosphatase, bile duct growth or obstruction should be suspected [ 11 ]. Other markers such as vitamin Bbinding protein, or haptocorrin, and neurotensin may be elevated [ 19 , 20 ]. It has been suggested that haptocorrin levels are associated with disease progression [ 20 ]. On ultrasound, it is characterized by being a well-defined mass with heterogeneous echogenicity [ 11 ].

Necrosis without intratumor hemorrhaging may also be found. In the arterial phase, it is hyperattenuating due to hypervascular tumor cells with hypovascular bands around them. On magnetic resonance, they are seen as hypointense tumors in T1W and hyperintense tumors in T2W, also with a central scar which is hypointense in both images. In the arterial phase with gadolinium, there is heterogeneous capture which washes out, showing a hypointense lesion in the portal venous phase [ 7 , 23 ].

Noncirrhotic hyperammonemic encephalopathy is a potentially lethal complication in patients with rapid growth liver tumors. There have been reported cases of hyperammonemia related to fibrolamellar carcinoma associated with intrahepatic shunts of nitrogenated compounds, due to the fact that the necrotic and neoplastic cells are unable to filter out this type of compounds [ 24 , 25 ].

It has also been proposed that FHCC may cause the release of an OCT ornithine transcarbamylase enzyme inhibitor or that there may be increased ornithine decarboxylase activity [ 26 , 27 ]. This type of encephalopathy may also be triggered in patients with fibrolamellar carcinoma who are receiving chemotherapy, which causes increased tumor lysis [ 27 ].

There is no protocol for the management of hyperammonemic encephalopathy. Chapuy et al. If the levels are elevated, the next step is to evaluate urea cycle dysfunction by measuring urinary and serum amino acids and urinary organic acids and analyzing orotic acid. Treatment is based on decreasing the nitrogen load, removing excess ammonia, and correcting the precipitating causes. Fluids with dextrose should be started to control dehydration and catabolism.

An increase of 1. Treatment with sodium benzoate and sodium phenylacetate, used in urea cycle disorders, is recommended if the ammonium levels are greater than uM [ 27 ]. If this treatment fails, or if the levels are over uM, hemodialysis should be started. Surgical resection is the mainstay of treatment, since it represents a curative option. Complete resection with negative margins and node dissection is the goal of this treatment. In the systematic review carried out by Mavros et al.

Fibrolamellar Hepatocellular Carcinoma and Noncirrhotic Hyperammonemic Encephalopathy

At six months, acute rejection was reported in 4. The factors associated with graft loss included bile duct complications, infection, and disease recurrence [ 31 ]. The factors associated with recurrence following liver transplantation include regional node involvement, metastasis, and stage IVB [ 30 ]. The role of adjuvant and neoadjuvant chemotherapy is still unclear, as there are no prospective studies to evaluate the different chemotherapeutic lines in FHCC. In some reports, it has been associated with a greater survival [ 32 ].

A comparison of the prognosis of patients with fibrolamellar carcinoma to that of patients with hepatocarcinoma shows improved survival RR 2. Cirrhosis is a poor prognostic factor in hepatocarcinoma; a subgroup analysis limited to patients without cirrhosis found no significant difference in five-year survival RR 1. Our patient had FHCC with noncirrhotic hyperammonemic encephalopathy secondary to intralesional shunts, which required ongoing hemodialysis to control the encephalopathy.

She had a large, inoperable lesion with no evidence of secondary extrahepatic involvement. A case was found in the literature of a year-old patient with coma secondary to hyperammonemia, who was also diagnosed with FHCC with no evidence of metastatic lesions, underwent transplantation with postoperative initiation of sorafenib, and was reported as disease-free after one year of follow-up [ 34 ]. Fibrolamellar hepatocellular carcinoma may produce noncirrhotic hyperammonemic encephalopathy due to enzyme deficits or secondary to portosystemic shunts. The treatment of choice is surgical resection, when possible; and, in selected patients, liver transplantation may be a definitive treatment option with adequate short-term results.

Written informed consent was obtained from the patient during hospitalization. The patient was sent a copy of the informed consent document, in which publication of this case report, along with any accompanying images and histology samples, is authorized. The report of this case was financed by the resources of the researchers; no resources were received from any institution.

Bibliographic Information

The authors declare that there are no conflicts of interest regarding the publication of this article. Jacqueline Mugnier chose the pathology images. All authors contributed to the revision of the manuscript. Case Reports in Hepatology. Journal Menu. Subscribe to Table of Contents Alerts. Table of Contents Alerts. Abstract Fibrolamellar hepatocarcinoma is an infrequent liver tumor, currently considered to be a variant different from hepatocarcinoma.

Introduction Fibrolamellar hepatocellular carcinoma FHCC is a rare primary liver tumor which was described by Edmondson in [ 1 ]. Case Report A year-old female patient consulted due to a two-week history of disorientation and somnolence which progressed to stupor, requiring invasive mechanical ventilation. Figure 1: Abdominal magnetic resonance images: a T1W, b arterial phase, and c portal phase. Focal hepatic lesion with lobulated borders and a 13 cms of diameter which has signal heterogeneity in T1 and T2 sequences, with restrictive regions in the diffusion sequence; the lesions are highlighted in the arterial phase; they are practically isointense in the portal and late phase.

Irregular hypointense linear area which corresponds to a scar zone. Figure 2: Histopathological findings of the tumor. Tumor made up of polygonal cells with a broad eosinophilic cytoplasm and a vesicular nucleus with a prominent central nucleolus. References H. Childrens' Oncology Group Includes information about childhood liver cancers, with sections on newly diagnosed, in treatment and after treatment. The group is composed of basic and clinical scientists coming from different European and beyond.

Constantly updated. Case study: A 2 year old girl with yolk sac ca. Clinical Trials - Childhood Liver Cancers. Hepatic Tumors. Pediatric Liver Tumors. Medscape Referenced article by Kenneth Gow MD covering benign and malignant liver tumors, surgical techniques and transplantation. This list of publications is regularly updated Source: PubMed. This page last updated: 9th March Displaying links verified within last 2 weeks at time of update.

Demystifying Medicine 2017: Hepatocellular Cancer and Liver Transplantation

Found this page useful? J Pediatr Surg. To improve outcomes, we should reconsider surgical procedures according to resectability and chemoresponsiveness. Anticancer Res.


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The present study analyzed the photoactive properties of curcumin on pediatric epithelial liver tumor cell lines. Response to chemotherapy improves hepatic reserve for patients with hepatocellular carcinoma and Child-Pugh B cirrhosis. Cancer Sci. There is no established treatment for patients with advanced hepatocellular carcinoma HCC with Child-Pugh class B cirrhosis.

We retrospectively reviewed the medical records of patients treated with HAIC between March and February Subjects included with Child-Pugh class B. Median overall survival was A multivariate analysis demonstrated that improved CPS, responses to HAIC and absence of extrahepatic lesions were independent favorable prognostic factors. Related: Liver Cancer. Three-dimensional conformal radiotherapy for locally advanced hepatocellular carcinoma with portal vein tumour thrombosis: evaluating effectiveness of the model for end-stage liver disease MELD score compared with the Child-Pugh classification.

Br J Radiol. In contrast, the Child-Pugh classification, tumour response, PVTT response and the number of prior interventional radiologic treatments were not significant on multivariate analysis. Eur J Surg Oncol. The therapeutic efficacy and complications were compared between the two procedures. The 1-, 3-, and 5-year DFS rates were Multidisciplinary effort in treating children with hepatoblastoma in China. Cancer Lett. The purpose of this study is to report the first nationwide protocol Wuhan Protocol developed by Chinese Children's Cancer Group and the results of multidisciplinary effort in treating hepatoblastoma.

In this study, we reported the final analysis, which includes hepatoblastoma patients in 13 hospitals from January to December The 6-year overall survival and event-free survival rates were The preliminary results from this study showed that patients who underwent treatment following Wuhan Protocol had similar OS and EFS rates compared to those in developed countries.

However, the protocol remains to be further optimized in standardizing surgical resection including liver transplantation , refining risk stratification and risk-based chemotherapy. Distinct set of chromosomal aberrations in childhood hepatocellular carcinoma is correlated to hepatitis B virus infection. Cancer Genet. This correlation is not easily explained, because in adults, HBV infections lead to the development of HCC only after decades, not within a few years. Similar analyses have not been reported for childhood HCC. Here, we investigated whether chromosomal changes were associated with childhood HCC.

In parallel, in 15 cases, we also analysed non-neoplastic liver tissues adjacent to the HCC. All samples were analysed with high resolution, microarray-based, comparative genomic hybridisation aCGH. Most interestingly, aberrations for chromosomes 7, 8, 9, 11, and 19 were also observed in corresponding non-neoplastic samples. A subset of aberrations might be essential in HCC carcinogenesis because they occurred in adjacent, non-neoplastic tissues. In particular, the gain in chromosome 19 appeared to be highly important.

J Clin Oncol. Eighty-five patients remained evaluable. Thirty-three patients had a delayed resection. Thirty-nine tumors never became resectable. Sixty patients died. Intensification of platinum agents in the S2 and S3 trials has not resulted in improved survival. New treatment approaches in pediatric HCC should be postulated. Clinical application of a three-dimensional imaging technique in infants and young children with complex liver tumors. Pediatr Surg Int. METHODS: This study was a retrospective analysis of 26 infants and young children with giant liver tumors involving the hepatic hilum who underwent precise hepatectomy at the Affiliated Hospital of Qingdao University between February and January All patients received upper abdominal contrast-enhanced CT scanning before surgery.

The clinical outcomes were analyzed and compared between the two groups. The 3D reconstruction of abdominal organs and blood vessels was generated using the Hisense CAS system. Diagnosis and preoperative planning assisted by the system was used for preoperative and intraoperative decision-making for precise hepatectomy.

The 3D models clearly demonstrated the association of liver tumors with the intrahepatic vascular system and provided a preoperative assessment of resectability, assisting surgeons in preoperative procedural planning. Anatomic hepatectomy was successfully completed in the reconstruction group. The mean operation time was shorter in the reconstruction group The 3D reconstruction model used in this study gave detailed and accurate anatomical information and allowed for the assessment of tumor resectability and provided a detailed road map for preoperative decision-making and predicted the postoperative liver function.

Surgical controllability, accuracy, and safety can be improved in infants and young children undergoing precise hepatectomy for complex liver tumors. BMJ Case Rep. To date, there are 12 reported cases of hepatoblastoma in trisomy 18 patients, three of whom had a mosaic chromosome pattern. We report on an month-old child who had hemihypertrophy and developmental delay, was found to have hepatoblastoma on surveillance ultrasound scan, and was subsequently diagnosed with mosaic trisomy 18 on array comparative genomic hybridisation from a peripheral blood sample and molecular cytogenetic analysis of the tumour specimen.

Although hemihypertrophy has been associated with mosaic trisomies, there are only a couple of published case reports of hemihypertrophy or asymmetry in mosaic trisomy 18 patients and none in the reported cases of hepatoblastoma in a mosaic trisomy 18 setting. We have reviewed the published case reports of hepatoblastoma in trisomy 18 patients and found that they seem to tolerate the intensive treatment very well if there are no significant comorbidities. Related: Chromosome 18 Hepatoblastoma Liver Cancer. Semin Liver Dis.

Primary hepatic malignancies are uncommon in pediatrics. Tumors such as hepatocellular carcinoma HCC develop typically in the setting of chronic liver disease. The incidence of HCC in Wilson's disease-related cirrhosis is disproportionately lower than in many other forms of end-stage liver disease.

A preadolescent girl presented with Wilson's disease cirrhosis and a HCC requiring orthotopic liver transplantation. This case highlights the need to consider hepatic malignancies even in young Wilson's disease patients. Pediatric Wilson's disease and the hepatic tumor literature are reviewed.

Mesohepatectomy for Centrally Located Tumors in Children. Eur J Pediatr Surg. It is indicated in central tumors to preserve functioning liver mass avoiding an extended right hepatectomy. The purpose of this article is to analyze our experience with this technique.

Diagnoses were hepatoblastoma PRETEXT III two cases , hepatic embryonal sarcoma one case , focal nodular hyperplasia one case , and vascular tumor with rapid growth in a newborn causing an acute liver failure, compartment syndrome, and multiple organ failure one case. In all cases, the tumor was centrally located, including the segment IVb, with large displacement of the hepatic pedicle in two cases.

All children are alive with a mean follow-up of 38 months. None of the children required reoperation because of bleeding. One child developed a biliary fistula in the cutting area that closed spontaneously. The newborn with the vascular tumor required the placement of a Gore-Tex patch W. He subsequently underwent partial embolization of the tumor and MH under vascular exclusion. Sci Rep. This study aimed to summarize the first experience with ultrasound-guided percutaneous ablation treatment PAT for recurrent hepatoblastoma HB after liver resection in children.

During the follow-up period, new intrahepatic recurrences after PAT were detected in two patients. One died due to tumor progression 4 months after ablation. The median overall survival time after PAT was PAT is a safe and promising therapy for children with recurrent HB after liver resection, and further investigation in large-scale randomized clinical trials is required to determine its role in the treatment of this disease.

Korean J Radiol. Selective chemoembolization was performed in all technically feasible cases to minimize procedure-related complications. The tumor response to chemoembolization was evaluated using the modified Response Evaluation Criteria In Solid Tumors. The mortality of study subjects at 30 days was 5. Major complications were observed in five 9.

The mean length of hospitalization was 6. The overall median survival was 7. Clinical significance of CD44 expression in children with hepatoblastoma.


  • ECR 2016 / C-0903.
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  • THE GODDESS ON THE MOUNT: The Pagan Identity of St Michaels Mount;
  • Genet Mol Res. The aim of this study was to investigate the expression of CD44 and its clinical significance in children suffering from hepatoblastoma HB. CD44 expression was detected with immunohistochemistry staining in 30 samples from hepatoblastoma children and 10 normal liver tissue samples from normal children.

    The data obtained was statistically analyzed using the chi-square test, using the SPSS v. The rate of CD44 expression was significantly higher Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways. In children with hepatocellular carcinoma pHCC the 5-year overall survival rate is poor.

    Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects.

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    Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines.

    As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified.