Surgical Debulking for Refractory Hyperammonemic Encephalopathy in Fibrolamellar Hepatocellular Carcinoma

Solipuram, Vinod; Baretti, Marina; Kim, Alexander Y.; Chen, Lucy X.; Fahrner, Jill A.; Gunay‐Aygun, Meral; Peng, Xiao; Hardenbergh, Dylan; Ferguson, Anna; Griffith, Paige; Wang, Yuxuan; Brancati, Madelena; Gopalakrishna, Harish; Kato, Tomoaki; Shubert, Chris; Laheru, Daniel A.; Yarchoan, Mark

doi:10.1002/hep.31998

Cited by 8 publications

(7 citation statements)

References 2 publications

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“…As another HCC subtype rich in stromal components, scirrhous carcinoma shared almost the same macroscopical clinical characteristics and prognoses with classic HCC, which was also supported by other researchers (19,21,(31)(32)(33). Interestingly, both the two rare subtypes might present unusual paraneoplastic manifestations: hyperammonemic encephalopathy (HAE) occurred in patients with fibrolamellar carcinoma, and hypercalcemia was found in scirrhous carcinoma sufferers (34)(35)(36)(37). However, for most patients, vague symptoms and nonspecific imaging features presented challenges in differential diagnoses of scirrhous carcinoma, especially from fibrolamellar carcinoma and cholangiocarcinoma.…”

Section: Discussionsupporting

confidence: 70%

Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Chen

Shi

et al. 2022

Front. Oncol.

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BackgroundHepatocellular carcinoma (HCC) is a highly heterogeneous tumor with several rare pathological subtypes and which is still poorly understood. This study aimed to describe the epidemiological and clinical spectrum of five rare HCC subtypes and develop a competing risk nomogram for cancer-specific survival prediction.MethodsThe study cohort was recruited from the Surveillance, Epidemiology, and End Results database. The clinicopathological data of 50,218 patients histologically diagnosed with classic HCC and five rare subtypes (ICD-O-3 Histology Code = 8170/3-8175/3) between 2004 and 2018 were reviewed. The annual percent change (APC) was calculated utilizing Joinpoint regression. The nomogram was developed based on multivariable competing risk survival analyses. Akaike information criterion, Bayesian information criterion, C-index, calibration curve, and area under the receiver operating characteristic curve were obtained to evaluate the prognostic performance. A decision curve analysis was introduced to examine the clinical value of the models.ResultsDespite scirrhous carcinoma, which showed a decreasing trend (APC = -6.8%, P = 0.025), the morbidity of other rare subtypes remained stable from 2004 to 2018. The incidence-based mortality was plateau in all subtypes during the period. Clear cell carcinoma is the most common subtype (n = 551, 1.1%), followed by subtypes of fibrolamellar (n = 241, 0.5%), scirrhous (n = 82, 0.2%), spindle cell (n = 61, 0.1%), and pleomorphic (n = 17, ~0%). The patients with fibrolamellar carcinoma were younger and more likely to have a non-cirrhotic liver and better prognoses. Scirrhous carcinoma shared almost the same macro-clinical characteristics and outcomes as the classic HCC. Clear cell carcinoma tended to occur in the Asia-Pacific elderly male population, and more than half of them were large HCC (Size>5cm). Sarcomatoid (including spindle cell and pleomorphic) carcinoma was associated with a larger tumor size, poorer differentiation, and more dismal prognoses. The pathological subtype, T stage, M stage, surgery, alpha-fetoprotein, and cancer history were confirmed as the independent predictors in patients with rare subtypes. The nomogram showed good calibration, discrimination, and net benefits in clinical practice.ConclusionThe rare subtypes had unique clinicopathological features and biological behaviors compared with the classic HCC. Our findings could provide a valuable reference for clinicians. The constructed nomogram could predict the prognoses with good performance, which is meaningful to individualized management.

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Section: Discussionsupporting

confidence: 70%

Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Chen

Shi

et al. 2022

Front. Oncol.

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“…Many of the alterations in the proteome of FLC tumor are in the mitochondrion, including enzymes involved in the interaction between ammonia metabolism and the urea cycle. A recurrent clinical problem in FLC is hyperammonemic encephalopathy (6,30,40,41,(49)(50)(51)(52)(53). Alterations in the proteome of key enzymes in ammonia metabolism such as OTC, OAT, PYCR1, GLUL, GLS, glutamate dehydrogenase 2 (GLUD2), the glutamate solute carrier family 38 member 1 (SLC38A1), and aldehyde dehydrogenase 18 family member A1 (ALDH18A1) were seen in tumors of patients with FLC relative to the adjacent nontransformed tissue.…”

Section: Proteomics and Hyperammonemic Encephalopathymentioning

confidence: 99%

Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma

et al. 2023

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Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and pathological alterations in FLC cells, including their drug sensitivity and glycolysis. Hyperammonemic encephalopathy is a recurrent problem in these patients, and established treatments based on the assumption of liver failure are unsuccessful. We show that many of the enzymes that produce ammonia are increased and those that consume ammonia are decreased. We also demonstrate that the metabolites of these enzymes change as expected. Thus, hyperammonemic encephalopathy in FLC may require alternative therapeutics.

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“…6,44,47 In very selected cases, palliative surgical tumor reduction can be performed in order to alleviate symptoms such as hyperammonemic encephalopathy but this is absolutely not standard. 48 Resection is a factor greatly influencing the prognosis, with 5-year survival rates reaching up to 86% for stage I patients. 43 Mavros et al reported of a 0% 5-year survival rate among patients who received chemotherapy (including palliative), intra-arterial therapy or other treatment instead.…”

Section: Surgical Treatment Primary Resection and Liver Transplantationmentioning

confidence: 99%

A Multidisciplinary Approach to the Management of Fibrolamellar Carcinoma: Current Perspectives and Future Prospects

Polychronidis¹,

Murtha-Lemekhova²,

Fuchs³

et al. 2022

OTT

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Fibrolamellar carcinoma (FLC) is a rare primary liver tumor affecting predominantly younger and otherwise healthy patients. Typically, FLC presents with advanced disease due to the paucity of typical symptoms and no history of underlying liver disease. Depending on tumor characteristics and the patient's general condition, surgical treatment is the most promising treatment modality. Aggressive resection and liver transplantation have been utilized and are presently indispensable curative treatment options. Under certain circumstances surgical resection is also possible for metachronous metastases or local recurrence. Recent tumor biology discoveries have contributed to improved diagnostic specificity and systemic treatment options.

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Surgical Debulking for Refractory Hyperammonemic Encephalopathy in Fibrolamellar Hepatocellular Carcinoma

Cited by 8 publications

References 2 publications

Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma

A Multidisciplinary Approach to the Management of Fibrolamellar Carcinoma: Current Perspectives and Future Prospects

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