Published December 2014 in European Journal of Pediatric Surgery

Fibrolamellar hepatocellular carcinoma (FLHCC) accounts for less than 1% of all liver cancer cases that originate in the liver. Surgery to remove the entire tumor remains the cornerstone of treatment of FLHCC; however, this may not always be possible as some patients present with advanced stage disease with larger tumors. As a rare liver cancer, FLHCC currently does not have a standardized chemotherapy regimen as other cancers do (i.e. breast cancer). Some investigators have looked at various chemotherapy regimens with varied results including: gemcitaibine/oxaliplatin (GEMOX) or 5-flurouracil (5-FU) with interferon alpha (IFN-a) and Folinic acid 5-FU/Oxaliplatin (FOLFOX). Various scientists have been investigating the biology of the tumor. Others have studied the mammalian target of rapamycin complex 1 (mTORC1) and fibroblast growth factor receptor 1 (FGFR1) signaling in FLHCC tumors implicating a potential role of these pathways in the disease process.

Advances in whole genome sequencing have revealed what may be the closest explanation for why FLHCC develops a chimera between two genes (DNAJB1-PRKACA) that was originally found in 15 out of 15 tumor samples. FLHCC is associated with more favorable outcomes compared with conventional hepatocellular carcinoma (HCC) when treated with surgery, with 5-year survival rates ranging from 58-82%. Multiple studies have shown the presence of FLHCC outside the liver is a predictor of overall and recurrence-free survival. Research in improved methods of diagnosis and response to non-operative therapies are still needed.

— Dr. Benjamin Farber, The Fibrolamellar Registry Scientific Advisory Board
Open access link to article via PatientInform

Published June 2014 in World Journal of Gastrointestinal Surgery

This case report describes a 35-year-old, previously healthy female patient who was diagnosed with an unresectable FL-HCC mass due to its invasion into the major blood vessels of the liver. The best treatment option for FL-HCC is surgical resection. The patient was unable to go to surgery initially and was started on Gemcitabine-Oxaliplatin (GEMOX) chemotherapy every 2 weeks for 11 months. The patient had CT Scans or MRI scans every 4 months for staging purposes. The patient’s tumor significantly reduced in size in response to chemotherapy allowing her to go on to surgery where a part of the right lobe of the liver, part of the inferior vena cava (IVC), and lymph nodes were resected.

–Dr. Benjamin Farber
Fibrolamellar Registry Scientific Advisory Board

Published in Science magazine, February 28, 2014.  Link to article

Honeyman JN1, Simon EP, Robine N, Chiaroni-Clarke R, Darcy DG, Lim II, Gleason CE, Murphy JM, Rosenberg BR, Teegan L, Takacs CN, Botero S, Belote R, Germer S, Emde AK, Vacic V, Bhanot U, LaQuaglia MP, Simon SM., Science 2014: PMID: 24578576

This is the first article to characterize the molecular causes for fibrolamellar hepatocellular carcinoma. The results show there is a small deletion in one of the two copies of chromosome 19 in every fibrolamellar patient tested. The deletion results in two different genes getting fused together in what is called a chimera. The deletion was only in the tumor tissue, not the adjacent tissue. This leads to a few conclusions:

• Fibrolamellar is not inherited (the glitch is not in any of the chromosomes of the normal tissue).
• Fibrolamellar seems to be one disease – all the patients have the same alteration.

For further information, see this video from one of the co-authors: