Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Primary Hepatic Carcinoma Treatment & Management

  • Author: Keith E Stuart, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
 
Updated: Apr 16, 2015
 

Medical Care

Available treatment options depend on the size, number, and location of tumors; presence or absence of cirrhosis; operative risk based on extent of cirrhosis and comorbid diseases; overall performance status; patency of portal vein; and presence of metastatic disease.[19, 20, 21]

Before instituting definitive therapy, it is best to treat the complications of cirrhosis with diuretics, paracentesis for ascites, lactulose for encephalopathy, ursodiol for pruritus, sclerosis or banding for variceal bleeding, and antibiotics for spontaneous bacterial peritonitis.

Surgical resection and liver transplantation are the only chances of cure but have limited applicability. The main prognostic factors for resectability are tumor size and liver function. Only about 5% of hepatocellular carcinoma patients are suitable for transplantation; these patients may have a 5-year survival of greater than 75% with tumor recurrence rates as low as 15% at 5 years.[22] Other local therapies are chemoembolization, ethanol ablation, radiofrequency ablation, cryoablation, and radiotherapy. Patients whose disease is downstaged following chemoembolization may be eligible for transplantation. Systemic treatment with chemotherapy may be used for advanced disease.

Systemic chemotherapy

For patients with advanced hepatocellular carcinoma who are not candidates for surgical resection, liver transplantation, or localized tumor ablation, systemic chemotherapy remains the mainstay of therapy. Unfortunately, hepatocellular carcinoma is a relatively chemotherapy-resistant tumor; therefore, outcomes using this mode of treatment are unsatisfactory. Resistance to chemotherapy may be caused by the universal expression of the multidrug resistance gene protein on the surface of the malignant cells, leading to active efflux of chemotherapeutic agents.

Chemotherapy is usually not well tolerated and seems to be less efficacious in patients with hepatocellular carcinoma with underlying hepatic dysfunction. Younger patients with well-compensated cirrhosis due to chronic hepatitis B or C infections have better outcomes with chemotherapy than older patients with alcoholic cirrhosis and other comorbid diseases.

The most active single agent drugs tested have been doxorubicin, cisplatin, and fluorouracil. Response rates are about 10%, and treatment shows no clear impact on overall survival.[23, 20] More recently, gemcitabine and capecitabine have been evaluated in clinical trials; response rates have been low and short term.

Various combination chemotherapy regimens have also been studied. Recently, cisplatin-based combination regimens, such as gemcitabine and oxaliplatin, have shown improved response rates around 20%, but to date, no survival advantage as compared to supportive care alone has been shown. No difference seems to exist in response rates between 2- or 3-drug regimens. Moreover, some of these combination regimens cause considerable toxicity.

Chemoimmunotherapy uses a combination of chemotherapy and immunomodulatory agents, such as interferon-alpha, to try to achieve better tumor response rates. Immunotherapy has had encouraging results in patients with certain types of cancers such as renal cell carcinoma and melanoma. PIAF is a combination of cisplatin, interferon-alpha, doxorubicin, and infusional 5-fluorouracil that is associated with a response rate of 26%, which is higher than the response rates with single chemotherapy agents. Although overall median survival is longer with PIAF than single-agent doxorubicin, treatment-related toxicity is significant. The best candidates for this therapy are young patients without liver cirrhosis and normal bilirubin levels.[24]

Antiangiogenesis agents

Antiangiogenesis agents (ie, bevacizumab), which work by disrupting the formation of blood vessels that feed tumors, are a new class of drugs that may prove to be of benefit in the treatment of hepatocellular carcinoma. The highly vascular nature of hepatocellular carcinoma tumors suggested that therapy with an antiangiogenesis agent might be effective. Bevacizumab by itself, however, is of limited clinical use. The combination of bevacizumab with gemcitabine and oxaliplatin, though, produced a 20% response rate with an additional 27% of patients who had stable disease.[25]

Tyrosine kinase inhibitors

Sorafenib, a multitargeted oral kinase inhibitor, has recently been shown in a phase III trial to prolong survival in patients with hepatocellular carcinoma.[26] This agent, which targets various pathways, including VEGFR, PDGFR, KIT, FLT-3, and RET, was compared to placebo in a trial of 602 patients. Median survival was prolonged significantly to 10.7 from 7.9 months, and time to progression was 5.5 months, compared with 2.8 in the placebo group. Currently, this is the only FDA-approved antineoplastic for hepatocellular carcinoma. The revised National Comprehensive Cancer Network (NCCN) guidelines for hepatocellular carcinoma recommend sorafenib as a treatment option at several points in the treatment algorithm.[19]

The benefit of sorafenib is also demonstrated in a study by Abou-Alfa et al, which shows a longer overall and progression-free survival with the addition of sorafenib to doxorubicin. The same study underlines the lack of efficacy of doxorubicin alone.[27] Still unanswered is the question of whether doxorubicin adds any benefit to treatment with sorafenib by itself.

Sunitinib is another multitargeted tyrosine kinase inhibitor with reported activity in hepatocellular carcinoma.[28] Erlotinib, an oral epidermal growth factor (EGF) receptor tyrosine kinase inhibitor, has also shown some activity against hepatocellular carcinoma when used alone or in combination with bevacizumab.[29, 30] One report has suggested that the mTOR inhibitor sirolimus may have benefit in the treatment of both cholangiocellular carcinoma and hepatocellular carcinoma.[30]

Next

Surgical Care

Partial hepatectomy

The videos below demonstrate a right hepatectomy.

Right hepatectomy. Part 1: Dissection of right portal vein. Courtesy of Memorial Sloan-Kettering Cancer Center, featuring Leslie H. Blumgart, MD. (From Blumgart LH. Video Atlas: Liver, Biliary & Pancreatic Surgery. Philadelphia, PA: Saunders; 2010.)
Right hepatectomy. Part 2: Devascularization of right liver. Courtesy of Memorial Sloan-Kettering Cancer Center, featuring Leslie H. Blumgart, MD. (From Blumgart LH. Video Atlas: Liver, Biliary & Pancreatic Surgery. Philadelphia, PA: Saunders; 2010.)
Right hepatectomy. Part 3: Suturing and dividing. Courtesy of Memorial Sloan-Kettering Cancer Center, featuring Leslie H. Blumgart, MD. (From Blumgart LH. Video Atlas: Liver, Biliary & Pancreatic Surgery. Philadelphia, PA: Saunders; 2010.)

In the United States, resection is possible in only 5% of patients. In general, solitary hepatocellular carcinoma lesions confined to the liver without vascular invasion with well-preserved hepatic function have the best outcomes. Although there are no strict criteria in terms of tumor size, many surgeons use less than 5 cm as their cutoff.

Five-year survival rates for resectable lesions vary widely from 30% to as high as 90% for very early stage hepatocellular carcinoma lesions.[31, 32] Fibrolamellar hepatocellular carcinoma may have a better prognosis for survival after surgical resection because of a more favorable size, predominantly left lobe location, and the absence of cirrhosis in the unaffected portion of the liver.

Appropriate evaluation of patients prior to resection is crucial since intraoperative mortality is doubled in cirrhotic versus noncirrhotic patients. Preoperative laparoscopic inspection aids in diagnosing both the tumor and extent of cirrhosis.

Local liver factors rather than tumor-associated characteristics may be instrumental in tumor recurrences following surgical resection. For instance, one study found that the level of HBV-DNA in the liver tissue surrounding the tumor was a strong determinant of recurrence, rather than the amount of HBV-DNA in the resected tumor itself.[33]

Transplantation

Many patients are not candidates for partial hepatectomy due to extent of underlying liver disease. Some of these patients are good candidates for liver transplantation since it has the potential for eliminating the cancer as well as curing the underlying liver disease.

Orthotopic liver transplantation can be considered for patients who meet the Milan criteria—one tumor less than 5 cm or up to 3 tumors all less than 3 cm. These highly selected patients have excellent survival rates, similar to those of patients who undergo liver transplantation for end-stage liver disease without hepatocellular carcinoma.[34, 35, 36, 37]

Although availability of donor organs is still limited, the Organ Procurement and Transplantation Network (OPTN) and the United Network for Organ Sharing (UNOS) have recognized the urgency of proceeding to transplantation in patients with limited stage hepatocellular carcinoma. Over the past 5 years, revision of the UNOS policy has established medical criteria by which a patient with early/small hepatocellular carcinoma can be assigned additional priority for liver allocation so as to increase the likelihood of a favorable transplant outcome. This has resulted in shorter wait times to transplantation and better overall outcomes. Bridging therapy with local therapies, such as chemoembolization or radiofrequency ablation (RFA), is sometimes considered for patients on the transplant waiting list.

Locally ablative therapy

Intratumoral injections of ethanol or acetic acid, heat (via radiofrequency, microwave, or laser ablation), or cold (cryoablation with liquid nitrogen) may be used to locally control tumors smaller than 4-5 cm. These techniques are frequently performed percutaneously as outpatient procedures. In general, these procedures are reserved for patients who do not meet criteria for surgical resection yet are candidates for a liver-directed procedure based on the presence of limited liver-only disease. This has generally been supplanted by other local modalities.

Radiofrequency ablation (RFA) is the delivery of radiofrequency thermal energy to the hepatocellular carcinoma lesion causing necrosis of the tumor. During RFA, a high frequency alternating current is delivered from the tip of an electrode into the surrounding tissue. The ions within the tissue attempt to follow the direction of the alternating current resulting in friction and eventual heating of the tissue. As tissue temperature elevates above 60°C, tumor cells begin to die resulting in an area of tumor necrosis. The needle electrode is advanced into the hepatocellular carcinoma lesion usually via a percutaneous route with the guidance of ultrasonography. The procedure can also be performed surgically via laparoscopy or laparotomy.

RFA is usually used for treatment of tumors less than 4 cm in size. For small tumors, studies show good initial local tumor control with an average local recurrence rate of 5-6% within the first 20 months. The treatment of larger tumors results in much higher rates of local recurrence. Unfortunately, a significant proportion of patients eventually develop clinically detectable hepatic or extrahepatic disease from their preexisting micrometastatic lesions. RFA is usually well-tolerated, but complications including fever, pain, bleeding, pleural effusion, hematoma, and intermittent transaminitis among others have been reported.[38, 39]

Cryoablation, using a liquid nitrogen–filled probe, can achieve similar results to RFA and is also used for tumors smaller than approximately 5 cm. The degree of collateral damage to uninvolved liver tissue or other organs may be more easily appreciated, so this technique is more useful for lesions near the surface of the liver, the gallbladder, or large blood vessels.

Percutaneous ethanol or acetic acid ablation is reserved for patients with small tumors; however, in many areas, the ease and efficacy of RFA has now replaced these older techniques. Radiation therapy is limited by dose-related radiation hepatitis, which precludes the administration of external beam radiation in doses effective for tumor eradication. Doses of 2500 cGy may be used for palliative measures.

CyberKnife system is a new technology that uses a combination of robotics and image guidance to deliver concentrated and highly focused beams of radiation to the tumor while minimizing radiation exposure to the surrounding healthy liver tissue. CyberKnife stereotactic radiosurgery is a promising new treatment tool for localized hepatocellular carcinoma lesions. Currently, its availability is limited to a few medical centers, and long-term efficacy for hepatocellular carcinoma lesions is yet to be determined.

Chemoembolization is the delivery of high concentrations of chemotherapeutic agents directly to the hepatocellular carcinoma tumor via the hepatic artery, which provides the tumor with most of its blood supply. The remainder of the liver may be spared because it can rely on the portal vein for its blood supply.[40]

Some centers are adding RFA to chemoembolization in the hope that the combined treatments would improve outcome by adding thermal ablation to arterial ischemia. A randomized controlled trial by Morimoto et al demonstrated an improved local control without a definite improvement in overall survival.[41] However, the study did not include a chemoembolization-alone arm, so it remains unclear whether both procedures together are necessary for local control.

Embolizing agents such as cellulose, microspheres,[42] lipoidal, and gelatin foam particles are used to deliver intra-arterial chemotherapy (mitomycin, doxorubicin, cisplatin) to the tumor via the hepatic artery. A relatively new technology using drug-eluting beads may offer similar efficacy with less toxicity.

Morbidity from this procedure is greatly dependent on the extent of cirrhosis. In general, patients with portal vein thrombosis, significant encephalopathy, or biliary obstruction are not candidates for chemoembolization.[43]

Response rates of 60-80% are seen. In addition, 2 clinical trials from Spain and Hong Kong showed a modest survival benefit with the use of doxorubicin (Adriamycin) or cisplatin with embolization as compared to supportive care only in patients with unresectable tumors.[44, 45, 46]

Radioembolization (or selective internal radiotherapy) uses 32-μm glass microspheres to carry yttrium-90 intra-arterially into the capillary beds of the tumor. This technique can cause excellent necrosis and tumor responses. Unlike chemoembolization, which uses larger particles, arterial embolization and ischemia are not necessary for the therapeutic effect, meaning this procedure may be performed for patients with portal vein thrombosis.[47, 48]

Previous
Next

Consultations

See the list below:

  • Hepatobiliary surgeon
  • Oncologist
  • Interventional radiologist
  • Interventional gastroenterologist
Previous
 
 
Contributor Information and Disclosures
Author

Keith E Stuart, MD Chairman, Department of Hematology and Oncology, Lahey Hospital and Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Zsofia K Stadler, MD Fellow, Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard University

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

N Joseph Espat, MD, MS, FACS Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center

N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, Surgical Infection Society

Disclosure: Nothing to disclose.

Additional Contributors

Antoni Ribas, MD Assistant Professor of Medicine, Division of Hematology-Oncology, University of California at Los Angeles Medical Center

Disclosure: Nothing to disclose.

References
  1. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999 Mar 11. 340(10):745-50. [Medline].

  2. El-Serag HB, Davila JA, Petersen NJ, McGlynn KA. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med. 2003 Nov 18. 139(10):817-23. [Medline].

  3. Schottenfeld D, Fraumeni JF eds. Cancer Epidemiology and Prevention. 3rd ed. Oxford University Press; 2006.

  4. El-Serag HB, Mason AC. Risk factors for the rising rates of primary liver cancer in the United States. Arch Intern Med. 2000 Nov 27. 160(21):3227-30. [Medline].

  5. Yasui K, Hashimoto E, Komorizono Y, et al. Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2011 May. 9(5):428-33; quiz e50. [Medline].

  6. American Cancer Society Facts and Figures 2011. Available at http://cacancerjournal.org.

  7. Bosch FX, Ribes J, Díaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004 Nov. 127(5 Suppl 1):S5-S16. [Medline].

  8. Di Bisceglie AM, Carithers RL Jr, Gores GJ. Hepatocellular carcinoma. Hepatology. 1998 Oct. 28(4):1161-5. [Medline].

  9. Cancer of the Liver and Biliary Tract. Adami A, Hunter D, and Trichopoulos D. Textbook of Cancer Epidemiology. Second Edition. Oxford England: Oxford University Press; 2008. 308-332.

  10. DeVita VT, Lawrence TS, Rosenberg SA, et al. Cancer. Principles and Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1 May 2008.

  11. Chang MH, Chen CJ, Lai MS, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med. 1997 Jun 26. 336(26):1855-9. [Medline].

  12. Bugianesi E. Non-alcoholic steatohepatitis and cancer. Clin Liver Dis. 2007 Feb. 11(1):191-207, x-xi. [Medline].

  13. Calle EE, Teras LR, Thun MJ. Obesity and mortality. N Engl J Med. 2005 Nov 17. 353(20):2197-9. [Medline].

  14. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut. 2005 Apr. 54(4):533-9. [Medline]. [Full Text].

  15. Manos M,and Murphy R. Viral hepatitis registry, Kaiser Permanente Northern California, Oakland, California.Trends in the incidence and etiology of hepatocellular carcinoma in a managed care population :the roles of viral hepatitis and fatty liver disease. Hepatology. 2007. 46:400A.

  16. Peng SY, Chen WJ, Lai PL, Jeng YM, Sheu JC, Hsu HC. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer. 2004 Oct 20. 112(1):44-50. [Medline].

  17. Lok AS, Sterling RK, Everhart JE, et al. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology. 2010 Feb. 138(2):493-502. [Medline]. [Full Text].

  18. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 1998 Sep. 28(3):751-5. [Medline].

  19. National Comprehensive Cancer Network. NCCN Hepatobiliary Cancers Clinical Practice Guidelines in Oncology (Version 2.2008). Available at http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf.

  20. Thomas MB, Zhu AX. Hepatocellular carcinoma: the need for progress. J Clin Oncol. 2005 May 1. 23(13):2892-9. [Medline].

  21. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005 Nov. 42(5):1208-36. [Medline].

  22. Rougier P, Mitry E, Barbare JC, Taieb J. Hepatocellular carcinoma (HCC): an update. Semin Oncol. 2007 Apr. 34(2 Suppl 1):S12-20. [Medline].

  23. Simonetti RG, Liberati A, Angiolini C, Pagliaro L. Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials. Ann Oncol. 1997 Feb. 8(2):117-36. [Medline].

  24. Leung TW, Tang AM, Zee B, et al. Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon-alpha, doxorubicin and 5-fluorouracil chemotherapy. Cancer. 2002 Jan 15. 94(2):421-7. [Medline].

  25. Zhu AX, Blaszkowsky LS, Ryan DP, et al. Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2006 Apr 20. 24(12):1898-903. [Medline].

  26. Llovet J, Ricci S, Mazzaferro V, et al. Sorafenib improves survival in advanced hepatocellular carcinoma (HCC): results of a phase III randomized placebo-controlled trial (SHARP trial). J Clin Oncol. 2007. 25(suppl):962s(abstract LBA1).

  27. Abou-Alfa GK, Johnson P, Knox JJ, et al. Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA. 2010 Nov 17. 304(19):2154-60. [Medline].

  28. Faivre S, Raymond E, Douillard J, et al. Assessment of safety and drug-induced tumor necrosis with sunitinib in patients (pts) with unresectable hepatocellular carcinoma. J Clin Oncol. 2007. 25:149s Abstract 3546.

  29. Philip PA, Mahoney MR, Allmer C, et al. Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J Clin Oncol. 2005 Sep 20. 23(27):6657-63. [Medline].

  30. Thomas M, Dutta A, Brown T, et al. A phase II open-label study of OSI-774 (NSC 718781) in unresectable hepatocellular carcinoma. Proc Am Soc Clin Oncol. 2005. 23:4083a.

  31. Poon RT, Fan ST, Lo CM, et al. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg. 2001 Jul. 234(1):63-70. [Medline]. [Full Text].

  32. Takayama T, Makuuchi M, Hirohashi S, et al. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology. 1998 Nov. 28(5):1241-6. [Medline].

  33. Choi JG, Chung YH, Kim JA, et al. High HBV-DNA titer in surrounding liver rather than in hepatocellular carcinoma tissue predisposes to recurrence after curative surgical resection. J Clin Gastroenterol. 2012 May-Jun. 46(5):413-9. [Medline].

  34. Hemming AW, Cattral MS, Reed AI, Van Der Werf WJ, Greig PD, Howard RJ. Liver transplantation for hepatocellular carcinoma. Ann Surg. 2001 May. 233(5):652-9. [Medline]. [Full Text].

  35. Vauthey JN, Klimstra D, Franceschi D, et al. Factors affecting long-term outcome after hepatic resection for hepatocellular carcinoma. Am J Surg. 1995 Jan. 169(1):28-34; discussion 34-5. [Medline].

  36. Iwatsuki S, Starzl TE, Sheahan DG, et al. Hepatic resection versus transplantation for hepatocellular carcinoma. Ann Surg. 1991 Sep. 214(3):221-8; discussion 228-9. [Medline]. [Full Text].

  37. Fong Y, Sun RL, Jarnagin W, Blumgart LH. An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg. 1999 Jun. 229(6):790-9; discussion 799-800. [Medline]. [Full Text].

  38. Curley SA, Izzo F, Ellis LM, Nicolas Vauthey J, Vallone P. Radiofrequency ablation of hepatocellular cancer in 110 patients with cirrhosis. Ann Surg. 2000 Sep. 232(3):381-91. [Medline]. [Full Text].

  39. Zhou Y, Zhao Y, Li B, et al. Meta-analysis of radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma. BMC Gastroenterol. 2010 Jul 9. 10:78. [Medline]. [Full Text].

  40. Stuart K. Chemoembolization in the management of liver tumors. Oncologist. 2003. 8(5):425-37. [Medline].

  41. Morimoto M, Numata K, Kondou M, Nozaki A, Morita S, Tanaka K. Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer. 2010 Dec 1. 116(23):5452-60. [Medline].

  42. Martin RC 2nd, Rustein L, Pérez Enguix D, et al. Hepatic arterial infusion of doxorubicin-loaded microsphere for treatment of hepatocellular cancer: a multi-institutional registry. J Am Coll Surg. 2011 Oct. 213(4):493-500. [Medline].

  43. Stuart K, Stokes K, Jenkins R, Trey C, Clouse M. Treatment of hepatocellular carcinoma using doxorubicin/ethiodized oil/gelatin powder chemoembolization. Cancer. 1993 Dec 1. 72(11):3202-9. [Medline].

  44. Bruix J, Llovet JM, Castells A, et al. Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution. Hepatology. 1998 Jun. 27(6):1578-83. [Medline].

  45. Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18. 359(9319):1734-9. [Medline].

  46. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May. 35(5):1164-71. [Medline].

  47. Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010 Jan. 138(1):52-64. [Medline].

  48. Salem R, Lewandowski RJ, Kulik L, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011 Feb. 140(2):497-507.e2. [Medline]. [Full Text].

  49. Sawada N, Inoue M, Iwasaki M, et al. Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma. Gastroenterology. 2012 Jun. 142(7):1468-75. [Medline].

  50. Kaneda K, Uenishi T, Takemura S, et al. The influence of postoperative glycemic control on recurrence after curative resection in diabetics with hepatitis C virus-related hepatocellular carcinoma. J Surg Oncol. 2012 May. 105(6):606-11. [Medline].

  51. Stuart KE, Anand AJ, Jenkins RL. Hepatocellular carcinoma in the United States. Prognostic features, treatment outcome, and survival. Cancer. 1996 Jun 1. 77(11):2217-22. [Medline].

  52. Collier J, Sherman M. Screening for hepatocellular carcinoma. Hepatology. 1998 Jan. 27(1):273-8. [Medline].

  53. American Cancer Society. Statistics for 2008. Available at http://www.cancer.org/docroot/stt/stt_0.asp.

  54. El-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology. 2004 Nov. 127(5 Suppl 1):S27-34. [Medline].

  55. Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010 Feb. 30(1):61-74. [Medline].

  56. Grieco A, Pompili M, Caminiti G, Miele L, Covino M, Alfei B. Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre. Gut. 2005 Mar. 54(3):411-8. [Medline].

  57. Guglielmi A, Ruzzenente A, Pachera S, et al. Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response. Am J Gastroenterol. 2008 Mar. 103(3):597-604. [Medline].

  58. Hsu CY, Hsia CY, Huang YH, Su CW, Lin HC, Lee PC. Selecting an optimal staging system for hepatocellular carcinoma: comparison of 5 currently used prognostic models. Cancer. 2010 Jun 15. 116(12):3006-14. [Medline].

  59. Hsu CY, Lee YH, Hsia CY, Huang YH, Su CW, Lin HC. Performance status in patients with hepatocellular carcinoma: determinants, prognostic impact, and ability to improve the Barcelona Clinic Liver Cancer system. Hepatology. 2013 Jan. 57(1):112-9. [Medline].

  60. Lin ZZ, Hsu C, Hu FC, Shao YY, Chang DY, Yang CH. Factors impacting prognosis prediction in BCLC stage C and Child-Pugh class A hepatocellular carcinoma patients in prospective clinical trials of systemic therapy. Oncologist. 2012. 17(7):970-7. [Medline].

  61. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999. 19(3):329-38. [Medline].

  62. Memon K, Kulik L, Lewandowski RJ, et al. Alpha-fetoprotein response correlates with EASL response and survival in solitary hepatocellular carcinoma treated with transarterial therapies: a subgroup analysis. J Hepatol. 2012 May. 56(5):1112-20. [Medline]. [Full Text].

  63. Rizell M, Andersson M, Cahlin C, Hafstrom L, Olausson M, Lindner P. Effects of the mTOR inhibitor sirolimus in patients with hepatocellular and cholangiocellular cancer. Int J Clin Oncol. 2008 Feb. 13(1):66-70. [Medline].

  64. Santambrogio R, Salceda J, Costa M, Kluger MD, Barabino M, Laurent A. External validation of a simplified BCLC staging system for early hepatocellular carcinoma. Eur J Surg Oncol. 2013 Aug. 39(8):850-7. [Medline].

  65. Shao YY, Lu LC, Lin ZZ, Hsu C, Shen YC, Hsu CH. Prognosis of advanced hepatocellular carcinoma patients enrolled in clinical trials can be classified by current staging systems. Br J Cancer. 2012 Nov 6. 107(10):1672-7. [Medline].

  66. Sherman M. Hepatocellular carcinoma: screening and staging. Clin Liver Dis. 2011 May. 15(2):323-34, vii-x. [Medline].

  67. Sirivatanauksorn Y, Tovikkai C. Comparison of staging systems of hepatocellular carcinoma. HPB Surg. 2011. 2011:818217. [Medline].

  68. Wang JH, Changchien CS, Hu TH, Lee CM, Kee KM, Lin CY. The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma - Survival analysis of 3892 patients. Eur J Cancer. 2008 May. 44(7):1000-6. [Medline].

  69. Wu YZ, Li B, Wang T, Wang SJ, Zhou YM. Radiofrequency ablation vs hepatic resection for solitary colorectal liver metastasis: a meta-analysis. World J Gastroenterol. 2011 Sep 28. 17(36):4143-8. [Medline]. [Full Text].

 
Previous
Next
 
Hepatic carcinoma, primary. Dilated collateral superficial abdominal veins in a 67-year-old man with cirrhosis, hepatocellular carcinoma (HCC), and portal vein occlusion.
Hepatic carcinoma, primary. Large multifocal hepatocellular carcinoma (HCC) in an 80-year-old man without cirrhosis.
Hepatic carcinoma, primary. Noncontrast CT scans at 1 day and 3 months following chemoembolization with doxorubicin/Ethiodol Gelfoam.
Hepatic carcinoma, primary. Unusual location of a bone metastasis from hepatocellular carcinoma (HCC).
Hepatic carcinoma, primary. Plain radiograph immediately following chemoembolization, demonstrating catheter placement and Ethiodol enhancement of tumors.
Right hepatectomy. Part 1: Dissection of right portal vein. Courtesy of Memorial Sloan-Kettering Cancer Center, featuring Leslie H. Blumgart, MD. (From Blumgart LH. Video Atlas: Liver, Biliary & Pancreatic Surgery. Philadelphia, PA: Saunders; 2010.)
Right hepatectomy. Part 2: Devascularization of right liver. Courtesy of Memorial Sloan-Kettering Cancer Center, featuring Leslie H. Blumgart, MD. (From Blumgart LH. Video Atlas: Liver, Biliary & Pancreatic Surgery. Philadelphia, PA: Saunders; 2010.)
Right hepatectomy. Part 3: Suturing and dividing. Courtesy of Memorial Sloan-Kettering Cancer Center, featuring Leslie H. Blumgart, MD. (From Blumgart LH. Video Atlas: Liver, Biliary & Pancreatic Surgery. Philadelphia, PA: Saunders; 2010.)
The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma. Image reproduced with permission reproduced with permission of the American Association for the Study of Liver Diseases (AASLD.org), from Bruix J and Sherman M (2011), Management of hepatocellular carcinoma: An update. Hepatology, 53: 1020–1022. doi: 10.1002/hep.24199.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.