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Liver Cancer Surgery

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Liver Cancer

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SURGERY

Surgery is the primary treatment option for patients with early liver cancer which has small tumors or has not spread.1 The type of surgery depends on the extent of the cancer and can include:

  • Partial hepatectomy – also called a liver resection, this procedure removes part of the liver to remove the tumor. Surgeons may remove one of the liver’s eight segments, more than one small segment, or a lobe.
  • Lobectomy – also called a hemi hepatectomy, this procedure removes a lobe of the liver.
  • Liver transplant – the entire liver is removed and a healthy liver from a donor is transplanted to replace it.

 

Surgical Resection

Patients with early-stage hepatocellular carcinoma (HCC)  may benefit from hepatic resection. The choice of performing a partial hepatectomy or lobectomy is determined by tumor size and location. Unfortunately, many patients cannot undergo surgical resection due to underlying health problems or locally advanced disease. Patients with a solitary tumor that has no signs of vascular invasion and who have a sufficient hepatic reserve are usually the best candidates for surgical research. While surgical resection for liver cancer has a 40% to 60% 5-year survival rate, depending on the disease stage, the presence of persistent liver inflammation following resection can increase the rate of cancer recurrence which can be as high as 70% after 5 years.2,3

When feasible, anatomic liver resection is preferred by many surgeons. This procedure removes a specific area of the liver, including tumor-bearing portal pedicles and liver parenchyma, while preserving blood flow and biliary drainage. This procedure is considered a curative option for early-stage HCC since the entire primary tumor is excise along with the adjacent liver parenchyma containing micrometastases, reducing the risk of intrahepatic metastases and the spread of the cancer through the portal vein. Anatomic resection has been shown to be associated with lower recurrence and better long-term outcomes compared to nonanatomic research, especially for tumors with microvascular invasion.4,5 Outcomes with nonanatomic research can be similar to anatomic resection adequate tumor margins are achieved.6,7

Liver

Liver Transplantation

Liver transplantation is typically regarded as the first option for patients with early-stage HCC, moderate-to-severe cirrhosis, and patients whose condition is incurable. The choice between a liver transplant and resection requires a number of considerations including tumor features, the presence of portal hypertension, the patient’s performance status, and their underlying liver function.

For patients with early-stage HCC, liver transplantation is considered the surgical option that provides the best opportunity for achieving beneficials long-term results. Liver transplantation provides the best curative treatment for HCC  with a 10-year recurrence-free survival rate ranging from 52% to 61% and a 10-year recurrence rate of 13% to 20% with patients whose disease is not downstaged prior to transplantation having longer survival and less recurrence.8

Historically, patients with cirrhosis, a limited tumor burden define by the Milan criteria (a single tumor measuring 2.5 cm to 5 cm in diameter or two or three tumors each measuring >1 cm and ≤3 cm in diameter) and not having substantial vascular involvement or extrahepatic disease were considered candidates for transplantation.9   More recently these criteria have been adjusted to expand the recipient pool to include tumor biology and response to bridging therapies with data supporting downstaging as an option in selecting suitable liver transplant candidates who tumors exceed the above criteria. Alternative criteria which have been studied include the University of California San Francisco (UCSF) criteria, the up-to-seven criteria, criteria based on the combination of total tumor volume and α- fetoprotein, and the combination of the Milan plus α- fetoprotein criteria.10-12 The  UCSF criteria is currently the only one that has been adopted as an upper limit of tumor burden for down- staging to Milan criteria for liver transplantation for HCC patients.13

Milan Criteria

  • Single lesion <5 cm or <3 nodules each <3 cm
  • Without vascular or extrahepatic invasion

UCSF Criteria

  • Single leSingle lesion <6.5 cm or <3 nodules with the largest tumor <4.5 cm and total tumor diameter <8 cm
  • Without vascular or extrahepatic invasion
 

More recently, the use of interventional procedures as neoadjuvant therapy to reduce tumor burden to achieve the Milan criteria for transplantation (downstaging) or to prevent tumor progression while waiting for transplantation have been explored.14,15 Including radiologic tumor response following neoadjuvant therapy has been proposed as a possible criteria for identifying potential candidates for liver transplantation.16  Including a decrease in α- fetoprotein levels while on the liver transplant waiting list has also been shown to correlate with recurrence- free survival following transplantation.17

In the United States, organ transplantation is regulated by the United Network OF Organ Sharing (UNOS). UNOS is a not-for-profit organization which manages the Organ Procurement and Transplantation Network (OPTN), the sole network which is responsible for procuring, matching and allocating donated human organs in the United States by maintaining the national organ transplant database.  The OPTN has developed standardized medical criteria for determining suitable transplant candidates and has established a priority ranking system based on objective and measurable medical criteria. UNOS uses a patient’s MELD (Model for End-Stage Liver Disease) score to determine prioritization for receiving a liver transplant. This score assesses disease severity and the risk of death within 3 months of not receiving a transplant. Patients with HCC can be granted an exception to the use of the MELD score if they achieve the Milan criteria and do not have T1 stage HCC macro-vascular invasion of main portal vein or hepatic vein, extra-hepatic metastatic disease, an AFP >1000 which does not respond to treatment to achieve an AFP below 500, or ruptured HCC. Patients who have been downstaged following locoregional therapy or immunosuppressive therapy are eligible for the MELD exception.

Unfortunately, the shortage of available cadaveric organs limits the availability of liver transplantation as an option for the treatment of hepatocellular carcinoma. Expanding the donor pool through the use of organs from margin donors who are older, have diabetes or other medical conditions which affect liver function, and the increased use of living donors are being explored as well as the potential use of xenotransplantation to address the shortage of organs.13,18

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References

  1. National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatocellular Carcinoma. Version 1.2024 — April 9, 2024.
  2. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30(6):1434–1440. doi:10.1002/hep.510300629
  3. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208–1236.
  4. Zhou JM, Zhou CY, Chen XP, Zhang ZW. Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion: a prospective cohort study. World J Gastrointest Oncol. 2021;13(12):2190–2202.
  5. Liu H, Hu FJ, Li H, Lan T, Wu H. Anatomical vs nonanatomical liver resection for solitary hepatocellular carcinoma: a systematic review and meta-analysis. World J Gastrointest Oncol. 2021;13(11):1833–1846.Neoptolemos JP, Stocken DD, Bassi C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 2010; 304:1073–81.
  6. Famularo S, Ceresoli M, Giani A, et al. Is it just a matter of surgical extension to achieve the cure of hepatocarcinoma? A Meta-analysis of propensity-matched and randomized studies for anatomic versus parenchyma-sparing liver resection. J Gastrointest Surg. 2021;25(1):94–103.
  7. Famularo S, Di Sandro S, Giani A, et al. Long-term oncologic results of anatomic vs. parenchyma-sparing resection for hepatocellular carcinoma. A propensity score-matching analysis. Eur J Surg Oncol. 2018;44(10):1580–1587.
  8. Tabrizian P, Holzner ML, Mehta N, et al. Ten-Year Outcomes of Liver Transplant and Downstaging for Hepatocellular Carcinoma. JAMA Surg.2022;157(9):779–788.
  9. Mazzaferro V, Regalia E, Doci R, Aet al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996 Mar 14;334(11):693-9.
  10. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001 Jun;33(6):1394-403.
  11. Yao FY, Xiao L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007 Nov;7(11):2587-96.
  12. Mazzaferro V, Llovet JM, Miceli R, et al; Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009 Jan;10(1):35-43. doi: 10.1016/S1470-2045(08)70284-5.
  13. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021 Jan 21;7(1):6.
  14. Kulik L, Heimbach JK, Zaiem F, et al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta-analysis. Hepatology. 2018 Jan;67(1):381-400.
  15. Yao FY, Mehta N, Flemming J, et al. Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria. Hepatology. 2015 Jun;61(6):1968-77.
  16. Cucchetti A, Serenari M, Sposito C, Di et al. Including mRECIST in the Metroticket 2.0 criteria improves prediction of hepatocellular carcinoma-related death after liver transplant. J Hepatol. 2020 Aug;73(2):342-348. 
  17. Halazun KJ, Tabrizian P, Najjar M, F, et al. Is it Time to Abandon the Milan Criteria?: Results of a Bicoastal US Collaboration to Redefine Hepatocellular Carcinoma Liver Transplantation Selection Policies. Ann Surg. 2018 Oct;268(4):690-699.
  18. Cross-Najafi AA, Lopez K, Isidan A, et al. Current Barriers to Clinical Liver Xenotransplantation. Front Immunol. 2022 Feb 23;13:827535.
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