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Page 2 of 10 Sullivan et al. Hepatoma Res 2018;4:68 I http://dx.doi.org/10.20517/2394-5079.2018.95

liver damage due to toxins like aflatoxin. Chronic liver disease caused by HCV is a significant contributor
to the rising trend in Western countries although widespread adoption of effective anti-hepatitis C
treatments using direct antiviral agents is beginning to reduce the number of HCV-related HCC cases.
Yet, a much larger threat stemming from non-alcoholic steatohepatitis (NASH) will continue to promote
the incidence of HCC worldwide as the obesity pandemic reaches all corners of the globe. Unlike those
with cirrhosis secondary to viral hepatitis or alcohol abuse, the surveillance for HCC in the setting of non-
cirrhotic NASH remains uncertain and without established guidelines. Much effort is focused on finding
cost-effective methods such as ultrasound evaluation and serum alpha-fetoprotein (AFP) measurement
for early cancer detection in this high-risk group with the understanding that the stage at which HCC is
diagnosed strongly influences the outcome of the disease.

As the majority of HCCs remain confined to the liver without distant metastases at the time of diagnosis,
liver-directed loco-regional approaches are the mainstay of current treatments. Over the last two decades,
the field has witnessed remarkable advances in many areas involving surgery, interventional radiology,
radiation oncology, and medical oncology, which are re-shaping the landscape of HCC treatments. In
this review, we will highlight progress made in minimally invasive techniques that are currently in use,
with the objective of comparing their efficacy based on available evidence. Due to the wide-ranging
disciplines and technical demands of individual treatment modalities, we strongly endorse an up-front
multi-disciplinary discussion for every case of newly diagnosed HCC. In our Liver Tumor Clinic at the
University of Washington, each patient is provided with a consensus recommendation from our multi-
disciplinary group consisting of surgeons, radiologists, interventional radiologists, medical oncologists,
and radiation oncologists. This approach is continued longitudinally to ensure the most appropriate
management given the high risk of recurrent disease. While many patients are considered for liver
transplantation, only a limited number undergo such procedure due to organ availability and variable
drop-out rates. For those with good liver reserve and limited tumor burden, definitive loco-regional
therapies provide excellent disease control. Here, we will summarize recent developments in minimally
invasive modalities and their relative efficacy in the treatment of HCC.

ADVANCES IN LIVER-DIRECTED THERAPIES
Minimally invasive techniques for hepatic resection
Surgical resection has remained the gold standard for treatment of localized hepatocellular carcinoma
in patients with good liver reserve (i.e., Child’s A, B7) and without significant portal hypertension (i.e.,
hepatic venous pressure gradient < 10 mmHg, platelet count > 100,000/μL). Other factors to be considered
include the tumor stage [usually Barcelona Clinic Liver Cancer (BCLC) 0, A], tumor biology, and patient’s
medical comorbidities. The presence of vascular invasion by the tumor and high AFP levels are predictors
of poor outcome, and such cases should be thoroughly discussed by a multi-disciplinary tumor board
before deciding on surgical resection.

Traditionally, hepatic resection has been performed as an open operation using a variety of abdominal
incisions, which are associated with major morbidities. Advances in surgical technique including
the application of minimally invasive approaches have significantly reduced morbidities following
hepatectomy. Laparoscopic hepatobiliary surgery carries the same advantages of minimally invasive
surgery in all other realms, namely decreased length of hospitalization, reduced wound complications,
and improved postoperative pain, which translate to faster resumption of normal activities. Another
notable benefit of laparoscopic hepatic surgery is the tamponade effect created by the carbon dioxide
insufflation to reduce hemorrhage from hepatic venous branches. Placement of patient in reverse
Trendelenburg position also aims to minimize blood loss by decreasing venous pressure. Early reports of
laparoscopic hepatectomy confirmed that the approach was safe with minimal mortality and produced
[3-5]
comparable overall survival (OS) and disease-free survival (DFS) to open hepatectomy . In cirrhotic