Page 15 - Read Online

Page 4 of 12 Ruff et al. Hepatoma Res 2023;9:17 https://dx.doi.org/10.20517/2394-5079.2023.18

patients with high-risk tumors (poorly differentiated, vascular invasion, extrahepatic lymphadenopathy,
large tumor size, high tumor burden, KRAS status, multifocality), chemotherapy may provide a “test of
time” to better elucidate the underlying biology and help select patients who will benefit the most from an
[27]
operation . Specifically, patients who progress on chemotherapy would likely have progressed with or
without an operation. Neoadjuvant chemotherapy affords these patients the opportunity to avoid a large
operation that likely would not have changed their overall prognosis.

Surgical considerations
Staging Laparoscopy
Peritoneal metastatic disease or locally advanced/invasive disease is not always appreciated on preoperative
imaging. A staging laparoscopy at the start of the operation can avoid unnecessary laparotomies in patients
with occult metastatic disease. In a retrospective study, metastatic disease was detected in 29% of patients
with hepatobiliary malignancy, including ICCA, on staging laparoscopy. In turn, one in five patients was
[28]
spared a laparotomy and the associated increase in hospital length-of-stay and morbidity . In a separate
study, 36% of patients who underwent a staging laparoscopy for CCA or gallbladder cancer had advanced or
unresectable disease . Even though a short amount of additional operative time is often required, staging
[29]
laparoscopy should be considered in patients with ICCA, given the high risk of occult metastatic disease or
unresectable disease. Laparoscopic ultrasound of the liver should also be performed at the time of surgery
for planning purposes and to help identify occult intrahepatic metastasis. Ultrasound is important to
evaluate the anatomic relationship between the ICCA tumor and major vascular structures within the liver.

Future Liver Remnant
An important preoperative consideration for ICCA is the patient’s functional status and future liver
remnant (FLR). Hepatectomy is a complex operation that stresses the body. Patients with multiple co-
morbidities may not have the physiologic reserve to recover well or cope with potential complications. After
the patient is deemed an appropriate candidate, it is crucial to ensure that the FLR is sufficient to prevent
postoperative hepatic insufficiency . Adequate FLR depends on the underlying functional status of the
[30]
liver (e.g., determined through Child-Pugh score and baseline laboratory tests). In addition to traditional
etiologies of liver damage (e.g., alcohol, hepatitis B, hepatitis C, non-alcoholic fatty liver disease), it is
important to also account for hepatic damage secondary to chemotherapeutic agents. An adequate FLR in
patients with a healthy liver typically is at least 20%, while patients with steatosis and/or cirrhosis often need
an FLR of 30% to 40% [31-37] . Liver volume can be calculated using computed tomography or MRI to
determine the postoperative FLR. In some cases, there may be a discrepancy between FLR volume and
postoperative liver function. Technetium-99m mebrofenin hepatobiliary scintigraphy is a quantitative test
that may be helpful in assessing FLR function . Quantitative liver function assessment with an indocyanine
[38]
green (ICG) clearance test can help predict hepatic functional reserve. A retention rate of 15 minutes has
been associated with post-hepatectomy liver failure . For patients that require a major hepatectomy with
[39]
suboptimal FLR, preoperative FLR modulation strategies, such as portal vein embolization or associating
liver partition and portal vein ligation for staged hepatectomy (ALPPS), can be employed to instigate
accelerated hypertrophy of the FLR to minimize the risk of postoperative hepatic insufficiency .
[38]
Minimally Invasive Approach
Minimally invasive surgery (MIS) has become the standard of care for many operations and is increasingly
being used for liver resection, including for benign lesions, as well as hepatocellular carcinoma, colorectal
liver metastases, and ICCA. The MIS approach often results in decreased postoperative pain, decreased
blood loss, fewer postoperative complications, and faster recovery time with shorter hospital length-of-
[40]
stay . In well selected patients with ICCA, laparoscopic liver resection (LLR) has comparable oncologic
outcomes to open resection. In well selected patients, LLR for ICCA may even be associated with decreased