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Page 6 of 19 Hewitt et al. Hepatoma Res 2021;7:75 https://dx.doi.org/10.20517/2394-5079.2021.83

preoperative optimization techniques (i.e., portal vein embolization, locoregional and systemic therapies)
have safely expanded the candidates of potentially resectable patients and improved outcomes [53,83-88] .

Management of intrahepatic cholangiocarcinoma
Hepatectomy with negative margins and a regional lymphadenectomy of the porta hepatis while
maintaining an adequate liver remnant offers the best chance at long-term survival for patients with ICCA.
Once the abdomen is entered, a thorough evaluation of the abdominal cavity for metastatic disease and
resectability should be performed. If exploration reveals distant metastatic disease or lymph node disease
beyond the porta hepatis, the procedure should be aborted as these are contraindications to resection. The
liver should be fully evaluated with intraoperative ultrasound, specifically looking for multifocal hepatic
disease and proximity of the tumor to intrahepatic structures that may prohibit resection. Intraoperative
ultrasound utilization can change surgical management in up to one-third of cases . Traditionally,
[89]
multifocal ICCA represented metastatic disease and a contraindication to surgical resection. In a large
[90]
database study, Yin et al. examined 580 patients with multifocal ICCA and demonstrated significantly
improved median survival in patients that underwent resection compared with patients who were managed
non-operatively.

Patients with microscopically negative margins (R0 resection) have significantly better outcomes compared
[91]
with patients who had a resection with microscopically positive margins (R1 resection) . However, the
optimal negative margin width is unclear as studies provide conflicting data [91,92] . While major hepatectomy
is often required to completely excise ICCA, wedge resection or segmental resection is acceptable as long as
an R0 resection is achieved. Conversely, aggressive surgical approaches may be an option for highly selected
patients with otherwise unresectable tumors and good liver function treated at high-volume centers by
[93]
experienced surgeons and multidisciplinary care teams. Initially described by Dr. Raab et al. , ex vivo liver
resection techniques include in-situ, ante-situm, and ex-situ approaches, which require veno-venous bypass,
liver perfusion, and major vascular reconstruction. The technically demanding procedure has a high
complication and mortality rate and, when performed for CCA, can have a high tumor recurrence rate .
[94]
Overall, over 76% to 92% of patients with ICCA receive an R0 resection when taken to the operating room
with curative intent based on preoperative workup [91,92,95-97] .

Management of perihilar cholangiocarcinoma
Surgical resection of PCCA begins in a similar fashion to ICCA resection with abdominal exploration for
metastatic disease and tumor evaluation with intraoperative ultrasound to confirm resectability. Particular
attention should be paid to potential tumor involvement of the contralateral bile ducts and vascular
structures.

Microscopically negative margins are critical to long-term outcomes for patients with PCCA as 5-year OS
drops form between 27%-45% for patients that received an R0 resection compared to 0%-23% for patients
with an R1 or R2 resection [12,54,98-100] . Aggressive surgical management is warranted in patients with adequate
functional FLR. The intraoperative frozen section of the proximal ductal margin can be used to guide
intraoperative decision-making. Patients that achieved R0 resection after re-resection of a positive frozen
section margin had comparable survival outcomes as patients initially with R0 resection while patients with
[101]
R1 resection had significantly decreased survival . Complete resection of PCCA includes removal of the
involved biliary tree, associated hemi-liver, and porta hepatis lymphadenectomy. The central location of
PCCAs generally requires a caudate lobe resection. The contralateral bile duct is usually reconstructed with
a Roux-en-Y hepaticojejunostomy. There may be tumors that require an extended liver resection and/or
vascular resection to achieve negative margins. Extended hepatectomy (e.g., trisectionectomy) and vascular
resection have acceptable outcomes when performed at specialized centers by high-volume surgeons and