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Ruff et al. Hepatoma Res 2023;9:17 https://dx.doi.org/10.20517/2394-5079.2023.18 Page 7 of 12

[5]
select instances .

Vascular Resection
A subset of patients with ICCA may need a concomitant vein resection in order to achieve a satisfactory
oncology outcome; however, this may increase morbidity/mortality. In a multi-institutional study of 1,087
patients who underwent curative intent hepatectomy for ICCA, Reames et al. reported that 128 (11.8%)
patients required a major vascular resection (16.4% inferior vena cava resection, 76.6% portal vein resection,
and 7% a combined resection) . Interestingly, the authors noted that a major vascular resection did not
[53]
increase the risk of complication or postoperative mortality. In addition, there was no difference in median
recurrence-free or overall survival. Patients who required a vein resection were more likely to have been
treated with neoadjuvant systemic therapy. In another retrospective review of 270 patients with ICCA, 31
patients (11.5%) required a vascular resection (15 portal vein resections, 16 inferior vena cava resections) .
[54]
In this study, patients who underwent a vascular resection did have increased morbidity and mortality. Of
note, after adjusting for clinical and pathologic factors on multivariable analysis, vascular resection was not
associated with worse long-term outcomes. In addition, patients who underwent an R0 resection and had
no lymph node metastases yet required a vascular resection had equivalent survival to patients who did not
undergo a vascular resection; in addition, patients who had a vascular resection to achieve an R0 margin had
better survival than individuals who underwent an R1 resection. In yet another study, Ali et al. reported on
121 patients who underwent a major hepatectomy for ICCA and noted that 14 (12%) patients required
[55]
vascular resection (5 portal veins, 9 inferior vena cava) . There was no difference in postoperative
complications or median overall survival among patients who did or did not have a vascular resection. As
such, vascular resection should be considered for patients with ICCA if needed to achieve an R0 margin.
Patients should have good performance status and, in general, have successfully completed neoadjuvant
therapy without progression to ensure that the operation will provide an oncologic benefit. The addition of
vascular resection and reconstruction can increase operative morbidity, and these types of operative
procedures should be performed at high-volume centers.

Hepatic Artery Infusion Pump Therapy
For patients with locally advanced or unresectable ICCA, placement of a hepatic artery infusion pump
(HAIP) can provide local control and potentially downstage patients. HAIP allows for direct delivery of
chemotherapy to the liver, where it is preferentially distributed to the cancer cells through the hepatic artery
and metabolized prior to entering the systemic circulation. This allows for directed treatment of the liver
[56]
while diminishing the toxic side effects . HAIP has primarily been studied in metastatic colorectal cancer,
but has also shown promising results in early studies of patients with ICCA. In a study of 319 patients with
multifocal ICCA, 141 patients received a HAIP and 178 underwent resection . The 30-day postoperative
[56]
mortality rate was higher in the resection cohort. There was no difference in overall survival between the
two groups, even when stratified by number of lesions. In a retrospective study of patients with multifocal
ICCA, there was no difference in overall or progression-free survival between patients who underwent
intra-arterial therapy (transarterial chemoembolization, transarterial radioembolization, or HAIP)
[57]
compared to resection . However, patients who specifically underwent HAIP therapy were shown to have
improved overall survival (39 months) compared to those who underwent surgery (20 months). Finally, in a
single institution phase II trial, 38 patients with unresectable ICCA were given floxuridine and gemcitabine/
oxaliplatin through the HAIP. Four patients were able to be downstaged and undergo resection, while 58%
achieved an objective radiographic response and 84% achieved disease control . HAIP is a promising liver-
[58]
directed therapy that may help control disease growth and even downstage appropriately selected patients
so that they may undergo curative resection.