Improving early return to function and minimizing complications are important considerations for patients with resectable cholangiocarcinoma (CCA), but data on minimally invasive liver surgery have been limited to single or multi-institutional retrospective studies. Of note, 2 randomized studies have shown that laparoscopic removal of colorectal liver metastases improved outcomes in complication rates, length of stay, and pain burden without compromising margin status compared with open surgery.1,2 However, long-term survival outcomes and return to intended oncologic therapy were shown to be similar between laparoscopic and open-surgery techniques.2,3 Biliary tract cancers (BTCs) have added challenges that include performing a lymphadenectomy, in which the American Joint Committee on Cancer guidelines recommend harvesting ≥6 lymph nodes. A large retrospective study in France found that laparoscopic surgery for intrahepatic CCA (iCCA) reduced blood loss and hospital length of stay compared with open surgery.4 However, significantly fewer clinicians performed a lymph node dissection using laparoscopy, and if they did, they were less likely to harvest the recommended 6 lymph nodes.4
Robotic surgery in BTC as an alternative surgical method to open and laparoscopic surgery is now a hot topic. Hop S. Tran Cao, MD, of MD Anderson Cancer Center, discussed this method in his presentation. Benefits to robotic surgery include a surgeon-controlled 3-dimensional camera with stable visualization, instrumentation that reduces tremors, a relatively easy learning curve, and utility in complex cases. A single-institution series showed that even with early experience, robotic surgery was used for more complex cases, larger tumors, and more major hepatectomies without compromising resection rates. Data from the National Cancer Database from 2010 to 2016 of patients who underwent a hepatectomy for iCCA demonstrated slightly reduced lengths of stay with robotic surgery compared with open and laparoscopic surgery; moreover, R0 resection rates were similar in all 3 groups.5 In addition, lymphadenectomy rates were lower with laparoscopy than with robotic surgery, and when performed, it was less likely that 6 lymph nodes were harvested.5 Overall, robotic surgery is more intuitive in nature and allows for a shorter learning curve with the possibility to improve oncologic outcomes; however, further follow-up and monitoring are needed to assess long-term results.
Only about 15% of BTCs are resectable at the time of diagnosis, with a 60% to 70% recurrence rate by 5 years.6 Because of this, the future of BTC treatment should involve the integration of targeted systemic therapy, locoregional treatment, and resection for patients with evidence of persistent disease or detection of minimal residual disease, as part of a multidisciplinary approach. Skye Mayo, MD, MPH, of Oregon Health & Science University (OHSU), discussed liver-directed therapy with hepatic arterial infusion (HAI) pumps for iCCA as a component of a multidisciplinary effort to treat BTC. He noted that HAI has historically been used at OHSU for select patients with locally advanced or multifocal iCCA to deliver floxuridine (FUDR) plus dexamethasone through the pump to the liver in combination with systemic therapy. FUDR undergoes extensive first-pass metabolism, resulting in significant concentration in the liver7,8; however, FUDR-mediated hepatic toxicity has been underreported, and treatments that minimize these toxicities may be more appropriate.
As the use of HAI pumps grows nationally, Dr Mayo described the necessary considerations to maximize responses and minimize toxicities in patients with unresectable iCCA, detailing 4 main goals when delivering high concentrations of chemotherapy to the liver. First, abnormal hepatic arterial anatomy must be identified and addressed to ensure the catheterized artery perfuses the entire liver. Second, all liver segments need to be perfused to ensure delivery of the drug to the entire hepatic parenchyma. Third, it is important to avoid extrahepatic perfusion, specifically to the pancreas and duodenum, and finally, the HAI delivery method needs to be durable. Although Dr Mayo emphasized the ease of surgically placing an HAI pump, he stressed the importance of addressing hepatic arterial anomalies, which may include requiring a cholecystectomy, dissecting out the hepatic arterial tree, and placing the catheter into the ligated gastroduodenal artery. When considering patient selection for HAI pumps, all major consensus guidelines recognize that patients with multifocal disease should not be considered for upfront resection and, therefore, may benefit from treatment with HAI and systemic therapy.9 A phase 2 trial of HAI with FUDR plus systemic chemotherapy in 38 patients with unresectable iCCA found that the 1-year overall survival was 90% with a median survival of 25 months.10 HELIX-1 is a phase 2 trial that investigated the integration of HAI with dose-reduced systemic therapy with FOLFIRINOX (folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin) in patients with unresectable iCCA.11 The first 5 patients had 100% disease control without biliary toxicity, which supported the feasibility for HELIX-2, a planned trial to investigate liver-directed therapy plus immunotherapy and chemotherapy.
A marked increase has been seen in the number of hepato-pancreato-biliary (HPB) surgeries performed, and data from the ACS NSQIP database show that overall morbidity from postoperative complications of HPB procedures is 28%. Although 1 in 5 patients will have serious postsurgical complications, mortality remains around 3%, as advanced techniques and experienced professionals are able to manage complications. In his presentation, Nipun Merchant, MD, from the University of Miami, described strategies to manage surgical complications. He stressed the importance of a thorough preoperative assessment of the patient as the principal strategy to prevent or mitigate complications. The feasibility of removing the tumor is an important consideration, along with liver quality, future liver remnant (FLR) volume, and the patient’s Eastern Cooperative Oncology Group performance status and comorbidities. Patients with elevated bilirubin are not candidates for surgery until they undergo endoscopic or percutaneous preoperative biliary drainage, which can decrease the risk of bacterial infection and sepsis.
Despite preoperative planning, surgical complications still occur and can include bleeding, bile leak, and postoperative hepatic insufficiency (PHI) or liver failure. To manage hemorrhage, the important preoperative considerations include blood inflow to the liver remnant left behind and understanding the hepatic vascular anatomy and the relationship of the tumor to the vasculature. Most of the bleeding occurs in the hepatic veins, which can be decreased with low central venous pressure anesthesia. Bile leaks are another frequent risk of surgery and occur more commonly in bile duct resection or reconstructions, extended or repeat hepatectomy, and intraoperative transfusion. Computed tomography or magnetic resonance imaging can be used preoperatively to determine the extent of the resection and the strategy to be used. Intraoperatively, surgeons may perform a cholangiogram by injecting contrast dye or air to detect leaks. Timely diagnosis and proper external drainage are important in managing bile leaks. Antibiotics can be used in the setting of sepsis or other infections, and endoscopic drainage or stent placement can be used when drain output does not decrease over time. One of the most devasting complications is PHI and liver failure. Early PHI is due to insufficient FLR volume or acute liver injury, whereas late PHI is due to insufficient FLR regeneration or intrinsic parenchymal injury. Preoperative planning is the best way to prevent PHI by calculating the FLR and ascertaining whether the liver remnant has the ability to regenerate. Portal vein embolization has also become useful in preventing PHI and increasing viability of liver remnants. Overall, postsurgical complications have significant consequences that can be managed with pre- and intraoperative techniques focused on prevention and planning.
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