Eight-Year Survival Following Left Hepatic Trisectionectomy With Combined Hepatic Artery And Portal Vein Resection For Advanced Perihilar Cholangiocarcinoma

Haitham Triki (  haitham.triki@hotmail.com ) Rennes 1 University: Universite de Rennes 1 https://orcid.org/0000-0002-9915-9219 Heithem Jeddou Rennes 1 University: Universite de Rennes 1 Stylianos Tzedakis Rennes 1 University: Universite de Rennes 1 Dihia Belabbas Rennes 1 University: Universite de Rennes 1 Solène Florence Kammerer-Jacquet Rennes 1 University: Universite de Rennes 1 Laurent Sulpice Rennes 1 University: Universite de Rennes 1 Karim Boudjema Rennes 1 University: Universite de Rennes 1


Introduction
The main goal of surgery for perihilar cholangiocarcinoma (PHC) is to achieve complete resection with negative margins. Due to the intimate anatomical relationship between the biliary con uence and the vascular in ow at the hepatic hilum, the tumor can rapidly invade the portal vein and/or the hepatic artery. In some patients with advanced disease, extended hepatectomies with vascular resection and reconstruction are required to reach tumor-free margins. In the hands of an experienced surgeon, this surgery can be performed with acceptable morbidity and mortality [1]; however, oncological results remain controversial.
Herein, we report the case of a patient with exceptional survival over 8 years after left trisectionectomy combined with portal vein and hepatic artery resection for advanced PHC.

Case Report
A 65-year-old woman with no previous medical conditions presented with jaundice. Biological tests showed severe cholestasis. Abdominal ultrasound revealed intrahepatic bile duct dilatation and a at gallbladder. Abdominal computed tomography (CT) scan and magnetic resonance cholangiopancreatography (MRCP) showed a 30 mm tumor originating from the biliary convergence suggestive of perihilar cholangiocarcinoma (Fig. 1). The tumor was mainly left sided involving the con uence of the left lateral sectional bile ducts (B2, 3) and left medial sectional branches (B4). On the right side, the tumor reached the con uence of the right anterior and posterior sectoral branches. The con uence of segment 6 (B6) and segment 7 (B7) bile ducts was free from tumor invasion. Concerning vascular involvement, there was an anatomical variation with a common hepatic artery emerging from the superior mesenteric artery. The left hepatic artery was totally included in the tumor. The right hepatic artery had an intratumoral course over a length of 10 mm with slight stenosis. The bifurcation between the right anterior and right posterior sectoral arteries was tumor-free. The portal vein presented a modal distribution; its left branch was invaded by the tumor, resulting in total left hepatic atrophy. The tumor extended to the portal vein bifurcation, but the right axis remained patent. The right anterior and right posterior portal bifurcation remained tumor free. Chest CT showed no pulmonary extension.
This PHC was classi ed as Bismuth IV and type X of Rennes [2]. It was decided to perform left trisectionectomy, caudate lobectomy and resection of the main bile duct with simultaneous resection of the portal vein and right hepatic artery. A percutaneous transhepatic biliary drain was inserted into the right posterior sectoral bile duct for external drainage. Two weeks later, jaundice disappeared, and the bilirubin level was 25 µmol//l. There was no sign of infection, and the nutritional status of the patient was adequate. The future remnant liver volume (right posterior sector) was 40% of the total liver volume.
Intraoperative exploration using visualization, palpation and intraoperative color-Doppler ultrasound (IOUS) con rmed the preoperative ndings. Liver parenchyma transection was performed under intermittent pedicle and vena cava clamping of 26 min in total. The hepatic artery was reconstructed using an autologous saphenous vein graft interposed between the right posterior sectoral artery and the common hepatic artery. The reconstruction lasted 32 min. Portal vein reconstruction was performed with end-to-end anastomosis between the main portal vein and the right posterior sectoral vein, while the liver remained arterialized. IOUS con rmed the patency of the reconstructed vessels and the adequate vascularization of the right posterior segments. Intraoperative frozen section analysis of B6, 7 con uence revealed that margins were positive, imposing a more proximal section. B6 and B7 were then separated.
Biliary reconstruction using the Roux-en-Y jejunum limb was performed over the two separate segmental bile ducts. Transanastomotic drainage of both ducts was performed according to Volker's technique.
The operative time and intraoperative blood loss were 365 min and 800 ml, respectively. Postoperative outcomes were mainly marked by the occurrence of bilioma treated with cutaneous drainage and antibiotics. The patient was discharged on postoperative day 32.
Macroscopic analysis of the specimen showed a sclerosing tumor that adhered to both the portal vein and right hepatic artery. Histological examination showed moderately differentiated biliary adenocarcinoma invading surrounding adipose tissue. However, no microscopic invasion of the portal vein or of the right hepatic artery was revealed. The distance between the tumor and the wall of the portal vein was 0.41 mm (Fig. 2). Perineural invasion was present. Three lymph nodes were found in the lymphadenectomy specimen and were tumor free. All margins were negative. Eventually, the tumor was classi ed as pT2aN0M0, R0, or stage II according to the TNM staging of perihilar bile duct tumors (AJCC 8th edition).
The patient was included in the French phase III randomized trial PRODIGE 12 and received 12 cycles of adjuvant gemcitabine-oxaliplatin (GEMOX). She is now healthy with no sign of recurrence 8 years after surgery.

Discussion
PHC type X, according to the Rennes classi cation, is de ned by the invasion of the left lateral sectional bile duct con uence (B2, 3). In PHC type X, the left lobe cannot be preserved. Since the biliary con uence of the right and left hemi livers is also invaded by the tumor, the right hepatic artery is commonly invaded. Indeed, the biliary con uence is shifted on the right side of the hepatic hilum and at a close vicinity of the right hepatic artery [2]. Type X PHC includes Type IIIb and type IV of the Bismuth-Corlette classi cation.
Hepatic arterial involvement is traditionally considered a contraindication to resection. For such advanced PHC, major hepatectomy combined with arterial and portal resection remains the only possibility for obtaining negative margins, although in some earlier studies, it showed higher mortality rates compared to hepatectomy without vascular resection [3][4]. Currently, experience and advances in complex hepatic and vascular surgical techniques have led to more aggressive approaches with acceptable outcomes [1,3,5]. Nagino et al. reported a large series of 50 combined arterial and portal resections with a perioperative mortality of 2%. In this study, the rate of complications related to vascular reconstruction was low [1]. In another study, concomitant hepatic artery resection showed no signi cant differences in the overall incidence of postoperative complications compared to standard resection, except for postoperative liver abscess [5].
The brotic peritumoral response leads to the development of brous tissue that may or may not contain islets of tumor cells. Therefore, some tumors seem to macroscopically invade the portal vein or hepatic artery without any microscopic involvement. Nagino et al. found microscopic invasion of the resected portal vein and hepatic artery in 88% and 54%, respectively [1]. At the time of resection, tumor separation from the vessels should not be attempted to avoid the risk of R1 resection and vascular injury. For such advanced tumors, the "no touch" technique is recommended to increase the likelihood of R0 resection.
Vascular invasion is related to more advanced disease and is known as a poor prognostic factor. However, compared to unresectable tumors or resection with positive margins, combined portal vein and hepatic artery resection offers improved survival when feasible [1,[3][4][5].

Conclusion
Our case report demonstrates that extended hepatectomy with combined portal vein and hepatic artery resection is feasible and that such extended surgery is the only way to obtain an R0 margin and eventually prolong survival. Innovations and advances in surgical techniques should continue to improve the resectability and long-term survival for advanced PHCs.
Con ict of interest/Competing interests: The authors have no con icts of interest to declare.
Ethics approval: For this type of study formal consent is not required.
Consent to participate: Not applicable.
Consent for publication: The patient has consented to the submission of the case report for submission to the journal. Preoperative images of perihilar cholangiocarcinoma Bismuth IV and type X of Rennes. A. Magnetic resonance cholangiopancreatography (MRCP) in coronal plane T1-weighted sequence with gadolinium injection at 3 min shows tumoral extension on the left side beyond the con uence of the left lateral sectional bile ducts (B2-3) (white arrows). The tumor reaches the roof of the con uence between the right anterior and posterior sectoral branches (head arrow). B. 3D-MRCP sequence, MIP reconstruction (Maximum Intensity Projection) demonstrates that the con uence of the right posterior inferior branch