Left hepatectomy extended to paracaval segment and anterior vena cava wall, with autologous venous graft reconstruction of middle hepatic vein under veno-venous bypass and “in situ” hypothermic liver perfusion: a surgical technique

Introduction

Background

Surgical resection is the gold standard for the treatment of intrahepatic cholangiocarcinoma (ICC), whenever possible. Five-year overall survival (OS) rate after resection ranges from 30% to 50% (1), while patients unsuitable for resection have a median survival of less than 12 months with a 5-year survival rate of 5–10% (2).

In the case of a particular size, position and invasiveness of the lesions an R0 resection may be difficult to achieve. Patients with involvement of the inferior vena cava (IVC), the hepatic veins or both were usually considered not suitable for surgical resection because of high risks of bleeding or air embolism (3).

Rationale

In well-selected patients and in high-volume centers, due to improvements in surgical techniques and perioperative management, an aggressive surgery that may require vascular resection-reconstruction appears to be a reasonably safe and feasible approach (3-5). When a major vascular resection is considered, several procedures have been proposed over the years including “ex-situ”, “ante situm” and “in situ” liver resection with or without the use of veno-venous bypass (VVB) or cold liver perfusion (3,6-9). However, in order to minimize blood loss, liver and abdominal organ damage, total vascular exclusion (TVE) associated with VVB and in situ hypothermic liver perfusion may be used (6,7,9,10).

Objective

This paper describes a liver resection with reconstruction of the vena cava (by a direct suture) and middle hepatic vein (utilizing the left portal branch harvested from left hemi-liver) using a VVB and hypothermic liver perfusion. The surgical procedure was performed in the Careggi University Hospital, tertiary center of Florence, Italy. The first operator is a certified skilled surgeon with liver transplantation experience. We present this article in accordance with the SUPER reporting checklist (available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-80/rc).

Preoperative preparations and requirements

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of anonymized personal data for scientific purposes. A copy of the written consent is available for review by the editorial office of this journal.

A 70-year-old woman with alcohol abuse history presented for an incidental diagnosis of a liver mass after an abdominal ultrasound evaluation. In her past medical history, there were also diabetes and hypertension. Despite a weight loss of 3 kg in the previous 6 months, her body mass index was 26 kg/m². The American Society of Anesthesiologists (ASA) score was 2.

The liver mass was located in the apical portion of segment I and its major diameter was 5.5 cm. Following an evaluation that included an abdomen computed tomography (CT) scan and magnetic resonance imaging, the presence of a neoplastic lesion infiltrating the anterior wall of the vena cava and the middle/left hepatic vein was confirmed. A needle biopsy resulted positive for an ICC on the top of macrovesicular steatosis of liver parenchyma. For this reason, in order to evaluate the liver functionality, an indocyanine green retention rate test was performed and the result was 10%.

A left hepatectomy extended to the segment I and the right paracaval portion (the so-called segment IX) along with the resection of the anterior wall of the vena cava and the middle hepatic vein was planned. Due to the steatotic infiltration, the reconstruction of the middle hepatic vein seemed therefore advisable to preserve the functionality of the liver at its best, postoperatively. As shown in Figure 1, the length of a vein graft used to fill the defect after the foreseen middle hepatic vein resection was 5.01 cm. Since the tumor did not infiltrate the hilum, we thought that the left branch of the portal vein could be used to fill the defect as shown in Figure 2. We also thought that the length of the procedures might exceed 60 minutes of TVE of the liver. For these reasons, according to Azoulay (5,6), we decided to perform the resection using a VVB and in situ cold liver perfusion.

Figure 1 Image from a contrast-enhanced abdominal magnetic resonance imaging scan. The length of a vein graft to be used to fill the defect after the foreseen middle hepatic vein resection was measured, and it was 5.01 cm.

Figure 2 Image from a contrast-enhanced abdominal magnetic resonance imaging scan. Since the tumor did not infiltrate the hilum, the left branch of the portal vein could be used to fill the defect. The left portal vein branch to be used for substitution of the middle hepatic vein measures in fact 3.03 cm of the proper left plus 2.18 cm of the Rex sinus.

Step-by-step description

The right radial artery was cannulated for hemodynamic monitoring. A central line was also inserted into the right internal jugular vein in order to monitor the central venous pressure.

A Mercedes-type incision was performed. No signs of extrahepatic diffusion were identified. The liver was completely mobilized and an intraoperative ultrasound was performed in order to confirm the infiltration of the middle and left hepatic veins and of the vena cava. Due to the presence of a nodular appearance in the liver, an intraoperative frozen section evaluation of the liver parenchyma was performed, in order to exclude the presence of cirrhosis, and it showed a macrovesicular steatosis. The liver was detached from the vena cava up to the level of its apparently infiltrated portion tying and cutting small hepatic veins. Cholecystectomy was performed. A lymphadenectomy of lymph nodal stations 6, 7, 8, 12 and 13 was performed. The common, right and left hepatic artery was then dissected, the left divided and subsequently cannulated in its proximal stump using a laparoscopic cholangiography catheter (14 fr) inserted and tied in order to perform a right liver hypothermic infusion of cold solution. The left portal vein was completely isolated and the branches for segments IV, III, II and I were separately tied and cut without a single distal ligation. The left portal vein was then transected and sutured with 5-0 Prolene running suture at the portal bifurcation. All the length of the harvested left portal branch along with the Rex sinus was stored in heparinized cold saline and subsequently utilized for substitution of the middle hepatic vein.

We did not consider the harvesting procedure on the specimen removed because in our opinion the technique we used required less time to get the vein graft ready to replace the middle hepatic vein, in order to have less liver ischemic time.

After heparin administration, the right saphenous vein, the inferior mesenteric vein and the left axillary vein were isolated and cannulated for the VVB using the bio-pump in order to preserve the hemodynamic stability and to preserve renal function as much as possible. TVE was started clamping the portal vein and the proper hepatic artery, and subsequently the IVC infra and supra-hepatic (Figure 3).

Figure 3 Typical veno-venous bypass setup used in orthotopic liver transplantation. Extracorporeal circulation is performed by a means of a Bio-Pump. The IVC is cannulated with an access through the right saphenous vein, while the portal system is drained via a cannulation of the inferior mesenteric vein. The blood is reinfused in the superior vena cava through the cannulation of the left axillary vein. IVC, inferior vena cava.

Hypothermic perfusion of the liver was then started with Ringer lactate solution chilled to 4 ℃ and a cavotomy on the anterior wall of the vena cava was performed to “vent out” the perfusate. Some saline ice slush was put around the right liver (Figure 4). Liver parenchyma was then transected on the left of the Cantlie line and middle hepatic vein using kellyclasia. Proximal to the point where the middle hepatic vein was infiltrated, the vein was divided and parenchymal transection was continued on the right margin of the middle hepatic vein at a safe distance from the tumor. We also considered an extended left hepatectomy including segments V and VIII but the condition of the liver (unhealthy for fatty infiltration) was at risk for liver failure. For this reason, we opted for a more conservative resection, but still radical with a more than 1 cm resection margin.

Figure 4 The ‘in situ’ hepatic cold perfusion using Ringer’s lactate at 4 ℃. This is achieved by cannulating the proximal left hepatic artery stump and performing a transverse cavotomy to vent-out the perfusate. IVC, inferior vena cava.

The middle-left hepatic vein trunk was cut at its caval confluence. Dissection was completed with the resection of the infiltrated part of the vena cava, and since the defect was not too large, directly repaired with a 4/0 prolene running suture. The middle hepatic vein was reconstructed with a “jump” graft using the left portal vein that was previously harvested and sutured with two 5/0 Prolene running sutures in an end-to-end fashion.

At the end of vascular reconstruction, the liver was perfused through the artery catheter with a 5% glucose solution at room temperature. The perfusate and the blood from portal and arterial de-clamping was vented out from the Nelaton catheter left through the caval suture, then it was removed and the caval suture eventually tied. The caval clamps were removed and the extracorporeal assistance was stopped, the saphenous and the inferior mesenteric veins were ligated, while the axillary vein was suture repaired. The anticoagulant was then reversed with protamine sulfate. The estimated blood loss was 700 cc. The duration of TVE of the liver and hypothermic perfusion lasted 40 minutes and the total time of surgery was 460 minutes. During the operation, 4 units of fresh plasma were infused. The procedure is summarized in the video attached to the manuscript (Video 1).

Postoperative considerations and tasks

After surgery, the patient was monitored in the ICU until the postoperative day (POD) 9. Mechanical ventilation was stopped and vasoactive drugs were progressively reduced within POD 1. On POD 7, a right pleural effusion was percutaneously drained. The postoperative course was also characterized by a transient elevation of alanine transaminase (ALT) and total bilirubin showing the development of a mild and transient hepatic failure. Ascites was treated with diuretics and albumin infusion. A therapy with low-molecular-weight heparin was daily administered.

The patient was discharged on POD 20 with oral diuretic therapy with progressive tapering.

The final histopathological response revealed a grade 2 ICC of 65 mm of maximum diameter with negative lymph nodes. The resected vena cava wall did not show infiltration as did instead showed the middle hepatic vein. Parenchymal resection margins were tumor-free.

Adjuvant chemotherapy was not performed due to R-0 surgery and patient global performance status.

From the date of surgery in 2014 the 5-year follow up was negative till the end, in 2019. The patient had been in good clinical condition with normal liver function tests, patent middle hepatic vein and disease-free remnant liver.

In September 2022, due to anemia, she performed a contrast medium abdomen CT scan which revealed a liver mass suspicious for neoplasm. After a biopsy, the histology reported cholangiocarcinoma.

Due to the supervening cirrhosis which eventually derived from steatosis, previously documented on intraoperative histology, and five years later, we can consider this neoplasm as a possible new primary neoplasm. In our opinion, it justifies such aggressive surgery.

The subsequent multidisciplinary board discussion decided for palliative treatment, consequently, positioning of transjugular intrahepatic portosystemic shunt (TIPS).

The patient eventually died in early 2023.

Tips and pearls

In our experience, the use of “in-situ” hypothermic liver perfusion under VVB during prolonged TVE, in expert hands resulted feasible and safe.

Furthermore the use of an autologous graft for venous reconstruction, harvested from the healthy part of surgical specimen, is possible and may avoid the use of other autologous, allogenic or synthetic grafts.

Discussion

Surgical highlights

The highlights of our procedure are the use of VVB during TVE, the cold perfusion of liver to extend the liver ischemic time and the guarantee of a good venous outflow thanks to an autologous venous graft from the resected specimen. Our aim is to describe an advanced surgical technique for treating liver tumors, with vascular infiltration with an overview of the relative literature.

Strengths and limitations

The main strength and novel aspect of our procedure is the reconstruction of the middle hepatic vein using a harvested left portal vein branch from the resected parenchyma as autologous graft.

The main limitation of our procedure is relative to the final histopathological report. In fact it showed no infiltration of the IVC. In the review of Zhou et al., they reported 62% of actual IVC infiltration compared to the preoperative evaluation. It underlines the difficulties in the correct preoperative imaging and intraoperative evaluation (3). Some authors suggest detaching the tumor from IVC (8) but this behavior may be related to severe complications such as tumor rupture and cell dissemination and major bleeding (3).

It is necessary to specify that it is not uncommon that the vein wall, apparently judged macroscopically infiltrated intraoperatively, can result not infiltrated at the final histology due to peritumoral inflammation/adhesions.

Comparison with other surgical techniques and researches

Hepatic malignant tumors with the involvement of IVC or hepatic veins are associated with a poor prognosis (3). However, during the last 20 years, improvements in surgical technique associated with ameliorations in the perioperative management of patients allowed a widening in surgical indication in complex cases. Nevertheless, postoperative outcomes became progressively better even when a major vascular reconstruction is needed (6,7).

In a systematic review including 258 patients who underwent a liver resection associated with IVC resection with evaluated long-term outcomes, Zhou et al. analyzed the safety and effectiveness of such aggressive surgery. They reported a morbidity rate of 43% with a 26% of liver failure rate after surgery with a global 30-day mortality of 5% and a 5-year OS of 37% in the case of ICC. They concluded that, even in the presence of bias and absence of alternative curative treatments, both mortality and OS rates were acceptable in such complex surgery (3). These results are consistent with the results of other published papers (2,11,12). Furthermore, outcomes of patients undergoing also a vascular resection are comparable with those who receive only a liver resection (2,3).

When reconstruction of hepatic veins or vena cava is required, in order to reduce blood loss, a liver TVE is routinely used. Furthermore, excluding the liver from circulation may cause hemodynamic instability and, therefore, a VVB is usually required. Moreover, splanchnic organ congestion may cause ischemia and, consequently, this may be associated with a chance of reperfusion damage. In order to prevent hemodynamic instability during TVE, a VVB with bio-pump is often associated. Despite the several advantages of VVB with bio-pump such as better myocardial oxygenation and kidney function preservation, there are some disadvantages such as a higher risk of bleeding and vascular complications (4). However, several papers report liver resections associated with vascular reconstructions performed without VVB with similar outcomes (8,13).

A normal liver may tolerate warm ischemia for up to 90 minutes. However, reperfusion injury on the liver remnant with the production of reactive oxygen species may significantly worsen postoperative outcomes (4). Hypothermic liver perfusion may reduce liver injury thus prolonging the tolerance to TVE, especially in cirrhotic livers (6-8). In the present case, the intraoperative biopsy did not show cirrhosis but the presence of severe liver steatosis which is a recognized negative factor for postoperative outcomes (14). Azoulay et al. (7) compared TVE with or without hypothermic liver perfusion: when TVE is longer than 60 minutes, hypothermic perfusion is associated with better outcomes in terms of liver and renal function with a lower morbidity rate (6). Another approach to liver and IVC surgery involving TVE consists, according to Azoulay et al. (15), in maintaining caval flow with a side clamping of the IVC at the outlet of the suprahepatic veins, while performing a cold perfusion of the residual liver by packing a temporary portocaval shunt. This avoids performing a VVB. This possibility would also have been useful in our case, in relation to the non-involvement of the anterior wall of the IVC on final histological examination. Anyway we were uncertain about the tumor’s involvement with the vena cava wall, the middle hepatic vein, or both. As a result, we opted for classic TVE with VVB, which would enable us to perform any type of vascular reconstruction, including patch reconstruction or prosthetic substitution of the IVC.

At the end of the resection, liver rewarming may produce coagulopathy and, consequently, blood loss (16).

The choice of liver perfusate is important. In the present case, Ringer’s solution was used. The University of Wisconsin solution has a high potassium concentration leading to possible cardiac arrhythmia if absorbed, while Celsior solution, a more recent perfusate, seems to be easier to handle than U.W. and certainly superior to Ringer’s solution (17).

“Ex situ” hypothermic liver resection was previously reported (8). Parenchymal resection and vessel reconstruction may be performed without the pressure of time. Some Authors advocate a higher rate of R0 resections with this approach (8). On the other hand, with this technique a complete division of the liver pedicle is necessary with all the possible related morbidities to the anastomoses, and the reported mortality rate raises up to 28% (6,7). At present, this technique is almost abandoned except in cases of extensive vascular infiltration (17). Something between the “in situ” and “ex-situ” techniques is the “ante-situm” technique where a complete mobilization of the liver from the retroperitoneum with the division of the hepatic veins from IVC is performed in order to rotate or to pull the liver out of the abdomen to have an optimal exposure of the liver structures (18,19). Even in the most recent literature, it is possible to appreciate how this technique has been successfully implemented (20).

In the present case, there was a complete infiltration of the middle hepatic vein for a tract of about 5 cm while the vena cava seemed infiltrated for a less than 2 cm tract. The vena cava was directly repaired, while the middle hepatic vein was reconstructed using the left portal vein from the resected specimen as a graft. Regarding the choice of the graft, we did consider using other autologous grafts, but we were unsure whether it would be safer and easier than the technique we employed.

In case of vein defects smaller than 2 cm, a direct suture may be performed. On the contrary, when the defect is larger than 2 cm, or when at least one-half of the vein circumference is involved, a graft should be used in order to reduce the chance of vein narrowing (3). Autologous or homologous grafts (peritoneal patch) are preferable because they are less thrombogenic and theoretically have greater resistance to infections when compared to synthetic grafts, but their utilization is not always technically possible and they may have a greater risk of outflow problems after some months due to degeneration (3). Actually, Dacron^® prosthetic grafts are seldom used while polytetrafluoroethylene (PTFE) grafts are preferred (3). Their greater advantages are the freedom of length and a higher rate of long-term patency (21).

Implications and actions recommended

Thanks to the use of a vein harvest from the resected parenchyma as autologous graft, this technique has a lower risk of thrombosis than the prosthetic implant, and it is also less invasive than taking a venous graft from other parts of the body such as the internal jugular, left renal or iliac veins.

This technique is, to our knowledge, not reported in literature before.

Our work could inspire a new approach to the management of liver tumor vascular infiltration.

Conclusions

This case report suggests that a major liver resection with complex vascular reconstruction is safe and feasible using TVE, VVB and hypothermic liver perfusion. An autologous vein graft, harvested from the specimen vein, may be used to reconstruct the infiltrated vein. With the diffusion of these vascular surgical techniques, accomplished with good perioperative outcomes, a greater number of curatively resected patients may be expected in the future.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the SUPER reporting checklist. Available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-80/rc

Peer Review File: Available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-80/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-80/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of anonymized personal data for scientific purposes. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Doussot A, Gonen M, Wiggers JK, et al. Recurrence Patterns and Disease-Free Survival after Resection of Intrahepatic Cholangiocarcinoma: Preoperative and Postoperative Prognostic Models. J Am Coll Surg 2016;223:493-505.e2. [Crossref] [PubMed]
2. Reames BN, Ejaz A, Koerkamp BG, et al. Impact of major vascular resection on outcomes and survival in patients with intrahepatic cholangiocarcinoma: A multi-institutional analysis. J Surg Oncol 2017;116:133-9. [Crossref] [PubMed]
3. Zhou Y, Wu L, Xu D, et al. A pooled analysis of combined liver and inferior vena cava resection for hepatic malignancy. HPB (Oxford) 2017;19:768-74. [Crossref] [PubMed]
4. Balci D, Ozcelik M, Kirimker EO, et al. Extended left hepatectomy for intrahepatic cholangiocarcinoma: hepatic vein reconstruction with in-situ hypothermic perfusion and extracorporeal membrane oxygenation. BMC Surg 2018;18:7. [Crossref] [PubMed]
5. Hemming AW, Reed AI, Langham MR Jr, et al. Combined resection of the liver and inferior vena cava for hepatic malignancy. Ann Surg 2004;239:712-9; discussion 719-21. [Crossref] [PubMed]
6. Azoulay D, Eshkenazy R, Andreani P, et al. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann Surg 2005;241:277-85. [Crossref] [PubMed]
7. Azoulay D, Lim C, Salloum C, et al. Complex Liver Resection Using Standard Total Vascular Exclusion, Venovenous Bypass, and In Situ Hypothermic Portal Perfusion: An Audit of 77 Consecutive Cases. Ann Surg 2015;262:93-104. [Crossref] [PubMed]
8. Dubay D, Gallinger S, Hawryluck L, et al. In situ hypothermic liver preservation during radical liver resection with major vascular reconstruction. Br J Surg 2009;96:1429-36. [Crossref] [PubMed]
9. Reiniers MJ, Olthof PB, van Golen RF, et al. Hypothermic perfusion with retrograde outflow during right hepatectomy is safe and feasible. Surgery 2017;162:48-58. [Crossref] [PubMed]
10. Emond JC, Kelley SD, Heffron TG, et al. Surgical and anesthetic management of patients undergoing major hepatectomy using total vascular exclusion. Liver Transpl Surg 1996;2:91-8. [Crossref] [PubMed]
11. Malde DJ, Khan A, Prasad KR, et al. Inferior vena cava resection with hepatectomy: challenging but justified. HPB (Oxford) 2011;13:802-10. [Crossref] [PubMed]
12. de Mathelin P, Cusumano C, Foguenne M, et al. Extended Right Hepatectomy to Inferior Vena Cava Under Total Vascular Exclusion, Veno-Venous Bypass and In Situ Hypothermic Perfusion of the Future Liver Remnant. Ann Surg Oncol 2023;30:8006. [Crossref] [PubMed]
13. Stättner S, Yip V, Jones RP, et al. Liver resection with concomitant inferior vena cava resection: experiences without veno-venous bypass. Surg Today 2014;44:1063-71. [Crossref] [PubMed]
14. Belghiti J, Hiramatsu K, Benoist S, et al. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg 2000;191:38-46. [Crossref] [PubMed]
15. Azoulay D, Salloum C, Allard MA, et al. Complex Hepatectomy Under Total Vascular Exclusion of the Liver Preserving the Caval Flow with Portal Hypothermic Perfusion and Temporary Portacaval Shunt: A Proof of Concept. Ann Surg Oncol 2024;31:6485-94. [Crossref] [PubMed]
16. Cauchy F, Brustia R, Perdigao F, et al. In Situ Hypothermic Perfusion of the Liver for Complex Hepatic Resection: Surgical Refinements. World J Surg 2016;40:1448-53. [Crossref] [PubMed]
17. Dinant S, Roseboom HJ, Levi M, et al. Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution. Langenbecks Arch Surg 2009;394:143-50. [Crossref] [PubMed]
18. Mehrabi A, Fonouni H, Golriz M, et al. Hypothermic ante situm resection in tumors of the hepatocaval confluence. Dig Surg 2011;28:100-8. [Crossref] [PubMed]
19. Yamamoto Y. Ante-situm hepatic resection for tumors involving the confluence of hepatic veins and IVC. J Hepatobiliary Pancreat Sci 2013;20:313-23. [Crossref] [PubMed]
20. Addeo P, de Mathelin P, Paul C, et al. Ante Situm Liver Resection for Tumors Invading the Inferior Vena Cava Hepatic Vein Confluence. Ann Surg Oncol 2024;31:7892-3. [Crossref] [PubMed]
21. Orimo T, Kamiyama T, Yokoo H, et al. Usefulness of artificial vascular graft for venous reconstruction in liver surgery. World J Surg Oncol 2014;12:113. [Crossref] [PubMed]