Maren Schulze, Yasser Elsheikh, Markus Ulrich Boehnert, Yasir Alnemary, Saleh Alabbad,Dieter Clemens Broering

Organ Transplant Center of Excellence, King Faisal Specialist Hospital & Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia

Keywords:Living liver donor Innovation Robotic donor surgery Donor safety Minimally invasive donor surgery

ABSTRACT Background: Over the past two decades robotic surgery has been introduced to many areas including liver surgery.Laparoscopic liver surgery is an alternative minimally invasive approach.However, moving on to the complexity of living donor hepatectomies, the advantages of robotic versus laparoscopic approach have convinced us to establish the robotic platform as a standard for living donor hepatectomy.

Introduction

Minimally invasive liver surgery (MILS) is advancing, experience in robotic surgery is gaining in the USA, and Europe is catching up with Asian and Middle Eastern experiences[1].Robotic surgery is considered equally, if not superior to laparoscopic liver surgery.However, lack of access and training often compromises its progress.It is of logical consequence to offer MILS to every potential living liver donor in order to profit from less scarring, more abdominal wall integrity and better quality of life.

Large volume experience in living donor liver transplantation(LDLT) is still mainly limited to Asia and the Middle East.LDLT was primarily developed in the early 1990s to reduce waiting list mortality resulted from an insufficient deceased donor organ pool.In countries with restrictive views regarding brain death and deceased organ donation, LDLT rapidly became a high-volume and impactful procedure as it was the only readily available option to cure patients with advanced liver disease and cancer[2].Minimiz-ing harm to the donor led by Cherqui et al.[3]to complete the first laparoscopic donor left lateral sectionectomy (L-LLS) in 2002.In 2013 the first reports of purely laparoscopic donor hepatectomies(PLDH) for the right lobe were published by Soubrane et al.in France[4], Rotellar et al.in Spain[5], Han et al.in Korea[6]and Troisi et al.in Belgium[7]for left lobe donors.Currently, PLDH for full lobe donors is limited to high-volume centers in Korea and,some selected institutions in India and the West[2].Wider spread of PLDH has been slow, due to the prolonged learning curve and the occurrence of some major (Clavien-Dindo grade ≥III) complications during early experiences [8–10].

Fig.1.Evolution of donor hepatectomy techniques during the period of 2011-2022 ?.

Despite these early hurdles, all supporters of MILS acknowledge the undeniable benefits, regarding abdominal wall trauma, disfigurement and improved postoperative pain profiles[2].Supporters of minimally invasive donor hepatectomy (MIDH) were relieved when an alternative approach became available.In 2011 Giulianotti et al.who had developed extensive experience in robotic liver surgery, carried out the first robotic right lobe donor hepatectomy (RDH) at the University of Illinois-Chicago using the da Vinci robotic system [11,12].In 2016 Chen et al.[13]reported the first series of 13 cases of RDH.MIDH nowadvanced to two viable technical platforms[2].In recent years, the Hong’s group from Korea has still favored the laparoscopic approach [14,15].Several highvolume centers including Choi et al.and Rho et al.(Korea), Varghese (India) and King Faisal Specialist Hospital and Research Center(KFSHRC) in Riyadh (Saudi Arabia) reported larger robotic donor hepatectomy experiences [16–21].With growing experience, our center slowly abandoned most other approaches for donor hepatectomy (Fig.1).Here the results of 501 purely robotic donor hepatectomies (PRDH) realized during the last 4 years in our transplant center are presented.

Methods

Between November 2018 and January 2022, 501 fully robotic living donor hepatectomies were performed.This study was conducted in accordance with the ethical principles intheDeclaration ofHelsinki(20 0 0), the International Conference on Harmonized Tripartite Good Clinical Practice Guidelines, the policies and guidelines of the institution, and the laws of Saudi Arabia.

Donor and recipients’ outcomes were analyzed using the prospectively kept institutional database.Donor evaluation included blood group, full laboratory workup including screening for hepatitis A, B and C, cytomegalic (CMV), human immunodeficiency(HIV) and Epstein-Barr viruses (EBV), hemoglobin electrophoresis,tumor markers and parasitic infections.According to donor age,cardiac workup included echocardiography and pulmonary function tests.Females were subjected to pregnancy tests and mammography.Imaging of the liver included abdominal computed tomography and magnetic resonance imaging (MRI) with vascular and biliary reconstructions.For full left and full right lobe donation liver biopsy was performed prior to final donor acceptance.

Donor files were analyzed for age, sex, body weight, body mass index (BMI), pediatric or adult recipient, type of transplant, rate of conversion, graft weight, operative time, graft to body weight ratio(GBWR), first warm ischemic time, blood loss, length of hospital stay, postoperative pain score (on days 1, 4) and complications according to Clavien-Dindo classification.Postoperative bile leakage was defined as the presence of “drain bilirubin>3 × serum bilirubin”.

Surgical techniques were performed as previously described by our team in 2020[11].A donor remnant GBWR<1% was not considered a contraindication for right lobe donation provided that the remnant was>30% in all donors, and a maximum of 10%of steatosis was accepted provided the remnant was>35%.For left lateral segments donors were accepted with BMI ≥30 kg/m2without biopsy.Donors for full left or right lobes underwent liver biopsy to grade steatosis, and fibrosis and to rule out other abnormalities.Multiple bile ducts, double arterial inflowand portal trifurcation were not considered contraindications to donation.

The recipients’ files were analyzed for age, sex, body weight,BMI, model of end-stage liver disease (MELD) score, blood loss,blood transfusion, operative time, cold ischemia time and length of hospital stay.Since the recipient’s outcome was not the main focus of this study, complications were summarized in categories.

Statistical analysis

Non-normally distributed continuous data are reported as median (range) values.Graft and patient actual survival curves were compared using the log-rank test.Statistical analysis was performed using the IBM SPSS version 20.0 for Windows (Armonk,New York, NY, USA).

Results

Donor characteristics

Of the 501 enrolled donors, 351 (70.1%) were male and 150(29.9%) were female.The median age was 28 years (range 18-50).The median body weight was 70 kg (range 41-107).The median donor BMI was 25 kg/m2(range 16-34).Graft weight ranged from 114 to 1070 g with a median of 416 g.The calculated GBWR for the recipient ranged from 0.5 to 7.5 (median 1).The median blood loss was 60 mL (range 20-800).The median donor operative time was 6.77 h (range 2.93-11.53).The median first warm ischemia time,defined from cross clamping to back table perfusion in the donor,was 7 minutes (range 3-22).The length of hospital stay for donors ranged from 2 to 22 days (median 4).The median donor pain scoredefined as the daily average from multiple assessments was 0 (0-3)on day one and 0 (0-4) on day 4 (Table 1).

Table 1KFSHRC-Riyadh fully robotic living donor hepatectomy during the study period ( n = 501).

Fig.2.Distribution of robotic donor surgeries by type of donated graft.

Fig.3.Distribution of grafts implanted in adult and pediatric recipients.

The evolution of the different donor hepatectomy techniques is shown inFig.1.Out of 501 robotic living donors, 177 underwent left lateral sectionectomy (LLS), and 112 had full left and 212 had full right lobes (Fig.2).Liver grafts were donated to 205 (40.9%)pediatric recipients and 296 (59.1%) adult recipients.One hundred and seventy-seven pediatric recipients received left lateral lobes and 28 full left lobes.Eighty-four adults received full left lobes and 212 received full right lobes (Fig.3).In two (0.4%) cases conversion to open donor hepatectomy was necessary.All grafts were implanted successfully.No donors received blood transfusions.The median follow-up period was 395 days (range 4-1170).

Donor outcome

There were no deaths.The overall complication rate was 6.4%(n= 32).One donor suffered from postoperative myocardial infarction (Clavien-Dindo grade ≥III ), and all other morbidities were classified Clavien-Dindo grade I and II.These included abdominal collections treated with antibiotics (n= 3, 0.6%), postoperative selflimiting bleeding (n= 2, 0.4%) and bile leakage from the resection plane (n= 9, 1.8%), none of which required further action; the drains were removed subsequently as the amount decreased, three(0.6%) donors experienced a minor pulmonary embolism.The most common complication was a wound hematoma at the Pfannenstiel incision (n= 12, 2.4%) (Table 2).

Recipient characteristics

Two hundred and eighty-three (56.5%) recipients were male and 218 (43.5%) were female.The median age was 36.9 years(range 0.1-85.3).The median body weight was 56 kg (range 3-115).The median BMI of adult recipients was 26 kg/m2(range 14.9-47.6).BMI was not calculated for children as it was not valid.The median MELD score for adult recipients was 22 (range 7-2).The median blood loss was 800 mL (range 50-16 250).The median amount of blood transfusion was 750 mL (range 6-16 250).In some cases, cell-saving auto-transfusion systems were used.The median recipient operative time was 6.25 h (range 2.97-17.08).The cold ischemia time of the graft ranged from 17 to 306 min, with a median of 85 min.The median length of hospital stay was 21 days(range 4-257).Pediatric recipients stayed from 5 to 97 days with a median of 21 days, and adult recipients stayed between 4 and 257 days with a median of 20 days (Table 3).

Recipient outcome

The three-year actual overall recipient survival was 91.4%; 97.1%in pediatric recipients with 6 deaths and 87.5% in adult recipients with 37 deaths (Fig.4A).The three-year actual overall graft survival was 90.6%; 95.1% in the pediatric recipients and 87.5% in the adult recipients (Fig.4B).Overall, in-hospital mortality was 6% (n= 30),27 (9.1%) adults and three (1.4%) children.Re-transplantation was needed 6 (1.2%) times: two adults died and four children survived.Overall recipient morbidity was 19.8% (n= 99).Twentyeight (5.6%) recipients had biliary complications that needed surgical revision.Postoperative bleeding occurred in 28 (5.6%) recipients.Seven (1.4%) recipients had a postoperative bowel perforation, one (0.2%) a deep vein thrombosis (DVT), and 7 (1.4%) an intra-abdominal or abdominal wall hematoma.Vascular complications were as follows: 11 (2.2%) arterial, 10 (2%) portal vein and one (0.2%) hepatic vein thrombosis.Surgical diaphragmatic hernias occurred in 3 (0.6%) children.Three (0.6%) recipients had wound dehiscence (Table 4).

Table 2KFSHRC-Riyadh robotic living donor hepatectomy: post-operative in-hospital donor morbidity and mortality ( n = 501).

Table 3KFSHRC-Riyadh living donor liver transplantation: recipient characteristics (adult: n = 296; children: n = 205).

Table 4KFSHRC-Riyadh robotic living donor recipient: post-operative in-hospital morbidity and mortality.

Discussion

To our knowledge, this is the first single-center report including over 500 fully robotic donor hepatectomies.The feasibility of robotic donor hepatectomy was first shown by the Chen’s team[13].They compared 13 patients receiving the robotic procedure to 54 patients receiving the open procedure.Both groups had similar blood loss, complication rates recovery of donor liver tests and outcomes.However, the operative time was significantly longer in the robotic group.These authors concluded that “therobotic platform would be a big step toward completing pure minimally invasive liver donor surgery”[13].Our previous results confirmed these results.Moreover, we experienced that visualizationof complex vascular and biliary anatomies was much easier in the robotic approach during parenchymal and hilar plate dissection[20].

Fig.4.A: Adult and pediatric patient survival; B: adult and pediatric graft survival.?: 2 adult recipients re-transplant; ??: 4 pediatric recipients re-transplanted and are still alive.

Despite our much larger experience with cavitron ultrasonic surgical aspiration (CUSA, Integra LifeSciences, Princeton, New Jersey, USA) based parenchymal dissection, the use of the Harmonic scalpel did not result in more (biliary) complications in our early robotic experience[20].Chen et al.similarly reported comparable bile leakage rates in open and robotic approaches[13].In our recent series very few (1.8%) minor biochemical bile leakage occurred in donors; these did not prolong the length of hospital stay.In particular, visualization of the bile ducts with intravenous injection of 0.5 mg/kg of indocyanine green for near-infrared fluorescence enhanced by magnification, is far superior compared to the laparoscopic approach.This combined method gives relief and security not to injure major bile ducts in the remaining donor liver while producing an optimal graft.

Previous series of laparoscopic right lobe donations reported some conversions to the open procedure [9,10].During their first robotic series, Chen et al.and Broering et al.did not report conversions to open surgery [13,20].Our now much larger series further confirmed the very low conversion rate (0.4%).The difference in conversion rate, when compared to the laparoscopic approach might point to a superior stitching capacity of the robotic platform which in fact is similar to the one experienced in open surgery.

A clear trend toward lower donor morbidity (6.4%), minimal postoperative pain and an average length of hospital stay of 4 days was seen in these series, regardless of the type of donated lobe [19,20].These results are far below those of the recently reported world experience showing an average donor morbidity reaching up to 36%[22].

As reported by other earlier experiences, the operative time was significantly decreased [8,20].Keeping in mind that the robotic approach requires a much longer preparation time, for positioning, securing access for anesthesia and robotic docking, a reduction in overall both donor operative and anesthesia time can only be achieved with dedication of the entire surgical, anesthesiologic, nursing and logistics teams.Now the operative time probably reached the plateau for our main primary console surgeon.With the ability to teach on the dual console, two further surgeons are currently in the steep phase of their learning curve.

The main focus in this study is on donors.Retransplantation rate was low (1.2%) as were the rates of biliary (5.6%) and vascular (4.4%) complications.None of the eleven (2.2%) recipients who presented with a hepatic artery thrombosis did require early thrombectomy.Their graft function remained stable despite the lack of arterial inflow, and in three of them arterial signals were regained later on.Two children with biliary atresia developed a portal vein thrombosis needing thrombectomy and one (0.2%) recipient had hepatic vein thrombosis resulting in impaired allograft outflow.Other complications included bowel perforation, hematoma, postoperative bleeding, wound dehiscence and diaphragmatic hernias.The outcome of the recipients was not further stratified between adult and pediatric recipients, which will be published in detail in an upcoming report.

It is our firm belief that better visualization of bile duct anatomy during donor hepatectomy is advantageous for the recipient, minimalizing bile duct devascularization and optimizing the area and angle of bile duct division.Further studies are needed to support this hypothesis.

After introducing robotic donor hepatectomy for only 3.5 years we have now fully immersed this technical platform.As a consequence, there are essentially no vascular or biliary anatomic, nor body habitus contraindications to robotic donor hepatectomy.It can be carefully concluded that the fully robotic donor hepatectomy is superior to the open procedure on the condition that such a type of donor hepatectomy is performed by surgeons with extensive knowledge of open living donor hepatectomy.Conversely experience in laparoscopic donor hepatectomy is not considered mandatory to proceed with the robotic platform [2,21].Indeed, the learning curve of robotic major hepatectomy is significantly less than that in laparoscopic surgery, with a mastering phase reached after a total number of 15 procedures instead of 45 required for the laparoscopic approach [23,24].As centers mainly specialized either in robotic or laparoscopic approaches, it will be very difficult to set up comparative studies addressing the proficiency curve of robotic versus laparoscopic donor hepatectomy, unless these centers decide to collaborate in multicenter studies.

The need to train more surgeons on the console, and the importance of the double console become evident.This set-up offers a privileged and very safe form of teaching because the proctor can guide (both vocally and manually) the surgeon through the dissection and resume the command when necessary.This important aspect needs indeed to be underlined, especially in the field of living donation, where safety is of primary concern.

Besides the Riyadh center, multiple high-volume robotic programs have now been established in countries that are highly dependent on LDLT.The teams of Choi and Rho in Korea and Binoj in India are important examples of this evolution [10,17,25].The rate at which more centers will be able to report good results will allow to further confirm the advantages of the robotic approach and thus encourage other institutions to embark onto the robotic platform, if MIDH is in their vision.Certainly, any potential living donor will in the near future look for all possible information about techniques of donor surgery including the possibility of robotic donor hepatectomy, both in the scientific literature and on social media.Being an altruistic act all together, every living donor should have the right to demand the safest and least morbid operation.It should be the united goal of the liver transplant community to establish extensive collaborations between living liver donor programs to offer guided proctorships in robotic donor hepatectomy to any center interested in this field of liver transplantation.

Acknowledgments

We thank Mrs.Kris Ann Hervera Marquez, senior clinical research coordinator, and Alria Datijan and Bilal Elmikkaoui, clinical analysts, for their assistance in extracting all the variables needed for the comparative and the outcome analyses.

CRediT authorship contribution statement

Maren Schulze :Data curation, Writing - original draft.Yasser Elsheikh :Investigation, Methodology.Markus Ulrich Boehnert :Supervision, Validation, Investigation, Methodology.Yasir Alnemary :Data curation, Visualization.Saleh Alabbad :Formal analysis, Resources.Dieter Clemens Broering :Conceptualization, Supervision, Writing - review & editing.

Funding

None.

Ethical approval

The present study was conducted in accordance with the ethical principles intheDeclarationofHelsinki(20 0 0), the International Conference on Harmonized Tripartite Good Clinical Practice Guidelines, the policies and guidelines of the institution, and the laws of the Saudi Arabia.

Competing interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.