Total robotic liver transplant: the final frontier of minimally invasive surgery.

The use of robotic surgery in transplantation is increasing; however, robotic liver transplantation (RLT) remains a challenging undertaking. To our knowledge, this is a report of the first RLT in North America and the first RLT using a whole graft from a deceased donor in the world. This paper describes the preparation leading to the RLT and the surgical technique of the operation. The operation was performed in a 62-year-old man with hepatitis C cirrhosis and hepatocellular carcinoma with a native Model for End-Stage Liver Disease score of 10. The total console time for the operation was 8 hours 30 minutes, and the transplant hepatectomy took 3 hours 30 minutes. Warm ischemia time was 77 minutes. Biliary reconstruction was performed in a primary end-to-end fashion and took 19 minutes to complete. The patient had an uneventful recovery without early allograft dysfunction or surgical complications and continues to do well after 6-months follow-up. This paper demonstrates the feasibility of this operation in highly selected patients with chronic liver disease. Additional experience is required to fully understand the role of RLT in the future of transplant surgery. Narrated video is available at https://youtu.be/TkjDwLryd3I.

Xenoreactive antibodies in α-granules of human platelets bind pig liver endothelial cells.

Pig liver xenotransplantation is limited by a thrombocytopenic coagulopathy that occurs immediately following graft reperfusion. In vitro and ex vivo studies from our lab suggested that the thrombocytopenia may be the result of a species incompatibility in platelet glycosylation. Realization that platelet α-granules contain antibodies caused us to reevaluate whether the thrombocytopenia in liver xenotransplantation could occur because IgM and IgG from inside platelet α-granules bound to pig liver sinusoidal endothelial cells (LSECs). Our in vitro analysis of IgM and IgG from inside α-granules showed that platelets do carry xenoreactive antibodies that can bind to known xenoantigens. This study suggests that thrombocytopenia occurring following liver xenotransplantation could occur because of xenoreactive antibodies tethering human platelets to the pig LSEC enabling the platelet to be phagocytosed. These results suggest genetic engineering strategies aimed at reducing xenoantigens on the surface of pig LSEC will be effective in eliminating the thrombocytopenia that limits survival in liver xenotransplantation.

The impact of a dedicated operating room team on robotic transplant program growth and fellowship training.

INTRODUCTION: Despite considerable interest in robotic surgery, successful incorporation of robotics into transplant programs has been challenging. Lack of a dedicated OR team with expertise in both robotics and transplant is felt to be a major barrier. This paper assesses the impact of a dedicated robotic transplant team (DART) on program growth and fellowship training at one of the largest robotic transplant programs in North America. METHODS: This is a single center, retrospective review of all robotic operations performed on the transplant surgery service from October 2017 to October 2022. DART was incorporated in February 2020 and included transplant first assists (RFAs), scrub technologists and circulating nurses who received robotic training. Robotic experience before and after DART was compared to assess its impact on program growth and training. RESULTS: Four hundred and two robotic cases were performed by five transplant surgeons: 63 pre-DART and 339 post-DART. 40% of cases were transplant-related and 59.5%, HPB. There was a significant increase in case volume (2.5-10.6 cases/month, p < .0001) and complexity (36.5% vs. 70.3% high complexity cases, p < .0001) post-DART. RFA case coverage increased from 17% to 95%, and participation of transplant fellows as primary surgeons increased from 17% to 95% post-DART period (both p < .05). Conversion rates (9.5% vs. 4.1%) and room turn-around-times (TAT) (58.4 vs. 40.3 min) were lower post-DART (p < .05). There were no emergent conversions, conversions in transplant patients, or robot-related complications in either group. CONCLUSION: OR teams with expertise in robotics and transplant surgery can accelerate growth of robotic transplant programs while maintaining patient safety.

The desirable donor pig to eliminate all xenoreactive antigens.

The humoral barrier has been the limiting factor in moving xenotransplantation towards the clinic. Improvements in somatic cell nuclear transfer and genome editing, particularly CRISPR-Cas9, have made it possible to create pigs with multiple glycan xenoantigen deletions for the purposes of reducing xenoreactive antibody binding to the xenografted organ. Recent studies have also considered the aetiology and existence of antibodies directed at the swine leucocyte antigen (SLA) complex, and potential genetic engineering strategies to avoid these antibodies. Evaluation of xenoreactive antibody binding is very important for the advancement of xenotransplantation, because if patients do not have any detectable xenoreactive antibody, then it is reasonable to expect that cellular rejection and not antibody-mediated rejection (AMR) will be the next hurdle to clinical application.

Evaluation of human and non-human primate antibody binding to pig cells lacking GGTA1/CMAH/ß4GalNT2 genes.

BACKGROUND: Simultaneous inactivation of pig GGTA1 and CMAH genes eliminates carbohydrate xenoantigens recognized by human antibodies. The ß4GalNT2 glycosyltransferase may also synthesize xenoantigens. To further characterize glycan-based species incompatibilities, we examined human and non-human primate antibody binding to cells derived from genetically modified pigs lacking these carbohydrate-modifying genes. METHODS: The Cas9 endonuclease and gRNA were used to create pigs lacking GGTA1, GGTA1/CMAH, or GGTA1/CMAH/ß4GalNT2 genes. Peripheral blood mononuclear cells were isolated from these animals and examined for binding to IgM and IgG from humans, rhesus macaques, and baboons. RESULTS: Cells from GGTA1/CMAH/ß4GalNT2 deficient pigs exhibited reduced human IgM and IgG binding compared to cells lacking both GGTA1 and CMAH. Non-human primate antibody reactivity with cells from the various pigs exhibited a slightly different pattern of reactivity than that seen in humans. Simultaneous inactivation of the GGTA1 and CMAH genes increased non-human primate antibody binding compared to cells lacking either GGTA1 only or to those deficient in GGTA1/CMAH/ß4GalNT2. CONCLUSIONS: Inactivation of the ß4GalNT2 gene reduces human and non-human primate antibody binding resulting in diminished porcine xenoantigenicity. The increased humoral immunity of non-human primates toward GGTA1-/CMAH-deficient cells compared to pigs lacking either GGTA1 or GGTA1/CMAH/ß4GalNT2 highlights the complexities of carbohydrate xenoantigens and suggests potential limitations of the non-human primate model for examining some genetic modifications. The progressive reduction of swine xenoantigens recognized by human immunoglobulin through inactivation of pig GGTA1/CMAH/ß4GalNT2 genes demonstrates that the antibody barrier to xenotransplantation can be minimized by genetic engineering.