Modelling acute antibody-mediated rejection of human kidney transplants using ex-vivo warm machine perfusion.

BACKGROUND: Transplant rejection is a major cause of graft loss and morbidity. Currently, no human models of antibody-mediated rejection (AMR) exist, limiting mechanistic investigation and organ-specific targeted therapy. Here, using 12 human kidneys and ex-vivo normothermic machine perfusion, we demonstrate phenotypes of AMR after addition of antibodies against either human HLA class I or blood group antigens (A, B), thus modelling clinical AMR that can follow HLA incompatible (HLAi) or blood group incompatible (ABOi) transplantation. METHODS: Discarded human kidneys with wide ranging demographics and cold ischaemia times (11-54 h) were perfused with red blood cells and fresh frozen plasma (FFP) as a source of complement/coagulation factors. For the HLAi model, 600 µg of W6/32 anti-class 1 HLA antibody was added to the circuit (time '0'). For the ABOi model, high titre FFP of the relevant blood group antibody was added. Renal blood flow index (RBFi, mL/min/100 g), C3 desArg, prothrombin fragments 1 + 2 and histology were determined. Our endpoints included haemodynamic changes, thrombosis, and biopsy proven complement deposition. FINDINGS: Compared to control kidneys perfused without anti-donor antibodies, both models demonstrated haemodynamic collapse after antibody perfusion with only the HLAi model showing glomerular C4d deposition. INTERPRETATION: We show that a clinically relevant human kidney model of AMR is feasible, and anticipate that these models, with refinements, could provide a basis to test different strategies to prevent AMR. FUNDING: The Rosetrees and Stonygate Trust, The Royal College of Surgeons of England Fellowship Grant, NIHR Biomedical Research Centre/KCL Early Career Grant, Kidney Research U.K.

Biological Mesh Repair of a Large Incisional Hernia Containing a Kidney Transplant in the Presence of Inflammation.

The incidence of incisional hernia after kidney transplantation varies between 1.1% and 3.8%. These are usually repaired electively using polypropylene mesh. We present here a case where a patient presented as an emergency, with a large painful incisional hernia over his kidney transplant, and evidence of local erythema and systemic inflammation. As this could have represented either infection or rejection, the patient was started on antibiotics and subsequently underwent graft nephrectomy and hernia repair using a biological (porcine-derived) acellular dermal matrix, Strattice™, with a satisfactory outcome. In addition, histology showed evidence of allograft rejection. This is the first reported case of an incisional hernia containing a rejecting kidney allograft, managed with nephrectomy and biological mesh repair.

Prophylaxis of Wound Infections-antibiotics in Renal Donation (POWAR): A UK Multicentre Double Blind Placebo Controlled Randomised Trial.

BACKGROUND: Postoperative infection after hand-assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections. METHODS: Eligible donors were randomly and blindly allocated to preoperative single-dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days, including surgical site infection (SSI), urinary tract infection (UTI), and lower respiratory tract infection (LRTI). FINDINGS: In all, 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). Among them, 99% (291/293) completed follow-up. The total infection rate was 40.7% (59/145) in the placebo group and 23% (34 of 148) in the antibiotic group (P = 0.001). Superficial SSIs were 20.7% (30/145 patients) in the placebo group versus 10.1% (15/148 patients) in the antibiotic group (P = 0.012). LRTIs were 9% (13/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.046). UTIs were 4.1% (6/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.72).Antibiotic prophylaxis conferred a 17.7% (95% confidence interval 7.2%-28.1%), absolute risk reduction in developing postoperative infection, with 6 donors requiring treatment to prevent 1 infection. INTERPRETATION: Single-dose preoperative antibiotic prophylaxis dramatically reduces post-HALDN infection rates, mainly impacting SSIs and LRTIs.

Dissemination of a novel organ perfusion technique: ex vivo normothermic perfusion of deceased donor kidneys.

Ex vivo normothermic perfusion (EVNP) technology is a promising means of organ preservation, assessment, and preconditioning prior to kidney transplantation, which has been pioneered by a single group. We describe the challenges of setting up clinical EVNP programs in 2 new centers, as well as early patient outcomes. Governance, training, and logistical pathways are described. In order to demonstrate safety and proficiency in this new technique, early patient outcomes are also described. Patient outcomes included the incidence of primary nonfunction, delayed graft function, graft and patient survival at 1 year. Contralateral kidneys undergoing static cold storage alone were used as a comparator group. Between March 2016 and July 2017, EVNP was performed on 14 kidneys from 12 donors (11 kidneys in center 1, 3 kidneys in center 2). Of the 14 kidneys that underwent EVNP, 12 organs were implanted into 10 recipients. Two pairs of kidneys were implanted as dual grafts and 1 kidney was implanted simultaneously with a pancreas. The remaining 7 kidneys were transplanted as single allografts. Seven pairs of kidneys were available for paired analysis comparing EVNP versus static cold storage. Graft and patient outcomes were comparable between the 2 preservation techniques. The introduction of a clinical EVNP service requires a careful multimodal approach, drawing on the expertise of specialists in transplantation, hematology, and microbiology. Both new clinical EVNP programs demonstrated proficiency and safety when a structured dissemination process was followed.

Comparison Between Robotic and Laparoscopic or Open Anastomoses: A Systematic Review and Meta-Analysis.

INTRODUCTION: Robotic surgery has been increasingly used in fashioning various surgical anastomoses. Our aim was to collect and analyze outcomes related to anastomoses performed using a robotic approach and compare them with those done using laparoscopic or open approaches through meta-analysis. METHODS: A systematic review was conducted for articles comparing robotic with laparoscopic and/or open operations (colectomy, low anterior resection, gastrectomy, Roux-en-Y gastric bypass (RYGB), pancreaticoduodenectomy, radical cystectomy, pyeloplasty, radical prostatectomy, renal transplant) published up to June 2019 searching Medline, Scopus, Google Scholar, Clinical Trials and the Cochrane Central Register of Controlled Trials. Studies containing information about outcomes related to hand-sewn anastomoses were included for meta-analysis. Studies with stapled anastomoses or without relevant information about the anastomotic technique were excluded. We also excluded studies in which the anastomoses were performed extracorporeally in laparoscopic or robotic operations. RESULTS: We included 83 studies referring to the aforementioned operations (4 randomized controlled and 79 non-randomized, 10 prospective and 69 retrospective) apart from colectomy and low anterior resection. Anastomoses done using robotic instruments provided similar results to those done using laparoscopic or open approach in regards to anastomotic leak or stricture. However, there were lower rates of stenosis in robotic than in laparoscopic RYGB (p=0.01) and in robotic than in open radical prostatectomy (p<0.00001). Moreover, all anastomoses needed more time to be performed using the robotic rather than the open approach in renal transplant (p≤0.001). CONCLUSION: Robotic anastomoses provide equal outcomes with laparoscopic and open ones in most operations, with a few notable exceptions.

A novel 3D-printed hybrid simulation model for robotic-assisted kidney transplantation (RAKT).

Robotic-assisted kidney transplantation (RAKT) offers key benefits for patients that have been demonstrated in several studies. A barrier to the wider uptake of RAKT is surgical skill acquisition. This is exacerbated by the challenges of modern surgery with reduced surgical training time, patient safety concerns and financial pressures. Simulation is a well-established method of developing surgical skill in a safe and controlled environment away from the patient. We have developed a 3D printed simulation model for the key step of the kidney transplant operation which is the vascular anastomosis. The model is anatomically accurate, based on the CT scans of patients and it incorporates deceased donor vascular tissue. Crucially, it was developed to be used in the robotic operating theatre with the operating robot to enhance its fidelity. It is portable and relatively inexpensive when compared with other forms of simulation such as virtual reality or animal lab training. It thus has the potential of being more accessible as a training tool for the safe acquisition of RAKT specific skills. We demonstrate this model here.

Atypical abdominal pain: post-traumatic transverse colon stricture.

A driver presented to the emergency department 1 day after an accident driving his excavator with abdominal pain and vomiting. He was admitted to the surgical ward 2 days later, after reattending. A CT scan revealed wall thickening and oedema in the transverse colon. This was supported by a subsequent CT virtual colonoscopy which raised the suspicion of neoplasia. A follow-up colonoscopy was not carried further than the transverse colon due to an indurated, tight stricture. Biopsies from that area showed ulceration and inflammatory changes non-specific for ischaemia, drug-induced changes or inflammatory bowel disease. As a consequence of the subocclusive symptoms and the possibility of a neoplastic diagnosis, a laparoscopic-assisted transverse colectomy was performed. The histology of the resected segment revealed post-traumatic inflammation and fibrosis with no evidence of neoplasia.

Apple-core lesion of the colon: a case report.

INTRODUCTION: The appearance of the apple-core lesion of the colon can be caused by several diseases. CASE PRESENTATION: A male patient was referred to the surgical clinic with melaena and weight loss. Clinical examination and investigations confirmed an apple-core lesion of the colon. He underwent surgery, but unfortunately, died of a chest infection two weeks after the operation. CONCLUSION: This case shows the use of computed tomography in demonstrating the primary cause of iron deficiency anaemia, and at the same time, staging the disease for loco-regional metastasis.