Banff 2022 Vascularized Composite Allotransplantation Meeting Report: Diagnostic criteria for vascular changes.

As more data become available, the Banff 2007 working classification of skin-containing vascularized composite allograft (VCA) pathology is expected to evolve and develop. This report represents the Banff VCA Working Group's consensus on the first revision of the 2007 scoring system. Prior to the 2022 Banff-CanXadian Society of Transplantation Joint Meeting, 83 clinicians and/or researchers were invited to a virtual meeting to discuss whether the 2007 Banff VCA system called for a revision. Unanimously, it was determined that the vascular changes were to be included in the first revision. Subsequently, 2 international online surveys, each followed by virtual discussions, were launched. The goals were (1) to identify which changes define severe rejection, (2) to grade their importance in the evaluation of severe rejection, and (3) to identify emerging criteria to diagnose rejection. A final hybrid (in-person and virtual) discussion at the Banff/Canadian Society of Transplantation Joint Meeting finalized the terminology, the definition, a scoring system, and a reporting system of the vascular changes. This proposal represents an international consensus on this topic and establishes the first revision of the Banff 2007 working classification of skin-containing vascularized composite allograft pathology.

Contemporary trends in choledochal cyst excision: An analysis of the pediatric national surgical quality improvement program.

BACKGROUND: Choledochal cysts are rare congenital anomalies of the biliary tree that may lead to obstruction, chronic inflammation, infection, and malignancy. There is wide variation in the timing of resection, operative approach, and reconstructive techniques. Outcomes have rarely been compared on a national level. METHODS: We queried the Pediatric National Surgical Quality Improvement Program (NSQIP) to identify patients who underwent choledochal cyst excision from 2015 to 2020. Patients were stratified by hepaticoduodenostomy (HD) versus Roux-en-Y hepaticojejunostomy (RNYHJ), use of minimally invasive surgery (MIS), and age at surgery. We collected several outcomes, including length of stay (LOS), reoperation, complications, blood transfusions, and readmission rate. We compared outcomes between cohorts using nonparametric tests and multivariate regression. RESULTS: Altogether, 407 patients met the study criteria, 150 (36.8%) underwent RNYHJ reconstruction, 100 (24.6%) underwent MIS only, and 111 (27.3%) were less than one year old. Patients who underwent open surgery were younger (median age 2.31 vs. 4.25 years, p = 0.002) and more likely underwent RNYHJ reconstruction (42.7% vs. 19%, p = 0.001). On adjusted analysis, the outcomes of LOS, reoperation, transfusion, and complications were similar between the type of reconstruction, operative approach, and age. Patients undergoing RNYHJ had lower rates of readmission than patients undergoing HD (4.0% vs. 10.5%, OR 0.34, CI [0.12, 0.79], p = 0.02). CONCLUSIONS: In children with choledochal cysts, most short-term outcomes were similar between reconstructive techniques, operative approach, and age at resection, although HD reconstruction was associated with a higher readmission rate in this study. Clinical decision-making should be driven by long-term and biliary-specific outcomes.

Improved survival and higher rates of surgical resection associated with hepatocellular carcinoma in children as compared to young adults.

Hepatocellular adenocarcinoma (HCC) is the second most common primary hepatic malignancy in children with a 5-year overall survival of 30%. Few studies have examined the similarities and differences between pediatric and adult HCC. This article aims to examine the relationship between tumor characteristics, treatments and outcomes in pediatric and adult patients with HCC. The 2019 National Cancer Database was queried for patients with HCC. Patients were stratified by age: pediatric <21 years (n = 214) and young adults 21 to 40 (n = 1102). Descriptive statistics and chi square were performed. The mean age at diagnosis was 15.5 years (SD 5.6) in the pediatric and 33 years (5.3) in the adult group. Children had a comparable rate of metastasis (30% vs 28%, P = .47) and increased fibrolamellar histology (32% vs 9%). Surgical resection was more common in children compared to adults (74% vs 62%, P < .001), children also had more lymph nodes examined (39% vs 19%, P < .001), positive lymph nodes (35% vs 17%, P = .02) and surgical resection when metastasis were present at diagnosis (46% vs 18%, P < .001). The 1-, 3- and 5-year overall survival was higher for pediatric patients than adults (81%, 65%, 55%, vs 70%, 54%, 48%). Despite higher prevalence of fibrolamellar histology, greater number of positive lymph nodes and comparable rates of metastasis at diagnosis, children with HCC have improved overall survival compared to adults. Age did not significantly contribute to survivorship, so it is likely that the more aggressive surgical approach contributed to the improved overall survival in pediatric patients.

A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery.

OBJECTIVE: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. BACKGROUND: Elective surgery is an opportunity to understand both the systemic and focal responses accompanying controlled and well-characterized injury to the human body. The overarching goal of this ongoing project is to define stereotypical responses to surgical injury, with the translational purpose of identifying targetable pathways involved in healing and resilience, and variations indicative of aberrant peri-operative outcomes. METHODS: Clinical data from the electronic medical record combined with large-scale biological data sets derived from blood, urine, fecal matter, and tissue samples are collected prospectively through the peri-operative period on patients undergoing 14 surgeries chosen to represent a range of injury locations and intensities. Specimens are subjected to genomic, transcriptomic, proteomic, and metabolomic assays to describe their genetic, metabolic, immunologic, and microbiome profiles, providing a multidimensional landscape of the human response to injury. RESULTS: The highly multiplexed data generated includes changes in over 28,000 mRNA transcripts, 100 plasma metabolites, 200 urine metabolites, and 400 proteins over the longitudinal course of surgery and recovery. In our initial pilot dataset, we demonstrate the feasibility of collecting high quality multi-omic data at pre- and postoperative time points and are already seeing evidence of physiologic perturbation between timepoints. CONCLUSIONS: This repository allows for longitudinal, state-of-the-art geno-mic, transcriptomic, proteomic, metabolomic, immunologic, and clinical data collection and provides a rich and stable infrastructure on which to fuel further biomedical discovery.

Definition and Analysis of Textbook Outcome: A Novel Quality Measure in Kidney Transplantation.

BACKGROUND: "Textbook outcome" (TO) is a novel composite quality measure that encompasses multiple postoperative endpoints, representing the ideal "textbook" hospitalization for complex surgical procedures. We defined TO for kidney transplantation using a cohort from a high-volume institution. METHODS: Adult patients who underwent isolated kidney transplantation at our institution between 2016 and 2019 were included. TO was defined by clinician consensus at our institution to include freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay > 75th percentile of kidney transplant patients, 90-day mortality, 30-day acute rejection, delayed graft function, and discharge with a Foley catheter. Recipient, operative, financial characteristics, and post-transplant patient, graft, and rejection-free survival were compared between patients who achieved and failed to achieve TO. RESULTS: A total of 557 kidney transplant patients were included. Of those, 245 (44%) achieved TO. The most common reasons for TO failure were delayed graft function (N = 157, 50%) and hospital readmission within 30 days (N = 155, 50%); the least common was mortality within 90 days (N = 6, 2%). Patient, graft, and rejection-free survival were significantly improved among patients who achieved TO. On average, patients who achieved TO incurred approximately $50,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in kidney transplantation was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer transplant centers a detailed performance breakdown to identify aspects of perioperative care in need of process improvement.

Using Radiographic Domain for Evaluating Indications in Abdominal Wall Transplantation.

BACKGROUND: There is currently no description of abdominal domain changes in small bowel transplantation population or consensus of criteria regarding which patients are at high risk for immediate postoperative abdominal wall complications or would benefit from abdominal wall vascularized composite allotransplantation. METHODS: A retrospective chart review was performed on 14 adult patients receiving intestinal or multivisceral transplantation. Preoperative and postoperative computed tomography scans were reviewed, and multiple variables were collected regarding abdominal domain and volume and analyzed comparing postoperative changes and abdominal wall complications. RESULTS: Patients after intestinal or multivisceral transplantation had a mean reduction in overall intraperitoneal volume in the immediate postoperative period from 9031 cm3 to 7846 cm3 (P = 0.314). This intraperitoneal volume was further reduced to an average of 6261 cm3 upon radiographic evaluation greater than 1 year postoperatively (P = 0.024). Patients with preexisting abdominal wound (P = 0.002), radiation, or presence of ostomy (P = 0.047) were significantly associated with postoperative abdominal wall complications. No preoperative radiographic findings had a significant association with postoperative abdominal wall complications. CONCLUSIONS: Computed tomography imaging demonstrates that intestinal and multivisceral transplant patients have significant reduction in intraperitoneal volume and domain after transplantation in the acute and delayed postoperative setting. Preoperative radiographic abdominal domain was not able to predict patients with postoperative abdominal wall complications. Patients with abdominal wounds, ostomies, and preoperative radiation therapy were associated with acute postoperative abdominal complications and may be considered for need of reconstructive techniques including abdominal wall transplantation.

Left lateral segment liver volume is not correlated with anthropometric measures.

BACKGROUND: Liver transplantation is definitive therapy for end stage liver disease in pediatric patients. Living donor liver transplantation (LDLT) with the left lateral segment (LLS) is often a feasible option. However, the size of LLS is an important factor in donor suitability - particularly when the recipient weighs less than 10 kg. In the present study, we sought to define a formula for estimating left lateral segment volume (LLSV) in potential LLS donors. METHODS: We obtained demographic and anthropometric measurements on 50 patients with Computed Tomography (CT) scans to determine whole liver volume (WLV), right liver volume (RLV), and LLSV. We performed univariable and multivariable linear regression with backwards stepwise variable selection (p < 0.10) to determine final models. RESULTS: Our study found that previously reported anthropometric and demographics variables correlated with volume were significantly associated with WLV and RLV. On univariable analysis, no demographic or anthropometric measures were correlated with LLSV. On multivariable analysis, LLSV was poorly predicted by the final model (R2 = 0.10, Coefficient of Variation [CV] = 42.2) relative to WLV (R2 = 0.33, CV = 18.8) and RLV (R2 = 0.41, CV = 15.8). CONCLUSION: Potential LLS living donors should not be excluded based on anthropometric data: all potential donors should be evaluated regardless of their size.

Correlation of preoperative imaging characteristics with donor outcomes and operative difficulty in laparoscopic donor nephrectomy.

This study aimed to understand the relationship of preoperative measurements and risk factors on operative time and outcomes of laparoscopic donor nephrectomy. Two hundred forty-two kidney donors between 2010 and 2017 were identified. Patients' demographic, anthropomorphic, and operative characteristics were abstracted from the electronic medical record. Glomerular filtration rates (GFR) were documented before surgery, within 24 hours, 6, 12, and 24 months after surgery. Standard radiological measures and kidney volumes, and subcutaneous and perinephric fat thicknesses were assessed by three radiologists. Data were analyzed using standard statistical measures. There was significant correlation between cranio-caudal and latero-lateral diameters (P < .0001) and kidney volume. The left kidney was transplanted in 92.6% of cases and the larger kidney in 69.2%. Kidney choice (smaller vs. larger) had no statistically significant impact on the rate of change of donor kidney function over time adjusting for age, sex and race (P = .61). Perinephric fat thickness (+4.08 minutes) and surgery after 2011 were significantly correlated with operative time (P ≤ .01). In conclusion, cranio-caudal diameters can be used as a surrogate measure for volume in the majority of donors. Size may not be a decisive factor for long-term donor kidney function. Perinephric fat around the donor kidney should be reported to facilitate operative planning.

Surgical Techniques for Revascularization in Abdominal Wall Transplantation.

BACKGROUND: Abdominal wall vascularized composite allotransplantation (AW-VCA) can be considered as a technically feasible option for abdominal wall reconstruction in patients whose abdomen cannot be closed using traditional methods. However, successful initial abdominal wall revascularization in the setting of visceral organ transplantation can pose a major challenge as graft ischemia time, operating in a limited surgical field, and variable recipient and donor anatomy must be considered. Several techniques have been reported to accomplish abdominal wall revascularization. METHODS: A literature review was performed using PubMed for articles related to "abdominal wall transplantation (AWT)." The authors of this study sorted through this search for relevant publications that describe abdominal wall transplant anatomy, technical descriptions, and outcomes of various techniques. RESULTS: A total of four distinct revascularization techniques were found in the literature. Each of these techniques was described by the respective authors and reported varying patient outcomes. Levi et al published a landmark article in 2003 that described technical feasibility of AWT with anastomosis between donor external iliac and inferior epigastric vessels with recipient common iliac vessels in end-to-side fashion. Cipriani et al described a microsurgical technique with anastomosis between donor and recipient inferior epigastric vessels in an end-to-end fashion. Giele et al subsequently proposed banking the abdominal wall allograft in the forearm to reduce graft ischemia time. Recently, Erdmann et al described the utilization of an arteriovenous loop for synchronous revascularization of abdominal wall and visceral transplants for reduction of ischemia time, operative time, while eliminating the need for further operations. CONCLUSION: Vascularized composite allotransplantation continues to advance with improving immunotherapy and outcomes in solid organ transplantation. Optimizing surgical techniques remains paramount as the field continues to grow. Refinement of the presented methods will continue as additional evidence and outcomes become available in AW-VCA.

Lymphocyte depletion and risk of acute rejection in renal transplant recipients at increased risk for delayed graft function.

Delayed graft function (DGF) is a risk factor for acute rejection (AR) in renal transplant recipients, and KDIGO guidelines suggest use of lymphocyte-depletion induction when DGF is anticipated. We analyzed the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) database to assess the impact of induction immunosuppression on the risk of AR in deceased kidney recipients based on pretransplant risk of DGF using a validated model. Recipients were categorized into 4 groups based upon the induction immunosuppression: (1) Rabbit anti-thymocyte globulin (rATG); (2) Alemtuzumab (C1H); (3) IL2-receptor antagonists (IL2-RA; basiliximab or daclizumab), and (4) No antibody induction. The primary endpoint for analysis was a composite endpoint of treated AR or graft failure by 1-year posttransplantation. Compared to no antibody induction, rATG and C1H had consistently lower adjusted odds of the composite endpoint across all risk strata for DGF risk, whereas IL2-Ra was associated with increased adjusted odds of the composite endpoint with increasing DGF risk. When the induction agents were compared, rATG and C1H were associated with decreasing adjusted odds for the composite endpoint with increasing risk of DGF, especially at the higher risk spectrum of DGF. Consideration must be given to use of lymphocyte-depletion induction when the anticipated risk of DGF is increased.

Small bowel and abdominal wall transplantation: A novel technique for synchronous revascularization.

Abdominal wall transplantation (AWT) was introduced in 1999 in the context of reconstruction of complex abdominal wall defects in conjunction with visceral organ transplantation. As of recently, 38 cases of total AWT have been performed worldwide, about half of which were performed in the United States. While AWT is technically feasible, one of the major challenges presenting to the reconstructive surgeon is time to revascularization of the donor abdominal wall (AW), given the immediate proximity of the visceral organ and AWT. The authors report a novel AW revascularization technique during a synchronous small bowel and AWT in a 37-year-old man.

Application of a Novel CT-Based Iliac Artery Calcification Scoring System for Predicting Renal Transplant Outcomes.

OBJECTIVE: The objective of our study was to assess whether the degree and distribution of iliac artery calcifications as determined by a CT-based calcium scoring system correlates with outcomes after renal transplant. MATERIALS AND METHODS: A retrospective review of renal transplant recipients who underwent CT of the pelvis within 2 years before surgery yielded 131 patients: 75 men and 56 women with a mean age of 52 years. Three radiologists assigned a separate semiquantitative score for calcification length, circumferential involvement, and morphology for the common iliac arteries and for the external iliac arteries. The operative and clinical notes were reviewed to determine which iliac arterial segment was used for anastomosis, the complexity of the operation, and whether delayed graft function (DGF) occurred. Renal allograft survival and patient survival were calculated using the Kaplan-Meier technique. RESULTS: Excellent interobserver agreement was noted for each calcification score category. The common iliac arteries showed significantly higher average calcification scores than the external iliac arteries for all categories. Advanced age and diabetes mellitus were independently predictive of higher scores in each category, whereas hypertension, cigarette smoking, hyperlipidemia, and sex were not. Based on multivariate analysis, only the calcification morphology score of the arterial segment used for anastomosis was independently predictive of a higher rate of surgical complexity and of DGF. None of the scores was predictive of graft or patient survival. However, patients with CT evidence of iliac arterial calcification had a lower 1-year survival after transplant than those who did not (92% vs 98%, respectively; p = 0.05). CONCLUSION: Only the calcification morphology score of the arterial segment used for anastomosis was significantly predictive of surgical complexity and of DGF. Routine pretransplant CT for calcification scoring in patients of advanced age or those with diabetes mellitus may enable selection of the optimal artery for anastomosis to optimize outcomes.

The need for inducing tolerance in vascularized composite allotransplantation.

Successful hand and face transplantation in the last decade has firmly established the field of vascularized composite allotransplantation (VCA). The experience in VCA has thus far been very similar to solid organ transplantation in terms of the morbidity associated with long-term immunosuppression. The unique immunological features of VCA such as split tolerance and resistance to chronic rejection are being investigated. Simultaneously there has been laboratory work studying tolerogenic protocols in animal VCA models. In order to optimize VCA outcomes, translational studies are needed to develop less toxic immunosuppression and possibly achieve donor-specific tolerance. This article reviews the immunology, animal models, mixed chimerism & tolerance induction in VCA and the direction of future research to enable better understanding and wider application of VCA.

Perioperative anticoagulation and antiplatelet therapy in renal transplant: is there an increase in bleeding complication?

BACKGROUND: Renal transplant recipients may have comorbidities requiring anticoagulation or antiplatelet therapy. While the effects of warfarin may be neutralized with plasma infusion, those of aspirin and clopidogrel are not easily reversible and may be associated with an increased risk of bleeding. We conducted this study to evaluate the risk of bleeding complications in patients receiving perioperative anticoagulation or antiplatelet therapy. METHODS: Medical records of patients who underwent renal transplantation from July 1, 2005 to April 30, 2009 were retrospectively reviewed. Patients receiving perioperative anticoagulation or antiplatelet therapy were identified. The incidence of reoperation, transfusion utilization and decrease in serum hemoglobin from pre-operative value (ΔHgb) were compared to those on no therapy. RESULTS: Of the 327 patients identified, 105 received pre-operative anticoagulation or antiplatelet therapy, 28 received therapy post-operatively, while 213 patients received no therapy. The incidence of reoperation, transfusion utilization and ΔHgb were not significantly increased with pre-operative anticoagulation or antiplatelet therapy. With post-operative heparin infusion, the incidence of reoperation and transfusion utilization were significantly increased (p values < 0.001). Patients with activated partial thromboplastin times (aPTT) >80 s experienced significant bleeding complications. CONCLUSION: A supratherapeutic aPTT with post-operative heparin infusion was associated with the greatest risk of bleeding complication.

CT and MR imaging evaluation of living liver donors.

Preoperative cross-sectional imaging evaluation of potential living liver donors allows to exclude donors with an increased risk for morbidity and mortality, and to assure that a suitable graft for the recipient can be obtained, minimizing the risk of complications in both the donor and the recipient. CT is routinely performed to delineate the anatomy of the liver, relevant vasculature, and liver volumes in whole right or left lateral segment donation. MR imaging is the gold standard for the assessment of biliary anatomy and allows a better quantification of hepatic steatosis compared to CT. Knowledge of normal and variant vascular and biliary anatomy and their surgical relevance for liver transplantation is of paramount importance for the radiologist. The purpose of this review is to outline the current role of CT and MR imaging in the assessment of hepatic parenchyma, hepatic vascular anatomy, biliary anatomy, and hepatic volumetry in the potential living liver donor with short notes on acquisition protocols and the relevant reportable findings.

Synchronous Abdominal Wall and Small-bowel Transplantation: A 1-year Follow-up.

Abdominal wall-vascularized composite allotransplantation (AW-VCA) has evolved as a technically feasible but challenging option in the rare event of abdominal wall reconstruction in patients whose abdomen cannot be closed by applying conventional methods. The authors conducted the first synchronous child-to-adult recipient AW-VCA using an arteriovenous loop technique. This article presents a 1-year follow-up of the patient's postoperative course. Frequent skin biopsies were performed in accordance with Duke Institutional Review Board protocol, with 3 episodes of rejection treated with high-dose steroids and Thymoglobulin (Genzyme Corp, Cambridge, Mass.). The patient developed an opportunistic fungal brain abscess secondary to immunosuppression, which led to temporary upper extremity weakness. Future considerations for AW-VCA include a modified surgical technique involving utilization of donor vein graft for arteriovenous loop formation. In addition, reduction in postoperative biopsy schedule and changes in immunosuppression regimen may lead to improved outcomes and prevent unnecessary high-dose immunosuppression.

Decreased graft loss following implementation of the kidney allocation score (KAS).

BACKGROUND: The Kidney Allocation System (KAS) was developed to improve equity and utility in organ allocation. We examine the effect of this change on kidney graft distribution and survival. METHODS: UNOS data was used to identify first-time adult recipients of a deceased donor kidney-alone transplant pre-KAS (Jan 2012-Dec 2014, n = 26,612) and post-KAS (Jan 2015-Dec 2017, n = 30,701), as well as grafts recovered Jan 2012-Jun 2019. RESULTS: Post-KAS, kidneys were more likely to experience cold ischemia time >24 h (20.0% vs. 18.8%, p < 0.001) and experienced more delayed graft function, though competing risks modeling demonstrated a lower hazard of graft loss post-KAS, HR 0.90 (95% CI 0.84-0.97, p = 0.007). Post-policy, KDPI >85% kidneys were more likely to be shared regionally (37% vs. 14%), and more likely to be discarded (60.6% vs. 54.9%) after the policy change. KDPI >85% graft and patient survival did not change. CONCLUSIONS: Implementation of the KAS has increased sharing of high-KDPI kidneys and has decreased the hazard of graft loss without an impact on patient survival.

The Systemic Immune-Inflammation Index Predicts Clinical Outcomes in Kidney Transplant Recipients.

BACKGROUND: Outcomes after kidney transplantation (KTx) remain limited by delayed graft function (DGF) and acute rejection. Non-invasive biomarkers may help identify patients at increased risk for these events. We examined the association between the systemic immune-inflammation index (SII), a novel inflammatory biomarker, and outcomes after KTx and evaluated its ability to predict post-transplant prognosis. PATIENTS AND METHODS: Adult patients who underwent primary KTx at our institution between 2016-2019 were included. SII was calculated from pre-transplant complete blood counts as the ratio of the neutrophil count to the lymphocyte count multiplied by the platelet count. The cutoff between high and low SII was determined by maximizing the area under the curve. Multivariable logistic and Cox regression were used to identify factors associated with DGF and patient, rejection-free, and graft survival respectively. RESULTS: Overall, 378 KTx recipients were included; 224 (59.3%) had high SII. On unadjusted analysis, high SII was associated with reduced odds of DGF, and improved patient and rejection-free survival. After adjustment, high SII was independently associated with improved patient survival alone. Multivariable models incorporating SII performed well for the prediction of DGF (c-statistic=0.755) and patient survival (c-statistic=0.786), though rejection-free survival was more difficult to predict (c-statistic=0.635). CONCLUSION: SII demonstrated limited utility as an independent predictor of outcomes after KTx. However, in combination with other clinically relevant parameters, SII is a useful predictor of post-KTx prognosis. Validation of this novel inflammatory biomarker in a multi-institutional study is needed to further elucidate its practical applications in transplantation.