Optimizing pediatric liver transplantation: Evaluating the impact of donor age and graft type on patient survival outcome.

BACKGROUND: We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. METHODS: A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. RESULTS: Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. CONCLUSIONS: Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.

The living donor evaluation as a life-saving event.

BACKGROUND: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem. While these problems may preclude donation, they may be lifesaving, as they are likely to be diagnosed and treated before the donor develops symptoms. PATIENTS AND METHODS: We looked at the incidence of occult cancer and other previously undiagnosed medical problems including renal disease, diabetes, hypertension, cardiac disease, and hepatitis C, in individuals volunteering to become a kidney donor at our center who proceeded with the evaluation between January 1, 1996 and May 31, 2011. RESULTS: Of 4088 potential donors, 19 (.46%) were discovered to have an unsuspected cancer, and 286 (7%) were found to have a previously undiagnosed medical problem. CONCLUSIONS: The living donor evaluation may lead to the early diagnosis of a life-threatening illness. This should be considered as one of the potential benefits of living donation.

Advances and innovations in living donor liver transplant techniques, matching and surgical training: Meeting report from the living donor liver transplant consensus conference.

The practice of LDLT currently delivers limited impact in western transplant centers. The American Society of Transplantation organized a virtual consensus conference in October 2021 to identify barriers and gaps to LDLT growth, and to provide evidence-based recommendations to foster safe expansion of LDLT in the United States. This article reports the findings and recommendations regarding innovations and advances in approaches to donor-recipient matching challenges, the technical aspects of the donor and recipient operations, and surgical training. Among these themes, the barriers deemed most influential/detrimental to LDLT expansion in the United States included: (1) prohibitive issues related to donor age, graft size, insufficient donor remnant, and ABO incompatibility; (2) lack of acknowledgment and awareness of the excellent outcomes and benefits of LDLT; (3) ambiguous messaging regarding LDLT to patients and hospital leadership; and (4) a limited number of proficient LDLT surgeons across the United States. Donor-recipient mismatching may be circumvented by way of liver paired exchange. The creation of a national registry to generate granular data on donor-recipient matching will guide the practice of liver paired exchange. The surgical challenges to LDLT are addressed herein and focuses on the development of robust training pathways resulting in proficiency in donor and recipient surgery. Utilizing strong mentorship/collaboration programs with novel training practices under the auspices of established training and certification bodies will add to the breadth and depth of training.

Robotic donor hepatectomy: A major breakthrough in living donor liver transplantation.

Living donation in many countries is the main resource of organs. Healthy, volunteering individuals deserve the highest safety standards possible in addition to the least invasive technique to procure the organs. Since the introduction of living donor liver transplantation, many efforts have been made to minimize the surgical trauma inherent to living donor surgery. The journey started with a large Mercedes incision and evolved to reverse L-shaped and small upper midline incisions before the introduction of minimally invasive laparoscopic techniques originated. The technical difficulties of the laparoscopic approach due to suboptimal instrumentation, challenging ergonomics, and the long learning curve limited the application of the fully laparoscopic approach to a few centers. The recent introduction of the robotic platform with its superb optical system and advanced instruments allows for the first time, a genuine emulation of open donor surgery in a closed abdomen, thus allowing all liver donors to benefit from minimally invasive surgery (better cosmesis, less pain and morbidity, and better quality of life) without compromising donor safety. This attribute in combination with the ubiquitous presence of the robot in major transplant centers may well lead to the desired endpoint of this technology, namely, the widespread dissemination of minimally invasive donor surgery.

Living donor liver transplantation in septuagenarians: Better late than never.

BACKGROUND: The coupling of increased life expectancy and improvements in both quality and access to chronic liver disease care, is culminating in an expanding population of septuagenarians (≥70 years) in need of liver transplantation (LT). The objective of this study is to partially alleviate this knowledge deficit and to add clarity to the current status and role of LDLT in this recipient population. METHODS: Of 295 adult patients underwent LDLT between January 1, 2011 and December 31, 2016. Twelve (4%) of these patients were septuagenarians and this group was compared to younger cohort (n = 283). RESULTS: Comorbidity profiles between the two groups were similar and no statistically significant differences were noted in warm/cold ischemia times, operative duration, or blood product utilization. ICU and total hospital stays were comparable. Septuagenarian 1-and 5-year graft and patient survivals were identical at 91.7%. Their younger counterparts had 1-and 5-year patient survivals of 91.1% and 84.0 % accompanied by 1-and 5-year graft survivals of 89.8% and 82.7%, respectively. CONCLUSION: Our study highlights a recognition that LDLT can afford highly-selected elderly patients to access to transplant with equivalent outcomes to those realized by younger recipients.

Robotic Versus Open Right Lobe Donor Hepatectomy for Adult Living Donor Liver Transplantation: A Propensity Score-Matched Analysis.

Robotic right lobe donor hepatectomy (RRLDH) is rarely performed, and data concerning its safety and efficacy are lacking. Here we compare our series of RRLDHs with a similar cohort undergoing open right lobe donor hepatectomy (ORLDH) with a propensity score-matched (PSM) analysis. Among 263 consecutive adult patients undergoing right lobe living donor hepatectomy from January 2015 until July 2019, 35 RRLDHs were matched to 70 ORLDHs. A 1:2 PSM analysis was performed to make the groups comparable for donor sex, age, and body mass index (BMI) and for recipient sex, age, BMI, Model for End-Stage Liver Disease score, and indication for transplant. Operative time was longer in RRLDHs compared with ORLDHs (504 ± 73.5 versus 331 ± 65.1 minutes; P < 0.001) but significantly decreased with the number of patients (P < 0.001). No conversions occurred. First warm ischemia time was longer and blood loss significantly less in RRLDHs (P = 0.001 and 0.003, respectively). Overall donor complications were similar: 2 (6%) in RRLDHs versus 12 (17%) in ORLDHs (P = 0.13). Biliary leak occurred in 1 (3%) patient receiving a robotic procedure and 2 (3%) patients receiving the conventional approach. Donors undergoing robotic surgery required less patient-controlled analgesia and had a shorter hospital stay compared with the open surgery group (P < 0.001 and P = 0.001, respectively). No significant differences in graft anatomical data and recipient outcomes were recorded. RRLDH is feasible, safe, and reproducible, with significantly decreased blood loss and a shorter hospital stay compared with the open procedure. The first 35 patients receiving the robotic procedure showed a substantial reduction in operative time, reflecting a rapid shortening of the learning curve.

Gastrointestinal side effects in liver transplant recipients taking enteric-coated mycophenolate sodium vs. mycophenolate mofetil.

In the setting of liver transplantation, mycophenolate mofetil (MMF) may be used as an adjuvant therapy for immunosuppression to prevent graft rejection; however, its use may be limited due to severe gastrointestinal (GI) side effects. In contrast, enteric-coated mycophenolate sodium (EC-MPS) may be associated with less severe side effects and hence better tolerability. We compared the side effects of EC-MPS to MMF in liver transplant patients in a de novo study (Study I-randomized, prospective, double-blinded) and a conversion study (Study II). In both studies, the severity of GI symptoms was assessed at various time points using the Gastrointestinal Symptoms Rating Scale (GSRS) survey, a validated survey of GI symptoms (abdominal pain, reflux, indigestion, diarrhea, and constipation). In Study I, the symptoms of 30 recipients receiving EC-MPS (n = 15) were compared to 15 recipients receiving MMF. A multivariate analysis of variance (MANOVA) of the total GSRS scores and symptom syndrome subscores revealed no significant difference (p > 0.05) between the two medications over time. A conversion study (Study II) with 29 participants, however, showed that over time, all GI symptoms improved significantly (p < 0.001) when the patients were treated with EC-MPS instead of MMF.

Complications related to invasive hemodynamic monitors during adult liver transplantation.

The rate of complications directly related to invasive monitors during liver transplantation (LT) was reviewed in 1206 consecutive adult LTs performed over 8.6 yr (1/1/2004-7/31/2012). The designated anesthesiologists placed intra-operative monitors, including two arterial catheters (via the radial and the right femoral arteries), central venous catheters (a 9 Fr. catheter and an 18 Fr. veno-venous bypass [VVB] return cannula in an internal jugular vein), a pulmonary artery catheter, and a transesophageal echocardiography (TEE) probe. A 17 Fr. VVB drainage cannula was placed via the left femoral vein. No Clavien-Dindo Grade V (death) or Grade IV (organ dysfunction) complication was identified. Nine Grade III complications (requiring surgical intervention) and 15 Grade II complications (conservative treatment) were noted. Seven (0.58% in 1206 cases) were related to a femoral arterial line with Grade III of four; seven (0.58%) were due to VVB return cannula in the femoral vein with Grade III of one; four (0.33%) were related to central venous catheters with Grade III of two; four (0.33%) were due to a TEE probe with Grade III of two; and two minor complications (0.17%) that were related to a radial arterial line. No complication was observed with a pulmonary arterial catheter. Current invasive monitors placed during LT have an acceptable risk.

The development of practice guidelines for independent living donor advocates.

The practice recommendations discussed here are based on the findings of the national survey as well as the opinions of the authors. The recommendations that are proposed here are not exhaustive and are aspirational in intent and are likely to evolve with time. Practice guidelines are recommended for legal and regulatory issues (e.g., state or federal laws), consumer or public benefit (e.g., improving service delivery, avoiding harm to the patient, decreasing disparities in underserved or vulnerable populations), and for professional guidance (e.g., new role, professional risk management issues, advances in practice). Without such practice guidelines, donors, and indirectly the candidates, may be at increased risk for possible bias or undue harm.

Maximizing utility of nondirected living liver donor grafts using machine learning.

Objective: There is an unmet need for optimizing hepatic allograft allocation from nondirected living liver donors (ND-LLD). Materials and method: Using OPTN living donor liver transplant (LDLT) data (1/1/2000-12/31/2019), we identified 6328 LDLTs (4621 right, 644 left, 1063 left-lateral grafts). Random forest survival models were constructed to predict 10-year graft survival for each of the 3 graft types. Results: Donor-to-recipient body surface area ratio was an important predictor in all 3 models. Other predictors in all 3 models were: malignant diagnosis, medical location at LDLT (inpatient/ICU), and moderate ascites. Biliary atresia was important in left and left-lateral graft models. Re-transplant was important in right graft models. C-index for 10-year graft survival predictions for the 3 models were: 0.70 (left-lateral); 0.63 (left); 0.61 (right). Similar C-indices were found for 1-, 3-, and 5-year graft survivals. Comparison of model predictions to actual 10-year graft survivals demonstrated that the predicted upper quartile survival group in each model had significantly better actual 10-year graft survival compared to the lower quartiles (p<0.005). Conclusion: When applied in clinical context, our models assist with the identification and stratification of potential recipients for hepatic grafts from ND-LLD based on predicted graft survivals, while accounting for complex donor-recipient interactions. These analyses highlight the unmet need for granular data collection and machine learning modeling to identify potential recipients who have the best predicted transplant outcomes with ND-LLD grafts.

First Experience in Living Liver Donation From Donors With Sickle Cell Trait.

Living donor liver transplantation is the main source of organs in the Middle East. Therefore, well balanced criteria are needed to avoid unnecessary exclusion of potential donors, while prioritizing donor safety. We face a high incidence of sickle cell trait (SCT; and disease). Therefore, there is vast experience in general and cardiac surgeries in SCT carriers at our center. After studying their management in detail, we considered accepting SCT carriers as living liver donors, on an exceptional basis. This the first single-center case series of living donor liver transplantation with SCT. Methods: Between January 2012 and September 2021, 20 donors with SCT were reviewed for age, gender, relation to the recipient, hemoglobin, hemoglobin S (HbS), surgical approach, intensive care unit stay, donor and recipients' complications, and graft and recipient survival. Results: Average age of donors was 28.4 y. Sixteen donated the left lateral segment, 4 the left lobe. Recipients were related children or adults. HbS ranged from 21.2% to 39.9%, being ≥30% in 14 donors. HbS was reduced by phlebotomy or exchange transfusion. We performed 7 open, one laparoscopic, and 12 robotic donor surgeries. Operating room time, blood loss, and intensive care unit stay were comparable to non-SCT donors. There was no SCT-related complication. All donors are alive and free of thromboembolic events. Graft and recipient survival is 100% until follow-up. Conclusion: Our experience should encourage other countries with high incidence of SCT to report their experience with this donor population.

Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults.

UNLABELLED: Liver transplantation (LT) is lifesaving for patients with Wilson disease (WD) presenting with fulminant hepatic failure (FHF) or chronic liver disease (CLD) unresponsive to treatment. AIM: To determine the outcome of LT in pediatric and adult patients with WD. METHODS: United Network for Organ Sharing data on LT from 1987 to 2008 were analyzed. Outcomes were compared for patients requiring LT for FHF and CLD after 2002. Multivariate logistic regression was used to determine risk factors for death and graft loss. RESULTS: Of 90,867 patients transplanted between 1987 and 2008, 170 children and 400 adults had WD. The one- and five-yr patient survival of children was 90.1% and 89% compared to 88.3% and 86% for adults, p = 0.53, 0.34. After 2002, 103 (41 children) were transplanted for FHF and 67 (10 children) for CLD. One- and five-yr patient survival was higher in children transplanted for CLD compared to FHF; 100%, 100% vs. 90%, 87.5% respectively, p = 0.30, 0.32. One- and five-yr patient survival was higher in adults transplanted for CLD compared to FHF; 94.7%, 90.1% vs. 90.3%, 89.7%, respectively, p = 0.36, 0.88. Encephalopathy, partial graft, and ventilator use were risk factors for death by logistic regression. CONCLUSION: LT is an excellent treatment option for patients with WD. Patients transplanted for CLD had higher patient survival rates than patients with FHF.

The beneficial impact of temporary porto-caval shunt in orthotopic liver transplantation: a single center analysis.

The use of temporary porto-caval shunt (TPCS) has been shown to improve hemodynamic stability and renal function in patients undergoing orthotopic liver transplantation (OLT). We evaluated the impact of TPCS in OLT and analyzed the differences according to model for end-stage liver disease (MELD), donor risk index (DRI) and D-MELD. This is a retrospective single-center analysis of 148 consecutive OLT. Fifty-eight OLT were performed using TPCS and 90 without TPCS. Donor and recipient data with pre-OLT, intraoperative and postoperative variables were reviewed. Overall graft survival was 89.9% at 3 months and 81.7% at 1 year. Graft survival at 3 months and 1 year was 93.1% and 79.2%, respectively, in TPCS group versus 85.6% and 82.2%, respectively, in non-TPCS group (P = NS). Intraoperative packed red blood cells requirement was lower in TPCS group (7.5 ± 5.8 vs. 12.2 ± 14.2, P = 0.006) and non-TPCS group required higher intraoperative total dose of phenylephrine (16% vs. 28%, P = 0.04). TPCS group had lower 30-day postoperative mortality (1.7% vs. 10%, P = 0.04), no difference was observed at 90 days. Graft survival was lower in patients with high DRI; in this group graft loss was higher at 1 month (25% vs. 4.3%, P = 0.005) and 3 months (25% vs. 4.3%, P = 0.005) when TPCS was not used. TPCS improves perioperative outcome, this being more evident when high-risk grafts are placed into high-risk patients.

Feasibility of Full-Right/Full-Left Split-Liver Transplant in Pediatric Deceased Donors for Pediatric Recipients.

This case report describes the first ex situ full-right/full-left splitting of a liver from a pediatric deceased donor in the Middle East with an excellent outcome for both recipients. The left lateral split-liver transplant requires division of the deceased donor liver into a left lateral lobe for a pediatric recipient and an extended right lobe for an adult recipient, thus producing only 1 graft for a pediatric recipient. Full-right/full-left liver transplant, which splits the liver along the line of Cantlie, is a much more complex and challenging surgery, even though the technique is fully developed, and is theoretically able to produce 2 sizeable grafts for 2 pediatric recipients. However, the full-right/full-left liver transplant remains limited because of the small vascular structures and therefore was not recommended and was not previously described in the literature.

Safety and Feasibility Report of Robotic-assisted Left Lateral Sectionectomy for Pediatric Living Donor Liver Transplantation: A Comparative Analysis of Learning Curves and Mastery Achieved With the Laparoscopic Approach.

BACKGROUND: There is a growing interest in left lateral sectionectomy for donor hepatectomy. No data are available concerning the safety of the robotic (ROB) approach. METHODS: A retrospective comparative study was conducted on 75 consecutive minimally invasive donor hepatectomies. The first 25 ROB procedures performed from November 2018 to July 2019 were compared with our first (LAP1) and last 25 (LAP2) laparoscopic cases performed between May 2013 and October 2018. Short-term donors and recipients' outcomes were analyzed. RESULTS: No conversions were noticed in ROB whereas 2 conversions (8%) were recorded in LAP1 and none in LAP2. Blood loss was significantly less in ROB compared with LAP1 (P ≤ 0.001) but not in LAP2. Warm ischemia time was longer in ROB (P ≤ 0.001) with respect to the other groups. Operative time was similar in the 3 groups (P = 0.080); however, the hospital stay was shorter in ROB (P = 0.048). The trend in operative time in ROB was significantly shorter compared to LAP1 and LAP2: linear R2 0.478, P≤0.001; R2 0.012, P = 0.596; R3 0.004, P = 0.772, respectively. Donor morbidity was nihil in ROB, similar in LAP1 and LAP2 (n=3%-12%; P = 0.196). ROB procedures required less postoperative analgesia (P = 0.002). Recipient complications were similar for all groups (P = 0.274), and no early retransplantations were recorded. CONCLUSIONS: Robotic left lateral sectionectomy for donor hepatectomy is a safe procedure with results comparable to the laparoscopy in terms of donor morbidity and overall recipients' outcome when the procedure is performed by experts. Certainly, its use is currently very limited.

Improved outcomes in pediatric liver transplantation for acute liver failure.

UNLABELLED: OLT is a life-saving option for ALF. AIM: To evaluate our outcomes in pediatric OLT for ALF. METHODS: Retrospective review of our data between 1992 and 2007. RESULTS: Of 142 children with ALF, 126 were listed, of which 40 spontaneously improved, nine died, and 77 underwent OLT (median waiting time four days). Fifty-three children received deceased donor grafts (34 whole and 19 split grafts), and there were 24 living donor grafts. The one- and five-yr patient survival was 87% and 80%, and graft survival 83% and 79%, respectively. Thirteen patients died after OLT, and there were nine retransplants in seven patients. Patient weight, length of stay, creatinine, and infection were significantly associated with death; increased weight and black ethnicity were associated with graft loss on univariate analysis, but not on multivariate analysis. There were no significant differences in patient survival (one and five yr), graft loss, or other complications between the groups. CONCLUSION: We report the largest single-center study of OLT in pediatric ALF, demonstrating no difference in outcomes between different graft types. Our liberal use of segmental grafts may allow earlier OLT in this high-risk cohort and contribute to our excellent outcomes.

Is It Justified to Use Liver Grafts From Living Donors for Retransplant? A Single-Center Experience.

OBJECTIVES: Liver retransplant is considered the only hope for patients with irreversible graft failure after primary transplant. In most Western centers, retransplantis done mainly from deceased donors; so far, only few published studies have reported on outcomes of liver retransplant with living donors. In this study, our aim was to analyze the outcomes of living-donor liver retransplant. MATERIALS AND METHODS: Patients who underwent liver retransplant between February 2011 and February 2019 were included in the study. Preoperative, operative, and postoperative data were analyzed. Results from 2 patient groups were compared: liver retransplant with living donors and liver retransplant with deceased donors. RESULTS: Thirty-two patients underwent liver retransplant (21 adult and 11 pediatric patients). The most common indications for liver retransplant were hepatic artery thrombosis (28.5%) and primary graft nonfunction (23.8%) in adults and hepatic artery thrombosis (45.5%) and chronic rejection (36.4%) in pediatric patients. Seventeen retransplant patients (53.1%) required early retransplant (within 1 mo), mainly due to hepatic artery thrombosis (52.9%) and primary graft nonfunction (35.3%). Late retransplant was mainly due to chronic rejection (40%) and recurrence of primary disease (26.7%). Seventeen patients (53.1%) underwent living-donor retransplant, and 5 donors underwent robotic right hepatectomy. Graft and patient survival rates at 1, 3, and 5 years were 81.3% for living-donor and 51.4% for deceased-donor liver retransplant recipients (P = .08). On multivariate analyses, we observed significant differences between both groups in pretransplant Model for End-Stage Liver Disease and Pediatric End-Stage Liver Disease scores (P = .05), preoperative international normalized ratio (P = .012), and cold ischemia time (P = .046). CONCLUSIONS: The use of living donors for liver retransplant, despite its technical demand, was shown to be a safe and feasible option, especially when there is scarcity of deceased donors.

A study of the main determinants of kidney allograft long-term survival in the era of new immunosuppressive drugs.

The outcome of long-term kidney allograft is extremely important. The present study aimed to discern the factors affecting long-term kidney allograft survival, including the type of donation and the use of extended criteria donors. Seven hundred and thirty-seven kidney transplant alone patients entered this retrospective cross-sectional study. The impact of different factors on death-censored long-term kidney allograft survival was evaluated. The Cox proportional survival model was employed to identify these factors. A value of P < 0.05 was considered statistically significant. The data were analyzed using IBM Statistical Package for the Social Sciences version 19.0. The study was conducted at the Mashhad University of Medical Sciences, Mashhad, Iran. In comparison with living kidney donations, both nontraumatic and traumatic brain death cadaveric kidney donations showed statistically significant inferior graft survival. Furthermore, the Kaplan-Meier survival analysis showed better durability of living kidney donations in comparison with traumatic and nontraumatic deceased donors (Log-rank test value = 0.001). Patients with delayed graft function (DGF) had a significantly shorter long-term death censured long-term graft survival in comparison with those without this complication. The Cox proportional models showed that DGF occurrence and the type of donation play a statistically significant role in long-term kidney graft survival. In addition, regarding graft survival, there was no difference between standard criteria and extended criteria donors. The occurrence of DGF and living or deceased types of donations have a significant effect on long-term kidney allograft survival.

The first two cases of living donor liver transplantation using dual grafts in Saudi Arabia.

The concept of dual-graft liver transplantation was introduced to overcome the discrepancy between liver transplantation demand and liver donation. Dual-graft transplantation also mitigates cumulative family risk by decreasing individual donor risk through minimization of the resected liver volume from each donor. Here, we describe the first two cases performed in Saudi Arabia wherein a dual-graft living donor liver transplantation was facilitated by the use of one left lobe graft and one left lateral segment in both cases. These are the first two cases of dual-graft liver transplantation reported from Saudi Arabia and the Middle East. SIMILAR CASES PUBLISHED: Nine on the same subject in other parts of the world (Korea, Japan, Germany, China, and Brazil).