US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery.

Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures: cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

Systematic review and meta-analysis of open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy.

The value of minimally invasive approaches for living donor hepatectomy remains unclear. Our aim was to compare the donor outcomes after open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy (OLDH vs. LALDH vs. PLLDH vs. RLDH). A systematic literature review of the MEDLINE, Cochrane Library, Embase, and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (up to December 8, 2021). Random-effects meta-analyses were performed separately for minor and major living donor hepatectomy. The risk of bias in nonrandomized studies was assessed using the Newcastle-Ottawa Scale. A total of 31 studies were included. There was no difference in donor outcomes after OLDH versus LALDH for major hepatectomy. However, PLLDH was associated with decreased estimated blood loss, length of stay (LOS), and overall complications versus OLDH for minor and major hepatectomy, but also with increased operative time for major hepatectomy. PLLDH was associated with decreased LOS versus LALDH for major hepatectomy. RLDH was associated with decreased LOS but with increased operative time versus OLDH for major hepatectomy. The scarcity of studies comparing RLDH versus LALDH/PLLDH did not allow us to meta-analyze donor outcomes for that comparison. There seems to be a marginal benefit in estimated blood loss and/or LOS in favor of PLLDH and RLDH. The complexity of these procedures limits them to transplant centers with high volume and experience. Future studies should investigate self-reported donor experience and the associated economic costs of these approaches.

Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study.

Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.

Liver Transplantation for Hepatic Adenoma: A UNOS Database Analysis and Systematic Review of the Literature.

BACKGROUND: Liver transplantation (LT) has been employed for hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA. METHODS: All patients listed or transplanted for HA in the United States were identified in the United Network for Organ Sharing (UNOS) database (1987-2020). A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. RESULTS: A total of 199 HA patients were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 HA patients underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 mo, death was reported in 18.3%. The 1-, 3-, and 5-y patient survival rates were 94.2%, 89.7%, and 86.3% in the UNOS cohort. The systematic review yielded 61 articles reporting on 99 nonoverlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), whereas 53.1% had glycogen storage disease. Over a median follow-up of 36.5 mo, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-y patient survival rates were all 95.0% in the systematic review. CONCLUSIONS: LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.

Laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma: An individual patient data survival meta-analysis.

BACKGROUND: We compared the outcomes of laparoscopic hepatectomy (LH) vs. open hepatectomy (OH) for intrahepatic cholangiocarcinoma (iCCA). METHODS: A systematic review of the MEDLINE, EMBASE, Scopus, and Cochrane Library databases was performed using PRISMA guidelines (end-of-search date: 08-June-2020). Individual patient data on overall survival (OS) and recurrence-free survival (RFS) were extracted. Random-effects meta-analyses, and one- and two-stage survival analyses were conducted. RESULTS: Eight retrospective cohort studies comparing LH (n = 544) vs. OH (n = 2256) were identified. LH demonstrated lower overall complication (Risk ratio [RR] = 0.64, 95% confidence interval [CI]: 0.46-0.90; p = 0.01), surgical lymphadenectomy (RR = 0.74, 95% CI: 0.58-0.93; p = 0.01) and margin-positive resection (RR = 0.78, 95% CI: 0.62-0.99; p = 0.04) rates, and higher recurrence-free rate (RR = 1.24, 95% CI: 1.01-1.51; p = 0.04) vs. OH. In Cox regression, no difference was observed regarding OS (Hazard Ratio [HR] = 1.11, 95% CI: 0.65-1.91; p = 0.70) and RFS (HR = 1.19, 95% CI: 0.74-1.90; p = 0.47). CONCLUSION: The use of LH should be considered when feasible in well-selected iCCA patients by hepatobiliary surgeons with experience in minimally-invasive surgery.

Liver Transplantation for Langerhans Cell Histiocytosis: A US Population-Based Analysis and Systematic Review of the Literature.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. Liver involvement is seen in 10.1% to 19.8% of patients with LCH and can lead to secondary sclerosing cholangitis requiring liver transplantation (LT). We describe the characteristics and outcomes of patients undergoing LT for LCH. All patients undergoing a first LT for LCH in the United States were identified in the Scientific Registry of Transplant Recipients (SRTR) database (1987-2018). The Kaplan-Meier curve method and log-rank tests evaluated post-LT survival. A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A total of 60 LCH LT recipients were identified in the SRTR, and 55 patients (91.7%) were children with median total bilirubin levels at LT of 5.8 mg/dL (interquartile range [IQR], 2.7-12.9). A total of 49 patients (81.7%) underwent deceased donor LT (DDLT). The 1-year, 3-year, and 5-year patient survival rates were 86.6%, 82.4%, and 82.4%, respectively. The systematic review yielded 26 articles reporting on 50 patients. Of the patients, 41 were children (82.0%), 90.0% had multisystem LCH, and most patients underwent DDLT (91.9%; n = 34/37). Pre-LT chemotherapy was administered in 74.0% and steroids in 71.7% (n = 33/46) of the patients, and a recurrence of LCH to the liver was reported in 8.0% of the patients. Of the 50 patients, 11 (22.0%) died during a median follow-up of 25.2 months (IQR, 9.0-51.6), and the 1-year patient survival rate was 79.4%. LT can be considered as a feasible life-saving option for the management of liver failure secondary to LCH in well-selected patients.

Liver Transplantation for Intrahepatic Cholangiocarcinoma: A Meta-analysis and Meta-regression of Survival Rates.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a contraindication to liver transplantation in most centers worldwide. Therefore, only a few such cases have been performed in each individual center, and the need for a systematic review and meta-analysis to cumulatively pool these results is apparent. METHODS: A systematic literature review was conducted using the MEDLINE and Cochrane Library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (end-of-search date: May 29, 2020). Meta-analyses of proportions were conducted to pool the overall survival (OS), recurrence-free survival (RFS), and overall recurrence rates using the random-effects model. Meta-regression was used to examine cirrhosis and incidental diagnosis as confounders on OS and RFS. RESULTS: Eighteen studies comprising 355 patients and a registry study of 385 patients were included. The pooled 1-, 3-, and 5-y OS rates were 75% (95% CI, 64%-84%), 56% (95% CI, 46%-67%), and 42% (95% CI, 29%-55%), respectively. The pooled 1-, 3-, and 5-y RFS rates were 70% (95% CI, 63%-75%), 49% (95% CI, 41%-57%), and 38% (95% CI, 27%-50%), respectively. Cirrhosis was positively associated with RFS, while incidental diagnosis was not. Neither cirrhosis nor incidental diagnosis was associated with OS. The pooled overall recurrence rate was 43% (95% CI, 33%-53%) over a mean follow-up of 40.6 ± 37.7 mo. Patients with very early (single ≤2 cm) iCCA exhibited superior pooled 5-y RFS (67%; 95% CI, 47%-86%) versus advanced iCCA (34%; 95% CI, 23%-46%). CONCLUSIONS: Cirrhotics with very early iCCA or carefully selected patients with advanced iCCA after neoadjuvant therapy may benefit from liver transplantation under research protocols.

Comparison of Wait-List Mortality Between Cholangiocarcinoma and Hepatocellular Carcinoma Liver Transplant Candidates.

Despite the divergent disease biology of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC), wait-list prioritization is identical for both diagnoses. We compared wait-list and posttransplant outcomes between CCA and HCC liver transplantation patients with Model for End-Stage Liver Disease exceptions using Scientific Registry of Transplant Recipients data. The 408 CCA candidates listed between 2003 and mid-2017 were matched to 2 HCC cohorts by listing date (±2 months, n = 816) and by Organ Procurement and Transplantation Network (OPTN) region and date (±6 months, n = 408). Cumulative incidence competing risk regression examined the effects of diagnosis, OPTN region, and center-level CCA listing volume on wait-list removal due to death/being too ill (dropout). Cox models evaluated the effects of diagnosis, OPTN region, center-level CCA volume, and waiting time on graft failure among deceased donor liver transplantation (DDLT) recipients. After adjusting for OPTN region and CCA listing volume (all P ≥ 0.07), both HCC cohorts had a reduced likelihood of wait-list dropout compared with CCA candidates (HCC with period matching only: subdistribution hazard ratio [SHR] = 0.63; 95% CI, 0.43-0.93; P = 0.02 and HCC with OPTN region and period matching: SHR = 0.60; 95% CI, 0.41-0.87; P = 0.007). The cumulative incidence rates of wait-list dropout at 6 and 12 months were 13.2% (95% CI, 10.0%-17.0%) and 23.9% (95% CI, 20.0%-29.0%) for CCA candidates, 7.3% (95% CI, 5.0%-10.0%) and 12.7% (95% CI, 10.0%-17.0%) for HCC candidates with region and listing date matching, and 7.1% (95% CI, 5.0%-9.0%) and 12.6% (95% CI, 10.0%-15.0%) for HCC candidates with listing date matching only. Additionally, HCC DDLT recipients had a 57% reduced risk of graft failure compared with CCA recipients (P < 0.001). Waiting time was unrelated to graft failure (P = 0.57), and there was no waiting time by diagnosis cohort interaction effect (P = 0.47). When identically prioritized, LT candidates with CCA have increased wait-list dropout compared with those with HCC. More granular data are necessary to discern ways to mitigate this wait-list disadvantage and improve survival for patients with CCA.

Population-Based Analysis of Hepatocellular Carcinoma in Children: Identifying Optimal Surgical Treatment.

BACKGROUND: Hepatocellular carcinoma (HCC) constitutes 0.5% of childhood malignancies and exhibits poor prognosis. Complete tumor extirpation either by partial liver resection (LR) or liver transplantation (LT) is the only curative treatment. Due to the poor initial outcomes of LT, LR has remained the mainstay of treatment for all but select children fulfilling the Milan criteria (originally designed for adults). METHODS: We conducted a retrospective cohort study of pediatric HCC patients (younger than 18 years of age) registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Survival analysis was performed by means of Kaplan-Meier methods, 2-sided stratified log-rank tests, and Cox regression models. RESULTS: Of 127 children with HCC, 46 did not undergo operation (36.2%), 32 underwent LT (25.2%), and 49 underwent LR (38.6%). Using the Kaplan-Meier method, the 5-year cancer-specific survival (CSS) rates for LT and LR were 87% and 63%, respectively. LT exhibited superior CSS vs LR (log-rank, p = 0.007). For T1 stage, LT showed equivalent CSS compared with LR (log-rank, p = 0.23), and for T2 and T3 stage, LT exhibited superior CSS (log-rank, p = 0.047 and p = 0.01, respectively). On multivariable Cox regression analysis, T3/T4 stage (adjusted hazard ratio 13.63; 95% CI, 2.9 to 64.07; p = 0.001), and LR (adjusted hazard ratio 7.51; 95% CI, 2.07 to 27.29; p = 0.002) were found to be independently associated with cancer-specific mortality. Fibrolamellar histology and lymph node status were not found to be associated with mortality. CONCLUSIONS: Our findings suggest that children diagnosed with nonmetastatic advanced-stage HCC have a favorable prognosis after LT compared with LR. Early inclusion of an LT consultation after the initial diagnosis is warranted, especially in children with unresectable HCC or when complete tumor extirpation with LR is not feasible.

Superior Patient and Graft Survival in Adult Liver Transplant with Rabbit Antithymocyte Globulin Induction: Experience with 595 Patients.

OBJECTIVES: The use of induction therapy in liver transplant is debatable. We aimed to compare clinical outcomes of different induction protocols in liver transplant recipients. MATERIALS AND METHODS: This was a retrospective cohort analyses using the University of Washington Transplant Database from January 2005 to May 2012 for adult (≥ 18 y old) primary liver transplant patients. All patients received induction therapy. Maintenance immunosuppressive agents were tacrolimus or tacrolimus-mycophenolate mofetil. Primary endpoints were acute cellular rejection, patient survival, and graft survival. In patients with chronic hepatitis C, the degree of histologic inflammation or fibrosis at 1 year was assessed. Cox proportional hazards models were constructed to evaluate variables associated with both patient and graft survival. RESULTS: We identified 595 patients: 322 patients received rabbit antithymocyte globulin and 273 received interleukin 2 receptor blocker. Acute cellular rejection was higher in patients who received interleukin 2 receptor blocker than in patients who received rabbit antithymocyte globulin (27% vs 18%; P < .03). Both patient survival at 1 year (95% vs 90%), 3 years (92% vs 87%), and 5 years (86% vs 80%) and graft survival at 1 year (93% vs 88%), 3 years (90% vs 86%), and 5 years (83% vs 78%) were superior with rabbit antithymocyte globulin than with the interleukin 2 receptor blocker (P < .002). In patients with hepatitis C virus, type of induction therapy did not have any effect on the timing of hepatitis C virus recurrence. At 1 year after transplant, 33.3% in the rabbit antithymocyte globulin group had grade 3/4 inflammation and 10.2% had stage 3/4 fibrosis, compared with 16.8% and 4.8% in the interleukin 2 receptor blocker group (P ≤ .002 and not significant). Female recipient, Model for End-Stage Liver Disease score, hepatocellular carcinoma, and high preoperative serum creatinine levels were associated with less favorable patient and graft survival. CONCLUSIONS: Rabbit antithymocyte globulin is associated with lower rejection rate and improved patient and graft survival in liver transplant. Type of therapy affects the degree of histologic hepatitis C virus recurrence.

Outcomes of adult liver re-transplant patients in the model for end-stage liver disease era: is it time to reconsider its indications?

OBJECTIVE: To better understand the outcomes and utility of liver re-transplantation in non-hepatitis C patients, we sought to identify predictors that impact post-transplant patient and graft survival comparing primary liver transplant patients to those receiving subsequent allografts. METHODS: We conducted a retrospective cohort analysis using the United Network for Organ Sharing database from February 2002 through December 2012, including non-hepatitis C infected adults (18 yr and older) who underwent primary and repeat liver transplantation. Patient and graft survival were compared between the two groups using the Kaplan-Meier estimator. Cox proportional hazards models were constructed to evaluate variables associated with both patient and graft survival. RESULTS: We identified 33 176 primary transplant recipients and 2710 re-transplants. Re-transplantation patients were more likely to be on dialysis prior to transplant (18% vs. 10%), hospitalized (26% vs. 16%), in the intensive care unit (ICU) (34% vs. 13%), on a ventilator (17% vs. 3%), and had higher model for end-stage liver disease (MELD) score (27 vs. 21). Re-transplants also received livers with a lower donor risk index (DRI) (1.57 vs. 1.64). We estimated an adjusted hazard ratio (HR) of 1.7 for patient survival (95% CI: 1.56-1.84) and 1.61 (95% CI: 1.5-1.73) for graft survival. CONCLUSIONS: Liver re-transplantation in non-hepatitis C patients, although life saving, has significantly inferior patient and graft survival compared to primary liver transplantation. Higher quality grafts are used inefficiently in a sicker patient population, suggesting that a more optimal strategy may include restricting their use to patients who obtain a longer term benefit.

A broad assessment of clinical outcomes after laparoscopic antireflux surgery.

OBJECTIVES: There is considerable discussion regarding "success" rates for laparoscopic antireflux surgery (LARS). We hypothesized that, in part, this was a reflection of the outcome variables used. We, therefore, defined 8 specific variables (within 3 categories) and assessed outcomes for each in a large cohort of patients. METHODS: Four hundred patients (208 women; median age 52 years old) who underwent LARS at the University of Washington from 1993 to 2008 were given a comprehensive questionnaire to assess various aspects of their outcomes from LARS. In addition, we analyzed all functional studies and all endoscopies performed in these patients in our institution, whether the patients had symptoms or not, and compared the findings to all available preoperative values. RESULTS: The median follow-up was 92 (6-175) months. CONCLUSIONS: The success or failure of LARS cannot be defined in a single domain. A comprehensive analysis of outcomes requires categorization that includes symptom response, side-effects, patient's perception and objective measurement of acid exposure, mucosal integrity, and the need for additional medical or surgical treatment. Only then can patients and physicians better understand the role of LARS and make informed decisions.

Assessment of a simple, novel endoluminal method for gastrotomy closure in NOTES.

BACKGROUND: A reliable method for gastrotomy closure in NOTES will be essential for NOTES to become viable clinically. However, methods using existing and widely available endoscopic accessories have been ineffective. The objective of this study was to evaluate the feasibility and safety of a new simple method for gastric closure (retracted clip-assisted loop closure) that uses existing endoscopic accessories with minor modifications. METHODS: The retracted clip-assisted loop closure technique involves deploying 3-4 Resolution(®) clips (modified by attaching a 90-cm length of suture to the end of each clip) along the margin of the gastrotomy with one jaw on the serosal surface and the other jaw on the mucosal surface. The suture strings are threaded through an endoloop. Traction is then applied to the strings causing the gastric wall to tent. The endoloop is secured below the tip of the clips, completing a full-thickness gastrotomy closure. The main outcome measures were feasibility, efficacy, and safety of the new retracted clip-assisted loop closure technique for NOTES gastrotomy closure. RESULTS: An air-tight seal was achieved in 100% (n = 9) of stomachs. The mean leak pressure was 116.3 (±19.4) mmHg. CONCLUSIONS: The retracted clip-assisted loop closure technique can be used to perform NOTES gastrotomy closure by using existing endoscopic accessories with minor modifications.

Laparoscopic splenopexy for wandering spleen: case report and review of the literature.

Wandering spleen is a rare condition in which the spleen lacks retroperitoneal fixation, thus its vascular pedicle can twist resulting in ischemia. Although splenectomy has traditionally been used for this condition, splenopexy is increasingly used in the pediatric population to anchor the spleen and preserve splenic function. We report an unusual case of wandering spleen in an adult with chronic torsion managed with laparoscopic splenopexy, suggesting splenic preservation is possible in adults with this presentation as well.