Methadone for Emergence Delirium in Ambulatory Pediatric Strabismus Surgery.

Background: Emergence delirium in children following strabismus surgery is a distressing and potentially dangerous condition and is likely attributable to visual disturbances, pain, and anesthetic gases. We explored whether a single intraoperative dose of methadone could reduce emergence delirium. Methods: Our study was an institutional review board-approved prospective, controlled, before-and-after investigation. Inclusion criteria were age <18 years and American Society of Anesthesiologists (ASA) classification 1 or 2. Patients were excluded for obesity, documented sleep apnea, significant neurologic disease, or inpatient status. Control group patients were recruited sequentially, and the anesthetic was performed per preference. The study group was recruited similarly and received an intravenous dose of methadone 0.15 mg/kg at induction. The primary outcome was peak score on the Pediatric Anesthesia Emergence Delirium (PAED) scale. Secondary outcomes included time to anesthetic emergence, postoperative pain scores, postanesthesia care unit (PACU) length of stay, and postdischarge respiratory complications. Results: Forty-nine control group and 55 study group patients were recruited. No significant differences were found between groups for age, sex, weight, ASA classification, or duration of surgery. The control group received more preoperative midazolam, intraoperative fentanyl, and intraoperative ketorolac. Compared to the control group, the study group had 42% and 85% reductions in peak and severe PAED scale scores, respectively, in the PACU and required less rescue pain medications. Anesthetic emergence time and length of stay were not different between the groups. No significant postoperative complications occurred. Conclusion: Emergence delirium following outpatient pediatric strabismus surgery was substantially mitigated by the use of intraoperative methadone without affecting PACU throughput. No significant complications occurred. Further study is warranted to corroborate routine use of this drug for emergence delirium.

Islet transplantation outcomes in type 1 diabetes and transplantation of HLA-DQ8/DR4: results of a single-centre retrospective cohort in Canada.

Background: In solid organ transplantation, HLA matching between donor and recipient is associated with superior outcomes. In islet transplantation, an intervention for Type 1 diabetes, HLA matching between donor and recipient is not performed as part of allocation. Susceptibility to Type 1 diabetes is associated with the presence of certain HLA types. This study was conducted to determine the impact of these susceptibility antigens on islet allograft survival. Methods: This is a single-centre retrospective cohort study. This cohort of transplant recipients (n = 268) received islets from 661 donor pancreases between March 11th, 1999 and August 29th, 2018 at the University of Alberta Hospital (Edmonton, AB, Canada). The frequency of the Type 1 diabetes susceptibility HLA antigens (HLA-A24, -B39, -DQ8, -DQ2 and-DQ2-DQA1∗05) in recipients and donors were determined. Recipient and donor HLA antigens were examined in relation to time to first C-peptide negative status/graft failure or last observation point. Taking into account multiple transplants per patient, we fitted a Gaussian frailty survival analysis model with baseline hazard function stratified by transplant number, adjusted for cumulative islet dose and other confounders. Findings: Across all transplants recipients of donors positive for HLA-DQ8 had significantly better graft survival (adjusted HRs 0.33 95% CI 0.17-0.66; p = 0.002). At first transplant only, donors positive for HLA-DQ2-DQA1∗05 had inferior graft survival (adjusted HR 1.96 95% CI 1.10-3.46); p = 0.02), although this was not significant in the frailty analysis taking multiple transplants into account (adjusted HR 1.46 95% CI 0.77-2.78; p = 0.25). Other HLA antigens were not associated with graft survival after adjustment for confounders. Interpretation: Our findings suggest islet transplantation from HLA-DQ8 donors is associated with superior graft outcomes. A donor positive for HLA-DQ2-DQA1∗05 at first transplant was associated with inferior graft survival but not when taking into account multiple transplants per recipient. The relevance of HLA-antigens on organ allocation needs further evaluation and inclusion in islet transplant registries and additional observational and interventional studies to evaluate the role of HLA-DQ8 in islet graft survival are required. Funding: None.

Perioperative clinical practice in liver transplantation: a cross-sectional survey.

PURPOSE: The objective of this study was to describe some components of the perioperative practice in liver transplantation as reported by clinicians. METHODS: We conducted a cross-sectional clinical practice survey using an online instrument containing questions on selected themes related to the perioperative care of liver transplant recipients. We sent email invitations to Canadian anesthesiologists, Canadian surgeons, and French anesthesiologists specialized in liver transplantation. We used five-point Likert-type scales (from "never" to "always") and numerical or categorical answers. Results are presented as medians or proportions. RESULTS: We obtained answers from 130 participants (estimated response rate of 71% in Canada and 26% in France). Respondents reported rarely using transesophageal echocardiography routinely but often using it for hemodynamic instability, often using an intraoperative goal-directed hemodynamic management strategy, and never using a phlebotomy (medians from ordinal scales). Fifty-nine percent of respondents reported using a restrictive fluid management strategy to manage hemodynamic instability during the dissection phase. Forty-two percent and 15% of respondents reported using viscoelastic tests to guide intraoperative and postoperative transfusions, respectively. Fifty-four percent of respondents reported not pre-emptively treating preoperative coagulations disturbances, and 91% reported treating them intraoperatively only when bleeding was significant. Most respondents (48-64%) did not have an opinion on the maximal graft ischemic times. Forty-seven percent of respondents reported that a piggyback technique was the preferred vena cava anastomosis approach. CONCLUSION: Different interventions were reported to be used regarding most components of perioperative care in liver transplantation. Our results suggest that significant equipoise exists on the optimal perioperative management of this population.

RéSUMé: OBJECTIF: L'objectif de cette étude était de décrire certaines composantes de la pratique périopératoire en transplantation hépatique telles que rapportées par les cliniciens. MéTHODE: Nous avons mené un sondage transversal sur la pratique clinique à l'aide d'un instrument en ligne comportant des questions sur des thèmes sélectionnés liés aux soins périopératoires des receveurs de greffe du foie. Nous avons envoyé des invitations par courriel à des anesthésiologistes canadiens, des chirurgiens canadiens et des anesthésiologistes français spécialisés en transplantation hépatique. Nous avons utilisé des échelles de type Likert à cinq points (de « jamais ¼ à « toujours ¼) et des réponses numériques ou catégorielles. Les résultats sont présentés sous forme de médianes ou de proportions. RéSULTATS: Nous avons obtenu des réponses de 130 participants (taux de réponse estimé à 71 % au Canada et à 26 % en France). Les répondants ont déclaré utiliser rarement l'échocardiographie transœsophagienne de routine, mais l'utiliser fréquemment pour l'instabilité hémodynamique, souvent en utilisant une stratégie de prise en charge hémodynamique peropératoire axée sur les objectifs, et jamais en utilisant une phlébotomie (médianes des échelles ordinales). Cinquante-neuf pour cent des répondants ont déclaré utiliser une stratégie restrictive de gestion liquidienne pour prendre en charge l'instabilité hémodynamique pendant la phase de dissection. Quarante-deux pour cent et 15 % des répondants ont déclaré utiliser des tests viscoélastiques pour guider les transfusions peropératoires et postopératoires, respectivement. Cinquante-quatre pour cent des répondants ont déclaré ne pas traiter préventivement les troubles préopératoires de la coagulation, et 91 % ont déclaré les traiter en peropératoire uniquement lorsque les saignements étaient importants. La plupart des répondants (48-64 %) n'avaient pas d'opinion sur les temps ischémiques maximaux du greffon. Quarante-sept pour cent des répondants ont déclaré qu'une technique de 'piggyback' (anastomose latéroterminale) était l'approche préférée pour l'anastomose de la veine cave. CONCLUSION: Différentes interventions ont été signalées pour la plupart des composantes des soins périopératoires dans la transplantation hépatique. Nos résultats suggèrent qu'il existe une incertitude significative concernant la prise en charge périopératoire optimale de cette population.

Long-term outcomes after normothermic machine perfusion in liver transplantation-Experience at a single North American center.

Normothermic machine perfusion (NMP) has emerged as a valuable tool in the preservation of liver allografts before transplantation. Randomized trials have shown that replacing static cold storage (SCS) with NMP reduces allograft injury and improves graft utilization. The University of Alberta's liver transplant program was one of the early adopters of NMP in North America. Herein, we describe our 7-year experience applying NMP to extend preservation time in liver transplantation using a "back-to-base" approach. From 2015 to 2021, 79 livers were transplanted following NMP, compared with 386 after SCS only. NMP livers were preserved for a median time of minutes compared with minutes in the SCS cohort (P < .0001). Despite this, we observed significantly improved 30-day graft survival (P = .030), although there were no differences in long-term patient survival, major complications, or biliary or vascular complications. We also found that although SCS time was strongly associated with increased graft failure at 1 year in the SCS cohort (P = .006), there was no such association among NMP livers (P = .171). Our experience suggests that NMP can safely extend the total preservation time of liver allografts without increasing complications.

COVID-19 Infection and Acute Pancreas Transplant Graft Thrombosis.

The coronavirus disease 2019 (COVID-19) pandemic created an unprecedented challenge for healthcare, and the world continues to struggle in recovering from its aftermath. COVID-19 has been clearly linked to hypercoagulable states and can lead to end-organ ischemia, morbidity, and mortality. Immunosuppressed solid organ transplant recipients represent a highly vulnerable population for the increased risk of complications and mortality. Early venous or arterial thrombosis with acute graft loss after whole pancreas transplantation is well-described, but late thrombosis is rare. We herein report a case of acute, late pancreas graft thrombosis at 13 years post pancreas-after-kidney (PAK) transplantation coinciding with an acute COVID-19 infection in a previously double-vaccinated recipient.

Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years.

OBJECTIVE: To provide the largest single-center analysis of islet (ITx) and pancreas (PTx) transplantation. SUMMARY BACKGROUND DATA: Studies describing long-term outcomes with ITx and PTx are scarce. METHODS: We included adults undergoing ITx (n=266) and PTx (n=146) at the University of Alberta from January 1999 to October 2019. Outcomes include patient and graft survival, insulin independence, glycemic control, procedure-related complications, and hospital readmissions. Data are presented as medians (interquartile ranges, IQR) and absolute numbers (percentages, %) and compared using Mann-Whitney and χ2 tests. Kaplan-Meier estimates, Cox proportional hazard models and mixed main effects models were implemented. RESULTS: Crude mortality was 9.4% and 14.4% after ITx and PTx, respectively ( P= 0.141). Sex-adjusted and age-adjusted hazard-ratio for mortality was 2.08 (95% CI, 1.04-4.17, P= 0.038) for PTx versus ITx. Insulin independence occurred in 78.6% and 92.5% in ITx and PTx recipients, respectively ( P= 0.0003), while the total duration of insulin independence was 2.1 (IQR 0.8-4.6) and 6.7 (IQR 2.9-12.4) year for ITx and PTx, respectively ( P= 2.2×10 -22 ). Graft failure ensued in 34.2% and 19.9% after ITx and PTx, respectively ( P =0.002). Glycemic control improved for up to 20-years post-transplant, particularly for PTx recipients (group, P= 7.4×10 -7 , time, P =4.8×10 -6 , group*time, P= 1.2×10 -7 ). Procedure-related complications and hospital readmissions were higher after PTx ( P =2.5×10 -32 and P= 6.4×10 -112 , respectively). CONCLUSIONS: PTx shows higher sex-adjusted and age-adjusted mortality, procedure-related complications and readmissions compared with ITx. Conversely, insulin independence, graft survival and glycemic control are better with PTx. This study provides data to balance risks and benefits with ITx and PTx, which could improve shared decision-making.

C-peptide Targets and Patient-centered Outcomes of Relevance to Cellular Transplantation for Diabetes.

BACKGROUND: C-peptide levels are a key measure of beta-cell mass following islet transplantation, but threshold values required to achieve clinically relevant patient-centered outcomes are not yet established. METHODS: We conducted a cross-sectional retrospective cohort study evaluating patients undergoing islet transplantation at a single center from 1999 to 2018. Cohorts included patients achieving insulin independence without hypoglycemia, those with insulin dependence without hypoglycemia, and those with recurrent symptomatic hypoglycemia. Primary outcome was fasting C-peptide levels at 6 to 12 mo postfirst transplant; secondary outcomes included stimulated C-peptide levels and BETA-2 scores. Fasting and stimulated C-peptide and BETA-2 cutoff values for determination of hypoglycemic freedom and insulin independence were evaluated using receiver operating characteristic curves. RESULTS: We analyzed 192 patients, with 122 (63.5%) being insulin independent without hypoglycemia, 61 (31.8%) being insulin dependent without hypoglycemia, and 9 (4.7%) experiencing recurrent symptomatic hypoglycemia. Patients with insulin independence had a median (interquartile range) fasting C-peptide level of 0.66 nmol/L (0.34 nmol/L), compared with 0.49 nmol/L (0.25 nmol/L) for those being insulin dependent without hypoglycemia and 0.07 nmol/L (0.05 nmol/L) for patients experiencing hypoglycemia ( P < 0.001). Optimal fasting C-peptide cutoffs for insulin independence and hypoglycemia were ≥0.50 nmol/L and ≥0.12 nmol/L, respectively. Cutoffs for insulin independence and freedom of hypoglycemia using stimulated C-peptide were ≥1.2 nmol/L and ≥0.68 nmol/L, respectively, whereas optimal cutoff BETA-2 scores were ≥16.4 and ≥5.2. CONCLUSIONS: We define C-peptide levels and BETA-2 scores associated with patient-centered outcomes. Characterizing these values will enable evaluation of ongoing clinical trials with islet or stem cell therapies.

Impact of late gadolinium enhancement extent, location, and pattern on ventricular tachycardia and major adverse cardiac events in patients with ischemic vs. non-ischemic cardiomyopathy.

Background: Left ventricular late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) has been associated with increased risk for life-threatening ventricular tachyarrhythmias. The differences in association between LGE characteristics and prognosis in patients with ischemic (ICM) vs. non-ischemic (NICM) cardiomyopathy is incompletely understood. Methods: A total of 168 consecutive patients who underwent CMR imaging with either ICM or NICM were included in our study. LGE extent, location and pattern were examined for association to the primary endpoint of ventricular tachycardia (VT) and secondary endpoint of major adverse cardiac events (MACE). Results: Of 68 (41%) patients with ICM and 97 (59%) patients with NICM, median LGE mass was 15% (IQR 9-28) for the ICM group and 10% (IQR 6-15) for the NICM group. On multivariate analysis for both groups, LGE characteristics were prognostic while LVEF was not. In patients with ICM, septal and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median) and inferior wall LGE independently predicted the primary endpoint. In patients with NICM, anterior, inferior and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median, number of LGE segments, LGE stratified per 5% increase) and midwall LGE were independent predictors of the primary endpoint. Conclusions: Although LGE was an independent predictor of prognosis in both groups, LGE extent, location, and pattern characteristics were more powerful correlates to worse outcomes in patients with NICM than ICM.

Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study.

BACKGROUND: Preliminary studies show promise for extrahepatic islet transplantation (ITx). However, clinical comparisons with intraportal ITx outcomes remain limited. METHODS: This single-center cohort study evaluates patients receiving extrahepatic or intraportal ITx between 1999 and 2018. Primary outcome was stimulated C-peptide level. Secondary outcomes were fasting plasma glucose, BETA-2 scores, and fasting C-peptide level. Multivariable logistic modeling evaluated factors independently associated with a composite variable of early graft failure and primary nonfunction within 60 d of ITx. RESULTS: Of 264 patients, 9 (3.5%) received extrahepatic ITx (gastric submucosal = 2, subcutaneous = 3, omental = 4). Group demographics were similar at baseline (age, body mass index, diabetes duration, and glycemic control). At 1-3 mo post-first infusion, patients receiving extrahepatic ITx had significantly lower stimulated C-peptide (0.05 nmol/L versus 1.2 nmol/L, P < 0.001), higher fasting plasma glucose (9.3 mmol/L versus 7.3 mmol/L, P < 0.001), and lower BETA-2 scores (0 versus 11.6, P < 0.001) and SUITO indices (1.5 versus 39.6, P < 0.001) compared with those receiving intraportal ITx. Subjects receiving extrahepatic grafts failed to produce median C-peptide ≥0.2 nmol/L within the first 60 d after transplant. Subsequent intraportal infusion following extrahepatic transplants achieved equivalent outcomes compared with patients receiving intraportal transplant alone. Extrahepatic ITx was independently associated with early graft failure/primary non-function (odds ratio 1.709, confidence interval 73.8-39 616.0, P < 0.001), whereas no other factors were independently predictive. CONCLUSIONS: Using current techniques, intraportal islet infusion remains the gold standard for clinical ITx, with superior engraftment, graft function, and glycemic outcomes compared with extrahepatic transplantation of human islets.

Higher subcutaneous adipose tissue radiodensity is associated with increased mortality in patients with cirrhosis.

Background & Aims: Association between sarcopenia and mortality in cirrhosis is well recognised; however, little is known about the clinical implications of adipose tissue radiodensity, indicative of biological features. This study aimed to determine an association between high subcutaneous adipose tissue (SAT) radiodensity and survival, compare the prevalence of high SAT radiodensity between healthy population and patients with cirrhosis, and identify an association between computed tomography (CT)-measured SAT radiodensity and histological characteristics. Methods: Adult patients with cirrhosis (n = 786) and healthy donors (n = 129) with CT images taken as part of the liver transplant (LT) assessment were included. Abdominal SAT biopsies (1-2 g) were harvested from the incision site at the time of LT from 12 patients with cirrhosis. Results: The majority of patients were male (67%) with a mean model for end-stage liver disease (MELD) score of 15 ± 8. SAT radiodensity above -83 HU in females (sub-distribution hazard ratio [sHR] 1.84, 95% CI 1.20-2.85, p = 0.006) and higher than -74 HU in males (sHR 1.51, 95% CI 1.05-1.18, p = 0.02) was associated with the highest mortality risk after adjusting for confounders in competing risk analysis. The frequency of high SAT radiodensity was 26% for those with cirrhosis, compared with 2% in healthy donors (p <0.001). An inverse correlation was found between SAT radiodensity and the mean cross-sectional area of SAT adipocytes (r = -0.67, p = 0.02). Shrunken, smaller adipocytes with expanded interstitial space were predominant in patients with high SAT radiodensity, whereas larger adipocytes with a thin rim of cytoplasm were observed in patients with low SAT radiodensity (744 ± 400 vs. 1,521 ± 1,035 µm2, p <0.001). Conclusion: High SAT radiodensity frequently presents and is associated with a higher mortality in cirrhosis. SAT morphological rearrangement in patients with high SAT radiodensity might indicate diminished lipid stores and alterations in tissue characteristics. Lay summary: Poor quality of subcutaneous adipose tissue (fat under the skin) is associated with higher mortality in patients with end-stage liver disease. Fat cells are smaller in patients with poor adipose tissue quality.

Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada.

BACKGROUND: Islet transplantation offers an effective treatment for selected people with type 1 diabetes and intractable hypoglycaemia. Long-term experience, however, remains limited. We report outcomes from a single-centre cohort up to 20 years after islet transplantation. METHODS: This cohort study included patients older than 18 years with type 1 diabetes undergoing allogeneic islet transplantation between March 11, 1999, and Oct 1, 2019, at the University of Alberta Hospital (Edmonton, AB, Canada). Patients who underwent islet-after-kidney transplantation and islet transplantation alone or islet transplantation before whole-pancreas transplantation (follow-up was censored at the time of whole-pancreas transplantation) were included. Patient survival, graft survival (fasting plasma C-peptide >0·1 nmol/L), insulin independence, glycaemic control, and adverse events are reported. To identify factors associated with prolonged graft survival, recipients with sustained graft survival (≥90% of patient follow-up duration) were compared with those who had non-sustained graft survival (<90% of follow-up duration). Multivariate binary logistic regression analyses were done to determine predictors of sustained graft survival. FINDINGS: Between March 11, 1999, and Oct 1, 2019, 255 patients underwent islet transplantation and were included in the analyses (149 [58%] were female and 218 [85%] were White). Over a median follow-up of 7·4 years (IQR 4·4-12·2), 230 (90%) patients survived. Median graft survival was 5·9 years (IQR 3·0-9·5), and graft failure occurred in 91 (36%) patients. 178 (70%) recipients had sustained graft survival, and 77 (30%) had non-sustained graft survival. At baseline, compared with patients with non-sustained graft survival, those with sustained graft survival had longer median type 1 diabetes duration (33·5 years [IQR 24·3-41·7] vs 26·2 years [17·0-35·5]; p=0·0003), median older age (49·4 years [43·5-56·1] vs 44·2 years [35·4-54·2]; p=0·0011), and lower median insulin requirements (0·53 units/kg per day [0·45-0·67] vs 0·59 units/kg per day [0·48-0·70]; p=0·032), but median HbA1c concentrations were similar (8·2% [7·5-9·0] vs 8·5% [7·8-9·2]; p=0·23). 201 (79%) recipients had insulin independence, with a Kaplan-Meier estimate of 61% (95% CI 54-67) at 1 year, 32% (25-39) at 5 years, 20% (14-27) at 10 years, 11% (6-18) at 15 years, and 8% (2-17) at 20 years. Patients with sustained graft survival had significantly higher rates of insulin independence (160 [90%] of 178 vs 41 [53%] of 77; p<0·0001) and sustained improvements in glycaemic control mixed-main-effects model group effect, p<0·0001) compared with those with non-sustained graft survival. Multivariate analyses identified the combined use of anakinra plus etanercept (adjusted odds ratio 7·5 [95% CI 2·7-21·0], p<0·0001) and the BETA-2 score of 15 or higher (4·1 [1·5-11·4], p=0·0066) as factors associated with sustained graft survival. In recipients with sustained graft survival, the incidence of procedural complications was lower (23 [5%] of 443 infusions vs 17 [10%] of 167 infusions; p=0·027), whereas the incidence of cancer was higher (29 of [16%] of 178 vs four [5%] of 77; p=0·015) than in those with non-sustained graft survival; most were skin cancers (22 [67%] of 33). End-stage renal disease and severe infections were similar between groups. INTERPRETATION: We present the largest single-centre cohort study of long-term outcomes following islet transplantation. Although some limitations with our study remain, such as the retrospective component, a relatively small sample size, and the absence of non-transplant controls, we found that the combined use of anakinra plus etanercept and the BETA-2 score were associated with improved outcomes, and therefore these factors could inform clinical practice. FUNDING: None.

Surgical outcomes and quality of life following exercise-based prehabilitation for hepato-pancreatico-biliary surgery: A systematic review and meta-analysis.

BACKGROUND: Hepato-pancreatico-biliary (HPB) patients experience significant risk of preoperative frailty. Studies assessing preventative prehabilitation in HPB populations are limited. This systematic review and meta-analysis evaluates outcomes for HPB patients treated with exercise prehabilitation. DATA SOURCES: A comprehensive search of MEDLINE (via Ovid), Embase (Ovid), Scopus, Web of Science Core Collection, Cochrane Library (Wiley), ProQuest Dissertations, Theses Global, and Google Scholar was conducted with review and extraction following PRISMA guidelines. Included studies evaluated more than 5 adult HPB patients undergoing ≥ 7-day exercise prehabilitation. The primary outcome was postoperative length of stay (LOS); secondary outcomes included complications, mortality, physical performance, and quality of life. RESULTS: We evaluated 1778 titles and abstracts and selected 6 (randomized controlled trial, n = 3; prospective cohort, n = 1; retrospective cohort, n = 2) that included 957 patients. Of those, 536 patients (56.0%) underwent exercise prehabilitation and 421 (44.0%) received standard care. Patients in both groups were similar with regards to important demographic factors. Prehabilitation was associated with a 5.20-day LOS reduction (P = 0.03); when outliers were removed, LOS reduction decreased to 1.85 days and was non-statistically significant (P = 0.34). Postoperative complications (OR = 0.70; 95% CI: 0.39 to 1.26; P = 0.23), major complications (OR = 0.83; 95% CI: 0.60 to 1.14; P = 0.24), and mortality (OR = 0.67; 95% CI: 0.17 to 2.70; P = 0.57) were similar. Prehabilitation was associated with improved strength, cardiopulmonary function, quality of life, and alleviated sarcopenia. CONCLUSIONS: Exercise prehabilitation may reduce LOS and morbidity following HPB surgery. Studies with well-defined exercise regimens are needed to optimize exercise prehabilitation outcomes.

The Transition to Microsurgical Technique for Hepatic Artery Reconstruction in Pediatric Liver Transplantation.

BACKGROUND: Hepatic artery thrombosis represents a potentially fatal complication following liver transplantation. Rates of hepatic artery thrombosis are significantly higher in children, with mortality reported up to 80 percent. Microsurgical anastomosis has been shown to decrease the rate of hepatic artery thrombosis and now represents the standard of care at the authors' institution. In this article, the authors present the largest study of its type directly comparing rates of hepatic artery thrombosis with and without microsurgical reconstruction of the hepatic artery. METHODS: All pediatric patients who underwent primary orthotopic liver transplantation between 1989 and 2018 were included. Patients were divided into two cohorts: standard anastomosis with loupes, and microsurgical anastomosis under the operating microscope. The authors' primary outcome was the rate of hepatic artery thrombosis. Secondary outcomes were graft survival, patient survival, retransplantation rate, requirement for intraoperative blood products, and length of stay. RESULTS: Two hundred thirty-one children met criteria for inclusion. One hundred eighty cases were performed with loupe magnification and 51 cases were performed under the microscope. The hepatic artery thrombosis rate was lower, but not significantly so (p = 0.114), in the microsurgical group [n = 1 (2.0 percent)] compared with the standard cohort [n = 15 (8.3 percent)]. Survival analysis revealed a significant increase in graft survival with microsurgical anastomosis (p = 0.020), but not patient survival (p = 0.196). The retransplantation rate was significantly lower with microsurgical anastomosis (p = 0.021). CONCLUSIONS: Microsurgical anastomosis was associated with a clinically important decrease in hepatic artery thrombosis compared with standard loupe anastomosis. The graft survival rate was significantly higher in the microsurgical cohort, with a reduced retransplantation rate at 1 year. On this basis, the authors recommend microsurgical hepatic artery anastomosis in cases of pediatric liver transplantation. . CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Total pancreatectomy with islet cell autotransplantation in a 2-year-old child with hereditary pancreatitis due to a PRSS1 mutation.

Acute recurrent and chronic pancreatitis in children carries high morbidity and burden. Compared to adults, ~75% of the cases of chronic pancreatitis in children are associated with underlying genetic mutations. The decision to intervene and the optimal timing poses unique challenges. Total pancreatectomy and islet cell autotransplantation (TPIAT) provides definitive therapy to relieve pain and improve quality of life while minimizing the risk of pancreatogenic diabetes. Substantial clinical data are available for adults; however, information on clinical outcomes in children remains scarce, particularly for very young children. Herein, we present an unusual, complex case of a 2-year-old child that underwent a successful TPIAT due to hereditary pancreatitis with an underlying mutation in PRSS1 gene, complicated by unremitting pancreatic ascites, hemorrhage, and sepsis. This is the youngest case to be reported in the literature. We provide a comprehensive report of the course and procedures implemented in this patient to guide other teams when considering these extraordinary measures in similar cases.

Liver Transplantation in Locally Unresectable, Undifferentiated Embryonal Cell Sarcoma.

BACKGROUND: Undifferentiated embryonal cell sarcoma (UESL) of the liver is the third most common malignant liver disease of childhood presenting as a rapidly enlarging intraabdominal mass. This systematic review explores the practicality of liver transplantation as a viable option in the treatment armamentarium for locally advanced undifferentiated embryonal cell sarcoma. METHODS: A systematic review of the literature was performed using Medline and Embase, from inception of databases to December 31, 2018. Keywords and MeSH headings used were embryonal sarcoma, mesenchymal sarcoma, and liver transplant. Reviews and manuscripts with incomplete data were excluded. RESULTS: Twenty-eight patients had orthotopic liver transplantation (OLT) as a curative treatment option. The median age at presentation was 8 and 27 years in the pediatric and adult population, respectively, with a similar male to female ratio. A majority of the patients presented with abdominal pain, palpable mass, and a normal alpha-feto-protein. The median tumor size was 15 cm mainly affecting the right lobe (62%) of the liver. Eighty-two percent of the patients underwent primary OLT and 5 patients had salvage OLT. One death (3.6%) was due to initial misdiagnosis and management for hepatoblastoma. Recurrence was noted in 7.1% of the population. The median follow-up was noted to be 28.5 months. The documented survival rate post-liver transplant for UESL was 96%. CONCLUSIONS: Based on available data and the very positive results therein, liver transplantation is a practical and justifiable use of a scarce resource as a treatment option for locally unresectable, undifferentiated embryonal cell sarcoma. The authors propose (accepting existence of different proposals) neoadjuvant therapy before curative resection, and if not achievable, then liver transplantation followed by adjuvant chemotherapy is an option for suitable candidates. For recurrent tumors after surgical resection, adjuvant therapy with salvage liver transplantation is an option.

Sarcopenia in Chronic Liver Disease: Impact on Outcomes.

Malnutrition is a common complication in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). Malnutrition and sarcopenia overlap in etiology and outcomes, with sarcopenia being defined as reduced skeletal muscle mass and muscle function. The purpose of this review was to identify the prevalence of sarcopenia with and without obesity in adults and children with ESLD and to assess the methodological considerations in sarcopenia diagnosis and the association of sarcopenia with pre- and post-LT outcomes. A total of 38 articles (35 adult and 3 pediatric articles) retrieved from PubMed or Web of Science databases were included. In adults, the prevalence rates of pre-LT sarcopenia, pre-LT sarcopenic obesity (SO), post-LT sarcopenia, and post-LT SO were 14%-78%, 2%-42%, 30%-100%, and 88%, respectively. Only 2 adult studies assessed muscle function in patients diagnosed with sarcopenia. The presence of pre-LT sarcopenia is associated with higher wait-list mortality, greater postoperative mortality, higher infection risk and postoperative complications, longer intensive care unit (ICU) stay, and ventilator dependency. The emerging pediatric data suggest that sarcopenia is prevalent in pre- and post-LT periods. In 1 pediatric study, sarcopenia was associated with poor growth, longer perioperative length of stay (total/ICU) and ventilator dependency, and increased rehospitalization in children after LT. In conclusion, there is a high prevalence of sarcopenia in adults and children with ESLD. Sarcopenia is associated with adverse clinical outcomes. The present review is limited by heterogeneity in the definition of sarcopenia and in the methodological approaches in assessing sarcopenia. Future studies are needed to standardize the sarcopenia diagnosis and muscle function assessment, particularly in the pediatric population, to enable early identification and treatment of sarcopenia in adults and children with ESLD.

A Back-to-Base Experience of Human Normothermic Ex Situ Liver Perfusion: Does the Chill Kill?

Normothermic machine perfusion (NMP) has been shown to protect livers from injury between procurement and transplantation in a randomized controlled trial, where the machine was transported to and from the donor center. The aim of this study was to determine whether an alternative, more practical back-to-base approach after initial static cold storage would compromise beneficial outcomes. Between February 2015 and June 2018, a nonrandomized pilot study was performed at a single site. Outcomes of back-to-base livers (n = 26) were compared with those of grafts procured locally that underwent immediate NMP (n = 17). The primary outcome measure (safety) was defined as 30-day patient and graft survival. A total of 46 liver grafts were perfused with NMP, of which 3 were discarded based on poor ex situ perfusion function. The 30-day patient and graft survival in the back-to-base and local NMP groups were both 100% (primary outcome: safety). Despite significantly prolonged mean cold ischemia time (6 versus 3.2 hours; P = 0.001), the back-to-base livers demonstrated no difference in graft function, incidence of complications, or graft and patient survival. In conclusion, the back-to-base approach was safe, did not compromise the overall benefit of NMP, and offers a practical alternative to portable normothermic ex situ machine transport.

Five year experience of gallbladder polyp surveillance and cost effective analysis against new European consensus guidelines.

BACKGROUND: Gallbladder polyp (GBP) surveillance seeks to identify early neoplasms, but practice varies amongst surgical units. Recent European consensus guidelines have recommended an evidence-based GBP surveillance strategy. In a tertiary centre Hepato-Pancreato-Biliary unit we examine GBP surveillance, malignant yield, and assess cost-effectiveness of the new European consensus guidelines. METHODS: Respective data were collected from all patients with ultrasonography-detected GBPs between January 2008 and January 2013. RESULTS: 558 patients had GBPs detected on ultrasonography. Following initial ultrasonography, 304 (54.5%) had further ultrasonography surveillance of which 168 were in a formal GBP surveillance programme. Pre-malignant/malignant pathology yield was 1.97% with an annual detection rate of 12.0 cases per 1000 GBPs surveyed. Cost-effectiveness analysis of European consensus guidelines calculated annual savings of £209 163 per 1000 GBPs surveyed. Compliance with these guidelines would result in an additional 12.5% of patients under surveillance requiring cholecystectomy. CONCLUSION: GBP surveillance uptake was suboptimal at 32.8%. The incidence of pre-malignant/malignant lesions in GBPs emphasises the importance of surveillance for early detection and management with a view to avoiding the poor outcomes associated with more advanced gallbladder cancer. Adherence to the new European consensus guidelines would be clinically cost-effective with significant potential savings demonstrated in this study.

Delayed Emergence in Pediatric Patients with Neurologic Disease Presenting for Ambulatory Surgery.

OBJECTIVES: Management of pediatric patients with neurological diagnoses can be challenging for anesthesiologists. We sought to determine whether preexisting neurologic disease could serve as an intrinsic risk factor for prolonged emergence. METHODS: Following institutional review board approval, we conducted a database search from 2012 to 2015. Included were patients aged 0 to 18 years undergoing ambulatory procedures, and carrying neurological diagnoses that profoundly affected their development. Patients were excluded if they received a total intravenous anesthetic, were not managed with an endotracheal tube, or were extubated deep. A healthy case-control group also was obtained for comparison. The primary outcome was emergence from anesthesia: time from anesthetic cessation to extubation. Our secondary outcome was time from extubation to discharge. Descriptive statistics were calculated for demographic data, outcomes were analyzed for differences using the Student t test, and regression analysis was performed. RESULTS: Data from 69 patients and 169 controls met criteria. There were no differences between study and control groups for age, sex, procedural length, or intraoperative temperatures. The study group had higher American Society of Anesthesiologists scores (2.4 vs 1.4). The primary outcome of time to emergence was longer in the study group (15.2 vs 11.0 min), and time to discharge also was prolonged (101.0 vs 86.1 min). Regression analysis on most differing variables did not yield a correlation to primary/secondary outcomes, but neurologic disease did correlate to both. CONCLUSIONS: In this case-controlled retrospective study, there was a prolongation of anesthetic emergence and hospital discharge times for pediatric patients with severe neurologic disease, mostly independent of external factors.

Surgical management of hepato-pancreatic metastasis from renal cell carcinoma.

AIM: To investigate the outcomes of liver and pancreatic resections for renal cell carcinoma (RCC) metastatic disease. METHODS: This is a retrospective, single centre review of liver and/or pancreatic resections for RCC metastases between January 2003 and December 2015. Descriptive statistical analysis and survival analysis using the Kaplan-Meier estimation were performed. RESULTS: Thirteen patients had 7 pancreatic and 7 liver resections, with median follow-up 33 mo (range: 3-98). Postoperative complications were recorded in 5 cases, with no postoperative mortality. Three patients after hepatic and 5 after pancreatic resection developed recurrent disease. Median overall survival was 94 mo (range: 23-94) after liver and 98 mo (range: 3-98) after pancreatic resection. Disease-free survival was 10 mo (range 3-55) after liver and 28 mo (range 3-53) after pancreatic resection. CONCLUSION: Our study shows that despite the high incidence of recurrence, long term survival can be achieved with resection of hepatic and pancreatic RCC metastases in selected cases and should be considered as a management option in patients with oligometastatic disease.