Publications by authors named "Nicolas Goldaracena"

71 Publications

Anonymous Living Liver Donation: Literature Review and Case Series Report.

Transplant Direct 2021 Aug 16;7(8):e726. Epub 2021 Jul 16.

Division of Transplant Surgery, University of Virginia Health System, Charlottesville, VA.

Background: Anonymous living liver donations (ALLDs) raise ethical concerns regarding the donors' motivations. Thus, ALLDs are not as widely accepted as directed donations from friends and family. Literature on ALLDs is limited. Understanding this particular group of individuals is crucial, as they could further help mitigate the shortage of liver grafts worldwide.

Methods: A literature review was performed to identify current definitions, ethical considerations, different approaches, and barriers to ALLD worldwide. Furthermore, we present our current experience after the establishment of a protocol to enable an ALLD program in our center and surveyed potential donors to better understand their motives throughout the process.

Results: Literature regarding ALLD is scarce. Canada leads the experience with the majority of case reports published to date. Survey-based evaluation of this unique group of individuals reflects the selflessness nature of anonymous living donors and shows that most of them experience the donation as a positive and life-changing event. In our experience, 41 individuals initiated the process of ALLD during the study period. Most were lost to follow-up or deemed ineligible. Five candidates fully completed the donation process and successfully underwent living liver donation. Given that 2 candidates have a follow-up period <3 mo from donation, we have only included data on the first 3 donors in this analysis. Eight individuals (19.5%) responded to the survey with respondents sharing similar reasons for initiating ALLD but varied and multifactorial reasons for terminating.

Conclusions: Different institutional protocols can be used to accomplish ALLD, including the one utilized by our institution. Adopting policies to allow for ALLDs and reducing modifiable factors that contribute to ending donation has the potential to increase grafts and decrease wait times.Supplemental Visual Abstract: http://links.lww.com/TP/C251.
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http://dx.doi.org/10.1097/TXD.0000000000001181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288903PMC
August 2021

Robot-assisted kidney transplantation is a safe alternative approach for morbidly obese patients with end-stage renal disease.

Int J Med Robot 2021 Jun 2:e2293. Epub 2021 Jun 2.

Division of Transplant Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.

Background: Many centres deny obese patients with a body mass index (BMI) >35 access to kidney transplantation due to increased intraoperative and postoperative complications.

Methods: From August 2017 to December 2019, 73 consecutive cases of kidney transplantation in morbidly obese patients were enrolled at a single university at the initiation of a robotic transplant surgery program. Outcomes of patients who underwent robotic assisted kidney transplant (RAKT) were compared to frequency-matched patients undergoing open kidney transplant (OKT).

Results: A total of 24 morbidly obese patients successfully underwent RAKT, and 49 obese patients received an OKT. The RAKT group developed fewer surgical site infections (SSI) than the OKT group. Graft function, creatinine, and glomerular filtration rate (GFR) were similar between groups 1 year after surgery. Graft and patient survival were 100% for both groups.

Conclusions: RAKT offers a safe alternative for morbidly obese patients, who may otherwise be denied access to OKT.
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http://dx.doi.org/10.1002/rcs.2293DOI Listing
June 2021

Lose Weight to Donate: Development of a Program to Optimize Potential Donors With Hepatic Steatosis or Obesity for Living Liver Donation.

Transplant Direct 2021 Jun 25;7(6):e702. Epub 2021 May 25.

Division of Transplant Surgery, University of Virginia Health System, Charlottesville, VA.

Background: Living donor liver transplantation offers an attractive option to reduce the waitlist mortality. However, in recent years, the rising prevalence of obesity and nonalcoholic fatty liver disease has posed a serious threat to the donor pool while simultaneously increasing demand for liver transplant. To our knowledge, there have been no major published studies in the United States documenting a diet and exercise intervention to expand the living donor pool. Hereby, we established a pilot program called "Lose Weight to Donate" and present our initial experience.

Methods: Our center instituted a remotely monitored diet and exercise pilot program to increase eligibility for living liver donation. Potential donors with any of the following were included: body mass index >30 kg/m, hepatic steatosis >5% on screening MRI, or isolated hypertension.

Results: Over 19 mo, 7 individuals enrolled in the program of remote monitoring for at least 6-8 wk. Initial and follow-up abdominal MRI was performed in 5 of these individuals to assess steatosis, anatomy, and volume. Initial steatosis was highly variable (fat signal fraction range, 8%-26%). Follow-up MRI fat signal fraction values and hepatic volume all decreased to varying degrees. Ultimately, 2 of 7 individuals donated, whereas a third was approved, but the intended recipient was transplanted in the interim.

Conclusions: These results indicate the feasibility of a remotely monitored program to expand donation in light of the rising incidence of hepatic steatosis and obesity.
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http://dx.doi.org/10.1097/TXD.0000000000001161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154492PMC
June 2021

Donor Morbidity Is Equivalent Between Right and Left Hepatectomy for Living Liver Donation: a Meta-Analysis.

Liver Transpl 2021 May 30. Epub 2021 May 30.

Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, VA.

Maximizing liver graft volume benefits the living donor liver recipient. Whether maximizing graft volume negatively impacts living donor recovery and outcomes remains controversial. Patient randomization between right and left hepatectomy has not been possible due to anatomic constraints; however, a number of published, nonrandomized observational studies summarize donor outcomes between 2 anatomic living donor hepatectomies. This meta-analysis compares donor-specific outcomes after right versus left living donor hepatectomy. Systematic searches were performed via PubMed, Cochrane, ResearchGate, and Google Scholar databases to identify relevant studies between January 2005 and November 2019. The primary outcomes compared overall morbidity and incidence of severe complications (Clavien-Dindo >III) between right and left hepatectomy in donors after liver donation. Random effects meta-analysis was performed to derive summary risk estimates of outcomes. A total of 33 studies (3 prospective and 30 retrospective cohort) were used to identify 7649 pooled patients (5993 right hepatectomy and 1027 left hepatectomy). Proportion of donors who developed postoperative complications did not significantly differ after right hepatectomy (0.33; 95% confidence interval [CI], 0.27-0.40) and left hepatectomy (0.23; 95% CI, 0.17-0.29; P = 0.19). The overall risk ratio (RR) did not differ between right and left hepatectomy (RR, 1.16; 95% CI, 0.83-1.63; P = 0.36). The relative risk for a donor to develop severe complications showed no differences by hepatectomy side (Incidence rate ratio, 0.97; 95% CI, 0.67-1.40; P = 0.86). There is no evidence that the overall morbidity differs between right and left lobe donors. Publication bias reflects institutional and surgeon variation. A prospective, standardized, multi-institutional study would help quantify the burden of donor complications after liver donation.
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http://dx.doi.org/10.1002/lt.26183DOI Listing
May 2021

Immunological organ modification during Ex Vivo machine perfusion: The future of organ acceptance.

Transplant Rev (Orlando) 2021 04 17;35(2):100586. Epub 2020 Oct 17.

Department of Surgery, Division of Transplantation, University of Wisconsin, Madison, WI, United States of America. Electronic address:

Ex vivo machine perfusion (EVMP) has gained revitalized interest in recent years due to the increasing use of marginal organs which poorly tolerate the standard preservation method static cold storage (SCS). EVMP improves on SCS in a number of ways, most notably by the potential for reconditioning of the donor organ prior to transplantation without the ethical concerns associated with organ modulation before procurement. Immunomodulatory therapies administered during EVMP can influence innate and adaptive immune responses to reduce production of inflammatory molecules and polarize tissue-resident immune cells to a regulatory phenotype. The targeted inhibition of an inflammatory response can reduce ischemia-reperfusion injury following organ reoxygenation and therefore reduce incidence of graft dysfunction and rejection. Numerous approaches to modulate the inflammatory response have been applied in experimental models, with the ultimate goal of clinical translatability. Strategies to target the innate immune system include inhibiting inflammatory signaling pathways, upregulating anti-inflammatory mediators, and decreasing mitochondrial damage while those which target the adaptive immune system include mesenchymal stromal cells. Inhibitory RNA approaches target both the innate and adaptive immune systems with a focus on MHC knock-down. Future studies may address issues of therapeutic agent delivery through use of nanoparticles and explore novel strategies such as targeting co-inhibitory molecules to educate T-cells to a tolerogenic state. In this review, we summarize the cellular and acellular contributors to allograft dysfunction and rejection, discuss the strategies which have been employed pre-clinically during EVMP to modulate the donor organ immune environment, and suggest future directions for immunomodulatory EVMP studies.
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http://dx.doi.org/10.1016/j.trre.2020.100586DOI Listing
April 2021

Outcomes of Highly Selected Live Donors With a Future Liver Remnant Less Than or Equal to 30%: A Matched-Cohort Study.

Transplantation 2020 Nov 24. Epub 2020 Nov 24.

Multi-Organ Transplant Unit, Toronto General Hospital, University of Toronto, Toronto, Canada.

Background: The main concern with live donor liver transplantation (LDLT) is the risk to the donor. Given the potential risk of liver insufficiency, most centres will only accept candidates with future liver remnants (FLR) >30%. We aimed to compare postoperative outcomes of donors who underwent LDLT with FLR ≤30% and >30%.

Methods: Adults who underwent right hepatectomy for LDLT between 2000 and 2018 were analyzed. Remnant liver volumes were estimated using hepatic volumetry. To adjust for between-group differences, donors with FLR ≤30% and >30% were matched 1:2 based on baseline characteristics. Postoperative complications including liver dysfunction were compared between the groups.

Results: 604 live donors were identified, 28 (4.6%) of which had a FLR ≤30%. Twenty-eight cases were successfully matched with 56 controls; the matched cohorts were mostly similar in terms of donor and graft characteristics. The calculated median FLR was 29.8 (range 28.0-30.0) and 35.2 (range 30.1-68.1) in each respective group. Median follow-up was 36.5 months (IQR 11.8-66.1). Postoperative outcomes were similar between groups. No difference was observed in overall complication rates (FLR ≤30%: 32.1% vs FLR >30%: 28.6%; odds ratio (OR) 1.22, 95% CI 0.46-3.27) or major complication rates (FLR ≤30%: 14.3% vs FLR >30%: 14.3%; OR 1.17, 95% CI 0.33-4.10). Posthepatectomy liver failure was rare, and no difference was observed (FLR ≤30%: 3.6% vs FLR >30%: 3.6% OR 1.09, 95% CI 0.11-11.1).

Conclusion: A calculated FLR between 28% and 30% on its own should not represent a formal contraindication for live donation.
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http://dx.doi.org/10.1097/TP.0000000000003559DOI Listing
November 2020

Proceedings of the 25th Annual Congress of the International Liver Transplantation Society.

Transplantation 2020 08;104(8):1560-1565

Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurugram, Delhi NCR, India.

The 25th Annual Congress of the International Liver Transplantation Society was held in Toronto, Canada, from May 15 to 18, 2019. Surgeons, hepatologists, anesthesiologists, critical care intensivists, radiologists, pathologists, and research scientists from all over the world came together with the common aim of improving care and outcomes for liver transplant recipients and living donors. Some of the featured topics at this year's conference included multidisciplinary perioperative care in liver transplantation, worldwide approaches to organ allocation, donor steatosis, and updates in pediatrics, immunology, and radiology. This report presents excerpts and highlights from invited lectures and select abstracts, reviewed and compiled by the Vanguard Committee of International Liver Transplantation Society. This will hopefully contribute to further advances in clinical practice and research in liver transplantation.
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http://dx.doi.org/10.1097/TP.0000000000003160DOI Listing
August 2020

Current status of liver transplantation in North America.

Int J Surg 2020 Oct 28;82S:9-13. Epub 2020 May 28.

Department of Surgery, University of Cincinnati College of Medicine, USA. Electronic address:

Liver transplantation is continuing to grow and evolve in North America. Changes in organ availability, recipient selection, indications and progressive approaches to oncologic treatment have occurred in the last five years. Despite increased activity in deceased and living donation in North America, there continues to be a high mortality on the waitlist as the recipient indications have changed over time which has led to new approaches to help patients with end-stage liver disease.
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http://dx.doi.org/10.1016/j.ijsu.2020.05.059DOI Listing
October 2020

Does donor muscularity "pump up" living donor liver transplant survival?

Am J Transplant 2020 12 25;20(12):3281-3282. Epub 2020 Jun 25.

Division of Transplant Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.

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http://dx.doi.org/10.1111/ajt.16072DOI Listing
December 2020

Expanding the donor pool for liver transplantation with marginal donors.

Int J Surg 2020 Oct 15;82S:30-35. Epub 2020 May 15.

Department of Surgery, Division of Liver Transplantation and Hepatobiliary Surgery, Weill Cornell Medical College, New York, NY, USA. Electronic address:

The current supply of acceptable donor livers is not sufficient to meet the demands of listed patients awaiting transplantation resulting in thousands of deaths each year. Increased utilization of marginal livers may help alleviate this supply/demand mismatch by expanding the donor liver pool. The current status of liver transplantation using marginal donor grafts and efforts to optimize usage are discussed with attention to elderly donors, steatotic livers, donors after circulatory death, and split liver grafts.
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http://dx.doi.org/10.1016/j.ijsu.2020.05.024DOI Listing
October 2020

Hepatic Artery Thrombosis and Takotsubo Syndrome After Liver Transplantation - Which Came First?

Am J Case Rep 2020 Apr 14;21:e920263. Epub 2020 Apr 14.

Department of Surgery, Division of Transplantation, University of Virginia, Charlottesville, VA, USA.

BACKGROUND Takotsubo syndrome is a transient, reversible, stress-induced cardiomyopathy that affects only 1.4% of liver transplant patients and can cause complications, including cardiogenic shock, arrhythmia, and thromboembolism. Hepatic artery thrombosis is also rare, affecting just 2-4% of these patients, but can have disastrous consequences. Here, we describe a case of concurrent takotsubo syndrome and hepatic artery thrombosis in a postoperative liver transplant recipient. CASE REPORT The patient was a 66-year-old man who underwent living donor liver transplantation for non-alcoholic steatohepatitis. On postoperative day 3, he became lethargic and tachycardic to the 120 s. Work-up, including EKG, troponin I, BNP, and transthoracic echocardiogram, was characteristic for takotsubo syndrome. His LVEF of 15-20% was markedly reduced compared to his baseline of 50-55% from 6 months prior. Hepatic ultrasonography showed no hepatic arterial flow, prompting emergent return to the OR, where intraoperative evaluation revealed hepatic artery thrombosis. The graft was salvaged after hepatic artery thrombectomy and arterial anastomosis revision. We are unable to determine which event caused the other in this case, as both takotsubo syndrome and hepatic artery thrombosis manifested within the same time frame. CONCLUSIONS It is important to recognize takotsubo syndrome as a potential cause of cardiac dysfunction and hepatic artery thrombosis in liver transplant patients, and also be aware that hepatic artery thrombosis can precipitate takotsubo syndrome.
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http://dx.doi.org/10.12659/AJCR.920263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176589PMC
April 2020

Pediatric living donor liver transplantation with large-for-size left lateral segment grafts.

Am J Transplant 2020 02 1;20(2):504-512. Epub 2019 Nov 1.

Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Usage of "large-for-size" left lateral segment (LLS) liver grafts in children with high graft to recipient weight ratio (GRWR) is controversial due to concerns about increased recipient complications. During the study period, 77 pediatric living donor liver transplantations (LDLTs) with LLS grafts were performed. We compared recipients with GRWR ≥2.5% (GR-High = 50) vs GRWR <2.5% (GR-Low = 27). Median age was higher in the GR-Low group (40 vs 8 months, P> .0001). Graft (GR-High: 98%, 98%, 98% vs GR-Low: 96%, 93%, 93%) and patient (GR-High: 98%, 98%, 98% vs GR-Low: 100%, 96%, 96%) survival at 1, 3, and 5 years was similar between groups (P = NS). Overall complications were also similar (34% vs 30%; P = .8). Hepatic artery and portal vein thrombosis following transplantation was not different (P = NS). Delayed abdominal fascia closure was more common in GR-High patients (17 vs 1; P = .002). Subgroup analysis comparing recipients with GRWR ≥4% (GR-XL = 20) to GRWR <2.5% (GRWR-Low = 27) revealed that delayed abdominal fascia closure was more common in the GR-XL group, but postoperative complications and graft and patient survival were similar. We conclude that pediatric LDLT with large-for-size LLS grafts is associated with excellent clinical outcomes. There is an increased need for delayed abdominal closure with no compromise of long-term outcomes. The use of high GRWR expands the donor pool and improves timely access to the benefits of transplantation without extra risks.
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http://dx.doi.org/10.1111/ajt.15609DOI Listing
February 2020

Donor outcomes in anonymous live liver donation.

J Hepatol 2019 11 4;71(5):951-959. Epub 2019 Jul 4.

Multi-Organ Transplant Program, University Health Network, Toronto, Canada; Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Canada.

Background & Aims: Death rates on liver transplant waiting lists range from 5%-25%. Herein, we report a unique experience with 50 anonymous individuals who volunteered to address this gap by offering to donate part of their liver to a recipient with whom they had no biological connection or prior relationship, so called anonymous live liver donation (A-LLD).

Methods: Candidates were screened to confirm excellent physical, mental, social, and financial health. Demographics and surgical outcomes were analyzed. Qualitative interviews after donation examined motivation and experiences. Validated self-reported questionnaires assessed personality traits and psychological impact.

Results: A total of 50 A-LLD liver transplants were performed between 2005 and 2017. Most donors had a university education, a middle-class income, and a history of prior altruism. Half were women. Median age was 38.5 years (range 20-59). Thirty-three (70%) learned about this opportunity through public or social media. Saving a life, helping others, generativity, and reciprocity for past generosity were motivators. Social, financial, healthcare, and legal support in Canada were identified as facilitators. A-LLD identified most with the personality traits of agreeableness and conscientiousness. The median hospital stay was 6 days. One donor experienced a Dindo-Clavien Grade 3 complication that completely resolved. One-year recipient survival was 91% in 22 adults and 97% in 28 children. No A-LLD reported regretting their decision.

Conclusions: This is the first and only report of the characteristics, motivations and facilitators of A-LLD in a large cohort. With rigorous protocols, outcomes are excellent. A-LLD has significant potential to reduce the gap between transplant organ demand and availability.

Lay Summary: We report a unique experience with 50 living donors who volunteered to donate to a recipient with whom they had no biological connection or prior relationship (anonymous living donors). This report is the first to discuss motivations, strategies and facilitators that may mitigate physical, social and ethical risk factors in this patient population. With rigorous protocols, anonymous liver donation and recipient outcomes are excellent; with appropriate clinical expertise and system facilitators in place, our experience suggests that other centers may consider the procedure for its significant potential to reduce the gap between transplant organ demand and availability.
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http://dx.doi.org/10.1016/j.jhep.2019.06.027DOI Listing
November 2019

Caval Replacement With Cadaveric External Iliac Vein in Pediatric Liver Transplant: Internal Iliac Vein as Optimal Site for Outflow Anastomosis.

Liver Transpl 2019 06 10;25(6):964-966. Epub 2019 Apr 10.

Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1002/lt.25440DOI Listing
June 2019

Living donor liver transplantation.

Curr Opin Organ Transplant 2019 04;24(2):131-137

Division of Abdominal Transplant Surgery, Department of Surgery, Duke University, Durham, North Carolina, USA.

Purpose Of Review: As experience grows, living donor liver transplantation (LDLT) has become an effective treatment option to overcome the deceased donor organ shortage.

Recent Findings: Donor safety is the highest priority in LDLT. Strict donor selection according to structured protocols and center experience are the main factors that determine donor safety. However, with increased experience, many centers have explored increasing organ availability within living donation by means of ABO incompatible LDLT, dual graft LDLT, and anonymous living donation. Also, this growing experience in LDLT has allowed the transplant community to cautiously explore the role of liver transplantation for hepatocellular carcinoma outside of Milan criteria and patients with unresectable colorectal liver metastases.

Summary: LDLT has become established as a viable strategy to ameliorate the organ shortage experienced by centers around the world. Improved understanding of this technique has allowed the improved utilization of live donor graft resources, without compromising donor safety. Moreover, LDLT may offer some advantages over deceased donor liver transplantation and a unique opportunity to assess the broader applicability of liver transplantation.
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http://dx.doi.org/10.1097/MOT.0000000000000610DOI Listing
April 2019

Live donor liver transplantation for patients with hepatocellular carcinoma offers increased survival vs. deceased donation.

J Hepatol 2019 04 8;70(4):666-673. Epub 2019 Jan 8.

Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada. Electronic address:

Background & Aims: There are conflicting reports on the outcomes after live donor liver transplantation in patients with hepatocellular carcinoma (HCC). We aimed to compare the survival of patients with HCC, with a potential live donor (pLDLT) at listing vs. no potential donor (pDDLT), on an intention-to-treat basis.

Methods: All patients with HCC listed for liver transplantation between 2000-2015 were included. The pLDLT group was comprised of recipients with a potential live donor identified at listing. Patients without a live donor were included in the pDDLT group. Survival was assessed by the Kaplan-Meier method. Multivariable Cox regression was applied to identify potential predictors of mortality.

Results: A total of 219 patients were included in the pLDLT group and 632 patients in the pDDLT group. In the pLDLT group, 57 patients (26%) were beyond the UCSF criteria whereas 119 patients (19%) in the pDDLT group were beyond (p = 0.02). Time on the waiting list was shorter for the pLDLT than the pDDLT group (4.8 [2.9-8.5] months vs. 6.2 [3.0-12.0] months, respectively, p = 0.02). The dropout rate was 32/219 (14.6%) in the pLDLT and 174/632 (27.5%) in the pDDLT group, p <0.001. The 1-, 3- and 5-year intention-to-treat survival rates were 86%, 72% and 68% in the pLDLT vs. 82%, 63% and 57% in the pDDLT group, p = 0.02. Having a potential live donor was a protective factor for death (hazard ratio [HR] 0.67; 95% CI 0.53-0.86). Waiting times of 9-12 months (HR 1.53; 95% CI 1.02-2.31) and ≥12 months (HR 1.69; 95% CI 1.23-2.32) were predictors of death.

Conclusion: Having a potential live donor at listing was associated with a significant decrease in the risk of death in patients with HCC in this intention-to-treat analysis. This benefit is related to a lower dropout rate and a shorter waiting period.

Lay Summary: Liver transplantation (LT) offers the best chance of survival for patients with hepatocellular carcinoma and can be performed using grafts from deceased donors or live donors. In this work, we aimed to assess the differences in survival after live donor LT when compared to deceased donor LT. We studied 219 patients listed for live donor LT and 632 patients listed for deceased donor LT. Patients who had a potential live donor at the time of listing had a higher survival rate. Therefore, being listed for a live donor LT was a protective factor against death.
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http://dx.doi.org/10.1016/j.jhep.2018.12.029DOI Listing
April 2019

Reply.

Liver Transpl 2019 02;25(2):341

Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1002/lt.25385DOI Listing
February 2019

Multicenter validation of a score to predict prognosis after the development of HCC recurrence following liver transplantation.

HPB (Oxford) 2019 06 1;21(6):731-738. Epub 2018 Nov 1.

Multi-Organ Transplant, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada. Electronic address:

Background: HCC recurrence after LT impacts negatively on survival. A recent study detected late recurrence (≥12 months), alpha-fetoprotein (AFP) <100 ng/mL at recurrence and being amenable for curative-intent treatments as good prognostic factors. With these variables a prognostic score was proposed. The objective of this study was to validate the prognostic score for hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT).

Methods: Data from the University of California, San Francisco, the University Hospital of Birmingham and Instituto Nazionale dei Tumori, Milan including patients with HCC recurrence after LT were analyzed. The previous reported score was applied to this cohort.

Results: From June 2002-December 2014, 1328 patients had a confirmed HCC in their explanted liver. The study group comprised 130 patients (9.8%) diagnosed with HCC recurrence after LT. Overall median survival after HCC recurrence was 12.4 (95% CI 10.2-16.3) months. Application of the previously reported score showed a significantly superior survival for the good prognosis group compared to moderate and poor prognosis groups (p < 0.0001).

Conclusion: The score continues to identify a group of patients who would benefit from aggressive treatment and experience significant improved survival following recurrent HCC after LT.
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http://dx.doi.org/10.1016/j.hpb.2018.10.005DOI Listing
June 2019

Living Donor Liver Transplantation Using Selected Grafts With 2 Bile Ducts Compared With 1 Bile Duct Does Not Impact Patient Outcome.

Liver Transpl 2018 11;24(11):1512-1522

Department of Surgery, Toronto General Hospital, Toronto, Canada.

The outcome after living donor liver transplantation (LDLT) using grafts with multiple bile ducts (BDs) remains unclear. We analyzed 510 patients who received an adult-to-adult right lobe LDLT between 2000 and 2015 and compared outcome parameters of those receiving grafts with 2 BDs (n = 169) with patients receiving grafts with 1 BD (n = 320). Additionally, patients receiving a graft with 3 BDs (n = 21) were analyzed. Demographic variables and disease severity were similar between the groups. Roux-en-Y reconstruction was significantly more common in the 2 BD group (77% versus 38%; P < 0.001) compared with the 1 BD group. No difference was found in biliary complication rates within 1 year after LDLT (1 BD versus 2 BD groups, 18% versus 21%, respectively; P = 0.46). In the 2 BD group, 82/169 (48.5%) patients were reconstructed with 2 anastomoses. The number of anastomoses did not negatively impact biliary complication rates. Recipients' major complication rate (Clavien ≥ 3b) was similar between both groups (1 BD versus 2 BD groups, 21% versus 24%, respectively; P = 0.36). Furthermore, no difference could be found between the 1 BD, the 2 BD, and the 3 BD groups in the frequency of developing biliary complications within 1 year (18%, 21%, 14%, respectively; P = 0.64), BD strictures (15%, 15%, 5%, respectively; P = 0.42), or BD leaks (10%, 11%, 10%, respectively; P = 0.98). In addition, the 1-year (90% versus 91%), 5-year (82% versus 77%), and 10-year (70% versus 66%) graft survival rates as well as the 1-year (92% versus 93%), 5-year (84% versus 80%), and 10-year (75% versus 76%) patient survival rates were comparable between the 1 BD and the 2 BD groups (P = 0.41 and P = 0.54, respectively). In conclusion, this study demonstrates that selected living donor grafts with 2 BDs can be used safely without negatively impacting biliary complication rates and graft or patient survival rates.
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http://dx.doi.org/10.1002/lt.25197DOI Listing
November 2018

Splenectomy as Flow Modulation Strategy and Risk Factors of De Novo Portal Vein Thrombosis in Adult-to-Adult Living Donor Liver Transplantation.

Liver Transpl 2018 09;24(9):1209-1220

Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada.

Portal vein thrombosis (PVT) is a severe complication after liver transplantation that can result in increased morbidity and mortality. Few data are available regarding risk factors, classification, and treatment of PVT after living donor liver transplantation (LDLT). Between January 2004 and November 2014, 421 adult-to-adult LDLTs were performed at our institution, and they were included in the analysis. Perioperative characteristics and outcomes from patients with no-PVT (n = 393) were compared with those with de novo PVT (total portal vein thrombosis [t-PVT]; n = 28). Ten patients had early portal vein thrombosis (e-PVT) occurring within 1 month, and 18 patients had late portal vein thrombosis (l-PVT) appearing later than 1 month after LDLT. Analysis of perioperative variables determined that splenectomy was associated with t-PVT (hazard ratio [HR], 3.55; P = 0.01), e-PVT (HR, 4.96; P = 0.04), and l-PVT (HR, 3.84; P = 0.03). In contrast, donor age was only found as a risk factor for l-PVT (HR, 1.05; P = 0.01). Salvage rate for treatment in e-PVT and l-PVT was 100% and 50%, respectively, without having an early event of rethrombosis. Mortality within 30 days did not show a significant difference between groups (no-PVT, 2% versus e-PVT, 10%; P = 0.15). No significant differences were found regarding 1-year (89% versus 92%), 5-year (79% versus 82%), and 10-year (69% versus 79%) graft survival between the t-PVT and no-PVT groups, respectively (P = 0.24). The 1-year (89% versus 96%), 5-year (82% versus 86%), and 10-year (79% versus 83%) patient survival was similar for the patients in the no-PVT and t-PVT groups, respectively (P = 0.70). No cases of graft loss occurred as a direct consequence of PVT. In conclusion, the early diagnosis and management of PVT after LDLT can lead to acceptable early and longterm results without affecting patient and graft survival.
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http://dx.doi.org/10.1002/lt.25212DOI Listing
September 2018

Live donor liver transplantation with older donors: Increased long-term graft loss due to HCV recurrence.

Clin Transplant 2018 08 16;32(8):e13304. Epub 2018 Jul 16.

Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada.

Using our prospectively collected database all adult hepatitis C virus (HCV)-positive patients receiving an adult-to-adult LDLT between October 2000 and May 2014 were identified. Outcome of LDLT with grafts from younger (<50 years=128) vs older donors (≥50 years=31) was compared. Post-transplant graft function, postoperative complications and incidence of HCV recurrence were evaluated. Long-term graft and patient survival was calculated. No difference in graft function was observed between younger and older grafts. Overall complications were similar between both groups. The severity of complications determined by the Dindo-Clavien score was similar. Graft loss from HCV recurrence was significantly less frequent in younger grafts (18% vs 62%, P = 0.001). Young vs older livers had a trend toward improved 1-, 5-, and 10-year graft survival (89% vs 87%, 77% vs 69%, 70% vs 55%, P = 0.096), while patient survival was comparable between both groups (91% vs 90%, 78% vs 69%, 71% vs 60%, P = 0.25). In conclusion, LDLT with older vs younger grafts are more frequently associated with long-term graft loss due to HCV recurrence. Differences in graft survival might be more prominent with prolonged (≥5-year) follow-up. Living donor-recipient matching is particularly important for younger HCV-positive recipients.
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http://dx.doi.org/10.1111/ctr.13304DOI Listing
August 2018

Liver Transplantation Without Venovenous Bypass: Does Surgical Approach Matter?

Transplant Direct 2018 May 24;4(5):e348. Epub 2018 Apr 24.

Multi-Organ Transplant Program, University of Toronto, Ontario, Canada.

Background: The use of venovenous bypass in liver transplantation has declined over time. Few studies have examined the impact of surgical approach in cases performed exclusively without venovenous bypass. We hypothesized that advances in liver transplant anesthesia and perioperative care have minimized the importance of surgical approach in the modern era.

Methods: Deceased donor liver transplants at the University of Toronto from 2000 to 2015 were reviewed, all performed without venovenous bypass. First, an unadjusted analysis was performed comparing perioperative outcomes and graft/patient survival for 3 different liver transplant techniques (caval interposition, piggyback, side-to-side cavo-cavostomy). Second, a propensity-matched analysis was performed comparing caval interposition to caval-preserving techniques.

Results: One thousand two hundred thirty-three liver transplants were included in the study. On unadjusted analysis, blood loss, transfusion requirement, postoperative complications, and graft/patient survival were equivalent for the 3 different techniques. To account for possible confounding patient variables, propensity matching was performed. Analysis of the propensity-matched cohorts also demonstrated similar outcomes for caval interposition versus caval-preserving approaches.

Conclusions: In the modern era at centers with a multidisciplinary team, the importance of specific liver transplant technique is minimized. Full or partial cross-clamping of the inferior vena cava is feasible without the use of venovenous bypass.
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http://dx.doi.org/10.1097/TXD.0000000000000776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959343PMC
May 2018

Intrahepatic cholangiocarcinoma, are we making progress?

Hepatobiliary Surg Nutr 2018 Apr;7(2):127-129

Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Canada.

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http://dx.doi.org/10.21037/hbsn.2017.12.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934134PMC
April 2018

Expanding the donor pool: Donation after circulatory death and living liver donation do not compromise the results of liver transplantation.

Liver Transpl 2018 06 14;24(6):779-789. Epub 2018 May 14.

Department of Surgery, Toronto General Hospital, Onatrio, Canada.

Because of the shortfall between the number of patients listed for liver transplantation (LT) and the available grafts, strategies to expand the donor pool have been developed. Donation after circulatory death (DCD) and living donor (LD) grafts are not universally used because of the concerns of graft failure, biliary complications, and donor risks. In order to overcome the barriers for the implementation of using all 3 types of grafts, we compared outcomes after LT of DCD, LD, and donation after brain death (DBD) grafts. Patients who received a LD, DCD, or DBD liver graft at the University of Toronto were included. Between January 2009 through April 2017, 1054 patients received a LT at our center. Of these, 77 patients received a DCD graft (DCD group); 271 received a LD graft (LD group); and 706 received a DBD graft (DBD group). Overall biliary complications were higher in the LD group (11.8%) compared with the DCD group (5.2%) and the DBD group (4.8%; P < 0.001). The 1-, 3-, and 5-year graft survival rates were similar between the groups with 88.3%, 83.2%, and 69.2% in the DCD group versus 92.6%, 85.4%, and 84.7% in the LD group versus 90.2%, 84.2%, and 79.9% in the DBD group (P = 0.24). Furthermore, the 1-, 3-, and 5-year patient survival was comparable, with 92.2%, 85.4%, and 71.6% in the DCD group versus 95.2%, 88.8%, and 88.8% in the LD group versus 93.1%, 87.5%, and 83% in the DBD group (P = 0.14). Multivariate Cox regression analysis revealed that the type of graft did not impact graft survival. In conclusion, DCD, LD, and DBD grafts have similar longterm graft survival rates. Increasing the use of LD and DCD grafts may improve access to LT without affecting graft survival rates. Liver Transplantation 24 779-789 2018 AASLD.
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http://dx.doi.org/10.1002/lt.25068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099346PMC
June 2018

Surgical Complications after Right Hepatectomy for Live Liver Donation: Largest Single-Center Western World Experience.

Semin Liver Dis 2018 05 22;38(2):134-144. Epub 2018 Mar 22.

Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.

The authors assessed the incidence, management, and risk factors for postoperative complications after right lobe (RL) live donor hepatectomy in a high-volume center in North America. All donors undergoing an RL live donor hepatectomy between 2000 and 2017 at our institution were included. The primary outcome was the development of complications (both medical and surgical). Predictors of postoperative complications were determined by logistic regression. A total of 587 patients underwent RL live donor hepatectomy. Among those, 187 postoperative complications were diagnosed in 141 (24%) patients. One patient had >90-day morbidity, and there were no donor deaths. Overall complications were significantly higher in the first era, 2000 to 2008 (81 [57.4%]) versus the second era, 2009 to 2017 (60 [42.6%]) ( = 0.01). On multivariate analysis, the only predictor of postoperative complications was the center volume of RL live donor hepatectomy in the previous 12 months with an odds ratio of 0.97 (95% confidence interval: 0.95-0.99). In conclusion, increasing center volume is associated with lower rates of postoperative complications after RL living liver donation.
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http://dx.doi.org/10.1055/s-0038-1636932DOI Listing
May 2018

Comparison of BQ123, Epoprostenol, and Verapamil as Vasodilators During Normothermic Ex Vivo Liver Machine Perfusion.

Transplantation 2018 04;102(4):601-608

Multi Organ Transplant Program, Toronto General Hospital, Toronto, ON, Canada.

Background: The optimal vasodilator to avoid hepatic artery vasospasm during normothermic ex vivo liver perfusion (NEVLP) is yet to be determined. We compared safety and efficacy of BQ123 (endothelin1 antagonist), epoprostenol (prostacyclin analogue), and verapamil (calcium channel antagonist).

Methods: Livers from porcine heart beating donors were perfused for 3 hours and transplanted into recipient pigs. Four groups were compared: group 1, livers perfused with a dose of 1.25 mg of BQ123 at baseline and at 2 hours of perfusion; group 2, epoprostenol at a continuous infusion of 4 mg/h; group 3, verapamil 2.5 mg at baseline and at 2 hours of perfusion; group 4, no vasodilator used during ex vivo perfusion. Liver injury and function were assessed during perfusion, and daily posttransplantation until postoperative day (POD) 3. All groups were compared with a cold storage group for postoperative graft function.

Results: Hepatic artery flow during NEVLP was significantly higher in BQ123 compared with verapamil, epoprostenol, and no vasodilator-treated livers. Aspartate aminotransferase levels were significantly lower with BQ123 and verapamil compared with epoprostenol and control group during perfusion. Peak aspartate aminotransferase levels were lower in pigs receiving BQ123 and verapamil perfused grafts compared with epoprostenol and control group. International Normalized Ratio, alkaline phosphatase, and total bilirubin levels were lower in the BQ123 and verapamil groups compared to epoprostenol group. Cold storage group had increased markers of ischemia reperfusion injury and slower graft function recovery compared to machine perfused grafts.

Conclusion: The use of BQ123, epoprostenol, and verapamil during NEVLP is safe. Livers perfused with BQ123 and verapamil have higher hepatic artery flow and reduced hepatocyte injury during perfusion compared with epoprostenol. Hepatic artery flow is significantly reduced in the absence of vasodilators during NEVLP.
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http://dx.doi.org/10.1097/TP.0000000000002021DOI Listing
April 2018

Reply.

Liver Transpl 2018 03 9;24(3):441. Epub 2018 Feb 9.

Multi-Organ Transplant Program Division of General Surgery Department of Surgery Toronto General Hospital, University Health Network University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1002/lt.24971DOI Listing
March 2018

Avoiding ICU Admission by Using a Fast-Track Protocol Is Safe in Selected Adult-to-Adult Live Donor Liver Transplant Recipients.

Transplant Direct 2017 Oct 18;3(10):e213. Epub 2017 Sep 18.

Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada.

Background: We evaluated patient characteristics of live donor liver transplant (LDLT) recipients undergoing a fast-track protocol without intensive care unit (ICU) admission versus LDLT patients receiving posttransplant ICU care.

Methods: Of the 153 LDLT recipients, 46 patients were included in our fast-track protocol without ICU admission. Both, fast-tracked patients and ICU-admitted patients were compared regarding donor and patient characteristics, perioperative characteristics, and postoperative outcomes and complications. In a subgroup analysis, we compared fast-tracked patients with patients who were admitted in the ICU for less than 24 hours.

Results: Fast-tracked versus ICU patients had a lower model for end-stage liver disease score (13 ± 4 vs 18 ± 7; < 0.0001), lower preoperative bilirubin levels (51 ± 50 μmol/L vs 119.4 ± 137.3 μmol/L; < 0.001), required fewer units of packed red blood cells (1.7 ± 1.78 vs 4.4 ± 4; < 0.0001), and less fresh-frozen plasma (2.7 ± 2 vs 5.8 ± 5; < 0.0001) during transplantation. Regarding postoperative outcomes, fast-tracked patients presented fewer bacterial infections within 30 days (6.5% [3] vs 29% [28]; = 0.002), no episodes of pneumonia (0% vs 11.3% [11]; = 0.02), and less biliary complications within the first year (6% [3] vs 26% [25]; = 0.001). Also, fast-tracked patients had a shorter posttransplant hospital stay (10.8 ± 5 vs 21.3 ± 29; = 0.002). In the subgroup analysis, fast-tracked vs ICU patients admitted for less than 24 hours had lower requirements of packed red blood cells (1.7 ± 1.78 vs 3.9 ± 4; = 0.001) and fresh-frozen plasma (2.7 ± 2 vs 5.8 ± 4.5; = 0.0001).

Conclusions: Fast-track of selected patients after LDLT is safe and feasible. An objective score to perioperatively select LDLT recipients amenable to fast track is yet to be determined.
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http://dx.doi.org/10.1097/TXD.0000000000000730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627744PMC
October 2017

Current status of liver transplantation for cholangiocarcinoma.

Liver Transpl 2018 02;24(2):294-303

Multi-Organ Transplant, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Cholangiocarcinoma (CCA) is the second most common liver cancer, and it is associated with a poor prognosis. CCA can be divided into intrahepatic, hilar, and distal. Despite the subtype, the median survival is 12-24 months without treatment. Liver transplantation (LT) is recognized worldwide as a curative option for hepatocellular carcinoma. On the other hand, the initial results for LT for CCA were very poor mainly due to a lack of adequate patient selection. In the last 2 decades, improvements have been made in the management of unresectable hilar CCA, and the results of LT after neoadjuvant chemoradiation have been shown to be promising. This has prompted a consideration of hilar CCA as an indication for LT in some centers. Furthermore, some recent research has shown promising results after LT for patients with early stages of intrahepatic CCA. A better understanding of the best tools to prognosticate the outcomes of LT for CCA is still needed. Here, we aimed to review the role of LT for the treatment of patients with perihilar and intrahepatic CCA. Also, we will discuss the most recent advances in the field and the future direction of the management of this disease in an era of transplantation oncology. Liver Transplantation 24 294-303 2018 AASLD.
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http://dx.doi.org/10.1002/lt.24955DOI Listing
February 2018

Pancreas Transplantation With Portal-Enteric Drainage for Patients With Endocrine and Exocrine Insufficiency From Extensive Pancreatic Resection.

Transplant Direct 2017 Sep 9;3(9):e203. Epub 2017 Aug 9.

Multi-Organ Transplant Program, University of Toronto, Toronto, Ontario, Canada.

Although the primary indication for pancreas transplantation is type I diabetes, a small number of patients requires pancreas transplantation to manage combined endocrine and exocrine insufficiency that develops after extensive native pancreatic resection. The objective of this case report was to describe the operative and clinical course in 3 such patients and present an alternative technical approach.
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http://dx.doi.org/10.1097/TXD.0000000000000721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585419PMC
September 2017
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