Publications by authors named "Roberto Hernandez-Alejandro"

94 Publications

The Rochester Relapse Risk Scale: Developing a Standardized Approach to Predicting Substance Relapse in Liver Transplant Candidates.

Exp Clin Transplant 2021 Sep;19(9):919-927

From the Department of Pharmacy, University of Rochester Medical Center, Rochester, USA.

Objectives: Substance abuse is a risk factor for nonadherence and graft failure after orthotopic liver transplant. This study aimed to evaluate the ability of an internally developed tool, the Rochester Relapse Risk Scale, to predict substance relapse in liver transplant candidates.

Materials And Methods: This single-center, retrospective, observational study included adult patients evaluated for orthotopic liver transplant using the Rochester Relapse Risk Scale. Primary outcome was rate of substance relapse, as measured by the risk scale, which stratified patients into relapse risk levels based on the number of factors present.

Results: In total, 303 patients (71.6% men, 90.4% White, median age of 55 years [interquartile range, 49-60 y]) were included. Median follow-up time was 212 days (interquartile range, 73-661 d). Seventy-four patients (24.4%) relapsed at 127 days (interquartile range, 55-461 d) after evaluation, with 60.8% who relapsed within 6 months. Relapse rates correlated with assigned risk level, with 8.3% relapsing at low, 19.0% at low-moderate, 25.3% at moderate, 33.8% at moderate-high, and 40.0% at high risk. High-risk cohorts had significantly shorter median time to relapse versus low-risk cohorts (104 vs 154 days; P = .001).

Conclusions: Assignment of relapse risk level according to the Rochester Relapse Risk Scale aligned with rates of relapse. Additional studies are needed to refine the tool, assess inter-rater reliability, and confirm findings in prospective, multicenter studies.
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http://dx.doi.org/10.6002/ect.2021.0034DOI Listing
September 2021

Evolution and Transformation of Uterine Transplantation: A Systematic Review of Surgical Techniques and Outcomes.

J Reconstr Microsurg 2021 Sep 17. Epub 2021 Sep 17.

Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York.

Background:  Uterine transplantation (UTx) is acknowledged to be on the second (2A) of five steps of development in accordance with the staging system for the evaluation of surgical innovations. Accordingly, we aimed to systematically review the available evidence of the surgical techniques and outcomes of UTx in terms of graft survival.

Methods:  A comprehensive search was conducted across PubMed Medline, Cochrane-EBMR, Scopus, Web of Science, and CENTRAL through November 2020.

Results:  Forty studies, reporting 64 recipients and 64 donors, satisfied inclusion criteria. The surgical time and the estimated blood loss were 515 minutes and 679 mL for graft procurement via laparotomy, 210 minutes and 100 mL for laparoscopic-assisted graft harvest, and 660 minutes and 173 mL for robotic-assisted procedures, respectively. Urinary tract infections ( = 8) and injury to the urinary system ( = 6) were the most common donor complications. Using the donor's internal iliac system, two arterial anastomoses were performed in all cases. Venous outflow was accomplished through the uterine veins (UVs) in 13 cases, a combination of the UVs and the ovarian/uteroovarian veins (OVs/UOVs) in 36 cases, and solely through the OVs/UOVs in 13 cases. Ischemia time was 161 and 258 minutes when using living donors (LD) and deceased donors (DD), respectively. Forty-eight uteri were successfully transplanted or fulfilled the purpose of transplantation, 41 from LDs and 7 from DDs. Twenty-five and four live childbirths from LDs and DDs have been reported, respectively.

Conclusion:  UTx is still experimental. Further series are required to recommend specific surgical techniques that best yield a successful transplant and reduce complications for donors and recipients.
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http://dx.doi.org/10.1055/s-0041-1735261DOI Listing
September 2021

GM-CSF drives myelopoiesis, recruitment and polarisation of tumour-associated macrophages in cholangiocarcinoma and systemic blockade facilitates antitumour immunity.

Gut 2021 Aug 19. Epub 2021 Aug 19.

Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA

Objective: Intrahepatic cholangiocarcinoma (iCCA) is rising in incidence, and at present, there are limited effective systemic therapies. iCCA tumours are infiltrated by stromal cells, with high prevalence of suppressive myeloid populations including tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Here, we show that tumour-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) and the host bone marrow is central for monopoiesis and potentiation of TAMs, and abrogation of this signalling axis facilitates antitumour immunity in a novel model of iCCA.

Methods: Blood and tumours were analysed from iCCA patients and controls. Treatment and correlative studies were performed in mice with autochthonous and established orthotopic iCCA tumours treated with anti-GM-CSF monoclonal antibody.

Results: Systemic elevation in circulating myeloid cells correlates with poor prognosis in patients with iCCA, and patients who undergo resection have a worse overall survival if tumours are more infiltrated with CD68 TAMs. Mice with spontaneous iCCA demonstrate significant elevation of monocytic myeloid cells in the tumour microenvironment and immune compartments, and tumours overexpress GM-CSF. Blockade of GM-CSF with a monoclonal antibody decreased tumour growth and spread. Mice bearing orthotopic tumours treated with anti-GM-CSF demonstrate repolarisation of immunosuppressive TAMs and MDSCs, facilitating T cell response and tumour regression. GM-CSF blockade dampened inflammatory gene networks in tumours and TAMs. Human tumours with decreased GM-CSF expression exhibit improved overall survival after resection.

Conclusions: iCCA uses the GM-CSF-bone marrow axis to establish an immunosuppressive tumour microenvironment. Blockade of the GM-CSF axis promotes antitumour T cell immunity.
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http://dx.doi.org/10.1136/gutjnl-2021-324109DOI Listing
August 2021

Refining the surgical playbook for treating colorectal cancer liver metastases.

Hepatobiliary Surg Nutr 2021 Jun;10(3):397-400

Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.

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http://dx.doi.org/10.21037/hbsn-21-31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188126PMC
June 2021

Donor Warm Ischemia Time in DCD Liver Transplantation-Working Group Report From the ILTS DCD, Liver Preservation, and Machine Perfusion Consensus Conference.

Transplantation 2021 06;105(6):1156-1164

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA.

Donation after circulatory death (DCD) grafts are commonly used in liver transplantation. Attributable to the additional ischemic event during the donor warm ischemia time (DWIT), DCD grafts carry an increased risk for severe ischemia/reperfusion injury and postoperative complications, such as ischemic cholangiopathy. The actual ischemia during DWIT depends on the course of vital parameters after withdrawal of life support and varies widely between donors. The ischemic period (functional DWIT) starts when either Spo2 or blood pressure drop below a certain point and lasts until the start of cold perfusion during organ retrieval. Over the years, multiple definitions and thresholds of functional DWIT duration have been used. The International Liver Transplantation Society organized a Consensus Conference on DCD, Liver Preservation, and Machine Perfusion on January 31, 2020 in Venice, Italy. The aim of this conference was to reach consensus about various aspects of DCD liver transplantation in context of currently available evidence. Here we present the recommendations with regards to the definitions used for DWIT and functional DWIT, the importance of vital parameters after withdrawal of life support, and acceptable thresholds of duration of functional DWIT to proceed with liver transplantation.
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http://dx.doi.org/10.1097/TP.0000000000003819DOI Listing
June 2021

Repeated hepatectomy after ALPPS for recurrence of colorectal liver metastasis: the edge of limits?

HPB (Oxford) 2021 Mar 1. Epub 2021 Mar 1.

Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Germany; Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany.

Background: Repeated liver resections for the recurrence of colorectal liver metastasis (CRLM) are described as safe and have similar oncological outcomes compared to first hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is performed in patients with conventionally non-resectable CRLM. Repeated resections after ALPPS has not yet been described.

Methods: Patients that underwent repeated liver resection in recurrence of CRLM after ALPPS were included in this study. The primary endpoint was morbidity and secondary endpoints were mortality, resection margin and survival.

Results: Thirty patients were included in this study. During ALPPS, most of the patients had classical split (60%, n = 18) and clearance of the FLR (77%, n = 23). Hepatic recurrence was treated with non-anatomical resection (57%, n = 17), resection combined with local ablation (13%, n = 4), open ablation (13%, n = 4), segmentectomy (10%, n = 3) or subtotal segmentectomy (7%, n = 2). Six patients (20%) developed complications (10% minor complications). No post-hepatectomy liver failure or perioperative mortality was observed. One-year patient survival was 87%. Five patients received a third hepatectomy.

Conclusion: Repeated resections after ALPPS for CRLM in selected patients are safe and feasible with low morbidity and no mortality. Survival seems to be comparable with repeated resections after conventional hepatectomy.
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http://dx.doi.org/10.1016/j.hpb.2021.02.008DOI Listing
March 2021

Living Donor Liver Transplantation in the United States: Evolution of Frequency, Outcomes, Center Volumes, and Factors Associated With Outcomes.

Liver Transpl 2021 07 24;27(7):1019-1031. Epub 2021 Jun 24.

Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL.

Recent modifications in organ allocation policies and increases in chronic liver diseases may have resulted in important changes in living donor liver transplantation (LDLT) in the United States. We examined the trends, outcomes, and factors associated with outcomes in adult LDLT. United Network for Organ Sharing data on 2566 adult LDLT recipients who received transplants from January 1, 2010, through December 31, 2019, were analyzed. LDLT graft and patient survival rates were compared with propensity score-matched deceased donor liver transplantation recipients by the Kaplan-Meier curve estimator. The association between preceding LDLT frequency and subsequent outcomes were assessed by Cox proportional hazards mixed effects modeling. After a stable annual frequency of LDLTs from 2010 to 2014 (~200 per year), the number of LDLTs doubled to 440 in 2019. The 1-year and 5-year graft survival rates for LDLT recipients were 88.4% and 78.1%, respectively, compared with 92.5% and 80.7% in the propensity score-matched donation after brain death recipients (P = 0.005), respectively. Older donor age and recipient diabetes mellitus and life support requirement were significantly associated with graft failure among LDLT recipients (P values <0.05). Average preceding LDLT frequencies of <3 per year, 3 to 20 per year, and >20 per year resulted in 1-year graft survival rates of 82%, 88% to 89%, and 93%, respectively (P values <0.05). There were 3 living donor deaths (0.12%). The frequency of LDLTs has doubled during the past decade, with good outcomes and acceptable donor safety profiles. However, there appear to be varying threshold transplant frequencies (volume/unit time) associated with acceptable (88%-89%) and aspirational (93%) 1-year graft survival rates. These data should be reassuring and encourage LDLT practice as efforts continue to expand the donor pool.
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http://dx.doi.org/10.1002/lt.26029DOI Listing
July 2021

Estimating the effect of increasing utilization of living donor liver transplantation using observational data.

Transpl Int 2021 04 26;34(4):648-656. Epub 2021 Feb 26.

Division of Transplantation/Hepatobiliary Surgery, Department of Surgery, University of Rochester, Rochester, NY, USA.

There has been a recent increase in enthusiasm for expansion of living donor liver transplantation (LDLT) programmes. Using all adults initially placed on the waiting list in the United States, we estimated the risk of overall mortality under national strategies which differed in their utilization of LDLT. We used a generalization of inverse probability weighting which can estimate the effect of interventions in the setting of finite resources. From 2005 to 2015, 93 812 eligible individuals were added to the waitlist: 51 322 received deceased donor grafts while 1970 underwent LDLT. Individuals who underwent LDLT had more favourable prognostic factors, including lower mean MELD score at transplant (14.6 vs. 20.5). The 1-year, 5-year and 10-year cumulative incidence of death under the current level of LDLT utilization were 18.0% (95% CI: 17.8, 18.3%), 41.2% (95% CI: 40.8, 41.5%) and 57.4% (95% CI: 56.9, 57.9%) compared to 17.9% (95% CI: 17.7, 18.2%), 40.6% (95% CI: 40.2, 40.9%) and 56.4% (95% CI: 55.8, 56.9%) under a strategy which doubles LDLT utilization. Expansion of LDLT utilization would have a measurable, modest effect on the risk of mortality for the entire cohort of individuals who begin on the transplant waiting list.
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http://dx.doi.org/10.1111/tri.13835DOI Listing
April 2021

Assessing resectability for colorectal liver metastases: agreeing that we disagree.

Hepatobiliary Surg Nutr 2020 Dec;9(6):797-800

Division of Abdominal Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.

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http://dx.doi.org/10.21037/hbsn.2020.03.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720064PMC
December 2020

Looking Beyond the Horizon: Patient-Specific Rehearsals for Complex Liver Surgeries With 3D Printed Model.

Ann Surg 2021 01;273(1):e28-e30

Department of Surgery, Division of Transplantation and Hepatobiliary Surgery, University of Rochester, Rochester, New York.

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http://dx.doi.org/10.1097/SLA.0000000000004491DOI Listing
January 2021

First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

Ann Surg 2020 11;272(5):793-800

Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Objectives: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS.

Background: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking.

Methods: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis.

Results: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001).

Conclusions: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.
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http://dx.doi.org/10.1097/SLA.0000000000004330DOI Listing
November 2020

Choices of Therapeutic Strategies for Colorectal Liver Metastases Among Expert Liver Surgeons: A Throw of the Dice?

Ann Surg 2020 11;272(5):715-722

Department of Radiology, University Hospital Zurich, Zurich, Switzerland.

Objective: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe.

Summary/background: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients.

Methods: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers.

Results: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries.

Conclusions: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.
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http://dx.doi.org/10.1097/SLA.0000000000004331DOI Listing
November 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

Variation in complications and mortality following ALPPS at early-adopting centers.

HPB (Oxford) 2021 Jan 23;23(1):46-55. Epub 2020 May 23.

Department of General Surgery, HM Sanchinarro Hospital, Madrid, Spain.

Background: Various, often conflicting, estimates for post-operative morbidity and mortality following ALPPS have been reported in the literature, suggesting that considerable center-level variation exists. Some of this variation may be related to center volume and experience.

Methods: Using data from seventeen centers who were early adopters of the ALPPS technique, we estimated the variation, by center, in standardized 90-day mortality and comprehensive complication index (CCI) for patients treated between 2012 and 2018.

Results: We estimated that center-specific 90-day mortality following treatment with ALPPS varied from 4.2% (95% CI: 0.8, 9.9) to 29.1% (95% CI: 13.9, 50.9), and that center-specific CCI following treatment with ALPPS varied from 17.0 (95% CI: 7.5, 26.5) to 49.8 (95% CI: 38.1, 61.8). Declines in estimated 90-day mortality and CCI were observed over time, and almost all individual centers followed this trend. Patients treated at centers with a higher number of ALPPS cases performed over the prior year had a lower risk of post-operative mortality.

Conclusion: Despite considerable center-level variation in ALPPS outcomes, perioperative outcomes following ALPPS have improved over time and treatment at higher volume centers results in a lower risk of 90-day mortality. Morbidity and mortality remain concerningly high at some centers.
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http://dx.doi.org/10.1016/j.hpb.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680722PMC
January 2021

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) procedure for colorectal liver metastasis.

Int J Surg 2020 Oct 16;82S:103-108. Epub 2020 Apr 16.

Division of Surgery, Miguel Servet University Hospital and University of Zaragoza School of Medicine, Zaragoza, Spain.

Since first described, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has garnered boisterous praise and fervent criticism. Its rapid adoption and employment for a variety of indications resulted in high perioperative morbidity and mortality. However recent risk stratification, refinement of technique to reduce the impact of stage I and progression along the learning curve have resulted in improved outcomes. The first randomized trial comparing ALPPS to two stage hepatectomy (TSH) for colorectal liver metastases (CRLM) was recently published demonstrating comparable perioperative morbidity and mortality with improved resectability and survival following ALPPS. In this review, as ALPPS enters the thirteenth year since conception, the current status of this contentious two stage technique is presented and best practices for deployment in the treatment of CRLM is codified.
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http://dx.doi.org/10.1016/j.ijsu.2020.04.009DOI Listing
October 2020

Liver transplantation for colorectal liver metastases: What do we need to know?

Int J Surg 2020 Oct 17;82S:87-92. Epub 2020 Apr 17.

Department of Surgery and Division of Abdominal Transplantation and Hepatobiliary Surgery, University of Rochester Medical Center, Rochester, USA.

Adenocarcinoma of the colon and rectum (CRC) is the second leading cause of cancer mortality, driven by stage IV disease (Rahib et al., 2014) [1]. While surgical resection of liver metastases has demonstrated a survival advantage, a minority of patients are candidates for resection due to anatomic involvement of disease. Recent advances in liver surgery, chemotherapy, and decision making guided by stratification at the time of presentation has better equipped us to perform aggressive metastasectomies, with resulting improved survival (Fong et al., 1999; Abdalla et al., 2001; Cremolini et al., 2017) [2-4]. As a result, there is a resurgent interest in the concept of total hepatectomy and liver transplantation (LT) for colorectal liver metastases (CRLM). As of this writing, eight prospective clinical trials in six countries are assessing the viability of split or whole LT for CRLM. However, LT for CRLM remains controversial. Recent prospective trials have illustrated the importance of patient selection, and a disciplined respect for tumor biology. Here we present the current status of LT for CRLM, and suggest clinical decision criteria aimed at matching survival benefit comparable to other indications for LT.
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http://dx.doi.org/10.1016/j.ijsu.2020.03.079DOI Listing
October 2020

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

Ann Surg Oncol 2020 May 30;27(5):1372-1384. Epub 2020 Jan 30.

Department of General, Visceral and Transplantation Surgery, University Hospital Frankfurt, Frankfurt, Germany.

Background: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC).

Methods: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis.

Results: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC.

Conclusion: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.
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http://dx.doi.org/10.1245/s10434-019-08192-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138775PMC
May 2020

How to Handle Arterial Conduits in Liver Transplantation? Evidence From the First Multicenter Risk Analysis.

Ann Surg 2020 Jan 16. Epub 2020 Jan 16.

Swiss HPB & Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland.

Objective: The aims of the present study were to identify independent risk factors for conduit occlusion, compare outcomes of different AC placement sites, and investigate whether postoperative platelet antiaggregation is protective.

Background: Arterial conduits (AC) in liver transplantation (LT) offer an effective rescue option when regular arterial graft revascularization is not feasible. However, the role of the conduit placement site and postoperative antiaggregation is insufficiently answered in the literature.

Study Design: This is an international, multicenter cohort study of adult deceased donor LT requiring AC. The study included 14 LT centers and covered the period from January 2007 to December 2016. Primary endpoint was arterial occlusion/patency. Secondary endpoints included intra- and perioperative outcomes and graft and patient survival.

Results: The cohort was composed of 565 LT. Infrarenal aortic placement was performed in 77% of ACs whereas supraceliac placement in 20%. Early occlusion (≤30 days) occurred in 8% of cases. Primary patency was equivalent for supraceliac, infrarenal, and iliac conduits. Multivariate analysis identified donor age >40 years, coronary artery bypass, and no aspirin after LT as independent risk factors for early occlusion. Postoperative antiaggregation regimen differed among centers and was given in 49% of cases. Graft survival was significantly superior for patients receiving aggregation inhibitors after LT.

Conclusion: When AC is required for rescue graft revascularization, the conduit placement site seems to be negligible and should follow the surgeon's preference. In this high-risk group, the study supports the concept of postoperative antiaggregation in LT requiring AC.
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http://dx.doi.org/10.1097/SLA.0000000000003753DOI Listing
January 2020

Understanding helping behaviors in an interprofessional surgical team: How do members engage?

Am J Surg 2020 02 17;219(2):372-378. Epub 2019 Dec 17.

Centre for Education Research & Innovation, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Faculty of Education, Western University, London, Ontario, Canada; Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Objective: In surgical environments, work must be flexible, allowing practitioners to seek help when required. How surgeons navigate the complexity of interprofessional teams and collaborative care whilst attending to their own knowledge/skill gaps can be difficult. This study aims to understand helping behaviours in interprofessional surgical teams.

Design: Thirteen semi-structured interviews with participants were completed. Data collection and inductive analysis were conducted iteratively using thematic analysis.

Results: We found several intersecting features that influenced helping engagement. Work context, including nested and cross-sectional identities, physical and hierarchical environments, diversity, support for risk-taking and innovation and perceptions of a "speak up" culture shaped the way helping scenarios were approached. Intrinsic attributes influenced decisions to dis/engage. When united, these features shaped how helping behaviours became enacted.

Conclusion: If we desire to create surgical teams that deliver quality care, we must consider not only individual attributes but the context in which teams are situated.
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http://dx.doi.org/10.1016/j.amjsurg.2019.12.014DOI Listing
February 2020

Surgical resection of calcifying nested stromal-epithelial tumor in an adolescent female: A case report.

Int J Surg Case Rep 2020 16;66:1-3. Epub 2019 Nov 16.

Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642-0001, USA.

Introduction: Calcifying nested stromal-epithelial tumor (CNSET) is an extremely rare, indolent tumor of the liver of uncertain cellular origin. With only 38 cases reported in the literature, pathogenesis and optimal therapeutic approach are not well characterized. Based on the available literature, the risk of recurrence is low with surgical resection with negative margins.

Presentation Of Case: In this case report, we describe an adolescent patient with CNSET who underwent right trisectionectomy.

Discussion: In order to avoid posthepatectomy liver failure, special consideration must be given to the amount of residual liver parenchyma after resection when considering surgical approach. Single stage right trisectionectomy and two stage via associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) were both considered for surgical approach in this case in order to provide sufficient functional liver parenchyma remnant.

Conclusion: Given that obtaining negative margins is important in reducing the risk of recurrence, the method of surgical resection utilized is based on the amount of future functional residual hepatic parenchyma.
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http://dx.doi.org/10.1016/j.ijscr.2019.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889362PMC
November 2019

Renal Impairment Is Associated with Reduced Outcome After Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy.

J Gastrointest Surg 2020 11 19;24(11):2500-2507. Epub 2019 Nov 19.

Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Rübenkamp 220, 22291, Hamburg, Germany.

Background: Impaired postoperative renal function is associated with increased morbidity and mortality after liver resection. The role of impaired renal function in the two-stage hepatectomy setting of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is unknown.

Methods: An international multicenter cohort of ALPPS patients captured in the ALPPS Registry was analyzed. Particular attention was drawn to the renal function in the interstage interval to determine outcome after stage 2 surgery. Interstage renal impairment (RI) was defined as an increase of serum creatinine of ≥ 0.3 mg/dl referring to a preoperative value or an increase of serum creatinine of ≥ 1.5× of the preoperative value on the fifth postoperative day after stage 1.

Results: A total of 705 patients were identified of which 7.5% had an interstage RI. Patients developing an interstage RI were significantly older. During stage 1, a longer operation time, higher rate of intraoperative transfusions, and additional procedures were observed in patients that developed interstage RI. After stage 1, interstage RI patients had more major complications and higher interstage mortality (1% vs. 8%, p < 0.001). Furthermore, these patients developed more and severe complications after completion of stage 2. Mortality of patients with interstage RI was 38% vs. 8% without interstage RI. In 41% of patients with interstage RI, the renal function recovered before stage 2; however, the mortality after stage 2 remained 28% in those patients. Risk factors for the development of an interstage RI were age over 67 years, prolonged operative time, and additional procedure during stage 1.

Conclusion: This study shows that interstage RI is a predictor for interstage and post-stage 2 morbidity and perioperative mortality. The causality of impaired renal function on outcome, however, remains unknown. Interstage RI may directly cause adverse outcome but may also be a surrogate marker for major complications.
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http://dx.doi.org/10.1007/s11605-019-04419-2DOI Listing
November 2020

Exercise Training for Liver Transplant Candidates.

Transplant Proc 2019 Dec 13;51(10):3330-3337. Epub 2019 Nov 13.

Department of Medicine, Division of Gastroenterology, Western University and London Health Sciences Centre, London, Ontario, Canada; Multi-Organ Transplant Program, Western University and London Health Sciences Centre, London, Ontario, Canada.

Background And Aims: Frailty is associated with increased morbidity and mortality, and this is tightly linked to liver decompensation and increased complication rates among liver transplant (LT) candidates. The aim of the study was to evaluate the efficacy of a structured in- and outpatient exercise training program for cirrhotic patients who were referred for liver transplant evaluation.

Methods: We retrospectively reviewed 458 consecutive LT patients. There were 200 patients who underwent LT prior to the implementation of an exercise training program (non-ETP) and 258 LT patients who underwent a comprehensive exercise training program (ETP). Baseline characteristics, readmission rate, and length of hospital stay (LOS) were analyzed and compared between the 2 groups.

Results: The ETP group were more likely to have diabetes mellitus and coronary artery disease. However, there was no significant difference in the postoperative complication rates between the 2 groups except for more infections in the ETP group compared to the non-ETP group. There was a trend toward lower 90-day readmission rate in the ETP group (17.9% vs 20%) and shorter LOS (14 vs 17 days).

Conclusion: There was a trend toward reduced 90-day readmission and shorter length of stay after implementation of an exercise training program.
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http://dx.doi.org/10.1016/j.transproceed.2019.08.045DOI Listing
December 2019

Defining Benchmark Outcomes for ALPPS.

Ann Surg 2019 11;270(5):835-841

Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Switzerland.

Objective: The aim of this study was to use the concept of benchmarking to establish robust and standardized outcome references after the procedure ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy).

Background And Aims: The recently developed ALPPS procedure, aiming at removing primarily unresectable liver tumors, has been criticized for safety issues with high variations in the reported morbidity/mortality rates depending on patient, disease, technical characteristics, and center experience. No reference values for relevant outcome parameters are available.

Methods: Among 1036 patients registered in the international ALPPS registry, 120 (12%) were benchmark cases fulfilling 4 criteria: patients ≤67 years of age, with colorectal metastases, without simultaneous abdominal procedures, and centers having performed ≥30 cases. Benchmark values, defined as the 75th percentile of the median outcome parameters of the centers, were established for 10 clinically relevant domains.

Results: The benchmark values were completion of stage 2: ≥96%, postoperative liver failure (ISGLS-criteria) after stage 2: ≤5%, ICU stay after ALPPS stages 1 and 2: ≤1 and ≤2 days, respectively, interstage interval: ≤16 days, hospital stay after ALPPS stage 2: ≤10 days, rates of overall morbidity in combining both stage 1 and 2: ≤65% and for major complications (grade ≥3a): ≤38%, 90-day comprehensive complication index was ≤22, the 30-, 90-day, and 6-month mortality was ≤4%, ≤5%, and 6%, respectively, the overall 1-year, recurrence-free, liver-tumor-free, and extrahepatic disease-free survival was ≥86%, ≥50%, ≥57%, and ≥65%, respectively.

Conclusions: This benchmark analysis sets key reference values for ALPPS, indicating similar outcome as other types of major hepatectomies. Benchmark cutoffs offer valid tools not only for comparisons with other procedures, but also to assess higher risk groups of patients or different indications than colorectal metastases.
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http://dx.doi.org/10.1097/SLA.0000000000003539DOI Listing
November 2019

Reply to: "Canadian liver transplant allocation for hepatocellular carcinoma".

J Hepatol 2019 11 7;71(5):1060. Epub 2019 Sep 7.

Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2019.08.001DOI Listing
November 2019

Watching the Clock in Donation After Circulatory Death Liver Transplantation.

Liver Transpl 2019 09;25(9):1305-1307

Department of Hepatobiliary Surgery and Abdominal Transplantation, University of Rochester Medical Center, Rochester, NY.

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http://dx.doi.org/10.1002/lt.25617DOI Listing
September 2019

Health and Economic Impact of Intensive Surveillance for Distant Recurrence After Curative Treatment of Colon Cancer: A Mathematical Modeling Study.

Dis Colon Rectum 2019 07;62(7):872-881

Department of Health Policy and Management and Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

Background: Intensive surveillance strategies are currently recommended for patients after curative treatment of colon cancer, with the aim of secondary prevention of recurrence. Yet, intensive surveillance has not yielded improvements in overall patient survival compared with minimal follow-up, and more intensive surveillance may be costlier.

Objective: The purpose of this study was to estimate the quality-adjusted life-years, economic costs, and cost-effectiveness of various surveillance strategies after curative treatment of colon cancer.

Design: A Markov model was calibrated to reflect the natural history of colon cancer recurrence and used to estimate surveillance costs and outcomes.

Settings: This was a decision-analytic model.

Patients: Individuals entered the model at age 60 years after curative treatment for stage I, II, or III colon cancer. Other initial age groups were assessed in secondary analyses.

Main Outcome Measures: We estimated the gains in quality-adjusted life-years achieved by early detection and treatment of recurrence, as well as the economic costs of surveillance under various strategies.

Results: Cost-effective strategies for patients with stage I colon cancer improved quality-adjusted life-expectancy by 0.02 to 0.06 quality-adjusted life-years at an incremental cost of $1702 to $13,019. For stage II, they improved quality-adjusted life expectancy by 0.03 to 0.09 quality-adjusted life-years at a cost of $2300 to $14,363. For stage III, they improved quality-adjusted life expectancy by 0.03 to 0.17 quality-adjusted life-years for a cost of $1416 to $17,631. At a commonly cited willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the most cost-effective strategy for patients with a history of stage I or II colon cancer was liver ultrasound and chest x-ray annually. For those with a history of stage III colon cancer, the optimal strategy was liver ultrasound and chest x-ray every 6 months with CEA measurement every 6 months.

Limitations: The study was limited by model structure assumptions and uncertainty around the values of the model's parameters.

Conclusions: Given currently available data and within the limitations of a model-based decision-analytic approach, the effectiveness of routine intensive surveillance for patients after treatment of colon cancer appears, on average, to be small. Compared with testing using lower cost imaging, currently recommended strategies are associated with cost-effectiveness ratios that indicate low value according to well-accepted willingness-to-pay thresholds in the United States. See Video Abstract at http://links.lww.com/DCR/A921.
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http://dx.doi.org/10.1097/DCR.0000000000001364DOI Listing
July 2019

The meaning of confounding adjustment in the presence of multiple versions of treatment: an application to organ transplantation.

Eur J Epidemiol 2019 Mar 23;34(3):225-233. Epub 2019 Jan 23.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Causal inference for treatments with many versions requires a careful specification of the versions of treatment. Specifically, the existence of multiple relevant versions of treatment has implications for the selection of confounders. To illustrate this, we estimate the effect of organ transplantation using grafts from donors who died due to anoxic drug overdose, on recipient graft survival in the US. We describe how explicitly outlining the target trial (i.e. the hypothetical randomized trial which would answer the causal question of interest) to be emulated by an observational study analysis helps conceptualize treatment versions, guides selection of appropriate adjustment variables, and helps clarify the settings in which causal effects of compound treatments will be of value to decision-makers.
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http://dx.doi.org/10.1007/s10654-019-00484-8DOI Listing
March 2019

Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience

Can J Surg 2019 02;62(1):44-51

From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro).

Background: Outcomes in liver transplantation with organs obtained via donation after cardiocirculatory death (DCD) have been suboptimal compared to donation after brain death, attributed mainly to the high incidence of ischemic cholangiopathy (IC). We evaluated the effect of a 10-year learning curve on IC rates among DCD liver graft recipients at a single centre.

Methods: We analyzed all DCD liver transplantation procedures from July 2006 to July 2016. Patients were grouped into early (July 2006 to June 2011) and late (July 2011 to July 2016) eras. Those with less than 6 months of follow-up were excluded. Primary outcomes were IC incidence and IC-free survival rate.

Results: Among the 73 DCD liver transplantation procedures performed, 70 recipients fulfilled the selection criteria, 32 in the early era and 38 in the late era. Biliary complications were diagnosed in 19 recipients (27%). Ischemic cholangiopathy was observed in 8 patients (25%) in the early era and 1 patient (3%) in the late era (p = 0.005). The IC-free survival rate was higher in the late era than the early era (98% v. 79%, p = 0.01). The warm ischemia time (27 v. 24 min, p = 0.049) and functional warm ischemia time (21 v. 17 min, p = 0.002) were significantly lower in the late era than the early era.

Conclusion: We found a significant reduction in IC rates and improvement in ICfree survival among DCD liver transplantation recipients after a learning curve period that was marked by more judicious donor selection with shorter procurement times.
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http://dx.doi.org/10.503/cjs.012017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351268PMC
February 2019

Performance validation of the ALPPS risk model.

HPB (Oxford) 2019 06 24;21(6):711-721. Epub 2018 Nov 24.

Swiss HPB and Transplantation Center, Department of Surgery, University Hospital Zurich, Switzerland. Electronic address:

Background: Based on the International ALPPS registry, we have recently proposed two easily applicable risk models (pre-stage1 and 2) for predicting 90-day mortality in ALPPS but a validation of both models has not been performed yet.

Methods: The validation cohort (VC) was composed of subsequent cases of the ALPPS registry and cases of centers outside the ALPPS registry.

Results: The VC was composed of a total of 258 patients including 70 patients outside the ALPPS registry with 32 cases of early mortalities (12%). Development cohort (DC) and VC were comparable in terms of patient and surgery characteristics. The VC validated both models with an acceptable prediction for the pre-stage 1 (c-statistic 0.64, P = 0.009 vs. 0.77, P < 0.001) and a good prediction for the pre-stage 2 model (c-statistic 0.77, P < 0.001 vs. 0.85, P < 0.001) as compared to the DC. Overall model performance measured by Brier score was comparable between VC and DC for the pre-stage 1 (0.089 vs. 0.081) and pre-stage 2 model (0.079 vs. 0087).

Conclusion: The ALPPS risk score is a fully validated model to estimate the individual risk of patients undergoing ALPPS and to assist clinical decision making to avoid procedure-related early mortality after ALPPS.
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http://dx.doi.org/10.1016/j.hpb.2018.10.003DOI Listing
June 2019

The Effect of the Opioid Epidemic on Donation After Circulatory Death Transplantation Outcomes.

Transplantation 2019 05;103(5):973-979

Division of Transplantation/Hepatobiliary Surgery, Department of Surgery, University of Rochester, Rochester, NY.

Background: The opioid epidemic and the deaths of otherwise healthy individuals due to drug overdose in the United States has major implications for transplantation. The current extent and safety of utilization of liver and kidney grafts from donation after circulatory death (DCD) donors who died from opioid overdose is unknown.

Methods: Using national data from 2006 to 2016, we estimated the cumulative incidence of graft failure for recipients of DCD grafts, comparing the risk among recipients of organs from donors who died of anoxic drug overdose and recipients of organs from donors who died of other causes.

Results: One hundred seventy-nine (6.2%) of 2908 liver graft recipients and 944 (6.1%) of 15520 kidney graft recipients received grafts from donors who died of anoxic drug overdose. Grafts from anoxic drug overdose donors were less frequently used compared with other DCD grafts (liver, 25.9% versus 29.6%; 95% confidence interval [CI] for difference, -6.7% to -0.7%; kidney, 81.0% versus 84.7%; 95% CI for difference, -7.3% to -0.1%). However, the risk of graft failure at 5 years was similar for recipients of anoxic drug overdose donor grafts and recipients of other grafts (liver risk difference, 1.8%; 95% CI, -7.8% to 11.8%; kidney risk difference, -1.5%; 95% CI, -5.4% to 3.1%).

Conclusions: In the context of the current opioid epidemic, utilization of anoxic drug overdose DCD donor grafts does not increase the risk of graft failure and may help to address waitlist demands.
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http://dx.doi.org/10.1097/TP.0000000000002467DOI Listing
May 2019
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