Publications by authors named "Neeta Vachharajani"

56 Publications

Novel Method of Evaluating Liver Transplant Surgery Fellows Using Objective Measures of Operative Efficiency and Surgical Outcomes.

J Am Coll Surg 2021 Apr 6. Epub 2021 Apr 6.

Section of Abdominal Transplant Surgery, Washington University School of Medicine, St Louis, MO. Electronic address:

Background: The majority of liver transplants (LT) in North America are performed by transplant surgery fellows with attending surgeon supervision. While a strict case volume requirement is mandatory for graduating fellows, no guidelines exist on providing constructive feedback to trainees during fellowship.

Study Design: A retrospective review of all adult LTs performed by abdominal transplant surgery fellows at a single ASTS-accredited academic institution from 2005-2019 was conducted. Data from the most recent 5 fellows were averaged to generate reference learning curves for eight variables representing operative efficiency (i.e. total operative time, warm ischemia time, cold ischemia time) and surgical outcomes (i.e. intraoperative blood loss, unplanned return to the operating room, biliary complications, vascular complications, patient/graft loss). Data for newer fellows were plotted against the reference curves at 3-month intervals to provide an objective assessment measure.

Results: 352 adult LTs were performed by 5 fellows during the study period. Mean patient age was 56 years; 67% were males; and average MELD at transplant was 22. For the eight primary variables, mean values included the following: total operative time 330 minutes, warm ischemia time 28 minutes, cold ischemia time 288 minutes, intraoperative blood loss 1.59 L, biliary complications 19.6%, unplanned return to OR 19.3%, vascular complications 2.3%. A structure for feedback to fellows was developed using a printed report card and through in-person meetings with faculty at 3-month intervals.

Conclusion: Comparative feedback using institution-specific reference curves can provide valuable objective data on progression of individual fellows. It can aid in the timely identification of areas in need of improvement, which enhances the quality of training and has the potential to improve patient care and transplant outcomes.
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http://dx.doi.org/10.1016/j.jamcollsurg.2021.03.029DOI Listing
April 2021

Access to Liver Transplantation for Hepatocellular Carcinoma: Does Candidate Age Matter?

J Am Coll Surg 2021 Feb 27. Epub 2021 Feb 27.

Department of Abdominal Organ Transplantation Surgery, Washington University School of Medicine, St Louis, MO. Electronic address:

Background: Liver transplantation (LT) offers an effective alternative treatment for unresectable hepatocellular carcinoma (HCC). Despite its growing acceptance and longer life expectancy rates, survival data in older patients are conflicting and consensus guidelines are lacking in terms of a cut-off age range for operations.

Study Design: We explored our prospectively maintained institutional database to identify patients diagnosed with HCC between January 1, 2002 and December 31, 2019. Long-term oncologic outcomes were analyzed in patients undergoing LT or hepatic resection, with patient age considered as the primary variable.

Results: In total, 1,629 patients with HCC were identified, of whom 700 were considered for curative operations (LT, n = 538; resection, n = 162). Patients older than 65 years were less likely to be considered for LT (p < 0.01), although there were no age-related differences in the de-listing rate among age groups (p = 0.90). Older patients had overall survival (OS) outcomes comparable with younger patients after LT (3-year OS: 85.5% vs 84%; 5-year OS: 73.9% vs 77%; p = 0.26). Long-term survival was lower in the group who underwent resection, however, older patients still demonstrated equivalent OS outcomes (3-year OS: 59% vs 64.8%; 5-year OS: 44.8% vs 49%; p = 0.13). There were no differences in the development of local or distant metastatic disease between groups.

Conclusions: Although older candidates were less likely to be considered for LT in the management of HCC, judicious matching can lead to OS data comparable with their younger counterparts. Previous age misconceptions need to be challenged without the concern of worse long-term oncologic outcomes after surgery.
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http://dx.doi.org/10.1016/j.jamcollsurg.2021.01.018DOI Listing
February 2021

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors.

J Am Coll Surg 2021 Apr 13;232(4):361-371. Epub 2020 Dec 13.

Washington University in St Louis, Saint Louis, MO.

Background: Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA.

Study Design: Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis.

Results: Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001).

Conclusions: Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.
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http://dx.doi.org/10.1016/j.jamcollsurg.2020.11.017DOI Listing
April 2021

Posttransplant Outcomes in Older Patients With Hepatocellular Carcinoma Are Driven by Non-Hepatocellular Carcinoma Factors.

Liver Transpl 2020 Dec 11. Epub 2020 Dec 11.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.
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http://dx.doi.org/10.1002/lt.25974DOI Listing
December 2020

Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.

J Hepatol 2021 Apr 23;74(4):881-892. Epub 2020 Sep 23.

Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA.

Background & Aims: Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. Previously we reported that the liver graft assessment following transplantation (L-GrAFT) risk score was superior to binary EAD or the model for early allograft function (MEAF) score for estimating 3-month graft failure-free survival in a single-center derivation cohort. Herein, we sought to externally validate L-GrAFT, and compare its prognostic performance to EAD and MEAF.

Methods: Accuracies of L-GrAFT, EAD, and MEAF were compared in a 3-center US validation cohort (n = 3,201), and a Consortium for Organ Preservation in Europe (COPE) normothermic machine perfusion (NMP) trial cohort (n = 222); characteristics were compared to assess generalizability.

Results: Compared to the derivation cohort, patients in the validation and NMP trial cohort had lower recipient median MELD scores; were less likely to require pretransplant hospitalization, renal replacement therapy or mechanical ventilation; and had superior 1-year overall (90% and 95% vs. 84%) and graft failure-free (88% and 93% vs. 81%) survival, with a lower incidence of 3-month graft failure (7.4% and 4.0% vs. 11.1%; p <0.001 for all comparisons). Despite significant differences in cohort characteristics, L-GrAFT maintained an excellent validation AUROC of 0.78, significantly superior to binary EAD (AUROC 0.68, p = 0.001) and MEAF scores (AUROC 0.72, p <0.001). In post hoc analysis of the COPE NMP trial, the highest tertile of L-GrAFT was significantly associated with time to liver allograft (hazard ratio [HR] 2.17, p = 0.016), Clavien ≥IIIB (HR 2.60, p = 0.034) and ≥IVa (HR 4.99, p = 0.011) complications; post-LT length of hospitalization (p = 0.002); and renal replacement therapy (odds ratio 3.62, p = 0.016).

Conclusions: We have validated the L-GrAFT risk score as a generalizable, highly accurate, individualized risk assessment of 3-month liver allograft failure that is superior to existing scores. L-GrAFT may standardize grading of early hepatic allograft function and serve as a clinical endpoint in translational studies (www.lgraft.com).

Lay Summary: Early allograft dysfunction negatively affects outcomes following liver transplantation. In independent multicenter US and European cohorts totaling 3,423 patients undergoing liver transplantation, the liver graft assessment following transplantation (L-GrAFT) risk score is validated as a superior measure of early allograft function that accurately discriminates 3-month graft failure-free survival and post-liver transplantation complications.
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http://dx.doi.org/10.1016/j.jhep.2020.09.015DOI Listing
April 2021

Feasibility and safety of non-operative management of portal vein aneurysms: a thirty-five year experience.

HPB (Oxford) 2021 Jan 16;23(1):127-133. Epub 2020 Jun 16.

Department of Abdominal Organ Transplantation Surgery, Washington University School of Medicine, St Louis, MO, USA. Electronic address:

Background: Portal vein aneurysms (PVAs) are rare, though clinically challenging with post-operative mortality approaching 20% and no evidence-based treatment guidelines. We aim to describe our experience with PVAs and recommend optimum management strategies.

Methods: Demographics and clinical details of patients with PVAs admitted to our institution from 1984 to 2019 were reviewed. Clinical presentation, management and outcomes were analysed.

Results: PVAs were identified in 18 patients (median age 56 years, range 20-101 years; 13 female); 10 were incidental and 8 diagnosed during abdominal pain work-up. Median aneurysm diameter at diagnosis was 3.4 cm (1.8-5.5 cm), remaining unchanged at 3.5 cm (1.9-4.8 cm) during a 3.2-year follow-up (4 months-31 years). Aneurysm sites were the main portal vein (n = 12), porto-splenic-junction (n = 3), splenic-SMV-junction (n = 2) and right portal vein (n = 1). Thrombosis occurred in 4 patients; 3 developed clinically insignificant cavernous transformation. Two patients underwent surgery for abdominal pain. Postoperatively, one developed PV thrombosis and PVA recurrence occurred in the second. No aneurysm ruptures or mortalities occurred during follow-up.

Conclusion: PVAs follow a clinically indolent course with structural stability and minimal complications over time. Non-operative management is feasible for most patients. Abdominal pain, large size or thrombosis don't appear to confer additional risks and should not, in isolation, merit surgical intervention.
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http://dx.doi.org/10.1016/j.hpb.2020.05.006DOI Listing
January 2021

Incisional hernia after liver transplantation: Risk factors, management strategies and long-term outcomes of a cohort study.

Int J Surg 2020 Jun 23;78:149-153. Epub 2020 Apr 23.

Division of Transplantation, Department of Surgery, Washington University in St Louis, USA.

Introduction: Incisional hernias (IH) develop in up to 40% of liver transplant (LT) recipients and can contribute to considerable morbidity.

Materials And Methods: A single center retrospective review of a prospectively maintained LT database was conducted to identify all patients diagnosed with IH after LT during a 13-year study period (2003-2015). Analyzed data included patient demographics, LT details, incidence and timing of IH, risk factors, management strategies and long-term outcomes.

Results: During the 13-year study period, IH was diagnosed in 16.7% (163/976) of LT recipients after a median of 19.6 months (range 6.7-49.5 months) from transplant surgery. Identified risk factors for developing IH included male gender (p < 0.001) while acute cellular rejection (ACR) was found to be negatively associated with the risk of developing IH (p = 0.014). Acute incarceration/strangulation was seen in 4 patients with IH while the remaining (n = 159) presented with non-emergent symptoms. Surgical repair was undertaken in 70/163 (43%) IH patients after medical optimization when possible (open repair 83%, mesh use 90%). IH recurrence rate was 14.3% (10/70) with comparable rates in no-mesh and with-mesh repairs (42.9% vs. 11.3%; p = 0.057) and open (15.8%) and laparoscopic (9.1%) approaches (p = 0.68).

Conclusion: IH is a late complication following LT and male gender is a consistent predictive marker. Acute presentation is infrequent and elective repair can be planned in most patients allowing for risk factor optimization to ensure promising long-term outcomes.
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http://dx.doi.org/10.1016/j.ijsu.2020.04.048DOI Listing
June 2020

Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria.

Hepatology 2020 12;72(6):2014-2028

Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Background And Aims: The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013).

Approach And Results: Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001).

Conclusions: In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.
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http://dx.doi.org/10.1002/hep.31210DOI Listing
December 2020

Liver transplantation for hepatitis C patients in the era of direct-acting antiviral treatment: A retrospective cohort study.

Int J Surg 2020 Mar 1;75:84-90. Epub 2020 Feb 1.

Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA. Electronic address:

Introduction: Direct-acting antivirals (DAA's) have revolutionized hepatitis-C virus (HCV) treatment, however controversy remains regarding timing of treatment in relation to liver-transplant (LT).

Methods: Single-center retrospective study assessing outcomes of listed HCV positive patients in the DAA-era (2014-2017). Patients treated with DAA's before LT (DAA pre-LT) were compared to those who were not treated before LT (No DAA pre-LT) RESULTS: 156 HCV positive patients were listed during study-period; 104 (67%) underwent LT while 52 (33%) were de-listed. Of transplanted patients, 48 (46%) received DAA pre-LT while 56 (54%) were treated post-LT. Both groups were comparable in age, gender, MELD, patient and graft survival and cure-rates (98% in DAA pre-LTvs.95% in No DAA pre-LT; p > 0.05). DAA pre-LT group required higher number of treatments-per-patient to clear virus (1.46vs.1.06; p = 0.0006), spent more time on waitlist (331d.vs150d; p = 0.0040) and were less likely to receive livers from HCV positive donors (6%vs.25%; p = 0.0148). Twenty-nine (56%) of the 52 delisted received DAA. They had lower listing-MELD (12vs.18; p = 0.0033), and were more likely to be delisted for "condition improved" (34%vs.4%; p = 0.0143) compared to the 23 (44%) delisted patients who did not receive DAA's.

Conclusions: DAA's were equally effective in clearing HCV in listed patients irrespective of timing. DAA pre-LT can disadvantage some patients through increase number of treatments needed and longer waitlist times, but treatment in some listed patients with low-MELD can improve condition and alleviate need for LT.
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http://dx.doi.org/10.1016/j.ijsu.2020.01.145DOI Listing
March 2020

Liver transplantation for hepatocellular carcinoma after successful treatment of macrovascular invasion - a multi-center retrospective cohort study.

Transpl Int 2020 05 20;33(5):567-575. Epub 2020 Feb 20.

Division of Transplantation, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.

Macrovascular invasion is considered a contraindication to liver transplantation for hepatocellular carcinoma (HCC) due to a high risk of recurrence. The aim of the present multicenter study was to explore the outcome of HCC patients transplanted after a complete radiological regression of the vascular invasion by locoregional therapies and define sub-groups with better outcomes. Medical records of 45 patients were retrospectively reviewed, and imaging was centrally assessed by an expert liver radiologist. In the 30 patients with validated diagnosis of macrovascular invasion, overall survival was 60% at 5 years. Pretransplant alpha-fetoprotein (AFP) value was significantly different between patients with and without recurrence (P = 0.019), and the optimal AFP cutoff was 10ng/ml (area under curve = 0.78). Recurrence rate was 11% in patients with pretransplant AFP < 10ng/ml. The number of viable nodules (P = 0.008), the presence of residual HCC (P = 0.036), and satellite nodules (P = 0.001) on the explant were also significantly different between patients with and without recurrence. Selected HCC patients with radiological signs of vascular invasion could be considered for transplantation, provided that they previously underwent successful treatment of the macrovascular invasion resulting in a pretransplant AFP < 10 ng/ml. Their expected risk of post-transplant HCC recurrence is 11%, and further prospective validation is needed.
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http://dx.doi.org/10.1111/tri.13586DOI Listing
May 2020

Assessment of Hepatic Arterial Infusion of Floxuridine in Combination With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial.

JAMA Oncol 2019 Oct 31. Epub 2019 Oct 31.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: Unresectable intrahepatic cholangiocarcinoma (IHC) carries a poor prognosis, with a median overall survival (OS) of 11 months. Hepatic arterial infusion (HAI) of high-dose chemotherapy may have potential benefit in these patients.

Objective: To evaluate clinical outcomes when HAI chemotherapy is combined with systemic chemotherapy in patients with unresectable IHC.

Design, Setting, And Participants: A single-institution, phase 2 clinical trial including 38 patients was conducted with HAI floxuridine plus systemic gemcitabine and oxaliplatin in patients with unresectable IHC at Memorial Sloan Kettering Cancer Center between May 20, 2013, and June 27, 2019. A confirmatory phase 1/2 study using the same therapy was conducted during the same time period at Washington University in St Louis. Patients with histologically confirmed, unresectable IHC were eligible. Resectable metastatic disease to regional lymph nodes and prior systemic therapy were permitted. Patients with distant metastatic disease were excluded.

Interventions: Hepatic arterial infusion of floxuridine and systemic administration of gemcitabine and oxaliplatin.

Main Outcomes And Measures: The primary outcome was progression-free survival (PFS) of 80% at 6 months.

Results: For the phase 2 clinical trial at Memorial Sloan Kettering Cancer Center, 42 patients with unresectable IHC were included and, of these, 38 patients were treated (13 [34%] men; median [range] age at diagnosis, 64 [39-81] years). The median follow-up was 30.5 months. Twenty-two patients (58%) achieved a partial radiographic response, and 32 patients (84%) achieved disease control at 6 months. Four patients had sufficient response to undergo resection, and 1 patient had a complete pathologic response. The median PFS was 11.8 months (1-sided 90% CI, 11.1) with a 6-month PFS rate of 84.1% (90% CI, 74.8%-infinity), thereby meeting the primary end point (6-month PFS rate, 80%). The median OS was 25.0 months (95% CI, 20.6-not reached), and the 1-year OS rate was 89.5% (95% CI, 80.2%-99.8%). Patients with resectable regional lymph nodes (18 [47%]) showed no difference in OS compared with patients with node-negative disease (24-month OS: lymph node negative: 60%; 95% CI, 40%-91% vs lymph node positive: 50%; 95% CI, 30%-83%; P = .66). Four patients (11%) had grade 4 toxic effects requiring removal from the study (1 portal hypertension, 2 gastroduodenal artery aneurysms, 1 infection in the pump pocket). Subgroup analysis showed significant improvement in survival in patients with IDH1/2 mutated tumors (2-year OS, 90%; 95% CI, 73%-99%) vs wild-type (2-year OS, 33%; 95% CI, 18%-63%) (P = .01). In the Washington University in St Louis confirmatory cohort, 9 patients (90%) achieved disease control at 6 months; the most common grade 3 toxic effect was elevated results of liver function tests, and median PFS was 12.8 months (1-sided 90% CI, 6.4).

Conclusions And Relevance: Hepatic arterial infusion plus systemic chemotherapy appears to be highly active and tolerable in patients with unresectable IHC; further evaluation is warranted.
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http://dx.doi.org/10.1001/jamaoncol.2019.3718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824231PMC
October 2019

Organ Procurement Organization Run Department of Motor Vehicle Registration and Drivers Licensing Offices Leads to Increased Organ Donor First Person Authorization Registrations.

Transplantation 2020 02;104(2):343-348

Department of Surgery, Division of Abdominal Organ Transplantation, Washington University in St. Louis School of Medicine, Saint Louis, MO.

Background: More people who have personally consented to organ donation via first person authorization (FPA) registration before death become organ donors than those not personally consenting. The majority of registrations occur at state-specific department of motor vehicle (DMV) and licensing offices, where people register their vehicles and obtain driver's licenses.

Methods: One organ procurement organization (OPO) ran 3 DMV offices and implemented an intervention: a donor-centric approach, including employee education, office decoration with donation materials, and customer experience improvements. Data about registry enrollment was collected before and during the 4-year OPO licensing office contract. A linear mixed model and interrupted time series analyses were performed to evaluate whether the intervention improved rates of registration.

Results: Preintervention registry enrollment rates per month were 10%-50%. Having the offices run by an OPO was associated with more enrollments independent of the increasing trend of enrollment (P < 0.001). Also, the DMV office with the lowest preimplementation registration rates had an immediate increase in enrollments after the intervention leading to higher registration rates (P < 0.001).

Conclusions: A donor-centric OPO-managed DMV experience increases FPA registration, especially at offices with low initial registration rates. However, even at the office with the highest percentage of FPA registrations, rates were only 65% at intervention conclusion. The transplant community should consider other opportunities for FPA registration.
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http://dx.doi.org/10.1097/TP.0000000000002842DOI Listing
February 2020

Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma: Analysis From the US Multicenter HCC Transplant Consortium.

Ann Surg 2020 04;271(4):616-624

Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Objective: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT).

Background: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study.

Methods: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression.

Results: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67).

Conclusions: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.
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http://dx.doi.org/10.1097/SLA.0000000000003253DOI Listing
April 2020

Systemic Therapy for Combined Hepatocellular-Cholangiocarcinoma: A Single-Institution Experience.

J Natl Compr Canc Netw 2018 10;16(10):1193-1199

Combined hepatocellular-cholangiocarcinoma tumors (cHCC-CCA) are a heterogeneous group of rare malignancies that have no established optimal treatment. We identified patients with cHCC-CCA treated at a tertiary center and retrospectively examined their histology, interventions, and outcomes. We calculated disease control rate (DCR), disease progression, overall survival, and progression-free survival (PFS) between treatment subgroups. A total of 123 patients were evaluable. Interventions included resection, locoregional therapy, transplant, chemotherapy, and targeted agents. Ultimately, 68 patients received systemic treatment-57 with gemcitabine plus either 5-fluoropyrimidine (5-FU) or a platinum combination. Disease progression was more common in the gemcitabine/5-FU group versus gemcitabine/platinum (=.028), whereas DCR favored gemcitabine/platinum (78.4% vs 38.5%; =.0143). Median PFS from time of initial diagnosis favored the gemcitabine/platinum group, but the difference did not reach statistical significance. Targeted agents had minimal to no effect on survival metrics. Gemcitabine/platinum seems to be a superior regimen for patients with cHCC-CCA who require systemic treatment. Further studies are needed to clarify the regimen's efficacy and applicability in patient subgroups.
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http://dx.doi.org/10.6004/jnccn.2018.7053DOI Listing
October 2018

Organ procurement center allows for daytime liver transplantation with less resource utilization: May address burnout, pipeline, and safety for field of transplantation.

Am J Transplant 2019 05 19;19(5):1296-1304. Epub 2018 Oct 19.

Division of Abdominal Organ Transplantation, Department of Surgery, Washington University School of Medicine, Saint Louis, Missouri.

Abdominal organ transplantation faces several challenges: burnout, limited pipeline of future surgeons, changes in liver allocation potentially impacting organ procurement travel, and travel safety. The organ procurement center (OPC) model may be one way to mitigate these issues. Liver transplants from 2009 to 2016 were reviewed. There were 755 liver transplants performed with 525 OPC and 230 in-hospital procurements. The majority of transplants (87.4%) were started during daytime hours (5 am-7 pm). Transplants with any portion occurring after-hours were more likely to have procurements in-hospital (P < .001). Daytime cases (n = 400) had more OPC procured livers and hepatitis C recipients and were less likely to have a donation after circulatory death donor (all P < .05). In adjusted analyses, daytime cases were independently associated with extubation in the operating room and less postoperative transfusion. There were no significant differences in short- or long-term postoperative outcomes. For exported livers, 54.3% were procured by a local team, saving 137 flights (151 559 miles). The OPC resulted in optimally timed liver transplants and decreased resource utilization with no negative impact on patient outcomes. It allows for ease in exporting organs procured by local surgeons, and potentially addresses provider burnout, the transplant surgery pipeline, and surgeon travel.
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http://dx.doi.org/10.1111/ajt.15129DOI Listing
May 2019

Mini-incision versus hand-assisted laparoscopic donor nephrectomy in living-donor kidney transplantation: A retrospective cohort study.

Int J Surg 2018 May 11;53:339-344. Epub 2018 Apr 11.

Transplant Outcomes Research, Department of General Surgery, Section of Abdominal Organ Transplant, Washington University in Saint Louis, 660 S. Euclid Ave, Campus Box 8109, Saint Louis, MO, 63110, United States. Electronic address:

Background: Increasing use of Living Donor Kidney Transplantation (LDKT) would decrease the discrepancy between patients awaiting transplantation and organ availability. Minimally invasive surgical approaches attempt to improve outcomes and foster living donation. This report compares outcomes of open minimal incision nephrectomy (Mini N) and a hand assisted laparoscopic nephrectomy (HALN).

Methods: This is a retrospective analysis of a prospectively maintained clinical database of LDKT using HALN or Mini N at a single institution between July 2007 and December 2015. Donor and recipient demographics, relevant pre-, intra- and post-operative factors, outcomes such as patient and graft survival rates, and complications were evaluated.

Results: Four hundred and fifty-four adult LDKT (243 Mini N, 211 HALN) were performed during the study period. Recipient and donor demographics were comparable except for higher BMI (p = 0.027) in HALN donors. One-, 3- and 5-year patient and graft survival rates were comparable. Six HALN donors experienced infectious wound complications or superficial skin dehiscence; none did in the Mini N group (p = 0.009). Eight HALN donors and one Mini N donor required an incisional hernia repair (p = 0.014). Recipients had similar warm ischemia times (33 v. 35 min, p = 0.491), but recipient surgeons of HALN nephrectomies subjectively noted higher anastomotic difficulty (10.4% v. 4.5%, p = 0.0183). Other parameters were similar between groups.

Conclusion: Both Mini N and HALN provide similar long term recipient and donor outcomes. Offering techniques such as Mini N and HALN for living donor kidney procurement facilitates the opportunity to provide living donors safer and better tolerated nephrectomy procedures.
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http://dx.doi.org/10.1016/j.ijsu.2018.04.003DOI Listing
May 2018

Cost Evaluation of a Donation after Cardiac Death Program: How Cost per Organ Compares to Other Donor Types.

J Am Coll Surg 2018 05 2;226(5):909-916. Epub 2018 Mar 2.

Department of Surgery, Division of Abdominal Organ Transplantation, Washington University School of Medicine, St Louis, MO. Electronic address:

Background: Donation after cardiac death (DCD) is one method of organ donation. Nationally, more than half of evaluated DCD donors do not yield transplantable organs. There is no algorithm for predicting which DCD donors will be appropriate for organ procurement. Donation after cardiac death program costs from an organ procurement organization (OPO) accounting for all evaluated donors have not been reported.

Study Design: Hospital, transportation, and supply costs of potential DCD donors evaluated at a single OPO from January 2009 to June 2016 were collected. Mean costs per donor and per organ were calculated. Cost of DCD donors that did not yield a transplantable organ were included in cost analyses resulting in total cost of the DCD program. Donation after cardiac death donor costs were compared with costs of in-hospital donation after brain death (DBD) donors.

Results: There were 289 organs transplanted from 264 DCD donors evaluated. Mean cost per DCD donor yielding transplantable organs was $9,306. However, 127 donors yielded no organs, at a mean cost of $8,794 per donor. The total cost of the DCD program was $32,020 per donor and $15,179 per organ. Mean cost for an in-hospital DBD donor was $33,546 and $9,478 per organ transplanted. Mean organ yield for DBD donors was 3.54 vs 2.21 for DCD donors (p < 0.0001), making the cost per DBD organ 63% of the cost of a DCD organ.

Conclusions: Mean cost per DCD donor is comparable with DBD donors, however, individual cost of DCD organs increases by almost 40% when all costs of an entire DCD program are included.
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http://dx.doi.org/10.1016/j.jamcollsurg.2018.02.005DOI Listing
May 2018

Patient and Graft Survival: Biliary Complications after Liver Transplantation.

J Am Coll Surg 2018 04 31;226(4):484-494. Epub 2018 Jan 31.

Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO. Electronic address:

Background: Biliary complications (BCs) affect up to to 34% of liver transplant recipients and are a major source of morbidity and cost. This is a 13-year review of BCs after liver transplantation (LT) at a tertiary care center.

Study Design: We conducted a single-center retrospective review of our prospective database to assess BCs in adult (aged 18 years or older) liver transplant recipients during a 13-year period (2002 to 2014). Biliary complications were divided into 3 subgroups: leak alone (L), stricture alone (S), and both leak and strictures (LS). Controls (no BCs) were used for comparison.

Results: There were 1,041 adult LTs performed during the study period; BCs developed in 239 (23%) of these patients: 55 (23%) L, 148 (62%) S, and 36 (15%) LS. One hundred and two (43%) were early (less than 30 d). Surgical revision was required in 42 cases (17%) (30 L, 10 LS, and 2 S), while the remaining 197 (83%) were managed nonsurgically (25 L, 26 LS, and 146 S), with a mean of 4.2 interventions/patient. One-, 3-, and 5-year overall patient and graft survival was significantly reduced in patients with bile leaks (84%, 71%, and 68% and 76%, 67%, and 64%, respectively) compared with controls (90%, 84%, and 78% and 88%, 81%, and 76%, respectively [p < 0.05]). Patients with BCs had higher incidence of cholestatic liver disease, higher pre-LT bilirubin, higher use of T-tubes, higher use of donor after cardiac death grafts, and higher rates of acute rejection (p < 0.05). Patients with BCs had longer ICU and hospital stays and higher rates of 30- and 90-day readmissions (p < 0.01). Multivariate analysis identified cholestatic liver disease, Roux-en-Y anastomosis, donor risk index >2, and T-tubes as independent BC predictors.

Conclusions: Biliary complications after LT can significantly decrease patient and graft survival rates. Careful donor and recipient selection and attention to anastomotic technique can reduce BCs and improve outcomes.
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http://dx.doi.org/10.1016/j.jamcollsurg.2017.12.039DOI Listing
April 2018

Serum alpha-fetoprotein level per total tumor volume as a predictor of recurrence of hepatocellular carcinoma after resection.

Surgery 2018 05 25;163(5):1002-1007. Epub 2017 Dec 25.

Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

Background: Alpha-fetoprotein has been used as a predictor of recurrence for hepatocellular carcinoma and disease-free survival post-resection. Studies in East Asia have shown that serum alpha-fetoprotein per total tumor volume ratio is a better prognostic indicator than alpha-fetoprotein alone. Similar studies in the United States evaluating serum alpha-fetoprotein to total tumor volume ratio have not been conducted. Its relevance is incompletely understood.

Methods: Consecutive patients undergoing resection for hepatocellular carcinoma at a single tertiary center between 2000 and 2013 were identified for inclusion in this retrospective cohort study. Patient demographics, associated liver disease, Child-Pugh and Model for End-Stage Liver Disease scores, preoperative imaging, surgical pathology, alpha-fetoprotein at diagnosis, last alpha-fetoprotein before surgery, and peak alpha-fetoprotein levels were recorded. Actual tumor volume by imaging volumetrics was used when available (n = 70). For the remaining cases, total tumor volume was calculated using the sum of the volumes of all the tumors ((4/3)πr) where "r" is the mean radius of each lesion. Peak serum alpha-fetoprotein was used to calculate the alpha-fetoprotein to total tumor volume ratio.

Results: A total of 124 patients resected for hepatocellular carcinoma between 2000 and 2013 were identified. Overall 1-, 3-, and 5-year survival post resection was 76%, 53%, and 35%, respectively. On multivariate analysis, peak alpha-fetoprotein to total tumor volume ratio > 20 (P < .001, HR = 3.72, 95% CI [1.82-7.58]) and lymphovascular space invasion (P = .002, HR = 3.30, 95% CI [1.57-6.94]) were found to affect hepatocellular carcinoma recurrence-free survival.

Conclusion: A variety of prognostic values predict the recurrence of hepatocellular carcinoma postresection. Peak preoperative alpha-fetoprotein to total tumor volume > 20 and lymphovascular space invasion has been shown to predict recurrence of hepatocellular carcinoma. Our study confirms findings from East Asian studies. But larger series are needed to establish this correlation in patients with hepatocellular carcinoma not treated by resection.
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http://dx.doi.org/10.1016/j.surg.2017.10.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853279PMC
May 2018

Long-term outcome of upper extremity arteriovenous fistula using pSLOT: single-center longitudinal follow-up using a protocol-based approach.

J Vasc Access 2017 Nov 29;18(6):515-521. Epub 2017 Jul 29.

Washington University in St. Louis School of Medicine, St. Louis, MO - USA.

Introduction: Functional arteriovenous fistula (AVF) is the best vascular access for end-stage renal disease patients. AVF maturation is variable and many require additional interventions to achieve functionality. Long-term benefits of such interventions are unclear. Using a protocol for AVF planning, creation, maturation evaluation and performing interventions based on objective findings along with maintaining a database on follow-up is necessary to evaluate this question.The aim of this study is to evaluate the long-term outcome of newly constructed AVFs using a protocol-based approach in a tertiary care academic center.

Methods: This is an observational study. Long-term outcomes of consecutive AVFs placed over a 5-year period using a protocol for creation, maturation evaluation and interventions based on objective findings were analyzed using a prospectively maintained clinical database.

Results: Functioning AVFs were achieved in 86.5% (n = 296) of 342 patients. Primary and secondary patency of 372 AVF procedures at 12, 24 and 60 months were 42.8%, 31.6% and 20.8%; and 81.8%, 77.6% and 71.7%, respectively. Functional patency at 12, 24 and 60 months were 95.1%, 88.7%, and 85.2%, respectively. Long-term function was similar for AVFs maturing with ≤4 interventions and without interventions. AVFs maturing with 2-4 interventions needed significantly more interventions to maintain long-term functional patency (p = 0.003).

Conclusions: Piggyback straight-line on-lay technique (pSLOT) improves early outcome providing opportunity to identify other problems contributing to non-maturation. A large number of AVFs needing planned interventions to mature provide good long-term function. Establishing process of care guidelines for creation and follow-up has a potential to improve AVF outcome.
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http://dx.doi.org/10.5301/jva.5000764DOI Listing
November 2017

The influence of functional warm ischemia time on DCD liver transplant recipients' outcomes.

Clin Transplant 2017 Oct 29;31(10). Epub 2017 Aug 29.

Division of Transplantation, University of Rochester, Rochester, NY, USA.

Background: Duration of functional warm ischemia (f-WIT) is thought to have a causal effect on outcomes in controlled donation after circulatory death (DCD) liver transplantation (LT).

Methods: A retrospective cohort study was conducted at five centers. Data were extracted on donor and recipient characteristics, with attention to parameters recorded during withdrawal of life support to in situ cold perfusion. F-WIT was the time elapsed from any of the hemodynamic and oxygenation parameters to the start of in situ cold perfusion. Parameters were as follows: MAP ≤ 50 mm Hg; SBP ≤ 50 mm Hg; and SPO2 ≤ 60%. The primary endpoint was a composite of disseminated ischemic cholangiopathy (IC), primary non-function (PNF), and early graft failure.

Results: 35 patients (14%) developed one or more of the primary outcomes. On univariate analysis, older donors and longer WITs were associated with greater likelihood of complications. Of the f-WIT variations analyzed, only f-WIT with SpO2 ≤ 60% was longer among patients with complications. On multivariate analysis, only donor age was a significant predictor of complications.

Conclusion: This study demonstrates that, of the f-WITs, f-WIT with SpO2 ≤ 60% is most predictive of post-DCD complications. However, results suggest that there may be an alternate etiology for poor outcomes, and that donor age plays a key role.
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http://dx.doi.org/10.1111/ctr.13068DOI Listing
October 2017

Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients From the US Multicenter HCC Transplant Consortium.

Ann Surg 2017 09;266(3):525-535

*Dumont-UCLA Liver Transplant and Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA †Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX ‡Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY §Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA ¶Department of Transplantation, Mayo Clinic, Jacksonville, FL ||New York Presbyterian Hospital, Columbia University, New York, NY **New York Presbyterian Hospital, Weill Cornell, New York, NY ††Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA ‡‡Cleveland Clinic Foundation, Cleveland, OH §§Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, MO ¶¶Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA ||||Department of Surgery, Stanford University, Palo Alto, CA ***Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Denver, CO †††Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, TX ‡‡‡Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA §§§Department of Surgery, University of Nebraska Medical Center, Omaha, NE ¶¶¶Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of California, San Diego, San Diego, CA ||||||Department of Surgery, Duke University Medical Center; Durham, NC ****Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI ††††Department of Surgery, Baylor College of Medicine, Houston, TX ‡‡‡‡Section of Hepatobiliary and Transplant Surgery, University of Louisville School of Medicine, Louisville, KY §§§§Medstar Georgetown Transplant Institute, Georgetown University, Washington, District of Columbia.

Objective: To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC).

Summary Background Data: Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited.

Methods: Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013).

Results: Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044).

Conclusions: Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.
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http://dx.doi.org/10.1097/SLA.0000000000002381DOI Listing
September 2017

Prediction of Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Resection: Validation of a Clinical Risk Score in an International Cohort.

Ann Surg 2017 10;266(4):693-701

*Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY †Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY ‡Department of Surgery, Washington University School of Medicine, St. Louis, MO §Department of Surgery, Université de Montréal, Montreal, Quebec, Canada ¶Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands ||Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore **Division of Surgical Oncology, National Cancer Center, Singapore, Singapore.

Objective: This study aims to validate a previously reported recurrence clinical risk score (CRS).

Summary Of Background Data: Salvage transplantation after hepatocellular carcinoma (HCC) resection is limited to patients who recur within Milan criteria (MC). Predicting recurrence patterns may guide treatment recommendations.

Methods: An international, multicenter cohort of R0 resected HCC patients were categorized by MC status at presentation. CRS was calculated by assigning 1 point each for initial disease beyond MC, multinodularity, and microvascular invasion. Recurrence incidences were estimated using competing risks methodology, and conditional recurrence probabilities were estimated using the Bayes theorem.

Results: From 1992 to 2015, 1023 patients were identified, of whom 613 (60%) recurred at a median follow-up of 50 months. CRS was well validated in that all 3 factors remained independent predictors of recurrence beyond MC (hazard ratio 1.5-2.1, all P < 0.001) and accurately stratified recurrence risk beyond MC, ranging from 19% (CRS 0) to 67% (CRS 3) at 5 years. Among patients with CRS 0, no other factors were significantly associated with recurrence beyond MC. The majority recurred within 2 years. After 2 years of recurrence-free survival, the cumulative risk of recurrence beyond MC within the next 5 years for all patients was 14%. This risk was 12% for patients with initial disease within MC and 17% for patients with initial disease beyond MC.

Conclusions: CRS accurately predicted HCC recurrence beyond MC in this international validation. Although the risk of recurrence beyond MC decreased over time, it never reached zero.
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http://dx.doi.org/10.1097/SLA.0000000000002360DOI Listing
October 2017

Development of immune response to tissue-restricted self-antigens in simultaneous kidney-pancreas transplant recipients with acute rejection.

Clin Transplant 2017 08 21;31(8). Epub 2017 Jun 21.

Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.

Simultaneous kidney-pancreas transplantation (SKP Tx) is a treatment for end-stage kidney disease secondary to diabetes mellitus. We investigated the role of immune responses to donor human leukocyte antigens (HLA) and tissue-restricted kidney and pancreas self-antigens (KSAgs and PSAgs, respectively) in SKP Tx recipients (SKP TxRs). Sera collected from 39 SKP TxRs were used to determine de novo Abs specific for KSAgs (collagen-IV, Col-IV; fibronectin, FN) and PSAgs (insulin, islet cells, glutamic acid decarboxylase, and pancreas-associated protein-1) by ELISA. KSAg-specific IFN-γ, IL-17, and IL-10 cytokines were enumerated by ELISpot. Abs to donor HLA classes I and II were determined by Luminex assay. Abs to KSAgs and PSAgs were detectable in recipients with rejection compared with stable recipients (P<.05). Kidney-only rejection recipients had increased Abs against KSAgs compared with stable (P<.05), with no increase in Abs against PSAgs. Pancreas-only rejection recipients showed increased Abs against PSAgs compared to stable (P<.05), with no Abs against KSAgs. SKP TxRs with rejection showed increased frequencies of KSAg-specific IFN-γ and IL-17 with reduction in IL-10-secreting cells. SKP TxRs with rejection developed Abs to KSAgs and PSAgs demonstrated increased frequencies of kidney or pancreas SAg-specific IFN-γ and IL-17-secreting cells with reduced IL-10, suggesting loss of peripheral tolerance to SAgs.
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http://dx.doi.org/10.1111/ctr.13009DOI Listing
August 2017

Neoadjuvant Locoregional Therapy and Recurrent Hepatocellular Carcinoma after Liver Transplantation.

J Am Coll Surg 2017 Jul 9;225(1):28-40. Epub 2017 Apr 9.

Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St Louis, MO. Electronic address:

Background: Neoadjuvant locoregional therapies (LRTs) have been widely used to reduce tumor burden or to downstage hepatocellular carcinoma (HCC) before orthotopic liver transplantation (OLT). We examined the impact of LRT response on HCC recurrence after OLT.

Study Design: We performed a retrospective study of 384 patients with HCC treated by OLT. Tumor necrosis was determined by pathologic evaluation. The vascular and lymphatic vessels were localized by immunofluorescence staining in formalin-fixed, paraffin-embedded tissue; expressions of vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 were analyzed by Western blot. Plasma vascular endothelial growth factor (VEGF)-A and VEGF-C levels of a consecutive cohort of 171 HCC patients were detected by ELISA.

Results: Of the 384 patients with HCC, 268 had undergone pretransplantation neoadjuvant LRTs. Patients with no tumor necrosis (n = 58; 5.2% recurrence) or complete tumor necrosis (n = 70; 6.1% recurrence) had significantly lower 5-year recurrence rates than those with partial tumor necrosis (n = 140; 22.6% recurrence; p < 0.001). Lymphatic metastases were significantly more numerous in patients with partial tumor necrosis than in those without tumor necrosis after OLT (p < 0.001). With immunofluorescence staining of peritumor zone, lymphatics were visualized around partially necrotic tumors, but not around tumors without necrosis. Plasma levels of VEGF-A and VEGF-C were elevated significantly in patients with evidence of tumor necrosis (n = 102) compared with those without necrosis (n = 69; p < 0.001). By Western blot, VEGFR-2 and VEGFR-3 expression in the peritumoral tissue associated with partially necrotic tumors was significantly higher than in peritumoral tissue of non-necrosis tumors (n = 3/group, p < 0.020 and p < 0.006, respectively).

Conclusions: Locoregional therapy-induced or spontaneous partially necrotic HCC was associated with increased risk of lymphatic metastases compared with tumors with no or complete tumor necrosis. Anti-lymphangiogenic agents with neoadjuvant LRTs can decrease the pattern of lymphatic metastasis after OLT.
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http://dx.doi.org/10.1016/j.jamcollsurg.2017.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777313PMC
July 2017

Liver Transplantation for Malignant Primary Pediatric Hepatic Tumors.

J Am Coll Surg 2017 Jul 20;225(1):103-113. Epub 2017 Feb 20.

Section of Transplant Surgery, Department of Surgery, Washington University, St Louis, MO.

Background: Malignant primary pediatric hepatic tumors (MPPHTs) are rare and account for approximately 1% of all childhood malignancies. In recent years, liver transplantation has emerged as a viable treatment options for select patients with MPPHTs.

Study Design: We performed a single-center retrospective study using a prospective database to compare outcomes of pediatric liver transplant recipients, with and without cancer, between January 2000 and December 2014.

Results: One hundred fifty-three children underwent 173 liver transplantations during the study period. Of these, 21 (12%) children received 23 (13.3%) transplants for unresectable MPPHTs: 16 hepatoblastomas (HBs), 3 embryonal cell sarcomas (ECS), and 2 hepatocellular carcinomas (HCCs). There was no significant difference in 1-, 3-, and 10-year patient and graft survival rates between MPPHT and non-MPPHT patients (95.2%, 81.2%, 81.2%, and 95.2%, 72,2%, 72.2% for MPPHT vs 92.7%, 89.8%, 87.6% and 85.4%, 81.1%, 75% for the non-MPPHT group, respectively) (p > 0.05). Rates of 1-, 5-, and 10-year disease-free survival for MPPHT patients were 76%, 76%, and 76%, respectively. Median age at transplantation for MPPHT patients was 3.1 years (range 58 days to 17 years), median listing time was 81 days, and median wait list time was 15 days. Eight (38%) children had 2 tumors or more and 4 of 16 (25%) HB patients had metastatic disease at presentation. All children received neoadjuvant treatment, with radiographic response in 19 of 21 patients. Presence of metastatic HB at presentation, International Society of Pediatric Oncology Epithelial Liver (SIOPEL) high risk status, and persistently elevated alpha fetoprotein levels after neoadjuvant chemotherapy might be risk factors for tumor recurrence and decreased survival.

Conclusions: Liver transplantation is an excellent option for select patients with unresectable MPPHTs, with outcomes comparable to those after transplantation for nonmalignant causes.
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http://dx.doi.org/10.1016/j.jamcollsurg.2017.02.006DOI Listing
July 2017

Liver Transplantation for Advanced Hepatocellular Carcinoma after Downstaging Without Up-Front Stage Restrictions.

J Am Coll Surg 2017 Apr 6;224(4):610-621. Epub 2017 Jan 6.

Department of Surgery, Washington University School of Medicine, St Louis, MO.

Background: The incidence of hepatocellular carcinoma (HCC) continues to increase dramatically worldwide. Liver transplantation (LT) is now the standard and optimal treatment for patients with HCC in the setting of cirrhosis, but only for tumors within Milan criteria. In patients presenting beyond Milan criteria, locoregional therapy (LRT) can downstage to within Milan criteria for consideration for LT. Although controversial, the current study aims to evaluate the outcomes of LT in patients presenting with advanced-stage HCC who underwent downstaging and compare these outcomes with those of patients who met Milan criteria at presentation.

Study Design: Our protocol does not set a priori limitations as long as HCC is confined to the liver. In this retrospective study between January 1, 2002 and December 31, 2014, we reviewed outcomes associated with 284 patients who presented within Milan criteria and patients who presented with more-advanced stage tumor who were potential transplantation candidates. The patients with advanced disease were then subdivided into those who were within or beyond University of California San Francisco criteria. Imaging, details of LRT, recurrence, and survival were compared between the groups.

Results: Sixty-three of 210 (30%) eligible patients were downstaged and underwent transplantation; 14 additional downstaged and listed patients were withdrawn for the following reasons: death while waiting (n = 4), disease progression (n = 8), development of other malignancy (n = 1), and declined LT (n = 1). Twelve patients underwent resection after downstaging and did not require LT. Survival for patients who were downstaged was similar to those who were within Milan criteria initially. Recurrence of HCC at 5 years was similar between groups (10.9% vs 10.8%; p = 0.84).

Conclusions: Patients with beyond-Milan criteria HCC who are otherwise candidates for LT should undergo aggressive attempts at downstaging without a priori exclusion. This highly selective approach allows for excellent long-term results, similar to patients presenting with earlier-stage disease.
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http://dx.doi.org/10.1016/j.jamcollsurg.2016.12.020DOI Listing
April 2017

Physician-Patient Communication is Associated With Hepatocellular Carcinoma Screening in Chronic Liver Disease Patients.

J Clin Gastroenterol 2017 May/Jun;51(5):454-460

*Department of Surgery, Division of Public Health Sciences †Department of Surgery, Section of Abdominal Transplantation, School of Medicine ‡Division of Biostatistics, School of Medicine, Washington University in St. Louis, MO.

Background: Patients with chronic liver disease are at high risk for developing liver cancer. Factors associated with screening awareness and doctor-patient communication regarding liver cancer were examined.

Study: Four hundred sixty-seven patients with chronic liver disease at a tertiary-care clinic participated in a phone survey regarding awareness of cancer screening, doctor-patient communication, and health behaviors. Medical records were retrospectively reviewed for data on liver disease etiology and dates of liver imaging tests.

Results: Seventy-nine percent of patients reported awareness of liver cancer screening, and 50% reported talking to their doctor about liver cancer. Patients with higher education, abstinence from alcohol, and liver cirrhosis were more likely to be aware of liver cancer screening (P=0.06, 0.005, <0.0001). Whites, patients with higher education, and those with cirrhosis were more likely to talk to their doctor about liver cancer (P=0.006; P=0.09, <0.0001). Awareness of liver cancer screening (79%) was similar to that of colorectal cancer screening (85%), lower than breast cancer screening (91%), and higher than prostate cancer screening (66%). Patients who were aware of liver cancer screening and reported talking to their doctor about liver cancer were significantly more likely to receive consistent liver surveillance (odds ratio, 4.81; 95% confidence interval, 2.62-8.84 and odds ratio, 1.97; 95% confidence interval, 1.19-3.28, respectively).

Conclusions: Our study demonstrates the importance of effective physician communication with chronic liver disease patients on the risks of developing liver cancer and the importance of regular screening, especially among nonwhites and patients with lower education.
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http://dx.doi.org/10.1097/MCG.0000000000000747DOI Listing
April 2019

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria.

Ann Surg 2016 10;264(4):650-8

*Division of Surgical Oncology, Section of Hepatobiliary and Pancreatic Surgery, University of Virginia, Charlottesville, VA †Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO ‡Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX §Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY ||Division of Transplantation and Hepatobiliary Surgery, University of California San Diego, San Diego, CA ¶Department of Surgery, Section of Hepatobiliary and Pancreas Surgery, Mayo Clinic College of Medicine, Rochester, MN.

Objectives: To assess survival after liver resection and transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan criteria.

Background: The role of liver resection and transplantation remains controversial for patients with HCC beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center.

Methods: Patients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival.

Results: Of 608 patients beyond Milan without vascular invasion, 480 (79%) patients underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (P < 0.001). Resection patients had larger tumors [median 9 cm, interquartile range (IQR): 6.5-12.9 cm vs. median 4.1, IQR: 3.4-5.3 cm, P < 0.001]; transplant patients were more likely to have multiple tumors (78% vs 28%, P < 0.001).Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all P < 0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared with propensity-matched liver resection patients (P ≥ 0.176); DFS in this propensity matched cohort was greater after liver transplantation (P ≤ 0.017).

Conclusions: Liver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.
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http://dx.doi.org/10.1097/SLA.0000000000001866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279918PMC
October 2016

Time-to-Surgery and Survival Outcomes in Resectable Colorectal Liver Metastases: A Multi-Institutional Evaluation.

J Am Coll Surg 2016 05 30;222(5):766-79. Epub 2016 Jan 30.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:

Background: Resection of colorectal liver metastases (CRLM) is associated with improved survival; however, the impact of time to resection on survival is unknown. The current multi-institutional study sought to evaluate the influence of time from diagnosis (Dx) to resection (Rx) on survival outcomes among patients with resectable, metachronous CRLM and to compare practice patterns across hospitals.

Study Design: Medical records of patients with ≤4 metachronous CRLM treated with surgery were reviewed and analyzed retrospectively. Time from Dx to Rx was analyzed as a continuous variable and also dichotomized into 2 groups (group 1: Dx to Rx <3 months and group 2: Dx to Rx ≥3 months) for additional analysis. Survival time distributions after resection were estimated using the Kaplan-Meier method. Between-group univariate comparisons were based on the log-rank test and multivariable analysis was done using Cox proportional hazards model.

Results: From 2000 to 2010, six hundred and twenty-six patients were identified. Type of initial referral (p < 0.0001) and use of neoadjuvant (p = 0.04) and/or adjuvant (p < 0.0001) chemotherapy were significantly different among hospitals. Patients treated with neoadjuvant chemotherapy (n = 108) and those with unresectable disease at laparotomy (n = 5) were excluded from final evaluation. Median overall survival and recurrence-free survival were 74 months (range 63.8 to 84.2 months) and 29 months (range 23.9 to 34.1 months), respectively. For the entire cohort, longer time from Dx to Rx was independently associated with shorter overall survival (hazard ratio = 1.12; 95% CI, 1.06-1.18; p < 0.0001), but not recurrence-free survival. Median overall survival for group 1 was 76 months (range 62.0 to 89.2 months) vs 58 months (range 34.3 to 81.7 months) in group 2 (p = 0.10). Among patients with available data pertaining to adjuvant chemotherapy (N = 457; 318 treated and 139 untreated), overall survival (87 months [range 71.2 to 102.8 months] vs 48 months [range 25.3 to 70.7 months]; p <0.0001), and recurrence-free survival (33 months [range 25.3 to 40.7 months] vs 22 months [range 14.5 to 29.5 months]; p = 0.05) were improved significantly.

Conclusions: In select patients undergoing initial resection for CRLM, longer time from Dx to Rx is independently associated with worse overall survival. In addition, despite uniform disease characteristics, practice patterns related to definitely resectable CRLM vary significantly across hospitals.
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http://dx.doi.org/10.1016/j.jamcollsurg.2016.01.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847545PMC
May 2016