Richard M. Ruiz M.D.

Levitsky, J., S. K. Asrani, M. Abecassis, R. Ruiz, L. W. Jennings and G. Klintmalm (2019). “External Validation of a Pre-Transplant Biomarker Model (REVERSE) Predictive of Renal Recovery after Liver Transplantation.” Hepatology Apr 19. [Epub ahead of print].

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In patients with end stage liver disease, the ability to predict recovery of renal function following liver transplantation alone (LTA) remains elusive. However, several important clinical decisions depend on whether renal dysfunction is recoverable after LTA. We used a cohort of patients undergoing LT to independently validate a pre-LT model predictive of post-LTA renal recovery (REVERSE: high osteopontin (OPN) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels, age <57, no diabetes). Serum samples pre-LT and 4-12 weeks post-LTA (n=117) were analyzed for kidney injury proteins from 3 groups of recipients: (1) estimated GFR (eGFR)<30ml/min/1.73m(2) prior to LTA and <30 ml/min/1.73m(2) after LTA (irreversible acute kidney injury = iAKI), (2) eGFR<30ml/min/1.73m(2) prior to LTA and >50 ml/min/1.73m(2) after LTA (reversible AKI = rAKI) (3) eGFR>50 ml/min/1.73m(2) prior to LTA and >50 ml/min/1.73m(2) after LTA (no AKI = nAKI). In patients with elevated pre-LTA serum levels of OPN and TIMP-1, recovery of renal function correlated with decreases in the level of both proteins. At four weeks post-LT (n=77 subset), the largest decline in OPN and TIMP-1 was seen in the rAKI group. Validation of the REVERSE model in this independent dataset had high area under the curve (AUC) (0.78) in predicting full post-LT renal recovery (sensitivity 0.86, specificity 0.6, PPV 0.81, NPV 0.69). Our eGFR findings were confirmed using measured GFR (mGFR). CONCLUSION: The REVERSE model, derived from an initial training set combining novel plasma biomarkers and clinical characteristics, demonstrated excellent external validation performance characteristics in an independent patient cohort using serum samples. Among patients with kidney injury pre-LTA, the predictive ability of this simple tool may prove beneficial in clinical decision-making both prior to and following transplantation.

Alhalel, N., N. O. Francone, A. M. Salazar, S. Primeaux, R. Ruiz, J. C. Caicedo and E. Gordon (2019). “Perceptions of a Culturally Targeted Hispanic Kidney Transplant Program: A Mixed Methods Study.” Clin Transplant Apr 29: e13577. [Epub ahead of print].

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Disproportionately fewer waitlisted Hispanics receive living donor kidney transplants (LDKTs) compared to non-Hispanic whites. Northwestern Medicine’s((R)) culturally targeted Hispanic Kidney Transplant Program (HKTP) is associated with a significant increase in LDKTs among Hispanics. This multi-site study assessed potential kidney recipients’ and donors’ and/or family members’ perceptions of HKTP’s cultural components through semi-structured interviews and validated surveys. Qualitative thematic analysis and descriptive statistics were performed. Thirty-six individuals participated (62% participation rate) comprising 21 potential recipients and 15 potential donors/family (mean age: 51 years, 50% female, 72% preferred Spanish). Participants felt confident about the educational information because a transplant physician delivered the education, and viewed the group format as effective. Participants felt that education sessions addressed myths about transplantation shared by Hispanics. Primary use of Spanish enhanced participants’ understanding of transplantation. While few knew about living donation before attending the HKTP, most were ‘more in favor of’ kidney transplantation (97%) and living donation (97%) afterwards. Few reported learning about the HKTP from outreach staff and suggested leveraging community leaders to promote HKTP awareness. Our findings suggest the HKTP’s cultural components were viewed favorably, and positively influenced perceptions of kidney transplantation and living donation, which may help reduce transplant disparities in Hispanics.

Bayer, J., C. A. Moulton, K. Monden, R. M. Goldstein, G. J. McKenna, G. Testa, R. M. Ruiz, T. L. Anthony, N. Onaca, G. B. Klintmalm and P. T. W. Kim (2018). “The role of multiorgan procurement for abdominal transplant in general surgery resident education.” Am J Surg 216(2): 331-336.

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BACKGROUND: To assess the impact of participation of multiorgan procurement (MP) by general surgery (GS) residents on surgical knowledge and skills, a prospective cohort study of GS residents during transplant surgery rotation was performed. METHODS: Before and after participation in MPs, assessment of knowledge was performed by written pre and post tests and surgical skills by modified Objective Structured Assessment of Technical Skill (OSATS) score. Thirty-nine residents performed 84 MPs. RESULTS: Significant improvement was noted in the written test scores (63.3% vs 76.7%; P < 0.001). Better surgical score was associated with female gender (15.4 vs 13.3, P = <0.01), prior MP experience (16.2 vs 13.7, P = 0.03), and senior level resident (15.1 vs 13.0, P = 0.03). Supraceliac aortic dissection (P = 0.0017) and instrument handling (P = 0.041) improved with more MP operations. CONCLUSIONS: Participation in MP improves residents' knowledge of abdominal anatomy and surgical technique.

Leal-Leyte, P., G. J. McKenna, R. M. Ruiz, T. L. Anthony, G. Saracino, T. Giuliano, G. B. Klintmalm and P. T. Kim (2018). “Eversion Bile Duct Anastomosis: A Safe Alternative for Bile Duct Size Discrepancy in Deceased Donor Liver Transplantation.” Liver Transpl. Apr 10. [Epub ahead of print].

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Introduction: Bile duct size discrepancy in liver transplantation may increase the risk of biliary complications. The aim of this study was to evaluate the safety and outcomes of the eversion bile duct anastomosis technique in deceased donor liver transplantation (DDLT) with duct to duct anastomosis. Methods: A total of 210 patients who received a DDLT with duct to duct anastomosis from 2012 to 2017 were divided into two groups: those who had eversion bile duct anastomosis (N=70) and standard bile duct anastomosis (N=140). Biliary complications rates were compared between the two groups. Results: There was no difference in the cumulative incidence of biliary strictures (P=0.20) and leaks (P=0.17) between the two groups. The biliary complication rate in the eversion group was 14.3% and 11.4% in the standard anastomosis group. All the biliary complications in the eversion group were managed with endoscopic stenting. A severe size mismatch (>/=3:1 ratio) was associated with a significantly higher incidence of biliary strictures (44.4%) compared to 2:1 ratio (8.2%), (P=0.002). Conclusion: The use of the eversion technique is a safe alternative for bile duct discrepancy in deceased donor liver transplantation; however, severe bile duct size mismatch may be a risk factor for biliary strictures with such technique.

Agopian, V. G., M. P. Harlander-Locke, R. M. Ruiz, G. B. Klintmalm, S. Senguttuvan, S. S. Florman, B. Haydel, M. Hoteit, M. H. Levine, D. D. Lee, C. B. Taner, E. C. Verna, K. J. Halazun, R. Abdelmessih, A. D. Tevar, A. Humar, F. Aucejo, W. C. Chapman, N. Vachharajani, M. H. Nguyen, M. L. Melcher, T. L. Nydam, C. Mobley, R. M. Ghobrial, B. Amundsen, J. F. Markmann, A. N. Langnas, C. A. Carney, J. Berumen, A. W. Hemming, D. L. Sudan, J. C. Hong, J. Kim, M. A. Zimmerman, A. Rana, M. L. Kueht, C. M. Jones, T. M. Fishbein and R. W. Busuttil (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 266(3): 525-535.

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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.