Downstaging Prior to Liver Transplantation for Hepatocellular Carcinoma: Advisable but at the Price of an Increased Risk of Cancer Recurrence – A Retrospective Study

Clinical question Does the original HCC stage have an impact on post-transplant outcome after successful downstaging?

Take-away point 
Despite an increase in post-transplant HCC recurrence in downstaged patients, similar survivals can be achieved to patients who do not require downstaging. Therefore, downstaging should be continued to be performed.

Reference
Toso, Christian et al. “Downstaging Prior to Liver Transplantation for Hepatocellular Carcinoma: Advisable but at the Price of an Increased Risk of Cancer Recurrence - a Retrospective study.(Report).” Transplant International 32.2 (2019): 163–172.

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Study design: Retrospective review

Funding source: Self-funded or unfunded

Setting: Multi-institution 

Figure 1. Disease-free survival according to downstaging based on TTV115/AFP400 (47% versus 80% at 5 years, =0.95).

Summary

Studies have shown that patients with advanced HCC can benefit from transplantation after downstaging, however, most of these studies used Milan criteria as the downstaging goal and most of the patients were marginally outside of Milan criteria. The authors of this retrospective review of a prospectively maintained database of patients from 2 institutions included patients within the total tumor volume (TTV)/alpha fetoprotein (AFP) criteria (TTV <115 cm3 and AFP < 400 ng/mL; included approximately 20% more patients compared to Milan criteria) and those with advanced HCC but who were successfully downstaged to and stable within this criteria for 3 months. 455 patients were listed for transplantation, 286 of whom were transplanted according to the TTV115/AFP400 criteria. 257 of the transplanted patients underwent a locoregional HCC treatment prior to transplantation which included TACE, RFA, alcohol ablation, SIRT, and resection. TACE, RFA, and alcohol ablation were the most commonly performed procedures. 29 patients were successfully downstaged. Downstaged patients demonstrated similar disease-free survivals (DFS, 74% vs. 80% at 5 years, P = 0.949), but a trend to more recurrences (14% vs. 5.8%, P = 0.10) than those always within TTV115/AFP400 criteria. Similarly, patients downstaged to Milan criteria (n = 80) demonstrated similar DFS (76% vs. 86% at 5 years, P = 0.258), but more recurrences (11% vs. 1.7%, P = 0.001) than those always within Milan (n = 177). Of note, patients treated by RFA or microwave ablation versus TACE prior to transplantation showed showed similar DFS (78.9% vs. 77.2% at 5 years, P = 0.74), and similar rates of post-transplant HCC recurrence (4/73, 5.5% vs. 13/164, 7.9%, P = 0.50).

Commentary

This paper suggests that patients with advanced HCC outside of expanded transplant criteria should have hope of achieving similar survival after transplantation compared to patients with lower AFP. The higher risk of recurrence is modest (~11%) and it does not appear that this should impact the decision to offer transplant versus palliation only for advanced HCC patients. Further study will need to be performed to determine which patients would benefit most from downstaging, especially considering the relatively small number of patients who were ultimately downstaged, but these results are promising for those patients for whom downstaging is successful.

Post author: Zagum Bhatti, MD
Assistant Professor
Department of Radiology, Interventional Radiology Division
University of Texas Health Science Center at Houston, Houston, TX
@ZagumBhatti

The Role of Simulation in Boosting the Learning Curve in EVAR Procedures 

Clinical Question
Does the use of simulator training for endovascular procedures, specifically EVAR, improve trainees quantitative and qualitative performance?

Take-away Point

Simulation training has the potential to alter the paradigm with which we teach IR trainees from one of apprenticeship to one that is a hybrid of simulator training and mentor training.

Reference
Vento V, Cercenelli L, Mascoli C, Gallitto E, Ancetti S, Faggioli G, Freyrie A, Marcelli E, Gargiulo M, Stella A. (2018). The Role of Simulation in Boosting the Learning Curve in EVAR Procedures. J of Surg Edu, 75(2), 534-540. Doi:10.1016/j.jsurg.2017.08.013 

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Study Design: Cohort Blinded Study

Funding Source: Self-funded

Setting: Vascular Surgery, Department of Experiment Diagnostic and Specialty Medicine, University of Bologna; Bologna, Italy. 

Figure 4. Overall mean qualitative performance: comparison of total performance score (TPS) between the trainee group (blackline) and the control group (gray line) at t0 and t1.

Summary

Conventional teaching in medicine is through an apprenticeship model however this is outdated and inadequate for training endovascular specialists of the new generation. Simulator training provides an opportunity to teach trainees prior to performing the procedure on a real patient. This study took 10 vascular surgery residents of varying levels and randomized them into two groups: control and trainee. Each group performed 2 simulated EVAR procedures (basic and complex) at time point 0 and again 2 weeks later. The trainee group additionally performed 6 simulated EVAR procedures over the two weeks, all with the Gore Excluder stent graft. Trainees were evaluated on total procedure time (T­P), total fluoroscopy time (TF), total contralateral gate cannulation time (TG), and contrast medium volume (CM). The qualitative evaluation was based on seven performance criteria including: respect for tissue, handling of endovascular material, knowledge of the tools and procedure, planning, performance, and quality of the final product.

The trainee group significant reduced their TP (48 min ± 12 vs 32 ±8), TF (18 min ± 7 vs 11 ± 6) and CM (121 cc ± 37 vs 85 ± 26); TG was not significantly changed. The control group did not significantly change between the pre- and post-sessions. The trainee group also significantly improved their qualitative score (13.3 ± 5.8 vs 25.4 ± 5.3) while the control group did not. This study demonstrates that both junior and senior residents in endovascular fields can benefit from simulator training for EVAR procedures.

Commentary

Simulator training has played a role in training throughout many different professions including pilots and astronauts; this method is translatable to interventional radiology as technology improves and the ability to make real-life simulators develops. Many different departments have simulators for vascular access, be it a chicken with an olive under the skin or an actual mannequin. Advances in technology have now allowed us to create more complex simulators including ones in which real patient information can be input. The use of the simulators has the potential to significantly alter the way IR residents are trained, shifting from an apprenticeship method to one that includes both simulator training and mentor training. Not only is this applicable to EVAR but it can be extrapolated to include ablations, TIPS, vessel selection, aneurysm coiling; the possibilities are endless. Simulator training also affords a better experience for trainee, attending and patient alike if the trainee has improved confidence and skill when performing the procedure. We must, however, also demonstrate that the skills learned in the sim lab translate to those performed in the IR suite.

Post Author:
Nicole A. Keefe, MD
Fellow Physician
Department of Radiology and Medical Imaging
University of Virginia
@NikkiKeefe