Improving the Safety of ALPPS Procedure: The Optimal Compromise Between Dropout and Mortality Risk. Comment on Schadde E et al Prediction of Mortality After ALPPS Stage-1

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To the Editor:
We read with great interest the article by Schadde et al1 about the short-term outcomes of ALPPS procedures. First of all, the Zurich group have to be congratulated for the great effort to standardize and optimize this technique, to disclose the biological basis of ALPPS-related hypertrophy, and to reduce high operative risks anticipated by preliminary analyses.1–3 The very high mortality rate reported in the first paper (12%) decreased to 8% to 9% in the most recent ones and in the Schadde et al4,5 analysis, but it is still too high in comparison with the 0% to 3% commonly experienced after liver surgery. Similar procedures have to be compared. When considering colorectal liver metastases, the standard reference for staged procedures is the two-stage hepatectomy whose mortality is about 3%.6 The safety of any new surgical technique is the basis for its final acceptance and inclusion in clinical practice.
In this direction works the article by Schadde et al. They analyzed risk factors for post-ALPPS mortality, focusing on data after the stage 1.1 Mortality risk at the second stage was increased 4-fold in patients who met International Study Group of Liver Surgery (ISGLS) criteria for postoperative liver failure after the first resection and 5-fold in those who reached a Model for End-Stage Liver Disease (MELD) score >10. The authors proposed these criteria to exclude patients from the second stage or to postpone it at recovery.
This proposal sounds logical but raises major concerns. De facto, the authors opened the door to a consistent dropout risk: 14% of patients had ISGLS liver failure after the first stage and it is unclear how many patients had MELD score >10. The main atout of ALPPS for colorectal metastases was exactly to avoid the dropout risk of two-stage hepatectomy (10%–30% of patients6) thanks to the accelerated hypertrophy and the very short interval between the 2 stages (7–10 d). In this new scenario, are the advantages of ALPPS still guaranteed?
If the second stage of ALPPS is definitively cancelled, a sort of “functional” dropout occurs. In the authors opinion this is not equivalent to standard “oncologic” dropout of two-stage hepatectomies (almost all the patients excluded from the second stage for disease progression) and is an evident loss of chance for the patients. Further, chemotherapy will be precluded or significantly delayed because of liver dysfunction.
If the second stage of ALPPS is just delayed, the risk of disease progression obviously increases and the actual distance from the standard two-stage hepatectomy shortens. Of note, in the original depiction of portal vein embolization technique, Makuuchi fixed the evaluation of liver hypertrophy 14 days after the portal occlusion.7 The MD Anderson group demonstrated that the liver hypertrophy after portal vein embolization has a peak during the first 21 days, while reaches a plateau without significant volume increase later on.8 The true benefits of ALPPS are early lost if the second stage is postponed. Some authors could argue about the different degree of hypertrophy after the 2 procedures (ALPPS vs portal vein occlusion), but this is still a debated issue.
To avoid dropout, a further approach to multiple bilobar colorectal liver metastases should be considered, the ultrasound-guided parenchyma-sparing one-stage hepatectomy (resection of all nodules in a single procedure).9 It relies on the detachment of metastases from vascular structures if not infiltrated; the partial resection and reconstruction of hepatic veins if marginally infiltrated; the identification of communicating vessels among hepatic veins to maintain an adequate outflow even after major vessels resection. Thanks to these technical features, the need for major hepatectomies and two-stage procedures is minimized.
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