Characterization of early recurrences following liver resection by ALPPS and two stage hepatectomy in patients with colorectal liver-metastases and small future liver remnants; a translational substudy of the LIGRO-RCT

Abstract

Background: Associated liver partition and portal vein ligation in staged hepatectomy (ALPPS) is an alternative resection method to portal vein embolization (PVE) in patients with small future liver remnants (FLR) but has been associated with early tumor recurrences. Methods: Twenty-four patients with colorectal liver metastases (CRLM) patients from the randomized multicenter LIGRO trial comparing outcome of ALPPS (n = 13) vs PVE (n = 11) were included in the study. Mutational analyses of the KRAS, NRAS, BRAF, PIC3CA and TP53 genes of the metastases were performed in 21 patients and correlated to early tumor recurrence. Results: Within 12 months, 13 patients experienced recurrences (6 in TSH group and 7 in ALPPS group). Nine of 13 patients with recurrences had mutations in the TP53 gene, while 3 of 8 patients without recurrence carried the same mutation. Only sporadic cases of the other mutations studied were identified. Conclusions: ALPPS did not appear to be associated with higher rate of rapid recurrences than PVE following radical resection of colorectal liver metastases. Mutations in genes associated with negative oncologic outcome after surgical resection most likely play a role for tumor recurrences in these patients.

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

“…This is in keeping with results from the European REBIRTH RCT, which demonstrated a 92.3% vs. 66.6% resection rate following radio-frequency ablation ALPPS and PVE respectively in patients with primary or secondary liver malignancy and insufficient FLR [57]. Furthermore, recurrence in the LIGRO trial after ALPPS was similar to TSH, with 7/13 patients who underwent ALPPS and 6/11 patients who underwent PVE and TSH experiencing recurrence of disease within a year [58].…”

“…Ann. Surg, 2019[54,58,59] . Abbreviations: ALPPS; associating liver partition with portal vein ligation for staged hepatectomy, TSH; two stage hepatectomy…”

How should liver hypertrophy be stimulated? A comparison of upfront associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and portal vein embolization (PVE) with rescue possibility

“…This study has not investigated the ultimate outcome of cancer surgery, survival. However, a small subset of the patients included in the current study have been analysed regarding early recurrence without signs of increased recurrence after ALPPS (23).…”

Liver transplantation versus liver resection for colorectal liver metastasis: a survival benefit analysis in patients stratified according to tumor burden score

“…As long as systemic chemotherapy was the only approved treatment in patients with unresectable CRLM [4], all the efforts by the surgical community have been focused on ways to transform an unresectable metastatic disease into a resectable one. Two-stage hepatectomies gained acceptance because of the benefit over chemotherapy, even if they are hampered by high morbidity, high mortality, and low long-term survival [18][19][20][21][32][33][34]. Moreover, the very definition of resectable disease is related to experience of the individual surgeons and the resources of the Center.…”

“…Recently, it has been showed that patients with unresectable CRLM and extensive liver tumor load have long OS after LT, exceeding the survival outcome of patients with similar tumor load but treated with PVE and LR [15]. Thus, although resectability is clearly related to better outcomes than palliative chemotherapy [16][17][18][19][20][21][22], resectability is first and foremost a technical and anatomical founded parameter rather than an objective biological predictor in patients with high hepatic tumor burden. Hence, there may be a threshold of tumor load for which LR yields acceptable survival so one might hypothesize whether LT could provide survival benefit over LR in a subset of patients with high tumor load.…”