Evolution of two-stage hepatectomy: 25 years of modifications and lessons learned.

108P Comparative analysis of two-stage hepatectomy and enhanced one-stage hepatectomy in the setting of bilobar colorectal liver metastases

Of patients with colorectal cancer, 30% to 50% present with liver metastasis at the time of diagnosis or develop metastasis later. Hepatectomy is the primary curative treatment option for patients with colorectal liver metastases (CRLMs). Patients with bilateral, multiple CRLMs and a small estimated tumor free future liver remnant (FLR) present a treatment challenge. These patients may need a two-stage hepatectomy (TSH) in which portal venous ligation (PVL) or portal venous embolization (PVE) is included in the first stage to stimulate hypertrophy of the FLR before final resection. This method generates a 27% to 39% increase in FLR volume in 4 to 8 weeks. The risks in this method are tumor progression during the waiting period and insufficient hypertrophy, making resection impossible in 25% to 38% of the patients preparing to undergo TSH. To increase liver growth rate and volume, which renders more patients resectable in a shorter time, a novel concept of liver resection, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), was described in 2011. However, in the early study 68% of the patients experienced complications and the surgical mortality rate was 12%. A recent, the only multicenter randomized controlled trial (RCT) revealed that compared with the use of TSH, the use of ALPPS for patients with CRLM resulted in a higher resection rate (92%) without a higher 90-day mortality rate (8.3%), a higher rate of severe complication rate (43%) or a lower rate of negative surgical margins in the liver. A previous meta-analysis including 9 retrospective studies showed that TSH for CRLM exhibited lower perioperative morbidity and mortality rates than ALPPS, suggesting the superiority of TSH. On the other hand, in a recent meta-analysis in 2020 including 7 retrospective studies and 1 RCT, compared with TSH, ALPPS for advanced CRLM resulted in superior surgical efficacy with comparable perioperative mortality rate and short-term oncological outcomes, while this was at the cost of increased perioperative minor complications. From a clinical perspective, traditional TSH has been frequently regarded as a preferred treatment modality in earlier studies, and ALPPS was reserved as an alternative, typically after failed PVE or PVL. At present, this paradigm may have changed, as there is growing evidence indicating that the surgical benefits given by ALPPS are at least not inferior to those given by TSH according to recent studies. ALPPS may be feasible for bilobar multiple colorectal liver metastasis. Still, long-term outcomes remain to be elucidated and therefore the role of ALPPS regarding oncological outcome remains uncertain.

Is the one-stage hepatectomy a safe and feasible alternative to the two-stage hepatectomy in the setting of multiple bilobar colorectal liver metastases? A comparative analysis of two pioneering centers

Systemic Chemotherapy and Two-Stage Hepatectomy for Extensive Bilateral Colorectal Liver Metastases: Perioperative Safety and Survival

Feasibility, safety and efficacy of two-stage hepatectomy for bilobar liver metastases of colorectal cancer: a LiverMetSurvey analysis

Efficacy and Safety of Portal Vein Embolization for Two-Stage Hepatectomy in Patients with Colorectal Liver Metastasis

To compare the overall survival (OS) and disease-free survival (DFS) of Tourniquet-ALPPS (T-ALPPS) and conventional two-stage hepatectomy (TSH) in patients with colorectal liver metastases (CRLM). A retrospective study from a prospectively collected database was performed between October 2000 and July 2016. TSH was performed before September 2011, after which time T-ALPPS became the technique of choice. A propensity score matching (PSM) was performed based on a 1:1 ratio with consideration of the following variables: number and size of metastases, bilobar disease presence, and chemotherapy received. Thirty-four patients received T-ALPPS; 41 patients received TSH. After PSM, 21 patients remained in each group, with 100% resectability in the T-ALPPS group and 90.5% resectability in the TSH group. The median OS for TSH was 41months; for T-ALPPS, the median OS was 36months (P = 0.925). The median DFS was 16months in the TSH group; the median DFS was 9months in the T-ALPPS group (P = 0.930). The 1-, 3-, and 5-year OS for TSH was 81%, 66.7%, and 23.8% vs. 76.2%, 57.1%, and 22.9% for T-ALPPS, respectively. The 1-, 3-, and 5-year DFS for TSH was 66.7%, 9.5%, and 5% vs. 44.6%, 11.1%, and 11.1% for T-ALPPS, respectively. The volume increase with T-ALPPS was superior to that with TSH (68% vs. 39%; P = 0.018). There were no differences in morbidity and mortality after stages 1 and 2. T-ALPPS produces a similar outcome to TSH, indicating that it could be a safe and effective alternative for curative hepatectomy for all patients.

Background: Two-stage hepatectomy (TSH) is the present standard for multiple bilobar colorectal metastases (CLM). As alternative, ultrasound-guided one-stage hepatectomy (E-OSH) has been proposed even for deep-located nodules to compare TSH and E-OSH. Methods: All consecutive TSH at the Paul Brousse Hospital and E-OSH at the Humanitas Research Hospital were considered. The inclusion criteria were ≥6 CLM, ≥3 CLM in the left liver, and ≥1 lesion with vascular contact. A total of 74 TSH and 35 E-OSH were compared. Results: The 2 groups had similar characteristics. Drop-out rate of TSH was 40.5%. In comparison with the cumulated hepatectomies of TSH, E-OSH had lower blood loss (500 vs. 1,100 mL, p = 0.009), overall morbidity (37.1 vs. 70.5%, p = 0.003), severe morbidity (14.3 vs. 36.4%, p = 0.04), and liver-specific morbidity (22.9 vs. 40.9%, p = 0.02). R0 resection rate was similar between groups. E-OSH and completed TSH had similar overall survival (5-year 38.2 vs. 31.8%), recurrence-free survival (3-year 17.6 vs. 17.7%), and recurrence sites. Conclusions: E-OSH is a safe alternative to TSH for multiple bilobar deep-located CLM. Whenever feasible, E-OSH should even be considered the preferred option because it has excellent safety and oncological outcomes equivalent to completed TSH, without the drop-out risk.

Introduction:Two-stage hepatectomy (TSH) enables patients to undergo surgery for colorectal liver metastasis (CRLM), which one-stage hepatectomy cannot remove. Although the outcome of TSH has been reported, there is no original report from Japan. The aim of this retrospective study was to evaluate the outcome of TSH in Japanese patients with CRLM.Methods:The authors conducted a retrospective cohort study using the nationwide database that included clinical information of 12 519 patients treated with CRLM between 2005 and 2017 in Japan. The primary outcome measure was overall survival. The second outcome measure was progression-free survival. Fisher’s exact test, χ2 test and Mann–Whitney U test were conducted to examine an intergroup difference. Univariate and multivariate analyses were performed using Cox regression model. Survival analysis was performed by Kaplan–Meier method and log-rank test.Results:Of the database, 53 patients undergoing TSH using portal vein embolization (PVE) were identified and analyzed. Their morbidity and in-hospital mortality rates at the second hepatectomy were 26.4% and 0.0%. The mean observation period was 21.8 months. The estimated 1-, 3- and 5-year overall survival rate were 92.5%, 70.8% and 34.7%. Multivariate analyses showed that more than 10 liver nodules significantly increased the mortality risk by 4.2-fold (95% CI 1.224–14.99, P= 0.023). Survival analysis revealed that repeat hepatectomy for disease progression after TSH was superior to chemotherapy in overall survival (mean: 49.6 vs. 18.7, months, P= 0.004).Conclusion:In the Japanese cohort, TSH was confirmed to be a safety procedure with an acceptable survival outcome. More than 10 liver nodules may be a predictor for unfavorable outcomes of patients with CRLM undergoing TSH. Furthermore, repeat hepatectomy can be a salvage treatment for resectable intrahepatic recurrence after TSH.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently emerged as a treatment choice for patients with colorectal liver metastases (CLM) and inadequate future liver remnant (FLR). The aim of this study was to define the results of ALPPS compared with two-stage hepatectomy (TSH) for patients with CLM. A meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Identification of eligible studies was performed using three distinct databases through February 2017; Medline, ClinicalTrials.gov and Cochrane library-Cochrane Central Register of Controlled Trials using a syntax including medical subject headings terms "portal vein ligation," "PVE," "staged hepatectomy," "staged liver resection," "liver resection," "two-stage hepatectomy," "TSH," "in situ liver transection with portal vein ligation," "associating liver partition and portal vein ligation for staged hepatectomy" and "ALPPS". Among the 634 records identified, 9 studies comparing ALPPS with TSH met the inclusion criteria. These studies included 657 patients with unresectable CLM (ALPPS, n=186 vs TSH, n=471). There was no difference in final postoperative FLR between ALPPS versus TSH (mean difference: 31.72, 95% CI: -27.33 to 90.77, p=0.29). The kinetic growth rate was faster with the ALPPS versus TSH (mean difference 19.07ml/day, 95% CI 8.12-30.02, p=0.0006). TSH had a lower overall and major morbidity versus ALPPS (overall morbidity: RR: 1.39, 95% CI: 1.07-1.8, p=0.01; I 2: 58%, p=0.01; major morbidity: RR: 1.57, 95% CI: 1.18-2.08, p=0.002; I 2: 0%, p=0.44). Overall survival was comparable following ALPPS versus TSH. While ALPPS may be a suitable approach for patients, the higher morbidity and mortality should be considered when determining the operative approach for patients with extensive CLM.

Health Economic Evaluation of Patients with Colorectal Liver Metastases Randomized to ALPPS or TSH - Analysis from the LIGRO Trial

From conventional two-stage hepatectomy to ALPPS: Fifteen years of experience in a hepatobiliary surgery unit

As surgical resection of colorectal liver metastases (CLM) remains the only treatment for cure, efforts to extend the surgical indications to include patients with multiple bilobar CLM have been made. This study evaluated the long-term outcome, safety and efficacy of two-stage hepatectomy (TSH) for CLM in a large cohort of patients. Patients undergoing surgery between December 1996 and December 2009 were reviewed. The early postoperative and long-term outcomes as well as the patterns of failure to complete TSH and its clinical implications were analysed. Eighty patients were scheduled to undergo TSH. Sixty-one patients had completion of TSH combined with (58 patients), or without (3) portal vein embolization/ligation (PVE/PVL). Five patients were excluded after first-stage hepatectomy and 14 after PVE/PVL. The 5-year overall survival rate and median survival in patients who completed TSH were 32 per cent and 39·6 months respectively, and corresponding recurrence-free values were 11 per cent and 9·4 months respectively. Six patients were alive beyond 5 years after TSH. Multivariable logistic regression analysis showed that failure to complete TSH was driven by two independent prognostic scenarios: three or more CLM in the future remnant liver (FRL) combined with age over 70 years predicted tumour progression after first-stage hepatectomy, and three or more CLM in the FRL combined with carcinomatosis at the time of first-stage hepatectomy predicted the development of additional FRL metastases after PVE/PVL. A therapeutic strategy using TSH provided acceptable long-term survival with no postoperative mortality. Further efforts are needed to increase the number of patients who undergo TSH successfully.

Two stage hepatectomy (TSH) versus ALPPS for initially unresectable colorectal liver metastases: A systematic review and meta-analysis

Characterization of early recurrences following liver resection by ALPPS and two stage hepatectomy (TSH) in patients with colorectal liver-metastases and small future liver remnants (FLR)