Objective: This is a preplanned, health economic evaluation from the LIGRO trial. One hundred patients with colorectal liver metastases (CRLM) and standardized future liver remnant <30% were randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or two-staged hepatectomy (TSH).

Summary background data: TSH, is an established method in advanced CRLM. ALPPS has emerged providing improved resection rate and survival. The health care costs and health outcomes, combining health-related quality of life (HRQoL) and survival into quality-adjusted life years (QALYs), of ALPPS and TSH have not previously been evaluated and compared.

Methods: Costs and QALYs were compared from treatment start up to 2 years. Costs are estimated from resource use, including all surgical interventions, length of stay after interventions, diagnostic procedures and chemotherapy, and applying Swedish unit costs. QALYs were estimated by combining survival and HRQoL data, the latter being assessed with EQ-5D 3L. Estimated costs and QALYs for each treatment strategy were combined into an incremental cost-effectiveness ratio (ICER). Nonparametric bootstrapping was used to assess the joint distribution of incremental costs and QALYs.

Results: The mean cost difference between ALPPS and TSH was 12,662€, [95% confidence interval (CI): -10,728-36,051; P = 0.283]. Corresponding mean difference in life years and QALYs was 0.1296 (95% CI: -0.12-0.38; P = 0.314) and 0.1285 (95% CI: -0.11-0.36; P = 0.28), respectively. The ICER was 93,186 and 92,414 for QALYs and life years as outcomes, respectively.

Conclusions: Based on the 2-year data, the cost-effectiveness of ALPPS is uncertain. Further research, exploring cost and health outcomes beyond 2 years is needed.

Objective: The objective of this study was to evaluate the long-term oncological outcomes of patients with colorectal liver metastasis (CRLM) randomized for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH).

Introduction: For advanced CRLM, TSH or ALPPS may be needed for tumor freedom. The randomized, controlled, multicenter trial LIGRO showed an increased resection rate in patients who underwent ALPPS but no difference in morbidity or mortality. The 2-year survival analysis revealed better overall survival in the ALPPS group. Here, the long-term survival analysis from the LIGRO trial is reported.

Methods: In the LIGRO trial, 100 patients were randomized to TSH or ALPPS, with the option of rescue ALPPS if insufficient growth was found after the initial step of TSH. Patients were enrolled between June 2014 and August 2016. Follow-up data for this study were collected between November 2022 and February 2023.

Results: In total, 16 patients were alive at the end of the follow-up period. The estimated median follow-up time was 93 months. Estimated median overall survival times were 45 months in the ALPPS group and 27 months in the TSH group (P = 0.057), with 5-year survival rates of 31% and 20%, respectively. Positive prognostic factors were liver tumor-free status at the first follow-up and rectal primary tumor. Negative prognostic factors were extrahepatic disease and increasing CLRM size.

Conclusion: Liver tumor-free status is a predictor of long-term survival, along with extrahepatic disease, large CRLM size, and rectal primary tumor. Survival did not significantly differ between patients treated with ALPPS or TSH.

Background: An adequate future liver remnant (FLR) is fundamental for major liver resections. To achieve sufficient FLR, portal vein embolization (PVE) may be used. The most effective material for PVE has yet to be determined. The aim of this study was to investigate the differences in FLR growth between n-butyl-cyanoacrylate glue (NBCA) and microparticles.Material/methodsa: retrospective study was performed at three Swedish hepatobiliary centers and included patients who underwent PVE 2013-2021. Electronic medical records were reviewed, and procedure-related data were collected. Data were analyzed with respect to embolizing material.Results: A total of 265 patients were included: 160 in the NBCA group and 105 in the microparticle group. The NBCA group had a higher degree of hypertrophy (12.1 vs. 9.4 % points, p = 0.003) and a higher resection rate (68 vs. 59 %, p = 0.01) than the microparticle group. Procedurerelated data all indicated the superiority of NBCA. No difference in inducing hypertrophy was observed when comparing patients who received chemotherapy before PVE with those who received chemotherapy before and after PVE within the NBCA group. Discussion/conclusion: This retrospective multicenter study supports the superiority of NBCA compared to microparticles in the setting of PVE. Chemotherapy after PVE does not seem to negatively affect hypertrophy.

Background: There is evidence that a high hospital volume of pancreaticoduodenectomy improves short-and long-term outcomes, but there are few population-based studies on the effect of a high resection rate in the population. The aim of this national, observational study was primarily to investigate differences in overall survival among elderly patients with cancer in the pancreatic head between high and low resection rate groups and secondarily to determine if counties with high resection rates of pancreaticoduodenectomy had more severe complications after surgery. Materials and methods: All patients in the Swedish National Registry for tumours in the pancreatic and periampullary region diagnosed between 2010 and 2018 with pancreatic head cancer were included in this retrospective cohort study. Patients were divided into low and high resection rate groups according to the yearly resection rates in the respective counties. For operative outcomes, all patients who had undergone pancreaticoduodenectomy were included regardless of diagnosis. The primary outcome of the study was overall survival among patients aged &gt;= 70 years with pancreatic head cancer. Results: Among 13 933 patients in the registry, 7661 were 70 years or older, of whom 3006 had pancreatic head cancer. Overall survival was longer in high resection rate groups for patients aged &gt;= 70 years, as for the age subgroups 70-79 years and &gt;= 80 years (all p &lt; 0.001). Among patients who had undergone pancreaticoduodenectomy aged &gt;= 80 years the high resection rate counties showed an increased rate of severe complications, but no increase in 90-day mortality. Conclusion: High resection rate groups show a significantly longer overall survival among elderly patients with pancreatic head cancer in Sweden. This implies that there could be a survival benefit from increasing resections in low resection rate groups. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of Surgical Associates Ltd.

Introduction: For patients with colorectal liver metastases (CRLM), the only treatment with a possibility for long-term survival and cure is radical resection. The majority of patients are at the time of diagnosis not assessed as resectable because they have advanced disease in the liver or unresectable extrahepatic disease or are too frail to withstand liver surgery. Patients who at the time of diagnosis are not assessed as resectable may be treated with conversion chemotherapy to downsize the tumor burden and render the patient eligible for resection. One concern with chemotherapy administered preoperatively has been the potential negative effect on the future liver remnant (FLR), especially for patients with a low volume of the FLR who are undergoing techniques to increase the volume. Established techniques to increase the volume are portal vein occlusion (PVO) and two-staged hepatectomy (TSH). A more recent method is Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS). Due to the relative novelty of ALPPS, the long-term oncological results are not known. For patients with CRLM, resection of liver metastases is more favorable from a health economic perspective than palliative treatment and results in a higher quality of life than palliative chemotherapy. For patients undergoing ALPPS as well as TSH, the data are scarce.

Aim: The aim of the first study was to determine whether preoperative chemotherapy has a negative impact on the volume increase for patients undergoing ALPPS. The aim of the second study was to analyze the temporal course of the volume increase in the FLR for patients undergoing PVO. The aim of the third study was to study the long-term outcome for patients randomized to ALPPS or TSH. The aim of the fourth study was to perform a health economic analysis of patients randomized to ALPPS or TSH.

Methods: The first study was based on data from the ALPPS registry, which is an international registry initiated 2012. All patients included in the registry between 2012 and 2016 were included. The patients were divided into the following four groups: no preoperative chemotherapy, 1 regimen of neoadjuvant chemotherapy, more than 1 regimen, and more than 1 regimen with the addition of monoclonal antibodies. The volume increase between interventions 1 and 2 was analyzed. In the second study, a retrospective analysis was performed of patients randomized to TSH. Forty-eight patients were included. The volume increase of the FLR was analyzed as the kinetic growth rate (KGR). The KGR was calculated from PVO until radical hepatectomy or exclusion, as well as between the first and second radiological evaluations. In the third and fourth studies, patients randomized to ALPPS and TSH were included. In the third study, survival, as well as factors affecting the outcome, were analyzed. In the fourth study, a calculation of resource use was performed, as was an analysis of health-related quality of life (HRQoL) for the groups.

Results: In the first study, it was found that chemotherapy had no negative impact on the volume increase for patients undergoing ALPPS. In the second study, it was found that the volume increase of the FLR was largest the first week after ALPPS. In the third study, it was found that patients randomized to ALPPS had a longer survival than those randomized to TSH. Of the factors affecting the outcome, resection of liver metastases had a significant impact. In the fourth study, no significant difference could be found in resource use or HRQoL for patients randomized to ALPPS over TSH.

Conclusion: Patients with advanced CRLM undergoing ALPPS should receive preoperative chemotherapy, if indicated. For those undergoing PVO, early evaluation is crucial to evaluate the volume increase, and for those with insufficient increase, additional techniques to increase the volume should be considered. Resection of liver metastases is an important factor to improve the outcome. Further studies are warranted to conclude whether ALPPS or TSH is most effective from a health economic perspective.

BACKGROUND: Portal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8 weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks.

METHODS: Patients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) < 30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy.

RESULTS: Forty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (± 4), compared to 1.5 (± 2) between the first and second CT (p < 0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (± 4) the first week, compared to 4.3 (± 2) for patients who failed to reach a sufficient volume (p = 0.4). During the interval between the first and second CT, the KGR was 2.2 (± 2), respectively (± 0.1) (p = 0.017).

DISCUSSION: The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.

Background: Colorectal liver metastases (CRLM) not amenable for resection have grave prognosis. One limiting factor for surgery is a small future liver remnant (FLR). Early data suggests that associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively increases the volume of the FLR allowing for resection in a larger fraction of patients than conventional two-stage hepatectomy (TSH) with portal vein occlusion (PVO). Oncological results of the treatment are lacking. The aim of this study was to assess the intermediate oncological outcomes after ALPPS in patients with CRLM. Material and methods: Retrospective analysis of all patients with CRLM operated with ALPPS at the participating centres between December 2012 and May 2014. Results: Twenty-three patients (16 male, 7 female), age 67 years (28-80) were operated for 6.5 (1-38) metastases of which the largest was 40 nun (14-130). Six (27.3%) patients had extra-hepatic metastases, 16 (72.7%) synchronous presentation. All patients received chemotherapy, 6 cycles (3-25) preoperatively and 16 (70%) postoperatively. Ten patients (43%) were rescue ALPPS after failed PVO. Severe complications occurred in 13.6% and one (4.5%) patient died within 90 days of surgery. After a median follow-up of 22.5 months from surgery and 33.5 months from diagnosis of liver metastases estimated 2 year overall survival was 59% (from surgery) and 73% (from diagnosis). Liver only recurrences (n = 8), were treated with reresection/ablation (n = 7) while lung recurrences were treated with chemotherapy. Conclusion: The overall survival, rate of severe complications and perioperative mortality associated with ALPPS for patients with CRLM is comparable to TSH. (C) 2016 Elsevier Ltd. All rights reserved.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has emerged as an additional tool to increase the size of the future liver remnant (FLR) in the settings of advanced tumor burden in the liver. Initial reports have indicated high feasibility but also high mortality and morbidity. The aim of this study was to assess the initial experience with ALPPS in Scandinavia regarding feasibility, morbidity, and mortality.

MATERIALS AND METHODS: We conducted a retrospective analysis of all patients who underwent ALPPS since its introduction at 3 Scandinavian hepatobiliary centers.

RESULTS: Thirty-six patients were identified, 21 male and 15 female. Median age was 67 years (22-83). Colorectal liver metastases (n = 25) were the most common indication for ALPPS followed by hepatocellular carcinoma (n = 4), cholangiocarcinoma (n = 4), and other (n = 3). Median growth of the FLR between the operations was 67% (-17 to 238) in 6 (5-13) days. All patients completed the second operation, and 71% of the resections were R0. Although the total percentage of patients with complication(s) was 92%, only 4 patients (11%) had a grade 3b complication according to the Clavien-Dindo classification, and no other severe complications were noted. There was no in-hospital mortality, but 1 (2.8%) patient died within 90 days of operation.

CONCLUSION: ALPPS is a highly feasible method to stimulate FLR growth in patients with colorectal liver metastases as well as primary hepatobiliary malignancies. The treatment can be carried out with relative safety.

Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is surgical resection. However, many patients retain a to small future liver remnant (FLR) to allow for resection directly. There are therefore strategies to decrease the tumor with neoadjuvant chemotherapy and to increase the FLR. An accepted strategy to increase the FLR is portal vein occlusion (PVO). A concern with this strategy is that a large proportion of patients will never be operated because of progression during the interval between PVO and resection. ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new procedure with a high resection rate. A concern with this approach is the rather high frequency of complications and high mortality, compared to PVO. In this review, it is shown that with ALPPS the resection rate was 97.1% for CRLM and the mortality rate for all diagnoses was 9.6%. The mortality rate was likely lower for patients with CRLM, but some data were lacking in the reports. Due to the novelty of ALPPS, the indications and technique are not yet established but there are arguments for ALPPS in the context of CRLM and a small FLR.