Background: Portal vein embolization (PVE) is a well-established technique for inducing liver hypertrophy in the future liver remnant (FLR) before major hepatectomy. A frequently used method in bilobar disease is the two-stage hepatectomy (TSH) technique combined with PVE (TSH-PVE). A novel approach is PVE, followed by a one-stage hepatectomy (OSH), combining major hepatectomy with clearing of the FLR (PVE-OSH). This study aimed to compare FLR hypertrophy between these two strategies for induced liver hypertrophy.

Material/methods: Patients with bilobar colorectal liver metastases (CRLM) who underwent PVE from January 2013 to December 2021 were included in this retrospective, multicenter study. Aspects of hypertrophy of the FLR were compared between the groups.

Results: The study included 188 patients, 127 in the PVE-OSH group and 61 in the TSH-PVE group. There were no statistically significant differences between the two groups regarding FLR hypertrophy measured by absolute and relative growth, degree of hypertrophy or kinetic growth rate. No major complications were reported.

Discussion/conclusion: No differences in FLR hypertrophy were demonstrated between the two different treatment strategies of TSH-PVE or PVE-OSH. This supports PVE-OSH as a feasible treatment option that reduces the surgical burden for patients with advanced, bilobar CRLM disease.

BackgroundVentilation as a function of elimination of CO2 during incremental exercise (VE/VCO2 slope) has been shown to be a valuable predictor of complications and death after major non-cardiac surgery. VE/VCO2 slope and partial pressure of end-tidal carbon dioxide (PetCO2) are both affected by ventilation/perfusion mismatch, but research on the utility of PetCO2 for risk stratification in major abdominal surgery is limited. AimWe aimed to determine the correlation between VE/VCO2 slope and PetCO2 measured during preoperative cardiopulmonary exercise testing (CPET) and its association with major cardiopulmonary complications (MCPCs) or death following oesophageal and other major abdominal cancer surgeries. MethodIn a retrospective cohort of 116 patients undergoing preoperative CPET 2008-2023, VE/VCO2 slope and PetCO2 (kPa) were recorded. The main outcome was MCPC during hospitalisation or death <= 90 days of surgery. We determined threshold values for each measure, corresponding to 90% specificity, using receiver operating characteristics analysis. ResultsA strong negative correlation was found between PetCO2 after a 5-minute warm-up and VE/VCO2 slope (Pearson r = -.88). In oesophagus cancer, VE/VCO2 slope >38 and PetCO2 < 4.1 kPa (30.8 mmHg) were both significant thresholds for the main outcome. For other major abdominal surgery patients, threshold analyses were non-significant. The area under the curve to predict outcome was similar using VE/VCO2 slope (0.70, 95% confidence interval 0.51-0.89) as compared to PetCO2 (0.71, 0.53-0-90). ConclusionBoth preoperative VE/VCO2 slope and PetCO2 could identify subjects with a very high risk of complications following oesophageal resection, with similar prognostic utility. PetCO2 can be measured with simpler equipment and could therefore be useful when CPET is not available.

IMPORTANCE The DIPLOMA trial showed comparable radical resection rates after minimally invasive left pancreatectomy (MILP) and open left pancreatectomy (OLP) in patients with upfront resectable pancreatic cancer. Data on long-term overall survival (OS) and disease-free survival (DFS) are currently lacking, but are required before the oncological efficacy of MILP can be confirmed. OBJECTIVE To determine the long-term oncological outcome, including OS and DFS, of MILP vs OLP in patients with upfront resectable left-sided pancreatic cancer in the DIPLOMA trial. DESIGN, SETTING, AND PARTICIPANTS The randomized, patient-blinded and pathologist-blinded DIPLOMA trial was conducted between 2018 and 2021, with a follow-up duration of at least 36 months. It was a multicenter international trial that took place in 35 centers in 12 countries worldwide. Patients with upfront resectable pancreatic ductal adenocarcinoma of the body or tail of the pancreas were included. INTERVENTIONS Participants were randomly assigned to undergo MILP (laparoscopic and robotic) or OLP. Patients were blinded for the surgical approach. MAIN OUTCOMES AND MEASURES Main outcomes included OS and DFS. Other outcomes include receipt of adjuvant therapy and time to start of adjuvant therapy. RESULTS Between May 2018 and May 2021, 258 patients were randomized to the MILP (131 patients) and OLP (127 patients) groups. After a median follow-up of 38 (IQR 36-46) months, 134 patients (52%) had died and 127 patients (55%) experienced disease recurrence. OS did not differ significantly between the MILP and OLP groups (median, 32 vs 34 months; stratified hazard ratio, 1.02; 95% CI, 0.72-1.44; P = .92). Also, DFS did not significantly differ between the MILP and OLP groups (median, 21 vs 17 months; stratified hazard ratio, 0.96; 95% CI, 0.68-1.35; P = .81). Adjuvant therapy was administered in 79 patients after MILP (79 of 113 [70%]) and 79 patients after OLP (79 of 110 [72%]) (P = .63). Time to adjuvant therapy was comparable between groups (median 59 vs 56 days; P = .92). CONCLUSIONS AND RELEVANCE In this long-term follow-up of the randomized DIPLOMA trial in patients with upfront resectable pancreatic cancer, oncological outcomes after MILP and OLP did not differ significantly, confirming the oncological safety of MILP. TRIAL REGISTRATION International Standard Registered Clinical/Social Study Number Registry Identifier: ISRCTN44897265

Minimally invasive surgery, including laparoscopic and robotic-assisted surgery, is gaining in popularity in the field of hepato-pancreato-biliary surgery with the aim to shorten the time to functional recovery by reducing postoperative pain and minimizing complications. Different procedures have been evaluated showing a probable benefit for minimally invasive surgery in distal pancreatectomy1 and liver resections2.

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Background: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. Methods: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. Results: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). Conclusion: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.

Liver metabolism is central to human physiology and influences the pathogenesis of common metabolic diseases. Yet, our understanding of human liver metabolism remains incomplete, with much of current knowledge based on animal or cell culture models that do not fully recapitulate human physiology. Here, we perform in-depth measurement of metabolism in intact human liver tissue ex vivo using global C-13 tracing, non-targeted mass spectrometry and model-based metabolic flux analysis. Isotope tracing allowed qualitative assessment of a wide range of metabolic pathways within a single experiment, confirming well-known features of liver metabolism but also revealing unexpected metabolic activities such as de novo creatine synthesis and branched-chain amino acid transamination, where human liver appears to differ from rodent models. Glucose production ex vivo correlated with donor plasma glucose, suggesting that cultured liver tissue retains individual metabolic phenotypes, and could be suppressed by postprandial levels of nutrients and insulin, and also by pharmacological inhibition of glycogen utilization. Isotope tracing ex vivo allows measuring human liver metabolism with great depth and resolution in an experimentally tractable system.

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.

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (&lt;6 months after resection) or late (&gt;6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B(+) natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B(+) NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.&lt;br /&gt;