Postoperative muscle loss, protein intake, physical activity and outcome associations.

BACKGROUND: Skeletal muscle loss is often observed in intensive care patients. However, little is known about postoperative muscle loss, its associated risk factors, and its long-term consequences. The aim of this prospective observational study is to identify the incidence of and risk factors for surgery-related muscle loss (SRML) after major abdominal surgery, and to study the impact of SRML on fatigue and survival. METHODS: Patients undergoing major abdominal cancer surgery were included in the MUSCLE POWER STUDY. Muscle thickness was measured by ultrasound in three muscles bilaterally (biceps brachii, rectus femoris, and vastus intermedius). SRML was defined as a decline of 10 per cent or more in diameter in at least one arm and leg muscle within 1 week postoperatively. Postoperative physical activity and nutritional intake were assessed using motility devices and nutritional diaries. Fatigue was measured with questionnaires and 1-year survival was assessed with Cox regression analysis. RESULTS: A total of 173 patients (55 per cent male; mean (s.d.) age 64.3 (11.9) years) were included, 68 of whom patients (39 per cent) showed SRML. Preoperative weight loss and postoperative nutritional intake were statistically significantly associated with SRML in multivariable logistic regression analysis (P < 0.050). The combination of insufficient postoperative physical activity and nutritional intake had an odds ratio of 4.00 (95 per cent c.i. 1.03 to 15.47) of developing SRML (P = 0.045). No association with fatigue was observed. SRML was associated with decreased 1-year survival (hazard ratio 4.54, 95 per cent c.i. 1.42 to 14.58; P = 0.011). CONCLUSION: SRML occurred in 39 per cent of patients after major abdominal cancer surgery, and was associated with a decreased 1-year survival.

Long-term follow-up of a randomized trial of biliary drainage in perihilar cholangiocarcinoma.

BACKGROUND AND AIMS: The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes. METHODS: Patients were randomized in four tertiary referral centers. Follow-up data were available for all included patients. Primary outcome was overall survival (OS). Secondary outcomes were readmissions, and re-interventions not including in-trial interventions. RESULTS: A total of 54 patients were randomized; 27 in both groups. Median follow-up for both groups was 62 months (95% CI 54-70). The median OS was 13 months (95% CI 7.9-18.1) in the EBD and 7 months (95% CI 0.0-17.2) in the PTBD group (P = 0.28). Twenty (37%, n = 8 EBD vs n = 12 PTBD, P = 0.43) of 54 patients were readmitted at least once, mostly due to drainage-related complications (n = 13, 24%). Of note, 14 out of the 54 patients died within the trial. A total of 76 drainage procedures (32 EBD and 44 PTBD) were performed in 28 patients. The median number of stent or drain placements was 2 (2-4) for the EBD group and 2 (1-3) for the PTBD group (P = 0.77). DISCUSSION: Although this follow-up study represented a small cohort, no long-term differences in survival, readmissions, and drainage procedures for EBD and PTBD were found, even when comparing the resected and unresected group. However, this study demonstrates the complexity of biliary drainage for patients with potentially resectable pCCA, even in tertiary referral centers.

Reducing cold ischemia time by donor liver "back-table" preparation under continuous oxygenated machine perfusion of the portal vein.

INTRODUCTION: Cold ischemia time is a well-known risk factor for the development of non-anastomotic biliary strictures (NAS) after liver transplantation. End-ischemic hypothermic oxygenated machine perfusion (HOPE) of DCD liver grafts reduces the incidence of NAS, and has the potential to reduce cold ischemia times. We hypothesized that if a part of the back-table procedure could be performed under continuous HOPE, cold ischemia times would be reduced. METHODS: In this prospective observational cohort study, all nationwide declined livers that underwent DHOPE-NMP between July 1st 2021 and January 1st 2022 were included. The back-table of ten consecutive high-risk donor livers was performed with ongoing HOPE. Sixty DHOPE-NMP procedures (August 1st 2017-July 1st 2021) with a conventional back-table procedure functioned as a control group. RESULTS: Compared to the control group, this technique led to a decrease in non-oxygenated back-table time from median 74 min (IQR 58-92 min) to median 25 min (IQR 21-31 min), p < .01. Median total cold preservation times were reduced from 279 min (IQR 254-297) to 214 min (IQR 132-254), p < .01. CONCLUSION: Cold ischemia time of liver grafts can be successfully reduced by over one hour by using portal vein only HOPE during back-table preparation.

Low health literacy is associated with worse postoperative outcomes following hepato-pancreato-biliary cancer surgery.

BACKGROUND: Low health literacy (HL) can lead to worse health outcomes for patients with chronic diseases and could also lead to worse postoperative outcomes. This retrospective cohort study investigates the association between HL and postoperative textbook outcome (TO) after hepato-pancreato-biliary (HPB) cancer surgery. METHODS: Patients that consented and underwent surgery for a premalignant andmalignant HPB tumor were included. Preoperatively, HL was measured by the brief health literacy screen (BHLS). Patients were categorized as having low or adequate HL. Primary outcome was TO (length of hospital stay (LOS) ≤ 75th percentile; and no severe complication; and no readmission and mortality within 30 days after discharge). Secondary outcomes were LOS and emergency department (ED) visits within 30 days after discharge. RESULTS: In total, 137 patients were included, of whom thirty-six patients had low HL. In patients with low HL (vs. adequate HL), rate of TO was lower (55.6% vs. 72.3%; p = 0.095), LOS was significantly longer (13.5 vs. 9 days; p = 0.007) and there was only a slight difference in ED visits (14.3% vs. 11.0%; p = 0.560). Patients with low HL had a significant lower chance of achieving TO (OR 0.400, 95%-CI 0.169-0.948; p = 0.037). CONCLUSION: Low HL leads to worse postoperative outcome after HPB cancer surgery. Better preoperative education and guidance of patients with low HL could lead to better postoperative outcomes. Therefore, HL could be the next modifiable risk factor before major surgery.

Liver transplantation in patients with post-hepatectomy liver failure - A Northern European multicenter cohort study.

BACKGROUND: Liver transplantation (LTX) has been described as a rescue treatment option in severe, intractable post-hepatectomy liver failure (PHLF), but is not considered to be indicated for this condition by many hepatobiliary and transplant surgeons. In this article we describe the clinical experience of five northern European tertiary centers in using LTX to treat selected patients with severe PHLF. METHODS: All patients subjected to LTX due to PHLF at the participating centers were identified from prospective clinical databases. Preoperative variables, surgical outcome (both resection surgery and LTX) and follow-up data were assessed. RESULTS: A total of 10 patients treated with LTX due to severe PHLF from September 2008 to May 2020 were identified and included in the study. All patients but one were male and the median age was 70 years (range 49-72). In all patients the indication for liver resection was suspected malignancy, but in six patients post-resection pathology revealed benign or pre-malignant disease. There was no 90-day mortality after LTX. Patients were followed for a median of 49 months (13-153) and eight patients were alive without recurrence at last follow-up. DISCUSSION: In selected patients with PHLF LTX can be a life-saving procedure with low short-term risk.

Hospital variation and outcomes of simultaneous resection of primary colorectal tumour and liver metastases: a population-based study.

BACKGROUND: The optimal treatment sequence for patients with synchronous colorectal liver metastases (CRLM) remains uncertain. This study aimed to assess factors associated with the use of simultaneous resections and impact on hospital variation. METHOD: This population-based study included all patients who underwent liver surgery for synchronous colorectal liver metastases between 2014 and 2019 in the Netherlands. Factors associated with simultaneous resection were identified. Short-term surgical outcomes of simultaneous resections and factors associated with 30-day major morbidity were evaluated. RESULTS: Of 2146 patients included, 589 (27%) underwent simultaneous resection in 28 hospitals. Simultaneous resection was associated with age, sex, BMI, number, size and bilobar distribution of CRLM, and administration of preoperative chemotherapy. More minimally invasive and minor resections were performed in the simultaneous group. Hospital variation was present (range 2.4%-83.3%) with several hospitals performing simultaneous procedures more and less frequently than expected. Simultaneous resection resulted in 13% 30-day major morbidity, and 1% mortality. ASA classification ≥3 was independently associated with higher 30-day major morbidity after simultaneous resection (aOR 1.97, CI 1.10-3.42, p = 0.018). CONCLUSION: Distinctive patient and tumour characteristics influence the choice for simultaneous resection. Remarkable hospital variation is present in the Netherlands.

Short-term postoperative outcomes after liver resection in the elderly patient: a nationwide population-based study.

BACKGROUND: Liver resection is high-risk surgery in particular in elderly patients. The aim of this study was to explore postoperative outcomes after liver resection in elderly patients. METHODS: In this nationwide study, all patients who underwent liver resection for primary and secondary liver tumours in the Netherlands between 2014 and 2019 were included. Age groups were composed as younger than 70 (70-), between 70 and 80 (septuagenarians), and 80 years or older (octogenarians). Proportion of liver resections per age group and 30-day major morbidity and 30-day mortality were assessed. RESULTS: In total, 6587 patients were included of whom 4023 (58.9%) were younger than 70, 2135 (32.4%) were septuagenarians and 429 (6.5%) were octogenarians. The proportion of septuagenarians increased during the study period (aOR:1.06, CI:1.02-1.09, p < 0.001). Thirty-day major morbidity was higher in septuagenarians (11%) and octogenarians (12%) compared to younger patients (9%, p = 0.049). Thirty-day mortality was higher in septuagenarians (4%) and octogenarians (4%) compared to younger patients (2%, p < 0.001). Cardiopulmonary complications occurred more frequently with higher age, liver-specific complications did not. Higher age was associated with higher 30-day morbidity and 30-day mortality in multivariable logistic regression. CONCLUSION: Thirty-day major morbidity and 30-day mortality are higher after liver resection in elderly patients, attributed mainly to non-surgical cardiopulmonary complications.

Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution.

Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin-based oxygen carrier (HBOC)-based perfusion fluid (DHOPE-COR-NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE-COR-NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was ≥10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3-month graft survival, was a 100%. In conclusion, sequential DHOPE-COR-NMP using an HBOC-based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation.

Implementation and first results of a mandatory, nationwide audit on liver surgery.

BACKGROUND: The Dutch Hepato Biliary Audit (DHBA) was initiated in 2013 to assess the national quality of liver surgery. This study aimed to describe the initiation and implementation of this audit along with an overview of the results and future perspectives. METHODS: Registry of patients undergoing liver surgery for all primary and secondary liver tumors in the DHBA is mandatory. Weekly, benchmarked information on process and outcome measures is reported to surgical teams. In this study, the first results of patients with colorectal liver metastases were presented, including results of data verification. RESULTS: Between 2014 and 2017, 6241 procedures were registered, including 4261 (68%) resections for colorectal liver metastases. For minor- and major liver resections for colorectal liver metastases, the median [interquartile range] hospital stay was 6 [4-8] and 8 [6-12] days, respectively. A postoperative complicated course (complication leading to >14 days of hospital stay, reintervention or death) occurred in 26% and 43% and the 30-day/in-hospital mortality was 1% and 4%, respectively. The completeness of data was 97%. In 3.6% of patients, a complicated postoperative course was erroneously omitted. CONCLUSION: Nationwide implementation of the DHBA has been successful. This was the first step in creating a complete evaluation of the quality of liver surgery.

Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial.

BACKGROUND: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage. METHODS/DESIGN: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality. DISCUSSION: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma. TRIAL REGISTRATION: Netherlands Trial Register [ NTR4243 , 11 October 2013].

Association of modified textbook outcome and overall survival after surgery for colorectal liver metastases: A nationwide analysis.

BACKGROUND: Textbook outcome (TO) represents a multidimensional quality measurement, encompassing the desirable short-term outcomes following surgery. This study aimed to investigate whether achieving TO after resection of colorectal liver metastases (CRLM) surgery is related to better overall survival (OS) in a national cohort. METHOD: Data was retrieved from the Dutch Hepato Biliary Audit. A modified definition of TO (mTO) was used because readmissions were only recorded from 2019. mTO was achieved when no severe postoperative complications, mortality, prolonged length of hospital stay, occurred and when adequate surgical resection margins were obtained. To compare outcomes of patients with and without mTO and reduce baseline differences between both groups propensity score matching (PSM) was used for patients operated on between 2014 and 2018. RESULTS: Out of 6525 eligible patients, 81 % achieved mTO. For the cohort between 2014 and 2018, those achieving mTO had a 5-year OS of 46.7 % (CI 44.8-48.6) while non-mTO patients had a 5-year OS of 33.7 % (CI 29.8-38.2), p < 0.001. Not achieving mTO was associated with a worse OS (aHR 1.34 (95 % CI 1.17-1.53), p < 0.001. Median follow-up was 76 months., PSM assigned 519 patients to each group. In the PSM cohort patients achieving mTO, 5-year OS was 43.6 % (95 % CI 39.2-48.5) compared to 36.4 % (95 % CI 31.9-41.2) in patients who did not achieve mTO, p = 0.006. CONCLUSION: Achieving mTO is associated with improved long-term survival. This emphasizes the importance of optimising perioperative care and reducing postoperative complications in surgical treatment of CRLM.

A nationwide assessment of hepatocellular adenoma resection: Indications and pathological discordance.

Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs < 50 mm compared to HCAs ≥ 50 mm. Changes in final postoperative diagnosis were assessed. We performed a retrospective study that included patients who underwent resection for (suspected) HCAs in the Netherlands from 2014 to 2019. Indication for resection was analyzed and stratified for small (<50 mm) and large (≥50 mm) tumors. Logistic regression analysis was performed on factors influencing change in tumor diagnosis. Out of 222 patients who underwent surgery, 44 (20%) patients had a tumor <50 mm. Median age was 46 (interquartile range [IQR], 33-56) years in patients with small tumors and 37 (IQR, 31-46) years in patients with large tumors ( p  = 0.016). Patients with small tumors were more frequently men (21% vs. 5%, p  = 0.002). Main indications for resection in patients with small tumors were suspicion of (pre)malignancy (55%), (previous) bleeding (14%), and male sex (11%). Patients with large tumors received operations because of tumor size >50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size <50 mm (adjusted odds ratio [aOR], 3.4; p  < 0.01), male sex (aOR, 3.7; p  = 0.03), and lack of hepatobiliary contrast-enhanced magnetic resonance imaging (CE-MRI) (aOR, 1.8; p  = 0.04). Resection for small (suspected) HCAs was mainly indicated by suspicion of (pre)malignancy, whereas for large (suspected) HCAs, tumor size was the most prevalent indication. Male sex, tumor size <50 mm, and lack of hepatobiliary CE-MRI were independent risk factors for postoperative change in tumor diagnosis.

Is surgical subspecialization associated with hand grip strength and manual dexterity? A cross-sectional study.

BACKGROUND: The aim of this study was to compare hand grip strength (HGS) and manual dexterity of academic, subspecialized surgeons. METHODS: A single-center cross-sectional study was performed among 61 surgeons. HGS was analysed with a hand dynamometer and manual dexterity was extensively analysed with a Purdue Pegboard Test. Correlations between HGS and manual dexterity and specific characteristics of the surgeons were analysed using Pearson's correlation coefficient (r). RESULTS: HGS and manual dexterity were comparable between surgeons from different specialities. HGS was positively correlated with male gender (r = 0.59, p < 0.001) and hand glove size (r = 0.61, p < 0.001), whereas manual dexterity was negatively correlated with male gender (r = -0.35, p = 0.006), age (r = -0.39, = 0.002), and hand glove size (r = -0.46, p < 0.001). CONCLUSIONS: Surgical subspecialization was not correlated with HGS or manual dexterity. Male surgeons have greater HGS, whereas female surgeons have better manual dexterity. Manual dexterity is also correlated with age, showing better scores for younger surgeons.

Actual postoperative protein and calorie intake in patients undergoing major open abdominal cancer surgery: A prospective, observational cohort study.

BACKGROUND: Adequate nutritional protein and energy intake are required for optimal postoperative recovery. There are limited studies reporting the actual postoperative protein and energy intake within the first week after major abdominal cancer surgery. The main objective of this study was to quantify the protein and energy intake after major abdominal cancer surgery. METHODS: We conducted a prospective cohort study. Nutrition intake was assessed with a nutrition diary. The amount of protein and energy consumed through oral, enteral, and parenteral nutrition was recorded and calculated separately. Based on the recommendations of the European Society for Clinical Nutrition and Metabolism (ESPEN), protein and energy intake were considered insufficient when patients received <1.5 g/kg protein and 25 kcal/kg for 2 or more days during the first postoperative week. RESULTS: Fifty patients were enrolled in this study. Mean daily protein and energy intake was 0.61 ± 0.44 g/kg/day and 9.58 ± 3.33 kcal/kg/day within the first postoperative week, respectively. Protein and energy intake were insufficient in 45 [90%] and 41 [82%] of the 50 patients, respectively. Patients with Clavien-Dindo grade ≥III complications consumed less daily protein compared with the group of patients without complications and patients with grade I or II complications. CONCLUSION: During the first week after major abdominal cancer surgery, the majority of patients do not consume an adequate amount of protein and energy. Incorporating a registered dietitian into postoperative care and adequate nutrition support after major abdominal cancer surgery should be a standard therapeutic goal to improve nutrition intake.

Guidelines for Perioperative Care for Liver Transplantation: Enhanced Recovery After Surgery (ERAS) Recommendations.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a multimodal, evidence-based, program of care developed to minimize the response to surgical stress, associated with reduced perioperative morbidity and hospital stay. This study presents the specific ERAS Society recommendations for liver transplantation (LT) based on the best available evidence and on expert consensus. METHODS: PubMed and ClinicalTrials.gov were searched in April 2019 for published and ongoing randomized clinical trials on LT in the last 15 y. Studies were selected by 5 independent reviewers and were eligible if focusing on each validated ERAS item in the area of adult LT. An e-Delphi method was used with an extended interdisciplinary panel of experts to validate the final recommendations. RESULTS: Forty-three articles were included in the systematic review. A consensus was reached among experts after the second round. Patients should be screened for malnutrition and treated whenever possible. Prophylactic nasogastric intubation and prophylactic abdominal drainage may be omitted, and early extubation should be considered. Early oral intake, mobilization, and multimodal-balanced analgesia are recommended. CONCLUSIONS: The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the e-Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.

Defining Textbook Outcome in liver surgery and assessment of hospital variation: A nationwide population-based study.

INTRODUCTION: Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event rates, which have less discriminating impact to detect differences between hospitals. This study aimed to assess factors associated with TO, and evaluate hospital and network variation after case-mix correction in TO rates for liver surgery. METHODS: This was a population-based retrospective study of all patients who underwent liver resection for malignancy in the Netherlands in 2019 and 2020. TO was defined as absence of severe postoperative complications, mortality, prolonged length of hospital stay, and readmission, and obtaining adequate resection margins. Multivariable logistic regression was used for case-mix adjustment. RESULTS: 2376 patients were included. TO was accomplished in 1380 (80%) patients with colorectal liver metastases, in 192 (76%) patients with other liver metastases, in 183 (74%) patients with hepatocellular carcinoma and 86 (51%) patients with biliary cancers. Factors associated with lower TO rates for CRLM included ASA score ≥3 (aOR 0.70, CI 0.51-0.95 p = 0.02), extrahepatic disease (aOR 0.64, CI 0.44-0.95, p = 0.02), tumour size >55 mm on preoperative imaging (aOR 0.56, CI 0.34-0.94, p = 0.02), Charlson Comorbidity Index ≥2 (aOR 0.73, CI 0.54-0.98, p = 0.04), and major liver resection (aOR 0.50, CI 0.36-0.69, p < 0.001). After case-mix correction, no significant hospital or oncological network variation was observed. CONCLUSION: TO differs between indications for liver resection and can be used to assess between hospital and network differences.

Nationwide oncological networks for resection of colorectal liver metastases in the Netherlands: Differences and postoperative outcomes.

INTRODUCTION: Widespread differences in patient demographics and disease burden between hospitals for resection of colorectal liver metastases (CRLM) have been described. In the Netherlands, networks consisting of at least one tertiary referral centre and several regional hospitals have been established to optimize treatment and outcomes. The aim of this study was to assess variation in case-mix, and outcomes between these networks. METHODS: This was a population-based study including all patients who underwent CRLM resection in the Netherlands between 2014 and 2019. Variation in case-mix and outcomes between seven networks covering the whole country was evaluated. Differences in case-mix, expected 30-day major morbidity (Clavien-Dindo ≥3a) and 30-day mortality between networks were assessed. RESULTS: In total 5383 patients were included. Thirty-day major morbidity was 5.7% and 30-day mortality was 1.5%. Significant differences between networks were observed for Charlson Comorbidity Index, ASA 3+, previous liver resection, liver disease, preoperative MRI, preoperative chemotherapy, ≥3 CRLM, diameter of largest CRLM ≥55 mm, major resection, combined resection and ablation, rectal primary tumour, bilobar and extrahepatic disease. Uncorrected 30-day major morbidity ranged between 3.3% and 13.1% for hospitals, 30-day mortality ranged between 0.0% and 4.5%. Uncorrected 30-day major morbidity ranged between 4.4% and 6.0% for networks, 30-day mortality ranged between 0.0% and 2.5%. No negative outliers were observed after case-mix correction. CONCLUSION: Variation in case-mix and outcomes are considerably smaller on a network level as compared to a hospital level. Therefore, auditing is more meaningful at a network level and collaboration of hospitals within networks should be pursued.