Outcomes of liver surgery:A decade of mandatory nationwide auditing in the Netherlands

Background: In 2013, the nationwide Dutch Hepato Biliary Audit (DHBA) was initiated. The aim of this study was to evaluate changes in indications for and outcomes of liver surgery in the last decade. Methods: This nationwide study included all patients who underwent liver surgery for four indications, including colorectal liver metastases (CRLM), hepatocellular carcinoma (HCC), and intrahepatic– and perihilar cholangiocarcinoma (iCCA – pCCA) between 2014 and 2022. Trends in postoperative outcomes were evaluated separately for each indication using multilevel multivariable logistic regression analyses. Results: This study included 8057 procedures for CRLM, 838 for HCC, 290 for iCCA, and 300 for pCCA. Over time, these patients had higher risk profiles (more ASA-III patients and more comorbidities). Adjusted mortality decreased over time for CRLM, HCC and iCCA, respectively aOR 0.83, 95%CI 0.75–0.92, P &lt; 0.001; aOR 0.86, 95%CI 0.75–0.99, P = 0.045; aOR 0.40, 95%CI 0.20–0.73, P &lt; 0.001. Failure to rescue (FTR) also decreased for these groups, respectively aOR 0.84, 95%CI 0.76–0.93, P = 0.001; aOR 0.81, 95%CI 0.68–0.97, P = 0.024; aOR 0.29, 95%CI 0.08–0.84, P = 0.021). For iCCA severe complications (aOR 0.65 95%CI 0.43–0.99, P = 0.043) also decreased. No significant outcome differences were observed in pCCA. The number of centres performing liver resections decreased from 26 to 22 between 2014 and 2022, while median annual volumes did not change (40–49, P = 0.66). Conclusion: Over time, postoperative mortality and FTR decreased after liver surgery, despite treating higher-risk patients. The DHBA continues its focus on providing feedback and benchmark results to further enhance outcomes.</p

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

Volume–outcome relationship of liver surgery: a nationwide analysis

Background: Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. Methods: This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien–Dindo grade IIIA or higher) and 30-day or in-hospital mortality. Results: A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non-CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. Conclusion: Hospital volume and postoperative outcomes were not associated

Case-mix adjustment to compare nationwide hospital performances after resection of colorectal liver metastases

Background: Differences in patient demographics and disease burden can influence comparison of hospital performances. This study aimed to provide a case-mix model to compare short-term postoperative outcomes for patients undergoing liver resection for colorectal liver metastases (CRLM). Methods: This retrospective, population-based study included all patients who underwent liver resection for CRLM between 2014 and 2018 in the Netherlands. Variation in case-mix variables between hospitals and influence on postoperative outcomes was assessed using multivariable logistic regression. Primary outcomes were 30-day major morbidity and 30-day mortality. Validation of results was performed on the data from 2019. Results: In total, 4639 patients were included in 28 hospitals. Major morbidity was 6.2% and mortality was 1.4%. Uncorrected major morbidity ranged from 3.3% to 13.7% and mortality ranged from 0.0% to 5.0%. between hospitals. Significant differences between hospitals were observed for age higher than 80 (0.0%-17.1%, p <0.001), ASA 3 or higher (3.3%-36.3%, p <0.001), histopathological parenchymal liver disease (0.0%-47.1%, p <0.001), history of liver resection (8.1%-36.3%, p <0.001), major liver resection (6.7%-38.0%, p <0.001) and synchronous metastases (35.5%-62.1%, p <0.001). Expected 30-day major morbidity between hospitals ranged from 6.4% to 11.9% and expected 30-day mortality ranged from 0.6% to 2.9%. After case-mix correction no significant outliers concerning major morbidity and mortality remained. Validation on patients who underwent liver resection for CRLM in 2019 affirmed these outcomes. Conclusion: Case-mix adjustment is a prerequisite to allow for institutional comparison of short-term postoperative outcomes after liver resection for CRLM. (C) 2020 University Medical Center Groningen. Published by Elsevier Ltd

Outcomes of liver surgery: A decade of mandatory nationwide auditing in the Netherlands

BACKGROUND: In 2013, the nationwide Dutch Hepato Biliary Audit (DHBA) was initiated. The aim of this study was to evaluate changes in indications for and outcomes of liver surgery in the last decade. METHODS: This nationwide study included all patients who underwent liver surgery for four indications, including colorectal liver metastases (CRLM), hepatocellular carcinoma (HCC), and intrahepatic- and perihilar cholangiocarcinoma (iCCA - pCCA) between 2014 and 2022. Trends in postoperative outcomes were evaluated separately for each indication using multilevel multivariable logistic regression analyses. RESULTS: This study included 8057 procedures for CRLM, 838 for HCC, 290 for iCCA, and 300 for pCCA. Over time, these patients had higher risk profiles (more ASA-III patients and more comorbidities). Adjusted mortality decreased over time for CRLM, HCC and iCCA, respectively aOR 0.83, 95%CI 0.75-0.92, P < 0.001; aOR 0.86, 95%CI 0.75-0.99, P = 0.045; aOR 0.40, 95%CI 0.20-0.73, P < 0.001. Failure to rescue (FTR) also decreased for these groups, respectively aOR 0.84, 95%CI 0.76-0.93, P = 0.001; aOR 0.81, 95%CI 0.68-0.97, P = 0.024; aOR 0.29, 95%CI 0.08-0.84, P = 0.021). For iCCA severe complications (aOR 0.65 95%CI 0.43-0.99, P = 0.043) also decreased. No significant outcome differences were observed in pCCA. The number of centres performing liver resections decreased from 26 to 22 between 2014 and 2022, while median annual volumes did not change (40-49, P = 0.66). CONCLUSION: Over time, postoperative mortality and FTR decreased after liver surgery, despite treating higher-risk patients. The DHBA continues its focus on providing feedback and benchmark results to further enhance outcomes

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Genome-Scale Modeling of Light-Driven Reductant Partitioning and Carbon Fluxes in Diazotrophic Unicellular Cyanobacterium Cyanothece sp. ATCC 51142

Genome-scale metabolic models have proven useful for answering fundamental questions about metabolic capabilities of a variety of microorganisms, as well as informing their metabolic engineering. However, only a few models are available for oxygenic photosynthetic microorganisms, particularly in cyanobacteria in which photosynthetic and respiratory electron transport chains (ETC) share components. We addressed the complexity of cyanobacterial ETC by developing a genome-scale model for the diazotrophic cyanobacterium, Cyanothece sp. ATCC 51142. The resulting metabolic reconstruction, iCce806, consists of 806 genes associated with 667 metabolic reactions and includes a detailed representation of the ETC and a biomass equation based on experimental measurements. Both computational and experimental approaches were used to investigate light-driven metabolism in Cyanothece sp. ATCC 51142, with a particular focus on reductant production and partitioning within the ETC. The simulation results suggest that growth and metabolic flux distributions are substantially impacted by the relative amounts of light going into the individual photosystems. When growth is limited by the flux through photosystem I, terminal respiratory oxidases are predicted to be an important mechanism for removing excess reductant. Similarly, under photosystem II flux limitation, excess electron carriers must be removed via cyclic electron transport. Furthermore, in silico calculations were in good quantitative agreement with the measured growth rates whereas predictions of reaction usage were qualitatively consistent with protein and mRNA expression data, which we used to further improve the resolution of intracellular flux values

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

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication