Background: Accurate preoperative prediction of length of hospital stay (LOS) after surgery for colorectal liver metastases (CRLMs) could improve patient counselling and resource planning, yet reliable risk tools are lacking. We aimed to develop an interpretable machine learning model predicting LOS following first-time liver-directed surgery for CRLMs. Methods: In this multicenter cohort study, we included patients who underwent first-time liver resection, ablation, or a combination for CRLMs at three Danish hepatobiliary centers between 2016 and 2023. Preoperative features from two national registries were used to train Elastic Net, Random Forest, HistGradientBoosting, and Explainable Boosting Machine (EBM) algorithms. Hyperparameters were optimized using five-fold cross-validation. Performance was evaluated on a 20% hold-out test sample using mean absolute error (MAE) with bootstrapped 95% confidence intervals (CIs). Results: Among 915 patients, median LOS was 4.0 days (interquartile range (IQR) 3.0-6.0). All four algorithms achieved comparable prediction error (MAE 3.0-3.1 days). The EBM (MAE 3.1 days, 95% CI 2.6-4.3) algorithm was selected for its inherent interpretability. Surgical approach was the strongest predictor, where percutaneous and laparoscopic approaches were associated with reductions of 1.9 and 1.2 days, respectively. Tumor burden, including number of lesions and largest lesion diameter, showed progressive non-linear associations with longer stays. Nonetheless, overall explained variance was low (R2 ≤ 0.10), and calibration showed systematic underestimation of stays beyond five days. Conclusions: An inherently interpretable machine learning model matched the predictive performance of opaque algorithms for LOS after CRLM surgery, although overall predictive accuracy was modest and longer stays were underestimated. Explainability analysis identified surgical approach and tumor burden as the most influential predictors. External validation in healthcare systems with different discharge practices is warranted.

Subclinical inflammation and fibrosis are common after liver transplantation and are associated with progressive fibrosis and cirrhosis, which are causes of graft loss. However, the association between early inflammation and fibrosis with graft loss remains insufficiently studied. In this multicenter cohort study, protocol biopsies collected one year posttransplant were assessed for inflammation and fibrosis. Fibrosis risk was assessed in recipients with paired biopsies at 1 year and ≥ 2 years posttransplantation. Associations of inflammation and fibrosis with graft loss and mortality were assessed using Cox regression. Graft loss was defined as re-transplantation or death due to liver complications. We included 446 liver transplant recipients. One year after transplantation, 54 recipients (18%) had inflammation, and 48 (12%) had fibrosis. In multivariable analysis, fibrosis was associated with graft loss, aHR 6.72 (95% CI: 1.36-33.29). In paired biopsies, recipients with fibrosis one year after transplantation had a fivefold higher risk of fibrosis at follow-up than those without. Inflammation was not associated with graft loss or mortality, and fibrosis was not associated with mortality. To conclude, recipients with fibrosis one year after transplantation had an increased risk of graft loss. Protocol biopsies remain valuable for detecting subclinical changes, pending further research to determine the effect on graft loss prevention.

Colorectal cancer is a leading cause of cancer-associated death. Metastatic disease in the liver is common and is associated with severely diminished survival rates. Despite various treatment modalities, comprehensive long-term survival data following surgical interventions for colorectal liver metastases (CRLM) is limited. This nationwide multicenter study used data from the Danish Liver Cancer Group registry. Patients undergoing initial surgery, including hepatic resection, ablation, or both, were included. Survival analysis was conducted using the Kaplan-Meier estimator and Cox proportional hazards models to evaluate the prognostic impact of clinical preoperative factors. Multiple imputation was performed for missing values. Among 2316 patients, median survival was four years, with 1-, 3-, 5-, and 7-year survival rates of 91

Graft inflammation and fibrosis are associated with progressive fibrosis and potential graft loss after liver transplantation, but diagnosis relies on invasive biopsies. Torque teno virus (TTV) may be a noninvasive marker of functional immunity, however its association with these changes remains unclear. In this Nordic multicenter cohort study, plasma samples collected with biopsies were analyzed for TTV load, and biopsies were scored for inflammation and fibrosis. Associations and performance of TTV versus tacrolimus were evaluated using logistic regression and ROC curves. TTV was categorized using the Youden Index. Among 287 liver transplant recipients, median age was 55, mean TTV load 5 log10 copies/mL and median time from transplantation to TTV measurement 12 months. Low TTV load was associated with higher odds of fibrosis (aOR 2.96 [95% CI 1.40-6.25], adjusted for time since transplantation). Compared with tacrolimus, TTV load remained associated with fibrosis (2.64 [1.19-5.85]), whereas tacrolimus did not (1.16 [0.95-1.42]). The model including both markers had the highest AUC (0.69 [0.60-0.78]). At the optimal threshold, TTV demonstrated 64% sensitivity and specificity, positive predictive value 20% and negative predictive value 93%. TTV load was not significantly associated with inflammation. In conclusion, TTV load may support risk-stratified biopsy strategies, requiring external validation.

OBJECTIVE:To evaluate the association of Epigenetic age acceleration (EAA), measured using the Horvath, Pheno, and Grim clocks, with overall survival (OS), postoperative complications, and failure of adjuvant chemotherapy completion in patients with resectable pancreatic ductal adenocarcinoma (PDAC). BACKGROUND:Surgical resection is the only curative option for patients with PDAC. However, perioperative morbidity remains substantial, and existing risk assessments inadequately predict postoperative complications, adjuvant chemotherapy completion, and OS. EAA measures biological aging through DNA methylation patterns and may provide insights into these outcomes. METHODS:This prospective cohort study was conducted between July 2009 and May 2023, with follow-up extending to August 2024. Patients aged >18 who were scheduled for pancreatic surgery at Copenhagen University Hospital, Rigshospitalet, were included. Exclusion criteria were non-PDAC histology, non-resectable disease, salvage surgery (gastroenterostomy/hepaticojejunostomy only), or neoadjuvant chemotherapy. DNA methylation of preoperative blood samples was analyzed using the Infinium MethylationEPIC v2.0 Kit (Illumina). RESULTS:Among 332 patients (45% female, median age 69 y), higher preoperative Grim EAA was associated with reduced OS (hazard ratio (HR 1.12; 95% CI 1.02-1.27; P=0.024), increased severe postoperative complications (OR 1.77; 95% CI 1.16-2.68; P=0.008) and failure to complete adjuvant chemotherapy (OR 1.47; 95% CI 1.20-1.81; P<0.0001). CONCLUSION:Grim EAA may serve as a preoperative risk assessment tool for patients with resectable PDAC, potentially guiding personalized treatment. Further validation is required for clinical integration.

The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05–4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43–1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).

Abstract Background Life-long immunosuppressive treatment after liver transplantation (LT) prevents graft rejection but predisposes the LT recipient to infections. Herpesvirus infections are associated with morbidity and mortality among LT recipients. Among those, especially cytomegalovirus (CMV) and varicella-zoster virus (VZV) pose challenges after LT. The aim of this study is to provide an in-depth characterization of the cellular immune response against CMV and VZV infections in LT recipients and identify potential risk factors for infection. Methods The Herpesvirus Infections in Solid Organ Transplant Recipients – Liver Transplant Study (HISTORY) consists of an epidemiological and immunological substudy. The epidemiological substudy is a retrospective observational cohort study that includes all patients who underwent LT in Denmark between 2010 and 2023 (N ≈ 500). Using data from nationwide hospital records and national health registries, the incidence of and clinical risk factors for CMV and VZV infections will be determined. The immunological substudy is an explorative prospective observational cohort study including patients enlisted for LT in Denmark during a 1.5-year period (N > 80). Participants will be followed with scheduled blood samples until 12 months after LT. CMV- and VZV-derived peptides will be predicted for their likelihood to be presented in participants based on their HLA type. Peptide-MHC complexes (pMHC) will be produced to isolate CMV- and VZV-specific T cells from peripheral blood mononuclear cells before and after CMV and VZV infection. Their frequency, T cell receptor sequences, and phenotypic characteristics will be examined, and in a subset of participants, CMV- and VZV-specific T cells will be expanded ex vivo. Discussion This study will provide novel insight into T cell immunity required for viral control of CMV and VZV and has the potential to develop a prediction model to identify LT recipients at high risk for infection based on a combination of clinical and immunological data. Furthermore, this study has the potential to provide proof-of-concept for adoptive T cell therapy against CMV and VZV. Combined, this study has the potential to reduce the burden and consequence of CMV and VZV infections and improve health and survival in LT recipients. Trial registration ClinicalTrials.gov (NCT05532540), registered 8 September 2022.

Introduction: Minimally invasive liver surgery is evolving worldwide and robot-assisted liver surgery may have obvious benefits for patients. Safe and proper implementation of a robot-assisted liver surgery program is of utmost importance. Here, we present the steps of establishing a robot-assisted liver surgery program against the background of the initial experience at our institution in Denmark. Methods: A robot-assisted liver surgery program was started at Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark in June 2019. After formal theoretical training and practical simulation training of surgeons and personnel, the program using the Da Vinci Surgical System® (RALS) was initiated and implemented. As time passed, robot-assisted liver surgical procedures have increased in number and difficulty. As of June 2021, 50 cases have been performed. Results: We will in detail discuss the training program, and implementation of the robot-assisted liver surgery program. We will present safety considerations with regard to proper patient selection and how we gradually increased the complexity of the procedures from minor liver resections to extended hemi-hepatectomies. We will present the results of the first 50 consecutive cases who underwent robotic-assisted liver surgery from June 2019 to June 2021 with no mortality, a very low conversion rate and a low rate of adverse events Conclusion: Safe and successful implementation of a robot-assisted liver surgery program is feasible when applying systematic theoretical and practical training, proper patient selection, and a gradual increase in complexity of the procedures.

Background During the COVID pandemic there has been limited access to elective surgery including oncologic surgery in several countries world-wide. The aim of this study was to investigate if there was any lockdown effect on pancreatic surgery with special focus on malignant pancreatic and periampullary tumours. Methods Patients who underwent pancreatic surgery during the two Danish lockdown periods from 11. March 2020 and the following 12 months were compared with patients who were operated the preceding 3 years. Data on patients’ characteristics, waiting time, operations, and clinical outcomes were evaluated. Results During lockdown and the previous three years the annual number of resections were 242, 232, 253, and 254, respectively (p = 0.851). Although the numbers were not significantly different, there were fluctuations in operations and waiting time during the lockdown. During the second outbreak of COVID October 2020 to March 2021 the overall median waiting time increased to 33 days (quartiles 26;39) compared to 23 (17;33) days during the first outbreak from March to May 2020 (p = 0.019). The same difference was seen for patients with malignant tumours, 30 (23;36) vs. 22 (18;30) months (p = 0.001). However, the fluctuations and waiting time during lockdown was like the preceding three years. Neither 30- nor 90-days mortality, length of stay, number of extended operations, and complications and tumour stage were significantly different from previous years. Conclusions There were significant fluctuations in waiting time for operations during the lockdown, but these variations were not different from the preceding three years, wherefore other explanations than an impact from COVID are conceivable.

Introduction: Robot-assisted liver surgery is increasingly performed worldwide. The advantages of robot-assisted surgery are improved view and increased precision in operative technique. Robot-assisted surgery may have obvious benefits for patients, though more evidence is needed on the advantages and disadvantages of robot-assisted surgery when compared to open surgery. At our institution, a robot-assisted liver surgery program was implemented after formal theoretical and practical training using the Da Vinci Surgical System® (RALS). Methods: We performed a matched case-control study of the first 50 consecutive patients who were operated with robot-assisted liver resection at our institution at Rigshospitalet, Copenhagen University Hospital, Denmark from June 2019 to June 2021. Patients operated with robot-assisted surgery were matched to patients who underwent open liver resection with regard to age, ASA-score, type of liver surgery, and ttumor type using MedCalc® Statistical Software. Results: We will present outcomes of the first 50 consecutive cases who underwent robot-assisted liver surgery compared with a matched group of 50 patients who underwent open liver surgery. We will report mortality, complications (using the Clavien-Dindo classification), procedure time, blood loss, duration of hospital admission, and rate of re-admissions. Conclusion: Favourable results can be achieved with robot-assisted liver surgery already at the start of the program. Our study adds to the necessary evidence required to establish the advantages and disadvantages of robot-assisted liver surgery when compared to open liver surgery.

Abstract Background Glucocorticoids modulate the surgical stress response. Previous studies showed that high-dose preoperative glucocorticoids reduce levels of postoperative inflammatory markers and specific biomarkers of liver damage compared with placebo, and suggested a reduced complication rate and shorter hospital stay after liver surgery. However, there are no studies with a clinical primary outcome or of early recovery outcomes. The aim of this study was to investigate whether a single high dose of preoperative glucocorticoid reduces complications in the immediate postoperative phase after liver surgery. Methods This was a single-centre, double-blinded, parallel-group RCT investigating preoperative methylprednisolone 10 mg/kg (high dose) versus dexamethasone 8 mg (standard-dose postoperative nausea prophylaxis) in patients scheduled for open liver resection. The primary outcome was number of patients with a complication in the postanaesthesia care unit; secondary outcomes included duration of hospital stay, pain and nausea during admission, and 30-day morbidity. Results A total of 174 patients (88 in high-dose group, 86 in standard-dose group) were randomized and analysed (mean(s.d.) age 65(12) years, 67.2 per cent men); 31.6 per cent had no serious co-morbidities and 25.3 per cent underwent major liver resection. Complications occurred in the postanaesthesia care unit in 51 patients (58 per cent) in the high-dose group and 58 (67 per cent) in the standard-dose group (risk ratio 0.86, 95 per cent c.i. 0.68 to 1.08; P = 0.213). Median duration of hospital stay was 4 days in both groups (P = 0.160). Thirty-day morbidity and mortality rates were similar in the two groups. Conclusion A high dose of preoperative glucocorticoids did not reduce acute postoperative complications after open liver resection compared with a standard dose. Registration number: NCT03403517 (http://www.clinicaltrials.gov); EudraCT 2017–002652-81 (https://eudract.ema.europa.eu/).

Egeland, Charlotte K. MD; Rostved, Andreas A. MD, PhD; Aagaard Schultz, Nikolai MD, PhD; Pommergaard, Hans-Christian MD, PhD; Daugaard, Thomas R. MD; Thoefner, Line B. MD; Hillingsoe, Jens MD, PhD; Rasmussen, Allan MD Author Information

OBJECTIVE:To explore the reliability and validity of the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale for point-of-care ultrasonography (POC US) performance.BACKGROUND:POC US is increasingly used by clinicians and is an essential part of the management of acute surgical conditions. However, the quality of performance is highly operator-dependent. Therefore, reliable and valid assessment of trainees' ultrasonography competence is needed to ensure patient safety.METHODS:Twenty-four physicians, representing novices, intermediates, and experts in POC US, scanned 4 different surgical patient cases in a controlled set-up. All ultrasound examinations were video-recorded and assessed by 2 blinded radiologists using OSAUS. Reliability was examined using generalizability theory. Construct validity was examined by comparing performance scores between the groups and by correlating physicians' OSAUS scores with diagnostic accuracy.RESULTS:The generalizability coefficient was high (0.81) and a D-study demonstrated that 1 assessor and 5 cases would result in similar reliability. The construct validity of the OSAUS scale was supported by a significant difference in the mean scores between the novice group (17.0; SD 8.4) and the intermediate group (30.0; SD 10.1), P = 0.007, as well as between the intermediate group and the expert group (72.9; SD 4.4), P = 0.04, and by a high correlation between OSAUS scores and diagnostic accuracy (Spearman ρ correlation coefficient = 0.76; P < 0.001).CONCLUSIONS:This study demonstrates high reliability as well as evidence of construct validity of the OSAUS scale for assessment of POC US competence. Hence, the OSAUS scale may be suitable for both in-training as well as end-of-training assessment.

BACKGROUND:Pancreatic trauma in children is a serious condition with high morbidity. Blunt traumatic pancreatic lesions in children can be treated non-operatively or operatively. For less severe, grade I and II, blunt pancreatic trauma a non-operative or conservative approach is usually employed. Currently, the optimal treatment, of whether to perform operative or non-operative treatment of severe, grade III to V, blunt pancreatic injury in children is unclear. OBJECTIVES:To assess the benefits and harms of operative versus non-operative treatment of blunt pancreatic trauma in children. SEARCH METHODS:We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (Issue 5, 2013), MEDLINE (OvidSP), EMBASE (OvidSP), ISI Web of Science (SCI-EXPANDED and CPCI-S) and ZETOC. In addition, we searched bibliographies of relevant articles, conference proceeding abstracts and clinical trials registries. We conducted the search on the 21 June 2013. SELECTION CRITERIA:We planned to select all randomised clinical trials investigating non-operative versus operative treatment of blunt pancreatic trauma in children, irrespective of blinding, publication status or language of publication. DATA COLLECTION AND ANALYSIS:We used relevant search strategies to obtain the titles and abstracts of studies that were relevant for the review. Two review authors independently assessed trial eligibility. MAIN RESULTS:The search found 83 relevant references. We excluded all of the references and found no randomised clinical trials investigating treatment of blunt pancreatic trauma in children. AUTHORS' CONCLUSIONS:This review shows that strategies regarding non-operative versus operative treatment of severe blunt pancreatic trauma in children are not based on randomised clinical trials. We recommend that multi-centre trials evaluating non-operative versus operative treatment of paediatric pancreatic trauma are conducted to establish firm evidence in this field of medicine.

Background and Aims: The objective was to determine the sensitivity and specificity of Focused Assessment with Sonography for Trauma (FAST) in patients with confirmed liver lesions and also to compare results from surgeons trained in FAST with results from radiologists trained in general abdominal ultrasound as part of the specialist training. Explorative laparotomy or CT served as gold standard. Materials and Methods: This retrospective study included all patients admitted to our institution from 2003 to 2010 registered with the diagnosis "Injury of the liver or gall-bladder". Of 405 patients, 135 patients were eligible for analysis. Seventy-two patients were examined by radiologists and 63 by surgeons. Results: We found FAST to have a sensitivity, specificity, PPV, and NPV of 79.6%, 100%, 100%, and 68.9%. There was no statistically significant difference between FAST performed by radiologists and surgeons trained in FAST. Conclusion: FAST remains an important screening tool in abdominal trauma including liver lesions, and can be performed at a satisfactory level by surgeons trained in the FAST procedure only.

We present the first case of a gastric bezoar caused by barium sulphate acting as an intermittently occluding mass in a patient who had undergone small bowel follow-through on suspicion of small bowel obstruction (SBO) after total pancreatectomy. The patient underwent acute surgery but intermittent symptoms of SBO persisted. A barium bezoar was seen on plain abdominal film and afterwards diluted and fragmented gastroscopically. A barium bezoar giving rise to SBO is a possible complication to barium follow-through in patients with impaired gastric transit time.

INTRODUCTION Hypovolaemic shock is a major course of death in trauma patients. The mortality in patients in profound shock at the time of arrival is extremely high and we wanted to investigate the outcome of patients undergoing laparotomy at the Trauma Care Unit (TCU). MATERIAL AND METHODS Forty-four emergency laparotomies performed at the TCU at Rigshospitalet between January 2003 and December 2009 were registered. The indication for surgical intervention was based on persisting, unstable haemodynamics and either positive findings at focused abdominal sonography in trauma (FAST) or penetrating injury. In some patients, laparotomy was performed despite a negative FAST because of ongoing instability. The patients were stratified according to their systolic blood pressure (BP). RESULTS After 24 hours, 46% (20 patients) of the patients were alive. The survival after 30 days was 41% (18 patients). Stratifying the patients into three categories according to the systolic BP at the time of arrival (BP > 80 mmHg (n = 14), 80 mmHg ≥ BP > 60 mmHg (n = 10) and BP ≤ 60 mmHg (n = 20) revealed a 64%, 50% and 34% survival rate within the first 24 hours (p = 0.04). In the group of patients with BP ≤ 60 mmHg, the survival decreased to 20% after 30 days. Stratification by penetrating or blunt trauma showed no significant difference in survival (40% versus 50% survival after 30 days) (p = 0.40). However, in those patients arriving with BP ≤ 60 mmHg (five penetrating and 15 blunt injuries), we found that the survival rate after laparotomy was 60% and 13%, respectively. CONCLUSION The present study shows that haemodynamically unstable patients with abdominal or suspected abdominal injuries undergoing emergency laparotomy have a high mortality, especially those with BP ≤ 60 mmHg. Patients with a penetrating trauma have a far better prognosis than those with a blunt trauma.

The article is a review of the literature concerning the use of topical negative pressure (TNP) in open abdomen. TNP appears to be superior to other methods in that the frequency of ventral hernia seems to be less after TNP than after other methods. TNP reduces both the cost of nursing and the damage to the abdominal wall. Vacuum-assisted closure (VAC) appears to be superior to the vacuum pack technique, but there is a lack of studies comparing the two methods of TNP in open abdomen.