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.

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 (<6 months after resection) or late (>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.<br />

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries. Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761).

AimThis study investigated healthcare professionals attitudes and perceptions towards the familys participation in surgical cancer care. DesignA prospective mixed method study. MethodsThe study was conducted at three hospitals in Sweden with registered nurses, assistant nurses and surgeons. Data included 43 completed Families Importance in Nursing Care (FINC-NA) questionnaires answered by registered nurses and qualitative data from 14 interviews with surgeons and assistant nurses. Data analysis was performed according to the Creswell convergent parallel mixed method. ResultsBoth quantitative and qualitative data demonstrated that the family was an important resource in nursing care, was highly valued as a conversational partner and had resources that should be considered. Each family should be supported in determining their role and as implements for maintaining a functioning family constellation and increasing their participation. Patient or Public ContributionNo patient or public contribution.

Background

Laparoscopic distal pancreatectomy is being implemented worldwide. The aim of this study was to perform a cost-effectiveness analysis from a health care perspective.

Methods

This cost-effectiveness analysis was based on the randomized controlled trial LAPOP, where 60 patients were randomized to open or laparoscopic distal pancreatectomy. For the follow-up of two years, resource use from a health care perspective was recorded, and health-related quality of life was assessed using the EQ-5D-5L. The per-patient mean cost and quality-adjusted life years (QALYs) were compared using nonparametric bootstrapping.

Results

Fifty-six patients were included in the analysis. The mean health care costs were lower, €3863 (95% CI: -€8020 to €385), for the laparoscopic group. Postoperative quality of life improved with laparoscopic resection and resulted in a gain in QALYs of 0.08 (95% CI: −0.09 to 0.25). The laparoscopic group had lower costs and improved QALYs in 79% of bootstrap samples. With a cost-per-QALY threshold of €50 000, 95.4% of the bootstrap samples were in favour of laparoscopic resection.

Conclusion

Laparoscopic distal pancreatectomy is associated with numerically lower health care costs and improvements in QALYs compared with the open approach. The results support the ongoing transition from open to laparoscopic distal pancreatectomies.

Background and objective: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. Methods: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. Results: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. Conclusions: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.

Study Purpose The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. Methods The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Results Not applicable. Conclusion DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR.

Objective Fast-track concepts have been implemented in hepatopancreatobiliary surgery cancer care to improve postoperative recovery. For optimal postoperative care, patient participation is also required. The aim was to investigate and analyse whether an intervention with patient-owned fast-track protocols (PFTPs) may lead to increased patient participation and improve information for patients who underwent surgery for hepatopancreatobiliary cancer. Methods A quantitative comparative design with a control and intervention group was used. The participants in the intervention group followed a PFTP during their admission. After discharge, the patients answered a questionnaire regarding patient participation. Data analyses were performed with descriptive statistics and ANCOVA. Results The results are based on a total of 222 completed questionnaires: 116 in the control group and 106 in the intervention group. It is uncertain whether the PFTP increased patient participation and information, but its use may indicate an improvement for the patient group. Conclusion A successful implementation strategy for the use of PFTP, with daily reconciliations, could be part of the work required to improve overall satisfaction with patient participation.

Background: Many patients with bi-lobar liver tumours are not eligible for liver resection due to an insufficient future liver remnant (FLR). To reduce the risk of posthepatectomy liver failure and the primary cause of death, regenerative procedures intent to increase the FLR before surgery. The aim of this systematic review is to provide an overview of the available literature and outcomes on the effectiveness of simultaneous portal and hepatic vein embolization (PVE/HVE) versus portal vein embolization (PVE) alone.

Methods: A systematic literature search was conducted in PubMed, Web of Science, and Embase up to September 2022. The primary outcome was resectability and the secondary outcome was the FLR volume increase.

Results: Eight studies comparing PVE/HVE with PVE and six retrospective PVE/HVE case series were included. Pooled resectability within the comparative studies was 75 per cent in the PVE group (n = 252) versus 87 per cent in the PVE/HVE group (n = 166, OR 1.92 (95% c.i., 1.13-3.25)) favouring PVE/HVE (P = 0.015). After PVE, FLR hypertrophy between 12 per cent and 48 per cent (after a median of 21-30 days) was observed, whereas growth between 36 per cent and 67 per cent was reported after PVE/HVE (after a median of 17-31 days). In the comparative studies, 90-day primary cause of death was similar between groups (2.5 per cent after PVE versus 2.2 per cent after PVE/HVE), but a higher 90-day primary cause of death was reported in single-arm PVE/HVE cohort studies (6.9 per cent, 12 of 175 patients).

Conclusion: Based on moderate/weak evidence, PVE/HVE seems to increase resectability of bi-lobar liver tumours with a comparable safety profile. Additionally, PVE/HVE resulted in faster and more pronounced hypertrophy compared with PVE alone.

Colorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver.