In patients undergoing parenchyma-sparing liver resection for colorectal metastases, laparoscopic surgery was associated with significantly less postoperative complications compared to open surgery. Laparoscopic resection was cost-effective compared to open resection with a 67% probability. The rate of free resection margins was the same in both groups. Our results support the continued implementation of laparoscopic liver resection.

Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.

My special appreciation goes to a talented surgeon, my colleague and friend Dr. Åsmund Fretland, who has been a remarkable co-supervisor to me. Your research and surgical skills, positiveness and the ability to solve problems quickly have always impressed me. Thank you for letting me to take over your work in the OSLO-COMET trial and for introducing me to all the details. It is always my great pleasure to draft articles together with you, be your assistant at liver surgery and attend conferences together with you. My classmate, colleague and friend Dr. Mushegh Sahakyan deserves my deepest gratitude. You are a role model for me as a young talented and hard-working researcher. I have learned a lot from our discussions about surgical procedures, article drafting, methodologies and statistics in research. I am very glad that you are back to Norway and our research group. I look forward to continuing our fruitful cooperation and Armenian barbeques together. I would like to thank Prof. Erik Fosse for the opportunity to work at the Intervention Centre, where you have created an outstanding multi-speciality research team. Communication with multidisciplinary research teams and professionals at IVS have extended my horizons. It was my pleasure to work alongside Marianne Berg, Linda Engvik, nurses and radiology team.

Objective: We conducted a randomized, controlled, noninferiority trial to investigate if intravenous, multimodal, patient-controlled analgesia (IV-PCA) could be noninferior to multimodal thoracic epidural analgesia (TEA) in patients undergoing open liver surgery. Summary Background Data: The increasing use of minimally invasive techniques and fast track protocols have questioned the position of epidural analgesia as the optimal method of pain management after abdominal surgery. Methods: Patients operated with open liver resection between February 2012 and February 2016 were randomly assigned to receive either IV-PCA enhanced with ketorolac/diclofenac (IV-PCA, n = 66) or TEA (n = 77) within an enhanced recovery after surgery protocol. Noninferiority would be declared if the mean pain score on the numeric rating scale (NRS) for postoperative days (PODs) 0 to 5 in the IV-PCA group was no worse than the mean pain score in the TEA group by a margin of <1 point on an 11-point scale (0–10). Results: The primary endpoint, mean NRS pain score was 1.7 in the IV-PCA group and 1.6 in the TEA group, establishing noninferiority. Pain scores were lower in the TEA group on PODs 0 and 1, but higher or equal on PODs 2 and 5. Postoperative hospital stay was significantly shorter for patients in the IV-PCA group (74 vs 104 h, P < 0.001). The total opioid consumption during the first 3 days was significantly lower in the IV-PCA group. Conclusions: IV-PCA was noninferior to TEA for the treatment of postoperative pain in patients undergoing open liver resection.

The material presented in this manuscript was partly reported as oral presentation at the 12th

Patients with colorectal liver metastases (CLM) commonly receive neoadjuvant chemotherapy (NACT) prior to surgical resection. NACT may induce immunogenic cell death with subsequent recruitment of T-cells to the tumor microenvironment, which could be exploited by immune checkpoint inhibition (ICI). In theory, this could expand the use of ICI to obtain responses also in microsatellite stable colorectal cancer, but evidence to suggest optimal treatment schedules are lacking. In this study, densities of total-, cytotoxic-, helper- and regulatory T-cells were quantified by immunohistochemistry in resected CLM from 92 patients included in the OSLO-COMET trial (NCT01516710). All but one patient had microsatellite stable tumors (91/92). Associations between T-cell densities and clinicopathological parameters were analyzed. Fluoropyrimidine-based NACT (in most cases with addition of oxaliplatin or irinotecan) was administered to 45 patients completed median 8 weeks prior to surgical resection. No overall association was found between NACT administration and intratumoral T-cell densities. However, within the NACT group, a short time interval (<9.5 weeks) between NACT completion and CLM resection was strongly associated with high intratumoral T-cell densities compared to the long-interval and no NACT groups (medians 491, 236, and 292 cells/mm 2 , respectively; P < .0001). The results from this study suggest that the observed increase in intratumoral T-cells after NACT administration may be transient. The significance of this finding should be further explored to ensure that optimal treatment schedules are chosen for studies combining cytotoxic chemotherapy and ICI.

BackgroundMetastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to identify molecular characteristics of metastatic disease and evaluate the clinical relevance.MethodsIn this ancillary study to the Oslo-CoMet trial, CLM and tumor-adjacent liver tissue from 46 patients were analyzed by profiling mutations (targeted sequencing), genome-wide copy number alteration (CNAs), and gene expression.ResultsSomatic mutations and CNAs detected in CLM were similar to reported primary CRC profiles, while CNA profiles of eight metastatic pairs suggested intra-patient divergence. A CMS classifier tool applied to gene expression data, revealed the cohort to be highly enriched for CMS2. Hierarchical clustering of genes with highly variable expression identified two subgroups separated by high or low expression of 55 genes with immune-related and metabolic functions. Importantly, induction of genes and pathways associated with immunogenic cell death (ICD) was identified in metastases exposed to neoadjuvant chemotherapy (NACT).ConclusionsThe uniform classification of CLM by CMS subtyping may indicate that novel class discovery approaches need to be explored to uncover clinically useful stratification of CLM. Detected gene expression signatures support the role of metabolism and chemotherapy in shaping the immune microenvironment of CLM. Furthermore, the results point to rational exploration of immune modulating strategies in CLM, particularly by exploiting NACT-induced ICD.

Background Most treatments for cancer cause a decline in patients' health‐related quality of life (HRQoL). Limiting this decline is a universal goal for healthcare providers. Using minimally invasive instead of open surgical techniques might be one way to achieve this. The aim of this study was to compare postoperative HRQoL after open and laparoscopic liver resection. Methods This was a predefined substudy of an RCT comparing open with laparoscopic liver resection. Patients with colorectal liver metastases were assigned randomly to open or laparoscopic parenchyma‐sparing liver resection. HRQoL was assessed with the Short Form 36 questionnaire at baseline, and 1 and 4 months after surgery. Results A total of 280 patients were randomized, of whom 273 underwent surgery (129 laparoscopic, 144 open); 682 questionnaires (83.3 per cent) were available for analysis. One month after surgery, patients in the laparoscopic surgery group reported reduced scores in two HRQoL domains (physical functioning and role physical), whereas those in the open surgery group reported reduced scores in five domains (physical functioning, role physical, bodily pain, vitality and social functioning). Four months after surgery, HRQoL scores in the laparoscopic group had returned to preoperative levels, whereas patients in the open group reported reduced scores for two domains (role physical and general health). The between‐group difference was statistically significant in favour of laparoscopy for four domains after 1 month (role physical, bodily pain, vitality and social functioning) and for one domain after 4 months (role physical). Conclusion Patients assigned to laparoscopic liver surgery reported better postoperative HRQoL than those assigned to open liver surgery. For role limitations caused by physical health problems, patients in the laparoscopic group reported better scores up to 4 months after surgery. Registration number: NCT01516710 ( http://www.clinicaltrials.gov).