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Background Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study. Methods The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons. Results A total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0–12% and 27–62%, and for permanently unresectable CRLM between 3–40% and 6–47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients. Conclusion Considerable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-based decisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice.

Additional file 1. Handbook histopathological features CRC – HGP.

Additional file 2. Supplementary File 2. Uni- and multivariable Cox regression analysis for overall survival.

Patients with constitutional mismatch repair deficiency syndrome(CMMRD) usually develop multiple tumors at a young age. Chemotherapywas previously shown to be less effective in these tumors. Recent reportssuggest immunotherapeutic treatment in CMMRD-associated tumors. Here,we present a CMMRD patient, successfully treated with immunotherapyfor metastasized colorectal cancer (CRC). A young adolescent male wasdiagnosed with T2N2M1 cecum carcinoma with liver metastases. Hereceived four initial doses of nivolumab (3 mg/kg) with ipilimumab (1 ml/kg) every three weeks, followed by 41 doses of nivolumab alone every twoweeks. A complete response was achieved; also pathological assessmentof removed liver metastases was indicative of a complete response. Atthe time of writing, 14 months after end of treatment, the CRC had notrecurred. Immunotherapeutic treatment resulted in a complete response ofthe primary CRC and metastases. Immunotherapy as first line treatmentshould be strongly considered in treatment of CMMRD-associated CRCs

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.

Additional file 1: Figure S1. The compatibility of different blood collection tubes with MeD-seq analysis. Percentages of A. LpnPI filtered reads and B. duplicate reads are shown for EDTA and CellSave tubes obtained during the same blood draw from 3 patients. For each sample, 10 ng cfDNA and maximal cfDNA input in 8 µl (> 10 ng) was analysed, in which the maximal amount was kept equal between EDTA and CellSave per patient.

Additional file 4: Figure S4. MeD-seq results for published biomarkers on cfDNA from HBDs and paired tissue, pre-operative and post-operative cfDNA from CRLM patients. Sequenced MeD-seq reads shown for BCAT1, IKZF1, SEPT9, B4GALT1, MAP3K14-AS1, and SHOX2 from pre-operative cfDNA (red) and post-operative cfDNA (orange) of CRLM-patients and cfDNA samples of HBDs (black). Results are visualized in Integrative Genomics Viewer (IGV) v.2.9.4.

Additional file 3: Figure S3. Leukocyte-specific markers in HBDs. A heat map of a subset of leukocyte-specific methylation markers described by Accomando et al. (17) shows consistent methylation patterns across the included healthy blood donors. Only regions showing at least 1 read in 9 HBD samples are included.

Additional file 5: Figure S5. Correlation between MeD-seq and qMSP for previously identified markers for CRLM. Scatterplots showing the Pearson correlations between MeD-seq and qMSP results for A. EYA4, B. GRIA4, C. MSC, and D. ITGA4.

Additional file 2: Figure S2. Observed correlations between biological replicates compared to HBDs. Boxplots show significant higher Pearson’s r between biological replicates per patient (n = 4), in white, compared to the Pearson’s r between these samples and unrelated HBD samples (n = 9), in grey (Mann–Whitney U, p = 0.015 for M4, p = 0.004 for M10, and p

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