Celina Limbecker

The Karolinska Liver Metastases (KaroLiver) cohort was established to investigate associations between clinical characteristics and histopathological features in patients treated with curative intent for colorectal cancer liver metastases (CRLM). The cohort combines whole-slide digital histopathology images with detailed oncological, surgical, radiological and survival data, enabling comprehensive analyses of treatment trajectories, clinical outcomes and metastatic tumour biology. KaroLiver is a retrospective observational cohort comprising all consecutive patients who received curative-intent, liver-directed treatment for CRLM at Karolinska University Hospital in Stockholm, Sweden. The hospital is the regional referral centre for hepatopancreatobiliary (HPB) surgery, serving the population of approximately 2.5 million people in the Stockholm-Gotland healthcare region. Patient enrolment is continuously updated in accordance with amended ethical approvals and evolving scientific questions. The cohort currently comprises 811 patients who underwent 1204 liver interventions between February 2012 and January 2022. Detailed clinical, oncological, surgical, pathological, molecular, recurrence and survival data are collected. Median overall survival (OS) in the current cohort is 51.0 months (95% CI 46.2 to 57.1 months), and median recurrence-free survival (RFS) is 10.4 months (95% CI 9.2 to 11.9 months). The 5-year OS rate is 44.9% (95% CI 41.2% to 48.8%). Studies using the cohort have so far identified a liver injury-derived stromal capsule in a subset of metastases associated with improved survival. The cohort has also enabled the identification of histopathological markers of tumour biology, sex-based differences in treatment and survival, and associations between post-hepatectomy liver failure and oncological outcomes. Current research priorities include advanced histology-based prognostic scoring, sex differences in recurrence and retreatment, tumour biology and outcomes in early-onset versus average-onset CRLM, as well as CT-based and MRI-based radiomics, all integrated within KaroLiver’s histopathological framework. Data sharing is supported, given that regulatory requirements are met. Retrospective accrual and outcome updates will continue for current and future studies, subject to the required approvals.

The increasing use of immune checkpoint inhibitors (ICI) has led to recognition of a broad spectrum of treatment‐associated inflammatory adverse events, including pancreatic injury. Histological overlap between ICI associated pancreatic injury (ICIPI) and so‐called autoimmune pancreatitis (AIP) has been suggested in isolated reports, but the extent and detailed histopathological features of this overlap remain poorly characterized. The aim of this study was to describe the clinicopathological and histological features of rare ICIPI cases with available tissues and to compare these findings with established histological patterns of AIP. Data were available for five cases. All patients except one were female. ICIPI occurred between 182–580 days after initiation of ICI therapy. All patients had received a combination ICI treatment (e.g., Ipilimumab + Nivolumab). Peak serum lipase levels ranged from 4 to 41 (µkat/L). Computed tomography demonstrated radiologic features consistent with autoimmune pancreatitis (AIP) in four cases, whereas one case raised suspicion of a metastatic lesion. Three patients were treated with steroids, following which pancreatitis (lipase and imaging) resolved. Two patients developed pancreatic atrophy or exocrine insufficiency. Two patients underwent surgical resection because of suspected cancer metastasis. Fine needle biopsy showed only nonspecific atrophy and mild chronic inflammation. In contrast, both surgical specimens demonstrated marked histological overlap with type 2 AIP, including duct‐centric inflammatory changes and granulocytic epithelial lesions, whereas increased IgG4‐positive plasma cells or other features characteristic of type 1 AIP were not identified. Our results, together with the limited published literature, suggest that ICIPI may encompass a heterogeneous spectrum of histological changes, with substantial overlap with type 2 AIP in a subset of cases. Recognition of these overlapping features is important in the histopathological diagnosis of pancreatic inflammatory lesions in patients receiving ICI therapy. Treatment of ICIPI should follow NCCN recommendations. The risk of developing a pancreatic exocrine insufficiency needs to be observed.

Purpose: The Karolinska Liver Metastases (KaroLiver) cohort was established to investigate associations between clinical characteristics and histopathological features in patients treated with curative intent for colorectal cancer liver metastases (CRLM). The cohort combines whole-slide digital histopathology images with detailed oncological, surgical, radiological and survival data, enabling comprehensive analyses of treatment trajectories, clinical outcomes and metastatic tumour biology. Participants: KaroLiver is a retrospective observational cohort comprising all consecutive patients who received curative-intent, liver-directed treatment for CRLM at Karolinska University Hospital in Stockholm, Sweden. The hospital is the primary regional referral centre for HPB surgery, serving the population of approximately 2.5 million people in the Stockholm-Gotland healthcare region. Patient enrolment is continuously updated in accordance with amended ethical approvals and evolving scientific questions. The cohort currently comprises 811 patients who underwent 1204 liver interventions between February 2012 and January 2022. Detailed clinical, oncological, surgical, pathological, molecular, recurrence and survival data are collected. Findings to date: Median overall survival (OS) in the current cohort is 51.0 months (95% CI 46.2–57.1 months), and median recurrence-free survival (RFS) is 10.4 months (95% CI 9.2–11.9 months). The five-year OS rate is 44.9% (95% CI 41.2–48.8%). Studies using the cohort have so far identified a liver injury-derived stromal capsule in a subset of metastases, associated with improved survival. The cohort has also enabled the identification of histopathological markers of tumour biology, sex-based differences in treatment and survival, and associations between post-hepatectomy liver failure and oncological outcomes. Future plans: Current research priorities include advanced histology-based prognostic scoring, sex differences in recurrence and retreatment, tumour biology and outcomes in early-onset versus average-onset CRLM, as well as CT- and MRI-based radiomics, all integrated within KaroLiver’s histopathological framework. Data sharing is supported, given that regulatory requirements are met. Retrospective accrual and outcome updates will continue for current and future studies, subject to the required approvals. Strengths and limitations of this study: □ Selection bias in KaroLiver is minimised through consecutive, population-based accrual of all patients receiving curative-intent liver-directed treatment for CRLM at a high-volume Swedish tertiary centre. □ Granular data on recurrence, including site, timing, and intent of retreatment, enable detailed analyses of disease trajectories beyond the index hepatectomy. □ KaroLiver is linked to CT and MRI examinations from diagnosis through recurrence; combined with detailed histopathological and molecular pathology data, this provides a platform for translational research, based on specific, defined research questions. □ The observational design limits causal inference, and changes in treatment strategies and follow-up protocols over the study period may introduce temporal confounding that must be accounted for in analyses. □ Molecular data, including RAS / RAF mutation status and mismatch repair status, are incomplete, reflecting real-world clinical practice and the gradual adoption of tumour profiling over the study period.