Sarcopenic Obesity Promotes Recurrence in Patients Undergoing Resection for Colorectal Liver Metastases (CRLM).

BACKGROUND/AIM: Sarcopenia, is predictive of a worse outcome after resection for colorectal liver metastases (CRLM). Obesity leads to a metabolic double burden if sarcopenia is as present, prompting malignancy progression, known as sarcopenic obesity (SO). This study aimed to compare sarcopenia and SO in patients undergoing CRLM resection, to prognostic parameters. PATIENTS AND METHODS: The skeletal muscle index (SMI) defined sarcopenia using sex specific cut off values (48.4 cm2/m2 for females and 59.1 cm2/m2 for males) by calculating the preoperative muscle mass at the vertebral height L3 using OSIRIX DICOM viewer. SO was determined as sarcopenia in patients showing obesity, as shown via fat percentage measurements on the preoperative CT scan. Established prognostic parameters (KRAS status, TNM classification, inflammatory response) were evaluated against SMI and SO to assess their predictability for postoperative outcomes. RESULTS: A total of 251 patients (62% female, median age 68 years) were included. Sarcopenic patients showed a threefold higher risk for postoperative death as compared to non-sarcopenic patients (p=0.04). Prevalent SO increased this risk to fivefold (p=0.01) compared to non-sarcopenic patients. COX regression analysis revealed SO and KRAS positivity as independent prognostic factors for disease-free survival (SO: p=0.038; KRAS: p=0.041; TNM, tumor size, Charlson Comorbidity Index, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio all not significant). Patients risk of death in case of KRAS positivity and SO was seven times higher (p=0.03). CONCLUSION: There seems to be a benefit in merging data on mutational status and muscle wasting in patients with CRLM to facilitate an individual, patient-tailored approach.

Mechanical upper bowel obstruction caused by a large trichobezoar in a young woman: A very unusual case report.

BACKGROUND: Bezoars usually compile human fibers and debris. A special form of bezoar in case of psychologically altered individuals is the trichobezoar. It consists of voluntarily swallowed hair bulks and is normally removed via gastroscopy. Trichobezoars leading to ileus have rarely been reported. CASE SUMMARY: A 24-year-old female patient presented to the emergency room with abdominal pain, nausea, and vomiting for 3 d. Her previous medical and psychiatric history was unremarkable. Laboratory analysis showed iron deficiency anemia, leukocytosis, and elevated liver enzymes. An abdominal CT scan revealed a dense structure in the patients' stomach which turned out to be a huge trichobezoar completely obstructing the pylorus. The trichobezoar had to be removed surgically. During her postoperative course, a subcutaneous seroma formed. After a single puncture, the rest of the recovery process was unremarkable, and the patient recovered fully. CONCLUSION: A mechanical bowel obstruction is a potentially life-threatening event for every patient. In our case a young female was suffering from severe symptoms of an obstruction which might have resulted in serious harm without successful surgical management.

Evolution of plant cell-type-specific cis -regulatory elements.

Cis -regulatory elements (CREs) are critical in regulating gene expression, and yet our understanding of CRE evolution remains a challenge. Here, we constructed a comprehensive single-cell atlas of chromatin accessibility in Oryza sativa , integrating data from 104,029 nuclei representing 128 discrete cell states across nine distinct organs. We used comparative genomics to compare cell-type resolved chromatin accessibility between O. sativa and 57,552 nuclei from four additional grass species ( Zea mays, Sorghum bicolor, Panicum miliaceum , and Urochloa fusca ). Accessible chromatin regions (ACRs) had different levels of conservation depending on the degree of cell-type specificity. We found a complex relationship between ACRs with conserved noncoding sequences, cell-type specificity, conservation, and tissue-specific switching. Additionally, we found that epidermal ACRs were less conserved compared to other cell types, potentially indicating that more rapid regulatory evolution has occurred in the L1 epidermal layer of these species. Finally, we identified and characterized a conserved subset of ACRs that overlapped the repressive histone modification H3K27me3, implicating them as potentially critical silencer CREs maintained by evolution. Collectively, this comparative genomics approach highlights the dynamics of cell-type-specific CRE evolution in plants.

Incidence of Diabetes Mellitus and Its Impact on Outcomes in Patients Undergoing Surgical Pancreatectomy for Non-Malignant and Malignant Pancreatobiliary Diseases-A Retrospective Analysis.

Diabetes mellitus (DM) is a prominent risk factor for malignant and non-malignant pancreatic diseases. Furthermore, the presence of DM predicts an unfavourable outcome in people with pancreatic cancer. This retrospective observational study investigated 370 patients who underwent pancreatic resection surgery for various indications (84.3% in malignant indication) in a single surgery centre in Graz, Austria. The preoperative and postoperative diabetes statuses were evaluated according to surgery method and disease entity and predictors for diabetes development after surgery, as well as outcomes (survival and cancer recurrence) according to diabetes status, were analysed. In the entire cohort, the postoperative diabetes (postopDM) incidence was 29%. PostopDM occurred significantly more frequently in malignoma patients than in those with benign diseases (31.3% vs. 16.7%; p = 0.040, OR = 2.28). In the malignoma population, BMI, longer surgery duration, and prolonged ICU and hospital stay were significant predictors of diabetes development. The 1- and 2-year follow-ups showed a significantly increased mortality of people with postopDM in comparison to people without diabetes (HR 1-year = 2.02, p = 0.014 and HR 2-years = 1.56, p = 0.034). Local cancer recurrence was not influenced by the diabetes status. Postoperative new-onset diabetes seems to be associated with higher mortality of patients with pancreatic malignoma undergoing pancreatobiliary surgery.

A rapid and sensitive, multiplex, whole mount RNA fluorescence in situ hybridization and immunohistochemistry protocol.

BACKGROUND: In the past few years, there has been an explosion in single-cell transcriptomics datasets, yet in vivo confirmation of these datasets is hampered in plants due to lack of robust validation methods. Likewise, modeling of plant development is hampered by paucity of spatial gene expression data. RNA fluorescence in situ hybridization (FISH) enables investigation of gene expression in the context of tissue type. Despite development of FISH methods for plants, easy and reliable whole mount FISH protocols have not yet been reported. RESULTS: We adapt a 3-day whole mount RNA-FISH method for plant species based on a combination of prior protocols that employs hybridization chain reaction (HCR), which amplifies the probe signal in an antibody-free manner. Our whole mount HCR RNA-FISH method shows expected spatial signals with low background for gene transcripts with known spatial expression patterns in Arabidopsis inflorescences and monocot roots. It allows simultaneous detection of three transcripts in 3D. We also show that HCR RNA-FISH can be combined with endogenous fluorescent protein detection and with our improved immunohistochemistry (IHC) protocol. CONCLUSIONS: The whole mount HCR RNA-FISH and IHC methods allow easy investigation of 3D spatial gene expression patterns in entire plant tissues.

Combining isotope ratios for provenancing Viking Age iron artefacts in the British Isles: a pilot study.

Stable and radiogenic isotope analysis - particularly using lead isotope analysis (LIA) - has previously been shown to be a useful tool for the provenancing of ancient metal artefacts of silver and copper and its alloys, but less progress has been made in the provenancing of iron artefacts, despite their importance and frequency in the archaeological record. In this pilot study we investigate for the first time the possibilities of iron isotope analysis in combination with trace strontium isotope analysis and LIA for the provenancing of iron objects believed to be from the Viking Age in the British Isles. Previous studies have shown that analysis of each of these isotopes can contribute to provenancing iron artefacts, but they are not individually resolutory. In this proof-of-concept study, we examine the Fe, Sr and Pb isotopes of 7 artefacts believed to derive from the Viking Age: 3 from Meols - a former Viking seaport on Wirral and 4 samples from the probable location of the AD 1066 Battle of Fulford in North Yorkshire. We also examine an additional artefact of unknown antiquity from Bebington Heath - a possible location of the AD 937 Battle of Brunanburh. Although the pilot data set is too small to make definitive conclusions, it has paved the way for a fuller study involving 100 samples (including 30 from the former Viking camp of Torksey, Lincolnshire) funded by the NEIF fund of the UK National Environmental Research Council. The high range of 87Sr/86Sr values in the present data set of 8 is beyond what would be expected for bog iron (with a cut-off ∼ 0.709) and suggests that mined ore was being used, a preliminary conclusion supported by the narrow range of Fe isotope data.

Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients.

BACKGROUND: Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. METHODS: This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. RESULTS: 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. DISCUSSION: Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting.

The regulation of chromatin configuration at AGAMOUS locus by LFR-SYD-containing complex is critical for reproductive organ development in Arabidopsis.

Switch defective/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are evolutionarily conserved, multi-subunit machinery that play vital roles in the regulation of gene expression by controlling nucleosome positioning and occupancy. However, little is known about the subunit composition of SPLAYED (SYD)-containing SWI/SNF complexes in plants. Here, we show that the Arabidopsis thaliana Leaf and Flower Related (LFR) is a subunit of SYD-containing SWI/SNF complexes. LFR interacts directly with multiple SWI/SNF subunits, including the catalytic ATPase subunit SYD, in vitro and in vivo. Phenotypic analyses of lfr-2 mutant flowers revealed that LFR is important for proper filament and pistil development, resembling the function of SYD. Transcriptome profiling revealed that LFR and SYD shared a subset of co-regulated genes. We further demonstrate that the LFR and SYD interdependently activate the transcription of AGAMOUS (AG), a C-class floral organ identity gene, by regulating the occupation of nucleosome, chromatin loop, histone modification, and Pol II enrichment on the AG locus. Furthermore, the chromosome conformation capture (3C) assay revealed that the gene loop at AG locus is negatively correlated with the AG expression level, and LFR-SYD was functional to demolish the AG chromatin loop to promote its transcription. Collectively, these results provide insight into the molecular mechanism of the Arabidopsis SYD-SWI/SNF complex in the control of higher chromatin conformation of the floral identity gene essential to plant reproductive organ development.

The Role and Activity of SWI/SNF Chromatin Remodelers.

SWITCH deficient SUCROSE NONFERMENTING (SWI/SNF) class chromatin remodeling complexes (CRCs) use the energy derived from ATP hydrolysis to facilitate access of proteins to the genomic DNA for transcription, replication, and DNA repair. Uniquely, SWI/SNF CRCs can both slide the histone octamer along the DNA or eject it from the DNA. Given their ability to change the chromatin status quo, SWI/SNF remodelers are critical for cell fate reprogramming with pioneer and other transcription factors, for responses to environmental challenges, and for disease prevention. Recent cryo-electron microscopy and mass spectrometry approaches have uncovered different subtypes of SWI/SNF complexes with unique properties and functions. At the same time, tethering or rapid depletion and inactivation of SWI/SNF have provided novel insight into SWI/SNF requirements for enhancer activity and into balancing chromatin compaction and accessibility in concert with Polycomb complexes. Given their importance, SWI/SNF recruitment to genomic locations by transcription factors and their biochemical activity is tightly controlled. This review focuses on recent advances in our understanding of SWI/SNF CRCs in animals and plants and discusses the multiple nuclear and biological roles of SWI/SNF CRCs and how SWI/SNF activity is altered by complex subunit composition, posttranslational modifications, and the chromatin context to support proper development and response to extrinsic cues.

Demystifying BRAF Mutation Status in Colorectal Liver Metastases : A Multi-institutional, Collaborative Approach to 6 Open Clinical Questions.

OBJECTIVE: To investigate the clinical implications of BRAF -mutated (mut BRAF ) colorectal liver metastases (CRLMs). BACKGROUND: The clinical implications of mut BRAF status in CRLMs are largely unknown. METHODS: Patients undergoing resection for mut BRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus non-V600E mutations, KRAS/BRAF comutation versus mut BRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management. RESULTS: A total of 240 patients harboring BRAF -mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs 144 mo, P =0.004), but not RFS compared with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P <0.001) but not OS (33.5 vs 41 mo, P =0.3) compared with MSI-high tumors, whereas patients with resected converted disease had slightly worse RFS (8 vs 11 mo, P =0.01) and similar OS (30 vs 40 mo, P =0.4) compared with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P <0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P =0.004). All results continued to hold true in the multivariable OS analysis. CONCLUSIONS: Although surgery may be futile in patients with BRAF -mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, second hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group, with regard to RFS while patients with non-V600E mutations have excellent prognosis.

Incidence and risk factors for anastomotic bile leakage in hepatic resection with bilioenteric reconstruction - A international multicenter study.

BACKGROUND: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions. METHODS: Data from consecutive patients who underwent liver resection and BR between 2004 and 2018 in 11 academic institutions in Europe were collected from prospectively maintained databases. RESULTS: Within 921 patients, AL rate was 5.4% with a 30d mortality of 9.6%. Pringle maneuver (p<0.001),postoperative external biliary (p=0.007) and abdominal drainage (p<0.001) were risk factors for clinically relevant AL. Preoperative biliary drainage (p<0.001) was not associated with a higher rate of AL. AL was more frequent in stented patients (76.5%) compared to PTCD (17.6%) or PTCD+stent (5.9%,p=0.017). AL correlated with increased incidence of postoperative liver failure (p=0.036), cholangitis, hemorrhage and sepsis (all p<0.001). CONCLUSION: This multicenter data provides the largest series to date of LR with BR and could help in the management of these patients which are often challenging and hampering the patients' postoperative course negatively.

Applying lead (Pb) isotopes to explore mobility in humans and animals.

Lead (Pb) isotopes provide a complementary method to other provenance tools for tracking the origin and movement of humans and animals. The method is founded in the geographic distribution of Pb isotope ratios. However, unlike the Sr isotope method that is closely linked to the lithology of underlying rocks, Pb more closely reflects the tectonic regimes. This makes it particularly pertinent to use in Britain as there is major tectonic boundary (the Iapetus Suture) that runs between Berwick-upon-Tweed and the Solway Firth providing a compositional boundary in Pb isotope domains that approximates to the geographic areas of Scotland versus England and Wales. Modern pollution makes it difficult to use modern floral or faunal samples to characterize biosphere variation, and so we use geological datasets to define isoscape variation and present the first Pb isotope map of Britain. We have validated the use of these data form biosphere studies using well provenanced samples. Reference fields of diagnostic compositions, are created in µ-T space and these have been used in a test case to assess the geographic origins of Neolithic animals in Great Britain.

Greenscreen: A simple method to remove artifactual signals and enrich for true peaks in genomic datasets including ChIP-seq data.

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is widely used to identify factor binding to genomic DNA and chromatin modifications. ChIP-seq data analysis is affected by genomic regions that generate ultra-high artifactual signals. To remove these signals from ChIP-seq data, the Encyclopedia of DNA Elements (ENCODE) project developed comprehensive sets of regions defined by low mappability and ultra-high signals called blacklists for human, mouse (Mus musculus), nematode (Caenorhabditis elegans), and fruit fly (Drosophila melanogaster). However, blacklists are not currently available for many model and nonmodel species. Here, we describe an alternative approach for removing false-positive peaks called greenscreen. Greenscreen is easy to implement, requires few input samples, and uses analysis tools frequently employed for ChIP-seq. Greenscreen removes artifactual signals as effectively as blacklists in Arabidopsis thaliana and human ChIP-seq dataset while covering less of the genome and dramatically improves ChIP-seq peak calling and downstream analyses. Greenscreen filtering reveals true factor binding overlap and occupancy changes in different genetic backgrounds or tissues. Because it is effective with as few as two inputs, greenscreen is readily adaptable for use in any species or genome build. Although developed for ChIP-seq, greenscreen also identifies artifactual signals from other genomic datasets including Cleavage Under Targets and Release Using Nuclease. We present an improved ChIP-seq pipeline incorporating greenscreen that detects more true peaks than other methods.

Gene Alterations, Mediators, and Artificial Intelligence in Colorectal Liver Metastases.

In this Special Issue of Cells, we seek articles that focus on the study of tumor biology in order to guide the scalpel [...].

Interdisciplinary Approach of Establishing PDAC Resectability: Biochemical, Radiological and NAT Regimen Prognostic Factors-Literature Review.

Background and Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal tumors, with a 5-year overall survival rate of less than 10%. To date, curative surgical resection remains the only favorable option for improving patients' survival. However, there is no consensus on which prognostic biochemical, radiological markers or neoadjuvant therapy regimens would benefit patients the most. Materials and Methods: A literature review was performed focusing on overall survival, R0 resection, 30-day mortality, adverse events (AEs), and elevated biomarkers. The electronic databases were searched from 2015 to 2020. Results: We reviewed 22 independent studies. In total, 20 studies were retrospective single- or multi-center reviews, while 2 studies were prospective Phase II trials. Conclusions: Patients with borderline resectable or locally advanced PDAC, who received neoadjuvant therapy (NAT) and surgery, have significantly better survival rates. The CA 19-9 biomarker levels in the neoadjuvant setting should be evaluated and considered as a specific biomarker for tumor resectability and overall survival.

Using Artificial Intelligence to Find the Optimal Margin Width in Hepatectomy for Colorectal Cancer Liver Metastases.

Importance: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width. Objective: To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics. Design, Setting, and Participants: The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité-University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021. Exposures: Hepatectomy. Main Outcomes and Measures: Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence-based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory-based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values. Results: This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort. Conclusions and Relevance: This cohort study used artificial intelligence-based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.

Life threatening rupture of the diaphragm after Covid 19 pneumonia: a case report.

BACKGROUND: The incidence of diaphragmatic rupture is low; however, it may be life threatening. Normally caused by blunt trauma, some cases are reported after pulmonary infections with extensive coughing. Covid 19 causes pulmonary infections and pneumonia and has been associated with weakening of the diaphragm after prolonged ventilation. We present a patient who suffered from diaphragmatic rupture 2 months after recovering from a severe Covid 19 pneumonia. CASE: A 71 years old male patient presented with massive thoraco-abdominal pain and severe dyspnea. At the time of admission, the patient was diagnosed with rupture of the diaphragm and developed cardiogenic shock. Intraoperatively there was a 4 cm diameter large rupture of the diaphragm with enterothorax (transverse colon, stomach, spleen, parts of the jejunum). Avulsion of the mesenteric arteries made a segmental resection of the jejunum together with the spleen necessary. A jejuno-jejunostomy was performed and organs were replaced into the abdomen. The rupture of the diaphragm underwent primary closure with non-resorbable suture material. The patient has shown an uneventful post-operative course, fully recovered and was discharged on day 11 after surgery. CONCLUSION: Covid 19 is a disease that is known to have various effects on different organs. The diaphragm is only paid heed in case of dysfunction. Also in the setting of Covid 19 it is not known as prominent effector organ. Nevertheless its affection by coughing caused by Covid 19 can lead to life threatening complications.

Nontumor related risk score: A new tool to improve prediction of prognosis after hepatectomy for colorectal liver metastases.

BACKGROUND: Prognostic stratification of patients with colorectal cancer liver metastasis based solely on tumor-related factors has only moderate discriminatory ability. We hypothesized that the inclusion of nontumor related factors can improve prediction of long-term prognosis of patients with colorectal cancer liver metastasis. METHODS: Nontumor related laboratory markers were assessed utilizing a training cohort from 2 U.S. institutions (n = 1,205). Factors independently associated with prognosis were used to develop a nontumor related prognostic score. The discriminatory ability, assessed by Harrell's C-statistics (C-index) and net reclassification improvement, was validated and compared with 3 commonly used tumor-related clinical risk scores: Fong clinical risk scores, m-clinical risk scores, and Genetic and Morphological Evaluation (GAME) score in an external validation cohort from 5 Asian (n = 1,307) and 3 European (n = 1,058) institutions. The discriminatory ability of nontumor related prognostic score combined with each of these 3 tumor-related prognostic scores was also estimated. RESULTS: Alkaline phosphatase (hazard ratio 1.43; 95% confidence interval, 1.11-1.84), albumin (hazard ratio 0.71; 95% confidence interval, 0.57-0.89), and mean corpuscular volume (hazard ratio 19.0, per log unit; 95% confidence interval, 4.79-75.0) were each independently associated with increased risk of death after resection of colorectal cancer liver metastasis (all P < .05). In turn, alkaline phosphatase, albumin, and mean corpuscular volume were combined to form a nontumor related prognostic score (2.942 × mean corpuscular volume + 0.399 × alkaline phosphatase-0.339 × albumin-12) × 10 (median, 16; range, 1-30). The nontumor related prognostic score had good-to-modest discriminatory ability in the external cohort (C-index = 0.58), which was comparable to the 3 established tumor-related prognostic scores (C-index: Fong clinical risk scores, 0.53, m-clinical risk scores, 0.55, GAME, 0.58). The addition of the nontumor related prognostic score to the tumor-related prognostic scores enhanced the discriminatory ability in the entire study cohort (C-index: nontumor related score+Fong, 0.60, nontumor related score+m-clinical risk scores, 0.61, nontumor related score+GAME, 0.64), as well reclassification improvement (42.5, 42.7%, and 21.2%, respectively). CONCLUSION: Nontumor related prognostic information may help improve the prognostic stratification of patients after resection of colorectal cancer liver metastasis. The nontumor related prognostic score may be combined with tumor-related prognostic tools to enhance prognostic stratification of patients with colorectal cancer liver metastasis.