Dataset Information

Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment.

ABSTRACT:

Background

Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment.

Methods

Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival.

Results

Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging.

Conclusion

A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.

SUBMITTER: van Vugt JLA

PROVIDER: S-EPMC6482985 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment.

van Vugt Jeroen L A JLA Gaspersz Marcia P MP Vugts Jaynee J Buettner Stefan S Levolger Stef S de Bruin Ron W F RWF Polak Wojciech G WG de Jonge Jeroen J Willemssen François E J A FEJA Groot Koerkamp Bas B IJzermans Jan N M JNM

Digestive surgery 20180216 2

<h4>Background</h4>Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment.<h4>Methods</h4>Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle ...[more]

PMID: 29455204

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Project description:BackgroundPhotodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways).MethodsTo assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm(2)). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo.ResultsPDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic.ConclusionsPDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways.

Project description:BackgroundAlthough offering the best chance of potential cure for patients with localized perihilar cholangiocarcinoma (pCCA), resection has been associated with high morbidity and sometimes poor long-term outcomes due to recurrence. We sought to develop a predictive model to identify individuals at high risk for very early recurrence (VER) after curative-intent surgery for pCCA.MethodsPatients who underwent curative-intent surgery for pCCA between 2000-2023 were identified from a multi-institutional database. An eXtreme Gradient Boosting (XGBoost) model was developed to estimate the risk of VER, defined as recurrence within 6 months after resection. The relative importance of clinicopathologic factors was determined using SHapley Additive exPlanations (SHAP) values.ResultsAmong 434 patients undergoing curative-intent resection for pCCA, 65 (15.0%) patients developed VER. Median overall survival (OS) among patients with and without VER was 8.4 [interquartile range (IQR) 6.6-11.3] versus 38.5 (IQR 31.9-45.7) months (P<0.001). An XGBoost model was able to stratify patients relative to the risk of VER [low-risk: 6-month recurrence-free survival (RFS) 94.6% vs. intermediate-risk: 6-month RFS 88.3% vs. high-risk: 6-month RFS 40.0%; P<0.001]. Similarly, 3-year OS incrementally worsened based on VER risk (low-risk: 75.3% vs. intermediate-risk: 19.5% vs. high-risk: 4.6%; P<0.001). The SHAP algorithm identified age, preoperative carbohydrate antigen 19-9 (CA19-9) levels, tumor size and differentiation/grade, as well as lymph node metastasis as the five most important predictors of VER. The predictive accuracy of the model was good in the training [c-index: 0.74, 95% confidence interval (CI): 0.67-0.81] and internal validation (c-index: 0.77, 95% CI: 0.71-0.83) cohorts. An easy-to-use risk calculator for VER was developed and made available online at: https://junkawashima.shinyapps.io/VER_hilar/.ConclusionsA novel, machine learning based model was able to predict accurately the chance of VER after curative-intent resection of pCCA. In turn, the tool may help surgeons in the selection of patients likely to benefit the most from resection, as well as counsel individuals about the anticipated risk of recurrence in the early post-operative period.

Dataset Information

Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment.

Background

Methods

Results

Conclusion

Publications

Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment.

Similar Datasets

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