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  • 1
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    Low thoracic muscle radiation attenuation is associated with postoperative pneumonia following partial hepatectomy for colorectal metastasis
    Elsevier BV ; 2020
    In:  HPB Vol. 22, No. 7 ( 2020-07), p. 1011-1019
    Details
    In: HPB, Elsevier BV, Vol. 22, No. 7 ( 2020-07), p. 1011-1019
    Materialart: Online-Ressource
    ISSN: 1365-182X
    URL: Article
    DOI: 10.1016/j.hpb.2019.10.1532
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2020
    ZDB Id: 2071267-4
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  • 2
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    Image_1.jpg
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-8-10)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-8-10)
    Kurzfassung: Computerized radiological image analysis (radiomics) enables the investigation of image-derived phenotypes by extracting large numbers of quantitative features. We hypothesized that radiomics features may contain prognostic information that enhances conventional body composition analysis. We aimed to investigate whether body composition-associated radiomics features hold additional value over conventional body composition analysis and clinical patient characteristics used to predict survival of pancreatic ductal adenocarcinoma (PDAC) patients. Methods Computed tomography images of 304 patients undergoing elective pancreatic cancer resection were analysed. 2D radiomics features were extracted from skeletal muscle and subcutaneous and visceral adipose tissue (SAT and VAT) compartments from a single slice at the third lumbar vertebra. The study population was randomly split (80:20) into training and holdout subsets. Feature ranking with Least Absolute Shrinkage Selection Operator (LASSO) followed by multivariable stepwise Cox regression in 1000 bootstrapped re-samples of the training data was performed and tested on the holdout data. The fitted regression predictors were used as “scores” for a clinical (C-Score), body composition (B-Score), and radiomics (R-Score) model. To stratify patients into the highest 25% and lowest 25% risk of mortality compared to the middle 50%, the Harrell Concordance Index was used. Results Based on LASSO and stepwise cox regression for overall survival, ASA ≥3 and age were the most important clinical variables and constituted the C-score, and VAT-index (VATI) was the most important body composition variable and constituted the B-score. Three radiomics features (SATI_original_shape2D_Perimeter, VATI_original_glszm_SmallAreaEmphasis, and VATI_original_firstorder_Maximum) emerged as the most frequent set of features and yielded an R-Score. Of the mean concordance indices of C-, B-, and R-scores, R-score performed best (0.61, 95% CI 0.56–0.65, p & lt;0.001), followed by the C-score (0.59, 95% CI 0.55-0.63, p & lt;0.001) and B-score (0.55, 95% CI 0.50–0.60, p=0.03). Kaplan-Meier projection revealed that C-, B, and R-scores showed a clear split in the survival curves in the training set, although none remained significant in the holdout set. Conclusion It is feasible to implement a data-driven radiomics approach to body composition imaging. Radiomics features provided improved predictive performance compared to conventional body composition variables for the prediction of overall survival of PDAC patients undergoing primary resection.
    Materialart: Online-Ressource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2023.1062937
    DOI: 10.3389/fonc.2023.1062937.s001
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2023
    ZDB Id: 2649216-7
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  • 3
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    Inflammation‐associated intramyocellular lipid alterations in human pancreatic cancer cachexia
    Wiley ; 2024
    In:  Journal of Cachexia, Sarcopenia and Muscle
    Details
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley
    Kurzfassung: Cancer cachexia is a multifactorial metabolic syndrome characterized by systemic inflammation and ongoing skeletal muscle loss resulting in weakness, poor quality of life, and decreased survival. Whereas lipid accumulation in skeletal muscle is associated with cancer cachexia as well as the prognosis of cancer patients, surprisingly little is known about the nature of the lipids that accumulate in the muscle during cachexia, and whether this is related to inflammation. We aimed to identify the types and distributions of intramyocellular lipids in patients with and without cancer cachexia. Methods Rectus abdominis muscle biopsies were collected during surgery of patients with pancreatic ductal adenocarcinoma ( n  = 10 without cachexia, n  = 20 cachectic without inflammation (CRP  〈  10 mg/L), n  = 10 cachectic with inflammation (CRP ≥ 10 mg/L). L3‐CT scans were analysed to assess body composition based on validated thresholds in Hounsfield units (HU). Muscle sections were stained with Oil‐Red O and H & E to assess general lipid accumulation and atrophy. Untargeted lipidomic analyses were performed on laser‐microdissected myotubes using LC–MS/MS. The spatial distribution of intramyocellular lipids with differential abundance between groups was visualized by mass‐spectrometry imaging. Genes coding for inflammation markers and enzymes involved in de novo ceramide synthesis were studied by qPCR. Results Muscle radiation attenuation was lower in cachectic patients with inflammation (median 24.3 [18.6–30.8] HU) as compared with those without inflammation (34.2 [29.3–38.7] HU, P  = 0.033) or no cachexia (37.4 [33.9–42.9] HU, P  = 0.012). Accordingly, intramyocellular lipid content was lower in non‐cachectic patients (1.9 [1.6–2.1]%) as compared with those with cachexia with inflammation (5.5 [4.5–7.3] %, P  = 0.002) or without inflammation (4.8 [2.6–6.0]%, P  = 0.017). Intramyocellular lipid accumulation was associated with both local IL‐6 mRNA levels ( r s  = 0.57, P  = 0.015) and systemic CRP levels ( r s  = 0.49, P  = 0.024). Compared with non‐cachectic subjects, cachectic patients had a higher relative abundance of intramyocellular glycerophospholipids and a lower relative abundance of glycerolipids. Furthermore, increases in several intramyocellular lipids such as SM(d36:1), PC(34:1), and TG(48:1) were found in cachectic patients with inflammation and correlated with specific cachexia features. Altered intramyocellular lipid species such as PC(34:1), LPC(18:2), and TG(48:1) showed an uneven distribution in muscle sections of cachectic and non‐cachectic patients, with areas featuring abundance of these lipids next to areas almost devoid of them. Conclusions Intramyocellular lipid accumulation in patients with cachexia is associated with both local and systemic inflammation, and characterized by changes in defined lipid species such as glycerolipids and glycerophospholipids.
    Materialart: Online-Ressource
    ISSN: 2190-5991 , 2190-6009
    URL: Article
    DOI: 10.1002/jcsm.13474
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2024
    ZDB Id: 2586864-0
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  • 4
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    Bile Salt and FGF19 Signaling in the Early Phase of Human Liver Regeneration
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Hepatology Communications Vol. 5, No. 8 ( 2021-08), p. 1400-1411
    Details
    In: Hepatology Communications, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 8 ( 2021-08), p. 1400-1411
    Kurzfassung: The involvement of bile salt–fibroblast growth factor 19 (FGF19) signaling in human liver regeneration (LR) is not well studied. Therefore, we studied aspects of bile salt–FGF19 signaling shortly after liver resection in patients. We compared plasma bile salt and FGF19 levels in arterial, portal and hepatic venous blood, calculated venous‐arterial differences (ΔVA), and determined hepatic transcript levels on two intra‐operative time points: before ( 〈 1 hour) and immediately after ( 〉 2‐3 hours) liver resection (i.e., following surgery). Postoperative bile salt and FGF19 levels were assessed on days 1, 2, and 3. LR was studied by computed tomography (CT)–liver volumetry. Following surgery, the liver, arterial, and portal bile salt levels were elevated ( P   〈  0.05). Furthermore, an increased amount of bile salts was released in portal blood and extracted by the remnant liver ( P   〈  0.05). Postoperatively, bile salt levels were elevated from day 1 onward ( P   〈  0.001). For FGF19, intra‐operative or postoperative changes of ΔVA or plasma levels were not observed. The bile salt–homeostatic regulator farnesoid X receptor ( FXR ) was markedly up‐regulated following surgery ( P   〈  0.001). Cell‐cycle re‐entry priming factors (interleukin 6 [ IL‐6 ], signal transducer and activator of transcription 3 [ STAT3 ], and cJUN ) were up‐regulated following surgery and were positively correlated with FXR expression (P   〈  0.05). Postoperative hyperbilirubinemia was preceded by postsurgery low FXR and high Na+/Taurocholate cotransporting polypeptide ( NTCP ) expression in the remnant liver coupled with higher liver bile salt content ( P   〈  0.05). Finally, bile salt levels on postoperative day 1 were an independent predictor of LR ( P   〈  0.05). Conclusion : Systemic, portal, and liver bile salt levels are rapidly elevated after liver resection. Postoperative bile salts were positively associated with liver volume gain. In the studied time frame, FGF19 levels remained unaltered, suggesting that FGF19 plays a minor role in human LR. These findings indicate a more relevant role of bile salts in human LR.
    Materialart: Online-Ressource
    ISSN: 2471-254X , 2471-254X
    URL: Article
    DOI: 10.1002/hep4.1728
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2021
    ZDB Id: 2881134-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-3-15)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-3-15)
    Kurzfassung: Cancer cachexia is a multifactorial syndrome characterized by body weight loss and systemic inflammation. The characterization of the inflammatory response in patients with cachexia is still limited. Lipocalin-2, a protein abundant in neutrophils, has recently been implicated in appetite suppression in preclinical models of pancreatic cancer cachexia. We hypothesized that lipocalin-2 levels could be associated with neutrophil activation and nutritional status of pancreatic ductal adenocarcinoma (PDAC) patients. Methods Plasma levels of neutrophil activation markers calprotectin, myeloperoxidase, elastase, and bactericidal/permeability-increasing protein (BPI) were compared between non-cachectic PDAC patients (n=13) and cachectic PDAC patients with high (≥26.9 ng/mL, n =34) or low ( & lt;26.9 ng/mL, n =34) circulating lipocalin-2 levels. Patients’ nutritional status was assessed by the patient-generated subjective global assessment (PG-SGA) and through body composition analysis using CT-scan slices at the L3 level. Results Circulating lipocalin-2 levels did not differ between cachectic and non-cachectic PDAC patients (median 26.7 (IQR 19.7-34.8) vs . 24.8 (16.6-29.4) ng/mL, p =0.141). Cachectic patients with high systemic lipocalin-2 levels had higher concentrations of calprotectin, myeloperoxidase, and elastase than non-cachectic patients or cachectic patients with low lipocalin-2 levels (calprotectin: 542.3 (355.8-724.9) vs . 457.5 (213.3-606.9), p =0.448 vs . 366.5 (294.5-478.5) ng/mL, p =0.009; myeloperoxidase: 30.3 (22.1-37.9) vs . 16.3 (12.0-27.5), p =0.021 vs . 20.2 (15.0-29.2) ng/mL, p =0.011; elastase: 137.1 (90.8-253.2) vs . 97.2 (28.8-215.7), p =0.410 vs . 95.0 (72.2-113.6) ng/mL, p =0.006; respectively). The CRP/albumin ratio was also higher in cachectic patients with high lipocalin-2 levels (2.3 (1.3-6.0) as compared to non-cachectic patients (1.0 (0.7-4.2), p =0.041). Lipocalin-2 concentrations correlated with those of calprotectin ( r s =0.36, p & lt;0.001), myeloperoxidase ( r s =0.48, p & lt;0.001), elastase ( r s =0.50, p & lt;0.001), and BPI ( r s =0.22, p =0.048). Whereas no significant correlations with weight loss, BMI, or L3 skeletal muscle index were observed, lipocalin-2 concentrations were associated with subcutaneous adipose tissue index ( r s =-0.25, p =0.034). Moreover, lipocalin-2 tended to be elevated in severely malnourished patients compared with well-nourished patients (27.2 (20.3-37.2) vs . 19.9 (13.4-26.4) ng/mL, p =0.058). Conclusions These data suggest that lipocalin-2 levels are associated with neutrophil activation in patients with pancreatic cancer cachexia and that it may contribute to their poor nutritional status.
    Materialart: Online-Ressource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2023.1159411
    DOI: 10.3389/fimmu.2023.1159411.s001
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2023
    ZDB Id: 2606827-8
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  • 6
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    Der Einfluss von Kachexie und Sarkopenie auf das postoperative Outcome
    Georg Thieme Verlag KG ; 2021
    In:  Zentralblatt für Chirurgie - Zeitschrift für Allgemeine, Viszeral-, Thorax- und Gefäßchirurgie Vol. 146, No. 03 ( 2021-06), p. 277-282
    Details
    In: Zentralblatt für Chirurgie - Zeitschrift für Allgemeine, Viszeral-, Thorax- und Gefäßchirurgie, Georg Thieme Verlag KG, Vol. 146, No. 03 ( 2021-06), p. 277-282
    Kurzfassung: Kachexie wird als multifaktorielles Syndrom definiert, das durch einen unfreiwillig fortschreitenden Gewichtsverlust infolge einer Verringerung der Skelettmuskelmasse mit oder ohne Reduktion des Fettgewebes gekennzeichnet ist. Der Abbau von Muskelgewebe wird als Sarkopenie bezeichnet. Diese wird klinisch als Verlust von Muskelmasse und/oder Muskelkraft definiert, wobei der Verlust von Muskelkraft im Vordergrund steht. Mit Sarkopenie verbunden ist der Zustand der Myosteatose, der durch eine Zunahme der intra- und extrazellulären Fettspeicher gekennzeichnet ist und mit einer verminderten Muskelfunktion einhergeht. Kachexie ist für den Tod von mindestens 20% aller Krebspatienten mitverantwortlich. Die Inzidenz variiert bei diesen Patienten je nach Art der Erkrankung zwischen 80% für Patienten mit Magen- und Bauchspeicheldrüsenkrebs, 50% für Patienten mit Lungen-, Dickdarm- und Prostatakrebs sowie etwa 40% für Patienten mit Brustkrebs oder Leukämie. Hierbei ist eine Unterscheidung zwischen tumorassoziierter Kachexie und einer durch Nebenwirkungen und Komplikationen der onkologischen Therapie bedingten Kachexie oft schwierig. Das wesentliche klinische Merkmal der Kachexie ist ein unfreiwilliger Gewichtsverlust, der sich jedoch nicht immer klinisch manifestiert, sodass die Identifizierung von Risikopatienten erheblich erschwert ist. Nicht nur das Langzeit-Outcome der Patienten wird von Kachexie und Sarkopenie beeinflusst. Auch die unmittelbaren postoperativen Komplikationsraten (Morbidität) werden erhöht und haben tiefgreifende Auswirkungen auf die Krankheitslast und das Leiden der Patienten nach einer chirurgischen Behandlung. Kachexie, Sarkopenie und Myosteatose sind somit für den klinischen Alltag hochrelevante Parameter, die einen signifikanten Einfluss auf das postoperative Outcome der Patienten haben. Es wurden verschiedene Methoden entwickelt, um die frühzeitige Identifizierung von Patienten mit einem erhöhten Risiko zu verbessern. Diese bieten die Möglichkeit, ungewollten Gewichtsverlust, verringerte Muskelkraft und die Fitness der Patienten zu testen. Derartige Maßnahmen sollten Teil unserer täglichen klinischen Routine werden, um diejenigen Patienten mit dem höchsten postoperativen Risiko zu erkennen. Entsprechend können neuartige Präkonditionierungskonzepte für bestimmte Patientengruppen in der Lage sein, die postoperative Morbidität zu verringern.
    Materialart: Online-Ressource
    ISSN: 0044-409X , 1438-9592
    URL: Article
    DOI: 10.1055/a-1447-1259
    Sprache: Deutsch
    Verlag: Georg Thieme Verlag KG
    Publikationsdatum: 2021
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  • 7
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    Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 3 ( 2021-01-30), p. 490-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 3 ( 2021-01-30), p. 490-
    Kurzfassung: B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome. The desmoplastic stroma is a complex system in which crosstalk takes place between cancer-associated fibroblasts, immune cells and cancer cells. Indirect and direct cellular interactions within the tumor microenvironment (TME) drive key processes such as tumor progression, metastasis formation and treatment resistance. In order to understand the aggressiveness of PDAC and its resistance to therapeutics, the TME needs to be further unraveled. There are some limited data about the influence of nerve fibers on cancer progression. Here we show that small nerve fibers are located at lymphoid aggregates in PDAC. This unravels future pathways and has potential to improve clinical outcome by a rational development of new therapeutic strategies.
    Materialart: Online-Ressource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10030490
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2662592-1
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  • 8
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    Is sarcopenia a risk factor for reduced diaphragm function following hepatic resection? A study protocol for a prospective observational study
    BMJ ; 2021
    In:  BMJ Open Vol. 11, No. 11 ( 2021-11), p. e053148-
    Details
    In: BMJ Open, BMJ, Vol. 11, No. 11 ( 2021-11), p. e053148-
    Kurzfassung: Sarcopenia is associated with reduced pulmonary function in healthy adults, as well as with increased risk of pneumonia following abdominal surgery. Consequentially, postoperative pneumonia prolongs hospital admission, and increases in-hospital mortality following a range of surgical interventions. Little is known about the function of the diaphragm in the context of sarcopenia and wasting disorders or how its function is influenced by abdominal surgery. Liver surgery induces reactive pleural effusion in most patients, compromising postoperative pulmonary function. We hypothesise that both major hepatic resection and sarcopenia have a measurable impact on diaphragm function. Furthermore, we hypothesise that sarcopenia is associated with reduced preoperative diaphragm function, and that patients with reduced preoperative diaphragm function show a greater decline and reduced recovery of diaphragm function following major hepatic resection. The primary goal of this study is to evaluate whether sarcopenic patients have a reduced diaphragm function prior to major liver resection compared with non-sarcopenic patients, and to evaluate whether sarcopenic patients show a greater reduction in respiratory muscle function following major liver resection when compared with non-sarcopenic patients. Methods and analysis Transcostal B-mode, M-mode ultrasound and speckle tracking imaging will be used to assess diaphragm function perioperatively in 33 sarcopenic and 33 non-sarcopenic patients undergoing right-sided hemihepatectomy starting 1 day prior to surgery and up to 30 days after surgery. In addition, rectus abdominis and quadriceps femoris muscles thickness will be measured using ultrasound to measure sarcopenia, and pulmonary function will be measured using a hand-held bedside spirometer. Muscle mass will be determined preoperatively using CT-muscle volumetry of abdominal muscle and adipose tissue at the third lumbar vertebra level (L3). Muscle function will be assessed using handgrip strength and physical condition will be measured with a short physical performance battery . A rectus abdominis muscle biopsy will be taken intraoperatively to measure proteolytic and mitochondrial activity as well as inflammation and redox status. Systemic inflammation and sarcopenia biomarkers will be assessed in serum acquired perioperatively. Ethics and dissemination This trial is open for recruitment. The protocol was approved by the official Independent Medical Ethical Committee at Uniklinik (Rheinish Westphälische Technische Hochschule (RWTH) Aachen (reference EK309-18) in July 2019. Results will be published via international peer-reviewed journals and the findings of the study will be communicated using a comprehensive dissemination strategy aimed at healthcare professionals and patients. Trial registration number ClinicalTrials. gov (EK309-18); Pre-results.
    Materialart: Online-Ressource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2021-053148
    Sprache: Englisch
    Verlag: BMJ
    Publikationsdatum: 2021
    ZDB Id: 2599832-8
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  • 9
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    ALPPS versus two-stage hepatectomy for colorectal liver metastases—–a comparative retrospective cohort study
    Springer Science and Business Media LLC ; 2020
    In:  World Journal of Surgical Oncology Vol. 18, No. 1 ( 2020-12)
    Details
    In: World Journal of Surgical Oncology, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2020-12)
    Kurzfassung: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and two stage hepatectomy with inter-stage portal vein embolization (TSH/PVE) are surgical maneuvers applied in patients with advanced malignancies considered unresectable by means of conventional liver surgery. The aim of this report is to compare the oncologic outcome and technical feasibility of ALPPS and TSH/PVE in the scenario of colorectal liver metastases (CRLM). Methods All consecutive patients who underwent either ALPPS or TSH/PVE for CRLM between 2011 and 2017 in one hepatobiliary center were analyzed and compared regarding perioperative and long-term oncologic outcome. Results A cohort of 58 patients who underwent ALPPS ( n = 21) or TSH/PVE ( n = 37) was analyzed. The median overall survival (OS) was 28 months and 34 months after ALPPS and TSH/PVE ( p = 0.963), respectively. The median recurrence-free survival (RFS) was higher following ALPPS with 19 months than following TSH/PVE with 10 months, but marginally failed to achieve statistical significance ( p = 0.05). There were no differences in morbidity and mortality after stages 1 and 2. Patients undergoing ALPPS due to insufficient hypertrophy after TSH/PVE (rescue-ALPPS) displayed similar oncologic outcome as patients treated by conventional ALPPS or TSH/PVE ( p = 0.971). Conclusions ALPPS and TSH/PVE show excellent technical feasibility and comparable long-term oncologic outcome in CRLM. Rescue ALPPS appears to be a viable option for patients displaying insufficient hypertrophy after a TSH/PVE approach.
    Materialart: Online-Ressource
    ISSN: 1477-7819
    URL: Article
    DOI: 10.1186/s12957-020-01919-3
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2020
    ZDB Id: 2118383-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    Macrophages protect against loss of adipose tissue during cancer cachexia
    Wiley ; 2019
    In:  Journal of Cachexia, Sarcopenia and Muscle Vol. 10, No. 5 ( 2019-10), p. 1128-1142
    Details
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley, Vol. 10, No. 5 ( 2019-10), p. 1128-1142
    Kurzfassung: Cancer cachexia represents a central obstacle in medical oncology as it is associated with poor therapy response and reduced overall survival. Systemic inflammation is considered to be a key driver of cancer cachexia; however, clinical studies with anti‐inflammatory drugs failed to show distinct cachexia‐inhibiting effects. To address this contradiction, we investigated the functional importance of innate immune cells for hepatocellular carcinoma (HCC)‐associated cachexia. Methods A transgenic HCC mouse model was intercrossed with mice harbouring a defect in myeloid cell‐mediated inflammation. Body composition of mice was analysed via nuclear magnetic resonance spectroscopy and microcomputed tomography. Quantitative PCR was used to determine adipose tissue browning and polarization of adipose tissue macrophages. The activation state of distinct areas of the hypothalamus was analysed via immunofluorescence. Multispectral immunofluorescence imaging and immunoblot were applied to characterize sympathetic neurons and macrophages in visceral adipose tissue. Quantification of pro‐inflammatory cytokines in mouse serum was performed with a multiplex immunoassay. Visceral adipose tissue of HCC patients was quantified via the L3 index of computed tomography scans obtained during routine clinical care. Results We identified robust cachexia in the HCC mouse model as evidenced by a marked loss of visceral fat and lean mass. Computed tomography‐based analyses demonstrated that a subgroup of human HCC patients displays reduced visceral fat mass, complementing the murine data. While the myeloid cell‐mediated inflammation defect resulted in reduced expression of pro‐inflammatory cytokines in the serum of HCC‐bearing mice, this unexpectedly did not translate into diminished but rather enhanced cachexia‐associated fat loss. Defective myeloid cell‐mediated inflammation was associated with decreased macrophage abundance in visceral adipose tissue, suggesting a role for local macrophages in the regulation of cancer‐induced fat loss. Conclusions Myeloid cell‐mediated inflammation displays a rather unexpected beneficial function in a murine HCC model. These results demonstrate that immune cells are capable of protecting the host against cancer‐induced tissue wasting, adding a further layer of complexity to the pathogenesis of cachexia and providing a potential explanation for the contradictory results of clinical studies with anti‐inflammatory drugs.
    Materialart: Online-Ressource
    ISSN: 2190-5991 , 2190-6009
    URL: Issue
    URL: Article
    DOI: 10.1002/jcsm.v10.5
    DOI: 10.1002/jcsm.12450
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2019
    ZDB Id: 2586864-0
    Standort Signatur Einschränkungen Verfügbarkeit
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