MC38 Tumors Induce Musculoskeletal Defects in Colorectal Cancer

Colorectal cancer (CRC) is a leading cause of cancer-related death, and the prevalence of CRC in young adults is on the rise, making this a largescale clinical concern. Advanced CRC patients often present with liver metastases (LM) and an increased incidence of cachexia, i.e., musculoskeletal wasting. Despite its high incidence in CRC patients, cachexia remains an unresolved issue, and animal models for the study of CRC cachexia, in particular, metastatic CRC cachexia, remain limited; therefore, we aimed to establish a new model of metastatic CRC cachexia. C57BL/6 male mice (8 weeks old) were subcutaneously (MC38) or intrasplenically injected (mMC38) with MC38 murine CRC cells to disseminate LM, while experimental controls received saline (n = 5–8/group). The growth of subcutaneous MC38 tumors was accompanied by a reduction in skeletal muscle mass (−16%; quadriceps muscle), plantarflexion force (−22%) and extensor digitorum longus (EDL) contractility (−20%) compared to experimental controls. Meanwhile, the formation of MC38 LM (mMC38) led to heighted reductions in skeletal muscle mass (−30%; quadriceps), plantarflexion force (−28%) and EDL contractility (−35%) compared to sham-operated controls, suggesting exacerbated cachexia associated with LM. Moreover, both MC38 and mMC38 tumor hosts demonstrated a marked loss of bone indicated by reductions in trabecular (Tb.BV/TV: −49% in MC38, and −46% in mMC38) and cortical (C.BV/TV: −12% in MC38, and −8% in mMC38) bone. Cell culture experiments revealed that MC38 tumor-derived factors directly promote myotube wasting (−18%) and STAT3 phosphorylation (+5-fold), while the pharmacologic blockade of STAT3 signaling was sufficient to preserve myotube atrophy in the presence of MC38 cells (+21%). Overall, these results reinforce the notion that the formation of LM heightens cachexia in an experimental model of CRC.

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Predictors of changes in skeletal muscle mass after esophagectomy in elderly patients with esophageal cancer

10.21203/rs.3.rs-213862/v1 ◽

2021 ◽

Author(s):

Tsuyoshi Harada ◽

Noriatsu Tatematsu ◽

Junya Ueno ◽

Yu Koishihara ◽

Nobuko Konishi ◽

...

Keyword(s):

Skeletal Muscle ◽

Esophageal Cancer ◽

Elderly Patients ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Quadriceps Muscle ◽

Computed Tomography Images ◽

Ratio Change ◽

Comprehensive Rehabilitation ◽

The Mean

Abstract Purpose : Although a change in skeletal muscle mass index (SMI) 4 months after esophagectomy impacts prognosis, predictors of a change in SMI have not been revealed. The purpose of this exploratory retrospective study was to clarify the predictors of a change in SMI after curative esophagectomy in elderly patients with esophageal cancer.Methods : Fifty-four patients who underwent esophagectomy and perioperative rehabilitation from 2015 to 2018 were enrolled. Preoperative and postoperative SMI (cm 2 /m 2 ) were calculated using computed tomography images. The ratio change in SMI was calculated as follows: (postoperative SMI − preoperative SMI) ÷ preoperative SMI × 100%. Potential predictors of a change in SMI ratio were analyzed by multiple regression. Results : The mean ratio change in SMI 4 months after esophagectomy was −7.1% ± 9.4%. The ratio change in quadriceps muscle strength in the first month after surgery ([postoperative strength − preoperative strength] ÷ preoperative strength × 100%) (standardized β = .273, p = .038) and neoadjuvant chemotherapy (NAC) (standardized β = .398, p = .006) were predictors of the ratio change in SMI independent of age, sex, pathological stage, and preoperative SMI. Conclusion : Quadriceps muscle weakness in the first month after esophagectomy and NAC were predictors of the ratio change in SMI after esophagectomy. Continuous postoperative comprehensive rehabilitation and supportive care may inhibit loss of skeletal muscle mass.

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Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Journal of Cachexia Sarcopenia and Muscle ◽

10.1002/jcsm.12337 ◽

2018 ◽

Vol 9 (5) ◽

pp. 909-919 ◽

Cited By ~ 21

Author(s):

Sophie A. Kurk ◽

Petra H.M. Peeters ◽

Bram Dorresteijn ◽

Pim A. de Jong ◽

Marion Jourdan ◽

...

Keyword(s):

Colorectal Cancer ◽

Skeletal Muscle ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Systemic Treatments ◽

Colorectal Cancer Patients

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Concurrent losses of skeletal muscle mass, adipose tissue and bone mineral density during bevacizumab / cytotoxic chemotherapy treatment for metastatic colorectal cancer

Clinical Nutrition ◽

10.1016/j.clnu.2020.02.017 ◽

2020 ◽

Vol 39 (11) ◽

pp. 3319-3330

Author(s):

Adeline Dolly ◽

Thierry Lecomte ◽

Olivier Bouché ◽

Christophe Borg ◽

Eric Terrebonne ◽

...

Keyword(s):

Colorectal Cancer ◽

Bone Mineral Density ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Metastatic Colorectal Cancer ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Cytotoxic Chemotherapy ◽

Chemotherapy Treatment ◽

Mineral Density

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Effect of tumor burden and subsequent surgical resection on skeletal muscle mass and protein turnover in colorectal cancer patients

American Journal of Clinical Nutrition ◽

10.3945/ajcn.112.045708 ◽

2012 ◽

Vol 96 (5) ◽

pp. 1064-1070 ◽

Cited By ~ 72

Author(s):

John P Williams ◽

Bethan E Phillips ◽

Kenneth Smith ◽

Philip J Atherton ◽

Debbie Rankin ◽

...

Keyword(s):

Colorectal Cancer ◽

Skeletal Muscle ◽

Cancer Patients ◽

Muscle Mass ◽

Surgical Resection ◽

Protein Turnover ◽

Skeletal Muscle Mass ◽

Tumor Burden ◽

Colorectal Cancer Patients

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Associations of pre-existing co-morbidities with skeletal muscle mass and radiodensity in patients with non-metastatic colorectal cancer

Journal of Cachexia Sarcopenia and Muscle ◽

10.1002/jcsm.12301 ◽

2018 ◽

Vol 9 (4) ◽

pp. 654-663 ◽

Cited By ~ 33

Author(s):

Jingjie Xiao ◽

Bette J. Caan ◽

Erin Weltzien ◽

Elizabeth M. Cespedes Feliciano ◽

Candyce H. Kroenke ◽

...

Keyword(s):

Colorectal Cancer ◽

Skeletal Muscle ◽

Metastatic Colorectal Cancer ◽

Muscle Mass ◽

Skeletal Muscle Mass

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MON-PO416: Effects of Preoperative Skeletal Muscle Mass and Neutrophil Lymphocyte Ratio on the Prognosis of Stage II and III Colorectal Cancer

Clinical Nutrition ◽

10.1016/s0261-5614(19)32249-6 ◽

2019 ◽

Vol 38 ◽

pp. S212-S213

Author(s):

Y. Nakata ◽

S. Furuya ◽

H. Shimizu ◽

H. Akaike ◽

N. Hosomura ◽

...

Keyword(s):

Colorectal Cancer ◽

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Stage Ii ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio

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Skeletal muscle mass loss and dose‐limiting toxicities in metastatic colorectal cancer patients

Journal of Cachexia Sarcopenia and Muscle ◽

10.1002/jcsm.12436 ◽

2019 ◽

Vol 10 (4) ◽

pp. 803-813 ◽

Cited By ~ 13

Author(s):

Sophie Kurk ◽

Petra Peeters ◽

Rebecca Stellato ◽

B. Dorresteijn ◽

Pim Jong ◽

...

Keyword(s):

Colorectal Cancer ◽

Skeletal Muscle ◽

Mass Loss ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Mass Loss ◽

Colorectal Cancer Patients

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SO018NON-INVASIVE ASSESSMENT AND MONITORING OF SKELETAL MUSCLE MASS IN CRITICALLY ILL PATIENTS WITH AKI BY QUADRICEPS MUSCLE ULTRASOUND

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa139.so018 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Alice Sabatino ◽

Giuseppe Regolisti ◽

Chiara Cantarelli ◽

Andrea Palladini ◽

Tommaso Di motta ◽

...

Keyword(s):

Skeletal Muscle ◽

Hospital Stay ◽

Critically Ill ◽

Muscle Mass ◽

Critically Ill Patients ◽

Skeletal Muscle Mass ◽

Muscle Wasting ◽

Quadriceps Muscle ◽

Invasive Technique ◽

Icu Stay

Abstract Background and Aims Critically ill patients undergo important muscle wasting during ICU stay, and a significant loss of muscle mass still occurs in the first few days of hospital stay. This may delay both functional recovery and weaning from mechanical ventilation, being also a well-known predictor of mortality. Quite often, muscle wasting is masked by fluid overload, increasing the risk for underestimating the presence of malnutrition, as frequently occurs in critically ill patients with AKI. An important concern in this clinical setting is the lack of adequate tools for routine bedside evaluation of the skeletal muscle mass. Lately, the use of ultrasound (US) for the assessment of muscle mass has aroused considerable interest. It is a non-invasive technique, applicable at the bedside and even in non-collaborative patients, it is economically viable, safe and do not require specialized staff. Recently, its reliability and validity have been demonstrated in critically ill patients with AKI. On this premise, in the present study, we aimed to evaluate the clinical application of US for both evaluation and monitoring of quadriceps muscle thickness in critically ill patients with AKI. Method This is an observational study, conducted in the renal ICU of the Parma University Hospital. All adult patients with AKI, with no distinction regarding the severity of AKI, admitted in the renal ICU from 15/03/2017 to 15/03/2018, with previous hospital stay less than 72h, with a likely ICU stay of at least 5 days were eligible for entering the study. The diagnosis of AKI was made according to KDIGO. Quadriceps rectus femoris and vastus intermedius thickness (QRFT and QVIT) were measured at the midpoint and at the border between the upper third and lower two-thirds between the anterior superior iliac spine (ASIS) and the upper pole of the patella. US was performed twice during ICU stay, i.e., at baseline (within 72h from admission) and after 5 days since the first measurement. Results We enrolled 30 patients, 70% (n= 21/30) were male, mean age ± SD age 74±11 years, APACHE II mean ± SD, 22 ± 5. Ultrasonography took less than 10 minutes to set up and complete image acquisition and less than 10 minutes per image to complete measurement analysis in all patients. A total of 472 images were analyzed across the 30 subjects.

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