Impact of low skeletal muscle mass and density on short and long-term outcome after resection of stage I-III colorectal cancer

doi:10.1016/j.ejso.2018.05.029

European Journal of Surgical Oncology

Volume 44, Issue 9, September 2018, Pages 1354-1360

https://doi.org/10.1016/j.ejso.2018.05.029 Get rights and content

Abstract

Background

Preoperative low skeletal muscle mass and density are associated with increased postoperative morbidity in patients undergoing curative colorectal cancer (CRC) surgery. However, the long-term effects of low skeletal muscle mass and density remain uncertain.

Methods

Patients with stage I-III CRC undergoing surgery, enrolled in a prospective observational cohort study, were included. Skeletal muscle mass and density were measured on CT. Patients with high and low skeletal muscle mass and density were compared regarding postoperative complications, disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS).

Results

In total, 816 patients (53.9% males, median age 70) were included; 50.4% had low skeletal muscle mass and 64.1% low density. The severe postoperative complication rate was significantly higher in patients with low versus high skeletal muscle and density (20.9% versus 13.6%, p = 0.006; 20.0% versus 11.8%, p = 0.003). Low skeletal muscle mass (OR 1.91, p = 0.018) and density (OR 1.87, p = 0.045) were independently associated with severe postoperative complications. Ninety-day mortality was higher in patients with low skeletal muscle mass and density compared with patients with high skeletal muscle mass and density (3.6% versus 1.7%, p = 0.091; 3.4% versus 1.0%, p = 0.038). No differences in DFS were observed. After adjustment for covariates such as age and comorbidity, univariate differences in OS and CSS diminished.

Conclusions

Low skeletal muscle mass and density are associated with short-term, but not long-term, outcome in patients undergoing CRC surgery. These findings recommend putting more emphasis on preoperative management of patients at risk for surgical complications, but do not support benefit for long-term outcome.

Introduction

Colorectal cancer is one of the leading causes of cancer-related death with an estimated total cancer burden of 7% and a great impact on disability-adjusted life years worldwide [1], [2]. Recently, there has been a rising interest in the impact of low skeletal muscle mass and density on short and long term outcome in cancer patients [3]. Skeletal muscle depletion may result from cancer, as part of the cancer-cachexia syndrome, and ageing (i.e. sarcopenia, the involuntary age-related loss of skeletal muscle mass and strength) [4].

The impact of low skeletal muscle mass and density on postoperative outcome (i.e. postoperative complications and mortality) [2], [5], [6], [7], [8] and chemotherapy toxicity [9], [10], [11] has frequently been described in colorectal cancer patients. Furthermore, low skeletal muscle mass and density are prognostic factors in patients undergoing surgery for colorectal metastases [12], [13] or chemotherapy for metastatic colorectal cancer [9], [14]. However, its effect on long-term outcome in patients with stage I-III colorectal cancer has been reported in only a few studies [15], [16], [17].

Therefore, the aim of the present study was to investigate the association between low skeletal muscle mass and density on both short and long-term outcome in patients undergoing colorectal cancer surgery with curative intent in a multi-center prospective study.

Section snippets

Study design and patient selection

Patients were selected from the MATCH-study, an ongoing prospective observational cohort study enrolling patients undergoing curative resection for primary colorectal cancer in seven centers in the region of Rotterdam, the Netherlands [18], [19]. The study was approved by the IRB and all patients provided written informed consent (MEC-2007-088). All aspects listed in the STROBE guidelines were followed, and the paper was written accordingly [20].

All patients with stage I-III colorectal cancer,

Patient characteristics

A total of 981 patients with stage I-III colorectal cancer were included in the MATCH-study in the given period. CT examinations were not available in 157 patients and BMI could not be retrieved from 8 patient charts, leaving a total cohort of 816 patients. The median time between CT and surgery was 33 (IQR 22–47) days. Baseline characteristics of included and excluded patients did not differ significantly, besides type of surgery (open surgery 41.9% versus 52.1%, p = 0.032), and number of

Discussion

In this study, we found that low skeletal muscle mass and density were predictors for short-term outcome (i.e. postoperative complications, mortality, LOS, and discharge status) in patients undergoing curative intent resection of colorectal cancer, but not for long-term outcome (i.e. overall, cancer-specific, and disease-free survival).

Our results are in line with the study of Sabel et al., which also found an association between psoas density and short-term, but not long-term outcome, after

Conflict of interest statement

The authors declare to have no conflict of interest with regard to the manuscript “Impact of Low Skeletal Muscle Mass and Density on Short and Long-Term Outcome after Resection of Stage I-III Colorectal Cancer”.

References (45)

C.C. Margadant et al.
Lower muscle density is associated with major postoperative complications in older patients after surgery for colorectal cancer
Eur J Surg Oncol
(2016)
P.D. Peng et al.
Sarcopenia negatively impacts short-term outcomes in patients undergoing hepatic resection for colorectal liver metastasis
HPB (Oxford)
(2011)
E. von Elm et al.
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies
Lancet (Lond Engl)
(2007)
M.E. Charlson et al.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chronic Dis
(1987)
C.M. Prado et al.
Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study
Lancet Oncol
(2008)
M.A. Makary et al.
Frailty as a predictor of surgical outcomes in older patients
J Am Coll Surg
(2010)
M.E. Hamaker et al.
Long-term changes in physical capacity after colorectal cancer treatment
J Geriatr Oncol
(2015)
J.R. Lieffers et al.
A viscerally driven cachexia syndrome in patients with advanced colorectal cancer: contributions of organ and tumor mass to whole-body energy demands
Am J Clin Nutr
(2009)
K.W. Reisinger et al.
Sarcopenia is associated with an increased inflammatory response to surgery in colorectal cancer
Clin Nutr
(2016)
S.T. McSorley et al.
The relationship between tumour stage, systemic inflammation, body composition and survival in patients with colorectal cancer
Clin Nutr
(2018)

D. Currow et al.

ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small cell lung cancer (NSCLC) patients with cachexia

Ann Oncol

(2017 Aug 1)

J.L. van Vugt et al.

Improving the outcomes in oncological colorectal surgery

World J Gastroenterol

(2014)

S. Levolger et al.

Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies

Br J Surg

(2015)

Y. Rolland et al.

Cachexia versus sarcopenia

Curr Opin Clin Nutr Metab Care

(2011)

D.D. Huang et al.

Sarcopenia, as defined by low muscle mass, strength and physical performance, predicts complications after surgery for colorectal cancer

Colorectal Dis

(2015)

K.I. Jones et al.

Simple psoas cross-sectional area measurement is a quick and easy method to assess sarcopenia and predicts major surgical complications

Colorectal Dis

(2015)

J.R. Lieffers et al.

Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery

Br J Cancer

(2012)

J.J. Tegels et al.

Sarcopenia is highly prevalent in patients undergoing surgery for gastric cancer but not associated with worse outcomes

J Surg Oncol

(2015)

S. Blauwhoff-Buskermolen et al.

Loss of muscle mass during chemotherapy is predictive for poor survival of patients with metastatic colorectal cancer

J Clin Oncol

(2016)

H.W. Jung et al.

Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy

Support Care Cancer

(2015)

M. Barret et al.

Sarcopenia is linked to treatment toxicity in patients with metastatic colorectal cancer

Nutr Cancer

(2014)

M.G. van Vledder et al.

Body composition and outcome in patients undergoing resection of colorectal liver metastases

Br J Surg

(2012)

Cited by (71)

Establishment and validation of novel nomograms to predict muscle quality in colorectal cancer patients
2024, Nutrition
The skeletal muscle mass index and skeletal muscle radiodensity have promise as specific diagnostic indicators for muscle quality. However, the difficulties in measuring low skeletal muscle mass index and low skeletal muscle radiodensity limit their use in routine clinical practice, impeding early screening and diagnosis. The objective of this study is to develop a nomogram that incorporates preoperative factors for predicting low skeletal muscle mass index and low skeletal muscle radiodensity.
A total of 1692 colorectal cancer patients between 2015 and 2021 were included. The patients were randomly divided into a training cohort (n = 1353) and a validation cohort (n = 339). Nomogram models were calibrated using the area under the curve, calibration curves, and the Hosmer-Lemeshow test to assess their predictive ability. Finally, a decision curve was applied to assess the clinical usefulness.
In a prediction model for low skeletal muscle mass index, age, body mass index, and grip strength were incorporated as variables. For low skeletal muscle radiodensity, age, sex, body mass index, serum hemoglobin level, and grip strength were included as predictors. In the training cohort, the area under the curve value for low skeletal muscle mass index was 0.750 (95% CI, 0.726–0.773), whereas for low skeletal muscle radiodensity, it was 0.763 (95% CI, 0.739–0.785). The Hosmer-Lemeshow test confirmed that both models fit well in both cohorts. Decision curve analysis was applied to assess the clinical usefulness of the model.
The incorporation of preoperative factors into the nomogram-based prediction model represents a significant advancement in the muscle quality assessment. Its implementation has the potential to early screen patients at risk of low skeletal muscle mass index and low skeletal muscle radiodensity.
Skeletal muscle gauge prediction by a machine learning model in patients with colorectal cancer
2023, Nutrition
Skeletal muscle gauge (SMG) was recently introduced as an imaging indicator of sarcopenia. Computed tomography is essential for measuring SMG; thus, the use of SMG is limited to patients who undergo computed tomography. We aimed to develop a machine learning algorithm using clinical and inflammatory markers to predict SMG in patients with colorectal cancer.
The least absolute shrinkage and selection operator regression model was applied for variable selection and predictive signature building in the training set. The predictive accuracy of the least absolute shrinkage and selection operator model, defined as linear predictor (LP)-SMG, was compared using the area under the receiver operating characteristic curve and decision curve analysis in the test set.
A total of 1094 patients with colorectal cancer were enrolled and randomly categorized into training (n = 656) and test (n = 438) sets. Low SMG was identified in 142 (21.6%) and 90 (20.5%) patients in the training and test sets, respectively. According to multivariable analysis of the test sets, LP-SMG was identified as an independent predictor of low SMG (odds ratio = 1329.431; 95% CI, 271.684–7667.996; P < .001). Its predictive performance was similar in the training and test sets (area under the receiver operating characteristic curve = 0.846 versus 0.869; P = .427). In the test set, LP-SMG had better outcomes in predicting SMG than single clinical variables, such as sex, height, weight, and hemoglobin.
LP-SMG had superior performance than single variables in predicting low SMG. This machine learning model can be used as a screening tool to detect sarcopenic status without using computed tomography during the treatment period.
Myosteatotic and sarcopenic obesity impact postoperative outcomes more robustly than visceral obesity in general surgery patients, with differences by sex
2023, Clinical Nutrition
Computed tomography (CT) defined myosteatotic, sarcopenic, and visceral obesity are associated with adverse surgical outcomes and mortality in patients with malignancies. These occult conditions may also be widely prevalent in today’s general surgery patients who tend to be overweight/obese. This study identified the predominant obesity phenotypes in 906 patients aged 18–85 years who were scheduled for laparoscopic resection for benign abdominal or colorectal disease at Vanderbilt University Medical Center between 2010 and 2017.
Sex and body mass index (BMI) specific cut-points were used to identify myosteatotic, sarcopenic, and visceral obesity phenotype from abdominal CT scan morphometrics. Multivariable regression modeling determined relationships between sex, obesity phenotype, and postoperative outcomes.
The myosteatostic + sarcopenic obesity phenotype associated with longer surgery duration and increased the likelihood for major complication (OR 1.34, 95%CI 1.01–1.74) and ICU admission (OR 1.39, 95%CI 1.04–1.90). Having myosteatotic obesity doubled the likelihood for hospital stay >7 days and discharge to a nursing home (OR 2.11, 95%CI 1.43,3.11), increasing the likelihood for readmission within 90 days. Obesity was more prevalent in females, but myosteatotic, sarcopenic, and visceral obesity were more prevalent in males, regardless of age or BMI. Males had more major complications (23.6% vs 17.7%, P = 0.03), particularly wound dehiscence or infection, and a 2-day longer hospital stay.
This study shows that sarcopenic and myosteatotic obesity phenotypes are highly prevalent, especially in male general surgery patients, regardless of age or BMI. Importantly, sarcopenic and myosteatostic obesity may be more detrimental than visceral obesity; these phenotypes robustly associated with adverse postoperative outcomes. Future work could use these findings for design of phenotype-specific interventions to reduce patient risk and prevent outcomes that are harmful and costly.
Psoas muscle mass index as a predictor of long-term mortality and severity of complications after major intra-abdominal colorectal surgery – A retrospective analysis
2023, Journal of Clinical Anesthesia
Determine if psoas muscle area measured in routine preoperative computed tomography scans (CT) can be used to identify patients at increased risk of adverse postoperative outcomes after major elective abdominal surgery.
Retrospective analysis of data from a single-centre cohort study conducted in York Hospital between the 1st August of 2015 and the 31st of august of 2020.
Preoperative clinic.
639 patients who attended the preoperative assessment clinic prior to major elective colorectal surgery and had an abdominal CT scan done up to 120 days before surgery.
None.
Psoas muscle area at the L3 level was measured in preoperative CT scans and normalised to patient height (psoas muscle index). The lowest sex-stratified tertile of psoas muscle index (PMI) was classed as sarcopenic.
The primary outcome was 2-year mortality. Secondary outcomes included postoperative complications assessed using Clavien-Dindo graded major and minor complications, comprehensive complication index (CCI), and length of stay.
Multivariable regression analysis showed that sarcopenia was associated with 2-year mortality (aOR 1.79, 95% CI 1.03–3.10; p = 0.037) and survival at 2-years was significantly reduced in sarcopenic patients (log-rank test, p = 0.012). Sarcopenia was the only statistically significant predictor of major complications in multivariable logistic regression analysis (aOR 1.69, 95% CI 1.04–2.74, p = 0.034) and associated with an estimated increase of 16.6% in the comprehensive complication index (CCI) score of patients that had complications in multivariable linear regression analysis. Sarcopenia was not associated with length of stay.
Sarcopenia defined by psoas muscle mass is an independent predictor of 2-year mortality, major complications and severity of complications after major colorectal surgery and may be used for preoperative risk assessment.
Evaluation of sarcopenia biomarkers in older patients undergoing major surgery for digestive cancer. SAXO prospective cohort study
2023, European Journal of Surgical Oncology
The aim of the study was to prospectively evaluate different biomarkers to identify the most reliable for anticipating complications after major abdominal surgery for digestive cancer in older patients and compare their performance to the existing definition and screening algorithm of sarcopenia from EWGSOP.
Ninety-five consecutive patients aged over 65 years who underwent elective surgery for digestive cancer were prospectively included in the SAXO study. Sarcopenia was defined according to EWGSOP criteria (four level from no sarcopenia to severe sarcopenia). Strength and physical performance were evaluated with the handgrip test (HGT) and gait speed test (GST), respectively. CT scan analysis was used to calculate the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Measures were adjusted to body mass index (BMI). Complication grading was performed using the Clavien‒Dindo classification. A doubly robust estimator with multivariable regression was used to limit bias.
Sixteen patients presented with sarcopenia. Adjusted to BMI, sarcopenic patients had an increased IMAT^BMI (0.35 vs. 0.22; p = 0.003) and increased VAT^BMI (7.85 vs. 6.13; p = 0.048). In multivariable analysis, IMAT was an independent risk factor for minor and severe complications (OR = 1.298; 95% CI [1.031: 1.635] p = 0.027), while an increased SAT area was a protective factor (OR = 0.982; 95% CI [0.969: 0.995] p = 0.007). Twenty-two patients were obese (BMI ≥30 kg/m²). While no association was observed between obesity and sarcopenia (according to EWGSOP definition), obese patients had increased IMAT^BMI (0.31 vs. 0.23; p = 0.010) and VAT^BMI (8.40 vs. 6.49; p = 0.019). The combination of SAT, VAT and IMAT performed well to anticipate severe complication (AUC = 0.759) while AUC of EWGSOP 2010 and 2019 algorithm were 0.660 and 0.519, respectively.
Non-invasive and imaging related measures of IMAT, SAT and VAT seems to be valuable tools to refine risk-assessment of older patients in surgery and specially to detect myosteatosis in obese ones.
Sarcopenia is a Prognostic Biomarker for Long-Term Survival after Endovascular Aortic Aneurysm Repair: A Systematic Review and Meta-Analysis
2022, Annals of Vascular Surgery
Sarcopenia is the loss of muscle mass and strength. It manifests as decreased core muscle area in axial abdominal computed tomography scans. The predictive value of sarcopenia in outcome research has been widely discussed. A systematic review was conducted to assess sarcopenia as a biomarker in patients undergoing endovascular abdominal aortic aneurysm repair (EVAR) and its association with long-term survival.
A systematic search of the English medical literature, published from 1991 to 2021, was conducted, using PubMed, EMBASE, and CENTRAL, as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA, 2020) guidelines. The study protocol was registered to the International Prospective Register of Systematic Reviews (CRD 42021260192). Observational studies reporting on sarcopenic and nonsarcopenic patients undergoing EVAR were included. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) risk of bias evaluation tool was used for the quality assessment. The outcomes were summarized as odds ratio (OR) along with their 95% confidence intervals (CI), through a paired meta-analysis. The primary outcome was 5-year survival following EVAR.
Eleven observational studies, including 2,385 patients (89.6% males) treated with EVAR, between 1999 and 2018, were included in the qualitative synthesis. The mean age was 72.9 years (range 70–76.4 years). Nine of the studies reported on a negative prognostic value of sarcopenia on survival during a long-term follow-up. Six studies stratified their cohorts in sarcopenic versus nonsarcopenic patients (40.3% sarcopenic). The cutoff values (mm² or mm²/m²) for defining sarcopenic patients were heterogeneous while ranging from 451 to 4,820 mm²/m² and 1,207 to 11,400 mm². Eight studies reported data on the mean follow-up duration, ranging from 27 to 101 months. Six studies reported on outcomes in terms of 5-year survival rates after EVAR, favoring nonsarcopenic over sarcopenic patients, with survival rates ranging from 58 to 93% and 24 to 60%, respectively. After a meta-analysis including 3 eligible studies, sarcopenia was associated with worse 5-year survival after EVAR (OR 0.77, 95% CI [0.58, 0.97], P < 0.001).
The available data derived from observational studies suggest an association between sarcopenia and worse long-term survival in patients treated with EVAR. There is a lack of a universally accepted definition for sarcopenia and future reporting standards should address this issue. Prospective studies are necessary to establish this negative prognostic value of sarcopenia on long-term survival.

View all citing articles on Scopus

View full text

Impact of low skeletal muscle mass and density on short and long-term outcome after resection of stage I-III colorectal cancer

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study design and patient selection

Patient characteristics

Discussion

Conflict of interest statement

Eur J Surg Oncol

HPB (Oxford)

Lancet (Lond Engl)

J Chronic Dis

Lancet Oncol

J Am Coll Surg

J Geriatr Oncol

Am J Clin Nutr

Clin Nutr

Clin Nutr

Ann Oncol

Improving the outcomes in oncological colorectal surgery

World J Gastroenterol

Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies

Br J Surg

Cachexia versus sarcopenia

Curr Opin Clin Nutr Metab Care

Sarcopenia, as defined by low muscle mass, strength and physical performance, predicts complications after surgery for colorectal cancer

Colorectal Dis

Simple psoas cross-sectional area measurement is a quick and easy method to assess sarcopenia and predicts major surgical complications

Colorectal Dis

Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery

Br J Cancer

Sarcopenia is highly prevalent in patients undergoing surgery for gastric cancer but not associated with worse outcomes

J Surg Oncol

Loss of muscle mass during chemotherapy is predictive for poor survival of patients with metastatic colorectal cancer

J Clin Oncol

Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy

Support Care Cancer

Sarcopenia is linked to treatment toxicity in patients with metastatic colorectal cancer

Nutr Cancer

Body composition and outcome in patients undergoing resection of colorectal liver metastases

Br J Surg