Previous studies have shown an association of sarcopenia with adverse short- and long-term outcomes in multiple gastrointestinal cancer types. We aimed to investigate the prognostic value of sarcopenia on the postoperative outcomes and survival rates of patients with colorectal cancer (CRC). A systematic literature search was performed using the PubMed, Embase, Cochrane, Google Scholar, and Scopus databases. We included studies that compared postoperative outcomes or survival rates in sarcopenic and non-sarcopenic patients with CRC. A total of 44 observational studies, comprising 18,891 patients, were included. The pooled prevalence of sarcopenia was 37% (n = 7009). The pooled analysis revealed an association between sarcopenia and higher risk of total postoperative complications (23 studies, OR = 1.84; 95% CI 1.35–2.49), postoperative severe complications (OR = 1.72; 95% CI 1.10–2.68), postoperative mortality (OR = 3.21; 95% CI 2.01–5.11), postoperative infections (OR = 1.40; 95% CI 1.12–1.76), postoperative cardiopulmonary complications (OR = 2.92; 95% CI 1.96–4.37), and prolonged length of stay (MD = 0.77; 95% CI 0.44–1.11) after colorectal cancer surgery. However, anastomotic leakage showed comparable occurrence between sarcopenic and non-sarcopenic patients (OR = 0.99; 95% CI 0.72 to 1.36). Regarding survival outcomes, sarcopenic patients had significantly shorter overall survival (25 studies, HR = 1.83; 95% CI = 1.57–2.14), disease-free survival (HR = 1.55; 95% CI = 1.29–1.88), and cancer-specific survival (HR = 1.77; 95% CI 1.40–2.23) as compared with non-sarcopenic patients. Among patients with colorectal cancer, sarcopenia is a strong predictor of increased postoperative complications and worse survival outcomes.

Sarcopenia predicts worse postoperative outcomes and decreased survival rates in patients with colorectal cancer: a systematic review and meta-analysis.

Updated systematic review and meta-analysis on diagnostic issues and the prognostic impact of myosteatosis: A new paradigm beyond sarcopenia.

The relationship between computed tomography (CT)-assessed sarcopenia and colorectal cancer (CRC) prognosis varies in different studies. This systematic review aimed to examine the impact of preoperative CT-assessed sarcopenia on complications and long-term survival in CRC patients. The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant literature up to September 10, 2020. Data and characteristics for each study were extracted. Long-term outcomes were assessed using a comprehensive HR with a 95% CI. Complications were assessed using a comprehensive OR with 95% CI. The heterogeneity and publication bias were also investigated, and subgroup and sensitivity analyses were performed. A total of 19 studies comprising 15,889 patients were included. The comprehensive results demonstrated that sarcopenia is significantly associated with overall survival of CRC patients (HR = 1.40, 95% CI = 1.25–1.58, p < 0.001). Patients with sarcopenia have a higher risk of complications compared to those without sarcopenia. In addition, sarcopenia is strongly associated with poor cancer-specific survival (HR = 1.49, 95% CI = 1.32–1.68, p < 0.001) and disease-free survival (HR = 1.59, 95% CI = 1.32–1.92, p < 0.001) in CRC patients. There is no significant relationship between sarcopenia and recurrence-free survival (HR = 1.32, 95% CI = 0.92–1.89, p = 0.126). Preoperative CT-assessed sarcopenia can be employed as an effective predictor of complications and long-term prognosis in CRC patients. Standardization of CT-assessed sarcopenia requires comprehensive consideration of race, muscle mass index, body mass index, and gender.

Preoperative computed tomography-assessed sarcopenia as a predictor of complications and long-term prognosis in patients with colorectal cancer: a systematic review and meta-analysis.

Pre-operative nutrition screening is recommended to identify cancer patients at risk of malnutrition, which is associated with poor outcomes. Low muscle mass (sarcopenia) and lipid infiltration to muscle cells (myosteatosis) are similarly associated with poor outcomes but are not routinely screened for. We investigated the prevalence of sarcopenia and myosteatosis across the nutrition screening triage categories of the Patient-Generated Subjective Global Assessment Short Form (PG-SGASF) in a pre-operative colorectal cancer (CRC) cohort. Data were prospectively collected from patients scheduled for surgery at two sites in Edmonton, Canada. PG-SGASF scores ≥ 4 identified patients at risk for malnutrition; sarcopenia and myosteatosis were identified using computed-tomography (CT) analysis. Patients (n = 176) with a mean age of 63.8 ± 12.0 years, 52.3% male, 90.3% with stage I-III disease were included. Overall, 25.2% had PG-SGASF score ≥ 4. Sarcopenia alone, myosteatosis alone or both were identified in 14.0%, 27.3%, and 6.4% of patients, respectively. Sarcopenia and/or myosteatosis were identified in 43.4% of those with PG-SGASF score < 4 and in 58.5% of those with score ≥ 4. Overall, 32.9% of the cohort had sarcopenia and/or myosteatosis with PG-SGASF score < 4. CT-defined sarcopenia and myosteatosis are prevalent in pre-operative CRC patients, regardless of the presence of traditional nutrition risk factors (weight loss, problems eating); therefore, CT image analysis effectively adds value to nutrition screening by identifying patients with other risk factors for poor outcomes.

https://www.mdpi.com/2072-6643/12/12/3745/pdf

Computed-Tomography Body Composition Analysis Complements Pre-Operative Nutrition Screening in Colorectal Cancer Patients on an Enhanced Recovery after Surgery Pathway

Introduction Low muscle attenuation, as governed by increased intramuscular fat infiltration (myosteatosis), may associate with adverse surgical outcomes. We aimed to determine whether myosteatosis is associated with an increased risk of postoperative complications and reduced long-term survival after oesophago-gastric (OG) cancer surgery. Methods Patients who underwent radical OG cancer surgery with preoperative abdominal computed tomography (CT) imaging were included. Myosteatosis was evaluated using previously defined cut-points for low skeletal muscle attenuation measured by CT. Oncological, surgical, complications, and outcome data were obtained from a prospective database. Results Of 108 patients, 56% (n = 61) had myosteatosis. Patients with myosteatosis were older (69.1 ± 9.1 vs. 62.8 ± 9.8 years, p = 0.001) and had a similar body mass index (BMI) (23.4 ± 5.3 vs. 25.9 ± 6.7 kg/m2, p = 0.766) compared to patients with normal muscle attenuation. Patients with myosteatosis had a higher rate of anastomotic leaks (15% vs. 2%, p = 0.041). On multivariate analysis, myosteatosis was an independent predictor of overall (OR 3.03, 95% CI 1.31–6.99, p = 0.009) and severe complications (OR 4.33, 95% CI 1.26–14.9, p = 0.020). Patients with myosteatosis had reduced 5 year overall (54.1% vs. 83%, p = 0.004) and disease-free (55.2% vs. 87.2%, p = 0.007) survival. Conclusion Myosteatosis is associated with a significantly increased risk of overall and severe complications as well as substantially reduced long-term survival. Assessment of muscle attenuation provides analysis beyond standard anthropometrics and may form part of preoperative physiological staging tools used to improve surgical outcomes.

Myosteatosis predicts higher complications and reduced overall survival following radical oesophageal and gastric cancer surgery

Background The aim of this study was to evaluate whether sarcopenia or myosteatosis have an impact on short- and long-term results in patients who were surgically treated for colorectal cancer. Methods During 2007–2011 curatively treated colorectal cancer patients (n = 348) were included in the study. Clinical data was collected retrospectively from patient registers. Skeletal muscle mass was measured at the L3 level via venous-phase computed tomography and patients were divided into sarcopenic and non-sarcopenic and into myosteatotic and non-myosteatotic. Postoperative morbidity and mortality were analysed in these groups. Results Sarcopenia was found in 208 patients (59.8%) and myosteatosis was found in 108 patients (31.2%). Sarcopenia was associated with increased risk of postoperative pneumonia (6.7% vs. 1.4%, p = 0.021). Sarcopenic colon cancer patients had higher rate of cardiorespiratory complications than non-sarcopenic (6.3% vs. 0.0%, p = 0.023) and sarcopenic rectum cancer patients had more often pneumonia than non-sarcopenic (8.5% vs. 0.0%, p = 0.041). Discharge to home was less common in myosteatotic patients than in non-myosteatotic patients (47.7% vs. 76.9%, p  Conclusions Sarcopenia increases the pneumonia and cardiorespiratory complication rates. Sarcopenia and myosteatosis predicts the need for institutional care after colorectal cancer surgery. Sarcopenia and myosteatosis seem to be negative factors for colorectal cancer patients’ survival. Myosteatosis is an independent risk factor for poor overall 5-year survival.

The impact of sarcopenia and myosteatosis on postoperative outcomes and 5-year survival in curatively operated colorectal cancer patients - A retrospective register study.

Abstract Background Colon cancer is one of the most common cancers in Finland and worldwide. Cancer-related malnutrition is a well-known risk factor for increased morbidity and mortality after surgery, and it is associated with complications and longer hospitalizations. There are no established recommendations on how to improve the nutritional status of colon cancer patients´ during the perioperative phase. Administration of simple oral nutritional supplements has been suggested to reduce complication rates, but evidence to support this practice is scarce. Methods The Peri-Nutri trial is a prospective, multicenter, randomized, controlled trial. Its primary endpoint is to evaluate whether perioperative oral nutritional support (ONS) decreases the number of complications during the 30-day follow-up after surgery. Secondary endpoints are to study the effect of ONS on quality of life after surgery, length of stay in institutional care, 90-day mortality rate, five-year disease-free survival and overall survival. The patients with a Nutritional risk screening 2002 (NRS-2002) questionnaire result between 2 and 5 (≥ 3 are classified at risk of malnutrition) will be randomized (1:1 ratio) into either the intervention or control group. The intervention group will receive preoperative ONS two weeks before the operation, and nutritional support will continue 10 days after the operation. The control group will not receive ONS. A total of 318 patients will be randomized into two groups and patients are followed five years. Discussion Peri-Nutri study evaluate the impact of ONS to short-term and long-term postoperative morbidity and mortality rates of colon cancer patients undergoing curative surgery. If ONS will decrease patients´ morbidity and mortality, that has a huge impact on patients´ quality of life and also to financial cost. Trial registration ClinicalTrials.gov, NCT03863236 , Registered 25 February 2019. 

/pdf/perioperative-oral-nutritional-support-for-patients-2wgw6lax.pdf

Perioperative oral nutritional support for patients diagnosed with primary colon adenocarcinoma undergoing radical surgical procedures -Peri-Nutri Trial: study protocol for a randomized controlled trial

Cancer patients commonly present sarcopenia, myosteatosis, and systemic inflammation, which are risk factors of poor survival. In this study, sarcopenia and myosteatosis were defined from preoperative body computed tomography scans of 222 colorectal cancer (CRC) patients and analyzed in relation to tumor and patient characteristics, markers of systemic inflammation (modified Glasgow prognostic score (mGPS), neutrophil–lymphocyte ratio (NLR), serum levels of C-reactive protein (CRP), albumin, and 13 cytokines, and survival. Of the systemic inflammation markers, sarcopenia and/or myosteatosis associated with elevated NLR (p = 0.005) and low albumin levels (≤35 g/L) (p = 0.018), but not with mGPS or serum cytokine levels. In addition, myosteatosis was associated with a proximal tumor location (p = 0.039), serrated tumor subtype (p < 0.001), and severe comorbidities (p = 0.004). Multivariable analyses revealed that severe comorbidities and serrated histology were independent predictors of myosteatosis, and older age and elevated NLR were independent indicators of sarcopenia. Myosteatosis associated with shorter overall survival in univariable analysis (HR 1.959, 95% CI 1.24–3.10, p = 0.004) but not in multivariable analysis (p = 0.075). We conclude that sarcopenia and myosteatosis were associated with inflammatory marker NLR, but not with mGPS. Moreover, patients with serrated CRC may have an increased risk of myosteatosis. Myosteatosis or sarcopenia were not independent predictors of patient survival.

/pdf/sarcopenia-and-myosteatosis-are-associated-with-neutrophil-1jrhycs2.pdf

Sarcopenia and Myosteatosis Are Associated with Neutrophil to Lymphocyte Ratio but Not Glasgow Prognostic Score in Colorectal Cancer Patients

Colorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations of tumour necrosis with tumour characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis in CRC.Three independent CRC cohorts, including 1413 patients, were analysed. Associations of the areal percentage of tumour necrosis with clinicopathologic parameters, tumour infiltrating immune cells, cytokine concentrations in systemic and mesenteric vein blood, and survival were examined.Higher tumour necrosis percentage associated with shorter colorectal cancer-specific survival independent of tumour grade, T, N or M-class, mismatch repair status, BRAF status, and other possible confounding factors. In the largest cohort (N = 1100), the HR for high tumour necrosis percentage (≥40% vs. <3%) was 3.22 (95% CI 1.68-6.17, Ptrend < 0.0001). Tumour necrosis percentage positively correlated with peripheral serum levels of CXCL8, a proinflammatory chemokine, and negatively correlated with mesenteric serum levels of CXCL10 and mast cell densities in the invasive margin of the tumour.Our results support the value of tumour necrosis as a prognostic factor in colorectal cancer. CXCL8 may have a role in the systemic effects of tumour necrosis. 

/pdf/immunological-and-prognostic-significance-of-tumour-necrosis-1yd41fn5.pdf

Raila Aro

Papers

The impact of sarcopenia and myosteatosis on postoperative outcomes and 5-year survival in curatively operated colorectal cancer patients - A retrospective register study.

Perioperative oral nutritional support for patients diagnosed with primary colon adenocarcinoma undergoing radical surgical procedures -Peri-Nutri Trial: study protocol for a randomized controlled trial

Sarcopenia and Myosteatosis Are Associated with Neutrophil to Lymphocyte Ratio but Not Glasgow Prognostic Score in Colorectal Cancer Patients

Immunological and prognostic significance of tumour necrosis in colorectal cancer