Sarcopenia and Charlson Comorbidity Index are Risk Factors for Short-Term Postoperative Prognosis of Elderly Patients with Gastrointestinal Tumor: A Retrospective Study

Background Sarcopenia is one of the most common syndromes in the older adults. Gastrointestinal tumor is a malignant disease with high incidence. This study aimed to investigate the risk factors of sarcopenia in older adults with gastrointestinal tumor, the prognostic indicators of and short-term outcomes after resection for gastrointestinal tumor, and to explore the relationship between sarcopenia and short-term postoperative prognosis. Method A total of 247 older patients with gastrointestinal tumors who underwent radical resection in 2019 were included in this study. Relevant indexes were calculated using L3 slice image of computed tomography (CT) to evaluate sarcopenia. Short-term postoperative complications and length of stay were considered as short-term outcome of this study.


Introduction
Sarcopenia is one of the most common syndromes in the older adults. As newly released guideline, sarcopenia is de ned as a decline in muscle quality, strength and function which are associated with aging [1]. The prevalence of sarcopenia varies among different regions and ethnic groups [2]. With the aging tendency of global population, the number of people with sarcopenia is increasing. Patients with sarcopenia have a higher risk of falls, fractures, and motor functional decline. In recent years, more and more studies on sarcopenia have been conducted, and guidelines have been constantly updated at home and abroad to help clinical work and related scienti c research. As previous research showed, nearly 1/10 older adults suffered with muscle quality decline [3], so that the society should attach more importance to sarcopenia.
Solid tumor of gastrointestinal tract is a malignant disease of high incidence. According to the GLOBOCAN 2018 data released by the World Health Organization (WHO) in 2018, colorectal cancer ranks the third and gastric cancer the fourth among the top ten tumors in terms of incidence [4]. There are about 1.4 million new cases of colorectal cancer and 1 million new cases of stomach cancer each year globally, and about 70 percent of stomach cancer occurs in developing countries [4]. In China, there are a large number of patients with colorectal cancer and stomach cancer, and the effective treatment for most of them potentially is surgical resection. Older adults with cancer have a higher incidence of sarcopenia [5]. Recent studies have shown that sarcopenia is correlated with the poor prognosis after resection surgery for colorectal cancer and stomach cancer [6,7]. However, relevant research in the Chinese population is still limited.
Therefore, this study explored the relationship between sarcopenia, common clinical indicators and shortterm postoperative complications in older patients with colorectal cancer and gastric cancer. We aimed to further identify prognostic indicators for older patients with resection and to intervene precisely.  [9];and postoperative outcomes included postoperative complications which was evaluated by Clavien-Dindo classi cation [10] and length of stay.

2.2.Imaging Analysis
The CT slice at L3 was analysed by Image J (NIH Image J version 1.52a). Referred to the former research, skeletal muscle threshold is -29HU to 150HU and the adipose tissue threshold is -190HU to -30HU [6]. An example is shown in Fig. 1, in which the red part represents muscle tissue, the dark green part represents subcutaneous fat tissue, and the light green part represents visceral fat tissue. This study measured the skeletal muscle area (SMA), subcutaneous fat areas (SFA) and visceral fat area (VFA). Obtained area values were divided by the square of the patient's height (m 2 ) to skeletal muscle index (SMI), SFI and VFI.
Visceral-to-subcutaneous ratio of fat area (VSR) was also calculated as a parameter. According to the previous large sample Chinese population study, male SMI ≤ 40.8 cm 2 /m 2 and female SMI ≤ 34.9 cm 2 /m 2 were de ned as sarcopenia [11].

2.3.Statistics
Data are given as means (with standard deviation) or medians (with interquartile range). Univariate and multivariate logistic regression were performed to analyse the related variables of postoperative complications. Results were expressed as odds ratios (ORs) with 95% con dence intervals (CIs). Linear regression was performed to analyse the related factors for length of stay. IBM SPSS 25 was used for all this analysis.

Patients characteristics
The characteristics of included patients were presented in Table 1    Several factors were found associated with postoperative complications as Table 3 presented. In univariate analysis, advanced age (p=0.012), higher Charlson comorbidity index (p=0.014), and sarcopenia (p=0.001) were associated with postoperative complications. Further multivariate logistic regression analysis showed that sarcopenia (OR:2.6; 95% CI:1.4 to 4.9; p=0.002), and higher Charlson comorbidity index (OR:2.1; 95% CI:1.1 to 3.9; p=0.026) were independent risk factors of postoperative complications.

Factors associated with length of stay
Linear regression was used to analyze the risk factors associated with length of stay. After the factors which were correlated with each other were excluded, it was found that Charlson comorbidity index (p=0.019), tumor site (p=0.016), and duration of surgery (p=0.045) were signi cantly correlated with length of hospital stay. Higher Charlson comorbidity index and longer operative time will result in longer hospital stays. The length of stay of patient with gastric cancer was signi cantly longer than those who with colorectal cancer.

Discussion
This study mainly investigated the risk factors of sarcopenia in older patients with digestive tract tumors and the relationship between sarcopenia and short-term postoperative outcome. This study found that the incidence of sarcopenia in older patients with gastric cancer or colorectal cancer was about 28.7%, which was clearly associated with history of abdominal surgery, lower BMI, and advanced age. The occurrence of postoperative complications was correlated with sarcopenia and higher Charlson comorbidity index.
The Asian Working Group for Sarcopenia (AWGS) released the latest expert consensus on the diagnosis and treatment of sarcopenia in 2019. Sarcopenia is de ned as age-related loss of muscle mass accompanied by a decline in muscle strength and function which is the same as 2014 edition [1]. The commonly used methods for muscle mass measurement are DXA or BIA, and CT is also recognized as a good method for skeletal muscle mass measurement especially for assessing muscle volume [12]. However, there is some debates on the diagnostic threshold. In general studies, L3 plane was selected to calculate the muscle area and SMI value. Sarcopenia was de ned by the cut-off value of SMI. A study published in The Lancet Oncology in 2008 suggested that men with SMI < 52.4 cm 2 /m 2 and women with SMI < 38.5 cm 2 /m 2 were considered to have sarcopenia [13]. This cut-off value is frequently used. Different ethnic groups suit different SMI cut-off value and some studies chose more complicated cut-off values according to both BMI value and SMI value [14]. Since the object of this study was Asian population, and there is a big difference in physique between the western population and Asian population, we referred to a dependable study of a large sample of Chinese population in which men with SMI≤40.8 cm 2 /m 2 and women with SMI≤34.9 cm 2 /m 2 were considered to have sarcopenia [11]. The prevalence of low muscle mass in older adults with cancer was higher than in which without cancer according to previous researches [15]. In this study, 71 patients (28.7%) were considered with sarcopenia.
Whether sarcopenia is a risk factor of short-term postoperative complications in older patients is still controversial. Some studies showed that the surgical complications of patients with oesophageal cancer had no relation with sarcopenia [16], while in some other cancer such as lung cancer and renal cell carcinoma, sarcopenia seemed to be related with prognosis of surgery [17][18]. This study suggested that sarcopenia was a dependent risk factor of short-term postoperative complications in older patients with gastric cancer or colorectal cancer, and con rmed that sarcopenia is an important indicator of postoperative prognosis which suggests the necessity of preoperative diagnosis of sarcopenia. This research did not show any relationship between tumor stage, histologic type and surgical prognosis. A larger sample size may be needed for further clari cation. In the univariate logistic regression analysis, this research also showed that advanced age and higher Charlson comorbidity index were risk factors for short-term surgical complications. Age was excluded in the multivariate logistic regression analysis because of the clear association between age and sarcopenia. A previous study showed that Charlson comorbidity index is an independent risk factor of short-and long-term mortality in hospitalized elderly patients and another one suggested that higher Charlson comorbidity index is related with postoperative complication and longer length of stay in patients with colorectal carcinoma [19]. This study was consistent with the previous research results. Sarcopenia was not found associated with the length of stay, while higher Charlson comorbidity index was a risk factor for longer length of stay, suggesting that patients with more underlying diseases should be taken better postoperative care.
Among the several factors related to sarcopenia found in this study, lower BMI and advanced age have been well discussed and recognized in previous studies [20]. But this research also found that higher BMI was a protective factor for sarcopenia, which may be somewhat controversial. Recently, many studies believed that obesity is also a risk factor for sarcopenia, and obesity sarcopenia became a hot research topic [1]. However, there also have been many papers suggesting that obesity is not associated with sarcopenia [21], and obesity sarcopenia was not made a clear de nition and diagnosis in the newly released sarcopenia guideline [1]. This study found that higher VFI is a risk factor for sarcopenia, while higher SFI is a protective factor for sarcopenia, that is, fat in different parts of the body has different effects on sarcopenia. Some research suggested that abdominal obesity is associated with the development of sarcopenia and parameter VSR is used as a parameter to de ne abdominal obesity [22].
VSR re ects differences in fat distribution, but cannot re ects the volume of fat. This study did not nd any correlation between VSR and sarcopenia or postoperative outcomes. The value of VSR in sarcopenia needs further research efforts. The relationship between obesity and sarcopenia is still controversial and the mechanism is still unknown, which needs to be clari ed by further studies. This study also found that the occurrence of sarcopenia was associated with a prior history of abdominal surgery which was not often mentioned in other studies. Abdominal surgery may lead to the functional decline of digestive system and results in emaciation.
This study was a retrospective study, and had some limitations. There was no follow-up of the long-term prognosis of the patients, such as long-term complications and quality of postoperative life. Due to the incompleteness of preoperative surgical examination, some possible relevant nutritional indicators, such as prealbumin, were not included in this study. Our team will continue investigating the subject.

Conclusions
Age, lower BMI, and history of abdominal surgery are independent risk factors of sarcopenia in the older patients with gastrointestinal tumor. Sarcopenia and Charlson comorbidity index can predict the shortterm prognosis of older patients undergoing gastrointestinal tumor resection.  Figure 1 skeletal muscle and fat tissue in L3