Journal of Clinical Gastroenterology and Hepatology Open Access

Sarcopenia in Gastric Cancer

Leping Li^*, Zhen Fang and Liang Shang Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
^*Correspondence: Leping Li, Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China, Email:

Received: 10-Mar-2021, Manuscript No. IPJCGH-22-12602; Editor assigned: 14-Mar-2021, Pre QC No. IPJCGH-22-12602(PQ); Reviewed: 28-Mar-2021, QC No. IPJCGH-22-12602; Revised: 10-Oct-2022, Manuscript No. IPJCGH-22-12602(R); Published: 17-Oct-2022

Introduction

Gastric Cancer (GC) is one of the most common cancers and is the third leading cause of cancer deaths in the world [1]. Most patients have already developed into advanced stage when they are diagnosed [2]. The 5 years survival rate of GC is low, causing a heavy burden on society and families, and has become a serious health and economic problem. GC patients have digestive symptoms at an early stage, which affects normal eating, digestion and absorption. In addition, malignant tumors are a wasting disease. The tumor consumes a lot of nutrients. Various factors make most patients with GC have varying degrees of malnutrition. Perioperative chemotherapy combined with radical gastrectomy is a main method for the treatment of GC. Postoperative complications increase the length of hospitalization and hospitalization costs, affects the outcomes of patients with GC. Studies have shown that the preoperative nutritional status of cancer patients is not only closely related to the incidence of complications, but also affects the long term prognosis. Looking for indicators that can effectively predict the complications and long term prognosis of GC patients, especially preoperative indicators, will help clinicians to formulate individualized treatment plans, which is of great significance for improving the outcomes of patients with GC. In clinical work, Body Mass Index (BMI) and serum albumin are often used as indicators to evaluate nutritional status. In recent years, it has been discovered that Dual energy X-Ray Absorptiometry (DXA), Bioelectrical Impedance Analysis (BIA) and Computer Tomography (CT) scanning techniques are used to detect the content of skeletal muscle and fat [3-8]. Compared with BMI, its assessment of overall nutritional status is more objective and accurate. Therefore, skeletal muscle content as a new nutritional evaluation index has attracted more and more attention.

Literature Review

The Concept and Development of Sarcopenia

The term sarcopenia comes from the greek words sarx (muscle) and penia (loss). It was first proposed by Professor Rosenberg in 1989. It is defined as a decrease in the content of skeletal muscle in the elderly, and initially only represents an age related decrease in skeletal muscle [9,10]. Professor Delmonico first proposed that Dual X-ray Absorptiometry (DXA) can be used to detect skeletal muscle content, and the diagnostic criteria for sarcopenia are defined as lower than normal young people 2 Standard Deviations (SD) in 1998 [11,12]. With the continuous development of economy and society, the definition of sarcopenia has also changed, and qualitative factors (skeletal muscle function) have gradually integrated into it. In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia as a progressive decrease in skeletal muscle mass, strength, and function, thereby increasing the risk of physical dependence, reduced quality of life [13]. In 2018, EWGSOP updated the consensus again. The new update brings greater clarity to the diagnosis of sarcopenia and a clearer diagnostic process, emphasizing the important value of muscle function, considered more valuable than loss of muscle mass [14,15]. The purpose of the updated consensus on sarcopenia is to make people realize that sarcopenia is a disease. It is hoped that clinicians can actively recognize and take actions to improve the early diagnosis of sarcopenia and prevent it in advance. At present, sarcopenia has been officially confirmed as a muscle disease, diagnosis code: ICD-10-MC [16]. ESPEN divides sarcopenia into primary sarcopenia and secondary sarcopenia in the guidelines. Primary sarcopenia refers to age related muscle degenerative changes, which are common in adults. Secondary sarcopenia, regardless of age, is related to insufficient exercise, malnutrition or chronic diseases. In the currently articles, sarcopenia is often regarded as a part of cachexia, because many cancer cachexia patients often have skeletal muscle attenuation [17-19].

Causes and Pathogenesis of Sarcopenia

Age: With age, skeletal muscle mass and muscle strength gradually decrease [20]. For healthy people, between 20 and 30 years old, skeletal muscle mass and muscle strength are maintained at the highest level; between 30-50 years old, the changes in muscle mass and strength are small, but after 50 years old, muscle attenuation begins to accelerate(about 15% every 10 years). The attenuation of skeletal muscle mass and muscle strength is particularly obvious after menopause. Changes in the synthesis and secretion of some important physiological regulators (such as hormones, growth factor, vit D) related to aging may be important factors affecting skeletal muscle mass and muscle strength.

Lack of exercise: Physical exercise is currently recognized as the most effective way to promote health and delay aging. Exercise can slow down the adverse effects of body aging (such as impaired insulin sensitivity, mitochondrial dysfunction, accelerated nuclear apoptosis and inflammatory response). Low intensity aerobic endurance exercise can improve the oxidation capacity of skeletal muscle and cardiovascular function. After aerobic exercise, the volume of intracellular mitochondria and enzyme activity increased significantly, and the anabolism of muscle protein and muscle mass increased accordingly. The increased muscle capillary network can greatly increase the oxygen supply of skeletal muscle and meet the oxygen demand of mitochondria. In aerobic endurance exercise, it can be observed that the spacing of muscle mitochondria increases, but it has no significant effect on the Cross Sectional Area (CSA) of muscle fibers. Compared with low-intensity endurance exercise, high load resistance aerobic endurance exercise has a certain effect on improving the CSA of muscle fibers and skeletal muscle function. The main reason is that it increases the number and volume of type II fast muscle fibers. Aerobic exercise can also reduce body fat content, including visceral fat, intramuscular infiltration fat and subcutaneous fat. Professor Lenders M reported the results of a study in 2013. The study took healthy elderly men and women as the research subjects, and conducted resistance exercise training 3 times a week for a total of 6 months, and dynamically measured skeletal muscle mass and muscle strength, function, muscle fiber characteristics and metabolic profile. The results showed that the muscle mass and CSA of the lower limbs increased in the elderly male group and the elderly female group. The two groups also control blood sugar and blood lipids very well, and there is no significant statistical difference. Research results show that exercise training can effectively improve the attenuation of skeletal muscle mass and muscle strength caused by aging.

Insufficient protein intake and excessive consumption: Skeletal muscle is the most important reservoir of body protein. There are many myofibrils in muscle fibers. The components of myofibrils are myofibril proteins. These muscle proteins are the basis for the function of skeletal muscle. The attenuation of the quantity and quality of muscle protein directly leads to abnormal skeletal muscle function. Reduced protein intake and increased abnormal consumption in patients with malignant tumors and chronic inflammation have significantly increased the risk of sarcopenia. Vitamin D deficiency is prominent among the elderly, and Vitamin D deficiency is also a common health problem worldwide. Studies on the mechanism of Vitamin D on skeletal muscle have shown that Vitamin D plays an important role in regulating the physiological functions of skeletal muscle. It can stimulate the proliferation and differentiation of skeletal muscle and is of great significance for maintaining skeletal muscle mass and strength. Due to impaired digestive system function, patients with GC have reduced food intake and a higher prevalence of Vitamin D deficiency, which increases the risk of skeletal muscle mass and strength decline. Adequate protein intake is an important guarantee to slow down muscle loss.

Metabolic disorders: Skeletal muscle is an important target organ for insulin. Insulin can effectively stimulate skeletal muscle cells to take up glucose and play an important role in protein synthesis and metabolism.

Diagnostic Criteria for Sarcopenia

The European Working Group on Sarcopenia in Older People (EWGSOP): In 2010, the EWGSOP issued guidelines. Sarcopenia is a syndrome characterized by progressive and extensive decline in skeletal muscle mass and strength, which may lead to physical disability, decreased quality of life and bad consequences such as death.

In 2018, the European Working Group on Elderly Sarcopenia (EWGSOP) updated its guidelines. Sarcopenia is a progressive and widespread skeletal muscle disease that is associated with an increased risk of adverse consequences such as falls, fractures, physical disability and death. This update clearly defines sarcopenia as a muscle disease. In the diagnostic criteria, the value of skeletal muscle strength attenuation in the diagnosis is more prominent.

The Asian Working Group for Sarcopenia (AWGS): In 2014, the AWGS issued consensus for sarcopenia. Consensuses agree that sarcopenia should be described as low muscle mass plus low muscle strength and/or low physical performance. The consensus proposed cutoff points suitable for Asians.

Application of Imaging Technology in Sarcopenia

Dual X-ray Absorptiometry (DXA): Dual energy X-ray Absorptiometry (DXA) is the most commonly used imaging technique for studying human body composition. Based on the attenuation of X-ray at two different energy levels, DXA can assess the bone density, fat mass and non-fat mass of the whole body or specific anatomical areas (such as arms, legs, and head). Skeletal Muscle Mass (SMM) is currently the most commonly used index to assess sarcopenia. It is calculated based on the sum of the muscle mass of the arms and legs. The ratio of SMM to height squared (SMM/m²) is defined as the Skeletal Muscle Mass Index (SMMI). At present, several SMMI cut off points can be used to diagnose sarcopenia. The SMMI value of less than 15% of young people or the SMMI value of less than 20% of the elderly can be used, or less than 1 or 2 Standard Deviations (SDs) of the average SMMI. As an effective tool for diagnosing sarcopenia, DXA can make accurate quantitative assessment of SMM. Low cost and radiation dose make DXA widely used in clinical work, but DXA cannot provide qualitative changes such as skeletal muscle density.

Computed Tomography (CT): Computerized Tomography (CT) is one of the most commonly used imaging techniques to assess body composition. At present, a large number of studies use CT to assess skeletal muscle and fat content, and its accuracy has been widely recognized. The L3 plane of CT images is commonly used in research. The ratio of the area of the bilateral psoas major muscle to the square of the height of the L3 plane is the Psoas Muscle Index (PMI), and the ratio of all muscle area to the square of the height is the Skeletal Muscle Index (SMI), using PMI/SMI to assess body muscle content. As age increases, in addition to the gradual loss of muscle mass, adipose tissue will be redistributed, and subcutaneous fat tissue will be transferred to locations harmful to the body, such as intramuscular and intramuscular fat tissue, or internal organs. Myosteatosis can be understood as the increase of intramuscular and intramuscular fat infiltration. When the intramuscular and/or intramuscular infiltration of excessive fat, it will cause the CT value of skeletal muscle in the cross sectional area to decrease, and the skeletal muscle function is weakened. Therefore, CT can not only assess muscle mass, but also indirectly reflect changes in muscle density and function through CT values. Muscle steatosis may be related to abnormal metabolism, physical fitness, and is an important indicator of muscle function. CT plays an important role in observing these body components.

Magnetic Resonance Imaging (MRI): Magnetic Resonance Imaging (MRI) can be used to assess SMM. It can better distinguish skeletal muscle from surrounding soft tissues. It is one of the important ways to diagnose sarcopenia. MRI can assess fat mass and non-fat tissue mass through cross sectional images, accurately reflect muscle fiber loss and fat infiltration, and quantitatively and qualitatively assess muscle attenuation. Different from other indirect methods of evaluating body composition (anthropometry, underwater weighing method, air displacement method, bioelectrical impedance method), MRI can minimize errors caused by individual variation and more accurately evaluate skeletal muscle and fat content. In terms of safety, MRI has no ionizing radiation, which has obvious advantages over DXA and CT. MRI is one of the reliable imaging methods for studying sarcopenia, but it has disadvantages such as high cost and complicated operation, which limits the application of MRI. The unique advantage of MRI in assessing body composition determines that it will be the main technical for in depth research in the future.

Ultrasound (US): Ultrasound (US) is a low cost and noninvasive imaging technique that can be used to study diseases such as muscle damage or atrophy. US are a dynamic technology that can dynamically observe the movement of skeletal muscle under normal and pathological conditions. International guidelines on sarcopenia do not strongly recommend the use of US to assess the loss of SMM, but US is a very good choice for assessing qualitative or quantitative changes in skeletal muscle. US can estimate SMM by measuring muscle thickness, and analyze the degree of fat infiltration in the muscle based on the gray value of echo intensity.

Bioelectrical Impedance Analysis (BIA): The BIA is a cheap, simple and non-invasive detection technology, mainly used to measure human body composition. The use of BIA to measure body composition has been widely recognized, and with the development of technology, its accuracy has also been greatly improved.

Discussion

Sarcopenia and GC

Increase the risk of GC: Professor Kim YM conducted a cohort study involving 8356 people. About 41.7% of patients with GC and 16.9% of patients with precancerous state were diagnosed with sarcopenia. Finally, it was found that sarcopenia was related to the occurrence of GC. It may be related to metabolic syndrome, because studies have also found that diabetes, hypertension and dyslipidemia are also closely related to the occurrence of GC. Sarcopenia was associated with GC and may be novel risk factors for gastric GC.

The relationship between sarcopenia and postoperative outcomes of GC: Some research results show that sarcopenia significantly increases the incidence of postoperative complications of GC and is an independent risk factor for prognosis analyzed the data of 187 GC patients and found that sarcopenia was significantly related to postoperative complications, and affected postoperative nutrition and inflammation analyzed the records of 119 patients undergoing radical gastrectomy and found that the short term survival rate was significantly related to age, TNM stage and SMM. Analyzed 148 GC patients and concluded that sarcopenia is significantly related to the long term prognosis of GC patients who have undergone radical gastrectomy. However, some studies have not found that sarcopenia is associated with postoperative complications analyzed the clinical data of 569 patients in 2017 and found that SMI is an important nutritional indicator that can be used to predict the Overall Survival (OS) of GC patients undergoing gastrectomy, but not affect the incidence of postoperative complications. Professors also came to the same conclusion that the proportion of sarcopenia in 152 patients with GC was as high as 57.5%, but there was no relationship between sarcopenia and postoperative complications. The reason for this contradiction may be that different studies have used different cutoff values. In addition, different countries, different races, tumor types and inclusion criteria may cause differences in results.

The relationship between sarcopenic obesity and postoperative outcomes of GC: Sarcopenic Obesity (SO) refers to the presence of sarcopenia and a higher fat content. According to reports, the incidence of SO is 2%-21.7%, which is closely related to body dysfunction, metabolic diseases and mortality. In the case of chronic inflammation, malignant tumors, body aging, etc., muscle mass gradually decreases while fat content may remain unchanged or increase. Low muscle mass and high fat content may be important characteristics of the aging process. It is well known that obesity is a risk factor for complications after upper abdominal surgery used preoperative CT to assess skeletal muscle and fat. Among 636 patients with GC, 39 (6.1%) were diagnosed with SO. The results of the study found that compared with the simple sarcopenia and simple obesity groups, the SO group had a higher risk of serious postoperative complications and a worse prognosis.

Interventions for Sarcopenia

Physical exercise: Exercise is the most effective intervention to delay muscle attenuation. Physical exercise can effectively improve muscle mass, strength and physical fitness. Some studies have found that exercise can increase the content of myofibrillar protein by activating satellite cells, and can significantly reduce intramuscular and intramuscular fat infiltration. Exercise can enhance the function of mitochondria, by increasing the proliferation activation receptor γ-PGC1α and muscle fatty acid binding protein, mitochondrial genes are activated and mitochondrial energy output is increased. Exercise can also significantly improve the body's inflammation and down regulate the levels of CReactive Protein (CRP) and Interleukin-6 (IL-6). For patients with sarcopenia, the improvement of muscle function is not only manifested in the increase of muscle mass and strength, compared with the decrease of muscle mass and strength, the decline of muscle function is more indicative of poor prognosis. The study of physical exercise on improving muscle function is still in the exploratory research stage, and further in depth randomized controlled clinical trials are needed. At present, a large number of studies have confirmed the importance of exercise to relieve and improve sarcopenia. Conducted a 6 months observational study on 30 elderly patients, and the results showed that active aerobic resistance exercise has positive effect on body composition, blood sugar and lipid control, leg muscle strength and walking in elderly patients. Professor Nathan J de Vos found that resistance training with different sizes of resistance can increase peak muscle strength, and there is a dose response relationship between training intensity and changes in muscle strength and endurance. Therefore, heavy load resistance aerobic exercise may be the most effective intervention strategy to improve the muscle mass, strength and endurance of the elderly. In short, for patients with sarcopenia before surgery, active and effective physical exercise is of great significance to improve the prognosis.

Nutritional support: The dynamic balance between protein synthesis and decomposition is a decisive factor in maintaining muscle mass. The formation of Sarcopenia is mainly due to weakened muscle anabolism and/or increased catabolism. The intake of protein and amino acids provides the most important materials for skeletal muscle synthesis and metabolism. The synthesis of muscle protein is regulated by a variety of stimulating factors. Among essential amino acids, branched chain amino acids are thought to directly stimulate muscle protein synthesis. Lucien was found to stimulate the mammalian kanamycin (mTOR) pathway and inhibit the activity of proteases, thereby increasing muscle protein synthesis and inhibiting decomposition. For patients with risk factors for Sarcopenia, it is necessary to take in more protein and amino acids to improve the attenuation of muscle mass and mass. Regarding the source of protein, there is no conclusive evidence that animal derived protein is different from plant derived protein. However, animal-derived proteins contain higher Essential Amino Acids (EAAs), which are theoretically easier to digest and absorb than plant derived proteins. Animal meat contains a large number of biologically active ingredients (such as creatine, carnitine, iron and cobalamin), which may have a positive effect on muscle physiology. Most studies have shown that the intake or supplement of protein and EAAs has a positive effect on muscle mass, strength and body function.

Conclusion

The occurrence of Sarcopenia is closely related to aging, insufficient nutrition, lack of exercise and disease. Among GC patients, more than half have malnutrition or muscle attenuation at the time of diagnosis. Attenuation of skeletal muscle mass and quality is an important factor leading to poor prognosis. A large number of studies have shown that sarcopenia is an unfavorable factor for postoperative complications and long term prognosis of GC. Sarcopenia has attracted more and more attention from nutritionists, clinicians and patients, and has been clearly defined as a muscle disease. Many international organizations concerned with sarcopenia have issued clinical guidelines, expounding the definition, epidemiology, etiology, pathogenesis, clinical diagnostic criteria and intervention measures of Sarcopenia in detail. With the continuous understanding of pathogenesis and the continuous development of auxiliary diagnostic technology, the content of the guide is constantly updated and improved. Large scale retrospective clinical research and prospective clinical research with high evidence based medical evidence have continuously improved people's awareness and attention to sarcopenia. Although Sarcopenia has received extensive attention from clinicians, and there are many international diagnosis and treatment guidelines, the diagnostic criteria are not uniform, which leads to the lack of widespread clinical application. Therefore, we need to carry out more extensive multi center research, provide a higher level of evidence based medicine, and formulate more scientific and reasonable intervention strategies.

Acknowledgements

Not applicable.

Ethics Approval and Consent to Participate

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Competing Interests

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