Identifying patients with different prognoses according to their clinical and pathological conditions is essential to provide individualized treatment and improving the efficacy of liposarcoma treatments. According to the publication of the European Working Group on Sarcopenia in Older People consensus in 2019 (EWGSOP2)  and the Asian Working Group for Sarcopenia (AWGS) 2019 , sarcopenia is characterized by a low skeletal muscle mass, low muscle strength, and poor low physical performance. Many reports have shown that sarcopenia is closely related to the prognosis of patients with various malignant tumors. [3, 6,7,8,9,10,11, 13, 19,20,21] However, different pathological types of sarcomas are not identical in treatment and prognosis, so we conducted a study on the exact pathological type of sarcomas and drew relevant conclusions. Meanwhile, the effect of sarcopenia on the post-surgical outcomes of patients with liposarcoma undergoing en bloc compartment resection has not been reported. This article is the first retrospective study to investigate the association between sarcopenia and a specific pathological type of sarcoma in a homogeneous population of patients with retroperitoneal liposarcoma treated by radical surgery performed in an independent large-volume institution.
Routine CT scans were easy to access, wherein the skeletal muscle index (SMI) is measured for sarcopenia determination. Currently, the cutoff value point of sarcopenia remains controversial mainly because of the differences among different ethnic groups. The previous definition mentioned by Guohao Wu et al. included 6447 samples, and the cutoff value was the lowest sex-specific quartile of SMI at L3 in those patients. Therefore, we chose the cutoff point defined by Guohao Wu et al. (43.13 cm2/m2 for men and 37.81 cm2/m2 for women).
The interest in pre- and post-operative nutrition is already recognized. Traditional metabolic and nutritional care of patients undergoing major elective surgery has emphasized preoperative fasting and reintroduction of oral nutrition 3–5 days after surgery . Because the RLS has an invasive tendency and the invasion of the intestine will be seen from time to time as well as combined multiple organ resection will be seen in many RLS patients, which causes a lengthy recovery period for the gastrointestinal function, and then prolonged fasting time and injure the nutritional condition of post-operation patients. That is why evaluating the nourishment level before the operation's implementation is essential. The post-operation nutritional condition is also vital to the recovery of patients. Furthermore, the poor preoperation nutritional condition will also increase the post-operation recovery time and incidence of death and complications . The results of this study showed that patients with sarcopenia had low BMI and hemoglobin levels. There was no association between sarcopenia and postoperative complications, but sarcopenia was associated with severe complications, which are defined as the Clavien-Dindo grade > 2. This means that RLPS patients with sarcopenia are more likely to expose to severe and fatal complications. In previous studies, the results showed that sarcopenia is not an independent predictor of postoperative complications . However, no one compared the association between sarcopenia and severe complications in patients with LPS.
Many reports showed that sarcopenia was related to poor RFS or distant metastasis-free survival (DMFS), such as Extrahepatic Cholangiocarcinoma, Pancreatic Ductal Adenocarcinoma, nasopharyngeal carcinoma, non-small cell lung cancer, and colorectal cancer. [5, 15, 23,24,25]The mean mechanism for this result might be that sarcopenia is associated with immune senescence and reduces cancer immunity, which induces the reduction of immunity to inflammation. The inflammatory microenvironment is changed, which is involved in carcinogenesis and cancer progression [26, 27]. However, in our study, there was no strong correlation between sarcopenia and the RFS and OS of patients with RLPS. We used Cox proportional hazard model, and univariable and multivariable analyses showed that the higher level of SCr was an independent risk factor for RFS and confirmed as a significant independent prognostic factor for worse overall survival, which is partly similar to previous studies [28, 29]. However, underlying mechanisms for this association in liposarcoma patients have not been elucidated. The possible reason is that creatine and Phosphocreatine are essential energy sources donating ATP. The serum creatinine as a waste product of the creatine metabolism for donating ATP might increase during cancer progression. Therefore, with highly active tumors, serum creatinine levels might be higher . The histologic subtype was an independent risk factor for RFS, and the preoperative symptom was a significant independent prognostic factor of OS.
Speculations on why there was no association between sarcopenia and the RFS and OS in RLPS are listed below. First, the pathological types of sarcomas are numerous and complicated. In previous studies, which demonstrated that sarcopenia was independently associated with poorer long-term prognosis in sarcoma, the pathological types of sarcomas were not stratified and analyzed, and they could not answer the specific influence of sarcopenia on a particular kind of pathological type of sarcoma. Second, the number of patients included in this study was limited, and the follow-up time was not long enough to see the outcome of every patient. Third, the biological origin and inflammatory microenvironment may differ in RLPS than in other kinds of carcinoma, so sarcopenia impacts fewer in RLPS than in different carcinomas. Although sarcopenia was predicted to cause worse surgical complications, there was no association between sarcopenia and relapse-free survival and overall survival in RLPS, which was consistent with the previous study . Therefore, further research should be done with a larger sample, a longer follow-up, and a deeper investigation of molecular and biological mechanisms of sarcopenia in LPS. Nevertheless, this is the first study to investigate the potential impact of sarcopenia on the long-term outcomes of patients with RLS. If the result is still widely applicable in an enlarged sample, then we can be reassured that there is no long-term oncologic penalty to be paid for sarcopenia in LPS.
Although RLPS is a sporadic disease, we collected all accessible cases. Nevertheless, this study still had some limitations. First, most patients with liposarcoma were primarily diagnosed, and the local recurrent cases were excluded, so the number of patients was limited, which may cause bias. Second, this study was a retrospective study conducted in a single institution and included the Asian population only; therefore, further prospective studies and data from Western countries should be investigated. Third, due to the relatively few cases of stratified analysis of pathological subtypes, we did not identify sarcopenia related to liposarcoma subtypes, which might affect the prognostic value of sarcopenia for liposarcoma. Therefore, we need a larger sample size to determine and verify the prognostic effect of sarcopenia on different pathological types of RLPS. Anyway, to our knowledge, this is the first study to explore the impact of sarcopenia on the short-term and long-term outcomes in patients with RLPS by using data from a single large-volume institution, thus providing a reference for future clinical trials.