Breast reconstruction is considered an important factor in recovery from breast cancer surgery, improving the quality of life and mental health of patients. Studies have demonstrated significantly improved quality of life in patients who underwent breast reconstruction compared to that of those who underwent mastectomy alone (1, 2). Despite the drawbacks, such as long operation times and possible complications, autologous tissue free-flap reconstruction is a rational choice for breast reconstruction. However, these disadvantages have lessened over time; appropriate patient selection and improved surgeon skill sets are associated with decreased complication rates (3).

Complications of autologous breast reconstruction include necrosis of the mastectomy flap, infections, hematoma, seroma, and, most importantly, vascular compromise (3). The well-known patient-related factors associated with high complication rates are smoking, diabetes, old age, and overweight (1). Overweight, defined by a body mass index (BMI) >25 kg/m², is a broad metabolic condition with varying presentations. High BMI values can occasionally originate from high muscle mass with adequate or less adipose tissue. Thus, recent reports have focused on the lack of muscle mass, known as sarcopenia, rather than on excessive total body weight (4, 5).

Sarcopenia is defined as an absolute muscle mass below two standard deviations from the mean value observed in healthy young adults (6). Recently, the European Working Group on Sarcopenia for Older People has updated the criteria for defining sarcopenia. These criteria propose screening patients with a suspicion of sarcopenia and confirming the diagnosis via muscle mass measurement. However, a global consensus regarding the definition of sarcopenia is lacking (7). Given the widespread use of computed tomography (CT) as an imaging modality, skeletal muscle mass cutoff values calculated by CT imaging are currently used in many clinical settings (7, 8). The prevalence of sarcopenia can range from 3% to 24%, depending on the diagnostic criteria and population age (9). Sarcopenia is also known to be related to inactivity and chronic diseases. The incidence of sarcopenia is increasing, and its association with chronic diseases has been reported (9). Since the association of sarcopenia with poor prognosis in patients with cancer was revealed in 2008 by Prado et al. (10), many follow-up studies have elucidated its clinical significance. Moreover, sarcopenia is also believed to hinder recovery from chemotherapy and surgery (11). Recent studies have revealed the association between complications observed in patients with breast cancer and sarcopenia (12, 13). However, these studies considered various onco-surgical complications instead of those directly related to breast reconstruction alone. Previous research has attempted to prove the importance of sarcopenia in breast reconstruction. Some studies have reported sarcopenia as a discouraging prognostic factor in autologous breast reconstruction; however, some reports have presented contradicting results (4, 5). Therefore, in our study, we attempted to confirm the association between the complications associated with autologous microsurgical breast reconstruction and the patient’s sarcopenia status before surgery. Establishing this connection could lead to more precise patient selection and stratification for autologous microsurgical breast reconstruction surgery, reducing severe complications such as flap detachments. Thus, we aimed to determine the relationship between sarcopenia and high complication rates in autologous microsurgical breast reconstruction.

We aimed to determine the relevance of sarcopenia in other breast reconstruction-related complications, such as peri- and postoperative complications. Major perioperative complications, such as total flap loss or emergency re-anastomosis, were irrelevant in patients with sarcopenia as indicated by the lack of statistical significance even after IPTW adjustment. In contrast, postoperative complications, such as infections and hematoma, were positively related to sarcopenia after IPTW adjustment.

Sarcopenia results from a multi-pathway pathogenesis and is not solely a consequence of a sedentary lifestyle (9, 16). Chronic inflammation, hormonal changes, reduced protein and vitamin D intakes, and low muscle satellite cell activation contribute to sarcopenia pathogenesis (17)— for instance, well-known conditions associated with it, such as aging and lack of exercise, can be attributed to aging-related inflammation and low muscle cell stimulation (17).

From the comparison of postoperative recipient site infection, we inferred that sarcopenia would adversely affect the patient’s immunity. Infection is usually determined by the patient’s immune system status and adherence to aseptic protocols in the institution. Previous reports have also implicated a relationship between sarcopenia and the immune system. Some studies in oncological surgery have suggested preoperative sarcopenia as a predictive factor for postoperative infection (18, 19). Takano et al. and Yasuhiro et al. reported the relationship between sarcopenia and high postoperative infection in gastric and colorectal cancer surgeries (20, 21). A recent study focused on the relationship between sarcopenia and the systemic immune system; however, the results were inconclusive (22). Our findings further reinforce the uncertain relationship between postoperative infection and sarcopenia.

Postoperative hematoma is another complication that is influenced by the prevalence of sarcopenia. However, unlike infection, studies evaluating the relationship between postoperative hematoma and sarcopenia in cancer surgeries are lacking. Nevertheless, similar reports have stated that preoperative sarcopenia is an independent risk factor for postoperative major organ bleeding in cardiovascular interventions, such as coronary stenting or left ventricular assist device support (23). While the cause remains unclear, the frailty of patients with sarcopenia might lead to a bleeding tendency due to the lack of coagulative components (23, 24). In cardiovascular interventions, sarcopenia is more pronounced and related to the outcome as it can directly affect cardiac mass and function (24), thus displaying a slightly different pathophysiology from that in onco-reconstructive surgeries. Some studies have focused on the relationship between serum coagulation factor levels and sarcopenia. Chen et al. reported that the fibrinogen levels were higher in patients with sarcopenia because of the high inflammatory conditions (25). This finding was not directly related to our results; however, sarcopenia may influence the coagulation pathway and systemic inflammation. Azuma et al. reported that sarcopenia is related to decreased serum vitamin K levels (26), which aligns with our results. These results suggest the presence of definite relationships between the coagulation pathway and sarcopenia. To our knowledge, ours is the first study to propose a positive relationship between postoperative hematoma and sarcopenia after an onco-reconstructive surgery.

In this study, the lumbar SMI based on CT images was used to classify sarcopenia. The SMI cutoff points for sarcopenia have not yet been standardized. The cutoff range for sarcopenia in women, determined using SMI, is 29.6–41 cm²/m² (13). The most common cutoff points are 52.4 cm²/m² (male individuals) and 38.5 cm²/m² (female individuals), which were suggested in a study that confirmed the association between muscle mass and mortality in 250 overweight patients with respiratory or gastrointestinal malignancies in Canada (10). Subsequently, Martin et al. confirmed the optimal threshold for muscle mass loss associated with increased mortality in patients with lung or gastrointestinal malignancies (27). Consequently, the threshold for men was 43 cm²/m² for those with BMI <25 and 53 cm²/m² for those with BMI >25. Additionally, 41 cm²/m² was suggested as an appropriate cutoff point for women regardless of BMI (27). Several recent studies have confirmed the association between sarcopenia and the survival rates of patients with breast cancer based on SMI <41 cm²/m² (28–30). Therefore, in this study, SMI of 41 cm²/m² was used as the cutoff point to classify participants with sarcopenia. Considering that the appropriate threshold for sarcopenia in patients with breast cancer remains unknown, the cutoff point used in this study (41 cm²/m²) may have resulted in overestimation or underestimation of sarcopenia. As such, our study proposed the first SMI cutoff value for sarcopenia definition in microsurgical breast reconstruction.

The patient factors that could serve as risk factors for breast reconstruction-related complications are presented in Supplementary Table S1 . Being overweight is a well-known risk factor for complications in autologous microsurgical reconstruction (31). Before IPTW adjustment, the BMI in the group without sarcopenia was higher than that in the group with sarcopenia. Thus, to establish a causal relationship between sarcopenia and complications, we deemed it necessary to adjust for BMI. After IPTW adjustment, the groups exhibited no significant difference in BMI, which allowed us to assess the risk of complications directly associated with sarcopenia. The multivariate analysis revealed that no specific patient factors, including BMI, were related to breast reconstruction-related complications, contrary to the results of a previous preliminary report (31). BMI and sarcopenia are often considered simultaneously, as both factors are related to body composition. We confirmed that sarcopenia can affect the perioperative complication rate. Furthermore, we suggested that, compared to BMI, sarcopenia might be a more sensitive predictor of microsurgical risk in patients with cancer. Further studies with a larger number of patients under various conditions are warranted to confirm this.

In addition, neoadjuvant chemotherapy is known to contribute to the development of sarcopenia and is also associated with poor prognosis during treatment (32). The proportion of patients who received neoadjuvant chemotherapy was not significantly different between the two groups (34.04 vs. 36.84) in the univariate analysis.

We conducted a comprehensive analysis of various factors related to breast reconstruction outcomes. However, a limitation regarding the statistical analyses employed should be acknowledged. We performed numerous statistical comparisons without applying adjustments for multiple testing. While providing insights into potential associations, this approach increases the likelihood of type I errors. Therefore, we recognize the need for caution in interpreting the statistical significance of individual results. To address this limitation, future research in this area may benefit from employing appropriate multiple testing corrections to ensure the robustness and reliability of findings. Furthermore, considering the low incidence of complications, the sample size was not large enough. Consequently, the low number of complications in each category might have limited the establishment of causality. Moreover, no widely accepted and established definition of sarcopenia is available; therefore, different definitions can yield conflicting results. Nonetheless, this study underscores the importance of considering sarcopenia in patients undergoing microsurgical breast reconstruction. When microsurgical breast reconstruction is planned for patients with sarcopenia, which can be easily determined by preoperative CT, lifestyle modification attempts and balanced nutrition intake, along with detailed risk assessment and information, are recommended.

In conclusion, preoperative sarcopenia is an independent risk factor for postoperative complications of autologous tissue breast reconstruction, such as postoperative infection and hematoma. The cause remains unknown, but frailty due to sarcopenic conditions, including decreased major organ function, might be crucial. Therefore, extra caution should be exercised when performing autologous microsurgical breast reconstruction in patients with sarcopenia.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

The studies involving humans were approved by the Severance Hospital Research Ethics Committee. The studies were conducted in accordance with the local legislation and institutional requirements. The human samples used in this study were acquired from primarily isolated data as part of a previous study for which ethical approval was obtained. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements.

S-JL and E-JY have made substantial contributions to the conception and design or data acquisition. D-WL, S-YS, and D-HL have made substantial contributions to data acquisition. Y-JY was involved in the analysis and interpretation of data. S-JL and E-JY were involved in drafting the manuscript or revising it critically for important intellectual content. All authors contributed to the article and approved the submitted version.