Abstract
Background/Aim: The thigh is divided into the anterior, medial, and posterior compartments, and malignant soft tissue tumours can occur in any compartment of the thigh. This study analysed the relationship between various factors, particularly tumour location and clinical outcome, in patients with primary soft tissue sarcoma of the thigh. Patients and Methods: Seventy-four patients were included in this retrospective study. The relationships between variables and prognosis were statistically analysed. Results: Multivariate analysis of the patient clinical data demonstrated that seromas developed more often in the medial compartment tumours and postoperative complications excluding seroma occurred more frequently in patients with two or more muscles resected or stage III tumours. A low Musculoskeletal Tumor Society score was associated with a long operative time (more than 120 min), anterior compartment tumours, and more than two muscle resections. In addition, soft tissue sarcomas in the medial compartment and stage III sarcomas were associated with a low 5-year metastasis-free survival. Conclusion: Soft tissue sarcomas in the medial compartment were associated with postoperative seroma and metastasis, whereas sarcomas in the anterior compartment correlated with low postoperative function.
Soft tissue sarcomas are rare tumours that represent <1% of all malignancies (1). Approximately one-third of all soft tissue sarcomas develop in the thigh (2), and the risk factors for developing a complication after soft tissue sarcoma resection include the tumour’s location in the lower extremity (3). Studies have revealed that within the lower extremity, tumours in the thigh have a higher rate of complications and reoperation (4-11). The thigh is divided into the anterior, medial, and posterior compartments. Each compartment is characterized by anatomical structures: the quadriceps in the anterior compartment, the femoral nerve and vessels in the medial compartment, and the sciatic nerve in the posterior compartment (12). Malignant soft tissue tumours can occur in any compartment of the thigh (anterior, 49%; medial, 23%; and posterior, 28%) (12). Postoperative complications have been more commonly observed in the medial compartment (12, 13). The number of postoperative complications for soft tissue sarcomas of the thigh may be reduced using LigaSure®. The LigaSure® vessel sealing and dividing system was reported by Levine et al. to be a safe and effective haemostatic tool for deep dissection in bone and soft tissue sarcoma surgery (14).
This study aimed to analyse whether clinical outcomes after resection of primary soft tissue sarcoma of the thigh were influenced by the tumour characteristics or the compartment location.
Patients and Methods
A non-controlled retrospective analysis was conducted based on medical record data. The authors did not receive any benefits or funding from any commercial party related directly or indirectly to the subject of this article. This study was approved by the Human Ethics Committee of Kanazawa University Hospital and adhered to the principles of the Declaration of Helsinki. Informed consent was obtained from all patients.
Patients who underwent wide excision of soft tissue sarcomas of the thigh without metastasis at the time of the initial visit between January 2006 and March 2018 were included in the study. One patient with a follow-up period of less than two years was excluded. Seventy-four patients (37 men and 37 women) met the inclusion criteria for our study. Sex, age, tumour size, operative time, tumour localization, amount of muscle resection, tumour stage [calculated using the 8th edition of the International Union against Cancer (UICC) / American Joint Committee on Cancer (AJCC) systems], postoperative radiotherapy, neoadjuvant and/or adjuvant chemotherapy, and use of the LigaSure® vessel sealing device were compared and assessed for the following outcomes: seroma with puncture, postoperative complications excluding seroma, the Musculoskeletal Tumor Society (MSTS) score (15) excluding the emotional acceptance score when the patients had the best condition, and prognosis. Regarding the amount of muscle removed, 1 and 0.5 points were given for complete resection and partial resection, respectively (16). Tumour size was measured using the longest axis of the MRI measurement. Histological grade was determined according to the French Federation of Cancer Center (FNCLCC) grades. Cases with grades 2 and 3 were classified as high grade. Atypical lipomatous tumours with wide excision were included as liposarcomas. Postoperative complications excluding seroma were defined as any event that required medical treatment. In addition, the relationship between the MSTS score and all postoperative complications was analysed. Disease recurrence and metastasis were confirmed by radiologists. Recurrence and metastasis were routinely surveyed using MRI or chest computed tomography (CT) scans at presentation with three- and six-month follow-up scans. Oncological survival outcomes were assessed by calculating the locoregional recurrence-free survival (LRFS), defined as the time from the date of the operation to the date of the first locoregional recurrence; the distant metastasis-free survival (DMFS), defined as the time from the date of the operation to the date of first metastatic recurrence; and the overall-survival (OS), defined as the time from the date of the operation to the date of death.
All statistical analyses were conducted using the EZR software (Saitama Medical Center, Jichi Medical University, Saitama, Japan). Associations between variables were tested using a Fisher’s exact test. Survival curves were compared using log-rank tests. Logistic regression and Cox regression analyses were used for multivariate analyses and were built using pvalue <0.5. Results with p>-values <0.05 were considered statistically significant.
Results
The mean patient age was 58.7 years (10-86 years), the mean follow-up period was 75 months (24-173 months), and the mean tumour size was 11.7 cm (0.7-24 cm). The tumours were histologically classified as follows: 36 cases of liposarcoma, 12 cases of malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma, 7 cases of myxofibrosarcoma, 4 cases of leiomyosarcoma, 4 cases of malignant peripheral nerve sheath tumour (MPNST), 3 cases of synovial sarcoma, 3 cases of extraskeletal osteosarcoma, 2 cases of fibrosarcoma, one case of rhabdomyosarcoma, 1 case of extraskeletal chondrosarcoma, and 1 case of low-grade myofibroblastic sarcoma. The UICC/AJCC stage I, stage II, and stage III was diagnosed in 31, 6, and 37 patients, respectively. The mean operation time was 136.1 min (36-410 min). A total of 37 tumours were predominantly located in the anterior compartment of the thigh, 17 in the medial compartment, and 20 in the posterior compartment. The mean amount of muscle removed was 2.2 (0.5-7) points. Three patients received postoperative radiotherapy, and twenty-three patients received neoadjuvant and/or adjuvant chemotherapy. LigaSure® was used in 16 patients (Table I). A total of 27 patients (36.5%) had postoperative complications; of these patients, seroma developed in 18 patients (24.3%, Figure 1), neurological complication in 5 patients (6.8%), anaemia with transfusion in 4 patients (5.4%), and surgical site infection in 4 patients (5.4%). The mean MSTS score was 20.9 (83.6%). The 5-year LRFS, DMFS, and OS rates were 82.4%, 82.6%, and 92%, respectively.
Patient characteristics.
Representative scans of a patient’s initial diagnosis and follow-up. (a) Coronal T2-weighted magnetic resonance image (MRI) of a 72-year-old man with a dedifferentiated liposarcoma in the right medial compartment of his thigh. (b) Axial MRI in short T1 inversion recovery (STIR). (c) Coronal T2-weighted MRI of three-month postoperative seroma in the same patient. (d) Axial MRI in STIR.
The use of the LigaSure® vessel-sealing device was significantly associated with seroma in multivariate analysis (p<0.05, Table II). The results of multivariate analysis are as follows: seromas developed more often in the medial compartment (p<0.05, Table II); postoperative complications excluding seroma occurred more often in patients with more than two muscles resected or stage III tumours (p<0.05, Table III); a lower MSTS score was associated with more than 120 min of operative time, anterior compartment tumours, and more than two muscle resections (p<0.05, Table IV); and soft tissue sarcomas in the medial compartment and stage III sarcomas were associated with a lower 5-year DMFS (p<0.05, Table V, Figure 2 and Figure 3).
Correlation between seroma with treatment and variables.
Correlation between postoperative complication excluded seroma and variables.
Correlation between MSTS score and variables.
Oncological outcomes of patients with DMFS.
Distant metastasis-free survival (DMFS) by tumour location. DMFS in months is shown for tumours either located in the medial or anterior/posterior compartments.
Distant metastasis-free survival (DMFS) by tumour stage. DMFS in months is shown for stage I/II or stage III tumours.
Discussion
In our analysis, medial compartment soft tissue sarcoma was associated with postoperative seroma and metastases, while anterior-compartment tumours were associated with lower MSTS scores. Several studies have assessed the clinical outcomes after surgery for malignant soft tissue tumours in the thigh; however, only few have investigated the correlation between postoperative results and each compartment.
The anterior compartment of the thigh contains the quadriceps. Ploutz-Snyder et al. (17) reported that the quadriceps are closely related to many activities of daily living; therefore, reduced quadriceps strength could be a useful indicator of difficulty in performing activities of daily living. The number of resected muscles had the greatest impact on knee extension strength; thus, it might be a useful preoperative predictor of postoperative muscle strength and function (16). In our multivariate analysis, a lower MSTS score was associated with the anterior compartment and more than two muscle resections but not with postoperative complications. Besides, Tanaka et al. (18) described that postoperative function was maintained for patients with adductor compartment resection as well as our study. These results indicate that the postoperative function can be attributed to anatomical excision. Our analysis may serve as a guide for setting rehabilitation goals.
The medial compartment of the thigh contains the major blood and lymphatic vessels. Moore et al. (5) reported that proximal lower extremity tumours predisposed patients to major wound complications, through both univariate and multivariate analyses of 256 soft tissue sarcoma patients. In addition, according to Nakamura et al. (13), since a branch of the obturator artery and the femoral artery are present around the attachment of the adductor muscle to the pubis, the management of soft tissue sarcomas of the medial compartment, especially when involving the proximal medial compartment, remains a challenge owing to the high risk of bleeding. Other reports suggest that the lymphatics found in the medial compartment are damaged during surgical dissection, and this damage may lead to seromas with subsequent wound complications (5, 12, 19, 20). Likewise, in our study, seroma developed more often in medial compartment tumours, and seroma with subsequent infection occurred in two patients. In addition, multivariate analysis conducted by Rimner et al. (12) revealed that medial compartment tumours were an independent predictor of seroma. In the current study, soft tissue sarcomas in the medial compartment were associated with a lower 5-year DMFS, and reconstruction of the femoral artery was required in two patients with medial compartment tumours. Carneiro et al. (21) described vascular invasion as an independent risk factor for metastasis in a multivariate analysis. In addition, Alitalo et al. (22) suggested that malignant cells could interact with lymphatic vessels to induce a conductive microenvironment for malignant cell survival in lymph nodes and at sites of distant metastasis. The proximity of the tumour to the femoral blood and lymphatic vessels may contribute to metastasis.
The LigaSure® vessel sealing and dividing system is an electrothermal bipolar vessel sealer that functions by denaturing collagen and elastin within the vessel wall and the surrounding tissue to create a seal (23). The main advantage of this device is that it simplifies the procedure and eliminates the need for clips and suture ligation while also achieving efficient haemostasis (24). In this study, use of the LigaSure® vessel-sealing device was significantly associated with postoperative seroma; however, a selection bias might have occurred while deciding whether to use LigaSure® for surgery. Reportedly, the use of vessel sealing systems can reduce intraoperative bleeding and blood transfusion volume as well as suppress postoperative wound complications (13, 14, 25-27). LigaSure® may be beneficial for patients with soft tissue sarcomas of the thigh.
Our study describes how sarcomas in different thigh compartments have different clinical outcomes and would guide future surgical decisions and rehabilitation goals. On the other hand, it also had certain limitations. First, the study was retrospective. Second, the study was conducted with a small sample size. Lastly, atypical lipomatous tumours that were not malignant were considered as liposarcomas.
In conclusion, soft tissue sarcomas that developed in the medial compartment were associated with postoperative seroma and metastasis. In addition, anterior muscle resection with a tumour resulted in lower postoperative limb function.
Acknowledgements
The Authors thank Editage (www.editage.com) for English language editing and publication support.
Footnotes
Authors’ Contributions
SM, AT, NY, KH, SM, KI, HY, YA, SS and HT designed the study. SM collected the data. SM, AT and NY analyzed the data and developed the methodology. SM was a major contributor in writing the manuscript. SM and AT analyzed and interpreted the patient data. HT oversaw the study. All Authors read and approved the final manuscript.
Conflicts of Interest
The Authors have declared that there are no competing interests.
- Received March 20, 2022.
- Revision received April 6, 2022.
- Accepted April 27, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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