Background: Seroma is a common complication of breast cancer surgery. Seroma can also interfere with healing, increase morbidity, and lead to delayed adjuvant treatment.

Objective: To compare seroma formation, seroma volume, total drain volume, and drain duration between the combined flap fixation and Harmonic scalpel technique with the Harmonic scalpel technique alone after a mastectomy and axillary lymph node dissection in a breast cancer patient.

Materials and Methods: A randomized control trial was conducted between October 2021 and October 2023 at the Department of Surgery, Surin Hospital. Sixty-four consecutive patients underwent mastectomies and axillary lymph node dissection. The patients were randomly assigned to Group 1 as Flap fixation and Harmonic scalpel technique with 32 patients and Group 2 as Harmonic scalpel technique alone, also with 32 patients.

Results: Ninety-two patients underwent mastectomies and 28 patients were excluded. Sixty-four patients underwent mastectomies and axillary lymph node dissection. The mean age was 55.08±12.58 years. Twenty-two patients (34.4%) developed clinical seroma, with five patients (15.6%, 95% CI 5.3 to 32.8) being in the combined flap fixation and Harmonic scalpel technique group and seventeen patients (53.1%, 95% CI 34.7 to 70.9) being in the Harmonic scalpel technique alone group. The combined flap fixation and Harmonic scalpel technique could reduce seroma formation and volume significantly compared to the Harmonic scalpel technique alone (p=0.002 and 0.007, respectively). No statistical significance was found in the total drain volume (p=0.742) and drain duration (p=0.457) between the two groups. The combined flap fixation and Harmonic scalpel technique was significantly correlated with longer operative time (p=0.004).

Conclusion: A randomized control trial showed that the combined flap fixation and Harmonic scalpel technique could reduce seroma formation and seroma volume after a mastectomy and axillary lymph node dissection in a breast cancer patient.