This prospective study was conducted in accordance with the ethical standards of the Declaration of Helsinki. Informed consent was obtained from all patients and the study was approved by the Institutional Review Board of our institution (Seoul National University Budang Hospital Instituitional Review Board Approval No. B-2112-724-103). Patients with Breast cancer who underwent breast reconstruction using free MS-TRAM between January 2018 and August 2021 were included. Female patients aged > 19 years, with breast cancer stage I~IIIA (AJCC 8th edition staging), and undergoing immediate breast reconstruction after nipple-sparing, skin-sparing, or total mastectomy or receiving delayed breast reconstruction were enrolled in the study. Patients with a pre-existing hematologic disorder or severe anemia requiring preoperative IV-FCM were excluded from the study. In addition, patients undergoing bilateral breast reconstructions or refusing blood transfusion were excluded.
Intravenous Ferric Carboxymaltose (Ferinject®)
A total of 84 patients undergoing free MS-TRAM flap breast reconstruction were injected with IV-FCM (Ferinject®, Vifor International, Switzerland) from March 2020 to August 2021. A single dose of 500 mg FCM mixed with 100 mL of 0.9% sodium chloride was injected intravenously within five hours from the end of the operation, regardless of the patient's postoperative Hb level or EBL during the surgery. The injection was performed slowly over 10 minutes, and the patients were closely monitored for any adverse reactions.
Historical control group
The abovementioned IV-FCM injection protocol was adopted at our department in March 2020. Since the adoption, all patients were enrolled as a part of our prospective study cohort (Ferinject group). For comparison, a historical control group of patients undergoing free MS-TRAM breast reconstruction from 2018 to February 2020 was enrolled.
All enrolled patients underwent either immediate or delayed breast reconstruction using a free MS-TRAM flap. For immediate reconstruction patients, reconstruction was performed following mastectomy and axillary lymph node dissection, if necessary, by a general surgeon. The operation was performed by a plastic surgeon only for delayed reconstruction patients.
In all patients, free MS-TRAM flaps were elevated in either muscle-sparing type I or II while incorporating an average of three to four perforators from medial and lateral rows of the deep inferior epigastric artery. For the recipient vessel, either internal mammary or thoracodorsal vessels were chosen. One arterial and one or two venous anastomoses were performed end-to-end.
Preoperative workups, including complete hematological analysis, were performed within one month of the scheduled operation. Hematological parameters including Hb level (grams/deciliter), Hct level (%), RBC count (million count/microliter) were the main clinical variables collected in this study. Other patient characteristics, including BMI, underlying comorbidities, baseline characteristics, along with surgical variables including mastectomy resection amount (grams), execution of axillary lymph node dissection, were collected. Furthermore, any IV-FCM injection-related complications such as hypersensitivity, skin discoloration, and surgical complications (hematoma, wound infection, flap congestion, and necrosis) were analyzed.
Patients received transfusions according to our strict transfusion protocol. One pack (300 mL) of whole RBC was transfused if the perioperative Hb level was < 8.75 gm/dL or the Hct level was < 30%. If laboratory results following the initial transfusion did not meet the above criteria, additional transfusions were performed until necessary.
The primary outcomes were transfusion rate and the amount of transfusion (total number of packed RBCs transfused during the hospital stay). The secondary outcomes were fluctuations in hematological parameters and flap or donor site-related complications between the study and control groups. Hematological parameter changes (RBC cell count, Hb level, and Hct level) were analyzed from preoperative levels to immediate postoperative, one-day, two-day, and three-day postoperative levels. Furthermore, any flap or donor site-related complications (re-admission or re-operation within 60 days postoperatively, infection, wound dehiscence, or fat necrosis of the flap or the abdominal donor site) were analyzed.
Baseline characteristics and transfusion rates were compared between the study and historical control groups using univariate analysis. Chi-square tests were performed for binary variables. To reduce the bias of confounding variables between the two groups, propensity score-matched analyses were performed. Logistic regression analysis was utilized to develop propensity scores by incorporating binary responses between the two groups as the dependent variable and IV-FCM injection status and other covariates (age, BMI, surgical risk factors, and operative details) as the independent variables. The propensity score was matched randomly with a 1:2 ratio (study vs. control) with a caliper width of 0.01.
Transfusion frequency and total transfusion amount were compared between the two propensity-matched groups. Subsequently, cross-analysis was performed using the chi-square and Fisher's exact tests. The patients were further grouped into two subgroups within each group depending on whether they received transfusions. Within the subgroups, the primary outcomes (Hb and Hct level changes between preoperative and immediately postoperative and 24 hours, 48 hours, and 72 hours postoperatively) were compared using an independent t-test and Leven's test. A two-sided significance level of 0.05 was set for statistical significance.