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Page 6 of 10           Dengsoe et al. Plast Aesthet Res 2024;11:25  https://dx.doi.org/10.20517/2347-9264.2024.20

               Three studies [16,22,25]  found that patients receiving free flap reconstruction started adjuvant treatment
               significantly later than patients receiving mastectomy only. The cause of this was found to be surgical
               complications, such as flap necrosis. Kontos concludes that this delay may affect survival for at least a
               proportion of patients, highlighting the need for microsurgical reconstructive procedures in high-volume
               centers with experienced teams in order to minimize surgical complications.

               O’Connell et al. found that free flap reconstruction was associated with a significantly longer time to
               initiation of adjuvant therapy compared to mastectomy only . The median difference was small, only five
                                                                   [24]
               days, and the authors comment that this difference hardly carries any clinical significance. Therefore, they
               conclude that free flap reconstruction does not result in clinically significant delays in the initiation of
               adjuvant therapy. The study also investigated complication rates and found that patients who developed
               complications - regardless of surgical procedure - were more likely to experience significant delays of more
               than 90 days compared to patients with no complications. Correspondently, they found that patients with
               free flap reconstructions developed significantly more complications, especially major complications
               resulting in readmission or further surgery, compared to patients treated with mastectomy only.

               It is noteworthy that patients with free flap reconstruction do not experience clinically significant delays in
               the initiation of adjuvant therapy despite the higher rate of surgical complications among these patients.
               The authors explain this paradox by looking into the patient selection for free flap reconstruction and
               reconstructive breast surgery in general. Patients selected for reconstructive surgery tend to be younger,
               have fewer comorbidities, have lower BMI, be non-smokers, and in general, have fewer risk factors for
               complications. To that, they are less likely to require adjuvant treatment because immediate reconstruction
               is often performed following mastectomy for low-stage disease where lymph node involvement is not
               anticipated. This patient- and disease-related pattern is evident in O’Connell et al.’s study and it
               corresponds well with the findings made in the other studies in this review and in general when reading the
               literature on this subject [24,27] . The tendency to refrain from immediate reconstruction in high-stage disease
               suggests that surgeons and medical oncologists are cautious in offering immediate reconstruction to
               patients who are likely to require adjuvant treatment because of the risk that longer recovery time and
               complications may delay the initiation of adjuvant treatment. This restraint toward immediate breast
               reconstruction among physicians was presented in a publication as early as 2002, where authors
               hypothesized that the low number of breast reconstructions performed at the time was partly due to
               inadequate knowledge and misinformation about breast reconstruction. The study found that nearly 40% of
               medical oncologists were concerned that immediate breast reconstruction would interfere with adjuvant
               treatment .
                       [28]
               Lee et al. registered a noteworthy shorter median time to initiation of chemotherapy compared to the other
               studies (27 days in the free-flap group compared to 25 days in the mastectomy-only group) . No statistical
                                                                                            [23]
               analysis comparing the two groups was performed, but it is evident that the difference is minimal and
               without clinical significance. Interestingly, they found the shortest median time to initiation of
               chemotherapy, shortest intervals to drain removal, and fewer admission days among patients with free flap
               reconstructions compared to patients receiving other methods of reconstruction (LD-flap and tissue
               expander/implant), although it should be noted that the difference was only significant concerning drain
               removal. This trend stands in contrast to the findings in, e.g., O’Connell et al. and Wilson et al., who both
               describe a shorter median time to initiation of chemotherapy among patients with implant-based
               reconstructions compared to free flap reconstructions [24,15] . It should be noted that the analyses concerning
               especially the free-flap subgroup were particularly limited due to the small number of patients, as only nine
                                                                             [23]
               patients with DIEP-flap reconstructions were included in Lee et al.’s study .
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