RESUMO
Thin women have not traditionally been considered ideal candidates for autologous breast reconstruction. The purpose of this study was to examine the use of deep inferior epigastric perforator (DIEP) flap reconstruction in thin women undergoing immediate unilateral breast reconstruction. A retrospective review of 1,040 consecutive patients was performed. In total, 381 patients met the inclusion criteria. To improve clinical interpretability, patients were divided into three groups based on body mass index: "thin" (BMI ≤ 22.99), "traditional" (>23 and ≤29.99), and "obese" (BMI >30) candidates. Flap characteristics were compared to mastectomy weights, and postoperative complications were analyzed. In all groups, flap size was generally more than sufficient to match the mastectomy specimen, as flap weight:mastectomy weight ratio ws greater than 1 in all groups with no significant difference between groups (1.1 in thin patients, 1.0 in traditional patients, and 1.0 in obese patients). Fat necrosis prevalence was lowest in the thin group (12.5%), compared to the traditional (15.9%, P = 0.443) or obese (14.4%, P = 0.698) groups. Prevalence of breast infection were lower in the thin patients (5.2%) versus the traditional (8.7%, P = 0.287) or obese (14.4%, P = 0.033). Abdominal wound healing complications and seroma were also lowest in thin patients. DIEP flap breast reconstruction may be an effective method for unilateral breast reconstruction in thin patients, with sufficient flap weights and lower incidence of complications than in heavier patients. As such, low BMI may not present a barrier in the reconstruction of a breast mound matching native breast size.
Assuntos
Índice de Massa Corporal , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia , Retalho Perfurante , Magreza/complicações , Adulto , Idoso , Neoplasias da Mama/complicações , Artérias Epigástricas/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicações , Retalho Perfurante/irrigação sanguínea , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Pharmacological targeting of metabolic processes in cancer must overcome redundancy in biosynthetic pathways. Deoxycytidine (dC) triphosphate (dCTP) can be produced both by the de novo pathway (DNP) and by the nucleoside salvage pathway (NSP). However, the role of the NSP in dCTP production and DNA synthesis in cancer cells is currently not well understood. We show that acute lymphoblastic leukemia (ALL) cells avoid lethal replication stress after thymidine (dT)-induced inhibition of DNP dCTP synthesis by switching to NSP-mediated dCTP production. The metabolic switch in dCTP production triggered by DNP inhibition is accompanied by NSP up-regulation and can be prevented using DI-39, a new high-affinity small-molecule inhibitor of the NSP rate-limiting enzyme dC kinase (dCK). Positron emission tomography (PET) imaging was useful for following both the duration and degree of dCK inhibition by DI-39 treatment in vivo, thus providing a companion pharmacodynamic biomarker. Pharmacological co-targeting of the DNP with dT and the NSP with DI-39 was efficacious against ALL models in mice, without detectable host toxicity. These findings advance our understanding of nucleotide metabolism in leukemic cells, and identify dCTP biosynthesis as a potential new therapeutic target for metabolic interventions in ALL and possibly other hematological malignancies.