Short-term cost-effectiveness of one-stage implant-based breast reconstruction with an acellular dermal matrix versus two-stage expander-implant reconstruction from a multicentre randomized clinical trial.

BACKGROUND: Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure and its economic impact is significant. This study aimed to analyse whether a direct one-stage IBBR with use of an acellular dermal matrix (ADM) is more cost-effective than two-stage (expander-implant) breast reconstruction. METHODS: The BRIOS (Breast Reconstruction In One Stage) study was an open-label multicentre RCT in which women scheduled for skin-sparing mastectomy and immediate IBBR were randomized between one-stage IBBR with ADM or two-stage IBBR. Duration of surgery and hospital stay, and visits for the primary surgery, unplanned and cosmetic procedures were recorded. Costs were estimated at an institutional level. Health status was assessed by means of the EuroQol Five Dimensions 5L questionnaire. RESULTS: Fifty-nine patients (91 breasts) underwent one-stage IBBR with ADM and 62 patients (92 breasts) two-stage IBBR. The mean(s.d.) duration of surgery in the one-stage group was significantly longer than that for two-stage IBBR for unilateral (2·52(0·55) versus 2·02(0·35) h; P < 0·001) and bilateral (4·03(1·00) versus 3·25(0·58) h; P = 0·017) reconstructions. Costs were higher for one-stage compared with two-stage IBBR for both unilateral (€12 448 (95 per cent c.i. 10 722 to 14 387) versus €9871 (9373 to 10 445) respectively; P = 0·025) and bilateral (€16 939 (14 887 to 19 360) versus €13 383 (12 414 to 14 669); P = 0·002) reconstructions. This was partly related to the use of relatively expensive ADM. There was no difference in postoperative health status between the groups. CONCLUSION: One-stage IBBR with ADM was associated with higher costs, but similar health status, compared with conventional two-stage IBBR. Registration number: NTR5446 ( http://www.trialregister.nl).

Predictors of complications after direct-to-implant breast reconstruction with an acellular dermal matrix from a multicentre randomized clinical trial.

BACKGROUND: In the multicentre randomized trial BRIOS (Breast Reconstruction In One Stage), direct-to-implant (DTI) breast reconstruction with an acellular dermal matrix (ADM) was associated with a markedly higher postoperative complication rate compared with two-stage tissue expander/implant breast reconstruction. This study aimed to identify factors that contribute to the occurrence of complications after DTI ADM-assisted breast reconstruction. METHODS: Data were obtained from the BRIOS study, including all patients treated with DTI ADM-assisted breast reconstruction. Logistic regression analyses were performed to identify factors predictive of postoperative complications. RESULTS: Fifty-nine patients (91 breasts) were included, of whom 27 (35 breasts) developed a surgical complication. Reoperations were performed in 29 breasts (32 per cent), with prosthesis removal in 22 (24 per cent). In multivariable analyses, mastectomy weight was associated with complications (odds ratio (OR) 1·94, 95 per cent c.i. 1·33 to 2·83), reoperations (OR 1·70, 1·12 to 2·59) and removal of the implant (OR 1·55, 1·11 to 2·17). Younger patients (OR 1·07, 1·01 to 1·13) and those who received adjuvant chemotherapy (OR 4·83, 1·15 to 20·24) more frequently required reoperation. In univariable analyses, adjuvant radiotherapy showed a trend towards more complications (OR 7·23, 0·75 to 69·95) and removal of the implant (OR 5·12, 0·76 to 34·44), without reaching statistical significance. CONCLUSION: Breast size appeared to be the most significant predictor of complications in DTI ADM-assisted breast reconstruction. The technique should preferably be performed in patients with small to moderate sized breasts. Registration number: NTR5446 ( http://www.trialregister.nl).

Mammaplasty in patients with large areola: Reducing the nipple-areola complex using intra-areolar incisions.

Minimal incision breast reduction techniques resulting in periareolar scars are widely used. However, this technique is less suitable for patients with large areola diameters and relatively small breasts, requiring a modest reduction or lift only. As a result of the large nipple-areola complex larger amounts of skin must be removed in order to resect the complete peripheral areola, increasing the risk of high-riding nipples, breast flattening and incomplete areola resection resulting in a rest on the vertical scar. This report describes a modified technique offering a solution to these problems. In this technique intra-areolar incisions are used to reduce areola size without resecting large volumes of breast tissue and skin. Complete peripheral areolar resection is always possible and high-riding nipples are avoided.

Pedicled prelaminated capsular flaps for coverage of skin defect in a rat model.

SUMMARY: In reconstructive surgery defects are closed using pedicled or free flaps. By raising these flaps the reconstructive surgeon creates new defects, which in turn are closed primarily or with the use of skin grafts. Inevitably, this results in extra scars that may be visible and may also lead to diminished function. In an attempt to avoid full-thickness donor site skin defects in reconstructive surgery, the principle of prefabrication has been modified to produce capsular flaps. In a rat model, we created prefabricated and prelaminated pedicled capsular flaps to fill a full-thickness skin defect. Both femoral vascular bundles in 10 Wistar rats were sandwiched between two silicone sheets. The capsule formed between the two sheets received its main blood supply from this vascular pedicle, and was used as carrier for a skin graft. After ligation of the distal femoral vessels a pedicled prelaminated capsular flap was raised on the proximal femoral vessels. The flap was brought to the surface for closure of an experimentally created abdominal skin defect. All 20 flaps survived, and there were no surgery-related complications. Comparison with controls indicated that flap survival was attributable to the blood supply from the vascular axis. Pedicled prelaminated capsular flaps can be created reliably and reproducibly, confirming the results of earlier studies, and are of value in reconstructive surgery.

Formation of a reliable capsular flap in a rat model.

UNLABELLED: Prefabrication can be used to produce capsular flaps; other researchers have confirmed the feasibility of such flaps. Before the possibilities of capsular flaps can be explored, a reliable method to create these flaps has to be established first. METHODS: To produce capsular flaps in a rat model, the femoral vascular bundle was sandwiched between two silicone sheets. Three different methods were used and described. The capsule that formed between the two silicone sheets receives its main blood supply from that vascular pedicle. In this way pedicled capsular flaps were created. These flaps were used as a carrier for a skin graft, thus pre-laminating them, to test their ability for reconstructive surgery. The results of the three different methods of creating capsular flaps in a rat model were described and their results were evaluated. Especially the amount of capsule formation and the viability of the skin grafts was observed and compared. The feasibility of pre-laminated capsular flaps is confirmed and the most reliable method of creating them is described.

In vivo release of rhBMP-2 loaded porous calcium phosphate cement pretreated with albumin.

In this study, the release of rhBMP-2 loaded porous Ca-P cement was studied in vitro and in vivo. We hypothesized that adsorption sites of Ca-P ceramic with high affinity for rhBMP-2 can be blocked by pretreatment of the ceramic with albumin prior to rhBMP-2 loading, which would result in weaker rhBMP-2 binding and enhanced release of rhBMP-2. Preset porous Ca-P cement discs with a diameter of 6.35 mm (volume: 75 mm3) were pretreated by incubation in a solution of 10% rat serum albumin for 24 h or in ddH2O (control group) prior to administration of 5 mug radiolabeled 131I-rhBMP-2. Release was assessed in vitro in phosphate buffered saline (PBS) and fetal calf serum and in vivo by longitudinal scintigraphic imaging of radiolabeled 131I-rhBMP-2 and gamma counting of dissected implants. In vitro release from pretreated discs was higher during the first day. For both formulations, release in PBS was limited compared to release in serum. In vivo release considerably exceeded in vitro release. In vivo release kinetics showed no significant difference of half-lives between pretreated and control discs. Both formulations showed sustained release during at least 4 weeks. Ex vivo gamma counting of retrieved samples confirmed scintigraphic results and showed that the capsule and surrounding tissues only contained a minor fraction rhBMP-2. We conclude that 1. scintigraphy of 131I-labeled rhBMP-2 provides a reliable method for longitudinal measurement of rhBMP-2 release kinetics in vivo. 2. albumin pretreatment of porous Ca-P cement does not results in relevant increase of initial release of rhBMP-2 in vivo, and 3. preset rhBMP-2 loaded porous Ca-P cement discs exhibit one phase exponential release kinetics in the rat ectopic model, characterized by a retention of 20-30% after 4 weeks.

Controlled release of rhBMP-2 loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement composites in vivo.

The release kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement (PLGA/Ca-P cement) composites were studied in vivo. RhBMP-2 was radiolabeled with (131)I and entrapped within PLGA microparticles or adsorbed onto the microparticle surface. PLGA microparticles were prepared of high molecular weight (HMW) PLGA (weight average molecular weight [M(w)] 49,100+/-1700) or low molecular weight (LMW) PLGA (M(w) 5,900+/-300) and used for preparation of 30:70 wt.% PLGA/Ca-P cement composite discs. Release of 131I-rhBMP-2 loaded composites was assessed by scintigraphic imaging according to a 2(2) two-level full factorial design in the rat ectopic model during four weeks. In vivo release kinetics varied among formulations. All formulations showed slow release without initial burst, and displayed a linear release from 3 to 28 days. Release of LMW entrapped rhBMP-2 composites (1.7+/-0.3%/day) was significantly faster than release from other formulations (p<0.01). After 28 days, retention within the composites was 65+/-5%, 75+/-4%, 50+/-4% and 70+/-6% of the initial rhBMP-2 for HMW entrapped, HMW adsorbed, LMW entrapped and LMW adsorbed rhBMP-2 composites, respectively. Release from the composite was probably slowed down by an interaction of rhBMP-2 and Ca-P cement after rhBMP-2 release from PLGA microparticles. We conclude that PLGA/Ca-P cement composites can be considered as sustained slow release vehicles and that the release and retention of rhBMP-2 can be modified according to the desired profile to a limited extent.

Growth factor-loaded scaffolds for bone engineering.

The objective of the study presented here was to investigate the bone inductive properties as well as release kinetics of rhTGF-beta1- and rhBMP-2-loaded Ti-fiber mesh and CaP cement scaffolds. Therefore, Ti-fiber mesh and porous CaP cement scaffolds were provided with these growth factors and inserted in subcutaneous and cranial implant locations in rats and rabbits. In vitro, a rapid release of rhTGF-beta1 was observed during the first 2 h of the Ti-fiber mesh scaffolds. During this time, more than 50% of the total dose of rhTGF-beta1 was released. Following this initial peak, a decline in the level of rhTGF-beta1 occurred. After 1 week, the entire theoretical initial dose was observed to have been released. This in contrast to the rhTGF-beta1 and rhBMP-2 release of the porous CaP cement scaffolds. Here, no substantial initial burst release was observed. The scaffolds showed an initial release of about 1% after 1 day, followed by an additional marginal release after 1 week. Histological analysis revealed excellent osteoconductive properties of non-loaded Ca-P material. Inside non-loaded Ti-mesh fiber scaffolds, also bone ingrowth occurred. Quantification of the bone ingrowth showed that bone formation was increased significantly in all scaffold materials by administration of rhTGF-beta1 and rhBMP-2. Consequently, we conclude that the release kinetics of growth factors from porous CaP cement differs from other scaffold materials, like metals and polymers. Nevertheless, orthotopic bone formation in a rabbit cranial defect model was stimulated in rhTGF-beta1- and rhBMP-2-loaded CaP cement and Ti-fiber mesh scaffolds compared with non-loaded implants.