Influence of Irradiation on Capsules of Silicone Implants Covered with Acellular Dermal Matrix in Mice.

BACKGROUND: In advanced breast cancer, radiotherapy is recommended as adjuvant therapy following breast reconstructive surgery. This inevitably led to growing concerns over possible complications of radiotherapy on implants. In this experimental animal study, we investigated the utility of acellular dermal matrix (ADM) wraps around implants as preventive management for radiotherapy complications. METHODS: Black mice (C57NL6; n = 32) were assigned to groups that either received radiation or did not: groups A and B underwent surgery using implants without radiotherapy; while groups C and D underwent surgery using implants with radiotherapy for one and three months, respectively. The hemispheric silicone implants with an 0.8-cm-diameter were inserted on the left back of each mouse, and implants wrapped by ADM were inserted on the right back. The Clinic 23EX LINAC model was used for irradiation at 10 Gy. The samples were evaluated by gross assessment, histological analysis, immunohistochemical analysis, and the Western blotting test. RESULTS: The H&E staining analysis showed that membrane thickness is smallest in group A, followed by groups C, D, and B. In a Masson trichrome histological analysis, collagen fibers became less dense and more widespread over time in the groups that received an ADM. Immunohistochemistry findings were similarly constant. However, the expression of TGF-ß1 was increased in the irradiated groups, whereas it was decreased in the non-irradiated groups as observed over time. CONCLUSIONS: Radiotherapy was shown to increase risk factors for capsular contracture, including inflammatory response, pseudoepithelium, thinning of membrane, and TGF-ß1 expression over time; however, the accompanying framework using an ADM as a barrier between implant and tissue was shown to be effective in alleviating these risks. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Medium-term results of cementation of a highly cross-linked polyethylene liner into a well-fixed acetabular shell in revision hip arthroplasty.

The present study was undertaken to document outcomes of cementation of a highly cross-linked polyethylene (PE) liner into a well-fixed acetabular metal shell in 36 hips. All operations were performed by a single surgeon using only one type of liner. Patients were followed for a mean of 6.1 years (range, 3-8 years). Mean Harris hip score improved from 58 points preoperatively to 91 points postoperatively. There were no cases of PE liner dislodgement or progressive osteolysis. 1 hip (2.8%) required revision surgery for acetabular cup loosening with greater trochanteric fracture. Complications included 1 peroneal nerve palsy and 1 dislocation. The results of this study and previous reports demonstrated that cementation of highly cross-linked PE liner into well-fixed metal shell could provide good midterm durability.

A murine model of radiation-induced capsule-tissue reactions around smooth silicone implants.

As the availability of breast reconstruction using implants is becoming widespread and many implant recipients undergo radiation therapy, there is an increasing interest in understanding the potential complications associated with capsule-tissue interactions in response to irradiation. Accordingly, our medical institution designed an animal experiment to investigate the effects of irradiation on capsular contracture. A total of 40 mice (C57BL6) were divided into four groups according to whether or not they received irradiation and the time from implantation to irradiation. After each mouse received a specially-fabricated, 1.5 cm semi-spherical silicone implant inserted into the area below the panniculus carnosus, half of the mice were irradiated using singe administration of a 10 Gy dose of radiation (6 MeV). Subsequently, data from gross inspection, histological analysis and immunohistochemical analysis were obtained at one and three months postoperatively and analyzed. Changes that occurred near the capsule led to the phenomenon of contracture subsequent to encapsulation. Our findings suggest that the inflammation reaction occurring near the implant becomes aggravated by 'radiation toxicity' and creates an environment conducive to capsular contracture. The present study demonstrated the process by which the complication of capsular contracture may occur during the treatment of human breast cancer via radiotherapy. These findings may serve as the basis for research and development of future treatments of capsular contracture.

Polymer micelle formulation for the proteasome inhibitor drug carfilzomib: Anticancer efficacy and pharmacokinetic studies in mice.

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic acid (CFZ-PM) and assessed its in vivo anticancer efficacy and pharmacokinetic profiles. Despite in vitro metabolic protection of CFZ, CFZ-PM did not display in vivo anticancer efficacy in mice bearing human lung cancer xenograft (H460) superior to that of the clinically used cyclodextrin-based CFZ (CFZ-CD) formulation. The plasma pharmacokinetic profiles of CFZ-PM were also comparable to those of CFZ-CD and the residual tumors that persisted in xenograft mice receiving CFZ-PM displayed an incomplete proteasome inhibition. In summary, our results showed that despite its favorable in vitro performances, the current CFZ-PM formulation did not improve in vivo anticancer efficacy and accessibility of active CFZ to solid cancer tissues over CFZ-CD. Careful consideration of the current results and potential confounding factors may provide valuable insights into the future efforts to validate the potential of CFZ-based therapy for solid cancer and to develop effective CFZ delivery strategies that can be used to treat solid cancers.