Andre Alcon

Three-Dimensional Virtual Surgery Accuracy for Free Fibula Mandibular Reconstruction: Planned Versus Actual Results

PURPOSE Virtual surgical planning (VSP) can promote efficiency, but the ability to transfer the proposed plan to the actual result has not been adequately studied. The purpose of this study was to morphometrically compare the virtually preplanned scenario with the postoperative 3-dimensional (3D) anatomic result. MATERIALS AND METHODS A retrospective review of 10 patients who underwent mandibular reconstruction using a free fibula flap and VSP were evaluated. Pre- and postoperative Digital Imaging and Communications in Medicine files were imported into Mimics 10.01 software (Materialise, Leuven, Belgium) for surgical planning. Preoperative VSP and 1-week postoperative computed tomographic (CT) scans were evaluated to assess surgical accuracy using VSP. The pre- and postoperative morphometric measurements were compared using the Student t test. RESULTS Twenty CT scans from 10 patients (mean age, 56.9±20.2 yr) who underwent partial mandibular resection were analyzed. The dimensions of the fibula segments after osteotomy showed no difference from the preoperative VSP (mean difference in fibula height, 1.2 mm; mean difference in width, 0.9 mm; mean difference in length, 1.3 mm). The postoperative anterior and posterior mandibular angles differed from the VSP by 12.4° and -12.5°, respectively. The condylar distance and inclination showed a discrepancy of only 1.7 mm and 4.6°, respectively, between VSP and postoperative CT scans. CONCLUSIONS VSP confers reproducible precision and accuracy for free fibular mandibular reconstruction. The benefit was most striking for large reconstructions requiring multiple fibular segments. Future directions include assessing the use of external registration devices to enhance surgical accuracy and to follow patients longitudinally to monitor the long-term benefit of VSP.

DNAM-1-based chimeric antigen receptors enhance T cell effector function and exhibit in vivo efficacy against melanoma

Abstract Chimeric antigen receptor (CAR) T cell therapies hold great potential for treating cancers, and new CARs that can target multiple tumor types and have the potential to target non-hematological malignancies are needed. In this study, the tumor recognition ability of a natural killer cell-activating receptor, DNAM-1 was harnessed to design CARs that target multiple tumor types. DNAM-1 ligands, PVR and nectin-2, are expressed on primary human leukemia, myeloma, ovarian cancer, melanoma, neuroblastoma, and Ewing sarcoma. DNAM-1 CARs exhibit high tumor cell cytotoxicity but low IFN-γ secretion in vitro. In contrast to other CAR designs, co-stimulatory domains did not improve the expression and function of DNAM-1 CARs. A DNAM-1/CD3zeta CAR reduced tumor burden in a murine melanoma model in vivo. In conclusion, DNAM-1-based CARs may have the potential to treat PVR and nectin-2 expressing hematological and solid tumors.

Wound healing complications with intraoperative brachytherapy for head and neck cancer: a unique form of radiation injury.

BackgroundIntraoperative brachytherapy (IOBT) to the tumor bed coupled with surgery has been shown to increase survival and to improve locoregional disease control after head and neck tumor extirpation. Flap reconstruction attempts to restore patient anatomy, while also covering the radioactive implants. The purpose of this study was to better characterize the wound healing complications experienced by patients undergoing reconstruction in the setting of IOBT after tumor ablation, as well as to identify risk factors predicting complications and the need for reoperation. MethodsA retrospective chart review of patients receiving IOBT for head and neck cancer at Yale-New Haven Hospital between 2005 and 2013 was conducted. Patient, tumor, treatment, and reconstructive details were recorded. The number and type of flap complications, as well as instances in which patients had to be taken back to the operating room, were documented. Bivariate and multivariate logistic regressions were performed to identify risk factors associated with the occurrence of 1 or more flap complications, as well as the need for reoperation. ResultsNinety-three patients aged 31 to 93 years (mean, 64 ± 12 years) who underwent IOBT with flap reconstruction were included in the study. Of these, 94% had a prior history of radiation (external beam or previous IOBT). Overall, 48 (51.6%) patients experienced at least 1 flap complication, the most common of which was flap dehiscence (32% of patients). Thirty-two patients (34% of the cohort) had to be taken back to the operating room at least once for flap debridement or a revision procedure. On multivariate analysis, only the placement of mandibular hardware during flap reconstruction was significantly associated with the risk of developing any type of flap complication (odds ratio, 3.7; P = 0.009) or with subsequent return to the operating room (odds ratio, 3.9; P = 0.012). ConclusionsThis study, the largest of its kind, demonstrated a very high complication rate for flaps used to cover brachytherapy implants in this patient cohort. However, many of the patient complications could be managed nonoperatively. Avoiding the use of mandibular hardware with IOBT suggests a method of reducing complications with reconstruction.

Rates of skin flap necrosis are increased in fat diabetic rats as compared to normal rat controls

The rat is an often-used animal model in plastic surgery research. Multiple studies investigating flap physiology have utilized the well-described Modified McFarlane flap. This flap is created on the dorsum of the rat by incising three sides of a rectangle while leaving the pedicled base intact. The size often ranges between 2 and 3 cm in width and 7e10 cm in length. While creating the flap, the researcher elevates skin, subcutaneous tissue, and panniculus carinosus. Although there are many studies that have utilized these flaps in the basic rat species (Sprague-Dawley, Wistar), no studies exist on the manipulation of the species of rat itself. The Zucker Diabetic Fatty (ZDF) rat is an established animal model of both obesity and Type 2 Diabetes. The development of obesity and hyperglycemia-related complications is common between male ZDF rats and humans with type 2 diabetes associated with obesity. The authors of this investigation hypothesize that skin flap necrosis is higher in the ZDF rat as compared to the Wistar rat. Rats were divided into two groups e the first included 17 Wistar rats and the second included 20 ZDF rats. All rats were

Osteogenesis of Crouzon-Mutated Cells in a Murine Model

Abstract Crouzon syndrome is an autosomal-dominant congenital disease due to a mutation in the fibroblast growth factor receptor 2 protein. The purpose of this study is to evaluate wound-healing potential of Crouzon osteoblasts and adipose-derived stem cells (ADSCs) in a murine model. Parietal skull defects were created in Crouzon and mature wild-type (WT) CD-1 mice. One group of WT and Crouzon mice were left untreated. Another group was transplanted with both WT and Crouzon adipose-derived stem cells. Additional groups compared the use of a fibrin glue scaffold and periosteum removal. Skulls were harvested from each group and evaluated histologically at 8-week and/or 16-week periods. Mean areas of defect were quantified and compared via ANOVA F-test. The average area of defect after 8 and 16 weeks in untreated Crouzon mice was 15.37 ± 1.08 cm2 and 16.69 ± 1.51 cm2, respectively. The average area of the defect in untreated WT mice after 8 and 16 weeks averaged 14.17 ± 1.88 cm2 and 14.96 ± 2.26 cm2, respectively. WT mice with autologous ADSCs yielded an average area of 15.35 ± 1.34 cm2 after 16 weeks while Crouzon mice with WT ADSCs healed to an average size of 12.98 ± 1.89 cm2. Crouzon ADSCs transplanted into WT mice yielded an average area of 15.47 ± 1.29 cm2 while autologous Crouzon ADSCs yielded an area of 14.22 ± 3.32 cm2. ANOVA F-test yielded P = .415. The fibroblast growth factor receptor 2 mutation in Crouzon syndrome does not promote reossification of critical-sized defects in mature WT and Crouzon mice. Furthermore, Crouzon ADSCs do not possess osteogenic advantage over WT ADSCs.

Bringing Breast Reconstruction to the Forefront

To the Editor: Breast cancer represents the second most common cancer diagnosed in women in the United States. According to data from the American Cancer Society an estimated 290,000 women were diagnosed in 2011 (1). Many of these women undergo mastectomies and are candidates for reconstructive surgery. Recognizing that the benefits of breast reconstruction extend beyond aesthetics, the government passed the Women’s Health and Cancer Rights Act of 1998 (WHCRA) mandating coverage by healthcare payers for post-mastectomy breast reconstruction, including prostheses and alloplastic and autologous techniques. Despite efforts to increase patient awareness, only 20% of eligible women undergo surgery, and a large proportion of women remain unaware of their treatment options (2). Thus, the government has introduced the Breast Cancer Patient Education Act of 2012 (BCPEA) to inform patients of their breast reconstructive options. Oncologic breast and plastic surgeons must remain cognizant of the intricacies of this act and join the advocacy efforts led by the American Society of Plastic Surgeons (ASPS) and the Plastic Surgery Foundation (PSF) to empower women and aid them in making an informed decision regarding their personal healthcare. The reasons for lower than expected reconstruction rates are multifactorial, with race-based inequalities, lack of access, and the patient–physician discussion all playing a significant role (3,4). Furthermore, in a national survey of 500 plastic surgeons, poor provider reimbursement and lack of resident coverage were found to negatively affect post-mastectomy breast reconstruction volume (5). While the WHCRA proved paramount for breast cancer patients, the BCPEA holds the potential to bolster reconstructive rates if enacted. The bipartisan act seeks to launch an educational campaign to disseminate knowledge to patients regarding the types, availability, and coverage of breast reconstruction. Almost all patients referred for reconstructive plastic surgery discover the available options via their oncologic breast surgeon. Therefore, the oncologic breast surgeon arguably holds the most potential to define the reconstructive landscape. While the ASPS and PSF continue to target plastic surgeons, a critical feature for diffusing the knowledge about breast reconstruction will hinge on involving the oncologic breast surgeon. Events such as the first national Breast Reconstruction Awareness (BRA) Day USA that brought oncologic breast and plastic surgeons together enable a stronger lobbying force for bills crucial to the empowerment of breast cancer patients. As patient advocates, oncologic breast and plastic surgeons must strive to implement the goals and objectives espoused by such measures as the BCPEA and BRA Day. The outstanding efforts by legislators and the breast surgery community to advance women’s health must continue, and it is imperative that they stay politically informed to ensure that legislation benefiting their patient population continues to garner support.