Reducing Peri-implant Capsule Thickness in Submuscular Rodent Model of Breast Reconstruction With Delayed Radiotherapy.

INTRODUCTION: Capsular contracture remains the most common complication following device-based breast reconstruction, occurring in up to 50% of women who also undergo adjuvant radiotherapy either before or after device-based reconstruction. While certain risk factors for capsular contracture have been identified, there remains no clinically effective method of prevention. The purpose of the present study is to determine the effect of coating the implant with the novel small molecule Met-Z2-Y12, with and without delayed, targeted radiotherapy, on capsule thickness and morphologic change around smooth silicone implants placed under the latissimus dorsi in a rodent model. METHODS: Twenty-four female Sprague Dawley rats each had 2 mL smooth round silicone breast implants implanted bilaterally under the latissimus dorsi muscle. Twelve received uncoated implants and twelve received implants coated with Met-Z2-Y12. Half of the animals from each group received targeted radiotherapy (20 Gray) on postoperative day ten. At three and 6 months after implantation, the tissue surrounding the implants was harvested for analysis of capsular histology including capsule thickness. Additionally, microCT scans were qualitatively analyzed for morphologic change. RESULTS: Capsules surrounding Met-Z2-Y12-coated implants were significantly thinner (P = 0.006). The greatest difference in capsule thickness was seen in the irradiated 6-month groups, where mean capsule thickness was 79.1 ± 27.3 µm for uncoated versus 50.9 ± 9.6 µm for Met-Z2-Y12-coated implants (P = 0.038). At the time of explant, there were no capsular morphologic differences between the groups either grossly or per microCT. CONCLUSIONS: Met-Z2-Y12 coating of smooth silicone breast implants significantly reduces capsule thickness in a rodent model of submuscular breast reconstruction with delayed radiotherapy.

Topical α-Gal Nanoparticles Enhance Wound Healing in Radiated Skin.

PURPOSE: Surgery within radiated tissue is associated with increased complication rates. It is hypothesized that impaired wound healing may result from aberrant inflammatory responses that occur in previously radiated tissues. Previous work has demonstrated that the topical application of naturally occurring antigen α-gal (Galα1-3Galß1-(3)4GlcNAc-R) nanoparticles (AGNs) within wounds accelerates macrophage recruitment and subsequent healing in both normal and diabetic wounds. Herein, we hypothesize that application of this antigen would similarly enhance wound healing in irradiated tissues. METHODS: To simulate human physiology, α-1,3-galactosyltransferase knockout (KO) mice were exposed to the antigen to produce anti-α-gal antibodies (anti-Gal). Ten days prior to wounding, the dorsal skin was irradiated with 1 session of 40 Gy. Bilateral dorsal 6-mm splinted full-thickness wounds were created within the radiated skin and treated with 50 µL of AGNs (50 mg/mL) immediately after wounding and again on postoperative day 1. A control KO group underwent similar irradiation and wounding protocols but was treated with phosphate-buffered saline (PBS) vehicle. Wild-type (WT) mice, which do not produce anti-Gal, went through the same irradiation and wounding. RESULTS: Histologic analysis demonstrated enhanced epithelial migration in the radiated/AGN-treated KO wounds, which was significantly elevated in comparison to radiated/PBS-treated KO wounds beginning by day 15 and continuing until the end of the study (p < 0.01). In WT mice, treatment with AGNs showed no effect on epithelial migration. CONCLUSIONS: Topical application of AGNs onto irradiated wounds significantly ameliorates the delayed wound healing classically seen in radiated skin and results in faster wound closure with only transient application.

Nipple Engineering: Maintaining Nipple Geometry with Externally Scaffolded Processed Autologous Costal Cartilage.

INTRODUCTION: Nipple reconstruction is the essential last step of breast reconstruction after total mastectomy, resulting in improved general and aesthetic satisfaction. However, most techniques are limited by secondary scar contracture and loss of neo-nipple projection leading to patient dissatisfaction. Approximately, 16,000 patients undergo autologous flap breast reconstruction annually, during which the excised costal cartilage (CC) is discarded. We propose utilizing processed CC placed within biocompatible 3D-printed external scaffolds to generate tissue cylinders that mimic the shape, size and biomechanical properties of native human nipple tissue while mitigating contracture and projection loss. METHODS: External scaffolds were designed and then 3D-printed using polylactic acid (PLA). Patient-derived CC was processed by mincing or zesting, then packed into the scaffolds, implanted into nude rats and explanted after 3 months for volumetric, histologic and biomechanical analyses. Similar analyses were performed on native human nipple tissue and unprocessed CC. RESULTS: After 3 months in vivo, gross analysis demonstrated significantly greater preservation of contour, projection and volume of the scaffolded nipples. Mechanical analysis demonstrated that processing of the cartilage resulted in implant equilibrium modulus values closer to that of the human nipple. Histologic analysis showed the presence of healthy and viable cartilage after 3 months in vivo, invested with fibrovascular tissue. CONCLUSIONS: Autologous CC can be processed intraoperatively and placed within biocompatible external scaffolds to mimic the shape and biomechanical properties of the native human nipple. This allows for custom design and fabrication of individualized engineered autologous implants tailored to patient desire, without the loss of projection seen with traditional approaches.

Muscle Flap Closure following Complex Spine Surgery: A Decade of Experience.

BACKGROUND: Advances in surgical technology and adjuvant therapies along with an aging and increasingly morbid U.S. population have led to an increase in complex spine surgery. With this increase comes an elevated risk of complications, including those related to the surgical wound, with some studies demonstrating wound complication incidences approaching 45 percent. The authors hypothesize that immediate muscle flap closure improves outcomes in high-risk patients. METHODS: Three hundred one consecutive index cases of spinal wound closure using local muscle flaps performed by the senior author at a single institution between 2006 and 2018 were reviewed. The primary outcome was major wound complication (reoperation and/or readmission because of surgical-site infection, late infection, dehiscence, seroma, or hematoma). Logistic regression analysis was performed to identify predictors of this endpoint. RESULTS: Major wound complications occurred in 6.6 percent of patients (reoperation, 3.6 percent; readmission, 3.0 percent), with a 6.0 percent infection rate and five cases requiring instrumentation removal because of infection. Risk factors identified included radiotherapy (OR, 5.9; p = 0.004), age 65 years or older (OR, 2.8; p = 0.046), and prior spine surgery (OR, 4.3; p = 0.027). The incidence of major wound complication increased dramatically with each additional risk factor. Mean drain dwell duration was 21.1 ± 10.0 days and not associated with major wound complications, including infection (OR, 1.04; p = 0.112). CONCLUSIONS: Immediate local muscle flap closure following complex spine surgery on high-risk patients is associated with an acceptable rate of wound complications and, as these data demonstrate, is safe and effective. Consideration should be given to immediate muscle flap closure in appropriately selected patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Periprosthetic Capsule Formation and Contracture in a Rodent Model of Implant-Based Breast Reconstruction With Delayed Radiotherapy.

INTRODUCTION: Capsular contracture (CC) is the most common complication of breast implantation, with an incidence of nearly 50% in patients undergoing breast reconstruction with subsequent radiotherapy. Although the move toward submuscular (SM) device placement led to a decreased incidence of CC, subcutaneous (SQ) implantation has seen a resurgence. The purpose of this study was to use a rodent model of breast reconstruction with smooth silicone implants and delayed radiotherapy to assess the occurrence of CC in SQ versus SM implantation. METHODS: Custom 2 mL smooth round silicone implants were placed bilaterally into 12 female Sprague Dawley rats that were randomized into 4 groups of 3, with each group differing by implantation plane (SQ vs SM) and irradiation status (irradiated vs nonirradiated). Rats from the SQ group received implants bilaterally underlying the skin on the flank. Rats in the SM groups received implants bilaterally under the latissimus dorsi muscle. Irradiated rats received 20 Gy localized to each implant on postoperative day 10. One rat from each group was imaged with a micro-computed tomography scanner at baseline and at explant 3 months later, whereupon capsules from all rats were examined histologically. RESULTS: Rats in the SQ group showed evidence of contracture on gross examination and greater evidence of morphologic disruption per micro-computed tomography scan. There was no evidence of contracture or morphologic disruption in either SM group. Mean ± SD capsule thickness was 39.0 ± 9.0 µm in the SQ versus 37.6 ± 9.8 µm in the SM nonirradiated groups and 43.9 ± 14.9 µm in the SQ versus 34.3 ± 8.3 µm in the SM irradiated groups (all P > 0.05). CONCLUSIONS: In a rodent model of smooth silicone breast implantation and delayed radiotherapy, although there did not appear to be differences in capsule thickness regardless of device placement plane, SQ implants demonstrated gross evidence of CC. These data indicate that capsule thickness is only part of a larger pathogenetic picture, which should take into consideration the contribution from all peri-implant tissue.

Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement.

Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL) presenting as localized lymphadenopathy in children. Unlike conventional adult FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL are lacking, and it is uncertain whether this indolent lymphoma is defined by age or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a separate cohort of 58 adult FL (≥ 18 years of age), all 13 BCL2-N/HPI cases were stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results confirm the highly indolent behavior of PFL and suggest that these are characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also occur in adults and are associated with indolent behavior in this patient population.