Brian H. Hwang

A systematic review and meta-analysis of complications associated with acellular dermal matrix-assisted breast reconstruction

Background:Multiple outcome studies have been published on the use of acellular dermal matrix (ADM) in breast reconstruction with disparate results. The purpose of this study was to conduct a systematic review and meta-analysis to determine an aggregate estimate of risks associated with ADM-assisted breast reconstruction. Methods:The MEDLINE, Web of Science, and Cochrane Library databases were queried, and relevant articles published up to September 2010 were analyzed based on specific inclusion criteria. Seven complications were studied including seroma, cellulitis, infection, hematoma, skin flap necrosis, capsular contracture, and reconstructive failure. A pooled random effects estimate for each complication and 95% confidence intervals (CI) were derived. For comparisons of ADM and non-ADM, the pooled random effects odds ratio (OR) and 95% CI were derived. Heterogeneity was measured using the I2 statistic. Results:Sixteen studies met the inclusion criteria. The pooled complication rates were seroma (6.9%; 95% CI, 5.3%–8.8%), cellulitis (2.0%; 95% CI, 1.2%–3.1%), infection (5.7%; 95% CI, 4.3%–7.3%), skin flap necrosis (10.9%; 95% CI, 8.7%–13.5%), hematoma (1.3%; 95% CI, 0.6%–2.4%), capsular contracture (0.6%; 95% CI, 0.1%–1.7%), and reconstructive failure (5.1%; 95% CI, 3.8%–6.7%). Five studies reported findings for both the ADM and non-ADM patients and were used in the meta-analysis to calculate pooled OR. ADM-assisted breast reconstructions had a higher likelihood of seroma (pooled OR, 3.9; 95% CI, 2.4–6.2), infection (pooled OR, 2.7; 95% CI, 1.1–6.4), and reconstructive failure (pooled OR, 3.0; 95% CI, 1.3–6.8) than breast reconstructions without the use of ADM. The relation of ADM use to hematoma (pooled OR, 2.0; 95% CI, 0.8–5.2), cellulitis (pooled OR, 2.0; 95% CI, 0.9–4.3), and skin flap necrosis (pooled OR, 1.9; 95% CI, 0.6–5.4) was inconclusive. Conclusions:In the studies evaluated, ADM-assisted breast reconstructions exhibited a higher likelihood of seroma, infection, and reconstructive failure than prosthetic-based breast reconstructions using traditional musculofascial flaps. ADM is associated with a lower rate of capsular contracture. A careful risk/benefit analysis should be performed when choosing to use ADM in implant-based breast reconstruction.

ANALYSIS OF RISK FACTORS ASSOCIATED WITH MICROVASCULAR FREE FLAP FAILURE USING A MULTI-INSTITUTIONAL DATABASE

There are numerous factors that may contribute to microvascular free flap failure. Although technical issues are dominant factors, patient and clinical characteristics are also contributory. The aim of this study was to investigate non‐technical variables associated with microsurgical free flap failure using a multi‐institutional dataset.

Topical application of recombinant type VII collagen incorporates into the dermal-epidermal junction and promotes wound closure.

Patients with recessive dystrophic epidermolysis bullosa (RDEB) have incurable skin fragility, blistering, and skin wounds due to mutations in the gene that codes for type VII collagen (C7) that mediates dermal-epidermal adherence in human skin. In this study, we evaluated if topically applied human recombinant C7 (rC7) could restore C7 at the dermal-epidermal junction (DEJ) and enhance wound healing. We found that rC7 applied topically onto murine skin wounds stably incorporated into the newly formed DEJ of healed wounds and accelerated wound closure by increasing re-epithelialization. Topical rC7 decreased the expression of fibrogenic transforming growth factor-β2 (TGF-β2) and increased the expression of anti-fibrogenic TGF-β3. These were accompanied by the reduced expression of connective tissue growth factor, fewer α smooth muscle actin (α-SMA)-positive myofibroblasts, and less deposition of collagen in the healed neodermis, consistent with less scar formation. In addition, using a mouse model in which skin from C7 knock out mice was grafted onto immunodeficient mice, we showed that applying rC7 onto RDEB grafts with wounds restored C7 and anchoring fibrils (AFs) at the DEJ of the grafts and corrected the dermal-epidermal separation. The topical application of rC7 may be useful for treating patients with RDEB and patients who have chronic skin wounds.Patients with recessive dystrophic epidermolysis bullosa (RDEB) have incurable skin fragility, blistering, and skin wounds due to mutations in the gene that codes for type VII collagen (C7) that mediates dermal-epidermal adherence in human skin. In this study, we evaluated if topically applied human recombinant C7 (rC7) could restore C7 at the dermal-epidermal junction (DEJ) and enhance wound healing. We found that rC7 applied topically onto murine skin wounds stably incorporated into the newly formed DEJ of healed wounds and accelerated wound closure by increasing re-epithelialization. Topical rC7 decreased the expression of fibrogenic transforming growth factor-β2 (TGF-β2) and increased the expression of anti-fibrogenic TGF-β3. These were accompanied by the reduced expression of connective tissue growth factor, fewer α smooth muscle actin (α-SMA)-positive myofibroblasts, and less deposition of collagen in the healed neodermis, consistent with less scar formation. In addition, using a mouse model in which skin from C7 knock out mice was grafted onto immunodeficient mice, we showed that applying rC7 onto RDEB grafts with wounds restored C7 and anchoring fibrils (AFs) at the DEJ of the grafts and corrected the dermal-epidermal separation. The topical application of rC7 may be useful for treating patients with RDEB and patients who have chronic skin wounds.

Risk factors associated with venous thromboembolism in 49,028 mastectomy patients

Venous thromboembolism (VTE) is a potentially preventable disease that carries significant morbidity and mortality. Although malignancy is associated with increased risk for VTE, it varies according to cancer type. Despite the fact that breast cancer is the most common form of cancer in women, the incidence and risk factors associated with VTE in patients undergoing mastectomy have not been well characterized. To address this we utilized the ACS-NSQIP database to identify and characterize independent risk factors for VTE in 49,028 mastectomy patients. We identified 116 cases of VTE in the 49,028 cases analyzed (0.23%). Obesity (BMI > 30, OR = 1.91, p < 0.001), inpatient status (OR = 3.75, p < 0.001), venous catheterization (OR = 2.67, p = 0.012), prolonged operative time >3 h (OR = 4.36, p < 0.001), and immediate reconstruction (OR = 3.23, p < 0.001) were found to be independent risk factors for VTE. While the incidence of VTE is rare in mastectomy patients, the heightened awareness and increased VTE prophylaxis should be considered in high risk groups.

Original ArticleTopical Application of Recombinant Type VII Collagen Incorporates Into the Dermal–Epidermal Junction and Promotes Wound Closure

Patients with recessive dystrophic epidermolysis bullosa (RDEB) have incurable skin fragility, blistering, and skin wounds due to mutations in the gene that codes for type VII collagen (C7) that mediates dermal-epidermal adherence in human skin. In this study, we evaluated if topically applied human recombinant C7 (rC7) could restore C7 at the dermal-epidermal junction (DEJ) and enhance wound healing. We found that rC7 applied topically onto murine skin wounds stably incorporated into the newly formed DEJ of healed wounds and accelerated wound closure by increasing re-epithelialization. Topical rC7 decreased the expression of fibrogenic transforming growth factor-β2 (TGF-β2) and increased the expression of anti-fibrogenic TGF-β3. These were accompanied by the reduced expression of connective tissue growth factor, fewer α smooth muscle actin (α-SMA)-positive myofibroblasts, and less deposition of collagen in the healed neodermis, consistent with less scar formation. In addition, using a mouse model in which skin from C7 knock out mice was grafted onto immunodeficient mice, we showed that applying rC7 onto RDEB grafts with wounds restored C7 and anchoring fibrils (AFs) at the DEJ of the grafts and corrected the dermal-epidermal separation. The topical application of rC7 may be useful for treating patients with RDEB and patients who have chronic skin wounds.Patients with recessive dystrophic epidermolysis bullosa (RDEB) have incurable skin fragility, blistering, and skin wounds due to mutations in the gene that codes for type VII collagen (C7) that mediates dermal-epidermal adherence in human skin. In this study, we evaluated if topically applied human recombinant C7 (rC7) could restore C7 at the dermal-epidermal junction (DEJ) and enhance wound healing. We found that rC7 applied topically onto murine skin wounds stably incorporated into the newly formed DEJ of healed wounds and accelerated wound closure by increasing re-epithelialization. Topical rC7 decreased the expression of fibrogenic transforming growth factor-β2 (TGF-β2) and increased the expression of anti-fibrogenic TGF-β3. These were accompanied by the reduced expression of connective tissue growth factor, fewer α smooth muscle actin (α-SMA)-positive myofibroblasts, and less deposition of collagen in the healed neodermis, consistent with less scar formation. In addition, using a mouse model in which skin from C7 knock out mice was grafted onto immunodeficient mice, we showed that applying rC7 onto RDEB grafts with wounds restored C7 and anchoring fibrils (AFs) at the DEJ of the grafts and corrected the dermal-epidermal separation. The topical application of rC7 may be useful for treating patients with RDEB and patients who have chronic skin wounds.

Determination of a Perfusion Threshold in Experimental Perforator Flap Surgery Using Indocyanine Green Angiography

AbstractIndocyanine green (ICG) angiography has been used in the evaluation of flap perfusion but the viability threshold has not been elucidated. In this study, we determined the threshold by comparing perfusion, using ICG imaging (SPY imaging system, LifeCell Corporation), to clinical evidence of nonviability in rat abdominal perforator flaps.Abdominal flaps, based on a single perforator, were elevated and re-inset in Sprague-Dawley rats. ICG imaging and clinical assessments were conducted preoperatively, as well as 0, 24, and 48 hours postoperatively. SPY-Q software allowed standardization of the perforator’s perfusion for comparison purposes. A total of 278 random percentage measurements were made from postoperative day 0 giving a mean (SE) percentage perfusion of 26.8% (1.6%) and 59.1% (1.3%), respectively, for necrosis and survival (P < 0.05). We demonstrate that ICG angiography can be readily analyzed in a perforator flap environment allowing a determination of the perfusion threshold.

Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps

The field of reconstructive microsurgery is experiencing tremendous growth, as evidenced by recent advances in face and hand transplantation, lower limb salvage after trauma, and breast reconstruction. Common to all of these procedures is the creation of a nutrient vascular supply by microsurgical anastomosis between a single artery and vein. Complications related to occluded arterial inflow and obstructed venous outflow are not uncommon, and can result in irreversible tissue injury, necrosis, and flap loss. At times, these complications are challenging to clinically determine. Since early intervention with return to the operating room to re-establish arterial inflow or venous outflow is key to flap salvage, the accurate diagnosis of early stage complications is essential. To date, there are no biochemical markers or serum assays that can predict these complications. In this study, we utilized a rat model of flap ischemia in order to identify the transcriptional signatures of venous congestion and arterial ischemia. We found that the critical ischemia time for the superficial inferior epigastric fasciocutaneus flap was four hours and therefore performed detailed analyses at this time point. Histolgical analysis confirmed significant differences between arterial and venous ischemia. The transcriptome of ischemic, congested, and control flap tissues was deciphered by performing Affymetrix microarray analysis and verified by qRT-PCR. Principal component analysis revealed that arterial ischemia and venous congestion were characterized by distinct transcriptomes. Arterial ischemia and venous congestion was characterized by 408 and 1536>2-fold differentially expressed genes, respectively. qRT-PCR was used to identify five candidate genes Prol1, Muc1, Fcnb, Il1b, and Vcsa1 to serve as biomarkers for flap failure in both arterial ischemia and venous congestion. Our data suggests that Prol1 and Vcsa1 may be specific indicators of venous congestion and allow clinicians to both diagnose and successfully treat microvascular complications before irreversible tissue damage and flap loss occurs.

Assessment of three-dimensional high-definition visualization technology to perform microvascular anastomosis

BACKGROUND AND AIM Traditional visualization techniques in microsurgery require strict positioning in order to maintain the field of visualization. However, static posturing over time may lead to musculoskeletal strain and injury. Three-dimensional high-definition (3DHD) visualization technology may be a useful adjunct to limiting static posturing and improving ergonomics in microsurgery. In this study, we aimed to investigate the benefits of using the 3DHD technology over traditional techniques. METHODS A total of 14 volunteers consisting of novice and experienced microsurgeons performed femoral anastomoses on male Sprague-Dawley retired breeder rats using traditional techniques as well as the 3DHD technology and compared the two techniques. Participants subsequently completed a questionnaire regarding their preference in terms of operational parameters, ergonomics, overall quality, and educational benefits. Efficiency was also evaluated by mean times to complete the anastomosis with each technique. RESULTS A total of 27 anastomoses were performed, 14 of 14 using the traditional microscope and 13 of 14 using the 3DHD technology. Preference toward the traditional modality was noted with respect to the parameters of precision, field adjustments, zoom and focus, depth perception, and overall quality. The 3DHD technique was preferred for improved stamina and less back and eye strain. Participants believed that the 3DHD technique was the better method for learning microsurgery. Longer mean time of anastomosis completion was noted in participants utilizing the 3DHD technique. CONCLUSIONS The 3DHD technology may prove to be valuable in improving proper ergonomics in microsurgery. In addition, it may be useful in medical education when applied to the learning of new microsurgical skills. More studies are warranted to determine its efficacy and safety in a clinical setting.