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AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay

Gersch, Robert P; Fourman, Mitchell S; Phillips, Brett T; Nasser, Ahmed; McClain, Steve A; Khan, Sami U; Dagum, Alexander B; Bui, Duc T
BACKGROUND: Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. METHODS: Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n >/= 9/group) groups. Delay rats had a 9 cm x 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (10(9) pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. RESULTS: AdVEGF (50.8 +/- 10.9 APU) and AdEgr-1 (39.3 +/- 10.6 APU) perfusion levels were significantly higher than controls (16.5 +/- 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 +/- 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 +/- 1.3 cm(2), P < 0.01 and 12.4 +/- 1.2 cm(2), P < 0.05, respectively) compared with Controls (8.7 +/- 0.7 cm(2)). CONCLUSIONS: AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not.
PMCID:4560227
PMID: 26495207
ISSN: 2169-7574
CID: 2039172

Comparing quantitative values of two generations of laser-assisted indocyanine green dye angiography systems: can we predict necrosis?

Phillips, Brett T; Fourman, Mitchell S; Rivara, Andrew; Dagum, Alexander B; Huston, Tara L; Ganz, Jason C; Bui, Duc T; Khan, Sami U
OBJECTIVE:Several devices exist today to assist the intraoperative determination of skin flap perfusion. Laser-Assisted Indocyanine Green Dye Angiography (LAICGA) has been shown to accurately predict mastectomy skin flap necrosis using quantitative perfusion values. The laser properties of the latest LAICGA device (SPY Elite) differ significantly from its predecessor system (SPY 2001), preventing direct translation of previous published data. The purpose of this study was to establish a mathematical relationship of perfusion values between these 2 devices. METHODS:Breast reconstruction patients were prospectively enrolled into a clinical trial where skin flap evaluation and excision was based on quantitative SPY Q values previously established in the literature. Initial study patients underwent mastectomy skin flap evaluation using both SPY systems simultaneously. Absolute perfusion unit (APU) values at identical locations on the breast were then compared graphically. RESULTS:210 data points were identified on the same patients (n = 4) using both SPY systems. A linear relationship (y = 2.9883x + 12.726) was identified with a high level or correlation (R(2) = 0.744). Previously published values using SPY 2001 (APU 3.7) provided a value of 23.8 APU on the SPY Elite. In addition, postoperative necrosis in these patients correlated to regions of skin identified with the SPY Elite with APU less than 23.8. CONCLUSION/CONCLUSIONS:Intraoperative comparison of LAICGA systems has provided direct correlation of perfusion values predictive of necrosis that were previously established in the literature. An APU value of 3.7 from the SPY 2001 correlates to a SPY Elite APU value of 23.8.
PMCID:4258931
PMID: 25525483
ISSN: 1937-5719
CID: 5939222

A systematic review of infection rates and associated antibiotic duration in acellular dermal matrix breast reconstruction

Phillips, Brett T; Bishawi, Muath; Dagum, Alexander B; Bui, Duc T; Khan, Sami U
INTRODUCTION/BACKGROUND:Reported infection rates in breast reconstruction with acellular dermal matrix (ADM) can exceed 31%. Prophylactic antibiotics remain controversial due to the absence of evidence-based literature. The purpose of this study was to examine published antibiotic regimens and their associated infection rates in this population. METHODS:Systematic electronic searches were performed in PubMed, OVID, and the Cochrane databases for studies that reported on prophylactic antibiotic use and infection in patients undergoing ADM breast reconstruction. Two independent authors reviewed studies between 1970 and 2012 for inclusion and data extraction. RESULTS:A total of 863 studies were identified and abstracts reviewed. A total of 24 articles were included, with 2148 patients and 3189 ADM reconstructions. Mean infection rates varied between 0% and 31.25%, with a combined average of 11.59%. When comparing antibiotic protocols of less than 24 hours and more than 24 hours, the average infection rate was 2.48% and 13.21%, respectively. CONCLUSION/CONCLUSIONS:The current literature lacks consensus on the necessary duration for postoperative antibiotic prophylaxis following breast reconstruction. The potential increased risk of infection associated with ADM remains controversial. Because of the lack of supportive evidence, we do not recommend prolonged postoperative antibiotics in ADM breast reconstruction. LEVEL OF EVIDENCE/METHODS:Therapeutic level III evidence.
PMCID:4233926
PMID: 25525481
ISSN: 1937-5719
CID: 5939212

Modeling fade patterns of nipple areola complex tattoos following breast reconstruction

Levites, Heather A; Fourman, Mitchell S; Phillips, Brett T; Fromm, Indira M; Khan, Sami U; Dagum, Alexander B; Bui, Duc T
BACKGROUND:Nipple-areolar complex (NAC) tattoos are an effective cosmetic solution for creating a finished look following breast reconstruction procedures. NAC tattoos are prone to significant fading, leading patients to seek revisions. This study was designed to quantify changes in NAC tattoo appearance over time. METHODS:A total of 71 images of 39 patients were analyzed for NAC tattoo color and shape by 5 blinded medical student graders using a customized scoring system. Subsequently, each image was analyzed using ColorPic software (Iconico, New York, NY). Red/green/blue and hue/saturation/value color parameters were collected. Color quantities were normalized to the individual patient's skin tone to control for variability in lighting. Spearman correlations and nonlinear regressions were calculated utilizing GraphPad Prism 6.0 (GraphPad, La Jolla, CA). RESULTS:The length of time after tattoo placement inversely correlated with color score (P < 0.0001) and shape score (P = 0.0007). The time following tattoo placement was also inversely correlated with all quantitative color parameters. Each color parameter fit a 1-phase exponential decay model. CONCLUSIONS:The decline in qualitative color and shape score agrees with clinical experience of tattoo quality declining over time. The color qualities of the tattoo approach those of the patient's skin over time, ultimately reaching a plateau. This can be modeled using a 1-phase decay equation. In practice, tattoo colors may be selected that compensate for the predictable changes that will occur. The results of this study will help optimize tattoo color and may alleviate the need for NAC tattoo revisions.
PMID: 24727445
ISSN: 1536-3708
CID: 5939202

An in vivo analysis of the effect and duration of treatment with botulinum toxin type A using digital image speckle correlation

Bhatnagar, Divya; Conkling, Nicole; Rafailovich, Miriam; Phillips, Brett T; Bui, Duc T; Khan, Sami U; Dagum, Alexander B
BACKGROUND:Use of Botulinum toxin type A (BTX-A) for facial wrinkles is well-documented, but current methods of subjective evaluation by clinicians and patients fail to objectively quantify the magnitude and duration of facial muscle paralysis. OBJECTIVE:(a) Determine the locus of facial muscular tension; (b) Quantify and monitor muscular paralysis and subsequent return; (c) Continuously correlate the appearance of wrinkles and muscular tension using non-invasive digital image speckle correlation (DISC) to measure treatment efficacy; (d) Corroborate objective data with existing rating scales (subject global assessment and facial lines outcome-11). METHODS:Two sequential images of slight facial motion (frowning, raising eyebrows) are taken with a camera for n = 6 patients pre- and post-treatment at different time points up to 24 weeks. DISC processes the images to produce a vector map of muscular displacement to obtain spatially resolved information regarding facial tension. RESULTS:We observed maximum paralysis (≥70%) at 2 weeks, and the rate of recovery varied widely ranging from 2 to 5 months, with two patients continuing to exhibit reduced contraction at 24 weeks. Vector analysis of pre-treatment contraction correctly predicted injection site and illustrated lines of maximum tension. CONCLUSIONS:Digital image speckle correlation can precisely track the degree of contraction of different muscle groups following BTX-A injection. It can help predict injection site, quantify muscle paralysis, and monitor the recovery following BTX-A injection. Results were found to be reproducible across six patients.
PMID: 23565582
ISSN: 1600-0846
CID: 5939182

A systematic review of antibiotic use and infection in breast reconstruction: what is the evidence?

Phillips, Brett T; Bishawi, Muath; Dagum, Alexander B; Khan, Sami U; Bui, Duc T
BACKGROUND:The literature reports overall complication rates in breast reconstruction to be as high as 60 percent. Infection rates can exceed 20 percent, much higher than anticipated in clean elective surgery. There is no consensus among surgeons regarding the necessary duration of antibiotic prophylaxis, although the Centers for Disease Control and Prevention guidelines suggest only 24 hours. This systematic review examines antibiotic regimens and associated infection rates in breast reconstruction. METHODS:Systematic electronic searches were performed in the PubMed, Ovid, and Cochrane databases using Medical Subject Headings terms for studies reporting antibiotic use and infection in all forms of breast reconstruction. Studies between 1970 and 2011 were reviewed. Included publications were required to report an antibiotic protocol and infection rate. RESULTS:A total of 834 abstracts were identified, 81 of which met inclusion criteria and were included in the review. The overall reported infection rates in the included studies varied between 0 and 29 percent (average, 5.8 percent). When comparing combined patient cohorts receiving no antibiotics, less than 24 hours, and greater than 24 hours, the average infection rates were 14.4, 5.8, and 5.8 percent, respectively. CONCLUSIONS:There is no consensus on the necessary duration of antibiotic prophylaxis following breast reconstruction. No benefit was found in patients who received more than 24 hours of postoperative antibiotics. Standardized definitions for antibiotic regimens, unit of analysis reporting, and a new breast reconstruction surgical-site infection grading system are offered to improve standardized outcome documentation. Randomized controlled trials are warranted to best determine an optimal antibiotic regimen. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, III.
PMID: 22965239
ISSN: 1529-4242
CID: 5939172

Intraoperative perfusion techniques can accurately predict mastectomy skin flap necrosis in breast reconstruction: results of a prospective trial

Phillips, Brett T; Lanier, Steven T; Conkling, Nicole; Wang, Eric D; Dagum, Alexander B; Ganz, Jason C; Khan, Sami U; Bui, Duc T
BACKGROUND:Intraoperative vascular imaging can assist assessment of mastectomy skin flap perfusion to predict areas of necrosis. No head-to-head study has compared modalities such as laser-assisted indocyanine green dye angiography and fluorescein dye angiography with clinical assessment. METHODS:The authors conducted a prospective clinical trial of tissue expander-implant breast reconstruction with intraoperative evaluation of mastectomy skin flaps by clinical assessment, laser-assisted indocyanine green dye angiography, and fluorescein dye angiography. Intraoperatively predicted regions of necrosis were photographically documented, and clinical assessment guided excision. Postoperative necrosis was directly compared with each prediction. The primary outcome was all-inclusive skin necrosis. RESULTS:Fifty-one tissue expander-implant breast reconstructions (32 patients) were completed, with 21 cases of all-inclusive necrosis (41.2 percent). Laser-assisted indocyanine green dye angiography and fluorescein dye angiography correctly predicted necrosis in 19 of 21 of cases where clinical judgment had failed. Only six of 21 cases were full-thickness necrosis, and five of 21 required an intervention (9.8 percent). Risk factors such as smoking, obesity, and breast weight greater than 1000 g were statistically significant. Laser-assisted indocyanine green dye angiography and fluorescein dye angiography overpredicted areas of necrosis by 72 percent and 88 percent (p = 0.002). Quantitative analysis for laser-assisted indocyanine green dye angiography in necrotic regions showed absolute perfusion units less than 3.7, with 90 percent sensitivity and 100 percent specificity. CONCLUSIONS:Laser-assisted indocyanine green dye angiography is a better predictor of mastectomy skin flap necrosis than fluorescein dye angiography and clinical judgment. Both methods overpredict without quantitative analysis. Laser-assisted indocyanine green dye angiography is more specific and correlates better with the criterion standard diagnosis of necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Diagnostic, I.
PMID: 22544108
ISSN: 1529-4242
CID: 5939152

Subjective rating of cosmetic treatment with botulinum toxin type A: do existing measures demonstrate interobserver validity?

Conkling, Nicole; Bishawi, Muath; Phillips, Brett T; Bui, Duc T; Khan, Sami U; Dagum, Alexander B
BACKGROUND:Throughout the literature, investigators have assessed the cosmetic efficacy of botulinum toxin (BT) treatment by using various subjective, qualitative measures, including the Facial Wrinkle Scale (FWS) and Subject Global Assessment (SGA). The widely used FWS and SGA attempt to quantify both the magnitude and duration of cosmetic outcomes as assessed by physician and patient. We sought to determine the interobserver validity of these scales relative to the level of observer experience. METHODS:Botulinum toxin injections were performed to cosmetic effect in 6 patients recruited as part of an institutional review board-approved investigation. Subjects were photographed at rest and during animation (raising eyebrows, frowning, and blinking) before treatment and at 1, 2, 4 weeks, and monthly with follow-up to 6 months. Standardized digital 8″×10″ prints were scored using the FWS by board-certified plastic surgeons (n=5), general surgery residents (n=3), and medical students (n=4). Photographs at each time point were then compared to baseline using the SGA. Statistical analysis of observer data was performed using SPSS v19. Cohen κ (FWS) and Spearman ρ (SGA) were calculated for each pairwise comparison of observer data, with a conservative α of 0.01. RESULTS:The FWS observer scores for the upper face overall were generally in agreement, with no negative κ values. The distribution, even among members of a single group, was highly variable. Agreement among plastic surgeons was the greatest (κ, 0.194-0.609). Resident concordance was moderate, and medical students displayed the most variable agreement. Spearman ρ for SGA scores was much higher, with surgeons approaching excellent agreement (κ, 0.443-0.992). In comparisons between members of different groups, agreement was unpredictable for both the FWS and SGA. Comparisons using scores from individual areas of the face were least concordant. CONCLUSIONS:The FWS and SGA represent the current standard of cosmetic outcomes measures; however, when subjected to scrutiny they display relatively unpredictable agreement even among plastic surgeons. Compared to the FWS, the SGA has a more acceptable user concordance, especially among plastic surgeons accustomed to using such scales. The interobserver variability of FWS and SGA scoring underlines the need to explore objective, quantitative cosmetic outcomes measures.
PMID: 22964674
ISSN: 1536-3708
CID: 5939162

The effect of acellular dermal matrix use on complication rates in tissue expander/implant breast reconstruction

Lanier, Steven T; Wang, Eric D; Chen, John J; Arora, Balvant P; Katz, Steven M; Gelfand, Mark A; Khan, Sami U; Dagum, Alexander B; Bui, Duc T
Tissue expander/implant breast reconstructions by 5 surgeons at a single institution from 2005 to 2008 were retrospectively identified and divided into 2 cohorts: use of acellular dermal matrix (ADM, n = 75) versus standard submuscular placement (n = 52). The ADM group had a statistically significant higher rate of infection (28.9% vs. 12.0%, P = 0.022), reoperation (25.0% vs. 8.0%, P = 0.011), expander explantation (19.2% vs. 5.3%, P = 0.020), and overall complications (46.2% vs. 22.7%, P = 0.007). When stratifying by breast size, a higher complication rate was not observed with the use of ADM in breasts less than 600 g, whereas ADM use in breasts larger than 600 g was associated with a statistically significant higher rate of infection when controlling for the occurrence of skin necrosis. The ADM cohort had a significantly higher mean initial tissue expander fill volume (256 mL vs. 74 mL, P < 0.001) and a significantly higher mean initial tissue expander fill ratio (49% vs. 17%, P < 0.001). Further work is needed to define the ideal patient population for ADM use in tissue expander/implant breast reconstruction.
PMID: 20395795
ISSN: 1536-3708
CID: 5939142

Two for one: salvage of bilateral lower extremities with a single free flap [Case Report]

Lau, Kwan N; Park, Daniel; Dagum, Alexander B; Bui, Duc T
It is thought that free muscle flaps may remain dependent on their original pedicle for more than 1-year postoperation, particularly in the lower extremity of patients with peripheral vascular disease. We present the first case report of bilateral lower extremity salvage with a single rectus abdominis myocutaneous free flap by transecting the main pedicle. The pedicle of the free flap, going to the contralateral extremity, was safely divided at 6-weeks postoperation. A tourniquet was used to compress the pedicle at the division point to assess viability of the flap distal to the point of occlusion prior to transection of the flap.
PMID: 18434821
ISSN: 1536-3708
CID: 5939132