Alexes Hazen, M.D.

Surgical management of facial nerve paralysis in the pediatric population
Barr, Jason S; Katz, Karin A; Hazen, Alexes
2011 Nov;46(11):2168-2176, Journal of pediatric surgery
BACKGROUND: In the pediatric patient population, both the pathology and the surgical managements of seventh cranial nerve palsy are complicated by the small size of the patients. Adding to the technical difficulty is the relative infrequency of the diagnosis, thus making it harder to become proficient in the management of the condition. The magnitude of the functional and aesthetic deficits these children manifest is significantly troubling to both the patient and the parents, which makes immediate attention, treatment, and functional restoration essential. METHODS: A literature search using PubMed (http://www.pubmed.org) was undertaken to identify the current state of surgical management of pediatric facial paralysis. RESULTS: Although a multitude of techniques have been used, the ideal reconstructive procedure that addresses all of the functional and cosmetic needs of these children has yet to be described. Certainly, future research and innovative thinking will yield progressively better techniques that may, one day, emulate the native facial musculature with remarkable precision. CONCLUSION: The necessity for surgical intervention in children with facial nerve paralysis differs depending on many factors including the acute/chronic nature of the defect as well as the extent of functional and cosmetic damage. In this article, we review the surgical procedures that have been used to treat pediatric facial nerve paralysis and provide therapeutic facial reanimation
— id: 141490, year: 2011, vol: 46, page: 2168, stat: Journal Article,

Fat grafting accelerates revascularisation and decreases fibrosis following thermal injury
Sultan SM; Barr JS; Butala P; Davidson EH; Weinstein AL; Knobel D; Saadeh PB; Warren SM; Coleman SR; Hazen A
2011 Feb;65(2):219-227, Journal of plastic, reconstructive & aesthetic surgery : JPRAS
BACKGROUND: Fat grafting has been shown clinically to improve the quality of burn scars. To date, no study has explored the mechanism of this effect. We aimed to do so by combining our murine model of fat grafting with a previously described murine model of thermal injury. METHODS: Wild-type FVB mice (n=20) were anaesthetised, shaved and depilitated. Brass rods were heated to 100 degrees C in a hot water bath before being applied to the dorsum of the mice for 10s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5cc of human fat/saline. Half were sacrificed 4 weeks following grafting, and half were sacrificed 8 weeks following grafting. Both groups underwent repeat Doppler scanning immediately prior to sacrifice. Burn scar samples were taken following sacrifice at both time points for protein quantification, CD31 staining and Picrosirius red staining. RESULTS: Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat=305+/-15.77mV, saline=242+/-15.83mV; p=0.026). Enzyme-linked immunosorbent assay (ELISA) analysis in fat-grafted animals demonstrated significant increase in vasculogenic proteins at 4 weeks (vascular endothelial growth factor (VEGF): fat=74.3+/-4.39ngml(-1), saline=34.3+/-5.23ngml(-1); p=0.004) (stromal cell-derived factor-1 (SDF-1): fat=51.8+/-1.23ngml(-1), saline grafted=10.2+/-3.22ngml(-1); p<0.001) and significant decreases in fibrotic markers at 8 weeks (transforming growth factor-ss1(TGF-ss): saline=9.30+/-0.93, fat=4.63+/-0.38ngml(-1); p=0.002) (matrix metallopeptidase 9 (MMP9): saline=13.05+/-1.21ngml(-1), fat=6.83+/-1.39ngml(-1); p=0.010). CD31 staining demonstrated significantly up-regulated vascularity at 4 weeks in fat-grafted animals (fat=30.8+/-3.39 vessels per high power field (hpf), saline=20.0+/-0.91 vessels per high power field (hpf); p=0.029). Sirius red staining demonstrated significantly reduced scar index in fat-grafted animals at 8 weeks (fat=0.69+/-0.10, saline=2.03+/-0.53; p=0.046). CONCLUSIONS: Fat grafting resulted in more rapid revascularisation at the burn site as measured by laser Doppler flow, CD31 staining and chemical markers of angiogenesis. In turn, this resulted in decreased fibrosis as measured by Sirius red staining and chemical markers
— id: 138703, year: 2011, vol: 65, page: 219, stat: Journal Article,

Human Fat Grafting Alleviates Radiation Skin Damage in a Murine Model
Sultan SM; Stern CS; Allen RJ; Thanik VD; Chang CC; Nguyen PD; Canizares O; Szpalski C; Saadeh PB; Warren SM; Coleman SR; Hazen A
2011 Aug;128(2):363-372, Plastic & reconstructive surgery
BACKGROUND: Autogenous fat grafting has been observed to alleviate the sequelae of chronic radiodermatitis. To date, no study has replicated this finding in an animal model. METHODS: The dorsa of adult wild-type FVB mice were shaved and depilitated. The dorsal skin was then distracted away from the body and radiated (45Gy) using a Varian 2300 Linear Accelerator. Four weeks following radiation, 1.5cc fat or sham grafts were placed in the dorsal subcutaneous space. Gross results were analyzed photometrically. The animals were sacrificed at 4 and 8 weeks following fat or sham grafting and their dorsal skin was processed for histologic analysis. Inflammation was assessed by epidermal thickness measurements on H&E stained sections. Vascular density was assessed using CD31 staining. Fibrosis was assessed using Smad-3 and Picrosirius Red staining. RESULTS: Hyperpigmentation and ulceration were grossly improved in fat-grafted mice compared to sham-grafted controls. Epidermal thickness measurements demonstrated decreased thickness in fat-grafted animals at both timepoints (20.6+/-1.5mum vs 55.2+/-5.6mum, p=0.004; 17.6+/-1.1mum vs 36.3+/-6.1mum, p=0.039). Vascular density was decreased in fat-grafted mice compared to sham-grafted at both timepoints (17.5+/-1.3 vessels/hpf vs 29+/-3.5, p=0.055; 13.25+/-1.4 vs 17.0+/-1.6, p=0.003). Intensity of Smad3 staining was significantly decreased in fat-grafted animals at both timepoints (2.77+/-0.3% vs 4.98+/-0.9%, p=0.004; 3.05+/-0.2% vs 5.81+/-0.3%, p=0.011). Picrosirius red staining demonstrated a diminished scar-index in fat-treated animals at both timepoints (.54+/-0.05 vs .74+/-0.07, p=0.034; .55+/-0.06 vs .93+/-.07, p=0.001). CONCLUSIONS: Fat grafting attenuates inflammation in acute radiodermatitis and slows the progression of fibrosis in chronic radiodermatitis
— id: 134340, year: 2011, vol: 128, page: 363, stat: Journal Article,

A novel mouse model of cutaneous radiation injury
Thanik, Vishal D; Chang, Christopher C; Zoumalan, Richard A; Lerman, Oren Z; Allen, Robert J Jr; Nguyen, Phuong D; Warren, Stephen M; Coleman, Sydney R; Hazen, Alexes
2011 Feb;127(2):560-568, Plastic & reconstructive surgery
BACKGROUND: : Radiation therapy is a cornerstone of oncologic treatment. Skin tolerance is often the limiting factor in radiotherapy. To study these issues and create modalities for intervention, the authors developed a novel murine model of cutaneous radiation injury. METHODS: : The dorsal skin was isolated using a low-pressure clamp and irradiated. Mice were followed for 8 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy specimens were taken and examined histologically. Tensiometry was performed and Young's modulus calculated. RESULTS: : High-dose radiation isolated to dorsal skin causes progressive changes in skin perfusion, resulting in dermal thickening, fibrosis, persistent alopecia, and sometimes ulceration. There is increased dermal Smad3 expression, and decreased elasticity and bursting strength. CONCLUSIONS: : This model of cutaneous radiation injury delivers reproducible localized effects, mimicking the injury pattern seen in human subjects. This technique can be used to study radiation-induced injury to evaluate preventative and therapeutic strategies for these clinical issues
— id: 122548, year: 2011, vol: 127, page: 560, stat: Journal Article,

Improved fat graft survival with mobilization of progenitor cells
Butala, Parag; Sultan, Steven M.; Davidson, Edward H.; Crawford, James L.; Szpaiski, Caroline; Knobel, Denis; Saadeh, Pierre B.; Warren, Stephen M.; Coleman, Sydney; Hazen, Alexes
2010 SEP ;211(3):S94-S95, Journal of the American College of Surgeons
— id: 113916, year: 2010, vol: 211, page: S94, stat: Journal Article,

FAT GRAFTING FOR THE TREATMENT OF MURINE RADIATION SKIN DAMAGE
Allen, RJ; Nguyen, PD; Varjabedian, L; Schachar, JS; Thanik, VD; Saadeh, PB; Coleman, SR; Hazen, A
2009 MAR-APR ;17(2):A18-A18, Wound repair & regeneration
— id: 97661, year: 2009, vol: 17, page: A18, stat: Journal Article,

Visualizing treatment options for breast reconstructive surgery
Qualter, John; Fana, Melissa; Deluccia, Nicolette; Colen, Kari; Scharf, Carrie; Hazen, Alexes
2009 ;142:262-264, Studies in health technology & informatics
We propose that high-fidelity animations enhanced with real-time 3d interactivity, that demonstrate various breast reconstruction procedures will assist in a patient's decision-making process. These computer based modules will in no way replace a consultation with the physician; instead they will be added to the armamentarium of patient education
— id: 100513, year: 2009, vol: 142, page: 262, stat: Journal Article,

A murine model for studying diffusely injected human fat
Thanik, Vishal D; Chang, Christopher C; Lerman, Oren Z; Allen, Robert J Jr; Nguyen, Phuong D; Saadeh, Pierre B; Warren, Stephen M; Levine, Jamie P; Coleman, Sydney R; Hazen, Alexes
2009 Jul;124(1):74-81, Plastic & reconstructive surgery
BACKGROUND: The study of human autologous fat grafting has been primarily anecdotal. In this study, the authors aim to develop a murine model that recapitulates human fat grafting to study the fate of injected fat and the cell populations contained within. METHODS: The authors' method of fat harvesting and refinement has been described previously. The authors injected nude and tie2/lacZ mice with 2 ml of human lipoaspirate placed on the dorsal surface in a multipass, fan-like pattern. Fatty tissue was injected in small volumes of approximately 1/30 ml per withdrawal. The dorsal skin and associated fat was excised at various time points. Sections were stained with hematoxylin and eosin and cytochrome c oxidase IV. Transgenic tie2/lacZ samples were stained with X-galactosidase. At the 8-week time point, volumetric analysis was performed. RESULTS: Volumetric analysis at the 8-week time point showed 82 percent persistence of the original volume. Gross analysis showed it to be healthy, nonfibrotic, and vascularized. Hematoxylin and eosin analysis showed minimal inflammatory or capsular reaction, with viable adipocytes. Fat grafted areas were vascularized with multiple blood vessels. Cytochrome c oxidase IV human-specific stain and beta-galactosidase expression revealed these vessels to be of human origin. CONCLUSIONS: The authors have developed a murine model with which to study the fate of injected lipoaspirate. There is a high level of persistence of the grafted human fat, with minimal inflammatory reaction. The fat is viable and vascularized, demonstrating human-derived vessels in a mouse model. This model provides a platform for studying the populations of progenitor cells known to reside in lipoaspirate
— id: 100530, year: 2009, vol: 124, page: 74, stat: Journal Article,

Treatment of radiation skin damage with Coleman fat grafting
Chang, CC; Thanik, VD; Lerman, OZ; Saadeh, PB; Warren, SM; Coleman, SR; Hazen, A
2007 NOV ;25(12):3280-3281, Stem cells
— id: 75629, year: 2007, vol: 25, page: 3280, stat: Journal Article,

Nonextremity replantation: the management of amputations of the facial parts and testicle
Flores, Roberto L; Hazen, Alexes; Galiano, Robert D; Klapper, Andrew M; Levine, Jamie P
2007 Apr;34(2):197-210, Clinics in plastic surgery
Successful nonextremity replantations, particularly of the facial anatomy and testicles, are rare procedures, and only a handful of cases have been reported. This article reviews the current literature in nonextremity replantations and representative cases performed at the authors' institution. Certain underlying themes and problems are consistently encountered in the surgical management of these cases. These are identified and reviewed. Although the replantation of these body parts remains technically challenging, all efforts should be made, when indicated, to repair these injuries microsurgically, because it currently offers the best reconstructive solution for these patients
— id: 71944, year: 2007, vol: 34, page: 197, stat: Journal Article,

Gustilo grade IIIB tibial fractures requiring microvascular free flaps: external fixation versus intramedullary rod fixation
Rohde, Christine; Greives, Matthew R; Cetrulo, Curtis; Lerman, Oren Z; Levine, Jamie P; Hazen, Alexes
2007 Jul;59(1):14-17, Annals of plastic surgery
BACKGROUND: Gustilo IIIB fractures involve high-energy tibial fractures for which there is inadequate soft tissue coverage. In addition to orthopedic fixation, these injuries require soft tissue reconstruction, often in the form of a microvascular free flap. Although the majority of orthopedic literature favorably compares intramedullary rod fixation to external fixation in open tibial fractures, these studies have not focused on the role of either method of fixation in relation to the soft tissue reconstruction. METHODS: Because we had noted numerous complications after providing free-flap coverage over intramedullary rodded fractures, we sought to investigate whether there were differences in outcomes between free flap-covered lower-extremity fractures which were fixated by external fixation versus intramedullary rods. A retrospective chart review was performed on all patients in our institution who had lower-extremity free flaps for coverage of Gustilo IIIB fractures from 1995-2005 in relation to the type of bony fixation. RESULTS: Of the 38 patients studied, 18 underwent external fixation of the tibial fracture, and 20 had intramedullary rodding. Overall flap survival was 95%, with 1 failure in each group. However, the intramedullary rod group had higher incidences of wound infection, osteomyelitis, and bony nonunion (25%, 25%, and 40%, respectively) than the external fixation group (6%, 11%, 17%, respectively). CONCLUSIONS: For Gustilo IIIB fractures that require free-flap coverage, the added bony and soft tissue manipulation required for intramedullary rodding may disrupt the surrounding blood supply and lead to higher rates of complications that threaten the overall success of the reconstruction. Plastic and orthopedic surgeons should discuss the optimal method of bony fixation for complex tibial fractures when a free flap will likely be needed for soft tissue coverage. This integrated team approach may help minimize complications
— id: 96611, year: 2007, vol: 59, page: 14, stat: Journal Article,

Biologic brachytherapy: ex vivo transduction of microvascular beds for efficient, targeted gene therapy
Michaels, Joseph 5th; Levine, Jamie P; Hazen, Alexes; Ceradini, Daniel J; Galiano, Robert D; Soltanian, Hooman; Gurtner, Geoffrey C
2006 Jul;118(1):54-65, Plastic & reconstructive surgery
BACKGROUND: Gene therapy for cancer holds enormous therapeutic promise, but its clinical application has been limited by the inability to achieve targeted, high-level transgene expression with limited systemic toxicity. The authors have developed a novel method for delivering genes to microvascular free flaps (commonly used during reconstructive surgery) to avoid these problems. METHODS: During the finite period in which a free flap is separated from the host (ex vivo), it can be perfused with extremely high titers of genetic material through the afferent artery, resulting in efficient transduction of the tissue. Before reanastomosis, unincorporated genetic material is flushed from the flap, minimizing systemic toxicity. RESULTS: In a rodent model using an adenoviral vector containing the lacZ reporter gene, high regional expression of beta-galactosidase was achieved in all the different cells in a microvascular free flap. Moreover, no beta-galactosidase staining was observed outside of the transduced flap, and viral sequence was undetectable by polymerase chain reaction analysis in other tissues. Further analysis confirmed that high-level transgene expression was precisely localized to the explanted tissue, with no collateral transduction. CONCLUSIONS: Targeting gene delivery with minimal systemic toxicity is essential for successful gene therapy. This form of 'biological brachytherapy' provides a new opportunity to deliver targeted therapeutic transgenes to patients undergoing reconstructive surgery and allows microvascular free flaps to perform therapeutic and reconstructive functions
— id: 64780, year: 2006, vol: 118, page: 54, stat: Journal Article,

In-vivo gene silencing using topical delivery of siRNA
Thanik, V; Greives, M; Seiser, N; Lerman, O; Hazen, A; Levine, J; Saadeh, P
2006 SEP ;203(3):S55-S56, Journal of the American College of Surgeons
— id: 69819, year: 2006, vol: 203, page: S55, stat: Journal Article,

Vascularized acellular dermal matrix island flaps for the repair of abdominal muscle defects
Chung, Seum; Hazen, Alexes; Levine, Jamie P; Baux, Germania; Olivier, Wendy-Ann M; Yee, Herman T; Margiotta, Michael S; Karp, Nolan S; Gurtner, Geoffrey C
2003 Jan;111(1):225-232, Plastic & reconstructive surgery
The potential widespread use of tissue-engineered matrices in soft-tissue reconstruction has been limited by the difficulty in fabricating and confirming a functional microcirculation. Acellular dermal matrix placed in a soft-tissue pocket acts as a scaffold to be incorporated by the host's fibrovascular tissue. A new method for noninvasive real-time observation of functional microvascular networks using orthogonal polarization spectral (OPS) imaging has recently been reported. Arterioles, venules, and capillaries can be directly visualized, and the movement of individual blood cells through them can be observed. The present study was performed to investigate the use of prefabricated acellular dermal matrix with an arteriovenous unit for the repair of abdominal muscle defects. OPS imaging was used to determine the presence of a functional microcirculation in the neovascularized matrix. In Sprague-Dawley rats, vascularized matrix was prefabricated by placing the superficial epigastric artery and vein on a 2-cm x 2-cm implant-type acellular dermal matrix in the thigh. Three weeks after implantation, the matrix-arteriovenous unit was elevated as an axial-type flap and a 2-cm x 2-cm full-thickness block of abdominal muscle immediately superior to the inguinal ligament was resected. Additional procedures were performed according to group: no repair (group 1, = 20); repair with nonvascularized acellular dermal matrix (group 2, = 20); repair with devascularized acellular dermal matrix (group 3, = 20); and repair with vascularized acellular dermal matrix (group 4, = 20). OPS imaging (field of view, 1 mm in diameter; scan depth range, 0.2 mm) was performed on both sides of each flap on a total of 10 random distal regions before and after pedicle transection in group 3 and with the pedicle preserved in group 4. Hernia rate and duration of survival were compared for 21 days. OPS imaging showed directional blood cell movement through the capillary network in all areas scanned in group 4. No microvascular perfusion was observed after pedicle transection in group 3. Hernia rates of 100, 80, 90, and 0 percent were seen in groups 1, 2, 3, and 4, respectively. Median survival times of 9, 11.5, 9, and 21 postoperative days were noted in groups 1, 2, 3, and 4, respectively. Histopathologic analysis with factor VIII revealed full-thickness infiltration of the matrix by endothelial cells, signifying newly formed blood vessels. Repair of abdominal muscle defects using vascularized acellular dermal matrix resulted in no hernia and survival of all animals for the duration of study. However, repairs using avascular or devascularized matrix resulted in significant rates of hernia and decreased survival. Acellular dermal matrix can be prefabricated into vascularized tissue using an arteriovenous unit and used successfully to repair abdominal muscle defects. OPS imaging allowed for high-contrast direct visualization of microcirculation in previously acellular tissue following prefabrication with an arteriovenous unit
— id: 33783, year: 2003, vol: 111, page: 225, stat: Journal Article,

Reliable assessment of skin flap viability using orthogonal polarization imaging
Olivier, Wendy-Ann M; Hazen, Alexes; Levine, Jamie P; Soltanian, Hooman; Chung, Seum; Gurtner, Geoffrey C
2003 Aug;112(2):547-555, Plastic & reconstructive surgery
Intraoperative evaluation of skin flap viability has primarily been dependent on clinical judgment. The purpose of this study was to determine whether an orthogonal polarization spectral imaging device could be used to accurately predict viability of random-pattern skin flaps. Orthogonal polarization spectral imaging is a newly developed technique that visualizes the microcirculation using reflected light without the use of fluorescent dyes and allows for noninvasive real-time observation of functional microvascular networks. In Sprague-Dawley rats (n = 24), three types of random skin flaps were designed with unknown zones of viability (n = 8 per group). After flap elevation, the skin flaps were evaluated by both clinical examination and orthogonal polarization spectral imaging. Areas of the flap determined to be nonviable by clinical examination were measured and marked. Orthogonal polarization spectral imaging was subsequently performed, and areas of the skin flap with stasis (i.e., cessation of red blood cell movement) in the dermal microcirculation on orthogonal polarization spectral imaging were measured and marked. The skin flaps were then secured in place. Flaps were evaluated on a daily basis for clinical signs of ischemia and necrosis. On postoperative day 7, the total amount of random skin flap necrosis was measured and recorded. Clinical examination of the random skin flaps significantly underestimated the actual amount of eventual flap necrosis, and as result was a very poor predictor of flap necrosis. By contrast, assessment of microcirculatory stasis using the orthogonal polarization spectral imaging device correlated well with the subsequent development of necrosis in all groups. In the three groups, the average amount of flap necrosis predicted by clinical examination deviated from actual necrosis by approximately 2 to 4 cm. However, the amount that orthogonal polarization spectral imaging differed from actual necrosis was 0.1 to 0.3 cm. Therefore, orthogonal polarization spectral imaging was an excellent predictor of eventual flap necrosis and much more accurate than clinical observation (p < 0.001). Intraoperative evaluation of axial and random pattern flap viability has traditionally been based on clinical examination as no other reliable, convenient test currently exists. The authors demonstrated that an orthogonal polarization spectral imaging device accurately predicts zones of necrosis in random pattern flaps by directly visualizing cessation of microcirculatory flow. Intraoperative stasis in the dermal microcirculation correlated precisely with subsequent flap necrosis. Orthogonal polarization spectral imaging was significantly more accurate than clinical examination, which consistently underestimated flap necrosis. The orthogonal polarization spectral imaging technique may have value in the intraoperative assessment of skin flap perfusion such as that required after skin-sparing mastectomy
— id: 41998, year: 2003, vol: 112, page: 547, stat: Journal Article,

Poland's syndrome and carcinoma of the breast: a case report
Katz SC; Hazen A; Colen SR; Roses DF
2001 Jan-Feb;7(1):56-59, Breast journal
Poland's syndrome is a rare congenital anomaly that may include mammary hypoplasia and has been described in association with various malignancies. We report the case of a 42-year-old woman with unilateral Poland's syndrome who developed carcinoma in the hypoplastic breast. A review of the literature reveals no previous report of carcinoma of the hypoplastic breast with Poland's syndrome
— id: 20671, year: 2001, vol: 7, page: 56, stat: Journal Article,