Faculty Bibliography

The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1alpha (HIF-1alpha) up-regulation in endothelial cells (ECs), a HIF-1alpha-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1alpha and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1alpha mRNA and abolition of HIF-1alpha protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1-mediated EC migration in hypoxic and/or radiation-treated media showed IR induced strong SDF-1-dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1alpha induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis

Chronic post-surgical lymphedema is common condition that afflicts nearly 2 million Americans. In the USA, it is most commonly encountered in the upper extremities of patients who have undergone axillary lymph node dissection for breast cancer. Lymphedema has a significant negative effect on cosmesis, limb function, and overall quality of life. Despite the impact of this condition, very little is known about how to effectively prevent or treat lymphedema. While therapeutic options for chronic extremity lymphedema remain limited, several surgical approaches have been suggested. These include techniques aimed at reducing limb volume, as well as techniques that aim to reconstitute disrupted lymphatic channels. Operations proposed to re-establish lymphatic continuity include lymphatico-venous anastomoses, lymphatico-lymphatico anastomoses, and tissue transfer.

BACKGROUND: Recent reports have demonstrated that lymphedema can occur after even minor pertubation of the axillary region such as sentinel lymph node biopsy (SLNB). The impact of breast reconstruction on the development of lymphedema, however, remains unknown. Therefore, the purpose of this study was to determine the impact of immediate tissue expander breast reconstruction on the risk of developing lymphedema. MATERIALS AND METHODS: We identified patients who had undergone mastectomy with SLNB or SLNB and axillary lymph node dissection (ALND) with or without breast reconstruction using our prospectively maintained lymphedema and breast reconstruction databases. The development of lymphedema was evaluated prospectively using arm measurements and a validated questionnaire. Associations between variables were examined. Logistic regression was used to examine the association of reconstruction on prevalence of lymphedema while adjusting individually for BMI, age, and weight gain after surgery. RESULTS: Characteristics of patients with or without reconstruction were similar except for age, BMI, and weight gain since surgery. Median follow-up was 5 years. Among patients treated with mastectomy with SLNB or SLNB/ALND, those undergoing reconstruction had a lower rate of measured lymphedema than those who did not (5% vs. 18%, P < .0004). The reconstructed group also had fewer patients with both measured and self-reported lymphedema (3% vs. 12%, P < .002). Differences in the rates of measured lymphedema between groups persisted following univariate logistical regression for differences in age, BMI, and weight gain. CONCLUSIONS: Tissue expander breast reconstruction in patients undergoing SLNB or SLNB/ALND does not increase the risk of developing measured or perceived lymphedema.

BACKGROUND: Neonatal upper airway obstruction demands urgent attention. Tracheostomy can prove to be lifesaving but has morbidities. Recently, the authors found reduced morbidity/mortality when using a distraction decision tree model compared with conventional "case-by-case" management. In this current study, the authors assess the long-term costs of (1) a decision tree model versus conventional treatment and (2) tracheostomy versus distraction osteogenesis. METHODS: An inpatient cost-matrix analysis study on neonates with upper airway obstruction and micrognathia was performed (n=149). In Part I, conventionally treated neonates managed on a case-by-case basis received home monitoring or a tracheostomy. Decision tree model-managed newborns had specialist consultations and diagnostic testing to determine whether home monitoring, tracheostomy, or distraction osteogenesis would be implemented. In Part II, tracheostomy treatment was compared directly to distraction osteogenesis. RESULTS: In Part I (conventional versus decision tree model), taking into account the costs of the distraction, tracheostomy, hospital stay, diagnostic studies, physician fees, and emergency department visits, the total per patient treatment cost was 1.5 greater in the conventional treatment group ($332,673) compared with the decision tree model ($225,998) (p<0.05). In Part II (tracheostomy versus distraction osteogenesis), the total per-patient treatment cost in the tracheostomy group was two times greater than in the distraction group ($382,246 versus $193,128) (p<0.05). CONCLUSIONS: In treating newborns with micrognathia and upper airway obstruction, a decision tree model with mandibular distraction decreases long-term health care costs compared with conventional treatment. Furthermore, when comparing distraction to tracheostomy, similar decreases in long-term health care costs occurred.

Complications and undesired outcomes happen to some patients of virtually all physicians, at all stages in their careers. Bad outcomes can be a consequence of disease processes, the premorbid condition of the patient, or the errors that occur in the process of health care. These errors include, but are by no means confined to, surgeon error. Regardless of the reason for the bad outcome, the surgeon is obligated to discuss the event with the patient and the family. This article reviews the benefits, barriers, and legal implications of the discussion and describes the disclosure process.

Mesenchymal and hematopoietic tissues are important reservoirs of adult stem cells. The potential of tissue resident mesenchymal stem cells (MSCs) to differentiate into cells of mesodermal and ectodermal lineages has been reported previously. We examined the hypothesis that adherent adipose tissue resident mesenchymal stem cells (ASCs) are capable of generating cells with hematopoietic characteristics. When cultured in differentiation media, clonally isolated ASCs develop into cells with hematopoietic attributes. The hematopoietic differentiated cells (HD) express early hematopoietic (c-kit, PROM1, CD4) as well as monocyte/macrophage markers (CCR5, CD68, MRC1, CD11b, CSF1R). Additionally, HD cells display functional characteristics of monocyte/macrophages such as phagocytosis and enzymatic activity of α-Naphthyl Acetate Esterase. HD cells are also responsive to stimulation by IL-4 and LPS as shown by increased CD14 and HLA-DRB1 expressions and release of IL-2, IL10, and TNF. Taken together, this study characterizes the potential of ASCs to generate functional macrophages in vitro, and therefore paves way for their possible use in cell therapy applications.

PURPOSE: Diagnosis and treatment of frontal sinus fractures (FSFs) have progressed over the previous 30 years. Despite advances in computed tomography, there is no current diagnostic uniformity with regard to classification and treatment. We developed a statistically valid treatment protocol for FSFs based on injury pattern, nasofrontal outflow tract (NFOT) injury, and complication(s). These data outlined predictable injury patterns based on specific computed tomographic findings critical to the diagnosis and ultimate treatment of this potentially fatal injury. MATERIALS AND METHODS: A retrospective review was conducted on patients with FSF from 1979 to 2005 under institutional review board approval. All computed tomographic scans were reviewed by the authors and fractures categorized by location, displacement, comminution, and degree of NFOT injury. RESULTS: One thousand ninety-seven patients with FSF were identified, 87 expired and 153 had inadequate data, leaving a group of 857 patients. Simultaneous displacement of anterior-posterior tables constituted the largest group (38.4%). NFOT injury occurred in most patients (70.7%) and was strongly associated with anterior (92%) and posterior (88%) table involvement (comminuted 98%). Sixty-seven percent of patients with NFOT injury had obstruction. Five hundred four patients (59.6%) had surgery with 10.4% complications and 353 patients were observed with 3.1% complications. All but 1 patient with complications had NFOT injury (98.5%). CONCLUSIONS: Predictable patterns of injury based on specific computed tomographic data play a pivotal role in classification and surgical management of potentially fatal frontal sinus injuries. Radiologic diagnosis of NFOT injury in FSFs, particularly obstruction, plays a decisive role in surgical planning.