Abstract Although constitutively activated nuclear factor-κB (NF-κB), attenuated transforming growth factor β (TGFβ) signaling, and TP53 mutations frequently occur in human cancers, how these pathways interact and together contribute to malignancy remains uncertain. Here, we found an association between overexpression of NF-κB–related genes, reduced expression of TGFβ receptor (TβR) subunits and downstream targets, and TP53 genotype in head and neck squamous cell carcinoma (HNSCC). In response to recombinant TGFβ1, both growth inhibition and TGFβ target gene modulation were attenuated or absent in a panel of human HNSCC lines. However, in HNSCC cells that retained residual TGFβ signaling, TGFβ1 inhibited both constitutive and tumor necrosis factor α–stimulated NF-κB activity. Furthermore, HNSCC lines overexpressing mutant (mt) TP53 and human tumor specimens with positive TP53 nuclear staining exhibited reduced TβRII and knocking down mtTP53 induced TβRII, increasing TGFβ downstream gene expression while inhibiting proinflammatory NF-κB target gene expression. Transfection of ectopic TβRII directly restored TGFβ signaling while inhibiting inhibitor κBα degradation and suppressing serine-536 phosphorylation of NF-κB p65 and NF-κB transcriptional activation, linking these alterations. Finally, experiments with TβRII conditional knockout mice show that abrogation of TGFβ signaling promotes the sustained induction of NF-κB and its proinflammatory target genes during HNSCC tumorigenesis and progression. Together, these findings elucidate a regulatory framework in which attenuated TGFβ signaling promotes NF-κB activation and squamous epithelial malignancy in the setting of altered TP53 status. [Cancer Res 2009;69(8):3415–24]

Supplementary Methods, Figures 1-6 from Attenuated Transforming Growth Factor β Signaling Promotes Nuclear Factor-κB Activation in Head and Neck Cancer

BackgroundRectus abdominis muscle harvest typically uses a long and continuous paramedian approach. To limit donor site morbidity, the senior author performs a limited incision approach particularly useful in medically vulnerable patients, including patients with sternal wound infections.MethodsAll patients of a single surgeon from 2000 to 2014 who underwent rectus harvest by one or two transverse incisions and use of lighted retractor were identified. Patients were categorized by indication, for sternal wound coverage or non-sternal wound coverage. Co-morbidities, operative notes, and post-operative courses were evaluated. Comparisons were made to patients undergoing harvest by paramedian approach.ResultsSeventeen patients with a mean age of 61 underwent limited-incision rectus harvest. Nine patients had indication for sternal wound coverage. Three patients had single transverse incision and six patients had double transverse incisions. One patient expired post-reconstruction day 3. One patient had complete abdominal and partial sternal wound dehiscence. No other donor site complications were observed. Eight patients had indication for non-sternal wound coverage, including seven patients requiring free rectus for lower extremity defects and one a pedicled rectus abominis for pelvic osteomyelitis. No post-operative complications were observed in these non-sternal wound coverage patients. There was a trend toward improved wound healing and hospitalization time using the transverse compared to paramedian technique, although this was not significant.ConclusionsThe morbidity of the traditional paramedian incision for rectus harvest may be avoided using a limited skin incision approach. This is useful in patients with attenuated healing capacity and offers a lower risk approach to a traditionally risky donor site.Level of Evidence: Level IV, therapeutic study.

A 4-year-old-boy required emergent craniectomy and drainage of a large right-sided acute subdural hematoma after head trauma, during which massive sinus hemorrhage with brain swelling occurred. Acute intraoperative management entailed dural cover using synthetic dural membrane substitute and scalp coverage over the herniated brain using acellular dermal matrix. After intensive monitoring and control of raised intracranial pressure over the next few days, the exposed brain was then covered by scalp and forehead flaps with cadaveric skin grafting to the donor site. This temporary coverage continued until adequate resolution of the intracranial swelling and control of the hydrocephalus using a ventriculoperitoneal shunt. Ultimately, the flaps were derotated and the craniectomy site was reconstructed with autologous banked bone. The child had a significant functional recovery with some residual left-sided weakness. This case is the first report of local tissue flaps used for temporary coverage of malignant brain herniation in a pediatric head trauma patient and highlights their effective use. Through serial surgical procedures the brain was successfully covered without significant blood loss and the patient's local tissues returned to their original donor sites with good cosmetic outcome, without sacrifice of the patient's own skin or free flap options.

BACKGROUND:Surgical decompression of a migraine headache may unmask headaches originating from secondary sites. A retrospective chart review investigated the incidence and characteristics of secondary trigger sites to identify clinical patterns that could aid in predicting and perhaps reducing postoperative migraines.METHODS:One hundred eighty-five charts for migraine patients who underwent surgery at the senior author's (B.G.) practice were reviewed. Sites from which migraine headaches initiated or occurred independently were considered primary. The sites that were not active at the time of preoperative evaluation but became active after surgery were considered secondary. Bivariate analysis was performed to characterize postoperative migraines.RESULTS:Of 185 patients, 33 (17.8 percent) developed secondary migraine headache trigger sites. Of patients with primary site I (frontal) symptoms, 20.83 percent had site III (septonasal) symptoms unmasked after surgery (versus 7 percent for patients with other primary sites; p = 0.04). Of the patients with site II (temporal) migraines, 17.14 percent had secondary frontal symptoms (versus 5.68 percent; p = 0.04). Primary site II symptoms predicted postoperative site IV (occipital) symptoms (11.43 versus 1.1 percent; p = 0.008), and primary occipital symptoms predicted postoperative temporal symptoms (11.1 versus 2.33 percent; p = 0.04).CONCLUSIONS:The authors observed that 17.8 percent of patients develop postoperative migraine headache triggers that are not reported during the initial assessment. Knowledge of secondary migraine emergence patterns, and the presence of some preoperative symptoms, can aid in predicting the migraines that will arise from a new site postoperatively.CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, IV.

Objective To review and collectively summarize our knowledge of simultaneous Le Fort III and Le Fort I osteotomies. Design A PubMed search using “Le Fort III,” “simultaneous Le Fort III and Le Fort I,” “combined Le Fort III and Le Fort I,” “dual midface,” and “segmental midface” was performed. Articles with relevant abstracts were obtained for formal review. A new case of simultaneous Le Fort III and Le Fort I is presented to describe and discuss specific operative indications and surgical decisions. Results There were 14 articles that met inclusion criteria with reports of simultaneous Le Fort III and Le Fort I osteotomies. A total of 20 cases were present in the literature. No major complications were reported. We performed combined Le Fort III with Le Fort I osteotomies in a 25-year-old patient with Crouzon syndrome who had undergone a previous Le Fort III at the age of 4 years. The patient tolerated the procedure well, and postoperatively, her exophthalmos and class III malocclusion were corrected. Conclusions Simultaneous Le Fort III and Le Fort I can correct differential upper and lower midface hypoplasia and is a well-tolerated procedure in the mature facial skeleton. This systematic review improves our understanding of the surgical technique and indications for a procedure that can correct complex midfacial deformities.

BACKGROUND:Current literature provides little information about the impact of environmental exposures on the severity of acquired blepharoptosis.OBJECTIVE:The authors assessed environmental factors that may contribute to eyelid ptosis in a population of identical twins.METHODS:Photographs of 286 sets of twins from a prospectively collected database from 2008 to 2010 were reviewed. The authors identified 96 sets of identical twins (192 individual persons) who had differing severity of ptosis. Digital photographs were analyzed, and the degree of ptosis was measured in each eye of every subject. The external factors that could potentially contribute to blepharoptosis were taken into consideration. The authors then assessed the correlations of 9 different environmental risk factors with ptosis. Generalized linear mixed model were constructed to determine the associations of ptosis measurements with environmental risk factors obtained from the subject survey database.RESULTS:The mean level of upper eyelid ptosis in the study population was 1.1 mm. The mean difference in ptosis between twins was 0.5 mm. Wearing contact lenses, either hard or soft, was significantly associated with ptosis. The mean ptosis measurement among twins who did not wear contact lenses was 1.0 mm; for those who wore soft contact lenses, the mean was 1.41 mm, and for those who wore hard contact lenses, the mean was 1.84 mm.CONCLUSIONS:Acquired ptosis is not linked to body mass index, smoking behavior, sun exposure, alcohol use, work stress, or sleep. Wearing either hard or soft lenses was associated with an increased risk of ptosis. These influences are independent of genetic predisposition.LEVEL OF EVIDENCE:3 Diagnostic.

The superficial inferior epigastric vasculature plays a critical role in free abdominal tissue transfer. However, its anatomic variations are incompletely characterized. An investigation was conducted on the preoperative imaging of patients undergoing free-flap breast reconstruction by a single surgeon between 2008 and 2013. This study included patients who underwent abdominal magnetic resonance angiogram (MRA). A coordinate system was used to draw the main trunk and primary branches from each patient's superficial inferior epigastric system. Each hemiabdomen's branching pattern was categorized as simple, complex, or absent. The number of superficial-to-deep inferior epigastric connections and the presence or absence of a superficial system crossing the midline were recorded. Interrater reliability was assessed for two raters. This analysis included 53 patients (106 hemiabdomens). A total of 80 (75%) hemiabdomens were categorized as having simple and 10 (9%) as complex branching patterns. A total of 16 (15%) hemiabdomens had no identifiable vessels. At least one superficial-to-deep connection was found among 89 hemiabdomens (84%). Superficial systems crossing the midline were found in 14 patients (26%). Our findings support the high degree of anatomic variation in the superficial inferior epigastric system, including a significant number of patients lacking superficial-to-deep connections and bilaterally communicating systems. These variations may be identified on preoperative MRA.

Objective: Limited data exist regarding the effect of radiation timing on complications of tissue expander/implant-based breast reconstruction. This study seeks to compare outcomes of tissue expander/implant reconstruction in patients undergoing postmastectomy radiotherapy, those with previous radiation therapy following breast conservation therapy, and those who did not receive radiation therapy.Methods: The records of the patients of a single surgeon were reviewed from January 2007 to July 2013. All patients undergoing tissue expander/implant breast reconstruction were placed into one of three groups based on the timing of radiation therapy: postmastectomy (Current), previously following breast conservation therapy (Prior), and no radiotherapy (No XRT). Medical records were reviewed for any reported complications, and statistical analysis was performed.Results: A total of 210 patients (265 breasts) were included in the analysis. Current patients were more likely than No XRT patients to experience expander infection (20% vs. 2.6%, p = 0.001) and expander removal (26% vs. 8.3%, p = 0.007). Prior patients were more likely than No XRT patients to undergo conversion to tissue flap reconstruction (10.5% vs. 0.6%, p = 0.031). No significant differences were found between groups with respect to cellulitis, abscess formation, hematoma, seroma, skin flap necrosis, expander exposure, implant exposure, or implant infection.Conclusions: This study supports the relative safety of tissue expander/implant breast reconstruction in selected groups of patients who have received radiation therapy. Differences in rates of expander infection, expander removal, and conversion to tissue flap reconstruction represent potential areas for further research. (C) 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Three-dimensional (3D) changes in the midface following malar calcium hydroxyapatite (CaHa) injection have not been systematically analyzed.The authors analyzed 3D volume changes in midface and naso-labial fold (NLF) volume, as well as lateral movement in the NLF/naso-labial crease (NLC) junction following malar injection of CaHa in a cadaver model.A single surgeon injected CaHa in the supraperiosteal plane. Sequential images were obtained with the VECTRA 3D system pre- and post-1.5- and 3-cc CaHa injections. All measurements were performed by a single examiner. Injection location was verified anatomically.Injections were performed in 16 fresh cadaver hemi-faces. Maximal increases in projection were centered on the malar injection site, with associated decreases in projection and volume in the infero-medial locations. Relative mean increases in volume of 3.16 cc and 4.94 cc were observed following the 1.5-cc and 3-cc injections, respectively. There was a relative decrease in the volume of the NLF of -0.3 cc and -0.4 cc following the 1.5- and 3-cc injections, respectively. Injection of CaHa was associated with lateral movements of the NLF-NLC junction at the level of the nasal sill, philtral columns, and oral commissure, measuring 2.7, 2.5, and 1.9 mm and 2.8, 2.9, and 2.4 mm following the 1.5- and 3-cc injections, respectively. Anatomical dissection verified the location in the supraperiosteal space and within the middle malar fat pad.Following malar CaHa injection, 3D photographic analysis showed a measureable lifting effect with recruitment of ptotic tissue and lateral movement of the NLF-NLC junction in a cadaver model.

The tear trough refers to the medial one third of the periorbital hollow formed by the junction of the thin eyelid skin and the thicker cheek and nasal skin. It is often one of the earliest signs of ageing present around the eye and a common complaint of patients presenting to the aesthetic surgeon. The tear trough is located at the infraorbital rim medially and then drops below the rim as it traverses laterally. 1 Hirmand H. Anatomy and nonsurgical correction of the tear trough deformity. Plast Reconstr Surg. Feb 2010; 125: 699-708 Crossref PubMed Scopus (105) Google Scholar Many surgical corrections have been well described, but non-surgical options have also become common practice. 2 Kane M.A. Treatment of tear trough deformity and lower lid bowing with injectable hyaluronic acid. Aesthetic Plast Surg. Sep–Oct 2005; 29: 363-367 Crossref PubMed Scopus (95) Google Scholar , 3 Viana G.A. Osaki M.H. Cariello A.J. Damasceno R.W. Osaki T.H. Treatment of the tear trough deformity with hyaluronic acid. Aesthetic Surg J. Feb 2011; 31: 225-231 Crossref PubMed Scopus (29) Google Scholar Currently no-injectable product is FDA approved for use in this area although various facial fillers have been advocated for periorbital rejuvenation. Injection of the tear-trough has raised concern from a safety standpoint because of its anatomic location near the eye. Many surgeons use blunt cannula tips to reduce the risk orbital and intravascular injection of filler. The process of using a blunt tip catheter often necessitates first puncturing the dermis with a slightly larger gauge needle, withdrawing and then inserting the blunted cannula through the prior puncture. The premise behind its use is that a blunted cannula is much less likely to pierce the periorbita, orbital septum, or vasculature and stay within the desired anatomic plane. 4 Funt D. Pavicic T. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. Clin Cosmet Investig Dermatol. 2013; 6: 295-316 PubMed Google Scholar The disadvantages of this technique are that bleeding occurs upon withdrawal of the sharp dermal puncture and there can be difficulty inserting the blunted tip into the small puncture site. While the drawbacks are relatively minor the extra step is viewed as unnecessary by many aesthetic surgical providers who strictly use sharp needles. 2 Kane M.A. Treatment of tear trough deformity and lower lid bowing with injectable hyaluronic acid. Aesthetic Plast Surg. Sep–Oct 2005; 29: 363-367 Crossref PubMed Scopus (95) Google Scholar The current literature provides no information if there is a difference in these two techniques in regards to anatomic plane violation and filler placement.

The literature surrounding pediatric burns has focused on inpatient management. The goal of this study is to characterize the population of burned children treated as outpatients and assess outcomes validating this method of burn care. A retrospective review of 953 patients treated the burn clinic and burn unit of a tertiary care center. Patient age, burn etiology, burn characteristics, burn mechanism, and referral pattern were recorded. The type of wound care and incidence of outcomes including subsequent hospital admission, infection, scarring, and surgery served as the primary outcome data. Eight hundred and thirty children were treated as outpatients with a mean time of 1.8 days for the evaluation of burn injury in our clinic. Scalds accounted for 53% of the burn mechanism, with burns to the hand/wrist being the most frequent area involved. The mean percentage of TBSA was 1.4% for the outpatient cohort and 8% for the inpatient cohort. Burns in the outpatient cohort healed with a mean time of 13.4 days. In the outpatient cohort, nine (1%) patients had subsequent admissions and three (0.4%) patients had concern for infection. Eight patients from the outpatient cohort were treated with excision and grafting. The vast majority of pediatric burns are small, although they may often involve more critical areas such as the face and hand. Outpatient wound care is an effective treatment strategy which results in low rates of complications and should become the standard of care for children with appropriate burn size and home support.

Background: This study focuses on the impact of preoperative narcotic medication use on outcomes of surgical treatment of migraine headaches. Methods: A retrospective comparative review was conducted with patients undergoing migraine surgery. Data gathered included demographic information, baseline migraine headache characteristics, migraine surgery sites, postoperative migraine headache characteristics 1 year or more following surgery, and preoperative migraine medication use. Patients were grouped based on preoperative narcotic medication use. The narcotic users were subdivided into low and high narcotic user groups. Preoperative migraine characteristics were comparable between groups and the outcomes of migraine surgery were compared between the groups. Results: Outcomes in 90 narcotic users were compared with those for 112 patients not using narcotic medications preoperatively. Narcotic users showed statistically significantly less reduction in frequency, severity, and duration of migraine headaches after surgery. Narcotic users had clinical improvement in 66.7 percent of patients and elimination in 18.9 percent versus 86.6 and 36.6 percent, respectively, in the nonnarcotic group. The group that consumed narcotics had significantly lower rates of improvement in all migraine indices. Conclusions: Previous studies have discouraged the routine use of narcotic medications in the management of migraine medications. The authors' study demonstrates that narcotic medication use before migraine headache surgery may predispose patients to worse outcomes postoperatively. Because pain cannot be objectively documented, the question remains of whether this failure to improve the pain was indeed a suboptimal response to surgery or the need for narcotic substances. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Background: The incidence of obesity is on the rise in the United States and worldwide. Complications following panniculectomy are higher for super obese patients, often requiring readmission and additional interventions. In this study, the authors compare the outcomes of patients who underwent primary closure of their resection wounds to the outcomes of patients who underwent initial open wound management with a negative-pressure dressing. Methods: The records of all patients who underwent panniculectomy between 2007 and 2012 were reviewed. Of 14 patients with a body mass index greater than 50, nine underwent primary closure and five were treated with open wound management. A retrospective chart review was performed. Results: There were no statistically significant differences in age or preoperative comorbidities, but body mass index was higher for the open wound management group (66.4 versus 58.9, p = 0.039). There were no statistically significant differences in mean operative time, resection weight, estimated blood loss, or hospital length of stay. The primary closure group had a 44 percent readmission rate and a 33 percent reoperation rate for wound complications. The open wound management group had no wound-related readmissions or secondary procedures for débridement. Conclusions: Open wound management in the massive panniculectomy patient reduces hospital readmission and secondary operations. This case series provides reasons to support the consideration of open wound management following massive panniculectomy in the super morbidly obese patient population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Background: The incidence of obesity is on the rise in the United States and worldwide. Complications following panniculectomy are higher for super obese patients, often requiring readmission and additional interventions. In this study, the authors compare the outcomes of patients who underwent primary closure of their resection wounds to the outcomes of patients who underwent initial open wound management with a negative-pressure dressing.Methods: The records of all patients who underwent panniculectomy between 2007 and 2012 were reviewed. Of 14 patients with a body mass index greater than 50, nine underwent primary closure and five were treated with open wound management. A retrospective chart review was performed.Results: There were no statistically significant differences in age or preoperative comorbidities, but body mass index was higher for the open wound management group (66.4 versus 58.9, p = 0.039). There were no statistically significant differences in mean operative time, resection weight, estimated blood loss, or hospital length of stay. The primary closure group had a 44 percent readmission rate and a 33 percent reoperation rate for wound complications. The open wound management group had no wound-related readmissions or secondary procedures for debridement.Conclusions: Open wound management in the massive panniculectomy patient reduces hospital readmission and secondary operations. This case series provides reasons to support the consideration of open wound management following massive panniculectomy in the super morbidly obese patient population.CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Background: Enophthalmos is a challenging surgical problem to correct. Standard techniques to adjust orbital volume require invasive maneuvers such as osteotomies. Fat injection may provide a simple and less-invasive way of augmenting orbital volume to correct enophthalmos.Methods: The right eye orbital volume of 10 New Zealand White rabbits was augmented with fat. Autologous fat was diced and injected into the retrobulbar space. Computed tomographic scans were evaluated for changes in globe position and retrobulbar volume. Visually evoked potentials were conducted to test the integrity of the optic tract. Rabbits were killed at 12 weeks after surgery. Orbital exenterations were performed to allow for gross and histologic evaluation.Results: Right globe position showed a mean increase in eye proptosis of 3.4 mm at postoperative day 1 and 0.9 mm at 11 weeks postoperatively in comparison with the left globe position. No significant change was noted in the left globe position. Retrobulbar volume demonstrated an initial mean increase of 31 percent and a final mean increase of 9.8 percent at 11 weeks in the right eye compared with the left eye. Visually evoked potentials revealed intact optic pathways in all animals. Gross anatomical evaluation showed deposition of fat grafts. Histologic analysis showed both revascularized and necrotic areas of fat. No retinal or optic nerve damage was identified.Conclusions: Fat injection can augment orbital volume in an animal model and preserve visual function. Further investigation is necessary to document the clinical safety and value of this technique in humans.

AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK

BACKGROUND:This study maps the course of the lesser occipital nerve and its potential compression sites in the posterior scalp.METHODS:Twenty sides of 10 fresh cadaveric heads were dissected. Two fixed anatomical landmarks were used: the y axis was the vertical midline in the posterior scalp through the midline of the cervical spine. The x axis was a horizontal line drawn between the most anterosuperior points of the external auditory meatus. A topographic map of the lesser occipital nerve and its potential compression points was created.RESULTS:The lesser occipital nerve emerged from the posterior border of the sternocleidomastoid muscle at an average of 6.4 ± 1.4 cm lateral to the y axis and 7.5 ± 0.9 cm caudal to the x axis. Branches of the occipital artery were found to interact with the lesser occipital nerve in 11 of the 20 hemiheads (55 percent). The mean location of the artery-nerve interaction was 5.1 ± 0.9 cm lateral to the y axis and 2 ± 1.45 cm caudal to the x axis. Two patterns of artery-nerve interaction were seen: a single site of artery crossing over the nerve in nine of 20 hemiheads (45 percent) and a helical intertwining relationship in two of 20 of hemiheads (10 percent). A fascial band was identified to compress the lesser occipital nerve in four of 20 hemiheads (20 percent).CONCLUSION:This anatomical study traced the lesser occipital nerve as it courses through the posterior scalp and mapped its potential decompression sites.