Surgical Technique for Nasal Cleft Repair.

BACKGROUND: Congenital nasal cleft is a very rare yet challenging deformity to reconstruct. Atypical craniofacial clefts that involve the nasal ala are designated as number 1 and number 2 under the Tessier classification system. These clefts typically present as notches in the medial one-third of either nasal ala and may be accompanied by a malpositioned cartilaginous framework. Nasal clefts are smaller and far less common than familiar clefts of the lip and palate, but they pose equally challenging reconstructive planning. METHODS: Our described technique relies on usage of existing nasal tissue near the cleft. Local tissue rearrangement using a laterally based rotational alar flap, a medially based triangular flap, and a nasal wall advancement flap restores normal anatomy and provides an aesthetically pleasing result. RESULTS: Five children with isolated nasal cleft were treated by the senior author (A.M.) between 2010 and 2017. All patients presented with clefts of the soft tissue with no underlying cartilaginous involvement. There were no postoperative complications. Excellent aesthetic outcome was achieved in all patients. CONCLUSION: Isolated nasal cleft can be properly corrected with the described procedure in a single stage and with optimal result.

Complications of Post-Burn Tissue Expansion Reconstruction: 9 Years Experience with 42 Pediatric and 26 Adult Patients.

BACKGROUND: Burn scar reconstruction is extremely challenging, even for the most proficient reconstructive surgeon. Within the arsenal of tools at the plastic surgeon's disposal, tissue expansion provides an efficient modality for reconstruction despite the reported complication rates. OBJECTIVES: To critically review our experience with tissue expansion for burn scar reconstruction, comparing particularly the adult and pediatric populations. METHODS: We conducted a retrospective study of the outcomes of patients who underwent burn scar reconstruction with tissue expansion at Hadassah Medical Center between January 2003 and July 2012. The data included patient age, anatomical site of expansion, number of procedures, and associated complications. The outcomes of the above-mentioned populations were also compared with those in a control group of patients undergoing reconstruction with tissue expansion for indications other than burn scars. RESULTS: Sixty-seven tissue expansion procedures were carried out in 50 patients, 42 in the pediatric population (< 16 years of age) and 25 in the adult population. Complications were observed in 10 of the 42 pediatric procedures (23.8%) and in 3 of the 25 adult procedures (12%). This difference was found to be statistically significant. When the complication rate for each population was compared to its control group (tissue expansion for indications other than burn scar reconstruction, such as reconstruction for motor vehicle accident scarring, congenital nevi, or vascular malformations), no statistically significant difference was found between them (complication rates 19.8% and 12.5%, respectively). Furthermore, there was no statistically significant difference in complication rates between the different anatomical areas of expansion within both populations undergoing burn scar reconstruction. Most of the complicated cases completed successful reconstruction. CONCLUSIONS: Tissue expansion is a useful surgical tool in post-burn scar reconstruction, both in the adult and pediatric populations and in all anatomic sites, despite consistently high complication rates, especially in the pediatric population. This complication rate is not higher than in patients undergoing tissue expansion for indications other than burn scar reconstruction.

Periorbital reconstruction with the expanded pedicled forehead flap.

BACKGROUND: The complexity of structures within the periorbital region makes reconstruction of this area particularly a challenging endeavor. Within the literature, different techniques have been described for reconstruction of the external lamellae of the upper and lower eyelids as well as the medial and lateral canthal regions.Herein, we present the expanded pedicled forehead flap as a versatile and useful surgical option for reconstruction of various defects around the eye globe. PATIENTS AND METHODS: A tissue expander is inserted underneath the forehead skin and serially expanded. The pedicle of the expanded pedicled flap is designed either from the superior portion of the expanded skin and interpolated to reconstruct the upper and lower eyelids, and the medial or lateral canthal areas; or from the inferior portion of the expanded skin and interpolated over the eyebrow to reconstruct the area between the upper eyelid crease and eyebrow.Fifteen patients with periorbital nevi or severe scarring were treated using the expanded forehead flap between the years 2003 and 2012. Thirteen patients had complex periorbital defects involving multiple anatomic areas, and 2 patients had defects confined to the upper eyelid area only. RESULTS: Operative and postoperative course for 13 patients was uneventful. One patient had a late infection of the tissue expander but nonetheless continued with the reconstructive process. In 1 patient, the tissue expander was removed due to infection, and subsequent reconstruction was not carried out. The aesthetic and functional results of reconstruction were very good, and with excellent skin color and thickness match. In 1 patient, the flap was defattened in an ancillary procedure. No partial or complete flap loss was observed in this study. SUMMARY: We conclude that the expanded pedicled forehead flap is a safe and reliable method for reconstruction of different segments of the periorbital region, while providing good aesthetic and functional reconstructive results with minimal donor-site morbidity.

The role of free tissue transfer in posterior neck reconstruction.

Reconstruction of the posterior neck is one of the rarer procedures performed by plastic surgeons; we used free flaps for the closure of defects in this area in six cases over the past 4 years. Six patients were located requiring posterior neck reconstruction between the years 2007 and 2013. Five of these patients required reconstruction due to oncologic resections, while one underwent serial removal of a giant congenital nevus. Five of these reconstructions involved the use of a free anterolateral thigh/vastus lateralis flap, and the sixth received a pre-expanded deep inferior epigastric perforator flap. Satisfactory dorsal neck reconstruction was achieved with the free flap approach: it produced excellent healing, contour and coverage of hardware. There was only one early minor complication, allowing early return to daily activities and continuation of planned oncologic treatment. Free flap reconstruction of the posterior neck area is a safe and relatively rapidly performed procedure that yields good results both functionally and aesthetically. In this article, we review the literature on the options available for reconstruction of the posterior neck, describe our surgical experience in such cases, and suggest an algorithm to guide in choosing the optimal approach for a given patient.

Changes of PI3K/AKT/BCL2 signaling proteins in congenital Giant Nevi: melanocytes contribute to their increased survival and integrity.

Congenital Giant Nevi (CGN) are rare melanocytic lesions with the potential to regress into malignant melanoma. Simultaneous up-regulation and cooperative interactions of signaling pathways are crucial events in the pathogenesis of melanocytes. Our study aimed to identify changes in the expression and activation of proteins controlling survival and/or apoptosis of the key signaling pathways PI3K/AKT/BCL2 and Wnt/ß-catenin of CGN melanocytes. We applied a model of cultured melanocytes from paired CGN and normal appearing skin, and Western blot (WB) analyzed the expression and activation profile of survival and anti-apoptotic proteins of these signaling pathways, growth pattern, cell cycle and apoptosis. WB analysis demonstrated a significant higher expression level of activated AKT and of BCL2 proteins in the CGN melanocytes compared with paired melanocytes from normal appearing skin. A relative increase in the level of GSK3 and FOXO1 proteins, down stream targets of AKT, as well as of pß-catenin was also detected in the CGN melanocytes compared with the controls. These changes were not affected by growth of the CGN melanocytes in reduced serum (starvation). Both cell populations shared a similar growth pattern, with no significant differences in the proportion of apoptotic cells and in cell cycle fractions. These data demonstrate for the first time, changes in signaling proteins of cultured CGN melanocytes. Further, suggesting that the changes in AKT/BCL2 signaling molecules might mediate growth and anti-apoptosis processes at least in part, thus increasing the survival potential of CGN melanocytes and maintaining their integrity.

Dorsal augmentation with diced cartilage enclosed with temporal fascia in secondary endonasal rhinoplasty.

BACKGROUND: Placement of diced cartilage enclosed within an autologous fascia sleeve (DC-F) for nasal dorsum reconstruction is common in open rhinoplasty, but there are no data regarding its use in closed rhinoplasty (the endonasal approach). OBJECTIVES: The authors describe a technique for augmenting the nasal dorsum in secondary rhinoplasty with DC-F grafts via an endonasal approach. METHODS: In this study, the authors retrospectively review the cases of 18 patients who underwent closed rhinoplasty with the authors' technique between 2008 and 2011. Cartilage harvested from the septum, rib, or concha was diced into 0.5- to 1-mm cubes. A rectangle of deep temporal fascia (approximately 5 × 5 cm) was harvested by means of a single V-shaped incision overlying the temporal fossa, then wrapped around another 1-mL syringe and secured. The fascial cylinder was filled with the desired amount of diced cartilage and then sutured closed at both ends. This graft was placed into the dorsum of the nose via the endonasal approach. RESULTS: Average age of the patients was 32 years. The patients were followed for a minimum of 15 months. Donor site for cartilage harvest was conchal in 8 patients, septal and conchal in 6 cases, and costal in 4. Complications were encountered in 3 patients, only 1 of whom required surgical revision for contour irregularity. No resorption of cartilage was encountered in any patient after 15 months. Smooth continuity of the nasal dorsum was achieved in all our patients. CONCLUSIONS: Despite the lack of a large volume of patients for overwhelming and conclusive results, our study provides further confirmation that this technique is indeed an attractive option for nasal dorsum reconstruction.

Surgical Management of Hidradenitis Suppurativa: Factors Associated with Postoperative Complications and Disease Recurrence.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder. Treatment of HS remains challenging, and surgical procedures commonly follow attempts of conservative therapy. To date, a consensus regarding the optimal surgical technique has not been reached, and the implications of conservative therapy on future surgical outcomes have yet to be studied. Methods: A retrospective cohort study of 65 patients surgically treated for HS at a tertiary care center was conducted. Patients' medical records were screened for demographical, clinical, and surgical characteristics. Statistical analysis was conducted to determine associations with postoperative complications and disease recurrence. Results: Fifty patients (75.8%) were treated with systemic antibiotics before opting for surgical resection. Previous treatment with systemic rifampicin was associated with higher rates of postoperative complications (P = 0.029); however, systemic cephalexin and topical clindamycin were associated with a lower rate of complications (P = 0.007 and 0.040, accordingly). Medical history of smoking and surgical management with split-thickness skin grafts were associated with higher rates of postoperative complications (P = 0.012 and 0.014, accordingly). Patients with a greater number of lesions, and those treated with split-thickness skin graft, had higher rates of disease recurrence (P = 0.0018 and 0.003, accordingly).In a multivariate analysis a greater number of lesions (P = 0.0498) and the use of autologous split-thickness skin graft (P = 0.022) were independently associated with higher rates of disease recurrence. Conclusions: Previous conservative medical therapy bears the potential to modulate postoperative outcomes in HS patients, and should be taken into consideration. Despite reports of reliable results with split-thickness skin grafts, we found them to be associated with increased rates of diseases recurrence and postoperative complications.

Imaging of patients after the Lap-Band System application.

OBJECTIVE: We describe the use of imaging in the management of adjustable gastric-banding patients, and describe complications of banding that are diagnosed by imaging. MATERIALS & METHODS: Using a four-year period as an example of complications of this type of laparoscopic approach, we have retrospectively identified all patients with laparoscopic bands who were imaged in the radiology department at our large multispecialty hospital. Included are patients who had their bands placed by the hospital's surgeons as well as patients referred for consultation from other practices. RESULTS: Twenty-two of 165 patients who had banding as their sole weight loss surgery had 23 complications diagnosed by imaging. Complications included band slip (3), device issues (4), esophageal dilation (8), esophageal dysmotility (5), symptomatic gallstones (2) and a gastroesphageal diverticulum (1). Complications were detected by fluoroscopy (17), CT (4) or ultrasound (2). 17 patients had banding as one of multiple bariatric surgeries, with 13 complications: band slip (4), port infection (1), esophageal dilation (1), esophageal dysmotility (5), anastomotic leak (1) and internal hernia (2). Complications were detected with fluoroscopy (12) and CT (1). CONCLUSIONS: Fluoroscopy is generally the primary imaging modality used to diagnose complications of gastric banding. Esophageal dilation and dysmotility, which appear to be long-term sequelae of banding, were the most common complications identified by imaging.

Mast cell-dependent contraction of human airway smooth muscle cell-containing collagen gels: influence of cytokines, matrix metalloproteases, and serine proteases.

In asthma, mast cells infiltrate the airway smooth muscle cell layer and secrete proinflammatory and profibrotic agents that contribute to airway remodeling. To study the effects of mast cell activation on smooth muscle cell-dependent matrix contraction, we developed coculture systems of human airway smooth muscle cells (HASM) with primary human mast cells derived from circulating progenitors or with the HMC-1 human mast cell line. Activation of primary human mast cells by IgE receptor cross-linking or activation of HMC-1 cells with C5a stimulated contraction of HASM-embedded collagen gels. Contractile activity could be transferred with conditioned medium from activated mast cells, implicating involvement of soluble factors. Cytokines and proteases are among the agents released by activated mast cells that may promote a contractile response. Both IL-13 and IL-6 enhanced contraction in this model and the activity of IL-13 was ablated under conditions leading to expression of the inhibitory receptor IL-13Ralpha2 on HASM. In addition to cytokines, matrix metalloproteinases (MMPs), and serine proteases induced matrix contraction. Inhibitor studies suggested that, although IL-13 could contribute to contraction driven by mast cell activation, MMPs were critical mediators of the response. Both MMP-1 and MMP-2 were strongly expressed in this system. Serine proteases also contributed to contraction induced by mast cell-activating agents and IL-13, most likely by mediating the proteolytic activation of MMPs. Hypercontractility is a hallmark of smooth muscle cells in the asthmatic lung. Our findings define novel mechanisms whereby mast cells may modulate HASM-driven contractile responses.

IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation.

OBJECTIVE: Mast cell and basophil activation contributes to inflammation, bronchoconstriction, and airway hyperresponsiveness in asthma. Because IL-33 expression is inflammation inducible, we investigated IL-33-mediated effects in concert with both IgE-mediated and IgE-independent stimulation. METHODS: Because the HMC-1 mast cell line can be activated by GPCR and RTK signaling, we studied the effects of IL-33 on these pathways. The IL-33- and SCF-stimulated HMC-1 cells were co-cultured with human lung fibroblasts and airway smooth muscle cells in a collagen gel contraction assay. IL-33 effects on IgE-mediated activation were studied in primary mast cells and basophils. RESULT: IL-33 synergized with adenosine, C5a, SCF, and NGF receptor activation. IL-33-stimulated and SCF-stimulated HMC-1 cells demonstrated enhanced collagen gel contraction when cultured with fibroblasts or smooth muscle cells. IL-33 also synergized with IgE receptor activation of primary human mast cells and basophils. CONCLUSION: IL-33 amplifies inflammation in both IgE-independent and IgE-dependent responses.

Feasibility of ex vivo FDG PET of the colon.

To facilitate future direct correlations between fluorine 18 fluorodeoxyglucose (FDG)-avid colonic lesions and immunohistochemical assay findings, the authors tested the feasibility of ex vivo FDG positron emission tomography (PET) of the colon resected from humans. In this institutional review board-approved, HIPAA-compliant study, the authors, after obtaining informed patient consent, injected FDG intraoperatively in five patients with neoplasms and imaged their resected colons approximately 3 hours later. The colon could be imaged during this fairly limited time interval, and polyps and cancers could be identified. No biologic tissue degradation occurred. The authors concluded that ex vivo FDG PET of the colon is feasible and, when combined with careful histologic and immunohistochemical analyses, may serve as a research tool to determine the mechanisms of the normal colonic uptake of FDG and the localization of FDG in polyps and cancers.

Pediatric tissue expansion: our experience with 103 expanded flap reconstructive procedures in 41 children.

BACKGROUND: Tissue expansion is a well-recognized technique for reconstructing a wide variety of skin and soft tissue defects. Its application in the pediatric population has enabled the plastic surgeon to achieve functional and aesthetic goals that were previously unobtainable. OBJECTIVES: To review the use of tissue expansion in the pediatric population, with particular emphasis on indication, operative technique, regional considerations and how to avoid complications. METHODS: We retrospectively reviewed data on 103 expanded flap reconstructions performed in 41 pediatric patients during the period 2003-2006. Tissue expanders were placed on a subcutaneous plane above the fascia and inflated weekly. The expanded skin was used as a transposition flap or a full thickness skin graft for the reconstruction of the involved area. Forty-three tissue expanders were inserted to the head and neck in 21 patients, 45 were inserted to the trunk in 13 patients and 15 were inserted to the groin and lower extremity in 8 patients. Twenty-eight patients had one round of tissue expansion, while 13 patients had two to six rounds. A plastic surgeon, medical student and a lawyer reviewed the patients' photographs and evaluated their aesthetic outcome: RESULTS: Eighty-six percent of the head and neck reconstructions and 40% of the trunk and extremity reconstructions were graded as having excellent aesthetic outcome, and 11% of the head and neck reconstructions and 37% of the trunk and extremity reconstructions were graded with good aesthetic outcome. The remaining patients were graded with moderate outcome. None of our patients was graded as poor aesthetic outcome. Complications included infection in 6 patients (6%), extrusion in 3 (3%), hematoma in 2 (2%), flap ischemia in one patient (1%), and expander perforation after percutaneous stabbing in one patient (1%). CONCLUSIONS: Tissue expansion is an efficient and valuable technique for reconstruction of large skin lesions and scars.

The GI fluoroscopy suite in the early twenty-first century.

Since the application of cross-sectional imaging to the examination of the gastrointestinal tract, dramatic changes have occurred in the modern gastrointestinal fluoroscopic suite. Besides the great decrease in use of fluoroscopy, the types of fluoroscopic examinations requested and performed nowadays are different from those of just 2 or 3 decades ago. This paper will review the recent history and the current uses of fluoroscopy in adults at the beginning of the twenty-first century, illustrated by case images and utilization data from a large academic medical center. Fluoroscopy survives because of its unique illustration of motility in real-time, its superior detection and accurate localization of leaks in post-operative patients, and its ability to provide immediate answers and targeted examinations tailored to the individual patient.

High-throughput determination of mode of inhibition in lead identification and optimization.

After finishing the primary high-throughput screening, the screening team is often faced with thousands of hits to be evaluated further. Effective filtering of these hits is crucial in identifying leads. Mode of inhibition (MOI) study is extremely useful in validating whether the observed compound activity is specific to the biological target. In this article, the authors describe a high-throughput MOI determination method for evaluating thousands of compounds using an existing screening infrastructure. Based on enzyme or receptor kinetics theory, the authors developed the method by measuring the ratio of IC(50) or percent inhibition at 2 carefully chosen substrate or ligand concentrations to define an inhibitor as competitive, uncompetitive, or noncompetitive. This not only facilitates binning of HTS hits according to their MOI but also greatly expands HTS utility in support of the medicinal chemistry team's lead optimization practice. Three case studies are presented to demonstrate how the method was applied successfully in 3 discovery programs targeting either an enzyme or a G-protein-coupled receptor.

Combined CT colonography and 18F-FDG PET of colon polyps: potential technique for selective detection of cancer and precancerous lesions.

OBJECTIVE: The purpose of this study was to determine the feasibility of imaging the colon with fused CT colonography (CTC) and 18F-FDG PET and to correlate the findings with the histologic features of polyps. SUBJECTS AND METHODS: Eighteen patients with suspected colorectal polyps enrolled in this prospective study. Before colonoscopy, 17 of the patients underwent a combination of FDG PET and CTC. CTC consisted of 4-MDCT merged with PET. PET of the abdomen and pelvis was performed after each CTC scan. One radiologist and one nuclear medicine physician in consensus analyzed PET and CTC fusion data. PET standard uptake value was correlated with the findings at histologic examination of polyps. Patient feasibility was defined as the ability to tolerate prolonged scanning with good colonic distention. Technical feasibility was determined by how closely anatomically matched polyps overlapped on fusion images. RESULTS: Seventeen of 18 patients tolerated scanning. Eighty-five percent of colon segments were optimally distended. Twenty-three of 27 FDG-avid polyps measuring 10 mm or more had excellent overlap at fusion imaging. PET depicted 23 of 39 premalignant polyps and even showed increased tracer activity associated with four small tubular adenomas (4-6 mm). Sixteen benign polyps (10-25 mm) were not depicted on PET. All nine cases of cancer (tumors measuring 11-60 mm) were detected with both PET and CTC. The standard uptake value of malignant tumors ranged from 4 to 20 (mean, 9). However, six benign flat polyps did not exhibit FDG avidity. CONCLUSION: The novel combination of CTC and PET was feasible in 17 of 18 patients and allowed excellent image correlation in 23 of 27 proven polyps measuring 10 mm or more on PET-CTC fusion. This technique shows promise in accurate anatomic correlation of both malignant and premalignant lesions evaluated with FDG PET.

E-cadherin suppression accelerates squamous cell carcinoma progression in three-dimensional, human tissue constructs.

We studied the link between loss of E-cadherin-mediated adhesion and acquisition of malignant properties in three-dimensional, human tissue constructs that mimicked the initial stages of squamous cell cancer progression. Suppression of E-cadherin expression in early-stage, skin-derived tumor cells (HaCaT-II-4) was induced by cytoplasmic sequestration of beta-catenin upon stable expression of a dominant-negative E-cadherin fusion protein (H-2Kd-Ecad). In monolayer cultures, expression of H-2Kd-Ecad resulted in decreased levels of E-cadherin, redistribution of beta-catenin to the cytoplasm, and complete loss of intercellular adhesion when compared with control II-4 cells. This was accompanied by a 7-fold decrease in beta-catenin-mediated transcription and a 12-fold increase in cell migration. In three-dimensional constructs, E-cadherin-deficient tissues showed disruption of architecture, loss of adherens junctional proteins from cell contacts, and focal tumor cell invasion. Invasion was linked to activation of matrix metalloproteinase (MMP)-mediated degradation of basement membrane in H-2Kd-Ecad-expressing tissue constructs that was blocked by MMP inhibition (GM6001). Quantitative reverse transcription-PCR showed a 2.5-fold increase in MMP-2 and an 8-fold increase in MMP-9 in cells expressing the H-2Kd-Ecad fusion protein when compared with controls, and gel zymography showed increased MMP protein levels. Following surface transplantation of three-dimensional tissues, suppression of E-cadherin expression greatly accelerated tumorigenesis in vivo by inducing a switch to high-grade carcinomas that resulted in a 5-fold increase in tumor size after 4 weeks. Suppression of E-cadherin expression and loss of its function fundamentally modified squamous cell carcinoma progression by activating a highly invasive, aggressive tumor phenotype, whereas maintenance of E-cadherin prevented invasion in vitro and limited tumor progression in vivo.