Detailed Management of Brachial Plexus Birth Injuries: The Miami Protocol at Nicklaus Children's Hospital.

The management of children with brachial plexus birth injuries is complex and requires a multidisciplinary approach. In the following article, we describe our approach to evaluation and management at Nicklaus Children's Hospital. It is our aim is to elucidate nuances in management.

Pediatric hand ultrasound: common indications, injury, inflammation and masses.

Ultrasound is a uniquely valuable tool for evaluating musculoskeletal problems in the pediatric hand. Acute and chronic injuries involving tendons and ligaments of the hand can be quickly assessed and can guide surgical decision-making. Using ultrasound, palpable lesions and masses can be evaluated for cystic and solid components aiding in differential diagnosis. Additionally, ultrasound provides evaluation of acute versus chronic changes of inflammatory arthritis, assessing disease severity and subclinical synovitis and serving as an adjunct to medical management. This review will cover common indications and ultrasound findings of the pediatric hand, focusing on common injuries, inflammatory arthritis and masses. Important anatomical features of the hand will be discussed as well as imaging technique and evaluation in the pediatric patient.

Direct Repair of the Lower Trunk to Residual Nerve Roots for Restoration of Finger Flexion After Total Brachial Plexus Injury.

PURPOSE: Residual nerve root stumps have been used to neurotize the median nerve in an attempt to restore finger flexion function in patients suffering from total brachial plexus injury. However, the results have been unsatisfactory mainly because of the need to use a long nerve graft. The authors have tried to improve the quality of restored finger flexion by direct approximation of available (ruptured) ipsilateral root stumps to the lower trunk (LT). We sought to validate these results using objective outcome measures. METHODS: This is a study of 27 cases of total posttraumatic brachial plexus palsies. In each case, the neck was explored and ruptured root stumps identified. The LT was mobilized by separating it from the posterior division and the medial cutaneous nerve of the forearm distally. The mobilized LT was then approximated directly to an ipsilateral root stump. The arm was immobilized against the trunk for 2 months. The patients were observed for return of function in the paralyzed upper limb. The presence and strength of finger flexion was measured using the British Medical Council grading. RESULTS: The follow-up period was 36 to 74 months (average, 56.9 ± 13.7 months). Recovery of active finger flexion was M4 in 10 patients, M3 in 8 patients, and M2 to M0 in 9 patients. Meaningful recovery (M3 or greater) of finger flexion was achieved in 18 of 27 patients. CONCLUSIONS: The results of active finger flexion can be improved by direct approximation of the LT to an ipsilateral root stump. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Aberrant lymphatic drainage and risk for melanoma recurrence after negative sentinel node biopsy in middle-aged and older men.

BACKGROUND: Aberrant lymphatic drainage is believed to contribute to the high recurrence rate of head and neck melanomas. The purpose of this study was to identify the clinical significance of unexpected lymphatic drainage patterns. METHODS: A single institution retrospective analysis was performed of middle-aged and older men (mean age, 66.2 years; range, 41-87 years) who underwent successful lymphoscintigraphy with sentinel lymph node biopsy (SLNB) from 1997 through 2012. Node status, distribution, and recurrence were assessed comparing patients with expected and unexpected drainage patterns. RESULTS: Sixty-six patients were identified with 55.8 months median follow-up (range, 5.6-206.1 months). Unexpected sentinel lymph node drainage was associated with multiple basin drainage (p < .01) and greater recurrence after negative SLNB (p = .03). Both groups had similar anatomic distribution, sentinel lymph node sampling, histopathologic characteristics, follow-up, and survival. CONCLUSION: Lymphatic drainage differing from expected patterns is associated with greater recurrence after negative SLNB in middle-aged and older men. © 2015 Wiley Periodicals, Inc. Head Neck 38: E754-E760, 2016.

Management of osteoarthrosis of the thumb joints.

We present current concepts and evidence to optimize diagnosis and management of osteoarthritis in the thumb joints. Numerous options and controversies exist for surgical treatment of carpometacarpal joint arthritis. Fewer options exist for metacarpophalangeal joint arthritis. Surgical treatment for interphalangeal arthritis is mainly arthrodesis.

Correlation of clinical disease severity to radiographic thumb osteoarthritis index.

PURPOSE: To determine if a slight modification of the 1987 Eaton-Glickel staging and interpreting 4 standardized radiographs for trapeziometacarpal (TMC) osteoarthritis (OA) improved analysis, to determine if a quantifiable index measurement from a single Robert (pronated anteroposterior) view enhanced reproducibility, and to examine whether improved radiographic staging correlated to clinically relevant disease and thus support validity. METHODS: We analyzed 4 thumb radiographs (posteroanterior, lateral, Robert, and stress views) in 60 consecutive subjects representing an adult population spectrum of asymptomatic to advanced disease. Two experienced hand surgeons (A.L.L. and A.P.C.W.), 1 chief resident (A.J.B.), and 1 medical student (J.M.M.) performed the analysis on each subject's radiographs. We analyzed all 4 radiographs for Eaton and modified Eaton staging and then later analyzed only the Robert view for the thumb osteoarthritis (ThOA) index measurement. The radiographs were randomized and reread a week later for each classification at separate times. Surgically excised trapeziums from 20/60 subjects were inspected for first metacarpal surface disease and correlated to the 3 classifications. RESULTS: All 3 staging classifications demonstrated high reproducibility, with the intraclass correlation coefficient averaging 0.73 for the Eaton, 0.83 for the modified Eaton, and 0.95 for the ThOA index. Articular wear and metacarpal surface eburnation correlated highest to the ThOA index, with advanced disease 1.55 or greater correlating to Eaton III/IV and modified Eaton stage 3/4 in a linear relationship. CONCLUSIONS: The ThOA index based on a Robert view provided a measurable alternative to Eaton staging and correlated to severity of surgically relevant thumb TMC OA. CLINICAL RELEVANCE: A simple reproducible radiographic measurement may enhance TMC OA classification and provide a reliable means to predict clinical disease. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Chronic cutaneous chest wall fistula and gallstone empyema due to retained gallstones.

We report a case of a 72-year-old man who presented with a persistent pleural effusion and painful abscess in the right lower chest wall 6 months following a laparoscopic cholecystectomy. The patient subsequently developed a chronic cutaneous chest wall fistula requiring a large resection and complex closure. The complication was likely secondary to intraoperative spillage of gallstones. While previous reports describe gallstone spillage in the abdominal cavity as benign, this case illustrates that stones left in the abdominal cavity can potentially lead to significant morbidity. Therefore, stones should be diligently removed from the abdominal cavity when spillage occurs. In addition, it is important that operative notes reflect the occurrence of stone spillage so stones may be suspected when a patient presents with an abdominal or thoracic infection following a cholecystectomy.

Intra- and interobserver reliability of the Eaton classification for trapeziometacarpal arthritis: a systematic review.

BACKGROUND: Trapeziometacarpal, or thumb carpometacarpal (CMC), arthritis is a common problem with a variety of treatment options. Although widely used, the Eaton radiographic staging system for CMC arthritis is of questionable clinical utility, as disease severity does not predictably correlate with symptoms or treatment recommendations. A possible reason for this is that the classification itself may not be reliable, but the literature on this has not, to our knowledge, been systematically reviewed. QUESTIONS/PURPOSES: We therefore performed a systematic review to determine the intra- and interobserver reliability of the Eaton staging system. METHODS: We systematically reviewed English-language studies published between 1973 and 2013 to assess the degree of intra- and interobserver reliability of the Eaton classification for determining the stage of trapeziometacarpal joint arthritis and pantrapezial arthritis based on plain radiographic imaging. Search engines included: PubMed, Scopus(®), and CINAHL. Four studies, which included a total of 163 patients, met our inclusion criteria and were evaluated. The level of evidence of the studies included in this analysis was determined using the Oxford Centre for Evidence Based Medicine Levels of Evidence Classification by two independent observers. RESULTS: A limited number of studies have been performed to assess intra- and interobserver reliability of the Eaton classification system. The four studies included were determined to be Level 3b. These studies collectively indicate that the Eaton classification demonstrates poor to fair interobserver reliability (kappa values: 0.11-0.56) and fair to moderate intraobserver reliability (kappa values: 0.54-0.657). CONCLUSIONS: Review of the literature demonstrates that radiographs assist in the assessment of CMC joint disease, but there is not a reliable system for classification of disease severity. Currently, diagnosis and treatment of thumb CMC arthritis are based on the surgeon's qualitative assessment combining history, physical examination, and radiographic evaluation. Inconsistent agreement using the current common radiographic classification system suggests a need for better radiographic tools to quantify disease severity.

Development of an affordable system for personalized video-documented surgical skill analysis for surgical residency training.

Surgical competency requires the development of decision-making and technical skills. Despite lectures, literature, and written and oral examinations, both skill sets are difficult to systematically teach and analyze. With the advent of head-mounted video cameras, we seek to incorporate a surgical video database into our surgical training curriculum. We hope to not only change the way and rate at which surgical trainees develop their surgical skills but to also introduce a novel tool for surgical skill assessment.

Histologic analysis of fetal bovine derived acellular dermal matrix in tissue expander breast reconstruction.

BACKGROUND: This study seeks to determine human host response to fetal bovine acellular dermal matrix (ADM) in staged implant-based breast reconstruction. METHODS: A prospective study was performed for patients undergoing immediate breast reconstruction with tissue expander placement and SurgiMend acellular fetal bovine dermis. At the time of exchange for permanent implant, we obtained tissue specimens of SurgiMend and native capsule. Histological and immunohistochemical assays were performed to characterize the extent of ADM incorporation/degradation, host cell infiltration, neovascularization, inflammation, and host replacement of acellular fetal bovine collagen. RESULTS: Seventeen capsules from 12 patients were included in our study. The average "implantation" time of SurgiMend was 7.8 months (range, 2-23 months). Histological analysis of the biopsy of tissue revealed rare infiltration of host inflammatory cells, even at 23 months. One patient had an infection requiring removal of the tissue expander at 2 months. Contracture, inflammatory changes, edema, and polymorphonuclear leukocyte infiltration were rare in the ADM. An acellular capsule was seen in many cases, at the interface of SurgiMend with the tissue expander. CONCLUSIONS: SurgiMend demonstrated a very infrequent inflammatory response. An antibody specific to bovine collagen allowed for direct identification of bovine collagen separate from human collagen. Cellular infiltration and neovascularization of SurgiMend correlated with the quality of the mastectomy skin flap rather than the duration of implantation. Future studies are needed to further characterize the molecular mechanisms underlying tissue incorporation of this product.

Growth and development of the orbit.

Every surgeon operating on the face, and particularly around the eye, should possess a working knowledge of the critical details related to development of the human orbit and recognized changes that occur during the course of aging. The anatomy of the orbit and periorbital region is complex, and the diagnosis and treatment of patients with orbital/periorbital disease requires expertise in congenital differences and awareness of the changes that occur as individuals age.

Malignant ameloblastoma: concurrent presentation of primary and distant disease and review of the literature.

Malignant ameloblastoma is a rare tumor of odontogenic origin with a metastatic focus. Distant metastatic disease is found most commonly in the lungs. A review of the literature shows that most cases of malignant ameloblastoma involve a disease-free period from primary tumor extirpation to the discovery of metastasis. This report describes the case of a 56-year-old man presenting with ameloblastoma of the maxilla and a solitary pulmonary metastasis concurrently. This represents a rare case in which there is a simultaneous diagnosis of primary ameloblastoma and a metastatic lesion. Appropriate workup for ameloblastoma includes surveillance for metastatic disease. Surgical resection of primary and distant disease is recommended. Chemotherapy and radiation may play a role in palliation when resection of metastatic disease is not feasible.

Melanoma prognostic model using tissue microarrays and genetic algorithms.

PURPOSE: As a result of the questionable risk-to-benefit ratio of adjuvant therapies, stage II melanoma is currently managed by observation because available clinicopathologic parameters cannot identify the 20% to 60% of such patients likely to develop metastatic disease. Here, we propose a multimarker molecular prognostic assay that can help triage patients at increased risk of recurrence. METHODS: Protein expression for 38 candidates relevant to melanoma oncogenesis was evaluated using the automated quantitative analysis (AQUA) method for immunofluorescence-based immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a cohort of 192 primary melanomas collected during 1959 to 1994. The prognostic assay was built using a genetic algorithm and validated on an independent cohort of 246 serial primary melanomas collected from 1997 to 2004. RESULTS: Multiple iterations of the genetic algorithm yielded a consistent five-marker solution. A favorable prognosis was predicted by ATF2 ln(non-nuclear/nuclear AQUA score ratio) of more than -0.052, p21(WAF1) nuclear compartment AQUA score of more than 12.98, p16(INK4A) ln(non-nuclear/nuclear AQUA score ratio) of < or = -0.083, beta-catenin total AQUA score of more than 38.68, and fibronectin total AQUA score of < or = 57.93. Primary tumors that met at least four of these five conditions were considered a low-risk group, and those that met three or fewer conditions formed a high-risk group (log-rank P < .0001). Multivariable proportional hazards analysis adjusting for clinicopathologic parameters shows that the high-risk group has significantly reduced survival on both the discovery (hazard ratio = 2.84; 95% CI, 1.46 to 5.49; P = .002) and validation (hazard ratio = 2.72; 95% CI, 1.12 to 6.58; P = .027) cohorts. CONCLUSION: This multimarker prognostic assay, an independent determinant of melanoma survival, might be beneficial in improving the selection of stage II patients for adjuvant therapy.

Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model.

This study demonstrates that in malignant melanoma, elevated levels of nuclear beta-catenin in both primary tumors and metastases correlate with reduced expression of a marker of proliferation and with improved survival, in contrast to colorectal cancer. The reduction in proliferation observed in vivo is recapitulated in B16 murine melanoma cells and in human melanoma cell lines cultured in vitro with either WNT3A or small-molecule activators of beta-catenin signaling. Consistent with these results, B16 melanoma cells expressing WNT3A also exhibit decreased tumor size and decreased metastasis when implanted into mice. Genome-wide transcriptional profiling reveals that WNT3A up-regulates genes implicated in melanocyte differentiation, several of which are down-regulated with melanoma progression. These findings suggest that WNT3A can mediate transcriptional changes in melanoma cells in a manner reminiscent of the known role of Wnt/beta-catenin signaling in normal melanocyte development, thereby altering melanoma cell fate to one that may be less proliferative and potentially less aggressive. Our results may explain the observed loss of nuclear beta-catenin with melanoma progression in human tumors, which could reflect a dysregulation of cellular differentiation through a loss of homeostatic Wnt/beta-catenin signaling.

Prognostic significance of cadherin-based adhesion molecules in cutaneous malignant melanoma.

BACKGROUND: The need for novel molecular prognostic markers that can supplement validated clinicopathologic correlates for cutaneous malignant melanoma is well recognized. Proteins that mediate the epithelial-mesenchymal transition, the process by which a cancer cell disengages from its parent tumor, are important candidates. METHODS: The prognostic relevance of E-cadherin, N-cadherin, and P-cadherin, calcium-dependent transmembrane glycoproteins that regulate cell-cell adhesion, and their adaptors, alpha-catenin, beta-catenin, and p120-catenin, was evaluated on a cohort of 201 primary and 274 metastatic melanoma tumors using fluorescence-based immunohistochemical methods and Automated Quantitative Analysis of protein expression on digitally captured photomicrographs. RESULTS: Increasing levels of N-cadherin expression improved overall survival (log-rank = 7.31; P = 0.03) but did not retain significance following adjustment for established clinicopathologic correlates (P = 0.50). Higher levels of E-cadherin approached significance for favorable prognosis on both univariate (P = 0.13) and multivariable (P = 0.10) analyses. Hierarchical clustering of the composite profiles for all six markers identified four unique clusters that yielded differential overall survival (log-rank = 10.54; P = 0.01). Cluster 4, expressing high E-cadherin and N-cadherin levels, possessed the most favorable outcome and cluster 2, featuring low E-cadherin and alpha-catenin but modest N-cadherin, showed least favorable outcomes. Cluster 2 remained significant on multivariable analysis (hazard ratio, 3.29; 95% confidence interval, 1.50-7.19; P = 0.003). CONCLUSIONS: Although none of the cadherin-based adhesion molecules were independently prognostic, multimarker profiles were significant. Similar to epithelial-derived tumors, loss of E-cadherin correlates with poor outcome. In contrast, for neural crest-derived cutaneous malignant melanoma, N-cadherin overexpression can be associated with either a successful epithelial-mesenchymal transition or a favorably differentiated tumor. Additional cadherin profiles are needed to discriminate these distinctive phenotypes.

Lack of extracellular signal-regulated kinase mitogen-activated protein kinase signaling shows a new type of melanoma.

The majority of human melanomas harbor activating mutations of either N-RAS or its downstream effector B-RAF, which cause activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase and the ERK MAPK cascade. The melanoma-relevant effectors of ERK activation, however, are largely unknown. In this work, we show that increased ERK activation correlates strongly with mutational status of N-RAS or B-RAF in 21 melanoma cell lines. Melanoma lines that were wild-type for RAS/RAF showed low levels of ERK activation comparable with primary human melanocytes. Through supervised analysis of RNA expression profiles, we identified 82 genes, including TWIST1, HIF1alpha, and IL-8, which correlated with ERK activation across the panel of cell lines and which decreased with pharmacologic inhibition of ERK activity, suggesting that they are ERK transcriptional targets in melanoma. Additionally, lines lacking mutations of N-RAS and B-RAF were molecularly distinct and characterized by p53 inactivation, reduced ERK activity, and increased expression of epithelial markers. Analysis of primary human melanomas by tissue microarray confirmed a high correlation among expression of these epithelial markers in a heterogeneous sample of 570 primary human tumors, suggesting that a significant frequency of primary melanomas is of this "epithelial-like" subtype. These results show a molecularly distinct melanoma subtype that does not require ERK activation or epithelial-mesenchymal transformation for progression.

Immunohistochemistry and quantitative analysis of protein expression.

CONTEXT: Immunohistochemistry has taken a central role in the field of pathology, and its role is destined to increase as companion diagnostics analogous to the HercepTest are required for new targeted therapeutics. However, the inherent subjectivity of the assessment of an objective value (the in situ protein concentration) suggests that new technologies to measure the protein concentration may be required to achieve the accuracy required for companion diagnostics. OBJECTIVE: This article discusses the state of immunohistochemistry and reviews the currently available devices for quantitative in situ assessment of protein expression. DATA SOURCES: Data for this work were collected from the published literature, the Internet, and from information provided by device vendors. CONCLUSIONS: Although there is a long history of efforts to quantify immunohistochemistry, there has been a lack of broad acceptance because the resultant objective accuracy has not significantly improved outcome measures compared with the traditional, conventional analysis by eye. As the demand grows for companion diagnostics with complex assessment requirements, we are likely to see increased usage of quantitative platforms, especially those with the capacity to do multiplexed analysis. This most likely will be driven by a requirement for outcomes that cannot be achieved by traditional methods.

Expression of tumor necrosis factor--related apoptosis-inducing ligand receptors 1 and 2 in melanoma.

PURPOSE: The proapoptotic receptors tumor necrosis factor--related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and TRAIL-R2 are targets of drugs in clinical development, and receptor expression levels may be important determinants of sensitivity to receptor agonists. We assessed TRAIL-R1 and TRAIL-R2 expression patterns in a large cohort of melanomas and benign nevi. EXPERIMENTAL DESIGN: We analyzed tissue microarrays containing 546 melanomas and 540 nevi using our automated quantitative method to measure protein levels in situ (AQUA). The system uses S100 to define pixels as melanoma (tumor mask) within the array spot and measures intensity of TRAIL-receptor expression using Cy5-conjugated antibodies within the mask. AQUA scores were correlated with clinical and pathologic variables. RESULTS: TRAIL-R1 and TRAIL-R2 expression was higher in melanomas than in nevi (P < 0.0001), and higher in primary than in metastatic specimens (P = 0.0031 and P < 0.0001, respectively). TRAIL-R1 and TRAIL-R2 expression exceeding the 95th percentile for nevi was found in 19% and 74% of melanoma specimens, respectively. Although on univariate analysis, high TRAIL-R2 expression correlated with increased survival (P = 0.0439), it was not associated with survival within the primary or metastatic subcohorts. TRAIL-R1 expression was not associated with survival. CONCLUSIONS: TRAIL-R1 and TRAIL-R2 expression is higher in malignant melanocytes than in their benign counterparts, suggesting that these receptors might be effective therapeutic targets in melanoma. Expression is higher in early-stage disease than in metastatic specimens, and expression exceeding that found in nevi is found in a substantially larger fraction of melanomas for TRAIL-R2 compared with TRAIL-R1. Assessment of baseline tumor TRAIL receptor expression may be important in analysis of clinical trials involving TRAIL receptor agonists.