Treatment Options for Distal Radioulnar Joint Arthritis: Balancing Functional Demand and Bony Resection.

The distal radioulnar joint is a complex anatomic structure that allows for a combination of rotation and translation with extrinsic and intrinsic stabilizers that maintain stability through a delicate equilibrium. Traumatic, congenital, inflammatory, and degenerative processes can disturb this sensitive balance, resulting in distal radioulnar joint arthritis. We discuss the joint's anatomy and biomechanics and the clinical approach to the patient. We review the surgical treatment options, expected outcomes, and their shortcomings. Selecting the best surgical intervention often means choosing the procedure with the set of complications and limitations best suited for the specific patient.

Paraoxonase 2 overexpression inhibits tumor development in a mouse model of ovarian cancer.

Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue. Using a mouse xenograft model of OC, we demonstrate that overexpression of PON2 prevents tumor formation. Mechanistically, PON2 decreases OC cell proliferation by inhibiting insulin like growth factor-1 (IGF-1) expression and signaling. Intriguingly, PON2 reduces c-Jun-mediated transcriptional activation of IGF-1 gene by decreasing mitochondrial superoxide generation. In addition, PON2 impairs insulin like growth factor-1 receptor (IGF-1R) signaling in OC cells by altering cholesterol homeostasis, which resulted in reduced caveolin-1/IGF-1R interaction and IGF-1R phosphorylation. Taken together, we report for the first time that PON2 acts as a tumor suppressor in the early stage of OC by reducing IGF-1 production and its signaling, indicating PON2 activation might be a fruitful strategy to inhibit early stage ovarian tumor.

Intraoperative Techniques for the Plastic Surgeon to Improve Pain Control in Breast Surgery.

In recent years, there has been a growing emphasis placed on reducing length of hospital stay and health costs associated with breast surgery. Adequate pain control is an essential component of enhanced recovery after surgery. Postoperative pain management strategies include use of narcotic analgesia, non-narcotic analgesia, and local anesthetics. However, these forms of pain control have relatively brief durations of action and multiple-associated side effects. Intraoperative regional blocks have been effectively utilized in other areas of surgery but have been understudied in breast surgery. The aim of this article was to review various intraoperative techniques for regional anesthesia and local pain control in breast surgery and to highlight areas of future technique development.

Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction.

Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction.

Orthognathic Consequences of Sphincter Pharyngoplasty in Cleft Patients: A 2-Institutional Study.

BACKGROUND: Understanding long-term sequelae of cleft treatment is paramount in the refinement of treatment algorithms to accomplish optimized immediate and long-term outcomes. In this study, we reviewed sphincter pharyngoplasties as a method of velopharyngeal insufficiency (VPI) treatment in relationship to orthognathic surgery. METHODS: Cleft lip/palate and cleft palate patients, 15 years of age and older, were reviewed for demographics, VPI surgery, revisions, and subsequent orthognathic surgery at 2 institutions. Chi-square test, Student's t test, and logistic regression analyses were performed. RESULTS: In 214 patients reviewed (mean age, 19.5 years), 61.7% were male, 18.2% had isolated cleft palate, 61.2% had unilateral cleft lip and palate, and 20.6% had bilateral cleft lip and palate. A total of 33.6% were diagnosed with VPI and received a sphincter pharyngoplasty (mean age, 11.9 years). When subsequent orthognathic surgery was examined, sphincter pharyngoplasty was not associated with maxillary advancement (P = 0.59) but did correlate with an increase in mandibular surgery from 2.8% to 11.1% (P = 0.02). The indications for mandibular surgery in the pharyngoplasty population were related to congenital micrognathia. When cephalometric analyses were evaluated, sphincter pharyngoplasty resulted in a decreased sella-to-nasion-to-B point angle (mean, 79.0-76.3 degrees, P = 0.02) and a higher incidence of normal to class II maxillomandibular relationships as defined by A point-to-nasion-to-B point angles >0.5 (P = 0.02). CONCLUSIONS: Sphincter pharyngoplasty decreases anterior mandibular growth and the discrepancy between maxillomandibular skeletal relationships because of the frequent predisposition of cleft patients to maxillary hypoplasia. In patients with congenital mandibular micrognathia, a small increase in mandibular surgeries may occur.

Diminishing relative contraindications for immediate breast reconstruction.

BACKGROUND: The rise in U.S. immediate breast reconstruction over the past decade may reflect greater patient awareness or expanding use in women not previously offered reconstruction. The purpose of the current study was to determine whether reconstruction in high-risk surgical and oncologic patients was a factor contributing to increased reconstruction rates, specifically using prosthetic techniques. METHODS: Information from a cohort of mastectomy patients from 2001 to 2012 was extracted from an institutional database, including the presence of high-risk surgical or oncologic features (age over 60 years old, body mass index greater than 30, comorbidities, smoking, advanced disease, and prior or postmastectomy radiotherapy). Trends in reconstruction rates and method were analyzed with Poisson regression. Reconstructive success was defined as tissue expander exchange to a permanent implant or autologous techniques without vascular complications. RESULTS: A total of 10,299 patients were included. Immediate reconstruction in high-risk patients increased from 45.0 to 70.7 of 100 mastectomies (p < 0.01). Although autologous use increased only for obese patients (p < 0.01), prosthetic techniques were greater for all high-risk features (p < 0.01). Reconstructive success was 88 percent in high-risk patients; however, the number of failures was greater, including tissue expander loss, implant explantation, and flap vascular complications. CONCLUSIONS: The proportion of high-risk patients undergoing immediate breast reconstruction-specifically using prosthetic-based techniques-increased over the study period. Increased complications may be a tradeoff for the benefits of reconstruction. These findings support diminishing relative contraindications for immediate breast reconstruction at a tertiary cancer center. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Immediate implant breast reconstruction with acellular dermal matrix for treatment of a large recurrent malignant phyllodes tumor.

UNLABELLED: Phyllodes tumors (PT) are rare fibroepithelial breast tumors representing less than 1 % of all breast malignancies. These tumors are unpredictable and fast growing with a high local recurrence rate, making this disease challenging to treat. Previous literature focused on surgical resection, and breast reconstruction following a mastectomy in patients with PT is rarely addressed. We report a case of a recurrent malignant PT treated with a nipple-sparing mastectomy followed by immediate single-stage silicone implant breast reconstruction. While PT is a rare breast malignancy that presents challenges with both surgical resection and reconstruction, we demonstrate that nipple-sparing mastectomy with immediate implant breast reconstruction with AlloMax is curative and can offer an appealing cosmetic option. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lymph node transplantation results in spontaneous lymphatic reconnection and restoration of lymphatic flow.

BACKGROUND: Although lymph node transplantation has been shown to improve lymphatic function, the mechanisms regulating lymphatic vessel reconnection and functional status of lymph nodes remains poorly understood. METHODS: The authors developed and used LacZ lymphatic reporter mice to examine the lineage of lymphatic vessels infiltrating transferred lymph nodes. In addition, the authors analyzed lymphatic function, expression of vascular endothelial growth factor (VEGF)-C, maintenance of T- and B-cell zone, and anatomical localization of lymphatics and high endothelial venules. RESULTS: Reporter mice were specific and highly sensitive in identifying lymphatic vessels. Lymph node transfer was associated with rapid return of lymphatic function and clearance of technetium-99 secondary to a massive infiltration of recipient mouse lymphatics and putative connections to donor lymphatics. T- and B-cell populations in the lymph node were maintained. These changes correlated with marked increases in the expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Newly formed lymphatic channels in transferred lymph nodes were in close anatomical proximity to high endothelial venules. CONCLUSIONS: Transferred lymph nodes have rapid infiltration of functional host lymphatic vessels and maintain T- and B-cell populations. This process correlates with increased endogenous expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Anatomical proximity of newly formed lymphatics and high endothelial venules supports the hypothesis that lymph node transfer can improve lymphedema by exchanges with the systemic circulation.

Obesity impairs lymphatic fluid transport and dendritic cell migration to lymph nodes.

INTRODUCTION: Obesity is a major cause of morbidity and mortality resulting in pathologic changes in virtually every organ system. Although the cardiovascular system has been a focus of intense study, the effects of obesity on the lymphatic system remain essentially unknown. The purpose of this study was to identify the pathologic consequences of diet induced obesity (DIO) on the lymphatic system. METHODS: Adult male wild-type or RAG C57B6-6J mice were fed a high fat (60%) or normal chow diet for 8-10 weeks followed by analysis of lymphatic transport capacity. In addition, we assessed migration of dendritic cells (DCs) to local lymph nodes, lymph node architecture, and lymph node cellular make up. RESULTS: High fat diet resulted in obesity in both wild-type and RAG mice and significantly impaired lymphatic fluid transport and lymph node uptake; interestingly, obese wild-type but not obese RAG mice had significantly impaired migration of DCs to the peripheral lymph nodes. Obesity also resulted in significant changes in the macro and microscopic anatomy of lymph nodes as reflected by a marked decrease in size of inguinal lymph nodes (3.4-fold), decreased number of lymph node lymphatics (1.6-fold), loss of follicular pattern of B cells, and dysregulation of CCL21 expression gradients. Finally, obesity resulted in a significant decrease in the number of lymph node T cells and increased number of B cells and macrophages. CONCLUSIONS: Obesity has significant negative effects on lymphatic transport, DC cell migration, and lymph node architecture. Loss of T and B cell inflammatory reactions does not protect from impaired lymphatic fluid transport but preserves DC migration capacity. Future studies are needed to determine how the interplay between diet, obesity, and the lymphatic system modulate systemic complications of obesity.

Glioblastoma biomarkers from bench to bedside: advances and challenges.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour, with few available therapies providing significant improvements in mortality. Biomarkers, which are defined by the National Institutes of Health as 'characteristics that are objectively measured and evaluated as indicators of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention', have the potential to play valuable roles in the diagnosis and treatment of GBM. Although GBM biomarker research is still in its early stages because of the tumour's complex pathophysiology, a number of potential markers have been identified which can be measured in either brain tissue or blood serum. In conjunction with other clinical data, particularly neuroimaging modalities such as MRI, these proteins could contribute to the clinical management of GBM by helping to classify tumours, predict prognosis and assess treatment response. In this article, we review the current understanding of GBM pathophysiology and recent advances in GBM biomarker research, and discuss the potential clinical implications of promising biomarkers. A better understanding of GBM pathophysiology will allow researchers and clinicians to identify optimal biomarkers and methods of interpretation, leading to advances in tumour classification, prognosis prediction and treatment assessment.

Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer.

We examined whether reduced levels of Apolipoprotein A-I (apoA-I) in ovarian cancer patients are causal in ovarian cancer in a mouse model. Mice expressing a human apoA-I transgene had (i) increased survival (P < 0.0001) and (ii) decreased tumor development (P < 0.01), when compared with littermates, following injection of mouse ovarian epithelial papillary serous adenocarcinoma cells (ID-8 cells). ApoA-I mimetic peptides reduced viability and proliferation of ID8 cells and cis-platinum-resistant human ovarian cancer cells, and decreased ID-8 cell-mediated tumor burden in C57BL/6J mice when administered subcutaneously or orally. Serum levels of lysophosphatidic acid, a well-characterized modulator of tumor cell proliferation, were significantly reduced (>50% compared with control mice, P < 0.05) in mice that received apoA-I mimetic peptides (administered either subcutaneously or orally), suggesting that binding and removal of lysophosphatidic acid is a potential mechanism for the inhibition of tumor development by apoA-I mimetic peptides, which may serve as a previously unexplored class of anticancer agents.

Validation of serum biomarkers for detection of early- and late-stage endometrial cancer.

OBJECTIVE: The objective of this study was to determine the efficacy of 3 previously described ovarian cancer serum biomarkers (apolipoprotein-1 [ApoA-I], prealbumin [TTR], transferrin [TF]) in the detection of endometrioid and papillary serous adenocarcinoma of the endometrium. STUDY DESIGN: ApoA-I, TTR, and TF levels were measured in serum samples that were obtained from 433 individuals that included 90 women with normal endometrium, 210 women with early-stage endometrial cancer, and 133 women with late-stage endometrial cancer. Multivariate regression models were constructed to evaluate the usefulness of the biomarkers in the detection of endometrial cancer. RESULTS: ApoA-I, TTR, and TF distinguished normal samples from early-stage endometrial cancer with a sensitivity of 71% (specificity, 88%) and normal samples from late stage endometrial cancer with a sensitivity of 82% (specificity, 86%). CONCLUSION: The biomarker panel that consists of ApoA-I, TTR, and TF may prove to be a useful clinical tool for the detection of endometrial cancer.