Autologous Costal Cartilage Harvest for Rhinoplasty with Simultaneous Breast Surgery: A Safe and Efficient Technique.

BACKGROUND: Autologous costal cartilage is frequently required for revision rhinoplasties and for challenging primary rhinoplasties. Patients undergoing a concomitant breast surgery can have costal cartilage harvested through their breast surgery incisions, thereby obviating an additional rib harvest scar. The safety and efficacy of this approach has yet to be described. OBJECTIVES: The aim of this study was to evaluate the outcomes, safety, and results of a new technique, described here, for harvesting costal cartilage during a concomitant breast operation. Specifically, the rates of capsular contracture and rhinoplasty revisions were of great interest. METHODS: A retrospective review was performed evaluating the senior author's experience with this technique. Data collected included patient demographics, operations performed, operative time, perioperative morbidity, and postoperative complications. Rates of capsular contracture and rhinoplasty revisions were compared with national averages. RESULTS: A total of 31 female patients were included. Ten (32.3%) breast complications occurred. There were 6 (19.4%) rhinoplasty complications, comprising 1 infection and 5 revisions. The capsular contracture rate was 6% and the rhinoplasty revision rate was 16%. Both of these rates are comparable to independent breast surgeries and rhinoplasties. There were no cases of perioperative mortality or major morbidity. CONCLUSIONS: Combining breast surgery and rhinoplasty surgery allows for autologous rib harvest through the breast surgery incisions. This is a safe technique that results in outcomes similar to either procedure performed alone. In addition, the patient is spared an additional surgery and donor site scar.

Techniques to Repair Implant Malposition after Breast Augmentation: A Review.

BACKGROUND: Implant malposition is a complication of breast augmentation that adversely affects aesthetic outcomes. It is one of the most common reasons for revisionary aesthetic breast surgery yet there is a lack of peer reviewed literature dedicated to the management of this complication. OBJECTIVES: The purpose of this article was to summarize the malposition literature, review the types and causes of this complication, and evaluate the strengths and weakness of procedures aimed at addressing it. METHODS: A review of the literature was performed using the PubMed database. Articles describing surgical techniques for correction of implant malposition, as well as outcome data for patients undergoing revision with described techniques, were included. Articles describing revisionary surgery following breast reconstruction were excluded. A series of cases are presented to illustrate techniques discussed. RESULTS: Search criteria resulted in 763 articles. Title and abstract review followed by application of inclusion and exclusion criteria resulted in a total of 21 clinical studies from 1988 to 2014 that were included in this review. All studies included in this study were of level IV or V evidence. CONCLUSIONS: Despite the overall low level of evidence in the literature regarding secondary breast augmentation, a thorough understanding of the corrective techniques presented will allow surgeons to make the most informed judgments. Weighing the strengths and weakness of these surgical techniques in the context of each patient will allow surgeons to develop the most appropriate treatment strategy. LEVEL OF EVIDENCE 4: Therapeutic.

Decrease in Seroma Rate After Adopting Progressive Tension Sutures Without Drains: A Single Surgery Center Experience of 451 Abdominoplasties Over 7 Years.

BACKGROUND: Abdominoplasty is a common aesthetic procedure in the United States. Pollock and Pollock described their progressive tension technique in 2000 and published a series of 597 patients in 2012 of their experience. The reported seroma rate in the literature ranges from 2% to 26% with drains and 0.1% to 4% with progressive tension sutures (PTS) without drains. OBJECTIVES: Given these data, we decided to use PTS and forego drains in abdominoplasty. Here we present our experience with the transition. METHODS: This is a retrospective chart review of 451 abdominoplasties performed at our outpatient surgery center over a 7-year period (2009-2015). We gathered data on patient demographics, concomitant liposuction, and complications and length of follow up. RESULTS: Five main differences were examined in PTS vs traditional abdominoplasty using drains groups. These included rate of seroma, wound complication, scar revision, hematoma, and follow up. We found a decreased rate of seroma in the PTS group, 2% vs 9%. Wound complications were similar. Scar revision was slightly higher in the PTS group at 17% vs 10% in traditional abdominoplasty, this association had a P value of .048. The rates of hematoma were similar (0% vs 1%). The mean follow up was 6 months in PTS and 9 months in traditional abdominoplasty. Addition of liposuction did not increase the rate of seroma. CONCLUSIONS: PTS without drains significantly decreased the seroma rate in our practice. Our experience adds to the mounting evidence that surgeons should consider using the PTS technique and abandon the use of drains in abdominoplasty. A well powered, multicenter, randomized controlled study is needed in order to definitively lay this question to rest. LEVEL OF EVIDENCE: 4 Therapeutic.

Outcomes Analysis of Biologic Mesh Use for Abdominal Wall Reconstruction in Clean-Contaminated and Contaminated Ventral Hernia Repair.

BACKGROUND: Repair of grade 3 and grade 4 ventral hernias is a distinct challenge, given the potential for infection, and the comorbid nature of the patient population. This study evaluates our institutional outcomes when performing single-stage repair of these hernias, with biologic mesh for abdominal wall reinforcement. METHODS: A prospectively maintained database was reviewed for all patients undergoing repair of grade 3 (potentially contaminated) or grade 4 (infected) hernias, as classified by the Ventral Hernia Working Group. All those patients undergoing repair with component separation techniques and biologic mesh reinforcement were included. Patient demographics, comorbidities, and postoperative complications were analyzed. Univariate analysis was performed to define factors predictive of hernia recurrence and wound complications. RESULTS: A total of 41 patients underwent single-stage repair of grade 3 and grade 4 hernias during a 4-year period. The overall postoperative wound infection rate was 15%, and hernia recurrence rate was 12%. Almost all recurrences were seen in grade 4 hernia repairs, and in those patients undergoing bridging repair of the hernia. One patient required removal of the biologic mesh. Those factors predicting hernia recurrence were smoking (P = 0.023), increasing body mass index (P = 0.012), increasing defect size (P = 0.010), and bridging repair (P = 0.042). No mesh was removed due to perioperative infection. Mean follow-up time for this patient population was 25 months. CONCLUSIONS: Single-stage repair of grade 3 hernias performed with component separation and biologic mesh reinforcement is effective and offers a low recurrence rate. Furthermore, the use of biologic mesh allows for avoidance of mesh explantation in instances of wound breakdown or infection. Bridging repairs are associated with a high recurrence rate, as is single-stage repair of grade 4 hernias.

Supratip-plasty: a completely cartilaginous tip complex to maintain nasal tip width.

BACKGROUND: Following primary rhinoplasty, the nasal tip may become wider on front view, possibly due to splaying of the lateral crura. OBJECTIVES: The authors describe a technique, the "supratip-plasty," to create an all-cartilaginous supratip that resists splaying and postoperative broadening of the nasal tip complex. METHODS: Thirteen consecutive primary rhinoplasty patients (10 women; 3 men) with broad nasal tips received a supratip-plasty (which preserved the cephalic part of the lateral crus, reducing it in size and securing it to the dorsal septum, resulting in a completely cartilaginous tip framework) and were followed for 11 to 17 months. Since the frontal tip width (TW) is relative to the frontal nasal base width (NBW), the TW/NBW ratio was contrasted to that of 19 unoperated aesthetically pleasing nasal tips. RESULTS: Of the 13 cases, all but 1 were considered to have a good result. The preoperative mean TW/NBW ratio was 0.68. The postoperative mean was 0.53, compared with 0.48 in the unoperated aesthetic tip group. No tip revisions were necessary; however, 2 patients did require revisionary surgery for nontip problems. CONCLUSIONS: Preserving a cephalic island of lateral crus, trimming it to fit the new supratip contour following suture tip-plasty, and securing it to the septum provides a completely cartilaginous nasal tip framework that tends not to widen postoperatively.

Laparoscopic treatment of liver tumours using a two-needle probe bipolar radiofrequency ablation device.

BACKGROUND: Many hepatobiliary centres are increasingly utilizing thermocoagulative devices such as bipolar-radiofrequency ablation (B-RFA). Compared with monopolar-radiofrequency ablation (M-RFA), B-RFA does not require grounding pads, thereby avoiding dermal burn injuries, and does not position probes directly into the tumour but rather on the perimeter. Additionally, B-RFA can precoagulate parenchyma to assist in hepatic resection. Herein, we report our early experience using B-RFA. METHODS: A retrospective review identified 68 patients who underwent M-RFA or B-RFA between June 2004 and September 2010 in an academic centre. Peri-operative metrics were analysed. RESULTS: M-RFA was used to treat 30 patients, whereas B-RFA was used for 17 patients. There were no differences in peri-operative metrics, survival or disease recurrence between M-RFA and B-RFA. Seventeen additional patients underwent B-RFA precoagulation during laparoscopic resection (segmentectomy in eleven patients and multi-segmental resection in six patients). Four patients with multifocal disease underwent procedures that combined B-RFA with resection. CONCLUSIONS: The early experience utilizing B-RFA demonstrates equivalency to M-RFA with respect to peri-operative metrics and survival. Moreover, B-RFA can be utilized to precoagulate tissue during a planned resection, making it not only a useful tool for tumour therapy but also a useful adjunct during surgical resections.

Thymosin beta4 is cytoprotective in human gingival fibroblasts.

Thymosin beta4 (Tbeta(4)) is a naturally occurring, ubiquitous, non-toxic protein with documented wound-healing, anti-inflammatory, anti-apoptotic, and tissue-repair properties in skin, the ocular surface, and the heart. The ability of Tbeta(4) to demonstrate similar protective properties in cells of the oral cavity was analyzed using an in vitro model of cultured human gingival fibroblasts. Thymosin beta 4 significantly suppressed the secretion of interleukin-8 (IL-8) following stimulation with tumor necrosis factoralpha (TNF-alpha), suggesting that it may suppress the inflammatory response initiated by pro-inflammatory cytokines. By contrast, Tbeta(4) was not effective in protecting fibroblasts from challenge with lipopolysaccharide purified from Porphyromonas gingivalis or Escherichia coli. Thymosin beta 4 was able to protect gingival fibroblasts against the known cytotoxic effects of chlorhexidine digluconate, a mouthrinse containing chlorhexidine digluconate, and carbamide peroxide. Additionally, Tbeta(4) was able to protect gingival fibroblasts from the apoptosis that is induced by stimulation with TNF-alpha or by exposure to chlorhexidine. Because of its multifunctional roles in protecting cells against damage, Tbeta(4) may have significant potential for use as an oral heathcare aid with combined antimicrobial, anti-inflammatory, anti-apoptotic, and cytoprotective properties.

The Role of Ellis-Van Creveld 2(EVC2) in Mice During Cranial Bone Development.

EvC syndrome is a type of autosomal-recessive chondrodysplasia. Previous case studies in patients suggest abnormal craniofacial development, in addition to dwarfism and tooth abnormalities. To investigate how craniofacial development is affected in EvC patients, surface models were generated from micro-CT scans of control mice, Evc2 global mutant mice and Evc2 neural crest-specific mutant mice. The anatomic landmarks were placed on the surface model to assess the morphological abnormalities in the Evc2 mutants. Through analyzing the linear and angular measurements between landmarks, we identified a smaller overall skull, shorter nasal bone, shorter frontal bone, and shorter cranial base in the Evc2 global mutants. By comparing neural crest-specific Evc2 mutants with control mice, we demonstrated that the abnormalities within the mid-facial regions are not accounted for by the Evc2 mutation within these regions. Additionally, we also identified disproportionate length to width ratios in the Evc2 mutants at all levels from anterior to posterior of the skull. Overall, this study demonstrates a more comprehensive analysis on the craniofacial morphological abnormalities in EvC syndrome and provides the developmental insight to appreciate the impact of Evc2 mutation within the neural crest cells on multiple aspects of skull deformities. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:46-55, 2018. © 2017 Wiley Periodicals, Inc.

Autologous Fat Grafting as a Novel Antiestrogen Vehicle for the Treatment of Breast Cancer.

BACKGROUND: Adipose fat transfer is increasingly used for contour corrections of the tumor bed after lumpectomy and breast reconstructions after mastectomy. The lipophilic nature of the fat tissue may render adipocytes an ideal vehicle with which to deliver a high boost of an antiestrogen to the tumor bed to serve as an adjunct systemic hormonal therapy. The authors therefore tested whether adipocytes could safely be loaded with an antiestrogen and allow for release at therapeutic concentrations to treat breast cancer. METHODS: Adipose tissue was collected from patients undergoing autologous fat grafting. The influence of adipose tissue on tumorigenesis was determined both in vitro and in vivo using breast cancer cell lines. Ex vivo, adipose tissue was assessed for its ability to depot fulvestrant and inhibit the growth of breast cancer cell lines. RESULTS: Adipose tissue harvested from patients did not promote breast cancer cell growth in vitro or in an in vivo mouse model. Adipose tissue was successfully loaded with fulvestrant and released at levels sufficient to inhibit estrogen receptor signaling and growth of breast cancer cells. CONCLUSIONS: This work supports the hypothesis that adipose tissue used for autologous fat grafting can serve as a novel method for local drug delivery. As this technique is used to reconstruct a variety of postsurgical defects following cancer resection, this approach for local drug delivery may be an effective alternative in therapeutic settings beyond breast cancer.

Techniques for diced cartilage with deep temporalis fascia graft.

Diced cartilage with deep temporalis fascia (DC-F) graft has become a popular technique for reconstruction of the nasal dorsum. Cartilage can be obtained from the septum, ear, or costal cartilage when employing the DC-F technique. The complications seen with DC-F grafts tend to occur early in the surgeon's implementation of this technique. Management of the complications varies depending on the severity of the problem. This article gives an overview of both the technique and the complications commonly encountered.

The TGR5 receptor mediates bile acid-induced itch and analgesia.

Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucine-enkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide- and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases.

Hepatic surgery at a VA tertiary medical center: lessons learned.

BACKGROUND: The development of a hepatic surgery center within a US Department of Veterans Affairs hospital is dependent on proper training and institutional support, which can translate into low operative morbidity and mortality rates. METHODS: Patients who underwent hepatic procedures between 2003 and 2009 were retrospectively reviewed. A subset analysis of laparoscopic liver resections for patients with hepatocellular cancer (HCC) was performed. One hundred twenty-six patients underwent 130 hepatic procedures, 65% of which were hepatic resections. Ninety-seven percent of cases were for malignant disease, including HCC (70%). RESULTS: The morbidity and mortality rates were 15.5% and 2.4%, respectively. For patients with HCC there was no difference in operative outcomes or overall survival when procedures were performed laparoscopically. CONCLUSIONS: A Veterans Affairs (VA) hospital specializing in hepatic surgery can achieve low complication rates comparable with those of high-volume centers. The numbers of patient referrals and hepatic resections and the proportion of laparoscopic operations increased after the creation of a dedicated hepatic surgery center within a single VA hospital.

Amyotrophic lateral sclerosis-like conditions in possible association with cholesterol-lowering drugs: an analysis of patient reports to the University of California, San Diego (UCSD) Statin Effects Study.

BACKGROUND: While cases of amyotrophic lateral sclerosis (ALS) or ALS-like conditions have arisen in apparent association with HMG-CoA reductase inhibitors ('statins') and/or other lipid-lowering drugs (collectively termed 'statins' in this paper for brevity), additional information is needed to understand whether the connection may be causal. The University of California, San Diego (UCSD) Statin Effects Study is a patient-targeted adverse event surveillance project focused on lipid-lowering agents, whose aim is to capitalize on patient reporting to further define characteristics and natural history of statin adverse effects (AEs), and to ascertain whether a patient-targeted surveillance system might lead to presumptive identification of previously unrecognized AEs. ALS was a candidate 'new' AE identified through this process. The aim of the analysis presented here was to examine characteristics and natural history of reported statin-associated ALS-like conditions with attention to factors that may bear on the issue of causality. METHODS: For the present analysis, we focused on cases of statin-associated ALS that were reported to our study group prior to publication of a possible statin-ALS association. Of 35 identified subjects who had contacted the UCSD Statin Effects Study group to report ALS or an ALS-like condition, 18 could not be reached (e.g. contact information was no longer valid). Six were unable to participate (e.g. due to progression of their disease). Of the 11 who could be contacted and were able to participate, one declined to give informed consent. The remaining ten, with either a formal or probable diagnosis of ALS in the context of progressive muscle wasting/weakness arising in association with lipid-lowering drug therapy, completed a mail or phone survey eliciting information about ALS symptom onset and change in association with drug use/modification and development of statin-associated AEs. We reviewed findings in the context of literature on statin antioxidant/pro-oxidant balance, as well as ALS mechanisms involving oxidative stress and mitochondrial dysfunction. RESULTS: All ten subjects reported amelioration of symptoms with drug discontinuation and/or onset or exacerbation of symptoms with drug change, rechallenge or dose increase. Three subjects initiated coenzyme Q10 supplementation; all reported initial benefit. All subjects reportedly developed statin AEs (not indicative of ALS) prior to ALS symptom onset, strongly disproportionate to expectation (p < 0.001). Since this reflects induction of pro-oxidant effects from statins, these findings lend weight to a literature-supported mechanism by which induction by statins of oxidative stress with amplification of mitochondrial dysfunction, arising in a vulnerable subgroup, may propel mechanisms underlying both AEs and, more rarely, ALS. CONCLUSION: A theoretical foundation and preliminary clinical observations suggest that statins (and other lipid-lowering drugs) may rarely be associated with ALS in vulnerable individuals in whom pro-oxidant effects of statins predominate. Our observations have explanatory relevance extending to ALS causes that are not statin associated and to statin-associated neurodegenerative conditions that are not ALS. They suggest means for identification of a possible vulnerable subgroup. Indeed whether statins may, in contrast, confer ALS protection when antioxidant effects predominate merits examination.

Development of reproducible histologic injury severity scores: skeletal muscle reperfusion injury.

BACKGROUND: Ischemia-reperfusion injury of skeletal muscle is a common clinical and experimental problem. To date, there has been no uniform and reproducible method to assess the extent of histologic injury. In this study, we developed a novel statistical methodology for evaluating injury in individual myocytes and 3 distinct methods for the interpretation of this data. METHODS: C57/BL6 mice underwent 2 h of hindlimb ischemia followed by reperfusion for 3 (n = 11), 24 (n = 12), or 48 (n = 10) h. The gastrocnemius muscles were harvested, stained, and evaluated under microscopy. Standardized criteria were applied to score individual myocytes as healthy or injured, and injury score was expressed as injured fibers/total fibers %. Three methods of analyzing myocyte data were developed and evaluated with statistical Block-Random Sampling to determine the number of counted fibers required to represent accurately the total injury. The Full-Frame Counting, Fourfold Divided Counting, and Stratified Individual Counting methods differ in the random order in which fibers or microscopic fields are scored. RESULTS: The 3 methods were found to be statistically sound at all experimental time points. Using the Full-Frame, Fourfold, and Stratified methods, the maximum number of required fibers at all time points was 600, 300, and 100, respectively, to obtain an estimation of injury with a 95% confidence interval. CONCLUSIONS: These criteria and statistical methods for histologic evaluation of ischemia-reperfusion injury in skeletal muscle are accurate and reproducible. The Fourfold method is the most practical and technically efficient method of assessing injury. Such a quantitative, direct assessment of injury is important and will be useful for future studies.

The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia-reperfusion.

Complement is an important mediator of the injuries observed after skeletal muscle ischemia and subsequent reperfusion. Although the classical pathway had been assumed to be the major pathway of activation leading to injury, the mannose-binding lectin (MBL) pathway might also play a contributing role. In this study, we found that MBL-deficient mice had significant protection after skeletal muscle reperfusion injury compared with wild-type, classical pathway-specific C1q-deficient mice, or MBL-deficient mice reconstituted with recombinant human MBL. MBL-deficient mice, however, were not protected from permeability edema or secondary lung injury after ischemia-reperfusion. These data indicate that blockade of the classical pathway alone (C1q) is protective against permeability edema and remote pulmonary injury but not protective against histologic muscle injury. In contrast, blocking the MBL pathway alone protects against histological injury but is not protective against permeability edema or lung injury. Thus, the activation of both pathways is likely responsible for the full spectrum of injuries observed after skeletal muscle reperfusion injury.

Modulation of deltaF508 cystic fibrosis transmembrane regulator trafficking and function with 4-phenylbutyrate and flavonoids.

Over 70% of patients with cystic fibrosis have the DeltaF508 mutation. This protein is a partially functional chloride (Cl-) channel that is prematurely degraded in the endoplasmic reticulum. Specific members of the flavonoid class of compounds have been shown to increase Cl- conductance of wild-type and DeltaF508 cystic fibrosis transmembrane regulator (CFTR). Although flavonoid effects on CFTR processing are unknown, evidence of effects on heat shock proteins, specifically those that have been shown to interact with CFTR, led us to believe that there would be an effect on CFTR processing through modulation of CFTR-chaperone interactions. We sought to determine (i) the effect of apigenin, genistein, kaempferol, and quercetin on CFTR processing in IB3-1 cells (F508/W1282X) and (ii) whether sequential treatment with 4-phenylbutyrate (4-PBA) to increase CFTR processing and flavonoid to directly stimulate CFTR would increase Cl- conductance. Our results show no significant effect on CFTR processing as measured by immunoblotting with 1 microM or 5 microM of apigenin, genistein, kaempferol, or quercetin. However, despite no effect on CFTR processing as determined by immunoblot, immunofluorescence demonstrated a favorable change in the intracellular distribution of CFTR with 24 h treatments of apigenin, kaempferol, and genistein. Furthermore, we observed an increase in Cl- conductance as measured by Cl- efflux in cells that were treated for 24 h with 4-PBA and then assayed with forskolin and 1 microM or 5 microM genistein, and also with cells treated for 24 h with either 4-PBA, 5 microM apigenin, or 1 microM quercetin. Thus, a combination of chronic treatment with 4-PBA or select flavonoids, followed by acute flavonoid exposure, may be beneficial in cystic fibrosis.