Publications by authors named "Manfred Frey"

62 Publications

A Novel Genetically Encoded Single Use Sensory Cellular Test System Measures Bicarbonate Concentration Changes in Living Cells.

Sensors (Basel) 2020 Mar 11;20(6). Epub 2020 Mar 11.

Steinbeis-Innovationszentrum Zellkulturtechnik, c/o University of Applied Sciences Mannheim, Paul-Wittsack-Str.10, D-68163 Mannheim, Germany.

Bicarbonate plays a central role in human physiology from cellular respiration to pH homeostasis. However, so far, the measurement of bicarbonate concentration changes in living cells has only been possible by measuring intracellular pH changes. In this article, we report the development of a genetically encoded pH-independent fluorescence-based single-use sensory cellular test system for monitoring intracellular bicarbonate concentration changes in living cells. We describe the usefulness of the developed biosensor in characterizing the bicarbonate transport activities of anionophores-small molecules capable of facilitating the membrane permeation of this anion. We also demonstrate the ability of the bicarbonate sensory cellular test system to measure intracellular bicarbonate concentration changes in response to activation and specific inhibition of wild-type human CFTR protein when co-expressed with the bicarbonate sensing and reporting units in living cells. A valuable benefit of the bicarbonate sensory cellular test system could be the screening of novel anionophore library compounds for bicarbonate transport activity with efficiencies close to the natural anion channel CFTR, which is not functional in the respiratory epithelia of cystic fibrosis patients.
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http://dx.doi.org/10.3390/s20061570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146495PMC
March 2020

Extraction With Sweat-Sebum Emulsion as a New Test Method for Leachables in Patch-Based Medical Devices, Illustrated by Assessment of Isobornylacrylate (IBOA) in Diabetes Products.

J Diabetes Sci Technol 2021 Jul 1;15(4):792-800. Epub 2020 Mar 1.

Steinbeis Innovationszentrum für Zellkulturtechnik, Mannheim, Germany.

Background: The increasing offering of patch-based medical devices is accompanied by growing numbers of reported adverse skin reactions. Procedures for testing leachables according to ISO 10993 may not be optimal for lipophilic substances that can be mobilized on skin by sweat and sebum. We propose an improved extraction method for targeted analysis of leachables using low volumes of a sweat-sebum emulsion. The approach is illustrated by the analysis of isobornylacrylate (IBOA), a compound found in some devices and suspected for allergenic potential.

Method: Three patch-based products were tested: an implantable device for continuous glucose monitoring (CGM), an intermittently scanned CGM (isCGM) device, and a micro-insulin pump. Quantification of IBOA was performed by gas chromatography and allergenic potential of IBOA levels was assessed by the KeratinoSens cell assay. Different combinations were used for extraction solvent (isopropanol, 5% ethanol-water solution, and sweat-sebum emulsion), extraction volumes (complete immersion vs partial immersion in 2 mm of solvent), and extraction time (3, 5, and 14 days).

Results: Isobornylacrylate was only found in the isCGM device. About 20 mg/L IBOA were eluted after 3 days in isopropanol but only about 1 mg/L in ethanol-water. Sweat-sebum emulsion dissolves IBOA better and gives a more stable solution than ethanol-water. Decomposition of IBOA solutions requires adjusted extraction timing or correction of results. In the sweat-sebum extract, IBOA levels were about 20 mg/L after 3 days and about 30 mg/L after 5 days, clearly above the threshold found in the KerationSens assay for keratinocyte activation (10 mg/L).

Conclusion: Extraction by low volumes of sweat-sebum emulsion can be a superior alternative for the targeted simulating-use assessment of leachables in patch-based medical devices.
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http://dx.doi.org/10.1177/1932296820908656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258535PMC
July 2021

Two novel real time cell-based assays quantify beta-blocker and NSAID specific effects in effluents of municipal wastewater treatment plants.

Water Res 2017 05 17;115:74-83. Epub 2017 Feb 17.

Steinbeis-Innovationszentrum Zellkulturtechnik, c/o University of Applied Sciences Mannheim, Paul-Wittsack-Str. 10, D-68163 Mannheim, Germany. Electronic address:

Pharmaceuticals, such as beta-blockers, nonsteroidal anti-inflammatory drugs (NSAIDs) as well as their metabolites are introduced into the water cycle via municipal wastewater treatment plant (WWTP) effluents in all industrialized countries. As the amino acid sequences of the biological target molecules of these pharmaceuticals - the beta-1 adrenergic receptor for beta-blockers and the cyclooxygenase for NSAIDs - are phylogenetically conserved among vertebrates it is reasonable that wildlife vertebrates including fish physiologically respond in a similar way to them as documented in humans. Consequently, beta-blockers and NSAIDs both exhibit their effects according to their mode of action on one hand, but on the other hand that may lead to unwanted side effects in non-target species. To determine whether residuals of beta-1 adrenergic receptor antagonists and cyclooxygenase inhibitors may pose a risk to aquatic organisms, one has to know the extent to which such organisms respond to the total of active compounds, their metabolites and transformation products with the same modes of action. To cope with this demand, two cell-based assays were developed, by which the total beta-blocker and cyclooxygenase inhibitory activity can be assessed in a given wastewater or surface water extract in real time. The measured activity is quantified as metoprolol equivalents (MetEQ) of the lead substance metoprolol in the beta-blocker assay, and diclofenac equivalents (DicEQ) in the NSAID assay. Even though MetEQs and DicEQs were found to surpass the concentration of the respective lead substances (metoprolol, diclofenac), as determined by chemical analysis by a factor of two to three, this difference was shown to be reasonably explained by the presence and action of additional active compounds with the same mode of action in the test samples. Thus, both in vitro assays were proven to integrate effectively over beta-blocker and NSAID activities in WWTP effluents in a very sensitive and extremely rapid manner.
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http://dx.doi.org/10.1016/j.watres.2017.02.036DOI Listing
May 2017

Worldwide Testing of the eFACE Facial Nerve Clinician-Graded Scale.

Plast Reconstr Surg 2017 Feb;139(2):491e-498e

Boston, Mass.; Los Angeles, Calif.; Nijmegen, The Netherlands; Anchorage, Alaska; Toronto, Ontario, Canada; Melbourne, Victoria, and Sydney, New South Wales, Australia; Madison, Wis.; Liverpool, United Kingdom; Vienna, Austria; Madrid, Spain; Iowa City, Iowa; Tacoma, Wash.; Ann Arbor, Mich.; Baltimore, Md.; and St. Louis, Mo.

Background: The electronic, clinician-graded facial function scale (eFACE) is a potentially useful tool for assessing facial function. Beneficial features include its digital nature, use of visual analogue scales, and provision of graphic outputs and scores. The authors introduced the instrument to experienced facial nerve clinicians for feedback, and examined the effect of viewing a video tutorial on score agreement.

Methods: Videos of 30 patients with facial palsy were embedded in an Apple eFACE application. Facial nerve clinicians were invited to perform eFACE video rating and tutorial observation. Participants downloaded the application, viewed the clips, and applied the scoring. They then viewed the tutorial and rescored the clips. Analysis of mean, standard deviation, and confidence interval were performed. Values were compared before and after tutorial viewing, and against scores obtained by an experienced eFACE user.

Results: eFACE feedback was positive; participants reported eagerness to apply the instrument in clinical practice. Standard deviation decreased significantly in only two of the 16 categories after tutorial viewing. Subscores for static, dynamic, and synkinesis all demonstrated stable standard deviations, suggesting that the instrument is intuitive. Participants achieved posttutorial scores closer to the experienced eFACE user in 14 of 16 scores, although only a single score, nasolabial fold orientation with smiling, achieved statistically significant improvement.

Conclusions: The eFACE may be a suitable, cross-platform, digital instrument for facial function assessment, and was well received by facial nerve experts. Tutorial viewing does not appear to be necessary to achieve agreement, although it does mildly improve agreement between occasional and frequent eFACE users.
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http://dx.doi.org/10.1097/PRS.0000000000002954DOI Listing
February 2017

Monitoring primary effects of pharmaceuticals in the aquatic environment with mode of action-specific in vitro biotests.

Environ Sci Technol 2015 Mar 13;49(5):2594-5. Epub 2015 Feb 13.

Animal Physiological Ecology, University of Tübingen , Auf der Morgenstelle 5, D-72076 Tübingen, Germany.

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http://dx.doi.org/10.1021/acs.est.5b00162DOI Listing
March 2015

Enhancement of facial nerve motoneuron regeneration through cross-face nerve grafts by adding end-to-side sensory axons.

Plast Reconstr Surg 2015 Feb;135(2):460-471

Vienna, Austria; Toronto, Ontario, Canada; and Cologne, Germany From the Division of Plastic and Reconstructive Surgery, Medical University of Vienna; the Division of Plastic and Reconstructive Surgery and the Research Institute, Program in Neuroscience, The Hospital for Sick Children; the Division of Plastic and Reconstructive Surgery and the Institute of Biomaterials and Biomedical Engineering, University of Toronto; and the Anatomical Institute, University of Cologne.

Background: In unilateral facial palsy, cross-face nerve grafts are used for emotional facial reanimation. Facial nerve regeneration through the grafts takes several months, and the functional results are sometimes inadequate. Chronic denervation of the cross-face nerve graft results in incomplete nerve regeneration. The authors hypothesize that donor axons from regional sensory nerves will enhance facial motoneuron regeneration, improve axon regeneration, and improve the amplitude of facial muscle movement.

Methods: In the rat model, a 30-mm nerve graft (right common peroneal nerve) was used as a cross-face nerve graft. The graft was coapted to the proximal stump of the transected right buccal branch of the facial nerve and the distal stumps of the transected left buccal and marginal mandibular branches. In one group, sensory occipital nerves were coapted end-to-side to the cross-face nerve graft. Regeneration of green fluorescent protein-positive axons was imaged in vivo in transgenic Thy1-green fluorescent protein rats, in which all neurons express green fluorescence. After 16 weeks, retrograde labeling of regenerated neurons and histomorphometric analysis of myelinated axons was performed. Functional outcomes were assessed with video analysis of whisker motion.

Results: "Pathway protection" with sensory axons significantly enhanced motoneuron regeneration, as assessed by retrograde labeling, in vivo fluorescence imaging, and histomorphometry, and significantly improved whisker motion during video analysis.

Conclusion: Sensory pathway protection of cross-face nerve grafts counteracts chronic denervation in nerve grafts and improves regeneration and functional outcomes.
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http://dx.doi.org/10.1097/PRS.0000000000000893DOI Listing
February 2015

Macroscopic in vivo imaging of facial nerve regeneration in Thy1-GFP rats.

JAMA Facial Plast Surg 2015 Jan-Feb;17(1):8-15

Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada3Department of Surgery, University of Toronto, Toronto, Ontario, Canada4Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada5I.

Importance: Facial nerve injury leads to severe functional and aesthetic deficits. The transgenic Thy1-GFP rat is a new model for facial nerve injury and reconstruction research that will help improve clinical outcomes through translational facial nerve injury research.

Objective: To determine whether serial in vivo imaging of nerve regeneration in the transgenic rat model is possible, facial nerve regeneration was imaged under the main paradigms of facial nerve injury and reconstruction.

Design, Setting, And Participants: Fifteen male Thy1-GFP rats, which express green fluorescent protein (GFP) in their neural structures, were divided into 3 groups in the laboratory: crush-injury, direct repair, and cross-face nerve grafting (30-mm graft length). The distal nerve stump or nerve graft was predegenerated for 2 weeks. The facial nerve of the transgenic rats was serially imaged at the time of operation and after 2, 4, and 8 weeks of regeneration. The imaging was performed under a GFP-MDS-96/BN excitation stand (BLS Ltd).

Intervention Or Exposure: Facial nerve injury.

Main Outcome And Measure: Optical fluorescence of regenerating facial nerve axons.

Results: Serial in vivo imaging of the regeneration of GFP-positive axons in the Thy1-GFP rat model is possible. All animals survived the short imaging procedures well, and nerve regeneration was followed over clinically relevant distances. The predegeneration of the distal nerve stump or the cross-face nerve graft was, however, necessary to image the regeneration front at early time points. Crush injury was not suitable to sufficiently predegenerate the nerve (and to allow for degradation of the GFP through Wallerian degeneration). After direct repair, axons regenerated over the coaptation site in between 2 and 4 weeks. The GFP-positive nerve fibers reached the distal end of the 30-mm-long cross-face nervegrafts after 4 to 8 weeks of regeneration.

Conclusions And Relevance: The time course of facial nerve regeneration was studied by serial in vivo imaging in the transgenic rat model. Nerve regeneration was followed over clinically relevant distances in a small number of experimental animals, as they were subsequently imaged at multiple time points. The Thy1-GFP rat model will help improve clinical outcomes of facial reanimation surgery through improving the knowledge of facial nerve regeneration after surgical procedures.

Level Of Evidence: NA.
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http://dx.doi.org/10.1001/jamafacial.2014.617DOI Listing
October 2015

The ErbB2 inhibitor Herceptin (Trastuzumab) promotes axonal outgrowth four weeks after acute nerve transection and repair.

Neurosci Lett 2014 Oct 8;582:81-6. Epub 2014 Sep 8.

Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Surgery, University of Toronto, 149 College Street, 5th Floor, Toronto, ON M5T 1P5, Canada; Institute of Medical Science, University of Toronto, 1 King's College Circle, Room 2374, Toronto, ON M5S 1A8, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Rosebrugh Building, RM 407 164 College Street, Toronto, ON M5S 3G9, Canada. Electronic address:

Accumulating evidence suggests that neuregulin, a potent Schwann cell mitogen, and its receptor, ErbB2, have an important role in regulating peripheral nerve regeneration. We hypothesized that Herceptin (Trastuzumab), a monoclonal antibody that binds ErbB2, would disrupt ErbB2 signaling, allowing us to evaluate ErbB2's importance in peripheral nerve regeneration. In this study, the extent of peripheral motor and sensory nerve regeneration and distal axonal outgrowth was analyzed two and four weeks after common peroneal (CP) nerve injury in rats. Outcomes analyzed included neuron counts after retrograde labeling, histomorphometry, and protein analysis. The data analysis revealed that there was no impact of Herceptin administration on either the numbers of motor or sensory neurons that regenerated their axons but histomorphometry revealed that Herceptin significantly increased the number of regenerated axons in the distal repaired nerve after 4 weeks. Protein analysis with Western blotting revealed no difference in either expression levels of ErbB2 or the amount of activated, phosphorylated ErbB2 in injured nerves. In conclusion, administration of the ErbB2 receptor inhibitor after nerve transection and surgical repair did not alter the number of regenerating neurons but markedly increased the number of regenerated axons per neuron in the distal nerve stump. Enhanced axon outgrowth in the presence of this ErbB2 inhibitor indicates that ErbB2 signaling may limit the numbers of axons that are emitted from each regenerating neuron.
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http://dx.doi.org/10.1016/j.neulet.2014.09.006DOI Listing
October 2014

Facial synkinesia before and after surgical reanimation of the paralyzed face.

Plast Reconstr Surg 2014 Jun;133(6):842e-851e

Vienna, Austria From the Department of Surgery, Division of Plastic and Reconstructive Surgery, Medical University of Vienna.

Background: Facial synkinesia is a common sequela of facial palsy, affecting 15 to 20 percent of patients. The rate of postoperative synkinesia after facial reanimation is not clearly established. The severity and type of synkinesia determine the degree of clinical relevance.

Methods: One hundred sixty-seven patients with facial palsy were included in this retrospective cohort study. Three-dimensional video analysis of facial movements was performed preoperatively and 18 months after facial reanimation. The severity of synkinesia was rated subjectively on a four-degree severity scale. Objective three-dimensional analysis of synkinesia was performed on patients with 18-month follow-up times.

Results: Preoperatively, 84.4 percent of patients were not affected by synkinesia, 9 percent presented with mild synkinesia, 4.2 percent presented with moderate synkinesia, and 2.4 percent presented with severe synkinesia. Postoperatively, 51 percent of all patients presented with facial synkinesia (41.8 percent mild, 17.3 percent moderate, and 1 percent severe synkinesia; some patients had more than one type). Patients treated with territorially differentiated gracilis muscle transplantation were most frequently affected (69.8 percent), followed by patients treated with gracilis muscle transplantation in combination with temporalis muscle transposition to the eye (51.8 percent). Oculo-oral synkinesia was the most frequent form of synkinesia.

Conclusions: After surgical reanimation of the paralyzed face, half of the patients presented with synkinesia. The majority of patients developed mild or moderate forms of synkinesia; therefore, the clinical relevance of synkinesia has to be seen in the context of total facial function. Because of the high prevalence of synkinesia, it should be documented and addressed in patients undergoing facial reanimation.

Clinical Question/level Of Evidence: Therapeutic, IV.
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http://dx.doi.org/10.1097/PRS.0000000000000218DOI Listing
June 2014

Birth brachial plexus palsy caused by cervical rib.

J Plast Reconstr Aesthet Surg 2014 Jul 26;67(7):1004-5. Epub 2014 Feb 26.

Div. of Plastic and Reconstructive Surgery, Dept. of Surgery, Medical University of Vienna, Austria; Christian Doppler Laboratory for Restoration of Extremity Function, Division of Plastic and Reconstructive Surgery, Medical University of Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.bjps.2014.02.020DOI Listing
July 2014

Comparison of three-dimensional surface-imaging systems.

J Plast Reconstr Aesthet Surg 2014 Apr 15;67(4):489-97. Epub 2014 Jan 15.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Austria.

Background: In recent decades, three-dimensional (3D) surface-imaging technologies have gained popularity worldwide, but because most published articles that mention them are technical, clinicians often have difficulties gaining a proper understanding of them. This article aims to provide the reader with relevant information on 3D surface-imaging systems. In it, we compare the most recent technologies to reveal their differences.

Methods: We have accessed five international companies with the latest technologies in 3D surface-imaging systems: 3dMD, Axisthree, Canfield, Crisalix and Dimensional Imaging (Di3D; in alphabetical order). We evaluated their technical equipment, independent validation studies and corporate backgrounds.

Results: The fastest capturing devices are the 3dMD and Di3D systems, capable of capturing images within 1.5 and 1 ms, respectively. All companies provide software for tissue modifications. Additionally, 3dMD, Canfield and Di3D can fuse computed tomography (CT)/cone-beam computed tomography (CBCT) images into their 3D surface-imaging data. 3dMD and Di3D provide 4D capture systems, which allow capturing the movement of a 3D surface over time. Crisalix greatly differs from the other four systems as it is purely web based and realised via cloud computing.

Conclusion: 3D surface-imaging systems are becoming important in today's plastic surgical set-ups, taking surgeons to a new level of communication with patients, surgical planning and outcome evaluation. Technologies used in 3D surface-imaging systems and their intended field of application vary within the companies evaluated. Potential users should define their requirements and assignment of 3D surface-imaging systems in their clinical as research environment before making the final decision for purchase.
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http://dx.doi.org/10.1016/j.bjps.2014.01.003DOI Listing
April 2014

Up-regulation of two distinct p53-DNA binding functions by covalent poly(ADP-ribosyl)ation: transactivating and single strand break sensing.

Cancer Invest 2013 Nov;31(9):563-70

Centennial Alumnus, University of North Texas System, TX, USA, 1.

We used a [(32)P] p53 sequence-specific oligodeoxynucleotide and Electrophoretic-Mobility-Shift-Assays to monitor p53 DNA sequence-specific binding with p53-R267W, a nonbinding point mutant; and p53-Δ30, a deletion-mutant which lacks the carboxy-terminus that recognizes DNA-strand-breaks. Recombinant p53 and poly(ADP-ribose)polymerase-1 (PARP-1) were incubated with labeled βNAD(+) with/without DNA. The poly(ADP-ribosyl)ation of each protein increased with incubation-time and βNAD(+) and p53 concentration(s). Since p53-Δ30 was efficiently labeled, poly(ADP-ribosyl)ation target site(s) of wt-p53 must reside outside its carboxy-terminal-domain. The poly(ADP-ribosyl)ation of p53-Δ30 did not diminish its DNA binding; Instead, it enhanced DNA-sequence-specific-binding. Therefore, we conclude that DNA-sequence-specific-binding and DNA-nick-sensing of mutant-p53 are differentially regulated by poly(ADP-ribosyl)ation.
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http://dx.doi.org/10.3109/07357907.2013.845670DOI Listing
November 2013

p53-autoantibody may be more sensitive than CA-125 in monitoring microscopic and macroscopic residual disease after primary therapy for epithelial ovarian cancer.

J Cancer Res Clin Oncol 2013 Jul 11;139(7):1207-10. Epub 2013 Apr 11.

Department of Gynecology and Obstetrics, Jena University Hospital, Bachstrasse 18, 07743 Jena, Germany.

Purpose: To evaluate the use of p53-autoantibodies (p53-aab) for monitoring minimal disease after standard therapy of advanced epithelial ovarian cancer (EOC).

Methods: Retrospective analysis of p53-aab in preoperative and long-term follow-up serum samples from 10 patients selected for representing three relevant EOC subgroups: platinum-sensitive disease after macroscopic complete debulking (n = 4) and platinum-sensitive (n = 3) or platinum-resistant disease (n = 3), both after suboptimal debulking with residual tumor of <1 cm diameter. p53-aab levels were quantified by a sandwich ELISA in two independent experiments. CA-125 values of all samples and clinical information were retrieved from medical records.

Results: Patients with early relapse (median PFS 7 months, n = 8) had high p53-aab levels throughout follow-up while CA-125 values had dropped below the cut-off after primary surgery during or after chemotherapy in these cases. Patients with seroconversion to p53-aab negativity experienced prolonged PFS (n = 2; #1: 50 months, #2: no evidence of disease for 36 months until last follow-up). Continued p53-aab positivity was not related to the resection status or platinum sensitivity.

Conclusions: p53-autoantibodies may be a highly sensitive marker for minimal residual tumor mass after surgery and/or chemotherapy rather than standard CA-125, possibly due to the different nature of these markers. CA-125 released by cancer cells is related to tumor mass, whereas p53-aab levels can indicate the presence of few tumor cells due to amplification by the immune system. Seroconversion of p53-aab could be associated with long-term survival.
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http://dx.doi.org/10.1007/s00432-013-1432-2DOI Listing
July 2013

Three-dimensional surface-imaging systems.

Plast Reconstr Surg 2013 Apr;131(4):668e-670e

Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna (Tzou) Institute of Computer Graphics and Algorithms, Pattern Recognition and Image-Processing Group, Vienna University of Technology (Artner, Kropatsch) Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria (Frey).

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http://dx.doi.org/10.1097/PRS.0b013e3182827abeDOI Listing
April 2013

Anatomy of the sural nerve: cadaver study and literature review.

Plast Reconstr Surg 2013 Apr;131(4):802-810

Vienna, Austria From the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna.

Background: The sural nerve is commonly used as donor for nerve grafting. Contrary to its constant retromalleolar position, formation and course of the proximal sural nerve show great variability. The coexistence of different and deceptive terminologies contributes to the complexity, and reviewing the international literature is confusing. Because detailed anatomical knowledge is essential for efficient and safe sural nerve harvesting, this study aims to bring clarity.

Methods: Previous sural nerve reports listed in the PubMed database and established anatomical textbooks were reviewed. Different terminologies were compared and adjusted. Anatomical details and variations were noted. Subtle prospective anatomical dissections and comparison with actual data followed.

Results: Two hundred twenty-one relevant reports were identified and worked up going back to the nineteenth century. Fourteen established German and English language anatomical textbooks were reviewed. Thirty lower limbs were dissected. In total, this study pools the information of more than 2500 sural nerves.

Conclusions: This study covers all information about the sural nerve anatomy published internationally. The coexistence of different and confusing terminologies is pinpointed and adjusted to allow comparison of previous reports and to gain a coordinated data pool of more than 2500 investigated sural nerves. Detailed features are clearly described and summarized, findings from the authors' own prospective dissections complete these data, and the prior existing anatomical confusion is resolved. Finally, clinical implications are described.
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http://dx.doi.org/10.1097/PRS.0b013e3182818cd4DOI Listing
April 2013

Prospective study on harvesting autologous bone grafts from the anterior iliac crest using a new specialized reamer.

Ann Plast Surg 2013 Nov;71(5):566-70

From the *Division of Plastic and Reconstructive Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; †Handcenter Ravensburg, Krankenhaus St. Elisabeth, Elisabethenstr. 19, 88212 Ravensburg, Germany; and ‡Clinic for Handsurgery Bad Neustadt, Salzburger Leite 1, 97616 Bad Neustadt/Saale, Germany.

The iliac crest remains the most frequent donor site for bone harvesting. Despite the surgical access to the iliac crest being relatively simple and the operation being carried out regularly, there are frequent complications. Therefore, a new, manual iliac crest reamer (R group) was compared to the classical harvesting of a corticocancellous bone graft by means of an oscillating saw (Con group) in a prospective study on 80 consecutive patients having hand surgery. Follow-up time was 3 months. Operation time and incidence of hematomas, seromas, and paresthesias in the R group were significantly shorter and less, respectively, than in the Con group. Pain at harvest site measured with the visual analogue scale (VAS) at 5 days, 6 weeks, and 12 weeks postoperatively was significantly less in group R as well. The utilization of the iliac crest reamer allows bone graft harvest in a relatively quick and simple operation with relatively few complications but with the limitation in that the maximum diameter of a bone cylinder that it can harvest is 20 mm.
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http://dx.doi.org/10.1097/SAP.0b013e31824f2500DOI Listing
November 2013

Role of KCNQ channels in skeletal muscle arteries and periadventitial vascular dysfunction.

Hypertension 2013 Jan 26;61(1):151-9. Epub 2012 Nov 26.

Centre for Biomedicine and Medical Technology Mannheim, Research Division Cardiovascular Physiology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

KCNQ channels have been identified in arterial smooth muscle. However, their role in vasoregulation and chronic vascular diseases remains elusive. We tested the hypothesis that KCNQ channels contribute to periadventitial vasoregulation in peripheral skeletal muscle arteries by perivascular adipose tissue and that they represent novel targets to rescue periadventitial vascular dysfunction. Two models, spontaneously hypertensive rats and New Zealand obese mice, were studied using quantitative polymerase chain reaction, the patch-clamp technique, membrane potential measurements, myography of isolated vessels, and blood pressure telemetry. In rat Gracilis muscle arteries, anticontractile effects of perivascular fat were inhibited by the KCNQ channel blockers XE991 and linopirdine but not by other selective K(+) channel inhibitors. Accordingly, XE991 and linopirdine blocked noninactivating K(+) currents in freshly isolated Gracilis artery smooth muscle cells. mRNAs of several KCNQ channel subtypes were detected in those arteries, with KCNQ4 channels being dominant. In spontaneously hypertensive rats, the anticontractile effect of perivascular fat in Gracilis muscle arteries was largely reduced compared with Wistar rats. However, the vasodilator effects of KCNQ channel openers and mRNA expression of KCNQ channels were normal. Furthermore, KCNQ channel openers restored the diminished anticontractile effects of perivascular fat in spontaneously hypertensive rats. Moreover, KCNQ channel openers reduced arterial blood pressure in both models of hypertension independent of ganglionic blockade. Thus, our data suggest that KCNQ channels play a pivotal role in periadventitial vasoregulation of peripheral skeletal muscle arteries, and KCNQ channel opening may be an effective mechanism to improve impaired periadventitial vasoregulation and associated hypertension.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.112.197566DOI Listing
January 2013

Prospective evaluation of a single-sided innervated gluteal artery perforator flap for reconstruction for extensive and recurrent pilonidal sinus disease: functional, aesthetic, and patient-reported long-term outcomes.

World J Surg 2012 Sep;36(9):2230-6

Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Background: Treating large and extensive pilonidal sinus disease is a challenging task. Long-term reports on flaps suitable for coverage of large, wide, local-excision defects are sparse. We prospectively evaluated data with a minimum 1-year follow-up of the use of a single-sided, innervated, superior gluteal artery perforator flap.

Methods: Twenty-one patients (1 woman, 20 men) with a median age of 26 years (min - max = 18 - 46) were included in the study period from September 2005 to April 2010. We recorded flap size, major and minor complications, hospital length of stay, impairment in activities of daily living, pain, aesthetic outcomes, and sensibility in the gluteal region (PSSD, pressure-specified sensory device) at 6 and 12 months postoperatively.

Results: The mean defect size (±SD) was 13.0 ± 1.9 × 8.6 ± 1.3 × 5.5 ± 1.2 cm (height × width × depth), and median length of hospital stay was 9 days (range = 7-11). Only two patients developed minor wound-healing complications. Visual analog pain scales significantly improved, with no pain detectable at 12 months postoperatively (p < 0.0001). The aesthetic appearance of the results was good in the majority of patients (61.9-85.7 %). PSSD showed gradual normalization, with retained sensibility in the flap area over 12 months postoperatively (p = 0.0232). During the median 36-month (range = 20-60) follow-up, we have not observed any recurrence in the operated area.

Conclusions: The innervated superior gluteal artery perforator flap is a useful technique for covering large and recurrent pilonidal sinus defects following wide local excision and represents an excellent tool in the surgical armamentarium for achieving long-lasting outcomes in this young group of patients.
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http://dx.doi.org/10.1007/s00268-012-1639-4DOI Listing
September 2012

After massive weight loss: patients' expectations of body contouring surgery.

Obes Surg 2012 Apr;22(4):544-8

Divison of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, General Hospital Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background: Massive weight loss following bariatric surgery leads to excess skin with functional and aesthetic impairments. Surplus skin can then contribute to problems with additional weight loss or gain. The aims of the current study were to evaluate the frequency of massive soft tissue development in gastric bypass patients, to determine whether males and females experience similar post-bypass body changes, and to learn about the expectations and impairments related to body contouring surgery.

Methods: A questionnaire addressing information on the satisfaction of body image, quality of life, and expectation of body contouring surgery following massive weight loss was mailed to 425 patients who had undergone gastric bypass surgery between 2003 and 2009. Of these 425 individuals, 252 (59%) patients completed the survey.

Results: Ninety percent of women and 88% of men surveyed rated their appearance following massive weight loss as satisfactory, good, or very good. However, 96% of all patients developed surplus skin, which caused intertriginous dermatitis and itching. In addition, patients reported problems with physical activity (playing sports) and finding clothing that fit appropriately. Moreover, 75% of female and 68% of male patients reported desiring body contouring surgery. The most important expectation of body contouring surgery was improved appearance, followed by improved self-confidence and quality of life.

Conclusions: Surplus skin resulting from gastric bypass surgery is a common issue that causes functional and aesthetic impairments in patients. Consequently, this increases the desire for body contouring surgery with high expectations for the aesthetic outcome as well as improved life satisfaction.
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http://dx.doi.org/10.1007/s11695-011-0551-6DOI Listing
April 2012

Correlation of functional recovery with the course of electrophysiological parameters after free muscle transfer for reconstruction of the smile in irreversible facial palsy.

Muscle Nerve 2011 Nov;44(5):741-8

Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Introduction: The aim of this study was to determine whether processes of denervation and reinnervation, as measured by electrodiagnostic methods, correlate with clinical function, as measured by three-dimensional (3D) video analysis and whether electrodiagnostic data can serve as a prognostic indicator.

Methods: Eighteen patients with facial palsy were investigated by 3D video analysis, needle electromyography, and electrical muscle testing at 6, 12, and 18 months after free muscle transplantation for smile reconstruction.

Results: Electrophysiological parameters determined 6 months postoperatively correlated significantly with the index of dynamic symmetry 12 and 18 months postoperatively.

Conclusions: Processes of reinnervation can be detected earlier by electrophysiological analysis than by quantified clinical analysis. Pathological spontaneous activity alone and combined assessment with motor unit action potentials in the early postoperative stage are strong prognostic indicators.
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http://dx.doi.org/10.1002/mus.22151DOI Listing
November 2011

3D video analysis of facial movements.

Facial Plast Surg Clin North Am 2011 Nov;19(4):639-46, viii

Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

This article presents a review of 3D video analysis for use in patients with facial paralysis. The difficulties inherent in quantifying the degree of facial paralysis and the effect of therapeutics that has led to the use of videos and computer-assisted 3D analysis are discussed, which can yield quantifiable results of treatment, allow the description and quantification of facial paralysis, and become a tool in the planning of operative procedures. The authors provide a step-by-step overview of video analysis, and present case studies from two specific techniques they have used in reconstruction surgery.
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http://dx.doi.org/10.1016/j.fsc.2011.07.007DOI Listing
November 2011

Evolution of 3D surface imaging systems in facial plastic surgery.

Facial Plast Surg Clin North Am 2011 Nov;19(4):591-602, vii

Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Recent advancements in computer technologies have propelled the development of 3D imaging systems. 3D surface-imaging is taking surgeons to a new level of communication with patients; moreover, it provides quick and standardized image documentation. This article recounts the chronologic evolution of 3D surface imaging, and summarizes the current status of today's facial surface capturing technology. This article also discusses current 3D surface imaging hardware and software, and their different techniques, technologies, and scientific validation, which provides surgeons with the background information necessary for evaluating the systems and knowledge about the systems they might incorporate into their own practice.
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http://dx.doi.org/10.1016/j.fsc.2011.07.003DOI Listing
November 2011

Coenzyme Q10 does not enhance preadipocyte viability in an in vitro lipotransfer model.

Aesthetic Plast Surg 2012 Apr 1;36(2):453-7. Epub 2011 Oct 1.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University Vienna, Währingergürtel 18-20, 1090, Vienna, Austria.

Background: Autologous fat is an attractive soft-tissue filler in plastic and reconstructive surgery. The success of the procedure relies strongly on the technique of transferring viable preadipocytes. Among other factors, preadipocyte viability is impaired by local anesthetics. Application of coenzyme Q10 is being performed by aesthetic plastic surgeons to enhance the success of lipotransfer. The aim of this study was to evaluate the effect of Q10 on preadipocyte viability with special regard to impairment after lidocaine treatment.

Methods: Preadipocytes were pretreated with coenzyme Q10 or vehicle control followed by incubation with lidocaine for 30 min. Viability and apoptosis were assessed by FACS analysis and Western blot.

Results: Coenzyme Q10 did not improve viability nor have any effect on investigated apoptosis parameters. Preadipocyte viability was reduced after lidocaine treatment. Surface binding of annexin V, cleavage of caspase-3, and abundance of subdiploid cells were not detectable though, suggesting that necrosis rather than apoptosis is the cause for reduced preadipocyte viability.

Conclusion: Our results indicate that Q10 does not improve preadipocyte viability. Preadipocyte cell death induced by lidocaine is not caused by apoptosis but by necrosis, which cannot be prevented by coenzyme Q10. These findings should be taken into account when searching for solutions to improve preadipocyte viability in the context of soft tissue engineering and autologous fat transfer.
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http://dx.doi.org/10.1007/s00266-011-9823-8DOI Listing
April 2012

Adipose tissue engineering: three different approaches to seed preadipocytes on a collagen-elastin matrix.

Ann Plast Surg 2011 Nov;67(5):484-8

Vienna Burn Centre, Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University Vienna, Währinger Gürtel 18–20, Vienna, Austria.

Background: Millions of plastic and reconstructive surgical procedures are performed each year to repair soft-tissue defects that result from significant burns, tumor resections, or congenital defects. Tissue-engineering strategies have been investigated to develop methods for generating soft-tissue. Preadipocytes represent a promising autologous cell source for adipose tissue engineering. These immature precursor cells, which are located between the mature adipocytes in the adipose tissue, are much more resistant to mechanical stress and ischemic conditions than mature adipocytes. To use preadipocytes for tissue-engineering purposes, cells were isolated from human adipose tissue and seeded onto scaffolds. Once processed, preadipocytes become subject to the human tissue act and require handling under much tighter regulations. Therefore, we intended to identify any influence caused by processing of preadipocytes prior to seeding on the reconstructed adipose tissue formation.

Material And Method: Human preadipocytes were isolated from subcutaneous adipose tissue obtained from discarded tissue during abdominoplasties of healthy men and women. Preadipocytes were divided into 3 groups. Cells of group I were seeded onto the scaffold directly after isolation, cells of group II were proliferated for 4 days before seeding, and cells of group III were proliferated and induced to differentiate before seeded onto the scaffold. A 3-dimensional scaffold (Matriderm, Dr. Otto Suwelack Skin and Health Care GmbH, Billerbeck, Germany) containing bovine collagen and elastin served as a carrier. Fourteen days after isolation, all scaffolds were histologically evaluated, using hematoxylin and eosin, anti-Ki-67 antibody, as well as immunofluorescence labeling with Pref-1 antibody (DLK (C-19), peroxisome proliferator-activated receptor gamma antibody, and DAPI (4',6-diamidino-2-phenylindole).

Results: Cells of all groups adhered to the scaffolds on day 21 after isolation. Cells of groups I (freshly isolated preadipocytes) and II (proliferated preadipocytes) adhered well and penetrated into deeper layers of the matrix. In group III (induced preadipocytes), penetration of cells was primarily observed to the surface area of the scaffold.

Discussion/conclusion: : The collagen-elastin matrix serves as a useful scaffold for adipose tissue engineering. Freshly isolated preadipocytes as well as proliferated preadipocytes showed good penetration into deeper layers of the scaffold, whereas induced preadipocytes attached primarily to the surface of the matrix. We conclude that there might be different indications for each approach.
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http://dx.doi.org/10.1097/SAP.0b013e31822f9946DOI Listing
November 2011

Bridging peripheral nerve defects using a single-fascicle nerve graft.

Plast Reconstr Surg 2011 Oct;128(4):861-869

Vienna, Austria From the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna.

Background: The criterion standard of nerve reconstruction is an autologous nerve graft, identical in cross-section to the severed nerve stumps. This study investigates single-fascicle nerve transplantation to bridge nerve defects.

Methods: Forty female Sprague-Dawley rats, each weighing approximately 225 g, were randomized into five groups. Groups A and B were the positive and negative control groups, respectively. In the experimental groups (groups C, D, and E), a nerve defect of 25 mm was created in the right sciatic nerve and reconstructed with a reversed sciatic nerve graft, a three-fascicle sural nerve graft, or a single-fascicle sural nerve graft, respectively.

Results: Functional muscle evaluation of the triceps surae differed significantly among the reverse nerve (group C, n=10; 600±154.16 mN), triple-fascicle (group D, n=10; 411±262 mN), and single-fascicle (group E, n=10; 324±215.8 mN) graft groups (p<0.05). The results of retrograde labeling of the reverse nerve group (group C, 518±2) showed that there were twice as many motor neurons as in the three-fascicle nerve group (group D, 221±19). In the single-fascicle nerve group, motor neurons were scarce and faintly labeled (group E, 180±25).

Conclusion: The results showed that single-fascicle nerve grafting has potential for good functional nerve regeneration.
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http://dx.doi.org/10.1097/PRS.0b013e31821b6369DOI Listing
October 2011

Train surfing and other high voltage trauma: differences in injury-related mechanisms and operative outcomes after fasciotomy, amputation and soft-tissue coverage.

Burns 2011 Dec 17;37(8):1427-34. Epub 2011 Aug 17.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Background: In the context of scarce reports on train surfers among high voltage electric injuries, we conducted a retrospective review between January 1994 and December 2008.

Methods: After matching for inclusion criteria we reviewed patient records of 37 true high voltage injuries (12 train surfers [TS] and 25 other high voltage injuries [HV]).

Results: TS were significantly younger (TS 15.8 years vs. HV 33.3 years, p<0.0001), and had a greater %TBSA (TS 49.7%TBSA vs. HV 21.5%TBSA, p=0.0003) without affecting the median length-of-stay (TS 52 days vs. HV 49 days) or number of operations (TS 4 vs. HV 3). TS had different injury patterns, with a higher percentage of affected extremities (TS 72.9% vs. HV 52.0%, p=0.0468) and associated injuries (TS 58% vs. HV 20%, n.s.) than HV. Both groups demonstrated comparable fasciotomy (TS 71.4% vs. HV 55.8%) and amputation rates (TS 17.1% vs. HV 15.4%). While TS required less flaps (TS 3/12 vs. HV 18/25; p=0.0153), soft-tissue reconstruction revealed an overall low incidence of complication rates (one partial pedicled flap loss and two total free flap losses).

Conclusions: Train surfers have proven to be a distinct group of patients among high-voltage injuries notably as a result of a younger age, a shorter electric contact duration and higher velocity-induced trauma. With a possibly declining trend of train surfing-related accidents in an aging society, it will be interesting to see if emerging economies will face comparable phenomena, for which prevention strategies remain key.
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http://dx.doi.org/10.1016/j.burns.2011.07.016DOI Listing
December 2011

Evolution of the 3-dimensional video system for facial motion analysis: ten years' experiences and recent developments.

Ann Plast Surg 2012 Aug;69(2):173-85

Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.

Since the implementation of the computer-aided system for assessing facial palsy in 1999 by Frey et al (Plast Reconstr Surg. 1999;104:2032-2039), no similar system that can make an objective, three-dimensional, quantitative analysis of facial movements has been marketed. This system has been in routine use since its launch, and it has proven to be reliable, clinically applicable, and therapeutically accurate. With the cooperation of international partners, more than 200 patients were analyzed. Recent developments in computer vision--mostly in the area of generative face models, applying active--appearance models (and extensions), optical flow, and video-tracking-have been successfully incorporated to automate the prototype system. Further market-ready development and a business partner will be needed to enable the production of this system to enhance clinical methodology in diagnostic and prognostic accuracy as a personalized therapy concept, leading to better results and higher quality of life for patients with impaired facial function.
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http://dx.doi.org/10.1097/SAP.0b013e3182223d96DOI Listing
August 2012

Comparison of meshed versus MEEK micrografted skin expansion rate: claimed, achieved, and polled results.

Plast Reconstr Surg 2011 Jul;128(1):40e-41e

Division of Plastic and Reconstructive Surgery; Department of Surgery; Medical University of Vienna; Vienna, Austria.

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http://dx.doi.org/10.1097/PRS.0b013e318217463aDOI Listing
July 2011

The prevalence of body contouring surgery after gastric bypass surgery.

Obes Surg 2012 Jan;22(1):8-12

Department of Surgery, Divison of Plastic and Reconstructive Surgery, Medical University of Vienna, General Hospital Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Background: As bariatric surgery has become more popular, more patients are undergoing body contouring surgery after massive weight loss. Many of the surgical procedures performed on the massive weight loss patient are complex and labor-intensive. Therefore, the plastic surgery unit needs to be prepared for a patient's demand. Little literature is available on how frequently patients who have undergone gastric bypass surgery receive body contouring surgery.

Methods: Two hundred fifty-two subjects (out of 425 who were mailed the questionnaire) who had undergone gastric bypass surgery between 2003 and 2009 completed the questionnaire, which obtained information on body image satisfaction and frequency of body contouring surgery after massive weight loss.

Results: Of all patients, 74% desire a body contouring surgery after gastric bypass surgery. Fifty-three patients (21%) have undergone a total of 61 body contouring procedures. The most common were abdominoplasties (59%), followed by lower body lifts (20%). In contrast to a positive judgment of the general aspect of the body image satisfaction after massive weight loss, both genders are unsatisfied with body areas like abdomen/waist, breast, and thighs.

Conclusions: Paralleling the increasing use of bariatric surgery, there is a high demand for body contouring surgery. A huge disparity exists between the number of subjects who desire a body contouring surgery and those who actually received it.
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http://dx.doi.org/10.1007/s11695-011-0459-1DOI Listing
January 2012

Forequarter amputation combined with chest wall resection: a single-center experience.

Ann Thorac Surg 2011 Jun;91(6):1702-8

Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.

Background: Forequarter amputation combined with chest wall resection is a rarely performed procedure. Six patients were treated for advanced malignancies with this operation in our institution since 1993. Uncontrollable pain, lymphedema, loss of function of the affected limb and, in some patients, localized ulceration of the tumor at the time of presentation, provided the indication for the operation. All patients underwent radical amputation of the upper limb and the structures of the shoulder girdle, in combination with resection of the thoracic chest wall in an extent of 2 to 7 ribs.

Methods: Chest wall reconstruction was achieved by implantation of a polytetrafluoroethylene patch (n=5) or a combination of a metal implant (Stratos System R, MedXpert GmbH, Heitersheim, Germany) and a polytetrafluoroethylene patch (n=1). Myocutaneous coverage of the defects was achieved by use of pedicled flaps from adjacent tissue (n=3) or by free myocutaneous flaps harvested from the amputated forearm (n=3).

Results: No perioperative mortality occurred; however, significant morbidity was seen after the use of the free forearm flaps based on occurring vascular problems. All 3 patients had to undergo surgical revision of the flap. Survival ranged from 5 to 50 months (median=23.5 months) with 3 patients still alive at the time of this investigation.

Conclusions: Forequarter amputation in combination with chest wall resection is a feasible and potentially curative treatment for malignant tumors of the shoulder girdle with invasion of the chest wall. The operation results in immediate palliation and long-term survival can be obtained in selected cases.
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http://dx.doi.org/10.1016/j.athoracsur.2011.02.056DOI Listing
June 2011
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