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In this review article, we discuss the current state of knowledge in cancer research under real and simulated microgravity conditions and point out further research directions in this field. Outer space is an extremely hostile environment for human life, with radiation, microgravity, and vacuum posing significant hazards. Although the risk for cancer in astronauts is not clear, microgravity plays a thought-provoking role in the carcinogenesis of normal and cancer cells, causing such effects as multicellular spheroid formation, cytoskeleton rearrangement, alteration of gene expression and protein synthesis, and apoptosis. Furthermore, deleterious effects of radiation on cells seem to be accentuated under microgravity. Ground-based facilities have been used to study microgravity effects in addition to laborious experiments during parabolic flights or on space stations. Some potential 'gravisensors' have already been detected, and further identification of these mechanisms of mechanosensitivity could open up ways for therapeutic influence on cancer growth and apoptosis. These novel findings may help to find new effective cancer treatments and to provide health protection for humans on future long-term spaceflights and exploration of outer space. ispartof: BIOMEDICINES vol:10 issue:1 ispartof: location:Switzerland status: published

Recently, we reported defect coverage in the clavicular region with a scar-sparing pectoralis major flap. We successfully combine this flap with a clavicular reconstruction by an iliac bone graft for non-union now. We propose this reconstructive combination for cases of clavicular non-union with lack of soft tissue coverage.

Background: Plastic surgery was first introduced as a sub-specialty of general surgery in Germany in 1978. Since then, this surgical subspecialty/discipline has evolved enormous potential, e.g., in the collaboration with other disciplines such as general and abdominal surgery. Aim: To highlight and summarize the basic potential, technical options and novel aspects of plastic surgery, which are relevant for the common interdisciplinary surgical strategies of plastic and general as well as abdominal surgery in clinical practice. Method: Short and compact narrative review based on i) a selection of relevant references from the medical scientific literature and ii) surgical experiences obtained in daily work. Results (selected corner points): 1) Biological protection procedures in vascular surgery by flap coverage after meticulous debridement with or without autogenic vascular reconstruction are used to overcome infection of a vascular prosthesis, a serious problem, associated with the risk of anastomotic rupture and bleeding by transfer of immunological competence due to tissue coverage and finally to induce healing in the area of an infected vascular prosthesis. 2) Fistula treatment for aorto-tracheal or aorto-duodenal fistulas, a big challenge for the referring general surgeon, can be treated by flap coverage, such as by using the interposition of a pectoralis-major flap and the omentum-majus flap, respectively. 3) With regard to nerve surgery, encouraging results after early microsurgical recurrent laryngeal nerve repair with improved subjective voice quality or concerning reconstitution of respiratory capacity in diaphragmatic palsy has been reported. 4) Lymphatic surgery for lymphedema occurring either primarily due to an absence or lack of lymphatic vessels or secondarily due to infection, trauma, radiation therapy or surgery can be indicated in specialized microsurgical centers, e.g., for surgical repair of the lymphatic pathway by i) the interrupted lymphatic system can be reconstructed by an interposition, or ii) the lymphatic fluid can be drained extraanatomically (e.g., by a lymphatico-venous anastomosis). Further techniques are free lymph-node transplantation included in a free vascularized groin flap or autologous lymphatic-vessel transfer or vein-graft interposition (used for lymphatic-vessel interposition). 5) Mass reduction such as dermolipectomy with subsequent split-thickness is a valuable option, which provides excellent volume reduction. 6) Defect coverage: A. Split- or full-thickness skin grafts are a common method of defect coverage in case that the wound bed is clean and well-vascularized and if there is a lack of donor skin, or if the graft bed is of questionable quality using various allogenic or xenogenic skin substitute materials. B. Further methods offer a wide-range armamentarium of local and free fasciocutaneus and musculocutaneous flaps, e.g., after abdomino-perineal rectum extirpation using the vertical rectus-abdominis myocutaneous flap (VRAM) or propeller flaps according to the “angiosome”. 7) Abdominal wall hernia closure with instable skin coverage, flap closure, either alone or in combination with mesh is superior to mesh closure only. 8) Free flaps: If there is no option for a local or pedicled flap availabe, free flaps can be well used for abdominal wall-defect closure (complication rate in experienced hands, low). Conclusion: Plastic surgery is an indispensable partner for specific surgical problems and clinical situations of general and abdominal surgery, which indicates that each general and abdominal surgeon should be well notified on the great options and surgical techniques, which modern plastic surgery can provide to achieve best outcome and quality of life for the patients by combined expertise of these two surgical disciplines.

BACKGROUND In obtaining human tenocytes for tendon tissue engineering, a low proliferation rate and phenotype loss during passaging is a problem. It was the authors' aim to evaluate the influence of vascular endothelial growth factor (VEGF) on human tenocyte growth and gene expression. METHODS Human tenocytes were exposed to human VEGF in various concentrations (5, 10, and 20 ng/ml) for 5 days. Cell proliferation was counted and expression of tendon-related genes was analyzed. RESULTS Tenocyte count was 1.4 × 10(5)/ml, 2.7 × 10(5)/ml, 2.3 × 10(5)/ml, and 3.7 × 10(5)/ml for 0, 5, 10, and 20 ng/ml VEGF, respectively. Expression of Col1 was up-regulated 6.4 ± 4.2-fold, 60.1 ± 21.6-fold, and 15.8 ± 10.2-fold for 5, 10, and 20 ng/ml VEGF; all differences were significant with p < 0.05. Col3 was down-regulated to 0.2 ± 0.1-fold, 0.3 ± 0.1-fold, and 0.1 ± 0.03-fold for 5, 10, and 20 ng/ml VEGF; all differences were significant. Eln was up-regulated 2.3 ± 1.7-fold, 25.5 ± 10.9-fold, and 16.6 ± 9.0-fold for 5, 10, and 20 ng/ml VEGF; differences were significant for 10 and 20 ng/ml VEGF. TSC was down-regulated to 0.3 ± 0.1-fold and 0.3 ± 0.1-fold for 5 and 20 ng/ml VEGF; differences were significant for 5 and 20 ng/ml. SCX was up-regulated to 31.3 ± 8.5-fold, 49.1 ± 23.4-fold, and 20.9 ± 9.5-fold for 5, 10, and 20 ng/ml VEGF; all changes were significant. CONCLUSIONS VEGF enhances proliferation and expression of tendon-related genes in human tenocytes. It could therefore be a useful addition for tenocyte cultivation.

Facial rejuvenation with injectable filler substances is a frequently applied outpatient procedure. However, light, moderate, and even severe complications may occur. A case of tissue necrosis at the upper lip after injection of highly cross-linked hyaluronic acid together with the following salvage procedure is presented here. We discuss this complication with respect to relevant anatomy and physicochemical properties of the filler substance and review the recommendations given in literature for decreasing the likelihood of such an adverse event.

Introduction Microgravity has been shown to impose various effects on breast cancer cells. We exposed human breast cancer cells to simulated microgravity and studied morphology and alterations in gene expression. Materials and methods Human breast cancer cells were exposed to simulated microgravity in a random positioning machine (RPM) for 24 h. Morphology was observed under light microscopy, and gene alteration was studied by qPCR. Results After 24 h, formation of three-dimensional structures (spheroids) occurred. BRCA1 expression was significantly increased (1.9×, p p p p MAPK1, MMP13, PTEN, and TP53. Conclusions Simulated microgravity induces spheroid formation in human breast cancer cells within 24 h and alters gene expression toward modified adhesion properties, enhanced cell repair, and phenotype preservation. Further insights into the underlying mechanisms could open up the way toward new therapies.

We studied the behavior of Ewing’s Sarcoma cells of the line A673 under simulated microgravity (s-µg). These cells express two prominent markers—the oncogene EWS/FLI1 and the chemokine receptor CXCR4, which is used as a target of treatment in several types of cancer. The cells were exposed to s-µg in a random-positioning machine (RPM) for 24 h in the absence and presence of the CXCR4 inhibitor AMD3100. Then, their morphology and cytoskeleton were examined. The expression of selected mutually interacting genes was measured by qRT-PCR and protein accumulation was determined by western blotting. After 24 h incubation on the RPM, a splitting of the A673 cell population in adherent and spheroid cells was observed. Compared to 1 g control cells, EWS/FLI1 was significantly upregulated in the adherent cells and in the spheroids, while CXCR4 and CD44 expression were significantly enhanced in spheroids only. Transcription of CAV-1 was upregulated and DKK2 and VEGF-A were down-regulated in both, adherent in spheroid cells, respectively. Regarding, protein accumulation EWS/FLI1 was enhanced in adherent cells only, but CD44 decreased in spheroids and adherent cells. Inhibition of CXCR4 did not change spheroid count, or structure. Under s-µg, the tumor marker EWS/FLI1 is intensified, while targeting CXCR4, which influences adhesion proteins, did not affect spheroid formation.

Teaching in surgery, one of the classical big clinical and main disciplines beside internal medicine, needs to be also associated with great attention in regard to a valuable final result at the end of the study of human medicine. In particular, surgery is not only the subject to a large number of lectures it also represents one third (four months) of the compulsory internship (practical year – in German, “Praktisches Jahr”) at the end of the study of medicine. Therefore, medical teaching of students should be always part of serious and steady attempts to optimize course und contents as a component of guiding activities focussing onto the substantial improvement of the study of medicine. In detail, the classical and traditionally established type of teaching, the (oral) lecture, has to be further developed and reasonably completed by numerous interactive and practice-oriented teaching, learning and examining modalities (obligatory or facultative seminars / courses, training in [very] small groups of students, bed-side teaching, individual practical exercises within the SkillsLab, groups of young researchers, research projects in teaching, scientific publications on topics and recommendable experiences ot teaching including students, ”Teach-the-teacher“ projects etc.). Although many novel concepts have been inaugurated and considerable advances have been achieved, there is a steady need for further improvement. In the presented representative but medical school-specific overview, the current complex surgical teaching concept, which has been continuously optimized over the last couple of years, at the Otto-von-Guericke University Medical School with University Hospital of Magdeburg (Germany) is described as a scientific and systematizing document as well as a manuscript associated with the ongoing preparation of an institutional “Teaching Manual” on surgical teaching and training for medical students. It should – last but not least – provide the basis for a public discussion, which vice versa might hopefully and possibly result in further structural reforms of (surgical) teaching in the near future.

Background: Lung cancer cells are known to change proliferation and migration under simulated microgravity. In this study, we sought to evaluate cell adherence, apoptosis, cytoskeleton arrangement, and gene expression under simulated microgravity. Methods: Human lung cancer cells were exposed to simulated microgravity in a random-positioning machine (RPM). Cell morphology and adherence were observed under phase-contrast microscopy, cytoskeleton staining was performed, apoptosis rate was determined, and changes in gene and protein expression were detected by real-time PCR with western blot confirmation. Results: Three-dimensional (3D)-spheroid formation was observed under simulated microgravity. Cell viability was not impaired. Actin filaments showed a shift in alignment from longitudinal to spherical. Apoptosis rate was significantly increased in the spheroids compared to the control. TP53, CDKN2A, PTEN, and RB1 gene expression was significantly upregulated in the adherent cells under simulated microgravity with an increase in corresponding protein production for p14 and RB1. SOX2 expression was significantly upregulated in the adherent cells, but protein was not. Gene expressions of AKT3, PIK3CA, and NFE2L2 remained unaltered. Conclusion: Simulated microgravity induces alteration in cell adherence, increases apoptosis rate, and leads to upregulation of tumor suppressor genes in human lung cancer cells.

Objective Weightlessness simulation due to the simulated microgravity has been shown to considerably affect behavior of tumor cells. It is aim of this study to evaluate characteristics of human breast cancer cells in this scaffold- free 3D culture model. Materials And Methods In this experimental study, the cells were exposed to simulated microgravity in a random- positioning machine (RPM) for five days. Morphology was observed under phase-contrast and confocal microscopy. Cytofilament staining was performed and changes in expression level of cytofilament genes, proliferation/differentiation genes, oncogenes and tumor suppressor genes were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), followed by western blot confirmation. Results After five days, distinct spheroid formation was observed. Rearrangement of the cytoskeleton into spherical shape was visible. VIM gene expression was significantly up-regulated for adherent cells and spheroids (3.3x and 3.6x respectively, P

The flexor tendon sheath is an ideal target for tissue engineering because it is difficult to reconstruct by conventional surgical methods. The authors hypothesized that decellularized porcine pericardium can be used as a scaffold for engineering a biologically active tendon sheath. The authors’ protocol removed cellular material from the pericardium and preserved the structural architecture in addition to the collagen and glycosaminoglycan content. The scaffold was successfully reseeded with human sheath synoviocytes and human adipose-derived stem cells. Cells were evaluated for 8 weeks after reseeding. The reseeded construct demonstrated continuous production of hyaluronic acid, the main component of synovial fluid. After being seeded on the membrane, adipose-derived stem cells demonstrated down-regulation of collagen I and III and up-regulation of hyaluronan synthase 2. The results indicate that decellularized porcine pericardium may be a potential scaffold for engineering a biologically active human tendon sheath.

Background For tendon tissue engineering, tenocyte-seeded scaffolds are a promising approach. Under conventional 2D culture however, tenocytes show rapid senescene and phenotype loss. We hypothesized that phenotype loss could be counteracted by simulated microgravity conditions. Methods Human tenocytes were exposed to microgravity for 9 days on a Random Positioning Machine (RPM). Formation of 3D-structures (spheroids) was observed under light microscopy, gene expression was measured by real-time PCR. Cells under conventional 2D-culture served as control group. Results Simulated microgravity reached a value of as low as 0.003g. Spheroid formation was observed after 4 days, and spheroids showed stable existance to the end of the observation period. After 9 days, spheroids showed a significantly higher gene expression of collagen 1 (Col1A1) compared to adherent cells under microgravity (4.4x, p=0.04) and compared to the control group (5.6x, p=0.02). Gene expression of collagen 3 (COL3A1) was significantly increased in spheroids compared to the control group (2.3x, p=0.03). Gene expressions of the extracellular matrix genes Tenascin C und Fibronectin (TNC and FN) were increased in adherent cells under microgravity compared to the 1g-control group, not reaching statistical significance (p=0.1 and p=0.3). For the gene expression of vimentin, no significant alteration was observed both in the adherent cells and in the spheroids compared to the 1g control group. Gene expression of the tenocyte-specific transcription factor scleraxis (SCX) was significantly increased in spheroids compared to the control group (3.7x, p=0.03). Conclusion Simulated microgravity could counteract tenocyte senescence in vitro and serve as a promising model for scaffold-free 3D cell culturing and tissue engineering. Level of evidence V (laboratory study).

Seeding acellularized tendons with cells is an approach for creating tissue-engineered tendon grafts with favorable biomechanical properties. It was the authors' aim to evaluate whether human adipose-derived stem cells could replace tenocytes for scaffold seeding.Adipose-derived stem cells and tenocytes were co-cultured in different ratios (3:1, 1:1, and 1:3) and with three different methods: (1) direct co-culture, (2) tenocyte-conditioned media on adipose-derived stem cells, and (3) an insert system to keep both cell types in the same media without contact. Proliferation, collagen production, and tenogenic marker expression were measured by hematocytometry, immunocytochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction.Proliferation and collagen production were similar for tenocytes and adipose-derived stem cells alone. Phenotype difference between adipose-derived stem cells and tenocytes was indicated by higher tenascin C and scleraxis expression in tenocytes. Proliferation was increased in direct co-cultures, especially at an adipose-derived stem cells-to-tenocyte ratio of 3:1, and for tenocytes in adipose-derived stem cell-conditioned media. Direct co-culture caused significant up-regulation in tenascin C expression in adipose-derived stem cells (4.0-fold; p005). In tenocyte-conditioned media, tenascin C expression was up-regulated 2.5-fold (p0.05). In the insert system, tenascin C expression was up-regulated 2.3-fold (p0.05).Adipose-derived stem cells are good candidates for tendon tissue engineering because they are similar to tenocytes in proliferation and collagen production. With an optimal ratio of 3:1, they increase proliferation in co-culture and change their phenotype toward a tenogenic direction.

The authors review the relevant anatomy and provide technical tips for endoscopic decompression of the cubital tunnel. Cubital tunnel syndrome is the second most common nerve compression syndrome in the upper extremity. Until recently, surgeons focused on open decompression combined with submuscular or subcutaneous transposition of the nerve. Decompression was usually limited to the region of the medial epicondyle, and related morbidity was relatively high. Endoscopic decompression is a promising technique because the dissection range can be extended and the scar length can be reduced. The authors review the relevant anatomy for the endoscopic approach and give some recommendations concerning the details of the surgical technique.

Treatment for giant cell tumors of the distal radius is challenging when motion is to be preserved. As standard wrist prostheses typically do not achieve favorable results, we treated a 36-year-old man with giant cell tumor of the distal radius with a new, custom-made implant.A custom-made wrist prosthesis with a long shaft was designed according to the patient's X-ray findings. After complete tumor resection, the prosthesis was subsequently implanted into the distal radius without complications.Two months after surgery, range of motion was 30°-0-25° for extension/flexion, 10°-0-5° for ulnar/radial abduction, 80°-0-0 for pronation/supination, complete range of motion for the fingers, and a grip strength of 6 kg. Two years after surgery, implant position was still correct and range of motion was 45°-0-10° for extension/flexion, 10°-0-20° for ulnar/radial abduction, and 80°-0-10° for pronation/supination. Grip strength was 16 kg, and DASH score was 25 compared to 39 before surgery. The patient returned to work as a craftsman.Custom-made wrist prostheses could become a practical option in patients with large defects of the distal radius who desire to preserve wrist motion.

In mutilating hand injuries, tissue engineered tendon grafts may provide a reconstructive solution. We have previously described a method to decellularize cadaveric human flexor tendons while preserving mechanical properties and biocompatibility. The purpose of this study is to evaluate the immunogenicity and strength of these grafts when implanted into an immunocompetent rat model.Cadaveric human flexor tendons were divided into two groups. Group 1 was untreated, and Group 2 was decellularized by treatment with sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), and peracetic acid (PAA). Both groups were then analyzed for the presence of major histocompatibility complexes by immunohistochemistry (IHC). Pair-matched tendons from each group were then placed into the dorsal subcutaneous tissue and anchored to the spinal ligaments of Wistar rats for 2 or 4 weeks, and harvested. The infiltration of B-cells and macrophages was determined using IHC. The explants where then subjected to mechanical testing to determine the ultimate tensile stress (UTS) and elastic modulus (EM). Statistical analysis was performed using a paired Student's t-test.The decellularization protocol successfully removed cells and MHC-1 complexes. At 2 weeks after implantation, there was increased infiltration of B-cells in Group 1 (untreated) compared with Group 2 (acellular), both in the capsule and tendon substance. There was improved ultimate tensile stress (UTS, 42.7 ± 8.3 vs. 22.8 ± 7.8 MPa, p0.05) and EM (830.2 ± 206.7 vs. 421.2 ± 171.3 MPa, p0.05) in tendons that were decellularized. At 4 weeks, there was continued B-cell infiltration in Group 1 (untreated) compared with Group 2 (acellular). There was no appreciable difference in macrophage infiltration at both time points. At 4 weeks Group 2 (acellular) demonstrated persistently greater UTS (40.5 ± 9.1 vs. 14.6 ± 4.2 MPa, p0.05) and EM (454.05 ± 101.5 vs. 204.6 ± 91.3 MPa, p0.05) compared with Group 1 (untreated).Human flexor tendons that were decellularized with SDS, EDTA, and PAA resulted in removal of cellular antigens and a decreased immune response when placed into Wistar rats. These grafts showed better mechanical properties at 2 and 4 weeks when compared with control tendons. Decellularization is an important step toward the use of tissue engineered flexor tendons in upper extremity reconstruction.

Tissue-engineered flexor tendon grafts may allow reconstruction of severe tendon losses. One critical factor is the optimization of cell proliferation and reseeding. Use of growth factors--basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF)-1, and platelet-derived growth factor (PDGF)-BB--may improve culture conditions for human fibroblasts, tenocytes, and adipose-derived stem cells and increase repopulation of a tendon scaffold.All cell types were plated at a density of 10,000 cells per well and cultured in F12 media supplemented with varying concentrations of bFGF, IGF-1, and PDGF-BB. After 72 hours, cell proliferation was determined using the CellTiter assay. Human flexor tendon segments were acellularized and reseeded in a cell suspension of 5 × 10(5) cells/ml. After 5 days, tendon repopulation was determined using the MTS assay and histology. Statistical significance was determined with analysis of variance and a t test.For all cell types, there was enhanced proliferation with growth factors. Among single growth factors, PDGF-BB at 50 ng/ml was the most efficient stimulator of proliferation. With multiple growth factors, the optimal concentration was determined to be 5 ng/ml bFGF, 50 ng/ml IGF-1, and 50 ng/ml PDGF-BB (increase when compared with control: fibroblasts, 2.92-fold; tenocytes, 2.3-fold; and adipose-derived stem cells, 2.4-fold; p0.05). Tendons reseeded with this optimal combination of growth factors showed improved reseeding compared with the control group (fibroblasts, 2.01-fold; tenocytes, 1.78-fold; and adipose-derived stem cells, 1.76-fold; p0.05).bFGF, IGF-1, and PDGF-BB can be used to improve cellular proliferation and repopulation of an acellularized scaffold. The use of growth factors may be an important step in the tissue engineering of human flexor tendons.

Human tendon tissue engineering attempts to address the shortage of autologous tendon material arising from mutilating injuries and diseases of the hand and forearm. It is important to maximize the tissue-engineered construct's (TEC's) biomechanical properties to ensure that the construct is in its strongest possible state before reimplantation. In this study, we sought to determine the bioreactor treatment parameters that affect these properties. Using small- and large-chamber three-dimensional-construct bioreactors (SCB and LCB, respectively), we applied cyclic axial load to TECs comprising reseeded human flexor and extensor tendons of the hand. First, small-sample pilot studies using the LCB were performed on matched-paired full-length flexor tendons to establish proof of concept. Next, large-sample studies using the SCB were performed on matched-paired extensor tendon segments to determine how reseeding, load duty cycle, load magnitude, conditioning duration, and testing delay affected ultimate tensile stress (UTS) and elastic modulus (EM). We found that compared with reseeded matched-paired controls under dynamic-loading at 1.25 N per TEC for 5 days, (1) acellular TECs had lower UTS (p=0.04) and EM (p0.01), (2) unloaded TECs had lower UTS (p=0.01) and EM (p=0.02), (3) static-loaded TECs had lower UTS (p=0.01) and EM (p0.01), (4) TECs conditioned for 3 days had lower UTS (p=0.03) and EM (p=0.04), and (5) TECs conditioned for 8 days had higher UTS (p=0.04) and EM (p=0.01). However, TECs conditioned at higher loads (2.5 N per TEC) and lower loads (0.625 N per TEC) possessed similar UTS (p=0.83 and p=0.89, respectively) and EM (p=0.48 and p=0.89, respectively) as controls stimulated with 1.25 N per TEC. After cycle completion, there is attrition of UTS (p=0.03) and EM (p=0.04) over a 2-day period. Our study showed that the material properties of human allograft TECs can be enhanced by reseeding and dynamic-conditioning. While conditioning duration has a significant effect on material properties, the load magnitude does not. The issue of attrition in biomechanical properties with time following cycle completion must be addressed before bioreactor preconditioning can be successfully introduced as a step in the processing of these constructs for clinical application.

Purpose:To determine transfection efficiency of FuGENE HD©lipofection and AMAXA©nucleofection on rat Schwann cells (SC).Methods:The ischiadic and median nerves of 6-8 week old Lewis rats were cultured in modified melanocyte-growth medium. SCs were genetically transfected with green fluorescent protein (GFP) as reporter gene using FuGENE HD©lipofection and AMAXA©nucleofection. Transfection rates were determined by visualization of GFP fluorescence under fluorescence microscopy and cell counting. Transfected cell to non-transfected cell relation was determined.Results:Purity of Schwann cell culture was 88% as determined by immunohistologic staining. Transfection rate of FuGENE HD©lipofection was 2%, transfection rate of AMAXA©nucleofection was 10%. With both methods, Schwann cells showed pronounced aggregation behavior which made them unfeasible for further cultivation. Settling of Schwann cells on laminin and poly-l-ornithine coated plates was compromised by either method.Conclusion:Non-viral transfection of rat SC with FuGENE HD©lipofection and AMAXA©nucleofection is basically possible with a higher transfection rate for nucleofection than for lipofection. As cell viability is compromised by either method however, viral transfection is to be considered if higher efficiency is required.

Ziel dieser Studie war es, den Stellenwert der minimal-invasiven Karpaltunnelspaltung gegenuber der offenen Karpaltunnelspaltung zu untersuchen. Im Rahmen einer retrospektiven Vergleichsstudie wurden 161 Patienten (105 offene Technik, 56 minimal-invasive Technik) bezuglich Funktion, Beschwerden und Lebensqualitat nachuntersucht. Wir konnten Vorteile zugunsten der minimal-invasiven Karpaltunnelspaltung zeigen: rasche Arbeitsfahigkeit, fruhe Wiederaufnahme alltaglicher Tatigkeiten, hohe Patientenzufriedenheit. In der Hand des geubten Operateurs stellt die minimal-invasive Karpaltunnelspaltung eine lohnende Alternative zur offenen Spaltung dar.

The surgical treatment of peripheral nerve injuries is still a challenging and highly demanding procedure. Past results have been improved upon by different advances in microsurgical techniques and algorithms. Nevertheless, results are not always satisfying, making secondary procedures necessary. Thus, these secondary procedures such as tendon transfers and arthrodesis of different joints must be taken into account during reconstructive planning. This review gives an overview of peripheral nerve reconstruction (nerve grafting, nerve repair) and the pertinent secondary procedures.

Die Wertigkeit der Vorverlagerung des Nervus ulnaris beim Kubitaltunnelsyndrom ist nicht vollig geklart. Ziel dieser Studie ist es, die Wertigkeit der Vorverlagerung des Nervus ulnaris bei intraoperativer Luxation zu analysieren. Vierundfunfzig Patienten nach Sulcus-ulnaris-Operation zwischen 2000 und 2006 wurden nachuntersucht. Der Nerv war jeweils bei Vorliegen einer intraoperativen Luxation verlagert worden. Zwolf Patienten wurden ohne Vorverlagerung und 42 Patienten mit Vorverlagerung operiert. Es gab keine signifikanten Unterschiede bez. Besserung der Beschwerden, Gebrauchsfahigkeit der Hand, Sensibilitatsstorungen und Dauer der Arbeitsunfahigkeit. Die seitenvergleichende Messung der groben Kraft und des Spitzgriffs ergab keinen signifikanten Unterschied in beiden Gruppen. Die 2-Punkte-Diskrimination des 8. bis 10 Fingernervs war zwischen den Gruppen ebenfalls nicht signifikant verschieden. Beim Kubitaltunnelsyndrom bringt die Vorverlagerung im Fall einer intraoperativen Nervenluxation keine Vorteile bez. Beschwerdebesserung, schnellerer Arbeitsfahigkeit, Verbesserung der Kraft und der Sensibilitat.

In this report, we describe the first case of using the partial phrenic nerve transfer and direct muscular implantation into the deltoid muscle for restoration of the shoulder function and stability. A patient suffering from the partial brachial plexus injury with absent axillary nerve underwent reconstructive surgery by an end-to-end nerve coaptation using two fascicles of the phrenic nerve and two autologous nerve grafts, and direct implantation of nerve grafts into the deltoid muscle. Eighteen months after the procedure, we found a functioning biceps with 90 degrees elbow flexion against gravity and 40 degrees shoulder abduction with satisfactory shoulder stability. Electrophysiology revealed reinnervation potentials in the deltoid and biceps muscle. This case demonstrates a satisfactory result after using transfer of the partial ipsilateral phrenic nerve in combination with muscular implantation to restore shoulder abduction and stability. We recommend the described techniques in cases without other reconstructive options. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009.

A 23-year-old male patient was operated for a soft tissue defect of the spine using a free musculocutaneous latissimus dorsi flap with two 21-cm long venous grafts connecting the flap to its vascular supply at the thoracodorsal vessels. This young patient suffered from Noonan's Syndrome that is a complex hereditary malformation syndrome with clinical features often leading to spinal deformities and gibbus development. The defect originated from a former internal vertebral fixation that was necessary for erective correction of such a spinal deformity. After perforation of the introduced material and debridement the defect was 4 x 8 cm in size, which was successfully closed by the free latissimus dorsi transfer. However, two venous grafts were necessary because the extension of the pedicled muscle was not sufficient to reach the defect. This is the first case in literature where a free flap was used with two venous grafts to close a soft tissue defect of the spine in the special case of a vertebral deformity based on a Noonan's Syndrome.

Silke Altmann,1 Hans-Georg Damert,1 Stephanie Klausenitz,2 Manfred Infanger,1 Armin Kraus1 1Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University Magdeburg, 2Private Institute for Pathology, Magdeburg, Germany Abstract: Aggressive digital papillary adenocarcinomas are rare malignant tumors often located on the digits of the hand. Due to lack of pain, slow growth, and an inconspicuous appearance, diagnosis is often missed or delayed. We report two cases and review the present literature to give recommendations for diagnosis and treatment. Keywords: aggressive digital papillary adenocarcinoma, tumor, sweat glands

Anterior interosseous nerve syndrome (Nevin–Kiloh syndrome) is a rare entity caused by compression of the purely motor anterior interosseous nerve in the forearm. Historically, conventional surgical treatment has consisted of open decompression of the nerve. Unfortunately, open decompression is often complicated by scarring and significant morbidity. Endoscopic decompression is an alternative means of surgical intervention in the hands of well-trained surgeons comfortable with soft tissue endoscopy. In this report, we review relevant anatomy, offer technical hints, and present our personal experience with 4 illustrative cases, all with greater than 1.5 years of follow-up. Our patients showed considerable improvement of their symptoms with minimal scarring. No significant complications occurred.

Cadaveric tendon allografts form a readily available and underutilized source of graft material. Because of their material properties, allografts are biomechanically and biologically superior to synthetic scaffolds. However, before clinical use, allografts must undergo decellularization to reduce immunogenicity and oxidation to increase porosity, leaving a nonvital biostatic scaffold. Ex vivo seeding, or revitalization, is thought to hasten graft incorporation and stimulate intrinsic tendon healing, permitting early mobilization and return to function. In this study, we examined physical and biochemical augmentation methods, including scaffold surface scoring (physical) and rehydration of lyophilized scaffolds in serum (biochemical). Scaffolds were divided into four groups: (1) scored scaffolds, (2) lyophilized scaffolds rehydrated in fetal calf serum (FCS), (3) scaffolds both scored and rehydrated in FCS, and (4) control scaffolds. Scaffolds were reseeded with adipose-derived stem cells (ADSCs). Reseeding efficacy was quantified by a live cell and total cell assays and qualified histologically with hematoxylin and eosin, live/dead and SYTO green nucleic acid stains, TUNEL apoptosis stains, procollagen stains, and transmission electron microscopy. Scaffold-seeded cell viability at up to 2 weeks in vitro and up to 4 weeks in vivo was demonstrated with bioluminescent imaging of scaffolds seeded with luciferase-positive ADSCs. The effect of seeding on scaffold biomechanical properties was demonstrated with evaluation of ultimate tensile stress (UTS) and an elastic modulus (EM). We found that scaffold surface scoring led to an increase in live and total cell attachment and penetration (MTS assay, p0.001 and DNA assay, p=0.003, respectively). Histology confirmed greater total cell number in both construct core and surface in scored compared with unscored constructs. Cells reseeded on scored constructs displayed reduced apoptosis, persistent procollagen production, and had a similar ultrastructural relationship to the surrounding matrix as native tenocytes on transmission electron microscopy. Rehydration of lyophilized scaffolds in serum did not improve reseeding. Seeded constructs demonstrated greater UTS and EM than unseeded constructs. Scaffolds seeded with ADSC-luc2-eGFP demonstrated persistent viability for at least 2 weeks in vitro. In conclusion, tendon surface scoring increases surface and core reseeding in vitro and may be incorporated as a final step in allograft processing before clinical implantation.

Hemostatic procedures by means of electrical coagulation or application of topical agents are widely used to avoid postoperative bleeding during microsurgical reconstruction of peripheral nerves. It is speculated, however, that extensive hemostasis could provoke significant nerve damage.To examine the effects of 2 intraoperative hemostatic procedures on peripheral nerve regeneration.In 36 adult rats divided into 3 groups, the median nerve was transected and repaired by end-to-end neurorrhaphy. During surgery, bleeding was treated in groups 2 and 3 by application of either the topical hemostatic agent Floseal or routine bipolar coagulation. The degree of nerve regeneration was assessed in terms of motor function recovery using weekly grasping test evaluation for 3 months, muscle mass recovery of flexor digitorum sublimis, and stereological assessment of myelinated axon regeneration.Neither of the 2 applied hemostatic methods induced any negative effects on nerve regeneration as defined by grip strength, muscle mass recovery, and morphology of myelinated nerve fibers. In contrast, Floseal-treated animals showed a faster progression of motor function recovery, and animals subjected to bipolar coagulation revealed a higher muscle mass recovery compared with the control group.Controlled application of bipolar coagulation or Floseal does not exert a negative effect on the nerve regeneration outcome in rats. We propose that these methods can be applied safely to patients.

Different bioartificial tubes were recommended for peripheral nerve reconstruction in the past. In order to replace autologous nerve grafts this materials are still under review in different animal studies. Most of them are dealing with the rodent peripheral nerves. One very popular animal model to study different materials is the rat median nerve model. With its easy excess, simple behavioral tests and reliable long term results it is attractive to many scientists in this field. This review gives an overview about the past, current and future options in this model for bioartificial nerve tubes. It summarizes the evolution of successful implantation of different materials across short nerve gaps and demonstrates the obstacles arising from long nerve gaps and the problems associated to them.

Background Hemostatic procedures by means of electrical coagulation or application of topical agents are widely used to avoid postoperative bleeding during microsurgical reconstruction of peripheral nerves. It is speculated, however, that extensive hemostasis could provoke significant nerve damage. Objective To examine the effects of 2 intraoperative hemostatic procedures on peripheral nerve regeneration. Methods In 36 adult rats divided into 3 groups, the median nerve was transected and repaired by end-to-end neurorrhaphy. During surgery, bleeding was treated in groups 2 and 3 by application of either the topical hemostatic agent Floseal or routine bipolar coagulation. The degree of nerve regeneration was assessed in terms of motor function recovery using weekly grasping test evaluation for 3 months, muscle mass recovery of flexor digitorum sublimis, and stereological assessment of myelinated axon regeneration. Results Neither of the 2 applied hemostatic methods induced any negative effects on nerve regeneration as defined by grip strength, muscle mass recovery, and morphology of myelinated nerve fibers. In contrast, Floseal-treated animals showed a faster progression of motor function recovery, and animals subjected to bipolar coagulation revealed a higher muscle mass recovery compared with the control group. Conclusion Controlled application of bipolar coagulation or Floseal does not exert a negative effect on the nerve regeneration outcome in rats. We propose that these methods can be applied safely to patients.

Purpose: The improvement of regeneration and functional recovery after peripheral nerve injury is a major challenge in neurosurgery. Although microsurgical techniques for nerve reconstruction have seen great advancements over the last years, the clinical outcome with patients is often unsatisfactory. The aim of the present study was to investigate if administration of the iron chelator Deferroxamine (DFO), can improve postoperative outcome in the rat median nerve reconstruction model. Methods: After complete transection, the right median nerve was repaired by end-to-end neurorrhaphy. The suture site was wrapped by a 1-cm-long external jugular vein segment, either empty or filled with DFO-loaded lipid particles (Perineurin c ) or with a vehicle (unloaded lipid particles) alone. Functional testing was carried out weekly by means of the grasping test. At the time of withdrawal, 12 weeks post-operatively, muscle tropism recovery was assessed by weighing flexor digitorum sublimis muscle that is innervated by the median nerve only. Before harvesting of the nerve specimens electrophysiological analyses were performed with measuring the latency, the threshold and the conduction velocity. Finally, the repaired nerves were withdrawn for immunocytochemistry with a neurofilament antibody and axon quantitative morphology. Results: The comparison between the groups showed that intraoperative application of the DFO-loaded lipid particles at the neurorrhaphy site led to a significant increase in the density of regenerating axons as well as to an accelerated recovery of both muscle tropism and motor function. The electrophysiological results demonstrated a decrease of the threshold, a lower latency, and a higher conduction velocity in the Perineurin c -treated animals. Conclusions: The results of the present study suggest that local administration of Perineurin c might have a therapeutic potential for improving the postoperative outcome after microsurgical nerve reconstruction in patients.

The efficacy of Schwann-cell cultivation can be enhanced by in vitro predegeneration of the harvested cells compared to immediate culture. The aim of this study was to improve Schwann-cell culture efficacy by comparing three different durations of predegeneration. The sciatic and median nerves of 6-8-week-old Lewis rats were harvested and subjected to either 2-day, 7-day, or 14-day predegeneration in Dulbecco's Modified Eagle's Medium supplemented with 10% fetal calf serum and 1% Penicillin/Streptomycin. Afterward, tissue was enzymatically dissociated and placed in a modified melanocyte growth medium. The cell count was determined immediately after dissociation while the cell purity was determined one subculture/trypsinization cycle later after cell attachment to the culture plate by means of optical microscopy and immunocytochemistry. Particular attention was then paid to the Schwann-cell-to-fibroblast relation. The cumulative cell count in the culture was 5.8 x 10(5) for 2-day, 1.12 x 10(6) for 7-day, and 1.48 x 10(6) for 14-day predegeneration. The culture purity was approximately equal for 2- and 7-day predegeneration (88% Schwann cells, 12% fibroblasts after 2 days; 85% Schwann cells, 15% fibroblasts after 7 days). After 14 days, however, cell cultures were significantly debased by fibroblast proliferation (57% Schwann cells, 43% fibroblasts). In vitro predegeneration is a particularly suitable procedural method to increase the cultural Schwann-cell yield. The number of cultivated rat Schwann cells is doubled by 7-day in vitro predegeneration in comparison to 2-day predegeneration. After 14-day predegeneration, however, the culture is significantly debased by fibroblasts. Therefore, 7-day in vitro predegeneration is an advisable predegeneration period.

Direct coaptation and interpositional nerve grafting (IPNG) of an injured peripheral nerve is still associated with poor functional recovery. Main reasons for that are thought to be an extensive collateral axonal branching at the site of transection and the polyinnervation of motor endplates due to terminal axonal and intramuscular sprouting. Moreover, severe changes occurring within the muscle after long-term denervation, like loss of muscle bulk and circulation as well as progressive fibrosis, have a negative effect on the quality of functional recovery after reinnervation. We have recently shown that manual stimulation (MS) of paralyzed vibrissal muscles in rat promotes full recovery after facial nerve coaptation. Furthermore, MS improved functional recovery after hypoglossal nerve repair, hypoglossal-facial IPNG of the facial nerve in rat. In contrary, MS did not improve recovery after injury of the median nerve in rat, which is however a mixed peripheral nerve comparing to the facial nerve. It is speculated that manually stimulated recovery of motor function requires an intact sensory input, which is affected in case of mixed peripheral nerves but not in case of pure motor nerves. In this article, we summarize our results of MS in several peripheral nerve injury models in order to illustrate the application potential of this method and to give insights into further investigations on that field.

In this report, we describe the first case of using the partial phrenic nerve transfer and direct muscular implantation into the deltoid muscle for restoration of the shoulder function and stability. A patient suffering from the partial brachial plexus injury with absent axillary nerve underwent reconstructive surgery by an end-to-end nerve coaptation using two fascicles of the phrenic nerve and two autologous nerve grafts, and direct implantation of nerve grafts into the deltoid muscle. Eighteen months after the procedure, we found a functioning biceps with 90 degrees elbow flexion against gravity and 40 degrees shoulder abduction with satisfactory shoulder stability. Electrophysiology revealed reinnervation potentials in the deltoid and biceps muscle. This case demonstrates a satisfactory result after using transfer of the partial ipsilateral phrenic nerve in combination with muscular implantation to restore shoulder abduction and stability. We recommend the described techniques in cases without other reconstructive options. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009.

After restitution of motor function the grasping test alone is insufficient to figure out any further differences of axonal nerve regeneration of the median nerve in rats. To avoid this problem we developed a standardized electrophysiologic method for testing median nerve regeneration. Threshold, latency, compound muscle action potentials (CMAP) and velocity of neuromuscular transduction were recorded in 54 rats 20 weeks post-operatively. Animals of group 1 served as control group, no transection of the median nerve was carried out. Animals of groups 2 and 3 underwent either primary nerve coaptation or autologous nerve grafting after transection of the median nerve. To ensure validity of the method additional correlation between all parameters was investigated. Reliable electrophysiological results were observed in all animals. As expected, group 1 animals showed lowest threshold and latency and highest CMAP levels. Transection of the median nerve and additional nerve repair leads to significant increase of threshold and latency as well as reduction of CMAP. Furthermore, animals of group 3 showed higher levels for threshold and latency and reduced CMAP levels compared with animals of group 2. The grasping test alone could not demonstrate these slight differences 20 weeks post-operatively. Additionally, we observed strong correlations between threshold, latency and CMAP using the Spearman correlation ranking. We describe the usage of motor neurography as a reproducible and valid tool which should be mandatory for detailed analysis of regeneration in the rat median nerve model.

Noch immer stellt die Verbesserung der Ergebnisse nach Verletzung peripherer Nerven eine Herausforderung fur die Wissenschaft dar. Ziel dieser Arbeit war es, den Einfluss eines Eisenchelators, namlich des Deferroxamins (DFO), auf die Regeration peripherer Nerven zu untersuchen. Bei Tieren der Gruppe I (n=12) wurde der rechte N. medianus nach dessen Durchtrennung mit einer einfachen End-zu-End-Nervennaht behandelt. Die Nahtseite wurde in Gruppe II (n=12) zusatzlich mit einem 1 cm langen V.-jugularis-externa-Segment umhullt. Bei Tieren der Gruppe III (n=12) wurde die Vene mit unbeladenen Lipidpartikeln und in Gruppe IV (n=12) mit DFO beladenen Partikeln (Perineurin©) gefullt. Zur Analyse der Regeneration des peripheren Nerven evaluierten wir postoperativ Greiftest, Histologie, Elektrophysiologie und das Muskelgewicht. Der Vergleich der Ergebnisse aller Gruppen zeigte eine erhohte Nervenfaserdichte sowie eine schnellere funktionelle Nervenregeneration im Greiftest bei Tieren der Gruppe IV. Die Anwendung von DFO fuhrte bei der Neurographie zu einer herabgesetzten Reizschwelle und Latenz sowie einer erhohten Nervenleitgeschwindigkeit. So belegen die Ergebnisse dieser Studie einen positiven Einfluss der lokalen Anwendung von DFO auf die Regeneration am peripheren Nerven nach einer einfachen Nervennaht.

Direct coaptation and interpositional nerve grafting (IPNG) of an injured peripheral nerve is still associated with poor functional recovery. Main reasons for that are thought to be an extensive collateral axonal branching at the site of transection and the polyinnervation of motor endplates due to terminal axonal and intramuscular sprouting. Moreover, severe changes occurring within the muscle after long-term denervation, like loss of muscle bulk and circulation as well as progressive fibrosis, have a negative effect on the quality of functional recovery after reinnervation. We have recently shown that manual stimulation (MS) of paralyzed vibrissal muscles in rat promotes full recovery after facial nerve coaptation. Furthermore, MS improved functional recovery after hypoglossal nerve repair, hypoglossal-facial IPNG of the facial nerve in rat. In contrary, MS did not improve recovery after injury of the median nerve in rat, which is however a mixed peripheral nerve comparing to the facial nerve. It is speculated that manually stimulated recovery of motor function requires an intact sensory input, which is affected in case of mixed peripheral nerves but not in case of pure motor nerves. In this article, we summarize our results of MS in several peripheral nerve injury models in order to illustrate the application potential of this method and to give insights into further investigations on that field.