Current patterns of care and outcomes for dermatofibrosarcoma protuberans: An international multi-institutional collaborative.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited. METHODS: Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed. RESULTS: Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N = 23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology. CONCLUSIONS: In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection.

Coverage of complex tissue defects following open cervicothoracic spine surgery with a lower trapezius island myocutaneous flap-an interdisciplinary approach.

The study design is a clinical case series. The objective of this study was to present the concept and efficacy of the lower trapezius island myocutaneous flap (LTIMF) for management of complex wound healing disorders following open cervicothoracic spine surgery. Wound healing disturbances with myocutaneous defects after open spine surgery at the cervical and upper thoracic spine are well-described complications. In severe cases, plastic reconstructive coverage is often required as a last resort. A review of all adult patients with deep wound dehiscence and tissue defects following open cervicothoracic spine surgery, who were managed with plastic surgery reconstruction using a LTIMF at our institution, was conducted. Synopses of these cases are presented. Seven patients with a mean age of 73 years ± 13 (range 50 to 89 years) were included in this case series. Six out of seven patients had instrumented posterior fusion added to their decompression. All patients were managed with a LTIMF for wound coverage. No spinal implants were removed prior to LTIMF surgery. The mean follow-up was 5.2 months (± 5.4 months). No major flap failure occurred, and all patients presented with satisfactory cosmetic results. The only minor complication was development of a sterile subcutaneous seroma in two patients, which were successfully managed by puncture and aspiration. The LTIMF is an effective and reliable salvage treatment option for spine surgery patients offering stable coverage of deep tissue defects resulting from complex wound healing disorders at the cervical and upper thoracic spine.

Perioperative predictors of early surgical revision and flap-related complications after microvascular free tissue transfer in head and neck reconstructions: a retrospective observational series.

OBJECTIVES: The aim of this study was to determine the influence of perioperative fluid management and administration of vasopressors on early surgical revision and flap-related complications in free tissue transfer. MATERIALS AND METHODS: Intraoperative amount of fluid and of vasopressors, relevant perioperative parameters, and comorbidities were recorded in 131 patients undergoing head and neck microvascular reconstruction and compared with early surgical complications, defined as interventions requiring surgery after a flap-related complication, and/or other surgical problems in the operating room within 30 days after initial surgery. The relationship between perioperative variables for each revision category was determined using an optimized multiple logistic regression. RESULTS: The administration of diuretics (p=0.001) as a treatment for perioperative fluid overload and the type of flap (p=0.019) was associated with a higher risk of early surgical revisions. Perioperative fluid overload (p=0.039) is significantly related to flap-related complications. We found no effect of intraoperative administration of vasopressors on early surgical revisions (p=0.8) or on flap-related complications (norepinephrine p=0.6, dobutamine p=0.5). CONCLUSION: Perioperative fluid overload is associated with higher risks of early surgical revision and flap-related complications. In contrast, the administration of vasopressors seemed to have no effect on either surgical revision rate or flap-related complications. CLINICAL RELEVANCE: In patients receiving microvascular reconstructions, a balanced fluid administration perioperatively and a targeted use of vasopressors should be the necessary strategy to reduce the complication rates in head and neck surgery.

Intra-graft injection of tacrolimus promotes survival of vascularized composite allotransplantation.

BACKGROUND: Immunosuppressive therapies derived from solid organ transplantation are effective in promoting survival of vascularized composite allotransplantation (VCA), but they cause serious side effects that are difficult to justify for this non-life-saving procedure. Unlike solid organ transplantation, hand and face transplants offer the possibility of site-specific immunosuppression for reducing systemic exposure while increasing intra-graft concentrations of the drug. Therefore, in this study, we tested whether a single intra-graft injection tacrolimus could promote VCA survival. METHODS: Brown Norway-to-Lewis hind limb transplantations were performed, and animals were left untreated (group I), treated with a daily injection of 1-mg/kg tacrolimus for 21 days (group 2) or injected with 7-mg tacrolimus directly into the transplanted limb on day 1 (group III). Graft rejection was monitored, and animals were sacrificed at grade 3 rejection or 200 days after transplantation. RESULTS: Intra-graft injection of tacrolimus significantly prolonged allograft survival as compared to untreated animals or animals treated with systemic tacrolimus. Half of the intra-graft-treated rats rejected their graft on average at day 70.5. Interestingly, the other half remained rejection-free for more than 200 days without signs of kidney or liver toxicity. In these animals, tacrolimus was detected in the VCA skin but not in the blood until day 200. Long-term survival was not linked to induction of donor-specific tolerance but to a higher level of lymphocyte chimerism. CONCLUSIONS: Intra-graft delivery of tacrolimus may promote VCA survival by increasing tissue drug availability and promoting the establishment of transient chimerism and thus long-term graft acceptance.

The influence of diabetes mellitus on survival of abdominal perforator flaps: an experimental study in rats with slowly induced diabetes mellitus.

BACKGROUND: Lower limb ulcers are a major source of morbidity and mortality in diabetic patients. Surgical coverage of these wounds is fraught with a high complication rate. Although clinically perforator flaps lead to good results in diabetic patients, there is little experimental data to support this finding. METHODS: A total of 60 Wistar rats were randomly assigned either to the diabetic (n = 30) or control (n = 30) group. Diabetes was induced by streptozotocin injection at 50 mg/kg body weight and was confirmed by blood glucose levels > 180 mg/dL preoperatively. In all rats, a cranial epigastric artery perforator flap was raised. At postoperative day 7, all flaps were raised, photographed by digital planimetry, and analyzed histologically. RESULTS: Mean glycemic levels preoperatively were 207.8 ± 16 in the diabetic group and 82.8 ± 5.1 in the control group (p < 0.05). Ninety percent of the flaps survived completely in the control group, compared with 66.7% in the diabetic group (p < 0.05). The mean flap survival area was lower in the diabetic group (83.3 ± 16.5%) than in the control group (96 ± 4%). There were significantly more perioperative complications in the diabetic group (46.7%) than in the control group (16.7%), but these did not affect flap survival. Superficial ulceration appeared only in the diabetic group as a complication. CONCLUSION: Perforator flaps can be successfully used for coverage of cutaneous defects in a rat diabetic model. These flaps show higher complication rates in diabetic versus nondiabetic animals; however, this complication rate has little influence on flap survival.

[The risk-reducing mastectomy: unnecessary hysteria or life-saving prophylaxis?]. / Die prophylaktische Mastektomie: unnötige Hysterie oder nötige Vorsorge.

The prophylactic (risk-reducing) mastectomy is a world-wide recognized method for specifically treating the increased breast cancer risk in patients showing a BRCA1 and/or BRCA2 mutation as well as other patient groups at increased breast cancer risk. This option should be offered to all patients having the pertinent risk profile. Breast reconstruction is an integral part of the risk-reducing mastectomy procedure and all possible methods of breast reconstruction, especially autologous tissue reconstruction should be offered to all patients having a medical indication and desiring this surgical treatment. These patients are best managed in certified Breast Care Centres where the different medical and surgical specialists can address interdisciplinary all aspects of genetic counselling, preoperative counselling, mastectomy and reconstructive techniques as well as the necessary postoperative surveillance.

Tacrolimus-loaded Drug Delivery Systems in Vascularized Composite Allotransplantation: Lessons and Opportunities for Local Immunosuppression.

Long-term systemic immunosuppression is needed for vascularized composite allotransplantation (VCA). The high rate of acute rejection episodes in the first posttransplant year, the development of chronic rejection, and the adverse effects that come along with this treatment, currently prevent a wider clinical application of VCA. Opportunistic infections and metabolic disturbances are among the most observed side effects in VCA recipients. To overcome these challenges, local immunosuppression using biomaterial-based drug delivery systems (DDS) have been developed. The aim of these systems is to provide high local concentrations of immunosuppressive drugs while reducing their systemic load. This review provides a summary of recently investigated local DDS with different mechanisms of action such as on-demand, ultrasound-sensitive, or continuous drug delivery. In preclinical models, ranging from rodent to porcine and nonhuman primate models, this approach has been shown to reduce systemic tacrolimus (TAC) load and adverse effects, while prolonging graft survival. Localized immunosuppression using biomaterial-based DDS represents an encouraging approach to enhance graft survival and reduce toxic side effects of immunosuppressive drugs in VCA patients. Preclinical models using TAC-releasing DDS have demonstrated high local immunosuppressive effects with a low systemic burden. However, to reduce acute rejection events in translational animal models or in the clinical reality, the use of additional low-dose systemic TAC treatment may be envisaged. Patients may benefit through efficient graft immunosuppression and survival with negligible systemic adverse effects, resulting in better compliance and quality of life.

Transcriptome profiling of immune rejection mechanisms in a porcine vascularized composite allotransplantation model.

Background: Vascularized composite allotransplantation (VCA) offers the potential for a biological, functional reconstruction in individuals with limb loss or facial disfigurement. Yet, it faces substantial challenges due to heightened immune rejection rates compared to solid organ transplants. A deep understanding of the genetic and immunological drivers of VCA rejection is essential to improve VCA outcomes. Methods: Heterotopic porcine hindlimb VCA models were established and followed until reaching the endpoint. Skin and muscle samples were obtained from VCA transplant recipient pigs for histological assessments and RNA sequencing analysis. The rejection groups included recipients with moderate pathological rejection, treated locally with tacrolimus encapsulated in triglycerol-monostearate gel (TGMS-TAC), as well as recipients with severe end-stage rejection presenting evident necrosis. Healthy donor tissue served as controls. Bioinformatics analysis, immunofluorescence, and electron microscopy were utilized to examine gene expression patterns and the expression of immune response markers. Results: Our comprehensive analyses encompassed differentially expressed genes, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways, spanning various composite tissues including skin and muscle, in comparison to the healthy control group. The analysis revealed a consistency and reproducibility in alignment with the pathological rejection grading. Genes and pathways associated with innate immunity, notably pattern recognition receptors (PRRs), damage-associated molecular patterns (DAMPs), and antigen processing and presentation pathways, exhibited upregulation in the VCA rejection groups compared to the healthy controls. Our investigation identified significant shifts in gene expression related to cytokines, chemokines, complement pathways, and diverse immune cell types, with CD8 T cells and macrophages notably enriched in the VCA rejection tissues. Mechanisms of cell death, such as apoptosis, necroptosis and ferroptosis were observed and coexisted in rejected tissues. Conclusion: Our study provides insights into the genetic profile of tissue rejection in the porcine VCA model. We comprehensively analyze the molecular landscape of immune rejection mechanisms, from innate immunity activation to critical stages such as antigen recognition, cytotoxic rejection, and cell death. This research advances our understanding of graft rejection mechanisms and offers potential for improving diagnostic and therapeutic strategies to enhance the long-term success of VCA.

A local drug delivery system prolongs graft survival by dampening T cell infiltration and neutrophil extracellular trap formation in vascularized composite allografts.

Introduction: The standard treatment for preventing rejection in vascularized composite allotransplantation (VCA) currently relies on systemic immunosuppression, which exposes the host to well-known side effects. Locally administered immunosuppression strategies have shown promising results to bypass this hurdle. Nevertheless, their progress has been slow, partially attributed to a limited understanding of the essential mechanisms underlying graft rejection. Recent discoveries highlight the crucial involvement of innate immune components, such as neutrophil extracellular traps (NETs), in organ transplantation. Here we aimed to prolong graft survival through a tacrolimus-based drug delivery system and to understand the role of NETs in VCA graft rejection. Methods: To prevent off-target toxicity and promote graft survival, we tested a locally administered tacrolimus-loaded on-demand drug delivery system (TGMS-TAC) in a multiple MHC-mismatched porcine VCA model. Off-target toxicity was assessed in tissue and blood. Graft rejection was evaluated macroscopically while the complement system, T cells, neutrophils and NETs were analyzed in graft tissues by immunofluorescence and/or western blot. Plasmatic levels of inflammatory cytokines were measured using a Luminex magnetic-bead porcine panel, and NETs were measured in plasma and tissue using DNA-MPO ELISA. Lastly, to evaluate the effect of tacrolimus on NET formation, NETs were induced in-vitro in porcine and human peripheral neutrophils following incubation with tacrolimus. Results: Repeated intra-graft administrations of TGMS-TAC minimized systemic toxicity and prolonged graft survival. Nevertheless, signs of rejection were observed at endpoint. Systemically, there were no increases in cytokine levels, complement anaphylatoxins, T-cell subpopulations, or neutrophils during rejection. Yet, tissue analysis showed local infiltration of T cells and neutrophils, together with neutrophil extracellular traps (NETs) in rejected grafts. Interestingly, intra-graft administration of tacrolimus contributed to a reduction in both T-cellular infiltration and NETs. In fact, in-vitro NETosis assessment showed a 62-84% reduction in NETs after stimulated neutrophils were treated with tacrolimus. Conclusion: Our data indicate that the proposed local delivery of immunosuppression avoids off-target toxicity while prolonging graft survival in a multiple MHC-mismatch VCA model. Furthermore, NETs are found to play a role in graft rejection and could therefore be a potential innovative therapeutic target.

The extended diep flap: extending the possibilities for breast reconstruction with tissue from the lower abdomen.

BACKGROUND: The classical DIEP-flap is considered state-of-the-art in microsurgical autologous breast reconstruction. Some patients may require additional volume to match the contralateral breast. This quality control study prospectively evaluates the feasibility and outcome of a surgical technique, which pursues the volumetric augmentation of the DIEP-flap by harvesting of additional subscarpal fat tissue cranial to the classical flap border. PATIENTS AND METHODS: For radiologically based estimation of volumetric flap-gain potential, abdominal CT-scans of 10 Patients were randomly selected and used for computerized volumetric estimates. Surgical evaluation of the technique was prospectively performed between 09/2009 and 09/2010 in 10 patients undergoing breast reconstruction with extended DIEP-flap at two institutions. The outcome regarding size, volume, and symmetry was evaluated. RESULTS: Radiologically, the mean computed volume gain of an extended DIEP was 16.7%, when compared with the infraumbilical unilateral flap volume. Clinically, the intraoperatively measured mean volume gain was of 98.6 g (range: 75-121 g), representing 13.8% of the flap volume. All 10 flaps survived without revision surgery. In three flaps, minor fat necrosis occurred in zone III and was treated conservatively. No fat necrosis was observed in the extended flap area. CONCLUSIONS: In this first prospective series, the extended DIEP-flap proved to be feasible, reliable and safe for its use in breast reconstruction. Both radiological estimation and intraoperative measurements demonstrated a statistically significant volume gain with no complications in the extended area. The technique is of benefit in selected patients requiring additional reconstructive volume than the one achieved with the classical DIEP-flap. LEVEL OF EVIDENCE: Therapeutic Level IV.

[Surgical therapy for reconstruction of body shape and contour following massive weight reduction]. / Chirurgische massnahmen zur wiederherstellung der körperform und -konturnach massiver gewichtsreduktion.

The consequences of massive weight loss through bariatric procedures as well as diet are overall positive. However, the sequelae of massive weight loss present themselves as soft tissue redundancies in the areas of the lower abdomen, upper thigh, upper arm and breast as well as face and neck. This condition presents significant mechanical, physical and social day-to-day limitations for the quality of life of these patients. Surgical techniques are indicated for the reconstruction of the body shape and therapy of the above named problems and the coexistent psychosocial component. These surgical techniques involve dermolipectomies in different body areas and can lead to significant improvement. In view of the worldwide increase of adipositas and the increasing need for bariatric surgery, a parallel increase in demand for such reconstructive post-bariatric interventions can be foreseen. Early and precise information is crucial for the patients before engaging in weight reduction, as is the coverage of the costs of the resulting secondary reconstructive body contouring interventions by the insurance companies.

Free Tissue Transfer in Head and Neck Reconstruction: A Multidisciplinary 15-Year Experience.

BACKGROUND: Free tissue transfer is considered the gold standard in reconstruction of extensive defects in head and neck surgery. The aim of this 15-year retrospective study is to analyze the outcomes of free tissue transfers in the head and neck area in a tertiary referral university hospital. MATERIALS AND METHODS: A retrospective, single-center study of all patients undergoing free tissue transfers for head and neck reconstruction between 2006 and 2020 was performed. Patient demographics, comorbidities, flap characteristics, outcomes and complications were assessed. RESULTS: A total of 353 free flaps were performed. The most common defect etiology was synchronous oncologic resection (74.2%). The majority of patients had at least one comorbidity (70.3%), with smoking recorded in 46.2% of the cases and alcohol consumption in 31.7%. The anterolateral thigh flap was the most commonly used flap (37.7%), followed by the osteoseptocutaneous fibula flap (26.9%). Our overall flap success rate was 97.7%, while the overall complication rate was 45.9%. CONCLUSIONS: Free tissue transfer in head and neck reconstruction is reliable. However, complication rates remain high due to the complexity of such cases and frequent presence of comorbidities. Nonetheless, when effectively managed within a multidisciplinary team, complications rarely jeopardize the overall reconstruction outcome.

The osteocutaneous SCIP flap: A detailed description of the surgical technique and retrospective cohort study of consecutive cases in a tertiary European centre.

INTRODUCTION: In the era of increasing popularity of the superficial circumflex iliac perforator (SCIP) flap, osteocutaneous variants of the flap have been described as well. Despite their benefits such as customizability and low donor site morbidity, these flaps have not yet gained broad acceptance. By reviewing our case series, we aim to promote the safe application of this promising new tool in osteoplastic reconstructions. PATIENTS AND METHODS: We performed a single-centre, retrospective chart review of all cases in which osteocutaneous SCIP-flaps were used. We describe our surgical technique and present the surgical, functional and aesthetic outcomes of the patients in our cohort. RESULTS: Since September 2019, we have used osteocutaneous SCIP flaps in six patients, five in the extremities and one for the head and neck region. The vascularised bone segment was measured on average 4.9 cm (range 4-7 cm) x 3 cm (range 1.5-4 cm) and was combined with a skin paddle of a mean length of 14.3 cm (range 8-20 cm) and width of 6.3 cm (range 5-8 cm). One flap underwent emergency revision due to venous congestion. All flaps survived and healed uneventfully. Long-term follow-up shows adequate bony integration and stable soft tissue coverage with good functional restoration and minimal donor site morbidity. CONCLUSION: The osteocutaneous SCIP flap provides a large and thin skin island and a "moderately sized" vascularised bone segment with minimal donor site morbidity and can be successfully used in selected cases of osteoplastic reconstruction.

Challenges and opportunities in vascularized composite allotransplantation of joints: a systematic literature review.

Background: Joint allotransplantation (JA) within the field of vascularized composite allotransplantation (VCA) holds great potential for functional and non-prosthetic reconstruction of severely damaged joints. However, clinical use of JA remains limited due to the immune rejection associated with all forms of allotransplantation. In this study, we aim to provide a comprehensive overview of the current state of JA through a systematic review of clinical, animal, and immunological studies on this topic. Methods: We conducted a systematic literature review in accordance with the PRISMA guidelines to identify relevant articles in PubMed, Cochrane Library, and Web of Science databases. The results were analyzed, and potential future prospects were discussed in detail. Results: Our review included 14 articles describing relevant developments in JA. Currently, most JA-related research is being performed in small animal models, demonstrating graft survival and functional restoration with short-term immunosuppression. In human patients, only six knee allotransplantations have been performed to date, with all grafts ultimately failing and a maximum graft survival of 56 months. Conclusion: Research on joint allotransplantation has been limited over the last 20 years due to the rarity of clinical applications, the complex nature of surgical procedures, and uncertain outcomes stemming from immune rejection. However, the key to overcoming these challenges lies in extending graft survival and minimizing immunosuppressive side effects. With the emergence of new immunosuppressive strategies, the feasibility and clinical potential of vascularized joint allotransplantation warrants further investigation.

Flap Reconstruction Outcome Following Surgical Resection of Soft Tissue and Bone Sarcoma in the Setting of (Neo)adjuvant Therapy: A Sarcoma Center Experience.

BACKGROUND: Soft tissue and bone sarcomas are heterogeneous groups of malignant tumors. The shift in their management, with an emphasis on limb salvage, has deemed the involvement of reconstructive surgeons an integral part of their multidisciplinary treatment. We present our experience with free and pedicled flaps in the reconstruction of sarcomas at a tertiary referral university hospital and major sarcoma center. MATERIALS AND METHODS: All patients undergoing flap reconstruction after sarcoma resection over a 5-year period have been included in the study. Patient-related data and postoperative complications were collected retrospectively, ensuring a minimum follow-up of 3 years. RESULTS: A total of 90 patients underwent treatment with 26 free flaps and 64 pedicled flaps. Postoperative complications occurred in 37.7% of patients, and the flap failure rate was 4.4%. Diabetes, alcohol consumption and male gender were associated with increased early necrosis of the flap. Preoperative chemotherapy significantly increased the occurrence of early infection and late dehiscence, while preoperative radiotherapy was associated with a higher incidence of lymphedema. Intraoperative radiotherapy was associated with late seromas and lymphedema. CONCLUSIONS: Reconstructive surgery with either pedicled or free flaps is reliable, but it can be demanding in the setting of sarcoma surgery. A higher complication rate is to be expected with neoadjuvant therapy and with certain comorbidities.

Development and implementation of a web-enabled 3D consultation tool for breast augmentation surgery based on 3D-image reconstruction of 2D pictures.

BACKGROUND: Producing a rich, personalized Web-based consultation tool for plastic surgeons and patients is challenging. OBJECTIVE: (1) To develop a computer tool that allows individual reconstruction and simulation of 3-dimensional (3D) soft tissue from ordinary digital photos of breasts, (2) to implement a Web-based, worldwide-accessible preoperative surgical planning platform for plastic surgeons, and (3) to validate this tool through a quality control analysis by comparing 3D laser scans of the patients with the 3D reconstructions with this tool from original 2-dimensional (2D) pictures of the same patients. METHODS: The proposed system uses well-established 2D digital photos for reconstruction into a 3D torso, which is then available to the user for interactive planning. The simulation is performed on dedicated servers, accessible via Internet. It allows the surgeon, together with the patient, to previsualize the impact of the proposed breast augmentation directly during the consultation before a surgery is decided upon. We retrospectively conduced a quality control assessment of available anonymized pre- and postoperative 2D digital photographs of patients undergoing breast augmentation procedures. The method presented above was used to reconstruct 3D pictures from 2D digital pictures. We used a laser scanner capable of generating a highly accurate surface model of the patient's anatomy to acquire ground truth data. The quality of the computed 3D reconstructions was compared with the ground truth data used to perform both qualitative and quantitative evaluations. RESULTS: We evaluated the system on 11 clinical cases for surface reconstructions and 4 clinical cases of postoperative simulations, using laser surface scan technologies showing a mean reconstruction error between 2 and 4 mm and a maximum outlier error of 16 mm. Qualitative and quantitative analyses from plastic surgeons demonstrate the potential of these new emerging technologies. CONCLUSIONS: We tested our tool for 3D, Web-based, patient-specific consultation in the clinical scenario of breast augmentation. This example shows that the current state of development allows for creation of responsive and effective Web-based, 3D medical tools, even with highly complex and time-consuming computation, by off-loading them to a dedicated high-performance data center. The efficient combination of advanced technologies, based on analysis and understanding of human anatomy and physiology, will allow the development of further Web-based reconstruction and predictive interfaces at different scales of the human body. The consultation tool presented herein exemplifies the potential of combining advancements in the core areas of computer science and biomedical engineering with the evolving areas of Web technologies. We are confident that future developments based on a multidisciplinary approach will further pave the way toward personalized Web-enabled medicine.

The role of androgens on hypoxia-inducible factor (HIF)-1α-induced angiogenesis and on the survival of ischemically challenged skin flaps in a rat model.

BACKGROUND: Effects of androgens on angiogenesis are controversial. Hypoxia-inducible factor (HIF)-1α promotes expression of vascular endothelial growth factor (VEGF) that stimulates angiogenesis. PURPOSE: This study investigates whether androgens stabilize HIF-1α in endothelial cells, and androgen depletion decreases VEGF concentrations and skin flap survival. MATERIALS AND METHODS: Male human umbilical vein endothelial cells (HUVECs) were exposed to dihydrotestosterone (DHT) and HIF-1α expression was measured. In male Wistar rats, standardized proximally based random pattern dorsal skin flaps (3 × 9 cm) were raised 4 weeks after orchiectomy and sham operation, respectively (n = 10, each). Flap VEGF concentrations (immunohistochemistry), perfusion (Laser Doppler), and viability (digital planimetry) were measured. RESULTS: DHT induced HIF-1α expression in HUVECs. Androgen depletion induced decreased VEGF expression (P = 0.003), flap perfusion (P < 0.05), and survival (44.4% ± 5.2%) compared to controls (35.5% ± 4.5%; P = 0.003). CONCLUSION: In vitro, androgens may stimulate HIF-1α under normoxic conditions. In rats, androgen depletion decrease VEGF expression and flap survival.

Schwannomas mistaken for metastases of melanoma in PET-CT: A diagnostic challenge with consequences.

The incidence of skin cancer and especially cutaneous malignant melanoma is rising, as are indications for staging examinations to detect metastasis. Schwannomas are common benign nerve tumors, which can be mistaken for metastasis even in highly specialized imaging. Risk of nerve lesion is high in inadvertent biopsy.