Hide-and-seek: Neurotropes Plattenepithelkarzinom der periorbitalen Region - eine Fallserie und Übersichtsarbeit aktueller Literatur.

Das Plattenepithelkarzinom ist nach dem Basalzellkarzinom das zweithäufigste Malignom der Haut und wird vorwiegend an sonnenexponierten Stellen wie der Gesichtshaut diagnostiziert. Diese meist lokal destruktiv wachsende Malignität kann durchaus auch invasives Wachstumsverhalten, wie perineurale Ausbreitungsmechanismen, aufweisen. Das Plattenepithelkarzinom der periorbitalen Region ist in bis zu 14 % der Fälle mit perineuraler Invasion assoziiert. Vor allem in diesem Bereich birgt die anatomische Nähe zu den Hirnnerven das Risiko einer Progression Richtung zentrales Nervensystem, was mit einer schlechteren Prognose assoziiert ist. Der klinisch unauffällige Charakter dieser Entität resultiert oft in einer Verzögerung der definitiven Diagnosestellung, wodurch die vollständige Resektion und anschließende Rekonstruktion erschwert werden. Eine aufmerksame klinische Evaluierung kann bereits vor Erlangen histologischer Befunde Hinweise für ein perineurales Wachstum liefern. Neben fünf herausfordernden Fällen analysiert diese Arbeit Risikofaktoren, klinische als auch histologische Merkmale und Behandlungsoptionen des periorbitalen Plattenepithelkarzinoms mit perineuraler Invasion.

Hide-and-seek: Neurotropic squamous cell carcinoma of the periorbital region - a series of five cases and review of the literature.

Squamous cell carcinoma is the second most common malignancy of the skin after basal cell carcinoma and mainly found in sun-exposed areas such as the face. This mostly locally destructive malignancy may show invasive growth and insidious mechanisms of dissemination such as perineural invasion. Periorbital squamous cell carcinoma is associated with perineural invasion in up to 14 % of cases. Specifically in this region, the proximity to cranial nerves and therefore the associated risk of progression to the central nervous system are associated with poor prognosis. The clinically concealed character of this entity often leads to a delay in diagnosis and consequently makes complete resection and reconstruction demanding. Careful clinical evaluation often hints at perineural invasion before obtaining histology. Aside from presenting five challenging cases, this work analyzes risk factors, clinical as well as histological features, and treatment options for periorbital squamous cell carcinoma with perineural invasion.

Long-term outcome after hand and forearm transplantation - a retrospective study.

Between 2000 and 2014, five patients received bilateral hand (n = 3), bilateral forearm (n = 1), and unilateral hand (n = 1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long-term results at 20 years. During the 6-20 years follow-up, 43 rejection episodes were recorded in total. Of these, 27.9% were antibody-related with serum donor-specific alloantibodies (DSA) and skin-infiltrating B-cells. The cell phenotype in rejecting skin biopsies changed and C4d-staining increased with time post-transplantation. In the long-term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients´ well-being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection-free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA.

[Fistula prophylaxis with muscle-sparing, myofascial pectoralis major lobe in salvage laryngectomy]. / Fistelprophylaxe mit muskelsparendem, myofaszialem Pectoralis-major-Lappen bei Salvage-Laryngektomie.

BACKGROUND: In recurrent hypopharyngeal/laryngeal squamous cell carcinoma after radiation salvage-laryngectomy (salvage-LE) represents the best curative treatment option. Pre-irradiation promotes development of pharyngocutaneous fistulas (pc-fistula). Transfer of unirradiated tissue to the surgical site reduces fistula rate. Frequently, a myocutaneous Pectoralis-major-flap (PMF) is applied. We describe a muscle sparing, myofascial PMF (ms-PMF) and its functional & aesthetic results. METHODS: For the ms-PMF, the pectoralis major is exposed via two 8 cm long subclavicular & submammary horizontal incisions. The pectoral branch of the thoracoacromial artery, which represents the blood supply for the ms-PMF, is identified between the clavicular and sternocostal aspect of the muscle. A craniocaudal stripe of the pectoralis major is recovered and supraclaviculary transposed towards the pharynx. The clavicular and sternocostal part of the muscle remain untouched.The clear-margin resection rate (CMRR), mean overall survival (OS), complications, median length of hospital stay, & functional & aesthetic outcome were assessed. RESULTS: In 25 patients, salvage-LE with ms-PMF was performed. The CMRR was 100 %, median OS 1.3 (follow-up 2.8) years, complications rate 16 % (4 complete lobe necroses, 3 pc-fistulas) and median inpatient stay 20 (11-78) days. Good functional outcome were observed: limitations of oral food intake occurred in 2-, limitations in voice rehabilitation in 3 patients. Wound healing disorders without lobe necrosis were not observed. The aesthetic results were appealing. CONCLUSION: The ms-PMF is a less invasive & safe procedure for fistula prophylaxis in salvage-LE with favorable functional & aesthetic results.

The Pectoralis Major Island Flap: Short Scar Modified Muscle-Sparing Harvesting Technique Improves Aesthetic Outcome in Reconstructive Head and Neck Surgery.

BACKGROUND: Pectoralis major flap reconstruction is often associated with large unappealing scars in head-neck surgery. We recently established an alternative harvesting technique that improves aesthetic outcome. OBJECTIVES: The objective of this study was to demonstrate a modified surgical technique that harvests the pectoralis major muscle as an island flap and focuses on minimizing incision lines and applying a muscle-sparing approach. METHODS: A retrospective analysis covering the period 2008-2018 was conducted. Patients who underwent pectoralis major island flap reconstruction for fistula prophylaxis after salvage laryngectomy at the Medical University of Innsbruck were included. Flap harvesting was performed subcutaneously using two small incision lines, thereby sparing the clavicular and upper sternocostal aspects of the pectoralis muscle. RESULTS: Twenty-three patients with squamous cell carcinoma of the larynx (n = 19) or pharynx (n = 4) underwent salvage laryngectomy and consecutive reconstruction using a pectoralis major island flap and our muscle-sparing technique. Mean overall operation time was 147 ± 48.6 min. The majority (70%) of patients had an uneventful course of recovery and showed satisfying aesthetic results and low donor site morbidity as compared to traditional harvesting techniques. Six (26%) patients had major complications that required surgical revision. Three (13%) cases were complicated with fistulas. CONCLUSION: The pectoralis major island flap is shown to be reliable in otolaryngeal surgery. This surgical technique minimizes scarring and preserves thoracic wall architecture by taking a less invasive approach, thereby improving aesthetic outcome and reducing overall patient morbidity.

Risk factors and complications after body-contouring surgery and the amount of stromal vascular fraction cells found in subcutaneous tissue.

Body contouring surgery following massive weight loss is often prone to complications. Subcutaneous adipose tissue is a rich source of stromal vascular fraction (SVF) cells, and moreover it plays an important role in the pathophysiology of obesity, metabolic syndrome, and wound healing. In this retrospective, single-centred appraisal, complications are examined and correlated with individual SVF numbers in abdominal subcutaneous fat tissue. We analysed whether the weight loss method affected complications. Eighty seven massive weight loss patients undergoing body contouring surgery between 2010 and 2017 were included in the study. In total, 57 cases with at least one complication were recorded (65.5%). Maximum lifetime weight was 109.6 kg (range 48-184 kg). Half of the complications (50.8%) were minor complications without the need for surgical revision. The mean number of SVF found in the resected tissue was 714 997.63 cells/g fat tissue. We found no statistical difference in complication rates dependent on cell numbers. Smoking (P = .049) and a high BMI at the time point of surgery (P = .031) led to significantly more complications. Also, a high resection weight (P = .057) showed a tendency for impaired wound healing. However, there was no difference in complication rates following body contouring procedures attributable to the method of weight loss in this study.

Human Macrophages Preferentially Infiltrate the Superficial Adipose Tissue.

Human abdominal subcutaneous adipose tissue consists of two individual layers—the superficial adipose tissue (SAT) and deep adipose tissue (DAT)—separated by the Scarpa’s fascia. The present study focuses on the analysis of morphological and immunological differences of primary adipocytes, adipose-derived stem cells (ASC), and tissue-infiltrating immune cells found in SAT and DAT. Adipocytes and stromal vascular fraction (SVF) cells were isolated from human SAT and DAT specimens and phenotypically characterized by in vitro assays. Ex vivo analysis of infiltrating immune cells was performed by flow cytometry. Primary adipocytes from SAT are larger in size but did not significantly differ in cytokine levels of LEPTIN, ADIPOQ, RBP4, CHEMERIN, DEFB1, VISFATIN, MCP1, or MSCF. ASC isolated from SAT proliferated faster and exhibited a higher differentiation potential than those isolated from DAT. Flow cytometry analysis indicated no specific differences in the relative numbers of ASC, epithelial progenitor cells (EPC), or CD3⁺ T-cells, but showed higher numbers of tissue-infiltrating macrophages in SAT compared to DAT. Our findings suggest that ASC isolated from SAT have a higher regenerative potential than DAT-ASC. Moreover, spatial proximity to skin microbiota might promote macrophage infiltration in SAT.

A small 'lick' will sink a great ship: fulminant septicaemia after dog saliva wound treatment in an asplenic patient.

Capnocytophaga canimorsus is a bacterium transmitted through the saliva of dogs. An infection can cause severe sepsis with acral necrosis and is potentially fatal. Here, we report the case of a 41-year-old man who was infected through a wound that was licked by his dog. He went into septic shock with disseminated intravascular coagulation and subsequently lost both lower legs, his nose and all the fingers on both hands.

Comparison of fasciocutaneous V-Y and rotational flaps for defect coverage of sacral pressure sores: a critical single-centre appraisal.

Pressure sore rates remain high in both nursing homes as well as in hospitals. Numerous surgical options are available for defect coverage in the sacral region. However, objective data is scarce as to whether a specific flap design is superior to another. Here, we aim to compare two fasciocutaneous flap designs for sacral defect coverage: the gluteal rotation flap and the gluteal V-Y flap. All primary sacral pressure sores of grades III-IV that were being covered with gluteal fasciocutaneous rotational or V-Y flaps between January 2008 and December 2014 at our institution were analysed. A total of 41 patients received a total of 52 flaps. Of these, 18 patients received 20 gluteal rotational flaps, and 23 patients received 32 V-Y flaps. Both groups were comparable with regards to demographics, comorbidities and complications. Significantly more V-Y flaps were needed to cover smaller defects. Mean length of hospital stay was significantly prolonged when surgical revision had to be carried out. Both flap designs have proven safe and reliable for defect coverage after sacral pressure sores. Gluteal rotational flaps appear to be more useful for larger defects. Both flap designs facilitate their reuse in case of pressure sore recurrence. Complication rates appear to be comparable in both designs and to the current literature.

The versatility of the medial thigh lift for defect coverage in the genito-perineal region.

Soft tissue defects in the genito-perineal region are predominantly because of trauma, infections, neoplasms or iatrogenic causes. As a result of the region's urological, reproductive and gastrointestinal function, defects in this area may cause devastating physical and psychological consequences as well as diminished sexual functioning. The purpose of this study was to examine the efficacy of implementing a medial thigh lift for defect coverage in the perineal region. A retrospective analysis of all medial thigh lift procedures for defect coverage in the genito-perineal region between November 2010 and March 2015 was conducted at three institutions. Ten consecutive patients underwent a medial thigh lift for defect coverage in the genito-perineal region. Nine patients were male, and one was female. The causative factors were Fournier's gangrene in eight patients, one patient had a straddle injury, and one suffered from extramammary Paget's disease. The mean follow-up time was 19·8 months. The average total defect size was 11·1 × 11 cm (length × width). The medial thigh lift procedure is a safe, technically easy and reliable technique with discrete scars. Outstanding aesthetic and functional outcomes result in a high rate of patient satisfaction. Through immediate wound closure, a reduction of recovery time can be achieved.

Reduction mammaplasty: outcome analysis based on bodyweight.

UNLABELLED: This retrospective study aimed to evaluate how reduction mammaplasty influences the bodyweight of patients 5 years after the procedure. The literature shows controversy regarding the effect of breast reduction on the progression of bodyweight. Between 1 January 2006 and 31 July 2007, 249 reduction mammaplasties were performed in the Department of Plastic, Reconstructive, and Aesthetic Surgery at the University Hospital Innsbruck. The exclusion criteria ruled out patients with oncoplastic breast reduction plasties, unilateral reduction mammaplasty, no documented preoperative weight, and bariatric procedures. The study finally included 50 women with a mean age of 44 ± 12 years. Of these 50 women, 26 (52 %) gained weight, 18 (36 %) lost weight, and 6 (12 %) remained stable during a 5-year follow-up period after the procedure. The mean weight gain was 4.50 ± 3.5 kg, and the mean weight loss was 3.44 ± 2.20 kg. The results of the study suggest that reduction mammaplasty is not a stimulus for weight loss. Although a tendency to gain weight was discovered, the weight gain compared with that of the standard population did not reach statistical significance. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Elimination of damaged mitochondria during UVB-induced senescence is orchestrated by NIX-dependent mitophagy.

Skin aging is the result of two types of aging, "intrinsic aging" an inevitable consequence of physiologic and genetically determined changes and "extrinsic aging," which is dependent on external factors such as exposure to sunlight, smoking, and dietary habits. UVB causes skin injury through the generation of free radicals and other oxidative byproducts, also contributing to DNA damage. Appearance and accumulation of senescent cells in the skin are considered one of the hallmarks of aging in this tissue. Mitochondria play an important role for the development of cellular senescence, in particular stress-induced senescence of human cells. However, many aspects of mitochondrial physiology relevant to cellular senescence and extrinsic skin aging remain to be unraveled. Here, we demonstrate that mitochondria damaged by UVB irradiation of human dermal fibroblasts (HDF) are eliminated by NIX-dependent mitophagy and that this process is important for cell survival under these conditions. Additionally, UVB-irradiation of human dermal fibroblasts (HDF) induces the shedding of extracellular vesicles (EVs), and this process is significantly enhanced in UVB-irradiated NIX-depleted cells. Our findings establish NIX as the main mitophagy receptor in the process of UVB-induced senescence and suggest the release of EVs as an alternative mechanism of mitochondrial quality control in HDF.

Depletion of growth differentiation factor 15 (GDF15) leads to mitochondrial dysfunction and premature senescence in human dermal fibroblasts.

Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine also known as a mitokine; however, its role in mitochondrial homeostasis and cellular senescence remained elusive. We show here that knocking down GDF15 expression in human dermal fibroblasts induced mitochondrial dysfunction and premature senescence, associated with a distinct senescence-associated secretory phenotype. Fibroblast-specific loss of GDF15 expression in a model of 3D reconstructed human skin induced epidermal thinning, a hallmark of skin aging. Our results suggest GDF15 to play a so far undisclosed role in mitochondrial homeostasis to delay both the onset of cellular senescence and the appearance of age-related changes in a 3D human skin model.

Single- versus two-stage reconstruction in patients with head and neck cancer: What are the benefits?

In head and neck oncology, surgical treatment frequently results in microvascular reconstruction. Oncologic resection followed by immediate reconstruction is often associated with prolonged working and surgical duration, challenging a surgeon's concentration level and potentially worsening patient outcome. To improve the surgeon's performance and to reduce risk of potential complications, we implemented a two-stage procedure in patients with head and neck cancer. This study critically analyzed the surgical outcomes, organizational benefits, and investigated job satisfaction among affected health care professionals. A retrospective data analysis of patients who had undergone microvascular reconstruction after oncologic head and neck surgery between 2010 and 2021 included 33 patients (n = 33). Twenty patients underwent single-stage reconstruction (group 1, n = 20) and 13 patients underwent two-stage reconstruction (group 2, n = 13) with 12.2 (± 7.4) days between surgeries. The mean surgical duration, and mean start and end time of the reconstructive surgery component differed significantly (p = 0.002). The mean total complication rate (p = 0.58) did not differ significantly, although a trend toward higher demands for blood products was observed in group 1. There was no significant difference in five-year survival (p = 0.28). A questionnaire on subjective work performance was answered by the affected health care professionals (n = 34) and it revealed that 88% preferred long surgeries to be scheduled first and that 97% work most efficiently in the morning. In conclusion, two-stage reconstruction is a suitable option in selected head and neck cancer patients offering the possibility of optimizing preoperative planning and organization. This may result in regular working hours, reduced surgeon fatigue, and improved job satisfaction without compromising patient outcomes or survival.

Delayed Reconstruction after Major Head and Neck Cancer Resection: An Interdisciplinary Feasibility Study.

A single immediate reconstruction with free tissue transfer is the method of choice after major head and neck cancer (HNC) resection, but this is frequently associated with long operating hours. Considering regulatory working hour constraints, we investigated whether a two-staged reconstructive approach with temporary defect coverage by an artificial tissue substitute would be feasible. HNC patients underwent either immediate or delayed reconstruction after tumor resection. Patients with delayed reconstruction received preliminary reconstruction with an artificial tissue substitute followed by definitive microvascular reconstruction in a separate, second procedure. Of the 33 HNC patients, 13 received delayed reconstruction and 20 received immediate reconstruction. Total anesthesia time (714 vs. 1011 min; p < 0.002) and the total duration of hospital stay (34 ± 13 vs. 25 ± 6 days; p = 0.03) were longer in the delayed reconstruction group. Perioperative morbidity (p = 0.58), functional outcome (p > 0.1) and 5-year postoperative survival rank (p = 0.28) were comparable in both groups. Delayed reconstruction after HNC resection was feasible. Perioperative morbidity, functional outcome and overall survival were comparable to immediate reconstruction.

Resection of Skin Cancer Resulting in Free Vascularized Tissue Reconstruction: Always a Therapeutic Failure?

The globally increasing incidence of cutaneous malignancies leads, in parallel, to increasing numbers of locally advanced skin cancer resulting in reconstructive surgery. Reasons for locally advanced skin cancer may be a patient's neglect or aggressive tumor growth, such as desmoplastic growth or perineural invasion. This study investigates characteristics of cutaneous malignancies requiring microsurgical reconstruction with the aim of identifying possible pitfalls and improving diagnostic and therapeutic processes. A retrospective data analysis from 2015 to 2020 was conducted. Seventeen patients (n = 17) were included. The mean age at reconstructive surgery was 68.5 (±13) years. The majority of patients (14/17, 82%) presented with recurrent skin cancer. The most common histological entity was squamous cell carcinoma (10/17, 59%). All neoplasms showed at least one of the following histopathological characteristics: desmoplastic growth (12/17, 71%), perineural invasion (6/17, 35%), or tumor thickness of at least 6 mm (9/17, 53%). The mean number of surgical resections until cancer-free resection margins (R0) were achieved was 2.4 (±0.7). The local recurrence rate and the rate of distant metastases were 36%. Identified high-risk neoplastic characteristics, such as desmoplastic growth, perineural invasion, and a tumor depth of at least 6 mm, require a more extensive surgical treatment without concerns about defect size.

Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization.

BACKGROUND: Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin wounds heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and the formation of granulation tissue, a type of premature scar tissue without epithelialization. Regenerative cells from the wound periphery contribute to the healing process, but little is known about their cellular fate in an inflammatory, macrophage-dominated wound microenvironment. METHODS: We examined CD45-/CD31-/CD34+ preadipocytes and CD68+ macrophages in human granulation tissue from pressure ulcers (n=6) using immunofluorescence, immunohistochemistry, and flow cytometry. In vitro, we studied macrophage-preadipocyte interactions using primary human adipose-derived stem cells (ASCs) exposed to conditioned medium harvested from IFNG/LPS (M1)- or IL4/IL13 (M2)-activated macrophages. Macrophages were derived from THP1 cells or CD14+ monocytes. In addition to confocal microscopy and flow cytometry, ASCs were analyzed for metabolic (OXPHOS, glycolysis), morphological (cytoskeleton), and mitochondrial (ATP production, membrane potential) changes. Angiogenic properties of ASCs were determined by HUVEC-based angiogenesis assay. Protein and mRNA levels were assessed by immunoblotting and quantitative RT-PCR. RESULTS: CD45-/CD31-/CD34+ preadipocytes were observed with a prevalence of up to 1.5% of total viable cells in human granulation tissue. Immunofluorescence staining suggested a spatial proximity of these cells to CD68+ macrophages in vivo. In vitro, ASCs exposed to M1, but not to M2 macrophage secretome showed a pro-fibrotic response characterized by stress fiber formation, elevated alpha smooth muscle actin (SMA), and increased expression of integrins ITGA5 and ITGAV. Macrophage-secreted IL1B and TGFB1 mediated this response via the PI3K/AKT and p38-MAPK pathways. In addition, ASCs exposed to M1-inflammatory stress demonstrated reduced migration, switched to a glycolysis-dominated metabolism with reduced ATP production, and increased levels of inflammatory cytokines such as IL1B, IL8, and MCP1. Notably, M1 but not M2 macrophages enhanced the angiogenic potential of ASCs. CONCLUSION: Preadipocyte fate in wound tissue is influenced by macrophage polarization. Pro-inflammatory M1 macrophages induce a pro-fibrotic response in ASCs through IL1B and TGFB1 signaling, while anti-inflammatory M2 macrophages have limited effects. These findings shed light on cellular interactions in chronic wounds and provide important information for the potential therapeutic use of ASCs in human wound healing.

The psychological assessment of candidates for reconstructive hand transplantation.

Standardized psychological assessment of candidates for reconstructive hand transplantation (RHT) is a new approach in transplantation medicine. Currently, international guidelines and standardized criteria for the evaluation are not established. Patients suffering from the loss of a hand or an upper extremity have to cope with multiple challenges. For a selected group of patients, RHT represents an option for restoring natural function and for regaining daily living independence. The identification of at-risk patients and those requiring ongoing counseling due to poor coping or limited psychological resources are the primary focus of the psychological assessment. We have developed the 'Innsbruck Psychological Screening Program for Reconstructive Transplantation (iRT-PSP)' which utilizes a semi-structured interview and standardized psychological screening procedures and continuous follow-up ratings. Between January 2011 and October 2011, four candidates were evaluated using the iRT-PSP. Psychological impairments including social withdrawal, embarrassment, reduced self-esteem, and a depressive coping style were identified and poor quality of life was reported. The motivation for transplantation was diverse, depending on many factors such as bi- or unilateral impairment, native or accidental loss of hand, and social integration.

Instep split skin grafts on muscle flaps to reconstruct pressure exposed soft tissue parts at the lower extremity.

BACKGROUND: Reconstructed mechanically stressed zones of the lower extremity frequently suffer from problems such as hyperkeratotic edges or chronic ulcerations in the transition zone between conventional thigh skin grafts and normal skin. Defect coverage with skin grafts harvested from the instep region and placed on muscle flaps is not yet an established alternative. METHODS: This is a retrospective study of a series of 12 clinical applications of soft tissue reconstruction at mechanically exposed zones of the lower extremity. Locally transposed or transplanted muscle flaps were covered with meshed instep skin instead of meshed thigh skin for the purpose to gain a superior stable skin surface and transition zones adjacent to normal skin. RESULTS: There is no ulceration found at follow-up from 6 to 72 months. Only one case presented with delayed graft take. Different thicknesses of the corneal layers of the healed instep versus thigh skin grafts were verified histologically. Instep skin grafts showed substantial durability as well as advantageous aesthetic appearance with respect to texture and coloring. All donor sites healed without notable scars or sensitivity disorders. CONCLUSIONS: The instep split skin graft is particularly well suited for defect coverage of muscle flaps transposed or transplanted to mechanically stressed zones of the foot or lower leg. The paramount advantage of transplanted instep skin as compared to thigh skin is given by the feasibility to create a durable graft with a thick horny layer and a stable transition zone at its periphery that is bordering normal skin.