Vascular study of decellularized porcine long bones: Characterization of a tissue engineering model.

INTRODUCTION: Massive bone allografts enable the reconstruction of critical bone defects in numerous conditions (e.g. tumoral, infection or trauma). Unfortunately, their biological integration remains insufficient and the reconstruction may suffer from several postoperative complications. Perfusion-decellularization emerges as a tissue engineering potential solution to enhance osseointegration. Therefore, an intrinsic vascular study of this novel tissue engineering tool becomes essential to understand its efficacy and applicability. MATERIAL AND METHODS: 32 porcine long bones (humeri and femurs) were used to assess the quality of their vascular network prior and after undergoing a perfusion-decellularization protocol. 12 paired bones were used to assess the vascular matrix prior (N = 6) and after our protocol (N = 6) by immunohistochemistry. Collagen IV, Von Willebrand factor and CD31 were targeted then quantified. The medullary macroscopic vascular network was evaluated with 12 bones: 6 were decellularized and the other 6 were, as control, not treated. All 12 underwent a contrast-agent injection through the nutrient artery prior an angio CT-scan acquisition. The images were processed and the length of medullary vessels filled with contrast agent were measured on angiographic cT images obtained in control and decellularized bones by 4 independent observers to evaluate the vascular network preservation. The microscopic cortical vascular network was evaluated on 8 bones: 4 control and 4 decellularized. After injection of gelatinous fluorochrome mixture (calcein green), non-decalcified fluoroscopic microscopy was performed in order to assess the perfusion quality of cortical vascular lacunae. RESULTS: The continuity of the microscopic vascular network was assessed with Collagen IV immunohistochemistry (p-value = 0.805) while the decellularization quality was observed through CD31 and Von Willebrand factor immunohistochemistry (p-values <0.001). The macroscopic vascular network was severely impaired after perfusion-decellularization; nutrient arteries were still patent but the amount of medullary vascular channels measured was significantly higher in the control group compared to the decellularized group (p-value <0.001). On average, the observers show good agreement on these results, except in the decellularized group where more inter-observer discrepancies were observed. The microscopic vascular network was observed with green fluoroscopic signal in almost every canals and lacunae of the bone cortices, in three different bone locations (proximal metaphysis, diaphysis and distal metaphysis). CONCLUSION: Despite the aggressiveness of the decellularization protocol on medullary vessels, total porcine long bones decellularized by perfusion retain an acellular cortical microvascular network. By injection through the intact nutrient arteries, this latter vascular network can still be used as a total bone infusion access for bone tissue engineering in order to enhance massive bone allografts prior implantation.

Exceptional manifestation of Madelung's disease after liver transplantation.

Unlike simple obesity, Madelung's disease (MD) is a rare disease characterized by symmetric accumulation of massive adipose tissue on the neck, the superior part of the trunk and limbs, leading to a pathognomonic cosmetic deformity. Here, we report an extremely rare case of MD associated with bilateral gynecomastia in a 61-year-old man, with a history of recent liver transplantation for alcoholic liver disease (ALD).

Role of flow magnetic resonance imaging in the monitoring of facial allotransplantations: preliminary results on graft vasculopathy.

Chronic vascular rejection characterized by the myointimal proliferation of smooth muscle cells that progressively obstruct the arterial graft lumen may become the main cause of long-term graft loss in vascularized composite allotransplantation (VCA), as observed in solid organ transplantation. As such, new diagnostic tools are required. The objective of this study was to evaluate the usefulness of flow magnetic resonance imaging (MRI) in the qualitative and quantitative monitoring of VCA in three patients transplanted between 2005 and 2012. Seven flow MRI acquisitions were performed concurrently with standardized clinical and histological monitoring between 2015 and 2017. A progressive reduction in the average flow rate and intraluminal diameter of the arterial pedicle of the grafts was demonstrated. During follow-up, two patients developed chronic vascular rejection requiring partial resection of the graft. For these patients, flow MRI acquisitions were characterized by a significant reduction in vascular signal, with a reduction in intravascular flow prior to anatomical injury. The results of this study confirm the feasibility of reproducible, non-invasive, and non-operator-dependent morphometric and haemodynamic radiological analysis, providing clinicians with new information on the vascular status of VCA over time and offering the prospect of an imaging technique specific to vascular outflow.

The value of reconstructive surgery in the management of refractory jaw osteoradionecrosis: a single-center 10-year experience.

Mandibular osteoradionecrosis (mORN) is a severe complication of head and neck irradiation. International consensus on the management of mORN is currently lacking. The present study sought to evaluate the effectiveness and benefits of early reconstructive surgery (resection of the diseased bone and immediate reconstruction with a free flap) in treatment-refractory mORN. A single-center retrospective study was carried out of operations performed in a French university medical center between 2003 and 2013 inclusive. For each patient, the surgical modalities and postoperative outcomes were recorded. A total of 55 operations (19 marginal resections and 36 segmental resections) were performed, and the overall success rate was 92.3%. Relative to marginal resections, segmental resections were associated with longer operating times (440±62min vs. 531±72min, respectively; P<0.05 in Student's t-test), a longer length of hospital stay (16.5±6.5 days vs. 25.6±11.3 days, respectively; P<0.05), and a higher complication rate (26.3% vs. 63.9%, respectively; P<0.05 in Fisher's test). Given the unpredictable progression of treatment-refractory mORN and the risk-benefit ratio observed here, the value of early reconstructive surgery with curative intent should be reassessed.

Treatment of mandibular osteoradionecrosis by periosteal free flaps.

Mandibular osteoradionecrosis (ORN) is one of the most serious complications of radiotherapy of the head and neck, and is characterised by hypoxia, hypovascularisation, and hypocellularity. Periosteal free flaps have intrinsic osteogenic, and extrinsic neoangiogenic, properties that are related to the periosteum. Our objective was to present our experience with the use of periosteal free flaps in the treatment of ORN (Notani class I or II) that are refractory to conservative management or have a large area of bone (≥2 cm) exposed. We organised a single-centre, retrospective study between 2003 and 2013 and describe the management of 11 patients (4 women and 7 men) who were being treated for refractory mandibular ORN. Thirteen periosteal free flaps were used: inner femoral condylar periosteum (n = 4), iliac crest (n = 1), external brachial with humeral periosteum (n = 1), and forearm with radial periosteum (n = 7). During follow-up we found three acute complications (haematoma, partial necrosis, and total vascular necrosis) that required immediate construction of a second periosteal free flap. There were also two chronic complications (fistula and post-traumatic fracture). With only one progressive lesion identified, the ORN was stopped in 11/12 patients. Two examples of osteoconduction were identified on postoperative images at six months and two years. Because of its osteoconductive and neoangiogenic capacities, the periosteal free flap seems to offer a real biological dimension to the treatment of ORN, and its efficiency favours its early revascularisation.

[Management of vascular anomalies in children]. / Prise en charge des anomalies vasculaires chez l'enfant.

Vascular anomalies, which are broadly identified as "angiomas", are rare entities and often unknown by the medical sphere. They are divided in two different categories which carry different prognosis and management: "vascular tumors" and "vascular malformations". Their precise identification is crucial and involves a good knowledge of the biological classification published by Mulliken and Glowacki and that has recently been updated by the International Society for the Study of Vascular Anomalies (ISSVA). Vascular tumors are benign, common, inborn or not and most of the time disappear with growth. Vascular malformations are always congenital and growth with the child. They can involve type of vessels solely or combined with others. A rheologic differentiation between slow and fast flow malformations is essential in order to characterize the seriousness of the lesion. Frequently, their diagnosis is clinically established and the anamnesis is conducted to answer three questions that are the time of revelation of the lesion ("When?"), its aspect ("What?") and its evolution ("How?"). Further investigations are usually not required but a non-invasive imaging technique such as Doppler ultrasound could be useful if a doubt exists. Surgery is not mandatory and must always be well thought because its consequences might be disastrous. It must be left to cosmetic sequelae of these lesions or to lesions that are totally resectable without causing any unacceptable deformation.

Involvement of mTOR and Regulation by AMPK in Early Iodine Deficiency-Induced Thyroid Microvascular Activation.

Iodine deficiency (ID) induces TSH-independent microvascular activation in the thyroid via the reactive oxygen species/nitric oxide-hypoxia-inducible factor-1α/vascular endothelial growth factor (VEGF) pathway. We hypothesized the additional involvement of mammalian target of rapamycin (mTOR) as a positive regulator of this pathway and AMP-activated protein kinase (AMPK) as a negative feedback regulator to explain the transient nature of ID-induced microvascular changes under nonmalignant conditions. mTOR and AMPK involvement was investigated using an in vitro model (human thyrocytes in primary cultures) and 2 murine models of goitrogenesis (normal NMRI and RET-PTC mice [a papillary thyroid cancer model]). In NMRI mice, ID had no effect on the phosphorylation of ribosomal S6 kinase (p70S6K), a downstream target of mTOR. However, rapamycin inhibited ID-induced thyroid blood flow and VEGF protein expression. In the RET-PTC model, ID strongly increased the phosphorylation of p70S6K, whereas rapamycin completely inhibited the ID-induced increase in p70S6K phosphorylation, thyroid blood flow, and VEGF-A expression. In vitro, although ID increased p70S6K phosphorylation, the ID-stimulated hypoxia-inducible factor/VEGF pathway was inhibited by rapamycin. Activation of AMPK by metformin inhibited ID effects both in vivo and in vitro. In AMPK-α1 knockout mice, the ID-induced increase in thyroid blood flow and VEGF-A protein expression persisted throughout the treatment, whereas both parameters returned to control values in wild-type mice after 4 days of ID. In conclusion, mTOR is required for early ID-induced thyroid microvascular activation. AMPK negatively regulates this pathway, which may account for the transient nature of ID-induced TSH-independent vascular effects under benign conditions.

Breast prosthesis infection and pets: A case report and review of the literature.

INTRODUCTION: Pets are not always the human's best friends, particularly in the presence of comorbidities such as wounds. The following case report describes a Pasteurella multocida infection of a reconstructive breast implant due to a close contact between a cat and its owner. PRESENTATION OF CASE: A 33-year-old woman developed a breast implant infection 13 days after an immediate breast reconstruction following a mastectomy for a multifocal ductal carcinoma. The wound was explored surgically and the implant removed. Culture extracted from fluid around the prosthesis evidenced the presence of P. multocida, a Gram-negative coccobacillus which is present in the oral commensal flora of cats and dogs. CONCLUSION: In the case of breast infection, surgical revision - with or without removal of the implant - is required in order to carry out a meticulous intraoperative cleaning. Antibiotherapy is always necessary in such cases. Particularly when patients presenting comorbidities are concerned, the focus must be put on avoiding close contact of the wound with pets.

The place of extensive surgery in locoregional recurrence and limited metastatic disease of breast cancer: preliminary results.

UNLABELLED: The aims of this study were first to clearly define two different entities: locoregional recurrences and limited metastatic disease and secondly to evaluate the place of extensive surgery in these two types of recurrence. MATERIAL AND METHODS: Twenty-four patients were followed from June 2004 until May 2014. All patients underwent surgery but for 1 patient this surgery was stopped because the tumour was unresectable. RESULTS: The median interval between surgery for the primary tumour and the locoregional recurrence or metastatic evolution was 129 months. Eight patients had pure nodal recurrences, 4 had nodal and muscular recurrences, 5 had muscular + skin recurrences, and 8 had metastatic evolution. Currently, all patients are still alive but 2 have liver metastases. Disease free survival was measured at 2 years and extrapolated at 5 years and was 92% at these two time points. No difference was observed for young or older women; limited metastatic evolution and locoregional recurrence exhibited the same disease free survival. CONCLUSION: Extensive surgery has a place in locoregional and limited metastatic breast cancer recurrences but this option must absolutely be integrated in the multidisciplinary strategy of therapeutic options and needs to be planned with a curative intent.

Requirements analysis and preliminary design of a robotic assistant for reconstructive microsurgery.

Microanastomosis is a microsurgical gesture that involves suturing two very small blood vessels together. This gesture is used in many operations such as avulsed member auto-grafting, pediatric surgery, reconstructive surgery - including breast reconstruction by free flap. When vessels have diameters smaller than one millimeter, hand tremors make movements difficult to control. This paper introduces our preliminary steps towards robotic assistance for helping surgeons to perform microanastomosis in optimal conditions, in order to increase gesture quality and reliability even on smaller diameters. A general needs assessment and an experimental motion analysis were performed to define the requirements of the robot. Geometric parameters of the kinematic structure were then optimized to fulfill specific objectives. A prototype of the robot is currently being designed and built in order to providing a sufficient increase in accuracy without prolonging the duration of the procedure.

Split temporalis muscle flap anatomy, vascularization and clinical applications.

INTRODUCTION: For more than a century, the temporalis muscle has been used for facial reconstructions. More recently, a split temporalis muscle flap elevated on the superficial temporal pedicle has been described, for which the resulting gain of length makes crossing of the midline possible, as well as reconstruction of substance losses exceeding the midline. MATERIALS AND METHODS: Fourteen fresh cadaveric dissections were performed to study the different techniques for splitting the temporalis muscle. Dissections with catheterization and injection of radio-opaque contrasting agent in the external carotid artery were then performed to specify the vascularization of the flap split on the superficial temporal pedicle. RESULTS: The duplication of the superficial temporal pedicle grants greater length compared to that of the deep pedicles, 57 mm versus 40 (p = 0.036). The middle temporal artery is capable of ensuring the vascularization, and therefore the viability, of the split flap. From these results, we spoke about the limitations of this study and we have inferred the main indications.

Techniques for coverage of infected vascular grafts in the groin.

Plastic surgeons expertise is requested for treatment of vascular graft exposures. Exposure within the femoral triangle (Scarpa) represents the majority of those cases. We intend to share our experience in the coverage of exposed vascular grafts: through the most common and safe procedures we are currently using, illustrated by some of our clinical cases. Our experience leaded us to formulate some guidelines and conclusions, to ensure vascular surgeons that coverage of a vascular graft can always be successfully done.

[Facial graft, archetype of microsurgical innovation?]. / La greffe de visage, archétype de l'innovation microchirurgicale.

Is innovation breaking of the way of thinking, breaker of taboos, concretisation of chimeras or simple benefit of an ineluctable evolution? The surgical act should be considered as innovation itself? From the first facial allotransplantation, innovation is declined in various ways, which could constitute the different answers regarding the planning and management to prepare such surgery, the realisation of the transplantation and also the multiple developments in terms of science and medicine. It is exactly in that meaning that could be really mentioned the term archetypal.

Prognostic factors and assessment of staging systems for head and neck soft tissue sarcomas in adults.

OBJECTIVES: The primary objectives of this study were to analyse the outcome of patients diagnosed with head and neck soft tissue sarcomas (HNSTS) and to identify relevant prognostic factors. As well as this, we compared the prognostic value of two staging systems proposed by the American Joint Committee on Cancer (AJCC) and the Memorial Sloan-Kettering Cancer Center (MSKCC). METHODS: From 07/1988 to 01/2008, the charts of 42 adult patients were retrospectively reviewed. Potential prognostic factors were analysed according to overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: At 5 years, OS was 57%, DFS 47% and DSS 72%. On univariate analysis, statistically significant prognostic factors were for OS, distant or lymph node metastasis at diagnosis (p=0.032), for DFS, margins after surgery (p=0.007), for DSS, regional or distant metastasis at diagnosis (p=0.002), initial AJCC and MSKCC stage (p=0.018 and p=0.048) and margins after surgery (p=0.042). On multivariate analysis, margins remained statistically significant for DFS (p=0.039) when there was a trend with the initial AJCC stage (p=0.054) for OS. The AJCC staging system was of more prognostic value than the MSKCC staging system. CONCLUSIONS: Achieving clear margins after surgery is vital for improved local control and the best chance of survival. Adjuvant chemotherapy and radiotherapy were not shown to provide additional benefit. To better identify prognostic factors, it seems essential to set up national and international databases allowing multicenter registration for those patients.

The use of grafting material in rhinoseptoplasty.

Grafting is one of the current range of instruments that rhinoplasticians deploy to achieve durable and desired aesthetic and functional outcomes. Grafts can be classified according to anatomical site and, in the vast majority of cases, they involve augmentation rhinoseptoplasty. Visible grafting material is used for aesthetic purposes and functional grafting may involve invisible grafts. This article reviews the more widely described and more common indications for grafts in rhinoseptoplasty. The authors' rhinoseptoplasty philosophy involves a preference for autogenous grafts rather than alloplastic implants to achieve both aesthetically and functionally favourable results, particularly in long-term follow-up. They also prefer grafts in an open approach, reserving graft insertion with an endonasal approach for selected cases. The rate of complications associated with grafting is very low. The aim of this paper is to discuss the relevant anatomy, functional purpose and terminology, and to describe the authors' philosophy for grafting in rhinoseptoplasty.

Orthodontic loading of titanium miniplates in dogs: microradiographic and histological evaluation.

OBJECTIVES: The objectives of this animal study were to evaluate if orthodontic loading has an impact on osseointegration of screws supporting miniplates, and to describe the histological components of the bone-screw interface. MATERIALS AND METHODS: Eighty orthodontic miniplates were placed in the jaws of 10 dogs. After 2 weeks, a 125 g force was applied between the miniplates of one upper quadrant of each dog and between those of the controlateral lower quadrant. The others, nonloaded miniplates, were considered as controls. Five dogs were sacrificed 7 weeks after implantation and the remaining five dogs after 29 weeks [Short Term (ST) and Long Term (LT) groups, respectively]. Fluorochromes were injected at implantation and at sacrifice. Jaw quadrants were dissected, embedded, cut into undecalcified transverse sections through the screws and finally submitted to microradiographic analysis to allow assessment of bone-implant contact (BIC) and bone volume/total volume (BV/TV). The sections were observed under UV light and stained in order to examine them under ordinary light. RESULTS: Osseointegration occurred around 90/160 screws and consisted mainly in limited repair and remodelling processes of lamellar bone, without inflammation. Wide variations were observed in BIC and BV/TV, but without any significant difference, neither between the loaded and the nonloaded screws, nor according to the direction of load, whereas they were significantly higher in the LT than in the ST group. Nonosseointegrated screws were surrounded by fibrous tissue. Osteoblastic activity, when present in front of these screws, was not sufficient to achieve stability. CONCLUSIONS: Osseointegration underlying orthodontic anchorage was not affected by loading. BIC increased with time and varied according to implantation site. Particularly the tight-fitting screw insertion appeared crucial in determining the appropriate bone healing response.

The versatility of the sub-mental flap: a case report.

The sub-mental flap has been used in four elderly patients (mean age: 83 years) for reconstruction of defects after oncological resection: three had basal cell carcinoma (cheek, temporal region and fronto-temporal region). One had a squamous cell carcinoma of the hard palate. We believe that the latter example is original and present it in this article. This case shows that the sub-mental flap in addition to its intrinsic qualities is a reliable flap which may be useful in difficult repairs. It can be used to repair wide palatal fistula which occurs after oncological resections.

[Mediatisation and "facial graft" or "to whom belongs the facial graft"?]. / Médiatisation et "greffe de visage" ou "à qui appartient la greffe de visage"?

Mediatisation of a scientific event could be neither controlled, nor verifiable. The experience which has been lived through the first worldwide allotransplantation of composite tissues of the face confirms that the actors of a surgical innovation are not the owners. Because there is neither confidentiality nor possible patent. Curiously the scientific world, providing with a sharing ethic, which rightly privileges the free spreading of knowledge in the way that most people could benefit of it. Obviously it is made without denied controversy, for truth as purpose. This scientific word that way joins the media one, with a specific ethic of the duty of information, but also interested in mercantile preoccupations quick to cultivate controversy not to enlighten this truth but to better sell pictures or papers. Than the author should only sustain this instrumentation which could certainly flatter him, and from which he could used, but in reality that paralysed him a little to go on in serenity with his shadow worker way.