Indocyanine green fluorescence angiography for free flap monitoring: A pilot study.

OBJECTIVE: We evaluated the feasibility and the tolerance of repeated fluorescent indocyanine green angiography in free flap monitoring, and determined the intraoperative predictive values of flap vitality. BACKGROUND: The free flap failure rate has been significantly reduced, but free flap loss still occurs and remains a costly disaster. Repeated clinical examinations are commonly used for flap monitoring, but they can be unreliable because of their subjectivity. Laser-induced fluorescence of indocyanine green is a new method for assessing tissue perfusion. METHODS: 20 patients undergoing microsurgical reconstruction were monitored by indocyanine green fluorescence angiography, intraoperatively, and during 4 days after surgery, with 18 injections. Monitoring was made by clinical examination, and then compared to angiographic findings. RESULTS: The vascular complication rate was 15% (3/20) with 2 cases of venous thrombosis and one case of partial necrosis of the flap skin paddle. Both cases of venous thrombosis were salvaged by secondary surgery. There was no total flap loss. ICG angiography allowed detecting each intra and postoperative complication, earlier than clinical examination. The mean per-operative intensity of fluorescence was significantly lower in flaps with vascular complications (23.8 GL/ms; p = 0.008). The postoperative slope (p = 0.02) and amplitude (p = 0.03) of the fluorescent signal were both significantly lower than for uncomplicated flaps, before surgical revision. These 2 parameters came back to normal values after secondary surgery. There was no adverse effect of ICG despite the repeated injections. CONCLUSION: ICG angiography is a feasible and safe technique for the detection of free flap vascular complications.

Toward noninvasive assessment of flap viability with time-resolved diffuse optical tomography: a preclinical test on rats.

The noninvasive assessment of flap viability in autologous reconstruction surgery is still an unmet clinical need. To cope with this problem, we developed a proof-of-principle fully automatized setup for fast time-gated diffuse optical tomography exploiting Mellin-Laplace transform to obtain three-dimensional tomographic reconstructions of oxy- and deoxy-hemoglobin concentrations. We applied this method to perform preclinical tests on rats inducing total venous occlusion in the cutaneous abdominal flaps. Notwithstanding the use of just four source-detector couples, we could detect a spatially localized increase of deoxyhemoglobin following the occlusion (up to 550 µM in 54 min). Such capability to image spatio-temporal evolution of blood perfusion is a key issue for the noninvasive monitoring of flap viability.

Perforator-based chimaeric thoracodorsal flap for foot reconstruction.

The reconstruction of severe defects of the ankle and foot is a challenge. The ideal solution should combine a thin skin flap on the dorsum to allow shoe fitting and a muscle flap with a split-thickness skin graft on the weight-bearing area. Perforator-based thoracodorsal chimaeric flaps allow us to achieve these two goals with minimal donor-site morbidity. We present a reconstruction of an extended circumferential defect of the ankle with an exposed heel using a chimaeric thoracodorsal perforator flap with a serratus muscle flap. The skin flap was transferred on the dorsal foot, whereas the serratus anterior muscle was transferred on the exposed heel. Postoperative recovery was uneventful and the patient began full weight bearing after 3 months. Twelve months after reconstruction, natural shape and walking function were successfully achieved.

Vascular anastomosis using controlled phase transitions in poloxamer gels.

Vascular anastomosis is the cornerstone of vascular, cardiovascular and transplant surgery. Most anastomoses are performed with sutures, which are technically challenging and can lead to failure from intimal hyperplasia and foreign body reaction. Numerous alternatives to sutures have been proposed, but none has proven superior, particularly in small or atherosclerotic vessels. We have developed a new method of sutureless and atraumatic vascular anastomosis that uses US Food and Drug Administration (FDA)-approved thermoreversible tri-block polymers to temporarily maintain an open lumen for precise approximation with commercially available glues. We performed end-to-end anastomoses five times more rapidly than we performed hand-sewn controls, and vessels that were too small (<1.0 mm) to sew were successfully reconstructed with this sutureless approach. Imaging of reconstructed rat aorta confirmed equivalent patency, flow and burst strength, and histological analysis demonstrated decreased inflammation and fibrosis at up to 2 years after the procedure. This new technology has potential for improving efficiency and outcomes in the surgical treatment of cardiovascular disease.

Management of chest wall reconstruction after resection for cancer: a retrospective study of 22 consecutive patients.

AIM: In this study, we report our experience on immediate reconstruction after resection of primary or metastatic chest wall tumors, to restore protective function and elasticity of chest or sternum. METHODS: Between 2005 and 2009, 22 patients underwent reconstruction using a free or pedicled flap combined, or not, to alloplastic materials (Goretex®) in order to cover full-thickness defects of the chest wall after cancer surgery. Reconstruction was immediate in all cases. RESULTS: Mean follow-up was 27 months. Of these, 18 patients were alive at the end of the study (81.5%). Eighteen patients had malignant tumors (82%); within these patients, 12 were alive without recurrence at the end of the study (67%). The average size of the chest wall defect was 255 cm². Goretex® Mesh was used in 8 patients. All patients benefited from reconstruction with a flap: pedicled or free latissimus dorsi flap (n = 15), pedicled great omentum (n=3), deep inferior epigastric perforator free flap (n = 3), and parascapular pedicled flap (n=1). CONCLUSION: In this series, we were able to achieve long-term palliation and even cure in some patients by resecting full-thickness chest wall in local primary or recurrence of breast cancer without increasing morbidity. The same process was used successfully in association with adjuvant treatment in other tumors like skin sarcoma. We have followed a surgical algorithm according to the tumor localization and etiology.

Nasal tip haemangiomas: guidelines for an early surgical approach.

The treatment of Cyrano nose haemangioma (CNH) is difficult because of its location and possible complications: psychological impact, severe skin infiltration and consequences on nasal growth. We suggest that the best treatment for nasal tip haemangiomas is an early surgery to remove the affected tissues and preserve the anatomy. A total of 39 children (32 females and seven males) underwent early surgery for the treatment of CNH. Mean age was 35 months. Skin infiltration was present in 15 cases. Cartilage lack or distortion was observed in 29 cases. Each patient was evaluated for global cosmetic appearance, reduction in volume of the tumour, improvement of skin texture and quality of the scar. Multiple surgical procedures were performed in 14 cases. The average postoperative follow-up was 48 months. Patients with low-volume tumours had only one surgery, whereas patients with large tumours underwent a mean of 1.9 surgeries. In 29 cases, distortion or lack of cartilaginous structures required dissection and approximation of the alar cartilages in their anatomical position. We could identify three types of CNH that lead to three distinct surgical approaches: type A (mild cases) is characterised by no cutaneous involvement, no misalignment of the cartilages and mild nasal volume increase; type B (moderate cases) entails partial cutaneous infiltration, misalignment of the cartilages and moderate nasal volume increase; and type C (severe cases) is characterised by cutaneous infiltration, misalignment of the cartilages and severe nasal volume increase.

Pinch and elbow extension restoration in people with tetraplegia: a systematic review of the literature.

PURPOSE: We conducted a systematic review of the literature to summarize the available data on reconstructive surgeries involving pinch reconstruction and elbow extension restoration in people with tetraplegia. METHODS: English-language and French-language articles and abstracts published between 1966 and February 2007, identified through MEDLINE and EMBASE searches, bibliography review, and expert consultation, were reviewed for original reports of outcomes with pinch reconstruction and elbow extension restoration in tetraplegic patients after a spinal cord injury. Two reviewers independently extracted data on patient characteristics, surgical methods, and patient outcomes. RESULTS: Our search identified 765 articles, of which 37 met eligibility criteria (one article contained information on both elbow and pinch procedures). Results from 377 pinch reconstructions in 23 studies and 201 elbow extension restorations in 14 studies were summarized. The mean Medical Research Council score for elbow extension went from 0 to 3.3 after reconstruction. The overall mean postoperative strength measured after surgery for pinch reconstruction was 2 kg. CONCLUSIONS: More than 500 patients having these procedures experienced a clinically important improvement for both procedures-one restoring elbow extension, and the other, pinch strength. Upper-limb surgeries markedly improved the hand function of people with tetraplegia. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Mesenchymal stem cells can participate in ischemic neovascularization.

BACKGROUND: Cells from the bone marrow contribute to ischemic neovascularization, but the identity of these cells remains unclear. The authors identify mesenchymal stem cells as a bone marrow-derived progenitor population that is able to engraft into peripheral tissue in response to ischemia. METHODS: A murine model of skin ischemia was used. Bone marrow, blood, and skin were harvested at different time points and subjected to flow cytometric analysis for mesenchymal and hematopoietic markers (n = 3 to 7 per time point). Using a parabiotic model pairing donor green fluorescent protein (GFP)-positive with recipient wild-type mice, progenitor cell engraftment was examined in ischemic tissue by fluorescence microscopy, and engrafted cells were analyzed by flow cytometry for endothelial and mesenchymal markers. In vitro, the ability of both bone marrow- and adipose-derived mesenchymal stem cells to adopt endothelial characteristics was examined by analyzing (1) the ability of mesenchymal stem cells to take up DiI-acetylated low-density lipoprotein and Alexa Fluor lectin, and (2) phenotypic changes of mesenchymal stem cells co-cultured with GFP-labeled endothelial cells or under hypoxic/vascular endothelial growth factor stimulation. RESULTS: In vivo, the bone marrow mesenchymal stem cell population decreased significantly immediately after surgery, with subsequent engraftment of these cells in ischemic tissue. Engrafted cells lacked the panhematopoietic antigen CD45, consistent with a mesenchymal origin. In vitro, bone marrow- and adipose-derived mesenchymal stem cells took up DiI-acetylated low-density lipoprotein and Alexa Fluor lectin, and expressed endothelial markers under hypoxic conditions. CONCLUSIONS: The authors' data suggest that mesenchymal precursor cells can give rise to endothelial progenitors. Consequently, cell-based therapies augmenting the mesenchymal stem cell population could represent powerful alternatives to current therapies for ischemic vascular disease.

Using genetically modified microvascular free flaps to deliver local cancer immunotherapy with minimal systemic toxicity.

BACKGROUND: Clinical use of cancer gene therapy has been prevented by the inability to deliver high levels of local transgene expression with acceptable host toxicity. The authors' laboratory has developed an ex vivo technique to genetically modify free flaps to deliver immunotherapy locally without systemic toxicity. METHODS: Superficial inferior epigastric flaps were dissected in Fischer rats, perfused with a viral vector expressing the antitumor interleukin-12 (IL-12) for 1 hour, and re-anastomosed. Beneath the flaps was a bolus of 1 x 10(6) beta-human chorionic gonadotropin-secreting MADB-106 tumor cells. Tumor growth was monitored using beta-human chorionic gonadotropin levels (secreted by the tumor) and size. IL-12 expression in tissue was assessed by enzyme-linked immunosorbent assay. Tumor inflammatory infiltrate was assessed using immunohistologic staining (CD8 and CD161) and enzyme-linked immunosorbent assay (interferon-gamma). Serum levels of liver enzymes and histologic analysis were used to assess systemic toxicity. RESULTS: IL-12 expression was confirmed in the flap and surrounding tissue. The rate of tumor growth in the IL-12-treated group was significantly suppressed compared with the control group (p < 0.001). Liver enzyme levels remained normal, and histological evaluation of the liver, lung, and spleen revealed no evidence of inflammation in the treated group. CONCLUSIONS: Using genetically modified free flaps, the authors were able to deliver IL-12 directly into the local environment of a tumor and suppress its growth without eliciting toxic systemic effects. This technique could provide valuable adjuvant treatment after oncologic surgery for soft-tissue cancers, with the transduced flap reconstructing the defect and supplying a therapeutic agent to the resected tumor bed.

Diabetes increases p53-mediated apoptosis following ischemia.

BACKGROUND: Diabetes impairs the ability of tissue to respond adequately to ischemia. The underlying mechanisms contributing to this impaired response remain unknown. Because increases in apoptosis have been linked to a spectrum of diabetic complications, the authors examined whether programmed cell death is involved in the pathogenesis of poor diabetic tissue responses to ischemia. METHODS: Analysis for apoptosis and levels of proaptotic protein, p53, were performed on streptozocin-induced diabetic mice and wild-type controls in a murine model of soft-tissue ischemia (n = 6). In vitro, chronic hyperglycemic culture conditions were used to test inducibility and reversibility of the diabetic phenotype. Small interfering RNA was used to assess the role of p53. RESULTS: Ischemia-induced apoptosis and p53 levels were increased significantly in diabetic dermal fibroblasts both in vivo and in vitro. Chronic hyperglycemic culture was sufficient to induce the increased apoptotic phenotype, and this was not reversible with long-term normoglycemic conditions. Blocking p53 with small interfering RNA resulted in significant protection against ischemic apoptosis. CONCLUSIONS: These findings suggest that diabetes causes an increased apoptotic response to ischemia through a p53-mediated mechanism. This increase is not reversible by exposure to low-glucose conditions. This suggests that glycemic control alone will be unable to prevent tissue necrosis in diabetic patients and suggests novel therapeutic strategies for this condition.

Hypoxia, hormones, and endothelial progenitor cells in hemangioma.

Hemangiomas are the most common tumor of infancy, and although the natural history of these lesions is well described, their etiology remains unknown. One current theory attributes the development of hemangiomas to placentally-derived cells; however, conclusive evidence to support a placental origin is lacking. While placental tissue and hemangiomas do share molecular similarities, it is possible that these parallels are the result of analogous responses of endothelial cells and vascular progenitors to similar environmental cues. Specifically, both tissue types consist of actively proliferating cells that exist within a low oxygen, high estrogen environment. The hypoxic environment leads to an upregulation of hypoxia inducible factor-1alpha (HIF-1alpha) responsive chemokines such as stromal cell derived factor-1alpha (SDF-1alpha) and vascular endothelial growth factor (VEGF), both of which are known to promote the recruitment and proliferation of endothelial progenitor cells. Increased hormone levels in the postpartum period further potentiate the growth of these lesions. In this model, increased stabilization of HIF-1 in concert with increased levels of estrogen create a milieu that promotes new blood vessel development, ultimately contributing to the pathogenesis of infantile hemangiomas.