Expanded Transoral Microvascular Mandibular Reconstruction: A Scar-Free Approach.

PURPOSE: We present our experience with transoral segmental mandibulectomy, in conjunction with vascularized osseous mandibular reconstruction, utilizing an intraoral anastomosis and free of extraoral incisions. Virtual surgical planning and intraoperative navigation were used to help achieve this minimally invasive and scar-free approach. METHODS: A retrospective study was performed on 9 patients who underwent transoral segmental mandibulectomy followed by vascularized osseous reconstruction using an intraoral anastomosis between January 2018 and October 2018. The anastomotic recipient vessels were the facial artery and vein. The outcome variable was defined as the flap survival. Postoperative panoramic radiographs and computed tomography images were obtained for assessment of the neo-mandible. In addition, we performed a cadaver dissection to highlight relevant anatomic details of the facial artery and vein. RESULTS: Successful transoral segmental mandibulectomy was achieved in 9 patients, with an intraoral anastomosis successfully achieved in 8 patients. In one patient, an extraoral anastomosis was required because of challenging facial vein anatomy. Both recipient and donor sites healed uneventfully with a 100% successful rate of flap survival. In all cases, a well-positioned neo-mandible with good occlusion was demonstrated on postoperative imaging and examination. A symmetric facial appearance with no restrictions in mouth opening was also achieved in each case. In our cadaver dissection, we describe the anatomical course of the facial artery and vein. An average angle of 30° between these vessels is identified. CONCLUSIONS: Transoral segmental mandibulectomy combined with intraoral microvascular mandibular reconstruction is a surgically achievable technique with the benefit of being scar free.

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Development of an Accurate and Proactive Immunomodulatory Strategy to Improve Bone Substitute Material-Mediated Osteogenesis and Angiogenesis.

Background: Treatment of large bone defects represents a major clinical problem worldwide. Suitable bone substitute materials are commonly required to achieve successful bone regeneration, and much effort has been spent to optimize their chemical compositions, 3D architecture and mechanical properties. However, material-immune system interactions are increasingly being recognized as a crucial factor influencing regeneration. Here, we envisioned an accurate and proactive immunomodulation strategy via delivery of IL-4 (key regulator of macrophage polarization) to promote bone substitute material-mediated regeneration. Methods: Four different IL-4 doses (0 ng, 10 ng, 50 ng and 100 ng) were delivered into rat large cranial bone defects at day 3 post-operation of decellularized bone matrix (DBM) material implantation, and the osteogenesis, angiogenesis and macrophage polarization were meticulously evaluated. Results: Micro-CT analysis showed that immunomodulation with 10 ng IL-4 significantly outperformed the other groups in terms of new bone formation (1.23-5.05 fold) and vascularization (1.29-6.08 fold), achieving successful defect bridging and good vascularization at 12 weeks. Histological analysis at 7 and 14 days showed that the 10 ng group generated the most preferable M1/M2 macrophage polarization profile, resulting in a pro-healing microenvironment with more IL-10 and less TNF-α secretion, a reduced apoptosis level in tissues around the materials, and enhanced mesenchymal stem cell migration and osteogenic differentiation. Moreover, in vitro studies revealed that M1 macrophages facilitated mesenchymal stem cell migration, while M2 macrophages significantly increased cell survival, proliferation and osteogenic differentiation, explaining the in vivo findings. Conclusions: Accurate immunomodulation via IL4 delivery significantly enhanced DBM-mediated osteogenesis and angiogenesis via the coordinated involvement of M1 and M2 macrophages, revealing the promise of this accurate and proactive immunomodulatory strategy for developing new bone substitute materials.

Acceptable clinical outcomes and recommended reconstructive strategies for secondary maxillary reconstruction with vascularized fibula osteomyocutaneous flap: A retrospective analysis.

BACKGROUND: We conducted a retrospective analysis of the clinical outcomes and evaluated the reconstructive strategies in patients who underwent secondary maxillary reconstruction with a vascularized fibula osteomyocutaneous flap (VFOF). METHODS: From May of 2001 to June of 2014, 34 patients who underwent secondary maxillary reconstruction with VFOF, with or without titanium mesh, were reviewed. The patients were divided into two groups of maxillary reconstruction, according to different planning and treatment strategies. In Group 1, presurgical planning was achieved using three-dimensional stereomodeling (n = 12). In Group 2, virtual surgical planning was performed and guided templates were produced (n = 22). The differences in the preoperative planning, intraoperative technique, postoperative complications, and long-term results between the two groups were analyzed. Statistical analysis was performed to determine the differences between the two groups and the risk factors for prognosis. RESULTS: Similar and accurate secondary maxillary reconstructions were successfully performed in Group 1 and 2. Postoperative complications were reported in 8 patients in Group 1 and 11 patients in Group 2. Complications were reported in patients who underwent radiotherapy. The incidence of postoperative complications in Group 2 were lower than that in Group 1 with the exception of midfacial collapse (P > 0.05). The long-term results of some patients with class 3 defects were not satisfactory because of midfacial collapse and lower eyelid ectropion. Stepwise regression analysis showed radiotherapy to be a risk factor for prognosis. CONCLUSIONS: The long-term results of secondary maxillary reconstruction were reported to be acceptable in our study. Radiotherapy was the risk factor for prognosis in secondary maxillary reconstruction. On the basis of these results, we highly recommend our strategy for secondary maxillary reconstruction. Good functional results could be achieved after the accurate restoration of maxillary alveolar ridge with several fibular segments using virtual surgical planning and dental restoration.

Control-released Alpha-lipoic acid-loaded PLGA microspheres enhance bone formation in type 2 diabetic rat model.

Since diabetes lead to alterations in bone metabolism with reductions in bone mineral content and delayed bone formation, the most effective method for bone regeneration in diabetes remains to be determined. In this study, type 2 diabetes were successfully induced via a high-fat diet and low-dose streptozotocin intraperitoneal injection. Excess reactive oxygen species (ROS) has been implicated in diabetes mellitus. Overexpression of ROS can lead to oxidative stress and subsequently to H2O2-mediated impaired proliferation and delayed cellular differentiation. As a result, antioxidant alpha-lipoic acid (ALA)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres were fabricated using the emulsion solvent evaporation method, and a sustained and controlled release of ALA was observed up to 27 days. It was demonstrated that biodegradable PLGA microspheres loaded with ALA acted as ROS scavengers and partially recover the mesenchymal stem cell proliferation and differentiation. The bone formation of ALA loaded scaffolds in rat cranial bone defects were greater than the prime three-dimensional collagen scaffold. These results suggest the application of ALA loaded PLGA microsphere exhibit good bioactivity and bone forming ability in diabetes.

Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer.

INTRODUCTION: Previous studies have produced controversial results regarding whether mesenchymal stem cells (MSCs) promote or inhibit tumor development. Given the dual role of MSCs in inflammation and cancer, in this study the colitis-associated colorectal cancer (CAC) model was used to examine whether umbilical cord tissue-derived MSCs could prevent neoplasm by inhibiting chronic inflammation. METHODS: MSCs were obtained and identified using flow cytometry. Colitis-associated colorectal cancer model was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) and MSCs were injected intravenously twice. Levels of immune cells in mesenteric lymph node including regulatory T (Treg) cells were detected using flow cytometry. Naïve T cells and Jurkat cells were co-cultured with MSCs and the effect of MSCs on Treg cells differentiation was evaluated. RESULTS: After injection through tail vein, MSCs could migrate to colon and suppress colitis-related neoplasm. This tumor suppressive effect was characterized by longer colon length, decreased tumor numbers and decreased expression of Ki-67. Moreover, MSCs alleviated the pathology of inflammation in the colitis stage of CAC model and inhibited inflammation cytokines both in colon and serum. Furthermore, Treg cells were accumulated in mesenteric lymph node of MSCs-treated mice while the percentage of T helper cells 2 (Th2) and Th17 were not changed. Of note, MSCs secreted transforming growth factor-ß (TGF-ß) enhanced the induction of Treg cells from naïve T cells. The conditioned medium of MSCs also activated Smad2 signaling, which has been reported to regulate Treg cells. CONCLUSIONS: These results proved that MSCs could migrate to colon tissues and induce the differentiation of Treg cells via Smad2 as so to inhibit the colitis and suppress the development of CAC.

Absolute ethanol embolization of arteriovenous malformations in the periorbital region.

OBJECTIVE: Arteriovenous malformations (AVMs) involving the periorbital region are technically challenging clinical entities to manage. The purpose of the present study was to present our initial experience of ethanol embolization in a series of 16 patients with auricular AVMs and assess the outcomes of this treatment. METHODS: Transcatheter arterial embolization and/or direct percutaneous puncture embolization were performed in the 16 patients. Pure or diluted ethanol was manually injected. The follow-up evaluations included physical examination and angiography at 1- to 6-month intervals. RESULTS: During the 28 ethanol embolization sessions, the amount of ethanol used ranged from 2 to 65 mL. The obliteration of ulceration, hemorrhage, pain, infection, pulsation, and bruit in most of the patients was obtained. The reduction of redness, swelling, and warmth was achieved in all the 16 patients, with down-staging of the Schobinger status for each patient. AVMs were devascularized 100 % in 3 patients, 76-99 % in 7 patients, and 50-75 % in 6 patients, according to the angiographic findings. The most common complications were necrosis and reversible blister. No permanent visual abnormality was found in any of the cases. CONCLUSION: Ethanol embolization is efficacious and safe in the treatment of AVMs in the periorbital region and has the potential to be accepted as the primary mode of therapy in the management of these lesions.

Is a swine model of arteriovenous malformation suitable for human extracranial arteriovenous malformation? A preliminary study.

OBJECTIVE: A chronic arteriovenous malformation (AVM) model using the swine retia mirabilia (RMB) was developed and compared with the human extracranial AVM (EAVM) both in hemodynamics and pathology, to see if this brain AVM model can be used as an EAVM model. METHODS: We created an arteriovenous fistula between the common carotid artery and the external jugular vein in eight animals by using end-to-end anastomosis. All animals were sacrificed 1 month after surgery, and the bilateral retia were obtained at autopsy and performed hematoxylin and eosin staining and immunohistochemistry. Pre- and postsurgical hemodynamic evaluations also were conducted. Then, the blood flow and histological changes of the animal model were compared with human EAVM. RESULTS: The angiography after operation showed that the blood flow, like human EAVM, flowed from the feeding artery, via the nidus, drained to the draining vein. Microscopic examination showed dilated lumina and disrupted internal elastic lamina in both RMB of model and nidus of human EAVM, but the thickness of vessel wall had significant difference. Immunohistochemical reactivity for smooth muscle actin, angiopoietin 1, and angiopoietin 2 were similar in chronic model nidus microvessels and human EAVM, whereas vascular endothelial growth factor was significant difference between human EAVM and RMB of model. CONCLUSIONS: The AVM model described here is similar to human EAVM in hemodynamics and immunohistochemical features, but there are still some differences in anatomy and pathogenetic mechanism. Further study is needed to evaluate the applicability and efficacy of this model.

Preoperative direct puncture embolization of advanced juvenile nasopharyngeal angiofibroma in combination with transarterial embolization: an analysis of 22 consecutive patients.

OBJECTIVE: This study was designed to evaluate the clinical application of preoperative auxiliary embolization for juvenile nasopharyngeal angiofibroma (JNA) by direct puncture embolization (DPE) of the tumor in combination with transarterial embolization (TAE). METHODS: The study included 22 patients. An 18-gauge needle was used to puncture directly into the tumor, and 20-25 % N-butyl cyanoacrylate was injected under the guidance of fluoroscopy after confirming the placement of the needle into the JNA and no leaking into the surrounding tissue. Tumors were obstructed later via TAE. RESULTS: The supplying arteries of JNA were from branches of the internal carotid and external carotid arteries. Control angiography showed the obliteration of contrast stain in the entire tumor mass and the distal supplying arteries disappeared after DPE in combination with TAE. Surgical resection was performed within 4 days after embolization and none of the patients required blood transfusion. CONCLUSIONS: The use of DPE in combination with TAE was a safe, feasible, and efficacious method. It can devascularize effectively the JNAs and reduce intraoperative bleeding when JNAs are extirpated.

Propranolol for problematic head and neck hemangiomas: an analysis of 37 consecutive patients.

OBJECTIVE: Infantile hemangiomas (IHs) on head and neck are frequently encountered. Recently, propranolol was introduced as a novel pharmacologic treatment for IH. But the impact of propranolol for the treatment of IHs especially the side effects have not yet been well described. This article aimed to describe the effects and side effects of propranolol treatment in 37 children with problematic hemangiomas on head and neck. STUDY DESIGN: Data were collected from the medical charts of patients treated between October 2008 and November 2010. Serial examinations and photographs were obtained to evaluate perceived therapeutic response and complications of oral propranolol in the course of their therapy. RESULTS: Thirty-seven infants with propranolol-treated problematic head and neck hemangiomas were included and all patients had a good response. Most of patients were subjectively noticed an obvious improvement within one week from the onset of therapy. 29 patients endured the treatment of propranolol for 3 months with no recurrence, 6 patients endured prolonged course of treatment for 5/6 months. 2 patients who endured the treatment of propranolol for 3 months were found recurrence in two weeks. So the propranolol was given again for another 3 months. There were no severe adverse reactions. Minor side effects included diarrhea, light sleeping, and nausea. CONCLUSION: Propranolol appears to be an effective and well-tolerated treatment for problematic IH on head and neck.