Molecular structure of monomorphic peptide fibrils within a kinetically trapped hydrogel network.

Most, if not all, peptide- and protein-based hydrogels formed by self-assembly can be characterized as kinetically trapped 3D networks of fibrils. The propensity of disease-associated amyloid-forming peptides and proteins to assemble into polymorphic fibrils suggests that cross-ß fibrils comprising hydrogels may also be polymorphic. We use solid-state NMR to determine the molecular and supramolecular structure of MAX1, a de novo designed gel-forming peptide, in its fibrillar state. We find that MAX1 adopts a ß-hairpin conformation and self-assembles with high fidelity into a double-layered cross-ß structure. Hairpins assemble with an in-register Syn orientation within each ß-sheet layer and with an Anti orientation between layers. Surprisingly, although the MAX1 fibril network is kinetically trapped, solid-state NMR data show that fibrils within this network are monomorphic and most likely represent the thermodynamic ground state. Intermolecular interactions not available in alternative structural arrangements apparently dictate this monomorphic behavior.

Primary surgical management with radial forearm free flap reconstruction in T4 oropharyngeal cancer: Complications and functional outcomes.

PURPOSE: Functional outcomes and complication rates after open surgery for advanced-stage oropharyngeal cancers are rarely reported. These measures are critical for choice of treatment modality and patient counseling. We describe the long term functional outcomes and associated complications of primary surgical management of T4 oropharyngeal cancers reconstructed with radial forearm free flaps. MATERIALS AND METHODS: A retrospective review was performed of 40 patients with T4 oropharyngeal cancers treated between 2005 and 2015 at a tertiary care center. RESULTS: Forty patients with T4 oropharyngeal cancers underwent open surgical resection and radial forearm free flap reconstruction at the time of surgery. Mandibulotomy was required in 33 (82.5%) cases. Thirty-five (87.5%) patients received adjuvant radiation or combined chemotherapy and radiation. Tracheostomy was performed in all patients, but every patient was eventually decannulated. Twenty (57.1%) patients required gastrostomy tube placement at some point during treatment; however, 91.4% were on a completely oral diet with a mean FOSS score of 1.6 by 1year after completion of treatment. The addition of adjuvant treatment was the only factor significantly associated with poorer FOSS scores. The overall rates of short and long-term complications were 60.0% and 57.1% respectively. The most common short and long-term complications were infection (30.0%) and velopharyngeal insufficiency (25.7%) respectively. CONCLUSIONS: Traditional open surgical approaches to large tumors of the oropharynx carry higher complication rates than more recent advanced transoral approaches. However, they can still be utilized with excellent long-term functional results in certain cases of advance oropharyngeal cancers not amenable to transoral approaches. With careful reconstruction of oropharyngeal defects, over 90% of patients can achieve a completely oral diet.

Transnasal odontoid resection: is there an anatomic explanation for differing swallowing outcomes?

OBJECT: Swallowing dysfunction is common following transoral (TO) odontoidectomy. Preliminary experience with newer endoscopic transnasal (TN) approaches suggests that dysphagia may be reduced with this alternative. However, the reasons for this are unclear. The authors hypothesized that the TN approach results in less disruption of the pharyngeal plexus and anatomical structures associated with swallowing. The authors investigate the histological and gross surgical anatomical relationship between pharyngeal plexus innervation of the upper aerodigestive tract and the surgical approaches used (TN and TO). They also review the TN literature to evaluate swallowing outcomes following this approach. METHODS: Seven cadaveric specimens were used for histological (n = 3) and gross anatomical (n = 4) examination of the pharyngeal plexus with the TO and TN surgical approaches. Particular attention was given to identifying the location of cranial nerves (CNs) IX and X and the sympathetic chain and their contributions to the pharyngeal plexus. S100 staining was performed to assess for the presence of neural tissue in proximity to the midline, and fiber density counts were performed within 1 cm of midline. The relationship between the pharyngeal plexus, clivus, and upper cervical spine (C1-3) was defined. RESULTS: Histological analysis revealed the presence of pharyngeal plexus fibers in the midline and a significant reduction in paramedian fiber density from C-2 to the lower clivus (p < 0.001). None of these paramedian fibers, however, could be visualized with gross inspection or layer-by-layer dissection. Laterally based primary pharyngeal plexus nerves were identified by tracing their origins from CNs IX and X and the sympathetic chain at the skull base and following them to the pharyngeal musculature. In addition, the authors found 15 studies presenting 52 patients undergoing TN odontoidectomy. Of these patients, only 48 had been swallowing preoperatively. When looking only at this population, 83% (40 of 48) were swallowing by Day 3 and 92% (44 of 48) were swallowing by Day 7. CONCLUSIONS: Despite the midline approach, both TO and TN approaches may injure a portion of the pharyngeal plexus. By limiting the TN incision to above the palatal plane, the surgeon avoids the high-density neural plexus found in the oropharyngeal wall and limits injury to oropharyngeal musculature involved in swallowing. This may explain the decreased incidence of postoperative dysphagia seen in TN approaches. However, further clinical investigation is warranted.

A Prospective Study of Mucosal Sparing Radiation Therapy in Resected Oropharyngeal Cancer Patients.

PURPOSE: Our objective was to report the prospective results of mucosal sparing radiation therapy in human papillomavirus-related oropharyngeal squamous cell carcinoma. METHODS AND MATERIALS: From March 2016 through May 2019, patients were enrolled in this institutional review board-approved prospective cohort study at a multisite institution. Inclusion criteria included p16+ American Joint Committee on Cancer seventh edition pathologic T1 or T2, N1 to N3, and M0 oropharyngeal cancers. Proton therapy (PT) was delivered to at-risk nodal regions, excluding the primary mucosal site. Secondary to insurance denial for PT, intensity modulated radiation therapy (IMRT) was allowed. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module and Patient-Reported Outcomes Measurement Information System surveys (quality of life [QOL]) and modified barium swallowing impairment profiles (MBSImP) were obtained at baseline before radiation therapy, then 3 and 12 months after radiation therapy. Kaplan-Meier estimates were calculated for time-to-event clinical outcomes, and repeated measures mixed models were used to explore changes in QOL over time. A comparison of QOL and swallowing outcomes with standard-of-care treatment was analyzed. RESULTS: There were 61 evaluable patients with a median follow-up of 38 months (range, 10-64); 44 (72%) were treated with PT and 17 (28%) were treated with IMRT. The 2-year local control, locoregional control, distant metastasis-free survival, and overall survival were 98%, 97%, 98%, and 100%, respectively. There were 6 grade ≥3 events related to treatment. Two IMRT patients required percutaneous endoscopic gastrostomy tube placement during treatment secondary to significant nausea due to dysgeusia. Patients noted significant QOL improvement over time in the pain, swallowing, speech, social eating, social contact, mouth opening, and use of pain medication domains (all P < .02). The MBSImP overall severity score as well as oral and pharyngeal impairment scores showed stability with no significant change over time. For the 44 patients treated with PT, the mean D95 to the primary target was 10.7 Gy (standard deviation = 12.5 Gy). CONCLUSIONS: Mucosal sparing radiation is well tolerated in select resected human papillomavirus-related oropharyngeal squamous cell carcinoma with a low risk of recurrence at the mucosal primary site, a low rate of percutaneous endoscopic gastrostomy tube placement, and few radiation-related grade ≥3 adverse events.

Transoral robotic surgery of the oropharynx: Clinical and anatomic considerations.

Transoral robotic surgery provides a mechanism to approach tumors of the upper aerodigestive tract through a natural body orifice--the mouth. The technique has been applied most often to malignant tumors of the oropharynx. The use of this technique, however, forces the surgeon to view the anatomy from a different vantage point. Head and neck surgeons are accustomed to the oropharynx from lateral to medial. The transoral approach forces surgeons to consider the anatomy from the oral cavity and oropharynx medial perspective. This article will discuss the relevant anatomy, operative goals, robotic technique, and clinical considerations of transoral robotic surgery of the oropharynx.

Long-Term Toxic Effects, Swallow Function, and Quality of Life on MC1273: A Phase 2 Study of Dose De-escalation for Adjuvant Chemoradiation in Human Papillomavirus-Positive Oropharyngeal Cancer.

PURPOSE: Patients with human papillomavirus oropharyngeal cancer are highly curable but risk significant long-term toxic effects with standard therapy. This study investigated a de-escalation strategy of decreased adjuvant radiation therapy and chemotherapy after transoral robotic surgery, and reports on long-term functional and quality of life (QOL) outcomes. METHODS AND MATERIALS: Eligible patients had a p16-positive oropharyngeal cancer and ≤10 pack-year smoking history and underwent surgery followed by treatment with either 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks with weekly docetaxel (15 mg/m2) if they had intermediate pathologic risk factors or 36 Gy in 1.8-Gy fractions twice per day over 2 weeks with the same chemotherapy if they had extranodal extension. Toxic effects, swallow function, and QOL were measured longitudinally. RESULTS: Seventy-nine patients (89.9% male) were treated and eligible for toxic effect and functional evaluation. Dry mouth was the most common grade 1 toxic effect at 1 year (55.6%), 2 years (53.3%), and 3 years (49.2%). The cumulative rates of grade 2 toxic effects at 1, 2, and 3 years were 1.4%, 6.7%, and 6.8%, respectively. There were only 2 grade 3 toxic effects at ≥1 year, including a grade 3 fatigue at 2.5 years, and a grade 3 superficial soft tissue fibrosis at 4 years. There were no grade 4 to 5 toxic effects. No patients were percutaneous endoscopic gastrostomy-dependent. Swallow function improved by 12 months posttreatment. QOL improved over time by all measurement tools and most patients returned to baseline level of function and QOL. CONCLUSIONS: De-escalated adjuvant therapy for select patients with human papillomavirus oropharyngeal cancer resulted in low rates of long-term toxic effects, excellent swallow outcomes, and preservation of global and xerostomia-related QOL.

Short and long-term outcomes of three-dimensional printed surgical guides and virtual surgical planning versus conventional methods for fibula free flap reconstruction of the mandible: Decreased nonunion and complication rates.

BACKGROUND: To determine whether virtual surgical planning and three-dimensional printed cutting guides (3D/VSP) improved radiographic bone union compared to conventional methods (CM) in fibula free flap (FFF) reconstruction of the mandibles. METHODS: Retrospective study from the years 2000-2018 at a tertiary hospital. Osseous union was evaluated by a radiologist blinded to each patient's treatment. RESULTS: Two hundred sixty patients who underwent FFF tissue transfer, 28 with VSP and 3D cutting guides. Bony union was not achieved in 46 (20%) patients who underwent CM compared to 1 (4%) of patients with VSP and guides (p = 0.036). FFF complication was significantly higher in CM with 87 patients (38%) compared to three patients (11%) in 3D/VSP (p = 0.005). Median time to bony union for patients who underwent CM was 1.4 years compared to 0.8 years in 3D/VSP. CONCLUSIONS: 3D/VSP reduced the rate of radiographic nonunion and flap-related complications in FFF reconstruction for mandibular defects.

Rapid Separation of Organophosphate Pesticides using Micellar Electrokinetic Chromatography and Short-end Injection.

Organophosphate (OP) pesticides are highly toxic substances and are frequently represented as poisons. In order to qualify and quantify the selected OP pesticides (methyl paraoxon, ethyl paraoxon, methyl parathion, fenitrothion, and ethyl parathion), micellar electrokinetic chromatography and short-end injection were investigated. This is the first time that this combination has been used to separate OP pesticides. A capillary with 8.5 cm effective length was used, and the analytes were separated within 2.1 min. Separation conditions including buffer (type, pH, and concentration), sodium dodecyl sulfate concentration, and separation voltage were optimized. The limit of detection (LOD) was estimated in the range of 10-20 µM. The OP pesticides spiked in artificial saliva and drinking water gave superior peak profiles, and good average recoveries 95.6% and 62.3%, respectively. Overall, a rapid method with excellent resolution and efficiency was developed and successfully applied in the analysis of potential sample matrixes.

A Next-Generation Single-Port Robotic Surgical System for Transoral Robotic Surgery: Results From Prospective Nonrandomized Clinical Trials.

IMPORTANCE: Transoral endoscopic head and neck surgery now plays an important role in the multidisciplinary management of oropharyngeal carcinoma. Previous generations of robotic surgical systems used a multiport system with a rigid stereo-endoscope and 2 wristed instruments that facilitated transoral robotic surgery. OBJECTIVE: To evaluate a new single-port robotic surgical system in head and neck surgery prospectively through concurrent nonrandomized clinical trials. DESIGN, SETTING, AND PARTICIPANTS: Two prospective clinical trials were conducted from December 16, 2016, to December 26, 2017, to assess the safety, feasibility, and performance of a flexible single-port robotic surgical system in 4 institutions, including 3 in the United States and 1 in Hong Kong. A total of 47 patients with tumors of the oropharynx were enrolled and underwent surgery. All patients were classified as having American Society of Anesthesiologists class I to III status and Eastern Cooperative Oncology Group status 0 to 1. An initial cohort of 7 patients underwent staging and endoscopic procedures for benign disease. The remaining 40 patients all had malignant tumors of the oropharynx. MAIN OUTCOMES AND MEASURES: Safety was measured by the incidence of device-related serious adverse events. Feasibility and performance were measured by the conversion rate from the use of the single-port robotic surgical system to either open surgery or the use of any other transoral technology required to complete the planned procedure. Secondary end points of swallowing function and surgical margins were also measured. RESULTS: All 47 patients (8 women and 39 men; mean [SD] age, 61 [8] years) safely underwent transoral resection with the single-port robotic surgical system without conversion to open surgery, laser surgery, or multiport robotic surgery. There were no intraoperative complications or device-related serious adverse events. Mean (SD) estimated intraoperative blood loss per procedure was 15.4 (23.9) mL; no patients received a transfusion. Two patients underwent a planned tracheotomy owing to medical comorbidity (previous chemoradiotherapy; obesity and severe sleep apnea). Two patients (4%) had grade III or IV postoperative hemorrhage, requiring a return to the operating room; however, both patients had medical comorbidities requiring the use of antithrombotic medication. The incidence of positive margins for patients with oropharyngeal malignancy was 3% (1 of 40). Within 30 days, 45 patients (96%) were eating by mouth and without the need for a percutaneous endoscopic gastrostomy tube. CONCLUSIONS AND RELEVANCE: This study describes the results of phase 2 clinical testing of a next-generation, robotic surgical system using a single-port architecture. The use of the device appears to be feasible, safe, and effective for transoral robotic surgery of oropharyngeal tumors. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03010813 and NCT03049280.

Effect of radiation on segmental distraction osteogenesis in rabbits.

OBJECTIVE: To determine whether consolidation can occur during radiotherapy after segmental distraction osteogenesis. Segmental distraction osteogenesis has potential as a reconstructive option after oncologic resection of the mandible. However, postoperative radiotherapy has potentially deleterious effects on bone consolidation after distraction osteogenesis. METHODS: Tibial defects of 1.0 cm were created in 5 New Zealand white rabbits. After a 6-day latency phase, a 1.0-cm distraction segment was created in 0.3-mm increments every 12 hours. Within 24 hours of the distraction completion, the tibia received the biologic equivalent of 6000 rad (60 Gy). After 6 weeks of consolidation, the animals were humanely killed. Bone was analyzed radiographically, grossly (at autopsy), and histomorphometrically. RESULTS: Four rabbits completed the 6-week consolidation period. All specimens had evidence of calcified bone in the segmental defect on radiographic analysis. At autopsy, the volume of new bone equaled that of the removed segment. On histologic examination, the volume of new trabecular bone was similar to adjacent cortical bone. CONCLUSIONS: Consolidation of segmental distraction osteogenesis defects can occur in rabbit tibia during external beam radiotherapy. To our knowledge, this study is the first to demonstrate successful consolidation of segmental distraction osteogenesis during external beam radiotherapy.

Primary vs Secondary Endosseous Implantation After Fibular Free Tissue Reconstruction of the Mandible for Osteoradionecrosis.

IMPORTANCE: The clinical and financial implications of the timing of dental rehabilitation after a fibula free tissue transfer (FFTT) for osteoradionecrosis (ORN) and osteonecrosis (ON) of the mandible have yet to be established. OBJECTIVE: To compare the outcomes of primary implantation vs secondary implantation after FFTT for ORN and ON of the mandible. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted of 23 patients at a single tertiary academic referral center undergoing primary implantation or secondary implantation after FFTT for ORN and ON from January 1, 2006, to November 10, 2015. INTERVENTIONS: All patients underwent FFTT with primary implantation (n = 12) or secondary implantation (n = 11). MAIN OUTCOMES AND MEASURES: Outcomes of FFTT, dental implantation, implant use, diet, speech, and disease-free survival were reviewed. Fixed unit costs were estimated based on the mean cost analysis. RESULTS: Twenty-three patients (7 women and 16 men; mean [SD] age, 62.4 [8.2] years [range, 24-81 years]) met the inclusion criteria. Of these, 18 had ORN and 5 had ON. Dental implantation was performed at the time of FFTT for 12 patients and was performed secondarily for 11 patients. There were a mean of 5.2 implants per patient performed, for a total of 121 implants. There was 1 complete flap failure in the primary implantation group. Neither flap nor implant complications were affected by the timing of the implantation. Overall, the implant survival rate was 95% (55 of 58) in the primary implantation group and 98% (62 of 63) in the secondary implantation group. Time from FFTT to abutment placement (primary implantation, 19.6 weeks; secondary implantation, 61.0 weeks) was significantly shorter after primary implantation (P < .001). There was no clinical difference in postoperative complications and implant outcomes for ORN vs ON. Improvement in speech and oral competence in the primary implantation group vs the secondary implantation group was not statistically significant, given an experiment-adjusted P = .001 set as significant (normal speech, 9 vs 3; P = .02; and normal oral competence, 9 vs 3; P = .02). Disease-free survival was 91% (20 of 22 patients) overall. Fixed unit (U) costs were 1.0 U for primary implantation and 1.24 U for secondary implantation. CONCLUSIONS AND RELEVANCE: Patients undergoing primary implantation after FFTT for ORN and ON had a similar rate of complications compared with those undergoing secondary implantation. However, primary implantation allowed a faster return than secondary implantation to oral nutrition and prosthesis use. The fixed unit cost was reduced for those undergoing primary implantation. Although dental implantation was safe and effective in both groups, the decreased time to use and the decreased overall cost should prompt surgeons to consider primary implantation after FFTT for ORN and ON. LEVEL OF EVIDENCE: 3.

Magnitude of benefit for adjuvant radiotherapy following minimally invasive surgery in intermediate to high risk HPV-positive oropharyngeal squamous cell carcinoma.

OBJECTIVE: To determine the outcomes and toxicities of minimally-invasive surgery with adjuvant intensity-modulated radiotherapy +/- chemotherapy (AT) compared to definitive surgical therapy (ST) in a contemporary cohort of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). METHODS: From 2005 to 2013, a consecutive cohort of 190 HPV-positive OPSCC patients was retrospectively reviewed from multi-institutional databases maintained by the Departments of Otorhinolaryngology and Radiation Oncology. A total of 116 AT patients and 42 ST patients with intermediate or high risk pathologic features were included in the final analysis. All patients received minimally invasive surgery. Time to recurrence and time to death from the onset of surgery were evaluated. Toxicity data collected included dysphagia or xerostomia requiring feeding tube placement >6 months, or mandibular osteonecrosis requiring surgery or hyperbaric oxygen. RESULTS: All AT patients received IMRT to a median dose of 60 Gy. Chemotherapy delivered to 67.2% of AT patients. AT group included more high-risk patients given higher nodal classification (p = 0.005) and extracapsular extension (p = 0.0005). AT improved disease-free survival (HR 2.77, CI 1.22-6.28; p = 0.02) and local-regional control (HR 14.83, CI 3.240-67.839; p = 0.001). Disease-free survival with AT and tumor extracapsular extension was improved when compared to ST (HR of 4.34, CI 1.540-12.213; p = 0.006). Dysphagia or mandibular osteonecrosis toxicity after AT vs. ST of 19.0% vs. 2.4%. CONCLUSIONS: AT improved local-regional control and disease-free survival but was associated with greater toxicity. The recurrence benefit was most pronounced in tumors with extracapsular extension.

Hemifacial Spasm Secondary to Parotid Pleomorphic Adenoma With Stylomastoid Foramen Extension.

OBJECTIVE: To report hemifacial spasm (HFS) as a rare presenting symptom of a benign parotid neoplasm involving the stylomastoid foramen. METHODS: Case report with literature review. RESULTS: An 18-year-old woman presented with a 1-year history of a progressively enlarging right infra-auricular mass with new onset ipsilateral severe HFS. Clinical vetting unveiled a palpable 2 cm, firm, minimally mobile mass medial to the angle of the mandible. Imaging revealed a heterogeneous intraparotid mass with tumor extension into the stylomastoid foramen. Diagnostic consideration was given to neurogenic tumors and neoplasms of parotid origin.The patient ultimately underwent superficial parotidectomy and the tumor was found superficial and extrinsic to the proximal facial nerve trunk but extended into the stylomastoid foramen. The tumor was removed after performing mastoidectomy with mastoid segment facial nerve decompression. Frozen section pathology was consistent with pleomorphic adenoma. Postoperatively the patient had normal facial nerve function with immediate and complete resolution of HFS. To date there are only three other published reports of benign parotid tumors presenting with HFS and this is the first illustrating intratemporal tumor extension. CONCLUSIONS: HFS is a rare presenting symptom associated with benign parotid neoplasms with scarce documentation in the literature. In this index case, tumor extirpation with mastoid segment facial nerve decompression provided immediate and durable resolution of symptoms.

Evaluation of Clinical Outcomes of Osseointegrated Dental Implantation of Fibula Free Flaps for Mandibular Reconstruction.

IMPORTANCE: Dental implantation has been used for oral rehabilitation to improve cosmesis and function. OBJECTIVE: We aim to evaluate the clinical outcomes and success rates of primary and secondary dental implant placement in vascularized fibula bone grafts used for segmental mandibulectomy defects. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed between November 2005 and July 2014 on all patients undergoing both fibula free tissue reconstruction of mandibular defects and endosseous dental implantation at an academic tertiary care referral hospital. INTERVENTIONS: Either primary (n = 20) or secondary (n = 26) dental implantation of the fibula was performed. MAIN OUTCOMES AND MEASURES: Timing of implantation, location of implants, history of tobacco, alcohol, and radiation, reason for mandibulectomy, and outcomes related to these parameters. RESULTS: Forty-six patients (31 males, 15 females; mean age, 58.0 years) underwent dental implantation to the fibula graft. A total of 227 implants were placed, with a mean of 5 implants per patient (range, 2-7). Of these, 44 were placed into native mandible and 183 into fibula flap. Twenty patients underwent primary implantation and received 96 implants, while 26 patients underwent secondary implantation and received 131 implants. There were no flap failures and 22 implant-related complications in 16 patients (implant failure, n = 10; granulation or soft-tissue overgrowth, n = 6; exposed bone around implant, n = 6). An implant failure occurred in 10 patients (22%) resulting in removal of 15 implants. Nine of these patients underwent successful dental rehabilitation, 5 without further implantation, and 4 with replaced implants. One patient was not rehabilitated secondary to failed implantation. Therefore, there was a 93% overall implant survival rate (n = 212) and 98% overall implant-supported prosthesis success rate (n = 45) at a mean follow-up of 22 months. There was no difference in implant survival between primary (94%) (n = 90) and secondary (93%) (n = 122) implantation. Neither a history of preimplant or postimplant radiation exposure nor the diagnosis of osteoradionecrosis affected implant survival. CONCLUSIONS AND RELEVANCE: Osseointegrated dental implantation is a relatively safe procedure with few complications. Vascularized fibula grafts are a suitable method of mandibular reconstruction and are amenable to successful primary and secondary endosseous implantation. LEVEL OF EVIDENCE: 4.

Orbital exenteration reconstruction with rectus abdominis microvascular free flap.

OBJECTIVES: To determine the course of reconstructive treatment and outcomes with use of the rectus abdominis free flap after orbital exenteration with or without total maxillectomy. STUDY DESIGN: Retrospective chart review of treatment and outcomes of patients who had rectus abdominis free-tissue transfer for orbital exenteration with or without total maxillectomy at the Mayo Clinic between 1994 and 2004. METHODS: Charts of patients who had rectus abdominis free flap reconstruction after orbital exenteration were retrospectively reviewed and the surgical technique evaluated. An explanation of the surgical technique for rectus abdominis free-tissue transfer to the orbital cavity is provided, along with a discussion of the advantages and disadvantages of this reconstructive method. RESULTS: Twelve of 13 patients who underwent reconstruction with rectus abdominis free-tissue transfer had a successful outcome (flap viability 92%). Cosmetic results were acceptable both to patients and to surgeons. CONCLUSIONS: Rectus abdominis microvascular free-tissue transfer for repair of orbital exenteration defects is a safe and reliable alternative to the use of the temporalis or the pectoralis major muscle as a pedicle flap; it provides a larger volume of well-vascularized tissue and greater placement flexibility without associated orientation problems; and the long vascular pedicle facilitates the use of multiple donor vessels within the head and neck, which is an advantage in previously irradiated patients. Postoperative care and the donor site defect are well tolerated. The flap allows reliable obturation of the oral maxillectomy defect, and it negates the need for cavity care in these patients.

Micron-scale magnetic resonance imaging of both liquids and solids.

We describe and demonstrate a novel apparatus for magnetic resonance imaging (MRI), suitable for imaging of both liquid and solid samples with micron-scale isotropic resolution. The apparatus includes a solenoidal radio-frequency microcoil with 170 µm inner diameter and a set of planar gradient coils, all wound by hand and supported on a series of stacked sapphire plates. The design ensures efficient heat dissipation during gradient pulses and also facilitates disassembly, sample changes, and reassembly. To demonstrate liquid state (1)H MRI, we present an image of polystyrene beads within CuSO4-doped water, contained within a capillary tube with 100 µm inner diameter, with 5.0 µm isotropic resolution. To demonstrate solid state (1)H MRI, we present an image of NH4Cl particles within the capillary tube, with 8.0 µm isotropic resolution. High-resolution solid state MRI is enabled by frequency-switched Lee-Goldburg decoupling, with an effective rotating frame field amplitude of 289 kHz. At room temperature, pulsed gradients of 4 T/m (i.e., 170 Hz/µm for (1)H MRI) are achievable in all three directions with currents of 10 A or less. The apparatus is contained within a variable-temperature liquid helium cryostat, which will allow future efforts to obtain MRI images at low temperatures with signal enhancement by dynamic nuclear polarization.

An Athymic Rat Model for Mandibular Osteoradionecrosis Allowing for Direct Translation of Regenerative Treatments.

OBJECTIVE: We aim to create a model of mandibular osteoradionecrosis in athymic rats. Athymic rats provide an immunosuppressed environment whereby human stem cells and biomaterials can be used to investigate regenerative solutions for osteoradionecrosis, bridging the gap between in vivo testing and clinical application. STUDY DESIGN: Prospective animal study. SETTING: Academic otolaryngology department laboratory. SUBJECTS AND METHODS: After Institutional Animal Care and Use Committee approval, 10 athymic nude rats were divided into 2 groups. The experimental group (n = 6) underwent irradiation (20 Gy), while the control group (n = 4) underwent sham irradiation catheter placement only. All 10 rats underwent extraction of the second mandibular molar 7 days later. The rats were sacrificed 28 days after dental extraction, and their mandibles were harvested. The mandibles were examined with histologic analysis and bone volume analysis based on 3-dimensional micro-computed tomography. RESULTS: All 10 rats survived the experiment period. Radiographic and histologic analysis revealed decreased bone formation in the experimental group compared with the control group. Jaw region volume ratio was 0.83 for the experimental group versus 0.97 in the control group (P = .003). The region-of-interest volume ratio was 0.75 in the experimental group and 0.97 in the control group (P = .005). Histologically, there were increased osteoclasts (P = .02) and decreased osteoblasts (P = .001) as well as increased fibrosis in the experimental group versus the control group. CONCLUSION: Mandibular osteoradionecrosis can be effectively and reproducibly produced in an athymic rat model. This will allow further research to study regenerative medicine in an athymic rat model.

Coronoid-temporalis pedicled rotation flap for orbital floor reconstruction of the total maxillectomy defect.

OBJECTIVES: Total maxillectomy creates a significant defect in the supporting framework of the orbit. Successful reconstruction of the deficit requires repair of the orbital floor to prevent early and late complications. This paper describes the recreation of the orbital floor using a coronoid-temporalis sling. STUDY DESIGN: Retrospective review of two patients who underwent total maxillectomy and subsequent coronoid-temporalis sling reconstruction of the surgical defect. METHODS: The charts of two patients who underwent coronoid-temporalis reconstruction of the orbital floor were retrospectively reviewed. The outcomes were evaluated. The authors present a method for reconstruction of the orbital floor and discuss the advantages and disadvantages of this method. RESULTS: Two patients underwent successful reconstruction of the orbital floor with a coronoid-temporalis sling procedure. Both patients display acceptable functional and cosmetic results. CONCLUSION: Coronoid-temporalis sling is a readily available and easily modified tissue for reconstruction of the orbital floor. It offers similar results to those previously described techniques in this area without need for further extensive surgery.

In vitro fibroblast and pre-osteoblastic cellular responses on laser surface modified Ti-6Al-4V.

The success of any implant, dental or orthopaedic, is driven by the interaction of implant material with the surrounding tissue. In this context, the nature of the implant surface plays a direct role in determining the long term stability as physico-chemical properties of the surface affect cellular attachment, expression of proteins, and finally osseointegration. Thus to enhance the degree of integration of the implant into the host tissue, various surface modification techniques are employed. In this work, laser surface melting of titanium alloy Ti-6Al-4V was carried out using a CO2 laser with an argon gas atmosphere. Investigations were carried out to study the influence of laser surface modification on the biocompatibility of Ti-6Al-4V alloy implant material. Surface roughness, microhardness, and phase development were recorded. Initial knowledge of these effects on biocompatibility was gained from examination of the response of fibroblast cell lines, which was followed by examination of the response of osteoblast cell lines which is relevant to the applications of this material in bone repair. Biocompatibility with these cell lines was analysed via Resazurin cell viability assay, DNA cell attachment assay, and alamarBlue metabolic activity assay. Laser treated surfaces were found to preferentially promote cell attachment, higher levels of proliferation, and enhanced bioactivity when compared to untreated control samples. These results demonstrate the tremendous potential of this laser surface melting treatment to significantly improve the biocompatibility of titanium implants in vivo.