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Purpose: Predicting individual patient sensitivity to radiation therapy (RT) for tumor control or normal tissue toxicity is necessary to individualize treatment planning. In head and neck cancer, radiation doses are limited by many nearby critical structures, including structures involved in swallowing. Previous efforts showed that imaging parameters correlate with RT dose; here, we investigate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) blood volume (BV) changes in predicting dysphagia., Methods and Materials: This study included 32 patients with locally advanced oropharyngeal squamous cell carcinoma treated with definitive chemoradiation on an institutional protocol incorporating baseline and early midtreatment DCE-MRI. BV maps of the pharyngeal constrictor muscles (PCM) were created, and BV increases midtreatment were correlated with the following parameters at 3 and 12 months post-RT: RT dose, Dynamic Imaging Grade of Swallowing Toxicity swallow score, aspiration frequency, European Organisation for Research and Treatment of Cancer HN35 patient-reported outcomes, physician-reported dysphagia, and feeding tube (FT) dependence., Results: The mean BV to the PCMs increased from baseline to fraction 10, which was significant for the superior PCM (P = .006) and middle PCM (P < .001), with a trend in the inferior PCM where lower mean doses were seen (P = .077). The factors associated with FT dependence at 3 months included BV increases in the total PCM (correlation, 0.48; P = .006) and middle PCM (correlation, 0.50; P = .004). A post-RT increase in aspiration was associated with a BV increase in the superior PCM (correlation, 0.44; P = .013),and the increase in the total PCMs was marginally significant (correlation, 0.34; P = .06). The best-performing models of FT dependence (area under the receiver operating curve [AUC] = 0.84) and aspiration increases (AUC = 0.78) included BV increases as well as a mean RT dose to middle PCM., Conclusions: Our results suggest that midtreatment BV increases derived from DCE-MRI are an early predictor of dysphagia. Further investigation of these promising imaging markers to assess individual patient sensitivity to treatment and the patient's subsequent risk of toxicities is warranted to improve personalization of RT planning., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Neurofibromatosis Type 1 (NF1) is a neurocutaneous tumour syndrome characterised by mutations in the NF1 gene and resultant neurofibromin protein. The condition is associated with several stigmata of variable penetrance, including various tumours. Massive and fatal haemorrhage arising from plexiform neurofibromas has been described in NF1 patients, though it is a rare clinical entity. The aetiology of massive haemorrhage in NF1 patients appears to be related to vasculopathy, including aneurysms and pseudoaneurysms, often arising within plexiform neurofibromas. There is currently no evidence-based consensus for managing this rare clinical emergency, likely as a result of its low incidence. We describe a case of massive haemorrhage in an NF1 patient managed via embolisation and discuss the literature., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Objectives: Improvements in the efficacy of extended endonasal approaches to resect skull base pathologies have created the need for new reconstructive alternatives. Hereby, we describe a novel pedicled myomucosal flap that allows the reconstruction of dural defects in the lower clivus and craniovertebral junction or to cover the paraclival and petrous segments of the internal carotid artery., Study Design: Anatomic description. Technical report. Feasibility., Methods: We describe a myomucosal flap with a cephalic pedicle based on the salpingopharyngeus muscle and its vessels. Subsequently, using a cadaveric model, we harvested the flap and explored its potential for the reconstruction of various dural defects or to cover the internal carotid artery., Results: Our study confirmed the feasibility of harvesting and transposing the myomucosal salpingopharyngeus (Dicle flap) flap for the reconstruction of inferior clival and craniovertebral junction defects or to cover the petrous and paraclival segments of the internal carotid artery., Conclusions: The Dicle flap is a feasible, reconstructive alternative for the reconstruction of select small- to medium-sized defects of the posterior and inferior aspects of the ventral skull base.

Purpose: To measure changes in perfusion of the pharyngeal constrictor muscles (PCM) using CT perfusion (CTP) imaging during a course of definitive radiotherapy (RT) in head-and-neck cancer (HNC) patients and correlate with dysphagia outcome after RT., Methods and Materials: Fifteen HNC patients underwent CTP imaging of the PCM at baseline and Weeks 2, 4, and 6 during RT and 6 weeks after RT. Blood flow and blood volume were measured in the PCM, and percentage change from baseline scan was determined. A single physician-based assessment of dysphagia was performed every 3 months after RT using the Common Terminology Criteria for Adverse Events, version 3.0 grading system., Results: With a median follow-up of 28 months (range, 6-44 months), Grade 3 dysphagia was present in 7 of 15 patients, and 8 patients experienced Grade 0-2 dysphagia. The CTP parameters at Week 2 of RT demonstrated an increase in mean PCM blood flow of 161.9% vs. 12.3% (p = 0.007) and an increase in mean PCM blood volume of 96.6% vs. 8.7% (p = 0.039) in patients with 6-month post-RT Grade 3 dysphagia and Grade 0-2 dysphagia, respectively. On multivariate analysis, when adjusting for smoking history, tumor volume, and baseline dysphagia status, an increase in blood flow in the second week of RT was significant for 3- and 6-month Grade 3 dysphagia (p < 0.05)., Conclusions: Perfusion changes in the PCM during Week 2 of RT in the PCM may predict the severity of dysphagia after HNC RT., Competing Interests: none., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Recent studies have demonstrated that the LIM homeodomain transcription factor Islet1 (Isl1) marks pluripotent cardiovascular progenitor cells and is required for proliferation, survival, and migration of recently defined second heart field progenitors. Factors that are upstream of Isl1 in cardiovascular progenitors have not yet been defined. Here we demonstrate that beta-catenin is required for Isl1 expression in cardiac progenitors, directly regulating the Isl1 promoter. Ablation of beta-catenin in Isl1-expressing progenitors disrupts multiple aspects of cardiogenesis, resulting in embryonic lethality at E13. beta-Catenin is also required upstream of a number of genes required for pharyngeal arch, outflow tract, and/or atrial septal morphogenesis, including Tbx2, Tbx3, Wnt11, Shh, and Pitx2. Our findings demonstrate that beta-catenin signaling regulates proliferation and survival of cardiac progenitors.

Background and Purpose: Middle cerebral artery occlusion (MCAO) by an intraluminal filament is a widely accepted animal model of focal cerebral ischemia. In this procedure, cutting of the external carotid artery (ECA) is a prerequisite for thread insertion. However, the implications of ECA transsection have not yet been described., Methods: After 90 minutes of filament MCAO or sham surgery, rats were evaluated for up to 14 days in terms of body weight development, core temperature, and motor performance. Repeated in vivo MRI of the head and neck was performed for quantification of brain edema and infarct volume. The temporal muscles were histologically analyzed postmortem., Results: In 47% of all rats, ischemic tissue damage to the ipsilateral ECA area, including temporal, lingual, and pharyngeal musculature, was detectable by MRI. Histology of temporal muscles confirmed acute ischemic myopathy. Animals with ECA territory ischemia (ECA-I) showed delayed body weight development and poorer recovery of motor function. There was no difference in the extent of brain edema or final cerebral lesion size between ECA-I-affected and unaffected rats., Conclusions: Filament MCAO was complicated by the consequences of ECA ischemia in approximately half of all rats. Impaired mastication and swallowing functions restricted ingestion and resulted in postsurgical body weight loss and worse motor performance. Impaired cerebral microperfusion resulting from dehydration and reduced spontaneous motor activity resulting from reduced food and water uptake might have contributed to poorer neurological recovery in ECA ischemic rats. Thus, adverse effects caused by extracerebral ischemia with potential impact on outcome have to be considered in this stroke model.

Fiberoptic imaging in an isolated, sealed upper airway was performed in 10 decerebrate cats to determine the effect of pharyngeal muscle activation on airway pressure-area relationships. Bilateral cuff electrodes stimulated the distal cut ends of the following nerves: medial and lateral hypoglossus, glossopharyngeus, and pharyngeal branch of vagus. At given intraluminal pressures ranging from +6 to -6 cm H2O, cross-sectional area was measured in the rostral oropharynx, velopharynx, and caudal oropharynx, with and without nerve stimulation. A mixed model analysis of variance indicated a relatively constant increase in area across the pressure range with glossopharyngeal stimulation at any given level. Significant interactions between pressure and stimulation were present in the rostral oropharynx with medial hypoglossus stimulation and in the caudal oropharynx with independent and combined hypoglossal branch stimulation and pharyngeal branch of vagus stimulation. With stimulation of the hypoglossal nerves, greater increases in area in these regions occurred in the lower pressure ranges. Stimulation of the pharyngeal branch of the vagus caused a greater decrease in area at the higher pressure ranges in the caudal oropharynx and velopharynx. The results indicate that the mechanical effects of pharyngeal muscle activation depend not only on the region and muscles activated but also on the intraluminal pressure.

The aim of this investigation was to examine the blood supply of the normal velopharyngeal musculature and its clinical implications. Detailed dissections were performed on each side of five fresh human adult cadaveric head and neck specimens (n = 10) following carotid artery injection with liquid neoprene latex stained with green pigment. The vascular network of the soft palate was situated within its glandular layer. The velopharyngeal muscles were supplied by the following four branches of the external carotid artery: (1) ascending palatine branch of the facial artery, which supplied the palatoglossus, palatopharyngeus, musculus uvulae, and the intravelar part of the levator veli palatini; (2) ascending pharyngeal artery, which supplied the superior constrictor; (3) the previously undescribed recurrent pharyngeal artery, which supplied the extravelar part of the levator veli palatini; and (4) maxillary artery, which supplied the tensor veli palatini. All muscles except the musculus uvulae had at least a dual blood supply. Analysis of this vascular anatomy suggests that (1) the overall generous blood supply of the velum allows it to tolerate the dissection performed during intravelar veloplasty and the Furlow double opposing Z-plasty; (2) dissection around the hamulus, along the medial pterygoid plate, and in the space of Ernst should be performed carefully to avoid damage to the ascending palatine artery, ascending pharyngeal, and recurrent pharyngeal arteries; (3) vertical pharyngeal flaps are random pattern in nature; and (4) the posterior tonsilar pillar flaps of the sphincter pharyngoplasty are adequately supplied by the hamular branch of the ascending palatine artery.

The inferior pharyngeal constrictor muscle plays an important role at the pharyngeal phase of deglutition and is anatomically composed of the thyropharyngeal muscle and cricopharyngeal muscle. In this study we investigated the distribution pattern of neuropeptidergic and catecholaminergic nerve fibers in the thyropharyngeal muscle and cricopharyngeal muscle of seven puppies by immunohistochemistry. Some of the calcitonin gene-related peptide-, substance P-, vasoactive intestinal polypeptide-, and tyrosine hydroxylase-immunoreactive nerve fibers were found to lie parallel to the muscle fibers in both the thyropharyngeal muscle and cricopharyngeal muscle. Nerve fibers with immunoreactivity to all substances examined were found to be associated with blood vessels in both the thyropharyngeal muscle and cricopharyngeal muscle, and the number of calcitonin gene-related peptide, neuropeptide Y, and tyrosine hydroxylase nerve fibers was higher than the number of substance P, vasoactive intestinal polypeptide, and galanin nerve fibers. Motor end plate-like structures with calcitonin gene-related peptide immunoreactivity were found in both the thyropharyngeal muscle and cricopharyngeal muscle. These structures in the cricopharyngeal muscle were clearly less than those in the thyropharyngeal muscle. Some clusters of neurons were detected only in the cricopharyngeal muscle of all dogs examined. Substance P-, vasoactive intestinal polypeptide-, galanin-, and neuropeptide Y-immunoreactive neurons were found in this ganglion, and the vasoactive intestinal polypeptide-immunoreactive neurons were the most abundant. Abundant calcitonin gene-related peptide- and vasoactive intestinal polypeptide-immunoreactive nerve fibers, and some substance P- and galanin-immunoreactive nerve fibers were distributed in the ganglion.(ABSTRACT TRUNCATED AT 250 WORDS)