In this study, we report a differential response of mitogen-activated protein kinase-kinase (MEK) inhibitor trametinib in 20 head and neck squamous cell carcinoma (HNSCC) patients' tumor-derived cell ...cultures. Relatively sensitive and resistant cases to trametinib were identified using high throughput metabolic assays and validated in extended dose response studies in vitro. High throughput metabolic assays exploring combination therapies with trametinib were subjected to synergy models and maximal synergistic dose analyses. These yielded several candidates, including axtinib, GDC-0032, GSK-690693, and SGX-523. The combination regimen of trametinib and AXL/MET/VEGFR inhibitor glesatinib showed initial efficacy both in vitro and in vivo (92% reduction in tumor volume). Sensitivity was validated in vivo in a patient-derived xenograft (PDX) model in which trametinib as a single agent effected reduction in tumor volume up to 72%. Reverse Phase Protein Arrays (RPPA) demonstrated differentially expressed proteins and phosphoproteins upon trametinib treatment. Furthermore, resistant cell lines showed a compensatory mechanism via increases in MAPK and non-MAPK pathway proteins that may represent targets for future combination regimens. Intrinsic-targeted options have potential to address paucity of medical treatment options for HNSCC cancer patients, enhance response to extrinsic targeted agents, and/or reduce morbidity as neoadjuvant to surgical treatments.
Abstract Melanotic neuroectodermal tumors of infancy (MNTI) are pigmented, rapidly growing, and occur predominantly within the bony head and neck structures. There are fewer than 400 cases reported ...in the literature with many of these described as single case reports due to their rarity. MNTIs are derived from the neural crest, and appear in areas that develop from neuroectodermal pathways; the most common of these is the maxilla.2 Locations in other intraosseous and extraosseous structures have been characterized, including the mandible (6%), skull, brain, and epididymis.1 Infants in the first year of life are usually affected, compelling prompt diagnosis and treatment as well as close monitoring. Prognosis is generally good despite the rapidity of growth. The incidence of recurrence is about 20% overall and perhaps higher (33%) in mandibular cases.1 Given the rarity of this disease, an overestimation of recurrence or metastases may be more frequently reported. The tumors are categorized as benign but aggressive, with rare reports of malignant features based on histology or metastasis. Surgical resection in the pursuit of tumor-free margins is the primary treatment modality for all tumors given its potential for extensive growth; this is especially true of malignant tumors, which comprise less than 25 cases in the literature.1,5 Chemotherapy and radiotherapy have been used as adjuncts in such cases, with varying reports of success in reducing morbidity and mortality.6-8 The management of a metatstatic mandibular tumor, in particular, has only been documented in one other case.9 The purpose of this case report is to present treatment and reconstruction considerations in a metastatic mandibular MNTI and to review the associated literature.
Background
Perioperative management of advanced osteoradionecrosis of the head and neck requiring free flap (FF) reconstruction varies. Our objectives included assessment of practice patterns and ...outcomes.
Methods
Multi‐institutional, retrospective review of FF reconstruction for head and neck osteoradionecrosis (n = 260).
Results
Administration of preoperative antibiotics did not correlate with reduction in postoperative complications. Preoperative alcohol use correlated with higher rates of hardware exposure (p = 0.03) and 30‐day readmission (p = 0.04). Patients with FF compromise had higher TSH (p = 0.04) and lower albumin levels (p = 0.005). Prealbumin levels were lower in patients who required neck washouts (p = 0.02) or a second FF (p = 0.03). TSH levels were higher in patients undergoing postoperative debridement (p = 0.03) or local flap procedures (p = 0.04).
Conclusion
Malnutrition, hypothyroidism, and substance abuse correlated with a higher incidence of postoperative wound complications in patients undergoing FF reconstruction for advanced osteoradionecrosis. Preoperative antibiotics use did not correlate with a reduction in postoperative wound complications.
The application of microvascular free tissue transfer for reconstruction of the head and neck is well established. Improved outcomes, as well as surgical and technologic advances, have broadened the ...applications of microvascular free flaps in these defects. Postoperative complications such as pharyngocutaneous fistulas, tracheal or esophageal stenoses, or recurrent pathology may occasionally require secondary or even tertiary reconstruction with free tissue transfers. The disrupted anatomy and fibrotic changes resulting from primary reconstruction, neck dissection, and irradiation present the surgeon with a high risk of provoking vascular or nervous injury when dissecting in previously operated or irradiated sites. This prompts a search for alternative recipient vessels for microvascular anastomosis. The transverse cervical, inferior thyroid, and thyrocervical trunk arteries have all been proposed as alternative recipient vessels. The internal mammary vessels (IMVs) have a proven record in breast reconstruction, but recently have been found to have an application in special circumstances in head and neck reconstruction. This investigation describes the advantages of the IMVs as suitable recipient vessels for head and neck reconstruction when access to traditional vasculature is unavailable.
The mandible is a critical structure of the lower facial skeleton which plays an important role in several vital functions. Segmental resection of the mandible is at times required in patients with ...advanced oral cavity malignancies, primary mandibular tumors, and radiation or medication induced osteonecrosis. Mandibulectomy can significantly decrease quality of life, and thus mandibular reconstruction is an important aspect of the operative plan. Mandibular reconstruction is challenging due to the complex three‐dimensional anatomy of the mandible, and the precision required to restore dental occlusion in dentate patients. Significant advances have been made over the past decade in the ability to reconstruct and rehabilitate patients after a segmental mandibulectomy. This review will highlight these advances and discuss the timing of dental implantation.
In this study a wireless sensor network for collecting information about indoor temperature, relative humidity and light level in four positions inside an office building is developed. Infrastructure ...of wireless sensor network is based on MAC and PHY layer of IEEE 802.15.4 standard and JenNet network protocol stack. The hardware of the system is built integrating JN5148 Evaluation Kit and a Hit65 GSM modem. Features integrated in the architecture of proposed system comprise: SQL database storage of results, real-time graphical trends of measured values, histograms with selection of the start and end date, adjustable sampling time, alarm notification via e-mail and SMS, and GSM and LAN remote access to the sensor readings. These implemented features give our system high practical value with possible application in large-scale environment monitoring of buildings aimed to improve work efficiency and thermal comfort of people and storage or working conditions for materials and equipment.
This study determined whether immediate reconstruction of the inferior alveolar nerve with a long (>4.5 cm) processed nerve allograft (PNA) in conjunction with simultaneous ablation and ...reconstruction of the mandible would be effective in safely restoring subjective sensation and achieving functional sensory recovery.
Patients (5 to 70 yr old) requiring resection of the unilateral or bilateral mandible for benign pathology were included. The graft had to be longer than 4.5 cm. Results of sensory nerve tests and 3 different surveys (Direct Path, Numerical Rating Scale, Word Choice) were collected before surgery and at 3, 6, and 12 months after surgery. Safety data were recorded.
Twenty-six patients participated in this study. Three patients served as positive controls (no nerve repair). Five in the repair group and 1 in the positive control group were lost to follow-up. Data during a 1-year period were collected on 18 patients (7 male and 11 female; mean age, 26.4 yr; range, 10 to 64 yr). The mean length of the PNA was 62.7 mm (range, 45 to 70 mm). Seventeen of 18 patients had S4 sensory scores preoperatively and the postoperative score was S4 at 3 months in 3, at 6 months in 3, and at 1 year in 12. Scores for positive control patients never exceeded S2. Numerical rating scales and word choices were not statistically different from presurgical scores at 6 and 12 months. There were no adverse events.
The PNA is safe and effective when immediately inserted with resection and reconstruction of the mandible: 90% of patients achieved functional sensory recovery and reported similar sensations to preoperative subjective values.
The purpose of this study was to examine the anatomical variation of the osseous and cartilaginous components of the nasal septum.
Fifty-seven cadaver specimens were digitally scanned and analyzed ...utilizing Bersoft Image software. Anatomical data were statistically analyzed utilizing SPSS 13.0. Evaluation of the area of the osseous/cartilaginous nasal septum as well as an estimation of the available cartilage for grafting was performed.
Septal specimens revealed males had greater variation in cartilaginous area compared to female specimens. The intranasal/extranasal cartilage contributes about 45%/55% of the total cartilage, respectively. The data indicate that the mean area of cartilage available for grafting is around 420 mm(2).
Significant variability in the cartilaginous elements of the nose is the rule rather than the exception. Key differences exist in the anatomic location of the graft material between males and females. This has important surgical implications given the critical attention required during graft harvesting in order to maintain support of the nose.
Reconstruction of mandibular defects is best accomplished by composite bony tissue. When the fibula is not available other sources must be used. Occasionaly tumor recurence will neccesitate a further ...resection and bony reconstruction. We report two cases in which osteocutaneous radial forearm free tissue transfer was used for secondary reconstructio after prior bony free flap reconstruction. Laryngoscope, 132:2177–2179, 2022
PDF
