Technical Nuances of Anterior Column Construction for the Treatment of Osteomyelitis-Induced Cervical Kyphoscoliotic Deformity: An Operative Video Illustration.

Pyogenic vertebral osteomyelitis is a bacterial infection of the vertebral body often caused by hematogenous spread from a distant site with 3%-11% of cases affecting the cervical spine.1,2 Patients at risk for osteomyelitis are intravenous drug users, patients with diabetes, patients in dialysis, and males older than 50 years of age. In severe cases where infection causes osseous destruction of the vertebral column lending to a loss of normal sagittal and coronal plane alignment, neurologic impairment, or spinal instability, surgical correction may be required.3 A 38-year-old woman with a medical history of intravenous drug use presented with a 1-week history of progressive paresthesias, subjective loss of lower extremity sensation, and severe right upper extremity weakness. Neurologic examination was notable for significant weakness in the right deltoids, biceps, and triceps. Magnetic resonance imaging cervical spine revealed significant kyphosis at C4-C5 secondary to destruction of the C4 and C5 vertebral bodies and anterior and posterior epidural fluid collection at C2-C3 and C7-T1, respectively. Surgery was proposed through a combined anteroposterior approach with head and neck surgeons. Anteriorly, she underwent a C2-C3 and C6-C7 ACDF and C4, C5 corpectomies (Video 1). The patient was then transitioned to the prone position and underwent C3-T3 posterior fusion with instrumentation and C3-C7 laminectomies. Correction of sagittal imbalance should restore normal physiologic spinal alignment while promoting a successful fusion.4 The patient was discharged to acute rehabilitation after an uneventful postoperative course. At 5-month follow-up, she has regained antigravity strength in right upper extremity and reports significant reduction in neck pain.

Treatment of Localized Amyloid Light Chain Amyloidosis With External Beam Radiation Therapy.

PURPOSE: Localized amyloidosis is a condition characterized by deposits of fibrillary proteins confined to a single organ. The most common subtype is amyloid light chain amyloidosis, which is caused by secretion of amyloidogenic light chain by a monoclonal population of plasma cells. We present a review and discussion of the literature in the context of a case presentation of localized amyloid light chain amyloidosis of the nasopharynx treated with radiation alone. METHODS AND MATERIALS: We reviewed literature relevant to this topic from 1970 to the present. Relevant studies, reports, and articles were summarized in table form. RESULTS: Surgical resection has historically been the primary therapeutic modality for these patients, with radiation being reserved for recurrent lesions or for those unfit for surgery. Although the data are limited to small retrospective series, radiation has been shown to provide good control with mild toxicity that is as good as or better than surgery. Doses range from 20 to 45 Gy, conventionally fractionated. There is no known risk of progression to systemic disease without local therapy. CONCLUSIONS: We recommend local therapy for symptomatic patients after systemic disease has been excluded. We generally recommend radiation in the setting of recurrent lesions, unacceptable toxicity with surgery, poor surgical candidates, and as the initial modality in select patients (elderly individuals with bothersome but nonobstructive lesions).

Melanoma In Situ of the Hard Palate.

Mucosal melanoma of the oral cavity is rare and highly aggressive, thought to represent less than 1% of melanomas. Within this subgroup, melanoma in situ has been rarely described. We describe the case of a 54-year-old male with history of tobacco use presented with extensive pigmented changes to the hard and soft palate. Biopsy demonstrated melanoma in situ. Mucosal surgical resection was performed with all peripheral epithelial margins involved and negative deep margins. After extensive multidisciplinary discussion, remaining mucosal margins were re-resected to the teeth and posteriorly onto the soft palate. Deep margins remained negative with melanoma in situ still present peripherally. The patient is routinely surveilled without evidence of recurrence. Oral cavity melanoma in situ has been rarely described. The treatment of choice is surgical excision, ranging from wide local excision to composite resections, with consideration given to medical adjuncts. This unique entity should be considered in pigmented oral abnormalities.

Near-total mandibular reconstruction following osteoradionecrosis with double scapula tip free flap: A case report.

Near-total mandibular reconstruction poses many challenges to reconstructive surgeons. The purpose of this article is to present a challenging case in a patient with osteoradionecrosis of the mandible requiring a near-total mandibular reconstruction using bilateral scapula tip free tissue reconstruction. A 68-year-old African-American male with a history of T2N0M0 squamous cell carcinoma of the tonsil presented with advanced stage osteoradionecrosis of the mandible. Reconstruction was planned using 3D Systems (Denver, CO), mandibular osteotomies were planned inferior to the sigmoid notch on the ascending rami. Neither fibula flap was amenable for harvesting due to poor vasculature of the patient's lower extremities, and bilateral scapula tip free flaps were subsequently planned. The post-operative course was complicated by venous congestion in the right scapula flap which required revision to the venous anastomosis on POD 1. The patient had intraoral breakdown that required debridement in the operating room and application of a cellular matrix. The patient fully recovered from the acute surgery and was discharged home without a tracheostomy. At the last follow up visit, the patient was taking 100% of diet peroral and had no signs of oral incompetence, mental projection was satisfactory, and the ability to verbally communicate was unimpaired. We report a complex case of near-total mandibular reconstruction using simultaneous bilateral scapula tip free flaps. While we do not advocate simultaneous bilateral scapula tip free flaps as the standard of care for large mandibulectomy defects, it may be considered for patients in which traditional osseous free flaps are not available.

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication.

PURPOSE: Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti-PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC. PATIENTS AND METHODS: This single-arm, multi-institution, phase II study (NCT02609503) enrolled 29 cisplatin-ineligible patients. Patients received radiotherapy concurrently with three cycles of pembrolizumab 200 mg every 3 weeks followed by three adjuvant cycles. The primary endpoint was a progression-free survival (PFS) of ≥16 months. Correlative studies included peripheral blood flow cytometry and Luminex cytokine profiling. RESULTS: Reasons for cisplatin ineligibility included otopathy (69.0%), nephropathy (20.7%), and neuropathy (6.9%). With median follow-up of 21 months, estimated 24-month PFS and overall survival rates were 71% (95% confidence interval, 49%-84%) and 75% (51%-88%). The primary PFS endpoint has exceeded the hypothesis and its median has not been reached. Toxicities were typical of radiotherapy; however, high rates of grade 3/4 lymphopenia (58.6%) were observed. Flow cytometry revealed a relative decline in CD4 T cells and B cells, but not CD8 T cells. Upon treatment, frequencies of transitional B cells and tissue-like memory B cells increased, while resting memory B cells decreased. Patients with progression had greater percentages of baseline naïve B cells and fewer marginal zone B cells. CONCLUSIONS: Pembrolizumab and radiotherapy is efficacious in LA-HNSCC and should be evaluated in a randomized trial. The observed changes in B-cell markers deserve further study both as potential biomarkers and as therapeutic targets.

PIK3CA Mutation in HPV-Associated OPSCC Patients Receiving Deintensified Chemoradiation.

PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventy-seven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of deintensified CRT (60 Gy intensity-modulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Of the 77 patients, nine had disease recurrence (two regional, four distant, three regional and distant). Thirty-four patients had mutation(s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4%, 95% confidence interval [CI] = 85.0% to 99.9% vs 68.8%, 95% CI = 26.7% to 89.8%; P = .004). On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (hazard ratio = 5.71, 95% CI = 1.53 to 21.3; P = .01). PIK3CA mutation is associated with worse disease-free survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with deintensified CRT.

Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer.

PURPOSE: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). EXPERIMENTAL DESIGN: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16-positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non-HPV-associated malignancy was also analyzed. RESULTS: Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diagnosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (>200 copies/mL) and >95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or >10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049). CONCLUSIONS: A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPV-associated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy.

Mandibular reconstruction with the scapula tip free flap.

INTRODUCTION: The scapula tip free flap has been described for reconstruction of short mandible defects with extensive soft tissue needs. The versatility of this flap has not been extensively described. METHODS: Retrospective case series of patients who underwent mandibulectomy and reconstruction with the scapula tip free flap from 2005 to 2016. Outcomes include bony union, complications, dental rehabilitation, and donor site morbidity. RESULTS: A total of 120 patients were identified. Average harvested bone was 7.7 cm, with 54% undergoing one osteotomy, and 76.7% harvested as a chimeric flap. Radiographically, average inset bone was 6.6 cm. Complete or partial bony union was observed at 74.4% of proximal and 82.6% of distal osteotomies. A 95% of reconstructions met criteria for dental implants. Mean disabilities of the arm, shoulder and hand score was 21.2. CONCLUSIONS: The scapular tip is an excellent option for reconstruction of segmental mandible defects with the option of osteotomy, excellent bony union rates, low donor site morbidity, and potential for dental rehabilitation.

Quality of Life for Patients With Favorable-Risk HPV-Associated Oropharyngeal Cancer After De-intensified Chemoradiotherapy.

PURPOSE: Oropharynx cancers associated with human papillomavirus (HPV) have a favorable prognosis, but current treatment approaches carry significant long-term morbidity. Strategies to de-intensify treatment in this population are under investigation, but the impact of these approaches on quality of life (QOL) is not well understood. We present patient-reported outcomes from 2 prospective studies examining de-intensified chemoradiotherapy. METHODS AND MATERIALS: This study included patients enrolled in 2 prospective phase 2 trials of de-intensified chemoradiotherapy in patients with HPV-associated oropharynx cancer who had at least 1 year of follow-up. Treatment included concurrent radiation therapy (60 Gy) and chemotherapy (weekly cisplatin, 30 mg/m2). Patients reported QOL and symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module-35, and the Eating Assessment Tool-10 instruments before treatment and at regular intervals thereafter. Changes in QOL and individual symptoms were examined over time, and multivariate analysis was used to identify clinical factors associated with recovery to baseline symptom levels. RESULTS: Of the 154 patients enrolled, 126 patients had at least 1 year of follow-up and were included in this study (median follow-up, 25 months). Global QOL, functional indices, and most individual symptoms returned to baseline 3 to 6 months after treatment. Swallowing (Eating Assessment Tool-10 score) returned to baseline function by 2 years, but dry mouth, sticky saliva, and taste/senses did not return to baseline levels. However, from 1 to 2 years, continued improvement occurred in dry mouth score (55 vs 48), sticky saliva score (35 vs 27), and senses score (24 vs 20). On multivariate analysis, unilateral radiation therapy was associated with returning to baseline level of swallowing and sticky saliva. CONCLUSIONS: The use of de-intensified chemoradiotherapy in HPV-associated oropharynx cancer led to favorable patient-reported outcomes, with early recovery of QOL and continued improvement of xerostomia and dysphagia beyond 1-year posttreatment.

Low-Grade, Nonintestinal Nonsalivary Sinonasal Adenocarcinoma Associated With an Exophytic Schneiderian Papilloma: A Case Report.

Sinonasal adenocarcinoma is a rare tumor of the head and neck accounting for 10% to 20% of all primary malignancies of the nose and paranasal sinuses. There tumors are classified as salivary, intestinal and nonintestinal, nonsalivary. Low-grade nonintestinal nonsalivary are rare tumors whose diagnosis is essentially that of exclusion. Here we present the first case of one such tumor associated with an exophyic Schneiderian papilloma. A 71-year-old retired aerospace engineer presented with a 1-year history of severe nasal obstruction. Endoscopy and compted tomography imaging demonstrated a polypoid lesion occupying his entire right nasal cavity extending into and filling the nasopharynx. Biopsy suggested adenocarcinoma, at least in situ and the patient subsequently underwent complete resection. Pathologic evaluation demonstrated polypoid tumor consistent with a low-grade papillary adenocarcinoma with micropapillary architecture associated with a small amount of residual exophytic Schneiderian papilloma. Immunohistochemistry revealed diffuse expression of CK7, CK 5/6, and S100 protein in tumor cells. Expression of p63 was seen in basal cells only. Tumor cells did not show expression of CK20, CDX2 (intestinal markers), mammaglobin, GATA3 (salivary markers), PAX8, WT1, nor estrogen, progesterone, or androgen receptors confirming its nonintestinal nonsalivary differentiation.

Cervical dedifferentiated liposarcoma with meningothelial-like whorling.

Liposarcomas are the most common soft-tissue sarcoma of adults, but rare in the head and neck. Recently, a subtype of dedifferentiated liposarcoma with meningiothelial-like whorls was reported and we present the first description of such a tumor in the head and neck. A 65 year old male underwent a resection of a calcified retroesophageal mass that was in close relation to the left hemithyroid and recurrent laryngeal nerve. It was resected en bloc with the left thyroid lobe. Initial pathologic evaluation suggested the mass was a schwanomma of the recurrent laryngeal nerve, but positive staining for MDM2 and CDK4 indicated the tumor was a dedifferentiated liposarcoma. Further evaluation elucidated the unique meningothelial-like whorls within the tumor. This case demonstrates dedifferentiated liposarcomas do appear in the head and neck. Furthermore, this is the first report in the head and neck of the mengiothelial-like whorling pattern type of dedifferentiated liposarcoma.

Complex role of the vitamin D receptor and its ligand in adipogenesis in 3T3-L1 cells.

The vitamin D receptor (VDR) and its ligand 1,25-OH2-VD3 (calcitriol) play an essential role in mineral homeostasis in mammals. Interestingly, the VDR is expressed very early in adipogenesis in 3T3-L1 cells, suggesting that the VDR signaling pathway may play a role in adipocyte biology and function. Indeed, it has been known for a number of years that calcitriol is a potent inhibitor of adipogenesis in this model but with no clear mechanism identified. In this study, we have further defined the molecular mechanism by which the unliganded VDR and calcitriol-liganded VDR regulate adipogenesis. In the presence of calcitriol, the VDR blocks adipogenesis by down-regulating both C/EBPbeta mRNA expression and C/EBPbeta nuclear protein levels at a critical stage of differentiation. In addition, calcitriol allows for the up-regulation of the recently described C/EBPbeta corerepressor, ETO, which would further inhibit the action of any remaining C/EBPbeta, whose action is required for adipogenesis. In contrast, in the absence of calcitriol, the unliganded VDR appears necessary for lipid accumulation, since knock-down of the VDR using siRNA both delays and prevents this process. Taken together, these data support the notion that the intracellular concentrations of calcitriol can play an important role in either promoting or inhibiting adipogenesis via the VDR and the transcriptional pathways that it targets. Further examination of this hypothesis in vivo may shed new light on the biology of adipogenesis.