Kenneth Newkirk

Fractionated Stereotactic Radiosurgery for Reirradiation of Head-and-Neck Cancer

PURPOSE Stereotactic radiosurgery (SRS) is an appealing treatment option after previous radiotherapy because of its precision, conformality, and reduced treatment duration. We report our experience with reirradiation using fractionated SRS for head-and-neck cancer. METHODS AND MATERIALS From 2002 to 2008, 65 patients received SRS to the oropharynx (n = 13), hypopharynx (n = 8), nasopharynx (n = 7), paranasal sinus (n = 7), neck (n = 7), and other sites (n = 23). Thirty-eight patients were treated definitively and 27 patients with metastatic disease and/or untreated local disease were treated palliatively. Nine patients underwent complete macroscopic resection before SRS. Thirty-three patients received concurrent chemoradiation. The median initial radiation dose was 67 Gy, and the median reirradiation SRS dose was 30 Gy (21-35 Gy) in 2-5 fractions. RESULTS Median follow-up for surviving patients was 16 months. Fifty-six patients were evaluable for response: 30 (54%) had complete, 15 (27%) had partial, and 11 (20%) had no response. Median overall survival (OS) for all patients was 12 months. For definitively treated patients, the 2-year OS and locoregional control (LRC) rates were 41% and 30%, respectively. Multivariate analysis demonstrated that higher total dose, surgical resection, and nasopharynx site were significantly associated with improved LRC; surgical resection and nonsquamous histology were associated with improved OS. Seven patients (11%) experienced severe reirradiation-related toxicity, including one treatment-attributed death. CONCLUSION SRS reirradiation for head-and-neck cancer is feasible. This study demonstrates encouraging response rates with acceptable toxicity. Fractionated SRS reirradiation with concurrent chemotherapy in select patients warrants further study.

Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Multicenter Review and an Algorithm for Airway Management

Angioedema is a nonpitting edema of which the presentation ranges from benign facial swelling to airway obstruction managed by intubation or tracheotomy. The presentation of this disease is reviewed, and a treatment algorithm based on initial signs and symptoms is proposed for proper airway management. We performed a retrospective review of 108 patients treated in 2 tertiary care centers in the Washington, DC, area over a 5-year period. Ninety-eight patients (90.7%) were African-American, and 81 (75%) were female. Seventy-four patients (68.5%) were taking angiotensin-converting enzyme inhibitors (ACEIs). A classification system was developed based on the location of the edema at initial presentation: 1) isolated facial swelling and oral cavity edema, excluding the floor of the mouth; 2) floor of mouth and/or oropharyngeal edema, and 3) oropharyngeal edema with glottic and/or supraglottic involvement. Fourteen patients (13%) needed airway intervention, 2 of whom underwent a cricothyrotomy after a failed intubation attempt. Eleven (78.6%) were taking ACEIs. The indication for each intubation was massive tongue and floor of mouth edema. The patients were extubated 48 to 72 hours later. No patient demonstrated symptom progression after medical treatment was initiated. Therapy included discontinuation of the ACEI or other inciting agent, a high-humidity face tent, an initial dose of intravenous antihistamines, and a continued course of intravenous steroids. Within 48 hours, most patients had a resolution of their edema. Only cases of significant tongue and oropharyngeal edema took longer than 48 hours to resolve. The ACEIs are a common cause of angioedema. Left untreated, angioedema may progress to involve the oropharynx and supraglottis, resulting in a life-threatening airway compromise. Marked floor of mouth and tongue edema are the indications for airway intervention. An algorithm based on the initial presentation is essential for proper airway and patient management. Once treatment has begun, angioedema is nonprogressive and often resolves within 24 to 48 hours.

Ultrasound-guided fine-needle aspiration and thyroid disease.

ABSTRACT BACKGROUND: Fine-needle aspiration represents a critical diagnostic test in determining proper management of thyroid disease and the use of ultrasound-guided fine-needle aspiration (USGFNA) has increased over the years. METHODS: A retrospective chart review of patients undergoing USGFNA. Two hundred fifteen patients underwent 234 procedures with 362 nodules aspirated within a 2 ½-year period. RESULTS: The mean ages of women and men were 51.9 and 57.8, respectively. The average size of nodules was 2.1 cm. A difficult to assess gland or nodule was the most common indication for USGF-NA (33%). The sensitivity was 88.2%, specificity was 80.0%, the PPV was 65.2%, the negative predictive value was 94.1%, and the accuracy was 82.5%. The cancer yield, inadequacy, and complication rates were 44%, 10.5%, and 8.5%, respectively. CONCLUSIONS: USGFNA aspiration is a safe and effective diagnostic modality in the management of thyroid disease, especially for nodules that are difficult to palpate.

Glutathione content but not gamma glutamyl cysteine synthetase mRNA expression predicts cisplatin resistance in head and neck cancer cell lines

Abstract Purpose: To correlate cellular glutathione content and γ-glutamyl cysteine synthetase (γGCS) mRNA expression with cisplatin sensitivity in a panel of seven head and neck squamous cancer cell lines. Methods: Cisplatin IC50 was determined for each cell line using a sodium tetreazolium (XTT) assay. Cellular glutathione content was measured by using a previously reported enzymic method. γGCS mRNA expression was measured using an RNase protection assay. Results: Total cellular glutathione was an excellent predictor of cisplatin sensitivity in this series of cell lines. The IC50 for cisplatin in the cell line with the highest glutathione concentration was approximately 90 times higher than in the cell line with the lowest glutathione concentration. Regression analysis showed a highly statistically significant positive correlation between cisplatin IC50 and cellular glutathione (coefficient of determination R2=0.81, P=0.0012). Somewhat surprisingly, in contrast to previous studies in ovarian cancer, γGCS mRNA expression in these cell lines was not significantly predictive of either total cellular glutathione or cisplatin sensitivity (R2=0.005, P=0.84). As expected, treatment of resistant cell lines with buthionine sulfoximine resulted in decreased cellular glutathione and enhanced cisplatin sensitivity. Conclusions: Our results suggest that glutathione may be an important determinant of cisplatin sensitivity in clinical head and neck cancer. Since cisplatin is the most active chemotherapy drug for the treatment of this disease, this correlation may have important clinical relevance. The lack of correlation between glutathione level and γGCS expression suggests that salvage or alternate synthetic pathways may be critical in these cells.

Association between expression of glutathione-associated enzymes and response to platinum-based chemotherapy in head and neck cancer

We examined the correlation between response to platinum-based chemotherapy and expression of glutathione S-transferase (GST), gamma-GGT (both by immunohistochemistry) and gamma-GCS (by in situ hybridization) in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (CR, PR) for patients with low GST scores was 88% (21 of 24), while among the patients with high GST scores, the overall response rate was 19% (6 of 32, P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST score was 70% (7 of 10), while among the patients with high GST scores, the overall response rate was 8.7% (2 of 23), P < 0.001). In contrast, both gamma-GCS and gamma-GGT showed a range of expression in these samples, but there was no significant correlation with treatment response. We conclude that GST expression correlates well with response to platinum based chemotherapy in head and neck cancer.

BRONCHOGENIC CYSTS OF THE NECK IN ADULTS

Bronchogenic cysts are congenital sacs that result from maldevelopment of the primitive foregut. Although they occur predominantly in the chest, there are reports of lesions in extrathoracic locations. The majority of reported bronchogenic cysts located in the neck are found in the pediatric population; a review of the literature reveals few reports of bronchogenic cysts of the neck among adults. The diagnosis of a bronchogenic cyst relies on the histology and location of the lesion. Here, we review our experience in the diagnosis and management of 2 adult patients with pathologically proven bronchogenic cysts. Both patients presented with solitary neck masses that proved to be bronchogenic cysts on histologic examination. Our purpose is to define the histopathologic and clinical characteristics of bronchogenic cysts and discuss the features that distinguish them from other cervical cysts. In conclusion, congenital bronchogenic cysts can occur in the neck of adults and should be considered in the differential diagnosis of cystic cervical masses in adults, as well as children.

Safety and efficacy of hypofractionated stereotactic body reirradiation in head and neck cancer: Long-term follow-up of a large series.

The purpose of this study was to report long‐term outcomes for a large cohort of patients with head and neck squamous cell carcinoma (HNSCC) who underwent stereotactic body radiotherapy (SBRT) reirradiation.

Tamoxifen therapy for Riedel's thyroiditis.

INTRODUCTION Riedel’s thyroiditis is an extremely rare condition. Although it is thought to be a benign condition, it can mimic carcinoma, and therefore an accurate diagnosis is necessary. With any patient who presents with a “woody” lump in the neck and a complaint of progressive pressure symptoms, Riedel’s thyroiditis should be in the differential diagnosis. We present a case of Riedel’s thyroiditis that originally underwent a tracheotomy to secure the airway and obtained tissue for a diagnosis. The patient was started on tamoxifen therapy postoperatively and had a complete remission of Riedel’s, thus enabling us to decannulate the patient.

Facial nerve hemangioma: A rare case involving the vertical segment

This case report and literature review reports on a rare case of facial nerve hemangioma (FNH) involving the vertical facial nerve (FN) segment, and discusses the clinical presentation, imaging, pathogenesis, and management of these rare lesions. A 53‐year‐old male presented with a 10‐year history of right hemifacial twitching and progressive facial paresis (House‐Brackmann grading score V/VI). The computed tomography and magnetic resonance imaging studies confirmed an expansile lesion along the vertical FN segment. Excision and histopathologic examination demonstrated FNH. FNHs involving the vertical FN segment are extremely rare. Despite being rare lesions, we believe that familiarity with the presentation and management of FNHs are imperative. Laryngoscope, 2012

A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

BackgroundChemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown.MethodsAttrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets) are the main outcome measures reported.ResultsThere was a high rate of dropout (51%) from the study, and the rates were significantly higher among smokers (64%) than non-smokers (36%). Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout) and non-smokers (18% dropout). Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%), but was associated with the lowest rate of dropout among non-smokers (4%).ConclusionsIn a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials.Trial registration numberISRCTN70410203