William B. Armstrong

Carotid body tumors: A review of 30 patients with 46 tumors

Minimal morbidity occurs with resection of most carotid body tumors (CBT). With larger tumors significant injury to the cranial nerves has been reported. In order to assess the operative sequelae rate, 30 patients with CBT were reviewed. Sixteen patients either presented with bilateral carotid body tumors or had previously undergone a resection of the contralateral carotid body tumors, for a total carotid body tumor count of 46. Sixteen patients demonstrated a familial pattern while 14 were nonfamilial. Within the familial group, 14 of 16 presented with multiple paragangliomas as compared to 6 of 14 in the nonfamilial group. Tumor size ranged from 0.8 to 12 cm. Vascular replacement occurred in 2 of 20 patients with tumors <5.0 cm, compared with 5 of 9 with tumors >5.0 cm. Four patients lost cranial nerves with the resection: superior laryngeal nerve (SLN), 4; cranial nerve X, 1; cranial nerve XII, 1. Ten patients developed baroreceptor failure secondary to bilateral loss of carotid sinus function. First‐bite pain occurred in 10 of 25 operative patients. Cranial nerve loss can be minimal with resection of carotid body tumors, however, baroreceptor failure and first‐bite pain are postoperative sequelae that are often disregarded in the postoperative period.

In Vivo Optical Coherence Tomography of the Human Larynx: Normative and Benign Pathology in 82 Patients

Objectives: Optical coherence tomography (OCT) is an emerging imaging modality that combines low‐coherence light with interferometry to produce cross‐sectional images of tissue with resolution about 10 μm. Patients undergoing surgical head and neck endoscopy were examined using a fiberoptic OCT imaging probe to study and characterize microstructural anatomy and features of the larynx and benign laryngeal pathology in vivo.

Optical coherence tomography of laryngeal cancer.

Objectives: Optical coherence tomography (OCT) is a high‐resolution optical imaging technique that produces cross‐sectional images of living tissues using light in a manner similar to ultrasound. This prospective study evaluated the ability of OCT to identify the characteristics of laryngeal cancer and measure changes in the basement membrane, tissue microstructure, and the transition zone at the edge of tumors.

Kimura's Disease: Two Case Reports and a Literature Review

Kimuras disease (KD) is an allergic, inflammatory disorder of unknown cause. The typical presentation is in a young Oriental male with nontender subcutaneous swellings in the head and neck region, lymphadenopathy, peripheral eosinophilia, and elevated serum IgE. Many patients with KD also develop renal involvement. Treatment options range from conservative observation for asymptomatic patients to surgical excision, steroid therapy, and radiotherapy for symptomatic patients. Two cases of KD are presented. These emphasize not only the variability of disease presentation, but also the pitfalls of therapy leading to frequent recurrences. The literature is reviewed, summarizing patient presentation, differential diagnosis, current theories on causation, and therapy. A treatment protocol is also proposed.

Lemierre syndrome: a pediatric case series and review of literature.

BACKGROUND Lemierre syndrome is a rare disease of the head and neck often affecting adolescents and young adults. Classically, infection begins in the oropharynx with thrombosis of the tonsillar veins followed by involvement of the parapharyngeal space and the internal jugular vein. Septicemia and pulmonary lesions develop as infection spreads via septic emboli. Although a rare entity in modern times, Lemierre syndrome remains a disease of considerable morbidity and potential mortality. METHODS This was a retrospective review of 3 cases and associated literature. RESULTS A common 1- to 2-week history of fever, sore throat, neck pain, and fatigue was observed in all patients. Patient 1 developed right facial swelling, neck tenderness, trismus, and tonsillar exudate. Patient 2 displayed right tonsillar erythema and enlargement with right neck tenderness. Patient 3 revealed bilateral tonsillar enlargement with exudate and left neck tenderness. Subsequent studies included blood cultures and computed tomography, after which empiric antibiotic therapy was started. Patient 1 underwent drainage of a right peritonsillar abscess, right pressure equalization tube placement, and ligation of the right external jugular vein. He subsequently developed subdural empyemas, cavernous sinus thrombosis, and carotid artery narrowing and required 9 weeks of antibiotic therapy. Patients 2 and 3 developed pulmonary lesions and received 6 weeks of antibiotic therapy. Timing was crucial in all cases. CONCLUSIONS Lemierre syndrome is a rare but severe opportunistic infection with poor prognostic outcomes if left untreated. Early diagnosis and treatment is essential. Aggressive antibiotic therapy coupled with surgical intervention, when necessary, provides excellent outcomes.

Development of the Bowman-Birk inhibitor for oral cancer chemoprevention and analysis of Neu immunohistochemical staining intensity with Bowman-Birk inhibitor concentrate treatment.

Objectives/Hypothesis: Cancer chemoprevention is a rapidly evolving approach to reverse or inhibit carcinogenesis, and there is active interest in development of effective chemopreventive agents against head and neck cancers. The retinoids are archetypal chemopreventive agents for oral premalignant lesions. They have significant clinical effect, but widespread use is limited by significant clinical toxicity. The Bowman‐Birk Inhibitor is one of several nontoxic compounds exhibiting both potent anticarcinogenic activity and minimal toxicity. The purposes of the study were to summarize the preclinical and clinical development of Bowman‐Birk Inhibitor and a Bowman‐Birk Inhibitor concentrate against oral premalignant lesions and to evaluate Neu immunohistochemical staining intensity for lesions and simultaneously obtained biopsy specimens of normal‐appearing mucosa from the Phase IIa Bowman‐Birk Inhibitor concentrate oral leukoplakia chemoprevention trial. Study Design: Part I is a selected literature review. Part II is a retrospective analysis of pathological specimens prospectively obtained from the Phase IIa clinical trial of Bowman‐Birk Inhibitor concentrate. Methods: Thirty‐two sets of biopsy specimens from lesions and uninvolved oral mucosa before and after treatment with Bowman‐Birk Inhibitor concentrate in doses ranging from 200 to 1066 chymotrypsin inhibitory units were examined in blinded fashion for Neu immunohistochemical staining intensity using the 3B‐5 monoclonal antibody. Staining intensity scores among the lesion and control biopsy specimens before and after Bowman‐Birk Inhibitor concentrate treatment were analyzed and compared with previously obtained values for serum Neu, oral mucosal cell Neu, protease activity, and clinical response to treatment. Results: Mean Neu staining score was significantly higher in lesions compared with uninvolved mucosa (P <.001). Pretreatment staining scores for biopsy specimens of lesions and control biopsy specimens of normal‐appearing tissues were correlated (Spearman correlation coefficient [r] = 0.375, P = .045), but no correlation between lesion and control biopsy specimen scores was evident after treatment. The change in Neu staining score with Bowman‐Birk Inhibitor concentrate treatment in control site biopsy specimens demonstrated an inverse relationship of change in lesion area with Bowman‐Birk Inhibitor concentrate treatment (Spearman r = −0.493, P <.007). Conclusion: Bowman‐Birk Inhibitor concentrate shows promise to become an effective nontoxic chemopreventive agent based on results of extensive preclinical studies, and Phase I and Phase IIa clinical trials. Bowman‐Birk Inhibitor concentrate has dose‐related clinical activity against oral leukoplakia and modulates levels of Neu and protease activity. The current investigation identified increased Neu staining intensity in hyperplastic lesions compared with simultaneously obtained biopsy specimens of normal‐appearing mucosa both before and after Bowman‐Birk Inhibitor concentrate treatment. This finding supports prior observations that increased Neu expression is present in a subset of oral premalignant lesions and head and neck cancers. The trend of increased Neu staining score in control biopsy tissues of subjects exhibiting decreased lesion area following Bowman‐Birk Inhibitor concentrate treatment raises questions about the mechanisms of Bowman‐Birk Inhibitor concentrate action. One possible explanation is that Bowman‐Birk Inhibitor stabilizes the extracellular domain of Neu, thereby preventing receptor truncation and internalization. Further study of modulation of Neu and protease activity by Bowman‐Birk Inhibitor concentrate treatment may provide insights into the role of proteases and protease inhibitors in oral premalignant lesions and the mechanisms underlying Bowman‐Birk Inhibitor concentrate effects. A Phase IIb randomized, placebo‐controlled clinical trial to determine the clinical effectiveness of Bowman‐Birk Inhibitor concentrate and further evaluate these candidate biomarkers is under way.

Diagnosis and Management of External Penetrating Cervical Esophageal Injuries

External penetrating injuries of the esophagus are more likely to cause serious morbidity and even mortality than those involving the pharynx. However, the cervical esophagus is extrathoracic in location, and controversy exists regarding the diagnosis and surgical management of penetrating injuries at this level. A retrospective review of 23 such injuries showed that contrast esophagography had only a 62% success rate in identification of cervical esophageal violations, compared to 100% for rigid esophagoscopy. Even large penetrations were successfully treated with limited debridement, primary repair when possible, muscle interposition flaps to separate common injuries of the tracheal wall, and, most important, external drainage of the adjacent neck spaces. Esophageal stricture occurred only when complex esophageal diversion procedures were performed, either as an unnecessary primary operation, or as a lifesaving secondary operation necessitated by infectious complications caused by delayed diagnosis and treatment of the esophageal violation. Penetrating injuries of the cervical esophagus can therefore be managed more as a pharyngeal injury if diagnosis and appropriate surgical treatment occur in a timely fashion.

Transoral laser microsurgery for laryngeal cancer: a primer and review of laser dosimetry.

Transoral laser microsurgery (TLM) is an emerging technique for the management of laryngeal and other head and neck malignancies. It is increasingly being used in place of traditional open surgery because of lower morbidity and improved organ preservation. Since the surgery is performed from the inside working outward as opposed to working from the outside in, there is less damage to the supporting structures that lie external to the tumor. Coupling the laser to a micromanipulator and a microscope allows precise tissue cutting and hemostasis; thereby improving visualization and precise ablation. The basic approach and principles of performing TLM, the devices currently in use, and the associated dosimetry parameters will be discussed. The benefits of using TLM over conventional surgery, common complications and the different settings used depending on the location of the tumor will also be discussed. Although the CO2 laser is the most versatile and the best-suited laser for TLM applications, a variety of lasers and different parameters are used in the treatment of laryngeal cancer. Improved instrumentation has lead to an increased utilization of TLM by head and neck cancer surgeons and has resulted in improved outcomes. Laser energy levels and spot size are adjusted to vary the precision of cutting and amount of hemostasis obtained.

Functional hemitongue reconstruction with the microvascular ulnar forearm flap.

Thirteen patients with squamous cell carcinoma of the tongue underwent full-thickness longitudinal resection of the hemitongue and immediate microvascular reconstruction using a large, contoured ulnar forearm flap. Six of the 13 patients had a composite resection for which an additional vascularized iliac crest graft was used to reconstruct the mandible and to provide support to the overlying contoured flap. To increase tongue mobility, the skin flap was designed for independent reconstruction of the hemitongue and the floor of mouth. Twelve patients were evaluated for swallowing and speech, including dietary assessment, cineradiography, and voice spectrographic analysis. Contrast cineradiography was performed to determine oral tongue mobility during the first phase of swallow. Nine patients with a narrow reconstructed tongue root and a large surface area in the floor of the mouth had good tongue mobility, allowing them to transfer food dynamically from the mouth into the pharynx for swallowing. The remaining three patients, who had a wide tongue root and an ill-defined floor of the mouth, had decreased tongue mobility and poor oral transport. The functional outcome of swallowing and speech strongly correlated with the shape of the root of the tongue, the proximity of the reconstructed tongue to the palate, and the surface area of the floor of the mouth.

Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial

Oral premalignancy serves as an ideal model for study of chemopreventive agents. Although 13-cis-retinoic acid showed reversal of oral premalignancy, toxicity, and reversal of clinical response after cessation of therapy obviated its widespread use. A search for nontoxic agents with cancer preventive activity led us to evaluate Bowman Birk Inhibitor (BBI) formulated as BBI Concentrate (BBIC). We previously reported encouraging results in a phase IIa trial of BBIC in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. On the basis of these results, we undertook a randomized, placebo controlled phase IIb trial with patients receiving BBIC or placebo for 6 months, with assessment of clinical response and change in lesion area as primary end point and an intent-to-treat analysis. One hundred and thirty two subjects were randomized; and 89 subjects completed six months on study drug or placebo. Both placebo and BBIC showed a statistically significant decrease in mean lesion area of 17.1% and 20.6%, respectively, and partial or greater clinical responses of 30% and 28% respectively. No significant difference between placebo and study drug arms was observed. Histologic review, review of photographs of lesions, and comparison of serum neu protein and oral mucosal cell protease activity also did not show significant differences between study arms. Probable reasons for these negative results were considered, are discussed, and include a placebo with non-BBIC clinical activity and reduced pharmacokinetic availability of the second batch of BBIC. This experience should be a strong cautionary note to those considering “Green” chemoprevention. Cancer Prev Res; 6(5); 410–8. ©2013 AACR.