Faculty Bibliography

We report on the response of medically refractory neuropathic trigeminal pain in three patients to intravenous administration of a combination of the kappa-partial agonist opioid nalbuphine and the opioid antagonist naloxone. Each of the three patients had developed a painful peripheral neuropathy as a complication of chemical or mechanical injury to the trigeminal nerve. Each patient had been tried on a number of analgesics, including mu-opioids, and had not gained relief or was not able to tolerate side effects of the medications. Pain intensity was measured for 3 h following drug administration using a 10 cm visual analog scale. All three patients reported marked decrease in pain following administration of the nalbuphine and naloxone combination. These findings suggest a novel approach to the management for neuropathic pain.

The molecular methodologies used in our laboratories have allowed us to define a group of Nocardia isolates from clinical samples which resemble the type strain of Nocardia veterana. Three patient isolates and the type strain of N. veterana gave identical and distinctive restriction fragment length polymorphisms (RFLPs) for an amplified portion of the 16S rRNA gene. These three isolates and the N. veterana type strain also gave identical RFLPs for an amplified portion of the 65-kDa heat shock protein gene, but this pattern was identical to that obtained for the Nocardia nova type strain. Sequence analysis of both a 1,359-bp region of the 16S rRNA gene and a 441-bp region of the heat shock protein gene of the patient isolates showed 100% identities with the same regions of the N. veterana type strain. DNA-DNA hybridization of the DNA of one of the patient isolates with the DNA of the N. veterana type strain showed a relative binding ratio of 82%, with 0% divergence, confirming that the isolate was N. veterana. Biochemical and susceptibility testing showed no significant differences among the patient isolates and the N. veterana type strain. Significantly, the results of antimicrobial susceptibility testing obtained for our isolates were similar to those obtained for N. nova, indicating that susceptibility testing alone cannot discriminate between these species. We present two case studies which show that N. veterana is a causative agent of pulmonary disease in immunocompromised patients residing in North America. We also describe difficulties encountered in using 16S rRNA gene sequences alone for discrimination of N. veterana from the related species Nocardia africana and N. nova because of the very high degree of 16S rRNA gene similarity among them.

Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disorder found in men and women of all ages, races, and geographic regions. There are three forms of the lesions (minor, major, and herpetiform), with major aphthous ulcers causing significant pain and potential for scarring. In HIV-infected individuals, these ulcers occur more frequently, last longer, and produce more painful symptoms than in immunocompetent persons. In addition, they may be associated with similar ulcerations involving the esophagus, rectum, anus, and genitals. The diagnosis of HIV-induced RAS requires a careful history of the condition, and a thorough extra- and intra-oral examination. Oral mucosal biopsies are required for non-healing ulcers in order to exclude the possibility of deep fungal infections, viral infections, and neoplasms. The cause of the ulcers in HIV-positive persons has not been elucidated--local diseases, genetic, immunologic, and infectious factors all probably play a role. The goals of current treatments are to promote ulcer healing, to reduce ulcer duration and pain while maintaining nutritional intake, and to prevent or diminish the frequency of recurrence. Initial therapy for infrequent RAS recurrences includes over-the-counter topical protective and analgesic products. Initial therapy for frequent RAS outbreaks requires topical anesthetics, binding agents, and corticosteroids. Major RAS and non-healing minor or herpetiform RAS may require intralesional corticosteroids and systemic prednisone. Second-line immunomodulators for frequent and non-healing ulcers includes thalidomide and other immunomodulators.

Locoregional recurrence remains a major obstacle to achieving cure of locally advanced head and neck cancers despite maximal resection and postoperative external beam radiation therapy (EBRT). Locoregional failure occurs in 30% to 40% of high-risk resected head and neck cancer patients after standard postoperative EBRT. In an effort to overcome this problem, a number of strategies have been designed to enhance the effectiveness of radiation including concurrent postoperative chemoradiation, accelerated radiation schedules, incorporation of targeted biologic therapies, and improved radiation delivery techniques such as intensity modulated radiation and high-dose rate (HDR) intraoperative radiation therapy. Intraoperative radiation therapy (IORT) represents an important approach to improve outcome in head and neck cancer patients treated with definitive surgery. High-dose rate IORT is defined as the delivery of a single, large dose of radiation at the time of surgery when the tumor bed is exposed. In conjunction with EBRT, HDR-IORT offers several advantages including: (1) conformal delivery of a large dose of radiation while the tumor bed is precisely defined, minimizing the risk of a geographic miss; (2) potential for subsequent dose reduction of EBRT; (3) shortening overall treatment time; and (4) dose-escalation. Because mucositis represents the dose-limiting acute toxicity and xerostomia ranks as the most common long-term quality-of-life complaint, a reduction of the EBRT dose may provide an important benefit in reducing toxicity, especially when combined with the radioprotectant amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD). The purpose of this article is to review the rationale for integrating HDR-IORT with a reduced dose of postoperative EBRT combined with amifostine to improve locoregional control and quality of life outcomes in advanced-stage resected head and neck cancer patients.

Fanconi anemia is an autosomal recessive disorder characterized by congenital malformations, bone marrow failure, and the development of squamous cell carcinomas (SCCs) and other cancers. Recent clinicopathologic evidence has raised the possibility that an environmental factor such as human papillomavirus (HPV) may be involved in the pathogenesis of SCCs in Fanconi anemia patients. Given the high prevalence of p53 mutations in SCCs among the general population and the lack of p53 mutations in HPV-related carcinogenesis, we evaluated the role of HPV and p53 mutations and polymorphisms in SCC from Fanconi anemia patients. We used polymerase chain reaction (PCR) screening and real-time PCR to detect and quantify HPV DNA in DNA extracted from microdissected SCCs obtained from 24 Fanconi anemia patients (n = 25 SCCs; case subjects) and 50 age-, sex-, and tumor site-matched SCC patients without Fanconi anemia (n = 50 SCCs; control subjects). We PCR-amplified and sequenced exons 4-9 of the p53 gene from SCC DNA. We detected HPV DNA in 84% of the SCC specimens from the case subjects and in 36% of the SCC specimens from the control subjects (P<.001). The prevalence of p53 mutations in SCCs from the case subjects (0%, 0/25) was statistically significantly lower than that of SCCs from the control subjects (36%, 12/33; P<.001). A greater proportion of patients with Fanconi anemia and SCC were homozygous for Arg72, a p53 polymorphism that may be associated with increased risk for HPV-associated human malignancies, than an ethnically-matched cohort of Fanconi anemia patients without SCC (75% versus 51%; P =.05). These data suggest that Fanconi anemia is associated with increased susceptibility to HPV-induced carcinogenesis

Pathologic examination of an excisional biopsy specimen of a subepidermal nodule from the nasal tip of a 37-year-old black man demonstrated papillae covered by eosinophilic columnar epithelial cells, suggesting cylindric cell papilloma or well-differentiated papillary adenocarcinoma of nasal mucosa. The patient did not submit to further investigation of the sinonasal tract but sought attention 15 months later because of local recurrence of the lesion. A protuberant, 3-cm, cystic nodule of the subcutis over the left nasal ala and tip was excised completely and found to have characteristics of hidradenoma papilliferum, an apocrine gland neoplasm most commonly occurring in the anogenital skin of white women. This case demonstrates how easily an apocrine neoplasm arising near a mucocutaneous junction can be confused with a mucosal tumor, potentially leading to inappropriate treatment

BACKGROUND: Distraction osteogenesis is an established technique for the lengthening of long bones and correction of selected craniofacial deformities. Regenerate osteoid bone matrix formed during the distraction phase is malleable and can recreate the three-dimensional form of native bones. Animal experiments and early clinical experience have confirmed that distraction osteogenesis can be used for the reconstruction of segmental bony defects. Herein we discuss the principles of distraction osteogenesis in reference to reconstruction of segmental bony defects and report its clinical application of the mandible continuity defects. PATIENTS AND METHODS: Four patients (age, 7-83 years) with critical segmental mandibular defects (range, 3.5 cm-6.5 cm), resulting from ablative oncologic head and neck surgery underwent primary mandibular reconstruction by transport distraction osteogenesis. Two defects were at the angle and body region, one at the body, and the other at the parasymphysis and body region. Synthes Titanium Multi-vector and Leibinger Multi-guide distractors in bifocal (n = 2) and trifocal (n = 2) architecture were used after the stabilization of the segmental continuity defect using a defect-bridging mandibular reconstruction plate. Osteodistraction was carried out at a rate of 1 mm per day, with once or twice a day rhythm, after a 1-week latency period. The consolidation period was equal to the period of distraction. RESULTS: All patients tolerated the distraction procedure. Satisfactory bone formation was observed in two patients, and partial bone formation was seen in one patient. Treatment failure was encountered in one patient who had a second oral cavity primary tumor observed during the consolidation period, requiring interruption of the treatment sequence. CONCLUSIONS: Mandibular reconstruction with distraction osteogenesis is a potentially useful technique in selected patients with segmental mandibular continuity defects after ablative head and neck cancer surgery

OBJECTIVES/HYPOTHESIS: Laser-assisted uvulopalatoplasty (LAUP) is a widely accepted procedure for the management of snoring, but its role in the treatment of obstructive sleep apnea syndrome is currently unclear. The objective of the study was to evaluate the role of LAUP in treating moderate and severe obstructive sleep apnea syndrome. STUDY DESIGN: Retrospective review of a surgical treatment protocol for obstructive sleep apnea syndrome. METHODS: Between October 1993 and January 1999, 80 patients with moderate or severe obstructive sleep apnea syndrome and a significant component of retropalatal obstruction were treated with surgery at the Department of Otolaryngology at Northwestern University Medical School (Chicago, IL). Surgery consisted of LAUP with tonsillectomy (if tonsils were present) with the patient under general anesthesia or LAUP alone with local anesthesia (if the tonsils were absent). No patients received traditional uvulopalatopharyngoplasty. Sixty-four of the 80 patients underwent both preoperative and postoperative polysomnograms. Surgical 'response' was defined as a 50% decrease in the apnea-hypopnea index (AHI) (the total number of apneic and hypopneic events per hour of sleep); surgical 'cure' was defined as a 50% decrease in AHI and a final AHI of less than 20. RESULTS: The surgical response rate was 59% (38 of 64 patients), and the surgical cure rate was 39% (25 of 64 patients). Twelve patients (18.8%) had a higher AHI after surgery. The AHI (mean +/- SD) changed significantly from 51.4 +/- 30.9 preoperatively to 26.3 +/- 20.8 on postoperative polysomnogram (P = 7.0 x 10-9). Laser-assisted uvulopalatoplasty alone was performed in 33 patients with a response rate of 61% and a cure rate of 42%. Laser-assisted uvulopalatoplasty with tonsillectomy was performed in 31 patients with a response rate of 58% and a cure rate of 35%. The overall incidence of nasopharyngeal insufficiency was 0%. CONCLUSION: The results of the study suggested that LAUP with adjunctive tonsillectomy is an effective treatment for patients with obstructive sleep apnea syndrome and retropalatal obstruction with a lower complication rate than standard surgical therapy (uvulopalatopharyngoplasty)