p16 mutation frequency and clinical correlation in head and neck cancer.

The tumor suppressor gene p16, when altered, has been shown to play a role in oncogenesis in many different tumor types including head and neck cancer. The goal of this study was to analyse alterations to p16 in squamous cell carcinoma (SCC) of the head and neck and to correlate these with clinical outcome. RNA was isolated from 26 SCC head and neck tumors and from 24 matched controls. A reverse transcription polymerase chain reaction was utilized to generate p16 cDNA, which was sequenced and analysed for alterations. In the 26 patient group 58% of the tumors had a p16 alteration, which were characterized by: 8 deletions, 1 insertion/deletion, 4 point mutations and 2 with no p16 expression. In 24 matched normal tissue samples there were no p16 alterations. Those patients with p16 alterations appear to have survival rates comparable to those without p16 alterations, although patients with p16 alterations appear to have more recurrences.

Tissue-conserving surgery for prognosis, treatment, and function preservation.

OBJECTIVES: To describe an approach based on initial tissue-conserving surgery used to obtain histologically determined prognostic information that has therapeutic implications and the potential to enhance preservation of function. STUDY DESIGN: Analysis of a group of patients with head and neck cancer treated initially with tissue-conserving surgery based on Mohs' histographic sectioning and selected neck dissection to derive histologically determined prognostic information with therapeutic implications and preservation in function. METHODS: This study is primarily based on an analysis of patients from January 1, 1989, through June 4, 1996 assigned to a protocol evaluating resection of oral cavity squamous cell cancer with margin control using Mohs' histographic technique and/or a group of patients with neck assessment of NO on clinical examination who are undergoing supraomohyoid neck dissections. RESULTS: Thirty-three primary tumor resections were performed using the Mohs' technique, and 54% required two or more Mohs' sections before clear histologic margins were obtained following resection based on clinically determined negative margins. There were 44 patients who underwent unilateral or bilateral supraomohyoid neck dissections, and 33% had occult, histologically positive nodes. When compared with the disease of the neck specimens, a preoperative computed tomography scan had a sensitivity of 25%, a specificity of 77%, and an accuracy of 63%. CONCLUSIONS: This report describes the effectiveness of Mohs' histographic sectioning and selective neck dissection as a means of determining prognostic information that can be used to develop a focused and cost-effective treatment program that, along with contemporary reconstructive techniques, provides a potential enhancement of function preservation.

Laryngeal carcinoma nodal metastases and their management.

Each of the three embryologically distinct portions of the larynx has a characteristic lymphatic drainage pattern. One section of this article describes these drainage patterns, along with clinical examples. Traditional and contemporary imaging techniques for the neck are included in a second section, and the final section describes the authors' preferences for treatment of the neck with the rationale for this approach.

One-stage reconstruction of partial laryngopharyngeal defects.

Advanced-stage lesions of the hypopharynx or tongue base often involve the larynx. The difficulty of reconstructing large partial laryngopharyngeal defects can result in total laryngectomy being performed to avoid the assumed problems with aspiration. This article describes the first reported experience using the pectoralis musculocutaneous flap for primary one-stage reconstruction of laryngopharyngeal defects following resection of advanced-stage lesions, to reconstruct both the laryngeal and the pharyngeal components of the defect. In this group of 21 patients, there were 16 with hypopharyngeal and 5 with tongue base cancers. Two had received prior treatment, and all received some form of postoperative radiotherapy and/or chemotherapy. Six patients experienced complications, including two fistulae, three wound infections, two myocardial infarctions, and one colon perforation. There were no instances of stenosis of the reconstructed segment. The length of hospitalization ranged from 9 to 60 days, the average being 17 days. Forty-seven percent (21) of the patients were not tolerating an oral diet at the time of discharge. However, 15 patients (71%) ultimately were eating by mouth, with 13 (62%) achieving an oral intake of liquids and solids. This analysis supports the hypothesis that the pectoralis major musculocutaneous flap is an effective one-stage primary reconstruction technique for laryngopharyngeal defects in patients either who have received prior therapy or who will receive postoperative therapy.

Microcystic adnexal carcinoma: management options based on long-term follow-up.

Microcystic adnexal carcinoma (MAC), a recently described neoplasm that frequently affects the head and neck, presents a confusing problem for the clinician due to its unusual behavior. The individual cells have a bland microscopic appearance, and there is a predilection for neural invasion. Four cases of MAC are reported. All four cases demonstrate the difficulty with pathologic diagnosis. Follow-up of as long as 33 years begins to delineate the protracted nature of MAC. In addition, this paper includes the first report of a case of lymph node metastasis. Although resection may result in a significant defect, negative margins may not be achieved. Despite this, the defect can heal, as demonstrated by the cases described. In addition, MAC may recur many years later, irrespective of the status of the margins at the time of surgery. Given these unusual characteristics and the slowly progressive nature of MAC, strong consideration must be given to less radical surgical procedures, with close follow-up for grossly recurrent disease.

Timolol-induced up-regulation of polymorphonuclear leukocyte beta 2-adrenergic receptors in the elderly.

Drug-induced up-regulation of beta-adrenergic receptors is impaired in the brains of aged rats but not in myocardia. To investigate age-related changes in receptor regulation in human beings, young (24 to 35 years of age) and elderly (62 to 78 years of age) healthy volunteers were treated with the beta-adrenergic receptor blocking agent timolol maleate (10 mg b.i.d.) for 8 days. Baseline densities of beta 2-adrenergic receptors on polymorphonuclear leukocyte (PMNL) membranes and heart rates were the same in the two age groups. However, systolic blood pressures were higher in the elderly subjects. Administration of timolol produced similar plasma levels in the two groups. In response to timolol, the density of PMNL beta-adrenergic receptors increased at a similar rate and to the same extent (threefold) in both age groups. Likewise, hemodynamic changes were not related to age. These results suggest that up-regulation of peripheral beta 2-adrenergic receptors in human beings is not impaired with aging.

Comparison between the effects of aging on antagonist and agonist interactions with beta-adrenergic receptors on human mononuclear and polymorphonuclear leukocyte membranes.

Age-related differences in the binding properties of beta-adrenergic receptors on lymphocyte membranes isolated from healthy individuals have been reported. The purpose of the present studies was to determine whether or not beta receptors on polymorphonuclear leukocyte (PMN) membranes showed similar age-related changes. Plasma Percoll gradients were used to isolate PMN and mononuclear leukocyte (MN) cells from blood drawn in the supine position from young (25-34 years) and elderly (60-76 years) healthy volunteers. Both blood pressures and plasma norepinephrine levels were significantly elevated in the elderly subjects. Saturation analysis with [125I]-(-) iodopindolol (IPIN) showed a 2.5-fold higher density of beta 2 receptors on the MN, but not PMN, membranes from the elderly. Neither the affinities of the receptor for IPIN or the agonist isoproterenol, nor the GTP-induced shift in agonist affinity, differed with subject age in either cell type. These results suggest that subpopulations of MN cells on which beta-adrenergic receptors are localized may increase in the elderly and that it is important to measure receptor properties on a more homogeneous leukocyte population such as PMN cells or subpopulations of MN cells as a function of aging.

Dopamine, acting through D-2 receptors, inhibits rat striatal adenylate cyclase by a GTP-dependent process.

This report demonstrates that the D-2 dopamine receptors that are present in rat striatum can directly inhibit the activity of adenylate cyclase in a GTP-dependent manner. N-n-propylnorapomorphine evoked a more pronounced inhibition than did dopamine. However, in the presence of the D-1-selective antagonist, SCH 23390, dopamine was also observed to inhibit the enzyme. Forskolin facilitated the detection of D-2 receptor-mediated inhibition by markedly stimulating striatal adenylate cyclase activity. The inhibition was antagonized in a dose-dependent manner by the D-2 receptor antagonist spiperone (Ki value = 70 pM) and was absolutely dependent on the presence of both GTP and sodium ions. Inhibition produced via D-2 receptors was additive with that produced via opiate or adenosine A1 receptors. The nonhydrolyzable GTP analogue, 5'-guanylylimidodiphosphate [Gpp(NH)p], did not substitute for GTP in promoting the D-2 receptor-mediated inhibition. It thus appears that D-2 receptors mediate adenylate cyclase inhibition by processes that have been observed for other neurotransmitters in the striatum and elsewhere. In addition, Gpp(NH)p displayed a Ca2+/calmodulin dependency for its inhibitory effects that was not shared by receptor-mediated, GTP-dependent inhibition.