Faculty Bibliography

Solid ectopic cervical thymus is an extremely uncommon etiology of a neck mass in an infant. It occurs in the line of descent of the thymus from the angle of the mandible to the superior mediastinum. Nine cases of ectopic cervical thymus in infants have been reported in the literature. Only two of nine cases were solid, the remaining seven were thymic cysts. A preoperative diagnosis is seldom considered and is often misdiagnosed as a possible malignancy or a lymph node. We present a case of a 2-month-old infant with an asymptomatic enlarging right neck mass. Patient underwent complete excision of the mass.

Five postlingually deaf patients (age range 28-58 years) with multichannel cochlear implants were examined with single photon emission tomography (SPECT) (triple-head rotating gamma camera). Changes in the regional cerebral blood flow (rCBF) after intravenous administration of technetium-99m ethyl cysteinate dimer (Tc-99m ECD) were assessed through a stimulation paradigm, consisting of: i) click stimuli (75 dB SPL) in the ear that was to be implanted, 2 weeks before surgery; ii) stimulation with the same click, one month after initial fitting; iii) stimulation with hearing sequential Spanish sentences one month after initial fitting. The results showed a significant increase in the rCBF in the primary left auditory area and in the right auditory cortex, in conditions ii) and iii). The rCBF also showed a significant asymmetrical increase in the frontal lobes when the patient was hearing sequential sentences (condition iii)) with asymmetrical distribution among patients. These results are discussed, principally the correlation between speech discrimination scores and the rCBF distribution in the frontal and temporal lobes.

The products of the Ha-, Ki-, and N-ras proto-oncogenes comprise a family of 21 kDa guanine nucleotide-binding proteins which play a crucial role in growth factor signal transduction and in the control of cellular proliferation and differentiation. Activating mutations in the ras oncogenes occur in a wide variety of human tumors. Ras proteins undergo a series of posttranslational processing events. The first modification is addition of the 15-carbon isoprene, farnesyl, to a Cys residue near the carboxy-terminus of Ras. Prenylation allows the Ras oncoprotein to localize to the plasma membrane where it can initiate downstream signalling events leading to cellular transformation. Inhibitors of the enzyme which catalyzes this step, farnesyl protein transferase (FPT), are a potential class of novel anticancer drugs which interfere with Ras function. SCH 59228 is a tricyclic FPT inhibitor which inhibits the farnesylation of purified Ha-Ras with an IC50 of 95 nM and blocks the processing of Ha-Ras in Cos cells with an IC50 of 0.6 microM. SCH 59228 has favorable pharmacokinetic properties upon oral dosing in nude mice. The in vivo efficacy of SCH 59228 was evaluated using a panel of tumor models grown in nude mice. These included several rodent fibroblast lines expressing mutationally-activated (val12) forms of the Ha-Ras oncogene. In some cases, these proteins contain their native C-terminal sequence (CVLS) which directs farnesylation. In one model, the C-terminal sequence was altered to CVLL, making the expressed protein a substrate for a distinct prenyl transferase, geranylgeranyl protein transferase-1. When dosed orally at 10 and 50 mg/kg (four times a day, 7 days a week) SCH 59228 significantly inhibited tumor growth of cells expressing farnesylated Ha-Ras in a dose-dependent manner; over 90% growth inhibition was observed at the 50 mg/kg dose. Tumor growth of cells expressing the geranylgeranylated form of Ha-Ras was less potently inhibited. Growth of tumors derived from a rodent fibroblast line expressing activated Ki-Ras containing its native C-terminal sequence (CVIM), which preferentially directs farnesylation, was also inhibited by SCH 59228. Inhibition in the Ki-Ras model was less than that observed in the Ha-Ras model. In contrast, tumors derived from cells transformed with the mos oncogene were not significantly inhibited even at the highest dose level. SCH 59228 also significantly and dose-dependently inhibited the growth of human colon adenocarcinoma DLD-1 xenografts (which express activated Ki-ras). These results indicate that SCH 59228 possesses in vivo antitumor activity upon oral dosing in tumor models expressing activated ras oncogenes. This is the first report of oral antitumor activity with an FPT inhibitor. These results are discussed in light of recent observations on alternative prenylation of some Ras isoforms.

Several altered fractionation schemes have evolved to exploit different aspects of head and neck cancer growth kinetics and normal tissue repair. Hyperfractionation schedules exploit the differential repair abilities of tumor and normal tissue, whereas accelerated fractionation regimens minimize the time of tumor repopulation. Significant clinical data have accumulated that indicate an improvement between 15% and 20% in locoregional control from altered fractionation. Preliminary analysis of a randomized Radiation Therapy Oncology Group trial testing four fractionation schemes confirms the benefit of one altered fractionation approach. Several promising concurrent chemoradiation treatments involving altered fractionation have been reported. Future trials will determine whether the addition of chemotherapy to altered fractionation schemes is warranted in light of the factor of added toxicity.

Phonation after partial laryngeal ablative surgery has not often been examined. Videolaryngostroboscopic recordings made after vertical partial laryngectomy (VPL) were retrospectively reviewed and correlated with patient historical and operative factors. Among VPL patients (n = 42), the most common site of vibration during phonation was the contralateral false vocal fold (17/42 patients or 40.5%), followed by the contralateral arytenoid mucosa (10/42 or 23.8%) and the contralateral true vocal fold (8/42 patients or 19.0%). There was no overall difference in vocal quality judgment with respect to site of vibration (ANOVA, p = .373). Vocal quality scores were similar with use of the pyriform mucosal flap versus other reconstructive methods (Student's t-test, p = .568). This study highlights the fact that reconstruction of a new vibratory source after VPL is important for voice production. Because VPL patients infrequently demonstrated true vocal fold vibration, alternative sites (ie, false vocal fold, arytenoid mucosa) must be considered as new phonatory sources after VPL.

A cohort of lower socioeconomic-economic children who experienced multi and prolonged episodes of otitis media during their first year of life and followed for 9 years showed that all of the children had poorer performance in linguistic tasks than did the control group. Differences were found in all of the OM + children at all ages. The effect of the otitis media and its accompanying hearing loss was noted in eight measures throughout the 9-year period of observation.