Faculty Bibliography

BACKGROUND: Given its rarity, varied histological presentation and often pseudosarcomatous appearance, nodular fasciitis is frequently misdiagnosed on pre-operative, intra-operative and final analyses. METHODS: Four cases of nodular fasciitis are reviewed. RESULTS: Physical and radiological findings were consistent with a parapharyngeal tumour, probably neurogenic, a level four neck mass suspicious for lymphoma; a sternoclavicular mass in a patient with a history of breast cancer suspicious for metastasis; and a cheek mass consistent with an accessory parotid tumour. Fine needle aspiration results were consistent with a neurogenic tumour in two patients and an undifferentiated malignancy in two patients. Frozen section examination most commonly included masses with spindle-type cells. The final diagnosis of nodular fasciitis was made only after permanent section and immunohistological analysis. CONCLUSIONS: In a patient with nonspecific results following investigation of a head or neck mass, nodular fasciitis should be considered. Use of appropriate immunohistochemical markers will aid in the final diagnosis

The standard treatment for locally advanced urothelial bladder carcinoma is radical cystectomy or chemoradiation. Sarcomatoid urothelial carcinoma, a rare tumour, is treated with radical cystectomy because the response to radiation therapy alone is poor in other sarcomas. We report a case of high-grade hyperinvasive urothelial bladder carcinoma with sarcomatoid differentiation. The patient refused cystectomy, and so a chemoradiation regimen was devised for her treatment. She completed the regimen and has since demonstrated a complete response to chemoradiation therapy clinically and pathologically by biopsy. The patient has therefore been able to attain a complete response while preserving a functional bladder

OBJECTIVE: We hypothesize that increasing regulation of human subject research has reduced the number of published reports of surgical innovation in otolaryngology. STUDY DESIGN: A systematic review of a predetermined subset of otolaryngology literature. METHODS: We randomly selected half of the articles published in 1988 and 2006 in three prominent journals. After identifying information was concealed, abstracts were classified independently by two authors into three groups: innovation, modification, or neither. Disagreements were resolved by a third author who read the entire article. Proportions were compared with chi(2) analysis. RESULTS: The proportion of articles classified as innovation or modification decreased significantly from 67 of 367 (18.3%) in 1988 to 59 of 548 (10.8%) in 2006 (P = 0.001). The elimination of radiology and pathology quiz cases yielded similar results: 11.1 percent vs 18.9 percent, P = 0.001. Innovation or modification in animal model research also decreased (0.9% vs 3.8%, P = 0.003). Overall, only 4 articles were actually classified as true innovation. CONCLUSIONS: The frequency of true innovation was low in both years, but articles that described surgical modifications decreased significantly over this 18-year period. One reason may be increased administrative barriers for clinical research approval. Although our analysis cannot determine cause and effect, it is an important finding that deserves further study.

OBJECTIVES: To pool and meta-analyze the reported outcomes in patients receiving radiotherapy for T2 glottic carcinoma with impaired vocal cord mobility. DATA SOURCES: A MEDLINE search and manual search were conducted to identify all studies published between January 1, 1950 and September 30, 2007, in English on the treatment of T2 glottic carcinoma. Search terms included laryngeal neoplasm, glottis, and glottic carcinoma. STUDY SELECTION: All studies of primary radiotherapy for T2 glottic carcinoma with explicit reporting of outcomes with regard to the presence or absence of vocal cord immobility were included in the meta-analysis. Studies with data reported elsewhere were excluded. DATA EXTRACTION: A meta-analysis using a fixed-effects model was conducted for outcome measures of local disease control, ultimate survival after salvage surgery, absolute survival, and disease-specific survival. Odds ratios (ORs), 95% confidence intervals (CIs), and tests for heterogeneity were reported. DATA SYNTHESIS: Thirty-five studies were identified, of which 21 met criteria for meta-analysis. All studies were retrospective. Comparison of 5-year local control of disease for lesions with impaired vocal cord mobility (T2b) vs those with normal vocal cord mobility (T2a) showed a statistically significant difference (OR, 1.83; 95% CI, 1.52-2.20; P < .001). Ultimate control after salvage surgery was reported in 7 studies, which also showed significantly better outcomes for T2a lesions over T2b lesions (OR, 1.90; 95% CI, 1.23-2.92; P = .005). CONCLUSIONS: This meta-analysis indicates that impaired vocal cord mobility has a negative impact on local disease control and ultimate disease control in patients receiving primary radiotherapy for the treatment of T2 glottic carcinoma. We recommend that the subdivision of glottic cancer to T2a and T2b be reviewed and considered by the American Joint Committee on Cancer for inclusion in the Cancer Staging Manual

In the inferior colliculus (IC), a brief period of acoustic conditioning can transiently enhance evoked discharge rate. The cellular basis of this phenomenon was assessed with whole cell current-clamp recordings in a gerbil IC brain slice preparation. The current needed to elicit a single action potential was first established for each neuron. A 5s synaptic stimulus train was delivered to the lateral lemniscus (LL), and followed immediately by the initial current pulse to assess a change in postsynaptic gain. The majority of IC neurons (66%) displayed an increase in current-evoked action potentials (Positive Gain). Despite the blockade of ionotropic glutamate receptors, this effect was correlated with membrane depolarization that occurred during the synaptic train. The postsynaptic mechanism for positive gain was examined by selective blockade of specific neurotransmitter receptors. Gain in action potentials was enhanced by antagonists of metabotropic glutamate, acetylcholine, GABA(A) and glycine receptors. In contrast, the gain was blocked or reduced by an antagonist to ionotropic serotonin receptors (5-HT(3)R). Blocking voltage-activated calcium channels with verapamil also reduced the effect. These results suggest that 5-HT(3)R activation, coupled with increased intracellular calcium, can transiently alter postsynaptic excitability in IC neurons

The endogenous peptide endothelin-1 (ET-1), originally identified as a potent vasoconstrictor, plays a role in a number of painful conditions. In this review article we discuss the mechanisms that are essential for local sensitization by subcutaneously administered ET-1, and report evidence of ET-1's ability to sensitize distant regions of the body, through the central nervous system and, likely, coupling through the spinal cord. In addition, we will review the latest information on the role of ET-1 in cancerous and non-cancerous conditions. Cancer pain has indeed been shown to be attenuated by antagonists of endothelin receptors, and ET-1 is known to be secreted by cancer cells of many different histologic types. Furthermore, a growing body of evidence links increased expression and secretion of ET-1 to the occurrence of non-cancer related pain syndromes, such as inflammatory and neuropathic pain syndromes.

OBJECTIVE: To determine what factors predispose patients with retrosternal goiters to median sternotomy. STUDY DESIGN: Retrospective review. METHODS: Analysis of a single surgeon experience with 113 substernal goiters operated upon during a 10-year period. RESULTS: 108 goiters were successfully removed through a cervical approach. Four patients required sternotomy, and it was concluded that one patient who did not receive sternotomy might have been better managed with sternotomy. Factors that led to sternotomy were malignancy, involvement of the posterior mediastinum, extensive substernal extension, and the presence of an ectopic nodule. The latter two were the most important factors. Revision surgery and tracheal compression did not influence the need for sternotomy. CONCLUSIONS: On the basis of preoperative imaging, it is possible to predict which patients with retrosternal goiters are likely to require median sternotomy. These factors are malignancy, extension into the posterior mediastinum, substernal extension inferior to the level of the aortic arch, and the lack of a solid attachment between the cervical and mediastinal components of the thyroid gland. Although previously reported, the latter factor has not received sufficient recognition in the management of retrosternal goiter.

We have previously described a novel conjugal DNA transfer process that occurs in Mycobacterium smegmatis. To identify donor genes required for transfer, we have performed a transposon mutagenesis screen; we report here that LpqM, a putative lipoprotein-metalloproteinase, is essential for efficient DNA transfer. Bioinformatic analyses predict that LpqM contains a signal peptide necessary for the protein's targeting to the cell envelope and a metal ion binding motif, the likely catalytic site for protease activity. Using targeted mutagenesis, we demonstrate that each of these motifs is necessary for DNA transfer and that LpqM is located in the cell envelope. The requirement for transfer is specific to the donor strain; an lpqM knockout mutant in the recipient is still proficient in transfer assays. The activity of LpqM is conserved among mycobacteria; homologues from both Mycobacterium tuberculosis and Mycobacterium avium can complement lpqM donor mutants, suggesting that the homologues recognize and process similar proteins. Lipoproteins constitute a significant proportion of the mycobacterial cell wall, but despite their abundance, very few have been assigned an activity. We discuss the potential role of LpqM in DNA transfer and the implications of the conservation of LpqM activity in M. tuberculosis.