Different cellular p16(INK4a) localisation may signal different survival outcomes in head and neck cancer.

BACKGROUND: Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status. METHODS: Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS). RESULTS: A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status. CONCLUSION: Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.

Chemoradiation for locally advanced squamous cell carcinoma of the head and neck for organ preservation and palliation.

OBJECTIVES: To measure the efficacy and toxic effects of our chemoradiotherapy regimen by means of response and survival in patients with advanced squamous cell carcinoma of the head and neck (HNSCC) for organ preservation in resectable disease or palliation in unresectable disease. DESIGN: All patients underwent evaluation by the multidisciplinary head and neck cancer team, with pathological diagnosis and staging. All patients underwent assessment for response to therapy using results of physical examination and radiologic imaging. Patients were followed up at 3-month intervals for a planned period of 5 years. SETTING: Academic center. PATIENTS: Thirty-eight previously untreated patients with newly diagnosed HNSCC were treated from June 1, 1996, through December 31, 1998, of whom 20 had resectable and 18 had unresectable tumors. INTERVENTION: Patients received intravenous cisplatin, 100 mg/m(2) for 1 hour on days 1 and 29; a 24-hour continuous infusion of fluorouracil, 1000 mg/m(2) on days 1 through 4 and 29 through 32; and radiation therapy, 150 rad twice daily for 12 days. The patients were given a 7- to 10-day break, and radiation therapy was restarted on day 29 for 12 additional days (total dose, 7200 rad). MAIN OUTCOME MEASURES: Complete, partial, and total response rates; disease-free survival; overall survival; and toxic effects. RESULTS: Toxic effects of treatment were moderately severe, including grades III to IV mucositis (89%), neutropenia (71%), and renal toxic effects (8%). In the 18 patients in the unresectable group, complete response in the 17 primary tumors and 15 cervical nodal metastases was achieved in 12 (71%) and 9 (60%), respectively; in the 20 patients undergoing organ preservation, complete response rates were 100% in the 23 primary tumors and 15 cervical nodal metastases. Complete response for all 38 patients was achieved in 31 (82%). In the unresectable group, the Kaplan-Meier relapse-free survival estimate is 56%, with follow-up from 29 to 45 months. In the organ preservation group, 75% of patients are alive without disease, and 8 have been followed up for 36 to 48 months. Of the 5 patients who have died, only 2 died of disease, with recurrences at 13.0 and 16.5 months. CONCLUSIONS: Chemoradiotherapy consisting of cisplatin, fluorouracil, and twice-daily external beam radiation is highly effective in achieving durable complete responses in patients with resectable HNSCC undergoing organ preservation and patients with unresectable HNSCC undergoing palliation. Toxic effects of this regimen were moderate to severe.

Reconstructive options for periocular defects.

Reconstruction of the periorbital area following skin cancer excision requires a thorough knowledge of orbital anatomy and eyelid function. Reconstructive procedures should maintain the function of periorbital structures while attempting to achieve optimal cosmesis. Generally, eyelid reconstruction can be considered in terms of the thickness and overall size of the defect. Both the anterior and posterior lamella should be restored, and at least one of these layers needs to be vascularized. The integrity of the canthal tendons should also be addressed. If severed, the tendons should be attached to bony landmarks in order to recreate the proper curvature of the eyelid against the globe. Finally, defects involving the lacrimal system should be assessed and properly reconstituted.

Effect of stenting after laryngotracheal reconstruction in a subglottic stenosis model.

OBJECTIVES: This study addresses the impact of stenting on early wound healing after laryngotracheal reconstruction (LTR) in a rabbit model with established subglottic stenosis. METHODS: Subglottic stenosis was created in 42 New Zealand white rabbits through a transoral, endoscopic technique. Three weeks later, endoscopy and axial CT were performed to document and grade the degree of stenosis. Subsequently, LTR was performed in all animals, with half of the animals receiving an intraluminal stent. Four rabbits from each group were euthanized on postoperative days 6, 9, 14, 21, and 28. Measurements of graft vascularization were obtained with a computerized image measurement program, and a comparison was made regarding the rate of vascularization. RESULTS: There was a statistically significant increase in the rate of vascularization in the stented group (mean 75% +/- 5% vs 56% +/- 3% at day 14; P < 0. 05). However, clinical and radiographic comparisons of the stented and nonstented specimens revealed a trend toward increased mucosal edema and granulation tissue in the stented group at later time intervals (days 21 and 28). CONCLUSION: This analysis suggests that stenting does not inhibit graft vascularization in the early postoperative period after LTR; however, complications were seen in the stented group at longer time intervals.

Subglottic stenosis: correlation between computed tomography and bronchoscopy.

The evaluation of subglottic stenosis has been limited by the lack of standardized methods for determining the cross-sectional area and length of the stenotic segment. A rabbit model was used to prospectively evaluate the correlation between computed tomography (CT) and bronchoscopy in the evaluation of this disease. Subglottic stenosis was produced in 39 New Zealand White rabbits by a transoral endoscopic technique. The animals were evaluated 3 weeks later with spiral CT, rigid bronchoscopy, and open laryngotracheal exploration. Spiral CT was performed with the location, degree, and length of subglottic stenosis being determined by a blinded observer. Each animal then underwent rigid bronchoscopy and open laryngotracheal exploration for determination of the same measurements. Data were analyzed to determine the correlation between the radiographic and surgical techniques in evaluating the airway stenosis. With regard to the degree of stenosis, 94% of the rabbits were determined to have CT and bronchoscopic measurements that were within 15% (Pearson correlation .94, p < .05). With regard to the length of stenosis, 94% of animals had a measurement on CT that was within 2 mm of that observed upon open exploration (Pearson correlation .81, p < .05). The CT evaluation of subglottic stenosis correlated well with the currently used method of visual inspection at bronchoscopy in evaluating tracheal stenosis in this animal model. These data suggest that CT could serve as a useful adjunct in the evaluation of tracheal stenosis, especially when serial examinations are required.

External laryngeal trauma analysis of 392 patients.

BACKGROUND: External laryngeal trauma (ELT) is a rare but clinically important injury. OBJECTIVE: To perform the first population-based, time series analysis of the epidemiology, management, and outcomes of ELT using an 11-state, inpatient sample database containing more than 54 million patients. PATIENTS: Three hundred ninety-two patients with a primary or secondary diagnosis of ELT were identified. Over a 5-year period, the incidence of ELT in this series was 1/137,000. The mean (+/-SD) age was 37 (+/-7) years, and the overall mortality rate was 2.04%. Two hundred forty-eight patients required surgical intervention. RESULTS: The average length of stay for 67 patients not requiring surgical intervention for any injury was 3 (+/-2) days, with no mortality. One hundred eighty patients underwent endoscopy, with 14 requiring tracheotomy alone and 57 requiring tracheotomy plus laryngeal repair. The average length of stay and the mortality rate were higher in these latter groups. Overall, 139 patients underwent tracheotomy, with a mortality rate of 5%, while 96 patients underwent laryngeal repair, with a mortality rate of 1%. Surgical treatment was performed in 140 patients with ELT within 24 hours after presentation, while another 60 received treatment within 48 hours. Associated injuries included skull base or intracranial injury (13%), open neck injury (9%), cervical spine injury (8%), and esophageal or pharyngeal injury (3%). CONCLUSION: External laryngeal trauma is a rare injury, with most patients requiring surgical intervention.

Transient vocal fold immobility.

Temporary vocal fold immobility resolving in 4 weeks or less is considered a transient immobility. Many different disorders may lead to this type of laryngeal motion impairment. It is important for otolaryngologists to be familiar with the differential diagnosis for transient vocal fold immobility in order to optimize the management of these unusual cases.

Pediatric zygomatico-orbital complex fractures: the use of resorbable plating systems. A case report.

Maxillofacial trauma in the pediatric population is infrequent--only 5% of all facial fractures occur in children. Operative intervention is indicated when a displacement of normal structures is present, resulting in either a functional or cosmetic deformity. Some midface fractures in children may be managed with closed reduction and maxillomandibular fixation. When open reduction is indicated, plate-and-screw fixation has been the preferred method of stabilization. This article presents a case of an isolated zygomatico-orbital complex fracture in a 6-year-old boy. Open reduction and internal fixation of the fractures through a preexisting facial wound were performed using a resorbable plate-and-screw system. A review of the literature and a discussion of the technique precede the case presentation. The rapid healing of pediatric facial bones does not obviate the need for fracture reduction and fixation with titanium plates and screws. The resorbable system offers an alternative with excellent results.

Effect of stenting on graft vascularization after laryngotracheoplasty.

The management of pediatric airway stenosis has been an important topic of debate over the last few decades as prolonged intubation has become more common in the neonate. Although many surgical options are available, most would agree that use of expansion techniques (laryngotracheoplasty) with cartilaginous grafting is the procedure of choice for the severely stenotic airway. Controversy persists, however, regarding the role of stents. Advocates feel that stents serve to counteract scar contracture and support the newly constructed airway. In contrast, recent studies suggest that stenting results in impaired wound healing and an increased complication rate. The present study addresses the effect of stenting on the vascularization of cartilaginous grafts in an animal model. Thirty-six New Zealand white rabbits were evaluated after laryngotracheoplasty with autogenous cartilage grafting. Half of the animals were stented with a 2-cm section of an endotracheal tube that was secured just below the glottis. Three rabbits from each group were then painlessly sacrificed on days 4, 6, 8, 10, 14, and 21. Gross and histologic comparisons of the stented and nonstented specimens revealed similar wound healing. Measurements of graft vascularization were obtained with a computerized image measurement program, and a comparison was made regarding the rate of vascularization. There was a statistically significant increase in the rate of vascularization in the stented group (mean 73% versus 55% at day 10; p < .05). This analysis suggests that stenting does not inhibit early wound healing and specifically graft vascularization after laryngotracheoplasty.

Composite graft survival. An auricular amputation model.

OBJECTIVE: To study the effects of corticosteroids and fibroblast growth factor on composite graft survival using a rabbit model of auricular amputation and reimplantation. DESIGN: Randomized, "blinded," placebo-controlled, prospective animal study. SETTING: Animal laboratory in tertiary care center. INTERVENTION: Amputation of the distal 2 cm of the rabbit ear as a composite graft and reimplantation with simple 6-0 prolene sutures. All animals underwent the same surgical procedure and were randomized into the following four groups: (1) surgical reimplantation alone; (2) 30 mg/kg intramuscular methylprednisolone sodium succinate for 5 days, starting immediately postoperatively; (3) topical basic fibroblast growth factor for 5 days postoperatively; and (4) delayed reimplantation with corticosteroids. In group 4, the ears of the animal were amputated, placed in iced saline containers for 90 minutes, and given 30 mg/kg intramuscular methylprednisolone for 5 days, with the first dose starting immediately prior to reimplantation. MAIN OUTCOME MEASURES: Percentage graft survival and histologic characteristics of viable and nonviable composite graft tissue. RESULTS: The groups that received corticosteroids and delayed reimplantation with corticosteroids had a statistically significant increase in percentage of graft survival compared with the control group (P < .003 and P < .006, respectively). The growth factor group showed no significant difference from the control group. CONCLUSION: Neovascularization occurred in the viable grafts, thus suggesting its role in graft survival. This study establishes the efficacy of corticosteroids in enhancing composite graft survival.

Unilateral supraglottitis in adults: fact or fiction.

Supraglottitis and epiglottitis have been described for many years by various authors. Haemophilus influenzae type b is the primary cause of childhood epiglottitis, which classically appears between the ages of 2 and 4 years. Onset is usually acute and the presentation can be dramatic with drooling, high temperatures, and stridor. Compared to childhood supraglottitis, adult supraglottitis usually pursues a more indolent course with no significant airway compromise and no identifiable pathogen. Rarely, adult supraglottitis can resemble its childhood counterpart with acute respiratory compromise secondary to H. influenzae infection. Although most incidences of adult supraglottitis are infectious in origin and involve the entire supraglottitis and epiglottis, we present two cases of unilateral supraglottitis caused by inhalation of a hot wire screen used as a filter for smoking crack cocaine.

Orbital osteology: a study of the surgical landmarks.

This study was conducted to re-examine the osteological anatomy of the orbit. Previous studies examined dried human skulls; this study looks at cadaveric specimens in a population that more closely resembles the population in the United States. Measurements were made of the bony orbit to define safe distances for surgical intervention and to identify distances to intraorbital fissures, canals, and foramina. Safe distances to the optic nerve were identified by subtracting 5 mm from the shortest measured specimen. The safe distances were as follows: medial quadrant, 29 mm; inferior quadrant, 39 mm; superior quadrant, 38 mm; and lateral quadrant, 36 mm. Staying close to the bony wall, not exceeding these parameters, and careful identification of anatomical structures should keep the surgeon from inadvertent damage to the intraorbital structures.

Fatal craniocervical necrotizing fasciitis in an immunocompetent patient: a case report and literature review.

BACKGROUND: Craniocervical necrotizing fasciitis (CCNF) is a rapidly progressive, severe bacterial infection of the superficial fascial planes of the head and neck. Group A beta-hemolytic Streptococcus, staphylococcus aureus, and obligate anaerobic bacteria are common pathogens. The disease usually results from a dental source or facial trauma. Extensive fascial necrosis and severe systemic toxicity are common manifestations of CCNF. Recently the lay press has referred to necrotizing fasciitis in several articles about "flesh eating" bacteria, which have resulted in several deaths. METHODS: We report the first case of a fatality in an otherwise immunocompetent patient. The patient was a 66-year-old black man with no identifiable source of infection and no history or evidence of immunocompromising disorders. RESULTS: Despite aggressive surgical debridement and broad-spectrum antibiotic coverage, he died 30 hours after admission from multisystem organ failure secondary to overwhelming sepsis. CONCLUSION: Treatment consists of early recognition of CCNF combined with aggressive surgical debridement and drainage of the involved necrotic fascia and tissue along with broad-spectrum intravenous antibiotic coverage. Although 11 other fatal cases of CCNF have been previously reported, all had an underlying medical problem which created an immunocompromised state, usually diabetes mellitus or chronic alcoholism. We present a case report and literature review along with a discussion of the related anatomy.

The influence of arterial insufficiency and venous congestion on composite graft survival.

A rabbit auricular amputation model was used to study the relative effects of arterial insufficiency (AI) and venous congestion (VC) on composite graft survival. The percentage of graft survival was significantly greater for the AI group (45.8%) than for the VC group (15.9%) 2 weeks postoperatively. The percentage of graft survival at 3 weeks for the VC, AI, and noligation groups were not statistically different. All three groups were statistically different from the control group, which had both the central artery and vein ligated. The VC group also exhibited significantly more graft edema, as measured by maximal graft thickness, than the other three groups. The impact of AI and VC on composite graft survival is investigated and discussed. These results suggest that venous congestion is more detrimental to early graft survival than arterial insufficiency.

Tracheal vascular response to hypertonic and hypotonic solutions.

One of the major roles of the upper respiratory mucosa is to humidify inspired air. This function requires the coordinated activity of respiratory epithelium and mucosal vasculature. It has been difficult to study this relationship in vivo. In the present study, we investigated the effects of osmolarity on the vessel diameter of mucosal vessels via a specially constructed chamber that allows direct visualization of the rat trachea microvasculature. With use of an anesthetized and instrumented rat preparation, the luminal surface of the dorsal wall of the trachea was superfused with physiological solutions at 37 degrees C. The osmolarities were varied by removing or adding NaCl or mannitol (200, 290, and 500 mosM). The mucosal vessels dilated when the airway surface was superfused with hypertonic solutions and constricted when superfused with hypotonic solution. The largest changes occurred in the arterioles (51 +/- 5.6 microns diam), which constricted by 10 +/- 2.18 microns (P = 0.0001) when exposed to a 200 mosM solution and dilated by 11 +/- 1.55 microns (P = 0.0001) when exposed to a 500 mosM NaCl-enriched solution. Smaller changes of similar pattern were seen in venules. The changes in vessel diameter were readily reversible upon replacement of the hypo- or hypertonic solutions by an isotonic solution. We conclude that increase or decrease of solution osmolarity on the epithelial surface of the trachea can regulate diameter of mucosal blood vessels.

Timing and dosage of postoperative radiotherapy for squamous cell carcinoma of the upper aerodigestive tract.

Seventy patients who received postoperative irradiation (PI) after curative surgery for stage III or IV squamous cell carcinoma of the upper aerodigestive tract were studied retrospectively to compare the rate of local and regional recurrence (LRR) and the effect of total dose on LRR rate in patients irradiated timely (n = 40) with those who were not (n = 30). Overall, the LRR rate was higher when PI was delayed than when timely (37% vs 20%). No advantage resulted from increasing total dose when PI was delayed; the LRR rate in the primary site and upper neck was 18% with less than 60 Gy and was 26% with 60 Gy or more; the LRR rate in the lower neck was 13% with 50 Gy or less and was 14% with more than 50 Gy. These data seem to corroborate the findings of other investigators regarding the importance of initiating timely PI, but not the observation that a pronounced delay is not detrimental provided higher tumoricidal doses are used.

Statistical considerations for cross-sectional data relating to tracheal reconstruction over time.

Complementary statistical analyses are performed on data concerning tracheal reconstruction in rats. The principal response criterion is vessel area as defined by the area of a graft onto the trachea covered by blood vessels. Postoperatively, this vessel area changes in a nonlinear fashion over time. Starting at 0% immediately postoperation, the vessel area increases to a peak and then sharply decreases to a certain level at which it remains. A total of 64 independently observed cross-sectional pairs (postop day, vessel area) are distributed among four treated groups. Analysis consists of two-way analysis of variance and piecewise linear regression under the usual assumptions of normality and variance homogeneity. Other analyses that relax these assumptions are also considered; treatment differences are established by nonparametric tests, and a quasi-likelihood analysis of the piecewise linear regression model is applied under the assumption of a binomial-like variance function. The resulting fit of the normal-theory-based piecewise linear model is compared to that of a nonlinear model whose shape is that of a gamma function integrand.

Special problems associated with carcinoma of the nose.

Because of its prominent location on the face, the nose is the primary target for sun-induced skin cancers. The unique anatomical features of the nose account for the unusually high rate of recurrence of tumors at this site. The reasons are multifactorial and have been discussed. Special care must be undertaken in managing cutaneous neoplasms arising in this region, for failure to control disease can lead to catastrophic events and eventually to the demise of the patient. Likewise, tumor recurrence and multiple therapeutic endeavors are associated with progressive facial deformity that impacts significantly on the patient's self-image and ability to interact socially. Reconstruction of nasal defects must be predicated on complete tumor ablation and documented by histologic evidence. Patients with high-risk lesions or in whom tumor margins are in question should undergo a period of observation before definitive reconstruction is contemplated. Although multiple reconstructive options are available, decisions relating to timing, advisability, and appropriate technique must be individualized. These judgments are based on the experience and bias of the surgeon as well as the goals and concerns of the patient.