Paediatric parotid neoplasms: a 10 year retrospective imaging and pathology review of these rare tumours.

AIM: To determine the relative incidence of benign and malignant paediatric parotid gland tumours and whether particular presenting symptoms or imaging characteristics were more likely to predict malignancy. MATERIALS AND METHODS: Hospital records were reviewed for all patients <18 years with histopathology-proven parotid neoplasms over the 10 year period from 2003-2013. Infantile haemangiomas and patients with neurofibromatosis type I were excluded. The presenting clinical symptoms for each patient were recorded. All available CT and MRI examinations for these patients were evaluated for tumour imaging characteristics. RESULTS: Seventeen patients (nine boys, eight girls; age range 2-17 years) were identified with neoplastic parotid masses; 11 tumours were malignant (65%) and six were benign (35%). The malignant tumours consisted of three acinic cell carcinomas, two mucoepidermoid carcinomas, one alveolar rhabdomyosarcoma, one poorly differentiated carcinoma, one low-grade adenocarcinoma, and three metastases (two melanoma, one orbital medulloepithelioma). The benign tumours consisted of five pleomorphic adenomas and one schwannoma. Presenting clinical symptoms were similar between benign and malignant tumours. Twelve MRI and six CT examinations were available for review with five patients undergoing both techniques. MRI features commonly identified with malignant tumours included: hypointense T2 signal, restricted diffusion, ill-defined borders, and focal necrosis. Only four of the six tumours imaged at CT were visualized, and of those, the margins were indeterminate in three patients. CONCLUSION: Paediatric parotid masses are more likely to be malignant than benign. Presenting clinical symptoms and CT are not helpful for distinguishing benign and malignant disease. MRI features such as T2 hypointensity, restricted diffusion, ill-defined borders, and focal necrosis, although not specific, should raise concern for malignancy.

Cytotoxicity, radiosensitization, antitumor activity, and interaction with hyperthermia of a Co(III) mustard complex.

A complex of Co(III) with a nitro group and a bis(2-chloroethyl)amine moiety was prepared in an effort to develop a new anticancer agent with radiosensitizing capabilities, direct antitumor activity, and the ability to interact positively with clinically relevant hyperthermia temperatures. The activity of this drug was compared to a similar Co(III) complex, nitro-bis(2,4-pentanedionato)(pyridine)cobalt(III) [Co(Py)], which bears a pyridine moiety mustard of bis(2-chloroethyl)amine and should have no alkylating abilities. In EMT6 cells nitro-bis(2,4- pentanedionato)(bis(2-chloroethyl)amine)cobalt(III) [Co(BCA)] was significantly more cytotoxic than Co(Py) and both drugs were more toxic toward normally oxygenated than hypoxic cells. Hyperthermia (42 degrees C, 1 h) increased the slope of the concentration-dependent survival curve for Co(BCA) but not for Co(Py) in normally oxygenated EMT6 cells. Co(BCA) was an effective radiosensitizer of hypoxic EMT6 cells in vitro, producing a dose-modifying factor of 2.40. In the human squamous cell line SCC-25 and the nitrogen mustard-resistant subline SCC-25/HN2 Co(BCA) was more cytotoxic than Co(Py), and the lethality of Co(BCA) was only minimally diminished in the SCC-25/HN2 line. In mice bearing the L1210 leukemia i.p., Co(BCA) had a broad range of therapeutically effective dosage and produced a greater than 60-day increase in life span at a dose 20-fold less than was lethally toxic. In addition, in the FSaIIC murine fibrosarcoma, Co(BCA) produced a tumor growth delay of 9.4 days at 75 mg/kg i.p. daily x 5, but Co(Py) produced a delay of only 2.9 days at 50 mg/kg daily x 5 and was lethally toxic above this dose. These results indicate that Co(BCA) has significant antineoplastic effects in vitro and in vivo and interacts positively with both radiation and mild hyperthermia. Its broad therapeutic dose range further suggests potential clinical utility.

Cross-resistance and glutathione-S-transferase-pi levels among four human melanoma cell lines selected for alkylating agent resistance.

A panel of four cell sublines, each selected for resistance to a different antineoplastic agent, has been developed from a human malignant melanoma cell line G3361. Following repeated exposure to escalating doses of the drug of interest, cloned sublines were developed that are 9-fold resistant to cisplatin (G3361/CP), 11-fold resistant to 4-hydroxyperoxy-cyclophosphamide (4-HC) (G3361/HC), 4-fold resistant to carmustine (BCNU) (G3361/BCNU), and 4-fold resistant to melphalan (G3361/PAM). The cross-resistance of each resistant cell line was determined for cisplatin, BCNU, 4-HC, melphalan, carboplatin, nitrogen mustard, and Adriamycin. In general, the alkylating agent-resistant cell lines were specifically resistant to the drug used for selection with the exception of the G3361/CP line, which was greater than 10-fold resistant to the cisplatin analogue carboplatin, 4-fold resistant to 4-HC, and slightly (1.5-fold) resistant to melphalan, and the G3361/BCNU line, which was slightly (1.8-fold) resistant to melphalan. Collateral sensitivity of the G3361/CP, G3361/PAM, and G3361/4HC lines to killing by BCNU was also observed. Glutathione-S-transferase activity was elevated in each of the alkylating agent-resistant cell lines by 3- to 5-fold with chlorodinitrobenzene substrate. On Western blotting, the glutathione-S-transferase-pi (GST-pi) isoenzyme protein was elevated in the resistant cells by 3- to 5-fold. A complementary DNA (pTS4-10) coding for GST-pi has been cloned from a lambda gt11 library, sequenced, and used as a probe to determine the relative levels of GST-pi mRNA in the alkylating agent-resistant cell lines. GST-pi mRNA levels were elevated (8- to 15-fold) in the resistant cell lines, indicating that the GST-pi increases were mediated through an increase in mRNA levels. GST-pi elevations are a frequent event in cells selected for alkylating agent resistance, and in some cases, of multiple drug resistance. However, the lack of cross-resistance among cell lines selected for resistance to different alkylating agents, all of which have elevated GST-pi levels, indicates that increased levels of GST-pi cannot be the predominate mechanism for resistance to the tested drugs in these cell lines.

Surgical outcomes and sleep endoscopy for children with sleep-disordered breathing and hypotonia.

OBJECTIVE: To study the efficacy of surgical management for obstructive sleep apnea (OSA) syndrome in children with hypotonia, and to identify common anatomic sites of airway obstruction. METHODS: Retrospective chart review of polysomnographic parameters and quality of life instrument scores for seventy eight children with hypotonia who underwent surgical intervention for sleep-disordered breathing at two tertiary children's hospitals, and analysis of drug-induced sleep endoscopy data using a previously validated scoring system. RESULTS: Children undergoing surgical intervention had baseline severe OSA with a statistically significant improvement in apnea-hypopnea index from 23.6 to 11.1 after surgery, but persistent severe OSA. OSA-18 sleep-related quality of life measurement and overall quality of life score showed statistically and clinically significant improvements, from 72.0 to 43.4 and from 5.3 to 7.6 respectively. Sleep endoscopy showed an average obstructive score of 7.2/15 (n = 39), with multi-level obstruction in 49% of children. Greater than 50% obstruction was observed at the tongue base in 64% of patients, velum in 46%, lateral pharyngeal wall in 38%, supraglottis in 38%, and adenoid in 23%. CONCLUSION: OSA syndrome is challenging to treat in hypotonic children. Severe residual OSA is common after surgical intervention, but improvement in quality of life is clinically and statistically significant. The tongue base is the most common site of persistent airway obstruction. Drug-induced sleep endoscopy can identify sites of airway obstruction and may aid in surgical planning for high-risk patients.

Effect of lonidamine on the cytotoxicity of four alkylating agents in vitro.

We examined the ability of lonidamine, which has been described as an inhibitor of cellular respiration and glycolysis, to enhance the cytotoxicity of alkylating agents to MCF-7 human breast-carcinoma cells. Lonidamine was increasingly cytotoxic to MCF-7 cells with increasing time of exposure. With a 12-h exposure, the IC50 for lonidamine was about 365 microM, and with a 24-h exposure it was about 170 microM. A drug concentration of 250 microM was chosen for use in the drug combination studies. Lonidamine appeared to have a dose-modifying effect on cisplatin (CDDP), producing increasingly supra-additive cell kill with increasing CDDP concentration. When simultaneously incubated with lonidamine for 1 h, 500 microM CDDP yielded a cell kill that was 2 log greater than additive cytotoxicity. Extending the exposure to lonidamine for 12 h after CDDP treatment led to a small, additional aliquot of cell kill of about 2.5-fold over the CDDP concentration range. Lonidamine also appeared to have a dose-modifying effect on melphalan cytotoxicity in the melphalan concentration range of 100-500 microM. Between concentrations of 10 and 100 microM melphalan, the drug combination survival after 1 h exposure fell within the envelope of additivity for the two agents. However, maintaining the presence of lonidamine for an additional 12 h increased the effect such that the combination was supra-additive over the entire concentration range of melphalan. Simultaneous exposure to 4-hydroperoxycyclophosphamide (4-HC) and lonidamine for 1 h resulted in greater than additive cell kill, and extending the lonidamine exposure period such that lonidamine was present during and 12 h after 4-HC treatment further increased this effect. Lonidamine had a moderate effect on the cytotoxicity of carmustine (BCNU) with a 1 h simultaneous exposure; however, this treatment combination reached greater than additive cytotoxicity only at the highest concentration of BCNU tested. Extending the lonidamine exposure time for an additional 12 h resulted in supra-additive cell kill over the BCNU concentration range. Therefore, when lonidamine was present during exposure to the alkylating agent and its presence was then extended for an additional 12 h, a synergistic cell kill was produced with all four alkylating agents tested.

Morphologic evidence for three cell types in the human spiral ganglion.

Although two types of spiral ganglion cells (large type I and smaller type II) have classically been described by anatomic studies in both animal and human spiral ganglion, there is physiologic and morphologic evidence for subtypes of the large type I ganglion cell. In addition, in the animal and human, a variety of morphologic differences based on cytoplasmic content, myelinization, immunostaining and morphometric analysis have suggested more than one variety of type I ganglion cell. Light and electron microscopic serial sections of the spiral ganglion in two human specimens in the basal, middle and upper middle turns were pooled for morphometric analysis of the cell area, nuclear area and axon diameter. Analysis of variance, bivariate scatter plots and multivariate cluster analysis provided evidence for 3 types of ganglion cells in the human spiral ganglion: large, intermediate and small, varying from each other significantly on the basis of cell area. It was suggested, based on the morphologic findings and prevalence of the cell types, that the large and intermediate cells were subtypes of the classic type I spiral ganglion cell, whereas the small ganglion cell was consistent with the classically described type II ganglion cell.

Immunohistochemical localization of nitric oxide synthase activity in upper respiratory epithelium.

Nitric oxide (NO) production in the respiratory epithelium of the upper airways has recently been described. To better delineate the role of epithelial NO, the authors of this study attempted to identify the cell type responsible for the production of NO in rat tracheal epithelium and human nasal epithelium. They localized the activity of NO through immunohistochemical analysis with an antibody to L-citrulline, a marker for activity of the L-arginine-dependent nitric oxide synthase (NOS) pathway. Using anti-inducible NOS (iNOS) and anti-constitutive NOS (cNOS) antibodies, they also attempted to identify the specific NO isotypes that were present. The tracheal and nasal epithelium demonstrated strong immunoreactivity to citrulline in ciliated cells. The ciliated cells of the nasal turbinates demonstrated strong iNOS positivity, but no significant cNOS immunoreactivity. The study findings that iNOS activity is present in ciliated epithelial cells of rat and human upper respiratory epithelium suggest that NO may play a role in epithelial homeostasis and could potentially play a role in the pathogenesis of mucociliary dysfunction.

Nitric oxide: a mediator of endotoxin-induced middle ear effusions.

Using a rat model, the authors investigated the role of nitric oxide (NO) in endotoxin-induced middle ear effusion (MEE). After the eustachian tube was obstructed, the middle ear was transtympanically injected with 35 microL of either 1 mg/mL lipopolysaccharide (LPS) or LPS and 1 mmol/L N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase. Over the next 6 hours, the fluid within the middle ear was collected every 2 hours, and the quantity of albumin in the fluid, an index of vascular leakage, was determined using enzyme-linked immunosorbent assay. L-NAME significantly reduced LPS-induced vascular extravasation into the middle ear. Inoculation of the ear with L-arginine, the substrate for NO synthase, reversed the effects of L-NAME. These results indicate that NO is a mediator of LPS-induced MEE. Therefore, inhibition of NO synthase may represent a novel approach to the treatment of otitis media with effusion.

Efficacy of postoperative follow-up telephone calls for patients who underwent adenotonsillectomy.

OBJECTIVE: To evaluate the efficacy and cost-effectiveness of postoperative follow-up telephone calls among pediatric patients who underwent adenotonsillectomy. DESIGN: Prospective study with a follow-up questionnaire administered by telephone. SETTING: Tertiary-care children's hospital. PATIENTS: One hundred thirty-four children between the ages of 4 and 18 years who underwent adenotonsillectomy between December 1997 and June 1998 and did not have associated cardiac, pulmonary, bleeding, or syndromic disorders were included in this pilot study. INTERVENTION: Parents of these patients were given the opportunity to participate in our study, and it was emphasized that, at any time during the child's care, if the parent desired a follow-up visit or if the child experienced any symptoms that caused concern, the parent should contact the clinic for a follow-up appointment. A telephone call was placed 3 to 4 weeks postoperatively by an otolaryngology nurse, and a questionnaire was filled out using the parents' responses. MAIN OUTCOME MEASURES: The incidence rates of voice change, velopharyngeal insufficiency, bleeding, constipation, dehydration, and pain were measured. Parent satisfaction, patient safety, and cost-benefit were also evaluated. RESULTS: Less than 5% of patients reported temporary velopharyngeal insufficiency, while 2% of patients required operative intervention for bleeding episodes and 1% required hospitalization. Voice change, reported by approximately 70% of all patients, was the most common complaint, but it resolved in all instances. Pain was reported to be most severe on postoperative day 1. Ninety-six percent of parents requested no further follow-up visit. CONCLUSIONS: Our pilot study revealed that a follow-up telephone call is a safe and cost-effective method of postoperative management for pediatric patients who have undergone adenotonsillectomy and that this method of follow-up is also desirable to parents.

Management of orbital subperiosteal abscess in children.

OBJECTIVES: To present guidelines for the management of an orbital subperiosteal abscess (SPA) in children and to assess the efficacy and safety of transnasal endoscopic drainage of an orbital SPA. SETTING: Tertiary care children's hospital. PATIENTS: Nineteen patients treated for an SPA between July 1997 and December 1999. The age of the patients ranged from 17 months to 14 years (mean, 6 years). The male-female ratio was 10:9. Treatment modalities included transnasal endoscopic drainage (n = 11), external drainage (n = 3), and intravenous antibiotics alone (n = 5). RESULTS: Bilateral pansinusitis was the most common cause. All patients received an initial trial of intravenous antibiotics. Based on the Fisher exact test, no statistically significant differences were detected for age, sex, presence of gaze restriction, and radiographic findings. Based on multiple logistic regression, degree of proptosis was the only significant multivariate predictor of surgery (P =.003). The estimated probability of surgery was 6% when there was no proptosis, and 92% for 2 mm of proptosis. The location of the SPA determined the route of surgical drainage. Eleven patients with a medially based SPA underwent drainage via the transnasal endoscopic approach, and 3 with a superior SPA underwent drainage externally. The external approach was associated with a longer hospital stay (median, 7 days) than either the endoscopic or the intravenous antibiotic approach (median, 5 days).

Immunohistochemical characterization of nitric oxide synthase activity in squamous cell carcinoma of the head and neck.

This study was designed to investigate the presence of nitric oxide in human squamous cell carcinoma of the head and neck. We localized the activity of nitric oxide synthase in these tumors through immunohistochemical analysis using antibodies to L-citrulline (a byproduct of nitric oxide synthase), to inducible nitric oxide synthase, and to constitutive nitric oxide synthase. We found presence of inducible enzyme in squamous cells throughout these tumors, with the highest intensity staining occurring directly around keratin pearls. Our findings suggest that inducible nitric oxide synthase activity is present in squamous cell carcinomas of the head and neck, leading us to conclude that inducible nitric oxide synthase may play a significant role in tumor growth.

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.

Endoscopic sinus surgery in cystic fibrosis: do patients benefit from surgery?

OBJECTIVE: To examine the effects of endoscopic sinus surgery on the pulmonary status of cystic fibrosis (CF) patients through the objective parameters of steroid use, pulmonary function tests (PFTs), and inpatient hospital days (IHDs). METHODS: Retrospective chart review of all patients with CF who underwent endoscopic sinus surgery from 1993 to 1999 at a tertiary care children's hospital. Preoperative pulmonary function, inhaler and steroid use, and IHDs were compared to postoperative parameters within a 1-year period. RESULTS: Sixty-six patients, including eight lung transplant patients, underwent a total of 112 endoscopic sinus surgery procedures; 25 patients underwent more than one procedure. Patients were taking oral steroids preoperatively in 28% of procedures and inhaled steroids in 40%. Postoperatively, there was no statistically significant change in oral or inhaled steroid use, or in postoperative pulmonary function. If the index hospitalization, which was often for reasons not related to sinus disease, was considered part of the preoperative time period, endoscopic sinus surgery (ESS) was noted to result in a marked reduction (9.5 days (adjusted), P=0.001) in hospital days during the subsequent 6 months. If the date of the procedure alone was used to define pre- and postoperative time periods, the reduction in postoperative days was more modest and not statistically significant (3.5 days (adjusted), P=0.21). CONCLUSIONS: Although we found no statistically significant difference in PFTs, or steroid requirements following ESS, ESS may have resulted in a reduced need for hospitalization in the 6 months following the procedure. Future prospective studies in a larger number of patients and using more detailed outcome measures are needed to better evaluate the effects of endoscopic sinus surgery in pediatric patients with CF.

Usefulness of patient symptoms and nasal endoscopy in the diagnosis of chronic sinusitis.

The diagnosis of chronic sinusitis can be difficult due to the variety and lack of specificity of presenting symptoms. Sinus CT scanning is presently considered the most sensitive and specific diagnostic method, but is expensive. In order to determine whether a combination of patient symptoms and nasal endoscopy could be used to predict which patients would have CT evidence of chronic sinusitis, we conducted a prospective study in which 92 consecutive patients referred for chronic sinusitis were required to fill out a questionnaire detailing their symptoms. Their responses were then correlated with subsequent findings on nasal endoscopy and CT scanning. Briefly, we found that patients with headache or facial pain as their chief complaint were less likely to have evidence of sinusitis than patients whose chief complaint was nasal obstruction or postnasal drip. Also, nasal endoscopy was shown to be moderately sensitive and highly specific in predicting results of CT scanning.

Oesophageal perforation presenting as oesophageal atresia in a premature neonate following difficult intubation.

Iatrogenic oesophageal perforation in neonates is well recognized in the medical and surgical literature with intubation injury listed as a possible contributing mechanism besides nasogastric tube placement and suctioning. Diagnosis can be difficult and sometimes confused with other entities. With early diagnosis, nonsurgical management often leads to complete resolution in neonates. We report the case of a 1-day-old premature neonate who was brought to the operating room with the preliminary diagnosis of proximal oesophageal atresia with stump perforation and distal tracheo-esophageal fistula. His intubation for respiratory distress at birth had been difficult due to Pierre-Robin sequence with micrognathia. Oesophagoscopy in the operating room revealed a patent oesophagus but perforations in the pharynx and in the proximal oesophagus with the nasogastric tube entering the pharyngeal perforation. Oesophageal perforation and the limitations of the difficult airway algorithm in small neonates are discussed.