BACKGROUND CONTEXT: Collet-Sicard syndrome (CSS) is a rare condition that includes palsies of cranial nerves IX, X, XI, and XII. There are multiple reported causes in the literature, although infection is particularly unusual. PURPOSE: To report an unusual case of CSS as a result of infection causing head-to-neck dissociation with involvement of the upper cervical spine. STUDY DESIGN: Case report. METHODS: A 56-year-old male with medical comorbidities developed a cranial-based infection secondary to initial incomplete treatment of otitis media. The mass effect of the infection resulted in multiple cranial nerve palsies and extremity symptoms initially confused with a cerebrovascular accident. Clinical course of the patient and a review of CSS are presented. RESULTS: With progression of the disease, further evaluation revealed a disseminated upper cervical and skull-based infection causing destructive head-to-neck infectious instability. This was treated with posterior occipitocervical debridement, fixation, and fusion and appropriate long-term antibiotics. Over the course of several months, the infection resolved and there was a significant improvement in his dysphagia, dysarthria, and hearing. CONCLUSIONS: Delay in diagnosis of CSS is common, and this syndrome should be considered in patients who present with a constellation of lower cranial nerve palsies. Early recognition and treatment should result in successful recovery, but even in cases of delayed detection, suitable intervention can result in substantial clinical improvement.

Little is known about pediatricians' counseling and clinical practices to reduce skin cancer risk among their patients. Thus our objectives were to characterize skin cancer preventive counseling and clinical practices in a sample of pediatricians and identify correlates of these practices. Physicians practicing general pediatrics in Harris County, Texas, received a mail survey that assessed their sun protection recommendations and skin cancer preventive counseling and clinical practices. Pediatrician, patient, and medical practice variables were assessed as correlates. Most (76%) pediatricians routinely recommended sunscreen; however, relatively few (24%) suggested reapplying it after prolonged periods outside. About half routinely recommended protective clothing (53%), shade (47%), or limiting midday sun exposure (46%). Even fewer pediatricians routinely discussed skin cancer risk factors, passed out sunscreen samples, made educational materials available, took a family history of skin cancer, or documented risk factors in a patient's chart. More than half reported that they routinely performed full-body skin examinations during a first visit (65%) and annually (56%). Perceived barriers, perceived relevance of skin cancer prevention, and personal sun protection practices were important factors associated with professional practices in this sample. Interventions are needed to increase pediatricians' counseling and clinical practices to reduce skin cancer risk among patients.

BACKGROUND: Inherited polymorphisms of DNA repair genes may contribute to genetic susceptibility to squamous cell carcinoma of the head and neck (SCCHN). The objective was to assess whether two polymorphisms in the nucleotide excision repair gene XPD (ERCC2) are markers of SCCHN risk. METHODS: We performed a hospital-based case-control study of 180 SCCHN patients and 400 cancer-free controls frequency matched on age, sex, smoking, and alcohol use. All subjects were non-Hispanic whites. XPD alleles 23047 and 23051 were assessed by digestion with the restriction enzymes XhoII and SphI after PCR amplification. RESULTS: The XPD 23047 G and XPD 23051 T alleles were extremely rare among both the cases and controls (allele frequencies<1.0%), and not statistically different between groups (P>0.6). CONCLUSIONS: The 23047 and 23051 variants of the DNA repair gene XPD are extremely rare and do not contribute significantly to the risk of SCCHN in the non-Hispanic white population.

BACKGROUND: Phenotypic differences in the ability to repair genetic damage induced by tobacco carcinogens may reflect genetic differences in susceptibility to squamous cell carcinoma of the head and neck (SCCHN). The objective of this study was to assess the variation in baseline expression of five nucleotide excision repair genes between individuals with SCCHN and cancer free controls. METHODS: The authors conducted a hospital-based case-control study of 57 SCCHN patients and 105 cancer free controls. Using peripheral blood lymphocytes, a multiplex reverse transcriptase-polymerase chain reaction assay was used to quantitate in vitro the mRNA levels of five genes (ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6, and XPC) involved in the nucleotide excision repair pathway. RESULTS: The levels of ERCC1, XPB/ERCC3, XPG/ERCC5, and CSB/ERCC6 transcripts were lower in cases than in controls (P =0.0001, 0.096, 0.001, and 0.0001, respectively). In multivariate logistic regression analysis (adjusting for age, gender, race, smoking status, and alcohol use), low expression of ERCC1, XPB/ERCC3, XPG/ERCC5, and CSB/ERCC6 was associated with a statistically significant increased risk for SCCHN (adjusted odds ratios [95% confidence intervals] 6.42 [2.63-15.69], 2.86 [1.39-5.90], 3.69 [1.73-7.90], and 2.46 [1.19-5.09], respectively). CONCLUSIONS: Reduced expression of ERCC1, XPB/ERCC3, XPG/ERCC5, and CSB/ERCC6 is associated with a more than two-fold increased risk of SCCHN.

BACKGROUND: Intraoperative lymphatic mapping and sentinel lymph node biopsy have been used successfully to stage regional lymphatics for trunk and extremity melanomas. However, the accuracy and applicability of these techniques in the head and neck have not been determined conclusively. OBJECTIVE: To report the results of a prospective trial of intraoperative lymphatic mapping and sentinel lymph node identification in patients with head and neck cutaneous melanoma. METHODS: Using technetium Tc 99m--labeled sulfur colloid and isosulfan blue, intraoperative lymphatic mapping and sentinel lymph node identification were performed in 43 patients with melanomas of intermediate thickness. After the sentinel lymph nodes were identified in situ, an elective dissection of levels I through V or II through V was performed, based on the location of the primary tumor. The parotid, postauricular, and suboccipital lymphatics were dissected as clinically indicated. The sentinel lymph nodes were isolated ex vivo and evaluated pathologically by serial sectioning, and the accuracy of the lymphatic mapping was determined. RESULTS: Intraoperative lymphatic mapping identified 155 sentinel lymph nodes in 94 nodal basins, with a mean of 3.6 sentinel nodes and 2.2 basins per patient. Sentinel nodes were located in the parotid gland in 19 patients (44%), necessitating superficial parotidectomies, and they were distributed throughout nonadjacent nodal basins in 18 patients (42%). Nine patients (21%) had metastatic disease in 1 or more sentinel nodes, 3 of whom had metastatic disease in a nonsentinel node. No patient who had negative sentinel nodes had a positive nonsentinel node (false-negative incidence, 0). CONCLUSIONS: Although intraoperative lymphatic mapping accurately identifies sentinel lymph nodes for head and neck cutaneous melanomas, the multiplicity of these nodes, their widespread distribution, and their frequent location within the parotid gland may preclude sentinel lymph node biopsy in many patients. Therefore, we advocate selective lymphadenectomy of sentinel nodal basins, allowing histological staging of the regional lymphatics with limited morbidity. However, further study is necessary to define the true role of sentinel lymph node identification for head and neck cutaneous melanoma.

Checkpoint kinase 2 (hCHK2/hCds1) is a tumor suppressor gene involved in cell-cycle control. A hCHK2/hCds1 polymorphism in codon 84 (A-->G at nucleotide 252) was recently identified in Li-Fraumeni syndrome patients. Because cell cycle regulates DNA repair that is associated with cancer risk, we hypothesized that this new polymorphism exists in the general population and is associated with cancer risk. To test this hypothesis, we evaluated the role of this polymorphism in a case-control study of 215 non-Hispanic white patients with newly diagnosed squamous cell carcinoma of the head and neck (SCCHN) and 229 frequency-matched cancer-free controls. We found that the hCHK2/hCds1 codon 84 variant was rare and less frequent in non-Hispanic white cases (0.0186) than in controls (0.0437; P = 0.033). Although no variant homozygotes were detected in these cases and controls, heterozygosity protected against SCCHN, representing a 60% reduction of risk (adjusted odds ratio = 0.40; 95% confidence intervals, 0.17-0.93) compared with wild-type homozygotes. The variant allele was also rare in other ethnic groups (0.0487, 0.0095 and 0.0541 in 115 African Americans, 105 Hispanic Americans and 111 native Chinese, respectively), and only one variant homozygous individual (a Chinese subject) was identified. These results suggest that this hCHK2/hCds1 codon 84 polymorphism is rare and may have a protective role in the aetiology of SCCHN in non-Hispanic whites. Larger studies are warranted to confirm this finding and further mechanistic studies are needed to understand biological relevance of this polymorphism.

PURPOSE: This retrospective study assessed the outcome and patterns of failure for patients with malignant submandibular tumors treated with surgery and postoperative radiation. METHODS AND MATERIALS: Between 1965 and 1995, 83 patients aged 11-83 years old received postoperative radiotherapy after resection of submandibular gland carcinomas. The most common radiation technique was an appositional field to the submandibular gland bed using electrons either alone or mixed with photons. Primary tumor bed doses ranged from 50 to 69 Gy (median, 60 Gy). Regional lymph nodes (ipsilateral Levels I-IV) were irradiated in 66 patients to a median dose of 50 Gy. Follow-up time ranged from 5 to 321 months (median, 82 months). RESULTS: Actuarial locoregional control rates were 90%, 88%, and 88% at 2, 5, and 10 years, respectively. The corresponding disease-free survival rates were 76%, 60%, and 53%, because 27 of 74 patients (36%) who attained locoregional control developed distant metastases. Adenocarcinoma, high-grade histology, and treatment during the earlier years of the study were associated with worse locoregional control and disease-free survival. The median survival times for patients with and without locoregional control were 183 months and 19 months, respectively. Actuarial 2-, 5-, and 10-year survival rates were 84%, 71%, and 55%, respectively. Late complications occurred in 8 patients (osteoradionecrosis, 5 patients). CONCLUSIONS: High-risk cancers of the submandibular gland have a historic control rate of approximately 50% when treated with surgery alone. In the current series, locoregional control rates for high-risk patients with submandibular gland cancers treated with surgery and postoperative radiotherapy were excellent, with an actuarial locoregional control rate of 88% at 10 years.

A G-->A polymorphism (G870A) in exon 4 of the cyclin D1 (CCND1) gene creates an alternative splice site in its mRNA, encoding a protein with an altered C-terminal domain. It has been suggested that DNA damage in cells with the A allele bypasses the G(1)/S checkpoint of the cell cycle more easily than damage in cells without the A allele. Because CCND1 plays a critical role in cell cycle control and reduced DNA repair capacity is associated with an increased risk for squamous cell carcinoma of the head and neck (SCCHN), we hypothesize that this CCND1 polymorphism modulates individual susceptibility to SCCHN. To test this hypothesis we evaluated the frequency of the polymorphism in a hospital-based case-control study of 233 newly diagnosed SCCHN patients and 248 non-cancer controls. The cases and controls were frequency matched by age (+/-5 years), sex and tobacco use. All subjects were non-Hispanic whites. We found that the A allele frequency was slightly higher in the cases (0.485) than in the controls (0.425), but the difference was borderline statistically significant (P = 0.064). The frequencies of the CCND1 AA, GA and GG genotypes were 23.6, 49.8 and 26.6%, respectively, in cases and 16.5, 52.5 and 31.5%, respectively, in controls. Multivariate logistic regression analysis adjusting for age (in years), sex, smoking and alcohol use was performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Compared with the wild-type CCND1 GG, the CCND1 A G genotype was associated with a non-significantly increased risk (adjusted OR 1.15, 95% CI 0.75-1.76), but the CCND1 AA genotype was associated with a significantly increased risk (adjusted OR 1.77, 95% CI 1.04-3.02) for SCCHN. Results from a trend test using a logistic regression model were statistically significant (P = 0.044). Among the cases the mean age of onset was 59.0, 56.8 and 55.5 years for the GG, GA and AA genotypes, respectively. In the stratification analysis the CCND1 AA variant genotype was associated with a >3-fold increased risk in individuals who were </=50 years old (OR 3.18, 95% CI 1.19-8.46), females (3.57, 1.26-10.0), non-smokers (3.71, 1.37-10.1) and non-alcohol users (4.76, 1.61-14.0). These results suggest that the CCND1 polymorphism is associated with early onset of SCCHN and contributes to susceptibility to SCCHN in this population.

The level of DNA adducts under the same conditions of carcinogen exposure and cell proliferation reflects an integrated measure of carcinogen metabolism and DNA repair. Therefore, such DNA adduct levels have the potential to be a biomarker for susceptibility to chemical carcinogenesis. In a pilot study of 91 patients with squamous cell carcinomas of the head and neck and 115 controls who were frequency matched by age, sex, ethnicity, and smoking status, we applied a newly developed in vitro assay of benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in short-term peripheral lymphocytes cultures. Levels of BPDE-DNA adducts were found to be significantly higher in cases than in controls (mean +/- SD, 76.8 +/- 77.4/10(7) and 47.1 +/- 48.0/10(7) nucleotides, respectively; p < 0.001). Using the median level of control values (35/10(7)) as the cut-off point, about 66% of cases were distributed above this level. Logistic regression analysis revealed that the level of BPDE-induced DNA adducts was an independent risk factor (odds ratio = 2.22; 95% confidence interval = 1.22--4.04) after adjustment for age, sex and smoking status. Further stratified analyses showed that levels of the induced adducts between cases and controls were significantly higher in both age groups, that is, younger or older than 60, as well as in both men and women. Smoking had a positive effect on the induced adducts. The highest level of induced adducts was seen in current smokers, then former smokers and non-smokers. There was a statistically significant dose--response relationship between the quartile levels of BPDE-induced DNA adducts and the risk of head and neck cancer (trend test, p = 0.003). Despite the relatively small sample size, the association of BPDE-induced DNA adducts and cancer risk suggests that this assay has the potential to complement with other biomarkers in identifying individuals at increased risk of developing tobacco-related cancers.