Faculty Bibliography

IMPORTANCE: Posttreatment surveillance (PTS) is a key component in the treatment of patients with head and neck cancer. It is unclear how beneficial this is in improving patients' survival. OBJECTIVE: To determine how compliance with follow-up affects clinical outcomes in patients with head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study at a tertiary academic center of a total of 332 patients with head and neck squamous cell carcinoma who had completed both treatment and follow-up at the University of Kansas Medical Center. Patient and tumor characteristics, socioeconomic status, and geographic data were collected. EXPOSURES: Compliance with PTS. MAIN OUTCOMES AND MEASURES: The effect of compliance with PTS on overall survival. RESULTS: Compliance with PTS, US Census tract income level, and the distance patients travel for follow-up had significant effects on survival (P = .001, P = .001, and P = .01, respectively). Cox proportional hazard models revealed that more advanced disease (hazard ratio [HR], 1.76 [95% CI, 1.21-2.58]; P = .003), middle (HR, 1.64 [95% CI, 1.13-2.39]; P = .009) and moderate (HR, 1.90 [95% CI, 1.18-3.06]; P = .008) census tract income level, and age (HR, 1.03 [95% CI, 1.01-1.04]; P < .001), were significantly associated with an increased risk of death. There was an association between compliance and tobacco cessation (P = .003), as well as the distance a patient lived from the medical center (P = .008). CONCLUSIONS AND RELEVANCE: Patients with head and neck squamous cell carcinoma were significantly more likely to survive with completion of follow-up and tobacco cessation. Compliance with PTS was associated with smoking cessation and traveling less than 200 miles for follow-up.

Although the preponderance of cerebellopontine angle lesions are schwannomas, focused attention to patient clinical history, imaging studies, and tissue biopsies when indicated will aid in detection of less common lesions that might otherwise be misdiagnosed. This is most critical for pathologies that dictate different management paradigms be undertaken.

RATIONALE: Preventing pulmonary complications during mechanical ventilation via tracheotomy is a high priority. OBJECTIVES: To investigate if the Blom tracheotomy tube with suction-above-the-cuff inner cannula reduced the quantity of normal flora and pathogens in supra- versus subglottic spaces. METHODS: We enrolled 20 consecutive medical ICU adults requiring tracheostomy for mechanical ventilation in this proof-of-concept, prospective, single-center study. All participants received a Blom tracheotomy tube with suction-above-the-cuff inner cannula to decontaminate microorganisms from the supra- and subglottic spaces. Supra- and subglottic sputum samples were obtained for microbiologic analysis while an endotracheal tube was in place before tracheotomy and once per week for up to 4 weeks of mechanical ventilation after tracheotomy. MEASUREMENTS AND MAIN RESULTS: Demographics, duration of endotracheal tube intubation, and duration of mechanical ventilation post-tracheotomy were recorded. There was a significant reduction for supraglottic (2.86 +/- 1.11 [mean +/- SD]) versus subglottic suction samples (2.48 +/- 1.07) (paired t test, P = 0.048; Wilcoxon test, P = 0.045) when all data pairs for normal flora and pathogens were combined across times. There was a significant reduction of normal flora pooled across times in 19 data pairs for supraglottic (3.00 +/- 1.05) versus subglottic suction samples (2.00 +/- 0.94) (paired t test, P = 0.0004; Wilcoxon test, P = 0.0007). There was no significant reduction of pathogens pooled across times in 25 data pairs for supraglottic (2.76 +/- 1.16) versus subglottic suction samples (2.84 +/- 1.03) (paired t test, P = 0.75; Wilcoxon test, P = 0.83). CONCLUSIONS: Proof-of-concept was confirmed. The Blom tracheotomy tube with disposable suction-above-the-cuff inner cannula decontaminated microorganisms from the subglottic space when normal flora and pathogens were combined. Future research should investigate if decreased quantity of normal flora and pathogens in the subglottic space reduces the incidence of ventilator-associated pulmonary complications in critically ill patients requiring ongoing mechanical ventilation via tracheotomy.

Cervical lymphadenopathy in adults has a broad differential diagnosis, including bacterial and viral infections, Kikuchi-Fujimoto disease, systemic lupus erythematosus, and various neoplasms. Many of its etiologies share similar symptomatology and presentations, which complicates the diagnosis. A thorough history and a comprehensive physical examination, to include nasopharyngoscopy and imaging as indicated by the specific case, are key to determining the origin of the lymphadenopathy and to avoid a missed or delayed diagnosis. Based on our review of the literature, we present the second reported case of anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma presenting in an adult with an obstructing adenoid/nasopharyngeal mass and lymphadenopathy. The mass, which occurred in a 19-year-old woman of Asian descent, caused nasal airway obstruction in the setting of cervical lymphadenopathy that was initially ascribed to mononucleosis.

BACKGROUND:Oral squamous cell carcinoma is the most common form of malignancy of the lip and oral cavity, often being proceeded by potentially malignant disorders (PMD). Early detection can reduce the malignant transformation of PMD and can improve the survival rate for oral cancer. The current standard of scalpel biopsy with histology is painful for patients and involves a delay whilst histology is completed; other tests are available that are unobtrusive and provide immediate results. OBJECTIVES/OBJECTIVE/: PRIMARY OBJECTIVE/OBJECTIVE:To estimate the diagnostic accuracy of index tests for the detection of oral cancer and PMD of the lip and oral cavity, in people presenting with clinically evident lesions. SECONDARY OBJECTIVE/OBJECTIVE:To estimate the relative accuracy of the different index tests. SEARCH METHODS/METHODS:The electronic databases were searched on 30 April 2013. We searched MEDLINE (OVID) (1946 to April 2013) and four other electronic databases (the Cochrane Diagnostic Test Accuracy Studies Register, the Cochrane Oral Health Group's Trials Register, EMBASE (OVID) and MEDION (Ovid)). There were no restrictions on language in the searches of the electronic databases. We conducted citation searches and screened reference lists of included studies for additional references. SELECTION CRITERIA/METHODS:We selected studies that reported the diagnostic test accuracy of the following index tests when used as an adjunct to conventional oral examination in detecting PMD or oral squamous cell carcinoma of the lip or oral cavity: vital staining, oral cytology, light-based detection and oral spectroscopy, blood or saliva analysis (which test for the presence of biomarkers in blood or saliva). DATA COLLECTION AND ANALYSIS/METHODS:Two review authors independently screened titles and abstracts for relevance. Eligibility, data extraction and quality assessment were carried out by at least two authors, independently and in duplicate. Studies were assessed for methodological quality using QUADAS-2. Meta-analysis was used to combine the results of studies for each index test using the bivariate approach to estimate the expected values of sensitivity and specificity. MAIN RESULTS/RESULTS:We included 41 studies, recruiting 4002 participants, in this review. These studies evaluated the diagnostic accuracy of conventional oral examination with: vital staining (14 studies), oral cytology (13 studies), light-based detection or oral spectroscopy (13 studies). Six studies assessed two combined index tests. There were no eligible diagnostic accuracy studies evaluating blood or salivary sample analysis.The summary estimates for vital staining obtained from the meta-analysis were sensitivity of 0.84 (95% CI 0.74 to 0.90) with specificity of 0.70 (0.59 to 0.79), with 14 studies were included in the meta-analysis. For cytology, sensitivity was 0.91 (0.81 to 0.96) and specificity was 0.91 (0.81 to 0.95) with 12 studies included in the meta-analysis. For light-based detection, sensitivity was 0.91 (0.77 to 0.97) and specificity was 0.58 (0.22 to 0.87) with 11 studies included in the meta-analysis. The relative test accuracy was assessed by adding covariates to the bivariate analysis, no difference in model fit was observed. AUTHORS' CONCLUSIONS/CONCLUSIONS:The overall quality of the included studies was poor. None of the adjunctive tests can be recommended as a replacement for the currently used standard of a scalpel biopsy and histological assessment. Given the relatively high values of the summary estimates of sensitivity and specificity for cytology, this would appear to offer the most potential. Combined adjunctive tests involving cytology warrant further investigation.

Improved survival rates among reproductive-age females diagnosed with cancer have increased the focus on long-term quality of life, including maintenance of the ability to conceive biological children. Cancer-directed therapies such as high-dose alkylating agents and radiation to the pelvis, which deplete ovarian reserve, radiation to the brain, which affects the hypothalamic-pituitary-gonadal axis, and surgical resection of reproductive structures can decrease the likelihood of having biological children. Standard fertility preservation strategies such as embryo and oocyte cryopreservation before the onset of therapy offer the opportunity to conserve fertility, but they may not be feasible because of the urgency to start cancer therapy, financial limitations, and a lack of access to reproductive endocrinologists. Ovarian tissue freezing is considered experimental, with limited data related to pregnancies, but it minimizes treatment delay. Studies evaluating gonadotropin-releasing hormone analogues have had mixed results, although a recent randomized, prospective study in women with breast cancer demonstrated a protective effect. Fertility preservation programs are increasingly being developed within cancer programs. In this article, we describe risks to infertility and options for preservation, raise psychosocial and ethical issues, and propose elements for establishing an effective fertility preservation program.

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.

Differential thermal nociception across inbred mouse strains has genetic determinants. Thermal nociception is largely attributed to the heat/capsaicin receptor TRPV1; however, the contribution of this channel to the genetics of thermal nociception has not been revealed. In this study we compared TRPV1 expression levels and electrophysiological properties in primary sensory neurons and thermal nociceptive behaviors between two (C57BL/6 and BALB/c) inbred mouse strains. Using immunofluorescence and patch-clamp physiology methods, we demonstrated that TRPV1 expression was significantly higher in isolectin B4 (IB4) -positive trigeminal sensory neurons of C57BL/6 relative to BALB/c; the expression in IB4-negative neurons was similar between the strains. Furthermore, using electrophysiological cell classification (current signature method), we showed differences between the two strains in capsaicin sensitivity in IB4-positive neuronal cell types 2 and 13, that were previously reported as skin nociceptors. Otherwise electrophysiological membrane properties of the classified cell types were similar in the two mouse strains. In publicly available nocifensive behavior data and our own behavior data from the using the two mouse strains, C57BL/6 exhibited higher sensitivity to heat stimulation than BALB/c, independent of sex and anatomical location of thermal testing (the tail, hind paw and whisker pad). The TRPV1 selective antagonist JNJ-17203212 inhibited thermal nociception in both strains; however, removing IB4-positive trigeminal sensory neurons with IB4-conjugated saporin inhibited thermal nociception on the whisker pad in C57BL/6, but not in BALB/c. These results suggest that TRPV1 expression levels in IB4-positive type 2 and 13 neurons contributed to differential thermal nociception in skin of C57BL/6 compared to BALB/c.