Faculty Bibliography

BACKGROUND:Lower T-junction wound dehiscence following breast reduction surgery or mastopexy constitutes a vexing and grievous complication both to the surgeon and the patient. Treatment modalities that can expedite wound healing and reepithelialization rates are highly craved. The objective of this study was to assess wound healing and epithelialization rates of open wounds following breast reduction and mastopexy wound dehiscence treated with charged polystyrene microspheres (CPM). MATERIALS AND METHODS/METHODS:Five female patients with wound dehiscence and subsequent open wounds following breast reduction and mastopexy were treated with daily with CPMsoaked dressings. Wound closure rates were documented. RESULTS:The wounds showed both accelerated granulation tissue formation as well as swift epithelialization rates. No complications or side effects were encountered. CONCLUSIONS:Charged polystyrene microspheres may offer a new and efficacious way to heal open wounds due to wound dehiscence following aesthetic breast surgery. Further research with a larger patient population is still needed to verify these findings. .

PURPOSE/OBJECTIVE:Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination. EXPERIMENTAL DESIGN/METHODS:Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m(2)) followed by 250 mg/m(2)/week and cisplatin 75 mg/m(2) q 3 weeks ×3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. RESULTS:A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median radiotherapy dose delivered was 70 Gy, 71.6% received all three cycles of cisplatin, and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% [95% confidence interval (CI), 33%-61%]. Two-year overall survival (OS) was 66% (95% CI, 53%-77%); median OS was not reached. Response rate was 66.7%. Most common grade ≥3 toxicities included mucositis (55%), dysphagia (46%), and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV(+) patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively). CONCLUSIONS:Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV(+) tumors.

OBJECTIVE:Deconditioning and frailty may contribute to dysphagia and aspiration. Early identification of patients at risk of aspiration is important. Aspiration prevention would lead to reduced morbidity and health care costs. We therefore wondered whether objective measurements of frailty could help identify patients at risk for dysphagia and aspiration. METHODS:Consecutive patients (n = 183) were enrolled. Patient characteristics and objective measures of frailty were recorded prospectively. Variables tested included age, body mass index, grip strength, and 5 meter walk pace. Statistical analysis tested for association between these parameters and dysphagia or aspiration, diagnosed by instrumental swallowing examination. RESULTS:Of variables tested for association with grip strength, only age category (P = .003) and ambulatory status (P < .001) were significantly associated with grip strength in linear regression models. Whereas walk speed was not associated with dysphagia or aspiration, ambulatory status was significantly associated with dysphagia and aspiration in multivariable model building. CONCLUSION/CONCLUSIONS:Nonambulatory status is a predictor of aspiration and should be included in risk assessments for dysphagia. The relationship between frailty and dysphagia deserves further investigation. Frailty assessments may help identify those at risk for complications of dysphagia.

BACKGROUND:The determination of in situ protein levels of ERCC1 with the 8F1 monoclonal antibody is prognostic of survival in patients with non-small cell lung cancer (NSCLC). The authors previously demonstrated that 8F1 recognizes a second nuclear antigen. This antigen was identified and its value as a biomarker of clinical outcomes analyzed. METHODS:The second antigen was identified by mass spectrometry. Protein identity and antibody specificity were confirmed through knockdown and overexpression experiments. Immunohistochemistry of 187 early-stage NSCLC samples and 60 head and neck squamous cell carcinomas (HNSCCs) was used to examine the influence of the second antigen on 8F1 immunoreactivity and its association with patient outcomes. RESULTS:Choline phosphate cytidylyltransferase-α (CCTα, also known as phosphate cytidylyltransferase 1 choline alpha [PCYT1A], a phospholipid synthesis enzyme regulated by RAS) is the second antigen recognized by 8F1. In NSCLC samples, CCTα contributed (rho, 0.38) to 8F1 immunoreactivity. In samples of squamous cell carcinomas of the lung, CCTα was found to be the dominant determinant of 8F1 immunoreactivity, whereas its contribution in other subtypes of lung cancer was negligible. High expression of CCTα, but not ERCC1, was found to be prognostic of longer disease-free survival (log-rank P = .002) and overall survival (log-rank P = .056). Similarly, in patients with HNSCC, CCTα contributed strongly to 8F1 immunoreactivity (rho, 0.74), and high CCTα expression was found to be prognostic of survival (log-rank P = .022 for disease-free survival and P = .027 for overall survival). CONCLUSIONS:CCTα is the second antigen detected by 8F1. High CCTα expression appears to be prognostic of survival in patients with NSCLC who are treated by surgery alone and patients with HNSCC. CCTα is a promising biomarker of patient survival and deserves further study.

Two forms of brainstem plasticity are known to occur: an immediate stimulus probability-based and learning-dependent plasticity. Whether these kinds of plasticity interact is unknown. We examined this question in a training experiment involving three phases: (1) an initial baseline measurement, (2) a 9-session training paradigm, and (3) a retest measurement. At the outset of the experiment, auditory brainstem responses (ABR) were recorded to two unfamiliar pitch patterns presented in an oddball paradigm. Then half the participants underwent sound-to-meaning training where they learned to match these pitch patterns to novel words, with the remaining participants serving as controls who received no auditory training. Nine days after the baseline measurement, the pitch patterns were re-presented to all participants using the same oddball paradigm. Analysis of the baseline recordings revealed an effect of probability: when a sound was presented infrequently, the pitch contour was represented less accurately in the ABR than when it was presented frequently. After training, pitch tracking was more accurate for infrequent sounds, particularly for the pitch pattern that was encoded more poorly pre-training. However, the control group was stable over the same interval. Our results provide evidence that probability-based and learning-dependent plasticity interact in the brainstem.

27 Background: Cancer is prevalent in the rapidly-growing Chinese-American community, yet little is known about symptom burden to guide comprehensive treatment planning. We evaluated symptom distress and symptom clusters in a large sample of Chinese-American patients with cancer. METHODS: Patients were consecutively recruited from four oncology practices and completed a translated cancer symptom scale. Latent class cluster analysis explored symptom distress clusters in patients. RESULTS: Of 1,436 patients screened, 94.4% were non-English speaking and 45.1% were undergoing active cancer therapy. The most common cancer sites were breast (32.6%), lung (14.8%), head and neck (12.5%), and hematologic (10.1%). Overall, 1,289 (89.8%) patients had > 1 symptom and 1,129 (78.6%) patients had > 2. The most prevalent symptoms were lack of energy (57.0%), dry mouth (55.6%), feeling sad (49.3%), worrying (47.5%), and difficulty sleeping (46.8%). Symptoms causing "quite a bit" or "very much" distress included: difficulty sleeping (37.9%), lack of appetite (37.2%), feeling nervous (35.8%), pain (35.2%), and worrying (34.0%). Four symptom distress clusters were identified: very low physical and psychological symptom distress (49.5%); very low physical and moderate psychological symptom distress (25.2%); moderate physical and psychological symptom distress (17.4%), and high physical and psychological symptom distress (7.8%). Patients in the last group reported lack of energy, difficulty sleeping, pain, feeling sad, and worrying. CONCLUSIONS: Symptom prevalence is high in community-dwelling, Chinese-American cancer patients and half experience moderate to high distress from clusters of physical symptoms, psychological symptoms, or both. These data have important implications for the development of effective interventions for symptom control.

Dysregulation of Janus kinase (JAK)-signal transducer and activator of transcription signaling is central to the pathogenesis of myelofibrosis (MF). JAK2 inhibitor therapy in MF patients results in a rapid reduction of the degree of splenomegaly, yet the mechanism underlying this effect remains unknown. The in vitro treatment of splenic and peripheral blood MF CD34(+) cells with the JAK1/2/3 inhibitor, AZD1480, reduced the absolute number of CD34(+), CD34(+)CD90(+), and CD34(+)CXCR4(+) cells as well as assayable hematopoietic progenitor cells (HPCs) irrespective of the JAK2 and calreticulin mutational status. Furthermore, AZD1480 treatment resulted in only a modest reduction in the proportion of HPCs that were JAK2V617F(+) or had a chromosomal abnormality. To study the effect of the drug on MF stem cells (MF-SCs), splenic CD34(+) cells were treated with AZD1480 and transplanted into immunodeficient mice. JAK2 inhibitor therapy did not affect the degree of human cell chimerism or the proportion of malignant donor cells. These data indicate that JAK2 inhibitor treatment affects a subpopulation of MF-HPCs, while sparing another HPC subpopulation as well as MF-SCs. This pattern of activity might account for the reduction in spleen size observed with JAK2 inhibitor therapy as well as the rapid increase in spleen size observed frequently with its discontinuation.

Maxillectomy followed by radiotherapy and/or chemotherapy can result in lacrimal blockage and the need for subsequent dacryocystorhinostomy (DCR). Endonasal endoscopic DCR, as opposed to external DCR, allows better accuracy and leaves no scar. To date no report was published regarding the results of endoscopic DCR in these patients. The current study presents a retrospective review of all patients with paranasal and skull base tumors who developed nasolacrimal duct blockage after ablative maxillectomy with or without radiotherapy and/or chemotherapy and underwent endonasal endoscopic DCR between January 2006 and October 2012 in a tertiary reference medical center. According to our results, ten patients underwent 11 subsequent endonasal endoscopic DCR. There were 6 men and 4 women with a median age of 55 years (range, 19-81 years); four suffered from benign tumors and six had malignant tumors. All underwent maxillectomy. Six received high-dose radiotherapy. Time interval between primary ablative surgery and endonasal endoscopic DCR was 18 months (range, 7-118 months). Silicone stents were removed after median period of 11 weeks (range, 1-57 weeks). Nine out of ten patients experienced symptomatic improvement following one endonasal endoscopic DCR. One patient had recurrent epiphora and underwent a successful endonasal endoscopic revision DCR. In conclusion, endonasal endoscopic DCR in patients with paranasal and skull base tumors, who previously underwent maxillectomy, is generally successful and not associated with a high rate of complications or failure. Moreover, our findings may suggest that silicone stents can be removed shortly after the operation with high success rate.

IMPORTANCE/OBJECTIVE:Prior to applying or interviewing, most prospective applicants turn to the Internet when evaluating residency programs, making maintenance of a comprehensive website critical. While certain "intangibles" such as reputation may not be communicated effectively online, residency websites are invaluable for conveying other aspects of a program. Prior analyses have reported that certain criteria such as research experience and didactics are important considerations for applicants. OBJECTIVE:To evaluate the comprehensiveness of otolaryngology residency websites. DESIGN AND PARTICIPANTS/METHODS:Review of otolaryngology residency program websites. Websites of 99 civilian residency programs were searched for the presence of 23 criteria. MAIN OUTCOMES AND MEASURES/METHODS:Presence of 23 criteria for application process, incentives, instruction, research, clinical training, and other. RESULTS:Only 5 programs contained at least three-quarters of the criteria analyzed; on average programs reported less than 50% of information sought. Among the 99 residency program websites, a description of the following criteria was noted: comprehensive faculty listing (88%), didactics (80%), contact e-mail (77%), current residents (74%), description of facilities (70%), intern schedule (70%), research requirements (69%), otolaryngology rotation schedule (64%), other courses (61%), ERAS (Electronic Residency Application Service) link (55%), year-to-year responsibility progression (47%), call schedule (40%), active/past research projects (37%), area information (34%), message from the program director (33%) or chair (23%), selection criteria (30%), salary (directly on site) (23%), surgical statistics (18%), parking (9%), and meal allowance (7%). The mean (SD) percentage present of factors encompassing "clinical training" was 55% (23%), significantly higher than the mean (SD) percentage of factors covered under the "incentives" category (19% [11%]; P = .01). The proportion of overall criteria present on websites did not differ on organizing programs by region (range, 42%-49%). Sites for "large" programs (≥3 residents per year) were more comprehensive (49% vs 42%; P = .04). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:While further survey of prospective applicants would be invaluable in determining which factors are of greatest interest, many residency websites appear to be inadequately comprehensive. Despite the relative comprehensiveness of criteria relevant to clinical training when compared with other aspects of websites such as incentives, several crucial aspects of training are still not addressed in many sites.

BACKGROUND:Patient characteristics, risk factors, and microbiology are important to consider in the management of complications of acute bacterial sinusitis (ABS) in pediatric patients. This study evaluates this subset of patients and compares them to patients that undergo surgery for chronic rhinosinusitis (CRS). METHODS:This study is a retrospective review of all pediatric patients from 2002 to 2011, who underwent sinus surgery at a tertiary hospital. Patients who underwent surgery for ABS complication were compared to patients who underwent surgery for CRS. Statistical analysis was completed using chi-square test or Fisher's exact test with a statistical significance set at p<0.05. RESULTS:Twenty-seven patients with a complication of ABS and 77 patients with CRS were analyzed. The groups did not differ demographically. Patients with a complication were statistically less likely to have seasonal allergies, prior sinusitis, prior nasal steroid use, or adenoidectomy (p<0.05). In addition, they had more frequent involvement of ethmoid and frontal sinuses (p<0.05). The most common cultures results were no growth (30.8%), Streptococcus milleri (30.8%), and normal flora (19.2%) in ABS for the with a complication group, and normal flora (41.5%), coagulase negative Staphylococcus (22%), and Propionobacterium (19.5%) for the CRS group. Most prevalent complications were preseptal cellulitis (55.5%), orbital subperiosteal abscess (29.6%), subgaleal abscess (22%), and epidural abscess (22%). Five patients had simultaneous orbital and intracranial complications. CONCLUSIONS:Patients who present with complications of ABS vary significantly from the CRS patients. Location of most commonly affected sinuses and microbiology also differ and is crucial for understanding the management of this disease process.