bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Translation‐Ready Combination Cancer Immunotherapy Regimen Based on Clinically Available Drugs
Authors: Kidwai Sarah M. , Jayaraman Padmini , Sikora Andrew G. 
Published: September 2014

Objectives:Immunosuppressive immunocytes induced by cancer‐associated inflammation, such as myeloid derived suppressor cells (MDSC) and T‐regulatory cells (Treg), mediate immune‐escape critical to development of solid tumors, including melanoma and oral squamous cell carcinoma (OSCC). Novel therapeutic approaches, which block tumor‐mediated immunosuppression, unmasking endogenous anti‐tumor immune responses, are thus a rational treatment approach. The aims of the study were: (1) Demonstrate that inhibition of inducible nitric oxide synthase (iNOS, critical for MDSC development) and Treg depletion in preclinical cancer models leads to potent anti‐tumor activity; (2) Design a regimen suitable for testing in clinical trials.Methods:Mouse bone marrow cells were co‐cultured with MT‐RET melanoma supernatants ex vivo to generate MDSC in the presence of doxycycline, an iNOS inhibitor. C57/BL6 wild‐type mice were injected with syngeneic MT‐RET‐1 melanoma. Tumor‐bearing mice were treated with injection(s) of cyclophosphamide and/or doxycycline. Tumor growth and survival times were measured, and tumors and spleens harvested for CD8+ T‐cell and other immunocyte levels.Results:In co‐cultures, induction of MDSC was significantly reduced in the presence of doxycycline. Treatment of MT‐RET melanoma‐bearing C57/B16 mice with doxycycline resulted in tumor‐infiltrating CD8+ T cells enhancement and tumor growth suppression. Treatment with cyclophosphamide suppressed intratumoral Treg accumulation. Dual treatment with cyclophosphamide and doxycycline suppressed tumor growth more efficiently than either alone.Conclusions:Treatment with the immunomodulators doxycycline and cyclophosphamide is a promising approach to reversing tumor‐mediated immunosuppression and suppressing cancer growth in solid tumors, like melanoma and OSCC. Thus, we have designed a window of opportunity clinical trial of doxycycline and cyclophosphamide before surgical resection of OSCC.
Early Oral Feeding versus Delayed Oral Feeding in Patients following Total Laryngectomy: A Systematic Review
Authors: Hay Ashley , Pitkin Lisa , Mathew Rajeev , Gurusamy Kurinchi 
Published: September 2014

Objectives:Assess the effects of early oral feeding in laryngectomy patients (before 7 days) versus delayed or late oral feeding (7 days or later).Methods:We considered randomized controlled trials (RCTs) irrespective of the use of blinding, language status, date of publication, setting, or sample sizes. The outcomes used were mortality, pharyngo‐cutaneous fistula rate, quality of life, hospital length of stay, and complications. To improve harmful effect estimates, trials with early oral feeding groups and a control group were also considered. We analyzed the data with fixed effect and random effect models and present the rate ratios, risk ratio, or mean difference.Results:We included 4 RCTs and 3 case controlled trials with 393 participants for assessment of harmful effects. The risk of bias in all trials was high. There was no statistically significant difference detected in mortality rates at 6 months, pharyngo‐cutaneous fistula rate, or complications between intervention and control groups. There was no data on quality of life. The length of hospital stay was shorter in the intervention early feeding group, mean difference effect estimate and confidence intervals using fixed effect model –2.72 [–5.34, –0.09] in favor of early oral feeding.Conclusions:The low quality of evidence does not support a change in practice. However, in an appropriate selected patient group early oral feeding has been used and there has been no detectable difference in mortality or complication rates. A shorter hospital stay was seen but was supported by limited evidence.
Factors Affecting Delays to Surgery for Oral Tongue Carcinoma in the National Cancer Data Base
Authors: Nocon Cheryl C. , Liederbach Erik , Sisco Mark , Yao Katherine , Gerber Mark E. , Lewis Carol M. , Bhayani Mihir K. 
Published: September 2014

Objectives:Surgery is the definitive treatment for oral tongue squamous cell carcinoma (OSCC). Studies have described correlates of delayed diagnosis. However, little is known about treatment delays after diagnosis. This study investigates time intervals from diagnosis to surgery for OSCC using the National Cancer Data Base (NCDB).Methods:The NCDB was queried for OSCC patients initially treated with surgery in 1998 through 2009. Patients were dichotomized based on time to surgery relative to the median. Chi‐square and multivariable logistic regression models were used for statistical analyses.Results:A total of 14,270 patients were identified. The median age was 60 years (range, 18‐90 years). For all stages, the median time from diagnosis to surgery was 27 days (SD = 42). Factors that predicted a longer interval to surgery included: advanced stage (28 days), Hispanic ethnicity (29 days), lack of health insurance (29 days), treatment at an academic/research facility (29 days), residence >75 miles from the hospital (31 days), treatment in the Middle (29 days) and South Atlantic (28 days) states, and having a referral to a different treating center (30 days). The strongest predictors of time delay were having a referral (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.83‐2.13, P <. 001) and geographic location (Middle Atlantic: OR 1.83, 95% CI 1.57‐2.14, P <. 001).Conclusions:There is significant variation in the time from diagnosis to surgery for patients with OSCC. Several patient, geographic, and facility factors predict treatment delays. These findings can be used as a benchmark for quality of care and to guide further investigation into whether timing disparities affect outcomes.
Head and Neck Cancers: Why Is It Better to HPV than Not to HPV?
Authors: Baruah Paramita , Lee Michael S. W. , Wilson Phil , Kaski Juan Carlos , Dumitriu Ingrid E. 
Published: September 2014

Objectives:Dissect the impact of human papillomavirus (HPV) on angiogenesis in head and neck cancers (HNSCC).Methods:We analyzed 18 newly diagnosed HNSCC patients and controls. HPV tumor status was ascertained by p16 staining. Eleven pro‐ and anti‐angiogenic factors were quantified in sera using a multiplex assay. Angiogenic factors were analyzed in the tumor tissue using immunohistochemistry.Results:We found that circulating levels of anti‐angiogenic factor endostatin were higher in all HNSCC patients compared with healthy subjects irrespective of HPV status. Notably, we detected higher levels of the proangiogenic factors angiopoetin‐1 and vascular endothelial growth factor (VEGF) in the circulation of HPV‐negative patients compared with patients with HPV‐positive tumors. Interestingly, levels of thrombospondin‐2, an antiangiogenic factor, were lower in the circulation of patients with HPV‐positive compared with HPV‐negative tumors and healthy controls. We next analyzed these angiogenic factors in the tumor tissue. Interestingly, while HPV‐negative tumors exhibited VEGF expression both in tumor tissue and stromal cells, only a fraction of HPV‐positive tumors exhibited VEGF expression in tumor tissue. Angiopoietin‐1 was expressed in tumor cells as well as endothelial cells in the stroma. Another interesting finding was that macrophages in HNSCC had an M2 “alternatively activated” phenotype and appeared to be the major source of endostatin in the stroma.Conclusions:Our novel results indicate that angiogenic factors are differentially expressed in the circulation and tumor tissue in HPV‐positive and HPV‐negative HNSCC and could potentially confer a more aggressive phenotype to HPV‐negative tumors.
Diode Laser for the Treatment of Telangiectasias following Hemangioma Involution
Authors: Cerrati Eric W. , O Teresa M. , Waner Milton 
Published: September 2014

Objectives:Infantile hemangiomas are the most common benign tumor of infancy and are well known for their rapid growth during the first 6 to 9 months of life, followed by a spontaneous but slow involution. The standard of care is to treat these lesions at an early age with propranolol to expedite the involution process. Residual telangiectasias often result following involution. We evaluated the efficacy of using a diode laser as an adjunct treatment for cervicofacial infantile hemangiomas.Methods:Twenty patients, aged 4 months to 11 years, underwent treatment with a 532‐nm diode laser as part of the management for their hemangiomas. The fluence was 10.2 to 25 J/cm2, pulse durations of 36 to 44 ms, spot sizes of 0.7 to 2 mm, and pulse frequency of 3 to 5 Hz. All procedures were performed in the operating room. In order to assess the efficacy, pre‐ and posttreatment digital photography were evaluated independently by the authors and ranked on a 0 to 4 point scale (0 = no change and 4 = complete response). Adverse reactions were also recorded.Results:The telangiectasias showed significant improvement following treatment. In more than half of the patients treated, the affected area demonstrated a complete response. No adverse reactions were noted.Conclusions:A 532‐nm diode laser effectively treats the remaining telangiectasias following hemangioma involution. The treatment is well tolerated and demonstrates excellent results. Whether used independently or in conjunction with other treatment modalities, the diode laser should be part of the surgical armamentarium when treating infantile hemangiomas.
Hospital Volume and Failure to Rescue in Head and Neck Cancer Surgery
Authors: Mulvey Carolyn L. , Gourin Christine G. 
Published: September 2014

Objectives:(1) Apply the concept of failure to rescue to outcomes research in head and neck cancer (HNCA) surgery. (2) Understand the relationship between hospital volume and failure to rescue.Methods:Discharge data from the Nationwide Inpatient Sample for 159,301 patients who underwent an ablative procedure for a malignant oral cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasm in 2001 to 2010 were analyzed using cross‐tabulations and multivariate regression modeling. Failure to rescue was defined as death after a major complication including acute myocardial infarction, acute renal failure, venous thromboembolism, pneumonia, gastrointestinal bleed, pulmonary failure, hemorrhage, or surgical site infection. We compared the incidence of mortality, complications, and failure to rescue across hospital volume tertiles.Results:The majority of hospitals performing HNCA surgery were low‐volume hospitals (N = 7635), which performed an average of 6 cases per year. Intermediate‐volume hospitals (N = 729) performed a mean of 37 cases per year, and high‐volume hospitals (N = 207) performed a mean of 131 cases per year. High‐volume hospitals were associated with significantly decreased odds of death (0.7% vs 1.0%, odds ratio [OR] 0.56 [0.46‐0.86]) compared with low‐volume hospitals. There was no significant difference in major complication rates at high‐volume hospitals compared with low‐volume hospitals (18.5% vs 15.6%, OR 0.96 [0.80‐1.15]); however, high‐volume hospitals were associated with significantly decreased failure to rescue rates (3.1% vs 4.4%, OR 0.56 [0.33‐0.97]) compared with low‐volume hospitals.Conclusions:Improved survival among patients undergoing HNCA surgery at high‐volume hospitals appears to be associated with differences in the response to and management of complications, rather than differences in complication rates.
Hypothyroidism following Hemithyroidectomy
Authors: Merchavy Shlomo , Marom Tal , Forest Veronique‐Isabelle , Wolff Benjamin M. , Mlynarek Alex M. , Hier Michael P. , Payne Richard J. 
Published: September 2014

Objectives:Assess the rate of hypothyroidism following hemithyroidectomy.Methods:A retrospective study in adult patients undergoing hemithyroidectomy at the McGill University Thyroid Cancer Centre, during the years 2007 through 2012. Patients with preoperative hypothyroidism were excluded. Patients were followed 12 to 60 months after the primary surgery, and preoperative thyroid stimulating hormone (TSH) and free T4 levels were compared before and after the surgery. Hypothyroidism was defined as TSH levels >4.5 mU/L.Results:Of the 181 eligible patients in this study, 137 (75%) were females, with a mean age of 49.1 ± 14.3 years. The most common indication for surgery was follicular lesion. Hypothyroidism occurred in 65 (35%) of the patients, and was diagnosed at 1 to 36 months after surgery. Age and sex were not found to be risk factors for post‐hemithyroidectomy hypothyroidism.Conclusions:In this study 35% of patients undergoing hemithyroidectomy develop postoperative hypothyroidism. Upon preoperative patient counseling, hypothyroidism is a major morbidity that should be thoroughly discussed.
Learning Curves of Syllabus Head and Neck Procedures; Monitoring Trainees Performance and Progress
Authors: Awad Zaid , Hayden Lindsay , Muthuswamy Keerthini , Ziprin Paul , Darzi Ara , Tolley Neil S. 
Published: September 2014

Objectives:Otolaryngology trainees undergo regular procedure‐based assessments (PBAs) throughout training; however, these are rarely used to analyze performance and monitor progress. The aim of the study was to validate PBA in assessing otolaryngology trainees in head and neck surgery (HNS) and identify the pattern by which trainees progress in syllabus HNS procedures.Methods:We analyzed all PBAs from North‐Thames otolaryngology trainees, during early years or core (CT) and more senior specialty training (ST) years from 2008 to 2013. We used mean scores and standard deviations to draw procedure‐specific learning curves. The PBA tool is procedure‐specific. It is produced by the Joint Committee of Surgical Training and is used in assessing UK surgical trainees performance in all specialties. The tool is composed of 6 main domains: consent, planning, preparation, exposure/closure, technique, and postoperative care.Results:A total of 3306 PBAs from 46 trainees were identified; 1806 were HNS. PBA reliability was shown by high internal consistency (Cronbach's Alpha:0.921) and discriminated between grades (CT and ST, Mann‐Whitney U: P <. 001) and levels (CT1‐2 and ST3‐8, Kruskal Wallis: P <. 001). All domains correlated with overall performance, but the best predictor was technical skills. A total of 7 HNS procedures achieved sufficient power to draw learning curves (n > 100, 90% confidence): tonsillectomy: 309, pan‐endoscopy: 186, microlaryngoscopy: 174, thyroidectomy: 152, tracheostomy: 137, adenoidectomy: 129, and lymphadenectomy: 101.Conclusions:Procedure‐specific learning curves can be drawn to set milestones and deliver targeted training. Curves of various HNS procedures plateau at different stages in training. This method is more robust and should replace arbitrary numbers as a measure of competence.
Limitations of 8F1 Biomarker for Platinum‐Resistance in HNSCC Are Explained by Co‐detection of PCYT1A
Authors: Kass Jason I. , Sheth Siddharth , Gooding William , Wang Lin , Vaezi Alec E. , Austin Melissa C. , Bauman Julie E. 
Published: September 2014

Objectives:(1) Recognize how ERCC1 biomarker development in HNSCC has been impaired by use of 8F1, a nonspecific ERCC1 antibody, which also recognizes PCYT1A, a protein unrelated to DNA repair capacity. (2) Verify that specific ERRC1 antibodies, 4F9 and FL297, were more useful than 8F1 for prognosis of HNSCC patients undergoing cisplatin‐radiation on a phase II trial. (3) Demonstrate the relative contribution of PCYT1A and ERCC1 in variation of 8F1 expression.Methods:We hypothesized that co‐detection of PCYT1A could explain variation in 8F1 expression, and account for lost prognostic performance as compared with 4F9 and FL297. Pre‐treatment tissue from 75 trial patients with previously characterized 4F9, FL297, and 8F1 expression was stained for PCYT1A. Quantitative digital IHC was performed, blinded to clinical outcomes. Expression was compared among the 4 antibodies.Results:High expression of 4F9 (hazard ratio [HR] 3.12; P =. 02) and FL297 (HR 2.45; P =. 025) were associated with poor progression‐free survival (PFS). Neither 8F1 (HR 1.55; P =. 29) nor PCYT1A expression (HR 1.89; P =. 13) was associated with PFS. 4F9 and FL297 demonstrated high correlation (0.878). 8F1 demonstrated moderate correlation with 4F9 (0.55) and FL297 (0.467), and high correlation with PCYT1A (0.725). In a three‐dimensional regression analysis, both 4F9 (T = 4.26, P <. 001) and PCYT1A (T = 4.58, P <. 001) were significant predictors of 8F1 variation, suggesting equivalent influence from ERCC1 and PCYT1A detection in 8F1 scoring.Conclusions:ERCC1 expression by specific antibodies is a resistance biomarker for platinum‐based therapy in HNSCC. Although 8F1 detects ERCC1, cross‐reactivity with PCYT1A confounds 8F1 scoring. Because of nonspecificity, 8F1 should be abandoned.
Metabolic Tumor Volume as a Prognostic Factor for Oral Cavity Cancer Treated with Primary Surgery
Authors: Zhang Han , Abele Jonathan T. , Jeffery Dean T. , Seikaly Hadi , Harris Jeffrey R. , O'Connell Daniel A. 
Published: September 2014

Objectives:Metabolic tumor volume (MTV) obtained from pretreatment 18F‐fluorodeoxydeglucose positron emission tomography with computed tomography (PET‐CT) has been validated as an independent predictive factor of outcomes in head and neck cancer patients (HNC) treated with primary chemoradiotherapy (CRT). However, its role in patients treated with primary surgery has not yet been studied. The aim of the study was to evaluate the prognostic value of MTV in patients treated with primary surgery for oral cavity squamous cell carcinoma (OCSCC).Methods:Demographic and survival data were obtained from patients diagnosed with OCSCC from 2008 to 2012 in Alberta, Canada. All patients included in the study had positron emission tomography–computed tomography (PET‐CT) scan before curative surgical resection. MTV and maximum standardized uptake value (SUVmax) was delineated from pretreatment PET‐CT scans using Segami Oasis software (Columbus, OH).Results:A total of 80 patients were analyzed using SPSS (SPSS Inc, Chicago, IL). Five‐year overall, disease‐specific, and disease‐free survival using Kaplan‐Meier curves were 72%, 79%, and 78% respectively. An increase in MTV of 17.5 mL (difference between the 75th and 25th percentile) was associated with a 1.9‐fold increase in risk of disease recurrence (P <. 001) and a 2.0‐fold increase in the risk of death (P <. 05). SUVmax was not associated with either outcome. Cox‐Regression analysis showed MTV predicted overall (hazard ratio [HR] = 1.22; P <. 0001), disease‐specific (HR = 1.62; P <. 0001), and disease‐free (HR = 1.97; P <. 0001) survival.Conclusions:This study shows that MTV is an adverse prognostic factor for death and disease recurrence in OCSCC treated with primary surgery.
Multimodality Management of High‐Risk Head and Neck Basal Cell Carcinoma Requiring Free Flap Reconstruction
Authors: Burch Major B. , Chung Thomas K. , Schmalbach Cecelia E. , Rosenthal Eben L. 
Published: September 2014

Objectives:(1) Determine the impact of adjuvant radiotherapy on high‐risk head and neck basal cell carcinoma (H&N BCC). (2) Analyze risk factors associated with recurrence and survival.Methods:Case series with planned chart review (2002‐2013) in an academic tertiary care center. A total of 431 consecutive patients presented with H&N defects requiring free flap reconstruction, 38 specifically for aggressive BCC. Cases were classified as high risk based on National Comprehensive Cancer Network (NCCN) criteria. Overall and disease‐free survival were examined using Kaplan‐Meier analysis. Independent variables included: site, recurrent tumor, radiation, bony involvement, and perineural invasion. Complications were reported.Results:Nineteen (50%) lesions were recurrent. Mean tumor diameter was 5.17 cm (1.2‐15.0cm). Mean follow‐up was 19.9 months. Overall 2‐year survival was 80%, falling to 66% at 5 years. Two‐year disease‐free survival was 72%. Six patients recurred (5 local; 1 distant). Adjuvant radiotherapy was utilized in 17 (44.7%) and did not significantly impact recurrence (P =. 15) or survival (P =. 48). Tumors >2.5 cm did not impact survival (P =. 09), regardless of subsite. Bony involvement was identified in 17 (44.7%) cases, but did not correlate with survival (P =. 18). Complication rates: 4 exposed bone, 4 hematoma/seroma, 3 infection, 2 osteoradionecrosis, 2 donor site evisceration, 2 ear canal stenosis, 1 severe trismus, 1 flap arterial insufficiency, 1 nasal obstruction.Conclusions:Larger H&N BCC do not confer worse outcomes, independent of subsite. Adjuvant radiotherapy does not improve survival or recurrence. Bony involvement does not correlate with survival and should not preclude surgical intervention, even in advanced cases.
The Impact of Physician Extenders in an Academic Otolaryngology Residency Program: Initial Experiences
Authors: Rajasekaran Karthik , Benninger Michael S. , Kominsky Alan , Bryson Paul C. 
Published: September 2014

Objectives:A physician extender is a licensed health care provider who performs medical activities typically performed by a physician. The term encompasses highly trained health care professionals such as physician assistants, nurse practitioners, and midlevel practitioners. In our academic, tertiary care otolaryngology residency‐training program, a physician extender was recently hired. The objective of this study was to evaluate his impact on resident quality of life and education as well as his productivity.Methods:All otolaryngology residents at an academic tertiary care medical center were issued a questionnaire that they answered anonymously. All inpatient consults seen by the physician extenders and residents over an 18‐month period between June 2012 and December 2013 were prospectively captured and evaluated.Results:The results of the survey indicated that all residents unanimously agreed that a physician extender had a positive impact on resident education, patient care, and quality of life. There was no statistically significant difference in the types of consults seen by a physician extender and those seen by a resident. The physician extender enhanced departmental productivity on the inpatient consultation service.Conclusions:Physician extenders are valuable assets to academic otolaryngology residency programs. Their presence enhances patient access, care, and departmental productivity. They have a positive impact on resident quality of life and augment resident education.