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To determine whether annual surgeon volume of lateral neck dissections for squamous cell carcinoma is associated with complication rates.Retrospective review.Two US databases spanning 2000 to 2014.Neck dissections for squamous cell carcinoma from the National Inpatient Sample and State Inpatient Databases were analyzed. The primary outcome was any in-hospital complication common to neck dissection. The principal independent variable was surgeon volume. A multivariable logistic generalized estimating equation with a piecewise linear spline for surgeon volume was fit to assess its association with complication.The National Inpatient Sample had 3517 discharges fitting criteria, a median surgeon volume of 12, and an 11.1% complication rate. A 1-unit increase in surgeon volume was associated with a 7% increase in the odds of complication when volume ranged between 4 and 19 (adjusted odds ratio [AOR], 1.07; 95% CI, 1.04-1.11) and with a 3% decrease in the odds of complication when volume ranged between 19 and 51 (AOR, 0.97; 95% CI, 0.96-0.99). The State Inpatient Databases had 2876 discharges fitting criteria, a median surgeon volume of 30, and a 13.5% complication rate. Surgeon volume was not associated with complication when27 (AOR, 1.01; 95% CI, 0.99-1.02), but a 5-unit increase in volume was associated with a 7% decrease in the odds of complication with volume ≥27 (AOR, 0.93; 95% CI, 0.88-0.98).Surgeon volume was associated with complications for most volume ranges and with lower odds of complication for high-volume surgeons.

ObjectivePharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide.Materials and MethodsFour healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration.ResultsThere were 3,076 human, 332 S. mitis, 102 G. haemolyans and 42 G. adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and ∼300 proteins that had a pConclusionThis pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotide’s effects on saliva and reports of improved PCF healing.

Surgical and traumatic defects of the face present a reconstructive challenge to restore facial symmetry. The cervicofacial flap is a rotational and advancement flap with random blood supply utilized to close moderate- to large-sized defects of the cheek. Subcutaneous dissection of the cervical region allows for a large amount of tissue mobilization. Depending on the location of the cheek defect, the flap can be pedicled either anteriorly or posteriorly. This article presents the authors’ preferred surgical technique as well as reported surgical variations. Routine postoperative care and management of potential complications are discussed.

Contains fulltext : 220094.pdf (Publisher’s version ) (Open Access) BACKGROUND: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. METHODS: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. RESULTS: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4-23.4) and 8.0% (95% CI 2.7-13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0-6.1%), 2.0% (95% CI 0.9-3.1) and 0.4% (95% CI 0-1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0-1.3). CONCLUSIONS: The incidence of occult lymph node metastasis is higher in supraglottic and T3-4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors.

Importance Pharyngocutaneous fistula (PCF) is a serious complication after total laryngectomy. Despite the well-described clinical risk factors for PCF and its association with poor quality of life, there is a paucity of data on the nonclinical factors that may be associated with this complication. Objective To determine whether nonclinical risk factors (eg, age, sex, race and ethnicity) are associated with an increased risk of developing a PCF after total laryngectomy, and whether or not the method of reconstruction explains any differences found. Design, setting, and participants This retrospective multicenter cohort study used data from a nationally validated, risk-adjusted, outcomes-based, surgical quality improvement database (the National Surgical Quality Improvement Program) to examine outcomes in patients who underwent a total laryngectomy from 2005 to 2018. The database was queried from January 1, 2005, to December 31, 2018; data analyses were performed from September 1, 2020, to March 31, 2021. Main outcomes and measures The primary outcome was development of a PCF within 30 days of a total laryngectomy. Patient characteristics, including age, sex, race and ethnicity, comorbidities, and mode of reconstruction, were analyzed. Results A cohort of 1573 adult patients (median age [IQR], 63 [56-71] years; 1280 [81.4%] men; 293 [18.6%] women; 1001 [63.6%] non-Hispanic White individuals) had undergone a total laryngectomy during the study period and were included in the analyses. The overall rate of PCF formation was 4.3% (68 of 1573 patients). Hispanic patients had the highest rate (9.5%; 9 of 95 patients) of PCF formation, which was more than twice the rate among non-Hispanic White patients (3.8%; 38 of 1001) and non-Hispanic Black patients (4.7%; 11 of 236). After adjusting for clinical and other covariates, women were 1.9 times more likely to develop a PCF compared with men (adjusted odds ratio, 1.90; 95% CI, 1.08-3.35). We also found that the odds of developing a PCF were 3-fold higher among Hispanic patients compared with non-Hispanic White patients (adjusted odds ratio, 2.96; 95% CI, 1.36-6.47). The type of reconstruction did not differ across age or race and ethnicity after controlling for clinical risk factors. Conclusions and relevance This multicenter cohort study found that 2 nonclinical risk factors-Hispanic ethnicity and female sex-were associated with an increased risk of PCF formation. Knowledge of these risk factors should be included in patient-physician decision-making as well as future interventions to decrease the rate of PCF formation after laryngectomy.

Squamous cell carcinoma of the hypopharynx is relatively uncommon, accounting for about 4 % of all head and neck tumors, with approximately 3400 new cases diagnosed annually. However, these tumors are associated with the lowest survival rates when compared to squamous cell carcinomas in other subsites of the head and neck. This in part is due to the fact that tumors in this location tend to cause symptoms late in the course of the disease and, thus, tend to present in advanced stages. Another characteristic is their predilection for local aggressiveness, submucosal spread, and high metastatic potential.

Report the prevalence and risk factors of liver metastasis in head and neck squamous cell carcinoma (HNSCC) while evaluating the utility of liver function tests (LFTs) in detection of such metastases.Case series with chart review.Tertiary referral center.Of 745 patients with newly diagnosed HNSCC (oral cavity, oropharynx, hypopharynx, larynx) treated at University of North Carolina hospitals from 1989 to 2005, 655 had sufficient data for analysis.Prevalence of liver metastasis was 3% (20/655) with 7 patients demonstrating early metastasis and 12 with late metastasis. Oropharyngeal and hypopharyngeal lesions constituted 65% of identified liver metastasis but only 39% of the study population. Patients with oropharyngeal lesions were most likely to develop liver metastasis (P = .047). Abnormal LFTs were seen in 26% of all patients. Overall sensitivity and specificity were 45% and 75%. Seventy-five percent of patients with liver metastasis had stage IV disease at diagnosis and were more likely to have abnormal LFTs than other stages (P = .048). In these patients, 2.2% (8/365) had liver metastases and abnormal LFTs, whereas 1.9% (7/365) had liver metastases and normal LFTs. Sensitivity for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase 0%, 10%, 20%, and 30%, respectively. Specificities ranged from 88.0% to 94.3%. Positive predictive values were poor, with the highest being 10.5%.Liver metastases are rare in HNSCC and often delayed in presentation. This study clearly reveals that LFTs do not reliably identify patients with liver metastasis and do not provide physicians with an adequate screening modality in this population.

Objectives/hypothesis Despite its negative impact on cancer patients, there are few animal models of cancer cachexia. Our hypothesis was that different human cell lines would variably induce cachexia. Study design Prospective animal study. Methods We established two xenograft models in athymic mice and compared these with a cachexigenic cell line, the murine adenocarcinoma 16 (MAC16) cell line. Eight-week-old female, athymic mice were injected with human head and neck cell lines (JHU022, JHU012) and the MAC16 cell line. Body weight, food intake, body composition, leg weights, serum cytokines, and lipid mobilizing factor (LMF) were compared. Results Mean food intake for all groups was equivalent. Mean percent change in body weight after 18 days was 18%, 19%, 12%, and 3% for control, JHU012, JHU022, and MAC16 experimental groups, respectively. Both JHU022- and MAC16-injected mice showed wasting even when tumor burden was low. In contrast, mice injected with JHU012 developed larger tumors yet lacked evidence of cachexia. These mice demonstrated loss of lean body mass but not fat mass. Serum cytokine levels for interleukin (IL)-1 alpha and IL-1 beta were elevated in JHU022-bearing mice, whereas IL-1 alpha, IL-6, interferon (IFN)-gamma, and tumor necrosis factor alpha (TNF)-alpha were elevated in MAC16-bearing mice. LMF was present in both the JHU022 and JHU012 cell lines. Conclusions The JHU022 cell line caused more severe cachexia than the JHU012 cells, suggesting these cell lines may be used to further study cancer cachexia. IL-1 alpha and IL-1 beta in the JHU022 model may be mediators of cachexia, whereas TNF-alpha, IFN-gamma, and IL-6 may be mediators in MAC16-induced cachexia.

Cancer cachexia is a morbid wasting syndrome common among patients with head and neck cancer. While its clinical manifestations have been well characterized, its pathophysiology remains complex. A comprehensive literature search on cancer cachexia was performed using the National Library of Medicine's PubMed. The Cochrane Library and Google search engine were also used. Recent evidence and new concepts on the pathophysiology of cancer cachexia are summarized. Targeted therapies are presented, and new concepts are highlighted. Cancer cachexia is characterized by complex, multilevel pathogenesis. It involves up-regulated tissue catabolism and impaired anabolism, release of tumor-derived catabolic factors and inflammatory cytokines, and neuroendocrine dysfunction. These culminate to create an energy-inefficient state characterized by wasting, chronic inflammation, neuroendocrine dysfunction, and anorexia.

Limited data exist regarding the feasibility of ultrasound-guided transcutaneous biopsy of the base of the tongue and floor of the mouth. This retrospective study reviewed 8 cases with lesions in the base of the tongue or floor of the mouth that were biopsied by fine-needle aspiration. Core biopsy was also needed in 1 case. All biopsies were technically successful, and all yielded squamous cell carcinoma. One biopsy yielded a false-positive result, as subsequent resection yielded high-grade dysplasia with no invasion. The other biopsy results were considered true-positive based on subsequent pathologic examinations (2 cases) or clinical/imaging follow-up (5 cases). There were no significant complications associated with the biopsies.

Objectives: To evaluate patients 25 years of age or younger who were treated for nasopharyngeal carcinoma. Study Design: Retrospective review, systematic literature review. Methods: Nasopharyngeal carcinoma (NPC) is rare in the Western world. In people younger than 30 years, it is even less common, with an incidence of 1 to 2 per million. This retrospective study was designed to analyze the outcomes of patients 25 years of age or younger who were treated for NPC at a tertiary care academic medical center. Between November 1982 and December 2004, 15 patients meeting the above criteria were treated. These patients form the basis for this report. A systematic review of all NPC trials published in the United States since 1990 was done and the results compared with those of our cohort. Results: Young African Americans represented 67% of the 15 cases seen at our institution and between 55% and 67% of the patients in the United States. With a mean follow-up of 5.36 years, disease-free survival and overall survival rates were 67% and 87%, respectively. Locoregional control was excellent after treatment with cisplatin-based combination chemoradiotherapy; however, four patients (27%) developed distant metastasis. Despite this, no patients died of disease. Toxicity was significant but manageable, and retreatment met with good success. Conclusions: In patients 25 years of age or younger, NPC is more common in African Americans. This may represent a genetic and racial predisposition of this unusual disease in the United States. Late-stage presentations and distant recurrences are common. Platinum-based combination chemoradiotherapy and aggressive management of metastatic disease, however, is associated with good long-term survival. Further study of the possibly changing epidemiology and racial genetics of this unusual tumor is warranted.

Age-related hearing loss – presbycusis – is the number one communication problem of the aged. A major contributor to presbycusis is the progressive degeneration of cochlear outer hair cells (OHCs). Distortion product otoacoustic emissions (DPOAEs) are effective in vivo, physiological measures of hearing, assessing the health and functioning of the OHCs in mammals. We and others have previously demonstrated that DPOAE amplitudes decline with age in humans and mice. The present study's objective was to measure age-related declines in the OHCs in CBA mice (slow, progressive age-related hearing loss) by comparing DPOAEs and auditory brainstem responses (ABRs) generated from females and males. Young adult (2.1–2.9 months) and middle-aged CBA (14.0–16.4 months) mice were tested, as well as old CBAs (24.3–29.0 months). DPOAE-grams were obtained with L 1=65 and L 2=50 dB SPL, f 1/ f 2=1.25, using eight points per octave covering a frequency range from 5.6 to 44.8 kHz (geometric mean frequency). ABRs ranged from 3 to 48 kHz. Analyses revealed that DPOAE levels decreased with age for middle-aged and old male CBAs, but for female CBAs, declines did not occur until old age – after menopause. In contrast, ABR amplitudes for female and male young adult and middle-aged CBAs were the same. Female ABR thresholds were lower than males for old CBAs. In conclusion, we discovered that pre-menopausal CBA female mice have healthier OHCs relative to middle-aged males, but much of this relative advantage is lost post-menopause. Understanding sex differences in age-related sensory disorders will be quite helpful for the goals of preventing, slowing or curing sensory problems in old age for both women and men.

BackgroundMuscle wasting and weight loss were observed when carcinomas were induced in a murine model of head and neck squamous cell carcinomas. Our hypothesis was C3H/HeN mice would develop evidence of cachexia when injected with tumor cellsMethodsAge- and weight-matched female mice were injected with SCCF/VII cells. Daily food intake and weights were measured. Body composition and analysis of circulating cytokines was performed. At the completion of experiments, hind legs were weighed. Muscle atrophy was detected using analysis for muscle ring finger 1 (MuRF1). The tumor-derived lipid mobilizing factor (LMF) was measured.ResultsDespite increased food intake, tumor-bearing mice lost weight and experienced reduced hind leg weights. Interleukin-1beta (IL-1beta) was increased and MuRF1 was present in tumor-bearing mice but not controls. LMF was present in SCCF/VII cells.ConclusionIn this immunocompetent murine model, we demonstrated the development of cancer cachexia in mice inoculated with SCCF cells, which express LMF. There was increased serum IL-1beta, weight loss, and muscle wasting and atrophy in tumor-bearing mice.

Background. Animal models suggest that cyclooxygenase-2 (COX-2) inhibitors may be beneficial in suppressing cancer cachexia. We investigated the effect of short-course celecoxib on body composition, inflammation, and quality of life (QOL) in patients with cancer cachexia in a phase II clinical pilot trial. Methods. Eleven cachectic patients with head and neck or gastrointestinal cancer were randomly assigned to receive placebo or celecoxib for 21 days while awaiting the initiation of cancer therapy. Body composition, resting energy expenditure, QOL, physical function, and inflammatory markers were measured on days 1 and 21. Results. Patients receiving celecoxib experienced statistically significant increases in weight and body mass index (BMI), while patients receiving placebo experienced weight loss and a decline in BMI. Patients receiving celecoxib also had increases in QOL scores. Conclusions. Cachectic patients receiving celecoxib gained weight, experienced increased BMI, and demonstrated improved QOL scores. Compliance was good and no adverse events were seen. © 2007 Wiley Periodicals, Inc. Head Neck, 2008

Objective To determine whether mice unable to mount an intact inflammatory response because of a Toll-like receptor (TLR) pathway defect will develop less severe cancer cachexia. Design Prospective animal study. Setting Academic research center. Subjects Six- to eight-week-old, female C3H/HeJ mice (17-18 g) and age-, weight-, and sex-matched wild-type C3H/HeN mice, differing in that the HeJ mice have nonfunctional TLR4 due to a TLR4 double mutation (TLR4 d/d ). Intervention The mice were inoculated with equal numbers of SCCF-VII cells and housed in individual cages. Main Outcome Measures Food intake, body weight, pretumor and posttumor body composition, circulating cytokines, and levels of a marker of muscle atrophy were analyzed. Results The wild-type HeN mice weighed less on average than the TLR4 d/d mice (2.6 g vs 4.9 g) ( P = .01). They consumed more food, had smaller tumors, and had less lean body mass and fat mass than the TLR4 d/d mice. Interleukin 1β level was significantly elevated in the tumor-bearing HeN mice (mean gain of 259 pg/mL) but not in the TLR4 d/d mice ( P = .03). Both mouse strains had evidence of muscle atrophy. Conclusions In spite of increased food intake and smaller tumors, the wild-type HeN mice had more severe cachexia than the TLR4 d/d mice. The impaired ability to secrete proinflammatory cytokines such as interleukin 1β may protect these animals from developing severe cancer cachexia. This animal model represents a novel system in which the host contributions to cachexia may be further studied.

Purpose: Cancer cachexia is a devastating and understudied illness in patients with head and neck squamous cell carcinoma (HNSCC). The primary objective was to identify clinical characteristics and serum levels of cytokines and cachexia-related factors in patients with HNSCC. The secondary objective was to detect the occurrence of cytokine and cachexia-related factor gene expression in HNSCC tumors. Experimental Design: For the primary objective, cross-sectional data were obtained from prospectively recruited patients identified as cachexia cases and matching cachexia-free controls. For the secondary objective, a retrospective cohort design with matched controls was used. Results: Clinical characteristics associated with cancer cachexia in HNSCC were T4 status (P = 0.01), increased C-reactive protein (P = 0.01), and decreased hemoglobin (P < 0.01). Exploratory multiplex analysis of serum cytokine levels found increased interleukin (IL)-6 (P = 0.04). A highly sensitive ELISA confirmed the multiplex result for increased IL-6 in cachectic patients (P = 0.02). Quality of life was substantially reduced in patients with cachexia compared with noncachectic patients (P < 0.01). All tumors of HNSCC patients both with and without cachexia expressed RNA for each cytokine tested and the cachexia factor lipid-mobilizing factor. There were no statistically significant differences between the cytokine and cachexia factor RNA expression of cachectic and noncachectic patients (each P > 0.05). No tumors expressed the cachexia factor proteolysis-inducing factor. Conclusion: We have identified clinical characteristics and pathophysiologic mechanisms associated with cancer cachexia in a carefully defined population of patients with HNSCC. The data suggest that the acute-phase response and elevated IL-6 are associated with this complex disease state. We therefore hypothesize that IL-6 may represent an important therapeutic target for HNSCC patients with cancer cachexia.

Background. Cancer cachexia is a debilitating, wasting condition that affects many cancer patients, including those with head and neck cancer. The overall incidence of cancer cachexia is quite high for some types of cancer, and cachexia will be the main cause of death for more than 20% of all cancer patients. This syndrome uniquely challenges patients with head and neck cancer. This article outlines the diagnosis of cancer cachexia, reviews its impact on patient quality of life (QOL) and survival, and updates the reader on potential therapies that may suppress it. Methods. A comprehensive literature search was performed using PubMed of the National Library of Medicine, which includes more than 15 million citations back to the 1950s. The Cochrane Library and Google search engine were used as well. Results. This syndrome differs significantly from starvation, and thus accurate and timely diagnosis is essential. Nutritional therapy alone is insufficient. Current management strategies include corticosteroids and megesterol acetate, in conjunction with nutritional therapy. Future strategies may include nutraceuticals, omega-3 fatty acids, inflammatory antagonists, and other targeted treatments. Conclusions. Because cancer cachexia differs significantly from starvation, nutritional supplementation must be used in conjunction with other anti-cachexia agents to reverse the chronic systemic inflammatory state and the effects of circulating tumor-derived factors seen in cachexia. Careful identification of patients at risk and those suffering from this syndrome will lead to better outcomes and treatments. Ultimately, more research is needed to better treat this devastating condition.

Background The greater palatine foramen injection is effective for minimizing bleeding during sinus surgery. The correct depth is important to minimize risk of orbital penetration. This study analyzed the length of the greater palatine canal using high-resolution computed tomography (HRCT). Methods HRCT sinus scans from 100 adults were analyzed. One thousand two hundred measurements were performed by three observers. Results The mean distance of the greater palatine foramen to the orbital floor was 40 ± 3 mm in men and 37 ± 3 mm in women (range, 32–46 mm). The mean distance of the greater palatine foramen to the sphenopalatine foramen was 28 ± 2 mm in men and 27 ± 2 mm in women (range, 23–33 mm). Conclusion The greater palatine foramen injection is an appropriate method to minimize bleeding during endoscopic sinus surgery. The authors recommend an injection depth of 25 mm in adults to minimize the risk of intraorbital complications.

ObjectivesTo compare the incidence rates of nasopharyngeal carcinoma (NPC) among US black, white, and Asian/Pacific Islander (Asian) populations, with a focus on those diagnosed before age 20 years and between ages 20 and 29 years. Our secondary objective was to determine differences in survival rates between US blacks, whites, and Asians with NPC who were younger than 30 years.DesignData from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) tumor registry system were used to determine incidence and survival rates for cases of NPC diagnosed in the specified age groups between 1973 and 2002.PatientsBlacks, whites, and Asians younger than 30 years with NPC.Main outcome measuresIncidence rates and 2- and 5-year survival rates.ResultsFrom 1973 to 2002, incidence rates per 1 million persons, adjusted to the 2000 standard population, for blacks, whites, and Asians younger than 20 years with NPC were 1.61 (n=43), 0.61 (n=99), and 0.95 (n=18), respectively. The incidence rate ratio of blacks to Asians younger than 20 years was 1.69 (95% confidence interval [CI], 0.96-3.12) (P=.07), while the rate ratio for blacks to whites was 2.66 (95% CI, 1.82-3.85) (P