Publications by authors named "Mark J Jameson"

52 Publications

Lymph Node Dissection: Principles and Postoperative Imaging.

Neuroimaging Clin N Am 2022 Feb;32(1):19-36

Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, VA 22903, USA. Electronic address:

The management of neck nodes in head and neck cancer is critical, given a markedly increased poor prognosis in patients with nodal metastasis. The surgical management of neck nodes has undergone radical changes secondary to a paradigm shift from curative surgery to nonsurgical organ and function-preserving options, such as radiation therapy. In the neck after treatment, radiologists should be familiar with imaging findings in various types of neck dissections and post-chemoradiation changes, along with signs of residual or recurrent disease. A multidisciplinary approach is essential with well-designed evidence-based surveillance imaging protocols and standardized reporting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nic.2021.09.001DOI Listing
February 2022

Phase II randomized study of preoperative calcitriol to prevent hypocalcemia following thyroidectomy.

Head Neck 2021 10 2;43(10):2935-2945. Epub 2021 Jun 2.

Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, USA.

Background: A prospective, stratified, randomized, double-blind, placebo-controlled study was conducted to observe the impact of preoperative calcitriol supplementation on serum calcium levels following total thyroidectomy.

Methods: Subjects were randomized 1:1 to receive 1 μg calcitriol or placebo for 1 week preceding thyroidectomy. The primary outcome measure was change in serum calcium from baseline to 18 h post-thyroidectomy. Subjects were also assessed for incidence of symptomatic hypocalcemia, length of stay, readmission for hypocalcemia, and intravenous calcium supplementation.

Results: Forty-seven patients underwent thyroidectomy; 23 received preoperative calcitriol supplementation, and 24 received placebo. Repeated measures regression demonstrated no difference in postoperative serum calcium over time (p = 0.22). There were no occurrences of hypocalcemia, intravenous calcium supplementation, or readmission in either group. No difference was observed in length of stay (p = 0.38). One patient in the calcitriol group developed Grade 3 hypercalcemia.

Conclusions: Preoperative calcitriol supplementation had no impact on postoperative serum calcium levels compared to placebo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.26775DOI Listing
October 2021

IGF1R and Src inhibition induce synergistic cytotoxicity in HNSCC through inhibition of FAK.

Sci Rep 2021 05 24;11(1):10826. Epub 2021 May 24.

Department of Microbiology Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.

Head and neck cancer is the sixth most common cancer worldwide with a 5-year survival of only 65%. Targeting compensatory signaling pathways may improve therapeutic responses and combat resistance. Utilizing reverse phase protein arrays (RPPA) to assess the proteome and explore mechanisms of synergistic growth inhibition in HNSCC cell lines treated with IGF1R and Src inhibitors, BMS754807 and dasatinib, respectively, we identified focal adhesion signaling as a critical node. Focal Adhesion Kinase (FAK) and Paxillin phosphorylation were decreased as early as 15 min after treatment, and treatment with a FAK inhibitor, PF-562,271, was sufficient to decrease viability in vitro. Treatment of 3D spheroids demonstrated robust cytotoxicity suggesting that the combination of BMS754807 and dasatinib is effective in multiple experimental models. Furthermore, treatment with BMS754807 and dasatinib significantly decreased cell motility, migration, and invasion in multiple HNSCC cell lines. Most strikingly, treatment with BMS754807 and dasatinib, or a FAK inhibitor alone, significantly increased cleaved-PARP in human ex-vivo HNSCC patient tissues demonstrating a potential clinical utility for targeting FAK or the combined targeting of the IGF1R with Src. This ex-vivo result further confirms FAK as a vital signaling node of this combinatorial treatment and demonstrates therapeutic potential for targeting FAK in HNSCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-90289-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144381PMC
May 2021

Examination of a distress screening intervention for rural cancer survivors reveals low uptake of psychosocial referrals.

J Cancer Surviv 2021 May 13. Epub 2021 May 13.

University of Virginia Cancer Center, Charlottesville, VA, USA.

Purpose: To determine the impact of a telemedicine-delivered intervention aimed at identifying unmet needs and cancer-related distress (CRD) following the end of active treatment on supportive care referral patterns.

Methods: We used a quasi-experimental design to compare supportive care referral patterns between a group of rural cancer survivors receiving the intervention and a control group (N = 60). We evaluated the impact of the intervention on the number and type of referrals offered and whether or not the participant accepted the referral. CRD was measured using a modified version of the National Comprehensive Cancer Network Distress Thermometer and Problem List.

Results: Overall, 30% of participants received a referral for further post-treatment supportive care. Supporting the benefits of the intervention, the odds of being offered a referral were 13 times higher for those who received the intervention than those in the control group. However, even among the intervention group, only 28.6% of participants who were offered a referral for further psychosocial care accepted.

Conclusions: A nursing telemedicine visit was successful in identifying areas of high distress and increasing referrals. However, referral uptake was low, particularly for psychosocial support. Distance to care and stigma associated with seeking psychosocial care may be factors. Further study to improve referral uptake is warranted.

Implications For Cancer Survivors: Screening for CRD may be inadequate for cancer survivors unless patients can be successfully referred to further supportive care. Strategies to improve uptake of psychosocial referrals is of high importance for rural survivors, who are at higher risk of CRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11764-021-01052-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116196PMC
May 2021

Predictors of False Negative Sentinel Lymph Node Biopsy in Clinically Localized Merkel Cell Carcinoma.

Ann Surg Oncol 2021 Nov 22;28(12):6995-7003. Epub 2021 Apr 22.

Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.

Background: Sentinel lymph node biopsy (SLNB) is routinely recommended for clinically localized Merkel cell carcinoma (MCC); however, predictors of false negative (FN) SLNB are undefined.

Methods: Patients from six centers undergoing wide excision and SLNB for stage I/II MCC (2005-2020) were identified and were classified as having either a true positive (TP), true negative (TN) or FN SLNB. Predictors of FN SLNB were identified and survival outcomes were estimated.

Results: Of 525 patients, 28 (5.4%), 329 (62.7%), and 168 (32%) were classified as FN, TN, and TP, respectively, giving an FN rate of 14.3% and negative predictive value of 92.2% for SLNB. Median follow-up for SLNB-negative patients was 27 months, and median time to nodal recurrence for FN patients was 7 months. Male sex (hazard ratio [HR] 3.15, p = 0.034) and lymphovascular invasion (LVI) (HR 2.22, p = 0.048) significantly correlated with FN, and increasing age trended toward significance (HR 1.04, p = 0.067). The 3-year regional nodal recurrence-free survival for males >75 years with LVI was 78.5% versus 97.4% for females ≤75 years without LVI (p = 0.009). Five-year disease-specific survival (90.9% TN vs. 51.3% FN, p < 0.001) and overall survival (69.9% TN vs. 48.1% FN, p = 0.035) were significantly worse for FN patients.

Conclusion: Failure to detect regional nodal microscopic disease by SLNB is associated with worse survival in clinically localized MCC. Males, patients >75 years, and those with LVI may be at increased risk for FN SLNB. Consideration of increased nodal surveillance following negative SLNB in these high-risk patients may aid in early identification of regional nodal recurrences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10031-zDOI Listing
November 2021

Feasibility of ecological momentary assessment to study depressive symptoms among cancer caregivers.

Psychooncology 2021 05 28;30(5):756-764. Epub 2021 Jan 28.

Department of Psychiatry and Neurobehavioral Sciences, Center for Behavioral Health and Technology, University of Virginia, Charlottesville, Virginia, USA.

Objective: Ecological momentary assessment (EMA) may help with the development of more targeted interventions for caregivers' depression, yet the use of this method has been limited among cancer caregivers. This study aimed to demonstrate the feasibility of EMA among cancer caregivers and the use of EMA data to understand affective correlates of caregiver depressive symptoms.

Methods: Caregivers (N = 25) completed a depressive symptom assessment (Patient Health Questionnaire-8) and then received eight EMA survey prompts per day for 7 days. EMA surveys assessed affect on the orthogonal dimensions of valence and arousal. Participants completed feedback surveys regarding the EMA protocol at the conclusion of the week-long study.

Results: Of 32 caregivers approached, 25 enrolled and participated (78%), which exceeded the a priori feasibility cutoff of 55%. The prompt completion rate (59%, or 762 of 1,286 issued) did not exceed the a priori cutoff of 65%, although completion was not related to caregivers' age, employment status, physical health quality of life, caregiving stress, or depressive symptoms or the patients' care needs (ps > 0.22). Caregivers' feedback about their study experience was generally positive. Mixed-effects location scale modeling showed caregivers' higher depressive symptoms were related to overall higher reported negative affect and lower positive affect, but not to affective variability.

Conclusions: Findings from this feasibility study refute potential concerns that an EMA design is too burdensome for distressed caregivers. Clinically, findings suggest the potential importance of not only strategies to reduce overall levels of negative affect, but also to increase opportunities for positive affect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pon.5627DOI Listing
May 2021

2015 American Thyroid Association guidelines and thyroid-stimulating hormone suppression after thyroid lobectomy.

Head Neck 2021 02 30;43(2):639-644. Epub 2020 Oct 30.

Department of Otolaryngology - Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, USA.

Background: 2015 American Thyroid Association (ATA) guidelines recommended more conservative treatment in low-risk well-differentiated thyroid cancer (WDTC), stating that lobectomy alone may be sufficient. The guidelines further recommend mild thyroid-stimulating hormone (TSH) level suppression (0.5-2 mU/L) for this population. Our goal is to evaluate the natural history of patients undergoing lobectomy to determine the percentage that would require postoperative levothyroxine supplementation under these guidelines.

Methods: Retrospective chart review of 168 patients that underwent lobectomy between 2010 and 2019 was performed. Preoperative and postoperative TSH values and the rate of patients prescribed levothyroxine were analyzed.

Results: Thirty-five percent of patients were prescribed levothyroxine postoperatively. At 6 weeks postoperatively, 66% had TSH value of >2; this increased to 76% by 6 to 12 months.

Conclusion: To adhere to ATA guidelines for WDTC managed with lobectomy alone, the majority of patients (76%) would require postoperative levothyroxine supplementation. Low preoperative TSH was found to be the most significant predictor for postoperative TSH < 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.26524DOI Listing
February 2021

Inhibition of Lysosomal Function Mitigates Protective Mitophagy and Augments Ceramide Nanoliposome-Induced Cell Death in Head and Neck Squamous Cell Carcinoma.

Mol Cancer Ther 2020 12 21;19(12):2621-2633. Epub 2020 Oct 21.

Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.

Therapies for head and neck squamous cell carcinoma (HNSCC) are, at best, moderately effective, underscoring the need for new therapeutic strategies. Ceramide treatment leads to cell death as a consequence of mitochondrial damage by generating oxidative stress and causing mitochondrial permeability. However, HNSCC cells are able to resist cell death through mitochondria repair via mitophagy. Through the use of the C6-ceramide nanoliposome (CNL) to deliver therapeutic levels of bioactive ceramide, we demonstrate that the effects of CNL are mitigated in drug-resistant HNSCC via an autophagic/mitophagic response. We also demonstrate that inhibitors of lysosomal function, including chloroquine (CQ), significantly augment CNL-induced death in HNSCC cell lines. Mechanistically, the combination of CQ and CNL results in dysfunctional lysosomal processing of damaged mitochondria. We further demonstrate that exogenous addition of methyl pyruvate rescues cells from CNL + CQ-dependent cell death by restoring mitochondrial functionality via the reduction of CNL- and CQ-induced generation of reactive oxygen species and mitochondria permeability. Taken together, inhibition of late-stage protective autophagy/mitophagy augments the efficacy of CNL through preventing mitochondrial repair. Moreover, the combination of inhibitors of lysosomal function with CNL may provide an efficacious treatment modality for HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-20-0182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121212PMC
December 2020

Non-HPV-Related Head and Neck Squamous Cell Carcinoma in a Young Patient Cohort.

Ear Nose Throat J 2020 Jun 25:145561320935839. Epub 2020 Jun 25.

Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, VA, USA.

Objectives: Head and neck squamous cell carcinoma (HNSCC) is rare in patients younger than 40 years. Many practitioners suspect HNSCC is a more aggressive disease in this age group, and perhaps increasing in incidence; however, there are scant and conflicting data to support this assertion. We sought to compare outcomes for young patients with non-human papillomavirus (HPV)-related HNSCC to those of older patients.

Methods: A retrospective chart review of patients with HNSCC treated from 2004 to 2016 at 2 tertiary referral centers. Patients aged 18 to 40 with p16-negative HNSCC were included in the young patient cohort (n = 59). A randomly selected stage- and subsite-matched cohort aged 55 to 65 was analyzed for comparison (n = 114).

Results: When considering all patients with HNSCC, patients younger than 40 were more likely to have oral tongue cancer (62.7%) compared to patients age 55 to 65 (16.9%). When an older patient cohort was stage- and subsite-matched to the young patient cohort, there were more never smokers (49.2% vs 17.5% of older patients, < .01) and females (40.7% vs 24.6% of older patients, = .028) in the young patient group. The young patient cohort had better average overall survival than the older group (14.4 vs 8.1 years, respectively, = .02), but similar average disease-free survival (6.2 years vs 6.6 years, respectively, = .67); 50.9% of young patients had tumors with adverse histologic features versus 42.0% of older patients ( = .28). The young patients demonstrated a superior average conditional survival after recurrence (9.8 years vs 3.2 years for older patients, < .01).

Conclusions: Despite the limitations of study design, these data suggest that young patients who develop non-HPV-related HNSCC tend to have similarly aggressive disease, but longer overall survival and better survival after recurrence. These findings may be attributable to better overall health as evidenced by fewer comorbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0145561320935839DOI Listing
June 2020

PRAS40 Phosphorylation Correlates with Insulin-Like Growth Factor-1 Receptor-Induced Resistance to Epidermal Growth Factor Receptor Inhibition in Head and Neck Cancer Cells.

Mol Cancer Res 2020 09 28;18(9):1392-1401. Epub 2020 May 28.

Department of Otolaryngology - Head & Neck Surgery, University of Virginia School of Medicine, Charlottesville, Virginia.

EGFR inhibitors have shown poor efficacy in head and neck squamous cell carcinoma (HNSCC) with demonstrated involvement of the insulin-like growth factor-1 receptor (IGF1R) in resistance to EGFR inhibition. IGF1R activates the PI3K-Akt pathway, which phosphorylates proline-rich Akt substrate of 40 kDa (PRAS40) to cease mTOR inhibition resulting in increased mTOR signaling. Proliferation assays separated six HNSCC cell lines into two groups: sensitive to EGFR inhibition or resistant; all sensitive cell lines demonstrated reduced sensitivity to EGFR inhibition upon IGF1R activation. Reverse phase protein microarray analysis and immunoblot identified a correlation between increased PRAS40 phosphorylation and IGFR-mediated resistance to EGFR inhibition. In sensitive cell lines, PRAS40 phosphorylation decreased 44%-80% with EGFR inhibition and was restored to 98%-196% of control by IGF1R activation, while phosphorylation was unaffected in resistant cell lines. Possible involvement of mTOR in this resistance mechanism was demonstrated through a similar pattern of p70S6K phosphorylation. However, addition of temsirolimus, an mTORC1 inhibitor, was insufficient to overcome IGF1R-mediated resistance and suggested an alternative mechanism. Forkhead box O3a (FOXO3a), which has been reported to complex with PRAS40 in the cytoplasm, demonstrated a 6-fold increase in nuclear to cytoplasmic ratio upon EGFR inhibition that was eliminated with concurrent IGF1R activation. Transcription of FOXO3a-regulated TRAIL and PTEN-induced putative kinase-1 (PINK1) was increased with EGFR inhibition in sensitive cell lines; this effect was diminished with IGF1R stimulation. IMPLICATIONS: These data suggest PRAS40 may play an important role in IGF1R-based therapeutic resistance to EGFR inhibition, and this likely occurs via inhibition of FOXO3a-mediated proapoptotic gene transcription.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1541-7786.MCR-19-0592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483558PMC
September 2020

Beyond broadband: digital inclusion as a driver of inequities in access to rural cancer care.

J Cancer Surviv 2020 10 11;14(5):643-652. Epub 2020 May 11.

University of Virginia Cancer Center, Charlottesville, VA, USA.

Purpose: Rural cancer survivors have worse quality of life than their urban counterparts. Telemedicine is a potential solution to connecting rural residents with specialized cancer providers during the survivorship period, but limitations in broadband may stifle the impact. Using data from a feasibility study evaluating a telemedicine intervention aimed at connecting rural Virginia cancer survivors with their care team located at a cancer center associated with an academic medical center, we sought to evaluate the ability of rural survivors to access the intervention and suggest strategies for improving access to rural cancer survivorship care.

Methods: We used a descriptive design with geospatial and quantitative methods to understand broadband access, driving time to a satellite telemedicine site, and ability to utilize a borrowed cellular-enabled tablet to participate in the intervention for cancer survivors living in Central Virginia.

Results: Our study participants resided in census tracts where an average of 58% of households have adequate broadband access necessary to support a telemedicine videoconferencing intervention. Average driving time to the nearest telemedicine site was 29.6 min. Those who utilized the borrowed tablet experienced considerable difficulty with utilizing the technology.

Conclusions: Rural cancer populations do not have equal access to a cancer survivorship telemedicine intervention.

Implications For Cancer Survivors: Telemedicine interventions aimed at connecting cancer survivors with their academic medical center-based cancer providers may be ineffective if survivors do not have access to either fixed broadband or a satellite clinic. Future research needs to evaluate other sites from which rural survivors can connect, such as rural public libraries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11764-020-00874-yDOI Listing
October 2020

Antitumor effect of insulin-like growth factor-1 receptor inhibition in head and neck squamous cell carcinoma.

Laryngoscope 2020 06 21;130(6):1470-1478. Epub 2019 Aug 21.

Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, U.S.A.

Objectives: The insulin-like growth factor-1 receptor (IGF1R) has been implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC), and small molecule tyrosine kinase inhibitors (TKIs) of IGF1R activity may have anticancer activity. Therefore, the relationship between survival and IGF1R expression was assessed for oral cavity (OC) cancer, and the antitumor effects of two IGF1R-TKIs, OSI-906 and BMS-754807, were evaluated in HNSCC cell lines in vitro.

Methods: Clinical outcome data and tissue microarray immunohistochemistry were used to generate IGF1R expression-specific survival curves. Immunoblot, alamarBlue proliferation assay, trypan blue exclusion viability test, clonogenic assay, flow cytometry, and reverse phase protein array (RPPA) were used to evaluate in vitro responses to IGF1R-TKIs.

Results: For patients with stage III/IV OCSCC, higher IGF1R expression was associated with poorer overall 5-year survival (P = 0.029). Both BMS-754807 and OSI-906 caused dose-dependent inhibition of IGF1R and Akt phosphorylation and inhibited proliferation; BMS-754807 was more potent than OSI-906. Both drugs reduced HNSCC cell viability; only OSI-906 was able to eliminate all viable cells at 10 μM. The two drugs similarly inhibited clonogenic cell survival. At 1 μM, only BMS-754807 caused a fourfold increase in the basal apoptotic rate. RPPA demonstrated broad effects of both drugs on canonical IGF1R signaling pathways and also inhibition of human epidermal growth factor receptor-3 (HER3), Src, paxillin, and ezrin phosphorylation.

Conclusion: OSI-906 and BMS-754807 inhibit IGF1R activity in HNSCC cell lines with reduction in prosurvival and proliferative signaling and with concomitant antiproliferative and proapoptotic effects. Such antagonists may have utility as adjuvants to existing therapies for HNSCC.

Level Of Evidence: NA Laryngoscope, 130:1470-1478, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.28236DOI Listing
June 2020

Survivin in Insulin-Like Growth Factor-Induced Resistance to Lapatinib in Head and Neck Squamous Carcinoma Cells.

Front Oncol 2019 23;9:13. Epub 2019 Jan 23.

Division of Head and Neck Oncologic and Microvascular Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, VA, United States.

Epidermal growth factor receptor (EGFR) inhibitors have limited efficacy in head and neck squamous cell carcinoma (HNSCC) due to various resistance mechanisms, such as activation of the insulin-like growth factor-1 receptor (IGF1R), which initiates pro-survival signaling. Survivin, a member of the inhibitor of apoptosis proteins family, is expressed at relatively high levels in malignant tissues and plays a role in cell division. Expression of survivin in tumors has been shown to correlate with poor prognosis due to chemotherapy resistance and anti-apoptotic behavior. We previously demonstrated that activation of the IGF1R reduces sensitivity to EGFR-tyrosine kinase inhibitors (TKIs) via reduced apoptosis suggesting a role of survivin in this process. This study evaluates the role of survivin in IGF1R-mediated lapatinib resistance. Using HNSCC cell lines FaDu and SCC25, survivin expression increased and lapatinib sensitivity decreased with IGF1R activation. Further, these effects were reversed by the survivin inhibitor YM-155. Conversely, survivin expression and lapatinib sensitivity were unchanged with IGF1R activation in UNC10 cells. YM-155 enhanced the inhibitory effect of lapatinib on UNC10 cells, regardless of activation of the IGF1R. These results demonstrate that enhanced survivin expression correlates with IGF1R-mediated lapatinib resistance in HNSCC cells and suggest that regulation of survivin expression may be a key mechanistic element in IGF1R-based therapeutic resistance. Combinatorial treatment with survivin antagonists and EGFR-TKIs warrants further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351440PMC
January 2019

Treatment of Comorbid Obstructive Sleep Apnea by Upper Airway Stimulation Results in Resolution of Debilitating Symptoms of Restless Legs Syndrome.

J Clin Sleep Med 2018 10 15;14(10):1797-1800. Epub 2018 Oct 15.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia.

Abstract: An association between restless legs syndrome (RLS) and obstructive sleep apnea (OSA) has been suggested for decades but has been questioned in recent years given the apparently similar prevalence of RLS among patients with OSA and the general population. Still, marked improvement in symptoms of RLS has been reported in patients with OSA treated with continuous positive airway pressure (CPAP). Whether the effect of OSA treatment on RLS extends to modalities of OSA treatment other than CPAP remains an open question. Here, we report the case of a patient with OSA and comorbid debilitating RLS who underwent upper airway stimulation device implantation and subsequently experienced near-resolution of her severe RLS symptoms. Upper airway stimulation devices may be an option for patients with OSA and severe RLS intolerant to conventional CPAP modalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5664/jcsm.7400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175797PMC
October 2018

Downregulation of IGF1R Expression Inhibits Growth and Enhances Cisplatin Sensitivity of Head and Neck Squamous Cell Carcinoma Cells In Vitro.

Horm Cancer 2019 02 23;10(1):11-23. Epub 2018 Oct 23.

Department of Otolaryngology - Head and Neck Surgery, Division of Head and Neck Oncologic and Microvascular Surgery, University of Virginia Health System, Charlottesville, VA, USA.

A lentivirus-mediated doxycycline-inducible pTRIPZ shRNAmir plasmid targeting IGF1R transcript was transfected into two head and neck squamous cell carcinoma (HNSCC) cell lines to silence IGF1R expression and to assess the effect of its downregulation on cisplatin sensitivity in vitro. In Cal27-regIGF1R and SCC25-regIGF1R cell lines, IGF1R protein expression was reduced by more than 90% after 72 h of incubation with doxycycline. Both basal and IGF-stimulated pIGF1R, pAKT, and pERK were significantly reduced, without influence on total AKT and ERK expression. Downregulation of the IGF1R was associated with decreased proliferation and cell viability in both cell lines. Reduced IGF1R expression was also associated with increased sub-G0/G1-phase and G0/G1-phase populations and decreased S-phase and G2/M-phase populations. IGF1R downregulation enhanced sensitivity to cisplatin with decrease of cisplatin IC from 15 to 7.1 in Cal27-regIGF1R cells and from 11 to 6.3 in SCC25-regIGF1R cells. Cisplatin exhibited increased pro-apoptotic activity by annexin V staining and PARP cleavage in both cells lines when cultured in doxycycline. Thus, in two HNSCC cell lines in vitro, reduced IGF1R expression results in reduced growth rate and increased sensitivity to cisplatin. Thus, IGF1R downregulation and/or inhibition may serve as a useful adjunct to platinum-based cytotoxic chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12672-018-0352-7DOI Listing
February 2019

Effect of Adipose-Derived Stem Cells on Head and Neck Squamous Cell Carcinoma.

Otolaryngol Head Neck Surg 2018 05 9;158(5):882-888. Epub 2018 Jan 9.

1 Division of Head and Neck Oncologic and Microvascular Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, USA.

Objective Patients with head and neck squamous cell carcinoma (HNSCC) have significant wound-healing difficulties. While adipose-derived stem cells (ASCs) facilitate wound healing, ASCs may accelerate recurrence when applied to a cancer field. This study evaluates the impact of ASCs on HNSCC cell lines in vitro and in vivo. Study Design In vitro experiments using HNSCC cell lines and in vivo mouse experiments. Setting Basic science laboratory. Subjects and Methods Impact of ASCs on in vitro proliferation, survival, and migration was assessed using 8 HNSCC cell lines. One cell line was used in a mouse orthotopic xenograft model to evaluate in vivo tumor growth in the presence and absence of ASCs. Results Addition of ASCs did not increase the number of HNSCC cells. In clonogenic assays to assess cell survival, addition of ASCs increased colony formation only in SCC9 cells (maximal effect 2.3-fold, P < .02) but not in other HNSCC cell lines. In scratch assays to assess migration, fluorescently tagged ASCs did not migrate appreciably and did not increase the rate of wound closure in HNSCC cell lines. Addition of ASCs to HNSCC xenografts did not increase tumor growth. Conclusion Using multiple in vitro and in vivo approaches, ASCs did not significantly stimulate HNSCC cell proliferation or migration and increased survival in only a single cell line. These findings preliminarily suggest that the use of ASCs may be safe in the setting of HNSCC but that further investigation on the therapeutic use of ASCs in the setting of HNSCC is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599817750361DOI Listing
May 2018

The Neddylation Inhibitor Pevonedistat (MLN4924) Suppresses and Radiosensitizes Head and Neck Squamous Carcinoma Cells and Tumors.

Mol Cancer Ther 2018 02 24;17(2):368-380. Epub 2017 Aug 24.

Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia.

The cullin RING E3 ubiquitin ligase 4 (CRL4) with its substrate receptor CDT2 (CRL4-CDT2) is emerging as a critical regulator of DNA replication through targeting CDT1, SET8, and p21 for ubiquitin-dependent proteolysis. The aberrant increased stability of these proteins in cells with inactivated CRL4-CDT2 results in DNA rereplication, which is deleterious to cells due to the accumulation of replication intermediates and stalled replication forks. Here, we demonstrate that CDT2 is overexpressed in head and neck squamous cell carcinoma (HNSCC), and its depletion by siRNA inhibits the proliferation of human papilloma virus-negative (HPV-ve) HNSCC cells primarily through the induction of rereplication. Treatment of HNSCC with the NEDD8-activating enzyme inhibitor pevonedistat (MLN4924), which inhibits all cullin-based ligases, induces significant rereplication and inhibits HNSCC cell proliferation in culture and HNSCC xenografts in mice. Pevonedistat additionally sensitizes HNSCC cells to ionizing radiation (IR) and enhances IR-induced suppression of xenografts in mice. Induction of rereplication via CDT2 depletion, or via the stabilization or activation of CDT1, also radiosensitizes HNSCC cells. Collectively, these results demonstrate that induction of rereplication represents a novel approach to treating radioresistant HNSCC tumors and suggest that pevonedistat may be considered as an adjuvant for IR-based treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-17-0083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805645PMC
February 2018

The EGFR Inhibitor Gefitinib Enhanced the Response of Human Oral Squamous Cell Carcinoma to Cisplatin In Vitro.

Drugs R D 2017 Dec;17(4):545-555

Division of Head and Neck Oncologic and Microvascular Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, VA, USA.

Introduction: The epidermal growth factor receptor (EGFR) is highly expressed in a variety of solid tumors including oral cavity squamous cell carcinoma (OSCC) and has been implicated in the resistance of these tumors to cisplatin. This study was performed to determine if the EGFR tyrosine kinase inhibitor gefitinib could enhance the cytotoxic effect of cisplatin on OSCC cells in vitro.

Methods: The expression of EGFR and the phosphorylation of its downstream signaling to ERK, and AKT pathway were detected by Western blotting. Cell proliferation and survival were determined by AlamarBlue and colony formation assay respectively. Cells apoptosis were determined by Western blotting for cleaved PARP protein and by flowcytometry of cells stained with Annexin V and PI.

Results: Cal27, OSC19, and SCC25 cells treated with gefitinib 1 μM demonstrated reduced phosphorylation of EGFR, AKT, and ERK proteins with very limited inhibition of proliferation. Cisplatin inhibited proliferation of the same cell lines in a dose-dependent manner. The concentration producing 50% inhibition (IC) for cisplatin decreased in the presence of gefitinib 1 μM, and a combination of cisplatin 5 µM and gefitinib 1 µM caused synergistic growth inhibition and synergistic reduction in cell survival. The growth inhibitory effect of the combination was associated with reduced ERK and AKT activation, increased poly ADP ribose polymerase (PARP) cleavage, and increased apoptosis.

Conclusion: Thus, in OSCC cells in vitro, inhibition of EGFR activity with gefitinib enhances the apoptotic effect of cisplatin. This has potential implications for enhancement of cisplatin effectiveness in tumors that over-express the EGFR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40268-017-0204-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694417PMC
December 2017

AHNS Series - Do you know your guidelines? Lip cancer.

Head Neck 2017 08 5;39(8):1505-1509. Epub 2017 Jun 5.

Department of Otolaryngology - Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia.

Background: Lip cancer is one of the most curable primary head and neck malignancies, as the prominent location typically lends to an early diagnosis. The incidence of lip cancer varies by sex, ethnicity, and region, but is estimated to be up to 2.5/100 000 in the United States (squamous cell carcinoma [SCC]).

Methods: This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of lip cancer.

Results: Resection of lip cancer with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy.

Conclusion: Lip cancer remains highly curable when diagnosed at an early stage. A multidisciplinary approach is crucial to treating patients with advanced-stage lip cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24817DOI Listing
August 2017

Microvascular anastomosis simulation using a chicken thigh model: Interval versus massed training.

Laryngoscope 2017 11 13;127(11):2490-2494. Epub 2017 Apr 13.

Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, U.S.A.

Objectives/hypothesis: To compare the effectiveness of massed versus interval training when teaching otolaryngology residents microvascular suturing on a validated microsurgical model.

Study Design: Otolaryngology residents were placed into interval (n = 7) or massed (n = 7) training groups. The interval group performed three separate 30-minute practice sessions separated by at least 1 week, and the massed group performed a single 90-minute practice session. Both groups viewed a video demonstration and recorded a pretest prior to the first training session. A post-test was administered following the last practice session.

Methods: At an academic medical center, 14 otolaryngology residents were assigned using stratified randomization to interval or massed training. Blinded evaluators graded performance using a validated microvascular Objective Structured Assessment of Technical Skill tool. The tool is comprised of two major components: task-specific score (TSS) and global rating scale (GRS). Participants also received pre- and poststudy surveys to compare subjective confidence in multiple aspects of microvascular skill acquisition.

Results: Overall, all residents showed increased TSS and GRS on post- versus pretest. After completion of training, the interval group had a statistically significant increase in both TSS and GRS, whereas the massed group's increase was not significant. Residents in both groups reported significantly increased levels of confidence after completion of the study.

Conclusions: Self-directed learning using a chicken thigh artery model may benefit microsurgical skills, competence, and confidence for resident surgeons. Interval training results in significant improvement in early development of microvascular anastomosis skills, whereas massed training does not.

Level Of Evidence: NA. Laryngoscope, 127:2490-2494, 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.26586DOI Listing
November 2017

Suprafascial Harvest of the Radial Forearm Free Flap Decreases the Risk of Postoperative Tendon Exposure.

Ann Otol Rhinol Laryngol 2017 Mar 6;126(3):224-228. Epub 2017 Jan 6.

1 Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, USA.

Objective: To determine if suprafascial harvest of the radial forearm free flap improves postoperative donor site outcomes compared to subfascial harvest.

Methods: Retrospective chart review.

Results: Forty-six patients underwent reconstruction of a head and neck defect with a radial forearm free flap (RFFF). Subfascial harvest of the RFFF was performed in 25 (53%) patients and suprafascial harvest performed in 22 (47%) patients. All donor sites were covered with a split thickness skin graft and a bolster that remained in place for 6 days. Postoperative tendon exposure at the donor site occurred in 5 (20%) of the patients in the subfascial group and in 0 (0%) of the patients in the suprafascial group ( P = .05; Fisher's exact test). Average tourniquet time was 117 minutes in the subfascial group and 102 minutes in the suprafascial group. Hematoma formation occurred at the donor site in 2 (8%) and 1 (5%) patients in the subfascial and suprafascial groups, respectively. There were no complete or partial flap losses in either group.

Conclusions: Suprafascial harvest of the RFFF decreases the risk of postoperative tendon exposure. The suprafascial harvest technique does not increase harvest time or donor site complications, nor does it negatively impact flap vascularity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003489416685322DOI Listing
March 2017

Incidental Large Left Masticator Space Mass.

JAMA Otolaryngol Head Neck Surg 2016 09;142(9):915-6

Division of Neuroradiology, Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2016.0092DOI Listing
September 2016

Prognostic value of albumin in patients with head and neck cancer.

Laryngoscope 2016 07 10;126(7):1567-71. Epub 2016 Feb 10.

Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, U.S.A.

Objectives/hypothesis: Albumin is an indicator of nutritional status and has been investigated as a predictor of cancer survival and perioperative outcomes. This study investigated the prognostic value of preoperative serum albumin in surgical patients with head and neck cancer (HNC).

Study Design: Retrospective cohort study.

Methods: A chart review was performed of patients who underwent HNC resection over a 6-year period at a single institution. Statistical analyses including Cox proportional hazards models, Pearson's correlation, and logistic regression were used to identify relationships between preoperative serum albumin and postoperative outcomes. Albumin was analyzed as a continuous variable.

Results: A total of 604 patients were studied representing all cancer types. There was no association between albumin and pneumonia, flap complications, or length of stay. Albumin was found to have statistically significant inverse associations with overall survival (OS) (hazard ratio [HR] = 0.685, P < .001) and postoperative wound infection (HR = 0.455, P = .001). In multivariate analysis of OS, albumin did not achieve significance as an independent predictor (HR = 0.78, P = .064), whereas hemoglobin, age, and cancer stage remained significant. In a subgroup of 280 patients with upper aerodigestive squamous cell carcinoma (SCCA), albumin maintained significance in multivariate analysis of OS (HR = 0.74, P = .046). When controlling for preoperative radiotherapy, salvage surgery, and cancer stage in multivariate analysis, albumin was a significant predictor of wound infection (OR = 0.55, P = .018).

Conclusions: In patients with HNC, lower preoperative serum albumin is associated with an increased rate of wound infection and poorer OS. The effect on OS is most pronounced in patients with upper aerodigestive SCCA.

Level Of Evidence: 2b Laryngoscope, 126:1567-1571, 2016.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.25877DOI Listing
July 2016

Rigid Esophagoscopy for Head and Neck Cancer Staging and the Incidence of Synchronous Esophageal Malignant Neoplasms.

JAMA Otolaryngol Head Neck Surg 2016 Jan;142(1):40-5

Division of Head and Neck Oncologic and Microvascular Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville.

Importance: Rigid esophagoscopy (RE) was once an essential part of the evaluation of patients with head and neck squamous cell carcinoma (HNSCC) due to the high likelihood of identifying a synchronous malignant neoplasm in the esophagus. Given recent advances in imaging and endoscopic techniques and changes in the incidence of esophageal cancer, the current role for RE in HNSCC staging is unclear.

Objective: To analyze the current role of RE in evaluating patients with HNSCC, and to determine the incidence of synchronous esophageal malignant neoplasms in patients with HNSCC.

Design, Setting, And Participants: In this retrospective study performed at an academic tertiary care center, 582 patients were studied who had undergone RE for HNSCC staging from July 1, 2004, through October 31, 2012. To assess the incidence of synchronous esophageal malignant neoplasms, a literature review was performed, and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data set was queried.

Main Outcomes And Measures: The primary outcome measure was the incidence of synchronous esophageal malignant neoplasms, as measured by retrospective review at our institution, SEER data set analysis, and literature review. Secondary outcome measures were RE complications and nonmalignant findings during RE.

Results: A total of 601 staging REs were performed in 582 patients. The mean age was 60.2 years and 454 (78.0%) were men. There were 9 complications (1.5%), including 1 esophageal perforation (0.2%). Rigid esophagoscopy was aborted in 50 cases. Of the 551 completed REs, no abnormal findings were noted in 523 patients (94.9%), and nonmalignant pathologic findings were identified in 28 patients (5.1%). No synchronous primary esophageal carcinomas were detected. The incidence of synchronous esophageal malignant neoplasms found on screening endoscopy based on literature review and on SEER data set analysis was very low and has decreased from 1980 to 2010 in North America. The incidence reported in South America and Asia was relatively high.

Conclusions And Relevance: Rigid esophagoscopy is safe, but the utility is low for cancer staging and for detection of nonmalignant esophageal disease. Review of the literature and analysis of a large national cancer data set indicate that the incidence of synchronous esophageal malignant neoplasms in patients with HNSCC is low and has been decreasing during the past 3 decades. Thus, screening esophagoscopy should be limited to patients with HNSCC who are at high risk for synchronous esophageal malignant neoplasms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2015.2815DOI Listing
January 2016

Development and evaluation of a rigid esophagoscopy simulator for residency training.

Laryngoscope 2016 Mar 24;126(3):616-9. Epub 2015 Nov 24.

Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, U.S.A.

Objectives/hypothesis: Rigid esophagoscopy is performed less frequently by resident trainees. Nonetheless, it remains important for certain indications, including foreign body extraction. This study describes the construction of a simulator and evaluates its utility in training residents.

Study Design: Simulator development, fabrication, and procedural evaluation of postgraduate trainees.

Methods: A simulator was developed and constructed in collaboration with a biomedical engineering team. Residents with varied experience in upper aerodigestive procedures performed rigid esophagoscopy on the model. Key steps and Accreditation Council for Graduate Medical Education's Objective Structured Assessment of Technical Skills (OSATS) criteria for rigid esophagoscopy were evaluated by a faculty surgeon. Pressure measurements were obtained from force sensors at the tip of the endoscope and incisors.

Results: Fourteen trainees were evaluated. Operative rigid esophagoscopy and direct laryngoscopy case numbers were noted for each subject. OSATS scores and key steps of the procedure correlated with resident experience (R(2)  = 0.75, P < .0001 and R(2)  = 0.66, P < .001, respectively). Maximal pressure exerted on the simulator esophagus by the esophagoscope was inversely correlated with case number and was statistically significant (R(2)  = 0.51, P = .02), whereas length of procedure did not correlate (R(2)  = 0.04, P = .49). Maximal pressure on the incisors did not correlate (R(2)  = 0.25, P = .15).

Conclusions: A simulator for training residents to perform rigid esophagoscopy was developed and utilized by a faculty proctor to objectively evaluate trainees. OSATS scores, performance of key procedural steps, and pressure exerted on the simulator tissue correlated with upper aerodigestive cases performed, demonstrating validity of the simulator.

Level Of Evidence: NA Laryngoscope, 126:616-619, 2016.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.25439DOI Listing
March 2016

Use of the Teres Major Muscle in Chimeric Subscapular System Free Flaps for Head and Neck Reconstruction.

JAMA Otolaryngol Head Neck Surg 2015 Sep;141(9):816-21

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of New Mexico Health Science Center, Albuquerque.

Importance: We present what we believe to be the first case series in which the teres major muscle is used as a free flap in head and neck reconstruction.

Objectives: To describe our experience with the teres major muscle in free flap reconstruction of head and neck defects and to identify advantages of this approach.

Design, Setting, And Participants: A retrospective review was performed at 2 tertiary care centers between February 1, 2007, and June 30, 2012. Data analysis was conducted from July 31, 2014, through December 1, 2014.

Intervention: Teres major muscle free flap for use in head and neck reconstruction.

Main Outcomes And Measures: Indications for use, complications, and outcomes including donor site morbidity.

Results: The teres major free flap was used in 11 patients as a component of chimeric subscapular system free flaps for a variety of complex head and neck defects. The teres major muscle was used to fill soft-tissue defects of the neck, face, and nasal cavity; it provided substantial soft-tissue volume but was less bulky than the latissimus dorsi muscle. The teres major muscle was also used to provide protection for vascular anastomoses and/or great vessels and to enhance soft-tissue coverage of the mandibular reconstruction plate. In addition, the muscle was selected as a substrate for skin grafting where inadequate neck skin remained. Flap survival occurred in 10 of 11 flaps (91%). Two flaps (18%) demonstrated venous congestion that was managed successfully. Two patients (18%) developed minor recipient-site complications (submental fistula and infection with recurrent wound dehiscence and plate exposure). All donor sites healed well, with chronic, mild shoulder pain noted in 2 patients (18%) and no postoperative seromas observed in any patient.

Conclusions And Relevance: Addition of the teres major muscle to a subscapular system free flap is an option for reconstruction of a variety of complex head and neck defects, particularly when a moderate amount of soft tissue is required. In select cases, the teres major muscle may have advantages over the latissimus dorsi muscle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2015.1485DOI Listing
September 2015

Accuracy of MRI for the diagnosis of metastatic cervical lymphadenopathy in patients with thyroid cancer.

Radiol Med 2015 Oct 1;120(10):959-66. Epub 2015 Mar 1.

UVA Department of Radiology, Neuroradiology Division, University of Virginia, Box 800170, Charlottesville, VA, 22908, USA.

Purpose: The aim of this study was to systematically compare a comprehensive array of magnetic resonance (MR) imaging features in terms of their sensitivity and specificity to diagnose cervical lymph node metastases in patients with thyroid cancer.

Materials And Methods: The study included 41 patients with thyroid malignancy who underwent surgical excision of cervical lymph nodes and had preoperative MR imaging ≤4weeks prior to surgery. Three head and neck neuroradiologists independently evaluated all the MR images. Using the pathology results as reference, the sensitivity, specificity and interobserver agreement of each MR imaging characteristic were calculated.

Results: On multivariate analysis, no single imaging feature was significantly correlated with metastasis. In general, imaging features demonstrated high specificity, but poor sensitivity and moderate interobserver agreement at best.

Conclusions: Commonly used MR imaging features have limited sensitivity at correctly identifying cervical lymph node metastases in patients with thyroid cancer. A negative neck MR scan should not dissuade a surgeon from performing a neck dissection in patients with thyroid carcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11547-014-0474-0DOI Listing
October 2015

Open reduction internal fixation for midline mandibulotomy: lag screws vs plates.

JAMA Otolaryngol Head Neck Surg 2014 Dec;140(12):1184-90

Division of Head and Neck Surgical Oncology, Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville.

Importance: Midline mandibulotomy is a common approach for resection of head and neck oral cavity and oropharyngeal tumors; however, there are limited data available on the outcomes of lag screw vs plate fixation.

Objective: To compare outcomes for midline mandibulotomy open reduction and internal fixation using plates vs lag screw technique.

Design, Setting, And Participants: Retrospective cohort study at a tertiary care academic medical center of patients undergoing midline mandibulotomy for head and neck tumor resection over a 6-year period.

Interventions: Mandibular fixation using lag screws or plates.

Main Outcomes And Measures: The medical records and computed tomographic (CT) scans of patients undergoing midline mandibulotomy for head and neck tumor resection over a 6-year period were retrospectively reviewed. The postoperative CT scans were reviewed by a neuroradiologist who graded the fusion site on a scale of 0 to 2 using a 2-pass method. The rates and grades of union were compared, as well as several factors that affect healing, for fixations performed with plates vs lag screws.

Results: Thirty-seven patients were included. The overall rate of radiologic union was 90% (9 out of 10) for lag screw technique and 41% (11 out of 27) for plates (P = .01). The average grade of radiologic union was 1.3 for lag screws and 0.67 for plates (P = .04). Hardware exposure occurred in 4 (15%) of the plate group and fistulae formed in 3 (11%); neither complication occurred in the lag screw group. In univariate analysis, both presence of dentition (odds ratio [OR], 5.50 [95% CI, 1.33-22.73]; P = .02) and plate technique (OR, 13.09 [95% CI, 1.45-11.62]; P = .02) were significantly associated with nonunion. In multivariate analysis, plate technique had an OR of 8.32 (95% CI, 0.85-81.75) for nonunion (P = .07).

Conclusions And Relevance: Fixation of midline mandibulotomy with lag screws results in a significantly increased rate of radiologic union compared with plates. Lag screws were also significantly better at achieving radiologic union in patients who underwent postoperative radiation, and the rates of fistula formation and hardware exposure were lower. Thus, lag screw fixation of midline mandibulotomy should be considered an excellent option, especially when patients will undergo postoperative adjuvant therapy and in patients at high risk for wound complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2014.2005DOI Listing
December 2014

Impact of blood transfusions on patients with head and neck cancer undergoing free tissue transfer.

Laryngoscope 2015 Jan 14;125(1):86-91. Epub 2014 Aug 14.

Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, U.S.A.

Objectives/hypothesis: To determine whether blood transfusions are associated with adverse outcomes in patients with head and neck cancer (HNC) undergoing microvascular free tissue transfer.

Study Design: Retrospective cohort study.

Methods: The records of all patients who underwent free flaps for reconstruction after HNC resection from July 2007 through February 2013 at a single institution were reviewed. Rates of overall survival (OS), recurrence free survival (RFS), and postoperative wound infection were determined. Statistical analyses included Cox proportional hazards models and chi-square tests.

Results: Of 167 patients, 90 received 0 to 2 units of blood and 77 received ≥ 3. After controlling for age, preoperative hemoglobin, preoperative albumin, cancer stage, and adverse pathologic features, transfusion of ≥ 3 (versus 0 to 2) units was associated with poorer OS (P = 0.0006; hazard ratio [HR] = 2.96) and RFS (P = 0.003; HR = 2.35). The rates of wound infection in patients who received 0, 1, 2, or ≥ 3 units were 13.3%, 21.2%, 33.3%, and 31.2%, respectively. There was a statistically significant difference in wound infection rates between those patients receiving 0 to 1 versus ≥ 2 units (P = 0.04).

Conclusions: Patients who receive ≥ 3 units of blood after free tissue transfer for HNC had a significantly increased risk of death after controlling for age, preoperative hemoglobin and albumin, cancer stage, and adverse pathologic features. Increased transfusions are also associated with higher wound infection rates. The increased tendency to transfuse free flap patients in order to maintain a threshold hematocrit may have a detrimental impact on survival and wound infections and should be revisited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.24847DOI Listing
January 2015

Synergistic apoptosis in head and neck squamous cell carcinoma cells by co-inhibition of insulin-like growth factor-1 receptor signaling and compensatory signaling pathways.

Head Neck 2015 Dec 6;37(12):1722-32. Epub 2015 Apr 6.

Department of Otolaryngology - Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia.

Background: In head and neck squamous cell carcinoma (HNSCC), resistance to single-agent targeted therapy may be overcome by co-targeting of compensatory signaling pathways.

Methods: A targeted drug screen with 120 combinations was used on 9 HNSCC cell lines.

Results: Multiple novel drug combinations demonstrated synergistic growth inhibition. Combining the insulin-like growth factor-1 receptor (IGF-1R) inhibitor, BMS754807, with either the human epidermal growth factor receptor (HER)-family inhibitor, BMS599626, or the Src-family kinase inhibitor, dasatinib, resulted in substantial synergy and growth inhibition. Depending on the cell line, these combinations induced synergistic or additive apoptosis; when synergistic apoptosis was observed, AKT phosphorylation was inhibited to a greater extent than either drug alone. Conversely, when additive apoptosis occurred, AKT phosphorylation was not reduced by the drug combination.

Conclusion: Combined IGF-1R/HER family and IGF-1R/Src family inhibition may have therapeutic potential in HNSCC. AKT may be a node of convergence between IGF-1R signaling and pathways that compensate for IGF-1R inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.23822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376763PMC
December 2015
-->