Publications by authors named "David Cognetti"

103 Publications

Improved efficiency of sialendoscopy procedures at an ambulatory surgery center.

Am J Otolaryngol 2021 Jan 22;42(3):102927. Epub 2021 Jan 22.

Thomas Jefferson University Hospital, Department of Otolaryngology - Head and Neck Surgery, 925 Chestnut St, Philadelphia, PA 19107, United States of America.

Objectives: To compare time spent on day of surgery and post-surgical outcomes for sialendoscopy procedures at an ambulatory surgery center versus in a hospital operating room.

Methods: Retrospective chart review for patients who underwent sialendoscopy for sialadenitis or sialolithiasis from March 2017 to May 2020 were included. Surgery location (ambulatory surgery center or hospital operating room) was compared. Primary outcomes included total time in hospital, operative time, total time in operating room. and recovery time. Secondary outcomes included rate of symptoms resolutions, requiring further medical management, and requiring further surgical intervention.

Results: A total of 321 procedures were included. Sialendoscopy in an ambulatory surgery center compared to main operating room decreased median hospital time (166 min reduction, p < 0.001), operative time (18 min reduction, p < 0.001), total time in operating room (34 min reduction, p < 0.001), and recovery time (64 min reduction, p < 0.001). Sialendoscopy in an ambulatory surgery center had similar rates of post-operative resolution of symptoms and further medical or surgical intervention compared to procedures in a hospital operating room.

Conclusion: Sialendoscopy can be safely performed in an ambulatory surgery center for sialadenitis or appropriate sialolithiasis cases while decreasing hospital time, operative time, total time in operating room time, and recovery time.
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http://dx.doi.org/10.1016/j.amjoto.2021.102927DOI Listing
January 2021

Functional Swallow-Related Outcomes Following Transoral Robotic Surgery for Base of Tongue Carcinoma.

Dysphagia 2021 Jan 25. Epub 2021 Jan 25.

Division of Biostatistics, Thomas Jefferson University, 1015 Chestnut Street, Suite 520, Philadelphia, PA, 19107, USA.

In an era where the incidence of oropharyngeal cancer is growing steadily, there have been few studies exploring functional outcomes for individuals whose definitive cancer management approach includes transoral robotic surgical (TORS) resection. This study was designed to examine swallow-related outcomes in individuals newly diagnosed with base of tongue cancer whose treatment plan included surgical resection via TORS. The aims of this study were to determine whether TORS resection for early stage BOT SCCA affected: (a) lingual strength, (b) swallow safety and efficiency, (c) oral intake, and (d) swallowing-related quality of life. Nine individuals meeting the inclusion criteria were recruited to participate from March 2017 to April 2018. Each participant was evaluated at four distinct time points: (a) preoperatively, (b) 1 week postoperatively, (c) 1 month postoperatively, and (d) 3 months postoperatively. The following data were collected at each time point: (a) maximum isometric lingual pressure, (b) Penetration-Aspiration Scale score, (c) Yale Pharyngeal Residue Severity Rating Scale scores, (d) Functional Oral Intake Scale score, and (e) EAT-10 score. Data analysis revealed that a significant decline in maximum isometric lingual pressure, EAT-10 scores, and Functional Oral Intake Scale scores occurred between preoperative baseline measurements and 1 week post surgery. All participants in the study demonstrated a return to levels at or near their baseline level of function for maximum isometric lingual pressure, EAT-10 score, and Functional Oral Intake Scale score by 1 or 3 months post surgery. There were no significant changes in swallow safety or efficiency observed at any time point during the study.
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http://dx.doi.org/10.1007/s00455-021-10246-yDOI Listing
January 2021

Impact of Lymph Node Yield in Patients Undergoing Total Laryngectomy and Neck Dissection.

Ann Otol Rhinol Laryngol 2020 Oct 14:3489420964824. Epub 2020 Oct 14.

Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA.

Objectives: To determine the impact of lymph node yield (LNY) in patients undergoing neck dissection at the time of total laryngectomy (TL). To determine the impact of radiation therapy (RT) on LNY.

Methods: Retrospective review of LNY and clinical outcomes in 232 patients undergoing primary or salvage total laryngectomy (TL) with ND.

Results: Preoperative RT significantly decreased mean LNY from 31.7 to 23.9 nodes ( < .001). In primary TL patients, age ( < .001) and positive margins ( = .044) were associated with decreased OS. In salvage TL patients, only positive margins was associated with poorer OS ( = .009). No LNY cutoff provided significant OS or DFS benefit.

Conclusions: Radiotherapy significantly reduces LNY in patients undergoing TL and ND. Within a single institution cohort, positive margins, but not LNY, is associated with survival in both primary and salvage TL patients. 4.
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http://dx.doi.org/10.1177/0003489420964824DOI Listing
October 2020

Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect.

Front Oncol 2020 2;10:566315. Epub 2020 Dec 2.

Department of Otolaryngology - Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, United States.

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.

Patients And Methods: Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent change in tumor volume from pretreatment to posttreatment CT scan. Responders were defined as those with a 10% reduction in the volume of the primary tumor or lymph nodes (LN). Pathologic treatment effect (PTE) was defined as the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor area.

Results: Sixteen of 32 patients (50%) with pathologic evidence of LN involvement exhibited discordant PTE between primary sites and LN. In four patients with widely discordant adjacent LN, increased PTE was associated with increased infiltration of tumor CD8 T cells and CD163 macrophages, whereas stromal regulatory T cells were associated with low nodal PTE. RVR correlated with PTE at both primary tumor (slope = 0.55, < 0.001) and in LN (slope = 0.62, < 0.05). 89% (16/18) of radiographic non-responders with T1-T3 primary sites had no (n = 7) or minimal PTE (n = 9), whereas 15/17 (88%) of radiographic responders had moderate (n = 12) or complete (n = 3) PTE.

Conclusion: Nivolumab often induces discordant treatment effects between primary tumor sites and metastatic lymph nodes within subjects. This treatment discordance was also demonstrated in adjacent lymph nodes, which may correlate with local immune cell makeup. Finally, although these data were generated by a relatively small population size, our data support the use of early radiographic response to assess immunotherapy treatment effect in HNSCC.
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http://dx.doi.org/10.3389/fonc.2020.566315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738605PMC
December 2020

Exploring Knowledge and Attitudes About Human Papillomavirus Vaccination Among School Nurses in an Urban School District.

J Sch Health 2021 Feb 13;91(2):125-132. Epub 2020 Dec 13.

Associate Professor, Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, 834 Chestnut Street, Suite 314, Philadelphia, PA, 19107., USA.

Background: Nurses in an urban school district completed a brief survey about their knowledge, attitudes, and practices related to human papillomavirus (HPV) vaccination.

Methods: Descriptive and bivariate analyses examined trends and differences.

Results: Among 208 nurses, only 3% correctly answered all 5 knowledge questions. Nurses with greater than 10 years of experience were more confident about where to refer a student for vaccination (p < .01) and less likely to be interested in providing the vaccine at their school (p < .001) compared to those with less than 10 years of experience. Almost one third (32%) of nurses reported having access to educational material about the HPV vaccine at their schools.

Conclusions: Whereas most nurses had positive attitudes about the vaccine, fewer were interested in administering the HPV vaccine in school. Educational resources for school nurses could increase awareness of the vaccine and promote linkages to care outside of school.
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http://dx.doi.org/10.1111/josh.12981DOI Listing
February 2021

Tracheostomy During the COVID-19 Pandemic: Comparison of International Perioperative Care Protocols and Practices in 26 Countries.

Otolaryngol Head Neck Surg 2020 Nov 3:194599820961985. Epub 2020 Nov 3.

Department of Otolaryngology-Head & Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has led to a global surge in critically ill patients requiring invasive mechanical ventilation, some of whom may benefit from tracheostomy. Decisions on if, when, and how to perform tracheostomy in patients with COVID-19 have major implications for patients, clinicians, and hospitals. We investigated the tracheostomy protocols and practices that institutions around the world have put into place in response to the COVID-19 pandemic.

Data Sources: Protocols for tracheostomy in patients with severe acute respiratory syndrome coronavirus 2 infection from individual institutions (n = 59) were obtained from the United States and 25 other countries, including data from several low- and middle-income countries, 23 published or society-endorsed protocols, and 36 institutional protocols.

Review Methods: The comparative document analysis involved cross-sectional review of institutional protocols and practices. Data sources were analyzed for timing of tracheostomy, contraindications, preoperative testing, personal protective equipment (PPE), surgical technique, and postoperative management.

Conclusions: Timing of tracheostomy varied from 3 to >21 days, with over 90% of protocols recommending 14 days of intubation prior to tracheostomy. Most protocols advocate delaying tracheostomy until COVID-19 testing was negative. All protocols involved use of N95 or higher PPE. Both open and percutaneous techniques were reported. Timing of tracheostomy changes ranged from 5 to >30 days postoperatively, sometimes contingent on negative COVID-19 test results.

Implications For Practice: Wide variation exists in tracheostomy protocols, reflecting geographical variation, different resource constraints, and limited data to drive evidence-based care standards. Findings presented herein may provide reference points and a framework for evolving care standards.
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http://dx.doi.org/10.1177/0194599820961985DOI Listing
November 2020

Comparison of general anesthesia and monitored anesthesia care for sialendoscopy procedures.

Am J Otolaryngol 2021 Jan - Feb;42(1):102809. Epub 2020 Oct 24.

Thomas Jefferson University Hospital, Department of Otolaryngology - Head and Neck Surgery, 925 Chestnut St, Philadelphia, PA 19107, United States of America.

Objectives: The literature remains scarce in terms of comparing different anesthesia modalities in sialendoscopy. Due to the lack of a standard of care or guidelines to anesthetic care, it is generally accepted that surgeons perform these surgeries under the anesthetic modality in which they are most comfortable. In this study, we evaluate time spent on the day of surgery and post-surgical outcomes for patients receiving sialendoscopy under monitored anesthesia care versus general anesthesia.

Materials And Methods: We retrospectively assessed patients who underwent sialendoscopy using a solely endoscopic approach for sialadenitis or sialolithiasis from March 2017 to December 2019. Anesthesia modality (monitored anesthesia care versus general anesthesia) was compared. Main outcomes included total time in hospital, operative time, total time in operating room, anesthesia time, and recovery time. Secondary outcomes included rate of resolution of symptoms, requiring further medical management, requiring further surgical intervention, and complications.

Results: A total of 172 procedures were included. Sialendoscopy under monitored anesthesia care center compared to general anesthesia decreased median hospital time (141 min reduction), anesthesia time (46 min reduction), operative time (24 min reduction), time in operating room (43 min reduction), and recovery time (56 min reduction). Utilizing monitored anesthesia care demonstrated similar rates of post-operative resolution of symptoms, complications, and further medical or surgical intervention compared to the general anesthesia cohort.

Conclusion: Sialendoscopy can be safely performed under monitored anesthesia care for appropriate sialadenitis or sialolithiasis cases while decreasing hospital time, operative time, time in operating room, anesthesia time, and recovery time while maintaining similar post-operative outcomes. Monitored anesthesia care should be considered for solely endoscopic cases as guided by surgeon and patient comfort.
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http://dx.doi.org/10.1016/j.amjoto.2020.102809DOI Listing
October 2020

Functional and survival outcomes in elderly patients undergoing transoral robotic surgery.

Oral Oncol 2020 12 19;111:104954. Epub 2020 Aug 19.

Department of Otolaryngology - Head and Neck Surgery, Thomas Jefferson University Hospitals, 6(th) floor, 925 Chestnut Street, Philadelphia, PA 19107, USA.

Objectives: To determine if elderly patients (≥70 years) have differences in functional and survival outcomes compared to non-elderly patients (<70 years) following transoral robotic surgery.

Materials And Methods: A retrospective cohort study was conducted on patients undergoing robotic surgery for head and neck cancer at a tertiary institution from 2011 to 2016. Functional status was evaluated with diet, enteric feeding status, Functional Oral Intake Scale (FOIS), tracheostomy tube placement, and unplanned readmission. Kaplan Meier method and Cox proportional hazard model were used to assess overall survival (OS) and disease-free survival (DFS) between elderly and non-elderly patients.

Results: Two hundred and forty-six patients met inclusion criteria. The mean age of the cohort was 63.5 ± 9.74 years. There were 64 patients (26.0%) that were ≥70 years. Elderly patients were more likely to be discharged with enteric access (p < 0.002). As early as 3 months, there was no significant difference in need for enteric feeds, diet, or FOIS score. There was no difference in tracheostomy tube rates and unplanned readmission between both cohorts. There was no significant difference in OS and DFS between age groups when stratified by p16 status.

Conclusions: Elderly patients are more likely to require perioperative enteric feeding, but 3-month, 1-year, and 2-year functional outcomes are comparable to younger patients. Survival outcomes are similar in both populations.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104954DOI Listing
December 2020

Comment on "Tracheostomy in COVID-19 Patients: Why Delay or Avoid?"

Otolaryngol Head Neck Surg 2021 03 18;164(3):684. Epub 2020 Aug 18.

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http://dx.doi.org/10.1177/0194599820953376DOI Listing
March 2021

The underappreciated role of auriculotemporal nerve involvement in local failure following parotidectomy for cancer.

Head Neck 2020 Nov 20;42(11):3253-3262. Epub 2020 Jul 20.

Department of Otolaryngology, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA.

Background: Locoregional recurrence rates following parotidectomy for cancer remain as high as 20-30%. The auriculotemporal nerve (ATN) may allow parotid cancers to spread from the facial nerve (FN) toward the skull base, causing local recurrence.

Methods: Retrospective review of 173 parotidectomies for malignancy. Preoperative and post-recurrence imaging were reviewed by a neuroradiologist for signs of tumor adjacent to the ATN.

Results: Clinical and imaging signs of possible ATN involvement correlated with FN weakness and sacrifice. Eight patients had pathologically confirmed tumor from the ATN or V3. Forty-four percent of local recurrences had post-recurrence imaging showing tumor along the course of the ATN. Locoregional failure along the ATN was also associated with preoperative FN weakness, intraoperative FN sacrifice, and failure to complete recommended adjuvant therapy.

Conclusions: Parotid cancers may invade the FN and spread to the skull base via the ATN. If not appropriately managed, this may lead to local recurrence.
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http://dx.doi.org/10.1002/hed.26372DOI Listing
November 2020

COVID-19 pandemic and health care disparities in head and neck cancer: Scanning the horizon.

Head Neck 2020 Jul 20;42(7):1555-1559. Epub 2020 Jun 20.

Department of Otolaryngology-Head & Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.

The COVID-19 pandemic has profoundly disrupted head and neck cancer (HNC) care delivery in ways that will likely persist long term. As we scan the horizon, this crisis has the potential to amplify preexisting racial/ethnic disparities for patients with HNC. Potential drivers of disparate HNC survival resulting from the pandemic include (a) differential access to telemedicine, timely diagnosis, and treatment; (b) implicit bias in initiatives to triage, prioritize, and schedule HNC-directed therapy; and (c) the marked changes in employment, health insurance, and dependent care. We present four strategies to mitigate these disparities: (a) collect detailed data on access to care by race/ethnicity, income, education, and community; (b) raise awareness of HNC disparities; (c) engage stakeholders in developing culturally appropriate solutions; and (d) ensure that surgical prioritization protocols minimize risk of racial/ethnic bias. Collectively, these measures address social determinants of health and the moral imperative to provide equitable, high-quality HNC care.
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http://dx.doi.org/10.1002/hed.26345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323088PMC
July 2020

Salivary gland disease in the era of COVID-19 pandemic.

Head Neck 2020 06 28;42(6):1339-1343. Epub 2020 Apr 28.

Hôpital de la Tour, Geneva University, Geneva, Switzerland.

Coronavirus disease 2019 (COVID-19) pandemic forced significant changes in current approach to outpatient evaluation of common otolaryngology complaints as hospitals around the world are trying to limit the spread of the virus and to preserve health care resources. These changes raise a lot of questions regarding patient triage and treatment decisions in clinical situations when it is unclear if the workup and management can be postponed. In this communication, we present our approach to evaluation and triage of new patients with complaints concerning for salivary gland disease.
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http://dx.doi.org/10.1002/hed.26210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267671PMC
June 2020

Tracheostomy Management during the COVID-19 Pandemic.

Otolaryngol Head Neck Surg 2020 07 28;163(1):67-69. Epub 2020 Apr 28.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA.

The ongoing coronavirus disease 2019 pandemic has led to unprecedented demands on the modern health care system, and the highly contagious nature of the virus has led to particular concerns of infection among health care workers and transmission within health care facilities. While strong data regarding the transmissibility of the infection are not yet widely available, preliminary information suggests risk of transmission among asymptomatic individuals, including those within health care facilities. We believe that the presence of a tracheostomy or laryngectomy stoma poses a unique risk of droplet and aerosol spread particularly among patients with unsuspected infection. At our institution, guidelines for the care of open airways were developed by a multidisciplinary open airway working group, and here we review those recommendations to provide practical guidance to other institutions.
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http://dx.doi.org/10.1177/0194599820923632DOI Listing
July 2020

Evaluating the impact of smoking on disease-specific survival outcomes in patients with human papillomavirus-associated oropharyngeal cancer treated with transoral robotic surgery.

Cancer 2020 01 7;126(9):1873-1887. Epub 2020 Feb 7.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.

Background: When treated nonsurgically with definitive chemoradiation, smokers with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a worse prognosis compared with their nonsmoking counterparts. To the authors' knowledge, the prognostic significance of smoking in surgically treated patients is unknown.

Methods: The current study is a retrospective case series of patients with HPV-positive OPSCC who underwent upfront transoral robotic surgery at a single institution from 2010 through 2017. Exclusion criteria were nonoropharyngeal primary tumors, histology other than SCC, HPV-negative tumors, previous history of head and neck cancer, and/or previous head and neck radiotherapy. Recurrence-free survival (RFS), overall survival, and disease-specific survival were compared using the Kaplan-Meier method and the log-rank test. Smoking history was categorized as never smokers (<1 pack-year), current smokers (smoking at the time of the cancer diagnosis), and former smokers.

Results: A total of 258 patients met the study criteria. The average age was 60 years, and approximately 87% of patients were male. A total of 148 patients (57.4%) were smokers whereas 110 (42.6%) reported never smoking. There were 44 active smokers (17.1%) and 104 former smokers (40.3%). The median follow-up was 3.23 years. There were 17 patients of disease recurrence. Smoking pack-year history was not found to be significant for RFS (hazard ratio, 1.01; 95% CI, 0.99-1.03 [P = .45]). There was no significant difference in RFS noted between never and ever smokers (92% vs 89.8%; P = .85) nor was there a difference observed between never, former, and current smokers (92% vs 91.5% vs 86.1%, respectively; P = .69).

Conclusions: A smoking history is common in patients with HPV-positive OPSCC. In the current study, HPV-positive smokers were found to have excellent survival and locoregional control, similar to their nonsmoking counterparts. The results of the current study do not support the exclusion of smokers with early-stage, HPV-positive OPSCC from transoral robotic surgery-based deintensification trials.
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http://dx.doi.org/10.1002/cncr.32739DOI Listing
January 2020

Survivorship support in head and neck cancer: American Head and Neck Society survey.

Head Neck 2020 05 10;42(5):939-944. Epub 2020 Jan 10.

Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan.

Background: The value of supporting cancer survivors beyond formal treatment has become increasingly recognized among clinicians who care for patients with head and neck cancer.

Methods: A survey was developed by the American Head and Neck Society (AHNS) Survivorship Committee and distributed to members of the AHNS electronically.

Results: The survey was distributed to 1403 AHNS members, with 202 responses (14.4%). Among survivorship topics, respondents were most likely to address detection of recurrence/second primary malignancies (97.5%), dysphagia (93.1%), and thyroid function (90.1%) with their patients; they were least likely to address sleep disturbance/apnea (27.7%) and body and self-image issues (29.7%.) Less than half provide patients with a written treatment summary (43.1%) or follow-up care plan (36.9%).

Conclusions: These results highlight the need for improved survivorship care planning and offer an opportunity for the development of educational and survivorship research in head and neck cancer care.
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http://dx.doi.org/10.1002/hed.26066DOI Listing
May 2020

Predictors of Mortality in HPV-Associated Oropharynx Carcinoma Treated With Surgery Alone.

Laryngoscope 2020 07 1;130(7):E423-E435. Epub 2019 Nov 1.

Division of Head and Neck Oncologic and Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, University of California-San Francisco, San Francisco, California.

Objective: Survival outcomes for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treated with surgery alone are unclear. To increase understanding, we assessed overall survival (OS) outcomes using the national cancer database (NCDB).

Methods: We conducted a retrospective analysis of OS of 736 NCDB HPV + OPSCC patients who underwent surgery alone from 2010 to 2014 using univariate and multivariate analyses and the Kaplan-Meir method.

Results: Multivariable analysis found the following independent risk factors for death: American Joint Commission on Cancer (AJCC) 8th edition pathologic stage(p)N2 versus pN0 disease (hazard ratio [HR], 5.5; P = 0.000006), macroscopic extranodal extension (ENE) versus non-ENE (HR, 4.9; P < 0.02), a positive lymph nodes (LN) percentage of ≥10% (HR, 4.2; P = 0.0002), and five or more positive LNs (HR, 4.9; P = 0.00004). Three-year OS was significantly worse for AJCC 8th edition pN2 versus pN0 but not for 7th edition pN2 versus pN0 disease. Five-year OS was significantly worse for positive versus negative surgical margins, AJCC 8th edition stage II versus I, and either microscopic or macroscopic ENE versus non-ENE positive LNs. For 523 (71%) AJCC 8th edition stage I patients and for 283 (38%) patients who were pT1-T2, with negative margins, pN0-N1, with ≤4 pathologic LNs, without ENE, and with >20 LNs removed during neck dissection, the 3-year OS rates were 93% and 95%, respectively, and the 5-year OS rates were 91% and 95%, respectively.

Conclusion: In the context of the lack of detail and possible inaccuracies found in the NCDB, surgery alone for AJCC 8th edition stage I HPV + OPSCC, particularly pT1-T2, pN0-N1 with ≤4 pathologic LNs, without ENE, and with negative surgical margins has a high OS.

Level Of Evidence: 4 Laryngoscope, 130:E423-E435, 2020.
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http://dx.doi.org/10.1002/lary.28344DOI Listing
July 2020

Metformin Effects on FOXP3 and CD8 T Cell Infiltrates of Head and Neck Squamous Cell Carcinoma.

Laryngoscope 2020 09 8;130(9):E490-E498. Epub 2019 Oct 8.

Department of Otolaryngology, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.

Objectives: Alterations of cellular metabolism have been implicated in immune dysfunction in the tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC). Metformin has recently emerged as a candidate of interest for combination with immunotherapy in HNSCC. This study investigated the effect of metformin on immune cell infiltrates of HNSCC.

Methods: Retrospective analysis of T cell infiltrates in primary tumor specimens from patients enrolled in a clinical window of opportunity trial of presurgical metformin. Metformin was titrated to a standard diabetic dose (2000 mg/day) for a minimum of 9 days (mean 13.6 days) prior to surgical resection. Pre and posttreatment surgical specimens from 36 patients (16 HPV , 20 HPV ) were comparatively analyzed. FOXP3 and CD8 immune cell infiltrates in the tumor and peritumoral stroma of pre and posttreatment HNSCC specimens were quantified by digital image analysis using Visiopharm software.

Results: Metformin treatment was associated with a 41.4% decrease in FOXP3 T cells in intratumor regions of interest (P = .004) and a 66.5% increase in stromal CD8 T cells at the leading edge of the tumor (P = .021) when compared to pretreatment biopsies. This was reflected in increased CD8 /FOXP3 cell ratios within the tumor (P < .001) and stromal compartments (P < .001). The effects of metformin occurred independently of HPV status.

Conclusion: Metformin treatment may favorably alter the immune TME in HNSCC independent of HPV status.

Level Of Evidence: 1b. This study is most accurately described as a non-randomized controlled trial and therefore may reflect a level of evidence below 1b but above 2a from the provided "levels of evidence" chart. Laryngoscope, 130:E490-E498, 2020.
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http://dx.doi.org/10.1002/lary.28336DOI Listing
September 2020

Evaluation of oncologic outcomes in head and neck cancer patients ≥80 years old based on adherence to NCCN guideline for postoperative adjuvant treatment.

Head Neck 2019 12 12;41(12):4128-4135. Epub 2019 Sep 12.

Department of Otolaryngology, Thomas Jefferson University, Philadelphia, Pennsylvania.

Background: There is a paucity of literature characterizing outcomes in older adult patients with head and neck cancer (HNC). This study aims to describe patients from this group, their adherence to National Comprehensive Cancer Network (NCCN) adjuvant treatment guidelines, and the impact of guideline adherence on overall survival (OS).

Methods: In this retrospective cohort study, we reviewed all patients ≥80 years old with HNC who underwent surgery with curative intent from 2008 to 2016. Adherence to NCCN guidelines was determined in blinded fashion, and quality metrics and OS were compared.

Results: One hundred fifty-nine patients met inclusion criteria. The majority of patients (n = 94, 59%) underwent treatment in accordance with NCCN recommendations while 65 (41%) deviated from NCCN guidelines. The two cohorts did not demonstrate a difference in 2-year OS (62% vs 66%, P = .50).

Conclusion: Older adult patient outcomes were not different when treatment deviated from NCCN guidelines.
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http://dx.doi.org/10.1002/hed.25950DOI Listing
December 2019

Risk factors for unplanned readmission in total laryngectomy patients.

Laryngoscope 2020 07 26;130(7):1725-1732. Epub 2019 Aug 26.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.

Objective: To determine which patient or surgical factors affect the likelihood of unplanned readmission (within 30 days) after total laryngectomy (TL).

Methods: Retrospective chart review of all patients who underwent TL at a single institution from April 2007 through August 2016. Primary outcome was unplanned readmission to the hospital within 30 days of discharge. Univariable and multivariable logistic regression were performed to identify risk factors for unplanned readmission.

Results: Two hundred seventy-eight patients met inclusion criteria. Twenty-nine patients (10.4%) had unplanned readmissions within 30 days. The most common reasons for readmission were pharyngocutaneous fistula (n = 15), neck abscess (n = 3), and wound breakdown (n = 4). Average time to unplanned readmission was 11.2 days (range 0-27 days). Fistula (OR 30.259; 95% CI, 9.186, 118.147; P ≤ .001), postoperative pneumonia (OR 9.491; 95% CI, 1.783, 53.015; P = .008), and history of cardiac disease (OR 7.074; 95% CI, 2.324, 25.088, P = .001) were independently associated with an increased risk of 30-day unplanned readmission on multivariate analysis. However, return to OR on initial admission was associated with a lower risk of unplanned readmission (OR 0.075; 95% CI, 0.009, 0.402; P = .007). Unplanned readmission was associated with a delay in initiation of adjuvant radiation (OR 1.494; 95% CI, 1.397, 1.599; P < .001).

Conclusion: Unplanned readmission occurs in a small but significant number of TL patients. Patients who have a 30-day unplanned readmission may be at risk for a delay in initiation of adjuvant therapy.

Level Of Evidence: 4 Laryngoscope, 130:1725-1732, 2020.
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http://dx.doi.org/10.1002/lary.28255DOI Listing
July 2020

Carotid dosimetry after re-irradiation with Cs permanent implant brachytherapy in recurrent, resected head and neck cancer.

J Contemp Brachytherapy 2019 Jun 28;11(3):221-226. Epub 2019 Jun 28.

Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: Permanent seed implant cesium-131 (Cs) brachytherapy provides highly localized radiation for patients with recurrent head and neck cancer (HNC), who may be ineligible for external beam radiation therapy due to a high-risk of toxicity. As carotid blowout is a concern in the setting of re-irradiation, a dose to the carotid artery was examined for Cs brachytherapy implants.

Material And Methods: Eleven patients were implanted with Cs adjacent to carotid at the time of resection for recurrent HNC. Vascularized tissue flaps were used in some patients. The carotid artery was contoured on the post-implant brachytherapy treatment plan, and the maximum carotid point dose and minimum carotid-seed distances are reported. The incidence of carotid blowout in the follow-up period was also measured.

Results: The maximum carotid dose was 77 ±52 Gy (range, 3-158 Gy). The closest seed to the carotid artery was 0.8 ±0.8 cm (range, 0.2-2.6 cm). One patient without a flap experienced carotid blowout, which was attributed to a non-healing wound rather than to high radiation doses.

Conclusions: Carotid artery doses from Cs are reported. Vascularized tissue flaps should be considered when planning Cs brachytherapy.
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http://dx.doi.org/10.5114/jcb.2019.86298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701389PMC
June 2019

Single institution implementation of permanent Cs interstitial brachytherapy for previously irradiated patients with resectable recurrent head and neck carcinoma.

J Contemp Brachytherapy 2019 Jun 28;11(3):227-234. Epub 2019 Jun 28.

Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States.

Purpose: Permanent interstitial brachytherapy is an appealing treatment modality for patients with locoregional recurrent, resectable head and neck carcinoma (HNC), having previously received radiation. Cesium-131 (Cs) is a permanent implant brachytherapy isotope, with a low average photon energy of 30 keV and a short half-life of 9.7 days. Exposure to medical staff and family members is low; patient isolation and patient room shielding are not required. This work presents a single institution's implementation process of utilizing an intraoperative, permanent Cs implant for patients with completely resected recurrent HNC.

Material And Methods: Fifteen patients receiving Cs permanent seed brachytherapy were included in this analysis. The process of pre-planning, selecting the dose prescription, seed ordering, intraoperative procedures, post-implant planning, and radiation safety protocols are described.

Results: Tumor volumes were contoured on the available preoperative PET/CT scans and a pre-implant treatment plan was created using uniform source strength and uniform 1 cm seed spacing. Implants were performed intraoperatively, following tumor resection. In five of the fifteen cases, intraoperative findings necessitated a change from the planned number of seeds and recalculation of the pre-implant plan. The average prescription dose was 56.1 ±6.6 Gy (range, 40-60 Gy). The average seed strength used was 2.2 ±0.2 U (3.5 ±0.3 mCi). Patients returned to a recovery room on a standard surgical floor and remained inpatients, without radiation safety restrictions, based on standard surgical recovery protocols. A post-implant treatment plan was generated based on immediate post-operative CT imaging to verify the seed distribution and confirm delivery of the prescription dose. Patients were provided educational information regarding radiation safety recommendations.

Conclusions: Cesium-131 interstitial brachytherapy is feasible and does not pose major radiation safety concerns; it should be considered as a treatment option for previously irradiated patients with recurrent, resectable HNC.
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http://dx.doi.org/10.5114/jcb.2019.85778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701381PMC
June 2019

Prognostic Significance of Tumor-Associated Macrophage Content in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis.

Front Oncol 2019 23;9:656. Epub 2019 Jul 23.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, United States.

Head and neck squamous cell carcinoma (HNSCC) exists within a microenvironment rich in immune cells. Macrophages are particularly abundant in and around tumor tissue, and have been implicated in the growth, malignancy, and persistence of HNSCC (1). However, current literature reports variable degrees of association between the density of tumor-associated macrophages (TAMs) and clinicopathologic markers of disease (2, 3). These inconsistent findings may be a result of differences in approach to TAM detection. Authors have measured total TAMs in tumor tissue, while others have stained tumor samples for individual subtypes of TAMs, which include pro-inflammatory (M1-like) and immunosuppressive (M2-like). Our aim is to more clearly define the prognostic significance of the phenotypes of tumor-associated macrophages in HNSCC. We conducted a meta-analysis of the existing publications investigating the relationship between TAMs (total and M2-like subtype) and T stage, nodal involvement, vascular invasion, lymphatic invasion, and tumor differentiation (). A total of 12 studies were included. Forest plots and risk ratios were generated to report overall effect. Higher density of both total and M2-like subtype of TAMs in the tumor microenvironment is associated with advanced T stage, increased rates of nodal positivity, presence of vascular invasion, and presence of lymphatic invasion ( < 0.0001; ). There is no significant association between TAM density, either total or M2-like subtype, and tumor differentiation (, ). Increased density of TAMs, including those of the M2-like phenotype, correlate with poor clinicopathologic markers in HNSCC. Our findings warrant additional investigation into the subpopulations of TAMs, the mechanisms behind their recruitment and differentiation, and the associated influence of each phenotype on tumor growth and invasion. A greater understanding of TAM dynamics in HNSCC is critical for directing further research and employing TAM-targeted adjunct therapies.
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http://dx.doi.org/10.3389/fonc.2019.00656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663973PMC
July 2019

Postoperative opioid-prescribing practices in otolaryngology: A multiphasic study.

Laryngoscope 2020 03 21;130(3):659-665. Epub 2019 Jun 21.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A.

Objectives: In otolaryngology, postoperative pain management lacks evidence-based guidelines. We designed a prospective, multiphasic study aimed to develop evidence-based guidelines for postoperative pain management within our institution. In this first phase of our project, we investigated opioid prescription and consumption as well as pain trends for common otolaryngologic procedures.

Methods: Patients (n = 161) who underwent procedures between July 2018 and February 2019 were surveyed on their postoperative opioid usage and pain from day of discharge to first clinic visit. Opioid prescriptions were converted to standardized units of morphine milligram equivalents (MME). The procedures selected for analysis were parathyroidectomy/thyroidectomy, parotidectomy, sialendoscopy, and transoral robotic surgery resection (TORS).

Results: In total, 19,748 MME were prescribed: 8,588 MME (43.5%) were used, leaving 11,159 MME (56.5%) unused. TORS average MME used: 221 ± 227; total MME unused: 38%. Sialendoscopy average MME used: 31 ± 46; total MME unused: 67%. Parathyroidectomy/thyroidectomy average MME used: 30 ± 37; total MME unused: 66%. Parotidectomy average MME used: 43 ± 53; total MME unused: 65%. Male gender, smoking (current and former), and psychiatric medication use were positive predictors of opioid consumption in postoperative patients (P < 0.001).

Conclusion: At our institution, over 50% of prescribed postoperative opioids went unused. This was most pronounced for nonmucosal surgeries. Postoperative pain management should account for this to minimize unnecessary opioid prescriptions. Based on our findings and review of current literature, we are in the process of developing prescribing recommendations to be implemented within our institution.

Level Of Evidence: 2 Laryngoscope, 130:659-665, 2020.
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http://dx.doi.org/10.1002/lary.28101DOI Listing
March 2020

Early squamous cell carcinoma of the oral tongue with histologically benign lymph nodes: A model predicting local control and vetting of the eighth edition of the American Joint Committee on Cancer pathologic T stage.

Cancer 2019 09 7;125(18):3198-3207. Epub 2019 Jun 7.

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: The eighth edition of the American Joint Committee on Cancer staging manual (AJCC8) added depth of invasion to the definition of pathologic T stage (pT). In the current study, the authors assess pT stage migration and the prognostic performance of the updated pT stage and compare it with other clinicopathologic variables in patients with early squamous cell carcinoma of the oral tongue (OTSCC; tumors measuring ≤4 cm) with histologically benign lymph nodes (pN0).

Methods: A multi-institutional cohort of patients with early OTSCC was restaged as per AJCC8. Primary endpoints were local recurrence (LR) and locoregional recurrence (LRR). Influential variables were identified and an LR/LRR prediction model was developed.

Results: There were a total of 494 patients, with 49 LR and 73 LRR. AJCC8 pT criteria resulted in upstaging of 37.9% of patients (187 of 494 patients), including 34.5% (64 of 185 patients) from pT2 to pT3, without improving the prognostication for LR or LRR. Both LR and LRR were found to be similar for patients with AJCC8 pT2 and pT3 disease. On multivariate analysis, LR was only found to be associated with distance to the closest margin (hazard ratio, 0.36; 95% CI, 0.20-0.64 [P = .0007]) and perineural invasion (hazard ratio, 1.92; 95% CI, 1.10-0.64 [P = .046]). Based on these 2 predictors, a final proportional hazards regression model (which may be used similar to a nomogram) was developed. The proposed model appeared to be superior to AJCC pT stage for estimating the probability of LR and LRR for individual patients with early OTSCC.

Conclusions: AJCC8 pT criteria resulted in pT upstaging of patients with pN0 disease without improved LR or LRR prognostication. The proposed model based on distance to the closest margin and perineural invasion, status outperformed pT as a predictor of LR and LRR in patients with early OTSCC.
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http://dx.doi.org/10.1002/cncr.32199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723468PMC
September 2019

Response to "Letter to the Editor": Eagle's Syndrome Requires Further Consideration.

Ann Otol Rhinol Laryngol 2019 09 1;128(9):880. Epub 2019 May 1.

1 Department of Otolaryngology/Head & Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, PA, USA.

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http://dx.doi.org/10.1177/0003489419845618DOI Listing
September 2019

Assessment of quality and consistency of monoclonal antibodies for CB1 and CB2 in head and neck squamous cell carcinoma.

Head Neck 2019 09 29;41(9):3105-3113. Epub 2019 Apr 29.

Department of Dermatology & Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.

Background: Marijuana has numerous roles as an agonist in the endocannabinoid signaling system (ESS). This study evaluated monoclonal antibodies across experimental techniques to establish a framework for studying ESS receptors, CB1 and CB2.

Methods: Tissue from five patients with head and neck cancer were used to generate cell lines and formalin-fixed paraffin-embedded (FFPE) sections, which were analyzed by western blot (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Subgroup analysis was performed on FFPE sections from 8 marijuana users and 10 controls by IHC. Results were compared across methods for consistency.

Results: In all patients, WB and IF were CB1 positive, whereas IHC was negative. Select samples were CB2 positive by WB, but failed IF and IHC applications. In subgroup analysis, 1 of 8 users and 3 of 10 nonusers were CB1 positive.

Conclusions: Interpretation of CB1/CB2 antibody data should be performed cautiously and confirmation of findings across multiple experimental methods is recommended.
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http://dx.doi.org/10.1002/hed.25794DOI Listing
September 2019

Sensitivity of Fine-Needle Aspiration and Imaging Modalities in the Diagnosis of Low-Grade Mucoepidermoid Carcinoma of the Parotid Gland.

Ann Otol Rhinol Laryngol 2019 Aug 16;128(8):755-759. Epub 2019 Apr 16.

1 Department of Otolaryngology-Head and Neck Surgery, BS, Thomas Jefferson University, Philadelphia, PA, USA.

Objective: To determine the diagnostic accuracy of fine-needle aspiration (FNA) and imaging modalities for low-grade mucoepidermoid carcinoma (MEC) of the parotid gland.

Methods: Retrospective chart review of patients diagnosed with low-grade MEC of the parotid gland following surgical excision between January 2010 and June 2018. Imaging from patients with MEC were randomly mixed with imaging from patients with benign pathology and reviewed in a blinded fashion. Main outcome measure was sensitivity.

Results: A total of 24 patients were confirmed to have had low-grade MEC on final pathology, with a total of 31 FNAs performed between them. Twelve of 31 FNAs were positive for low-grade MEC, with a sensitivity of 39%. A total of 27 imaging studies were reviewed, which included 16 patients with low-grade MEC and 11 patients with benign pathology. Of these 27 imaging studies, 10 were declared indeterminate. Of the remaining 17 imaging studies, 13 were reviewed as malignant (11 true positive and 2 false positive) and 4 as benign (4 true negative). Overall magnetic resonance imaging (MRI) sensitivity for low-grade MEC was 100% (9/9) with 95% CI (0.66-1.0) when considering indeterminate results as positive for malignancy.

Conclusion: This study reaffirms that for low-grade MEC, sensitivity of FNA is poor. MRI provides an important diagnostic tool in the evaluation of salivary gland neoplasms, due to its increased sensitivity for low-grade MEC when considering indeterminate results as positive. This provides confidence in the diagnosis of benign tumors and allows appropriate counseling of all options to the patient, including observation. Imaging and low threshold of excision should be considered despite an inflammatory or benign FNA.
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http://dx.doi.org/10.1177/0003489419842582DOI Listing
August 2019

Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer.

Head Neck 2019 08 21;41(8):2655-2664. Epub 2019 Mar 21.

Head and Neck Academic Centre, Department of Head and Neck Surgery, University College London Hospital, London, UK.

Background: The eighth international symposium for sentinel node biopsy (SNB) in head and neck cancer was held in 2018. This consensus conference aimed to deliver current multidisciplinary guidelines. This document focuses on the surgical aspects of SNB for oral cancer.

Method: Invited expert faculty selected topics requiring guidelines. Topics were reviewed and evidence evaluated where available. Data were presented at the consensus meeting, with live debate from panels comprising expert, nonexpert, and patient representatives followed by voting to assess the level of support for proposed recommendations. Evidence review, debate, and voting results were all considered in constructing these guidelines.

Results/conclusion: A range of topics were considered, from patient selection to surgical technique and follow-up schedule. Consensus was not achieved in all areas, highlighting potential issues that would benefit from prospective studies. Nevertheless these guidelines represent an up-to-date pragmatic recommendation based on current evidence and expert opinion.
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http://dx.doi.org/10.1002/hed.25739DOI Listing
August 2019

Pigmented Melanotic Schwannoma of the Neck: Report of 2 Cases and Review of the Literature.

Ear Nose Throat J 2019 Feb 13;98(2):102-106. Epub 2019 Feb 13.

1 Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, USA.

Background:: Melanotic schwannoma is a rare tumor with indeterminate biologic behavior and varying treatment recommendations.

Methods:: We report 2 cases of pigmented melanotic schwannoma of the head and neck and perform literature review. The pathologic and immunohistochemical characteristics of melanotic schwannoma are reviewed.

Results:: Two cases of melanotic schwannoma are presented. Both cases underwent surgical resection with one patient receiving adjuvant radiation therapy.

Conclusions:: Melanotic schwannoma is a rare nerve sheath tumor that is frequently mistaken for malignant melanoma. We describe 2 cases of pigmented melanotic schwannoma of the head and neck with different presentations and review the histopathological and immunohistochemical features.
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http://dx.doi.org/10.1177/0145561319826542DOI Listing
February 2019

In Reference to Should the Contralateral Tonsil Be Removed in Cases of HPV-Positive Squamous Cell Carcinoma of the Tonsil?

Laryngoscope 2019 06 5;129(6):E194. Epub 2019 Mar 5.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1002/lary.27876DOI Listing
June 2019