Publications by authors named "Robert M Brody"

44 Publications

Definitive tumor directed therapy confers a survival advantage for metachronous oligometastatic HPV-associated oropharyngeal cancer following trans-oral robotic surgery.

Oral Oncol 2021 Oct 30;121:105509. Epub 2021 Aug 30.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.

Objectives: To assess the prognostic significance of oligometastatic versus polymetastatic disease in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), and to evaluate the impact of definitive tumor directed therapy on the survival outcomes for patients with oligometastatic disease when compared to systemic therapy.

Materials And Methods: This was a retrospective observational cohort study of patients with HPV-associated OPSCC who developed distant metachronous metastatic disease after undergoing initial primary surgical management from 2008 to 2017. We classified patients based on the extent of metastatic disease [Oligometastatic (≤5 metastases) and polymetastatic (>5 metastases)], and the initial treatment of metastatic disease [definitive tumor directed therapy (all metastases treated with surgery or radiotherapy) versus upfront systemic therapy].

Results: Among 676 patients undergoing primary surgical management for HPV-associated OPSCC, 39 patients (5.8%) developed metastases after a median follow-up of 29.6 months (range 4.5-127.0). Of the 34 metastatic patients who met study criteria, 26 (76.5%) were oligometastatic and 8 (23.5%) were polymetastatic. Oligometastatic patients had improved median overall survival (OS) compared to polymetastatic patients (47.9 vs. 22.7 months, p = 0.036). For oligometastatic patients, definitive tumor directed therapy was associated with an improved median progression free survival (not reached vs 6.13 months, p = 0.001) and median OS (not reached vs 40.7 months, p = 0.004).

Conclusion: In a cohort of patients surgically treated for HPV-associated OPSCC, metachronous metastatic disease was uncommon and, in most cases, considered oligometastatic. Oligometastasis portends a favorable prognosis and definitive tumor directed therapy may be associated with improved overall survival in these patients. Future multi-institutional efforts are warranted to further demonstrate the impact of definitive tumor directed therapy on disease outcomes.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105509DOI Listing
October 2021

Compliance with sentinel lymph node biopsy guidelines for invasive melanomas treated with Mohs micrographic surgery.

Cancer 2021 Oct 22;127(19):3591-3598. Epub 2021 Jul 22.

Department of Dermatology, University of Pennsylvania Health System, Philadelphia, Pennsylvania.

Background: Sentinel lymph node biopsy (SLNB) has not been studied for invasive melanomas treated with Mohs micrographic surgery using frozen-section MART-1 immunohistochemical stains (MMS-IHC). The primary objective of this study was to assess the accuracy and compliance with National Comprehensive Cancer Network (NCCN) guidelines for SLNB in a cohort of patients who had invasive melanoma treated with MMS-IHC.

Methods: This retrospective cohort study included all patients who had primary, invasive, cutaneous melanomas treated with MMS-IHC at a single academic center between March 2006 and April 2018. The primary outcomes were the rates of documenting discussion and performing SLNB in patients who were eligible based on NCCN guidelines. Secondary outcomes were the rate of identifying the sentinel lymph node and the percentage of positive lymph nodes.

Results: In total, 667 primary, invasive, cutaneous melanomas (American Joint Committee on Cancer T1a-T4b) were treated with MMS-IHC. The median patient age was 69 years (range, 25-101 years). Ninety-two percent of tumors were located on specialty sites (head and/or neck, hands and/or feet, pretibial leg). Discussion of SLNB was documented for 162 of 176 (92%) SLNB-eligible patients, including 127 of 127 (100%) who had melanomas with a Breslow depth >1 mm. SLNB was performed in 109 of 176 (62%) SLNB-eligible patients, including 102 of 158 melanomas (65%) that met NCCN criteria to discuss and offer SLNB and 7 of 18 melanomas (39%) that met criteria to discuss and consider SLNB. The sentinel lymph node was successfully identified in 98 of 109 patients (90%) and was positive in 6 of those 98 patients (6%).

Conclusions: Combining SLNB and MMS-IHC allows full pathologic staging and confirmation of clear microscopic margins before reconstruction of specialty site invasive melanomas. SLNB can be performed accurately and in compliance with consensus guidelines in patients with melanoma using MMS-IHC.
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http://dx.doi.org/10.1002/cncr.33651DOI Listing
October 2021

Postoperative Radiation Therapy Refusal in Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

Laryngoscope 2021 Jul 13. Epub 2021 Jul 13.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, U.S.A.

Objectives/hypothesis: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct clinical entity with good prognosis, unique demographics, and a trend toward treatment deintensification. Patients with this disease may opt out of recommended postoperative radiation therapy (PORT) for a variety of reasons. The aim of this paper was to examine factors that predict patient refusal of recommended PORT in HPV-associated OPSCC, and the association of refusal with overall survival.

Study Design: Retrospective population-based cohort study of patients in the National Cancer Database.

Methods: We conducted a retrospective cohort study of patients in the National Cancer Database diagnosed with OPSCC between January 2010 and December 2015. We primarily assessed overall survival and the odds of refusing PORT based on demographic, socioeconomic, and clinical factors. Analysis was conducted using multivariable logistic regression and multivariable Cox proportional hazards model.

Results: A total of 4229 patients were included in the final analysis, with 156 (3.7%) patients opting out of recommended PORT. On multivariable analysis, patient refusal of PORT was independently associated with a variety of socioeconomic factors such as race, insurance status, comorbidity, treatment at a single facility, and margin status. Lastly, PORT refusal was associated with significantly lower overall survival compared to receipt of recommended PORT (hazard ratio 1.69, confidence interval 1.02-2.82).

Conclusions: Patient refusal of recommended PORT in HPV-associated OPSCC is rare and associated with variety of disease and socioeconomic factors. PORT refusal may decrease overall survival in this population. Our findings may help clinicians when counseling patients and identifying those who may be more likely to opt out of recommended adjuvant therapy.

Level Of Evidence: 3 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29743DOI Listing
July 2021

Impact of Race and Insurance Status on Primary Treatment for HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

Otolaryngol Head Neck Surg 2021 Jul 13:1945998211029839. Epub 2021 Jul 13.

Department of Otolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: To assess the impact of sociodemographic factors on primary treatment choice (surgery vs radiotherapy) in patients with human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC).

Study Design: Retrospective analysis of the National Cancer Database.

Setting: Data from >1500 Commission on Cancer institutions (academic and community) via the National Cancer Database.

Methods: Our sample consists of patients diagnosed with HPV+ OPSCC from 2010 to 2015. The primary outcome of interest was initial treatment modality: surgery vs radiation. We performed multivariable logistic models to assess the relationship between treatment choice and sociodemographic factors, including sex, race, treatment facility, and insurance status.

Results: Of the 16,043 patients identified, 5894 (36.7%) underwent primary surgery while 10,149 (63.3%) received primary radiotherapy. Black patients were less likely than White patients to receive primary surgery (odds ratio [OR], 0.80; 95% CI, 0.66-0.96). When compared with privately insured patients, those who were uninsured or on Medicaid or Medicare were also less likely to receive primary surgery (OR, 0.70 [95% CI, 0.56-0.86]; OR, 0.77 [95% CI, 0.65-0.91]; OR, 0.85 [95% CI, 0.75-0.96], respectively). Patients receiving treatment at an academic/research cancer program were more likely to undergo primary surgery than those treated at comprehensive community cancer programs (OR, 1.33; 95% CI, 1.14-1.56).

Conclusion: In this large sample of patients with HPV+ OPSCC, race and insurance status affect primary treatment choice. Specifically, Black and nonprivately insured patients are less likely to receive primary surgery as compared with White or privately insured patients. Our findings illuminate potential disparities in HPV+ OPSCC treatment.
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http://dx.doi.org/10.1177/01945998211029839DOI Listing
July 2021

Anterolateral thigh osteomyocutaneous flap in head and neck: Lessons learned.

Microsurgery 2021 Jun 26. Epub 2021 Jun 26.

Departments of Oral and Maxillofacial Surgery and Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Concerns regarding iatrogenic femur fracture may deter adoption of the anterolateral thigh osteomyocutaneous (ALTO) flap as an alternative reconstructive technique for large composite defects of the head and neck. We describe the evolution of our experience with this flap and the lessons learned in femur management.

Methods: Records from a prospective database (July 2009-January 2020) were reviewed to identify patients with composite osseous free tissue reconstructions. Venous thromboembolic events (VTE), femur fracture, estimated blood loss (EBL), procedure time, blood transfusions, and length of stay (days) were compared for ALTO flaps prior to and after the adoption of intramedullary fixation protocol.

Results: ALTO represented 10.5% (n = 23) of total osseus (n = 219) flaps. For large composite reconstructions with either ALTO flap, double flap (n = 2), or subscapular mega flaps (n = 14), ALTO flaps were most frequently used (59%, n = 23/59). There were no differences in operative time prior to and after implementation of prophylactic fixation [median (range): 5.4 (1.7-19.2) vs. 5.8 (1.7-15.0), p = .574]. Additionally, there were no differences in VTE, femur fracture, EBL, blood transfusion, or length of stay (p > .05) with adoption of prophylactic intramedullary fixation.

Conclusions: The ALTO flap represents a useful tool to consider in the armamentarium of reconstructive options for large through and through defects of the head and neck. In our experience, the ALTO flap is a reasonable alternative to subscapular or double flap reconstructions and especially in the setting of unusable fibular flaps or when bone need exceeds that available from the scapula.
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http://dx.doi.org/10.1002/micr.30779DOI Listing
June 2021

Survival and toxicity in patients with human papilloma virus-associated oropharyngeal squamous cell cancer receiving trimodality therapy including transoral robotic surgery.

Head Neck 2021 Oct 25;43(10):3053-3061. Epub 2021 Jun 25.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Patients with oropharyngeal cancer who undergo transoral robotic surgery (TORS) and have high-risk features generally receive adjuvant chemoradiotherapy or trimodality therapy (TMT). The notion that TMT leads to high toxicity is largely based on studies that included human papilloma virus (HPV)-negative cancers and/or nonrobotic surgery; we sought to describe outcomes in HPV-associated oropharyngeal squamous cell cancer (HPV + OPSCC) undergoing TORS-TMT.

Methods: In consecutive patients with HPV + OPSCC receiving TMT at an academic center from 2010 to 2017, survival was estimated using Kaplan-Meier methodology, and toxicities were ascertained via chart review.

Results: In our cohort of 178 patients, 5-year survival was 93.6%. Feeding tube rates were 25.8% at therapy completion and 0.7% at 1 year. Rates of grade ≥ 3 kidney injury, anemia, and neutropenia in cisplatin-treated patients were 2.7%, 3.4%, and 11.0%, respectively.

Conclusions: Patients with HPV + OPSCC who underwent TORS-TMT had excellent survival and low rates of toxicity and feeding tube dependence. These outcomes compare favorably to historical cohorts treated with definitive chemoradiotherapy.
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http://dx.doi.org/10.1002/hed.26797DOI Listing
October 2021

Oncologic outcomes of transoral robotic surgery for HPV-negative oropharyngeal carcinomas.

Head Neck 2021 Oct 8;43(10):2923-2934. Epub 2021 Jun 8.

Department of Otorhinolaryngology - Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Patients with human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) continue to experience disappointing outcomes following chemoradiotherapy (CRT) and appreciable morbidity following historical surgical approaches. We aimed to investigate the oncologic outcomes and perioperative morbidity of a transoral robotic surgery (TORS) approach to surgically resectable HPV-negative OPSCC.

Methods: Retrospective analysis HPV-negative OPSCC patients who underwent TORS, neck dissection and pathology-guided adjuvant therapy (2005-2017).

Results: Fifty-six patients (91.1% stage III/IV) were included. Three-year overall survival, locoregional control, and disease-free survival were 85.5%, 84.4%, and 73.6%, respectively (median follow-up 30.6 months, interquartile range 18.4-66.6). Eighteen (32.1%) patients underwent adjuvant radiotherapy and 20 (39.3%) underwent adjuvant CRT. Perioperative mortality occurred in one (1.8%) patient and hemorrhage occurred in two (3.6%) patients. Long-term gastrostomy and tracheostomy rates were 5.4% and 0.0%, respectively.

Conclusion: The TORS approach for resectable HPV-negative OPSCC can achieve encouraging oncologic outcomes with infrequent morbidity.
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http://dx.doi.org/10.1002/hed.26776DOI Listing
October 2021

Locoregional Recurrence in p16-Positive Oropharyngeal Squamous Cell Carcinoma After TORS.

Laryngoscope 2021 Jun 2. Epub 2021 Jun 2.

Department of Otorhinolaryngology: Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Objective: To analyze the patterns, risk factors, and salvage outcomes for locoregional recurrences (LRR) after treatment with transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC).

Study Design: Retrospective analysis of HPV+ OPSCC patients completing primary TORS, neck dissection, and NCCN-guideline-compliant adjuvant therapy at a single institution from 2007 to 2017.

Methods: Features associated with LRR, detailed patterns of LRR, and outcomes of salvage therapy were analyzed. Disease-free survival (DFS) and overall survival (OS) were calculated for subgroups of patients receiving distinct adjuvant treatments.

Results: Of 541 patients who completed guideline-indicated therapy, the estimated 5-year LRR rate was 4.5%. There were no identifiable clinical or pathologic features associated with LRR. Compared to patients not receiving adjuvant therapy, those who received indicated adjuvant radiation alone had a lower risk of LRR (HR 0.28, 95% CI [0.09-0.83], P = .023), but there was no difference in DFS (P = .21) and OS (P = .86) between adjuvant therapy groups. The 5-year OS for patients who developed LRR was 67.1% vs. 93.9% for those without LRR (P < .001). Patients who initially received adjuvant chemoradiation and those suffering local, in-field, and/or retropharyngeal node recurrences had decreased disease control after salvage therapy.

Conclusion: LRR rates are low for HPV+ OPSCCs completing TORS and guideline-compliant adjuvant therapy. Patients without indication for adjuvant therapy more often suffer LRR, but these recurrences are generally controllable by salvage therapy. Improved understanding of the patterns of recurrence most amenable to salvage therapy may guide treatment decisions, counseling, and adjuvant therapy de-escalation trials.

Level Of Evidence: 3 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29659DOI Listing
June 2021

Palliative care in metastatic head and neck cancer.

Head Neck 2021 09 21;43(9):2764-2777. Epub 2021 May 21.

Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Background: Due to inherent impact on quality of life, metastatic head and neck cancer patients are well-suited to benefit from palliative care (PC). Our objective was to examine factors that shape PC utilization and implications for overall survival in stage IVc head and neck cancer patients.

Methods: A retrospective study of patients with stage IVc head and neck cancer in the National Cancer Database from 2004 and 2015 was conducted.

Results: 7794 cases met inclusion criteria, of which 19.3% received PC. PC use was associated with more recent years of diagnosis, Northeast facility geography, and non-private insurances (p < 0.05). Compared to no PC, "interventional" PC, defined as palliative surgery, radiation, and/or chemotherapy, and "pain management only" PC were associated with lower overall survival (p < 0.05).

Conclusions: PC use increased over time and was associated with demographic and clinical factors. There remains opportunity for improvement in optimal implementation of palliative care.
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http://dx.doi.org/10.1002/hed.26761DOI Listing
September 2021

Evaluation of an interactive virtual surgical rotation during the COVID-19 pandemic.

World J Otorhinolaryngol Head Neck Surg 2021 Apr 24. Epub 2021 Apr 24.

Department of Otorhinolaryngology - Head & Neck Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.

Objective: To evaluate medical student and attending surgeon experiences with a novel interactive virtual Otolaryngology - Head and Neck Surgery (OHNS) medical student elective during the COVID-19 pandemic.

Study Design: A virtual OHNS elective was created, with three components: (1) interactive virtual operating room (OR) experience using live-stream video-conferencing, (2) telehealth clinic, (3) virtual didactics.

Setting: OHNS Department at the University of Pennsylvania (May 2020 to June 2020).

Methods: Six medical students from the University of Pennsylvania; five attending otolaryngologists. Two surveys were designed and distributed to participating medical students and attending surgeons. Surveys included 5-point Likert scale items, with 1 indicating "not at all" and 5 indicating "very much so".

Results: Response rate was 100% for both surveys. Students on average rated the educational value of the telehealth experience as 4.2 ± 1.2, and the virtual OR experience as 4.0 ± 0.6. Most students ( = 5, 83%) indicated that they had enough exposure to faculty they met on this rotation to ask for a letter of recommendation (LOR) for residency if needed, while attending surgeons had an average response of 3.0 ± 1.0 when asked how comfortable they would feel writing a LOR for a student they met through the rotation. A majority of students ( = 4, 67%) felt they connected enough with faculty during the rotation to ask for mentorship. Half the students ( = 5, 50%) indicated that the rotation allowed them to evaluate the department's culture either "extremely well" or "somewhat well".

Conclusions: Overall, participating students described this innovative virtual surgical rotation as an educationally and professionally valuable experience. With the continued suspension of visiting student rotations due to the COVID-19 pandemic, this virtual model may have continued relevance to medical education.
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http://dx.doi.org/10.1016/j.wjorl.2021.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064875PMC
April 2021

Oncologic and survival outcomes for resectable locally-advanced HPV-related oropharyngeal cancer treated with transoral robotic surgery.

Oral Oncol 2021 Jul 28;118:105307. Epub 2021 Apr 28.

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Objectives: To determine whether up-front trans-oral robotic surgery (TORS) for clinically-staged locally-advanced human papillomavirus (HPV)-related oropharyngeal cancer is associated with oncologic and survival outcomes comparable to early-stage (cT1/T2) tumors.

Materials And Methods: Retrospective cohort study of 628 patients with HPV-related oropharyngeal cancer who underwent up-front TORS from 2007 to 2017. Patients were stratified into two cohorts based on early-stage (cT1/2) versus locally-advanced (cT3/4) tumor at presentation.

Results: We identified 589 patients who presented with early-stage tumors, and 39 patients with locally-advanced tumors. Of these, 73% of patients required adjuvant radiation, and 33% required adjuvant chemoradiation. There was no significant difference in the administration of adjuvant radiation or chemoradiation between the two cohorts. Patients in the locally-advanced disease cohort were significantly more likely to have Stage II/III disease by clinical and pathologic criteria by American Joint Committee on Cancer 8th edition criteria (p < 0.001). However, there was no significant difference in 5-year overall survival (OS) or recurrence-free survival (RFS) based on Kaplan-Meier survival estimates between the two cohorts (p = 0.75, 0.6, respectively), with estimated OS of 91% at 5 years, and estimated RFS of 86% at 5 years across the study population.

Conclusions: Up-front TORS offers favorable survival outcomes for appropriately selected locally-advanced cases of HPV-related oropharyngeal cancer. Furthermore, up-front TORS is comparably effective in allowing avoidance of adjuvant therapy, particularly chemotherapy, in both cT1/T2 and locally-advanced HPV-positive oropharyngeal cancer. In the absence of clear technical contraindication to surgery, cT3/T4 classification should not be considered an absolute contraindication to surgery.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105307DOI Listing
July 2021

Objective screening for olfactory and gustatory dysfunction during the COVID-19 pandemic: a prospective study in healthcare workers using self-administered testing.

World J Otorhinolaryngol Head Neck Surg 2021 Feb 12. Epub 2021 Feb 12.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA.

Background: Smell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID-19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID-19 patients suggests that self-reported measures are insufficient for capturing patients with chemosensory dysfunction.

Objectives: The purpose of this study was to quantify the impact of recent COVID-19 infection on chemosensory function and demonstrate the use of at-home objective smell and taste testing in an at-risk population of healthcare workers.

Methods: Two hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self-administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one-month follow-up surveys were completed.

Results: Among subjects with prior SARS-CoV-2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self-reported smell and taste loss were both strong predictors of COVID-19 positivity. Subjects with evidence of recent SARS-CoV-2 infection (<45 days) had significantly lower olfactory scores but equivalent gustatory scores compared to other subjects. There was a time-dependent increase in smell scores but not in taste scores among subjects with prior infection and chemosensory symptoms. The overall infection rate was 4.4%, with 2.5% reported by PCR swab.

Conclusion: Healthcare workers with recent SARS-CoV-2 infection had reduced olfaction and normal gustation on self-administered objective testing compared to those without infection. Rates of infection and chemosensory symptoms in our cohort of healthcare workers reflect those of the general public.
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http://dx.doi.org/10.1016/j.wjorl.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879131PMC
February 2021

Primary Orbital Melanoma: An Investigation of a Rare Malignancy Using the National Cancer Database.

Laryngoscope 2021 08 11;131(8):1790-1797. Epub 2021 Feb 11.

Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Objectives: Primary orbital melanoma (POM) is a rare disease with limited data on survival and best treatment practices. Here we utilize the National Cancer Database (NCDB) to determine the overall survival (OS) and covariates that influence mortality.

Study Design: Retrospective cohort study.

Methods: All patients diagnosed with POM from 2004 to 2016 were identified in the NCDB. Patient and oncologic data were analyzed using the Kaplan-Meier method and multivariate models for the primary outcome of OS.

Results: A total of 129 patients were identified. Median OS was 36.9 months (95% confidence interval [CI] 24.1-78.7 months) with mean 5-year survival of 42.0% (CI 33.2%-53.2%). Treatments received included surgery alone (43.4%), radiation alone (23.3%), and surgery followed by radiation (20.2%). The multivariate model demonstrated an increased risk of death associated with age over 80 years (hazard ratio [HR] 3.41, CI 1.31-8.86, P = .012), a Charlson-Deyo comorbidity score of 2 or greater (HR 5.30, CI 1.87-15.03, P = .002), and no treatment (HR 2.28, CI 1.03-5.06, P = .042). For every 1 cm increase in tumor size, there was an increased risk of death (HR 1.06, CI 1.00-1.13, P = .039). When compared to surgery alone, no other treatment modality had an effect on OS.

Conclusions: This study leveraged multiyear data from the NCDB to provide prognostic and demographic information on the largest known cohort of POM cases. Increased age, increased comorbidities, not receiving treatment, and larger tumor size were associated with increased mortality. There was no clear survival advantage for specific treatments.

Level Of Evidence: 4 Laryngoscope, 131:1790-1797, 2021.
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http://dx.doi.org/10.1002/lary.29428DOI Listing
August 2021

Role of elective neck dissection and adjuvant radiation therapy in patients with polymorphous adenocarcinoma.

Eur Arch Otorhinolaryngol 2021 Sep 3;278(9):3459-3466. Epub 2021 Jan 3.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, 800 Walnut Street, 18th Floor, Philadelphia, PA, 19107, USA.

Purpose: To evaluate the role of elective neck dissection (END) and of adjuvant radiation (aRT) in polymorphous adenocarcinoma (PAC), previously known as polymorphous low-grade adenocarcinoma (PLGA).

Methods: Retrospective cohort study of patients in the National Cancer Database with a histology of PAC (coded as PLGA) at a head and neck site diagnosed between 2004 and 2015. Multivariable Cox proportional hazard modeling was used to assess overall survival in the overall population, and in sub-analyses of clinically N0 disease, positive resection margins, and late stage disease.

Results: A total of 922 patients [66.8% female; mean (SD) age, 60.9 (13.9) years] met inclusion criteria. 74.7% of patients received surgery alone, and 18.0% received surgery and aRT. Only 7.6% of patients with clinically N0 disease received an END, with 10.6% of these having at least one positive node. END did not have a survival benefit compared to no END [HR 1.28 (0.61-2.68)]. Compared to surgery alone, aRT did not have significantly increased survival in the overall population or in late stage [HR 0.68 (0.39-1.19) and HR 0.46 (0.18-1.22), respectively]. On sub-analysis of patients with positive resection margins, aRT had a significant survival benefit compared to surgery alone [HR 0.37 (0.14-0.99)].

Conclusion: PAC is a rare, slow-growing malignant tumor typically treated with surgical excision, with undefined indications for END or aRT. Our findings show END to not have a benefit to overall survival. In patients with positive resection margins, there was a survival benefit for aRT.
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http://dx.doi.org/10.1007/s00405-020-06539-xDOI Listing
September 2021

Increased rate of recurrence and high rate of salvage in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma with adverse features treated with primary surgery without recommended adjuvant therapy.

Head Neck 2021 04 16;43(4):1128-1141. Epub 2020 Dec 16.

Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Some patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) do not receive guideline-recommended postoperative radiation therapy (PORT) following primary transoral robotic surgery (TORS).

Methods: Three-hundred and sixty-four patients with treatment-naïve, HPV-associated OPSCC were recommended to receive PORT based on clinicopathological features following TORS. Patients were stratified based on if they received PORT. Oncologic outcomes were compared.

Results: The 3-year locoregional failure (LRF) was 32% in patients who did not receive PORT and 4% in patients who received PORT (P < .001). Despite increased LRF, avoiding PORT was not associated with increased 3-year distant metastasis rates (8% vs 4%, P = .56) or worse 3-year survival (95% vs 98%, P = .34). Recurrences in the surgery alone cohort varied between local and regional sites and were often successfully salvaged.

Conclusions: Patients with HPV-associated OPSCC who do not receive indicated PORT have an increased risk of LRF but similar survival due to high salvage rates.
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http://dx.doi.org/10.1002/hed.26578DOI Listing
April 2021

Surgical Resection of Nodular Lymphocyte-Predominant Hodgkin Lymphoma of the Parotid Gland.

Laryngoscope 2021 04 17;131(4):E1096-E1098. Epub 2020 Aug 17.

Department of Otorhinolaryngology - Head & Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

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http://dx.doi.org/10.1002/lary.28972DOI Listing
April 2021

Revisiting the Recommendation for Contralateral Tonsillectomy in HPV-Associated Tonsillar Carcinoma.

Otolaryngol Head Neck Surg 2021 06 3;164(6):1222-1229. Epub 2020 Nov 3.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: Despite epidemiologic evidence that second primaries occur infrequently in HPV (human papillomavirus)-associated oropharyngeal squamous cell carcinoma, recent recommendations advocate for elective contralateral palatine tonsillectomy. We aimed to study this discordance and define the necessary extent of up-front surgery in a large contemporary cohort with long-term follow-up treated with unilateral transoral robotic surgery. We hypothesized that second primaries are discovered exceedingly rarely during follow-up and that survival outcomes are not compromised with a unilateral surgical approach.

Study Design: Retrospective cohort analysis.

Setting: Tertiary care academic center between 2007 and 2017.

Methods: Records for patients with p16-positive oropharyngeal squamous cell carcinoma of the tonsil and workup suggestive of unilateral disease who underwent ipsilateral transoral robotic surgery were analyzed for timing and distribution of locoregional recurrence, distant metastases, and second primary occurrence as well as survival characteristics.

Results: Among 295 included patients, 21 (7.1%) had a locoregional recurrence; 17 (5.8%) had a distant recurrence; and 3 (1.0%) had a second primary during a median follow-up of 48.0 months (interquartile range, 29.5-62.0). Only 1 (0.3%) had a second primary found in the contralateral tonsil. The 2- and 5-year estimates of overall survival were 95.5% (SE, 1.2%) and 90.1% (SE, 2.2%), respectively, while the 2- and 5-year estimates of disease-free survival were 90.0% (SE, 1.8%) and 84.7% (SE, 2.3%).

Conclusion: Second primary occurrence in the contralateral tonsil was infrequent, and survival outcomes were encouraging with unilateral surgery. This provides a rationale for not routinely performing elective contralateral tonsillectomy in patients whose workup suggests unilateral disease.
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http://dx.doi.org/10.1177/0194599820968800DOI Listing
June 2021

Oncologic Outcomes Following Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Carcinoma in Older Patients.

JAMA Otolaryngol Head Neck Surg 2020 12;146(12):1167-1175

Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania, Philadelphia.

Importance: While early epidemiologic studies ascribed increases in the incidence of human papillomavirus-associated oropharyngeal cancers to middle-aged patients, recent analyses have demonstrated an increasing median age of diagnosis. Treatment of patients older than 70 years is controversial as their inclusion in the practice-defining clinical trials has been limited and the survival benefit conferred by chemotherapy may be outweighed by treatment toxic effects.

Objective: To assess the oncologic outcomes of older adults with human papillomavirus-associated oropharyngeal cancer who underwent upfront transoral robotic surgery and pathologic characteristics-guided adjuvant therapy in a large cohort of patients with close follow-up.

Design, Setting, And Participants: A retrospective cohort analysis was conducted in a tertiary care academic medical center between January 1, 2010, and December 30, 2017. Patients aged 70 years or older at time of diagnosis with biopsy-proven and surgically resectable p16-positive oropharyngeal cancers were included. Data analysis was conducted from March 1 to June 1, 2020.

Exposures: Transoral robotic surgery oropharyngeal resection and neck dissection with pathologic characteristic-guided adjuvant therapy.

Main Outcomes And Measures: Three-year estimates of disease-specific survival, overall survival, and disease-free survival, as well as rates of adjuvant therapy (radiotherapy and chemoradiotherapy) and perioperative complications.

Results: Seventy-seven patients were included (median age, 73.0; interquartile range, 71.0-76.0; range, 70-89 years); of these, 58 were men (75.3%). Perioperative mortality was 1.3% and the rate of oropharyngeal hemorrhage was 2.6%. Twenty-seven patients (35.1%) underwent postoperative radiotherapy and 20 patients (26.0%) underwent postoperative chemoradiotherapy. The median length of follow-up was 39.6 (range, 0.1-96.2) months, and the 3-year estimates of survival were 92.4% (95% CI, 82.4%-96.9%) for disease-specific survival, 90.0% (95% CI, 79.4%-95.0%) for overall survival, and 84.3% (95% CI, 73.4%-91.0%) for disease-free survival.

Conclusions And Relevance: The findings of this cohort study suggest that transoral robotic surgery and pathologic characteristic-guided adjuvant therapy can provide beneficial survival outcomes, infrequent perioperative mortality, and, for most carefully selected older adults, obviate the need for chemotherapy.
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http://dx.doi.org/10.1001/jamaoto.2020.3787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596684PMC
December 2020

Current Indications for Transoral Robotic Surgery in Oropharyngeal Cancer.

Otolaryngol Clin North Am 2020 Dec 7;53(6):949-964. Epub 2020 Sep 7.

Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, 3400 Spruce Street, 5th Floor Silverstein Building, Philadelphia, PA 19104, USA. Electronic address:

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing dramatically and is conclusively linked to increasing rates of human papillomavirus (HPV) infection. HPV-related oropharyngeal cancers have been shown to occur in a unique demographic group and show favorable oncologic outcomes compared with HPV-negative OPSCC. There has been a paradigm shift in the treatment of early-stage OPSCC, with most patients now undergoing primary surgery in the United States. Transoral robotic surgery is associated with excellent oncologic and functional outcomes in the treatment of OPSCC and is increasingly being used for a broader range of oropharyngeal indications.
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http://dx.doi.org/10.1016/j.otc.2020.07.007DOI Listing
December 2020

Predictors of Nodal Metastasis in Mucoepidermoid Carcinoma of the Oral Cavity and Oropharynx.

ORL J Otorhinolaryngol Relat Spec 2020;82(6):327-334. Epub 2020 Aug 18.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA,

Introduction: Mucoepidermoid carcinoma (MEC) of the upper aerodigestive tract (UADT) is an uncommon malignancy, with limited literature available on its clinical and pathologic characteristics. Here, we describe the behavior of MEC of the UADT including pathologic characteristics and predictors of nodal metastasis.

Methods: Retrospective cohort study of patients with MEC of the UADT treated at an academic medical center from January 2008 to May 2018. Data was collected about demographics and tumor characteristics including clinical and histological data. The two-tailed Student t test and χ2 analysis were performed to assess for predictors of nodal metastasis.

Results: We identified 44 patients with minor salivary gland MEC of the oral cavity (OC) and oropharynx (OP). All patients were treated with primary site surgery. The primary site was the OC in 25 patients (57%) and OP in 19 (43%). Low-grade histology was seen in 27 specimens (61.4%), intermediate histology in 9 specimens (20.5%), and high-grade histology in 8 specimens (18.2%). Perineural invasion was noted in 10 specimens (22.7%). Neck dissection was performed in 17 patients (39%), with pathologically positive nodes found in 9 (20.5%). Notably, 5 of the 9 positive nodal specimens were found in clinically node-negative necks. Pathologically positive cervical lymph nodes were significantly associated with the OP as the primary site (p = 0.0005), perineural invasion (p = 0.012), lymphovascular invasion (p < 0.001), and high-grade histology (p = 0.004) in the primary specimen.

Discussion: MEC of the UADT is an uncommon malignancy. Our findings suggest elective neck dissection should be considered with perineural and lymphovascular invasion, high-grade tumor, and the OP as the primary site.
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http://dx.doi.org/10.1159/000509142DOI Listing
March 2021

Impact of Lymph Node Yield on Survival in Surgically Treated Oropharyngeal Squamous Cell Carcinoma.

Otolaryngol Head Neck Surg 2021 01 21;164(1):146-156. Epub 2020 Jul 21.

University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.

Objectives: (1) To estimate the association between neck dissection lymph node yield (LNY) and survival among patients with surgically treated human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). (2) To identify a clinically relevant quality metric for surgical treatment of HPV-related OPSCC.

Study Design: Retrospective cohort study.

Setting: National Cancer Database.

Subjects And Methods: From the National Cancer Database, 4130 patients were identified with HPV-associated OPSCC treated with primary surgery from 2010 to 2016. Based on prior literature, an adequate neck dissection LNY was defined as ≥18 lymph nodes. To determine whether LNY is associated with survival, univariable and multivariable Cox proportional hazards regression was performed. Analysis was stratified by adjuvant therapy regimen.

Results: A total of 2113 patients (51.2%) underwent surgery with or without adjuvant radiation (S ± RT), and 2017 patients (48.8%) underwent surgery with adjuvant chemoradiation. LNY ≥18 was associated with a 5-year survival benefit of 7.15% (91.7% for LNY ≥18, 84.5% for LNY <18, = .004) for the S ± RT cohort on unadjusted survival analysis. For the S ± RT group, LNY ≥18 was associated with decreased hazard of death (hazard ratio, 0.45; 95% CI, 0.29-0.70; < .001) after adjustment for patient characteristics, TNM staging, surgical margins, extranodal extension, and treating facility characteristics. For surgery with adjuvant chemoradiation, the adjusted hazard ratio estimate for LNY ≥18 was 0.64 (95% CI, 0.41-1.00), but the result was not statistically significant ( = .052).

Conclusion: An adequate LNY from a neck dissection may affect survival when HPV-related OPSCC is treated with up-front surgery.
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http://dx.doi.org/10.1177/0194599820936637DOI Listing
January 2021

Creation of an Interactive Virtual Surgical Rotation for Undergraduate Medical Education During the COVID-19 Pandemic.

J Surg Educ 2021 Jan-Feb;78(1):346-350. Epub 2020 Jul 1.

Department of Otorhinolaryngology - Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: During the coronavirus 2019 pandemic, medical student involvement in direct patient care has been severely limited. Rotations mandatory not only for core curricula but also for informing decisions regarding specialty choice have been postponed during a critical window in the application cycle. Existing virtual rotations are largely observational or lack patient-facing components.

Setting: A virtual Otolaryngology - Head and Neck Surgery rotation at the University of Pennsylvania (Philadelphia, Pennsylvania) was implemented for medical students, comprising interactive live-streamed surgeries, outpatient telehealth visits, and virtual small group didactics.

Results: Medical students enrolled in the virtual surgical rotation were able to engage with attending surgeons and operating room staff while remotely viewing surgical procedures captured with first-person audiovisual technology. Students participated in several different aspects of care delivery in both the inpatient and outpatient setting, similar to their typical responsibilities of an in-person rotation.

Conclusions: The authors will continue to develop the virtual surgical education methodology to further disseminate an interactive video-based medical student elective to other procedural specialties and institutions.
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http://dx.doi.org/10.1016/j.jsurg.2020.06.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328635PMC
January 2021

Retropharyngeal Internal Carotid Artery Management in TORS Using Microvascular Reconstruction.

Laryngoscope 2021 03 4;131(3):E821-E827. Epub 2020 Jul 4.

Department of Otorhinolaryngology - Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Objectives: Guidelines for transoral robotic surgery (TORS) have generally regarded patients with retropharyngeal carotid arteries as contraindicated for surgery due to a theoretical risk of intraoperative vascular injury and/or perioperative cerebrovascular accident. We aimed to demonstrate that careful TORS-assisted resection and free flap coverage could not only avoid intraoperative injury and provide a physical barrier for vessel coverage but also achieve adequate margin control.

Study Design: Retrospective cohort analysis.

Methods: Retrospective review of patients with oropharyngeal malignancies and radiologically confirmed retropharyngeal carotid arteries who underwent TORS, concurrent neck dissection, and free flap reconstruction between 2015 and 2019.

Results: Twenty patients were included, 19 (95.0%) with tonsillar tumors and one (5.0%) with a tongue base tumor with significant tonsillar extension. Eighteen patients (90.0%) received a radial artery forearm flap, one (5.0%) an ulnar artery forearm flap, and one (5.0%) an anteromedial thigh flap. All 20 (100%) flaps were inset through combined transcervical and transoral approaches without mandibulotomy. There were no perioperative mortalities, carotid injuries, oropharyngeal bleeds, cervical hematomas, or cerebrovascular accidents. One patient (5.0%) had a free flap failure requiring explant. All patients underwent decannulation and resumed a full oral diet. The mean length of hospitalization was 6.8 (standard deviation 1.2) days. One (5.0%) patient had a positive margin.

Conclusion: In this analysis, 20 patients with oropharyngeal malignancy and retropharyngeal carotid arteries underwent TORS, neck dissection, and microvascular reconstruction without serious complication (perioperative mortality, vascular injury, or neurologic sequalae) with an acceptable negative margin rate. These results may lead to a reconsideration of a commonly held contraindication to TORS.

Level Of Evidence: 3 Laryngoscope, 131:E821-E827, 2021.
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http://dx.doi.org/10.1002/lary.28876DOI Listing
March 2021

Penn Medicine Head and Neck Cancer Service Line COVID-19 management guidelines.

Head Neck 2020 Jul 25;42(7):1507-1515. Epub 2020 Jun 25.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Introduction: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has altered the health care environment for the management of head and neck cancers. The purpose of these guidelines is to provide direction during the pandemic for rational Head and Neck Cancer management in order to achieve a medically and ethically appropriate balance of risks and benefits.

Methods: Creation of consensus document.

Results: The process yielded a consensus statement among a wide range of practitioners involved in the management of patients with head and neck cancer in a multihospital tertiary care health system.

Conclusions: These guidelines support an ethical approach for the management of head and neck cancers during the COVID-19 epidemic consistent with both the local standard of care as well as the head and neck oncological literature.
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http://dx.doi.org/10.1002/hed.26318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362039PMC
July 2020

The Difficult Airway and Aerosol-Generating Procedures in COVID-19: Timeless Principles for Uncertain Times.

Otolaryngol Head Neck Surg 2020 11 23;163(5):934-937. Epub 2020 Jun 23.

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

The impact of the COVID-19 pandemic on otolaryngology practice is nowhere more evident than in acute airway management. Considerations of preventing SARS-CoV-2 transmission, conserving personal protective equipment, and prioritizing care delivery based on acuity have dictated clinical decision making in the acute phase of the pandemic. With transition to a more chronic state of pandemic, heightened vigilance is necessary to recognize how deferral of care in patients with tenuous airways and COVID-19 infection may lead to acute airway compromise. Furthermore, it is critical to respect the continuing importance of flexible laryngoscopy in diagnosis. Safely managing airways during the pandemic requires thoughtful multidisciplinary planning. Teams should consider trade-offs among aerosol-generating procedures involving direct laryngoscopy, supraglottic airway use, fiberoptic intubation, and tracheostomy. We share clinical cases that illustrate enduring principles of acute airway management. As algorithms evolve, time-honored approaches for diagnosis and management of acute airway pathology remain essential in ensuring patient safety.
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http://dx.doi.org/10.1177/0194599820936615DOI Listing
November 2020

Changes in head and neck oncologic practice during the COVID-19 pandemic.

Head Neck 2020 Jul 11;42(7):1448-1453. Epub 2020 Jun 11.

Department of Otolaryngology-Head and Neck Surgery, University of Kansas, Kansas City, Kansas, USA.

Introduction: The COVID-19 pandemic has raised controversies regarding safe and effective care of patients with head and neck cancer. It is unknown how much the pandemic has changed surgeon practice.

Methods: A questionnaire was distributed to head and neck surgeons assessing opinions related to treatment and concerns for the safety of patients, self, family, and staff.

Results: A total of 88 head and neck surgeons responded during the study period. Surgeons continued to recommend primary surgical treatment for oral cavity cancers. Respondents were more likely to consider nonsurgical therapy for patients with early glottic cancers and HPV-mediated oropharynx cancer. Surgeons were least likely to be concerned for their own health and safety and had the greatest concern for their resident trainees.

Conclusions: This study highlights differences in the willingness of head and neck surgeons to delay surgery or alter plans during times when hospital resources are scarce and risk is high.
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http://dx.doi.org/10.1002/hed.26233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267666PMC
July 2020

Topical preparations to reduce SARS-CoV-2 aerosolization in head and neck mucosal surgery.

Head Neck 2020 06 25;42(6):1268-1272. Epub 2020 Apr 25.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Aim: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put health care workers at risk when exposed to aerosolized viral particles during upper airway mucosal surgery. The objective of this review was to discuss topical preparations that could be utilized preoperatively to help to decrease viral load and potentially reduce the risks of viral transmission.

Methods: A PubMed/MEDLINE database review of articles was performed querying topical preparations with virucidal activity against coronaviruses.

Results: Povidone-iodine (PVP-I) solutions ranging from 0.23% to 7% have been found to demonstrate highly effective virucidal activity against a broad range of viruses including several coronaviruses responsible for recent epidemics including SARS-CoV-1 and MERS-CoV.

Conclusions: While specific evidence regarding SARS-CoV-2 is lacking, PVP-I-based preparations have been successfully demonstrated to reduce viral loads of coronaviruses. They are relatively safe to use in the upper airway and may reduce risk of SARS-CoV-2 aerosolization during upper airway mucosal surgery.
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http://dx.doi.org/10.1002/hed.26200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267296PMC
June 2020

Impact of the COVID-19 Pandemic on the Management of Head and Neck Malignancies.

Otolaryngol Head Neck Surg 2020 06 21;162(6):816-817. Epub 2020 Apr 21.

Department of Otorhinolaryngology: Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on the management of head and neck cancer must be addressed. Immediate measures to reduce transmission rates and protect patients and providers take priority and necessitate some delays in care, particularly for patients with mild symptoms or less aggressive cancers. However, strict guidelines have yet to be developed, and many unintentional delays in care are to be expected based on the magnitude of the looming public health crisis. The medical complexity of head and neck cancer management may lead to prolonged delays that worsen treatment outcomes. Therefore, those caring for patients with head and neck cancer must take action to reduce these negative impacts as the country rallies to overcome the challenges posed by this pandemic.
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http://dx.doi.org/10.1177/0194599820921413DOI Listing
June 2020

Perforator-based propeller flap for fibula free flap donor site repair: A novel surgical technique.

Laryngoscope 2020 05 10;130(5):1233-1235. Epub 2019 Aug 10.

Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, South Carolina.

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http://dx.doi.org/10.1002/lary.28232DOI Listing
May 2020
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