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1.
Cancer ; 130(6): 863-875, 2024 03 15.
Article En | MEDLINE | ID: mdl-37788128

BACKGROUND: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications. METHODS: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017-2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. Regression analysis to estimate odds ratios was performed. RESULTS: A total of 463 patients met inclusion criteria. Free flap reconstruction constituted 28.9% of patients and TORS constituted 71.1% of patients. nICI was administered in 83 of 463 (17.9%) patients. There was no statistically significant difference in surgical, medical, or overall complications between patients receiving surgery with or without nICI. In the unmatched cohort, multivariable model identified non-White race, former/current smoking history, free flap surgery, and perineural invasion as factors significantly associated with increased complications. In the matched cohort, multivariable model identified advanced age and free flap surgery as factors significantly associated with increased complications. PLAIN LANGUAGE SUMMARY: It is safe to give immunotherapy before major surgery in patients who have head and neck cancer. Advanced age, non-White race, current/former smoking, free flap surgery, and perineural invasion may be associated with increased the odds of surgical complications.


Head and Neck Neoplasms , Plastic Surgery Procedures , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/surgery , Ligands , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/surgery , Retrospective Studies
2.
J Immunother Cancer ; 11(8)2023 08.
Article En | MEDLINE | ID: mdl-37536941

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Exploratory endpoints included the association of baseline programmed death-ligand 1 (PD-L1) expression as well as on-treatment changes in immune bias with treatment outcomes. RESULTS: Twenty-four patients were enrolled. With a median follow-up of 36.1 months, grade 3 or higher treatment-related adverse events were reported in 21 individuals (88%); 5 individuals developed in-field soft tissue ulceration during consolidation immunotherapy, resulting in one fatality. The 3-year PFS and OS rates were 74% (95% CI 58% to 94%) and 96% (95% CI 88% to 100%), respectively. PD-L1 combined positive score (CPS) did not correlate with death or disease progression. Decreases in extracellular vesicle PD-L1 within the concurrent RIT phase were associated with prolonged PFS (p=0.006). Also, interval decreases in circulating interleukin (IL)4, IL9, IL12, and IL17a during concurrent RIT were associated with subsequent ulceration. CONCLUSIONS: Definitive RIT with nivolumab and ipilimumab has sufficient clinical activity to support further development. Early changes in circulating biomarkers appear able to predict treatment outcomes as well as ensuing in-field soft tissue ulceration. TRIAL REGISTRATION NUMBER: NCT03162731.


Head and Neck Neoplasms , Nivolumab , Humans , Nivolumab/pharmacology , Nivolumab/therapeutic use , Ipilimumab/pharmacology , Ipilimumab/therapeutic use , B7-H1 Antigen , Squamous Cell Carcinoma of Head and Neck/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Head and Neck Neoplasms/drug therapy
3.
Mol Carcinog ; 62(9): 1428-1443, 2023 09.
Article En | MEDLINE | ID: mdl-37401875

Therapy using anti-PD-1 immune checkpoint inhibitors (ICI) has revolutionized the treatment of many cancers including head and neck squamous cell carcinomas (HNSCC), but only a fraction of patients respond. To better understand the molecular mechanisms driving resistance, we performed extensive analysis of plasma and tumor tissues before and after a 4-week neoadjuvant trial in which HNSCC patients were treated with the anti-PD-1 inhibitor, nivolumab. Luminex cytokine analysis of patient plasma demonstrated that HPVpos nonresponders displayed high levels of the proinflammatory chemokine, interleukin-8 (IL-8), which decreased after ICI treatment, but remained higher than responders. miRNAseq analysis of tetraspanin-enriched small extracellular vesicles (sEV) purified from plasma of HPVpos nonresponders demonstrated significantly lower levels of seven miRNAs that target IL-8 including miR-146a. Levels of the pro-survival oncoprotein Dsg2, which has been to down-regulate miR-146a, are elevated with HPVpos tumors displaying higher levels than HPVneg tumors. Dsg2 levels decrease significantly following ICI in responders but not in nonresponders. In cultured HPVpos cells, restoration of miR-146a by forced expression or treatment with miR-146a-loaded sEV, reduced IL-8 level, blocked cell cycle progression, and promoted cell death. These findings identify Dsg2, miR-146a, and IL-8 as potential biomarkers for ICI response and suggest that the Dsg2/miR-146a/IL-8 signaling axis negatively impacts ICI treatment outcomes and could be targeted to improve ICI responsiveness in HPVpos HNSCC patients.


Extracellular Vesicles , Head and Neck Neoplasms , MicroRNAs , Papillomavirus Infections , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/genetics , Interleukin-8/genetics , Nivolumab/pharmacology , Nivolumab/therapeutic use , Neoadjuvant Therapy , MicroRNAs/genetics , MicroRNAs/metabolism , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/genetics , Extracellular Vesicles/metabolism
4.
JAMA Otolaryngol Head Neck Surg ; 149(11): 980-986, 2023 11 01.
Article En | MEDLINE | ID: mdl-37422846

Importance: Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear. Objectives: To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT. Design, Setting, and Population: This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform. Exposure: Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy. Main Outcomes and Measures: Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT. Results: Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79). Conclusions and Relevance: This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.


Deglutition Disorders , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Robotic Surgical Procedures , Male , Humans , Aged , Female , Squamous Cell Carcinoma of Head and Neck , Cohort Studies , Treatment Outcome , Deglutition Disorders/etiology , Head and Neck Neoplasms/therapy
5.
Head Neck ; 45(1): 237-242, 2023 01.
Article En | MEDLINE | ID: mdl-36300998

BACKGROUND: Few standardized methods exist for evaluating the postoperative outcomes of osteocutaneous free flaps. We propose an anatomic-based scoring system for midface free flap reconstruction. METHODS: One hundred and twelve patients across four institutions underwent osteocutaneous reconstruction of the midface. Postoperative scans were scored based on the number of independent osseous subunits reconstructed (Subunit Score), the number of different bony appositions with bony contact (Contact Score), and the number of osseous segments in anatomic position (Position Score). These were added together to create a Total Score. RESULTS: Osteocutaneous radial forearm flaps had the lowest Subunit Score (p = 0.001). Fibula flaps had the highest Contact Score (p = 0.0008) and Position Score (p = 0.001). Virtual surgical planning was associated with an increased Subunit Score (p = 0.02) and Total Score (p = 0.04). CONCLUSIONS: We propose a novel scoring system for osseous midface reconstruction based on postoperative imaging scans. This can help guide management decisions and create a common language to compare outcomes.


Free Tissue Flaps , Plastic Surgery Procedures , Humans , Free Tissue Flaps/surgery , Face/surgery , Postoperative Period , Fibula/surgery , Retrospective Studies
6.
Otolaryngol Head Neck Surg ; 168(4): 782-789, 2023 04.
Article En | MEDLINE | ID: mdl-35943815

OBJECTIVE: To assess whether preoperative tracheostomy (PreOT) increases risk of complications after total laryngectomy (TL) and to determine if timing of tracheostomy creation is associated with an increased risk. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital between 2007 and 2020. METHODS: Inclusion criteria were patients who underwent primary or salvage TL for oncologic treatment. Dependent variables of interest included surgical complications, such as wound dehiscence, infection, hematoma, complete flap failure, fistula formation, and stoma stenosis, as well as medical complications. Categorical variables were compared with chi-square test or Fisher exact test, and continuous variables were compared with an independent t test. Multivariable regression was conducted to assess predictors of complications after laryngectomy. RESULTS: A total of 306 patients were included. Primary TL was performed in 161 (53%) patients and salvage in 145 (47%) patients. Of the patients undergoing primary laryngectomy, 105 (65%) received a PreOT. Of the patients undergoing salvage laryngectomy, 86 (59%) received a PreOT. In both primary and salvage cases, there was no association between PreOT and surgical or medical complications. Additionally, there was no significant association between timing of tracheostomy and surgical complications. On multivariable analysis, the presence of a PreOT was not associated with surgical complications. In salvage cases, those with a PreOT had a significantly longer average length of stay than those without a PreOT (12 vs 9 days, P = .008). CONCLUSION: PreOT in patients undergoing primary and salvage laryngectomies was not associated with surgical or medical complications postlaryngectomy. Timing of tracheostomy in relation to laryngectomy was not found to adversely affect clinical outcomes.


Cutaneous Fistula , Laryngeal Neoplasms , Pharyngeal Diseases , Humans , Retrospective Studies , Tracheostomy/adverse effects , Laryngeal Neoplasms/surgery , Laryngeal Neoplasms/etiology , Pharyngeal Diseases/surgery , Postoperative Complications/etiology , Salvage Therapy
7.
Laryngoscope ; 133(1): 105-108, 2023 01.
Article En | MEDLINE | ID: mdl-35848774

Nasopharyngeal tumors in the proximity of the internal carotid artery are often difficult to dissect. Here, we describe a combined transcervical and endoscopic endonasal approach that provides improved internal carotid artery protection and confident tumor resection. Laryngoscope, 133:105-108, 2023.


Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Neoplasms/surgery , Nasopharyngeal Neoplasms/pathology , Maxilla/surgery , Carotid Artery, Internal , Neoplasm Recurrence, Local/pathology
8.
Laryngoscope ; 133(1): 95-104, 2023 01.
Article En | MEDLINE | ID: mdl-35562185

OBJECTIVE: Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction. STUDY DESIGN: Retrospective review of prospectively collected databases. METHODS: Consecutive patients undergoing head and neck microvascular free flap reconstruction between January 2010 and December 2019 (n = 1972) were included. Preoperative, operative and postoperative variables were correlated with discharge destination (home, skilled nursing facility [SNF], rehabilitation facility, death). RESULTS: The mean age of patients discharged home was lower (60 SD ± 13, n = 1450) compared to those discharged to an SNF (68 SD ± 14, n = 168) or a rehabilitation facility (71 SD ± 14, n = 200; p < 0.0001). Operative duration greater than 10 h correlated with a higher percentage of patients being discharged to a rehabilitation or SNF (25% vs. 15%; p < 0.001). Patients were less likely to be discharged home if they had a known history of cardiac disease (71% vs. 82%; p < 0.0001). Patients were less likely to be discharged home if they experienced alcohol withdrawal (67% vs. 80%; p = 0.006), thromboembolism (59% vs. 80%; p = 0.001), a pulmonary complication (46% vs. 81%; p < 0.0001), a cardiac complication (46% vs. 80%; p < 0.0001), or a cerebral vascular event (25% vs. 80%; p < 0.0001). There was no correlation between discharge destination and occurrence of postoperative wound infection, salivary fistula, partial tissue necrosis or free flap failure. Thirty-day readmission rates were similar when stratified by discharge destination. CONCLUSION: There was no correlation with the anatomic site, free flap donor selection, or free flap survival and discharge destination. Patient age, operative duration and occurrence of a medical complication postoperatively did correlate with discharge destination. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:95-104, 2023.


Alcoholism , Free Tissue Flaps , Head and Neck Neoplasms , Substance Withdrawal Syndrome , Humans , Alcoholism/complications , Risk Factors , Substance Withdrawal Syndrome/complications , Free Tissue Flaps/blood supply , Patient Discharge , Retrospective Studies , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology
9.
Clin Neurol Neurosurg ; 222: 107452, 2022 11.
Article En | MEDLINE | ID: mdl-36209518

Iatrogenic chyle leak (CL) following lymphatic vessel damage is an uncommon but serious complication of neck dissections. In the setting of anterior cervical discectomy and fusion (ACDF), left-sided CL are an exceedingly rare complication, with an incidence of only 0.02 %. Only three cases of right-sided CL during an ACDF have been reported. The case presented is the first right-sided CL to be successfully identified intraoperatively and treated. Intraoperative and postoperative management are discussed. This case will hopefully bring clinical and surgical awareness to providers caring for patients undergoing an ACDF.


Chyle , Spinal Fusion , Humans , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Spinal Fusion/adverse effects , Diskectomy/adverse effects , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Postoperative Complications/surgery , Treatment Outcome
10.
J Pathol ; 258(2): 103-105, 2022 Oct.
Article En | MEDLINE | ID: mdl-35894839

Precancerous lesions provide insight into tumor development as well as prognostication, since distinguishing high-risk from benign disease will stratify clinical management. In a recent issue of The Journal of Pathology, Ghosh et al performed comprehensive genomic characterization of the precancerous lesion leukoplakia, comparing RNA and DNA with peripheral blood, normal mucosa, and squamous cell carcinoma (SCC) of the gingivobuccal region of the oral cavity from the same 28 individuals. The data paint a picture of increasing mutation and early caspase-8 inactivation on the background of inflammation with decreasing immune surveillance in the progression from benign leukoplakia to SCC. This research points to an opportunity for disease intercept at the premalignant niche prior to the development of malignancy. © 2022 The Pathological Society of Great Britain and Ireland.


Carcinoma, Squamous Cell , Mouth Neoplasms , Precancerous Conditions , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Humans , Leukoplakia, Oral/genetics , Leukoplakia, Oral/pathology , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Precancerous Conditions/genetics , Precancerous Conditions/pathology
11.
Head Neck ; 44(8): 1896-1908, 2022 08.
Article En | MEDLINE | ID: mdl-35665975

BACKGROUND: Outcomes and cost of soft tissue versus bony midface free flap reconstruction (MR) with and without virtual surgical planning (VSP) were evaluated. METHODS: Retrospective review of MR including ischemic time (IT), operative duration (OD), length of stay (LOS), and total cost (TC). Eighty-one soft tissue and 76 bony MR (VSP = 23) were reviewed. RESULTS: Bony MR was used for higher complexity defects (p = 0.003) and was associated with higher IT (p < 0.001), OD (p < 0.001), LOS (p = 0.032), and TC (p < 0.001). VSP was associated with a mean 111.2 ± 37.9 minute reduction in OD (p = 0.004) compared to non-VSP bony flaps. VSP was associated with higher itemized cost, but no increase in TC (p = 0.327). CONCLUSIONS: Bony MR was used for higher complexity MR and was associated with increased TC, LOS, OD, and IT. VSP shortened OD with no significant increase in TC.


Free Tissue Flaps , Plastic Surgery Procedures , Face , Humans , Patient Care Planning , Retrospective Studies
12.
Am J Otolaryngol ; 43(4): 103483, 2022.
Article En | MEDLINE | ID: mdl-35580419

OBJECTIVE: To compare the experiences of patients who received sialendoscopy under general anesthesia (GA) with those who received monitored anesthesia care (MAC). METHODS: Patients who underwent sialendoscopy for sialadenitis or sialolithiasis from July 1, 2020, to July 31, 2021, were offered inclusion to this prospective observational study. A survey was sent to consenting patients on post-operative day 1 to record aspects of their pre-, intra-, and post-operative experience. The primary outcome was overall satisfaction. Secondary outcomes included pain tolerability and preference for similar anesthetic modality in the future. RESULTS: Seventy-five patients completed the post-operative survey (86% response rate), of which 39 patients received GA and 36 received MAC. Patient overall satisfaction was similar between groups (GA: "Poor/Average/Good" = 23%, "Excellent" = 77%; MAC: "Poor/Average/Good" = 25%, "Excellent" = 75%, p = 1.00). Tolerability of immediate post-operative pain was likewise similar between the GA (82%) and MAC (97%) groups (p = 0.058). Patients who received MAC reported intra-operative pain as "none/tolerable" 72% of the time and "uncomfortable" 28% of the time. Patients who received GA would prefer the same anesthetic in the future more often than in the MAC group (85% versus 61%, respectively, OR 3.50, 95% CI 1.17-10.50, p = 0.035). CONCLUSION: In regard to patient satisfaction, both MAC and GA are acceptable anesthetic choices in sialendoscopy for appropriate cases. Patients report similar overall satisfaction and post-operative pain tolerance under either anesthetic modality. Patients who undergo GA report higher rates of preference for similar anesthetic modality in the future. Further study is needed to determine the most appropriate criteria for anesthesia modality selection.


Anesthesia, General , Salivary Gland Calculi , Humans , Pain, Postoperative , Patient Outcome Assessment , Retrospective Studies , Salivary Gland Calculi/surgery , Treatment Outcome
13.
Laryngoscope ; 132(6): 1196-1204, 2022 06.
Article En | MEDLINE | ID: mdl-34709651

OBJECTIVES/HYPOTHESIS: To assess the efficacy and mechanism of action of a novel approach to mitigate acute and chronic radiation toxicity in a validated animal model. STUDY DESIGN: Randomized, prospective study using an in vivo rat model. METHODS: Experimental animal study utilizing Sprague-Dawley rats divided into three cohorts: 1) radiation + dimethyl sulfoxide (DMSO) (inert vehicle); 2) radiation + RTA-408 (therapeutic drug); and 3) no radiation + DMSO. All animals in the radiation cohorts underwent 40 Gy of radiation with subsequent inferior epigastric axial rotational flap 30 days later in all cohorts with percentage of flap necrosis and vascular density calculated by blinded observers. In a second experiment, an additional three cohorts, underwent serial punch biopsies of the abdominal skin before, during, and after radiation and drug/vehicle control treatment. Transcriptome analysis utilizing gene set enrichment analysis and digital polymerase chain reaction were performed at various time points. RESULTS: The first experiment revealed average flap necrosis of 20% (95% confidence interval [CI] 16-45) in the radiation control group, 3% (95% CI 0-11) in the nonirradiated control, and 3% (95% CI 0.2-10) in the radiation group treated with RTA-408. Vascular density was preserved in the treatment group as compared to the radiated control. Nine rats were included in the second experiment, and transcriptome analyses in the treatment group revealed robust activation of antioxidant pathways with induced expression of genes associated with hypoxia and adipogenesis/angiogenesis. CONCLUSIONS: Administration of RTA-408 during radiation treatment in a rat model resulted in transcriptome changes which appear to mitigate the toxic effects of radiation, preserving capillary networks and improving flap survival and tissue healing after subsequent surgery. LEVEL OF EVIDENCE: Foundational Evidence, Animal Research Laryngoscope, 132:1196-1204, 2022.


Dimethyl Sulfoxide , Triterpenes , Animals , Humans , Necrosis , Prospective Studies , Rats , Rats, Sprague-Dawley , Triterpenes/therapeutic use
14.
Laryngoscope ; 132(4): 772-780, 2022 04.
Article En | MEDLINE | ID: mdl-34415067

OBJECTIVE: Determine if age correlated with surgical or medical complications following head and neck free flap reconstruction. STUDY DESIGN: Retrospective review of prospectively collected databases. METHODS: Patients undergoing head and neck free flap reconstruction at three tertiary care institutions were included (n = 1972). Cohorts were based on age (<65, 65-75, 75-85, and >85). Outcomes reviewed operative duration, length of stay, surgical complications (free flap failure, fistula, hematoma, dehiscence, and infection), and medical complications (thromboembolism, stroke, cardiac, and pulmonary). RESULTS: Anatomic site (P < .0001) and donor site varied by age (P < .0001). There was no difference in operative duration (P = .3) or length of hospitalization (P = .8) by age. The incidence of medical complications increased with increasing age. Pulmonary complication rates: <65 (3.9%), 65 to 75 (4.8%), 75 to 85 (7.1%), and >85 (11%) (P = .02). Cardiac complication rates: <65 (2.0%), 65 to 75 (7.3%), 75 to 85 (6.1%), and >85 (16.4%) (P < .0001). Mortality increased with age: <65 (0.4%), 65 to 75 (0.8%), 75 to 85 (1.1%), and >85 (4.1%) (P < .003). Medical complications correlated with mortality rates: pulmonary (3.5% vs. 0.6%; OR: 5.5; 95% CI: 1.5-20.0; P = .004); cardiac (3.3% vs. 0.6%; OR: 6.0; 95% CI: 1.6-21.8; P = .002); thromboembolism (4.6% vs. 0.7%; OR: 7.3; 95% CI: 1.6-33.6; P = .003); stroke (42% vs. 0.5%; OR: 149; 95% CI: 40-558; P < .0001); and sepsis (5% vs. 0.7%; OR 7.5; 95% CI: 1.0-60.5; P = .03). Age did not correlate with free flap success (P = .5), surgical complications (hematoma, P = .33; fistula, P = .23; infection, P = .07; and dehiscence, P = .37), or thirty-day readmission (P = .3). CONCLUSION: Following free flap reconstruction, patient age did not correlate with development of a surgical complication. Patient age did correlate with development of a medical complication. Postoperative medical complications were found to correlate with perioperative mortality. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:772-780, 2022.


Free Tissue Flaps , Head and Neck Neoplasms , Plastic Surgery Procedures , Stroke , Thromboembolism , Free Tissue Flaps/adverse effects , Free Tissue Flaps/surgery , Head and Neck Neoplasms/surgery , Hematoma/complications , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Plastic Surgery Procedures/adverse effects , Retrospective Studies , Stroke/surgery
15.
Dysphagia ; 37(1): 28-36, 2022 Feb.
Article En | MEDLINE | ID: mdl-33492468

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.


Carcinoma , Robotic Surgical Procedures , Tongue Neoplasms , Humans , Quality of Life , Robotic Surgical Procedures/adverse effects , Tongue/surgery , Tongue Neoplasms/surgery
16.
Clin Cancer Res ; 28(5): 915-927, 2022 Mar 01.
Article En | MEDLINE | ID: mdl-34911681

PURPOSE: We hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC). PATIENTS AND METHODS: We conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status. Patients in both arms received nivolumab 240 mg intravenously on days 1 and 15 followed by surgery on day 28. Those in the combination therapy arm also received tadalafil 10 mg orally once daily for 4 weeks. Imaging, blood, and tumor were obtained pretreatment and posttreatment for correlative analysis. RESULTS: Neoadjuvant therapy was well-tolerated with no grade 3 to 5 adverse events and no surgical delays. Twenty-five of 46 (54%) evaluable patients had a pathologic treatment response of ≥20%, including three (7%) patients with a complete pathologic response. Regardless of HPV status, tumor proliferation rate was a negative predictor of response. A strong pretreatment T-cell signature in the HPV-negative cohort was a predictor of response. Tadalafil altered the immune microenvironment, as evidenced by transcriptome data identifying enriched B- and natural killer cell gene sets in the tumor and augmented effector T cells in the periphery. CONCLUSIONS: Preoperative nivolumab ± tadalafil is safe in HNSCC and results in more than 50% of the patients having a pathologic treatment response of at least 20% after 4 weeks of treatment. Pretreatment specimens identified HPV status-dependent signatures that predicted response to immunotherapy while posttreatment specimens showed augmentation of the immune microenvironment with the addition of tadalafil.


Head and Neck Neoplasms , Neoadjuvant Therapy , Squamous Cell Carcinoma of Head and Neck , Head and Neck Neoplasms/drug therapy , Humans , Neoadjuvant Therapy/adverse effects , Nivolumab/therapeutic use , Papillomavirus Infections/complications , Squamous Cell Carcinoma of Head and Neck/drug therapy , Tadalafil/therapeutic use , Treatment Outcome , Tumor Microenvironment
18.
Otolaryngol Head Neck Surg ; 165(5): 636-646, 2021 11.
Article En | MEDLINE | ID: mdl-33618563

OBJECTIVE: Review long-term clinical and quality-of-life outcomes following free flap reconstruction for osteonecrosis. STUDY DESIGN: Retrospective multi-institutional review. SETTING: Tertiary care centers. METHODS: Patients included those undergoing free flap reconstructions for osteonecrosis of the head and neck (N = 232). Data included demographics, defect, donor site, radiation history, perioperative management, diet status, recurrence rates, and long-term quality-of-life outcomes. Quality-of-life outcomes were measured using the University of Washington Quality of Life (UW-QOL) survey. RESULTS: Overall flap success rate was 91% (n = 212). Relative to preoperative diet, 15% reported improved diet function at 3 months following reconstruction and 26% at 5 years. Osteonecrosis recurred in 14% of patients (32/232); median time to onset was 11 months. Cancer recurrence occurred in 13% of patients (29/232); median time to onset was 34 months. Results from the UW-QOL questionnaire were as follows: no pain (45%), minor or no change in appearance (69%), return to baseline endurance level (37%), no limitations in recreation (40%), no changes in swallowing following reconstruction (28%), minor or no limitations in mastication (29%), minor or no speech difficulties (93%), no changes in shoulder function (84%), normal taste function (19%), normal saliva production (27%), generally excellent mood (44%), and no or minimal anxiety about cancer (94%). CONCLUSION: The majority of patients maintained or had advancement in diet following reconstruction, with low rates of osteonecrosis or cancer recurrence and above-average scores on UW-QOL survey suggesting good return of function and quality of life.


Bisphosphonate-Associated Osteonecrosis of the Jaw/surgery , Free Tissue Flaps/blood supply , Jaw Diseases/etiology , Jaw Diseases/surgery , Osteonecrosis/surgery , Plastic Surgery Procedures/methods , Quality of Life , Adult , Aged , Aged, 80 and over , Female , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Osteonecrosis/etiology , Osteonecrosis/pathology , Radiotherapy/adverse effects , Recovery of Function , Retrospective Studies , Tertiary Care Centers
19.
Oral Oncol ; 115: 105220, 2021 04.
Article En | MEDLINE | ID: mdl-33592564

OBJECTIVES: Local reconstruction of central skull base defects may be inadequate for large defects or reoperative cases; free tissue transfer may be necessary. Inset of the flap and management of the pedicle can be challenging. We report our experience and approaches. METHODS: Retrospective review identifying seven patients with central skull base defects who underwent free flap reconstruction from 2016 to 2020. RESULTS: Four patients with recurrent nasopharyngeal carcinoma, one with recurrent craniopharyngioma, one with clival-cervical chordoma, and one with meningioma of the middle cranial fossa were analyzed. Six defects were closed with an anterolateral thigh free flap and one with a radial forearm free flap. In two patients, the flap was secured in an onlay fashion to the defect via a Caldwell-Luc transmaxillary approach. In one patient, the flap was passed transorally, and the pedicle was delivered into the neck via Penrose drain. In two patients, a parapharyngeal technique and in two others, a retropharyngeal was used for nasopharyngeal inset with endoscopic assistance. There were no flap failures, with an average follow-up time of 20.1 (range 3.2-47.1) months. One patient required flap repositioning on postoperative day three due to midline shift and intracranial contents compression. The transoral inset flap necessitated flap repositioning on postoperative day 13 to improve the nasopharyngeal airway. CONCLUSION: Free flap reconstruction of the central skull base is challenging, but transmaxillary, transoral, parapharyngeal, and retropharyngeal approaches can be used with endoscopic assistance to ensure secure inset flap and avoid airway obstruction.


Free Tissue Flaps/surgery , Plastic Surgery Procedures/methods , Skull Base/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Skull Base/pathology
20.
Am J Otolaryngol ; 42(3): 102927, 2021.
Article En | MEDLINE | ID: mdl-33516124

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.


Ambulatory Care Facilities , Ambulatory Surgical Procedures/methods , Efficiency , Endoscopy/methods , Operating Rooms , Quality Improvement , Quality of Health Care , Salivary Gland Calculi/surgery , Sialadenitis/surgery , Length of Stay/statistics & numerical data , Operative Time , Surgery Department, Hospital , Treatment Outcome
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