RESUMO
Pantothenate kinase-associated neurodegeneration (PKAN) is a progressive movement disorder that is due to mutations in PANK2. Pathologically, it is a member of a class of diseases known as neurodegeneration with brain iron accumulation (NBIA) and features increased tissue iron and ubiquitinated proteinaceous aggregates in the globus pallidus. We have previously determined that these aggregates represent condensed residue derived from degenerated pallidal neurons. However, the protein content, other than ubiquitin, of these aggregates remains unknown. In the present study, we performed biochemical and immunohistochemical studies to characterize these aggregates and found them to be enriched in apolipoprotein E that is poorly soluble in detergent solutions. However, we did not determine a significant association between APOE genotype and the clinical phenotype of disease in our database of 81 cases. Rather, we frequently identified similar ubiquitin- and apolipoprotein E-enriched lesions in these neurons in non-PKAN patients in the penumbrae of remote infarcts that involve the globus pallidus, and occasionally in other brain sites that contain large γ-aminobutyric acid (GABA)ergic neurons. Our findings, taken together, suggest that tissue or cellular hypoxic/ischemic injury within the globus pallidus may underlie the pathogenesis of PKAN.
Assuntos
Apolipoproteínas E/química , Isquemia Encefálica/genética , Neurônios GABAérgicos/química , Neurodegeneração Associada a Pantotenato-Quinase/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Agregação Patológica de Proteínas/genética , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Estudos de Casos e Controles , Criança , Feminino , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/patologia , Expressão Gênica , Globo Pálido/metabolismo , Globo Pálido/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neurodegeneração Associada a Pantotenato-Quinase/complicações , Neurodegeneração Associada a Pantotenato-Quinase/metabolismo , Neurodegeneração Associada a Pantotenato-Quinase/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/deficiência , Agregação Patológica de Proteínas/complicações , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/patologia , Ubiquitina/química , Ubiquitina/genética , Ubiquitina/metabolismoRESUMO
Importance: Papillary thyroid microcarcinomas (PTMCs) have been associated with increased thyroid cancer incidence in recent decades. Total thyroidectomy (TT) has historically been the primary treatment, but current guidelines recommend hemithyroidectomy (HT) for select low-risk cancers; however, the risk-benefit ratio of the 2 operations is incompletely characterized. Objective: To compare surgical complication rates between TT and HT for PTMC treatment. Data Sources: SCOPUS, Medline via the PubMed interface, and the Cochrane Central Register of Controlled Trials (CENTRAL); through January 1, 2021, with no starting date restriction. Terms related to papillary thyroid carcinoma and its treatment were used for article retrieval. This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. Study Selection: Original investigations of adults reporting primary surgical treatment outcomes in PTMC and at least 1 complication of interest were included. Articles evaluating only secondary operations or non-open surgical approaches were excluded. Study selection, data extraction, and risk of bias assessment were performed by 2 independent reviewers and conflicts resolved by a senior reviewer. Data Extraction and Synthesis: Pooled effect estimates were calculated using a random-effects inverse-variance weighting model. Main Outcomes and Measures: Cancer recurrence and site, mortality (all-cause and disease-specific), vocal fold paralysis, hypoparathyroidism, and hemorrhage/hematoma. Risk of bias was assessed using the McMaster Quality Assessment Scale of Harms scale. Results: In this systematic review and meta-analysis, 17 studies were analyzed and included 1416 patients undergoing HT and 2411 patients undergoing TT (HT: pooled mean [SD] age, 47.0 [10.0] years; 1139 [84.6%] were female; and TT: pooled mean [SD] age, 48.8 [10.0] years; 1671 [77.4%] were female). Patients undergoing HT had significantly lower risk of temporary vocal fold paralysis compared with patients undergoing TT (3.3% vs 4.5%) (weighted risk ratio [RR], 0.4; 95% CI, 0.2-0.7), temporary hypoparathyroidism (2.2% vs 21.3%) (weighted RR, 0.1; 95% CI, 0.0-0.4), and permanent hypoparathyroidism (0% vs 1.8%) (weighted RR, 0.2; 95% CI, 0.0-0.8). Contralateral lobe malignant neoplasm recurrence was 2.3% in the HT group, while no such events occurred in the TT group. Hemithyroidectomy was associated with a higher overall recurrence rate (3.8% vs 1.0%) (weighted RR, 2.6; 95% CI, 1.3-5.4), but there was no difference in recurrence in the thyroid bed or neck. Conclusions and Relevance: The results of this systematic review and meta-analysis help characterize current knowledge of the risk-benefit ratio of HT vs TT for treatment of PTMC and provide data that may have utility for patient counseling surrounding treatment decisions.
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Hipoparatireoidismo , Neoplasias da Glândula Tireoide , Paralisia das Pregas Vocais , Carcinoma Papilar , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Estudos Observacionais como Assunto , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Paralisia das Pregas Vocais/epidemiologia , Paralisia das Pregas Vocais/etiologia , Paralisia das Pregas Vocais/cirurgiaRESUMO
BACKGROUND: Critical review of current head and neck reconstructive practices as related to free flap donor sites and their impact on clinical outcomes and cost. METHODS: Retrospective multicenter review of free tissue transfer reconstruction of head and neck defects (n = 1315). Variables reviewed: defect, indication, T classification, operative duration, and complications. A convenience sample was selected for analysis of overall (operative and inpatient admission) charges per hospitalization (n = 400). RESULTS: Mean charges of hospitalization by donor tissue: radial forearm free flap (RFFF) $127 636 (n = 183), osteocutaneous RFFF (OCRFFF) $125 456 (n = 70), anterior lateral thigh $133 781 (n = 54), fibula $140 747 (n = 42), latissimus $208 890 (n = 24), rectus $169 637 (n = 18), scapula $128 712 (n = 4), and ulna $110 716 (n = 5; P = .16). Mean operative times for malignant lesions stratified by T classification: 6.9 hours (±25 minutes) for T1, 7.0 hours (±16 minutes) for T2, 7.3 hours (±17 minutes) for T3, and 7.8 hours (±11 minutes) for T4 (P < .0001). Complications correlated with differences in mean charges: minor surgical ($123 720), medical ($216 387), and major surgical ($169 821; P < .001). Operations for advanced malignant lesions had higher mean charges: T1 lesions ($106 506) compared to T2/T3 lesions ($133 080; P = .03) and T4 lesions ($142 183; P = .02). On multivariate analysis, the length of stay, operative duration, and type a postoperative complication were factors affecting overall charges for the hospitalization (P < .018). CONCLUSION: Conclusion: The RFFF and OCRFFF had the lowest complication rates, length of hospitalization, duration of operation, and mean charges of hospitalization. Advanced stage malignant disease correlated with increased hospitalization length, operative time, and complication rates resulting in higher hospitalization charges.
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Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/economia , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/fisiopatologia , Adulto , Idoso , Estudos de Coortes , Análise Custo-Benefício , Seguimentos , Retalhos de Tecido Biológico/transplante , Rejeição de Enxerto , Sobrevivência de Enxerto , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Esvaziamento Cervical/métodos , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of the present study is to address the paucity of data on long-term trends in postoperative complication rates in head and neck surgery. Specifically, this study assesses trends in morbidity and mortality following head and neck surgery over a 20-year period from 1995 to 2015 and identifies risk factors for the development of complications. STUDY DESIGN: Retrospective cross-sectional analysis of Veterans Affairs Surgical Quality Improvement Program database from 1995 to 2015. SETTING: Veterans Affairs medical centers across the United States. SUBJECTS AND METHODS: Using the Veterans Affairs Surgical Quality Improvement Program database, we selected 44,161 patients undergoing head and neck procedures from 1995 to 2015. Trends in 30-day morbidity and mortality were assessed, and univariate and multivariate analyses of risk factors for complications were performed. RESULTS: From 1995-2000 to 2011-2015, overall complication rates decreased >45% (from 10.9% to 5.9%), and 30-day postsurgical mortality decreased nearly 70% (from 1.3% to 0.4%). Postoperative hospital stays also significantly declined. Major procedures, such as free flap cases and total laryngectomies, had less change in complication rate as compared with less invasive procedures. CONCLUSION: Substantial improvement in postoperative morbidity and mortality has taken place in head and neck surgery over the past decades. Static complication rates in some procedures may reflect that the improvement of surgical techniques allow for the treatment of sicker patients. The trends seen in this study speak to the importance of probing further why high rates of complications are still seen in certain procedures and ensuring that effective treatment is balanced with limiting morbidity and mortality.
Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Venous thromboembolism (VTE) may cause significant postoperative morbidity and mortality; research in other surgical fields suggests an elevated VTE risk persists up to 30â¯days after surgery, beyond hospital discharge. We performed a review of the Veteran's Affairs Surgical Quality Improvement Project (VASQIP) database to determine the 30-day incidence of VTE following head and neck surgery and assess the proportion of VTE that occur post-discharge. MATERIALS AND METHODS: A retrospective review was performed of all head and neck ablative procedures captured in the VASQIP database between 1991 and 2015. Post-operative VTE incidence was determined and the relationship of pre-operative data and post-operative mortality to VTE incidence was assessed. RESULTS: 48,986 patients were included in the study; there were 152 VTE events (0.31%) and 39 (25.7%) occurred post-discharge. Lower VTE rates were found in parotidectomies (0.22%) and thyroid/parathyroid cases (0.23%), and higher rates in free flap (1.52%) and laryngectomy cases (0.69%). Age >70, recent weight loss, low serum albumin, and increased surgical time were all associated with increased VTE incidence on multivariate analysis. 90-day mortality in patients without VTE was 2.1% compared to 19.7% in patients who experienced a VTE. CONCLUSION: While the documented rate of VTE in a national dataset is relatively low following head and neck surgeries, it is elevated with certain procedure categories and following long operations, and a significant proportion of VTE occur post-discharge. This study provides baseline data to better inform efforts to risk-stratify and customize thromboprophylaxis for patients undergoing head and neck procedures.
Assuntos
Sistemas de Gerenciamento de Base de Dados , Neoplasias de Cabeça e Pescoço/cirurgia , Melhoria de Qualidade , Procedimentos Cirúrgicos Operatórios/normas , United States Department of Veterans Affairs , Tromboembolia Venosa/epidemiologia , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia , Tromboembolia Venosa/complicações , Tromboembolia Venosa/mortalidadeRESUMO
IMPORTANCE: In recent years, transoral robotic surgery (TORS) has emerged as a useful treatment for oropharyngeal squamous cell carcinoma (OPSCC). In appropriately selected patients, the use of TORS may allow avoidance of adjuvant chemotherapy and/or radiotherapy, thereby avoiding the long-term adverse effects of these therapies. OBJECTIVE: To compare functional speech, swallowing, and quality-of-life outcomes longitudinally between those undergoing TORS only and those undergoing TORS and adjuvant radiotherapy (TORS+RT) or TORS and chemoradiotherapy (TORS+CRT). DESIGN, SETTING, AND PARTICIPANTS: This prospective, longitudinal cohort study performed from June 1, 2013, through November 31, 2015, included 74 patients undergoing TORS for initial treatment of OPSCC at a single tertiary academic hospital. MAIN OUTCOMES AND MEASURES: Data were collected at baseline, postoperatively (7-21 days), at short-term follow-up (6-12 months), and at long-term follow-up (>12 months). The quality-of-life metrics included the 10-item Eating Assessment Tool and the University of Michigan Head and Neck Quality of Life instrument. Data were also collected on tumor staging, surgical and adjuvant therapy details, patient comorbidities, tracheostomy and feeding tube use, and functional speech and swallowing status using the Performance Status Scale for Head and Neck Cancer Patients. RESULTS: Seventy-four patients were enrolled in the study (mean [SD] age, 61.39 [7.99] years; 68 [92%] male). Median long-term follow-up was 21 months (range, 12-36 months). The response rates were 86% (n = 64) postoperatively, 88% (n = 65) at short-term follow-up, and 86% (n = 64) at long-term follow-up. In all 3 groups, there was a significant worsening in pain and all swallowing-related measures postoperatively. There was subsequent improvement over time, with different trajectories observed across the 3 intervention groups. Postoperative dysphagia improved significantly more quickly in the TORS-only group. At long-term follow-up, weight loss differed between the TORS-only and TORS+RT groups (mean difference, -16.1; 97.5% CI, -29.8 to -2.4) and the TORS-only and TORS+CRT groups (mean difference, -14.6; 97.5% CI, -29.2 to 0) in a clinically meaningful way. In addition, the TORS-only group had significantly better scores than the TORS+CRT group on the Performance Status Scale-Eating in Public scale (mean difference, 21.8; 97.5% CI, 4.3-39.2) and Head and Neck Quality of Life-Eating scale (mean difference, 21.2; 97.5% CI, 4.0-38.3). CONCLUSIONS AND RELEVANCE: Patients who underwent TORS+CRT demonstrated poorer long-term outcomes, with continued dysphagia more than 1 year after surgery. These findings support the investigation of adjuvant de-escalation therapies to reduce the long-term adverse effects of treatment.
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Objective To characterize and identify risk factors for 30-day surgical site infections (SSIs) in patients with head and neck cancer who underwent microvascular reconstruction. Study Design Cross-sectional study with nested case-control design. Setting Nine American tertiary care centers. Subjects and Methods Hospitalized patients were included if they underwent head and neck cancer microvascular reconstruction from January 2003 to March 2016. Cases were defined as patients who developed 30-day SSI; controls were patients without SSI at 30 days. Postoperative antibiotic prophylaxis (POABP) regimens were categorized by Gram-negative (GN) spectrum: no GN coverage, enteric GN coverage, and enteric with antipseudomonal GN coverage. All POABP regimens retained activity against anaerobes and Gram-positive bacteria. Thirty-day prevalence of and risk factors for SSI were evaluated. Results A total of 1307 patients were included. Thirty-day SSI occurred in 189 (15%) patients; median time to SSI was 11.5 days (interquartile range, 7-17). Organisms were isolated in 59% of SSI; methicillin-resistant Staphylococcus aureus (6%) and Pseudomonas aeruginosa (9%) were uncommon. A total of 1003 (77%) patients had POABP data: no GN (17%), enteric GN (52%), and antipseudomonal GN (31%). Variables independently associated with 30-day SSI were as follows: female sex (adjusted odds ratio [aOR], 1.6; 95% CI, 1.1-2.2), no GN POABP (aOR, 2.2; 95% CI, 1.5-3.3), and surgical duration ≥11.8 hours (aOR, 1.9; 95% CI, 1.3-2.7). Longer POABP durations (≥6 days) or antipseudomonal POABP had no association with SSI. Conclusions POABP without GN coverage was significantly associated with SSI and should be avoided. Antipseudomonal POABP or longer prophylaxis durations (≥6 days) were not protective against SSI. Antimicrobial stewardship interventions should be made to limit unnecessary antibiotic exposures, prevent the emergence of resistant organisms, and improve patient outcomes.
Assuntos
Antibioticoprofilaxia , Neoplasias de Cabeça e Pescoço/cirurgia , Microvasos/cirurgia , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Procedimentos Cirúrgicos VascularesRESUMO
Objective Sialoendoscopy is a minimally invasive technique for the treatment of obstructive sialadenitis. We aim to describe treatment considerations and report our ultimate rate of gland preservation. Study Design Case series with chart review. Setting Academic tertiary hospital. Subject and Methods A total of 128 consecutive sialoendoscopy cases for obstructive sialadenitis between 2009 and 2015 were evaluated. Procedures included endoscopic stricture dilation, basket-assisted stone retrieval, Holmium laser lithotripsy, and combined endoscopic transoral stone excision. Resolution of symptoms, need for additional procedures, and rate of subsequent adenectomy were investigated. Results Sialoendoscopy was completed in 120 of 128 patients (94%). There were 87 parotid gland cases and 41 submandibular gland cases. Endoscopic stricture dilation was attempted in 97 patients and successful in 99%. A sialolith was identified in 31 cases and removed by basket-assisted stone retrieval (10 cases), Holmium:YAG laser stone fragmentation (10 cases), and combined endoscopic transoral stone extraction (4 cases). In 8 cases overall, sialoendoscopy failed, with immediate adenectomy. At a mean follow-up of 18 months, 39 patients (33%) reported recurrence of symptoms, with 90% in the stricture group. For the entire cohort, gland preservation occurred in 112 of 128 patients (88%). Conclusions Sialoendoscopy is an effective technique, with few patients requiring additional procedures. Newer interventional approaches allow for stone retrieval without adenectomy. Patients in the stricture group were more likely to have recurrent symptoms as compared with the sialolithiasis group but often benefit from additional sialoendoscopic procedures, leading to a high overall rate of long-term gland preservation of 91%.
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Endoscopia/métodos , Sialadenite/cirurgia , Feminino , Humanos , Litotripsia a Laser , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Glândula Parótida/cirurgia , Recidiva , Glândula Submandibular/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Transoral robotic-assisted surgery (TORS) is increasingly utilized in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Postoperative bleeding is a significant and potentially fatal complication of TORS. Prophylactic ligation of ipsilateral external carotid artery (ECA) branches is a recognized strategy to reduce postoperative bleeding risk. We examined the incidence and sequelae of postoperative oropharyngeal bleeding with and without routine ECA ligation. METHODS: OPSCC patients treated with TORS between 2010 and 2015 with minimum 30days follow up were included. Clinicopathological data, operative details, and postoperative course were abstracted for analysis. Cases of postoperative bleeding were classified as Minor, Intermediate, Major, and Severe. The incidence and severity of bleeding was compared between patients treated with and without prophylactic ECA ligation. RESULTS: Bleeding after TORS was documented in 13/201 (6.5%) patients. The majority of bleeding episodes were observed among anticoagulated or previously radiated patients. By surgeon preference, 52 patients had prophylactic ECA ligation during neck dissection while the remaining 149 patients did not. There was no significant difference in overall incidence of postoperative bleeding between patients with prophylactic ECA ligation (3/52, 5.8%) and patients without (10/149, 6.7%) [p=0.53]. However, severe bleeding complications (4, 2.0%) were only observed in patients without prophylactic ligation. CONCLUSION: A small but meaningful risk of bleeding after TORS for OPSCC exists, particularly among anticoagulated or previously radiated patients. Prophylactic ECA ligation did not significantly impact the overall incidence of postoperative bleeding but may reduce the risk of severe (life-threatening) bleeding.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Artéria Carótida Externa/cirurgia , Ligadura , Neoplasias Orofaríngeas/cirurgia , Hemorragia Pós-Operatória/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Objective To compare outcomes after microvascular reconstructions of head and neck defects between overlapping and nonoverlapping operations. Study Design Retrospective cohort study. Setting Tertiary care center. Subjects and Methods Patients undergoing microvascular free tissue transfer operations between January 2010 and February 2015 at 2 tertiary care institutions were included (n = 1315). Patients were divided into 2 cohorts by whether the senior authors performed a single or consecutive microvascular reconstruction (nonoverlapping; n = 773, 59%) vs performing overlapping microvascular reconstructions (overlapping; n = 542, 41%). Variables reviewed were as follows: defect location, indication, T classification, surgical details, duration of the operation and hospitalization, and complications (major, minor, medical). Results Microvascular free tissue transfers performed included radial forearm (49%, n = 639), osteocutaneous radial forearm (14%, n = 182), anterior lateral thigh (12%, n = 153), fibula (10%, n = 135), rectus abdominis (7%, n = 92), latissimus dorsi (6%, n = 78), and scapula (<1%, n = 4). The mean duration of the overlapping operations was 21 minutes longer than nonoverlapping operations ( P = .003). Mean duration of hospitalization was similar for nonoverlapping (9.5 days) and overlapping (9.1 days) cohorts ( P = .39). There was no difference in complication rates when stratified by overlapping (45%, n = 241) and nonoverlapping (45%, n = 344) ( P = .99). Subset analysis yielded similar results when minor, major, and medical complications between groups were assessed. The overall survival rate of free tissue transfers was 96%, and this was same for overlapping (96%) and nonoverlapping (96%) operations ( P = .71). Conclusions Patients had similar complication rates and durations of hospitalization for overlapping and nonoverlapping operations.
Assuntos
Retalhos de Tecido Biológico , Cabeça/cirurgia , Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Retalhos de Tecido Biológico/irrigação sanguínea , Humanos , Masculino , Microvasos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Treatment of head and neck cancer is complex, and a multidisciplinary clinic may improve the coordination of care. The value of a head and neck multidisciplinary clinic has not yet been established in oropharyngeal squamous cell carcinoma (SCC). METHODS: A retrospective review was conducted of Veterans Affairs patients with oropharyngeal SCC undergoing concurrent chemoradiation before and after implementation of the head and neck multidisciplinary clinic. RESULTS: Fifty-two patients before and 54 patients after multidisciplinary clinic were included in this study. Age, tobacco use, and p16+ status were similar between groups. With multidisciplinary clinic, time to treatment decreased, and utilization of supportive services, including speech pathology, dentistry, and nutrition increased. The 5-year disease-specific survival rate increased from 63% to 81% (p = .043) after implementation of the multidisciplinary clinic. Multivariate analysis showed that disease stage (p = .016), p16 status (p = .006), and multidisciplinary clinic participation (p = .042) were predictors of disease-specific survival. CONCLUSION: Implementation of a multidisciplinary clinic improved care coordination and disease-specific survival in patients with oropharyngeal SCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1106-1112, 2017.