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OBJECTIVES: Acinic cell carcinoma (ACC) most frequently arises in the parotid gland. Treatment consists of surgical resection and sometimes adjuvant therapy. ACC is most often a low-grade malignancy with good prognosis. Higher-grade tumors are often treated aggressively with total parotidectomy, neck dissection, and adjuvant therapy; however, the effect of parotid gland resection extent on oncologic outcomes has not been studied. Herein, we examine predictors of oncologic outcomes, including the effect of extent of resection. METHODS: Patients with diagnosis of parotid ACC treated at our institution were included in this retrospective study. Patient factors were examined, and patients were grouped by extent of resection and tumor grade. RESULTS: 58 patients, including 32 low-grade, 7 intermediate-grade, and 14 high-grade were included. Patients with low-grade tumors were more likely to undergo lesser extent of parotidectomy and less likely to undergo neck dissection. Two patients with low grade tumors developed recurrence, one local and one regional. Recurrence rate did not differ with resection extent in low-grade tumors. High tumor grade was found to be associated with disease progression. There was no association with adjuvant treatment and outcomes. Across all tumor grades advanced AJCC stage was found to be associated with disease progression. CONCLUSIONS: In ACC patients with low-grade tumors and lower disease stage who undergo lesser extent of surgical resection oncologic outcomes were favorable. Patients with high-grade tumors carry a high risk of recurrence, despite aggressive treatment. AJCC stage and histopathologic grade may predict outcomes and guide treatment.
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INTRODUCTION: There has been historical controversy regarding the extent of resection in the management of pleomorphic adenomas. This study aims to evaluate the extent of surgery and short-term postoperative outcomes of partial superficial parotidectomy (PSP) for the management of pleomorphic adenomas at a tertiary, high-volume center. METHODS: A retrospective chart review of patients who underwent PSP was performed. Variables included demographics, pre-operative facial nerve function, operative techniques, postoperative complications/facial nerve function, and recurrence. RESULTS: 151 adults who underwent PSP for pleomorphic adenoma from January 1st, 2000 to December 31st, 2022 were identified. Median age was 55 (IQR 40-66) years with females representing 74 % of the cohort. Median tumor size at presentation was 1.8 (IQR 1.3-2.3) cm. Baseline facial nerve function was excellent for most patients (House-Brackmann I, 99 %). Most patients underwent a superficial inferior parotidectomy (88 %). Modified Blair incision (70 %) was the most common incision. Intraoperatively, the facial nerve was identified in 149 (99 %) patients. The main trunk was identified in 126 (85 %) patients. No patient had tumor spillage. Only two patients required parotid bed reconstruction. The most common complication was ear numbness (60 %). Postoperatively, 114 patients were House-Brackmann grade I at both preoperative and postoperative assessment, 8 went from grade I to II, and 1 went from grade VI to II (Bell's palsy that resolved to grade II following surgery). Median follow-up was 1(IQR 1-5) month. CONCLUSION: PSP is efficacious in the management of pleomorphic adenomas with preservation of facial nerve function, and minimal post-operative complications. Future study is needed to assess long term recurrence risk.
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Adenoma Pleomorfo , Neoplasias Parotídeas , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Glândula Parótida/cirurgia , Glândula Parótida/patologia , Adenoma Pleomorfo/cirurgia , Adenoma Pleomorfo/patologia , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: Parotidectomies have historically been performed on an inpatient basis despite being well-tolerated surgeries with minimal postoperative wound care and low rates of complications at high-volume institutions. Past studies have supported the safety of outpatient surgery for parotidectomy but have been limited to superficial parotidectomy and have not addressed the patient experience surrounding the surgical intervention such as pre-operative and post-operative care and communication. PURPOSE: This study assesses the impact of outpatient superficial, deep, and partial parotid surgery on various parameters including surgical safety, distance traveled for care, utilization of telehealth, and patient-initiated communication. MATERIALS AND METHODS: Retrospective study from January 2020 to October 2021. Patients undergoing superficial lobe, deep lobe, and partial parotidectomies for benign and malignant pathologies were divided into inpatient and outpatient cohorts. A multivariable model examined the relationship between admission status and surgical complications, adjusted for age, sex, and tumor size. RESULTS: 159 patients total, 94 outpatient and 65 inpatients. No statistical difference in rates of surgical complications with the exception of salivary leak. There was an increased rate of salivary leak reported in the inpatient group (OR 5.4, 95 % CI 1.6 to 18.0, p = 0.01). Mean patient travel distance of 354 miles one-way. Post-operatively, 76 % were evaluated via video visit. Following discharge, >55 % of patients initiated communication with the surgical team, which was not statistically different between the groups. CONCLUSIONS: Outpatient parotidectomy is safe and can be more convenient, but telehealth communication must be balanced with rigorous attention to patient education.
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Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Pacientes Ambulatoriais , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Glândulas Salivares/patologia , Glândula Parótida/cirurgia , Glândula Parótida/patologiaRESUMO
Enhancing the thermostability of enzymes without impacting their catalytic function represents an important yet challenging goal in protein engineering and biocatalysis. We recently introduced a novel method for enzyme thermostabilization that relies on the computationally guided installation of genetically encoded thioether "staples" into a protein via cysteine alkylation with the noncanonical amino acid O-2-bromoethyl tyrosine (O2beY). Here, we demonstrate the functionality of an expanded set of electrophilic amino acids featuring chloroacetamido, acrylamido, and vinylsulfonamido side-chain groups for protein stapling using this strategy. Using a myoglobin-based cyclopropanase as a model enzyme, our studies show that covalent stapling with p-chloroacetamido-phenylalanine (pCaaF) provides higher stapling efficiency and enhanced stability (thermodynamic and kinetic) compared to the other stapled variants and the parent protein. Interestingly, molecular simulations of conformational flexibility of the cross-links show that the pCaaF staple allows fewer energetically feasible conformers than the other staples, and this property may be a broader indicator of stability enhancement. Using this strategy, pCaaF-stapled variants with significantly enhanced stability against thermal denaturation (ΔTm' = +27 °C) and temperature-induced heme loss (ΔT50 = +30 °C) were obtained while maintaining high levels of catalytic activity and stereoselectivity. Crystallographic analyses of singly and doubly stapled variants provide key insights into the structural basis for stabilization, which includes both direct interactions of the staples with protein residues and indirect interactions through adjacent residues involved in heme binding. This work expands the toolbox of protein stapling strategies available for protein stabilization.
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OBJECTIVE: Management of ectopic lingual thyroid (ELT) must balance the morbidity of disease with the morbidity of treatment. We investigate clinical outcomes associated with modern treatment options and analyze the role of transoral surgery in the treatment algorithm for ELT. METHODS: This was a retrospective chart review of ELT patients treated at a tertiary care center from 1/1/1979 to 12/31/2019. In addition, a systematic review of the literature from 1979 to 2021 for reports of ELT was performed. Symptoms defined as high-risk were dysphagia, dysphonia, dyspnea, neck swelling, bleeding, and obstructive sleep apnea (OSA). RESULTS: 36 patients within the institutional cohort (IC) and 224 cases in the systematic review (SRC) met criteria. The most common presenting symptoms for both cohorts were dysphagia, globus sensation, and dysphonia. One third of each cohort were hypothyroid, while 3% (n = 1) and 9% (n = 21) of the IC and SRC, respectively, had clinical suspicion of malignancy at presentation. 27% (n = 10) of the IC and 55% (n = 121) of the SRC underwent surgical therapy. There was a 4% (3/72) transoral bleed rate for all patients undergoing transoral surgery. Other reported complications were minor. There were no tracheostomies, and no deaths. Among observed, medically treated, and surgically treated patients, symptoms improved during follow up for 43% or 68% in the IC and SRC, respectively. Following surgery, symptoms improved or resolved for 86% or 93% in the IC and SRC, respectively. CONCLUSIONS: Asymptomatic ELTs with no concern for malignancy can be managed with observation. Patients with mild symptoms or hypothyroidism may trial thyroid suppressive therapy or RAI. RAI can be considered for patients with high-risk symptoms. For patients with symptoms resistant to conservative therapy, concern for malignancy or high-risk symptoms not conducive to RAI, surgery should be considered. Transoral approaches offer acceptable morbidity, and most patients experience resolution of symptoms following this approach.
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Transtornos de Deglutição , Disfonia , Hipotireoidismo , Tireoide Lingual , Transtornos de Deglutição/etiologia , Humanos , Tireoide Lingual/cirurgia , Estudos Retrospectivos , Língua/patologiaRESUMO
PURPOSE: Determine rates of intra-parotid and neck nodal metastasis, identify risk factors for recurrence, and report outcomes in patients with primary high-grade parotid malignancy who undergo total parotidectomy and neck dissection. MATERIALS & METHODS: Retrospective review of patients undergoing total parotidectomy and neck dissection for high-grade parotid malignancy between 2005 and 2015. The presence and number of parotid lymph nodes, superficial and deep, as well as cervical lymph nodes involved with metastatic disease were assessed. Risk factors associated with metastatic spread to the parotid deep lobe were identified and recurrence rates reported. RESULTS: 75 patients with median follow-up time of 47 months. 35 patients (46.7%) had parotid lymph node metastasis. Seven patients (9.3%) had deep lobe nodal metastasis without metastasis to the superficial lobe nodes. Nine patients (12%) had positive intra-parotid nodes without positive cervical nodes. Cervical nodal disease was identified in 49.3% patients (37/75). Local, parotid-bed recurrence rate was 5.3% (4/75). Regional lymph node recurrence rate was also 5.3% (4/75). Rate of distant metastasis was 30.6% (23/75). The overall disease free survival rate for all patients at 2 and 5 years were 71% and 60% respectively. CONCLUSION: Parotid lymph node metastasis occurred at a similar rate to cervical lymph node metastasis (46.7% and 49.3%, respectively). Deep lobe parotid nodal metastasis occurred in nearly a quarter of patients and can occur without superficial parotid nodal metastasis. Rate of recurrence in the parotid bed, which may represent local or regional recurrence, was similar to regional cervical lymph node recurrence. Total parotidectomy and neck dissection should be considered high-grade parotid malignancy regardless of clinical nodal status.
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Procedimentos Cirúrgicos do Sistema Digestório/métodos , Esvaziamento Cervical , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pescoço , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Glândula Parótida/patologia , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To compare clinical, surgical, and cost outcomes in patients undergoing head and neck free-flap reconstructive surgery in the setting of postoperative intensive care unit (ICU) against general floor management. METHODS: Retrospective analysis of head and neck free-flap reconstructive surgery patients at a single tertiary academic medical center. Clinical data was obtained from medical records. Cost data was obtained via the Mayo Clinic Rochester Cost Data Warehouse, which assigns Medicare reimbursement rates to all professional billed services. RESULTS: A total of 502 patients were included, with 82 managed postoperatively in the ICU and 420 on the general floor. Major postoperative outcomes did not differ significantly between groups (Odds Ratio[OR] 1.54; p = 0.41). After covariate adjustments, patients managed in the ICU had a 3.29 day increased average length of hospital stay (Standard Error 0.71; p < 0.0001) and increased need for take-back surgery (OR 2.35; p = 0.02) when compared to the general floor. No significant differences were noted between groups in terms of early free-flap complications (OR 1.38;p = 0.35) or late free-flap complications (Hazard Ratio 0.81; p = 0.61). Short-term cost was $8772 higher in the ICU (range = $5640-$11,903; p < 0.01). Long-term cost did not differ significantly. CONCLUSION: Postoperative management of head and neck oncologic free-flap patients in the ICU does not significantly improve major postoperative outcomes or free-flap complications when compared to general floor care, but does increase short-term costs. General floor management may be appropriate when cardiopulmonary compromise is not present.
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Retalhos de Tecido Biológico/economia , Neoplasias de Cabeça e Pescoço/economia , Neoplasias de Cabeça e Pescoço/cirurgia , Custos de Cuidados de Saúde , Unidades de Terapia Intensiva/economia , Quartos de Pacientes/economia , Procedimentos de Cirurgia Plástica/economia , Procedimentos de Cirurgia Plástica/métodos , Cuidados Pós-Operatórios/economia , Adulto , Idoso , Feminino , Retalhos de Tecido Biológico/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Thermostabilization represents a critical and often obligatory step toward enhancing the robustness of enzymes for organic synthesis and other applications. While directed evolution methods have provided valuable tools for this purpose, these protocols are laborious and time-consuming and typically require the accumulation of several mutations, potentially at the expense of catalytic function. Here, we report a minimally invasive strategy for enzyme stabilization that relies on the installation of genetically encoded, nonreducible covalent staples in a target protein scaffold using computational design. This methodology enables the rapid development of myoglobin-based cyclopropanation biocatalysts featuring dramatically enhanced thermostability (ΔTm = +18.0 °C and ΔT50 = +16.0 °C) as well as increased stability against chemical denaturation [ΔCm (GndHCl) = 0.53 M], without altering their catalytic efficiency and stereoselectivity properties. In addition, the stabilized variants offer superior performance and selectivity compared with the parent enzyme in the presence of a high concentration of organic cosolvents, enabling the more efficient cyclopropanation of a water-insoluble substrate. This work introduces and validates an approach for protein stabilization which should be applicable to a variety of other proteins and enzymes.
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Enzimas/química , Modelos Químicos , Engenharia de Proteínas/métodos , Biocatálise , Biologia Computacional , Estabilidade Enzimática , Cinética , Modelos Estruturais , Estrutura Molecular , Solubilidade , TemperaturaRESUMO
PURPOSE: To compare recurrent pleomorphic adenoma tumor burden as detected on magnetic resonance and computerized tomography imaging with postoperative histopathology. MATERIALS AND METHODS: 44 patients were identified at a tertiary medical center between 2000 and 2015. Patients were included if they had viewable preoperative imaging and a postoperative diagnosis of recurrent pleomorphic adenoma. Primary outcomes were differences in the number and size of lesions detected on imaging and pathology. RESULTS: The size in greatest dimension between pathology and imaging was not significant on aggregate MRI + CT (p = 0.78), MRI (p = 0.41), or CT (p = 0.69). There were more lesions found on pathology compared to both aggregate MRI + CT (p = 0.003) and CT alone (p = 0.014). The number of lesions between MRI and pathology failed to reach significance (p = 0.06). On univariate analysis, the interval between imaging and pathology (recurrent surgery) did not significantly affect the number of lesions detected (p = 0.18). On multivariable analysis, CT as the primary imaging modality and >1 recurrence was independently associated with greater inaccuracy with respect to number of lesions detected (p = 0.006; p = 0.008). CONCLUSION: The size of the largest lesion on pathology can be accurately determined with imaging. Compared to MRI, CT scans significantly underpredict the number of lesions found on pathology. MRI should be prioritized unless contraindications exist. These findings will help guide imaging choice, preoperative planning, and patient counseling.
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Adenoma Pleomorfo/diagnóstico por imagem , Adenoma Pleomorfo/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Carga Tumoral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Engineered myoglobins were recently shown to be effective catalysts for abiological carbene and nitrene transfer reactions. Here, we investigated the impact of substituting the conserved heme-coordinating histidine residue with both proteinogenic (Cys, Ser, Tyr, Asp) and non-proteinogenic Lewis basic amino acids (3-(3'-pyridyl)-alanine, p-aminophenylalanine, and ß-(3-thienyl)-alanine), on the reactivity of this metalloprotein toward these abiotic transformations. These studies showed that mutation of the proximal histidine residue with both natural and non-natural amino acids result in stable myoglobin variants that can function as both carbene and nitrene transferases. In addition, substitution of the proximal histidine with an aspartate residue led to a myoglobin-based catalyst capable of promoting stereoselective olefin cyclopropanation under nonreducing conditions. Overall, these studies demonstrate that proximal ligand substitution provides a promising strategy to tune the reactivity of myoglobin-based carbene and nitrene transfer catalysts and provide a first, proof-of-principle demonstration of the viability of pyridine-, thiophene-, and aniline-based unnatural amino acids for metalloprotein engineering.
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OBJECTIVES: To review swallowing, airway and speech outcomes following transoral robotic surgery (TORS)⯱â¯adjuvant therapy for human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV[+]OPSCC). METHODS: Patients underwent TORS ± standard adjuvant therapy from 5/1/2007-5/31/2015. Clinical data were recorded and descriptive analysis was performed. RESULTS: 267 patients met criteria. All patients underwent surgery at Mayo, however, only 41/81 and 71/119 patients received RT and CRT at a Mayo Clinic site. A PEG was placed in 77 patients (3 prior to any treatment, 74 reactively during adjuvant therapy), with 3 PEG dependent and 3 partially PEG reliant at last follow-up. Tracheostomy was performed in 30 (11%) patients; 28 were decannulated. Swallow evaluations were completed for 20/81 undergoing RT and 50/119 undergoing CRT at a median of 3.8 and 7.6â¯months post-treatment, respectively. An unrestricted oral diet was reported by 5% following RT and 12% following CRT on the Functional Oral Intake Scale. HN-PSS normalcy of diet scores indicated a diet beyond soft chewable foods for 27% following RT and 46% following CRT. No restriction of place, food, or companion was reported for the HN-PSS for public eating in 13% after RT and 33% after CRT. Aspiration of thin liquid was present in 17% and 28% following RT and CRT, respectively. HN-PSS understandability of speech was "always understandable" in 60% and 63%, following RT and CRT, respectively. Hoarseness was reported in 56% and 45% following RT and CRT respectively. CONCLUSION: Long-term PEG and tracheostomy dependence in this cohort is low. However, these outcomes under-represent the decrement in patient speech and swallowing following TORS ± standard adjuvant therapy for HPV(+)OPSCC.
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Carcinoma de Células Escamosas/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Neoplasias Orofaríngeas/cirurgia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Procedimentos Cirúrgicos Robóticos/métodos , Centros Médicos Acadêmicos , Adulto , Idoso , Institutos de Câncer , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Nutrição Enteral/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Boca , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/epidemiologia , Infecções por Papillomavirus/diagnóstico , Cuidados Pós-Operatórios/métodos , Prognóstico , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estatísticas não Paramétricas , Traqueostomia/métodos , Resultado do TratamentoRESUMO
Hemoproteins have recently emerged as promising biocatalysts for promoting a variety of carbene transfer reactions including cyclopropanation and Y-H insertion (Y = N, S, Si, B). For these and synthetic carbene transfer catalysts alike, achieving high chemoselectivity toward cyclopropanation in olefin substrates bearing unprotected Y-H groups has proven remarkably challenging due to competition from the more facile carbene Y-H insertion reaction. In this report, we describe the development of a novel artificial metalloenzyme based on an engineered myoglobin incorporating a serine-ligated Co-porphyrin cofactor that is capable of offering high selectivity toward olefin cyclopropanation over N-H and Si-H insertion. Intramolecular competition experiments revealed a distinct and dramatically altered chemoselectivity of the Mb(H64V,V68A,H93S)[Co(ppIX)] variant in carbene transfer reactions compared to myoglobin-based variants containing the native histidine-ligated heme cofactor or other metal/proximal ligand substitutions. These studies highlight the functional plasticity of myoglobin as a "carbene transferase" and illustrate how modulation of the cofactor environment within this metalloprotein scaffold represents a valuable strategy for accessing carbene transfer reactivity not exhibited by naturally occurring hemoproteins or transition metal catalysts.
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Hemeproteínas/síntese química , Transferases/metabolismo , Catálise , Hemeproteínas/química , Estrutura Molecular , Engenharia de Proteínas , Transferases/síntese químicaRESUMO
PURPOSE: Functional outcomes and complication rates after open surgery for advanced-stage oropharyngeal cancers are rarely reported. These measures are critical for choice of treatment modality and patient counseling. We describe the long term functional outcomes and associated complications of primary surgical management of T4 oropharyngeal cancers reconstructed with radial forearm free flaps. MATERIALS AND METHODS: A retrospective review was performed of 40 patients with T4 oropharyngeal cancers treated between 2005 and 2015 at a tertiary care center. RESULTS: Forty patients with T4 oropharyngeal cancers underwent open surgical resection and radial forearm free flap reconstruction at the time of surgery. Mandibulotomy was required in 33 (82.5%) cases. Thirty-five (87.5%) patients received adjuvant radiation or combined chemotherapy and radiation. Tracheostomy was performed in all patients, but every patient was eventually decannulated. Twenty (57.1%) patients required gastrostomy tube placement at some point during treatment; however, 91.4% were on a completely oral diet with a mean FOSS score of 1.6 by 1year after completion of treatment. The addition of adjuvant treatment was the only factor significantly associated with poorer FOSS scores. The overall rates of short and long-term complications were 60.0% and 57.1% respectively. The most common short and long-term complications were infection (30.0%) and velopharyngeal insufficiency (25.7%) respectively. CONCLUSIONS: Traditional open surgical approaches to large tumors of the oropharynx carry higher complication rates than more recent advanced transoral approaches. However, they can still be utilized with excellent long-term functional results in certain cases of advance oropharyngeal cancers not amenable to transoral approaches. With careful reconstruction of oropharyngeal defects, over 90% of patients can achieve a completely oral diet.
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Antebraço/cirurgia , Retalhos de Tecido Biológico , Osteotomia Mandibular/métodos , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Incidência , Masculino , Osteotomia Mandibular/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: With the rise of oropharyngeal squamous cell carcinoma associated with human papillomavirus (HPV), appropriate treatment strategies continue to be tailored toward minimizing treatment while preserving oncologic outcomes. This study aimed to compare the outcomes for those undergoing transoral resection with or without adjuvant therapy for HPV-related oropharyngeal carcinoma. METHODS: A case-match cohort analysis was performed at two institutions on patients with HPV-related oropharyngeal squamous cell carcinoma. All the subjects underwent transoral surgery and neck dissection. The patients treated with surgery alone were matched 1:1 to those treated with surgery and adjuvant therapy using two groups identified as confounders: T-stage (T1/2 or T3/4) and number of pathologically positive lymph nodes (≤4 or >4). RESULTS: The study identified 105 matched pairs, with a median follow-up period of 42 months (range 3.1-102.3 months). The patients were staged as T1/T2 (86%) or T3/4 (14%). Each group had five patients with more than four positive lymph nodes. Adjuvant therapy significantly improved disease-free survival (hazard ratio [HR] 0.067; 95% confidence interval [CI] 0.01-0.62) and was associated with a lower risk of local and regional recurrence (risk ratio [RR] 0.096; 95% CI 0.02-0.47). No difference in disease-specific survival (HR 0.22; 95% CI 0.02-2.57) or overall survival (HR 0.18; 95% CI 0.01-2.4) was observed with the addition of adjuvant therapy. The risk of the gastrostomy tube was higher for those receiving adjuvant therapy (RR 7.3; 95% CI 2.6-20.6). CONCLUSIONS: Transoral surgery is an effective approach for the treatment of HPV-related oropharyngeal carcinoma. The addition of adjuvant therapy appears to decrease the risk of recurrence and improve disease-free survival but may not significantly improve overall survival.
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Carcinoma de Células Escamosas/mortalidade , Neoplasias Bucais/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Orofaríngeas/mortalidade , Infecções por Papillomavirus/mortalidade , Procedimentos Cirúrgicos Robóticos/mortalidade , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virologia , Estudos de Casos e Controles , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/terapia , Neoplasias Bucais/virologia , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/virologia , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/virologia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Engineered myoglobins have recently emerged as promising scaffolds for catalyzing carbene-mediated transformations. In this work, we investigated the effect of altering the metal center and its first-sphere coordination environment on the carbene transfer reactivity of myoglobin. To this end, we first established an efficient protocol for the recombinant expression of myoglobin variants incorporating metalloporphyrins with non-native metals, including second- and third-row transition metals (ruthenium, rhodium, iridium). Characterization of the cofactor-substituted myoglobin variants across three different carbene transfer reactions (cyclopropanation, N-H insertion, S-H insertion) revealed a major influence of the nature of metal center, its oxidation state and first-sphere coordination environment on the catalytic activity, stereoselectivity, and/or oxygen tolerance of these artificial metalloenzymes. In addition, myoglobin variants incorporating manganese- or cobalt-porphyrins were found capable of catalyzing an intermolecular carbene C-H insertion reaction involving phthalan and ethyl α-diazoacetate, a reaction not supported by iron-based myoglobins and previously accessed only using iridium-based (bio)catalysts. These studies demonstrate how modification of the metalloporphyrin cofactor environment provides a viable and promising strategy to enhance the catalytic properties and extend the reaction scope of myoglobin-based carbene transfer catalysts.
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Herein, we present the case of a previously healthy 54year-old female who developed several weeks of unilateral tinnitus and aural fullness. She subsequently underwent unilateral pressure equalization tube placement at an outside institution after exam demonstrated a middle ear effusion, conductive hearing loss and normal nasopharyngoscopy. Ultimately, an MRI revealed an occult mass in the infratemporal fossa (ITF), which was successfully removed via an endoscopic transnasal ITF approach. Following resection of a histopathologically confirmed benign neurofibroma, she reported complete resolution of her symptoms. The antiquated diagnostic algorithm of unilateral effusion suggests that normal nasopharyngscopy successfully "rules out" a causative neoplastic process; however, Eustachian tube occlusion by occult skull base lesions may be missed without further investigation. This case highlights the need for additional radiological investigation of unexplained unilateral persistent middle ear effusion in the setting of normal nasopharyngoscopy.
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Neoplasias Mandibulares/diagnóstico por imagem , Neoplasias Mandibulares/cirurgia , Neurofibroma/diagnóstico por imagem , Neurofibroma/cirurgia , Fossa Pterigopalatina/diagnóstico por imagem , Fossa Pterigopalatina/cirurgia , Diagnóstico Diferencial , Feminino , Perda Auditiva Condutiva/cirurgia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Otite Média com Derrame/cirurgia , Zumbido/cirurgiaRESUMO
PURPOSE: The utility of sentinel lymph node biopsy in desmoplastic melanoma has been questioned due to multiple reports of a low rate of occult nodal metastasis in this variant of melanoma. We describe a single institution experience with management of desmoplastic melanoma of the head and neck and discuss the utility of sentinel lymph node biopsy. MATERIALS AND METHODS: A retrospective review was performed of 49 patients with desmoplastic melanoma of the head and neck at a tertiary care center from 1994 to 2014. RESULTS: Sentinel lymph node biopsy was performed in 15 patients. Only 1 (6.7%) of these patients was found to have a positive sentinel node. Of the 46 patients without evidence of neck disease at presentation, 3 (6.5%) were found to have occult nodal disease or developed neck recurrences. When looking at the entire cohort, there were a total of 16 recurrences in 14 patients (28.6%). The majority (85.7%) of recurrences were either local or distant metastasis with only 2 (14.3%) recurrences being in regional lymph node basins. The overall rates of local, regional, and distant recurrences were 14.2%, 4.1%, and 10.2% respectively. The mixed pathologic subtype was not associated with a higher rate of nodal metastasis. CONCLUSIONS: Desmoplastic melanoma has a low rate of occult nodal metastasis and a high propensity to recur locally or as a distant metastasis, regardless of regional node status. Our experience combined with the uncertain impact that sentinel node status has on survival raises the question of the utility of routine sentinel node biopsy in this specific variant of melanoma.
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Neoplasias de Cabeça e Pescoço/patologia , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Melanoma/mortalidade , Melanoma/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Taxa de Sobrevida , Melanoma Maligno CutâneoRESUMO
PURPOSE: The purpose of this study is to evaluate the impact of perioperative fluid administration on the rates of postoperative complications following head and neck reconstruction with fibular free flaps (FFF). METHODS: A retrospective cohort study of subjects undergoing head and neck reconstruction with FFF was completed. The primary predictor variable was the total volume of perioperative fluids administered on the day of surgery. The primary outcome variable was the presence of medical and surgical complications occurring within 30 days of surgery. Medical and surgical complications were stratified as major or minor based on severity level. Basic demographic information, comorbidity indices, and intraoperative parameters were abstracted as covariates. Univariable and multivariable models were developed to assess for associations between total fluid volume administered on the day of surgery and postoperative medical/surgical complications occurring within 30 days of surgery. RESULTS: In 154 subjects, the partial flap failure rate was 3% and there were no complete flap failures. Total fluid volume was significantly associated with the presence of postoperative medical/surgical complications (OR = 1.21; 95% CI: 1.02-1.44; p = 0.032). A cutpoint for total fluid volume predicting any severity level of postoperative complication was identified at 5,500 mL. A cutpoint for total fluid volume predicting major postoperative complications was identified at 7,000 mL. CONCLUSIONS: The results of this study suggest that liberal fluid administration is associated with increased rates of medical/surgical complications following head and neck reconstruction with FFF. © 2016 Wiley Periodicals, Inc. Microsurgery 37:128-136, 2017.
Assuntos
Fíbula/irrigação sanguínea , Fíbula/transplante , Hidratação/efeitos adversos , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hidratação/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Complicações Pós-Operatórias/etiologia , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: The surgical Apgar score (SAS) is a recently devised risk-stratifying metric that relies on 3 intraoperative parameters to predict postoperative complications in surgical patients. The purpose of this study was to validate the SAS externally in a cohort of patients undergoing microvascular head and neck reconstruction with fibular free flaps. MATERIALS AND METHODS: A retrospective cohort study of patients undergoing head and neck microvascular reconstruction with fibular free flaps was completed. The primary predictor variable was the calculated SAS. The primary outcome variable was the presence of medical and surgical complications occurring within 30 days of surgery. Basic demographic information, comorbidity indices, and perioperative parameters were abstracted as covariates. Medical and surgical complications were categorized as minor or major depending on severity level. Univariable and multivariable logistic regression models were used to evaluate associations with 30-day postoperative complications. RESULTS: In 154 patients, the partial flap failure rate was 3% and there were no complete flap failures. There were 110 patients (71%) who developed at least 1 30-day postoperative complication and 51 (33%) who developed a major complication. The median SAS was 7. The SAS was not significantly associated with the presence of any 30-day postoperative complication (odds ratio [OR] = 1.02; 95% confidence interval [CI], 0.74-1.42; P = .89) or the presence of any major postoperative complication (OR = 0.08; 95% CI, 0.59-1.09; P = .16) in a univariable setting. The SAS did not achieve statistical significance after multivariable adjustment. CONCLUSION: Despite validation in numerous other surgical specialties, the SAS might not be useful as a metric for risk stratification among patients undergoing major head and neck reconstruction with fibular free flaps.