RESUMEN
PURPOSE: To compare human papillomavirus (HPV) testing, prevalence, and association with prognosis between head and neck squamous cell carcinoma (HNSCC) subsites. MATERIALS AND METHODS: This study utilized the National Cancer Database (NCDB) to identify patients diagnosed with HNSCC between 2010 and 2017. Rates of HPV testing, HPV-positivity, and changes in these rates over time were measured by subsite. The impact of HPV-positivity on overall survival across six head and neck subsites was assessed using multivariable-adjusted Cox proportional hazards analysis. RESULTS: A total of 121,550 patients were included. Of this cohort, 87,575 (72.1%) were tested for HPV, with the oropharynx (55,049/64,158; 85.8%) displaying the highest rates of testing and the sinonasal tract (1519/2853; 53.2%) displaying the lowest testing rates. Of the 86,136 with a definitive result, 46,878 (54.4%) were HPV-positive, with the oropharynx (40,313/54,205; 74.4%) displaying the highest rates of HPV-positivity and the oral cavity (1818/11,505; 15.8%) displaying the lowest. HPV-positive malignancy was associated with significantly improved adjusted overall survival in the oropharynx (HR = 0.42 [95% CI: 0.43-0.47]), oral cavity (HR = 0.86 [95% CI: 0.79-0.95]), sinonasal tract (HR = 0.63 [95% CI: 0.48-0.83]), larynx (HR = 0.78 [95% CI: 0.71-0.87]), and hypopharynx (HR = 0.56 [95% CI: 0.48-0.66]), but not the nasopharynx (HR = 0.93 [95% CI: 0.77-1.14]). CONCLUSION: HPV testing rates were significantly lower in non-oropharyngeal subsites. This is relevant as HPV-associated disease displayed significantly improved overall survival in both the oropharynx and four of five non-oropharyngeal subsites. While validation with prospective studies is necessary, these findings may warrant HPV testing in all HNSCC subsites.
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Neoplasias de Cabeza y Cuello , Infecciones por Papillomavirus , Carcinoma de Células Escamosas de Cabeza y Cuello , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bases de Datos Factuales , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/virología , Virus del Papiloma Humano/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Prevalencia , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Salivary fistulas remain a significant problem in patients undergoing major head and neck reconstructive surgery. Surgical sealants have become increasingly used in cutaneous and non-cutaneous wound closure, providing a barrier to fluids/gases and promoting healing. The purpose of this study was to determine the efficacy of a common surgical sealant, 2-Octyl Cyanoacrylate (2-OCA, Dermabond®), in the prevention of salivary fistulas following free flap reconstruction of the oral cavity. METHODS: In this non-randomized, single arm prospective trial, patients undergoing free flap reconstruction of gravity-dependent oral cavity defects were recruited. Application of 2-OCA was performed along flap inset suture lines at the time of surgery. Prospectively collected trial data were propensity score matched to a control cohort to compare outcomes. Data collected include demographics, medical co-morbidities, previous treatments, primary tumor site, and subsites reconstructed. The primary outcome measure was rate of salivary fistula formation. Secondary outcomes were time to development of leak and percentage of patients tolerating oral feeding at one month post-operatively. RESULTS: In the 46 propensity score matched pairs, eight (17.4%) out of 46 patients in the 2-OCA prospective cohort and seven (15.2%) out of 46 patients in the control cohort developed postoperative salivary fistulas within the one-month study interval (p = 1.00). The average time to postoperative leak in the 2-OCA group was 12.5 days versus 7.1 days in the control cohort (p = 0.10). In the 2-OCA group, 30 (65.2%) patients were tolerating regular diet at one month post-operatively compared to 33 (71.7%) in the control cohort (p = 0.65). CONCLUSION: Salivary fistula rates after application of a 2-OCA surgical sealant were not improved compared to a control cohort in this single institutional trial. There are several surgical sealants available, each with varying elasticity and adhesiveness. Future studies are needed to identify surgical sealants that are able to provide sufficient strength and adhesion to seal closures and combat corrosive saliva, but elastic enough to handle motion related tension during swallowing and post-operative movements in the head and neck.
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Cianoacrilatos/administración & dosificación , Colgajos Tisulares Libres , Boca/cirugía , Resultados Negativos , Procedimientos Quirúrgicos Orales/métodos , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/prevención & control , Fístula de las Glándulas Salivales/prevención & control , Adhesivos Tisulares/administración & dosificación , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: Evaluate the epidemiologic makeup of a population of HPV+ OPSCC patients treated at one institution over approximately a decade. STUDY DESIGN: Prospective survey study of HPV+ OPSCC treated between 2007 and 2016. SETTING: Mount Sinai Health System SUBJECTS AND METHODS: Patients aged 18+ who underwent treatment for HPV+ OPSCC. 223 patients were asked to complete a health survey including substance use and sexual history in order to specifically characterize the social behaviors of patients with HPVâ¯+â¯OPSCC. RESULTS: Eighty-two patients responded, 70 male (85.4%) and 12 female (14.6%). While half of patients were nonsmokers, 18.3% had a smoking history of <15 pack years, and 32.9% had a 15+ pack-year smoking history. Nearly 25% reported significant drinking history (3+ drinks/day). Males had an average of 18 lifetime sexual partners, and females had 7 partners. Eight patients reported >100 sexual partners. CONCLUSIONS: HPV+ OPSCC was more prevalent in white males with a high number of lifetime sexual partners, as expected. Careful evaluation revealed other findings of significance that are not generally associated with this population. Half of our patients had significant historical tobacco and alcohol consumption. One quarter of patients had a history of another malignancy. These findings highlight the importance of taking a comprehensive history when determining appropriate treatment or designing future de-escalation trials in HPV+ OPSCC.
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Neoplasias Orofaríngeas/complicaciones , Neoplasias Orofaríngeas/epidemiología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Conducta Sexual , Conducta Social , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/psicología , Infecciones por Papillomavirus/psicología , Prevalencia , Estudios Prospectivos , Fumar , Adulto JovenRESUMEN
PURPOSE: To determine the risk factors for unanticipated readmission, prolonged index admission, and discharge to a facility after vestibular schwannoma surgery. MATERIALS AND METHODS: Retrospective cohort study of those undergoing surgery for vestibular schwannoma in the Nationwide Readmissions Database (2013-2014). Main outcome measures included readmission rate, length of stay, discharge destination. RESULTS: There were 4585 cases identified. The overall unanticipated readmission rate was 8.1%, and 9.1% had a prolonged length of stay (PLOS) of ≥7â¯days. Mean and median LOS were 4.63 and 4.00â¯days, respectively, and >90% of patients were discharged after 7â¯days. Disposition to a facility occurred in 6.7% of cases. Teaching hospitals were protective against unintended readmission (odds ratio [OR] 0.44, pâ¯<â¯.001). Major functional loss was associated with PLOS (OR 12.55, pâ¯<â¯.001). High volume centers were associated with decreased risk of PLOS (OR 0.46, pâ¯<â¯.001) and facility discharge (OR 0.68, pâ¯<â¯.001). The most common readmission diagnoses included "other nervous system complications" (nâ¯=â¯128), cerebrospinal fluid leak (nâ¯=â¯71), "other postoperative infection" (nâ¯=â¯61), and meningitis (nâ¯=â¯59). CONCLUSIONS: Unanticipated readmission and prolonged LOS following vestibular schwannoma surgery are common, with varied sociodemographic, hospital, and patient factors independently associated with each. Further studies are needed to investigate targeted interventions aimed at minimizing readmission and prolonged LOS using the factors outlined above.
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Tiempo de Internación , Neuroma Acústico/cirugía , Readmisión del Paciente , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos , Adulto JovenRESUMEN
Ankle fractures are common orthopedic injuries with favorable outcomes when managed with open reduction and internal fixation (ORIF). Several patient-related risk factors may contribute to poor short-term outcomes, and machine learning may be a valuable tool for predicting outcomes. The objective of this study was to evaluate machine-learning algorithms for accurately predicting short-term outcomes after ORIF for ankle fractures. The Nationwide Inpatient Sample and Nationwide Readmissions Database were queried for adult patients ≥18 years old who underwent ORIF of an ankle fracture during 2013 or 2014. Morbidity and mortality, length of stay >3 days, and 30-day all-cause readmission were the outcomes of interest. Two machine-learning models were created to identify patient and hospital characteristics associated with the 3 outcomes. The machine learning models were evaluated using confusion matrices and receiver operating characteristic area under the curve values. A total of 16,501 cases were drawn from the Nationwide Inpatient Sample and used to assess morbidity and mortality and length of stay >3 days, and 33,504 cases were drawn from the Nationwide Readmissions Database to assess 30-day readmission. Older age, Medicaid, Medicare, deficiency anemia, congestive heart failure, chronic lung disease, diabetes, hypertension, and renal failure were the variables associated with a statistically significant increased risk of developing all 3 adverse events. Logistic regression and gradient boosting had similar area under the curve values for each outcome, but gradient boosting was more accurate and more specific for predicting each outcome. Our results suggest that several comorbidities may be associated with adverse short-term outcomes after ORIF of ankle fractures, and that machine learning can accurately predict these outcomes.
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Fracturas de Tobillo/cirugía , Fijación Interna de Fracturas , Mortalidad Hospitalaria , Tiempo de Internación/estadística & datos numéricos , Aprendizaje Automático , Reducción Abierta , Complicaciones Posoperatorias/epidemiología , Factores de Edad , Algoritmos , Anemia/epidemiología , Fracturas de Tobillo/epidemiología , Estudios Transversales , Bases de Datos Factuales , Diabetes Mellitus/epidemiología , Femenino , Insuficiencia Cardíaca/epidemiología , Humanos , Hipertensión/epidemiología , Enfermedades Pulmonares/epidemiología , Masculino , Medicaid , Medicare , Persona de Mediana Edad , Insuficiencia Renal/epidemiología , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Rigid flatfoot deformity is a debilitating condition that can be managed by triple arthrodesis surgery. Triple arthrodesis has the potential to restore health-related quality of life, but it is also associated with several complications. Few studies have examined the 30-day readmission rates after triple arthrodesis. The objective of this study was to investigate risk factors for 30-day all-cause readmissions after triple arthrodesis. The nationwide readmission database was queried from 2013. By using International Classification of Disease, Ninth Revision, procedure codes, all triple arthrodesis procedures were identified. Demographic factors, comorbidities, insurance status, and hospital characteristics were statistically compared between patients who experienced a 30-day readmission and those who did not. Multivariable logistic regression was used to identify independent risk factors for 30-day readmission. Overall, 1916 triple arthrodesis cases were identified. The overall 30-day readmission rate after triple arthrodesis was 4.6%. Univariate analysis revealed a statistically higher proportion of patients with electrolyte abnormalities (13.8% vs 4.6%; p < .01) in the patients who were readmitted within 30 days compared with those who were not. Multivariable analysis demonstrated Medicaid insurance, relative to private insurance, as the only statistically significant predictor of 30-day readmission with an odds ratio of 4.43 (p < .05). These results suggest that patients of lower socioeconomic status may be at a greater risk for development of a short-term readmission after triple arthrodesis surgery. These findings are important for surgeon and patient communication, counseling, and postoperative care when choosing to pursue triple arthrodesis surgery.
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Artrodesis/efectos adversos , Pie Plano/cirugía , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Artrodesis/estadística & datos numéricos , Bases de Datos Factuales , Femenino , Humanos , Modelos Logísticos , Masculino , Medicaid , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Factores Socioeconómicos , Estados UnidosRESUMEN
BACKGROUND: End-stage ankle arthritis is a debilitating condition that negatively impacts patient quality of life. Tibiotalar fusion and total ankle replacement are treatment options for managing ankle arthritis. Few studies have examined short term readmission rates of these two procedures. The objective of this study was compare all-cause 30-day readmission rates between patients undergoing tibiotalar fusion vs. total ankle replacement. METHODS: This study queried the Nationwide Readmission Database (NRD) from 2013-2014 and used international classification of disease, 9th revision (ICD-9) procedure codes to identify all patients who underwent a tibiotalar fusion or a total ankle replacement. Comorbidities, insurance status, hospital characteristics, and readmission rates were statistically compared between the two cohorts. Risk factors were then identified for 30-day readmission. RESULTS: A total of 5660 patients were analyzed with 2667 in the tibiotalar fusion cohort and 2993 in the total ankle replacement cohort. Univariate analysis revealed that the readmission rate after tibiotalar fusion (4.4%) was statistically greater than after total ankle replacement (1.4%). Multivariable regression analysis indicated that deficiency anemia (OR 2.18), coagulopathy (OR 3.51), renal failure (OR 2.83), other insurance relative to private (OR 3.40), and tibiotalar fusion (OR 2.51) were all statistically significant independent risk factors for having a readmission within 30-days. CONCLUSIONS: These findings suggest that during the short-term period following discharge from the hospital, patients who received a tibiotalar fusion are more likely to experience a 30-day readmission. These findings are important for decision making when a surgeon encounters a patient with end stage ankle arthritis. LEVEL OF EVIDENCE: Level III, cohort study.
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Articulación del Tobillo/cirugía , Artrodesis , Artroplastia de Reemplazo de Tobillo , Readmisión del Paciente/estadística & datos numéricos , Anciano , Anemia/epidemiología , Artritis/cirugía , Estudios de Cohortes , Coagulación Intravascular Diseminada/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal/epidemiología , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND/AIMS: Depression is common in patients with end-stage renal disease (ESRD) on hemodialysis (HD). Although, depression is associated with mortality, the effect of depression on in-hospital outcomes has not been studied as yet. METHODS: We analyzed the National Inpatient Sample for trends and outcomes of hospitalizations with depression in patients with ESRD. RESULTS: The proportion of ESRD hospitalizations with depression doubled from 2005 to 2013 (5.01-11.78%). Hospitalized patients on HD with depression were younger (60.47 vs. 62.70 years, p < 0.0001), female (56.93 vs. 47.81%, p < 0.0001), white (44.92 vs. 34.01%, p < 0.0001), and had higher proportion of comorbidities. However, there was a statistically significant lower risk of mortality in HD patients within the top 5 reasons for admissions. CONCLUSION: There were significant differences in demographics and comorbidities for hospitalized HD patients with depression. Depression was associated with an increased rate of adverse effects in discharged patients, and decreased in-hospital mortality.
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Depresión/fisiopatología , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Depresión/mortalidad , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Diálisis Renal/mortalidad , Diálisis Renal/psicología , Insuficiencia Renal Crónica/mortalidad , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: The epidemiology and outcomes of acute kidney injury (AKI) in prevalent non-renal solid organ transplant recipients is unknown. METHODS: We assessed the epidemiology of trends in acute kidney injury (AKI) in orthotopic cardiac and liver transplant recipients in the United States. We used the Nationwide Inpatient Sample to evaluate the yearly incidence trends (2002 to 2013) of the primary outcome, defined as AKI requiring dialysis (AKI-D) in hospitalizations after cardiac and liver transplantation. We also evaluated the trend and impact of AKI-D on hospital mortality and adverse discharge using adjusted odds ratios (aOR). RESULTS: The proportion of hospitalizations with AKI (9.7 to 32.7% in cardiac and 8.5 to 28.1% in liver transplant hospitalizations; ptrend<0.01) and AKI-D (1.63 to 2.33% in cardiac and 1.32 to 2.65% in liver transplant hospitalizations; ptrend<0.01) increased from 2002-2013. This increase in AKI-D was explained by changes in race and increase in age and comorbidity burden of transplant hospitalizations. AKI-D was associated with increased odds of in hospital mortality (aOR 2.85; 95% CI 2.11-3.80 in cardiac and aOR 2.00; 95% CI 1.55-2.59 in liver transplant hospitalizations) and adverse discharge [discharge other than home] (aOR 1.97; 95% CI 1.53-2.55 in cardiac and 1.91; 95% CI 1.57-2.30 in liver transplant hospitalizations). CONCLUSIONS: This study highlights the growing burden of AKI-D in non-renal solid organ transplant recipients and its devastating impact, and emphasizes the need to develop strategies to reduce the risk of AKI to improve health outcomes.
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Lesión Renal Aguda/epidemiología , Trasplante de Corazón/tendencias , Hospitalización/tendencias , Trasplante de Hígado/tendencias , Diálisis Renal/tendencias , Lesión Renal Aguda/diagnóstico , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
Type II restriction endonucleases require metal ions to specifically cleave DNA at canonical sites. Despite the wealth of structural and biochemical information, the number of Mg(2+) ions used for cleavage by EcoRV, in particular, at physiological divalent ion concentrations has not been established. In this work, we employ a single-turnover technique that uses osmotic stress to probe reaction kinetics between an initial specific EcoRV-DNA complex formed in the absence of Mg(2+) and the final cleavage step. With osmotic stress, complex dissociation before cleavage is minimized and the reaction rates are slowed to a convenient time scale of minutes to hours. We find that cleavage occurs by a two-step mechanism that can be characterized by two rate constants. The dependence of these rate constants on Mg(2+) concentration and osmotic pressure gives the number of Mg(2+) ions and water molecules coupled to each kinetic step of the EcoRV cleavage reaction. Each kinetic step is coupled to the binding 1.5-2.5 Mg(2+) ions, the uptake of â¼30 water molecules, and the cleavage of a DNA single strand. We suggest that each kinetic step reflects an independent, rate-limiting conformational change of each monomer of the dimeric enzyme that allows Mg(2+) ion binding. This modified single-turnover protocol has general applicability for metalloenzymes.
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Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Magnesio/farmacología , Presión Osmótica , Desoxirribonucleasas de Localización Especificada Tipo II/química , Cinética , Magnesio/química , Conformación Proteica , Multimerización de ProteínaRESUMEN
Circulating tumor human papillomavirus DNA (ctHPVDNA) testing using digital-droplet polymerase chain reaction (PCR) detects fragments of tumor-modified human papillomavirus (HPV) in the plasma of patients with HPV-associated head and neck squamous cell carcinomas (HNSCCs). Its impact on tumor surveillance and primary diagnosis is limited by unresolved issues relating to sensitivity and specificity. The study population consisted of patients with HNSCC who had undergone ctHPVDNA testing. HPV status was determined by p16 immunohistochemistry and PCR-HPV genotyping on the tumor samples. For discrepant cases (HPV-positive/ctHPVDNA-negative), HPV status was confirmed by RNA in situ hybridization and, when possible, targeted single-nucleotide polymorphisms genotyping. A total of 167 patients had ctHPVDNA testing, and 141 tumors were HPV positive by p16 immunohistochemistry and PCR genotyping. Genotypes included types 16 (91.5%), 33 (4.3%), 35 (2.1%), and 18 (2.1%). ctHPVDNA was detected in 133 (94.3%) of HPV-positive HNSCCs but in none of the HPV-negative HNSCCs. Four of the 5 p16-positive cases that were negative by PCR and ctHPVDNA were positive by RNA in situ hybridization, and in 2 of these cases, rare high-risk genotypes were identified. ctHPVDNA had a sensitivity of 91.7%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 63.6%. The likelihood that patients with HPV-positive HNSCC have detectable ctHPVDNA is high. Non-HPV16 genotypes contribute to discrepancies but only in a small subset of cases. This finding validates ongoing efforts to use ctHPVDNA as a surveillance tool, and even as a primary diagnostic assay in patients presenting with masses in the neck and/or oropharynx.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Carcinoma de Células Escamosas/patología , Virus del Papiloma Humano , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Genotipo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Papillomaviridae/genética , Neoplasias de Cabeza y Cuello/genética , ARN , ADN , ADN Viral/genéticaRESUMEN
BACKGROUND: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Testing for plasma tumor tissue modified viral (TTMV)-HPV DNA has emerged as a biomarker strategy for post-treatment surveillance to identify recurrent disease. We aimed to understand the prognostic and predictive potential of TTMV-HPV DNA when monitoring patients who had developed recurrent or metastatic (R/M) HPV+OPSCC. METHODS: This retrospective observational cohort study included 80 patients from 4 academic centers with R/M HPV+OPSCC if they had ≥ 1 plasma TTMV-HPV DNA test obtained at any point during their R/M disease course. Physician-reported clinical data and treatment history were captured in a centralized database, along with investigator-assessed response to therapy and survival. Descriptive statistics and non-parametric tests of association were employed along with survival analyses (Kaplan-Meier method). RESULTS: Sixteen (20 %) patients had ≥ 5 test results over time. Consecutive TTMV-HPV DNA tests were performed a median of 73 days apart. Median TTMV-HPV DNA scores were higher with an increasing per-patient number of metastatic sites (<2 vs. 2+; p < 0.01). Score changes over time were influenced by R/M treatment modality and became undetectable in 67 % (12/18) of patients who achieved a complete response to R/M therapy. Patients with detectable scores at last follow-up had significantly worse survival compared with those who were undetectable (log-rank test, p < 0.01). CONCLUSIONS: TTMV-HPV DNA appears useful as a prognostic tool for monitoring response to therapy in the R/M setting. In the future, TTMV-HPV DNA could be explored as an exploratory clinical trial endpoint in the metastatic setting.
RESUMEN
BACKGROUND: Traditionally, patients undergoing free flap reconstruction for oral cavity defects have been given nothing by mouth for 6-14 days post-operatively due to concern for orocutaneous fistula development. METHODS: Multiple databases were screened for studies assessing the rate of orocutaneous fistula formation in early (≤5 days) versus late (>5 days) feeding groups following oral cavity free flap reconstruction. Fixed- and random-effects meta-analyses were used. RESULTS: One randomized controlled trial, one prospective cohort, and three retrospective cohort studies were included. The early feeding group displayed no significant increase in orocutaneous fistula formation (RD = -0.02, p = 0.06) or free flap failure (RD = -0.01, p = 0.39), with a significantly shorter hospital length of stay (mean difference [days] = -2.43, p < 0.01). CONCLUSIONS: While further prospective trials are necessary, initiation of oral intake before post-operative day 5 may be appropriate in properly selected patients following oral reconstruction.
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Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Humanos , Procedimientos de Cirugía Plástica/métodos , Factores de Tiempo , Boca/cirugía , Neoplasias de la Boca/cirugía , Femenino , Masculino , Fístula Oral/etiología , Fístula Oral/cirugía , Cuidados Posoperatorios/métodos , Tiempo de Internación/estadística & datos numéricos , Fístula Cutánea/cirugía , Fístula Cutánea/etiología , Complicaciones PosoperatoriasRESUMEN
OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.
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ADN Viral , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Neoplasias Orofaríngeas/virología , Femenino , Masculino , Persona de Mediana Edad , ADN Viral/análisis , Estudios Retrospectivos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Anciano , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , AdultoRESUMEN
BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a biomarker of systemic inflammation that is associated with adverse oncologic and surgical outcomes. We investigated the use of NLR as a prognostic indicator of complications of head and neck cancer (HNC) surgeries. METHODS: We conducted a retrospective study of 11 187 Veterans who underwent HNC surgery between 2000 and 2020. We calculated preoperative NLR values and fit logistic regression models adjusting for potential confounding factors, comparing high-NLR patients to low-NLR patients. RESULTS: The cohort had a median age of 63 and was 98% men. High-NLR patients had increased odds of 30-day mortality (p < 0.001), having 1+ perioperative complications (p < 0.001), sepsis (p = 0.03), failure to wean from mechanical ventilation (p = 0.04), pneumonia (p < 0.001), and pulmonary embolism (p = 0.02) compared with low-NLR patients. CONCLUSION: NLR was a robust, independent predictor of 30-day mortality, having 1+ surgical complications, sepsis, failure to wean from mechanical ventilation, pneumonia, and pulmonary embolism.
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Neoplasias de Cabeza y Cuello , Sepsis , Masculino , Humanos , Femenino , Neutrófilos , Recuento de Linfocitos , Estudios Retrospectivos , Linfocitos , Pronóstico , Neoplasias de Cabeza y Cuello/cirugía , Resultado del Tratamiento , Sepsis/etiologíaRESUMEN
Importance: There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue-modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials. Objective: To establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting. Design, Setting, and Participants: This retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy. Main Outcomes and Measures: Per-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing. Results: Of 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days. Conclusions and Relevance: This cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay's performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Masculino , Persona de Mediana Edad , Femenino , Virus del Papiloma Humano , Estudios de Cohortes , Estudios Retrospectivos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Carcinoma de Células Escamosas/patología , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/complicaciones , Biopsia LíquidaRESUMEN
PURPOSE: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. EXPERIMENTAL DESIGN: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). RESULTS: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively. CONCLUSIONS: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.
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BACKGROUND: Percutaneous endoscopic gastronomy (PEG) tubes are commonly used to administer enteral nutrition during head and neck cancer (HNC) treatment. However, the benefits of placing a prophylactic feeding tube (PFT; prior to radiotherapy [RT]) or reactive feeding tube (RFT, after RT initiation) are unclear. We sought to compare survival, body mass trends, and hospitalization rates between strategies. METHODS: We conducted a retrospective cohort study of 11,473 Veterans with stages III-IVC HNC treated with chemoradiotherapy. Patients with PEG tube placement within 30 days prior to treatment initiation (PFT) were compared to all other patients (non-PFT) or patients with PEG tube placement within 3 months after treatment initiation placement (RFT). We compared survival, longitudinal body mass changes, and hospitalization rates for PFT versus non-PFT or RFT patients in propensity score (PS)-matched Cox regression models. RESULTS: 3,186 (28 %) patients received PFT and 8,287 (72 %) were non-PFT, of which 1,874 (23 %) received RFT. After PS-matching, there were no significant differences in overall survival (HR 0.97, 95 % CI 0.92-1.02), HNC-specific survival (HR 0.98, 95 % CI 0.92-1.09), change in BMI (p = 0.24), or hospitalization rates between PFT and non-PFT groups. Significant differences in hospitalization rates between PFT and RFT groups persisted after PS-matching (-0.11 hospitalizations/month), but no differences were found for other outcomes. CONCLUSION: Timing of PEG tube placement in Veterans with HNC was not associated with any significant survival or body mass advantage. However, patients who received PFT had a lower hospitalization rate than those who received RFT.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Estudios Retrospectivos , Intubación Gastrointestinal , Gastrostomía/efectos adversos , Carcinoma de Células Escamosas/etiología , Neoplasias de Cabeza y Cuello/etiologíaRESUMEN
Background: Overall survival for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) has differed by sex, but little is known regarding cancer-specific outcomes. We assessed the independent association of sex with cancer-specific survival in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods: We identified 14,183 patients from the Surveillance, Epidemiology, and End Results (SEER) program with OPSCC and tumor HPV status. We used Kaplan-Meier methods to compare overall survival (OS) and OPSCC-specific survival (HNCSS) by patient sex and by tumor HPV status. We then separately fit multivariable survival and competing risk models evaluating the association of sex on these outcomes by tumor HPV status and stratified by the use of guideline-concordant OPSCC treatment. Results: A total of 10,210 persons with HPV-positive tumors (72.0%) and 3,973 with HPV-negative tumors (28.0%) were identified. A larger proportion of women had HPV-negative tumors (24.0%) versus HPV-positive tumors (13.2%; p < 0.001). Women with HPV-positive tumors were less likely to receive guideline-concordant treatment compared to men. In unadjusted survival analyses, women did not differ in OS or HNCSS compared to men for HPV-positive tumors but had worse OS and HNCSS for HPV-negative tumors. After adjustment, men and women with HPV-positive OPSCC did not differ in OS or HNCSS. However, women with HPV-negative tumors faced worse overall survival (hazard ratio (HR) 1.15, 95% CI 1.02-1.29) that persisted even after stratifying for stage-appropriate treatment (HR 1.28, 95% CI 1.11-1.47). Conclusions: Women with HPV-positive OPSCC had similar survival outcomes compared to men, but those with HPV-negative tumors have worse overall and cancer-specific survival.
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Background: Human papillomavirus associated oropharyngeal squamous cell carcinoma (HPVOPSCC) usually affects a younger patient population. As such, the risk for long term toxicity associated with therapy is an important consideration. Multiple trials focused on de-escalation of therapy to preserve survival outcomes while minimizing treatment toxicity are currently in progress, however the question of which patients are ideal candidates for de-escalation remains unanswered. Circulating tumor DNA (cfHPVDNA) has emerged as a means of monitoring disease in patients with HPVOPSCC. Undetectable postoperative cfHPVDNA levels portend a better prognosis and by extension, may identify ideal candidates for de-escalation therapy. We propose an overview and rationale for a new institutional clinical trial protocol focusing on the use of cfHPVDNA to risk stratify patients for adjuvant therapy. We hypothesize that many surgical patients currently receiving radiation therapy may be clinically observed without adjuvant therapy. Methods: Patients with measurable cfHPVDNA and clinically resectable HPVOPSCC will undergo TORS resection of tumors and neck dissection. Patients with undetectable cfHPVDNA at 3 weeks post-op will be allocated to low or high-risk treatment protocol groups. The low risk group consists of patients with <4 positive lymph nodes, ≤2 mm extranodal extension (ENE), and perineural invasion (PNI) or lymphovascular invasion (LVI) alone. The high-risk group is made up of patients with ≥4 positive lymph nodes, gross ENE, positive margins, N2c disease and/or the combination of both PNI and LVI. The low-risk group will be allocated to an observation arm, while the high-risk group will receive 46 Gy of adjuvant radiotherapy and weekly cisplatin therapy. The primary outcome of interest is 2-year disease recurrence with secondary outcomes of 2-year disease free survival, locoregional control, overall survival, and quality of life measures. A sample of 126 patients in the low-risk group and 73 patients in the high-risk group will be required to evaluate non-inferiority to the standard of care. Discussion: This study will provide much needed recurrence and survival data for patients that undergo primary TORS followed by observation or de-escalated adjuvant therapy. Additionally, it will help delineate the role of cfHPVDNA in the risk stratification of patients that undergo treatment de-intensification.