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Most laboratory models of head and neck squamous cell cancer (HNSCC) rely on established immortalized cell lines, which carry inherent bias due to selection and clonality. We established a robust panel of HNSCC tumor cultures using a "conditional reprogramming" (CR) method, which utilizes a rho kinase inhibitor (Y-27632) and co-culture with irradiated fibroblast (J2 strain) feeder cells to support indefinite tumor cell survival. Sixteen CR cultures were successfully generated from 19 consecutively enrolled ethnically and racially diverse patients with HNSCC at a tertiary care center in the Bronx, NY. Of the 16 CR cultures, 9/16 were derived from the oral cavity, 4/16 were derived from the oropharynx, and 3/16 were from laryngeal carcinomas. Short tandem repeat (STR) profiling was used to validate culture against patient tumor tissue DNA. All CR cultures expressed ΔNp63 and cytokeratin 5/6, which are markers of squamous identity. Human papillomavirus (HPV) testing was assessed utilizing clinical p16 staining on primary tumors, reverse transcription polymerase chain reaction (RT-PCR) of HPV16/18-specific viral oncogenes E6 and E7 in RNA extracted from tumor samples, and HPV DNA sequencing. Three of four oropharyngeal tumors were p16 and HPV-positive and maintained HPV in culture. CR cultures were able to establish three-dimensional spheroid and murine flank and orthotopic tongue models. CR methods can be readily applied to all HNSCC tumors regardless of patient characteristics, disease site, and molecular background, providing a translational research model that properly includes patient and tumor diversity.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Animais , Humanos , Camundongos , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA Viral/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , Bancos de Espécimes BiológicosRESUMO
The aim is to summarize the guidelines for tracheostomy management during the COVID-19 pandemic. This is a comparative study analysis and literature review using articles found in the PubMed/MEDLINE database. Here we summarize published work on tracheostomy timing, technique, outcomes, mortality, and decannulation rates during the COVID-19 pandemic, with a focus on expertise from our own institution. Among 12 studies, 2,692 tracheostomies were performed at an average of 17.5 days from intubation. 66.4% were performed open, and 33.6% percutaneously. A total of 85.6% were performed bedside, and 14.4% in the operating room. 19.5% experienced all-cause mortality, and 43.4% were decannulated. In these studies, only 1 proceduralist became infected with COVID-19. Early COVID-19 recommendations advocated for tracheostomy a minimum of 14 days from intubation. Currently, tracheostomy is performed more closely to prepandemic criteria. Bedside tracheostomy comprised most procedures during the pandemic. Tracheostomy in COVID-19 patients, when performed with techniques to minimize aerosolization, is safe and poses minimal risk of infection to providers performing the procedure.
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BACKGROUND: Nonadherence to NCCN Guidelines during time from surgery to postoperative radiotherapy (S-PORT) can alter survival outcomes in head and neck squamous cell carcinomna (HNSCC). There is a need to validate this impact in an underserved urban population and to understand risk factors and reasons for delay. We sought to investigate the impact of delayed PORT with outcomes of overall survival (OS) in HNSCC, to analyze predictive factors of delayed PORT, and to identify reasons for delay. METHODS: We conducted a retrospective cohort study in an urban, community-based academic center. A total of 184 patients with primary HNSCC were identified through the Montefiore Medical Center cancer registry who had been treated between March 1, 2005, and March 8, 2017, and met the inclusion and exclusion criteria. The primary exposure was S-PORT. OS, recurrence, and risk factors and reasons for treatment delay were the main outcomes and measures. RESULTS: Among 184 patients with HNSCC treated with PORT, the median S-PORT was 48.5 days (interquartile range, 41-67 days). The S-PORT threshold that optimally differentiated worse OS outcomes was >50 days (46.7% of our cohort; n=86). Independent of other relevant factors, patients with HNSCC and S-PORT >50 days had worse OS (hazard ratio, 2.30; 95% CI, 1.34-3.95) and greater recurrence (odds ratio, 3.51; 95% CI, 1.31-9.39). Predictors of delayed S-PORT included being underweight or obese, prolonged postoperative length of stay, and age >70 years. The most frequent reasons for PORT delay were complications related to surgery (22.09%), unrelated medical comorbidities (18.60%), and nonadherence/missed appointments (6.98%). CONCLUSIONS: Delayed PORT beyond 50 days after surgery was associated with decreased OS and greater recurrence. Identification of predictive factors and reasons for treatment delay helps to target at-risk patients and facilitates interventions in underserved populations.
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There is growing recognition of the need for a coordinated, systematic approach to caring for patients with a tracheostomy. Tracheostomy-related adverse events remain a pervasive global problem, accounting for half of all airway-related deaths and hypoxic brain damage in critical care units. The Global Tracheostomy Collaborative (GTC) was formed in 2012 to improve patient safety and quality of care, emphasising knowledge, skills, teamwork, and patient-centred approaches. Inspired by quality improvement leads in Australia, the UK, and the USA, the GTC implements and disseminates best practices across hospitals and healthcare trusts. Its database collects patient-level information on quality, safety, and organisational efficiencies. The GTC provides an organising structure for quality improvement efforts, promoting safety of paediatric and adult patients. Successful implementation requires instituting key drivers for change that include effective training for health professionals; multidisciplinary team collaboration; engagement and involvement of patients, their families, and carers; and data collection that allows tracking of outcomes. We report the history of the collaborative, its database infrastructure and analytics, and patient outcomes from more than 6500 patients globally. We characterise this patient population for the first time at such scale, reporting predictors of adverse events, mortality, and length of stay indexed to patient characteristics, co-morbidities, risk factors, and context. In one example, the database allowed identification of a previously unrecognised association between bleeding and mortality, reflecting ability to uncover latent risks and promote safety. The GTC provides the foundation for future risk-adjusted benchmarking and a learning community that drives ongoing quality improvement efforts worldwide.
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Cooperação Internacional , Participação do Paciente/métodos , Segurança do Paciente , Guias de Prática Clínica como Assunto , Melhoria de Qualidade , Traqueostomia/educação , Traqueostomia/métodos , Humanos , Comunicação Interdisciplinar , Traqueostomia/normasRESUMO
BACKGROUND: Orbital decompression is frequently performed in the management of patients with sight-threatening and disfiguring Graves' ophthalmopathy. The quantitative measurements of the change in orbital volume after orbital decompression procedures are not definitively known. Furthermore, the quantitative effect of septal deviation on volume change has not been previously analyzed. OBJECTIVES: To provide quantitative measurement of orbital volume change after medial and inferior endoscopic decompression and describe a straightforward method of measuring this change using open-source technologies. A secondary objective was to assess the effect of septal deviation on orbital volume change. METHODS: A retrospective review was performed on all patients undergoing medial and inferior endoscopic orbital decompression for Graves' ophthalmopathy at a tertiary care academic medical center. Pre-operative and post-operative orbital volumes were calculated from computed tomography (CT) data using a semi-automated segmenting technique and Osirix™, an open-source DICOM reader. Data were collected for pre-operative and post-operative orbital volumes, degree of septal deviation, time to follow-up scan, and individual patient Hertel scores. RESULTS: Nine patients (12 orbits) were imaged before and after decompression. Mean pre-operative orbital volume was 26.99 cm(3) (SD=2.86 cm(3)). Mean post-operative volume was 33.07 cm(3) (SD=3.96 cm(3)). The mean change in volume was 6.08 cm(3) (SD=2.31 cm(3)). The mean change in Hertel score was 4.83 (SD=0.75). Regression analysis of change in volume versus follow-up time to imaging indicates that follow-up time to imaging has little effect on change in volume (R=-0.2), and overall mean maximal septal deviation toward the operative side was -0.5mm. Negative values were attributed to deviation away form the operative site. A significant correlation was demonstrated between change in orbital volume and septal deviation distance site (R=0.66), as well as between change in orbital volume and septal deviation angle (R=0.67). Greater volume changes were associated with greater degree of septal deviation away from the surgical site, whereas smaller volume changes were associated with greater degree of septal deviation toward the surgical site. CONCLUSION: A straightforward, semi-automated segmenting technique for measuring change in volume following endoscopic orbital decompression is described. This method proved useful in determining that a mean increase of approximately 6 cm in volume was achieved in this group of patients undergoing medial and inferior orbital decompression. Septal deviation appears to have an effect on the surgical outcome and should be considered during operative planning.
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Descompressão Cirúrgica , Endoscopia , Oftalmopatia de Graves/diagnóstico por imagem , Oftalmopatia de Graves/cirurgia , Órbita/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Septo Nasal/diagnóstico por imagem , Órbita/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada EspiralRESUMO
BACKGROUND: The choice of the recipient vessels for microsurgical reconstruction is based on proximity to the defect, vessel caliber, anatomic reliability, and ease of dissection. Traditionally in head and neck reconstruction, the superficial temporal artery and vein (STA/V) have been reserved as secondary recipient vessels. Others, including the facial artery (FA) and vein have been the preferred choice for facial reconstruction. METHODS: A retrospective analysis of all consecutive head and neck reconstructions using the STA/V by the senior author (E.S.G.) over a 5-year period was performed. Perioperative data were reviewed for all the patients. In a subset of patients, radiographic analysis was used to delineate STA and FA anatomy including vessel diameter and distances to standard anatomic landmarks. RESULTS: A total of 31 patients had 32 microsurgical reconstructions using the STA/V as recipient vessels. Radiographic analysis revealed no significant difference between the STA and FA diameters. The distances from the STA to the upper and middle face were significantly shorter relative to the FA, 64 versus 102 mm (p < 0.0001) and 72 versus 80 mm (p < 0.04), respectively. The distances from the lower face to the STA and FA were 56 and 30 mm, respectively (p < 0.0001). CONCLUSIONS: The STA/V can be used as first choice recipient vessels in head and neck reconstruction. Key features of these vessels include proximity to defect, acceptable caliber, predictable anatomic location, and relative ease of dissection. We recommend that the STA/V be considered recipient vessels of choice for reconstruction of defects of the face and scalp.
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Face/irrigação sanguínea , Face/cirurgia , Microcirurgia/métodos , Procedimentos de Cirurgia Plástica/métodos , Couro Cabeludo/irrigação sanguínea , Couro Cabeludo/cirurgia , Artérias Temporais , Veias , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Face/diagnóstico por imagem , Feminino , Humanos , Imageamento Tridimensional , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Couro Cabeludo/diagnóstico por imagem , Retalhos Cirúrgicos/irrigação sanguínea , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
While its prognostic significance remains unclear, p16(INK4a) protein expression is increasingly being used as a surrogate marker for oncogenic human papillomavirus (HPV) infection in head and neck squamous cell carcinomas (HNSCC). To evaluate the prognostic utility of p16 expression in HNSCC, we prospectively collected 163 primary tumor specimens from histologically confirmed HNSCC patients who were followed for up to 9.4 years. Formalin fixed tumor specimens were tested for p16 protein expression by immunohistochemistry (IHC). HPV type-16 DNA and RNA was detected by MY09/11-PCR and E6/E7 RT-PCR on matched frozen tissue, respectively. P16 protein expression was detected more often in oropharyngeal tumors (53%) as compared with laryngeal (24%), hypopharyngeal (8%) or oral cavity tumors (4%; p<0.0001). With respect to prognosis, p16-positive oropharyngeal tumors exhibited significantly better overall survival than p16-negative tumors (log-rank test p=0.04), whereas no survival benefit was observed for nonoropharyngeal tumors. However, when both p16 and HPV DNA test results were considered, concordantly positive nonoropharyngeal tumors had significantly better disease-specific survival than concordantly negative nonoropharyngeal tumors after controlling for sex, nodal stage, tumor size, tumor subsite, primary tumor site number, smoking and drinking [adjusted hazard ratio (HR)=0.04, 0.01-0.54]. Compared with concordantly negative nonoropharyngeal HNSCC, p16(+)/HPV16(-) nonoropharyngeal HNSCC (n=13, 7%) demonstrated no significant improvement in disease-specific survival when HPV16 was detected by RNA (adjusted HR=0.83, 0.22-3.17). Our findings show that p16 IHC alone has potential as a prognostic test for oropharyngeal cancer survival, but combined p16/HPV testing is necessary to identify HPV-associated nonoropharyngeal HNSCC with better prognosis.
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Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Papillomaviridae/genética , Infecções por Papillomavirus/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/virologia , DNA Viral/genética , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/virologia , Testes de DNA para Papilomavírus Humano , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: The objective was to determine patient and gland characteristics associated with difficult intubation in patients undergoing thyroidectomy for goiter and to assess different methods of intubation in these patients. METHODS: This study was an IRB-approved, retrospective chart review of 112 consecutive patients undergoing hemithyroidectomy or total thyroidectomy for thyroid goiter from 2009-2012 at an academic tertiary care facility in Bronx, New York. Patient demographics, thyroid gland characteristics (gland weight and nodule size), presence of preoperative symptoms (dyspnea, dysphagia, and hoarseness), and radiographical findings (tracheal compression, tracheal deviation, and substernal extension of the thyroid gland) were recorded. Anesthesia records were reviewed for method of intubation, as well as success or failure of intubation attempts. RESULTS: Nineteen patients (17.0%) were men and 93 (83.0%) were women. The age of the patients included in the study ranged from 14 to 86 years with a mean ± SD age of 53.5 ± 14.7 years. Difficult intubation was noted with 13 (11.6%) patients. Only patient age was significantly associated with difficult intubation. The mean age of patients with airway difficulty was 60.7 ± 3.7 years compared to 52.1 ± 1.5 years in those who did not experience airway difficulty (P = .04). No other reviewed risk factors were found to be significantly associated with difficult intubation. Fiberoptic intubation (FOI) was used in 38 patients and difficult intubation occurred in 18.4% (7/38). Direct laryngoscopy with transoral intubation (LTOI) was used in 58 patients, in whom 3.4% (2/58) experienced a difficult intubation. FOI was aborted 6 times and LTOI was subsequently successful in each of these cases. CONCLUSIONS: Our results suggest that benign nodular goiter disease does not pose significant challenges to intubation in our patient cohort. The technique of intubation deviated from the initial plan several times in the FOI group, whereas LTOI was ultimately successful in every case. Our data suggest that the role of fiberoptic intubation for patients with large goiters should be further refined.
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Obstrução das Vias Respiratórias/terapia , Bócio Nodular/cirurgia , Intubação Intratraqueal/métodos , Laringoscopia , Tireoidectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Obstrução das Vias Respiratórias/etiologia , Feminino , Bócio Nodular/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVES: The utility of intensive posttreatment surveillance of head and neck squamous cell carcinoma (HNSCC) has been debated. The objective is to investigate adherence to the National Comprehensive Cancer Network (NCCN) posttreatment follow-up guidelines and assess the association with recurrence and survival. METHODS: A total of 452 patients diagnosed with HNSCC at an academic medical center in a socioeconomically disadvantaged, urban setting were categorized by adherence to NCCN follow-up guidelines. Survival analyses were conducted to study the association between adherence and the 5-year overall survival and disease-specific survival in the entire cohort and subset of patients with documented recurrence. RESULTS: We found that 23.5% of patients were adherent to NCCN follow-up guidelines in the first year after treatment, and 15.9% were adherent over 5 years. Adherence in the first year was significantly associated with 5-year overall survival (HR 0.634; 95% CI 0.443-0.906; p = 0.0124) and disease-specific survival (HR 0.556; 95% CI 0.312-0.992; p = 0.0470), but consistent adherence over 5 years did not show a significant association. Among the 21.7% of the cohort with recurrence, adherence was not associated with early-stage recurrence (AJCC stage I/II). In this subset, first year adherence was associated with improved disease-specific but not overall survival, and adherence over 5 years was not associated with survival. CONCLUSION: Adherence to NCCN follow-up guidelines in the first year after treatment was associated with a better chance of 5-year overall and disease-specific survival, but this significant association was not observed among those who demonstrated consistent adherence over 5 years. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:708-716, 2024.
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Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Seguimentos , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias de Cabeça e Pescoço/terapiaRESUMO
BACKGROUND: Tracheostomies are associated with high rates of complications and preventable harm. Safe tracheostomy management requires highly functioning teams and systems, but health care providers are poorly equipped with tracheostomy knowledge and resources. In situ simulation has been used as a quality improvement tool to audit multidisciplinary team emergency response in the actual clinical environment where care is delivered but has been underexplored for tracheostomy care. METHODS: From July 2021 to May 2022, the study team conducted in situ simulations of a tracheostomy emergency scenario at Montefiore Medical Center to identify human errors and latent safety threats (LSTs). Simulations included structured debriefs as well as audiovisual recording that allowed for blind rating of these human errors and LSTs. Provider knowledge deficits were further characterized using pre-simulation quizzes. RESULTS: Twelve human errors and 15 LSTs were identified over 20 simulations with 88 participants overall. LSTs were divided into the following categories: communication, equipment, and infection control. Only 50.0% of teams successfully replaced the tracheostomy tube within the scenario's five-minute time limit. In addition, knowledge gaps were highly prevalent, with a median pre-simulation quiz score of 46% (interquartile range 36-64) among participants. CONCLUSION: An in situ simulation-based quality improvement approach shed light on human errors and LSTs associated with tracheostomy care across multiple settings in one health system. This method of engaging frontline health care provider key stakeholders will inform the development, adaptation, and implementation of interventions.
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Erros Médicos , Traqueostomia , HumanosRESUMO
BACKGROUND: Delay in time to treatment initiation (TTI) is associated with worsened survival outcomes in laryngeal squamous cell carcinoma (LSCC). It is unclear whether this is due to tumor growth or an increased risk of metastatic disease. METHODS: This retrospective cohort study at one academic center included patients with LSCC who underwent radiotherapy/chemoradiotherapy between 2005 and 2017. We examined the association between tumor growth rate (TGR) and survival outcomes. RESULTS: Among 105 patients (mean age, 63.8 ± 11.1 years; 72% male), the threshold between "slow-growing" and "fast-growing" tumors was >0.036 mL/day (survival) and >0.082 mL/day (recurrence). Faster growth was associated with worse overall survival (OS) (hazard ratio, 1.97; 95% confidence interval [CI], 0.94-4.13) and increased recurrence (odds ratio, 9.10; 95% CI, 2.40-34.4). CONCLUSIONS: TGR >0.036 mL/day during TTI was associated with decreased OS, and >0.082 mL/day was associated with increased recurrence. Tumor measurement in patients experiencing delay may identify those who could benefit from escalated therapy.
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BACKGROUND: Total thyroidectomy for hyperthyroidism is typically followed by overnight admission to monitor for complications including thyrotoxicosis. Outpatient thyroid surgery is increasingly common, but its safety in patients with hyperthyroidism has not been well studied. METHODS: This retrospective study reviewed 183 patients with hyperthyroidism who underwent total thyroidectomy from 2015 to 2022 at one urban, academic center. The main outcomes were rates of thyroid storm, surgical complications, and 30-day ED visits and readmissions. RESULTS: Among 183 patients with hyperthyroidism (mean age, 45 ± 14.5 years; 82.5% female), there were no cases of thyroid storm and complications included recurrent laryngeal nerve (RLN) palsy (7.0%), symptomatic hypocalcemia (4.4%), and hematoma (1.6%). ED visits were present in 1.1% and no patients were readmitted. CONCLUSION: Total thyroidectomy was not associated with thyroid storm and <6% of patients required inpatient management. Ambulatory total thyroidectomy for hyperthyroidism warrants further consideration through identification of predictive factors for postoperative complications.
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Crise Tireóidea , Paralisia das Pregas Vocais , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Crise Tireóidea/complicações , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Pacientes Internados , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Paralisia das Pregas Vocais/etiologiaRESUMO
OBJECTIVE: To establish and characterize a diverse library of head and neck squamous cell cancer (HNSCC) cultures using conditional reprogramming (CR). METHODS: Patients enrolled on an IRB-approved protocol to generate tumor cell cultures using CR methods. Tumor and blood samples were collected and clinical information was recorded. Successful CR cultures were validated against banked reference tumors with short tandem repeat genotyping. Cell morphology was archived with photodocumentation. Clinical and demographic factors were evaluated for associations with successful establishment of CR culture. Human papilloma virus (HPV) genotyping, clonogenic survival, MTT assays, spheroid growth, and whole exome sequencing were carried out in selected cultures. RESULTS: Forty four patients were enrolled, with 31 (70%) successful CR cultures, 32% derived from patients who identified as Black and 61% as Hispanic. All major head and neck disease sites were represented, including 15 (48%) oral cavity and 8 (26%) p16-positive oropharynx cancers. Hispanic ethnicity and first primary tumors (vs. second primary or recurrent tumors) were significantly associated with successful CR culture. HPV expression was conserved in CR cultures, including CR-024, which carried a novel HPV-69 serotype. CR cultures were used to test cisplatin responses using MTT assays. Previous work has also demonstrated these models can be used to assess response to radiation and can be engrafted in mouse models. Whole exome sequencing demonstrated that CR cultures preserved tumor mutation burden and driver mutations. CONCLUSION: CR culture is highly successful in propagating HNSCC cells. This study included a high proportion of patients from underrepresented minority groups. LEVEL OF EVIDENCE: Not Applicable Laryngoscope, 134:2748-2756, 2024.
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Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/genética , Feminino , Masculino , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Pessoa de Meia-Idade , Células Tumorais Cultivadas , Idoso , Sequenciamento do Exoma , Reprogramação Celular/genética , Adulto , Técnicas de Reprogramação CelularRESUMO
Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4-96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.
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OBJECTIVE: We report a case of an elderly female with primary diffuse large B-cell thyroid lymphoma causing an extensive tracheal defect that was managed expectantly with good results. METHOD: Case report RESULTS: This is the only known reported case of a patient with tracheal invasion and perforation caused by primary thyroid lymphoma who has subsequently survived. CONCLUSION: Due to the rarity of invasive primary thyroid lymphoma there is currently no standard surgical management of the airway. We propose that expectant management with temporary airway protection is an alternative to invasive procedures such as tracheotomy or tracheal stent placement, even in the scenario of serious airway defects.
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Linfoma/complicações , Neoplasias da Glândula Tireoide/complicações , Traqueia/patologia , Doenças da Traqueia/etiologia , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Linfoma/diagnóstico , Invasividade Neoplásica , Ruptura Espontânea , Neoplasias da Glândula Tireoide/diagnóstico , Tomografia Computadorizada por Raios X , Traqueia/diagnóstico por imagem , Doenças da Traqueia/diagnósticoRESUMO
OBJECTIVES: Laryngoceles are pathologic air filled dilations of the laryngeal ventricle. They are most often benign and incidental findings. Resection may be necessary in the setting of infection, airway obstruction, dysphagia, and phonatory disturbances. External laryngoceles are almost universally treated with open resection via a lateral or midline cervical approach. Care must be taken to resect the laryngocele in its entirety to avoid recurrence. In cases of recurrent infection, normal surgical planes are often fibrosed and obscured increasing the risk of neurovascular sacrifice and functional losses. METHODS: We are reporting a case of recurrent infections in a large, palpable external laryngocele. During resection the patient was ventilated using an endotracheal tube (ETT). Additionally, a laryngeal mask airway (LMA) was inserted posterior to the ETT, resting in the hypopharynx and attached to a Jackson Rees circuit. Air was passed through the LMA to inflate the laryngocele and better define its borders. The LMA was also used to identify the root of the laryngocele in the paraglottic space and ensure its airtight closure. RESULTS: The LMA assisted our dissection and helped progress the surgery safely in a fibrosed surgical field. We have not seen this method described previously. The patient continues to be free of recurrence 2 years after surgery. CONCLUSION: While in most cases, with careful surgical technique, even a fibrotic and scarred laryngocele can be excised in its entirety without neurovascular sacrifice. In some cases where this may be difficult with a traditional approach, we offer the intra-operative trumpet maneuver as a viable method of better delineating the borders of a laryngocele.
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Cuidados Intraoperatórios/instrumentação , Máscaras Laríngeas , Laringocele/cirurgia , Adulto , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Intubação IntratraquealRESUMO
OBJECTIVES: Biphenotypic sinonasal sarcoma (BSNS), previously low-grade sinonasal sarcoma with neural and myogenic features, is a rare tumor of the sinonasal tract first described in 2012. Due to its rarity, limited literature is available in providing clinicians with a standardized treatment regimen, particularly in cases of positive surgical margins. This article aims to provide a clinical review of the currently available reported cases of BSNS, as well as presenting clinical, radiologic, and pathologic details of 2 novel cases. METHODS: Online electronic databases include PubMed and Embase where queried for reports of biphenotypic sinonasal sarcoma or low-grade sinonasal sarcoma with neural and myogenic features. Two previously unpublished cases were included in the results. Data including clinical presentation, epidemiologic data, radiologic evaluation, intraoperative details, histopathology, treatment modality, and postoperative follow-up information were included. RESULTS: A total of 100 previously published cases were identified in 12 prior articles. Mean age at presentation was 52.9 years. Extrasinonasal extension was observed in 27.4% of cases with most common site of extension being cribriform plate. Forty-seven cases included treatment details with surgical excision being the most common modality. Recurrence rates were identical for both surgical excision alone and surgical excision with adjuvant radiotherapy (33.3%). CONCLUSIONS: Biphenotypic sinonasal sarcoma is a slow-growing tumor that is amenable to surgical resection. Recurrence rates are similar between surgical excision and surgical excision with adjuvant radiation therapy, but limited data in reported cases preclude a determination of treatment superiority.
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Neoplasias dos Seios Paranasais , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/terapia , Neoplasias dos Seios Paranasais/patologia , Sarcoma/diagnóstico , Sarcoma/terapia , Sarcoma/patologia , Biomarcadores TumoraisRESUMO
A left maxillary sinus soft tissue mass was discovered on computed tomography in a 70-year-old woman who had been experiencing blood-tinged mucus for 2 years. The lesion demonstrated mild enhancement, and bony destruction. Magnetic resonance imaging displayed a cerebriform appearance of the mass, which mimicked the appearance of inverted papilloma. However, histology and staining identified the lesion as ameloblastoma. Resection of the tumor was successful with no recurrence 1 month later on follow-up computed tomography. This case represents an unusual imaging presentation of ameloblastoma, and an opportunity to avoid the misdiagnosis of inverted papilloma in similar future cases.
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OBJECTIVE: Various risk stratification systems for cytologically indeterminate thyroid nodules are available. However, malignancy risk assessment data, such as ultrasound features, are not always used when the decision is to order molecular testing or not. Our aim was to investigate the utility of molecular testing after incorporating an algorithm with ultrasound-based risk of malignancy (ROM) estimation. STUDY DESIGN: Diagnostic/prognostic study. SETTING: Single-institution urban tertiary care center. METHODS: We performed a single-institution retrospective chart review of all thyroid nodules that had undergone molecular testing. A web-based Malignancy Risk Estimation System for Thyroid Nodules was utilized with ultrasound findings to stratify malignancy risk according to the Korean Thyroid Imaging Reporting and Data System (TI-RADS), French TI-RADS, American Association of Clinical Endocrinology guideline, and American Thyroid Association guideline. A novel algorithm for utilizing molecular testing at our institution was developed with the Korean TI-RADS and with recommendations from the American Thyroid Association and National Comprehensive Cancer Network. RESULTS: The Korean TI-RADS performed best in our population (area under the curve = 0.83). A positive molecular test result had a positive association with a higher ROM according to all 4 models (P < .05). Use of our algorithm prior to molecular testing would have prevented 38% of benign/low-ROM negative nodules (n = 28) from being tested. CONCLUSION: In patients with indeterminate thyroid nodules, an algorithm built on pre- and posttest probability to guide molecular testing might reduce unnecessary testing of benign and low-risk nodules.