Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
Pediatrics ; 153(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38602032

RESUMO

Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS). Adenoidectomy and/or tonsillectomy are the usual first interventions employed to treat OSA in children with DS but sometimes do not achieve adequate resolution of clinical signs. Positive airway pressure treatment is often used next, but this treatment is poorly tolerated by this population. Persistent OSA can adversely affect a child's health and cognitive development. Hypoglossal nerve stimulation (HGNS), previously shown to be safe and effective in adults with OSA, has been used in children as young as 10 years old with DS and has achieved measurable neurocognitive benefits. The US Food and Drug Administration recently lowered the age for HGNS implantation to 13 years for children with DS. However, questions remain regarding treatment of refractory OSA in younger children. Here, we report the case of a 4-year-old boy with DS and treatment-refractory OSA who underwent successful HGNS implantation. The decision to proceed with HGNS implantation in such a young child involved discussions about anatomic feasibility and potential neurocognitive benefits. The device was implanted without complication and with minimal postoperative bulk. This case suggests a possible treatment option that can be discussed in the course of shared decision-making between clinicians and families of young children with DS and treatment-refractory OSA.


Assuntos
Síndrome de Down , Terapia por Estimulação Elétrica , Nervo Hipoglosso , Apneia Obstrutiva do Sono , Humanos , Síndrome de Down/complicações , Síndrome de Down/terapia , Apneia Obstrutiva do Sono/terapia , Masculino , Terapia por Estimulação Elétrica/métodos , Pré-Escolar
2.
Otolaryngol Head Neck Surg ; 171(3): 678-684, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38591729

RESUMO

OBJECTIVE: Patient preferences regarding thyroid nodules are poorly understood. Our objective is to (1) employ a discrete choice experiment (DCE) to explore risk tradeoffs in thyroid nodule management, and (2) segment respondents into preference phenotypes. STUDY DESIGN: DCE. SETTING: Thyroid surgery clinic, online survey. METHODS: A DCE including 5 attributes (cancer risk, voice concerns, incision/scar, medication requirement, follow-up frequency) was refined with qualitative patient and physician input. A final DCE including 8 choice tasks, demographics, history, and risk tolerance was administered to participants with and without thyroid disease. Analysis was performed with multinomial logit modeling and latent class analysis (LCA) for preference phenotyping. RESULTS: A total of 1026 respondents were included; 480 had thyroid disease. Risk aversion was associated with increasing age (P < .001), female gender (P < .001), and limited education (P = .038), but not previous thyroid disease. Cancer risk most significantly impacted decision-making. Of the total possible utility change from thyroid nodule decision-making, 47.8% was attributable to variations in cancer risk; 20.0% from medication management; 14.9% from voice changes; 12.7% from incision/scar; and 4.6% from follow-up concerns. LCA demonstrated 3 classes with distinct preference phenotypes: the largest group (64.2%) made decisions primarily based on cancer risk; another group (18.2%) chose based on aversion to medication; the smallest group (17.7%) factored in medication and cancer risk evenly. CONCLUSION: Cancer risk and the need to take medication after thyroid surgery factor into patient decision-making most heavily when treating thyroid nodules. Distinct preference phenotypes were demonstrated, reinforcing the need for individual preference assessment before the treatment of thyroid disorders.


Assuntos
Preferência do Paciente , Fenótipo , Nódulo da Glândula Tireoide , Humanos , Masculino , Feminino , Nódulo da Glândula Tireoide/patologia , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Comportamento de Escolha , Idoso , Medição de Risco
3.
Lancet Respir Med ; 10(10): 997-1008, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35863360

RESUMO

Human papillomavirus (HPV) types 6 and 11 can infect the squamous epithelium of the respiratory tract. Up to 8·9% of patients with HPV-associated recurrent respiratory papillomatosis (RRP) have pulmonary involvement. Pulmonary manifestations of HPV infection are associated with considerable morbidity, in part because treatment options and management guidelines are lacking. Patients with pulmonary RRP have a 32-times increased lifetime risk of malignant transformation compared with the overall RRP population. We review the clinical and radiographic presentation, pathological features, and genetics of pulmonary RRP, and we provide management algorithms based on our clinical experience with this complex patient population. In patients with suspected pulmonary involvement, tissue-sparing procedures to address growing lesions might be warranted given the chronicity and multifocality of the disease over a patient's lifetime. However, malignant transformation of pulmonary lesion(s) warrants standard-of-care treatment for primary lung squamous cell carcinoma. Large cohort studies are needed to understand the clinical course of pulmonary RRP and to identify molecular markers of increased risk of malignant transformation in order to develop guidelines for optimal and standardised surveillance and treatment.


Assuntos
Infecções por Papillomavirus , Infecções Respiratórias , Transformação Celular Neoplásica/patologia , Humanos , Pulmão/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções Respiratórias/complicações , Infecções Respiratórias/epidemiologia
4.
Laryngoscope ; 132(11): 2285-2292, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35363394

RESUMO

BACKGROUND: Recurrent laryngeal nerve (RLN) invasion by thyroid carcinoma represents an advanced disease status with potentially significant co-morbidity. METHODS: In a retrospective single-center study, we included patients with invaded RLNs operated on while using nerve monitoring techniques. We studied pre-, intra-, and postoperative parameters associated with postoperative vocal cord paralysis (VCP); 5-year recurrence-free survival (RFS); and 5-year overall survival (OS) in addition to two subgroup analyses of postoperative VCP in patients without preoperative VCP and based on source of RLN invasion. RESULTS: Of 65 patients with 66 nerves-at-risk, 39.3% reported preoperative voice complaints. Preoperative VCP was documented in 43.5%. The RLN was invaded by primary tumor in 59.3% and nodal metastasis in 30.5%. Papillary thyroid carcinoma was the most common pathologic subtype (80%). After 6 months, 81.8% had VCP. Complete tumor resection of the RLN was not associated with 5-year RFS (p = 0.24) or 5-year OS (p = 0.9). Resecting the RLN did not offer statistically significant benefit on 5-year RFS (p = 0.5) or 5-year OS (p = 0.38). Radioactive Iodine (RAI) administration was associated with improvement in 5-year RFS (p = 0.006) and 5-year OS (p = 0.004). Patients without preoperative VCP had higher IONM amplitude compared with patients with VCP. After a mean follow-up of 65.8 months, 35.9% of patients had distant metastases, whereas 36.4% had recurrence. CONCLUSION: Preoperative VCP accompanies less than half of patients with RLN invasion. Invaded RLNs may have existent electrophysiologic stimulability. Complete tumor resection and RLN resection were not associated with better 5-year RFS or OS, but postoperative RAI was. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:2285-2292, 2022.


Assuntos
Neoplasias da Glândula Tireoide , Paralisia das Pregas Vocais , Humanos , Radioisótopos do Iodo , Nervo Laríngeo Recorrente , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/efeitos adversos
5.
Int J Colorectal Dis ; 36(12): 2603-2611, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34296325

RESUMO

PURPOSE: To compare the characteristics and outcomes of rectal cancer patients with local recurrence at a perianastomotic site (PA), a surgical field (SF) site, or in lateral lymph nodes (LLN). METHODS: A total of 114 consecutive patients who underwent surgery for recurrent, non-metastatic rectal cancer at a single comprehensive cancer center between 1997 and 2012 were grouped on the basis of radiographic assessment of type of recurrence: PA, 76 (67%) patients; SF, 25 (22%) patients; LLN, 13 (11%) patients. Demographic, clinical, and pathological features were compared between the three groups, as were disease-free survival (DFS) and overall survival (OS). RESULTS: Recurrence type was associated with positive circumferential margin in the primary resection (PA, 4 [6%]; SF, 4 [19%]; LLN, 3 [25%]; P = 0.027), prior neoadjuvant therapy for the primary tumor (PA, 57 [75%]; SF, 18 [72%]; LLN, 4 [31%]; P = 0.007), and location of the primary tumor in the upper rectum (PA, 33 [45%]; SF, 5 [23%]; LLN, 1 [8%]; P < 0.001). Patients with PA had longer median DFS (PA, 5.1 years; SF, 1.5 years; LLN, 1.2 years; P = 0.036). There was a non-significant trend toward longer OS and higher rates of R0 resection for PA. CONCLUSION: Type of recurrence after salvage surgery for locally recurrent rectal cancer is associated with longer DFS in patients with PA recurrence.


Assuntos
Neoplasias Retais , Reto , Intervalo Livre de Doença , Humanos , Excisão de Linfonodo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Reto/patologia , Estudos Retrospectivos
6.
Head Neck ; 43(5): 1409-1414, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33474814

RESUMO

BACKGROUND: The optimal extent of surgery and/or radiation to the contralateral lymph node region is unknown in early-stage human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). METHODS: To investigate the pathologic incidence of and risk factors for contralateral nodal disease (CND) in cT1-T2 HPV-related OPSCC treated with transoral robotic surgery (TORS) and bilateral neck dissection (BND), the records of 120 patients were reviewed. RESULTS: Eleven patients displayed pathologic contralateral nodal disease (pCND), including 7.1% of tonsil and 10.9% of base of tongue (BOT) cases. Medial hemistructure involvement and cN2 disease were significantly associated with pCND. Zero cN0 patients had pCND, and on multivariate analysis only cN classification remained significantly associated with pCND. Four percent of BOT patients and 2% of tonsil patients with a well-lateralized primary and cN0/N1 neck demonstrated pCND. CONCLUSIONS: HPV-related OPSCC that are cN0-N1 have exceedingly low rates of pCND. Well-lateralized HPV-related BOT primaries with limited clinical nodal disease may be candidates for ipsilateral only treatment.


Assuntos
Alphapapillomavirus , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Metástase Linfática , Esvaziamento Cervical , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/cirurgia , Papillomaviridae , Estudos Retrospectivos
8.
Oral Maxillofac Surg Clin North Am ; 32(3): 339-354, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32482559

RESUMO

Global health has evolved to focus on reducing health inequity and obtaining the highest attainable standard of health for all people. To do this, a range of actors now pursue interventions and policy with an eye toward global targets that place strong emphasis on improving health systems. Within global health, global surgery has sought to delineate the burden of surgical disease and propose policy to improve access to surgery. Oral and maxillofacial surgery has been underrepresented in global health but has a vital role in reducing the global health inequity attributable to the impact of oral and craniofacial conditions.


Assuntos
Cirurgia Bucal , Desenvolvimento Sustentável , Humanos
9.
Am J Otolaryngol ; 41(4): 102467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32234256

RESUMO

OBJECTIVES: Recommendations for polysomnography (PSG) in pediatric sleep disordered breathing (SDB) vary between the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the American Academy of Pediatrics (AAP). We determined the rates of preoperative PSG in children without risk factors outlined in the AAO-HNS Clinical Practice Guidelines and described the postoperative course of those patients following T&A. METHODS: Patients aged 3-17 undergoing T&A for SDB or OSA who did not have an indication for preoperative PSG were included. We conducted retrospective review to describe the rate, type, and timing of respiratory complications for patients with and without PSG following T&A, and discuss cases where disposition was changed due to PSG results. RESULTS: 1135 patients without risk factors underwent T&A for SDB or OSA. 196 (17%) had a preoperative PSG, of whom 85 (43.3%) had AHI >10 and 38 (24.8%) had an O2 nadir <80%. 69 (85%) patients with PSG-diagnosed severe OSA were admitted overnight. Of the entire cohort, 5 patients (0.44%) had hypoxemia requiring blow-by oxygen or repositioning. 4 (0.43%) patients without PSG experienced respiratory events and were converted to overnight stay. The timing of respiratory events for all children ranged from immediately following extubation in the operating room to 3 h postoperatively. CONCLUSION: PSG in children without risk factors results in admission of otherwise healthy patients following T&A who would have otherwise undergone ambulatory surgery. PSG alone in pediatric patients with no AAO-HNS risk factors should not influence postoperative disposition. These patients should be monitored for 3 h post-T&A and discharged in the absence of complications. EVIDENCE LEVEL: 2b.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Monitorização Fisiológica , Polissonografia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/diagnóstico
10.
Dis Colon Rectum ; 63(7): 897-902, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32217857

RESUMO

BACKGROUND: A watch-and-wait strategy is a nonoperative alternative to sphincter-preserving surgery for patients with locally advanced rectal cancer who achieve a clinical complete response after neoadjuvant therapy. There are limited data about bowel function for patients undergoing this organ-preservation approach. OBJECTIVE: The purpose of this study was to compare bowel function in patients with rectal cancer managed with a watch-and-wait approach with bowel function in patients who underwent sphincter-preserving surgery (total mesorectal excision). DESIGN: This was a retrospective case-control study using patient-reported outcomes. SETTINGS: The study was conducted at a comprehensive cancer center. PATIENTS: Twenty-one patients underwent a watch-and-wait approach and were matched 1:1 with 21 patients from a pool of 190 patients who underwent sphincter-preserving surgery, based on age, sex, and tumor distance from the anal verge. MAIN OUTCOME MEASURES: Bowel function was measured using the Memorial Sloan Kettering Cancer Center Bowel Function Instrument. RESULTS: Patients in the watch-and-wait arm had better bowel function on the overall scale (median total score, 76 vs 55; p < 0.001) and on all of the subscales, with the greatest difference on the urgency/soilage subscale (median score, 20 vs 12; p < 0.001). LIMITATIONS: The study was limited by its retrospective design, small sample size, and temporal variability between surgery and time of questionnaire completion. CONCLUSIONS: A watch-and-wait strategy correlated with overall better bowel function when compared with sphincter-preserving surgery using a comprehensive validated bowel dysfunction tool. See Video Abstract at http://links.lww.com/DCR/B218. FUNCIÓN EVACUATORIA INFORMADA POR PACIENTES EN CÁNCER RECTAL MANEJADO CON UNA ESTRATEGIA DE OBSERVAR Y ESPERAR DESPUÉS DE LA TERAPIA NEOADYUVANTE: UN ESTUDIO DE CASOS Y CONTROLES: Observar y esperar es una alternativa no operativa a la cirugía de preservación del esfínter para pacientes con cáncer rectal localmente avanzado que logran una respuesta clínica completa después de la terapia neoadyuvante. Hay datos limitados sobre la función evacuatoria en pacientes sometidos a este abordaje para preservación de órganos.Evaluar la función evacuatoria en pacientes con cáncer rectal manejados con observar y esperar comparado a pacientes sometidos a cirugía de preservación de esfínteres (escisión mesorrectal total).Estudio retrospectivo de casos y controles utilizando resultados reportados por pacientes.Centro especializado oncológico.21 pacientes se sometieron a observar y esperar y se compararon con 21 pacientes de un grupo de 190 pacientes que se sometieron a cirugía de preservación de esfínteres controlando por edad, sexo y la distancia del tumor al borde anal.Función evacuatoria utilizando un instrumento de valoración del Centro de Cáncer Memorial Sloan Kettering.Los pacientes de observar y esperar demostraron mejor función evacuatoria en la escala general (puntuación total media, 76 versus 55; p <0,001) y en todas las subescalas, con la mayor diferencia en la subescala de urgencia / ensuciamiento fecal (puntuación media, 20 versus 12; p <0,001).Diseño retrospectivo, numero de muestra pequeño y variabilidad temporal entre la cirugía y el tiempo de finalización del cuestionario.Observar y esperar se correlacionó con mejor función evacuatoria en general en comparación con la cirugía de preservación del esfínter utilizando una herramienta integral validada para la disfunción evacuatoria. Consulte Video Resumen en http://links.lww.com/DCR/B218. (Traducción-Dr. Adrián Ortega).


Assuntos
Defecação/fisiologia , Terapia Neoadjuvante/métodos , Neoplasias Retais/terapia , Conduta Expectante/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Preservação de Órgãos/métodos , Medidas de Resultados Relatados pelo Paciente , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Tempo
11.
BMJ Glob Health ; 5(2): e002162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133197

RESUMO

Innovation ecosystems and emerging technologies can potentially accelerate the access to safe, affordable surgical care in low-resource settings. There is a need to develop localised innovation ecosystems that can establish an initial culture and catalyse the creation, adoption and diffusion of innovation. The surgathon model outlines one approach to seeding surgical innovation ecosystems. International academic institutions collaborated on six global surgery, innovation and ethics-themed hackathons ('surgathons') across India and Rwanda between 2016 and 2019. Over 1598 local multidisciplinary students participated, learning about challenges in the delivery of surgical care and ideating solutions that could leverage appropriate technology and resources for impact. Pursuing student ideas and evaluating their implementation past the surgathons continues to be an active effort. Surgathons have unfolded in different permutations based on local faculty, institution and health system context. The surgathon model is a novel method of priority setting challenges in global surgery and utilises locally driven expertise and innovation capacity to derive ethical solutions. The model offers a path for low-resource setting students and faculty to learn, advocate and innovate for improved surgical care.


Assuntos
Ecossistema , Universidades , Humanos , Índia
12.
J Neurooncol ; 147(3): 557-566, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32193690

RESUMO

INTRODUCTION: To improve the standard treatment paradigm for glioblastoma (GBM), efforts have been made to explore the efficacy of epigenetic agents as chemosensitizers. Recent data suggest possible synergy between decitabine (DAC), a DNA hypomethylating agent, and temozolomide (TMZ) in GBM, but the mechanism remains unclear. The objective of this study was to determine the effects of DAC on TMZ sensitization in a consecutively derived set of primary GBM cultures, with a focus on mismatch repair (MMR) proteins. METHODS: Half maximal inhibitory concentrations (IC50) of TMZ were calculated in eleven consecutive patient-derived GBM cell lines before and after preconditioning with DAC. MMR protein expression changes were determined by quantitative immunoblots and qPCR arrays. Single-molecule real-time (SMRT) sequencing of bisulfite (BS)-converted PCR amplicons of the MLH1 promoter was performed to determine methylation status. RESULTS: TMZ IC50 significantly changed in 6 of 11 GBM lines of varying MGMT promoter methylation status in response to DAC preconditioning. Knockdown of MLH1 after preconditioning reversed TMZ sensitization. SMRT-BS sequencing of the MLH1 promoter region revealed higher levels of baseline methylation at proximal CpGs in desensitized lines compared to sensitized lines. CONCLUSIONS: DAC enhances TMZ cytotoxicity in a subset of GBM cell lines, comprising lines both MGMT methylated and unmethylated tumors. This effect may be driven by levels of MLH1 via E2F1 transcription factor binding. Using unbiased long-range next-generation bisulfite-sequencing, we identified a region of the proximal MLH1 promoter with differential methylation patterns that has potential utility as a clinical biomarker for TMZ sensitization.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/genética , Decitabina/administração & dosagem , Epigênese Genética/efeitos dos fármacos , Glioblastoma/genética , Proteína 1 Homóloga a MutL/metabolismo , Temozolomida/administração & dosagem , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Glioblastoma/metabolismo , Humanos , Concentração Inibidora 50
13.
Otolaryngol Head Neck Surg ; 162(3): 296-303, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31906785

RESUMO

OBJECTIVE: We aimed to describe the mortality burden and macroeconomic effects of head and neck cancer as well as delineate the role of surgical workforce in improving head and neck cancer outcomes. STUDY DESIGN: Statistical and economic analysis. SETTING: Research group. SUBJECTS AND METHODS: We conducted a statistical analysis on data from the World Development Indicators and the 2016 Global Burden of Disease study to describe the relationship between surgical workforce and global head and neck cancer mortality-to-incidence ratios. A value of lost output model was used to project the global macroeconomic effects of head and neck cancer. RESULTS: Significant differences in mortality-to-incidence ratios existed between Global Burden of Disease study superregions. An increase of surgical, anesthetic, and obstetric provider density by 10% significantly correlated with a reduction of 0.76% in mortality-to-incidence ratio (P < .0001; adjusted R2 = 0.84). There will be a projected global cumulative loss of $535 billion US dollars (USD) in economic output due to head and neck cancer between 2018 and 2030. Southeast Asia, East Asia, and Oceania will suffer the greatest gross domestic product (GDP) losses at $180 billion USD, and South Asia will lose $133 billion USD. CONCLUSION: The mortality burden of head and neck cancer is increasing and disproportionately affects those in low- and middle-income countries and regions with limited surgical workforces. This imbalance results in large and growing economic losses in countries that already face significant resource constraints. Urgent investment in the surgical workforce is necessary to ensure access to timely surgical services and reverse these negative trends.


Assuntos
Efeitos Psicossociais da Doença , Saúde Global , Neoplasias de Cabeça e Pescoço/economia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Feminino , Humanos , Incidência , Masculino
14.
Clin Cancer Res ; 26(5): 1077-1085, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31719050

RESUMO

PURPOSE: We aimed to investigate genomic correlates underlying extremes of survivorship in metastatic colorectal cancer and their applicability in informing survival in distinct subsets of patients with metastatic colorectal cancer. EXPERIMENTAL DESIGN: We examined differences in oncogenic somatic alterations between metastatic colorectal cancer cohorts demonstrating extremes of survivorship following complete metastasectomy: ≤2-year (n = 17) and ≥10-year (n = 18) survivors. Relevant genomic findings, and their association with overall survival (OS), were validated in two independent datasets of 935 stage IV and 443 resected stage I-IV patients. RESULTS: In the extremes-of-survivorship cohort, significant co-occurrence of KRAS hotspot mutations and TP53 alterations was observed in ≤2-year survivors (P < 0.001). When validating these findings in the independent cohort of 935 stage IV patients, incorporation of the cumulative effect of any oncogenic Ras/B-raf (i.e., either KRAS, NRAS, or BRAF) and TP53 alteration generated three prognostic clusters: (i) TP53-altered alone (median OS, 132 months); (ii) Ras/B-raf-altered alone (65 months) or Ras/B-raf- and TP53 pan-wild-type (60 months); and (iii) coaltered Ras/B-raf-TP53 (40 months; P < 0.0001). Coaltered Ras/B-raf-TP53 was independently associated with mortality (HR, 2.47; 95% confidence interval, 1.91-3.21; P < 0.001). This molecular profile predicted survival in the second independent cohort of 443 resected stage I-IV patients. Coaltered Ras/B-raf-TP53 was associated with worse OS in patients with liver (n = 490) and lung (n = 172) but not peritoneal surface (n = 149) metastases. Moreover, coaltered Ras/B-raf-TP53 tumors were significantly more likely to involve extrahepatic metastatic sites with limited salvage options. CONCLUSIONS: Genomic analysis of extremes of survivorship following colorectal cancer metastasectomy identifies a prognostic role for coaltered Ras/B-raf-TP53 and its association with distinct patterns of colorectal cancer metastasis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Estudos de Coortes , Neoplasias Colorretais/classificação , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Taxa de Sobrevida
15.
Nat Med ; 25(10): 1607-1614, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31591597

RESUMO

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlated with the clinical responses noted in individual patients' tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive RC followed by metastasis to lung and liver. Importantly, engrafted tumors displayed the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, ex vivo platform coupled with in vivo endoluminal propagation in animals.


Assuntos
Quimiorradioterapia , Organoides/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Animais , Fluoruracila/farmacologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Camundongos , Metástase Neoplásica , Organoides/efeitos dos fármacos , Organoides/efeitos da radiação , Neoplasias Retais/patologia
16.
Cancer Med ; 8(15): 6538-6548, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31503397

RESUMO

BACKGROUND: Resection of colorectal liver metastases (CLM) can cure disease, but many patients with extensive disease cannot be fully resected and others recur following surgery. Hepatic arterial infusion (HAI) chemotherapy can convert extensive liver disease to a resectable state or decrease recurrence risk, but response varies and no biomarkers currently exist to identify patients most likely to benefit. METHODS: We performed a retrospective cohort study of CLM patients receiving HAI chemotherapy whose tumors underwent MSK-IMPACT sequencing. The frequency of oncogenic alterations and their association with overall survival (OS) and objective response rate were analyzed at the individual gene and signaling pathway levels. RESULTS: Three hundred and seventy patients met inclusion criteria: 189 (51.1%) who underwent colorectal liver metastasectomy followed by HAI + systemic therapy (Adjuvant cohort), and 181 (48.9%) with unresectable CLM (Metastatic cohort) who received HAI + systemic therapy, consisting of 63 (34.8%) with extrahepatic disease and 118 (65.2%) with liver-restricted disease. Genomic alterations were similar in each cohort, and no individual gene or pathway was significantly associated with objective response. Patients in the adjuvant cohort with concurrent Ras/B-Raf alteration and SMAD4 inactivation had worse prognosis while in the metastatic cohort patients with co-alteration of Ras/B-Raf and TP53 had worse OS. Similar findings were observed in a validation cohort. CONCLUSIONS: Concurrently altered Ras/B-Raf and SMAD4 mutations were associated with worse survival in resectable patients, while concurrent Ras/B-Raf and TP53 alterations were associated with worse survival in unresectable patients. The mutual exclusivity of Ras/B-Raf, SMAD4, and TP53 may have prognostic value for CLM patients receiving HAI.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Análise de Sequência de DNA/métodos , Proteína Smad4/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
17.
Can J Anaesth ; 66(11): 1425-1426, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414380

RESUMO

The legend of the Figure currently reads: "A formula for advancing surgical system strengthening and World Health Assembly resolution 68.15 through the World Health Organization's thirteenth General Programme of Work (GPW-13). This graphic depicts the three strategic shifts outlined in GPW-13 and ties them to specific avenues for surgical system strengthening to achieve overarching goals. GPW-13 = Thirteenth General Programme of Work; NSOAPs = National Surgical, Obstetric, and Anesthesia Plans; PHC = primary healthcare; SDG 3 = Sustainable Development Goal 3; UHC = universal health coverage; WHA 68.18 = World Health Assembly resolution 68.15. " The corrected Figure legend should read: A formula for advancing surgical system strengthening and World Health Assembly resolution 68.15 through the World Health Organization's thirteenth General Programme of Work (GPW-13). This graphic depicts the three strategic shifts outlined in GPW-13 and ties them to specific avenues for surgical system strengthening to achieve overarching goals. GPW-13 = Thirteenth General Programme of Work; NSOAPs = National Surgical, Obstetric, and Anesthesia Plans; PHC = primary healthcare; SDG 3 = Sustainable Development Goal 3; UHC = universal health coverage; WHA 68.15 = World Health Assembly resolution 68.15.

18.
Adv Radiat Oncol ; 4(3): 520-531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360809

RESUMO

PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is the most aggressive primary pediatric brain tumor, with <10% of children surviving 2 years. Radiation therapy (RT) remains the mainstay of treatment, but there is a great clinical need for improvements and advancements in treatment strategies. The aim of this systematic review was to identify all available studies in which RT was used to treat patients with DIPG. METHODS AND MATERIALS: A literature search for studies published up to March 10, 2018 was conducted using the PubMed database. We identified 384 articles using search items "diffuse intrinsic pontine glioma" and 221 articles using search items "diffuse brainstem glioma radiotherapy." Included studies were prospective and retrospective series that reported outcomes of DIPG treatment with RT. RESULTS: We identified 49 studies (1286 patients) using upfront conventionally fractionated RT, 5 studies (92 patients) using hypofractionated RT, and 8 studies (348 patients) using hyperfractionated RT. The mean median overall survival (OS) was 12.0 months, 10.2 months, and 7.9 months in patients who received conventional, hyperfractionated, and hypofractionated RT regimens, respectively. Patients undergoing radiosensitizing therapy had a mean median OS of 11.5 months, and patients who did not receive concomitant systemic therapy had an OS of 9.4 months. In patients who received salvage RT, the mean median OS from initial diagnosis was 16.3 months. CONCLUSIONS: As one of the largest systematic reviews examining RT for DIPG, this report may serve as a useful tool to help clinicians choose the most appropriate treatment approach, while also providing a platform for future investigations into the utility of RT and systemic therapy.

20.
Head Neck ; 41(9): 3009-3022, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30997703

RESUMO

BACKGROUND: With increasing adoption of transoral robotic surgery (TORS) for oropharyngeal cancer (OPC), more patients may receive trimodality therapy. We sought to investigate outcomes and toxicities in this cohort. METHODS: A retrospective study of patients with OPC treated with trimodality therapy at a tertiary-care hospital, comparing those receiving bilateral vs unilateral neck radiation. RESULTS: Four hundred thirty-six patients underwent TORS, 17% receiving adjuvant chemoradiation. Of the 46 patients completing adjuvant treatment in-house, contralateral neck was spared in 20%. There were no significant differences in survival, and patient-reported outcomes in salivary function, mood, and anxiety were superior in those patients receiving unilateral neck radiation and directly correlated with mean dose to local structures. CONCLUSIONS: Surgery for OPC offers the potential for reduction in radiation volumes by omitting the contralateral neck in those who may have required definitive chemoradiation. Even in patients receiving concurrent chemotherapy, unilateral neck radiation has a favorable toxicity profile without compromising survival.


Assuntos
Quimiorradioterapia Adjuvante , Neoplasias Orofaríngeas/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural , Órgãos em Risco , Neoplasias Orofaríngeas/terapia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA