RESUMEN
PURPOSE: Guidelines recommend that health-related information for patients should be written at or below the sixth-grade level. We sought to evaluate the readability level and quality of online patient education materials regarding epidural and spinal anesthesia. METHODS: We evaluated webpages with content written specifically regarding either spinal or epidural anesthesia, identified using 11 relevant search terms, with seven commonly used readability formulas: Flesh-Kincaid Grade Level (FKGL), Gunning Fox Index (GFI), Coleman-Liau Index (CLI), Automated Readability Index (ARI), Simple Measure of Gobbledygook (SMOG), Flesch Reading Ease (FRE), and New Dale-Chall (NDC). Two evaluators assessed the quality of the reading materials using the Brief DISCERN tool. RESULTS: We analyzed 261 webpages. The mean (standard deviation) readability scores were: FKGL = 8.8 (1.9), GFI = 11.2 (2.2), CLI = 10.3 (1.9), ARI = 8.1 (2.2), SMOG = 11.6 (1.6), FRE = 55.7 (10.8), and NDC = 5.4 (1.0). The mean grade level was higher than the recommended sixth-grade level when calculated with six of the seven readability formulas. The average Brief DISCERN score was 16.0. CONCLUSION: Readability levels of online patient education materials pertaining to epidural and spinal anesthesia are higher than recommended. When we evaluated the quality of the information using a validated tool, the materials were found to be just below the threshold of what is considered good quality. Authors of educational materials should provide not only readable but also good-quality information to enhance patient understanding.
RéSUMé: OBJECTIF: Les lignes directrices recommandent que les informations relatives à la santé destinées aux patient·es soient rédigées pour un niveau de sixième année ou en dessous. Nous avons cherché à évaluer le niveau de lisibilité et la qualité des matériels d'éducation disponibles en ligne pour les patient·es concernant l'anesthésie péridurale et la rachianesthésie. MéTHODE: Nous avons évalué les pages web dont le contenu était spécifiquement rédigé à propos de l'anesthésie rachidienne ou péridurale, identifiées à l'aide de 11 termes de recherche pertinents, avec sept formules de lisibilité couramment utilisées : Niveau scolaire Flesh-Kincaid (FKGL), Indice Gunning Fox (GFI), Indice Coleman-Liau (CLI), Indice de lisibilité automatisé (ARI), Mesure simple du charabia (SMOG), Facilité de lecture de Flesch (FRE) et New Dale-Chall (NDC). Deux personnes ont évalué la qualité du matériel de lecture à l'aide de l'outil Brief DISCERN. RéSULTATS: Nous avons analysé 261 pages web. Les scores de lisibilité moyens (écart type) étaient les suivants : FKGL = 8,8 (1,9), GFI = 11,2 (2,2), CLI = 10,3 (1,9), ARI = 8,1 (2,2), SMOG = 11,6 (1,6), FRE = 55,7 (10,8) et NDC = 5,4 (1,0). Le niveau de lecture moyen était plus élevé que le niveau recommandé de sixième année lorsqu'il a été calculé à l'aide de six des sept formules de lisibilité. Le score moyen de Brief DISCERN était de 16,0. CONCLUSION: Les niveaux de lisibilité des documents d'éducation en ligne relatifs à l'anesthésie péridurale et à la rachianesthésie destinés aux patient·es sont plus élevés que ceux recommandés. Lorsque nous avons évalué la qualité de l'information à l'aide d'un outil validé, nous avons constaté que les documents se situaient juste en dessous du seuil de ce qui est considéré comme de bonne qualité. Les personnes rédigeant du matériel éducatif doivent fournir des informations non seulement lisibles, mais aussi de bonne qualité afin d'améliorer la compréhension des patient·es.
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Anestesia Epidural , Anestesia Raquidea , Comprensión , Internet , Educación del Paciente como Asunto , Humanos , Educación del Paciente como Asunto/normas , Educación del Paciente como Asunto/métodos , Anestesia Epidural/normas , Anestesia Epidural/métodos , Alfabetización en SaludRESUMEN
The backlog of cases on surgical wait lists is a substantial problem for surgical patients, their families, surgeons, health care systems and governments. There are several approaches governments can take to improve the health, well-being and surgical outcomes of waiting patients. First, provinces should consider patient-centred approaches to triaging that reflect pain, symptoms or functional gain, and approaches using multidisciplinary teams or centralized triage. Second, governments could provide prehabilitation and mental health supports aligned with patients' and families' preferences during unavoidable waits. Wait times are not going to shorten any time soon; provinces should not only find innovative approaches to reducing waits, but also organize services to improve the health and well-being of waiting patients. Such changes will allow for optimization of patients' surgical outcomes and reduce the complexity of managing the wait list for their surgeons.
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Procedimientos Quirúrgicos Electivos , Prioridades en Salud , Humanos , Canadá , Salud Mental , Calidad de la Atención de SaludRESUMEN
BACKGROUND: It remains unclear how thyroid surgical oncologic quality indicators (TSOQIs) are related to each other, and how to best interpret and apply these measures within the context of surgical quality assurance. We aimed to examine the relation between 3 TSOQIs: postoperative serum thyroglobulin level, 24-hour radioactive iodine uptake (RAIU) and metastatic lymph node ratio (MLNR). METHODS: We conducted a retrospective review of patients who underwent total thyroidectomy for treatment of papillary thyroid cancer (PTC) performed by a single high-volume thyroid surgeon at a tertiary referral centre between 2012 and 2017. To establish the strength of correlation between pairs of quality indicators and the MACIS (metastasis, age, completeness of resection, invasion and size) prognostic score, we performed tests of normality and used the Spearman correlation coefficient to determine the correlation of nonnormal data containing outliers. RESULTS: A total of 139 patients with PTC were included in the study. Their mean MACIS score was 5.0 (standard deviation 1.5). Fifteen patients had high-risk thyroid cancer (MACIS score > 6.99). A weak correlation was found between serum thyroglobulin level and RAIU (r s = 0.27, p = 0.006) and a moderate correlation was found between serum thyroglobulin level and MLNR (r s = 0.40 p = 0.002). A weak correlation between serum thyroglobulin level and MACIS score was also observed (r s = 0.20, p = 0.05). CONCLUSION: Based on our findings, we propose that the postoperative serum thyroglobulin level represents the quality metric that has the most clinical utility because it is measurable in all patients and also correlates with both RAIU and MLNR. With further research, surgeons seeking to evaluate the oncologic quality of thyroidectomy performed for PTC may consider applying a quality indicator to their future practice.
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Carcinoma Papilar , Neoplasias de la Tiroides , Carcinoma Papilar/tratamiento farmacológico , Carcinoma Papilar/cirugía , Humanos , Radioisótopos de Yodo/uso terapéutico , Recurrencia Local de Neoplasia , Indicadores de Calidad de la Atención de Salud , Estudios Retrospectivos , Tiroglobulina , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
Summary: Differentiated thyroid cancer (DTC) has long been recognized as having a worse prognosis in older people. We retrospectively evaluated the clinical and pathological characteristics of 973 sequentially treated patients with primary DTC stratified into 2 age groups, ≥ 55 or < 55 years, based on the current American Joint Committee on Cancer (AJCC) DTC staging system. We found that older patients had a higher frequency of extrathyroidal cancer extension and larger cancers, and that their cancers were less commonly completely resectable.
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Adenocarcinoma Folicular/patología , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Adenocarcinoma Folicular/epidemiología , Adenocarcinoma Folicular/terapia , Adulto , Factores de Edad , Colombia Británica/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cáncer Papilar Tiroideo/epidemiología , Cáncer Papilar Tiroideo/terapia , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/terapiaRESUMEN
SUMMARY: The impact of waiting for surgery on the mental health of patients usually receives little attention. Because of the coronavirus disease 2019 (COVID-19) pandemic, the waits for elective surgery have been lengthening, potentially inducing or exacerbating mental health burdens. Provinces' health systems need to provide better support to assess not only patients' physical health, but also their mental health, and provide them with timely access to care based on need. A stepped care approach is needed to mitigate negative mental health effects associated with prolonged waits for elective operations. To provide the best care possible, we need to recognize and address both the physical and mental health problems of our waiting patients.
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Infecciones por Coronavirus/prevención & control , Procedimientos Quirúrgicos Electivos/psicología , Control de Infecciones/normas , Salud Mental , Pandemias/prevención & control , Neumonía Viral/prevención & control , Cuidados Preoperatorios/métodos , Betacoronavirus/patogenicidad , COVID-19 , Canadá/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Procedimientos Quirúrgicos Electivos/normas , Accesibilidad a los Servicios de Salud/normas , Humanos , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , SARS-CoV-2 , Factores de Tiempo , Tiempo de Tratamiento , Listas de EsperaRESUMEN
Summary: The coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on waits for elective operations, with tens of thousands of scheduled surgeries being cancelled or postponed across Canada. Provincial governments will likely not only reopen elective surgical capacity when it is deemed safe, but also target new funding to address the backlog of cases. There is a dearth of research on whether the provinces' approaches to managing wait lists are equitable from a patients' needs perspective or if they are associated with patients' perception of outcomes. The surgical cost models used in the past won't be useful to governments and hospital managers. New models based on hospitals' marginal costs, associated with running on weekends or off-hours and social distancing parameters, will be needed. Surgeon input, collaboration and leadership during the strategy development, implementation and management of surgical wait lists postpandemic will be imperative, as these decisions will significantly affect the health and lives of many Canadians.
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Infecciones por Coronavirus/epidemiología , Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/organización & administración , Pandemias , Neumonía Viral/epidemiología , Triaje/normas , Listas de Espera , COVID-19 , Canadá/epidemiología , Procedimientos Quirúrgicos Electivos/economía , Accesibilidad a los Servicios de Salud/economía , Accesibilidad a los Servicios de Salud/normas , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Triaje/organización & administraciónRESUMEN
OBJECTIVE: To compare the efficacy and safety of patient-controlled analgesia (PCA) to epidural analgesia in adults undergoing open hepatic resection. BACKGROUND: Effective pain management in patients undergoing open hepatic resection is often achieved with epidural analgesia. However, associated risks have prompted investigation of alternative analgesic methods in this patient population. METHODS: A comprehensive systematic literature review via Medline, Embase, and the Cochrane databases from inception until December 2, 2017 was conducted, followed by meta-analysis. Abstract and full-text screening, data extraction, and quality assessment were conducted by 2 investigators. Odds ratios (OR), mean differences (MD), and 95% confidence intervals were calculated using RevMan 5.3. RESULTS: Four randomized controlled trials with 278 patients were identified. All studies compared the use of PCA to epidural, with differing regimens. Pooled MD and 95% confidence interval for pain score were higher for PCA at rest 24âhours postoperatively (0.59 [0.30, 0.88]), and with movement at 48âhours postoperatively (0.95 [0.31, 1.60]. Pooled MD for hospital length of stay was 1.23 days (-2.72, 5.19). Pooled OR was 0.68 (0.36, 1.3) and 0.24 (0.04, 1.36) for overall and analgesia-related complications, respectively. Need for blood transfusion had a pooled OR of 1.14 (0.31, 4.18). CONCLUSIONS: Epidural analgesia was observed to be superior to PCA for pain control in patients undergoing open hepatic resection, with no significant difference in hospital length of stay, complications, or transfusion requirements. Thus, epidural analgesia should be the preferred method for the management of postoperative pain in this patient population.
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Analgesia Epidural , Analgesia Controlada por el Paciente , Hepatectomía/efectos adversos , Dolor Postoperatorio/prevención & control , Analgesia Epidural/efectos adversos , Analgesia Epidural/métodos , Analgesia Controlada por el Paciente/efectos adversos , Analgesia Controlada por el Paciente/métodos , Analgésicos Opioides/administración & dosificación , Transfusión Sanguínea , Hematoma Espinal Epidural/etiología , Humanos , Infusiones Intravenosas , Tiempo de Internación , Satisfacción del Paciente , Complicaciones PosoperatoriasRESUMEN
People living with HIV (PLWHA) with adequate access to modern combination antiretroviral therapy (cART) are living longer and experiencing reduced AIDS-related morbidity and mortality. However, increases in non-AIDS related conditions, such as certain cancers, have accompanied these therapeutic advances over time. As such, our study objective was to determine the impact of HIV on all-cause and lung cancer-specific mortality amongst PLWHA with diagnoses of non-small-cell lung cancer (NSCLC) and HIV-negative individuals with NSCLC. This analysis was inclusive of PLWHA on and off cART over the age of 19 years and a 10% comparison sample from the BC population ≥19 years, over a 13-year period (2000-2013). Kaplan-Meier estimates, Cox PH models, and competing risk analysis for all-cause and cause-specific mortality (respectively) compared PLWHA to HIV-negative individuals, controlling for age, gender, cancer stage, co-morbidities; and nadir CD4 count, viral load, and injection drug use for a HIV-positive specific analysis. We identified 71 PLWHA and 2463 HIV-negative individuals diagnosed with NSCLC between 2000 and 2013. PLWHA with NSCLC were diagnosed at a significantly younger age than HIV-negative individuals (median age 57 vs 71 years, p < 0.01). We found no significant difference in lung cancer-specific mortality. However, in multivariate analysis, HIV was associated with greater all-cause mortality (adjusted hazard ratio [aHR]:1.44; 95% confidence interval [CI]: 1.08-1.90), with median survival of 4 months for PLWHA, and 10 months for HIV-negative. Higher nadir CD4 count was protective against mortality (aHR: 0.33, 95% CI: 0.17-0.64) amongst PLWHA in multivariate analysis. Our analysis suggests that PLWHA in the modern cART era experience similar lung cancer survival outcomes compared to the general BC population with NSCLC. However, we also observed significantly higher all-cause mortality among PLWHA with NSCLC, which may warrant further inquiry into the role of HIV in exacerbating mortality among PLWHA with comorbidities and cancer.
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Terapia Antirretroviral Altamente Activa , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Neoplasias Pulmonares/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Anciano , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Papillary carcinomas that measure 1.0cm or less are diagnosed as papillary thyroid microcarcinomas (PTMs). The clinical significance and recommendations for management of these PTMs is still evolving. The objective of the study was to compare the characteristics of small (<5mm) to large (≥ 5mm) papillary thyroid microcarcinomas. METHODS: Amongst 1459 sequential patients undergoing thyroid surgery at a single center, 132 (9%) cases were diagnosed with PTM. We performed a retrospective analysis of these cases using Fisher's Exact Test. The statistical significance was set at p < 0.05 a priori. RESULTS: A relationship between large PTM and high risk features was observed only for extra-thyroidal cancer extension (ETE). Six of 57 large PTM (11%) but none of the 75 small PTM had ETE (p < 0.01). Lymph node metastases were associated with both small PTM (5/9 cases) and large PTM (4/9 cases). A distant metastases was diagnosed in association with a small PTM. CONCLUSIONS: For PTM, neither small cancer size, nor the absence of high-risk features, excluded the possibility of synchronous lymph node metastases.
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Carcinoma Papilar/epidemiología , Neoplasias de la Tiroides/epidemiología , Adulto , Carcinoma Papilar/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de la Tiroides/diagnósticoRESUMEN
BACKGROUND: The objective of this study is to evaluate the incidence of non-AIDS defining malignancies (NADMs) among people living with HIV/AIDS (PLWHA) in British Columbia, focusing on clinical correlates, highly active antiretroviral therapy (HAART) use, and survival, in order to elucidate mechanisms for NADM development. METHODS: A retrospective population based analysis was carried out for individuals with HIV/AIDS that began their treatment between 1996 and 2008. RESULTS: There were 145 (2.95%) NADMs and 123 (2.50%) AIDS defining malignancies (ADMs) identified in 4918 PLWHA in the study population. NADMs were represented by a range of cancer types including, most commonly, lung cancer, followed by anal, breast, head/neck, prostate, liver, rectal, and renal cancers. PLWHA had a SIR of 2.05 (CI:1.73, 2.41) for the development of NADMs compared to individuals without an HIV/AIDS diagnosis in the general population. Independent factors significantly associated with a NADM were: male gender, older age, lower CD4 cell counts, previous NADM, absence of HAART (non-HAART versus HAART) and treatment during the early-HAART era (before 2000 versus after 2000). CONCLUSIONS: NADMs represent an important source of morbidity for PLWHA. Use of HAART with its associated improvement in immune-restoration, and tailored targeted cancer screening interventions, may be beneficial and improve outcomes in this unique patient population.
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Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Neoplasias/epidemiología , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Síndrome de Inmunodeficiencia Adquirida/patología , Adulto , Factores de Edad , Fármacos Anti-VIH/administración & dosificación , Colombia Británica/epidemiología , Femenino , Infecciones por VIH/mortalidad , Infecciones por VIH/patología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Neoplasias/virología , Estudios Retrospectivos , Factores SexualesRESUMEN
PURPOSE: The objective of the study was to evaluate the performance of magnetic resonance imaging (MRI) for the diagnosis of appendicitis during pregnancy. METHODS: We conducted a retrospective review of all MRI scans performed at our institution, between 2006 and 2012, for the evaluation of suspected appendicitis in pregnant women. Details of the MRI scans performed were obtained from the radiology information system as well as details of any ultrasounds carried out for the same indication. Clinical and pathological data were obtained by retrospective chart review. RESULTS: The study population comprised 63 patients, and 8 patients underwent a second MRI scan during the same pregnancy. A total of 71 MRI scans were reviewed. The appendix was identified on 40 scans (56.3%). Sensitivity of MRI was 75% and specificity was 100% for the diagnosis of appendicitis in pregnant women. When cases with right lower quadrant inflammatory fat stranding or focal fluid, without appendix visualization, were classified as positive for appendicitis, MRI sensitivity increased to 81.3% but specificity decreased to 96.4%. CONCLUSIONS: MRI is sensitive and highly specific for the diagnosis of appendicitis during pregnancy and should be considered as a first line imaging study for this clinical presentation.
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Apendicitis/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Complicaciones del Embarazo/diagnóstico por imagen , Adulto , Canadá , Diagnóstico Diferencial , Femenino , Humanos , Embarazo , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
SUMMARY: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. Observed clinical and pathological differences between the sexes of PTC patients have been reported. There is currently no consensus regarding the impact of sex on PTC prognostication. We studied 566 PTC patients and observed that there was a higher PTC incidence in women, that PTC diagnosis was more challenging in women, and that men tended to present with larger cancers. However, once PTC is diagnosed, both sexes have a similar cancer prognosis, as evaluated using the MACIS (Metastasis, Age, Completeness of Resection, Invasion, Size) score. Our observations suggest that research efforts should be especially directed at improving the diagnostic yield of preoperative fine needle aspiration biopsy in women who present with nodular thyroid disease.
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Carcinoma/diagnóstico , Carcinoma/epidemiología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Colombia Británica/epidemiología , Carcinoma/terapia , Carcinoma Papilar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/terapia , Adulto JovenRESUMEN
ABSTRACT: A cancer-related factor that is not included in papillary thyroid cancer (PTC) prognostic scoring systems is bilaterality. While it may seem that bilaterality should be considered during the management of PTC, its clinical importance has been debated. This controversy exists because the extent of surgery for PTC has not been found to affect survival in low-risk individuals, despite their potential for PTC bilaterality. We sought to determine if PTC bilaterality is a cancer prognosticator based upon its association with known clinical and pathological PTC prognosticators, and MACIS scores. In this article we discuss our findings and their potential clinical implications.
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Carcinoma/patología , Glándula Tiroides/patología , Neoplasias de la Tiroides/patología , Carcinoma/diagnóstico , Carcinoma/cirugía , Carcinoma Papilar , Humanos , Pronóstico , Estudios Retrospectivos , Cáncer Papilar Tiroideo , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
IL-15 has pivotal roles in the control of CD8(+) memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-γ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-γ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-γ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-γ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy.
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Neoplasias de la Mama/genética , Linfocitos T CD8-positivos/efectos de los fármacos , Carcinoma Ductal de Mama/genética , Interferón gamma/biosíntesis , Interleucina-15/farmacología , Proteínas de la Membrana/inmunología , Anciano , Anticuerpos/farmacología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Carcinoma Ductal de Mama/inmunología , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Proliferación Celular/efectos de los fármacos , Femenino , Galectinas/farmacología , Expresión Génica , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Inmunoterapia Adoptiva/métodos , Interleucina-10/biosíntesis , Interleucina-2/farmacología , Activación de Linfocitos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunología , Células Tumorales CultivadasRESUMEN
BACKGROUND: Anaplastic thyroid carcinoma is the most undifferentiated form of thyroid cancer and one of the deadliest of all adult solid malignancies. Here we report the first genomic and transcriptomic profile of anaplastic thyroid cancer including those of several unique cell lines and outline novel potential drivers of malignancy and targets of therapy. METHODS: We describe whole genomic and transcriptomic profiles of 1 primary anaplastic thyroid tumor and 3 authenticated cell lines. Those profiles augmented by the transcriptomes of 4 additional and unique cell lines were compared to 58 pairs of papillary thyroid carcinoma and matched normal tissue transcriptomes from The Cancer Genome Atlas study. RESULTS: The most prevalent mutations were those of TP53 and BRAF; repeated alterations of the epigenetic machinery such as frame-shift deletions of HDAC10 and EP300, loss of SMARCA2 and fusions of MECP2, BCL11A and SS18 were observed. Sequence data displayed aneuploidy and large regions of copy loss and gain in all genomes. Common regions of gain were however evident encompassing chromosomes 5p and 20q. We found novel anaplastic gene fusions including MKRN1-BRAF, FGFR2-OGDH and SS18-SLC5A11, all expressed in-frame fusions involving a known proto-oncogene. Comparison of the anaplastic thyroid cancer expression datasets with the papillary thyroid cancer and normal thyroid tissue transcriptomes suggested several known drug targets such as FGFRs, VEGFRs, KIT and RET to have lower expression levels in anaplastic specimens compared with both papillary thyroid cancers and normal tissues, confirming the observed lack of response to therapies targeting these pathways. Further integrative data analysis identified the mTOR signaling pathway as a potential therapeutic target in this disease. CONCLUSIONS: Anaplastic thyroid carcinoma possessed heterogeneous and unique profiles revealing the significance of detailed molecular profiling of individual tumors and the treatment of each as a unique entity; the cell line sequence data promises to facilitate the more accurate and intentional drug screening studies for anaplastic thyroid cancer.
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Carcinoma/genética , Perfilación de la Expresión Génica/métodos , Genómica/métodos , Carcinoma Anaplásico de Tiroides/genética , Neoplasias de la Tiroides/genética , Carcinoma/tratamiento farmacológico , Carcinoma Papilar , Línea Celular Tumoral , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Heterogeneidad Genética , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Mutación , Proto-Oncogenes Mas , Análisis de Secuencia de ADN , Cáncer Papilar Tiroideo , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológicoRESUMEN
BACKGROUND: The aim of this study was to evaluate the axillary reverse lymphatic mapping (ARM) procedure for reducing the risk of arm lymphedema after breast cancer surgery. METHODS: The ARM procedure was carried out with a subareolar injection of technetium-99 sulfur colloid the morning of surgery, and a patent blue dye injection into the upper inner arm after anesthesia. RESULTS: Fifty-two women made up our study population. Thirty-seven patients underwent sentinel lymph node biopsy (SLNB) and 15 patients underwent an axillary lymph node dissection (ALND) for known nodal metastasis. The sentinel lymph node was identified in 36 of the 37 cases who underwent SLNB alone and in 12 of 15 patients who underwent on ALND. In 13 patients, both blue and radioactive lymph nodes or lymphatics were clearly identified (25%) and 5 patients had a clear crossover with nodes being both blue and hot. Only a single patient with crossover lymphatics had metastases present in their sentinel node. CONCLUSION: The ARM technique did not prevent identification of the SLN and we identified much greater crossover than reported. We had a single patient, who underwent a sentinel node biopsy, with mild arm lymphedema (1.9%) after 2 years of follow up.
Asunto(s)
Brazo/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Brazo/patología , Brazo/cirugía , Axila , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Linfedema/prevención & control , Mastectomía , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Cintigrafía , Azufre Coloidal Tecnecio Tc 99mRESUMEN
Parathyroid carcinoma is a rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level, and the deleterious effects of hypercalcaemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested potential roles for the tumour suppressor MEN1 and proto-oncogene RET in benign parathyroid tumourigenesis, while the tumour suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumour specimens were analysed using high-throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well-characterized cancer genes such as mTOR, MLL2, CDKN2C, and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumours revealed loss of PIK3CA activating mutation during the evolution of the tumour from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of the short arm of chromosome 1, along with somatic missense and truncating mutations in CDKN2C and THRAP3, respectively, provides new evidence for the potential role of these genes as tumour suppressors in parathyroid cancer. The key somatic mutations identified in this study can serve as novel diagnostic markers as well as therapeutic targets.
Asunto(s)
Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Genómica , Recurrencia Local de Neoplasia/genética , Neoplasias de las Paratiroides/genética , Adulto , Secuencia de Bases , Calcio/sangre , Transformación Celular Neoplásica , Fosfatidilinositol 3-Quinasa Clase I , Inhibidor p18 de las Quinasas Dependientes de la Ciclina/genética , ADN de Neoplasias/química , ADN de Neoplasias/genética , Proteínas de Unión al ADN/genética , Dosificación de Gen , Fusión Génica , Humanos , Masculino , Datos de Secuencia Molecular , Mutación , Proteínas de Neoplasias/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Hormona Paratiroidea/metabolismo , Neoplasias de las Paratiroides/patología , Neoplasias de las Paratiroides/cirugía , Fosfatidilinositol 3-Quinasas/genética , Polimorfismo de Nucleótido Simple , Proto-Oncogenes Mas , ARN Neoplásico/genética , Serina-Treonina Quinasas TOR/genética , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: This is the first study of Canadian thyroid and parathyroid surgery legal decisions, and the first study of surgical malpractice using the Canadian Legal Information Institute (CanLII) database. The objective was to identify quality improvement opportunities in surgical practice, to increase patient safety and satisfaction. METHODS: Legal decisions relating to thyroid and parathyroid surgery in the CanLII database were screened. Cases were included if a surgeon was listed as applicant or respondent; they related to pre-, intra-, or post-operative management of thyroid or parathyroid disease; and malpractice was alleged. Cases were excluded if surgery was mentioned incidentally or for non-surgical focus. RESULTS: Of the 347 unique legal decisions screened, 14 met inclusion and exclusion criteria. Surgeries occurred between 1976 and 2012, with 13 thyroid surgeries, 1 parathyroidectomy, and 4 mortalities. CONCLUSIONS: Quality improvement lessons include communication, pre-operative patient education and documentation of risks discussed, and in-person assessment of complications.