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Errores Diagnósticos , Imagen por Resonancia Magnética , Meningioma , Meningitis , Humanos , Meningitis/diagnóstico , Meningitis/sangre , Meningitis/inmunología , Meningioma/diagnóstico , Meningioma/diagnóstico por imagen , Inmunoglobulina G/sangre , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , HipertrofiaRESUMEN
The understanding of schwannoma tumorigenesis has been reshaped by the recent identification of SH3PXD2A::HTRA1 fusion in 10% of intracranial/spinal schwannomas. Nonetheless, pathologic features of schwannomas harboring this fusion, as well as its prevalence outside intracranial/spinal locations, have not been characterized. We screened 215 consecutive schwannomas for their clinicopathologic characteristics and fusion status using reverse-transcriptase polymerase chain reaction (RT-PCR). Among 29 (13.5%) fusion-positive schwannomas, the most prevalent location was peripheral somatic tissue (30.7%, 19/62), followed by spinal/paraspinal (18.4%, 7/38), body cavity/deep structures (10%, 2/20), intracranial (1.3%, 1/75), and viscera (0/13). All 8 cellular, 4 microcystic/reticular, and 3 epithelioid schwannomas were fusion-negative, as were 41/42 nonschwannomatous peripheral nerve sheath tumors. Remarkably, a distinct 'serpentine' palisading pattern, comprising ovoid/plump cells shorter than usual schwannian cells in a hyalinized stroma, was identified in most fusion-positive cases and the schwannomatous component of the only fusion-positive malignant peripheral nerve sheath tumor. To validate this finding, 60 additional cases were collected, including 36 with (≥10% arbitrarily) and 24 without appreciable serpentine histology, of which 29 (80.6%) and 2 (8.3%) harbored the fusion, respectively. With percentages of 'serpentine' areas scored, 10% was determined as the optimal practical cut-off to predict the fusion status (sensitivity, 0.950; specificity, 0.943). Fusion positivity was significantly associated with serpentine histology, smaller tumors, younger patients, and peripheral somatic tissue, while multivariate logistic linear regression analysis only identified serpentine histology and location as independent fusion-predicting factors. RNA in situ hybridization successfully detected the fusion junction, highly concordant with RT-PCR results. Gene expression profiling on 18 schwannomas demonstrated segregation largely consistent with fusion status. Fusion-positive cases expressed significantly higher HTRA1 mRNA abundance, perhaps exploitable as a biomarker. In summary, we systematically characterize a series of 60 SH3PXD2A::HTRA1 fusion-positive schwannomas, showing their distinctive morphology and location-specific prevalence for the first time.
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Neoplasias de la Vaina del Nervio , Neurilemoma , Humanos , Neurilemoma/patología , Neoplasias de la Vaina del Nervio/patología , Transformación Celular Neoplásica , Proteínas Adaptadoras del Transporte VesicularRESUMEN
Background and Objectives: Women with interstitial cystitis (IC) suffer from spontaneous serious bladder pain symptoms without immediate resolution. Women with IC may lack knowledge of how to help themselves. Therefore, a measurement of IC self-help and medical-resource-seeking for women with IC is needed. Materials and Methods: This study recruited 100 women with IC from a teaching hospital in Northern Taiwan. The reliability and validity of the Interstitial Cystitis Self-Help and Medical Resources Scale (ICSR) were assessed using expert validity, confirmatory factor analysis (CFA) to test the construct validity, composite reliability to evaluate the internal consistency, and item analysis to test the discrimination validity of each item. Results: The results showed that the ICSR had accurate goodness-of-fit indices and the component reliability ranged from 0.42 to 0.83, indicating good reliability and validity. Conclusions: The ICSR is recommended for screening the self-help and medical-resource-seeking abilities of women with IC to aid in diagnosing IC and providing more precise medical treatments.
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Cistitis Intersticial , Cistitis Intersticial/diagnóstico , Cistitis Intersticial/terapia , Femenino , Conductas Relacionadas con la Salud , Humanos , Reproducibilidad de los Resultados , TaiwánRESUMEN
CONTEXT.: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced, adverse T-cell-mediated hypersensitivity reaction that most often involves skin. The pathologic findings of DRESS-related lymphadenopathy have been described infrequently in the literature. OBJECTIVE.: To present a case series of DRESS-related lymphadenopathy with an emphasis on the morphologic spectrum. DESIGN.: We describe detailed clinical and pathologic findings along with the literature review. We focus on the differential diagnosis between DRESS lymphadenopathy and angioimmunoblastic T-cell lymphoma (AITL). RESULTS.: There were 4 men and 1 woman with a mean age of 41 years (range, 23-59 years). One patient (20%) died. Three lymph node biopsy specimens showed a pattern reminiscent of AITL (AITL-like pattern) and 2 cases showed necrotizing lymphadenitis (Kikuchi-like pattern), associated with vasculitis in 1 case. The AITL-like morphology of DRESS-related lymphadenopathy may be difficult to distinguish from genuine AITL. The clinical information is important for differential diagnosis, including history of drug exposure, age, and the rarity or absence of AITL-associated manifestations such as hemolytic anemia and hypergammaglobulinemia. Molecular analysis of the T-cell receptor genes is helpful, typically revealing a polyclonal pattern in DRESS-related lymphadenopathy. CONCLUSIONS.: In the literature, 4 histologic patterns of DRESS lymphadenopathy have been described: reactive lymphoid hyperplasia, necrotizing lymphadenitis, Hodgkin lymphoma-like, and AITL-like. These patterns, particularly those that resemble lymphoma, highlight the importance of correct diagnosis to avoid unnecessary therapies.
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Síndrome de Hipersensibilidad a Medicamentos , Eosinofilia , Linfadenopatía Inmunoblástica , Linfadenitis , Adulto , Diagnóstico Diferencial , Síndrome de Hipersensibilidad a Medicamentos/complicaciones , Síndrome de Hipersensibilidad a Medicamentos/etiología , Eosinofilia/patología , Femenino , Humanos , Linfadenopatía Inmunoblástica/patología , Linfadenitis/complicaciones , MasculinoRESUMEN
Technological advances in thyroid surgery have rapidly increased in recent decades. Specifically, recently developed energy-based devices (EBDs) enable simultaneous dissection and sealing tissue. EBDs have many advantages in thyroid surgery, such as reduced blood loss, lower rate of post-operative hypocalcemia, and shorter operation time. However, the rate of recurrent laryngeal nerve (RLN) injury during EBD use has shown statistically inconsistent. EBDs generate high temperature that can cause iatrogenic thermal injury to the RLN by direct or indirect thermal spread. This article reviews relevant medical literatures of conventional electrocauteries and different mechanisms of current EBDs, and compares two safety parameters: safe distance and cooling time. In general, conventional electrocautery generates higher temperature and wider thermal spread range, but when applying EBDs near the RLN adequate activation distance and cooling time are still required to avoid inadvertent thermal injury. To improve voice outcomes in the quality-of-life era, surgeons should observe safety parameters and follow the standard procedures when using EBDs near the RLN in thyroid surgery.
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Monitoreo Intraoperatorio/métodos , Complicaciones Posoperatorias/prevención & control , Nervio Laríngeo Recurrente/cirugía , Instrumentos Quirúrgicos/tendencias , Tiroidectomía/tendencias , Voz/fisiología , Animales , Electrocoagulación/efectos adversos , Electrocoagulación/tendencias , Humanos , Complicaciones Posoperatorias/etiología , Traumatismos del Nervio Laríngeo Recurrente/etiología , Traumatismos del Nervio Laríngeo Recurrente/prevención & control , Instrumentos Quirúrgicos/efectos adversos , Glándula Tiroides/inervación , Glándula Tiroides/cirugía , Tiroidectomía/efectos adversos , Resultado del Tratamiento , Terapia por Ultrasonido/efectos adversos , Terapia por Ultrasonido/tendenciasRESUMEN
Hepatitis C virus (HCV) reactivation occurs in 23% of HCV-infected cancer patients receiving chemotherapy. Forty-three percent of the patients with reactivation of HCV during chemotherapy develop a hepatitis flare. Most of the cancer patients with HCV reactivation have an unremarkable clinical course following an HCV-related hepatitis flare during chemotherapy. However, 26%-57% of the cancer patients developing an acute flare of chronic hepatitis C during chemotherapy require unanticipated discontinuation or dose reduction of chemotherapy, which results in deleterious changes in the cancer treatment plan. Although an optimal strategy for HCV screening in cancer patients receiving chemotherapy has not been established, universal pre-chemotherapy HCV testing for patients with hematological malignancies is recommended by current guidelines. All the currently approved direct-acting antivirals (DAAs) can be used in cancer patients, but the use of DAAs during chemotherapy should avoid drug-drug interactions between chemotherapy and antiviral agents. If there are no contraindications or anticipated drug-drug interactions, DAAs treatment can be administered before, during, or after chemotherapy. In conclusion, HCV reactivation occurs in approximately one-fourth of HCV-infected cancer patients receiving chemotherapy. An HCV-related hepatitis flare during chemotherapy may lead to the discontinuation of potentially life-saving chemotherapy. Currently, universal HCV screening is recommended in hematological malignancy patients before chemotherapy, but there is no evidence-based guideline for other cancer patients. DAAs treatment can cure HCV infection and prevent HCV reactivation during chemotherapy.
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Hepatitis B Crónica , Hepatitis C Crónica , Hepatitis C , Antivirales/efectos adversos , Hepacivirus , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Brote de los Síntomas , Activación ViralRESUMEN
BACKGROUND: Global pandemic resulted from the coronavirus disease-19 (COVID-19) demands mental health concerns on the affected population. We examine the time-course shift of psychological burden among suspected and confirmed COVID-19 patients. METHODS: Participants with suspected or confirmed COVID-19 were included in the cohort. Consecutive surveys were conducted upon hospital admission, discharge, and during outpatient follow-up by adapting the 5-item brief symptom rating scale (BSRS-5) assessing psychological symptoms including anxiety, depression, hostility, interpersonal sensitivity, and insomnia. The sixth measure to observe suicidal ideation was also included. RESULTS: A total of 109 eligible patients participated in the study, in which 83.49% reported no distress upon hospital admission, while 2.75%, 3.66%, and 10.1% patients were assessed as being with severe, moderate and mild psychological distress, respectively. Overall, age, sex, and history of contact did not significantly differ between patients with and without psychological distress. Multivariate logistic regression revealed that patients admitted during April-May (OR: 7.66, 95% CI: 1.46-40.28) and presented with symptoms including sore throat (OR: 4.24, 95% CI: 1.17-15.29) and malaise (OR: 5.24, 95% CI: 1.21-22.77) showed significantly higher risk of psychological distress. Cough symptom interestingly showed lower risk of emotional distress (OR: 0.25, 95% CI: 0.08-0.81). Subsequent surveys upon hospital discharge and during outpatient follow-up revealed steadily declining distress among all cohort. CONCLUSION: At least 16.5% of our cohort reported psychological distress upon hospital admission, with distinct time-dependent decline. Access to mental health support, alongside with promoting positive activities for good mental health are pivotal for those directly affected.
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COVID-19 , Distrés Psicológico , Ansiedad , Estudios de Cohortes , Estudios Transversales , Depresión , Humanos , SARS-CoV-2 , Estrés Psicológico/diagnóstico , Estrés Psicológico/epidemiología , Encuestas y CuestionariosRESUMEN
No guidelines have been developed for the management of HCV-infected cancer patients receiving chemotherapy. The current study aimed to investigate the incidence of severe acute exacerbation of HCV infection in cancer patients receiving chemotherapy and to search for risk factors predicting severe acute exacerbation of HCV infection. This retrospective cohort study reviewed the clinical data of the cancer patients receiving chemotherapy in our institute from August 2012 to December 2017. Incidences of severe acute exacerbation of HCV infection in different kinds of cancers were assessed, and risk factors were analysed. Cancer patients with HCV infection (n = 306) had a higher frequency of severe acute liver injury (2.3% vs 0.7%; P = .003) than those without HCV infection (n = 4419). The incidence of severe acute exacerbation in HCV-infected haematological cancer patients was higher than that in those with HCC and non-HCC solid tumours (9.4% vs 1.9% and 1.1%). Rituximab-containing chemotherapy and haematological malignancy were the risk factors related to the acute exacerbation (P < .001 and P = .004, respectively). None of the patients with severe acute HCV flares developed hepatic decompensation or mortality. However, 57.1% of them discontinued chemotherapy due to liver dysfunction. In conclusion, HCV infection increases the risk of acute severe liver injury in cancer patients undergoing chemotherapy. Rituximab-containing chemotherapy and haematological malignancy are the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. Pre-chemotherapy HCV testing is therefore mandatory before rituximab-containing chemotherapy for the treatment of haematological malignancy.
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Carcinoma Hepatocelular , Neoplasias Hematológicas , Hepatitis C , Neoplasias Hepáticas , Antivirales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/virología , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/virología , Hepatitis C/complicaciones , Hepatitis C/patología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/virología , Estudios Retrospectivos , Factores de Riesgo , Rituximab/efectos adversos , Rituximab/uso terapéutico , Brote de los SíntomasRESUMEN
BACKGROUND: This study aims to investigate the self-perception of symptoms, medical help seeking, and self-help strategies of women with interstitial cystitis (IC). METHODS: A mixed method of qualitative and quantitative approaches was employed. The qualitative approach used in-depth interviews about the subjective experience of symptoms, medical help seeking, and self-help strategies for their IC. The quantitative inquiry was conducted by a yes or no response to the question "Did self-perceived severe symptoms of IC interfere with your daily life?" A loglinear model was applied to investigate the associations between possible factors. RESULTS: This study recruited 68 women aged 20 to 69 years, of whom 22 were interviewed for qualitative data. About 72.1% of the women responded that self-perceived severe IC symptoms interfered with their daily life. A significant negative association between employment and self-perceived severe IC symptoms (P < .05) was observed. Qualitative results revealed three important themes: (1) bothersome symptoms-all-day bladder pain and lower urinary tract symptoms and deteriorated quality of life, (2) medical help seeking-exhaustion and frustration, (3) self-help strategies-coexisting with IC or feeling helpless. CONCLUSIONS: IC women feel exhausted and frustrated by seeking medical attention for this incurable disease for a long time. IC women have troubled and uneasy daily lives. Being employed or engaging in activities can divert attention to alleviate symptoms. IC patient support groups allow patients to share their self-help experiences with interdisciplinary medical teams to provide physical and psychological treatment.
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Cistitis Intersticial/psicología , Cistitis Intersticial/terapia , Aceptación de la Atención de Salud , Autocuidado , Autoimagen , Adulto , Anciano , Dolor Crónico/etiología , Dolor Crónico/psicología , Empleo , Femenino , Frustación , Humanos , Persona de Mediana Edad , Calidad de VidaRESUMEN
Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere with breathing. In recent years, intraoperative neural monitoring (IONM) has been widely adapted as an adjunct technique to localize the RLN, detect RLN injury, and predict vocal cord function during the operations. Many studies have also used animal models to investigate new applications of IONM technology and to develop reliable strategies for preventing intraoperative RLN injury. The aim of this article is to introduce a standard protocol for using a porcine model in IONM research. The article demonstrates the procedures for inducing general anesthesia, performing tracheal intubation, and experimental design to investigate the electrophysiological characteristics of RLN injuries. Applications of this protocol can improve overall efficacy in implementing the 3R principle (replacement, reduction and refinement) in porcine IONM studies.
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Traumatismos del Nervio Laríngeo Recurrente/etiología , Nervio Laríngeo Recurrente/cirugía , Glándula Tiroides/cirugía , Tiroidectomía/métodos , Animales , Humanos , Complicaciones Intraoperatorias , Modelos Animales , PorcinosRESUMEN
BACKGROUND: This study aimed to investigate the effectiveness of monotherapy acetylsalicylic acid (ASA) and warfarin for stroke prevention in low-risk atrial fibrillation (AF) by using a population- -based cohort study in Taiwan. METHODS: A newly diagnosed low-risk AF patient cohort were identified by using National Health Insurance Research Database (NHIRD) in Taiwan in 2008. The study cohort was observed with a follow-up of 2 years to examine the onset of ischemic stroke (IS) (to 2010). The longitudinal data were analyzed by using generalized estimation equations (GEE). RESULTS: A total of 8,065 newly-diagnosed low-risk AF patients were identified in 2008. 7.4% were prescribed with ASA and 4.6% were prescribed with warfarin. The GEE results showed that low-risk AF patients with hypertension who received warfarin were associated with a statistically significant 58.4% reduction of IS risk (OR = 0.416, p = 0.024, 95% CI 0.194-0.891). Additionally, low-risk AF patients with hyperlipidemia who received warfarin were associated with a 69.3% reduction of IS risk (OR = 0.307, p = 0.044, 95% CI 0.097-0.969). CONCLUSIONS: Warfarin is suggested to be prescribed in preventing IS for low-stroke-risk AF patients with hypertension and hyperlipidemia.
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Anticoagulantes/uso terapéutico , Aspirina/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Isquemia Encefálica/prevención & control , Accidente Cerebrovascular/prevención & control , Warfarina/uso terapéutico , Adulto , Anciano , Anticoagulantes/efectos adversos , Aspirina/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Investigación sobre la Eficacia Comparativa , Bases de Datos Factuales , Femenino , Humanos , Hiperlipidemias/epidemiología , Hipertensión/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Taiwán/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Warfarina/efectos adversos , Adulto JovenRESUMEN
To evaluate clinical outcomes and to identify prognostic factors in isolated para-aortic lymph node (PALN) recurrence, we retrospectively reviewed 65 patients who developed PALN recurrence as the first site of tumor progression from a total of 1521 patients who were treated with curative pelvic radiation therapy (RT) for uterine cervical carcinoma between May 1993 and January 2017. Forty-five of the 65 patients received salvage therapy. The median salvage PALN radiation dose was 54 Gy (range: 18 to 62 Gy). Prognostic factors for overall survival (OS) and distant metastases (DMs) were analyzed with univariate and multivariate Cox regression. The median follow-up period for surviving patients was 61 months (4-202 months). The median OS was 27.7 months (0.3-202 months). The highest level of PALN metastases at or above the L1 spinal level (hazard ratio [HR] 9.88, 95% confidence interval [CI] 3.44-28.38, P<0.001) and the presence of leg edema and/or back pain at recurrence (HR 3.25, 95% CI 1.57-6.75, P=0.002) were significantly associated with worse OS. A significantly higher incidence of DMs (HR 5.97, 95% CI 2.05-17.35, P=0.001) was found in the patients with a high level (≥L1) of PALN metastases. Salvage RT (HR 0.35, 95% CI 0.17-0.71, P=0.004) and restaging with positron emission tomography/computed tomography (PET/CT) (HR 0.2, 95% CI 0.04-0.93, P=0.039) were independent predictors of a better OS. In conclusion, a high level (≥L1) of PALN metastases predicts poor survival and a high rate of DMs. Periodic surveillance for early detection and restaging by PET/CT imaging to identify the optimal treatment at recurrence is recommended.
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BACKGROUND: Intraoperative neural monitoring (IONM) has gained widespread acceptance as an adjunct to the gold standard of visual identification of the recurrent laryngeal nerve (RLN) during thyroid surgery. Currently, laryngeal electromyography (EMG) recording during IONM is almost always performed using endotracheal tube (ETT) surface electrodes placed adjacent to vocal folds originating from the inner surface of the thyroid cartilage (TC). Therefore, it was hypothesized that surface recording electrodes placed on the outer surface of the TC should enable access to the EMG response of the vocal folds during IONM. The aim of this experimental study was to evaluate the feasibility of the transcartilage approach for laryngeal EMG recording during IONM. METHODS: A porcine model (12 pigs and 24 RLN sides) with well established applicability in IONM research was used for the experiments. Both ETT electrodes adjacent to vocal folds and adhesive pre-gelled electrodes on the TC were used for EMG recording during IONM. Electrically evoked EMG signals detected by both electrode types were recorded and analyzed. EMG changes during tracheal displacement and RLN traction injury were compared. RESULTS: Both the ETT and TC recording electrodes recorded typical laryngeal EMG waveforms evoked by a 1 mA stimulus current applied on both sides of the RLNs and vagus nerves (VNs). Under RLN stimulation, the mean EMG amplitudes recorded with the ETT and TC electrodes were 973 ± 79 µV and 695 ± 150 µV, respectively. Under VN stimulation, the mean amplitudes were 841 ± 163 µV and 607 ± 162 µV, respectively. When upward displacement of the trachea was experimentally induced, the TC electrodes showed less variation in recorded EMG signals compared to ETT electrodes. When RLN traction stress was experimentally induced, both the ETT and TC electrodes accurately recorded the typical EMG pattern of progressively degrading amplitude and gradual recovery after release of traction. CONCLUSIONS: This study confirms the feasibility of using transcartilage surface electrodes for recording laryngeal EMG signals evoked during IONM in an animal model. However, before practical application of this approach in clinical thyroid surgery, further studies are needed to improve electrode designs by optimizing their shapes and sizes, and increasing their adhesive stability and sensitivity.
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Monitorización Neurofisiológica Intraoperatoria , Traumatismos del Nervio Laríngeo Recurrente/prevención & control , Glándula Tiroides/cirugía , Tiroidectomía/efectos adversos , Animales , Electromiografía , Estudios de Factibilidad , Modelos Animales , Traumatismos del Nervio Laríngeo Recurrente/etiología , PorcinosRESUMEN
BACKGROUND: To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT). METHODS: A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed. Cox model was used to screen the prognostic factors of late toxicities and four survival outcomes including locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS). RESULTS: Statistically significant inter-correlations were observed between the values of EBV-DNA, some hematologic inflammatory markers, GTV, and N classification. The 5-year LRRFS, DMFS, FFS, and OS rates were 87.9%, 89.4%, 79.4%, and 81.3%, respectively. Multivariate analysis revealed that advanced N classification (N2-3 vs. N0-1) remained the only significant negative prognosticator for all the four survival outcomes. An increased monocyte percentage and a decreased lymphocyte-to-monocyte ratio were significantly associated with poorer FFS and OS, respectively. Larger GTV was observed to be predictive of poorer LRRFS. Patients with T3-4 (HR: 3.5, 95% CI: 1.0-12.1, p = 0.048) or higher GTV (HR: 1.006, 95% CI: 1.001-1.011, p = 0.027) were associated with higher incidence of radiation neuropathy. CONCLUSION: N classification remains the most significant survival predictor for NPC patients treated by SIB-IMRT after adjusting these biomarkers. GTV impacts not only on locoregional control but also radiation neuropathy.
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Carcinoma/patología , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/radioterapia , Traumatismos por Radiación/epidemiología , Radioterapia de Intensidad Modulada/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Traumatismos por Radiación/etiología , Radioterapia de Intensidad Modulada/métodos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Patients treated with radiotherapy are at risk of developing a second cancer during their lifetime, which can directly impact treatment decision-making and patient management. The aim of this study was to qualify and compare the secondary cancer risk (SCR) after intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: We analyzed the treatment plans of a cohort of 10 NPC patients originally treated with IMRT or VMAT. Dose distributions in these plans were used to calculate the organ equivalent dose (OED) with Schneider's full model. Analyses were applied to the brain stem, spinal cord, oral cavity, pharynx, parotid glands, lung, mandible, healthy tissue, and planning target volume. RESULTS: We observed that the OED-based risks of SCR were slightly higher for the oral cavity and mandible when VMAT was used. No significant difference was found in terms of the doses to other organs, including the brain stem, parotids, pharynx, submandibular gland, lung, spinal cord, and healthy tissue. In the NPC cohort, the lungs were the organs that were most sensitive to radiation-induced cancer. CONCLUSION: VMAT afforded superior results in terms of organ-at-risk-sparing compared with IMRT. Most OED-based second cancer risks for various organs were similar when VMAT and IMRT were employed, but the risks for the oral cavity and mandible were slightly higher when VMAT was used.
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oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent atherosclerosis.
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Andrographis/química , Colesterol/metabolismo , Diterpenos/farmacología , Células Espumosas/metabolismo , Lipoproteínas LDL/efectos adversos , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Animales , Antiinflamatorios , Antineoplásicos Fitogénicos , Antioxidantes , Aterosclerosis/etiología , Transporte Biológico/genética , Antígenos CD36/genética , Antígenos CD36/metabolismo , Línea Celular , Expresión Génica/efectos de los fármacos , Receptores X del Hígado/fisiología , Ratones , ARN Mensajero/metabolismo , Receptores Depuradores/fisiologíaRESUMEN
Propensity score matching evaluates the treatment incidence of radiation-induced pneumonitis (RP) and secondary cancer risk (SCR) after intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for breast cancer patients. Of 32 patients treated with IMRT and 58 who received VMAT were propensity matched in a 1:1 ratio. RP and SCR were evaluated as the endpoints of acute and chronic toxicity, respectively. Self-fitted normal tissue complication probability (NTCP) parameter values were used to analyze the risk of RP. SCRs were evaluated using the preferred Schneider's parameterization risk models. The dosimetric parameter of the ipsilateral lung volume receiving 40 Gy (IV40) was selected as the dominant risk factor for the RP NTCP model. The results showed that the risks of RP and NTCP, as well as that of SCR of the ipsilateral lung, were slightly lower than the values in patients treated with VMAT versus IMRT (p ≤ 0.01). However, the organ equivalent dose and excess absolute risk values in the contralateral lung and breast were slightly higher with VMAT than with IMRT (p ≤ 0.05). When compared to IMRT, VMAT is a rational radiotherapy option for breast cancer patients, based on its reduced potential for inducing secondary malignancies and RP complications.