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BACKGROUND: The utility of repeated surgical interventions in hepatoblastoma to achieve no evidence of disease (NED) is not well-defined. We examined the effect of aggressive pursuit of NED status on event-free (EFS) and overall survival (OS) in hepatoblastoma with subgroup analysis of high-risk patients. METHODS: Hospital records were queried for patients with hepatoblastoma from 2005 to 2021. Primary outcomes were OS and EFS stratified by risk and NED status. Group comparisons were performed using univariate analysis and simple logistic regression. Survival differences were compared with log-rank tests. RESULTS: Fifty consecutive patients with hepatoblastoma were treated. Forty-one (82%) were rendered NED. NED was inversely correlated with 5-year mortality (OR 0.006; CI 0.001-0.056; P < .01). Ten-year OS (P < .01) and EFS (P < .01) were improved by achieving NED. Ten-year OS was similar between 24 high-risk and 26 not high-risk patients when NED was attained (P = .83). Fourteen high-risk patients underwent a median of 2.5 pulmonary metastasectomies, 7 for unilateral disease, and 7 for bilateral, with a median of 4.5 nodules resected. Five high-risk patients relapsed, and three were salvaged. CONCLUSIONS: NED status is necessary for survival in hepatoblastoma. Repeated pulmonary metastasectomy and/or complex local control strategies to obtain NED can achieve long-term survival in high-risk patients. LEVEL OF EVIDENCE: Level III - Treatment Study - Retrospective Comparative Study.
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Hepatoblastoma , Neoplasias Hepáticas , Metastasectomía , Humanos , Hepatoblastoma/cirugía , Estudios Retrospectivos , Supervivencia sin EnfermedadRESUMEN
Histone lysine demethylases facilitate the activity of oncogenic transcription factors, including possibly MYC. Here we show that multiple histone demethylases influence the viability and poor prognosis of neuroblastoma cells, where MYC is often overexpressed. We also identified the approved small-molecule antifungal agent ciclopirox as a novel pan-histone demethylase inhibitor. Ciclopirox targeted several histone demethylases, including KDM4B implicated in MYC function. Accordingly, ciclopirox inhibited Myc signaling in parallel with mitochondrial oxidative phosphorylation, resulting in suppression of neuroblastoma cell viability and inhibition of tumor growth associated with an induction of differentiation. Our findings provide new insights into epigenetic regulation of MYC function and suggest a novel pharmacologic basis to target histone demethylases as an indirect MYC-targeting approach for cancer therapy. Cancer Res; 77(17); 4626-38. ©2017 AACR.
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Antifúngicos/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Histona Demetilasas/antagonistas & inhibidores , Neuroblastoma/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-myc/metabolismo , Piridonas/farmacología , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclopirox , Epigénesis Genética , Histonas/metabolismo , Humanos , Ratones , Ratones SCID , Neuroblastoma/enzimología , Neuroblastoma/patología , Fosforilación Oxidativa/efectos de los fármacos , Proteínas Proto-Oncogénicas c-myc/genética , ARN Interferente Pequeño/genética , Transcripción Genética/efectos de los fármacos , Células Tumorales CultivadasRESUMEN
PURPOSE: Longer survival for children with sarcoma has led to the recognition of chronic health conditions related to prior therapy. We sought to study the association of sarcoma therapy with the development of scoliosis. METHODS: We reviewed patient demographics, treatment exposures, and functional outcomes for patients surviving >10 years after treatment for sarcoma between 1964 and 2002 at our institution. The diagnosis of scoliosis was determined by imaging. Functional performance and standardized questionnaires were completed in a long-term follow-up clinic. RESULTS: We identified 367 patients, with median age at follow-up of 33.1 years. Scoliosis was identified in 100 (27.2%) patients. Chest radiation (relative risk (RR), 1.88 (95% confidence interval (CI), 1.21-2.92), p < 0.005) and rib resection (RR, 2.64 (CI, 1.79-3.89), p < 0.0001) were associated with an increased incidence of scoliosis; thoracotomy without rib resection was not. Of 21 patients who underwent rib resection, 16 (80.8%) had the apex of scoliosis towards the surgical side. Scoliosis was associated with worse pulmonary function (RR, 1.74 (CI, 1.14-2.66), p < 0.01) and self-reported health outcomes, including functional impairment (RR, 1.60 (CI, 1.07-2.38), p < 0.05) and cancer-related pain (RR, 1.55 (CI, 1.11-2.16), p < 0.01). Interestingly, pulmonary function was not associated with performance on the 6-min walk test in this young population. CONCLUSIONS: Children with sarcoma are at risk of developing scoliosis when treatment regimens include chest radiation or rib resection. Identification of these risk factors may allow for early intervention designed to prevent adverse long-term outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors at risk of developing scoliosis may benefit from monitoring of pulmonary status and early physical therapy.
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Pulmón/patología , Pruebas de Función Respiratoria/métodos , Sarcoma , Escoliosis/etiología , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sarcoma/complicaciones , Sarcoma/mortalidad , Sarcoma/patología , Sarcoma/terapia , Autoinforme , Encuestas y Cuestionarios , Sobrevivientes/estadística & datos numéricos , Adulto JovenRESUMEN
OBJECTIVES: The purpose of this study was to perform a comprehensive assessment of long-term renal function in patients treated at our institution for synchronous bilateral Wilms tumor (BWT) and to determine the optimal method for estimating glomerular filtration rate (eGFR). METHODS: Surgical approach, adjuvant therapy, and pathology reports were reviewed for patients with at least six months follow-up from definitive surgery. eGFRs, as assessed by the Schwartz and Chronic Kidney Disease in Children (CKiD) formulas, were compared to measured GFR (mGFR) determined by 99mTc-DTPA scanning. Urine studies, including microalbumin, ß-microglobulin, and FENa were also reviewed. RESULTS: Forty-two patients were identified. Of 36 living patients, 28 (77.8%) had greater than 6months follow-up, with a median overall follow-up of 5.2years (range: 1.4-13.4). The median mGFR was 97mL/min/1.73m2, while the median eGFRSchwartz and eGFRCKiD were 103.3mL/min/1.73m2 and 79.7mL/min/1.73m2, respectively, (p=0.13 and p=0.75, compared to mGFR). Eleven (39.3%) patients had at least one abnormal urine study (microalbumin >30µg/g creatinine, n=3; ß-2 microglobulin >133µg/g creatinine, n=9; FENa>1%, n=4). CONCLUSIONS: In our series, few patients had an abnormally low GFR. Neither method for estimating GFR gave a significantly different result from measured GFR, suggesting that the Schwartz equation is adequate, although specific urine tests may be more sensitive for detecting subtle renal dysfunction. LEVEL OF EVIDENCE: Level IV - retrospective case series with no comparison group.
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Quimioradioterapia Adyuvante , Tasa de Filtración Glomerular , Neoplasias Renales/fisiopatología , Nefrectomía , Tumor de Wilms/fisiopatología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Neoplasias Renales/terapia , Masculino , Nefrectomía/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Tumor de Wilms/terapiaRESUMEN
BACKGROUND: Osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) are the most common primary pediatric bone malignancies. We sought to assess the diagnostic accuracy of initial tumor biopsies in patients with OS or ESFT at a pediatric cancer center. METHODS: All biopsies performed at initial presentation of patients with OS or ESFT at our institution from 2003 to 2012 were retrospectively reviewed. Diagnostic accuracy and incidence of complications were correlated with study variables using logistic regression analysis. RESULTS: One hundred forty-two biopsies were performed in 105 patients (median age 13.4years, range: 1.8-23.0), 104 (73.2%) OS and 38 (27.8%) ESFT. Thirty-one (21.8%) were performed on metastatic sites. Eighty-five (76.6%) of 111 primary site biopsies were open procedures, and 26 were percutaneous (23.4%). Primary site biopsies were successful in 94.1% of open and 73.1% of percutaneous procedures. Odds of obtaining a successful diagnostic specimen were 7.8 times higher with open approach (CI: 1.6-36.8). Metastatic site biopsies were successful in 66.7% of percutaneous and 100% of open and thoracoscopic procedures. CONCLUSION: Biopsy of metastatic sites was equal to primary site in obtaining diagnostic material with the added benefit of accurate staging, with few adverse events and high diagnostic yield.
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Neoplasias Óseas/patología , Osteosarcoma/patología , Sarcoma de Ewing/patología , Adolescente , Biopsia , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0125838.].
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A majority of breast cancers are driven by estrogen via estrogen receptor-α (ERα). Our previous studies indicate that hypoxia-inducible factor 1α (HIF-1α) cooperates with ERα in breast cancer cells. However, whether ERα is implicated in the direct regulation of HIF-1α and the role of HIF-1α in endocrine therapy response are unknown. In this study we found that a subpopulation of HIF-1α targets, many of them bearing both hypoxia response elements and estrogen response elements, are regulated by ERα in normoxia and hypoxia. Interestingly, the HIF-1α gene itself also bears an estrogen response element, and its expression is directly regulated by ERα. Clinical data revealed that expression of the HIF-1α gene or a hypoxia metagene signature is associated with a poor outcome to endocrine treatment in ERα(+) breast cancer. HIF-1α was able to confer endocrine therapy resistance to ERα(+) breast cancer cells. Our findings define, for the first time to our knowledge, a direct regulatory pathway between ERα and HIF-1α, which might modulate hormone response in treatment.
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Neoplasias de la Mama/tratamiento farmacológico , Moduladores de los Receptores de Estrógeno/uso terapéutico , Receptor alfa de Estrógeno/fisiología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Transducción de Señal , Tamoxifeno/uso terapéutico , Transcripción Genética/fisiologíaRESUMEN
OBJECTIVES: Wilms tumor is the most common renal cancer in children. Approximately 5% of children with Wilms tumor present with disease in both kidneys. The treatment challenge is to achieve a high cure rate while maintaining long-term renal function. We retrospectively reviewed our institutional experience with nephron sparing surgery (NSS) in patients with synchronous bilateral Wilms tumor (BWT) operated on between 2001 and 2014. METHODS: Imaging studies, surgical approach, adjuvant therapy, and pathology reports were reviewed. Outcomes evaluated included surgical complications, tumor recurrence, patient survival, and renal function, as assessed by estimated glomerular filtration rate. RESULTS: A total of 42 patients with BWT were identified: 39 (92.9%) patients underwent bilateral NSS; only 3 patients (7.1%) underwent unilateral nephrectomy with contralateral NSS. Postoperative complications included prolonged urine leak (10), infection (6), intussusception (2), and transient renal insufficiency (1). Three patients required early (within 4 months) repeat of NSS for residual tumor. In the long-term, 7 (16.7%) patients had local tumor recurrence (managed with repeat NSS in 6 and completion nephrectomy in 1) and 3 had an episode of intestinal obstruction requiring surgical intervention. Overall survival was 85.7% (mean follow-up, 4.1 years). Of the 6 patients who died, 5 had diffuse anaplastic histology. All of the patients had an estimated glomerular filtration rate more than 60âmL/min/1.73âm at the last follow-up; no patient developed end-stage renal disease. CONCLUSIONS: In patients with synchronous, BWT, bilateral NSS is safe and almost always feasible, thereby preserving maximal renal parenchyma. With this approach, survival was excellent, as was maintenance of the renal function.
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Neoplasias Renales/cirugía , Nefrectomía , Tumor de Wilms/cirugía , Niño , Preescolar , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/fisiopatología , Masculino , Recurrencia Local de Neoplasia , Nefrectomía/métodos , Nefrectomía/mortalidad , Nefronas/cirugía , Complicaciones Posoperatorias , Estudios Retrospectivos , Resultado del Tratamiento , Tumor de Wilms/mortalidad , Tumor de Wilms/fisiopatologíaRESUMEN
Neonatal neuroblastoma accounts for less than 5% of all cases of neuroblastoma but carries a favorable prognosis with most patients being stratified into low- or intermediate-risk groups for recurrence of disease. The epidemiology of neonatal (age less than 30 days) neuroblastoma contrasts greatly with patients older than 30 days. Owing to the unique potential for spontaneous regression of this tumor type, several groups have sought to reduce therapy given to neonates with neuroblastoma and use a watch-and-wait approach for many low-risk patients. Ongoing studies also seek to reduce therapy for some intermediate-risk patients in an attempt to lessen exposure to surgical intervention and cytotoxic chemotherapy. In this review, we discuss the epidemiology, clinical presentation, staging, and treatment for neonates with neuroblastoma.
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Recurrencia Local de Neoplasia/prevención & control , Neuroblastoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Recién Nacido , Enfermedades del Recién Nacido , Estadificación de Neoplasias , Neuroblastoma/terapia , Pronóstico , Tasa de SupervivenciaRESUMEN
Background. Mesenchymal chondrosarcoma is an aggressive, uncommon histologic entity arising in bone and soft tissues. We reviewed our institutional experience with this rare diagnosis. Methods. We conducted a retrospective chart review on patients with mesenchymal chondrosarcoma over a 24-year period. Clinicopathologic and radiographic features were reviewed. Results. Twelve patients were identified. Nine were females; median age was 14.5 years (1.2-19.7 years). The most common site was the head/neck (7/12). Disease was localized in 11/12 patients (one with lung nodules). Six with available tissue demonstrated NCOA2 rearrangement by FISH. Six underwent upfront surgical resection, and six received neoadjuvant therapy (2 chemotherapy alone and 4 chemotherapy and radiation). All patients received adjuvant chemotherapy (most commonly ifosfamide/doxorubicin) and/or radiation (median dose 59.4 Gy). At a median follow-up of 4.8 years, 5-year disease-free survival and overall survival were 68.2% (95% CI 39.8%, 96.6%) and 88.9% (95% CI 66.9%, 100%). Two patients had distant recurrences at 15 and 42 months, respectively. Conclusion. Aggressive surgical resection of mesenchymal chondrosarcoma with chemoradiotherapy yields excellent local control and may reduce likelihood of late recurrence. Characterization of downstream targets of the HEY1-NCOA2 fusion protein, xenograft models, and drug screening are needed to identify novel therapeutic strategies.
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Malignant glioblastoma (GBM) is a highly aggressive brain tumor with a dismal prognosis and limited therapeutic options. Genomic profiling of GBM samples has identified four molecular subtypes (Proneural, Neural, Classical and Mesenchymal), which may arise from different glioblastoma stem-like cell (GSC) populations. We previously showed that adherent cultures of GSCs grown on laminin-coated plates (Ad-GSCs) and spheroid cultures of GSCs (Sp-GSCs) had high expression of stem cell markers (CD133, Sox2 and Nestin), but low expression of differentiation markers (ßIII-tubulin and glial fibrillary acid protein). In the present study, we characterized GBM tumors produced by subcutaneous and intracranial injection of Ad-GSCs and Sp-GSCs isolated from a patient-derived xenoline. Although they formed tumors with identical histological features, gene expression analysis revealed that xenografts of Sp-GSCs had a Classical molecular subtype similar to that of bulk tumor cells. In contrast xenografts of Ad-GSCs expressed a Mesenchymal gene signature. Adherent GSC-derived xenografts had high STAT3 and ANGPTL4 expression, and enrichment for stem cell markers, transcriptional networks and pro-angiogenic markers characteristic of the Mesenchymal subtype. Examination of clinical samples from GBM patients showed that STAT3 expression was directly correlated with ANGPTL4 expression, and that increased expression of these genes correlated with poor patient survival and performance. A pharmacological STAT3 inhibitor abrogated STAT3 binding to the ANGPTL4 promoter and exhibited anticancer activity in vivo. Therefore, Ad-GSCs and Sp-GSCs produced histologically identical tumors with different gene expression patterns, and a STAT3/ANGPTL4 pathway is identified in glioblastoma that may serve as a target for therapeutic intervention.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Heterogeneidad Genética , Glioblastoma/genética , Glioblastoma/patología , Células Madre Neoplásicas/patología , Proteína 4 Similar a la Angiopoyetina , Angiopoyetinas/metabolismo , Animales , Neoplasias Encefálicas/irrigación sanguínea , Adhesión Celular/efectos de los fármacos , Separación Celular , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/irrigación sanguínea , Humanos , Masculino , Mesodermo/efectos de los fármacos , Mesodermo/patología , Ratones SCID , Clasificación del Tumor , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , Piridinas/farmacología , Factor de Transcripción STAT3/metabolismo , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Tejido Subcutáneo/patología , Análisis de Supervivencia , Tirfostinos/farmacología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Partial nephrectomy is considered by some for children with unilateral Wilms tumor (UWT) to avoid the theoretical complication of renal insufficiency. In the current study, the authors evaluated the prevalence of hypertension and impaired renal function in long-term survivors of nonsyndromic UWT who were treated without nephrotoxic chemotherapy or ionizing radiation. METHODS: Eligibility included age ≤15 years at the time of diagnosis of nonsyndromic UWT, treatment receipt before 2002, and maintenance of disease remission after unilateral nephrectomy without receipt of abdominal irradiation or nephrotoxic chemotherapy. Renal function was assessed by urinalysis and estimated glomerular filtration rate (eGFR). Patients receiving antihypertensive medication or those with blood pressure readings of >140/90 mm Hg were considered to be hypertensive. RESULTS: A total of 75 patients with a median age at diagnosis of 3.2 years (range, 0.2-12.1 years) met eligibility criteria. The median length of follow-up was 19.6 years (range, 10.0-32.8 years). All but 1 patient had stage I/II disease. Sixty-eight patients (90.7%) patients had WT with favorable histology and 7 patients had anaplastic histology. Sixteen patients (21.3%) had an eGFR <90 mL/minute/1.73m(2), 2 of whom also had proteinuria (12.5%). No patient had an eGFR <60 mL/minute/1.73m(2). Five patients (6.7%) had hypertension, 3 of whom were receiving antihypertensive medications. At the time of last follow-up, no patient had developed end-stage renal disease. CONCLUSIONS: Patients with UWT who were treated with unilateral radical nephrectomy without nephrotoxic chemotherapy or ionizing radiation appear to be at low risk of developing significant long-term renal dysfunction. For this patient population, the routine use of partial nephrectomy does not appear justified. However, monitoring and counseling are important for identifying the rare patient who develops subtle renal insufficiency and therefore might be at an increased risk of adverse cardiovascular sequelae.
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Tasa de Filtración Glomerular , Neoplasias Renales/fisiopatología , Neoplasias Renales/cirugía , Riñón/fisiopatología , Nefrectomía , Tumor de Wilms/fisiopatología , Tumor de Wilms/cirugía , Adolescente , Adulto , Presión Sanguínea , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/epidemiología , Hipertensión/etiología , Lactante , Masculino , Nefrectomía/métodos , Prevalencia , Proteinuria/epidemiología , Proteinuria/etiología , Insuficiencia Renal/epidemiología , Insuficiencia Renal/etiología , Sobrevivientes/estadística & datos numéricos , Adulto JovenRESUMEN
PURPOSE: Antiangiogenic agents show significant antitumor activity against various tumor types. In a study evaluating the combination of sorafenib, bevacizumab, and low-dose cyclophosphamide in children with solid tumors, an unexpectedly high incidence of pneumothorax was observed. We evaluated patient characteristics and risk factors for the development of pneumothorax in patients receiving this therapy. PATIENTS AND METHODS: Demographics, clinical course, and radiographic data of 44 patients treated with sorafenib, bevacizumab and cyclophosphamide were reviewed. Risk factors associated with the development of pneumothorax were analyzed. RESULTS: Pneumothorax likely related to study therapy developed in 11 of 44 (25%) patients of whom 33 had pulmonary abnormalities. Median age of patients was 14.7 years (range, 1.08-24.5). Histologies associated with pneumothorax included rhabdoid tumor, synovial sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and renal cell carcinoma. Cavitation of pulmonary nodules in response to therapy was associated with pneumothorax development (P<0.001). Median time from start of therapy to development of pneumothorax was 5.7 weeks (range, 2.4-31). CONCLUSION: The development of cavitary pulmonary nodules in response to therapy is a risk factor for pneumothorax. As pneumothorax is a potentially life-threatening complication of antiangiogenic therapy in children with solid tumors, its risk needs to be evaluated when considering this therapy.
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Inhibidores de la Angiogénesis/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Neumotórax/inducido químicamente , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma Sinovial/tratamiento farmacológico , Tumor de Wilms/tratamiento farmacológico , Adolescente , Adulto , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/efectos adversos , Bevacizumab/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Niacinamida/efectos adversos , Niacinamida/análogos & derivados , Niacinamida/uso terapéutico , Osteosarcoma/tratamiento farmacológico , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Neumotórax/diagnóstico , Sorafenib , Adulto JovenRESUMEN
BACKGROUND: Tumor biopsies are central to the diagnosis and management of cancer and are critical to efforts in personalized medicine and targeted therapeutics. In the current study, the authors sought to evaluate the safety and accuracy of biopsies in children with cancer. METHODS: All biopsies performed in children at the study institution with a suspected or established diagnosis of cancer from 2003 through 2012 were reviewed retrospectively. Patient characteristics and disease-related and procedure-related factors were correlated with procedure-related complications and diagnostic accuracy using logistic regression analysis. RESULTS: A total of 1073 biopsies were performed in 808 patients. Of 1025 biopsies with adequate follow-up, 79 (7.7%) were associated with an adverse event, 35 (3.4%) of which were minor (grade 1-2) and 32 (3.1%) of which were major (grade 3-4) (grading was performed according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The most common major adverse events were blood transfusion (>10 mL/kg; 24 cases) and infection requiring intravenous antibiotics (6 cases). Eleven deaths (1.4%) occurred within 30 days after the procedure, but the procedure may have contributed to the outcome in only 2 cases. A total of 926 biopsies (90.3%) provided definitive histologic diagnoses. Using multivariable analysis, biopsy site, preprocedure hematocrit level, and body mass index were found to be associated with the risk of postprocedural complications (P<.0001, P<.0001, and P =.0029, respectively). Excisional biopsy and biopsy site were found to be independently associated with obtaining a diagnostic result (P =.0002 and P =.0008, respectively). CONCLUSIONS: Tumor biopsies in children with cancer are associated with a low incidence of complications and a high rate of diagnostic accuracy. The predictive factors identified for adverse outcomes may aid in risk assessment and preprocedural counseling.
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Biopsia/efectos adversos , Neoplasias/diagnóstico , Neoplasias/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Estadificación de Neoplasias , Pronóstico , Seguridad , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: We previously conducted a randomized, clinical trial comparing early appendectomy with interval appendectomy for perforated appendicitis. The purpose of the present study was to evaluate the effect this clinical trial had on subsequent practice patterns and outcomes for patients with perforated appendicitis at the free-standing children's hospital conducting the trial. METHODS: A retrospective study was conducted comparing children with perforated appendicitis treated before the trial (2005-2006) and after the trial (2009-2011). Early appendectomy was performed within 24 hours of diagnosis; interval appendectomy occurred 4-6 weeks after initial treatment with antibiotics. Patient characteristics, treatment variables, and outcomes were collected and compared. RESULTS: The pretrial group consisted of 92 patients-62 (67%) underwent early appendectomy, and 30 (33%) patients had interval appendectomy. The posttrial group was composed of 103 patients, with 87 (84%) undergoing early appendectomy and 16 (16%) interval appendectomy (P = .005). The groups were similar in patient and admission characteristics, although the posttrial group had a lower percentage of self-pay patients and fewer computed tomography scans; health care use was similar between groups. Overall, the posttrial group had fewer adverse events (18% vs 34%, P = .02), specifically fewer wound infections (2% vs 14%, P = .001) and fewer unplanned readmissions (7% vs 16%, P = .04) than the pretrial group. In the posttrial group, those patients selected for interval appendectomy were more likely to complete the planned course of therapy than in the pretrial group. CONCLUSION: A clinical trial conducted at our institution to evaluate currently available treatment options for perforated appendicitis did change practice patterns at our hospital. After the trial, there was an increase in the use of early appendectomy, a decrease in the number of computed tomography scans performed per patient, and a reduction in the overall adverse event rate.
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Apendicectomía/métodos , Apendicitis/cirugía , Adolescente , Antibacterianos/uso terapéutico , Apendicectomía/efectos adversos , Apendicitis/diagnóstico por imagen , Apendicitis/tratamiento farmacológico , Niño , Preescolar , Medicina Basada en la Evidencia , Femenino , Humanos , Lactante , Masculino , Readmisión del Paciente , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Infección de la Herida Quirúrgica/etiología , Factores de Tiempo , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Resultado del TratamientoRESUMEN
BACKGROUND: A significant percentage of estrogen receptor (ER)-positive breast cancers are resistant to tamoxifen therapy. Seven in Absentia Homolog 2 (SIAH2), an E3 ubiquitin protein ligase, has been shown to be associated with resistance to antiestrogens. We sought to assess its role in the resistance of a breast cancer cell line, MCF-7, to the ER antagonist, tamoxifen. MATERIALS AND METHODS: A bioinformatic approach was used for the analysis of SIAH2 expression in breast cancer. MCF-7 and MDA-MB-231, which are ER-positive and -negative breast cancer cell lines, respectively, were used for in vitro studies. SIAH2 and ER-α were selectively knocked down in these cell lines with small-interfering RNAs. Knockdowns were confirmed with Western blot analysis and quantitative real-time polymerase chain reaction. Cells with SIAH2 knockdown were treated with tamoxifen and compared with controls. RESULTS: Knockdown of SIAH2 followed by treatment with tamoxifen resulted in a significant decrease in the sensitivity of treated ER-positive cells. Of note, knockdown of SIAH2 resulted in downregulation of ER-α, whereas knockdown of ER-α had minimal effect on SIAH2. Consistent with this result, the bioinformatic analysis of clinical data revealed that SIAH2 expression is significantly correlated with ER positivity in human breast cancers, and low SIAH2 expression is associated with a poorer response to tamoxifen. CONCLUSIONS: SIAH2 appears to be an important modulator of tamoxifen sensitivity in ER-positive MCF-7 cells, mediated, at least in part, through regulation of ER-α expression. Low expression of SIAH2 may be one of the mechanisms that contribute to tamoxifen resistance in human breast cancer.