Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and ratio...
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Πέμπτη 22 Φεβρουαρίου 2018
CDK9 inhibitors in acute myeloid leukemia
Establishment and characterization of in vivo orthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice
Abstract
Osteosarcoma is one of the most common primary bone tumors in childhood and adolescence. Metastases occurrence at diagnosis or during disease evolution is the main therapeutic challenge. New drug evaluation to improve patient survival requires the development of various preclinical models mimicking at best the complexity of the disease and its metastatic potential. We describe here the development and characteristics of two orthotopic bioluminescent (Luc/mKate2) cell-derived xenograft (CDX) models, Saos-2-B-Luc/mKate2-CDX and HOS-Luc/mKate2-CDX, in different immune (nude and NSG mouse strains) and bone (intratibial and paratibial with periosteum activation) contexts. IVIS SpectrumCT system allowed both longitudinal computed tomography (CT) and bioluminescence real-time follow-up of primary tumor growth and metastatic spread, which was confirmed by histology. The murine immune context influenced tumor engraftment, primary tumor growth, and metastatic spread to lungs, bone, and spleen (an unusual localization in humans). Engraftment in NSG mice was found superior to that found in nude mice and intratibial bone environment more favorable to engraftment compared to paratibial injection. The genetic background of the two CDX models also led to distinct primary tumor behavior observed on CT scan. Saos-2-B-Luc/mKate2-CDX showed osteocondensed, HOS-Luc/mKate2-CDX osteolytic morphology. Bioluminescence defined a faster growth of the primary tumor and metastases in Saos-2-B-Luc/mKate2-CDX than in HOS-Luc/mKate2-CDX. The early detection of primary tumor growth and metastatic spread by bioluminescence allows an improved exploration of osteosarcoma disease at tumor progression, and metastatic spread, as well as the evaluations of anticancer treatments. Our orthotopic models with metastatic spread bring complementary information to other types of existing osteosarcoma models.
New osteosarcoma preclinical models in an orthotropic bone setting with the possibility to follow in vivo both primary tumor growth and metastatic spread will further help testing and development of new drug in this disease which outcome has not improved since several decades.
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LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer
Abstract
To study the regulatory effect of lncRNA HOTAIR/miR-20a-5p/HMGA2 axis on breast cancer (BC) cell growth, cell mobility, invasiveness, and apoptosis. The microarray data of lncRNAs and mRNAs with differential expression in BC tissues were analyzed in the Cancer Genome Atlas (TCGA) database. LncRNA HOX transcript antisense RNA (lncRNA HOTAIR) expression in BC was assessed by qRT-PCR. Cell viability was confirmed using MTT and colony formation assay. Cell apoptosis was analyzed by TdT-mediated dUTP nick-end labeling (TUNEL) assay. Cell mobility and invasiveness were testified by transwell assay. RNA pull-down and dual luciferase assay were used for analysis of the correlation between lncRNA HOTAIR and miR-20a-5p, as well as relationship of miR-20a-5p with high mobility group AT-hook 2 (HMGA2). Tumor xenograft study was applied to confirm the correlation of lncRNA HOTAIR/miR-20a-5p/HMGA2 axis on BC development in vivo. The expression levels of the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis. MiR-20a-5p was a target of lncRNA HOTAIR and had a negative correlation with lncRNA HOTAIR. MiR-20a-5p overexpression in BC suppressed cell growth, mobility, and invasiveness and facilitated apoptosis. HMGA2 was a target of miR-20a-5p, which significantly induced carcinogenesis of BC. BC cells progression was mediated by lncRNA HOTAIR via affecting miR-20a-5p/HMGA2 in vivo. LncRNA HOTAIR affected cell growth, metastasis, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer.
The expression levels of the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis. LncRNA HOTAIR affected cell growth, metastasis, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer.
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Prognostic variables for temporal lobe injury after intensity modulated-radiotherapy of nasopharyngeal carcinoma
Abstract
To determine predictive factors for temporal lobe injury (TLI) in nasopharyngeal carcinoma patient (NPC) treated with intensity-modulated radiation therapy (IMRT). A total of 695 NPC cases treated with IMRT were retrospectively analyzed. TLI was diagnosed on MRI images. Volume-dose histograms for 870 evaluable temporal lobes were analyzed, and the predictive factors for the occurrence of TLI was evaluated. Receiver operating characteristic curve (ROC) and Logistic regression analysis was used to determine volume-dose parameters that predict temporal lobe injury (TLI). Univariate and multivariate analysis were used to analyze the predictive factors for TLI. The radiation dose-tolerance model of temporal lobe was calculated by logistic dose-response model. The median follow-up time was 73 months. A total of 8.5% patients were diagnosed with TLI. Among all the volume-dose parameters, logistic regression model showed D2cc (the dose Gray delivered to 2 cubic centimeter volume) was an only independent predictive factor. Multivariate analysis showed D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the independent predictive factors for TLI. Logistic dose-response model has indicated the TD5/5 and TD50/5 of D2cc are 60.3 Gy and 76.9 Gy, respectively. D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the possible independent predictive factors for TLI after IMRT of NPC. Biologic effective doses (TD5/5 and TD50/5) of D2cc are considered to prevent TLI.
A total of 695 NPC cases treated with IMRT were retrospectively analyzed with the radiation-induced temporal lobe injury on MRI images. D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the possible independent predictive factors for TLI after IMRT of NPC. Biologic effective doses (TD5/5 and TD50/5) of D2cc are considered to prevent TLI.
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CGB5 expression is independently associated with poor overall survival and recurrence-free survival in patients with advanced gastric cancer
Abstract
The human CGB5 gene encodes chorionic gonadotropin (hCG)β 5, which is aberrantly expressed in trophoblastic neoplasm and in some non-trophoblastic neoplasms. Fucntional studies observed that it involved tumor initiation, growth, and metastatic outgrowth. In this study, using data from the International Cancer Genome Consortium (ICGC) and the Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD), we assessed the independent prognostic value of CGB5 expression in patients with primary gastric cancer (GC). Results showed that CGB5 expression was nearly not expressed in normal GC tissues. In comparison, its expression was detected in 214 of the 415 primary GC cases (51.6%) in TCGA-STAD and was associated with poor response to primary therapy and a higher risk of recurrence and death. In early stages, CGB5 expression was not a prognostic factor in terms of OS (HR: 1.448; 95% CI: 0.811–2.588, P = 0.211) or RFS (HR: 1.659; 95% CI: 0.778–3.540, P = 0.190). However, its expression was independently associated with unfavorable OS (HR: 1.719; 95% CI: 1.115–2.651, P = 0.014) and RFS (HR: 3.602; 95% CI: 1.708–7.598, P = 0.001) in advanced stages. Using deep sequencing data from TCGA-STAD, we found that CGB5 expression was not related to its genetic amplification or DNA methylation in GC. Based on these findings, we infer that CGB5 expression is common in GC patients and its expression might independently predict poor OS and RFS in advanced stages, but not in early stages of GC.
CGB5 expression is common in gastric cancer patients, and its expression might independently predict poor overall survival and recurrence-free survival in advanced stages, but not in early stages of gastric cancer.
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Risk factors and survival outcomes in patients with breast cancer and lung metastasis: a population-based study
Abstract
The risk factors for morbidity and mortality in breast cancer lung metastases (BCLM) patients still remain poorly identified. The aim of this study was to assess the incidence and survival of BCLM and associated risk factors. Patients with BCLM were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate logistic regression analysis was used to determine the risk factors for BCLM. Predictors of factors associated with death were analyzed in Cox regression and Fine and Gray's test. Of the 11568 patients with stage IV breast cancer, 4213 (36.4%) had BCLM and 1214 (10.5%) had metastases confined to lungs. The median survival time for patients with BCLM was 21 months, and 15.5% of the patients were alive more than 3 years. The tumor subtype distribution was 45.3% HR−/HER2−, 12.2% HR+/HER2+, 7.8% HR−/HER2+, and 15.0% triple-negative subtype. Compared with patients without BCLM, those with BCLM were more likely to be aged, female, black, higher tumor grade, HR−/HER2+, HR+/HER2+, and triple-negative subtypes at diagnosis. Survival analysis showed that the aged, black race, HR−/HER2+, triple-negative subtype, higher grade were the independent risk factor for BCLM patients' survival, while HR+/HER2+ subtype, insured status, and married status suggested better prognosis. In conclusion, the incidence and prognosis of BCLM varied by tumor subtypes, age, and race. Elderly patients with HER2-positive or triple-negative tumors were more likely to have BCLM.
The aim of this study was to assess the incidence and survival in patients with breast cancer and lung metastases (BCLM) and associated risk factors on a population level. Of the 11,568 patients with stage IV breast cancer, 4213 (36.42%) had BCLM and 1214 (10.49%) had BCLM confined to lungs. Survival analysis showed that the aged, black race, HR−/HER2+, triple-negative subtype, higher grade were the independent risk factor for BCLM patients' survival, while HR+/HER2+ subtype, insured status, and married status suggested better prognosis.
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Prediction of radiotherapy response with a 5-microRNA signature-based nomogram in head and neck squamous cell carcinoma
Abstract
Radiotherapy is unlikely to benefit all patients with head and neck squamous cell carcinoma (HNSCC). Therefore, novel method is warranted to predict the radiotherapy response. Our study aimed to construct a microRNA (miRNA)-based nomogram to predict clinical outcomes of patients with HNSCC receiving radiotherapy. We screened out 56 differential miRNAs by analyzing 44 paired tumor and adjacent normal samples miRNA expression profiles from The Cancer Genome Atlas (TCGA). A total of 307 patients with HNSCC receiving adjuvant radiotherapy were randomly divided into a training set (n = 154) and a validation set (n = 153). In the training set, we combined the differential miRNA profiles with clinical outcomes, and LASSO regression model was applied to establish a 5-miRNA signature. The prediction accuracy of the 5-miRNA signature was further validated. In addition, target genes of these miRNAs were predicted, and Gene Ontology (GO) analysis as well as KEGG pathway analysis was executed. A 5-miRNA signature including miR-99a, miR-31, miR-410, miR-424, and miR-495 was identified. With a cutoff value of 1.2201 from Youden's index, the training set was divided into high-risk and low-risk groups, and the 5-year overall survival was significantly different (30% vs. 73%, HR 3.65, CI 2.46–8.16; P < 0.0001). Furthermore, our 5-miRNA signature revealed that only low-risk group would benefit from radiotherapy. Then, a nomogram combining 5-miRNA signature with clinical variables to predict radiotherapy response was constructed. The analysis of 108 target genes of these miRNAs revealed some potential mechanisms in HNSCC radiotherapy response for future investigations. In conclusion, the 5-miRNA signature-based nomogram is useful in predicting radiotherapy response in HNSCC and might become a promising tool to optimize radiation strategies.
We used LASSO regression model to establish a 5-miRNA signature, which serve as a novel and reliable biomarker for prediction of clinical outcomes in patients with HNSCC receiving radiotherapy. What's more, we developed a nomogram integrating the 5-miRNA signature with clinical features of each patient with HNSCC, which could be further used in the evaluation of radiotherapy responses. In addition, target genes of these miRNAs were predicted, and Gene Ontology (GO) analysis as well as KEGG analysis was executed to reveal some potential mechanisms in HNSCC radiotherapy response for future investigations.
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Treatment-related mortality in newly diagnosed pediatric cancer: a population-based analysis
Abstract
Using a previously developed reliable and valid treatment-related mortality (TRM) definition, our objective was to describe the proportion of children newly diagnosed with cancer experiencing TRM and to identify risk factors for TRM in a population-based cohort. We included children with cancer <19 years diagnosed and treated in Ontario who were diagnosed between 2003 and 2012. Children with cancer were identified using data in a provincial registry. Cumulative incidence of TRM was calculated where progressive disease death was considered a competing event. Among the 5179 children included, 179 had TRM, 478 died of progressive disease, and 4522 were still alive. At 5 years, the cumulative incidence of TRM among the entire cohort was 3.9% (95% confidence interval (CI) 3.3–4.5%). When compared to brain tumor patients, leukemia and lymphoma patients had a significantly higher risk of TRM (hazard ratio (HR) 2.5, 95% CI: 1.6–4.0; P < 0.0001). Infants were at significantly higher risk of TRM across diagnostic groups. Other factors associated with higher risks of TRM were metastatic disease (P < 0.0001), diagnosis prior to 1 January 2008 (P = 0.001), hematopoietic stem cell transplantation (HSCT) (P < 0.0001), and relapse (P < 0.0001). The 5-year cumulative incidence of TRM was 3.9% among newly diagnosed children with cancer. Infants were at higher risk of TRM across diagnostic groups. Other risk factors for TRM were leukemia or lymphoma, metastatic disease, earlier diagnosis year, HSCT, and relapse. Future work should further refine prognostic factors by specific cancer diagnosis to best understand when and how to intervene to improve outcomes.
Objective was to describe the proportion of children newly diagnosed with cancer experiencing treatment-related mortality (TRM) and to identify risk factors for TRM in a population-based cohort. When compared to brain tumor patients, leukemia and lymphoma patients had a significantly higher risk of TRM. Infants were at significantly higher risk of TRM across diagnostic groups.
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Antero-cervical thermophysiological characterization of obstructive sleep apnea patients
Abstract
Purpose
Obstructive sleep apnea syndrome (OSAS) is characterized by upper airway inflammation. The aim of this study was to characterize thermal profile of the antero-cervical region in OSAS patients through medical thermal imaging and to compare the respective subjects with non-OSAS individuals.
Methods
Image capture followed the Glamorgan Protocol. A dynamic thermographic examination of the anterior cervical region (at baseline and after a cold stimulus) was conducted in 26 patients diagnosed with overnight polysomnography (PSG). PSG results stratified the subjects into OSAS and non-OSAS groups and their thermograms were compared.
Results
Eleven non-OSAS and 15 OSAS subjects were evaluated. Antero-cervical right side (RS) temperature was higher in OSAS group at baseline (p = 0.014). Right side index (RSI) temperature—the difference between RS and submental region, considered as control—was lower in OSAS subjects at baseline (p = 0.020) and 10 min after the cold stimuli was applied (p = 0.008), indicating higher absolute temperatures in this group. Left side index (LSI) was also lower at 10 min in OSAS group (p = 0.021). Statistical correlation was found between apnea-hypopnea index and RS at baseline (r = 0.424, p = 0.031) and at 10 min (r = 0.403, p = 0.041) and RSI at baseline (r = − 0.458, p = 0.019) and 10 min after cold provocation was applied (r = − 0.435, p = 0.025).
Conclusions
OSAS patients have shown higher antero-cervical temperatures compared with non-OSAS counterparts and temperature was associated with severity of the condition. Medical thermography may be a suitable tool in the setting of OSAS suspicion.
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Transoral radical tonsillectomy and retropharyngeal lymph node dissection with a flexible next generation robotic surgical system
Abstract
Background
The purpose of this study was to describe the use of a novel flexible, single-arm robot in performing a transoral radical tonsillectomy and retropharyngeal lymph node dissection.
Methods
A 63-year-old man with a T1N2bM0 (American Joint Committee on Cancer seventh edition classification) squamous cell carcinoma (SCC) of the left tonsil underwent a transoral robotic radical tonsillectomy and retropharyngeal lymph node dissection, followed by a left selective neck dissection of levels I to IV.
Results
The tonsillar tumor was removed completely with a negative margin that was followed by a dissection and removal of a retropharyngeal lymph node, completed with primary closure of the site. A left selective neck dissection was then performed. The patient was tolerating an oral diet on postoperative day 1 and had no robotic or surgically related complications at 30-day follow-up.
Conclusion
It is feasible and safe to use this novel, flexible, single-arm robot in performing a transoral robotic radical tonsillectomy and retropharyngeal lymph node dissection.
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Mixed adenoneuroendocrine carcinoma of the tongue arising within a congenital enteric cyst
Abstract
Background
Primary intestinal-type adenocarcinoma of the tongue is rare. This represents the first reported case of a primary mixed adenoneuroendocrine carcinoma (MANEC) of the tongue arising within a congenital enteric cyst.
Methods
A 52-year-old man presented with a midline tongue mass that was connected to the mucosal surface with an epithelial-lined sinus tract. Morphological examination and immunohistochemical profiling of the neoplasm were performed.
Results
Histopathological evaluation showed a primary MANEC arising within a preexisting congenital enteric cyst, comprising both adenocarcinoma and neuroendocrine components. The adenocarcinoma had a colonic-type morphology and coexpressed CK7, CK20, and CDX2. Imaging and colonoscopy excluded a distant primary colorectal neoplasm.
Conclusion
The association of primary MANEC of the tongue with a gastrointestinal heterotopic cyst supports an origin from entrapped endodermal elements as opposed to salivary duct origin. This case raises the awareness of a rare yet prognostically important complication of a gastrointestinal heterotopic cyst.
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Double-blind placebo-controlled multicenter phase II trial to evaluate D-methionine in preventing/reducing oral mucositis induced by radiation and chemotherapy for head and neck cancer
Abstract
Background
The purpose of this study was to test if oral D-methionine (D-met) reduced mucositis during chemoradiotherapy.
Methods
We conducted a placebo-controlled double-blind randomized phase II trial of D-met (100 mg/kg p.o. b.i.d.) testing the rate of severe (grades 3-4) mucositis.
Results
Sixty patients were randomized. Grade 2 + oral pain was higher with placebo (79% vs 45%; P = .0165), whereas grade 2 + body odor was greater with D-met (3% vs 41%; P = .0015). Mucositis was decreased with D-met by the physician (World Health Organization [WHO], P = .007; Radiation Therapy Oncology Group [RTOG], P = .009) and patient functional scales (RTOG, P = .0023). The primary end point of grades 3 to 4 mucositis on the composite scale demonstrated a decrease with D-met (48% vs 24%; P = .058), which was borderline in significance. A planned secondary analysis of a semiquantitative scoring system noted decreased oral ulceration (2.2 vs 1.5; P = .023) and erythema (1.6 vs 1.1; P = .048) with D-met.
Conclusion
Although not meeting the primary end point, results of multiple assessments suggest that D-met decreased mucositis.
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Effect of Water Table Depth on Nutrient Concentrations Below the Water Table in a Spodosol
Abstract
Water table depth manipulations as implemented in sugarcane fields of Southwestern Florida, USA, were hypothesized to influence the nutrient concentrations below the water table. Concentrations of phosphorus (P), potassium (K), nitrogen (N), and bromide (Br−) were monitored above and below the water table using a column leaching experiment. Three columns were packed with Immokalee soil (A, E, and Bh horizons) classified as a spodosol and fertilizers (NPK) were applied on the soil surface as solids using rates of 11 kg P ha−1, 166 kg K ha−1, and 200 kg N ha−1. A fourth column where fertilizer mixture and bromide were not added acted as a blank. Potassium was also applied as KBr with bromide used as tracer for water movement. Water table was maintained at 30 cm for 6 weeks and lowered to 50 cm deep for another 6 weeks. Samplers were placed in A, E, and Bh horizons and outlets were placed at 30 and 50 cm deep to obtain solutions for monitoring nutrients and tracer. Solution samplers placed in E and Bh horizons were located below the water table. Slightly elevated P, N, and K concentrations in E horizon for a 50-cm water table depth treatment were observed. For both water table treatments, minimal loss of applied N, P, and K below the water table was observed. The results of the study have shown that movement of nutrients below the water table is slow, and depends on the type of nutrients applied and the water table depth.
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Remediating Montreal’s Tree Pit Soil Applying an Ash Tree-Derived Biochar
Abstract
Biochar as a soil amendment in street tree pits can be used to increase the soil's ability to retain contaminants found in urban runoff. The increased retention can potentially decrease peak concentrations of soluble trace metals and de-icing salts in the soil solution, thereby decreasing the amounts taken up by tree roots or percolated out of the tree pits into the ground water. A leaching test measured the retention of trace metals (Cd, Zn, Cu, and Pb) and deicing salts (Na) by different kinds of biochar. The biochar was produced from hardwood (North American ash tree, Fraxinus americana) under different pyrolysis conditions, with three temperatures (350, 465 and 550 °C) and two residence times (10 and 30 min). Biochar pyrolyzed at 550 °C for 30 min significantly reduced the soluble concentrations of Zn, Cu, and Pb in the column leachate, most likely due to the its higher pH, surface area, and ash content. The pH of each treatment group was measured while the increase in ash content and surface area was inferred according to relevant literature. This biochar was then combined with soil and compost at rates ranging from 0 to 7.5% by dry weight to determine the proportion that optimally sorbed the contaminants. An application rate of 7.5% biochar by dry weight increased the soil mixture's sorption capacity for Cd and Na while maintaining similar sorption of Cu, Zn, and Pb. The role of organic matter, such as that in compost, was especially important for the sorption of Zn and Cu. Hardwood biochar can thus improve the health of street trees and groundwater quality by sequestering trace metals and de-icing salts. Biochar can also be a useful tool to remediate contaminated soil, especially in urban environments.
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The Generalized Anxiety Disorder Screener (GAD-7) and the anxiety module of the Hospital and Depression Scale (HADS-A) as screening tools for generalized anxiety disorder among cancer patients
Abstract
Objective
Anxiety in cancer patients may represent a normal psychological reaction. To detect patients with pathological levels, appropriate screeners with established cut-offs are needed. Given that previous research is sparse, we investigated the diagnostic accuracy of two frequently used screening tools in detecting generalized anxiety disorder (GAD).
Methods
We used data of a multi-center study including 2141 cancer patients. Diagnostic accuracy was investigated for the Generalized Anxiety Disorder Screener (GAD-7) and the anxiety module of the Hospital Anxiety and Depression Scale (HADS-A). GAD, assessed with the Composite International Diagnostic Interview for Oncology, served as a reference standard. Overall accuracy was measured with the area under the receiver operating characteristics curve (AUC). The AUC of the two screeners were statistically compared. We also calculated accuracy measures for selected cut-offs.
Results
Diagnostic accuracy could be interpreted as adequate for both screeners, with an identical AUC of .81 (95 % CI: .79 – .82). Consequently, the two screeners did not differ in their performance (p = .86). The best balance between sensitivity and specificity was found for cut-offs ≥ 7 (GAD-7) and ≥ 8 (HADS-A). The officially recommended thresholds for the GAD-7 (≥ 10) and the HADS-A (≥11) showed low sensitivities of 55 % and 48 %, respectively.
Conclusions
The GAD-7 and HADS-A showed AUC of adequate diagnostic accuracy and hence are applicable for GAD screening in cancer patients. Nevertheless, the choice of optimal cut-offs should be carefully evaluated.
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Post-traumatic growth in head and neck cancer survivors: is it possible and what are the correlates?
Abstract
Objectives
Posttraumatic growth (PTG) is a possible positive consequence of a traumatic event, such as cancer. Head and neck cancer (HNC) may be particularly traumatic, given its adverse effects on functional, psychological and social wellbeing. We investigated: extent of PTG; factors associated with PTG; and associations between PTG and health-related quality-of-life (HRQoL) in HNC survivors.
Methods
HNC survivors (ICD10 C00-C14, C32), identified from the population-based National Cancer Registry Ireland, completed a postal survey. PTG was assessed using the Posttraumatic Growth Inventory (PTG-I) and HRQoL with FACT-G and FACT-HN. Associations between socio-economic characteristics, social support, and clinical variables and PTG were examined using multivariable linear regression. Total HRQoL scores were compared in those with none-low PTG vs moderate-high PTG.
Results
583 survivors participated (response rate=59%). The mean PTG score was 55.74 (95%CI 53.15-58.33); 60% had moderate-high PTG. Survivors scored highest in the PTG-I domain appreciation of life. In multivariable analysis, being female, being younger, having more social support and having cancer-related financial stress were significantly associated with more PTG. HRQoL was significantly higher in those with moderate-high than no-little PTG (p<0.01)
Conclusion
A notable proportion of HNC survivors report PTG but growth is, on average, lower than reported for other cancers. Nonetheless, higher PTG appears related to better HRQoL. Further research would be valuable to understand the pathways by which HNC may lead to PTG and inform development of strategies to support and encourage PTG in this survivor population.
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Antero-cervical thermophysiological characterization of obstructive sleep apnea patients
Abstract
Purpose
Obstructive sleep apnea syndrome (OSAS) is characterized by upper airway inflammation. The aim of this study was to characterize thermal profile of the antero-cervical region in OSAS patients through medical thermal imaging and to compare the respective subjects with non-OSAS individuals.
Methods
Image capture followed the Glamorgan Protocol. A dynamic thermographic examination of the anterior cervical region (at baseline and after a cold stimulus) was conducted in 26 patients diagnosed with overnight polysomnography (PSG). PSG results stratified the subjects into OSAS and non-OSAS groups and their thermograms were compared.
Results
Eleven non-OSAS and 15 OSAS subjects were evaluated. Antero-cervical right side (RS) temperature was higher in OSAS group at baseline (p = 0.014). Right side index (RSI) temperature—the difference between RS and submental region, considered as control—was lower in OSAS subjects at baseline (p = 0.020) and 10 min after the cold stimuli was applied (p = 0.008), indicating higher absolute temperatures in this group. Left side index (LSI) was also lower at 10 min in OSAS group (p = 0.021). Statistical correlation was found between apnea-hypopnea index and RS at baseline (r = 0.424, p = 0.031) and at 10 min (r = 0.403, p = 0.041) and RSI at baseline (r = − 0.458, p = 0.019) and 10 min after cold provocation was applied (r = − 0.435, p = 0.025).
Conclusions
OSAS patients have shown higher antero-cervical temperatures compared with non-OSAS counterparts and temperature was associated with severity of the condition. Medical thermography may be a suitable tool in the setting of OSAS suspicion.
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Prostatectomies for localized prostate cancer: a mixed comparison network and cumulative meta-analysis
Abstract
No consensus has been attained regarding the utility of open retropubic radical prostatectomy (RRP), laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALRP) for localized prostate cancer (PCa). We carried out a network meta-analysis and cumulative meta-analysis comparing RRP, LRP and RALRP on peri-operative and functional outcome measures. Electronic databases were searched for either randomized clinical trials or cohort studies comparing RALRP either with LRP or RRP in patients with localized PCa. Outcome measures were as follows: overall, pT2 and pT3-positive surgical margins (PSMs); biochemical recurrence (BCR); complication rates; estimated blood loss; blood transfusion rate; continence and potency rates; duration of catheterization and hospital stay. Publication bias, risk of bias and inconsistency were assessed. Inverse heterogeneity model was used for analysis. A total of 45 studies were included for the final analysis. We observed that RALRP and LRP did not differ significantly from RRP with regard to the following outcomes: overall PSM; pT2 and pT3 PSMs; OT; complication rate; continence and potency rates; total blood loss and hospital stay. Duration of catheterization was significantly shorter in RALRP than LRP and RRP while significant reductions in the need for blood transfusion and BCR were observed for both RALRP and LRP in comparison with RRP. To conclude, similar functional, operative and oncologic outcomes were observed for both RALRP and LRP compared to RRP.
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Developmental and degenerative cardiac defects in the Taiwanese mouse model of severe spinal muscular atrophy
Abstract
Spinal muscular atrophy (SMA), an autosomal recessive disease caused by a decrease in levels of the survival motor neuron (SMN) protein, is the most common genetic cause of infant mortality. Although neuromuscular pathology is the most severe feature of SMA, other organs and tissues, including the heart, are also known to be affected in both patients and animal models. Here, we provide new insights into changes occurring in the heart, predominantly at pre- and early symptomatic ages, in the Taiwanese mouse model of severe SMA. Thinning of the interventricular septum and dilation of the ventricles occurred at pre- and early symptomatic ages. However, the left ventricular wall was significantly thinner in SMA mice from birth, occurring prior to any overt neuromuscular symptoms. Alterations in collagen IV protein from birth indicated changes to the basement membrane and contributed to the abnormal arrangement of cardiomyocytes in SMA hearts. This raises the possibility that developmental defects, occurring prenatally, may contribute to cardiac pathology in SMA. In addition, cardiomyocytes in SMA hearts exhibited oxidative stress at pre-symptomatic ages and increased apoptosis during early symptomatic stages of disease. Heart microvasculature was similarly decreased at an early symptomatic age, likely contributing to the oxidative stress and apoptosis phenotypes observed. Finally, an increased incidence of blood retention in SMA hearts post-fixation suggests the likelihood of functional defects, resulting in blood pooling. These pathologies mirror dilated cardiomyopathy, with clear consequences for heart function that would likely contribute to potential heart failure. Our findings add significant additional experimental evidence in support of the requirement to develop systemic therapies for SMA capable of treating non-neuromuscular pathologies.
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Cause-specific mortality in patients with head and neck cancer: Long-term follow-up of a population-based cohort from 1986 to 2012 accounting for competing risks
Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Janne A. Väisänen, Olli-Pekka Alho, Petri T. Koivunen, Esa Läärä
ObjectivesRecent recommendations for treating head and neck cancer (HNC) patients favor an individualized approach. Expected long-term survival – together with short-term survival – after diagnosis is the primary focus in assessing the treatment modality and follow-up scheme. "Disease-specific" survival up to five years is often used for measuring the prognosis and for assessing treatment methods. However, especially long-term survival is strongly affected by competing causes of death among HNC patients.Materials and MethodsThe long-term prognosis of patients with HNC in terms of mortality from both cancer and competing causes was analyzed according to recent methodological guidelines by examining cumulative incidence functions and models for cause-specific hazards and sub-distribution hazards in a population based cohort of 220 patients treated in a tertiary care center in Northern Finland.ResultsIn addition to well-known tumor-related factors, mortality from HNC was associated with older age. The mortality from other causes of death was strongly dependent on age and Charlson's Comorbidity Index, but less on gender. When demonstrating the importance of individualized approach in simulated patients, the mortality was highly variable across patients with similar cancer status, but with different comorbidities or age.ConclusionThe overall survival pattern of HNC patients depends not only on their cancer characteristics, but also varies greatly according to their age and comorbidities. Our findings support the need for individualized treatment and follow-up protocols, and active management of comorbid diseases. Appropriate methods for analyzing competing risks should be used when presenting survival estimates of cancer patients.
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The impact of HPV status on weight loss and feeding tube use in oropharyngeal carcinoma
Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Belinda Vangelov, Damian P. Kotevski, Janet R. Williams, Robert I. Smee
ObjectivesIt has been well established that patients with oropharyngeal carcinoma are at high nutritional risk, with significant weight loss and tube feeding common. Human papillomavirus (HPV)-associated disease has led to a change in the "typical" presentation and nutritional profile of this population. The aim of our study was to determine whether the need for a feeding tube, and weight loss during radiotherapy (RT) in patients with oropharyngeal carcinoma differed with HPV status.Materials and methodsPatients who received curative RT ± chemotherapy from January 2011 to January 2016 were included (n = 100). We retrospectively evaluated feeding tube use and timing of insertion (prophylactic vs reactive), percentage weight loss during RT and the prevalence of critical weight loss (CWL) ≥5%.ResultsHPV-positive patients had significantly higher weight loss during RT compared to the rest of the cohort (8.4% vs 6.1%, 95%CI 0.8–3.9, p = 0.003). CWL was observed in 86% and in a higher proportion with HPV-positive disease (93%, p = 0.011). Conditional probability modelling analysis revealed, with 74% accuracy, concurrent chemoradiotherapy and HPV-positive status were predictors of CWL when comparing HPV-positive patients to HPV-negative (96%, p = 0.001 and 98%, p = 0.012 respectively). More HPV-positive patients required feeding tubes (n = 43, 63%, p = 0.05), most being reactive (n = 27, 63%). All patients with reactive tubes experienced CWL.ConclusionThe high incidence of CWL in patients with HPV-positive oropharyngeal carcinoma is of concern. Tube feeding continues to be a necessary nutritional intervention in this population and predicting who will require a tube is challenging. Larger, prospective cohort studies are required.
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Tumor volume as a predictor of survival in T3 glottic carcinoma: A novel approach to patient selection
Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Peter T. Dziegielewski, William J. Reschly, Chris G. Morris, Reordan Danny DeJesus, Natalie Silver, Brian J. Boyce, Inocente Santiago, Robert J. Amdur, William M. Mendenhall
BackgroundThe optimal treatment for T3 glottic cancers continues to be debated. Organ preservation has become the standard of care, but not all tumors respond equally. The purpose of this was to investigate the long-term survival outcomes of organ preservation protocols based on tumor volume.MethodsA retrospective review of prospectively collected data from 1966 to 2016 was performed. Patients with T3 vocal cord cancer treated with radiation therapy (RT) at the University of Florida were included. Local control rates as well as survival rates were determined with a Kaplan Meier and Cox regression analysis. Survival was analyzed as a function of tumor volume and an optimal cut point was determined.Results107/234 patients were included. 79% received RT and 21% chemo-RT. 5-year local control was 61.5% and 5-year disease specific survival was 79.3%. Tumor volume was a significant predictor of survival (p = 0.007). An optimal cut point for tumor volume was 2.5 cc. Patients with tumor volumes ≥2.5 cc had significantly worse (p < 0.05) tumor control rates (100% vs. 70.4%).ConclusionTumor volume is a significant predictor of survival outcomes in T3 vocal cord cancers, but will need external validation. Tumors <2.5 cc have favorable outcomes. Those with higher volume tumors should be counselled appropriately and be considered for primary surgical management.
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Central nervous system relapse in patients over 80 years with diffuse large B-cell lymphoma: an analysis of two LYSA studies
Abstract
CNS relapse is reported in 2–5% of diffuse large B-cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03-7B, LNH09-7B) evaluating the addition of rituximab or ofatumumab to mini-CHOP as front-line therapy. No patients received CNS prophylaxis. CNS relapse was evaluated according to cumulative incidence, patient characteristics, risk factors, and survival. Median age was 83 years (range: 79–95). After a median follow-up of 28.7 months, eight patients had CNS relapse (3.0%). Median time between inclusion and CNS relapse was 19.2 months (range: 3.2–32.6). Patients survived a median of 1.5 months after CNS relapse (range: 0.4–4.1). Median OS from relapse was significantly lower in CNS relapse patients (1.5 months, 95% CI: 0.4–3.5) compared to patients with non-CNS relapse (6.6 months; 95% CI: 4.6–11.9). No baseline characteristics were associated with CNS relapse. The proportion of patients with CNS disease did not differ significantly between patients with low-intermediate risk according to CNS-IPI and patients with high risk (3% vs. 2.8%, P = 1.00). CNS relapse cumulative incidence in very elderly treatment-naive patients is 1.8% at 2 years and is associated with poor survival. This population had a long median time to CNS relapse. Absence of prophylaxis did not strongly impact CNS relapse incidence.
Cumulative incidence of CNS relapse at 2 years in patients with diffuse large B-cell lymphoma aged over than 80 is 1.8% and is associated with a very poor survival. The absence of prophylaxis did not appear to have a strong impact on CNS relapse incidence. Consequently CNS prophylaxis can be avoided in this population given the potential for a negative impact of the associated toxicities.
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Employment benefits and job retention: evidence among patients with colorectal cancer
Abstract
A "health shock," that is, a large, unanticipated adverse health event, can have long-term financial implications for patients and their families. Colorectal cancer is the third most commonly diagnosed cancer among men and women and is an example of a specific health shock. We examined whether specific benefits (employer-based health insurance, paid sick leave, extended sick leave, unpaid time off, disability benefits) are associated with job retention after diagnosis and treatment of colorectal cancer. In 2011–14, we surveyed patients with Stage III colorectal cancer from two representative SEER registries. The final sample was 1301 patients (68% survey response rate). For this study, we excluded 735 respondents who were not employed and 20 with unknown employment status. The final analytic sample included 546 respondents. Job retention in the year following diagnosis was assessed, and multivariable logistic regression was used to evaluate associations between job retention and access to specific employment benefits. Employer-based health insurance (OR = 2.97; 95% CI = 1.56–6.01; P = 0.003) and paid sick leave (OR = 2.93; 95% CI = 1.23–6.98; P = 0.015) were significantly associated with job retention, after adjusting for sociodemographic, clinical, geographic, and job characteristics.
A "health shock," that is, a large, unanticipated adverse health event, can have long-term financial implications for patients and their families. We examined whether specific benefits (employer-based health insurance, paid sick leave, extended sick leave, unpaid time off, disability benefits) are associated with job retention after diagnosis and treatment of colorectal cancer, an example of a specific health shock. Employer-based health insurance and paid sick leave were associated with job retention.
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Intranasally Delivered Wnt3a Improves Functional Recovery after Traumatic Brain Injury by Modulating Autophagic, Apoptotic, and Regenerative Pathways in the Mouse Brain
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Adult Wilms tumor with inferior vena cava thrombus and distal deep vein thrombosis – a case report and literature review
Abstract
Background
Adult Wilms tumor (WT, nephroblastoma) is a rare, but well-described renal neoplasm. Although inferior vena cava tumor thrombosis is present in up to 10% of Wilms tumors in childhood, only few cases of this clinical manifestation in adults have been reported. To the best of our knowledge, this is the first case of adult WT infiltrating into inferior vena cava (IVC) with concomitant distal deep vein thrombosis.
Case presentation
A 28-year-old male patient with gross hematuria and right flank pain was diagnosed with right kidney tumor penetrating to IVC. Preoperatively, acute distal thrombosis in inferior vena cava and lower extremities veins occurred. Right radical nephrectomy with tumor thrombectomy via cavotomy was performed. In order to prevent pulmonary embolism, IVC was ligated below left renal vein level. Histopathological examination revealed a triphasic nephroblastoma without anaplastic features. Postoperatively, patient was diagnosed with metastatic liver disease, which was treated with two lines of chemotherapy followed by radiotherapy with achievement of complete response.
Conclusions
Adult WT occurs usually in young patients, under 40 years of age. Neoadjuvant chemotherapy proved to be effective in children, resulting with tumor shrinkage and venous tumor thrombus regression. Therefore, percutaneous biopsy should be always considered in young patients presenting with renal tumor invading venous system. IVC ligation is a safe treatment option in the event of complete inferior vena cava occlusion due to distal thrombosis concomitant to tumor thrombus, provided collateral venous pathways are well-developed.
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Prediction of suboptimal cytoreductive surgery in patients with advanced ovarian cancer based on preoperative and intraoperative determination of the peritoneal carcinomatosis index
Abstract
Background
The peritoneal carcinomatosis index (PCI) can be used to quantify the tumor burden in patients with advanced ovarian cancer. The aim of the present study was to establish a predictive model for suboptimal cytoreductive surgery (SCS) (residual tumor of > 1 cm) using preoperative and intraoperative determination of the PCI.
Methods
In total, 110 consecutive patients treated for advanced ovarian cancer during a 4-year period in our institution were assessed. Eighty of these patients were eligible for primary debulking surgery and thus included in the present study. All data were prospectively collected and retrospectively evaluated. We determined the PCI both preoperatively and intraoperatively and assessed postoperative complications.
Results
A PCI of > 20 was the best cut-off with which to predict a risk of SCS among all three diagnostic techniques assessed in this study (computed tomography, laparoscopy, and laparotomy). Intraoperative PCI determination was associated with the lowest risk of false negatives for SCS when detecting a PCI of < 20. The combination of preoperative computed tomography and laparoscopy, when both techniques predicted SCS, was associated with the lowest risk of false positives for SCS when detecting a PCI of > 20.
Conclusion
The combination of computed tomography and laparoscopy to obtain the PCI can help to determine which patients with advanced ovarian cancer are suitable for primary debulking surgery and which should undergo neoadjuvant chemotherapy.
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The extremity localized classic osteosarcomas have better survival than the axial non-classics
Abstract
Background
Osteosarcoma is one of the most malignant primary bone cancers, while is rarely reported in China. Of note, very few data of prognosis has been documented in this region. Thus, we carried a retrospective study to identify prognostic factors and to analyze outcomes in patients of both classic and non-classic high-grade osteosarcomas. Classic osteosarcoma is defined as of high-grade histology, age below 40 years, with extremity localized primary tumor, and without detectable metastasis at primary diagnosis.
Methods
A total of 98 patients (68 classic and 30 non-classic) aged from 4 to 64 years old were diagnosed as high-grade osteosarcoma from 2008 to 2015 in Nanfang Hospital, Guangzhou, China. Univariate and multivariate analyses were performed to identify the independent predictors for overall survival and event-free survival. Kaplan-Meier method was used for survival analysis.
Results
The median overall survival was 117 vs. 21 months, and the median event-free survival was 31 vs. 6 months in classic and non-classic osteosarcoma, respectively. The most frequently found tumor site was around the knee. The classic osteosarcoma had better overall survival and event-free survival than the non-classics. Tumor site and primary metastasis were found to be associated with overall survival and event-free survival in the univariate analysis. In the multivariate Cox regression analysis, tumor site and primary metastasis were each verified as independent prognostic factors. However, no similar result was found in elevated serum alkaline phosphatase or lactate dehydrogenase. Amputation or limb salvage surgery had no significant effect on overall survival and event-free survival in the extremity osteosarcomas. Classic osteosarcomas with extremity tumor site and free of primary metastasis exhibited better overall survival and event-free survival, while the axial and metastatic non-classics exhibited the worse.
Conclusions
The extremity classic osteosarcomas have better survivals than the axial non-classic cases. Amputation and limb salvage surgery make no significant change in overall survival and event-free survival in the extremity osteosarcomas.
Trial registration
Nanfang2013071; Date of registration: 7 September 2013 (retrospectively registered).
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Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS
Publication date: Available online 22 February 2018
Source:Cancer Cell
Author(s): Takuji Yamauchi, Takeshi Masuda, Matthew C. Canver, Michael Seiler, Yuichiro Semba, Mohammad Shboul, Mohammed Al-Raqad, Manami Maeda, Vivien A.C. Schoonenberg, Mitchel A. Cole, Claudio Macias-Trevino, Yuichi Ishikawa, Qiuming Yao, Michitaka Nakano, Fumio Arai, Stuart H. Orkin, Bruno Reversade, Silvia Buonamici, Luca Pinello, Koichi Akashi, Daniel E. Bauer, Takahiro Maeda
To identify novel targets for acute myeloid leukemia (AML) therapy, we performed genome-wide CRISPR-Cas9 screening using AML cell lines, followed by a second screen in vivo. Here, we show that the mRNA decapping enzyme scavenger (DCPS) gene is essential for AML cell survival. The DCPS enzyme interacted with components of pre-mRNA metabolic pathways, including spliceosomes, as revealed by mass spectrometry. RG3039, a DCPS inhibitor originally developed to treat spinal muscular atrophy, exhibited anti-leukemic activity via inducing pre-mRNA mis-splicing. Humans harboring germline biallelic DCPS loss-of-function mutations do not exhibit aberrant hematologic phenotypes, indicating that DCPS is dispensable for human hematopoiesis. Our findings shed light on a pre-mRNA metabolic pathway and identify DCPS as a target for AML therapy.
Graphical abstract
Teaser
Yamauchi et al. perform in vitro and in vivo CRISPR-Cas9 genetic screening of p53 WT AML to identify potential therapeutic targets. They find that AML relies on the DCPS decapping enzyme, and a DCPS inhibitor shows anti-leukemia activity in tumor models without impacting normal hematopoiesis.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GDNXlw
The role of tonsillectomy in the Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis syndrome; a literature review
Tonsillectomy (TE) or adenotonsillectomy (ATE) may have a beneficial effect on the clinical course in children with the Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis (PFAPA) syndrome. ...
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Dural Invasion Predicts the Laterality and Development of Neck Metastases in Esthesioneuroblastoma
J Neurol Surg B
DOI: 10.1055/s-0038-1625977
Objectives Neck metastases in patients with esthesioneuroblastoma (ENB) constitute the most significant predictor of poor long-term survival. Recently, researchers discovered the existence of dural lymphatic channels that drain to the cervical lymph nodes. From this physiologic basis, we hypothesized that patients with ENB who develop dural invasion (DI) would exhibit a proclivity for neck metastases. Design Retrospective review. Setting Tertiary referral center. Participants All patients treated for ENB from January 1, 1994 to December 31, 2015. Main Outcome Measures Incidence, laterality, and recurrence rate of neck metastases by DI status. Results Sixty-one patients were identified (38% female; median age 49, range, 10–80), 34 (56%) of whom had DI and 27 (44%) did not. Of patients with DI, 50% presented with or developed neck disease following treatment compared with just 22% of those without DI (p = 0.026). Bilateral neck disease was more common in patients with DI (11/34, 32%) compared with those without (2/27, 7%) (p = 0.018). Five-year regional recurrence-free survival rates were 88% for those without and 64% for those with DI (p = 0.022). Kadish C patients with DI were more likely to develop regional recurrence when compared with Kadish C without DI and Kadish A/B (p = 0.083). Further, Kadish C patients with DI displayed worse overall survival than Kadish C without DI and Kadish A/B. Kadish D patients displayed the worst overall survival. The difference in overall survival among these four groups was significant (p < 0.001). Conclusion DI by ENB is associated with increased incidence of cervical nodal metastases, bilateral neck disease, worse regional recurrence-free survival, and poorer overall survival. These data support the division of Kadish C by DI status.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Ixazomib in the management of relapsed multiple myeloma
Future Oncology, Ahead of Print.
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Reporting guidelines for oncology research: helping to maximise the impact of your research
Reporting guidelines for oncology research: helping to maximise the impact of your research
Reporting guidelines for oncology research: helping to maximise the impact of your research, Published online: 22 February 2018; doi:10.1038/bjc.2017.407
Reporting guidelines for oncology research: helping to maximise the impact of your research
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EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting
EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting
EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting, Published online: 22 February 2018; doi:10.1038/bjc.2017.427
EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting
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Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery
Publication date: Available online 22 February 2018
Source:Brain Stimulation
Author(s): Martin Keller, Wolfgang Taube, Benedikt Lauber
BackgroundMotor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions.ObjectiveThe aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions.MethodsH-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest.ResultsIn contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions.ConclusionsThis study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex.
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Mass spectrometry-based proteomics reveals potential roles of NEK9 and MAP2K4 in resistance to PI3K inhibitors in triple negative breast cancers
Activation of phosphoinositide 3-kinase (PI3K) signaling is frequently observed in triple-negative breast cancer (TNBC), yet PI3K inhibitors have shown limited clinical activity. To investigate intrinsic and adaptive mechanisms of resistance, we analyzed a panel of patient-derived xenograft models of TNBC with varying responsiveness to buparlisib, a pan-PI3K inhibitor. In a subset of patient-derived xenografts, resistance was associated with incomplete inhibition of PI3K signaling and upregulated MAPK/MEK signaling in response to buparlisib. Outlier phosphoproteome and kinome analyses identified novel candidates functionally important to buparlisib resistance, including NEK9 and MAP2K4. Knockdown of NEK9 or MAP2K4 reduced both baseline and feedback MAPK/MEK signaling and showed synthetic lethality with buparlisib in vitro. A complex in/del frameshift in PIK3CA decreased sensitivity to buparlisib via NEK9/MAP2K4-dependent mechanisms. In summary, our study supports a role for NEK9 and MAP2K4 in mediating buparlisib resistance and demonstrates the value of unbiased omic analyses in uncovering resistance mechanisms to targeted therapy.
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Genetic Mosaicism and Cancer: Cause and Effect
Increasing theoretical and experimental evidence suggests that the genomes of both normal and cancer cells are subject to continuous changes as a result of copying errors during replication, defects in chromosome segregation during mitosis, and direct chemical attacks by reactive oxygen species. The process of cellular genetic diversification begins during embryonic development and continues throughout life, leading to the phenomenon of somatic mosaicism. New information about the genetic diversity of cells composing the body makes us reconsider the existing concepts of cancer etiology and pathogenesis. Here, I suggest that a progressively deteriorating microenvironment ("soil") generates the cancerous "seed" and favors its development. Cancer Res; 78(6); 1–4. ©2018 AACR.
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Managing unsolicited findings in genomics: a qualitative interview study with cancer patients.
Abstract
Objective
Next-generation sequencing (NGS) is increasingly being employed in the context of personalized cancer treatment. Anticipating unsolicited findings that may arise during a NGS procedure is a key consideration; however, little is known about cancer patients' intentions, needs, and preferences concerning the return of unsolicited findings.
Methods
A qualitative design using individual semi-structured interviews with 24 cancer patients was utilized to explore patients' decisions on whether to receive unsolicited findings from NGS. These interviews were subsequently analyzed using the constant comparative method to develop codes and themes.
Results
We identified four interrelated themes that emerged in the context of the return of unsolicited findings. First, we describe how cancer patients expressed a strong need to control their lives. Second, we show the importance of family dynamics. Third, the NGS procedure regarding unsolicited findings is perceived as cognitively complex, and fourth, the procedure is also considered emotionally complex.
Conclusions
The results of our study contribute to a better understanding of what cancer patients consider important and what may motivate and influence them when making decisions on the disclosure of unsolicited findings following NGS. We show how Joel Feinberg's classification of autonomy may help clinicians to better understand cancer patients' desire for autonomous decision making while also acknowledging the emotional and cognitive difficulties regarding the disclosure of unsolicited findings.These insights could be helpful for clinicians to guide patients through this complex process.
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Youmans and Winn Neurological Surgery, 7th edition, H. Richard Winn (Ed.). Elsevier (2016), 4320 pages
Source:World Neurosurgery, Volume 112
Author(s): William J. Mack
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Adult Tethered Cord Syndrome Following Chiari Decompression
Source:World Neurosurgery, Volume 112
Author(s): Christina Jackson, Brian W. Yang, Wenya Linda Bi, E. Antonio Chiocca, Michael W. Groff
BackgroundAdult tethered cord syndrome is a rare neurologic disorder that classically presents with back or leg pain, weakness, and urinary dysfunction. Spinal cord tethering has been associated with acquired Chiari malformations. Whereas the effects of tethered cord release on Chiari malformation symptoms have been described previously, we report an unusual case of acquired tethered cord syndrome following Chiari decompression.Case DescriptionWe report a 68-year-old man with a history of distant T12-level spinal cord injury and 2 weeks of progressive bilateral lower extremity weakness. The patient underwent a T12-L1 laminectomy in 1977, complicated by arachnoiditis and syringomyelia, with eventual placement of a syringopleural shunt. He remained neurologically stable until 2012, when he underwent a suboccipital craniectomy for Chiari decompression for new-onset headache and dysphagia. Ten days later, the patient noted progressive leg weakness and radiographic evidence of spinal cord tethering at the T11-T12 level. A T10-L1 laminectomy and medical facetectomy was undertaken for detethering with postoperative recovery of ambulatory function with assistance.ConclusionsOur patient exhibited an unusual acquisition of tethered cord syndrome. The tethering of the spinal cord may have been triggered by arachnoid adhesions from initial lumbar surgery 35 years before presentation and subsequently exacerbated by alterations of cerebrospinal fluid dynamics after Chiari decompression. Given the potentially devastating sequelae of tethered cord syndrome, investigation of cerebrospinal fluid flow dynamics may be beneficial before operative intervention in patients with risk factors for a tethered cord who exhibit adult-onset Chiari malformation.
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Ectopic Prolactinoma Presenting as Bacterial Meningitis: A Diagnostic Conundrum
Source:World Neurosurgery, Volume 112
Author(s): Oluwaseun O. Akinduro, Olutomi T. Akinduro, Vivek Gupta, Ronald Reimer, Osarenoma Olomu
BackgroundProlactinomas may rarely present with meningitis and cerebrospinal fluid (CSF) rhinorrhea secondary to erosion of the wall of the sella turcica. It is even more uncommon for this abnormal communication to be caused by an ectopic prolactinoma arising from the sphenoid sinus and eroding into the sella. This atypical growth pattern makes diagnosis very difficult because there may be no displacement of the normal pituitary gland. The first reported case of a patient with an ectopic prolactinoma originating within the sphenoid sinus presenting primarily with meningitis is presented, and the management strategy and surgical and nonsurgical treatment options are discussed.Case DescriptionA 48-year-old woman presented with confusion, low-pressure headache, and fever. A lumbar puncture revealed Streptococcus pneumoniae meningitis, and she was placed on intravenous penicillin G. After initiation of antibiotics, she noticed salty tasting postnasal fluid leakage. Imaging was remarkable for bony erosion of the sphenoid sinus wall by a soft tissue mass growing from within the sinus, with no disruption of the normal pituitary gland. A biopsy was then performed with an endoscopic transnasal transsphenoidal approach, and the CSF leak was repaired with a pedicled nasoseptal flap. The final pathology was prolactinoma, and she was placed on cabergoline.ConclusionsEctopic prolactinomas may rarely present as meningitis secondary to retrograde transmission of bacteria through a bony defect in the sphenoid sinus, and must be included in the differential diagnosis of any sphenoid sinus mass. Management should first address the infection, followed by surgical repair of the bony defect.
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Is Psychiatric Depression a Presenting Neurologic Sign of Meningioma? A Critical Review of the Literature with Causative Etiology
Source:World Neurosurgery, Volume 112
Author(s): Remi A. Kessler, Joshua Loewenstern, Karan Kohli, Raj K. Shrivastava
BackgroundBenign meningiomas constitute 80%–90% of all meningiomas and represent the most common type of central nervous system tumor in adults. The vast majority of meningiomas are minimally symptomatic or asymptomatic early in their onset and thereby can often result in delayed diagnosis. Early diagnosis of meningioma is critical, as it can maximize treatment options and improve outcomes and survival. Although seizures and focal neurologic deficits are considered to be the most prevalent symptoms, depression also may be an important and significant sign. A subtle neurologic depression may be an even early presenting sign of meningioma and may precede more traditional presenting symptoms.MethodsWe performed a comprehensive literature review that analyzes the results of prospective studies and case reports on this topic.ResultsOur findings show evidence to suggest that depression may be correlated with meningioma presentation. Its prevalence is possibly increased with an anterior location of the tumor.ConclusionsFor patients who exhibit nuances of depression without a history of psychiatric illness, an index of suspicion for meningioma may be warranted.
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Brain Abscess of Basal Ganglia Presenting with Persistent Hiccups
Source:World Neurosurgery, Volume 112
Author(s): Jared Sweeney, Alexa Bodman, Walter A. Hall
BackgroundBrain abscesses are well-known to neurologic surgeons with well-recognized presentations, which include seizures, neurologic deficit, and headache. Rare symptoms may lead to a delay in diagnosis, which can be life threatening in the setting of a brain abscess.Case DescriptionWe present the case of a 46-year-old male with intractable hiccups found to have an abscess of the right basal ganglia. The brain abscess was treated by frameless stereotactic-guided aspiration. The patient's hiccups improved after surgical aspiration and medical management.ConclusionsA comprehensive literature review confirmed brain abscess as a rare cause of intractable hiccups. In addition, there are few reports of lesions of the basal ganglia causing intractable hiccups. Aspiration and medical therapy resulted in resolution of the hiccups. Knowledge of the hiccup reflex arc and unusual presentation of basal ganglia lesions may shorten time to diagnosis.
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Laser-Induced Thermal Therapy in Neuro-Oncology: A Review
Source:World Neurosurgery, Volume 112
Author(s): Omar Ashraf, Nitesh V. Patel, Simon Hanft, Shabbar F. Danish
ObjectivesLaser therapy has become an appealing treatment modality in neurosurgery. In this review, we report on the history, physics, surgical steps, indications and uses, and complications that have been reported to date.MethodsAn extensive literature search was performed for laser interstitial thermal therapy (LITT) and laser therapy in the context of glial tumors, metastatic lesions, pediatric brain tumors, and radiation necrosis. Reported complications in each series also were reviewed.ResultsIn the past decade, multiple studies have demonstrated the use, outcomes, and complications associated with LITT in neurosurgery. These same studies have consistently reported an overall benefit of LITT in cases in which traditional surgical approaches may be limited by the patient's clinical status, tumor location, or overall prognosis. However, there have been complications reported from local effects of thermal damage, technical error, and edema development. Increased experience has reduced complications and brought more promising results.ConclusionsWith the advent of real-time monitoring and damage estimation, LITT has gained ground in the management of intracranial tumors. Larger scale trials must be performed to develop standard protocols to define specific indications for use. Further large clinical studies for LITT in non-oncologic cases are also of interest.
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Cervical Epidural Hematoma That Induced Sudden Paraparesis After Cervical Spine Massage: Case Report and Literature Review
Source:World Neurosurgery, Volume 112
Author(s): Je Il Ryu, Myung Hoon Han, Jae Min Kim, Choong Hyun Kim, Jin Hwan Cheong
BackgroundMost people understand spinal manipulation therapy to be a safe procedure, and in many cases treatment is provided without a diagnosis if there is musculoskeletal pain. Cervical epidural hematoma occurs in extremely rare cases after cervical manipulation therapy. This study reports a case of epidural hematoma that occurred in the anterior spinal cord after cervical massage.Case DescriptionA 38-year-old male patient was admitted to the emergency department for sudden weakness in the lower extremity after receiving a cervical spine massage. No fracture was found using cervical radiographs, and there were no particular findings on performing brain computed tomography or diffusion magnetic resonance imaging. However, using cervical magnetic resonance imaging, an acute epidural hematoma was observed in the anterior spinal cord from the C6 and C7 vertebrae to the T1 vertebra, compressing the spinal cord. There were no fractures or ligament injury. No surgical treatment was required as the patient showed spontaneous improvements in muscle strength and was discharged after just 1 week, following observation of the improvement in his symptoms.ConclusionAlthough cervical epidural hematoma after cervical manipulation therapy is extremely rare, if suspected, a thorough examination must be performed in order to reduce the chances of serious neurologic sequelae.
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Intracranial Vessel Wall Imaging with Magnetic Resonance Imaging: Current Techniques and Applications
Source:World Neurosurgery, Volume 112
Author(s): Haur Wey Tan, Xiao Chen, Julian Maingard, Christen D. Barras, Caitriona Logan, Vincent Thijs, Hong Kuan Kok, Michael J. Lee, Ronil V. Chandra, Mark Brooks, Hamed Asadi
Vessel wall magnetic resonance imaging (VW-MRI) is a modern imaging technique with expanding applications in the characterization of intracranial vessel wall pathology. VW-MRI provides added diagnostic capacity compared with conventional luminal imaging methods. This review explores the principles of VW-MRI and typical imaging features of various vessel wall pathologies, such as atherosclerosis, dissection, and vasculitis. Radiologists should be familiar with this important imaging technique, given its increasing use and future relevance to everyday practice.
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Endoscopic Endonasal Transrotundum Middle Fossa Exposure: Technique of Transpterygoid Maxillary Nerve Transposition
Source:World Neurosurgery, Volume 112
Author(s): Ricky H. Wong
ObjectiveMiddle fossa floor access can be challenging. Open skull base approaches have associated morbidity and yield suboptimal working angles around the temporal lobe. Endoscopic endonasal approaches to the middle fossa are poorly described, but provide an improved angle. I hypothesized that the length of the maxillary nerve can be transposed out of the foramen rotundum to provide a path to expose the full width of the middle fossa floor through the anterolateral and anteromedial triangle.MethodsEndoscopic endonasal transpterygoid dissections to expose the middle fossa were performed bilaterally on 2 silicone-injected cadaveric heads (4 sides). Transposition of V2 was then performed on all sides, and additional middle fossa exposure was achieved. High-resolution computed tomography imaging was obtained to quantify the extent of exposure. A transzygomatic approach was also performed for comparison.ResultsThe maxillary nerve was successfully transposed in each dissection. A periosteal fold was identified to assist in the mobilization of the infraorbital nerve. The average middle fossa exposure achieved without transposition was 50% (of the medial to lateral width). Transposition increased that to 95%. Comparison with the open transzygomatic approach demonstrated superior surgical trajectory (inferior to superior) with the endonasal route.ConclusionsEndoscopic endonasal transpterygoid approaches with or without transposition of the maxillary nerve provide a reasonable option for sequentially exposing the entire medial to lateral extent of the anterolateral triangle. It provides an advantageous inferior to superior surgical angle and can be considered for treatment of select middle fossa floor pathology.
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Cerebellar Vermian Epidermoid Tumor: A Report of 2 Cases
Source:World Neurosurgery, Volume 112
Author(s): James A. Balogun, Nurudeen A. Adeleke, Ayodeji O. Salami, Timothy O. Odebode
BackgroundEpidermoid tumors are rare, benign slow-growing congenital tumors, most frequently located in the cerebellopontine angle of the intracranial cavity. They usually grow to a large size before patients become symptomatic. Although these tumors are amenable to surgery, their adherence to neurovascular structures poses a surgical challenge that results in subtotal resection, thus increasing the risk of recurrence.Case DescriptionWe report 2 adult patients whose imaging studies revealed epidermoid tumors located in the cerebellar vermis, an uncommon site for such tumors. The patients presented with variable symptomatology. We highlight the imaging features and challenges of surgery. Both patients had good outcomes, with resolution of symptoms and neurologic deficits.ConclusionsA safe complete excision of epidermoid tumor and its capsule is possible with a good understanding of their clinical and radiologic features and a high index of suspicion. To the best of our knowledge, this is the first report of cerebellar vermian epidermoid tumors from sub-Saharan Africa.
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Extraventricular Neurocytoma in the Left Frontal Lobe: A Case Report and Literature Review
Source:World Neurosurgery, Volume 112
Author(s): Fan Chen, Rihua Jin, Xinmin Wu, Zengping Dong, Dawei Chen
BackgroundNeurocytoma is a rare brain neoplasm of neuroepithelial origin that occurs predominantly in the ventricular system adjacent to the interventricular foramen and septum pellucidum. However, extraventricular neurocytoma is an extremely rare entity, with poor clinical, radiologic, and histopathological characterization. Here we report a case of an extraventricular parafalcine neurocytoma in the left frontal lobe. We also examine previously reported cases of extraventricular neurocytoma in an attempt to provide an up-to-date summary of the condition.MethodsA literature search was performed using PubMed with specific key terms, inclusion criteria, and exclusion criteria. Selected case studies and case series were then compared, and statistical analyses were performed where appropriate. We report a 59-year-old woman presenting with weakness in her right leg and urinary incontinence. Physical examination revealed muscle strength of grade 3/5 in the right lower extremity. Brain magnetic resonance imaging showed a parafalcine mass in the left frontal lobe, with perilesional edema; the cerebral falx and lateral ventricle were shifted due to the compression. Gross total resection was performed.ResultsHistopathological examination revealed a neurocytoma. Immunohistochemical staining showed diffuse positivity for synaptophysin. MIB-1 staining for Ki-67 antibody showed a labeling index of 20%. No adjuvant radiation or chemotherapy was administered. Brain computed tomography performed at a 3-month follow-up showed no signs of recurrence.ConclusionExtraventricular neurocytoma occurring in the brain parenchyma is a very rare central nervous system tumor. Its clinical and radiologic manifestations are nonspecific. The diagnosis depends on histopathological and immunohistochemical examination. Surgical resection should be the first-choice treatment.
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Rapid Intraoperative in Situ Synthetic Cranioplasty
Source:World Neurosurgery, Volume 112
Author(s): Christopher C. Young, Brian W. Hanak, Anoop P. Patel, Laligam N. Sekhar
Craniectomy is a frequently performed neurosurgical procedure, and coverage of the cranial defect is necessary for protection of the underlying brain, cosmesis, and patient satisfaction. We report a new technique for intraoperative in situ synthetic cranioplasty that provides one-step resection of skull osteomas and reconstruction of cranial defects. Strategies of intraoperative cranioplasty are reviewed. A 48-year-old man who presented with a suspected benign osteoma over his forehead was offered surgical excision and primary cranioplasty in a one-step procedure using hydroxyapatite bone cement, a dural prosthetic, and a resorbable plate. Following craniectomy around the lesion, there was evidence of dural and bone involvement. The craniectomy was enlarged, and the involved dura was resected. SYNTHECEL dura repair was used to repair the dural defect and at the same time fashioned to form a receptacle for the cranioplasty by fixation of the dural substrate to the cut vertical bone edges. DirectInject hydroxyapatite bone cement was used to fill the receptacle and contoured to the curvature of the adjacent skull. A Delta resorbable plate was then placed over the bone cement and fixed to the skull. This technique provided a satisfactory cosmetic outcome following craniectomy for benign skull tumor excision. When possible, one-step surgery with primary cranioplasty should be considered.
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Massive Primary Intraventricular Hemorrhage Due to Idiopathic Lateral Posterior Choroidal Artery Aneurysm: Case Illustration
Source:World Neurosurgery, Volume 112
Author(s): Gökhan Bozkurt, Mesut Emre Yaman, Serdar Çevik, İsmail Kırbaş, Banu Yağmurlu
Peripheral aneurysms of the lateral posterior choroidal artery are rare and mostly in association with vascular and occlusive pathologies such as moyamoya disease. To the best of our knowledge, pure lateral posterior choroidal artery aneurysms without association of any other vascular diseases are unique and only 3 cases have been reported in the literature.
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Malignant Peripheral Nerve Sheath Tumor of the Trigeminal Nerve Involving the Middle and Posterior Cranial Fossa
Source:World Neurosurgery, Volume 112
Author(s): Aijun Liang, Bin Xi, Chaoyang Zhou, Yu Yang, Jianzhong Zhang, Shaogao Gui, Fanghua Xu, Dengfeng Wan
BackgroundAlthough benign trigeminal schwannomas are uncommon, malignant peripheral nerve sheath tumors (MPNSTs) of the trigeminal nerve are extraordinarily rare.Case DescriptionA 56-year-old female presented with a 2-month-long history of numbness of the right face and progressive weakness of the left limbs. Preoperative neuroimages indicated a giant tumor involving the middle and posterior cranial fossa with similar radiologic characteristics to benign trigeminal schwannomas. However, histopathologic and immunochemical examinations confirmed the tumor to be an MPNST. A nearly gross total resection was obtained with a combined frontotemporal extradural and subtemporal anterior petrosal approach. The postoperative course was uneventful, and the patient received adjuvant radiotherapy subsequently. There was no recurrence of the tumor with a 6-month-long follow-up.ConclusionMPNSTs of the trigeminal nerve are exceedingly rare. This study described the 21st case of MPNSTs of the trigeminal nerve. MPNSTs of the trigeminal nerve showed similar radiologic characteristics to benign trigeminal schwannomas, and accurate diagnosis depended on pathologic and immunochemical examinations. Gross total resection followed by radiotherapy is the usual treatment.
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IV Brazilian Consensus on Rhinitis - an update on allergic rhinitis,
Abstract Introduction The guidelines on allergic rhinitis aim to update knowledge about the disease and care for affected patients. The initiative called "Allergic Rhinitis and its Impact on Asthma", initially published in 2001 and updated in 2008 and 2010, has been very successful in disseminating information and evidence, as well as providing a classification of severity and proposing a systemized treatment protocol. In order to include the participation of other medical professionals in the treatment of allergic rhinitis, it is important to develop algorithms that accurately indicate what should and can be done regionally. Objective To update the III Brazilian Consensus on Rhinitis - 2012, with the creation of an algorithm for allergic rhinitis management. Methods We invited 24 experts nominated by the Brazilian Association of Allergy and Immunology, Brazilian Association of Otorhinolaryngology and Head and Neck Surgery and Brazilian Society of Pediatrics to update the 2012 document. Results The update of the last Brazilian Consensus on Rhinitis incorporated and adapted the relevant information published in all "Allergic Rhinitis and its Impact on Asthma" Initiative documents to the Brazilian scenario, bringing new concepts such as local allergic rhinitis, new drugs and treatment evaluation methods. Conclusion A flowchart for allergic rhinitis treatment has been proposed.
Resumo Introdução As diretrizes sobre rinite alergica visam atualizar os conhecimentos sobre a doença e os cuidados para com esses pacientes. A iniciativa designada "Rinite Alergica e seu Impacto na Asma", cujo relatorio inicial foi publicado em 2001 e atualizada em 2008 e 2010, tem sido muito bem sucedida na disseminaçao de informaçoes e evidencias, bem como na formulaçao da classificaçao de gravidade e proposta de sistematizaçao do tratamento. Entretanto, visando a participaçao de outros profissionais medicos no atendimento da rinite alergica, e importante o desenvolvimento de algoritmos que indiquem com precisao o que deve e pode ser feito regionalmente. Objetivo Atualizar o III Consenso Brasileiro sobre Rinites-2012, com elaboraçao de algoritmo para conduta da rinite alergica. Método Foram convidados 24 especialistas indicados pelas Associaçao Brasileira de Alergia e Imunologia, Associaçao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial e Sociedade Brasileira de Pediatria para atualizaçao do documento de 2012. Resultados A atualizaçao do ultimo Consenso Brasileiro sobre Rinites, incorporou e adaptou para a realidade brasileira as informaçoes relevantes publicadas em todos os documentos da Iniciativa "Rinite Alergica e seu Impacto na Asma", trazendo novos conceitos como a rinite alergica local, novos medicamentos e metodos de avaliaçao de tratamento. Conclusão Proposto um fluxograma de tratamento para a rinite alergica.
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Bayesian analysis of high-resolution ultrasonography and guided fine needle aspiration cytology in diagnosis of palpable thyroid nodules
Abstract Introduction To evaluate diagnostic accuracy of high-resolution ultrasonography in differentiation of benign and malignant thyroid nodules in comparison to results of guided fine needle aspiration cytology based on the Bayes rule. Objective To assess the validity of ultrasonography results of thyroid nodules in comparison to guided fine needle aspiration cytology findings. Methods This study was done on randomly chosen 80 patients presented with palpable thyroid nodules, undergone real-time sonographic evaluation of thyroid nodules to characterize features, internal consistency, margins, echotexture, calcification, peripheral lucent halo and vascularity. Ultrasonography guided fine needle aspiration cytology studies of thyroid nodules were done. Results Palpable thyroid nodules were highly prevalent in fourth and fifth decades of life with female-male ratio, 4:1. Solid internal consistency was demonstrated by 75% malignant nodules. Hypoechogenicity and intra-nodular micro-calcifications were observed in 92% malignant nodules; 83% malignant nodules had intra-nodular vascularity and absence of peripheral halo. The pre-test prevalence of malignant nodules in the targeted population was 17.5%. As type I error, 2.5% false-positive cases and as type II error, 5.0% false-negative cases were detected. Values of sensitivity and specificity of the ultrasonography test were 71.43 and 96.97%, respectively. Conclusion Malignant thyroid nodules demonstrated ultrasonography characteristics of hypoechoic texture, intra-nodular micro-calcifications, solid consistency, internal vascularity and absence of peripheral halo. The ultrasonography test has 92.5% diagnostic accuracy to differentiate malignant from benign lesions in comparison to the gold standard fine needle aspiration cytology test.
Resumo Introdução Avaliar a precisão diagnóstica da ultrassonografia de alta resolução na diferenciação de nódulos tireoidianos benignos e malignos em comparação com os resultados da citologia de aspiração por agulha fina baseada na regra de Bayes. Objetivo Avaliar a validade dos resultados da USG de nódulos da tireoide em comparação com os resultados obtidos por citologia de aspiração por agulha fina. Método Este estudo foi feito em 80 pacientes selecionados aleatoriamente, que apresentavam nódulos palpáveis da tireoide, submetidos à avaliação ultrassonográfica em tempo real de nódulos da tireoide para estabelecer características, consistência interna, margens, ecotextura, calcificação, halo lucente periférico e vascularização. Foram feitos estudos por citologia de aspiração por agulha fina guiados pela USG dos nódulos de tireoide. Resultados Nódulos palpáveis da tireoide foram altamente prevalentes na quarta e quinta décadas de vida com uma razão sexo feminino-masculino de 4:1. A consistência interna sólida foi demonstrada em 75% de nódulos malignos. Hipoecogenicidade e microcalcificações intranodulares foram observadas em 92% de nódulos malignos; 83% dos nódulos malignos apresentaram vascularidade intranodular e ausência de halo periférico. A prevalência pré-teste de nódulos malignos na população alvo foi de 17,5%. Como erro tipo I, houve 2,5% de casos falso-positivos e como erro tipo II, foram detectados 5,0% de casos falso-negativos. Os valores de sensibilidade e especificidade do exame por USG foram de 71,43 e 96,97%, respectivamente. Conclusão Nódulos malignos da tireoide mostraram características de textura hipoecoica, microcalcificações intranodulares, consistência sólida, vascularidade interna e ausência de halo periférico na USG. O exame por USG tem 92,5% de precisão diagnóstica para diferenciar lesões malignas de benignas em comparação com o padrão ouro da citologia de aspiração por agulha fina.
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Intratympanic steroid injection and hyperbaric oxygen therapy for the treatment of refractory sudden hearing loss
Abstract Introduction Controversy surrounds the use of salvage therapies to treat sudden sensorineural hearing loss (SSNHL), with no consensus on recommendations. While several studies have demonstrated the effectiveness of intratympanic administration of steroids (ITS) and hyperbaric oxygen (HBO) treatment, few have compared the efficacy of ITS and HBO therapy in patients with refractory SSNHL. Objective We evaluated the efficiency of ITS and HBO therapy in patients with refractory SSNHL. Methods Patients who did not adequately benefit from systemic treatment were evaluated retrospectively. Refractory patients were defined as those who gained less than 20 dB in hearing after initial treatment. All refractory patients were informed about salvage therapy options: ITS or HBO therapy, the advantages and disadvantages of which were explained briefly. ITS involved 4 mg/mL dexamethasone administered through a 25 gauge needle. Patients underwent HBO therapy in a hyperbaric chamber where they breathed 100% oxygen for 120 min at 2.5 atmospheric pressure. The hearing levels of both groups were evaluated before the salvage therapy and at 3 months after treatment. Improvements in hearing were evaluated according to the Furahashi criteria. We also compared the two therapies in terms of speech discrimination scores (SDSs) and the recovery of all frequencies. Results The salvage therapies generated similar results. Changes in pure tone averages and SDSs were similar for ITS and HBO therapy (p = 0.364 and p = 0.113). Comparison of SDSs and hearing thresholds at all frequencies showed similar levels of improvement. Conclusion ITS and HBO therapy produced similar improvements in SSNHL patients, but the sample size was too small to draw definitive conclusions. Further randomized controlled studies are needed to identify the best therapy for patients with refractory sudden hearing loss.
Resumo Introdução Há muita controvérsia sobre o uso de terapias de resgate para tratar a perda auditiva neurossensorial súbita (PANSS), sem consenso sobre as recomendações. Embora vários estudos tenham demonstrado a eficácia do uso de corticoides intratimpânicos (CIT) e o tratamento com oxigenoterapia hiperbárica (HBO), poucos têm comparado a eficácia da terapia ITS e HBO em pacientes com PANSS refratária. Objetivo Avaliamos a eficiência da terapia com CIT e HBO em pacientes com PANSS refratária. Método Pacientes que não se beneficiaram adequadamente do tratamento sistêmico foram avaliados retrospectivamente. Pacientes refratários foram definidos como aqueles que ganharam menos de 20 dB na audição após o tratamento inicial. Todos os pacientes refratários foram informados sobre as opções de terapia de resgate: terapia com CIT ou HBO, cujas vantagens e desvantagens foram explicadas brevemente. O CIT envolveu 4 mg/mL de dexametasona administrada através de uma agulha de calibre 25. Os pacientes foram submetidos à terapia HBO em uma câmara hiperbárica onde respiraram 100% de oxigênio por 120 min a 2,5 pressão atmosférica. Os níveis de audição de ambos os grupos foram avaliados antes da terapia de resgate e três meses após o tratamento. As melhorias na audição foram avaliadas de acordo com os critérios de Furahashi. Também comparamos as duas terapias em termos de Escores de Discriminação de Fala (EDF) e a recuperação de todas as frequências. Resultados As terapias de resgate demonstraram resultados semelhantes. As alterações nas médias de tons puros e nas EDF foram semelhantes para a terapia com CIT e HBO (p = 0,364 e p = 0,113). A comparação dos EDF e dos limiares de audição em todas as frequências mostrou níveis de melhoria semelhantes. Conclusão CIT e HBO produziram melhorias semelhantes nos pacientes com PANSS, mas o tamanho da amostra era muito pequeno para tirarmos conclusões definitivas. Estudos randomizados e controlados adicionais são necessários para identificar a melhor terapia para pacientes com perda auditiva repentina refratária.
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