Improvement of the mechanical, tribological and antibacterial properties of glass ionomer cements by fluorinated graphene

Publication date: Available online 19 March 2018
Source:Dental Materials
Author(s): Li Sun, Zhuanjun Yan, Youxin Duan, Junyan Zhang, Bin Liu
ObjectiveThe aim of this study was to improve the mechanical properties, wear resistance and antibacterial properties of conventional glass ionomer cements (GICs) by fluorinated graphene (FG), under the premise of not influencing their solubility and fluoride ion releasing property.Materials and methodsFG with bright white color was prepared using graphene oxide by a hydrothermal reaction. Experimental modified GICs was prepared by adding FG to the traditional GICs powder with four different weight ratios (0.5wt%, 1wt%, 2wt% and 4wt%) using mechanical blending. Compressive and flexural strength of each experimental and control group materials were investigated using a universal testing machine. The Vickers microhardness of all the specimens was measured by a Vicker microhardness tester. For tribological properties of the composites, specimens of each group were investigated by high-speed reciprocating friction tester. Fluoride ion releasing was measured by fluoride ion selective electrode methods. The antibacterial effect of GICs/FG composites on selected bacteria (Staphylococci aureus and Streptococcus mutans) was tested with pellicle sticking method.ResultsThe prepared GICs/FG composites with white color were successfully fabricated. Increase of Vickers microhardness and compressive strength and decrease of friction coefficient of the GICs/FG composites were achieved compared to unreinforced materials. The colony count against S. aureus and S. mutans decreased with the increase of the content of FG. And the antibacterial rate of S. mutans can be up to 85.27% when the FG content was 4wt%. Additionally, fluoride ion releasing property and solubility did not show significant differences between unreinforced and FG reinforced GICs.SignificanceAdding FG to traditional GICs could not only improve mechanical and tribological properties of the composites, but also improve their antibacterial properties. In addition, the GICs/FG composites had no negative effect on the color, solubility and fluoride ion releasing properties, which will open up new roads for the application of dental materials.



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Human Papillomavirus-Related Neuroendocrine Carcinomas of the Head and Neck

Abstract

Human papillomavirus (HPV)-related head and neck carcinoma (HNC) represents an important subgroup of head and neck cancer that is characterized by a consistent microscopic appearance and a favorable prognosis. A growing experience with HPV testing, however, has uncovered variants that deviate from the prototypic HPV-HNC with respect to morphology. While these HPV-HNCs may deviate morphologically from the prototype, they do not appear to stray far from the favorable clinical outcome assigned to HPV-positive status. In effect, HPV positivity trumps traditional prognostic features predicated on morphology such as tumor grade and histologic subtype when it comes to predicting clinical behavior. For the diagnostic pathologist, the pedestrian task of tumor grading and subtyping would seem to be of little prognostic or therapeutic relevance when it comes to HPV-HNC. Recognition and documentation of neuroendocrine differentiation is a most notable exception. Forms of HPV-HNC have now been reported that morphologically resemble small cell carcinoma (SCC) and large cell neuroendocrine carcinoma (LCNEC) of other sites, and that immunohistochemically exhibit neuroendocrine differentiation. Despite the presence of HPV, these SCCs and LCNECs share the same aggressive clinical behavior of their counterparts in the lung and other sites where the high grade neuroendocrine phenotype is associated with early distant spread and poor overall survival. Consequently, the high grade neuroendocrine phenotype should be regarded as an aggressive form of HPV-HNC where tumor morphology displaces HPV positivity as the most important prognostic feature.

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Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma—An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin

Abstract

Salivary neuroendocrine carcinomas are rare and the overwhelming majority is high-grade. The parotid gland is the most commonly involved site followed by the submandibular gland. Most arise de novo but rare examples occurring as a high-grade transformation of another type of salivary gland neoplasm exist. There is significant morphologic and immunophenotypic overlap with neuroendocrine carcinomas of other sites, especially the skin. Like cutaneous neuroendocrine (or Merkel cell) carcinomas, approximately three-fourths are cytokeratin 20 positive. Cytokeratin 20 positive salivary neuroendocrine carcinomas are often referred to as being of the 'Merkel cell type' since most other non-cutaneous neuroendocrine carcinomas are cytokeratin 20 negative. Salivary neuroendocrine carcinomas may be challenging to separate from Merkel cell carcinomas of the head and neck on pathologic grounds because the latter often metastasize to the parotid gland. Clinical history is often relied upon to separate primary salivary tumors from cutaneous metastases but may not be helpful in all cases. Here we review the clinical, pathologic and molecular features of salivary neuroendocrine carcinomas focusing on high-grade major salivary gland tumors. The difficulty in separating salivary tumors from metastatic Merkel cell carcinoma will be highlighted.

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Update on Merkel Cell Carcinoma

Abstract

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Incidence of MCC continues to rise, and risk factors include advanced age, pale skin, chronic sun exposure, and immune suppression. Diagnosing MCC utilizes a combination of morphology and immunohistochemistry. Merkel cell polyomavirus (MCPyV) is present in approximately 70–80% of MCCs and represents a key pathogenic driver in those MCCs. In contrast, MCPyV-negative MCCs arise through progressive accumulation of ultraviolet-light induced somatic mutations. Staging of MCC proceeds according to the American Joint Commission on Cancer (AJCC) 8th Edition, which utilizes features of the primary tumor together with regional lymph node(s) (clinically and/or pathologically detected) and/or distant metastases. Many potentially useful biomarkers have been studied to refine risk stratification in MCC. In recent years, the host immune infiltrate has been leveraged as immune checkpoint blockade has emerged as an efficacious mode of treatment for patients with advanced MCC.

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Human Papillomavirus-Related Neuroendocrine Carcinomas of the Head and Neck

Abstract

Human papillomavirus (HPV)-related head and neck carcinoma (HNC) represents an important subgroup of head and neck cancer that is characterized by a consistent microscopic appearance and a favorable prognosis. A growing experience with HPV testing, however, has uncovered variants that deviate from the prototypic HPV-HNC with respect to morphology. While these HPV-HNCs may deviate morphologically from the prototype, they do not appear to stray far from the favorable clinical outcome assigned to HPV-positive status. In effect, HPV positivity trumps traditional prognostic features predicated on morphology such as tumor grade and histologic subtype when it comes to predicting clinical behavior. For the diagnostic pathologist, the pedestrian task of tumor grading and subtyping would seem to be of little prognostic or therapeutic relevance when it comes to HPV-HNC. Recognition and documentation of neuroendocrine differentiation is a most notable exception. Forms of HPV-HNC have now been reported that morphologically resemble small cell carcinoma (SCC) and large cell neuroendocrine carcinoma (LCNEC) of other sites, and that immunohistochemically exhibit neuroendocrine differentiation. Despite the presence of HPV, these SCCs and LCNECs share the same aggressive clinical behavior of their counterparts in the lung and other sites where the high grade neuroendocrine phenotype is associated with early distant spread and poor overall survival. Consequently, the high grade neuroendocrine phenotype should be regarded as an aggressive form of HPV-HNC where tumor morphology displaces HPV positivity as the most important prognostic feature.

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Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma—An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin

Abstract

Salivary neuroendocrine carcinomas are rare and the overwhelming majority is high-grade. The parotid gland is the most commonly involved site followed by the submandibular gland. Most arise de novo but rare examples occurring as a high-grade transformation of another type of salivary gland neoplasm exist. There is significant morphologic and immunophenotypic overlap with neuroendocrine carcinomas of other sites, especially the skin. Like cutaneous neuroendocrine (or Merkel cell) carcinomas, approximately three-fourths are cytokeratin 20 positive. Cytokeratin 20 positive salivary neuroendocrine carcinomas are often referred to as being of the 'Merkel cell type' since most other non-cutaneous neuroendocrine carcinomas are cytokeratin 20 negative. Salivary neuroendocrine carcinomas may be challenging to separate from Merkel cell carcinomas of the head and neck on pathologic grounds because the latter often metastasize to the parotid gland. Clinical history is often relied upon to separate primary salivary tumors from cutaneous metastases but may not be helpful in all cases. Here we review the clinical, pathologic and molecular features of salivary neuroendocrine carcinomas focusing on high-grade major salivary gland tumors. The difficulty in separating salivary tumors from metastatic Merkel cell carcinoma will be highlighted.

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Human Papillomavirus-Related Neuroendocrine Carcinomas of the Head and Neck

Abstract

Human papillomavirus (HPV)-related head and neck carcinoma (HNC) represents an important subgroup of head and neck cancer that is characterized by a consistent microscopic appearance and a favorable prognosis. A growing experience with HPV testing, however, has uncovered variants that deviate from the prototypic HPV-HNC with respect to morphology. While these HPV-HNCs may deviate morphologically from the prototype, they do not appear to stray far from the favorable clinical outcome assigned to HPV-positive status. In effect, HPV positivity trumps traditional prognostic features predicated on morphology such as tumor grade and histologic subtype when it comes to predicting clinical behavior. For the diagnostic pathologist, the pedestrian task of tumor grading and subtyping would seem to be of little prognostic or therapeutic relevance when it comes to HPV-HNC. Recognition and documentation of neuroendocrine differentiation is a most notable exception. Forms of HPV-HNC have now been reported that morphologically resemble small cell carcinoma (SCC) and large cell neuroendocrine carcinoma (LCNEC) of other sites, and that immunohistochemically exhibit neuroendocrine differentiation. Despite the presence of HPV, these SCCs and LCNECs share the same aggressive clinical behavior of their counterparts in the lung and other sites where the high grade neuroendocrine phenotype is associated with early distant spread and poor overall survival. Consequently, the high grade neuroendocrine phenotype should be regarded as an aggressive form of HPV-HNC where tumor morphology displaces HPV positivity as the most important prognostic feature.

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Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma—An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin

Abstract

Salivary neuroendocrine carcinomas are rare and the overwhelming majority is high-grade. The parotid gland is the most commonly involved site followed by the submandibular gland. Most arise de novo but rare examples occurring as a high-grade transformation of another type of salivary gland neoplasm exist. There is significant morphologic and immunophenotypic overlap with neuroendocrine carcinomas of other sites, especially the skin. Like cutaneous neuroendocrine (or Merkel cell) carcinomas, approximately three-fourths are cytokeratin 20 positive. Cytokeratin 20 positive salivary neuroendocrine carcinomas are often referred to as being of the 'Merkel cell type' since most other non-cutaneous neuroendocrine carcinomas are cytokeratin 20 negative. Salivary neuroendocrine carcinomas may be challenging to separate from Merkel cell carcinomas of the head and neck on pathologic grounds because the latter often metastasize to the parotid gland. Clinical history is often relied upon to separate primary salivary tumors from cutaneous metastases but may not be helpful in all cases. Here we review the clinical, pathologic and molecular features of salivary neuroendocrine carcinomas focusing on high-grade major salivary gland tumors. The difficulty in separating salivary tumors from metastatic Merkel cell carcinoma will be highlighted.

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Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study

Abstract

Background

Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS).

Methods

This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted.

Results

A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P < 0.001). In internal validation, the model maintained good discriminant functions on tumor response (c-index, 0.825) and 12-month survival (AUC, 0.803), and good calibration functions (all P > 0.05 between expected and observed values).

Conclusions

This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.

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Prognostic value of metformin for non-small cell lung cancer patients with diabetes

Abstract

Background

The anti-cancer role of metformin has been reported in many different kinds of solid tumors, but how it affects non-small cell lung cancer (NSCLC) is currently elusive. The aim of this study was to investigate the influence of metformin treatment on diabetic NSCLC.

Methods

Two hundred fifty-five patients of diabetic NSCLC receiving therapy in our hospital from 2014 to 2016 were enrolled in our study. The information on clinical diagnosis, pathology, and prognosis as well as the influence of metformin in diabetic NSCLC were collected and assessed. Univariate and multivariate analytical techniques were applied to explore how metformin affect the survival of NSCLC.

Results

One hundred fifty of the 255 diabetic NSCLC patients took metformin. The median overall survival time (OST) and disease-free survival time (DFST) were significantly prolonged with metformin treatment compared to without metformin treatment (OST 25.0 vs 11.5 months, p = 0.005; DFST 15.6 vs 8.5 months, p = 0.010). Multivariate analysis indicated that metformin treatment could be used to predict the long-term outcome of diabetic NSCLC independently (HR = 0.588, 95% CI 0.466–0.895, p = 0.035).

Conclusion

Our study revealed that the metformin could help in improving the final outcome of NSCLC patients with diabetes in the long term and thus could be applied to treat NSCLC.

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Perioperative Management of Patients with Inflammatory Rheumatic Diseases Undergoing Major Orthopaedic Surgery: A Practical Overview

Abstract

Patients with inflammatory rheumatic diseases often need orthopaedic surgery due to joint involvement. Total hip replacement and total knee replacement are frequent surgical procedures in these patients. Due to the complexity of the inflammatory rheumatic diseases, the perioperative management of these patients must envisage a multidisciplinary approach. The frequent association with extraarticular comorbidities must be considered when evaluating perioperative risk of the patient and should guide the clinician in the decision-making process. However, guidelines of different medical societies may vary and are sometimes contradictory. Orthopaedics should collaborate with rheumatologists, anaesthesiologists and, when needed, cardiologists and haematologists with the common aim of minimising perioperative risk in patients with inflammatory rheumatic diseases. The aim of this review is to provide the reader with simple practical recommendations regarding perioperative management of drugs such as disease-modifying anti-rheumatic drugs, corticosteroids, non-steroidal anti-inflammatory drugs and tools for a risk stratification for cardiovascular and thromboembolic risk based on current evidence for patients with inflammatory rheumatic diseases.

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Update on Merkel Cell Carcinoma

Abstract

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Incidence of MCC continues to rise, and risk factors include advanced age, pale skin, chronic sun exposure, and immune suppression. Diagnosing MCC utilizes a combination of morphology and immunohistochemistry. Merkel cell polyomavirus (MCPyV) is present in approximately 70–80% of MCCs and represents a key pathogenic driver in those MCCs. In contrast, MCPyV-negative MCCs arise through progressive accumulation of ultraviolet-light induced somatic mutations. Staging of MCC proceeds according to the American Joint Commission on Cancer (AJCC) 8th Edition, which utilizes features of the primary tumor together with regional lymph node(s) (clinically and/or pathologically detected) and/or distant metastases. Many potentially useful biomarkers have been studied to refine risk stratification in MCC. In recent years, the host immune infiltrate has been leveraged as immune checkpoint blockade has emerged as an efficacious mode of treatment for patients with advanced MCC.

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Update on Merkel Cell Carcinoma

Abstract

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Incidence of MCC continues to rise, and risk factors include advanced age, pale skin, chronic sun exposure, and immune suppression. Diagnosing MCC utilizes a combination of morphology and immunohistochemistry. Merkel cell polyomavirus (MCPyV) is present in approximately 70–80% of MCCs and represents a key pathogenic driver in those MCCs. In contrast, MCPyV-negative MCCs arise through progressive accumulation of ultraviolet-light induced somatic mutations. Staging of MCC proceeds according to the American Joint Commission on Cancer (AJCC) 8th Edition, which utilizes features of the primary tumor together with regional lymph node(s) (clinically and/or pathologically detected) and/or distant metastases. Many potentially useful biomarkers have been studied to refine risk stratification in MCC. In recent years, the host immune infiltrate has been leveraged as immune checkpoint blockade has emerged as an efficacious mode of treatment for patients with advanced MCC.

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Myxoid liposarcoma: local relapse and metastatic pattern in 43 patients

Abstract

Background

Liposarcomas are the second most common type of soft tissue sarcomas, 30–50% of these are of myxoid subtype. The aim of this retrospective study was to analyze the local control rate, the metastatic pattern and survival of patients in a consecutive single-institution series.

Methods

From 1983 to 2015, 43 patients with myxoid liposarcoma of the extremities and trunk wall underwent resections. The margin was defined as R0 (wide) or R1 (marginal). Patients were followed for evidence of local recurrence or distant metastasis. Overall and recurrence-free survival was calculated.

Results

The mean age was 48.6 years. The lower extremity was involved in 40 cases, the mean tumour size was 12 cm. In 31 cases a wide and in 12 cases a marginal resection was performed. Grading was G1 in 14, G2 in 25 and G3 in 4 cases.

Nine patient died in follow-up, 4 of them with metastatic disease, all nonpulmonary. 5-year local recurrence (LR) free survival was 82%. 4 (9.3%) patients developed LR (all R1). Overall survival (OS) was 81% after 5 and 72% after 10 years. In multivariate analysis age and Grading proved to be significant on OS. According to univariate analysis, only age over 48 years and distant metastasis had a significant impact on overall survival.

Conclusions

Patients with myxoid liposarcomas have a good prognosis. Myxoid liposarcoma has a distinct pattern of nonpulmonary metastatic disease. Therefore, patients with high-risk extremity myxoid liposarcoma should undergo imaging studies of the chest, abdomen, spine and pelvis as part of their staging and follow-up examinations preferably with whole body MRI, or CT scans and MRI of the spine and pelvic region for detection of suspected metastatic disease.

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Transverse Cervical Artery Pseudoaneurysm: An Unusual Delayed Complication of Radical Neck Dissection

Abstract

Pseudoaneurysm formation in the transverse cervical artery, post radical neck dissection, leading to massive hemorrhage, is a rare but life threatening occurrence. We report a patient with pseudoaneurysm of transverse cervical artery, post salvage radical neck dissection, presenting with recurrent and significant hemorrhage after 3 weeks of surgery. A pseudoaneurysm involving transverse cervical artery was revealed by digital subtraction angiography and treated by endovascular coil embolization.

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The Role of Preoperative Computed Tomography of Temporal Bone in Atticotomy as a New Tool for Determining the Approach

Abstract

The temporal bone is a complex anatomical structure and so preoperatively computed tomography (CT) of the temporal bone is important for choice of the surgical procedure. In this study, evaluation of the surgical difficulty to conduct transmastoid atticotomy with the coronary cut of CT temporal bone. Additional, attic pathology intraoperative is evaluated. The current research is a retrospective study of 79 patients with chronic suppurative otitis media (safe type) with the preoperative opacity of the attic in CT temporal bone. The researcher correlates difficulty to do transmastoid attictomy with the distance in mm between the roof of external audiatory canal (EAC) and tegmen with ruler directly in the coronary cut of CT temporal bone at the the level of internal auditory canal (IAC). The researcher also compares attic pathology intraoperative with preoperative CT attic opacity. In group of surgically difficulty average distance between the superior wall of EAC and tegmen on preoperative CT at the level of IAC is 2–5 mm while distance in easily surgical approach is from 6 to 10 mm. 68.4%(54/79) of cases had pathology in attic in the form of granulation tissue in 50 cases and glue in 4 cases. Preoperative CT temporal bone is very important to detect atticotomy approach either transmastoid or transcanal, through measuring the distance in mm between the roof of EAC and tegmen with ruler directly in the coronal cut of CT temporal bone at the level of internal auditory canal. The opacity of the attic in Preoperative CT does not mean that there is a pathology in the attic.

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Evaluation of the effects of different sand particles that used in dental implant roughened for osseointegration

Abstract

Background

Successful dental implant treatment is directly related to osseointegration. In achieving osseointegration, the surface property of the implant is of great importance. Sandblasting is the most commonly used basic method for modifying the surface. Many companies use different sand particles for surface roughening and claim their sand is the best. This leads clinicians to mix their minds in product selection. In this study, we tried to find the appropriate sand material by working objectively without praising any brand. We believe that the results of the study will help clinicians choose the right dental implant. In this study, machined-surfaced implants and implants sandblasted with Aluminum oxide (Al₂O₃), Titanium dioxide (TiO₂) and Silicon dioxide (SiO₂) were compared via biomechanical testing.

Methods

For the study, four 2 year-old sheep, weighing 45 kilograms (kg), were used. Eight implants (Al₂O₃, TiO₂, and SiO₂ sandblasted implants and machined-surfaced implants), each with different surface characteristics, were inserted into the bilateral tibia of each sheep under general anesthesia. Results of the initial Resonance Frequency Analysis (RFA) were recorded just after implant insertion. The sheep were then randomly divided into two groups, each with 2 sheep, to undergo either a 1-month or a 3-month assessment. At the end of the designated evaluation period, RFA and removal torque tests were performed.

Results

Although there were no statistically significant differences between the groups, the implants sandblasted with Al₂O₃ showed a higher Implant Stability Quotient (ISQ) and removal torque value at the end of the 1st and 3rd month.

Conclusions

In short, the results of the study demonstrate that Aluminum oxide is superior to other sand particles.

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Pretreatment prognostic factors of survival and late toxicities for patients with nasopharyngeal carcinoma treated by simultaneous integrated boost intensity-modulated radiotherapy

Abstract

Background

To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT).

Methods

A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed. Cox model was used to screen the prognostic factors of late toxicities and four survival outcomes including locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS).

Results

Statistically significant inter-correlations were observed between the values of EBV-DNA, some hematologic inflammatory markers, GTV, and N classification. The 5-year LRRFS, DMFS, FFS, and OS rates were 87.9%, 89.4%, 79.4%, and 81.3%, respectively. Multivariate analysis revealed that advanced N classification (N2–3 vs. N0–1) remained the only significant negative prognosticator for all the four survival outcomes. An increased monocyte percentage and a decreased lymphocyte-to-monocyte ratio were significantly associated with poorer FFS and OS, respectively. Larger GTV was observed to be predictive of poorer LRRFS. Patients with T3–4 (HR: 3.5, 95% CI: 1.0–12.1, p = 0.048) or higher GTV (HR: 1.006, 95% CI: 1.001–1.011, p = 0.027) were associated with higher incidence of radiation neuropathy.

Conclusion

N classification remains the most significant survival predictor for NPC patients treated by SIB-IMRT after adjusting these biomarkers. GTV impacts not only on locoregional control but also radiation neuropathy.

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Underutilization and disparities in access to EGFR testing among Medicare patients with lung cancer from 2010 – 2013

Abstract

Background

Tumor testing for mutations in the epidermal growth factor receptor (EGFR) gene is indicated for all newly diagnosed, metastatic lung cancer patients, who may be candidates for first-line treatment with an EGFR tyrosine kinase inhibitor. Few studies have analyzed population-level testing.

Methods

We identified clinical, demographic, and regional predictors of EGFR & KRAS testing among Medicare beneficiaries with a new diagnosis of lung cancer in 2011–2013 claims. The outcome variable was whether the patient underwent molecular, EGFR and KRAS testing. Independent variables included: patient demographics, Medicaid status, clinical characteristics, and region where the patient lived. We performed multivariate logistic regression to identify factors that predicted testing.

Results

From 2011 to 2013, there was a 19.7% increase in the rate of EGFR testing. Patient zip code had the greatest impact on odds to undergo testing; for example, patients who lived in the Boston, Massachusetts hospital referral region were the most likely to be tested (odds ratio (OR) of 4.94, with a 95% confidence interval (CI) of 1.67–14.62). Patient demographics also impacted odds to be tested. Asian/Pacific Islanders were most likely to be tested (OR 1.63, CI 1.53–1.79). Minorities and Medicaid patients were less likely to be tested. Medicaid recipients had an OR of 0.74 (CI 0.72–0.77). Hispanics and Blacks were also less likely to be tested (OR 0.97, CI 0.78–0.99 and 0.95, CI 0.92–0.99), respectively. Clinical procedures were also correlated with testing. Patients who underwent transcatheter biopsies were 2.54 times more likely to be tested (CI 2.49–2.60) than those who did not undergo this type of biopsy.

Conclusions

Despite an overall increase in EGFR testing, there is widespread underutilization of guideline-recommended testing. We observed racial, income, and regional disparities in testing. Precision medicine has increased the complexity of cancer diagnosis and treatment. Targeted interventions and clinical decision support tools are needed to ensure that all patients are benefitting from advances in precision medicine. Without such interventions, precision medicine may exacerbate racial disparities in cancer care and health outcomes.

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Relationship between time elapsed since completion of radiotherapy and quality of life of patients with breast cancer

Abstract

Background

To investigate the relationship between time elapsed since completion of radiotherapy (RT) and quality of life (QOL) of patients with breast cancer.

Methods

A total of 300 patients with breast cancer were treated at the First Affiliated Hospital of Anhui Medical University between January 2013 and April 2016. Of these, 212 patients were included in the study. Patients were divided into 4 groups based on the time elapsed since completion of RT. The generic cancer questionnaire, EORTC QLQ-30, and the breast cancer-specific questionnaire, QLQ-BR23, were used to assess the QOL.

Results

Analysis of time elapsed since completion of RT and QOL revealed changes in the scores for role function with passage of time; the third year's scores were the highest. Pain symptoms during the 3rd and 4th years after RT were lower than those during the 1st and 2nd years after RT; scores for financial difficulties fluctuated with passage of time; perception of own body scores improved within first 3 years; sexual activity and enjoyment of sexual activity showed a significant decrease during the 2nd to 4th year post RT. Scores pertaining to concerns about future state of health showed a significant increase during the 2nd to 4th year after RT, while breast symptoms score showed fluctuations with passage of time.

Conclusions

Social function, pain symptoms, and concerns about future state of health tended to improve with passage of time after RT. Other scales showed no correlation with time elapsed since completion of RT.

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A feasibility study on adaptive 18 F-FDG-PET-guided radiotherapy for recurrent and second primary head and neck cancer in the previously irradiated territory

Abstract

Purpose

To evaluate feasibility, disease control, survival, and toxicity after adaptive ¹⁸F-fluorodeoxyglucose (FDG) positron emisson tomography (PET) guided radiotherapy in patients with recurrent and second primary head and neck squamous cell carcinoma.

Methods

A prospective trial investigated the feasibility of adaptive intensity modulated radiotherapy (IMRT) ± concomitant cetuximab in 10 patients. The primary endpoint was achieving a 2-year survival free of grade >3 toxicity in ≥30% of patients. Three treatment plans based on 3 PET/CT scans were consecutively delivered in 6 weeks. The range of dose painting was 66.0–85.0 Gy in the dose-painted tumoral volumes in 30 fractions.

Results

Two-year locoregional and distant control rates were 38 and 76%, respectively. Overall and disease-free survival at 2 years was 20%. No grade 4 or 5 acute toxicity was observed in any of the patients, except for arterial mucosal hemorrhage in 1 patient. Three months after radiotherapy, grade 4 dysphagia and mucosal wound healing problems were observed in 1/7 and 1/6 of patients, respectively. Grade 5 toxicity (fatal bleeding) was seen in 2 patients, at 3.8 and 4.1 months of follow-up. Data on 2‑year toxicity could only be assessed in 1 of the 2 surviving patients, in whom grade 4 mucosal wound healing problems were observed; no other grade >3 toxicity was observed. In this respect, a 30% 2‑year survival free of grade >3 toxicity will not be achieved.

Conclusions

Adaptive PET-guided reirradiation is feasible. However, due to slow accrual and treatment results that seemed inconsistent with achieving the primary endpoint, the trial was stopped early.

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Recent advances in medical therapy for metastatic urothelial cancer

Abstract

Cytotoxic chemotherapy has been the mainstay of medical therapy for metastatic urothelial cancer. Currently, the gemcitabine/cisplatin regimen is widely used worldwide as the standard first-line medical treatment. Very recently, in 2017, pembrolizumab, a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1, was approved as a second-line treatment to be used after platina-based chemotherapy for metastatic urothelial cancer in Japan. Based on its promising anti-tumor efficacy and manageable safety profile as demonstrated in the phase III KEYNOTE-045 trial, pembrolizumab therapy is expected to be rapidly introduced for treating metastatic urothelial cancer in clinical practice. The paradigm of medical treatment for patients with metastatic UC is dramatically changing through the introduction of this and other immune-checkpoint inhibitors. In this article, we provide a brief overview of these immune-checkpoint inhibitors and a comprehensive summary of the use of cytotoxic chemotherapy for metastatic urothelial cancer, including ongoing clinical trials.

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Occurrence of Endocrine and Thyroid Cancers Among Alaska Native People, 1969–2013

Thyroid, Ahead of Print.


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Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways

Abstract

Background

Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-tumor effects in many cancers, including multiple myeloma (MM); however, the underlying molecular mechanisms have not been clearly elucidated.

Methods

The anti-myeloma effects of metformin were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo NOD-SCID murine xenograft MM model. Cell viability was assessed with CCK8 and cell proliferation was measured by EdU incorporation assay. Cell cycle distribution and apoptosis were examined by flow cytometry. Transmission electron microscopy was used to visualized autophagosomes. Activation of AMPK and inhibition of mTORC1/C2 pathways was assessed by Western blot analysis. RPMI8226 cells and U266 cell lines with AMPK knockdown were generated by transfection with small interfering RNA targeting the AMPK-α1 and α2 subunits using Lipofectamine 2000 reagent.

Results

Metformin effectively inhibited the proliferation of MM cell lines, an effect that was associated with the induction of autophagy and G0/G1 cell cycle arrest, but not apoptosis. Metformin activated AMPK and repressed both mTORC1 and mTORC2 signaling pathways in myeloma cells as well as downstream molecular signaling pathways, such as p-4EBP1 and p-AKT. AMPK activation resulted in direct phosphorylation and activation of tuberous sclerosis complex 2 (TSC2), leading to inhibition of the mammalian target of rapamycin (mTOR). In addition, metformin inhibited myeloma cell growth in an AMPK-dependent manner. The xenograft mouse model further confirmed that metformin inhibited tumor growth by upregulation of AMPK and downregulation of mTOR.

Conclusions

Metformin inhibits the proliferation of myeloma cells by inducing autophagy and cell-cycle arrest. Our results suggest that the molecular mechanism involves dual repression of mTORC1 and mTORC2 pathways via AMPK activation. Our study provides a theoretical basis for the development of novel strategies for the treatment of MM using metformin as an already approved and safe drug.

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Induction of apoptosis in imatinib sensitive and resistant chronic myeloid leukemia cells by efficient disruption of bcr-abl oncogene with zinc finger nucleases

Abstract

Background

The bcr-abl fusion gene is the pathological origin of chronic myeloid leukemia (CML) and plays a critical role in the resistance of imatinib. Thus, bcr-abl disruption-based novel therapeutic strategy may warrant exploration. In our study, we were surprised to find that the characteristics of bcr-abl sequences met the design requirements of zinc finger nucleases (ZFNs).

Methods

We constructed the ZFNs targeting bcr-abl with high specificity through simple modular assembly approach. Western blotting was conducted to detect the expression of BCR-ABL and phosphorylation of its downstream STAT5, ERK and CRKL in CML cells. CCK8 assay, colony-forming assay and flow cytometry (FCM) were used to evaluate the effect of the ZFNs on the viablity and apoptosis of CML cells and CML CD34⁺ cells. Moreover, mice model was used to determine the ability of ZFNs in disrupting the leukemogenesis of bcr-abl in vivo.

Results

The ZFNs skillfully mediated 8-base NotI enzyme cutting site addition in bcr-abl gene of imatinib sensitive and resistant CML cells by homology-directed repair (HDR), which led to a stop codon and terminated the translation of BCR-ABL protein. As expected, the disruption of bcr-abl gene induced cell apoptosis and inhibited cell proliferation. Notably, we obtained similar result in CD34⁺ cells from CML patients. Moreover, the ZFNs significantly reduced the oncogenicity of CML cells in mice.

Conclusion

These results reveal that the bcr-abl gene disruption based on ZFNs may provide a treatment choice for imatinib resistant or intolerant CML patients.

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High Intensity Interval Training Increases Natural Killer Cell Number and Function in Obese Breast Cancer-challenged Mice and Obese Women.

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High Intensity Interval Training Increases Natural Killer Cell Number and Function in Obese Breast Cancer-challenged Mice and Obese Women.

J Cancer Prev. 2017 Dec;22(4):260-266

Authors: Barra NG, Fan IY, Gillen JB, Chew M, Marcinko K, Steinberg GR, Gibala MJ, Ashkar AA

Abstract
High intensity interval training (HIIT) boosts natural killer (NK) cell number and activity in normal weight breast cancer patients; however, whether this occurs in obese individuals is not well established. The goal of this study was to determine whether HIIT effectively boosts NK cells as a therapeutic strategy against breast cancer in an obese mouse model and in overweight/obese women. Diet induced female C57Bl/6 obese mice were assigned to undergo HIIT for four weeks or remain sedentary. Female participants were subjected to a six weeks HIIT protocol. HIIT mice acclimatized to treadmill running were subsequently injected with 5 × 105 polyoma middle T (MT) breast cancer cells intravenously. NK cell number and activation were monitored using flow cytometry, and tumor burden or lipid content evaluated from histological lung and liver tissues, respectively. In both mice and humans, circulating NK cell number and activation (CD3-NK1.1+CD27+ and CD3-CD56+, respectively) markedly increased immediately after HIIT. HIIT obese mice had reduced lung tumor burden compared to controls following MT challenge, and had diminished hepatic lipid deposition despite minimal body weight loss. Our findings demonstrate that HIIT can benefit obese individuals by enhancing NK cell number and activity, reducing tumor burden, and enhancing metabolic health.

PMID: 29302585 [PubMed]

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TP53 R72P Polymorphism and Susceptibility to Human Papillomavirus Infection Among Women With Human Immunodeficiency Virus in Morocco: A Case-control Study.

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TP53 R72P Polymorphism and Susceptibility to Human Papillomavirus Infection Among Women With Human Immunodeficiency Virus in Morocco: A Case-control Study.

J Cancer Prev. 2017 Dec;22(4):248-253

Authors: Lahsen AO, Baba H, Bensghir R, Fayssel N, Sodqi M, Marih L, Nadifi S, Wakrim L, El Filali KM, Ezzikouri S

Abstract
Background: Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. HPV is the main causative agent for cervical cancer. The HPV oncoprotein E6 binds to the tumor suppressor gene product p53, promoting its degradation; the Arg allele of TP53 R72P polymorphism binds more ardently with HPV E6 than the Pro variant. Here, we investigated whether TP53 R72P gene variant, rs104252, was associated with susceptibility to HPV infection in women with human immunodeficiency virus (HIV).
Methods: We analyzed 200 HPV-positive and 68 uninfected women with HIV. Genomic DNA was isolated from cervical swab. The TP53 R72P polymorphism was genotyped by PCR-RFLP. Unconditional logistic regression was used to assess the association between polymorphism and the clinical, lifestyle, and behavioral data.
Results: The genotype and allele frequencies of rs104252 variant did not differ between women without or with HPV infection (P > 0.05). Moreover, the p53 polymorphism was not associated with cervical cytology. In contrast, when we analyzed according to behavior factors, the P72P genotype was more frequent among HPV-positive smoker women. However, no significant relationship was found between alcohol, contraceptive use, and number of partners with TP53 R72P genotype distributions among HPV-positive cases (P > 0.05).
Conclusions: The R72 variant of p53 R72P is not associated with HPV infection and progression of lesions. There was no association between this variant and behavior factors in HPV-positive cases. The P72P genotype may be more frequent among HPV-positive smoker women.

PMID: 29302583 [PubMed]

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Secondary Primary Prostate Cancer after Colorectal Cancer: A Nationwide Population-based Cohort Study in Korea.

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Secondary Primary Prostate Cancer after Colorectal Cancer: A Nationwide Population-based Cohort Study in Korea.

J Cancer Prev. 2017 Dec;22(4):241-247

Authors: Kim HS, Choi YJ, Shin DW, Han KD, Yoon H, Shin CM, Park YS, Kim N, Lee DH

Abstract
Background: Colorectal cancer (CRC) and prostate cancer frequently occur in developed countries. There are several reports on the association between CRC and prostate cancer; however, the conclusions are inconsistent to investigate the association of the development of secondary primary prostate cancer among patients with prior primary CRC using a nationwide population-based dataset.
Methods: Patients registered in the Republic of Korea National Health Insurance System database who were diagnosed with CRC between 2007 and 2012 were followed-up until the end of 2015, and we investigated the new diagnosis secondary primary prostate cancer. We compared the incidence of prostate cancer in age-matched controls using the Cox proportional hazards models.
Results: We analyzed a total of 85,455 first primary CRC survivors. During the follow-up period of 494,222 person-years, 2,005 patients (2.30%) developed secondary primary prostate cancer (incidence rate 4.06/1,000 person-years). The median duration of follow-up was 5.78 years. Compared with the general population, CRC patients had a significantly increased risk of secondary primary prostate cancer (HR = 2.30, 95% CI = 2.18-2.43; P < 0.001). Multivariate analysis (including age, sex, body mass index, hypertension, diabetes mellitus, dyslipidemia, and income) showed that age < 55 years (HR = 20.74, 95% CI = 11.81-36.41; P < 0.001) is a significant independent predictor of secondary primary prostate cancer development.
Conclusions: Men diagnosed with colorectal cancer are at an increased risk of secondary primary prostate cancer, particularly those aged < 55 years. The data suggests that colorectal cancer patients aged < 55 years require regular screening for prostate cancer.

PMID: 29302582 [PubMed]

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Novel Genetic Associations Between Lung Cancer and Indoor Radon Exposure.

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Novel Genetic Associations Between Lung Cancer and Indoor Radon Exposure.

J Cancer Prev. 2017 Dec;22(4):234-240

Authors: Choi JR, Koh SB, Park SY, Kim HR, Lee H, Kang DR

Abstract
Background: Lung cancer is the leading cause of cancer-related death worldwide, for which smoking is considered as the primary risk factor. The present study was conducted to determine whether genetic alterations induced by radon exposure are associated with the susceptible risk of lung cancer in never smokers.
Methods: To accurately identify mutations within individual tumors, next generation sequencing was conduct for 19 pairs of lung cancer tissue. The associations of germline and somatic variations with radon exposure were visualized using OncoPrint and heatmap graphs. Bioinformatic analysis was performed using various tools.
Results: Alterations in several genes were implicated in lung cancer resulting from exposure to radon indoors, namely those in epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), NK2 homeobox 1 (NKX2.1), phosphatase and tensin homolog (PTEN), chromodomain helicase DNA binding protein 7 (CHD7), discoidin domain receptor tyrosine kinase 2 (DDR2), lysine methyltransferase 2C (MLL3), chromodomain helicase DNA binding protein 5 (CHD5), FAT atypical cadherin 1 (FAT1), and dual specificity phosphatase 27 (putative) (DUSP27).
Conclusions: While these genes might regulate the carcinogenic pathways of radioactivity, further analysis is needed to determine whether the genes are indeed completely responsible for causing lung cancer in never smokers exposed to residential radon.

PMID: 29302581 [PubMed]

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Protective Effect of Allium tuberosum Extract on Vascular Inflammation in Tumor Necrosis Factor-α-induced Human Vascular Endothelial Cells.

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Protective Effect of Allium tuberosum Extract on Vascular Inflammation in Tumor Necrosis Factor-α-induced Human Vascular Endothelial Cells.

J Cancer Prev. 2017 Dec;22(4):228-233

Authors: Hur HJ, Lee AS

Abstract
Background: Endothelial adhesion molecule expression induced by pro-inflammatory cytokine plays an important role in vascular endothelial cell injury, leading to vascular disease. Allium tuberosum (AT), which is used as a functional food, has a thrombolytic effect. It contains vitamin A, vitamin C, carbohydrate, calcium, iron, and phosphorus. There are many carotenes that turn into vitamin A in the body. Also, it helps blood circulation and stimulates metabolism. The purpose of the this study was to estimate the anti-inflammatory effects of the AT extract.
Methods: Human vascular endothelial cells were pre-treated with 100 μg/mL AT extract for 30 minutes and subsequently co-treated with TNF-α (10 ng/mL) and AT extract (100 μg/mL) for 1, 4, and 6 hours. After treatment, the cells were lysed and used for quantitative reverse transcription PCR, Western blot analysis, and monocyte adhesion assay.
Results: We examined the effect of the AT extract on inflammatory gene expression in TNF-α-induced human umbilical vein endothelial cells (HUVECs). The extract reduced the expression levels of mRNA and protein of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in TNF-α-stimulated HUVECs. It also inhibited the TNF-α-induced phosphorylation of the NF-κB p65 subunit and degradation of IκBα. Furthermore, the AT extract prevented the increased adhesion capacity of monocyte to TNF-α-stimulated vascular endothelial cells by reducing ICAM-1 and VCAM-1 expression.
Conclusions: The AT extract has preventive and anti-inflammatory effect against vascular disease and has potential for supporting prevention against the early process of atherosclerosis.

PMID: 29302580 [PubMed]

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Myricetin Inhibits Angiogenesis by Inducing Apoptosis and Suppressing PI3K/Akt/mTOR Signaling in Endothelial Cells.

Related Articles

Myricetin Inhibits Angiogenesis by Inducing Apoptosis and Suppressing PI3K/Akt/mTOR Signaling in Endothelial Cells.

J Cancer Prev. 2017 Dec;22(4):219-227

Authors: Kim GD

Abstract
Background: Myricetin has been shown to possess potential antiangiogenic effects in endothelial cells. However, the underlying mechanisms are not fully understood. Therefore, we evaluated its antiangiogenic effects in human umbilical vascular endothelial cells (HUVECs).
Methods: HUVECs were cultured in endothelial cell growth medium-2 to induce proliferation and angiogenesis and treated with different doses of myricetin (0.25, 0.5, and 1 μM) for 24 hours. Cell proliferation was analyzed by the MTT and lactate dehydrogenase release assays; angiogenesis was determined by the tube formation assay. In addition, cell signaling pathways related to angiogenesis were investigated by Western blotting.
Results: Myricetin induced apoptosis and procaspase-3 cleavage though the induction of reactive oxygen species (ROS). It significantly inhibited cell migration, tube formation, and PI3K/Akt/mTOR signaling in HUVECs.
Conclusions: Myricetin exerts antiangiogenic effects by inducing ROS-mediated apoptosis and inhibiting PI3K/Akt/mTOR signaling in HUVECs.

PMID: 29302579 [PubMed]

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Epigenomic Hard Drive Imprinting: A Hidden Code Beyond the Biological Death of Cancer Patients.

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Epigenomic Hard Drive Imprinting: A Hidden Code Beyond the Biological Death of Cancer Patients.

J Cancer Prev. 2017 Dec;22(4):211-218

Authors: Nilendu P, Sharma NK

Abstract
Several genetic and epigenetic theories have been suggested to explain the intricacies of life and death. However, several questions remain unsettled regarding cellular death events, particularly of living tissue in the case of cancer patients, such as the fate and adaptation of cancer cells after biological death. It is possible that cancer cells can display the intent to communicate with the external environment after biological death by means of molecular, genetic, and epigenetic pathways. Whether these cancer cells contain special information in the form of coding that may help them survive beyond the biological death of cancer patients is unknown. To understand these queries in the cancer field, we hypothesize the epigenomic hard drive (EHD) as a cellular component to record and store global epigenetic events in cancerous and non-cancerous tissues of cancer patients. This mini-review presents the novel concept of EHD that is reinforced with the existing knowledge of genetic and epigenetic events in cancer. Further, we summarize the EHD understanding that may impart much potential and interest for basic and clinical scientists to unravel mechanisms of carcinogenesis, therapeutic markers, and differential drug responses.

PMID: 29302578 [PubMed]

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RNA Binding Protein as an Emerging Therapeutic Target for Cancer Prevention and Treatment.

Related Articles

RNA Binding Protein as an Emerging Therapeutic Target for Cancer Prevention and Treatment.

J Cancer Prev. 2017 Dec;22(4):203-210

Authors: Hong S

Abstract
After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis. To develop therapeutic strategies targeting RBPs, RNA interference-based oligonucleotides or small molecule inhibitors have been screened based on reduced RBP-RNA interaction and changed level of target RNAs. Identification of binding RNAs with high-throughput techniques and integral analysis of multiple datasets will help us develop new therapeutic drugs or prognostic biomarkers for human cancers.

PMID: 29302577 [PubMed]

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Pre-S2 Start Codon Mutation of Hepatitis B Virus Subgenotype B3 Effects on NF-κB Expression and Activation in Huh7 Cell Lines

Viral Immunology, Ahead of Print.


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Pre-operative neutrophil count and neutrophil-lymphocyte count ratio (NLCR) in predicting the histological grade of paediatric brain tumours: a preliminary study

Abstract

Introduction

The neutrophil-lymphocyte count ratio (NLCR) is an established prognostic marker for renal, lung and colorectal carcinomas and has been suggested to be predictive of histological grade and outcome in adult intracranial tumours. The purpose of this study was to determine whether a correlation of the pre-operative neutrophil count (NC) and NLCR with the final histological grade exists in paediatric intracranial tumours.

Methods

A retrospective analysis was undertaken at a single centre. Patients less than 18 years old at the time of surgery who underwent tumour-related procedures from 2006 to 2015 were included. Patients with recurrent tumours, previous bone marrow transplant and metastases were excluded. Pre-operative full blood counts (FBC), collected before the diagnosis of intracranial pathology and before administration of steroids, were matched with histological diagnosis for each patient. Post-operative FBC was also recorded, together with survival data where applicable.

Results

A total of 116 patients (74 male, 42 female; mean age, 8 ± 0.9 years) with a diagnosis of primary intracranial tumours had pre-operative FBC that could be matched to final histological grade. Pre-operative NC and NLCR were higher with increasing grade of tumour: grade 1 (NC 4.29 10⁹/l, NLCR 2.26), grade 2 (NC 4.59 10⁹/l, NLCR 2.38), grade 3 (NC 5.67 10⁹/l, NLCR 2.72) and grade 4 (NC 6.59 10⁹/l, NLCR 3.31). Patients with WHO grade 1 and 2 tumours pooled together had a lower NC (4.37 95% CI ± 0.67 10⁹/l) compared to WHO grade 3 and 4 patients (6.41 95% CI ± 0.99 10⁹/l, p = 0.0013). The NLCR was lower in grade 1 and 2 tumours (2.29 ± 0.59) (compared to grade 3 and 4 tumours; 3.20 ± 0.76) but this did not reach significance (p = 0.069). The subgroup of patients with pilocytic astrocytoma had a significantly lower NC when compared to patients with high-grade tumours (p = 0.005). Medulloblastoma and supratentorial PNET subgroups had significantly higher NC compared to the low-grade group (p = 0.033, p = 0.002). Post-operative NC was significantly higher in the high-grade tumours (p = 0.034), but no difference was observed for NLCR (p = 0.28).

Conclusions

No evidence exists to support the correlation of pre-operative NC or NLCR to histological diagnosis in paediatric intracranial tumours. Our results indicate that a higher pre-operative NC/NLCR correlates with a higher histological grade of tumour. This suggests that immunological mechanisms may be involved in the pathogenesis of paediatric brain tumours, and a further prospective study is required to substantiate and expand these findings.

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Trigeminal neuropathy in vestibular schwannoma: a treatment algorithm to avoid long-term morbidity

Abstract

Background

Trigeminal neuropathy (TGN) can occur as a presenting feature of vestibular schwannoma (VS) or as an adverse effect of radiosurgery. This study was designed to evaluate a treatment algorithm for presenting symptoms of TGN in patients with VS, and a new radiosurgery dosimetric tolerance to avoid TGN after treatment. Outcome was measured after microsurgery (MS), stereotactic radiosurgery (SRS), hypofractionated stereotactic radiotherapy (HSRT), and fractionated radiotherapy (FRT).

Methods

A prospectively held VS database was retrospectively analysed from 2011 to 2016 at a tertiary university hospital. All patients who underwent MS from 2011 and all patients who underwent radiotherapy (SRS, HSRT, FRT) from 2015 were studied. Patients on surveillance and neurofibromatosis type 2 patients were not included. Patient demographic data, tumour characteristics, presenting symptoms, and post-treatment outcomes were analysed.

Results

Eighty-eight patients were included in the study (43 microsurgery, 45 radiotherapy). Twenty-seven (31%) patients presented with TGN symptoms. The median age of patients included was 56.5 (range 6–72 years), with a median follow-up for MS and SRS of 38 and 20 months, respectively (range 10–80 months). All 27 patients with TGN were offered MS as per protocol. Three patients declined, or were not fit for surgery, and received FRT. Complete resolution of TGN symptoms was achieved in all 24 patients who underwent MS and 33% (1/3) of patients with FRT. Eleven patients experienced transient post-operative complications (pseudomeningocele (6), meningitis (3), venous sinus thrombosis, cerebellar haemorrhagic contusion, and posterior fossa haematoma). Of the 45 patients in the radiotherapy cohort, 36 were suitable for SRS, of which 30 patients who met the dose-volume constraints for trigeminal nerve underwent single-fraction SRS and 6 patients who did not meet the constraints received HSRT. Nine patients (20%) received FRT including three patients with pre-treatment TGN. None of the patients developed new TGN symptoms following SRS or HSRT.

Conclusions

Our algorithm to select the optimal treatment modality appears to achieve comparable or better long-term outcome. Microsurgical resection in our cohort resulted in complete resolution of symptoms in all patients. None of our SRS- or HSRT-treated patients developed TGN during the follow-up period. The adherence to strict trigeminal nerve dose-volume constraints for SRS remains critical to minimise TGN post treatment. Fractionated radiotherapy is an alternative for patients who refuse surgery or those who are unfit for surgery.

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The role of computed tomography in the screening of patients presenting with symptoms of an intracranial tumour

Abstract

Background

To improve the quality of care for brain cancer patients, the Danish Ministry of Health has set standards for the diagnosis and treatment. When a patient is suspected of having a malignant tumour involving the brain, it is required that a magnetic resonance imaging of the cerebrum (MRI-C) be obtained within seven calendar days of referral from a primary care provider. This standard has the potential to consume MR imaging time that might otherwise be used for evaluation or treatment monitoring of other patients. This study primarily aims to assess the sensitivity of computed tomography of the brain (CT-C) for the detection of intracranial tumour as the initial diagnostic imaging.

Methods

This is a single-center retrospective study of patients referred to the IBCP with brain cancer suspicion. The average follow-up was 37 months. All included patients underwent a CT-C scan and subsequently a MRI-C if deemed necessary. The study population was divided into two groups based on the findings: tumour versus non-tumour. Sensitivity and specificity of the CT-C was calculated.

Results

Eight hundred seventeen patients were included. Median age was 55 years and 50% were male. CT-C had a sensitivity of 98.5% and a specificity of 98.4%. The overall mortality rate was 7% in the non-tumour group and 58% in the tumour group over the course of the study period. The tumour group was on average older compared to the non-tumour group (65 years [55–75 years] vs 52 years [38–65 years]) p < .001). The only symptom associated with brain tumour was the presence of a focal deficit (p = .002).

Conclusion

This study shows that CT-C scans are highly sensitive and specific and can be used as the primary screening tool for patients referred with a suspicion for brain cancer.

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Thoracic ossification of ligamentum flavum manifesting holocord syringomyelia: case report

Abstract

It has been reported that syringomyelia is rarely associated with degenerative spinal disorders, but the case of holocord syringomyelia is never reported. We here present a case of a 59-year-old woman with right shoulder pain, dysesthesia of the right hand, and gait disturbance. Radiographically, examinations of the spine demonstrated holocord syringomyelia with ossification of ligamentum flavum at T2/3 level. Holocord syringomyelia was reduced remarkably after posterior decompression at the T2/3 level, and her symptoms also improved. We speculated that holocord syringomyelia might have developed due to craniospinal pressure dissociation caused by focal compression of dural sac from extradural degenerative change.

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Impact of early access to multidisciplinary care on treatment outcomes in patients with skull base chordoma

Abstract

Objective

To determine if early access to multidisciplinary surgical care affects outcomes in patients with skull base chordoma.

Method

A retrospective chart review of prospectively collected data was performed on 51 patients treated from 1993 to 2014. The cohort was divided into those presenting (1) for initial management (ID, n = 21) or (2) with persistent/progressive disease after prior biopsy/surgery (PD, n = 30) outside of a multidisciplinary setting. The impact of initial surgical management in a multidisciplinary center on progression-free survival (PFS) was assessed with Kaplan-Meier and log-rank analyses.

Results

Mean follow-up, median PFS, median overall survival (OS), and 10-year OS for the entire cohort was 70 months, 47 months, 159 months, and 19%, respectively. Initial management in a multidisciplinary center resulted in a significant improvement in PFS versus initial surgery with or without radiotherapy (XRT) outside of this setting (64 vs 25 months, p = 0.035). Initial surgical resection outside of a multidisciplinary setting increased the risk of recurrence/progression on univariate (HR, 2.276; p = 0.022) and multivariate analysis (HR, 2.831; p = 0.006), respectively.

Conclusions

The results from this study emphasize the impact that coordinated multidisciplinary surgical care has on patient outcomes for chordomas of the clivus. Biopsy followed by attempted radical resection at a dedicated center does not affect PFS and, therefore, represents a reasonable first step in management for patients presenting outside of multidisciplinary setting.

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Can patients with symptomatic Tarlov cysts be differentiated from patients with specific low back pain based on comprehensive history taking?

Abstract

Background

Tarlov cysts (TCs) are expanded nerve root sheaths that occur near the dorsal root ganglion and result from increased intraspinal hydrostatic pressure. TCs most frequently affect the lumbosacral plexus and therefore may cause specific symptoms such as perineal pain and neurogenic bladder, bowel, and sphincter problems. It has been estimated that 1% of the population has symptomatic Tarlov cysts (STCs). However, STCs appear to be underdiagnosed, with the pain reported by patients commonly attributed to degenerative alterations seen on MRI. The aim of the present study is to investigate the utility of a comprehensive questionnaire for use by physicians in establishing the diagnosis of STCs.

Methods

We compared questionnaire responses regarding patient history between 33 patients diagnosed with symptomatic TCs and 42 patients with chronic low back pain and sciatica due to disc problems or degenerative or inflammatory disorders. The diagnosis of STCs was confirmed using nerve conduction studies (NCS) and electromyography (EMG) of the sacral myotomes by an expert neurophysiologist.

Results

The questionnaire responses revealed specific differences in perineal symptoms (perineal pain, dyspareunia, coccygodynia), bowel symptoms (constipation, diarrhea), bladder symptoms (hesitation, retention, frequency), and anal sphincter problems (anal pain, mild fecal incontinence). Additionally, sitting, walking, and straining aggravated pain more frequently in STC patients, and STC patients were more often forced to stop working and/or reduce their social activities.

Conclusions

Including the above-listed items in the patient history might facilitate differentiation of low back pain and sciatica due to STCs from that due to disc problems or degenerative or inflammatory disorders.

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On government-regulated access to diagnostic imaging in neurosurgery

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Computer tomography-based morphometric analysis of the cervical spine pedicles C3–C7

Abstract

Background

Our aim was to examine the specific dimensions of cervical pedicles in a large Caucasian cohort on high dissolving CT scans.

Methods

A retrospective analysis of 100 cervical spine CT scans with a maximum slice thickness of 1 mm in axial, sagittal, and coronal reconstructions was performed. The pedicle axial length (PAL), inner and outer pedicle diameter (IPD/OPD), pedicle sagittal and transverse angle (PSA/PTA), pedicle height (PH), pedicle width (PW), and the cortical thickness (COT) at different margins were measured by two independent observers. A total of 1000 cervical pedicles (C3–C7) of 52 male (age 58 ± 17.47 years, height 177.97 ± 8.17 cm) and 48 female patients (age 57 ± 19.07 years, height 165.50 ± 7.44) were measured.

Results

Cortical thickness at the medial limitation of the pedicle was 1.77 ± 0.43 and 0.90 ± 0.36 mm at the lateral limitation (p < 0.001). The mean PAL ranged from 30.5 mm at C4 level to 35.3 mm at C6 level. PW and PAL were smaller in the female than in the male patients. The smallest values for PW were at C3 with 29.17% of males and 52.88% of females < 4.5 mm. The percentage of patients with PW < 4.5 mm decreased caudally with less than 10% of pedicles below C4 in male participants and below C6 in female participants. Mean PTA ranged from 34.6° to 48.02° peaking at C4 and C5 levels. No gender-specific difference was found for PTA and PSA (p ≥ 0.13). IPD and OPD were larger in males (p < 0.001), and body height correlated significantly with IPW (p ≤ 0.019) and OPW (p ≤ 0.003). The interrater reliability was very good for PW, PH, and IPD (0.84–0.86), good for OPD, PTA, and PSA (0.64–0.79), and moderate for PAL (0.54) and cortical thickness (0.44).

Conclusions

Peculiarities of pedicle dimension of this central European cohort are comparable to morphometric studies in other ethnicities. Preoperative planning before cervical pedicle screw insertion on fine-cut CT scans demonstrates good interrater reliability for all important dimensions and angulations. More than half of female patients and almost a third of male patients had a PW of less than 4.5 mm at C3 level. Even though this percentage decreases caudally, pedicle screws might not be safe to insert in a noteworthy percentage of patients.

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Distal transsylvian keyhole approach for unruptured anterior circulation small aneurysms

Abstract

Background

To reduce complications associated with conventional pterional craniotomy, a transsylvian keyhole approach for unruptured small anterior circulation aneurysms is proposed.

Methods

A 7-cm linear scalp incision is made along the hairline, beginning at the zygoma, followed by minimal temporal muscle dissection. Two burr holes are drilled out at McCarty's point and the temporal bone, and a 3-cm equilateral triangle bone flap is made, whose apex is located above the sylvian point. After the sphenoid ridge is drilled off, aneurysms are exposed and clipped with conventional microsurgical instruments.

Conclusions

This approach permits access to aneurysms via the transsylvian corridor with a smaller area of potential injury of superficial structures.

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Endplate changes after lumbar discectomy with and without implantation of an annular closure device

Abstract

Background

The implantation of a bone-anchored annular closure device (ACD) might be associated with the developed new endplate changes (EPC) after surgery.

Methods

A post hoc analysis has been done in patients from a prospective randomized multicenter study. All patients underwent limited lumbar discectomy with intraoperative randomization into the groups limited lumbar discectomy alone or additional ACD implantation. Low-dose lumbar computed tomography (CT) and clinical investigations were performed preoperatively and 12 months after the operation.

Results

A total of 554 patients were randomized. After exclusion of dropouts, the per-protocol population included 493 patients (251 in the control group and 242 in the ACD group); the follow-up rate was ≥ 90%. The number of patients showing EPC at baseline was similar in both groups. The number of patients showing EPC and the total EPC lesion area significantly increased in both groups over time, but significantly increased more in the EPC group for the superior and inferior endplate (all P < 0.0001). There was no association of pre-existing number and size of EPC with sex, age, or smoking habits. Correlation of clinical variables showed no relation with number, size, and increase of EPC area after surgery.

Conclusions

Patients with primary lumbar disc herniation show EPC in the corresponding segments. There is a significant increase of lesion number and size within 12 months after discectomy. This increase is significantly more pronounced in the ACD group. Presence and growth of EPC is not correlated with low-back pain or ODI.

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Single-stage total resection of giant dumbbell-shaped hypoglossal schwannoma: a case report

Abstract

Extensive large dumbbell-shaped hypoglossal schwannoma is extremely rare, and total resection is nearly impossible. We present a case of a 61-year-old male with a giant-size hypoglossal schwannoma with moderate tongue atrophy. The tumor extended from the enlarged hypoglossal canal to the brainstem intradurally and the high cervical region extradurally. Through the extreme lateral infrajugular transcondylar (ELITE) skull base approach, the tumor was totally removed in a single-stage operation. Single-stage total resection is feasible by an experienced skull base team utilizing transcondylar skull base techniques and high cervical dissection.

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Parapharyngeal neuroglial heterotopia appearing as high uptake on 18 F–FDG PET: case report and literature review of radiographical findings

Abstract

Parapharyngeal neuroglial heterotopia is a rare entity, and the specific radiographical findings are unclear. We present a case of parapharyngeal neuroglial heterotopia examined with proton magnetic resonance spectroscopy (¹H–MRS) and ¹⁸F–fluorodesoxyglucose positron emission tomography (¹⁸F–FDG PET). Our neonate patient presented with neck mass and polyhydramnios during gestation. Computed tomography and magnetic resonance imaging demonstrated the morphological characteristics, but failed to establish the diagnosis. ¹H–MRS showed a non-malignant pattern, but ¹⁸F–FDG PET demonstrated high glucose metabolism. Complete resection was achieved and the histopathological diagnosis was neuroglial heterotopia. Assessment of biological activity may be useful for both preoperative diagnosis and postoperative evaluation of residual lesions.

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Clinical applications of dynamic CT angiography for intracranial lesions

Abstract

Background

Dynamic CT angiography (dCTA) augments traditional CTA with temporal resolution and has been demonstrated to influence operative planning in skull base surgery.

Methods

Three hundred twenty-five dynamic CTA cases from a single institution were reviewed for indication of study, findings, and comparison to other modalities of imaging.

Results

The most frequent application of dCTA was pre-operative surgical planning (59.4%); resection of skull base tumors represented the majority of these pre-operative studies (93.3%). It was also used to evaluate new neurological symptoms (20.9%). Of these, the most common symptoms prompting a dCTA study included headache (22.1%) and visual field deficit (11.8%). The most commonly visualized vascular lesions were partial (22.9%) and complete vascular occlusions (9.0%). Dynamic CTA has also been useful in post-operative imaging for vascular malformations (9.5%) and tumors (2.5%). Finally, dCTA was employed to evaluate ambiguous abnormal findings observed on other imaging modalities (7.7%). Cerebral dCTA ruled out inconclusive abnormal vascular findings visualized on other imaging modalities (64.0%) more frequently than it confirmed them (32.0%), and was inconclusive in a singular case (4.0%).

Conclusions

Cerebral dCTA is an evolving new technology with a diverse spectrum of potential applications. In addition to its role in guiding pre-operative planning for skull base surgical cases, dynamic CTA offers excellent spatial and temporal resolution for assessment of vascular lesions.

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Subthalamic deep brain stimulation under general anesthesia and neurophysiological guidance while on dopaminergic medication: comparative cohort study

Abstract

Objectives

The authors have previously reported on the technical feasibility of subthalamic nucleus deep brain stimulation (STN DBS) under general anesthesia (GA) with microelectrode recording (MER) guidance in Parkinsonian patients who continued dopaminergic therapy until surgery. This paper presents the results of a prospective cohort analysis to verify the outcome of the initial study, and report on wider aspects of clinical outcome and postoperative recovery.

Methods

All patients in the study group continued dopaminergic therapy until GA was administered. Baseline characteristics, intraoperative neurophysiological markers, and perioperative complications were recorded. Long-term outcome was assessed using selective aspects of the unified Parkinson's disease rating scale motor score. Immediate postoperative recovery from GA was assessed using the "time needed for extubation" and "total time of recovery." Data for the "study group" was collected prospectively. Examined variables were compared between the "study group" and "historical control group" who stopped dopaminergic therapy preoperatively.

Results

The study group, n = 30 (May 2014–Jan 2016), were slightly younger than the "control group," 60 (51–64) vs. 64 (56–69) years respectively, p = 0.043. Both groups were comparable for the recorded intraoperative neurophysiological parameters; "number of MER tracks": 60% of the "study group" had single track vs. 58% in the "control" group, p = 1.0. Length of STN MER detected was 9 vs. 7 mm (median) respectively, p = 0.037. A trend towards better recovery from GA in the study group was noted, with shorter "total recovery time": 60 (50–84) vs. 89 (62–120) min, p = 0.09. Long-term improvement in motor scores and reduction in l-dopa daily equivalent dose were equally comparable between both groups. No cases of dopamine withdrawal or problems with immediate postop dyskinesia were recorded in the "on medications group." The observed rate of dopamine-withdrawal side effects in the "off-medications" group was 15%.

Conclusions

The continuation of dopaminergic treatment for patients with PD does not affect the feasibility/outcome of the STN DBS surgery. This strategy appears to reduce the risk of dopamine-withdrawal adverse effects and may improve the recovery in the immediate postoperative period, which would help enhance patients' perioperative experience.

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Risk of de novo aneurysm formation in patients with unruptured intracranial aneurysms

Abstract

Background and purpose

The rate of de novo aneurysm formation in patients with unruptured aneurysm without history of subarachnoid hemorrhage is scarcely defined in literature. We report the incidence of de novo aneurysm formation in a large contemporary series of patients with unruptured intracranial aneurysm (UIA) undergoing serial neurovascular imaging.

Methods

Neurovascular imaging studies of 321 consecutive UIA patients with no prior history of subarachnoid hemorrhage, with at least 3 years of follow-up imaging, were reviewed by a neuroradiologist and a neurosurgeon. Rate of de novo aneurysm formation was reported on a per-patient and per-patient-year basis.

Results

Of the 321 included patients, three patients (0.9%) developed a de novo aneurysm over a mean follow-up period of 5.2 years, for an incidence rate of 0.18% per patient-year. No de novo aneurysms ruptured and all three were 2 mm in size.

Conclusions

The rate of de novo aneurysm formation in patients with unruptured aneurysms and no history of subarachnoid hemorrhage is very low. These data are useful to advice patients with unruptured aneurysms from another aneurysm and to plan imaging follow-ups in these patients.

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Intraoperative tools for cerebral bypass surgery

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The novel deubiquitinase inhibitor b-AP15 induces direct and NK cell-mediated antitumor effects in human mantle cell lymphoma

Abstract

The first therapeutic proteasome inhibitor bortezomib has clinical efficacy in mantle cell lymphoma (MCL) which resulted in its incorporation in treatment algorithms for this disease. Impairment of proteasomal function by bortezomib is mediated via inhibition of the 20S core particle. However, proteasome function can also be modified by targeting upstream components of the ubiquitin–proteasome system. Recently, b-AP15 has been identified as a small molecule achieving proteasome inhibition by targeting the deubiquitinase (DUB) activity of the 19S regulatory subunit and was found to inhibit cancer cell growth in preclinical analyses. In the present study, both direct antitumor effects and the possibility to induce natural killer group 2 member D ligands (NKG2DL) to reinforce NK cell immunity with b-AP15 were investigated to provide a rational basis for clinical evaluation of this novel DUB inhibitor in MCL. Treatment with b-AP15 resulted in reduced viability as well as induction of apoptosis in a time- and dose-dependent manner, which could be attributed to caspase activation in MCL cells. In addition, treatment with b-AP15 differentially induced NKG2DL expression and subsequent NK cell lysis of MCL cells. These results indicate that the DUB inhibitor b-AP15 displays substantial antitumor activity in human MCL and suggest that b-AP15 might be a novel therapeutic option in the treatment of MCL that warrants clinical investigation.

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Einfluss der psychosozialen Situation auf die CI-Versorgung der 1. Generation – „Ich hatte nichts zu verlieren“

Sprache Stimme Gehör 2018; 42: 35-37
DOI: 10.1055/s-0044-100316

© Georg Thieme Verlag KG Stuttgart · New York

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Aryüberkreuzung

Sprache Stimme Gehör 2018; 42: 14-15
DOI: 10.1055/s-0044-101701

© Georg Thieme Verlag KG Stuttgart · New York

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Gutachter 2017

Sprache Stimme Gehör 2018; 42: 6-6
DOI: 10.1055/s-0044-101805

© Georg Thieme Verlag KG Stuttgart · New York

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Die Inputspezifizierung

Sprache Stimme Gehör 2018; 42: 5-5
DOI: 10.1055/s-0043-124056

© Georg Thieme Verlag KG Stuttgart · New York

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Klassenwiederholung wegen Hörschwäche

Sprache Stimme Gehör 2018; 42: 6-6
DOI: 10.1055/s-0043-117874

© Georg Thieme Verlag KG Stuttgart · New York

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Alter und Emotion: Wie verändern sich die Gefühle älterer Menschen und die Art, mit ihnen umzugehen?

Sprache Stimme Gehör 2018; 42: 6-8
DOI: 10.1055/s-0044-100311

© Georg Thieme Verlag KG Stuttgart · New York

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Dysgrammatismus

Sprache Stimme Gehör 2018; 42: 12-13
DOI: 10.1055/s-0044-101861

© Georg Thieme Verlag KG Stuttgart · New York

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Spezifische Sprachentwicklungsstörung und mütterliche bzw. familiäre Merkmale

Sprache Stimme Gehör 2018; 42: 8-9
DOI: 10.1055/s-0043-121254

© Georg Thieme Verlag KG Stuttgart · New York

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Subjektive Hörfähigkeit und Versorgung hochaltriger Personen

Sprache Stimme Gehör 2018; 42: 18-23
DOI: 10.1055/s-0043-119117

© Georg Thieme Verlag KG Stuttgart · New York

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Spielqualität und Zahl der Spielzeuge bei Kleinkindern

Sprache Stimme Gehör 2018; 42: 9-10
DOI: 10.1055/s-0044-101692

© Georg Thieme Verlag KG Stuttgart · New York

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Diagnostik und Therapie von Schwerhörigkeit inkl. Cochlea-Implantat bei Migranten in Deutschland

Sprache Stimme Gehör 2018; 42: 30-34
DOI: 10.1055/s-0043-119118

© Georg Thieme Verlag KG Stuttgart · New York

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Wie im Schlaf aus Lauten Wörter werden

Sprache Stimme Gehör 2018; 42: 10-11
DOI: 10.1055/s-0043-119276

© Georg Thieme Verlag KG Stuttgart · New York

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Dysarthrie bei Multipler Sklerose

Sprache Stimme Gehör 2018; 42: 38-39
DOI: 10.1055/s-0043-121255

© Georg Thieme Verlag KG Stuttgart · New York

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Der leicht reizbare Kehlkopf

Sprache Stimme Gehör 2018; 42: 46-46
DOI: 10.1055/s-0043-120470

© Georg Thieme Verlag KG Stuttgart · New York

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Liebe Leserinnen und Leser,

Sprache Stimme Gehör 2018; 42: 1-1
DOI: 10.1055/s-0043-125406

© Georg Thieme Verlag KG Stuttgart · New York

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Prospective evaluation of plasma Epstein–Barr virus DNA clearance and fluorodeoxyglucose positron emission scan in assessing early response to chemotherapy in patients with advanced or recurrent nasopharyngeal carcinoma

Prospective evaluation of plasma Epstein–Barr virus DNA clearance and fluorodeoxyglucose positron emission scan in assessing early response to chemotherapy in patients with advanced or recurrent nasopharyngeal carcinoma

Prospective evaluation of plasma Epstein–Barr virus DNA clearance and fluorodeoxyglucose positron emission scan in assessing early response to chemotherapy in patients with advanced or recurrent nasopharyngeal carcinoma, Published online: 20 March 2018; doi:10.1038/s41416-018-0026-9

Prospective evaluation of plasma Epstein–Barr virus DNA clearance and fluorodeoxyglucose positron emission scan in assessing early response to chemotherapy in patients with advanced or recurrent nasopharyngeal carcinoma

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Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study

Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study

Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study, Published online: 20 March 2018; doi:10.1038/s41416-018-0011-3

Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study

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Transcription factor FoxM1 is the downstream target of c-Myc and contributes to the development of prostate cancer

Abstract

Background

Prostate cancer is a common malignancy and the second leading cause of cancer death in men. Elevated expression of the transcription factor FoxM1 and c-Myc has been identified in prostate cancer. However, the potential mechanism of elevated FoxM1 and c-Myc to the development of prostate cancer has not been identified.

Methods

In this report, the mRNA level of FoxM1 and c-Myc was detected in 30 prostate cancer and para-cancer tissues. Then, we detected the expression level of FoxM1 by real-time PCR and Western blot after disturbance of the expression level of c-Myc in PC-3 cells. Whether c-Myc could bind to FoxM1 promoter was identified by ChIP assay. Finally, the migratory, invasive, and proliferative abilities in FoxM1 overexpressing and silencing PC-3 cells were detected by wound healing, transwell assay, CCK-8 assays, and Ki-67 protein level.

Results

We found that the expression level of FoxM1 and c-Myc were both increased in prostate cancer samples compared with para-cancer samples. The expression level of FoxM1 was changed consistent with the protein level of c-Myc. ChIP assay detected the direct binding of c-Myc in FoxM1 gene promoter. Lastly, overexpression of FoxM1 increased the migratory, invasive, and proliferative abilities of PC-3 cells, and its downregulation significantly decreased the migratory, invasive, and proliferative abilities.

Conclusions

In conclusion, FoxM1 was significantly increased in prostate cancer samples, and it could regulate the proliferative and invasive ability of prostate cancer cells which might be a new target for prostate cancer. Besides, c-Myc could regulate the expression level of FoxM1 by directly binding to its gene promoter.

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Impact of donor type in patients with AML given allogeneic hematopoietic cell transplantation after low-dose TBI based regimen

Purpose: We assessed the impact of donor type in acute myeloid leukemia (AML) patients transplanted with 2 Gy total body irradiation (TBI)-based nonmyeloablative conditioning regimen. Experimental Design: Data from 1715 adult patients, with AML in CR1 or CR2 were included in this retrospective survey. Results: Donors consisted either of HLA-matched sibling donors (MSD, n=701), 10/10 HLA-matched unrelated donors (MUD, n=611), HLA-haplo-identical donors (haplo, n=112) or single or double umbilical cord bloods (CBT, n=291). Chronic graft-versus-host disease (GVHD) was less frequent in CBT (28%) and in haplo (30%) patients than in MSD (50%) and MUD (51%) recipients (P<0.001). Two-year incidence of relapse was 32%, 30%, 34% and 34% in MSD, MUD, CBT and haplo patients, respectively (P=0.7). Two-year overall (OS) and GVHD-free relapse free survival (GRFS) were 59% and 29% in MSD patients, 56% and 39% in CBT recipients, 53% and 23% in MUD recipients, and 43% and 37% in haplo patients, respectively. In multivariate analyses, MUD patients had lower GRFS than MSD patients beyond day 100 (HR 1.3, P=0.001) while CBT was associated with a better GRFS than MSD beyond day 100 (HR 0.6, P=0.002).  Conclusions: In this large cohort of AML patients transplanted following low-dose TBI-based conditioning the relapse incidence was not affected by donor type suggesting that the intensity of GVL effects might be comparable with these four transplant approaches. Further, CBT was associated with better GRFS beyond day 100 than MSD while the opposite was observed for MUD.

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Salivary gland cancer patient-derived xenografts enable characterization of cancer stem cells and new gene fusions associated with tumor progression

Purpose: Salivary gland cancers (SGC) frequently present with distant metastases many years after diagnosis, suggesting a cancer stem cell (CSC) subpopulation that initiates late recurrences; however current models are limited both in their availability and suitability to characterize these rare cells. Experimental Design: Patient-derived xenografts (PDX) were generated by engrafting patient tissue onto nude mice from one acinic cell carcinoma (AciCC), four adenoid cystic carcinoma (ACC), and three mucoepidermoid carcinoma (MEC) cases, which were derived from successive relapses from the same MEC patient. Patient and PDX samples were analyzed by RNA-seq and Exome-seq. Sphere formation potential and in vivo tumorigenicity was assessed by sorting for Aldefluor (ALDH) activity and CD44 expressing subpopulations. Results: For successive MEC relapses we found a time-dependent increase in CSCs (ALDH+CD44high), increasing from 0.2% to 4.5% (P=0.033), but more importantly we observed an increase in individual CSC sphere formation and tumorigenic potential. A 50% increase in mutational burden was documented in subsequent MEC tumors, and this was associated with increased expression of tumor promoting genes (MT1E, LGR5, LEF1), decreased expression of tumor suppressor genes (CDKN2B, SIK1, TP53), and higher expression of CSC-related proteins such as SOX2, MYC, and ALDH1A1. Finally, genomic analyses identified a novel NFIB-MTFR2 fusion in an ACC tumor and confirmed previously reported fusions (NTRK3-ETV6 and MYB-NFIB). Conclusions: Sequential MEC PDX models preserved key patient features and enabled the identification of genetic events putatively contributing to increases in both CSC proportion and intrinsic tumorigenicity, which mirrored the patient's clinical course. 

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