Greatly Improved Oil-in-Water Emulsion Separation Properties of Graphene Oxide Membrane upon Compositing with Halloysite Nanotubes

Abstract

Graphene oxide (GO)-based membranes provide an encouraging opportunity for oil-in-water emulsion separation with high separation efficiency. In this work, novel hierarchically structured membrane consisting of GO and halloysite nanotubes (HNTs) was successfully fabricated by vacuum-assisted filtration method. XRD and TEM measurements showed the successful intercalation of HNTs into the interlayers of GO nanosheets. With the incorporation of the one-dimensional hollow tubular structure halloysite nanotubes, GO-HNTs(GOH) membrane possessed combined advantages of high oil rejection rate and excellent fouling resistance properties. The permeate fluxes increased from 286.6 L/(m²·h) for GO membrane to 716 L/(m²·h) for GOH membrane. The results indicate that the GOH membranes have great potential applications in water purification and wastewater treatment.

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Hydrodynamic Conditions Influence Bacterial Growth and Phenol Biodegradation of Strains with Different Morphology and Motility

Abstract

Microorganisms are frequently exposed to flowing fluid, thus to investigate bacterial characteristics under different hydrodynamic conditions is of great importance in microbial ecology. This study characterized bacterial growth and phenol biodegradation of three strains, i.e., Microbacterium oxydans (rod-shaped, non-motile), Alcaligenes faecalis (rod-shaped, motile), and Staphylococcus haemolyticus (spherical, non-motile) in shake-flask cultures at various rotating speeds. For all the strains, a higher rotating speed always resulted in a shorter lag phase, indicating that the strains showed a superior adaptability under higher hydrodynamic conditions. The maximum specific growth rate of M. oxydans, A. faecalis, and S. haemolyticus increased rapidly with the increase of energy dissipation rate till the highest value of 0.386, 0.240, and 0.323 1/h and then decreased as the rotating speed further increased. The phenol biodegradation rate was also dependent on rotating speed, and the trends were consistent with the growth rate variations. A predictive model similar to Haldane model was proposed and was fitted well (R² > 0.913) with bacterial growth under different hydrodynamic conditions. According to the predictive model, the optimum hydrodynamic conditions for the growth of M. oxydans, A. faecalis, and S. haemolyticus were 3.099, 2.197, and 2.289 m²/s³, respectively. The results suggested that non-motile and rod-shaped bacteria were more dependent on hydrodynamic conditions than motile and spherical ones, which could be attributed to the discrepancies in bacterial morphology and motility. The results provide a better understanding on bacterial responses to various hydrodynamic conditions and could be further applied in the bioremediation of contaminated water.

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Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Ramón García-Escudero, Carmen Segrelles, Marta Dueñas, María Pombo, Claudio Ballestín, Marina Alonso-Riaño, Pablo Nenclares, Roberto Álvarez-Rodríguez, Gregorio Sánchez-Aniceto, Ana Ruíz-Alonso, José Luis López-Cedrún, Jesús M. Paramio, Corina Lorz
ObjectivesPhosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved.Material and methodsMutation and copy-number variation in PIK3CA, and whole-genome expression profiles, were analyzed in primary HNSCC tumors from The Cancer Genome Atlas (TCGA) cohort (n = 243). The results were validated in an independent cohort form the University Hospital of A Coruña (UHAC, n = 62). Expression of the PIK3CA gene protein product (PI3K p110α) and nuclear YAP were assessed in tissue microarrays in a cohort from the University Hospital 12 de Octubre (UH12O, n = 91).ResultsOnly high expression of the PIK3CA gene was associated with poor clinical outcome. The study of gene expression, transcription factor and protein signatures suggested that the activation of the Hippo-YAP pathway, involved in organ size, stem cell maintenance and tumorigenesis, could underlie tumor progression in PI3KCA overexpressing tumors. Tissue arrays showed that PI3K p110α levels correlated with YAP nuclear localization in HNSCC tumors.ConclusionsHigh expression of PIK3CA in HNSCC primary tumors identifies patients at high risk for recurrence. In these tumors, progression could rely on the Hippo-YAP pathway instead of the canonical Akt/mTOR pathway. This observation could have important implications in the therapeutic options for patients.

Graphical abstract

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Phase I study of taselisib in Japanese patients with advanced solid tumors or hormone receptor-positive advanced breast cancer

Summary

Taselisib is a potent and selective phosphatidylinositide 3-kinase (PI3K) inhibitor. This paper reports the first study of taselisib administration in Japanese patients. The aim of this two-stage, phase I, multicenter, open-label, dose-escalation study was to evaluate the safety, pharmacokinetics, and preliminary efficacy of taselisib as monotherapy in Japanese patients with advanced solid tumors (Stage 1), and as part of combination therapy in Japanese patients with hormone receptor (HR)-positive locally advanced or recurrent breast cancer (Stage 2). In Stage 1, oral taselisib tablets 2, 4, and 6 mg/day were administered in 28-day cycles. In Stage 2, successive cohorts of patients received oral taselisib tablets (2 or 4 mg/day) with intramuscular fulvestrant 500 mg. Nine and six patients were enrolled in Stage 1 and Stage 2, respectively. Taselisib was well tolerated. No dose-limiting toxicities were experienced in any cohort of patients and no deaths were observed. The most common treatment-related adverse events in Stage 1 and Stage 2 were rash (55.6%, 66.7%), diarrhea (44.4%, 66.7%), stomatitis (44.4%, 66.7%). Taselisib was rapidly absorbed after administration; its half-life was 12.9–32.0 hours in Stage 1 and 16.1–26.5 hours in Stage 2. Two patients achieved partial response (PR) and five patients had stable disease (SD) in Stage 1, and one patient had PR and five patients had SD in Stage 2. All patients with PR were positive for PIK3CA gene mutations. These preliminary data suggest that taselisib may be effective in patients with PIK3CA-mutated solid tumors or HR-positive advanced breast cancer.

This article is protected by copyright. All rights reserved.

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Taxane use in breast cancer and risk of brain metastases

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La azatioprina reduce el riesgo de recaída audiométrica en hipoacusia inmunomediada

Publication date: Available online 2 March 2018
Source:Acta Otorrinolaringológica Española
Author(s): Nieves Mata-Castro, Javier Gavilanes-Plasencia, Rafael Ramírez-Camacho, Alfredo García-Fernández, José Ramón García-Berrocal
IntroducciónLos esquemas actuales de tratamiento de la hipoacusia inmunomediada con corticoides, a dosis baja y pauta corta, son insuficientes.MétodosPara determinar el papel de la azatioprina en el control del deterioro auditivo se ha llevado a cabo un estudio observacional descriptivo longitudinal con 20 pacientes tratados con azatioprina por vía oral (1,5-2,5mg/kg/día en dos dosis) durante 1año. Se consideró recaída la pérdida de 10dB en dos frecuencias consecutivas o de 15dB en una frecuencia aislada.ResultadosLa edad media de los pacientes fue de 52,50años (IC95%: 46,91-58,17), y la mitad fueron mujeres. La afectación bilateral fue del 65%. Un 75% presentaban enfermedad organoespecífica y un 25%, enfermedad autoinmune sistémica. La diferencia entre la PTA basal (46,49 dB; DE18,90) y la PTA a los 12meses (45,47dB; DE18,88) no alcanzó significación estadística (p=0,799). Existía una correlación positiva moderada entre sexo femenino y presencia de enfermedad sistémica (R=0,577). Aplicando t de Student para datos apareados se obtuvo una diferencia significativa (p=0,042) entre el descenso de la PTA en frecuencias hasta 1.000Hz (PTA125-1.000Hz). La tasa relativa de incidencia de recaída por año fue de 0,52 recaídas/año (IC95%: 0,19-1,14). El tiempo medio de supervivencia libre de recaída audiométrica fue de 9,70meses (DE1,03).ConclusionesLa azatioprina mantiene el umbral de audición, disminuye el riesgo de recaída y frena la velocidad con la que los pacientes recaen, alterando el curso de la enfermedad inmunomediada del oído interno.IntroductionCurrent schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient.MethodsTo determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5-2.5mg/kg/day into two doses) for 1year. The loss of 10dB on two consecutive frequencies or 15dB on an isolated frequency was considered as relapse.ResultsThe mean age of the patients was 52.50years (95%CI: 46.91-58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49dB; DS18.90) and PTA at 12months (45.47dB; DS18.88) did not reach statistical significance (P=.799). There was a moderate positive correlation between female sex and the presence of systemic disease (R=.577). By applying Student's t for paired data, a significant difference (P=.042) was obtained between the PTA in frequencies up to 1000 Hz (PTA125-1000Hz). The relative incidence rate of relapse per year was .52 relapses/year (95%CI: .19-1.14]). The median time to audiometric relapse-free was 9.70months (DS1.03).ConclusionsAzathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease.



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The Chemical Sensitivity and Electrical Activity of Individual Olfactory Sensory Neurons to a Range of Sex Pheromones and Food Odors in the Goldfish

Abstract

Although it is well established that the olfactory epithelium of teleost fish detects at least 6 classes of biologically-relevant odorants using five types of olfactory sensory neurons (OSNs), little is understood about the specificity of individual OSNs and thus how they encode identity of natural odors. In this study we used in vivo extracellular single-unit recording to examine the odor-responsiveness and physiological characteristics of 109 individual OSNs in mature male goldfish to a broad range of biological odorants including feeding stimuli (amino acids, polyamines, nucleotides), sex pheromones (sex steroids, prostaglandins) and a putative social cue (bile acids). Sixty-one OSNs were chemosensitive, with over half of these (36) responding to amino acids, 7 to polyamines, 7 to nucleotides, 5 to bile acids, 9 to prostaglandins, and 7 to sex steroids. Approximately a quarter of the amino acid-sensitive units also responded to polyamines or nucleotides. Three of 6 amino acid-sensitive units responded to more than one amino acid compound, and 5 sex pheromone-sensitive units detected just one sex pheromone. While pheromone-sensitive OSNs also responded to the adenylyl cyclase activator, forskolin, amino acid-sensitive OSNs responded to either forskolin or a phospholipase C activator, imipramine. Most OSNs responded to odorants and activators with excitation. Our results suggest that pheromone information is encoded by OSNs specifically tuned to single sex pheromones and employ adenylyl cyclase, suggestive of a labeled-line organization, while food information is encoded by a combination of OSNs that use both adenylyl cyclase and phospholipase C and are often less specifically tuned.

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Discriminatory miRNAs for the Management of Papillary Thyroid Carcinoma and Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features

Thyroid , Vol. 0, No. 0.


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ASP2215 in the treatment of relapsed/refractory acute myeloid leukemia with FLT3 mutation: background and design of the ADMIRAL trial

Future Oncology, Ahead of Print.


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New Signia Hearing Aids Combine Convenience, Discretion, and Quality Sound

Signia's (http://ift.tt/29sqzaU) newest hearing aids Pure Charge&Go offers wireless rechargeability and natural sound quality. With a lithium-ion power cell and an inductive charger, Pure Charge& Go can be simply placed in the charger for charging at night and will remain charged all day. The lithium-ion cell technology in this hearing aid lasts significantly longer than traditional zinc-based rechargeable batteries, even after multiple years of use, eliminating the need to change batteries frequently. Wearers can enjoy streaming up to five hours per day via Bluetooth and still have 17 hours of battery cell run time, or 19 hours of run time without streaming. Built with Signia's Own Voice Processing technology, Pure Charge&Go is equipped to identify the user's voice and processes it separately from other sounds and create the most natural-sounding own voice for its user.
 
Other features include access to Signia's myControl App, which allows users to change the settings on their smartphones, and the myHearing App, which provides support, exercises, and user guides. Users can also access TeleCare, which allows them to schedule remote consultations with their hearing care professionals.

Published: 3/2/2018 5:11:00 PM

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Low Incidence of esophageal toxicity following Lung SBRT: Are current esophageal dose constraints too conservative?

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Vivian Yau, Patricia Lindsay, Lisa Le, Anthea Lau, Olive Wong, Daniel Glick, Andrea Bezjak, B.C.John Cho, Andrew Hope, Alex Sun, Meredith Giuliani
IntroductionTumours in close proximity to the esophagus present a challenge for lung SBRT, as potential esophageal toxicity must be balanced with the goal of tumour control. The purpose of this study was to explore and quantify the relationship between esophageal dose and toxicity.MethodsWe conducted this analysis based on a prospective study of patients treated with SBRT at our institution from October 2004 to December 2015. Most patients were treated with 54Gy/3, 48Gy/4 alternate days, or 60Gy/8 daily. Toxicity was prospectively graded using CTCAE v3.0. Logistic regression was used to estimate the risk of esophageal toxicity as a function of radiotherapy dose, in 2-Gy-equivalent dose (EQD2), using an alpha-beta ratio of 3 Gy in the linear-quadratic model.Results632 patients were analyzed. The median follow up was 20.8 months. Median overall survival was 35.3 months. The rate of late or acute, grade 1 or greater esophageal toxicity, including dysphagia, odynophagia, and esophagitis, was 3.3% (n=21). The median (range) esophageal doses were 11.8Gy (0.2-48.2Gy), 10.34Gy (0.17- 44.5Gy), and 9.63Gy (0.08- 43Gy) for Dmax, D1cc and D2cc, respectively. A 15% risk of esophageal toxicity was associated with EQD2 of Dmax 141.6Gy, D1cc 123.61, and D2cc 117.6Gy. Of the 21 patients who experienced esophageal toxicity, only 1 patient had grade 3 toxicity and the remainder had grade 2 or lower toxicity.Discussion: The observed rate of toxicity was low, despite some patients receiving relatively high doses to the esophagus. A prospective study in a targeted population, for example patients with ultracentral tumours, may provide more accurate dose-toxicity parameters.



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A Phase II Study of Stereotactic Body Radiotherapy and Stereotactic Body Proton Therapy for High-Risk Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Chonnipa Nantavithya, Daniel R. Gomez, Xiong Wei, Ritsuko Komaki, Zhongxing Liao, Steven H. Lin, Melenda Jeter, Quynh-Nhu Nguyen, Heng Li, Xiaodong Zhang, Falk Poenisch, X Ronald Zhu, Peter A. Balter, Lei Feng, Noah C. Choi, Radhe Mohan, Joe Y. Chang
PurposeTo report the feasibility of conducting a randomized study to compare the toxicity and efficacy of stereotactic body radiotherapy (SBRT) versus stereotactic body proton therapy (SBPT) for high-risk medically inoperable early-stage non-small cell lung cancer (NSCLC).Methods and MaterialsWe randomly assigned patients with medically inoperable NSCLC with high-risk features (centrally located or <5 cm-T3 tumor or isolated lung parenchymal recurrences) to SBRT or SBPT. Radiation dose was 50 Gy(RBE) in four 12.5-Gy(RBE) fractions prescribed to the planning target volume. SBRT was given using 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT), and SBPT was given using passive scattering. Consistency in patient setup was ensured with on-board cone-beam computed tomography for the SBRT group and with orthogonal X-rays for the SBPT group.ResultsThe study closed early owing to poor accrual, largely because of insurance coverage, and lack of volumetric imaging in the SBPT group. Ultimately, 21 patients were enrolled, and 19 patients who received 50 Gy in 4 fractions were included for analysis (9 SBRT, 10 SBPT). At a median follow-up time of 32 months, median overall survival (OS) time was 28 months in the SBRT group and not reached in the SBPT group. Three-years OS was 27.8% and 90%, 3-year local control (LC) was 87.5% (8/9) and 90.0% (9/10) and 3-years regional control (RC) was 47.6% (5/9) and 90% (9/10) in SBRT and SBPT respectively. One patient in the SBPT group developed grade 3 skin fibrosis. No patients experienced grade 4/5 toxicity.ConclusionPoor accrual, due to lack of volumetric image and insurance coverage for proton therapy led to early closure of the trial and precluded accurate assessment of efficacy and toxicity. Comparable maturity of two radiotherapy modalities, particularly on-board image, and better insurance coverage for SBPT should be considered for the future studies.

Teaser

A phase II randomized study to compare SBRT vs. SBPT was terminated early due to poor accrual; treatment outcomes after SBPT appeared no worse than those after SBRT numerically with low treatment related toxicity in both groups. Lack of volumetric imaging and insurance coverage for patients treated with SBPT were the major barriers to accrual. In addition to financial issues, similar maturity of treatment planning and imaged-guided delivery are essential for future comparison studies between proton and photon therapy.


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Correlation Between Tumor Metabolism and Semiquantitative Perfusion MRI Metrics in Non-small Cell Lung Cancer

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sang Ho Lee, Andreas Rimner, Emily Gelb, Joseph O. Deasy, Margie A. Hunt, John L. Humm, Neelam Tyagi
PurposeTo correlate semiquantitative parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) and ¹⁸F-FDG-PET for non-small cell lung cancer (NSCLC).MethodsTwenty-four NSCLC patients who underwent pretreatment ¹⁸F-FDG-PET and DCE-MRI were analyzed. The maximum standardized uptake value (SUVmax) was measured from ¹⁸F-FDG-PET. DCE-MRI was obtained on 3T MRI scanner using four-dimensional T1-weighted high-resolution imaging with volume excitation sequence. DCE-MRI parameters consisting of mean, median, standard deviation (SD), and median absolute deviation (MAD) of peak enhancement, time-to-peak (TTP), time-to-half-peak (TTHP), wash-in slope (WIS), wash-out slope (WOS), initial gradient, wash-out gradient, signal enhancement ratio, and initial area under the relative signal enhancement curve taken up to 30, 60, 90, 120, 150, and 180 s, TTP, and TTHP (IAUCtthp) were calculated for each lesion. Univariate analysis (UVA) was performed using Spearman correlation. A linear regression model to predict SUVmax from DCE-MRI parameters was developed by multivariate analysis (MVA) using least absolute shrinkage selection operator in combination with leave-one-out cross-validation (LOOCV).ResultsIn UVA, mean(WOS) (ρ = -0.456, p = 0.025), mean(IAUCtthp) (ρ = -0.439, p = 0.032), median(IAUCtthp) (ρ = -0.543, p = 0.006), and MAD(IAUCtthp) (ρ = -0.557, p = 0.005) were statistically significant; all these parameters were negatively correlated with SUVmax. In MVA, a linear combination of SD(WIS), SD(TTP), MAD(TTHP), and MAD(IAUCtthp) was statistically significant for predicting SUVmax (LOOCV-based adjusted R² = 0.298, p = 0.0006). A decrease in SD(WIS), MAD(TTHP), and MAD(IAUCtthp) and an increase in SD(TTP) were associated with a significant increase in SUVmax.ConclusionAssociation was found between SUVmax, the SD, and MAD of DCE-MRI metrics derived during contrast uptake in NSCLC, reflecting that intratumoral heterogeneity in wash-in contrast kinetics is associated with tumor metabolism. Although MAD(IAUCtthp) was a significant feature in both UVA and MVA, the LASSO-based multivariate regression model yielded better predictability of SUVmax than a univariate regression model using MAD(IAUCtthp). This study will facilitate understanding of the complex relationship between tumor vascularization and metabolism, and eventually help in guiding targeted therapy.

Teaser

Balance between vascularity and glucose metabolism in tumor could prove to be an important indicator of its biological status and resistance to treatment. This study evaluates the use of semiquantitative dynamic contrast-enhanced MRI parameters for predicting the ¹⁸F-FDG-PET maximum standardized uptake value in non-small cell lung cancer (NSCLC). It was found that intratumoral heterogeneity in wash-in contrast kinetics is associated with tumor metabolism. Investigating vascular-metabolic relationship will help in guiding personalized targeted therapy in NSCLC.


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Measurement of Tumor Hypoxia in Patients with Locally Advanced Cervical Cancer using Positron Emission Tomography (PET) with 18F-Fluoroazomyin Arabinoside (18F-FAZA)

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Kathy Han, Tina Shek, Douglass Vines, Brandon Driscoll, Anthony Fyles, David Jaffray, Harald Keller, Ur Metser, Melania Pintilie, Jason Xie, Ivan Yeung, Michael Milosevic
PurposePoor tumor oxygenation (hypoxia) is associated with inferior survival in cervical cancer and resistance to radiotherapy. Positron emission tomography (PET) imaging of tumor hypoxia is minimally invasive and allows evaluation of the entire tumor, but has not been widely studied in cervical cancer. This study assesses cervical tumor hypoxia using hypoxia tracer ¹⁸F-fluoroazomycin arabinoside (¹⁸F-FAZA), and compares different reference tissues and thresholds for quantifying tumor hypoxia.Methods and MaterialsTwenty-seven patients with cervical cancer were studied prospectively by PET imaging with ¹⁸F-FAZA before starting standard chemoradiation. The hypoxic volume (HV) was defined as all voxels within a tumor (T) with standardized uptake values (SUVs) greater than 3 standard deviations from the mean gluteus maximus muscle SUV value (M), or SUVs greater than 1–1.4 times the mean SUV value of the left ventricle, a blood (B) surrogate. The hypoxic fraction (HF) was defined as the ratio of the number of hypoxic voxels to the total number of tumor voxels.ResultsA ¹⁸F-FAZA PET HV could be identified in the majority of cervical tumors (89% when using T/M or T/B >1.2 as threshold) on the 2-hour static scan. The HF ranged from 0-99% (median 31%) when defined using the T/M threshold, and 0-78% (median 32%) with the T/B >1.2 threshold. HVs derived from the different thresholds were highly correlated (Spearman's correlation coefficient ρ between T/M and T/B >1–1.4 were 0.82-0.91), as were HFs (0.75-0.85). Compartmental analysis of the dynamic scans showed k3, the FAZA accumulation constant, to be strongly correlated with HF defined using the T/M (Spearman's ρ=0.72) and T/B >1.2 thresholds (0.76).ConclusionsHypoxia was detected in the majority of cervical tumors on ¹⁸F-FAZA-PET imaging. The extent of hypoxia varied markedly between tumors, but not significantly with different reference tissues/thresholds.



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Using Big Data Analytics to Advance Precision Radiation Oncology

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Todd R. McNutt, Stanley H. Benedict, Daniel A. Low, Kevin Moore, Ilya Shpitser, Wei Jiang, Pranav Lakshminarayanan, Zhi Cheng, Peijin Han, Xuan Hui, Minoru Nakatsugawa, Junghoon Lee, Joseph A. Moore, Scott P. Robertson, Veeraj Shah, Russ Taylor, Harry Quon, John Wong, Theodore DeWeese
Big Clinical Data Analytics as a primary component of precision medicine is discussed, ] identifying where these emerging tools fit in the spectrum of genomic and radiomic research. A learning health system (LHS) is conceptualized that utilizes clinically acquired data with machine learning to advance the initiatives of precision medicine. The LHS is comprehensive and can be used for clinical decision support, discovery, and hypothesis derivation. These developing uses can positively impact the ultimate management and therapeutic course for patients. The conceptual model for each use of clinical data, is however different, and an overview of the implications is discussed. With advancement in technologies and culture to improve the efficiency, accuracy and breadth of measurements of the patient condition, the concept of a LHS may be realized in precision radiotherapy.



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Demonstration of safety and feasibility of hydrogel marking of the pancreas-duodenum interface for image-guided radiation therapy (IGRT) in a porcine model: Implications in IGRT for pancreatic cancer patients

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Avani D. Rao, Eun Ji Shin, Sarah E. Beck, Caroline Garrett, Seong-Hun Kim, Nam Ju Lee, Eleni Liapi, John Wong, Joseph Herman, Amol Narang, Kai Ding
PurposeLimitations in cone beam computed tomography (CBCT) soft-tissue contrast prohibit clinicians from clearly identifying the dose-limiting proximal duodenum in unresectable pancreatic cancer patients treated with radiation therapy (RT). This study tests the feasibility and safety of injecting a high-contrast hydrogel marker at the head of the pancreas (HOP) and duodenum interface and assesses the marker visibility on CBCT to localize this important boundary during image-guided RT in a porcine model.Methods and MaterialsThis was a two-stage study. The feasibility/visibility stage evaluated the ability to place the hydrogel using endoscopic ultrasound-guidance on 8 swine (4 euthanized at post-injection day 8, 4 euthanized at post-injection day 22) and assessed the quality of visibility of the marked location on CBCT in the longer-surviving group. The risk assessment stage evaluated the toxicity of targeted intrapancreatic injections (3 swine) and intramural duodenal wall injections (3 swine) to assess toxicity of a misplaced hydrogel injection. All swine underwent post-mortem examination and histopathological studies.ResultsThe HOP-duodenum interface was successfully marked using hydrogel in 6 of the 8 swine. Histopathologic examination of the 6 successful hydrogel injections showed mild/minimal (4 cases) or moderate (2 cases) reactive inflammation isolated to the injection site. Of the 4 swine survived to 22 days, 3 demonstrated successful hydrogel placement at the HOP-duodenum interface, and this marked location was clearly visible for positional guidance on CBCT. There was no evidence of pancreatitis or duodenal toxicity in the swine undergoing targeted intrapancreatic or intramural duodenum injections for the risk assessment stage.ConclusionsWe demonstrate the feasibility and safety of injecting a hydrogel marker to highlight the HOP-duodenum interface that has acceptable visibility on CBCT. This technique, translated to humans, enables on-board visualization of this important boundary between the radiation target and dose-limiting, radiosensitive duodenum, facilitating efforts to safely deliver dose-escalated RT.

Teaser

This study presents the feasibility and safety of marking the pancreas and duodenum interface with a high-contrast hydrogel and demonstrates acceptable visibility of the marked location on cone beam computed tomography using a porcine model. Translation of this technique to the radiotherapy treatment of pancreatic cancer patients would enable on-board visualization of this important boundary between the radiation target and the dose-limiting duodenum, facilitating future efforts towards safe dose-escalation.


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Repeat stereotactic radiosurgery for Cushing’s disease: outcomes of an international, multicenter study

Abstract

Stereotactic radiosurgery (SRS) is frequently used for Cushing's disease (CD) after failed pituitary surgery. Management of patients with persistent CD after failed SRS is complex, as the alternative therapeutic options harbor significant risks. The outcomes of repeat pituitary radiosurgery, however, have not been described. We sought to determine the outcomes of repeat SRS in patients with CD. We pooled data from five institutions participating in the International Gamma Knife Research Foundation for patients with recurrent or persistent CD ≥ 12 months after initial SRS. Patients were included in the study if they had ≥ 6 months endocrine follow-up after repeat SRS. Twenty patients were included in the study. Repeat single-session SRS was performed 1.3–9.7 years after initial SRS. Median endocrine follow-up was 6.6 years (1.4–19.1 years). Median margin dose was 20 Gy (range 10.8–35 Gy). Endocrine remission after second SRS was noted in 12 patients (60%), with a median time to remission of 6 months (range 2–64 months). Biochemical recurrence occurred in two patients (17%) after initial remission. Overall, the cumulative rates of durable endocrine remission at 5 and 10 years were 47 and 53%, respectively. Two patients (10%) experienced adverse radiation effects, including transient visual loss and permanent diplopia. Repeat SRS achieves lasting biochemical remission in approximately half of patients with CD refractory to both prior microsurgery and SRS. Because of the morbidity of refractory or recurrent CD, repeat SRS should be considered for carefully selected patients with hypercortisolism confirmed one or more years after initial SRS.

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Instructions for Contributors

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TOC

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In Memoriam: Minoru Hirano

Minoru Hirano was born on December 10th, 1932 and passed away on November 27th, 2017. He was one of the giants in laryngology.

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An Updated Subsequent Injury Categorisation Model (SIC-2.0): Data-Driven Categorisation of Subsequent Injuries in Sport

Abstract

Background

Accounting for subsequent injuries is critical for sports injury epidemiology. The subsequent injury categorisation (SIC-1.0) model was developed to create a framework for accurate categorisation of subsequent injuries but its operationalisation has been challenging.

Objectives

The objective of this study was to update the subsequent injury categorisation (SIC-1.0 to SIC-2.0) model to improve its utility and application to sports injury datasets, and to test its applicability to a sports injury dataset.

Methods

The SIC-1.0 model was expanded to include two levels of categorisation describing how previous injuries relate to subsequent events. A data-driven classification level was established containing eight discrete injury categories identifiable without clinical input. A sequential classification level that sub-categorised the data-driven categories according to their level of clinical relatedness has 16 distinct subsequent injury types. Manual and automated SIC-2.0 model categorisation were applied to a prospective injury dataset collected for elite rugby sevens players over a 2-year period. Absolute agreement between the two coding methods was assessed.

Results

An automated script for automatic data-driven categorisation and a flowchart for manual coding were developed for the SIC-2.0 model. The SIC-2.0 model was applied to 246 injuries sustained by 55 players (median four injuries, range 1–12), 46 (83.6%) of whom experienced more than one injury. The majority of subsequent injuries (78.7%) were sustained to a different site and were of a different nature. Absolute agreement between the manual coding and automated statistical script category allocation was 100%.

Conclusions

The updated SIC-2.0 model provides a simple flowchart and automated electronic script to allow both an accurate and efficient method of categorising subsequent injury data in sport.

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Chemotherapy induces breast cancer stemness in association with dysregulated monocytosis

Purpose: Preoperative or neoadjuvant therapy (NT) is increasingly used in patients with locally advanced or inflammatory breast cancer (BC) to allow optimal surgery and aim for pathological response. However, many BCs are resistant or relapse after treatment. Here, we investigated conjunctive chemotherapy-triggered events occurring systemically and locally, potentially promoting a cancer stem-like cell (CSC) phenotype and contributing to tumor relapse. Experimental Design: We started by comparing the effect of paired pre- and post-NT patient sera on the CSC properties of BC cells. Using cell lines, patient-derived xenograft models and primary tumors, we investigated the regulation of CSCs and tumor progression by chemotherapy-induced factors. Results: In human patients and mice, we detected a therapy-induced CSC-stimulatory activity in serum, which was attributed to therapy-associated monocytosis leading to systemic elevation of monocyte chemoattractant proteins (MCPs). The post-NT hematopoietic regeneration in the bone marrow highlighted both altered monocyte-macrophage differentiation and biased commitment of stimulated hematopoietic stem cells towards monocytosis. Chemotherapeutic agents also induce monocyte expression of MCPs through a JNK-dependent mechanism. Genetic and pharmacological inhibitions of the MCP-CCR2 pathway blocked chemotherapy's adverse effect on CSCs. Levels of nuclear Notch and ALDH1 were significantly elevated in primary BCs following NT, whereas higher levels of CCR2 in pre-NT tumors were associated with a poor response to NT. Conclusions: Our data establish a mechanism of chemotherapy-induced cancer stemness by linking the cellular events in the bone marrow and tumors, and suggest pharmacological inhibition of CCR2 as a potential co-treatment during conventional chemotherapy in neoadjuvant and adjuvant settings.

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IDO1 inhibition synergizes with radiation and PD-1 blockade to durably increase survival against advanced glioblastoma

Purpose: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with a median survival of 15-20 months. Numerous approaches and novel therapeutics for treating GBM have been investigated in the setting of phase III clinical trials, including a recent analysis of the immune checkpoint inhibitor, Nivolumab (anti-PD-1), which failed to improve recurrent GBM patient survival. However, rather than abandoning immune checkpoint inhibitor treatment for GBM, which has shown promise in other types of cancer, ongoing studies are currently evaluating this therapeutic class when combined with other agents. Experimental Design: Here, we investigated immunocompetent orthotopic mouse models of GBM treated with the potent CNS-penetrating IDO1 enzyme inhibitor, BGB-5777, combined with anti-PD1 mAb, as well as radiation therapy (RT), based on our recent observation that tumor-infiltrating T cells directly increase immunosuppressive IDO1 levels in human GBM, the previously-described enhancement of immune cell functions after PD-1 blockade, as well as the pro-inflammatory effects of radiation. Results: Our results demonstrate a durable survival benefit from this novel three-agent treatment, but not for any single- or dual-agent combination. Unexpectedly, treatment efficacy required IDO1 enzyme inhibition in non-GBM cells, rather than tumor cells. Timing of effector T cell infiltration, animal subject age and usage of systemic chemotherapy, all directly impacted therapy-mediated survival benefit. Conclusions: These data highlight a novel and clinically-relevant immunotherapeutic approach with associated mechanistic considerations that have formed the basis of a newly-initiated phase I/II trial for GBM patients.

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Sequencing pancreatic juice: squeezing the most out of surveillance

Next-generation sequencing of pancreatic juice can detect and quantify tumor-promoting mutations, supporting imaging and cytology findings to predict the degree of dysplasia in patients at high risk for pancreatic cancer. Future studies are needed to optimize this approach and determine how it best fits into clinical practice.

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A Phase 1 Clinical Trial of Guadecitabine and Carboplatin In Platinum-Resistant, Recurrent Ovarian Cancer: Clinical, Pharmacokinetic And Pharmacodynamic Analyses

Purpose: Epigenetic changes are implicated in acquired resistance to platinum. Guadecitabine is a next-generation hypomethylating agent (HMA). Here we report the clinical results, along with pharmacokinetic (PK) and pharmacodynamic analyses of the phase 1 study of guadecitabine and carboplatin (G+C) in patients with recurrent, platinum resistant high-grade serous ovarian cancer (OC), primary peritoneal carcinoma (PPC), or fallopian tube cancer (FTC). Experimental Design: Guadecitabine was administered once daily on Days 1-5 followed by carboplatin IV on Day 8 of a 28-day cycle. Patients had either measurable or detectable disease. Safety assessments used CTCAE v4. Results: Twenty patients were enrolled and treated. Median age was 56 years (38-72). Median number of prior regimens was 7 (1-14). In the first cohort (N=6), the starting doses were guadecitabine 45 mg/m² and carboplatin AUC5. Four patients experienced dose-limiting toxicity (DLT; neutropenia and thrombocytopenia) leading to dose de-escalation of guadecitabine to 30 mg/m² and of carboplatin to AUC4. No DLTS were observed in the subsequent 14 patients. Grade ≥3AEs ≥10% were neutropenia, leukopenia, anemia, nausea, vomiting, ascites, constipation, hypokalemia, pulmonary embolism, small intestinal obstruction, and thrombocytopenia. Three patients had a partial response (PR) and six patients had stable disease (SD) >3 months, for an overall response rate (ORR) and clinical benefit rate of 15% and 45%, respectively. LINE-1 demethylation in PBMCs and promoter demethylation/gene re-expression in paired tumor biopsies/ascites were recorded. Conclusions: G+C was tolerated and induced clinical responses in a heavily pretreated platinum resistant OC population, supporting a subsequent randomized phase 2 trial.

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A mechanistic linkage between oral lichen planus and autoimmune thyroid disease

Abstract

Objective

To determine the levels of antithyroid antibodies and thyroid hormones in the sera of patients with oral lichen planus (OLP), and to quantify the expression of thyroid proteins in OLP lesions.

Subjects and methods

Venous blood samples were drawn from 110 patients with OLP who had no history of thyroid disease or levothyroxine supplementation (OLP+/LT₄-). A random population sample of 657 healthy subjects was used as the control group. Two additional groups were used as comparators. Immunohistochemical and qPCR analyses were performed on tissue specimens collected from the patients with OLP and thyroid disease and healthy subjects.

Results

No association was found between the presence of antithyroid antibodies and OLP. More patients in the OLP+/LT₄- group showed high levels of thyroid-stimulating hormone and low levels of free thyroxine than were seen in the control group. Thyroid-stimulating hormone receptor was more highly expressed in the OLP lesions of patients with thyroid disease than in the healthy oral mucosa.

Conclusions

A significant number of patients with OLP who are not previously diagnosed with thyroid disease have thyroid parameters that are compatible with hypothyroidism. The expression of thyroid-stimulating hormone receptor in OLP lesions suggests that mechanisms related to autoimmune thyroid disease are involved in the aetiology of OLP.

This article is protected by copyright. All rights reserved.

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The NCX1/TRPC6 complex mediates TGF{beta}-driven migration and invasion of human hepatocellular carcinoma cells

Transforming growth factor β (TGFβ) plays an important role in the progression and metastasis of hepatocellular carcinoma (HCC), yet the cellular and molecular mechanisms underlying this role are not completely understood. In this study, we investigated the roles of Na+/Ca2+ exchanger 1 (NCX1) and canonical transient receptor potential channel 6 (TRPC6) in regulating TGFβ in human HCC. In HepG2 and Huh7 cells, TGFβ stimulated intracellular Ca2+ increases through NCX1 and TRPC6 and induced the formation of a TRPC6/NCX1 molecular complex. This complex-mediated Ca2+ signaling regulated the effect of TGFβ on the migration, invasion, and intrahepatic metastasis of human HCC cells in nude mice. TGFβ upregulated TRPC6 and NCX1 expression, and there was a positive feedback between TRPC6/NCX1 signaling and Smad signaling. Expression of both TRPC6 and NCX1 were markedly increased in native human HCC tissues, and their expression levels positively correlated with advancement of HCC in patients. These data reveal the role of the TRPC6/NCX1 molecular complex in HCC and in regulating TGFβ signaling, and they implicate TRPC6 and NCX1 as potential targets for therapy in HCC.

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Outcome after PSMA PET/CT based radiotherapy in patients with biochemical persistence or recurrence after radical prostatectomy

Abstract

Background

PSMA PET/CT visualises prostate cancer residual disease or recurrence at lower PSA levels compared to conventional imaging and results in a change of treatment in a remarkable high number of patients. Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival. Thus, it can be hypothesised that PSMA PET/CT-based radiotherapy might improve the prognosis of these patients.

Methods

One hundred twenty-nine patients underwent PSMA PET/CT due to biochemical persistence (52%) or recurrence (48%) after radical prostatectomy without evidence of distant metastases (February 2014–May 2017) and received PSMA PET/CT-based radiotherapy. Biochemical recurrence free survival (PSA ≤ 0.2 ng/ml) was defined as the study endpoint.

Results

Patients with biochemical persistence were significantly more often high-risk patients with significantly shorter time interval before PSMA PET/CT than patients with biochemical recurrence. Patients with biochemical recurrence had significantly more often no evidence of disease or local recurrence only in PSMA PET/CT, whereas patients with biochemical persistence had significantly more often lymph node involvement. Seventy-three patients were started on antiandrogen therapy prior to radiotherapy due to macroscopic disease in PSMA PET/CT. Cumulatively, 70 (66–70.6) Gy was delivered to local macroscopic tumor, 66 (63–66) Gy to the prostate fossa, 61.6 (53.2–66) Gy to PET-positive lymph nodes and 50.4 (45–52.3) Gy to lymphatic pathways. Median PSA after radiotherapy was 0.07 ng/ml with 74% of patients having a PSA ≤ 0.1 ng/ml. After a median follow-up of 20 months, median PSA was 0.07 ng/ml with ongoing antiandrogen therapy in 30 patients. PET-positive patients without antiandrogen therapy at last follow-up (45 patients) had a median PSA of 0.05 ng/ml with 89% of all patients, 94% of patients with biochemical recurrence and 82% of patients with biochemical persistence having a PSA ≤ 0.2 ng/ml. Post-radiotherapy PSA ≤ 0.1 ng/ml and biochemical recurrence vs. persistence were significantly associated with a PSA ≤ 0.2 ng/ml at last follow-up.

Conclusions

PSMA PET/CT-based radiotherapy is an effective local salvage treatment option with significant PSA response in patients with biochemical recurrence or persistence after radical prostatectomy leading to deferral of long-term ADT or systemic therapy.

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A meta-analysis of the efficacy of cognitive behavior therapy on quality of life and psychological health of breast cancer survivors and patients

Abstract

Objective

The aim of this study was to examine the effect of Cognitive Behavior Therapy (CBT) on Quality of Life (QOL) and psychological health of breast cancer survivors and patients.

Methods

A total of 1289 references were examined from an overall literature search in PubMed, Embase, CINAHL, and the Cochrane Database of Systematic Reviews. Randomized controlled trials assessing the efficacy of CBT compared with a range of comparators in cancer survivors. We assessed the effect of CBT using the standardized mean difference as effect size.

Results

Among 1289 abstracts and 292 full-text articles reviewed, 10 studies were included. At the post-treatment period, the pooled effect size for CBT on QOL was 0.57 (95% CI, 0.44 to 0.69; P <0.001), on depression was -1.11 (95% CI, -1.28 to -0.94; P <0.001), on stress was -0.40 (95% CI, -0.53 to -0.26; P <0.001), on anxiety was -1.10 (95% CI, -1.27 to -0.93; P <0.001), and on hyperarousal cluster of symptoms was-0.18 (95% CI, -0.30 to -0.05; P <0.001). The QOL was considered statistically medium effect sizes. The depression and anxiety were considered statistically large effect sizes.

Conclusions

CBT is an effective therapy for psychological symptoms of cancer survivors and patients, with meaningfully clinical effect sizes. These findings suggested that CBT should be used as the intervention for breast cancer survivors and patients when possible.

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"Ear Nose Throat J"[jour]; +22 new citations

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Ear Nose Throat J"[jour]

These pubmed results were generated on 2018/03/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Impact of different concentrations of an octenidine dihydrochloride mouthwash on salivary bacterial counts: a randomized, placebo-controlled cross-over trial

Abstract

Objectives

This bi-centric, placebo-controlled, randomized, evaluator-blinded, incomplete cross-over clinical phase II trial was initialized to identify the most appropriate concentration of octenidine dihydrochloride (OCT) in mouth rinses.

Materials and methods

Rinses of 0.10, 0.15, and 0.20% OCT were compared to a saline placebo rinse regarding the reduction of salivary bacterial counts (SBCs) in 90 gingivitis patients over 4 days. Changes in plaque (PI) and gingival index (GI), taste perception, and safety issues were evaluated.

Results

At baseline, the first OCT (0.10, 0.15, 0.20%) rinse resulted in a decrease of SBC (reduction by 3.63–5.44 log₁₀ colony forming units [CFU]) compared to placebo (p < 0.001). Differences between OCT concentrations were not verified. After 4 days, the last OCT rinse again resulted in a significant SBC decrease (3.69–4.22 log₁₀ CFU) compared to placebo (p < 0.001). Overall, SBC reduction between baseline and day 4 was significantly higher in OCT 0.15 and 0.20% groups compared to OCT 0.10% and placebo. Mean GI/PIs were significantly lower in OCT groups than in the placebo group (p < 0.001). Differences in GI/PI between OCT groups were not verified. Adverse effects increased with increasing OCT concentrations.

Conclusions

Considering antibacterial efficacy, frequency of adverse events, and user acceptance, 0.10% OCT was identified as the preferred concentration to be used in future clinical trials.

Clinical relevance

Due to its low toxicity and pronounced antibacterial properties, octenidine dihydrochloride (OCT) is a promising candidate for the use in antiseptic mouth rinses. OCT concentrations of 0.10% are recommended for future clinical trials evaluating the plaque-reducing properties of OCT mouth rinses.

(www.clinicaltrials.gov, NCT022138552)

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Uvulopalatopharyngoplasty vs CN XII stimulation for treatment of obstructive sleep apnea: A single institution experience

Hypoglossal nerve stimulation (HNS) therapy is an emerging surgical treatment for select patients with obstructive sleep apnea (OSA). This study aims to compare outcomes in patients with moderate to severe OSA who underwent HNS surgery (Inspire Medical Systems) and those who underwent traditional airway reconstructive surgery, specifically uvulopalatopharyngoplasty (UPPP).

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Partial parotidectomy under local anesthesia for benign parotid tumors - An experience of 50 cases

Benign parotid tumors are adequately treated with partial parotidectomy, which is often performed under general anesthesia (GA). We have reported our preliminary results on the feasibility to perform parotidectomy under local anesthesia (LA). We hereby present our accumulated experience of partial parotidectomy under LA to further consolidate its feasibility, efficacy and safety in a larger series.

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Is the caudate nucleus capable of generating seizures? Evidence from direct intracerebral recordings

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Evaluation of Magnetic Coagulant (α-Fe 2 O 3 -MO) and its Reuse in Textile Wastewater Treatment

Abstract

The textile industries are characterized as one of the biggest consumers of potable water and chemical products throughout its process, being responsible for the elevated wastewater generation with intense coloration and wide polluting potential. In this context, the present study proposes the development and application of a new coagulant material for textile wastewater treatment. The proposed coagulant (α-Fe₂O₃-MO) was composed by hematite nanoparticles (α-Fe₂O₃) obtained by a simple non-pollutant methodology, associated with Moringa oleifera (MO) seeds saline extract compounds. Coagulation/flocculation (CF) efficiency was evaluated by removal of physicochemical parameters such as apparent color, turbidity, and compounds with absorption at UV_254nm (UV_254nm) through CF tests carried out on Jar test equipment and sedimentation carried out in the presence and absence of external magnetic field (600 k Am⁻¹). Kinetics sedimentation was from 0 to 90 min. The use of this new coagulant allowed the removal of 92.37% for apparent color, 91.43% for turbidity, and 46.09% for UV_254nm, indicating that the proposed coagulant association was efficient in the treatment of this type of wastewater under external magnetic field with only 10 min of sedimentation. In addition, the resulting sludge from CF process was tested as base material for a new coagulant synthesis, demonstrating great reuse potential. Therefore, the new proposed coagulant, composed of α-Fe₂O₃ and the compounds present in the seed extract of MO, has applicability for textile wastewater treatment demonstrating high removal rate for all evaluated parameters with cost reduction in the proposed treatment for this wastewater.

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Cost analysis of enhanced recovery after surgery in microvascular breast reconstruction

Enhanced recovery after surgery (ERAS) pathways has been shown in multiple surgical speciaalties to decrease hospital length of stay (LOS) after surgery. ERAS in breast reconstruction has been found to decrease hospital length of stay and inpatient opioid use. ERAS protocols can facilitate a patient's recovery and is a systemwide improvement that can potentially increase the quality of care while decreasing costs.

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Application of new instruments for beginner lymphatic supermicrosurgeon

Dear Sirs,

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“Diagnostic accuracy of bioimpedance spectroscopy in patients with lymphedema - a retrospective cohort analysis”

Bioimpedance spectroscopy (BIS) is used by healthcare specialists to diagnose lymphedema. BIS measures limb fluid content by assessing tissue resistance to the flow of electric current. However, there is debate regarding the validity of BIS in diagnosing early lymphedema. Indocyanine green (ICG) lymphography has been established as the most accurate diagnostic modality to date for lymphedema diagnosis. In this retrospective study, we test the sensitivity, specificity, and diagnostic accuracy of BIS in diagnosing lymphedema by referencing its results with ICG lymphography.

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Respiratory Tract Infections and Voice Quality in 4-Year-old Children in the STEPS Study

Health-related factors are part of the multifactorial background of dysphonia in children. Respiratory tract infections affect the same systems and structures that are used for voice production. The purpose of this study was to investigate if the number of respiratory tract infections or the viral etiology were significant predictors for a more hoarse voice quality.

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Neural Foraminal Lesions: An Imaging Overview

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Effect on passive range of motion and functional correlates following a long-term lower limb self-stretch program in patients with chronic spastic paresis

In current health systems, long duration stretching, performed daily, cannot be obtained through prescriptions of physical therapy. In addition, the short-term efficacy of the various stretching techniques is disputed and their long-term effects remain undocumented.

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Dosimetric Analysis of Stereotactic Body Radiotherapy for Pancreatic Cancer using MR-Guided Tri-60Co Unit, MR-Guided LINAC, and Conventional LINAC Based Plans

Publication date: Available online 1 March 2018
Source:Practical Radiation Oncology
Author(s): S.J. Ramey, K.R. Padgett, N. Lamichhane, H.J. Neboori, D. Kwon, E.A. Mellon, K. Brown, M. Duffy, J. Victoria, N. Dogan, L. Portelance
PurposeTo perform a dosimetric comparison of two MR-guided radiotherapy systems capable of performing on-line adaptive radiotherapy (ART) versus a conventional radiotherapy system for pancreas stereotactic body radiation therapy.Methods and MaterialsTen cases of patients with pancreatic adenocarcinoma previously treated in our institution were used for this analysis. MR-Cobalt and MR-LINAC plans were generated and compared to conventional LINAC (VMAT) plans. The prescription dose was 40Gy in five fractions covering 95% of the planning tumor volume (PTV40) for the 30 plans. The same organs at risk (OARs) dose constraints were used in all plans. Dose volume-based indices were used to compare PTV coverage and OAR sparing.ResultsThe PTV40 conformity index (CI) demonstrated higher conformity in both LINAC-based plans compared to MR-Cobalt plans. While there was no difference in mean CI betweenLINAC and MR-LINAC plans (1.08 in both), there was a large difference between LINAC and MR-Cobalt plans (1.08 vs. 1.52). Overall, 79%, 72%, and 78% of critical structure dosimetric constraints were met with LINAC, MR-Cobalt, and MR-LINAC plans. The MR-Cobalt plans delivered more dose to all OARs when compared to the LINAC plans. In contrast, the doses to the OARs of the MR-LINAC plans were similar to LINAC plans except in two cases—liver mean dose (MR-LINAC—2 .8Gy versus LINAC—2.1Gy) and volume of duodenum receiving at least 15Gy (MR-LINAC—13.2 cubic centimeters [cc] versus LINAC—15.4cc). Both differences are likely not clinically significant.ConclusionThis study demonstrates that dosimetrically similar plans were achieved with conventional LINAC and MR-LINAC while doses to OARs were statistically higher for MR-Cobalt compared to conventional LINAC plans due to low dose spillage. Given the improved tumor-tracking capabilities of MR-LINAC, further studies should evaluate potential benefits of ART-capable MR-guided LINAC treatment.



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Long-term improvement of Recalcitrant Hailey-Hailey Disease with electron beam radiotherapy: Case Report and Review

Publication date: Available online 2 March 2018
Source:Practical Radiation Oncology
Author(s): Nicole Leung, Adela R. Cardones, Nicole Larrier




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Comparison between burning mouth syndrome patients with and without psychological problems

The purpose of this study was to compare clinical and socio-demographic characteristics between burning mouth syndrome (BMS) patients with and without psychological problems. Of 644 patients with symptoms of oral burning, 224 with primary BMS were selected on the basis of laboratory testing, medical history, and psychometric tests: 39 with psychological problems (age 62.5±11.5years) and 185 without psychological problems (age 58.4±11.4years). Comprehensive clinical and socio-demographic characteristics, including psychological profiles and salivary flow rates, were compared between the two groups.

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Retrobulbar abscess: rare complication after repair of an oroantral communication

We present the case of a retrobulbar abscess that developed secondary to the repair of an oroantral communication. Orbital abscesses have been described in relation to odontogenic infections, facial injury, sinusitis, and after dental extractions but, to the best of our knowledge, none has been reported in these circumstances. Retrobulbar abscess is a rare complication, but early clinical and radiological diagnosis, and urgent decompression are vital because it comes with considerable risk of irreversible visual impairment.

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Ophthalmological injuries associated with fractures of the orbitozygomaticomaxillary complex

Our aim was to evaluate ophthalmological injuries associated with fractures of the orbitozygomaticomaxillary complex that required operative treatment, and we collected data retrospectively over a period of five years (2012-2016 inclusive). Of the 190 patients, 162 were male with a median age of 31 (IQR 25 -39) years. Assault was the most common mechanism of injury (125/190, 66%). Minor ophthalmic injuries (those unlikely to cause permanent visual disturbance) and major ophthalmic injuries (those with the potential to cause permanent visual disturbance) were recorded.

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Efficacy of Propranolol, Bisoprolol, and Pyridostigmine for Postural Tachycardia Syndrome: a Randomized Clinical Trial

Abstract

Postural tachycardia syndrome (POTS) is a form of dysautonomia which presents with complex symptoms including orthostatic intolerance. Several medications are prescribed for POTS; however, the efficacy of sustained medical treatment has not been well-investigated. Here, we conducted a 2 × 2 factorial design, randomized, clinical trial of a 3-month medical treatment regimen in POTS patients. Patients were randomly allocated to 4 treatment groups (Group 1: propranolol; Group 2: bisoprolol; Group 3: propranolol + pyridostigmine; Group 4: bisoprolol + pyridostigmine). The orthostatic intolerance questionnaire (OIQ), Beck depression inventory-II (BDI-II), and short-form health survey (SF-36) were conducted at baseline, 1 and 3 months after treatment. Seventy-seven patients who completed the 3-month follow-up were analyzed. In total, every clinical score improved significantly after medical treatment. The OIQ score was significantly lower than that at baseline (18.5 ± 6.7) after 1 month (12.5 ± 4.5, P < 0.01), which decreased further after 3 months (7.8 ± 5.7, P < 0.01). The OIQ score improvements were consistent across every treatment group. In the subgroup analysis of 59 patients who did not receive antidepressants, the BDI-II score significantly decreased after treatment, regardless of the regimen. Physical components of the SF-36 improved after 3 months in every group, while mental components improved only in Group 3. The amount of changes in each score was similar among groups throughout the comparisons. Sustained medical treatment is beneficial to POTS patients, not only for orthostatic intolerance symptoms but also for depression and diminished quality of life, even without prescriptions for antidepressants. The efficacy of each regimen in POTS patients was comparable. Trial registration: NCT02171988

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The VenaSeal™ Abnormal Red Skin Reaction: Looks Like but is not Phlebitis!

Publication date: Available online 2 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Tjun Y. Tang, Alok Tiwari




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Response to “Re. Nutcracker Syndrome: An Update on Current Diagnostic Criteria and Management Guidelines”

Publication date: Available online 2 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Kajaluxy Ananthan




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Comparison Between Duplex Ultrasound and Multigate Quality Doppler Profile Software in the Assessment of Lower Limb Perforating Vein Direction

Publication date: Available online 2 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Sergio Gianesini, Erica Menegatti, Francesco Sisini, Savino Occhionorelli, Federico Annoni, Byung-Boong Lee, Paolo Zamboni
ObjectivesThe aim was to assess more accurately the net flow of the lower limb perforating veins (PVs).Material and methodsThis was an observational prospective study. Two hundred and twenty one limbs with chronic venous disease (C1–6EpAs,pPr) of 193 patients underwent a duplex ultrasound (DUS). All identified PVs were scanned also by means of quality Doppler profile (QDP) multigate analysis in order to determine their net inward and outward flow direction. A comparison between the traditional pulsed wave Doppler analysis and QDP was performed to detect potential discrepancy between the traditional definition of PV incompetence and a net outward flow.ResultsThe DUS investigation identified 774 PVs. Only 7.7% of the PVs showed an outward flow lasting more than 500 ms. Among the PVs showing a longer than 500 ms outward flow, QDP assessment revealed net outward flow in only 84% of the PVs along the thigh and in 28.6% along the lower leg. Among the PVs showing a shorter than 500 ms outward flow, QDP assessment reported a net outward flow in 2.4% of the PVs along the thigh and in 47.3% of those along the lower leg. The sensitivity of an outward flow lasting more than 500 ms in detecting an actual net outward flow was 13.9% (9–20.1%). The specificity of an outward flow lasting less than 500 ms in detecting a net inward flow was 96.4% (93.2–98.3%).ConclusionsA lack of overlap exists between the finding of a PV outward flow lasting more than 500 ms and the net outward flow of the same vessel. The traditional definition of PV incompetence is challenged by the reported data and further investigations are required to identify a gold standard assessment.



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Using a Biopsychosocial Model to Understand Long-term Outcomes in Persons with Burn Injuries

Publication date: Available online 2 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Shelley Wiechman, Michael A. Hoyt, David R. Patterson
ObjectiveTo determine the importance of preburn adjustment, injury related variables and selection of coping style on various outcome measures using a biopsychosocial model.DesignLongitudinal. Setting: Outpatient burn clinics. Participants: A total of 231 burn survivors participated in this study as part of a larger burn model system study of 645 patients with major burn injuries.InterventionsN/A/. Main Outcome Measures: The SF-36 was used to assess pre burn adjustment. Other outcome measures entered into the model included the ways of Coping Checklist-revised, the Brief Symptom Inventory, the Beck Depression Inventory-II, the Davidson Trauma Scale.ResultsCorrelational and mediational analysis revealed that preburn emotional health predicted better adjustment at year one and more PTSD symptoms at year two. Better preburn emotional health was also related to less use of avoidant coping strategies, which was also found to be a mediator of the effect of preburn emotional health and PTSD symptoms. Burn injury characteristics were not significantly associated with psychological adjustment at either year one or year two.ConclusionsThe results indicate that there is a complex relation between premorbid mental health and the selection of coping strategies that impact long term adjustment in persons recovering from a burn injury. This relation seems to have more impact on long-term outcome than preburn emotional or physical health alone or the severity of the burn.



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On the Reporting of Experimental and Control Therapies in Stroke Rehabilitation Trials: A Systematic Review

Publication date: Available online 2 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Keith R. Lohse, Anupriya Pathania, Rebecca Wegman, Lara A. Boyd, Catherine E. Lang
ObjectiveTo use the Centralized Open-Access Rehabilitation database for Stroke to explore reporting of both experimental and control interventions in randomized controlled trials for stroke rehabilitation (including upper and lower extremity therapies).Data SourcesThe Centralized Open-Access Rehabilitation database for Stroke was created from a search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Cumulative Index of Nursing and Allied Health from the earliest available date to May 31, 2014.Study SelectionA total of 2892 titles were reduced to 514 that were screened by full text. This screening left 215 randomized controlled trials in the database (489 independent groups representing 12,847 patients).Data ExtractionUsing a mixture of qualitative and quantitative methods, we performed a text-based analysis of how the procedures of experimental and control therapies were described. Experimental and control groups were rated by 2 independent coders according to the Template for Intervention Description and Replication criteria.Data SynthesisLinear mixed-effects regression with a random effect of study (groups nested within studies) showed that experimental groups had statistically more words in their procedures (mean, 271.8 words) than did control groups (mean, 154.8 words) (P<.001). Experimental groups had statistically more references in their procedures (mean, 1.60 references) than did control groups (mean, .82 references) (P<.001). Experimental groups also scored significantly higher on the total Template for Intervention Description and Replication checklist (mean score, 7.43 points) than did control groups (mean score, 5.23 points) (P<.001).ConclusionsControl treatments in stroke motor rehabilitation trials are underdescribed relative to experimental treatments. These poor descriptions are especially problematic for "conventional" therapy control groups. Poor reporting is a threat to the internal validity and generalizability of clinical trial results. We recommend authors use preregistered protocols and established reporting criteria to improve transparency.



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Clinical and Genetic Implications of Mutation Burden in Squamous Cell Carcinoma of the Lung

Abstract

Background

Lung squamous cell carcinoma (LSCC) is a major histological subtype of lung cancer. In this study, we investigated genomic alterations in LSCC and evaluated the clinical implications of mutation burden (MB) in LSCC.

Methods

Genomic alterations were determined in Japanese patients with LSCC (N = 67) using next-generation sequencing of 415 known cancer genes. MB was defined as the number of non-synonymous mutations per 1 Mbp. Programmed death-ligand 1 (PD-L1) protein expression in cancer cells was evaluated by immunohistochemical analysis.

Results

TP53 gene mutations were the most common alteration (n = 51/67, 76.1%), followed by gene alterations in cyclin-dependent kinase inhibitor 2B (CDKN2B; 35.8%), CDKN2A (31.3%), phosphatase and tensin homolog (30.0%), and sex-determining region Y-box 2 (SOX2, 28.3%). Histological differentiation was significantly poorer in tumors with high MB (greater than or equal to the median MB) compared with that in tumors with low MB (less than the median MB; p = 0.0446). The high MB group had more tumors located in the upper or middle lobe than tumors located in the lower lobe (p = 0.0019). Moreover, cancers in the upper or middle lobes had significantly higher MB than cancers in the lower lobes (p = 0.0005), and tended to show higher PD-L1 protein expression (p = 0.0573). SOX2 and tyrosine kinase non-receptor 2 amplifications were associated with high MB (p = 0.0065 and p = 0.0010, respectively).

Conclusions

The MB level differed according to the tumor location in LSCC, suggesting that the location of cancer development may influence the genomic background of the tumor.

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Traditional herbal medicine prevents postoperative recurrence of small hepatocellular carcinoma: A randomized controlled study

BACKGROUND

To explore the clinical efficacy of traditional herbal medicine (THM) in the prevention of disease recurrence of small hepatocellular carcinoma after surgery, a prospective randomized controlled study was conducted between October 2006 and May 2010. The results indicated that THM prevented the recurrence of SHCC with an efficacy that was superior to that of transarterial chemoembolization (TACE) during a median follow-up of 26.61 months.

METHODS

The patients were followed up every 6 months, and the clinical data before October 20, 2015 were analyzed. The primary outcome measure was recurrence-free survival (RFS), and the secondary outcome measure was overall survival (OS).

RESULTS

The 364 patients included 180 in the THM group and 184 in the TACE group. At the time of the data cutoff of October 20, 2015, a total of 205 patients demonstrated disease recurrence, including 85 patients in the THM group and 120 patients in the TACE group. The median RFS of the THM and TACE groups demonstrated a statistically significant difference (P<.001). Until October 20, 2105, there were 91 deaths, including 34 in the THM group and 57 in the TACE group. The median OS demonstrated a significant difference between the 2 groups (P = .008). Multivariate analysis indicated that THM was an independent factor influencing RFS and OS.

CONCLUSIONS

The efficacy of THM was found to be superior to that of TACE in preventing disease recurrence in patients with small hepatocellular carcinoma and prolonging OS. Cancer 2018. © 2018 American Cancer Society.

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Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer

BACKGROUND

To the authors' knowledge, the survival benefit of local therapy in the setting of advanced prostate cancer remains unknown. The authors investigated whether prostate-directed treatment with either surgery or radiotherapy versus conservative treatment in the setting of locally advanced or metastatic disease was associated with improved survival within a cohort of men from the Centers for Disease Control and Prevention's (CDC) Breast and Prostate Cancer Data Quality and Patterns of Care Study (CDC POC-BP).

METHODS

Men diagnosed with locally advanced (cT3-T4 or N+ and M0) or metastatic prostate cancer were identified. The authors compared survival by treatment type, categorized as conservative (androgen deprivation therapy only) versus aggressive (radical prostatectomy or any type of radiotherapy). Nine-year overall survival and prostate cancer-specific survival were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine factors independently associated with 9-year prostate cancer-specific survival.

RESULTS

For men with advanced, nonmetastatic prostate cancer, conservative treatment alone was associated with a 4 times higher likelihood of prostate cancer mortality compared with men treated with surgery (hazard ratio, 4.18; 95% confidence interval, 1.44-12.14). In contrast, no difference was found between conservative versus aggressive treatment after adjusting for covariates for men with metastatic disease. The 9-year prostate cancer-specific survival rate was 27% for those receiving aggressive treatment versus 24% for men undergoing conservative treatment.

CONCLUSIONS

The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption. Cancer 2018. © 2018 American Cancer Society.

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Screening for human papillomavirus-driven oropharyngeal cancer: Considerations for feasibility and strategies for research

The incidence and burden of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) is expected to increase for decades, thus motivating discussions regarding possibilities for screening. This article addresses issues related to the validity and timeliness of screening for HPV-driven OPC, and raises important questions, highlights deficits and confusion in the existing literature, and proposes needed steps in the research agenda.

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Neural and behavioral effects of subordinate-level training of novel objects across manipulations of color and spatial frequency

Abstract

Perceptual expertise is marked by subordinate-level recognition of objects in the expert domain. In the present study, participants learned one family of full-color, artificial objects at the subordinate (species) level and another family at the basic (family) level. Discrimination of trained and untrained exemplars was tested before and after training across several image manipulations (full-color, greyscale, low spatial frequency (LSF), and high spatial frequency (HSF)) while event-related potentials (ERPs) were recorded. Regardless of image manipulation, discrimination (indexed by d') of trained and of untrained exemplars was enhanced after subordinate-level training, but not after basic-level training. Enhanced discrimination after subordinate-level training generalized to untrained exemplars and to greyscale images and images in which LSF or HSF information was removed. After training, the N170 and N250, recorded over occipital and occipitotemporal brain regions, were both more enhanced after subordinate-level training than after basic-level training. However, the topographic distribution of enhanced responses differed across components. The N170 latency predicted reaction time after both basic- and subordinate-level training, highlighting an association between behavioral and neural responses. These findings further elucidate the role of the N170 and N250 as ERP indices of subordinate-level expert object processing and demonstrate how low-level manipulations of color and spatial frequency impact behavior and the N170 and N250 components independent of training or expertise.

This article is protected by copyright. All rights reserved.

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Processing of performance-matched visual object categories: faces and places are related to lower processing load in the frontoparietal executive network than other objects

Abstract

The present study aimed to explore the differential role of the frontoparietal network in processing different visual object categories, matched for difficulty level, during a 1-back paradigm. To achieve this goal we first mapped the effort-related frontoparietal saliency network, by contrasting activation elicited by face, object, place, body and verbal stimulus categories, which were matched for performance level, and speed of processing, with difficult scrambled stimuli. We then computed the weight of object predictors on that specific network, using an independent orthogonal analysis.

Overall, our results demonstrated that face (and to some extent also places) stimuli were associated with lower processing load in regions of the frontoparietal network comparing to other visual categories, suggesting that face/place processing does require to a much smaller extent the recruitment of the frontoparietal control network than any other object categories.

Thus, face and place detection seem to be routed in specific neuronal systems that readily encode the holistic nature of this type of objects. We conclude that the more limited recruitment of frontoparietal networks reflects the automaticity of face and place processing and their smaller dependence on general capacity limits.

This article is protected by copyright. All rights reserved.

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Programmed death ligand 1 testing in non–small cell lung carcinoma cytology cell block and aspirate smear preparations

BACKGROUND

Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) receptor and its ligand, programmed death ligand 1 (PD-L1), have emerged as a therapeutic approach for patients with non–small cell lung carcinoma (NSCLC). PD-L1 expression, assessed by immunohistochemistry (IHC), is used to select patients for PD-1/PD-L1 inhibitor therapy. Most studies have been performed with histology specimens, with limited data available on the performance in cytology specimens. This study evaluated PD-L1 in cytology specimens and compared the results with those from paired core-needle biopsy for concordance.

METHODS

Forty-one NSCLC fine-needle aspiration cases that had paired core-needle biopsy specimens with PD-L1 IHC were selected. A Papanicolaou-stained direct smear and a cell block section from each case were stained with a Dako PD-L1 pharmDx antibody (clone 22C3). Only slides with 100 or more tumor cells (37 smears and 38 cell blocks) were evaluated. Tumor proportion scores (TPS) were assessed on the basis of the partial/complete membranous staining of tumor cells and were correlated with those of paired core-needle biopsy.

RESULTS

All 9 smears that were negative for PD-L1 staining showed 100% concordance with the paired core-needle biopsy, whereas 28 smears with PD-L1 expression showed a similar TPS, except for 1 smear that was discordant. In contrast, 10 negative paired core-needle biopsy cases corresponded to 9 concordant negative cell blocks, whereas 1 cell block had a TPS of 1% to 5%. The remaining 28 cell blocks demonstrated PD-L1 expression, with 22 cases showing a TPS similar to that of the paired core-needle biopsy, whereas 6 cell blocks were discordant, likely because of intratumoral heterogeneity.

CONCLUSIONS

The results show that NSCLC cytology samples evaluated for PD-L1 have high concordance with paired core-needle biopsy samples and can be used for assessing PD-L1 expression. Cancer Cytopathol 2018. © 2018 American Cancer Society.

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Clinical and Genetic Implications of Mutation Burden in Squamous Cell Carcinoma of the Lung

Abstract

Background

Lung squamous cell carcinoma (LSCC) is a major histological subtype of lung cancer. In this study, we investigated genomic alterations in LSCC and evaluated the clinical implications of mutation burden (MB) in LSCC.

Methods

Genomic alterations were determined in Japanese patients with LSCC (N = 67) using next-generation sequencing of 415 known cancer genes. MB was defined as the number of non-synonymous mutations per 1 Mbp. Programmed death-ligand 1 (PD-L1) protein expression in cancer cells was evaluated by immunohistochemical analysis.

Results

TP53 gene mutations were the most common alteration (n = 51/67, 76.1%), followed by gene alterations in cyclin-dependent kinase inhibitor 2B (CDKN2B; 35.8%), CDKN2A (31.3%), phosphatase and tensin homolog (30.0%), and sex-determining region Y-box 2 (SOX2, 28.3%). Histological differentiation was significantly poorer in tumors with high MB (greater than or equal to the median MB) compared with that in tumors with low MB (less than the median MB; p = 0.0446). The high MB group had more tumors located in the upper or middle lobe than tumors located in the lower lobe (p = 0.0019). Moreover, cancers in the upper or middle lobes had significantly higher MB than cancers in the lower lobes (p = 0.0005), and tended to show higher PD-L1 protein expression (p = 0.0573). SOX2 and tyrosine kinase non-receptor 2 amplifications were associated with high MB (p = 0.0065 and p = 0.0010, respectively).

Conclusions

The MB level differed according to the tumor location in LSCC, suggesting that the location of cancer development may influence the genomic background of the tumor.

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The C-Reactive Protein/Albumin Ratio is a Novel Significant Prognostic Factor in Patients with Malignant Pleural Mesothelioma: A Retrospective Multi-institutional Study

Abstract

Background

Malignant pleural mesothelioma (MPM), a devastating neoplasm, is traditionally considered to be resistant to antitumor therapy. Identification of clinical prognostic indicators is therefore needed. Although the C-reactive protein/albumin ratio (CAR) has been used to predict the prognosis of many types of malignancy, its utility in patients with MPM is unknown.

Methods

The data of 100 patients diagnosed as having MPM from 1995 to 2015 at the National Kyushu Cancer Center and Kyushu University were analyzed. The CAR was calculated as serum C-reactive protein concentration divided by albumin concentration. A cutoff for CAR was set at 0.58 according to a receiver operating characteristics curve for 1-year survival.

Results

Thirty-five of the 100 (35.0%) patients were classified as having a high CAR. A high CAR was significantly associated with advanced clinical stage (p < 0.001) and chemotherapy alone (p = 0.002). Patients with a high CAR had significantly shorter overall survival (OS) (p < 0.001) and disease- or progression-free survival (DFS/PFS) (p < 0.001). These associations between CAR and prognosis remained significant after propensity score-matching. In multivariate analysis, a high CAR was an independent predictor of shorter OS and DFS/PFS (p = 0.003 and p = 0.008, respectively). Multivariate analyses of the subgroups of patients who had received chemotherapy and of patients who had undergone surgery also showed that a high CAR was an independent predictor of shorter OS and DFS/PFS.

Conclusions

CAR is an independent predictor of prognosis in MPM patients. This prognostic index contributes to clinicians' ability to predict benefit from treatment. Further larger, prospective studies are necessary to validate these findings.

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The Rationale and Emerging Use of Neoadjuvant Immune Checkpoint Blockade for Solid Malignancies

Abstract

Unprecedented advances in the treatment of cancer have occurred through the use of immunotherapy, with several agents currently approved by the Food and Drug Administration (FDA) for the treatment of widespread metastatic disease across cancer types. Immune checkpoint blockade represents a particularly promising class of agents that block inhibitory molecules on the surface of T cells, resulting in their activation and propagation of an immune response. Treatment with these agents may re-invigorate anti-tumor immunity, resulting in therapeutic responses, and use of these agents currently is being studied in the adjuvant setting. Additionally, a strong rationale exists for their use in the neoadjuvant setting for high-risk resectable disease (e.g., regional nodal disease in the case of melanoma). This rationale is based on the relatively high risk of relapse for these patients, as well as on scientific evidence suggesting that long-term immunologic memory and tumor control may be superior in the setting of treatment for an intact tumor (i.e., neoadjuvant therapy) as opposed to treatment in the setting of micrometastatic disease (e.g., adjuvant treatment). The potential advantages of this approach and the current landscape for neoadjuvant immune checkpoint blockade is discussed in this report, as well as caveats that should be considered by clinicians contemplating this strategy.

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Impact of Micro- and Macroscopically Positive Surgical Margins on Survival after Resection of Adrenocortical Carcinoma

Abstract

Purpose

Adrenocortical carcinoma (ACC) is a rare, aggressive cancer; complete surgical resection offers the best chance for long-term survival. The impact of surgical margin status on survival is poorly understood. Our objective was to determine the association of margin status with survival.

Methods

Patients with ACC were identified from the National Cancer Data Base, 1998–2012, and stratified based on surgical margin status (negative vs. microscopically positive [+] vs. macroscopically [+]). Univariate/multivariate regression/survival analyses were utilized to determine factors associated with margin status and overall survival (OS).

Results

A total of 1553 patients underwent surgery at 589 institutions: 86% had negative, 12% microscopically (+), and 2% macroscopically (+) margins. Those with microscopically (+) and macroscopically (+) margins more often received adjuvant chemotherapy (39.4% macroscopically (+) vs. 38.5% microscopically (+) vs. 25.2% negative margins, p < 0.001). For unadjusted analysis, there was a significant difference in OS between the groups (log-rank p < 0.001), with median survival times of 58 months (95% confidence interval [CI] 49–66) for those with negative margins, 22 months (95% CI 18–34) microscopically (+), and 14 months (95% CI 6–27) macroscopically (+) margins. After adjustment, both microscopically (+) (HR 1.76, p < 0.001) and macroscopically (+) (HR 2.10, p = 0.0019) margin status were associated with compromised survival.

Conclusions

Having micro- or macroscopically (+) margin status after ACC resection is associated with dose-dependent compromised survival. These results underscore the importance of achieving negative surgical margins for optimizing long-term patient outcomes.

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Haematinic deficiencies and patient clinical profiles in Polish patients with recurrent aphthous stomatitis (RAS)

Abstract

Background

RAS is a common ulcerative disorder of the oral mucosa, where the immune impairment may develop in genetically predisposed subjects exposed to certain environmental factors. The aim of the study was to investigate the frequency of anaemia, iron and vitamin B12 deficiency in RAS and to explore its impact on the clinical presentation of RAS.

Methods

A total of 141 adults including: 71 subjects with RAS and 70 controls were enrolled in the study. A detailed dental and haematological assessment, including full blood count, serum iron and vitamin B12 evaluation was performed in all study participants. The results were statistically analysed with Mann-Whitney, Kruskal-Wallis, χ2 and Fisher tests with p<0.05 designated as a significance level.

Results

RAS patients were found to suffer anaemia, iron and vitamin B12 deficiency more frequently than the controls. The mean serum iron levels were also significantly lower in RAS subjects than in controls, although still within the norm. The lowest mean serum iron levels were observed in patients with a mild course of RAS. No significant differences in mean serum iron and vitamin B12 levels were revealed as a function of stratification according to the number of lesions per single flare-up.

Conclusions

The results of our study indicate an association between iron and vitamin B12 deficiency and RAS in a Polish population. However, as the haematinic deficiencies did not significantly modify the course and clinical phenotype of the disease, further studies to explore their role in RAS aetiology are required.

This article is protected by copyright. All rights reserved.

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The significance of an algorithm for human papilloma virus detection in HNSCC

Abstract

We read with great interest the article titled "The role of human papillomavirus in p16-positive oral cancers" by Belobrov et al. [1]. We appreciate the author's efforts on their interesting contribution to the complex paradigm of Human papillomavirus (HPV) detection which has been prevalent in literature for a long time. We would like to further emphasize the importance of their findings with reference to two aspects.

This article is protected by copyright. All rights reserved.

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New on NCI Websites, March 2018

NCI periodically provides updates on new websites and other online content of interest to the cancer community.

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The C-Reactive Protein/Albumin Ratio is a Novel Significant Prognostic Factor in Patients with Malignant Pleural Mesothelioma: A Retrospective Multi-institutional Study

Abstract

Background

Malignant pleural mesothelioma (MPM), a devastating neoplasm, is traditionally considered to be resistant to antitumor therapy. Identification of clinical prognostic indicators is therefore needed. Although the C-reactive protein/albumin ratio (CAR) has been used to predict the prognosis of many types of malignancy, its utility in patients with MPM is unknown.

Methods

The data of 100 patients diagnosed as having MPM from 1995 to 2015 at the National Kyushu Cancer Center and Kyushu University were analyzed. The CAR was calculated as serum C-reactive protein concentration divided by albumin concentration. A cutoff for CAR was set at 0.58 according to a receiver operating characteristics curve for 1-year survival.

Results

Thirty-five of the 100 (35.0%) patients were classified as having a high CAR. A high CAR was significantly associated with advanced clinical stage (p < 0.001) and chemotherapy alone (p = 0.002). Patients with a high CAR had significantly shorter overall survival (OS) (p < 0.001) and disease- or progression-free survival (DFS/PFS) (p < 0.001). These associations between CAR and prognosis remained significant after propensity score-matching. In multivariate analysis, a high CAR was an independent predictor of shorter OS and DFS/PFS (p = 0.003 and p = 0.008, respectively). Multivariate analyses of the subgroups of patients who had received chemotherapy and of patients who had undergone surgery also showed that a high CAR was an independent predictor of shorter OS and DFS/PFS.

Conclusions

CAR is an independent predictor of prognosis in MPM patients. This prognostic index contributes to clinicians' ability to predict benefit from treatment. Further larger, prospective studies are necessary to validate these findings.

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The Rationale and Emerging Use of Neoadjuvant Immune Checkpoint Blockade for Solid Malignancies

Abstract

Unprecedented advances in the treatment of cancer have occurred through the use of immunotherapy, with several agents currently approved by the Food and Drug Administration (FDA) for the treatment of widespread metastatic disease across cancer types. Immune checkpoint blockade represents a particularly promising class of agents that block inhibitory molecules on the surface of T cells, resulting in their activation and propagation of an immune response. Treatment with these agents may re-invigorate anti-tumor immunity, resulting in therapeutic responses, and use of these agents currently is being studied in the adjuvant setting. Additionally, a strong rationale exists for their use in the neoadjuvant setting for high-risk resectable disease (e.g., regional nodal disease in the case of melanoma). This rationale is based on the relatively high risk of relapse for these patients, as well as on scientific evidence suggesting that long-term immunologic memory and tumor control may be superior in the setting of treatment for an intact tumor (i.e., neoadjuvant therapy) as opposed to treatment in the setting of micrometastatic disease (e.g., adjuvant treatment). The potential advantages of this approach and the current landscape for neoadjuvant immune checkpoint blockade is discussed in this report, as well as caveats that should be considered by clinicians contemplating this strategy.

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Impact of Micro- and Macroscopically Positive Surgical Margins on Survival after Resection of Adrenocortical Carcinoma

Abstract

Purpose

Adrenocortical carcinoma (ACC) is a rare, aggressive cancer; complete surgical resection offers the best chance for long-term survival. The impact of surgical margin status on survival is poorly understood. Our objective was to determine the association of margin status with survival.

Methods

Patients with ACC were identified from the National Cancer Data Base, 1998–2012, and stratified based on surgical margin status (negative vs. microscopically positive [+] vs. macroscopically [+]). Univariate/multivariate regression/survival analyses were utilized to determine factors associated with margin status and overall survival (OS).

Results

A total of 1553 patients underwent surgery at 589 institutions: 86% had negative, 12% microscopically (+), and 2% macroscopically (+) margins. Those with microscopically (+) and macroscopically (+) margins more often received adjuvant chemotherapy (39.4% macroscopically (+) vs. 38.5% microscopically (+) vs. 25.2% negative margins, p < 0.001). For unadjusted analysis, there was a significant difference in OS between the groups (log-rank p < 0.001), with median survival times of 58 months (95% confidence interval [CI] 49–66) for those with negative margins, 22 months (95% CI 18–34) microscopically (+), and 14 months (95% CI 6–27) macroscopically (+) margins. After adjustment, both microscopically (+) (HR 1.76, p < 0.001) and macroscopically (+) (HR 2.10, p = 0.0019) margin status were associated with compromised survival.

Conclusions

Having micro- or macroscopically (+) margin status after ACC resection is associated with dose-dependent compromised survival. These results underscore the importance of achieving negative surgical margins for optimizing long-term patient outcomes.

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Left hippocampal dosimetry correlates with visual and verbal memory outcomes in survivors of pediatric brain tumors

BACKGROUND

Radiotherapy (RT) in the pediatric brain tumor population causes late neurocognitive effects. In the current study, the authors investigated associations between clinical and dosimetric risk factors and memory outcomes in a cohort of patients treated with proton radiotherapy (PRT).

METHODS

A total of 70 patients (median age at PRT, 12.1 years [range, 5.0-22.5 years]) who were treated with PRT were identified with baseline and follow-up evaluations of visual and verbal memory (Children's Memory Scale and the third edition of the Wechsler Memory Scale). Whole-brain as well as bilateral hippocampal and temporal lobe contours were delineated for the calculation of dosimetric indices. Multivariate analyses were performed to assess associations of score changes over time with clinical factors and dosimetric indices.

RESULTS

The median neurocognitive follow-up was 3.0 years (range, 1.1-11.4 years). For the entire cohort, delayed and immediate verbal memory scaled scores demonstrated small declines. The mean decline for delayed verbal memory scores was 0.6 (P = .01), and that for immediate verbal memory scores was 0.5 (P = .06). Immediate and delayed visual memory scores were not found to change significantly (+0.1 and -0.3, respectively; P>.30). A higher left hippocampal V_20GyE (percentage of the volume of a particular anatomical region receiving at least a 20 gray equivalent) was correlated with a score decline in all 4 measures. Female sex was found to be predictive of lower delayed verbal memory follow-up scores (P = .035).

CONCLUSIONS

Only delayed verbal memory scores were found to have declined statistically significantly at follow-up after PRT, reflecting some weakness in verbal memory retrieval. Given a correlation of left hippocampal dosimetry and memory outcomes after PRT, left hippocampal-sparing PRT plans may assist patients with pediatric brain tumors in preserving memory-retrieval abilities. Cancer 2018. © 2018 American Cancer Society.

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