Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer

Abstract

Background

There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC.

Patients and methods

In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m² intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS).

Results

A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%).

Conclusions

Vinflunine 280 mg/m² q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m² merits evaluation. ClinicalTrials.gov: NCT01091168.

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Computational prediction of neoantigens: do we need more data or new approaches?

Abstract

Personalized cancer immunotherapy may benefit from improved computational algorithms for identifying neoantigens. Recent results demonstrate that machine learning can improve accuracy. Additional improvements may require more genomic data paired with in vitro T cell reactivity measurements, and more sophisticated algorithms that take into account T cell receptor specificity.

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Immunohistochemical expression of CD44 in oral squamous cell carcinoma in relation to histomorphologic parameters and clinicopathological factors

Abstract

Objectives

Oral squamous cell carcinoma (OSCC) is characterized by its variable clinical course. In addition to the routinely used TNM/UICC systems, patient-specific prognostic/predictive biomarkers are needed. Promising biomarkers include the determination of the cancer stem cell (CSC) compartment, which can be identified by CD44 expression (amongst others).

Materials and Methods

A well-characterized cohort of 108 therapy-naïve OSCC with complete long-term follow-up and matched lymph node metastases were evaluated for CD44 expression by immunohistochemistry. CD44 expression was correlated with histomorphological characteristics (including tumor differentiation, tumor budding), clinicopathological parameters and follow-up data.

Results

Overexpression of CD44 was detected in 37% of OSCC within tumor center, 39% at the invasive margin and 16% of lymph-node metastases. CD44 overexpression at the invasive margin was significantly correlated with poor histopathological differentiation and specifically with high tumor budding activity and single cell invasion as signs of epithelial to mesenchymal tumor transformation (EMT). CD44 overexpression within tumor core region and in lymph node metastasis was identified as an independent prognostic factor for poor overall, disease-specific and disease-free survival in subsets of patients with advanced OSCC.

Conclusion

Our study demonstrates the association of CD44 with tumor aggressiveness and EMT as well as the independent prognostic impact of CD44 in a subset of OSCC, which underlines the role of tumor cell stemness as a key factor in malignant behaviour in this disease.

This article is protected by copyright. All rights reserved.

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Podoplanin-positive myofibroblasts: a pathologic hallmark of pleuroparenchymal fibroelastosis

Abstract

Pathologic differential diagnoses of pleuroparenchymal fibroelastosis (PPFE) include usual interstitial pneumonia (UIP) and pulmonary apical cap (PAC); however, there are no specific immunostaining makers to distinguish between these diseases. We performed immunohistochemistry using several pleural mesothelial cell-related markers, including cytokeratin-5/6, CAM5.2, WT-1, calretinin, desmin and podoplanin, for PPFE (n = 4), UIP (n = 10) and PAC (n = 3) lung sections. Among the examined markers, in PPFE and PAC lungs, podoplanin commonly showed positivity for spindle cells both in thickened pleura and subpleural fibroelastosis lesions; these cells were also stained with α-smooth muscle actin, a marker of myofibroblasts. However, even in elastic fibre-rich cases, UIP lungs did not show such podoplanin-positive myofibroblasts in pleura/subpleura and fibroblastic foci. These findings were also verified using immunofluorescence. By contrast, immunohistochemically as well as morphologically, the difference between PPFE and PAC was not apparent. The presence of podoplanin-positive myofibroblasts could be a pathologic hallmark of PPFE, suggesting a pathogenic process distinct from UIP but common to PAC.

This article is protected by copyright. All rights reserved.

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Immunopanning Purification and Culture of Retinal Ganglion Cells from Mouse

Publication date: Available online 21 February 2018
Source:Journal of Neuroscience Methods
Author(s): Lijun Fang, Tianwen Huang, Catherine Tsilfidis




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Designing GABA-Edited Magnetic Resonance Spectroscopy Studies: Considerations of Scan Duration, Signal-To-Noise Ratio and Sample Size

Publication date: Available online 21 February 2018
Source:Journal of Neuroscience Methods
Author(s): Mark Mikkelsen, Rachelle S. Loo, Nicolaas A.J. Puts, Richard A.E. Edden, Ashley D. Harris
BackgroundThe relationships between scan duration, signal-to-noise ratio (SNR) and sample size must be considered and understood to design optimal GABA-edited magnetic resonance spectroscopy (MRS) studies.New methodSimulations investigated the effects of signal averaging on SNR, measurement error and group-level variance against a known ground truth. Relative root mean square errors (measurement error) and coefficients of variation (group-level variance) were calculated. GABA-edited data from 18 participants acquired from five voxels were used to examine the relationships between scan duration, SNR and quantitative outcomes in vivo. These relationships were then used to determine the sample sizes required to observe different effect sizes.ResultsIn both simulated and in vivo data, SNR increased with the square root of the number of averages. Both measurement error and group-level variance were shown to follow an inverse-square-root function, indicating no significant impact of cumulative artifacts. Comparisons between the first two-thirds of the data and the full dataset showed no statistical difference in group-level variance. There was, however, some variability across the five voxels depending on SNR, which impacted the sample sizes needed to detect group differences in specific brain regions.Comparison with Existing methodsTypical scan durations can be reduced if taking into account a statistically acceptable amount of variance and the magnitudes of predicted effects.ConclusionsWhile scan duration in GABA-edited MRS has typically been considered in terms of SNR, it is more appropriate to think in terms of the amount of measurement error and group-level variance that provides sufficient statistical power.



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High Frequency Oscillations in Epileptic Rodents: Are We Doing It Right?

Publication date: Available online 21 February 2018
Source:Journal of Neuroscience Methods
Author(s): Maxime Lévesque, Siyan Wang, Jean Gotman, Massimo Avoli
BackgroundThe detection of high-frequency oscillations (HFOs, ripples: 80–200 Hz, fast ripples: 250–500 Hz) is often based on considering ripples or fast ripples in isolation; overlapping ripples and fast ripples are excluded from further analysis. Here, we studied overlapping HFOs during spontaneous seizures in pilocarpine-treated animals.New methodSpontaneous seizures (n = 6 animals) presented with either hypersynchronous- (HYP, n = 18) or low-voltage fast-onset (LVF, n = 21) pattern. Ripples and fast ripples overlapping by more than 30% were analysed.ResultsOverlapping HFOs could show a unimodal power spectrum between 80 to 500 Hz (n = 188, 58.9%) or a bimodal power spectrum, with peaks in power between 80–200 Hz and between 250–500 Hz (n = 131, 41.1%,). Overlapping HFOs occurred at higher rates during HYP seizures compared to the pre-ictal period in seizure onset zones (p < 0.001) and regions of secondary spread (p < 0.001). When comparing HYP and LVF seizures, we found that overlapping HFOs occurred at higher rates before LVF seizures (p < 0.05) compared to HYP seizures but, during the ictal period, HYP seizures showed higher rates of overlapping HFOs than LVF seizures (p < 0.001).Comparison with existing methodsWe have analysed overlapping ripples and fast ripples shortly before and during seizures.ConclusionsAlthough overlapping ripples and fast ripples represent a minority of HFOs, they may provide additional information on the excitability of neuronal networks that generate seizures in animal models and patients presenting with mesial temporal lobe epilepsy.



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The cholinergic anti-inflammatory pathway revisited

Abstract

Inflammatory bowel disease negatively affects the quality of life of millions of patients around the world. Although the precise etiology of the disease remains elusive, aberrant immune system activation is an underlying cause. As such, therapies that selectively inhibit immune cell activation without broad immunosuppression are desired. Inhibition of immune cell activation preventing pro-inflammatory cytokine production through neural stimulation has emerged as one such treatment. These therapeutics are based on the discovery of the cholinergic anti-inflammatory pathway, a reflex arc that induces efferent vagal nerve signaling to reduce immune cell activation and consequently mortality during septic shock. Despite the success of preclinical and clinical trials, the neural circuitry and mechanisms of action of these immune-regulatory circuits are controversial. At the heart of this controversy is the protective effect of vagal nerve stimulation despite an apparent lack of neuroanatomical connections between the vagus and target organs. Additional studies have further emphasized the importance of sympathetic innervation of these organs, and that alternative neural circuits could be involved in neural regulation of the immune system. Such controversies also extend to the regulation of intestinal inflammation, with the importance of efferent vagus nerve signals in question. Experiments that better characterize these pathways have now been performed by Willemze et al. in this issue of Neurogastroenterology & Motility. These continued efforts will be critical to the development of better neurostimulator based therapeutics for inflammatory bowel disease.

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Cover Image

The cover image, by K.-S. Ng et al., is based on the Original Article Quantification and neurochemical coding of the myenteric plexus in humans: No regional variation between the distal colon and rectum, DOI: 10.1111/nmo.13193.

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Issue Information

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Expressional analysis of APLNR, an essential gene for cancer immunotherapy, in colon and prostate cancers

Publication date: Available online 22 February 2018
Source:Pathology - Research and Practice
Author(s): Nam Jin Yoo, Min Sung Kim, Ju Hwa Lee, Chang Hyeok An, Sug Hyung Lee




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The degree of overlap between the follicular dendritic cell meshwork and tumor cells in mantle cell lymphoma is associated with prognosis

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Weihua Hou, Ping Wei, Jianlan Xie, Yuanyuan Zheng, Yanlin Zhang, Xiaoge Zhou
This study concerning mantle cell lymphoma (MCL) investigated retrospectively an association between patient prognosis and the percentage of the total number of lymphoma cells found in the follicular dendritic cell (FDC) meshwork, that is, the degree of overlap of lymphoma cells. Two hundred and nine MCL patients were apportioned to grades I–III, in which the CD21-positive FDC meshwork covered ≤50%, 51%-89%, and ≥90% of the tumor area, respectively. Significant differences among the grades (all, P < 0.01) were found in the following: duration of disease (from onset of clinical manifestation to diagnosis); clinical staging; extranodal involvement (non-lymphoid organs); histological subtype; and Ki-67 proliferation index (PI). After removing the aggressive variants, the overall survival rates of grade I (n = 92) and II (n = 57) patients were similar. The overall survival rates of grade III (n = 46) patients differed from that of grade I + II patients (P < 0.01). The grades negatively correlated with the Ki-67 PI value (r = −0.234, P = 0.001). At each grade the OSR of patients with Ki-67 PI ≤30% was similar to that of patients with Ki-67 >30%. In the Ki-67 PI ≤30% group, the OSRs of the patients differed significantly among the grades. In the Ki-67 >30% group the OSRs of the grades were similar. The results of multivariate Cox regression analysis showed that the degree of overlap, age and Ki-67 PI was the independent prognostic factors of the OSRs of MCL patients. Our data suggests that MCL patients in whom there was a high degree of overlap between the FDC meshwork and tumor area have a better clinical prognosis. The degree of overlap correlates well with the Ki-67 PI, which can be used to predict the prognosis of patients.



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Intradepartmental Consultations in Surgical Pathology: Review of a Standardized Process and Factors Influencing Consultation Rates and Practices in an Academic and Community Hospital Setting

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Emily A. Goebel, Helen Ettler, Joanna C. Walsh
Intradepartmental consultations (ICs) are important for quality assurance (QA) and ensuring diagnostic accuracy in surgical pathology. Few studies have reviewed pathologist factors that influence IC rates. Our study reviews IC data and factors that influence both formal (written) and informal (verbal) consultation practices among pathologists in academic and community hospital settings. Formal IC records from the academic hospital were collected and academic and community pathologists were invited to complete a survey about their IC practices. All centers had a formalized process for documenting ICs; however, 92% of academic and 90% of community pathologists also requested informal IC. The top reasons for selecting a particular colleague for IC was perceived level of expertise; however, interpersonal relationships and office proximity had a greater impact on informal IC practice. Top reasons for requesting a formal IC were mandatory (subspecialty defined) consultation and uncertainty regarding pathological findings. Advice on wording was a common reason for informal IC. Written documentation of IC aids in QA and determination of IC metrics; however, informal, undocumented ICs still occur. Reasons for IC and choice of consulting pathologist are multifactorial, and identifying these can help target quality improvement initiatives.



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Bex1 attenuates neuronal apoptosis in rat intracerebral hemorrhage model

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Mingqing He, Yueju Wang, Jiabing Shen, Chengwei Duan, Xiang Lu, Jianzhong Li
Brain expressed x-linked gene 1 (Bex1) which is at high levels in several populations of central nervous system (CNS) neurons, belongs to a family of small proteins of unknown function, playing roles as adaptors or modulators of intracellular signaling pathways. But its distribution and function in CNS remains unclear. Neuronal apoptosis is the major pathogenesis in secondary brain injury of intracerebral hemorrhage (ICH). In this study, the roles of Bex1 were explored in the pathophysiology of ICH. Western blot, immunohistochemistry, and immunofluorescence showed that obvious up-regulation of Bex1 in neurons adjacent to the hematoma after ICH. Furthermore, the increase of Bex1 expression was accompanied by the enhanced expression of Bax and active caspase-3, and decreased expression of B-cell lymphoma 2 (Bcl-2) following ICH. The in vitro study using Bex1 siRNA transfection in hemin-exposed PC12 cells suggested that Bex1 exerted anti-apoptotic function. Therefore, Bex1 may play the neuronal anti-apoptosis role following ICH, implying a novel molecular target for the therapy of ICH.



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Protective effects of Schisandrin on high glucose-induced changes of RhoA and eNOS activity in human umbilical vein endothelial cells

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Rong-Jin Zhang, Hui-Yao Hao, Qing-Juan Liu, Hong-Ye Zuo, Ying-Na Chang, Zhong-Ji Zhi, Peng-Peng Guo, Yong-Mei Hao
Schisandrin, derived from the Chinese medicinal herb Schisandra chinensis, has been found to confer protective effects on circulation systems. But the underlying molecular mechanisms remain unclear. The aim of this study was to investigate the effects of a high level of glucose on RhoA and eNOS activity in human umbilical vein endothelial cells(HUVECs) and how Schisandrin plays a role in mediating these effects. To find the optimal treatment time, HUVECs were cultured at a high glucose concentration (30 mM) for different lengths of time (0, 12, 24, and 48 hours). Subsequently, the cells were randomized into five groups: a normal group, a high glucose group, and three high glucose groups that were given different doses (5, 10, and 20 μM) of Schisandrin. The cells were pretreated with Schisandrin for 24 hours before stimulation with high glucose. The morphology of HUVECs in the various groups was assessed under a light microscope. Immunocytochemical staining was used to detect the level of p-MYPT1 expression. The levels of RhoA activity were determined using the RhoA Activation Assay Biochem Kit. The levels of eNOS activity were examined using a nitrate reduction test. The results showed that in the high glucose group, the activity of RhoA was increased and the activity of eNOS was reduced, thus decreasing the secretion of NO. However, after pretreatment with Schisandrin (10, 20 μM), the activity of RhoA was inhibited and the activity of eNOS increased, which led to an increase in NO production compared with the high glucose group. There was no evident difference between the 5 μM Schisandrin group and the high glucose group. Taken together, these findings indicate that Schisandrin can improve the function of endothelial cells by lowering the activity of RhoA/Rho kinase and raising both the activity of eNOS and the production of NO.



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Role of upregulated miR-136-5p in lung adenocarcinoma: a study of 1242 samples utilizing bioinformatics analysis

Publication date: Available online 22 February 2018
Source:Pathology - Research and Practice
Author(s): Tian-tian Li, Xiang Gao, Li Gao, Bin-liang Gan, Zu-cheng Xie, Jing-jing Zeng, Gang Chen
BackgroundIt is generally acknowledged that miRNAs play pivotal roles in the initiation and development of cancer. The aim of the current study is to investigate the clinicopathological role of miR-136-5p in lung adenocarcinoma and its underlying molecular mechanism.Materials and methodsData of a cohort of 1242 samples were provided by the Gene Expression Omnibus and The Cancer Genome Atlas to evaluate miR-136-5p expression in lung adenocarcinoma. A comprehensive meta-analysis integrating the expression data from all sources was performed, followed by a summary receiver operating curve plotted to appraise the upregulated expression of miR-136-5p in lung adenocarcinoma. Candidate targets of miR-136-5p were launched by the intersection of differentially expressed genes in The Cancer Genome Atlas and genes predicted by 12 web-based platforms. Then, hub genes were illustrated by a protein-protein interaction network. Furthermore, Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Protein Analysis Through Evolutionary Relationships analyses of potential target genes were carried out via bioinformatics tools.ResultsMiR-136-5p expression was upregulated in lung adenocarcinoma versus normal tissues (standard mean difference = 0.43, 95% confidence interval: 0.27-0.58). The summary receiver operating characteristic curve further verified the upregulation of miR-136-5p in lung adenocarcinoma (area under curve = 0.7459). A total of 311 candidate target genes of miR-136-5p were gathered to create a protein-protein interaction network. Molecular mechanism analysis unveiled the potential miR-136-5p target genes participated in cell adhesion molecules, focal adhesion, complement and coagulation cascades and blood coagulation.ConclusionMiR-136-5p is overexpressed in lung adenocarcinoma and is involved in the molecular mechanism of lung adenocarcinoma via suppressing the expressions of downstream targets, especially claudin-18, sialophorin and syndecan 2 that participate in cell adhesion.



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Brain-derived neurotrophic factor induces angiogenin secretion and nuclear translocation in human umbilical vein endothelial cells

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Ayako Mori, Yusuke Nishioka, Mai Yamada, Yuka Nishibata, Sakiko Masuda, Utano Tomaru, Naoyuki Honma, Takanori Moriyama, Akihiro Ishizu
Brain-derived neurotrophic factor (BDNF) is a well-known humoral protein that induces growth of neurons. Recent studies have suggested that BDNF could act as an angiogenesis inducer similar to vascular endothelial growth factor (VEGF). Angiogenin is a strong mediator of angiogenesis. It has particular characteristics both as a secreted protein and a transcription factor. After being incorporated into the cytoplasm, angiogenin is immediately transferred to the nucleus and then mediates the angiogenic effects of angiogenesis inducers, including VEGF. The aim of this study is to determine the association between BDNF and angiogenin. At first, we determined the secretion of angiogenin from human umbilical vein endothelial cells (HUVEC) induced by BDNF with enzyme-linked immunosorbent assay. Next, we determined BDNF-induced nuclear translocation of angiogenin by immunofluorescent staining. In addition, we examined the mRNA expression of angiogenin in HUVEC before and after BDNF stimulation by quantitative reverse transcriptase-polymerase chain reaction. As a result, we noted that BDNF induced angiogenin secretion and nuclear translocation without an increase in the mRNA expression in HUVEC. Furthermore, we demonstrated that BDNF-induced HUVEC proliferation was significantly suppressed when neomycin, a specific inhibitor of nuclear translocation of angiogenin, was administered. These findings indicate that nuclear translocation of angiogenin is critically involved in BDNF-induced proliferation of HUVEC. In conclusion, angiogenin contributes to angiogenesis induced by BDNF.



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Local delievery of thalidomide to inhibit neointima formation in rat model with artery injury

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Shougang Sun, Quan Zhang, Qiongying Wang, Qiang Wu, Guangli Xu, Peng Chang, Hao Hu, Feng Bai
ObjectiveTo observe the effect of local administration of thalidomide on neointimal formation after balloon-induced carotid artery injury in rats.MethodsForty-eight male Sprague-Dawley rats were randomly divided into 3 groups (n = 16): Sham operation group (group A), alone operation group (group B) and Thalidomide group (group C). The carotid arteries of group B and group C were injured by a conventional percutaneous transluminal coronary angioplasty (PTCA) balloon catheter. Group C was treated by local delivery of thalidomide, and group B did not receive thalidomide. The arteries of group A were not injured. Seven and 14 days after balloon injury, rats were sacrificed. Serum concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Neointima area, lumen area, macrophage infiltration and local expression of VEGF were measured using morphometric and immunohistochemical analyses. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to examine VEGF mRNA expression.ResultsThe VEGF levels were significantly increased in group B than in group C at 7 days (4.82 ± 0.17 pg/ml vs 0.98 ± 0.1 pg/mL, P < 0.01) and 14 days (6.3 ± 0.16 pg/ml vs 1.03 ± 0.09 pg/mL, P < 0.01). The TNF-α levels were also significantly increased in group B than in group C at 7 days (83 ± 1.01 pg/mL vs 76.37 ± 0.75 pg/mL, P < 0.01) and 14 days (84.06 ± 1.11 pg/mL vs 78.46 ± 0.94 pg/mL, P < 0.01). However, the area of neointimal formation was significantly reduced in group C than in group B at 14 days (0.07± 0.01 mm² vs 0.12± 0.04 mm², P < 0.01). Macrophage infiltration and local expression of VEGF in the injured arteries were significantly reduced in group C than in group B at 14 days. VEGF mRNA expression was significantly reduced in Group C than in group B at 14 days (6.3 ± 0.16 vs 1.02 ± 0.1, P < 0.01).ConclusionsThalidomide, which is a specific VEGF inhibitor, significantly inhibited neointimal hyperplasia and vascular restenosis after balloon injury to the carotid artery in rats, thus potentially providing a novel method for the prevention and treatment of restenosis, especially in-stent restenosis.



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Indoleamine 2, 3-dioxygenase and B7-H1 expressions as prognostic and follow-up markers in human pancreatic carcinoma

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Liancai Wang, Qingyong Ma, Deyu Li, Senmao Mu, Yong Li, Yafeng Wang, Pengfei Shi, Haibo Yu, Chunhui Gao, Kun Guo, Zhuoli Zhang
This study was to test hypotheses that indoleamine 2, 3-dioxygenase and B7-H1 expressions can be used as prognostic markers in human pancreatic carcinoma (PC). Ninety-five patients were recruited who had undergone radical surgical resection for PC. IDO and B7-H1 expressions in PC tissue specimens were evaluated by immunohistochemistry (IHC) techniques. The clinical and pathological features of these specimens were analyzed.IDO positive, B7-H1 positive, and combined IDO/B7-H1 positive tumors exhibited significant correlations with lymphocytic infiltration, perineural invasion, TNM status, and pathologic grade (p < 0.05), which tended to show strong correlations with malignant progression of PC. Also, IDO correlated with diabetes mellitus (DM) and HAD scale and B7-H1 correlated with smoke (p < 0.05). In addition, the correlation analysis indicated that IDO had a positive correlation with B7-H1 (p < 0.05). Moreover, the results showed that a combination of IDO and B7-H1 expressions could serve as independent prognostic marker after adjusting by Cox proportional hazards regression models (p < 0.05). IDO and B7-H1 expressions were observed in patient with PC tissues and are important markers for PC malignant progression. A combination of IDO and B7-H1 expression can be served as an independent prognostic marker for PC.



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Detection of the DICER1 hotspot mutation alongside immunohistochemical analysis may provide a better diagnostic measure for ovarian Sertoli-Leydig cell

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Xiaobo Zhang, Danhua Shen, Ying Wang
BackgroundTo evaluate the clinicopathological and histopathological characteristics of ovarian Sertoli-Leydig cell tumors (SLCTs) in relation to differential diagnosis, and patient prognosis.MethodsA review of clinical data, pathological morphology and immunohistochemical analysis of SLCTs were performed in 18 SLCTs patients. The DICER1 gene mutation was assessed in eight cases that were obtained from in-house surgical resections.ResultsAmong 18 SLCTs patients, three cases had well-differentiated tumors, 8 cases had moderately-differentiated tumors, and the remaining 7 cases had poorly-differentiated tumors. Among the moderately-differentiated tumors, three cases occurred coincidently with other diseases – one case occurred with endometrial carcinoma (grade I), and two cases with endometrial carcinoma of the ovary (grade 2 and grade 3). Immunohistochemical staining for α-inhibin, calretinin, and FOXL2 was positive in all the biopsies tested. The intensity of staining varied depending on the percentage of Sertoli cells and the primitive gonad interstitial composition. DICER1 mutations were detected in three of eight cases that were evaluated and were significantly more in low age range patients (P < 0.05). The initial symptoms of these three cases were sexual changes and elevation of androgen levels. The follow-up time in this study ranged from 3 to 87 months with the mean follow-up time of 29.1 months. Prognosis was generally favorable. There was no recurrence or metastasis in any patient, except for one case with recurrence of endometrial carcinoma.ConclusionThe clinical presentation of SLCTs can be both varied and complex. Pathological examination is imperative for both diagnostic and prognostic grading. Immunohistochemical stain of α-inhibin, FOXL2, and calretinin and genetic testing for DICER1 mutations will be more potent for differential diagnosis.



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MicroRNA-30d/JAG1 axis modulates pulmonary fibrosis through Notch signaling pathway

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Silin Zhao, Xuefei Xiao, Shuang Sun, Da Li, Wei Wang, Yan Fu, Fuyuan Fan
Pulmonary fibrosis (PF) is a fibroproliferative disease which can finally end up fatal lung failure. PF is characterized by abnormal proliferation of fibroblast, dysregulated fibroblast differentiation to myofibroblast and disorganized collagen and extracellular matrix (ECM) production, deposition and degradation. JAG1/Notch signaling has been reported to play a key role in tissue fibrosis including PF. Herein, we confirmed the abnormal upregulation of JAG1 mRNA expression and protein levels in PF tissue specimens; JAG1 knockdown reduced TGF-β1-induced α-SMA and Collagen I protein levels. From the aspect of miRNA regulation, we searched for candidate miRNAs which might target JAG1 to inhibit its expression. Among the selected miRNAs, miR-30d expression was downregulated in PF tissues; miR-30d overexpression attenuated TGF-β1-induced primary normal human lung fibroblast (NHLF) proliferation, as well as α-SMA and Collagen I protein levels. Through directly binding to the 3′-UTR of JAG1, miR-30d significantly inhibited JAG1 mRNA expression and protein level. Furthermore, JAG1 overexpression partially reversed the effect of miR-30d on NHLF proliferation and α-SMA and Collagen I proteins upon TGF-β1 stimulation; miR-30d could suppress TGF-β1 function on NHLFs through blocking JAG1/Notch signaling. Rescuing miR-30d expression to suppress TGF-β1-induced activation of JAG1/Notch signaling may present a promising strategy for PF treatment.



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Metastasis-associated protein 1 (MTA1) in gastric cancer tissues is positively associated with poorer prognosis

Publication date: Available online 21 February 2018
Source:Pathology - Research and Practice
Author(s): Zhen-ye Lv, Zhong-Sheng Zhao, Zai-Yuan Ye, Yuan-Yu Wang, Hui-Ju Wang, Qiong Yang
BackgroundThe present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer.MethodsParaffin-embedded resected tissues of gastric cancer mucosa (n = 436) and adjacent normal mucosa (n = 92) were assessed immunohistochemically for MTA1 protein, and scored according to the percentage of cells positively stained for MTA1 combined with stain intensity. Associations between MTA1 staining scores and clinicopathological factors, including survival time, were evaluated.ResultsThe staining scores for MTA1 were significantly higher in gastric cancer tissues than in matched normal tissues. MTA1 scores positively correlated with tumor size, depth of invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distal metastasis, and advanced clinical staging. Patients with high MTA1 scores in gastric cancer tissues had a significantly lower five-year survival rate compared with patients with low MTA1 scores. The multivariate analysis indicated that MTA1 protein levels in resected gastric cancer tissues, as reflected by immunohistochemical staining, are an independent prognostic index of gastric carcinoma (P < 0.01).ConclusionMTA1 immunopositivity was significantly associated with progression of gastric cancer, and may be helpful in gastric cancer prognosis.



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Health-related quality of life in patients undergoing cervico-thoracic osteotomies for fixed cervico-thoracic kyphosis in patients with ankylosing spondylitis

Abstract

Purpose

Ankylosing spondylitis (AS) can result in severe cervico-thoracic kyphotic deformity (CTKD). Few studies have addressed the relationship between cervico-thoracic osteotomies in AS and health-related quality of life scores. The aim of this study is to evaluate the impact of cervico-thoracic osteotomy (CTO) on improving quality of life for patients with fixed CTKD.

Methods

A database of all patients who underwent a CTO for CTKD in patients with AS was created. Data entered into the database consisted of patients' demographics and comorbidities, as well as surgical, clinical and radiological data. The outcome measures used in our study were Neck Disability Index (NDI), EuroQol 5D-5L (EQ-5D-5L) and Visual Analogue Scale. We also measured the following radiological parameters: chin-brow to vertical angle (CBVA), C7-Slope, C2–7 angle, Regional Kyphosis Angle, C2–C7 sagittal vertical axis (SVA) and C7–S1 SVA.

Results

A total of 13 male patients with AS were included in our study. The mean age was 57.5 years (40–74); and mean follow-up was 37.6 months (12–78). Following the C7–T1 osteotomy (10 Smith Peterson Osteotomies and 3 Pedicle Subtraction Osteotomies), NDI improved from a mean of 65.54 (SD 8.95) to a mean of 22.09 (SD 6.99). The EQ-5D-5L improved from a mean of 0.41 (SD 0.16) to 0.86 (SD 0.088). Pre-operative CBVA was on average 54° (40°–75°) and post-operative was 7° (2°–12°). There were no major complications, 1 superficial infection and 5 minor nerve root irritations.

Conclusions

Cervical osteotomy for the management of fixed flexion deformity of cervical spine in ankylosing spondylitis is a safe procedure and can result in restoration of horizontal gaze and sagittal balance with significant improvement of the patient's health-related quality of life.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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Granulomatous-Lymphocytic Interstitial Lung Disease in 22q11.2 Deletion Syndrome: a Case Report and Literature Review

Abstract

Purpose of Review

Granulomatous-lymphocytic interstitial lung disease (GLILD) has classically been associated with common variable immune deficiency (CVID), but is increasingly being reported in other immunodeficiencies. We describe the second reported case of GLILD in a patient with 22q11.2 deletion syndrome (22q11.2DS) and review the recent literature surrounding GLILD.

Recent Findings

GLILD is characterized by granulomata and lymphoproliferation. Consensus statements and retrospective and case-control studies have better elucidated the clinicopathological and radiographic manifestations of GLILD, allowing for its differentiation from similar conditions like sarcoidosis. Gaps of knowledge remain, however, particularly regarding optimal management strategies. Combination therapies targeting T and B cell populations have recently shown favorable results.

Summary

GLILD is associated with poorer outcomes in CVID. Its recognition as a rare complication of 22q11.2DS and other immunodeficiencies therefore has important therapeutic and prognostic implications. Additional research is needed to better understand the natural history and pathogenesis of GLILD and to develop evidence-based practice guidelines.

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The Effect of Inhalant Organic Dust on Bone Health

Abstract

Purpose of Review

Agriculture remains a major economic sector globally, and workers experience high rates of chronic inflammatory lung and musculoskeletal diseases. Whereas obstructive pulmonary diseases are known risk factors for bone loss, the underlying relationship between lung inflammation and bone health is not well known.

Recent Findings

An agriculture organic dust extract inhalation animal model has recently linked lung injury-induced inflammation to systemic bone loss. This process is dependent upon lipopolysaccharide and the toll-like receptor 4 (TLR4) signaling pathway. Downstream systemic interleukin-6 is a key mediator that subsequently activates osteoclastogenesis. Age is a host factor that impacted bone disease with younger mice demonstrating increased susceptibility to bone loss following inhalant exposures as compared to older mice. Supplemental dietary vitamin D was shown to prevent organic dust-induced bone loss, but not lung disease, in animals.

Summary

Recent animal studies provide new mechanistic insight into the lung-bone inflammatory axis. Host factors, diet, and lipopolysaccharide/TLR4 signaling pathways play a significant role in explaining how inhalant organic dust exposures impact bone health. These investigations might lead to specific targeted therapeutic approaches.

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Current Status of Potential Therapies for IgE-Mediated Food Allergy

Abstract

Purpose of Review

The goal of this review is to provide the reader with an updated summary of published trial data regarding the use of oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) for treatment of IgE-mediated food allergies.

Recent Findings

Data from phase 2 trials for treatment of peanut allergy with OIT and EPIT reveal an increase in the threshold of reactivity for peanut-allergic children. Compared to EPIT, OIT promotes a greater increase in the threshold of reactivity; however, adverse events are more common with OIT.

Summary

OIT, EPIT, and SLIT appear to modulate the immune response for some food-allergic individuals. Data regarding utility for treatment of food allergies regardless of modality is limited to few foods, as is investigation into treatment of food-allergic infants, young children, and adults. Future trials are likely to focus on young children, food allergies other than peanut, and treatment of multifood-allergic individuals.

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Diagnostic Tools for Inborn Errors of Human Immunity (Primary Immunodeficiencies and Immune Dysregulatory Diseases)

Abstract

Purpose of Review

The purpose of this review is to provide an overview of diagnostic testing in primary immunodeficiency and immune dysregulatory disorders (PIDDs), particularly focusing on flow cytometry and genetic techniques, utilizing specific examples of PIDDs.

Recent Findings

Flow cytometry remains a vital tool in the diagnosis and monitoring of immunological diseases. Its utility ranges from cellular analysis and specific protein quantitation to functional assays and signaling pathway analysis. Mass cytometry combines flow cytometry and mass spectrometry to dramatically increase the throughput of multivariate single-cell analysis. Next-generation sequencing in combination with other molecular techniques and processing algorithms has become more widely available and identified the diverse and heterogeneous genetic underpinnings of these disorders.

Summary

As the spectrum of disease is further clarified by increasing immunological, genetic, and epigenetic knowledge, the careful application of these diagnostic tools and bioinformatics will assist not only in our understanding of these complex disorders, but also enable the implementation of personalized therapeutic approaches for disease management.

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Indoor Environmental Interventions and their Effect on Asthma Outcomes

Abstract

Purpose of Review

The use of environmental interventions to improve outcomes in asthmatics has long been an elusive goal. While numerous interventions have been studied, the results of clinical trials have been mixed. This review aims to identify combinations of interventions that have been proven to be effective and to propose a model for using them in a clinical setting.

Recent Findings

An NIH workshop emphasized a need for research to identify effective interventions for reducing indoor exposures and improving asthma outcomes. A number of innovative measures were described, though evidence supporting their use was lacking. A recent systematic review described various interventions for which evidence is available. The greatest challenge for this approach is the same as that for the medical approach to treatment: nonadherence.

Summary

Given evidence for effective interventions, control of environmental exposures should lead to improved asthma outcomes. Methods to improve adherence need to be identified.

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Impact of Particulate Air Pollution on Cardiovascular Health

Abstract

Purpose of Review

Air pollution is established as an independent risk factor for cardiovascular diseases (CVDs). Ambient particulate matter (PM), a principal component of air pollutant, has been considered as a main culprit of the adverse effects of air pollution on human health.

Recent Findings

Extensive epidemiological and toxicological studies have demonstrated particulate air pollution is positively associated with the development of CVDs. Short-term PM exposure can trigger acute cardiovascular events while long-term exposure over years augments cardiovascular risk to an even greater extent and can reduce life expectancy by a few years. Inhalation of PM affects heart rate variability, blood pressure, vascular tone, blood coagulability, and the progression of atherosclerosis. The potential molecular mechanisms of PM-caused CVDs include direct toxicity to the cardiovascular system or indirect injury by inducing systemic inflammation and oxidative stress in circulation.

Summary

This review mainly focuses on the acute and chronic effects of ambient PM exposure on the development of cardiovascular diseases and the possible mechanisms for PM-induced increases in cardiovascular morbidity and mortality. Additionally, we summarized some appropriate interventions to attenuate PM air pollution-induced cardiovascular adverse effects, which may promote great benefits to public health.

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Late Inflammatory Response to Hyaluronic Acid Dermal Fillers

Are you aware of this rare complication associated with the use of injectable hyaluronic acid-based fillers? Find out what there is to know.
Plastic Reconstructive Surgery-Global Open (PRS Global Open)

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Robotics confers an advantage in right hemicolectomy with intracorporeal anastomosis when matched against conventional laparoscopy

Abstract

Comparisons between robotic and laparoscopic right hemicolectomy have been confounded by variations in operative technique. This study evaluates the two procedures after standardizing the intraoperative steps and perioperative management. Patients who underwent robotic right hemicolectomy with intracorporeal bowel anastomosis between July 2015 and June 2017 were matched with a laparoscopic group. Perioperative management was in accordance to an enhanced recovery protocol. Outcomes and histopathological data were compared. Thirty-two patients were included. Amongst the patients who did not undergo complete mesocolic excision, the median operative time did not differ between the two groups (p = 0.413). The robotic group recorded a statistically shorter time for intracorporeal anastomosis (13 vs 19 min, p = 0.024). Postoperative recovery and complication rates were similar, except for a greater lymph node harvest in the robotic group (41 vs 31, p = 0.038). Robotic surgery achieves short-term results comparable to existing conventional laparoscopy, notwithstanding the advantages of enhanced ergonomics.

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Adverse mental health outcomes in a population-based cohort of survivors of childhood cancer

BACKGROUND

The elevated risk for physical late effects in childhood cancer survivors (CCS) is well documented, but their risk for mental health problems is less well described.

METHODS

The authors assembled a cohort of all 5-year CCS who were diagnosed before age 18 years and treated in an Ontario pediatric cancer center between 1987 and 2008. Patients were matched to population controls and linked to health administration databases. The authors calculated rates of mental health care visits (family physician, psychiatrist, emergency department, hospitalization) and the risk for a severe mental health event (emergency department, hospitalization, suicide). Outcomes were compared using recurrent event and survival analyses.

RESULTS

Compared with 20,269 controls, 4117 CCS had a higher rate of mental health visits (adjusted relative rate [RR], 1.34; 95% confidence interval [CI], 1.12-1.52). Higher rates were associated with female gender (RR, 1.39; CI, 1.10-1.75; P = .006) and being diagnosed at ages 15 to 17.9 years (compared with ages 0-4 years: RR, 1.81; 95% CI, 1.17-2.80; P = .008). Cancer type, treatment intensity, and treatments targeting the central nervous system were not significant predictors. Survivors were at increased risk for a severe event compared with controls (adjusted hazard ratio, 1.13; 95% CI, 1.00-1.28; P = .045). CCS who were diagnosed with cancer at age 4 years or younger were at greatest risk: 16.3% (95% CI, 13.2%-19.8%) had experienced a severe event by age 28 years.

CONCLUSIONS

CCS experienced higher rates of mental health visits and a greater risk for a severe event than the general population. Survivors of adolescent cancer have a higher rate of mental health visits overall, whereas survivors of cancer before age 4 years have a markedly elevated risk of severe events. Cancer 2018. © 2018 American Cancer Society.

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Sequential injection of radioactive nanosized colloids followed by indocyanine green for sentinel lymph node detection in oral squamous cell carcinoma: A proof of concept

Publication date: Available online 21 February 2018
Source:Oral Oncology
Author(s): Antoine Digonnet, Romain Barbieux, Marie Quiriny, Esther Willemse, Michel Moreau, Nicolas de Saint Aubain, Matteo Cappello, Pierre Bourgeois




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CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of minimal residual disease in chronic lymphocytic leukemia

Future Oncology, Ahead of Print.


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Peripheral blood clinical laboratory variables associated with outcomes following combination nivolumab and ipilimumab immunotherapy in melanoma

Abstract

Both the combination of nivolumab + ipilimumab and single-agent anti-PD-1 immunotherapy have demonstrated survival benefit for patients with advanced melanoma. As the combination has a high rate of serious side effects, further analyses in randomized trials of combination versus anti-PD-1 immunotherapy are needed to understand who benefits most from the combination. Clinical laboratory values that were routinely collected in randomized studies may provide information on the relative benefit of combination immunotherapy. To prioritize which clinical laboratory factors to ultimately explore in these randomized studies, we performed a single-center, retrospective analysis of patients with advanced melanoma who received nivolumab + ipilimumab either as part of a clinical trial (n = 122) or commercial use (n = 87). Baseline routine laboratory values were correlated with overall survival (OS) and overall response rate (ORR). Kaplan–Meier estimation and Cox regression were performed. Median OS was 44.4 months, 95% CI (32.9, Not Reached). A total of 110 patients (53%) responded (CR/PR). Significant independent variables for favorable OS included the following: high relative eosinophils, high relative basophils, low absolute monocytes, low LDH, and a low neutrophil-to-lymphocyte ratio. These newly identified factors, along with those previously reported to be associated with anti-PD-1 monotherapy outcomes, should be studied in the randomized trials of nivolumab + ipilimumab versus anti-PD-1 monotherapies to determine whether they help define the patients who benefit most from the combination versus anti-PD-1 alone.

The combination of nivolumab and ipilimumab is a highly effective treatment for patients with melanoma, and little is known about the patients who do the best after treatment. For the first time, we report basic clinical laboratory variables which are associated with overall survival following treatment.

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A Multilinear Tongue Model Derived from Speech Related MRI Data of the Human Vocal Tract

Publication date: Available online 21 February 2018
Source:Computer Speech & Language
Author(s): Alexander Hewer, Stefanie Wuhrer, Ingmar Steiner, Korin Richmond
We present a multilinear statistical model of the human tongue that captures anatomical and tongue pose related shape variations separately. The model is derived from 3D magnetic resonance imaging data of 11 speakers sustaining speech related vocal tract configurations. To extract model parameters, we use a minimally supervised method based on an image segmentation approach and a template fitting technique. Furthermore, we use image denoising to deal with possibly corrupt data, palate surface information reconstruction to handle palatal tongue contacts, and a bootstrap strategy to refine the obtained shapes. Our evaluation shows that, by limiting the degrees of freedom for the anatomical and speech related variations, to 5 and 4, respectively, we obtain a model that can reliably register unknown data while avoiding overfitting effects. Furthermore, we show that it can be used to generate plausible tongue animation by tracking sparse motion capture data.



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Type 1 Narcolepsy in anti-Hu antibodies mediated encephalitis: a case report

Publication date: Available online 21 February 2018
Source:Sleep Medicine
Author(s): Maria Vitiello, Elena Antelmi, Fabio Pizza, Emanuela Postiglione, Rosalba Poggi, Rocco Liguori, Giuseppe Plazzi




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CaV3.2 drives sustained burst-firing, which is critical for absence seizure propagation in reticular thalamic neurons

Summary

Objective

Genetic alterations have been identified in the CACNA1H gene, encoding the Ca_V3.2 T-type calcium channel in patients with absence epilepsy, yet the precise mechanisms relating to seizure propagation and spike-wave-discharge (SWD) pacemaking remain unknown. Neurons of the thalamic reticular nucleus (TRN) express high levels of Ca_V3.2 calcium channels, and we investigated whether a gain-of-function mutation in the Cacna1h gene in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) contributes to seizure propagation and pacemaking in the TRN.

Methods

Pathophysiological contributions of Ca_V3.2 calcium channels to burst firing and absence seizures were assessed in vitro using acute brain slice electrophysiology and quantitative real-time polymerase chain reaction (PCR) and in vivo using free-moving electrocorticography recordings.

Results

TRN neurons from GAERS display sustained oscillatory burst-firing that is both age- and frequency-dependent, occurring only in the frequencies overlapping with GAERS SWDs and correlating with the expression of a Ca_V3.2 mutation-sensitive splice variant. In vivo knock-down of Ca_V3.2 using direct thalamic injection of lipid nanoparticles containing Ca_V3.2 dicer small interfering (Dsi) RNA normalized TRN burst-firing, and in free-moving GAERS significantly shortened seizures.

Significance

This supports a role for TRN Ca_V3.2 T-type channels in propagating thalamocortical network seizures and setting the pacemaking frequency of SWDs.

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Response to comment: Eustachian tube diameter: Is it associated with chronic otitis media development?

Publication date: Available online 3 February 2018
Source:American Journal of Otolaryngology
Author(s): Ceki Paltura, Tuba Selçuk Can, Behice Kaniye Yılmaz, Mehmet Emre Dinç, Ömer Necati Develioğlu, Mehmet Külekçi




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Salvage of recurrence after surgery and adjuvant therapy: A systematic review

Publication date: Available online 2 February 2018
Source:American Journal of Otolaryngology
Author(s): Joseph Zenga, Jennifer Gross, Susan Fowler, Jenny Chen, Peter Vila, Jeremy D. Richmon, Mark A. Varvares, Patrik Pipkorn
PurposeTo determine the oncologic and functional outcomes of patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma after initial management with surgery and adjuvant therapy.Data sourcesOvid Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov.Review methodsA structured search was performed of the literature to identify studies that included patients undergoing surgical salvage for local, regional, or locoregional recurrent head and neck squamous cell carcinoma without known distant metastases who had been treated with initial surgery and post-operative adjuvant radio- or chemoradiotherapy. Studies were excluded if they did not report at least 1-year survival estimates, included patients who underwent primary non-surgical management, or included those treated with non-surgical salvage therapies or supportive care alone.ResultsThe search strategy yielded 3746 abstracts. After applying exclusion and inclusion criteria, 126 full-texts were reviewed and six studies were included with a total of 222 patients. All studies were retrospective in design and included diverse disease subsites and stages. Complications and functional outcomes were inconsistently reported. Five-year survival estimates ranged between 10% and 40% between studies.ConclusionsPatients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma after initial surgery and adjuvant therapy may have a particularly poor prognosis. Future studies are needed to determine functional and quality of life outcomes in this patient population and to identify specific prognostic factors for re-recurrence and survival.



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Systematic review of hearing loss after traumatic brain injury without associated temporal bone fracture

Publication date: Available online 1 February 2018
Source:American Journal of Otolaryngology
Author(s): Jenny X. Chen, Michael Lindeborg, Seth D. Herman, Reuven Ishai, Renata Knolls, Aaron Remenschneider, David Jung, Elliott D. Kozin
ObjectiveWhile hearing loss following temporal bone fracture is a well-described phenomenon, few data exist on auditory dysfunction in patients with traumatic brain injury (TBI) without temporal bone fracture. Herein, we aim to systematically review hearing loss after TBI without bony fracture and describe its etiologies.Data sourcesPubmed, Embase, Cochrane databases.Review methodsA systematic review of the literature from 1966 to January 2017 was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations. Data were obtained from studies that investigated hearing loss in TBI without skull fracture according to an a priori protocol with inclusion and exclusion criteria. Variables included type and severity of hearing loss, as well as pathophysiology of hearing loss.ResultsThere were 13 studies with 773 patients that met study criteria. Overall, there was one prospective cohort study, four retrospective cohort studies, two case-control studies, and six case reports. The studies with the highest level of evidence report a change in hearing of at least 10–15 dB across a range of frequencies in as many as 58% percent of TBI patients without bony fracture, which was transient or chronic. The mechanism/severity of injury may impact the rate of hearing loss.ConclusionsHearing loss after TBI in the absence of bony injury appears to be a clinically significant but poorly characterized phenomenon.



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Anatomical anomalies of the Eustachian tube and chronic otitis media

Publication date: Available online 1 February 2018
Source:American Journal of Otolaryngology
Author(s): Zhengcai Lou, Zihan Lou




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Prognostic significance of HPV status in the re-irradiation of recurrent and second primary cancers of the head and neck

Publication date: Available online 7 February 2018
Source:American Journal of Otolaryngology
Author(s): Maria A. Velez, Pin-Chieh Wang, Sophia Hsu, Robert Chin, Philip Beron, Elliot Abemayor, Maie St. John, Allen M. Chen
PurposeTo evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field.Methods and materialsThe medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test.ResultsHPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40).ConclusionsThe favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.



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Surgical indications or inclusion/exclusion criteria of explorative tympanotomy on sudden sensorineural hearing

Publication date: Available online 1 February 2018
Source:American Journal of Otolaryngology
Author(s): Zhengcai Lou, Zihan Lou




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Tonsillectomy sparing transoral robot assisted styloidectomy

Publication date: Available online 31 January 2018
Source:American Journal of Otolaryngology
Author(s): Sameep Kadakia, Ameya Jategaonkar, Ansley Roche, Raymond L. Chai
Eagle Syndrome can present with a variety of symptoms and be caused by an elongated styloid process or calcified stylohyoid ligament. Patients failing medical management of this disorder may be treated with surgical excision of the styloid process. In the literature, transoral and transcervical approach have both been described. Although transoral approaches typically begin with a tonsillectomy, tonsil-sparing approaches have also been utilized. With the advent of robotic surgery, the potential for a tonsillectomy sparing approach has become a feasible alternative, preventing the pain and morbidity associated with adult tonsillectomy while continuing to provide superior exposure and instrumentation. We report three successful cases of patients treated with tonsillectomy sparing transoral robot assisted styloidectomy. This represents the first application of this technique in the literature and suggests the potential for a paradigm shift in the surgical management of this disease.



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Preoperative laboratory data are associated with complications and surgical site infection in composite head and neck surgical resections

Publication date: Available online 31 January 2018
Source:American Journal of Otolaryngology
Author(s): Nicholas B. Abt, Rosh K. Sethi, Sidharth V. Puram, Mark A. Varvares
Objectives1) Describe normal/abnormal preoperative laboratory testing incidence in head and neck (H&N) composite resections and 2) determine complication, surgical site infection (SSI), and transfusion predictors by laboratory test.MethodsThe 2006 to 2013 NSQIP databases were queried for H&N composite resections. Laboratory data was categorized within, under, or above the normal reference range according to NSQIP definitions. Overall complications and SSI were analyzed with multivariable logistic regression analysis.ResultsFrom 2006 to 2013, there were 1193H&N composite resections, of which 1135 (95.1%) underwent ≥1 preoperative laboratory test. Complete blood counts were obtained in 92.3%, basic metabolic panels in 90.7%, coagulation studies in 56.2%, and liver function tests (LFTs) in 52.6%. Low sodium was found in 11.5%, increasing complication odds by 2.30 (p = 0.005). High AST comprised 10.0% and increased complication odds (OR = 2.93, p = 0.012). Additionally, 9.2% had a high white blood cell (WBC) count and 3.5% had high platelets, increasing complications by 1.92 (p = 0.030) and 3.13 (p = 0.015), respectively. BUN, creatinine, total bilirubin, albumin, alkaline phosphatase, INR, PT, and aPTT abnormal values did not affect postoperative complications. Increased SSI odds were appreciated with low sodium (OR: 2.83, p = 0.002), high AST (OR: 6.85, p < 0.001), and high alkaline phosphatase (OR: 5.46, p = 0.007). Importantly, INR had no effect on transfusion rates. High PT, aPTT, or low platelets did not change transfusion odds.ConclusionInflammatory markers are associated with complications but not SSI. High LFTs and low sodium are associated with complications and SSI. Coagulopathies did not increase transfusion rates. These findings identify laboratory studies to focus on during H&N resection preoperative assessments.



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Simple laryngeal suspension procedure by suturing the digastric muscle to the periosteum of the mandible in neck dissection for tongue cancer

Publication date: Available online 31 January 2018
Source:American Journal of Otolaryngology
Author(s): Akira Ohkoshi, Takenori Ogawa, Shun Sagai, Ayako Nakanome, Kenjiro Higashi, Ryo Ishii, Kengo Kato, Yukio Katori
PurposeIn this article, a simple, new laryngeal suspension procedure is described. The effect of hyoid bone suspension by suturing the digastric muscle to the periosteum of the mandible is analyzed.Materials and methodsTo elucidate the effect of hyoid bone suspension, CT scans of 26 patients who underwent ipsilateral neck dissection with primary resection of tongue cancer were retrospectively reviewed, and the distance between the hyoid bone and the mandible was measured on the operated and unoperated sides of the neck. A total of 14 patients who underwent suturing of the digastric muscle to the mandible (digastric muscle-sutured group) and the 12 patients who did not (control group) were compared.ResultsIn the digastric muscle-sutured group, the average distance between the hyoid bone and the mandible was significantly smaller on the operated side (17.8 ± 0.57 mm) than on the unoperated side (19.8 ± 0.93 mm; p < 0.05). In the control group, there was no significant difference between the operated side (21.0 ± 1.42 mm) and the unoperated side (19.7 ± 1.39 mm). The difference in the distance between the operated and unoperated sides was significantly larger in the digastric muscle-sutured group (1.97 ± 0.79 mm) than in the control group (−1.32 ± 0.61; p < 0.05).ConclusionsIt was shown for the first time that suturing of the digastric muscle to the periosteum of the mandible in neck dissection with primary resection of tongue cancer resulted in hyoid bone suspension. This simple procedure can be useful for laryngeal suspension.



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The treatment of vocal process granuloma

Publication date: Available online 31 January 2018
Source:American Journal of Otolaryngology
Author(s): Zhengcai-LouZihan-Lou




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Thirty-day readmissions following parathyroidectomy: Evidence from the National Readmissions Database, 2013–2014

Publication date: Available online 10 January 2018
Source:American Journal of Otolaryngology
Author(s): Adam M. Kravietz, Jessica L. Buicko, Joshua P. Parreco, Michael A. Lopez, Robert A. Kozol
PurposeParathyroidectomy is one of the most common procedures performed in the United States, and are increasingly being performed safely in the outpatient setting. However, complications from surgery can be life-threatening, and thus an understanding of who may be at risk is essential. We analyzed and compared the risk factors for patients readmitted within 30 days following inpatient parathyroidectomy for primary or secondary hyperparathyroidism.Materials and methodsWe reviewed the National Readmissions Database from 2013 to 2014 for patients who received inpatient parathyroidectomy for primary or secondary hyperparathyroidism. The primary outcome was non-elective readmission within 30 days. Multivariate logistic regression was used to analyze risk factor odds ratios for readmission.Results7171 patients underwent inpatient parathyroidectomies in 2013 and 2014. 59.89% of parathyroidectomies were performed for primary hyperparathyroidism, with a 5.6% readmission rate. Most common causes of readmission were septicemia (13.69%), hypocalcemia (12.86%), heart failure (10.79%) and renal failure (9.54%). Having Medicare (OR: 1.71, CI:1.14–2.59, p = .01), Medicaid (OR: 3.24, CI: 2.03–5.17, p < .001), and self-paying (OR: 2.43, CI: 1.11–5.32, p = .02), were associated with increased odds of readmission for those with primary hyperparathyroidism. 21.99% of parathyroidectomies were performed for secondary hyperparathyroidism, with a 19.4% readmission rate. Most common causes of readmission were hypocalcemia (22.88%), hungry bone syndrome (14.38%), electrolyte disorders (13.73%), and renal failure (11.11%).ConclusionPatients with secondary hyperparathyroidism are older, poorer and have more comorbidities than patients with primary hyperparathyroidism, and are more likely to be readmitted within 30 days of parathyroidectomy.



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Risk variants of the α-synuclein locus and REM sleep behavior disorder in Parkinson’s disease: a genetic association study

Parkinson's disease is a heterogeneous disorder where genetic factors may underlie clinical variability. Rapid eye movement sleep behavior disorder (RBD) is a parasomnia strongly linked to synucleinopathies, i...

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Radiation Biology and Circulating Tumor Cells

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Brian Marples, Scott M. Welford




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In Regard to Kumar et al

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Pervin Hurmuz, Mustafa Cengiz, Faruk Zorlu, Fadil Akyol




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Radiation Therapy in a Time of Disaster

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Sue S. Yom, Anthony L. Zietman




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Puerto Rico: After María

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Angélica Pérez-Andújar




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Natural Disasters and the Importance of Minimizing Subsequent Radiation Therapy Interruptions for Locally Advanced Lung Cancer

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Michael C. Roach, Cliff G. Robinson, Jeffrey D. Bradley




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Issue Highlights

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4





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When Disaster Strikes: Mitigating the Adverse Impact on Head and Neck Cancer Patients

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Sue S. Yom, Paul M. Harari




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Role of Overall Treatment Time in the Management of Prostate Cancer Patients: How to Manage Unscheduled Treatment Interruptions

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Howard M. Sandler




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Radiation Oncology in the Face of Natural Disaster: The Experience of Houston Methodist Hospital

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Matthew Mireles, Ramiro Pino, Bin S. Teh, Andrew Farach, Adrienne Joseph, E. Brian Butler




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Radiation Oncology and Related Oncology Fields in the Face of the 2011 “Triple Disaster” in Fukushima, Japan

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Akihiko Ozaki, Masaharu Tsubokura




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Meetings

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4





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Hippocampal Sparing During Craniospinal Irradiation: What Did We Learn About the Incidence of Perihippocampus Metastases?

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Laetitia Padovani, Frédérique Chapon, Nicolas André, Mohamed Boucekine, Anne Geoffray, Franck Bourdeau, Julien Masliah-Planchon, Line Claude, Aymeri Huchet, Anne Laprie, Stephane Supiot, Bernard Coche-Dequéant, Christine Kerr, Claire Alapetite, Julie Leseur, Tandat Nguyen, Sophie Chapet, Valerie Bernier, Pierre-Yves Bondiau, Georges Noel, Jean Louis Habrand, Stephanie Bolle, François Doz, Christelle Dufour, Xavier Muracciole, Christian Carrie
PurposeTo identify the incidence of patients with perihippocampal metastases to assess the risk of brain relapse when sparing the hippocampal area. Medulloblastoma (MB) represents 20% of pediatric brain tumors. For high-risk MB patients, the 3- to 5-year event-free survival rate has recently improved from 50% to >76%. Many survivors, however, experience neurocognitive side effects. Several retrospective studies of patients receiving whole brain irradiation (WBI) have suggested a relationship between the radiation dose to the hippocampus and neurocognitive decline. The hippocampal avoidance-WBI (HA-WBI) approach could partially reduce neurocognitive impairment in children treated for high-risk MB.Methods and MaterialsFrom 2008 to 2011, 51 patients with high-risk MB were treated according to the French trial primitive neuroectodermal tumor HR+5. Hippocampal contouring was manually generated on 3-dimensional magnetic resonance images according to the Radiation Therapy Oncology Group 0933 atlas. The distribution of metastases was assessed relative to the hippocampus: 0 to 5 mm for the first perihippocampal area and 5 to 15 mm for the rest of the perihippocampal area.ResultsThe median patient age was 8.79 years (33% female). After a follow-up of 2.4 years, 43 patients were alive; 28 had had brain metastasis at diagnosis and 2 at relapse, with 16% in the first perihippocampal area and 43% in the rest of the perihippocampal area. Of the 18 patients without brain metastases at diagnosis, including M1 patients, none developed secondary lesions within the first or the rest of the perihippocampal area, after receiving 36 Gy. No clinical or biological factor was significantly associated with the development of perihippocampal metastases.ConclusionsOur results suggest the HA-WBI strategy should be evaluated for the subgroup of high-risk MB patients without metastatic disease.



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CTV Guidance for Head and Neck Cancers

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Beth M. Beadle, Carryn M. Anderson




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Phase 1 Dose Escalation Trial of Ipilimumab and Stereotactic Body Radiation Therapy in Metastatic Melanoma

Publication date: 15 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4
Author(s): Nora Sundahl, Katrien De Wolf, Vibeke Kruse, Annabel Meireson, Dries Reynders, Els Goetghebeur, Mireille Van Gele, Reinhart Speeckaert, Benjamin Hennart, Lieve Brochez, Piet Ost
PurposeTo report the results of a phase 1 trial evaluating the safety of the ipilimumab/radiation therapy combination in patients with metastatic melanoma.Patients and MethodsThirteen patients with metastatic melanoma were enrolled. Trial treatment consisted of 4 cycles of ipilimumab in combination with concurrent dose-escalated high-dose radiation therapy to 1 lesion administered before the third cycle of ipilimumab.ResultsGrade 3 or 4 ipilimumab-related adverse events occurred in 25% of patients. The maximum tolerated radiation therapy dose was not reached. Local control of the irradiated lesions was achieved in 11 of 12 irradiated patients (1 patient had progressive disease before irradiation and dropped out of the trial). Evaluation of the nonirradiated lesions demonstrated that 3 of 13 patients experienced clinical benefit, with 1 patient developing a partial response and 2 patients having confirmed stable disease. Immunomonitoring data showed that in patients without clinical benefit, factors linked to immunotolerance increased early after the initiation of ipilimumab, suggesting that early initiation of radiation therapy might be more effective if combined with ipilimumab.ConclusionsOur findings suggest that the combination of ipilimumab and high-dose radiation therapy is feasible and safe.



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Comparison of cortical responses to the activation of retina by visual stimulation and transcorneal electrical stimulation

Publication date: Available online 21 February 2018
Source:Brain Stimulation
Author(s): Pengcheng Sun, Heng Li, Zhuofan Lu, Xiaofan Su, Zengguang Ma, Jianpin Chen, Liming Li, Chuanqing Zhou, Yao Chen, Xinyu Chai
BackgroundElectrical stimulation has been widely used in many ophthalmic diseases to modulate neuronal activities or restore partial visual function. Due to the different processing pathways and mechanisms, responses to visual and electrical stimulation in the primary visual cortex and higher visual areas might be different. This differences would shed some light on the properties of cortical responses evoked by electrical stimulation.ObjectiveThis study's goal was to directly compare the cortical responses evoked by visual and electrical stimulation and investigate the cortical processing of visual information and extrinsic electrical signal.MethodsOptical imaging of intrinsic signals (OIS) was used to probe the cortical hemodynamic responses in 11 cats. Transcorneal electrical stimulation (TES) through an ERG-jet contact lens electrode was used to activate visual cortices. Full-field and peripheral drifting gratings were used as the visual stimuli.ResultsThe response latency evoked by TES was shorter than that responding to visual stimulation (VS). Cortical responses evoked by VS were retinotopically organized, which was consistent with previous studies. On the other hand, the cortical region activated by TES was preferentially located in the secondary visual cortex (Area 18), while the primary visual cortex (Area 17) was activated by a higher current intensity. Compared with the full-field VS, the cortical response in Area 18 to TES with a current intensity above 1.2 mA was significantly stronger.ConclusionAccording to our results, we hypothesized that the cortical processing of TES was influenced by the distribution of the electrical field in the retina and the activating threshold of different retinal ganglion cells.



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Paediatric Autoimmune Neuropsychiatric Disorder Associated with Group A Beta-Haemolytic Streptococcal Infection: An Indication for Tonsillectomy? A Review of the Literature

Background. Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS) is the acute onset of neuropsychiatric symptoms following group A beta-haemolytic streptococcal infection. The aetiology remains elusive. However, with group A streptococcus being the most common bacterial cause of tonsillitis, surgical intervention in the form of tonsillectomy has often been considered as a potential therapy. Methods. A MEDLINE® search was undertaken using keywords "PANDAS" or "paediatric autoimmune neuropsychiatric disorders associated with streptococcus" combined with "tonsillectomy". Results. Six case reports and 3 case series met the inclusion criteria. Demesh et al. (case series) reported a dramatic reduction in neuropsychiatric symptom severity in the patient cohort undergoing tonsillectomy. Two case series suggest that there is no association between tonsillectomy and resolution of PANDAS. Conclusion. Due to the lack of uniform data and sporadic reports, tonsillectomy should be carefully adopted for the treatment of this disorder. In particular, tonsillectomies/adenoidectomies to alleviate neuropsychiatric symptoms should be avoided until more definitive evidence is at our disposal. This review highlights the importance of a potential collaborative prospective study.

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Cholesterol Depletion by TASIN-1 Induces Apoptotic Cell Death through the ER Stress/ROS/JNK Signaling in Colon Cancer Cells

TASIN-1 (Truncated APC Selective INhibitor-1) is a recently identified small molecule that selectively kills colorectal cancer cells that express truncated APC by reducing cellular cholesterol levels. However, the downstream mechanism responsible for its cytotoxicity is not well understood. In this study, we show that TASIN-1 leads to apoptotic cell death via inducing ER stress-dependent JNK activation in human truncated APC colon cancer cells, accompanied by production of reactive oxygen species (ROS). In addition, TASIN-1 inhibits Akt activity through a cholesterol-dependent manner. Human colon tumor xenografts in immunodeficient mice also show the same TASIN-1 induced molecular mechanisms of tumor cell death as observed in vitro. Taken together, cholesterol depletion by TASIN-1 treatment induces apoptotic cell death through activating ER stress/ROS/JNK axis and inhibiting Akt pro-survival signaling in colon cancer cells with truncated APC both in vitro and in vivo.

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JAK2 inhibitor SAR302503 abrogates PD-L1 expression and targets therapy resistant non-small cell lung cancers

Lung cancer is the leading cause of cancer deaths worldwide. Approximately 85% of all lung cancers are non-small-cell histology (NSCLC). Modern treatment strategies for NSCLC target driver oncogenes and immune checkpoints. However, less than fifteen percent of patients survive beyond five years. Here, we investigated the effects of SAR302503 (SAR), a selective JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to NSCLC cells which exhibit resistance to genotoxic therapies, such as ionizing radiation, cisplatin, and etoposide. We demonstrate that constitutive interferon-stimulated gene expression, including an Interferon-Related DNA Damage Resistance Signature (IRDS), predicts for sensitivity to SAR. Importantly, tumor cell-intrinsic expression of PD-L1 is interferon-inducible and abrogated by SAR. Taken together, these findings suggest potential dual roles for JAK2 inhibitors, both as a novel monotherapy in NSCLCs resistant to genotoxic therapies, and in tandem with immune checkpoint inhibition.

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Pharmacological and structural characterizations of naquotinib, a novel third generation EGFR tyrosine kinase inhibitor, in EGFR mutated non-small-cell lung cancer

Multiple epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) have been developed to effectively inhibit EGFR-derived signals in non-small cell lung cancer (NSCLC). In this study, we assessed the efficacy of EGFR-TKIs, including a novel third-generation inhibitor naquotinib (ASP8273), in clinically relevant EGFR mutations, including L858R, exon 19 deletion, L858R+T790M, exon 19 deletion+T790M with or without a C797S mutation, and several exon 20 insertion mutations. Using structural analyses, we also elucidated the mechanism of activation and sensitivity/resistance to EGFR-TKIs in EGFR exon 20 insertion mutations. The efficacy of naquotinib in cells with L858R, exon 19 deletion, and exon 19 deletion+T790M was comparable to that of osimertinib. Interestingly, naquotinib was more potent than osimertinib for L858R+T790M. Additionally, naquotinib and osimertinib had comparable efficacy and a wide therapeutic window for cells with EGFR exon 20 insertions. Structural modeling partly elucidated the mechanism of activation and sensitivity/resistance to EGFR-TKIs in two EGFR exon 20 insertion mutants, A767_V769dupASV and Y764_V765insHH. In summary, we have characterized the efficacy of EGFR-TKIs for NSCLC using in vitro and structural analyses, and suggested the mechanism of activation and resistance to EGFR-TKIs of EGFR exon 20 insertion mutations. Our findings should guide the selection of appropriate EGFR-TKIs for the treatment of NSCLC with EGFR mutations, and help clarify the biology of EGFR exon 20 insertion mutations.

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Short overview on the current standard of treatment in newly diagnosed multiple myeloma

Summary

The treatment of newly diagnosed multiple myeloma has changed dramatically over the past 20 years, from near uniform application of chemotherapy to a patient performance status- and risk-based approach. Furthermore, initiation of treatment criteria have evolved from a pure end-organ damage-based definition to include risk factors of transformation to frank myeloma. Besides, the mainly cytogenetically defined Multiple Myeloma (MM) risk status, transplant eligibility of patients still serves primarily to allocate patients within a rational treatment algorithm.

While all transplant-eligible MM patients should receive a triplet induction therapy followed by autologous transplantation and, in most cases, lenalidomide maintenance, other therapeutic elements (e. g., other maintenance strategies, consolidation, tandem transplantation,..) have to be decided on an individualized appraisal of risk and toxicities. Standard-risk patients should never be undertreated, as they derive the highest relative benefit from using the best available registered therapies. However, high-risk patients should be preferentially treated inside clinical trials testing additive innovative treatments, as the improvement in the prognosis of this group of patients by standard therapies has been underwhelming. Furthermore, the evaluation process of non-transplant-eligible patients should always comprise an evaluation of performance status, frailty, and comorbidities (e. g., a comprehensive geriatric assessment) to facilitate the allocation of individualized therapies.

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Correction to: Report from the WCLC 2017 Congress, Yokohama, 15th–18th October, 2017

Correction to:

memo 2017

http://ift.tt/2EYYUBd

Unfortunately, the title of this article was published incorrect.

The correct title is: Report from the WCLC 2017 Congress, Yokohama, 15th–18th October, 2017.

The original article has been …

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Novel guidelines on surveillance for breast cancer, cardiomyopathy, male gonadotoxicity, and premature ovarian insufficiency from the PanCare and International Guideline Harmonization Group on long-term follow-up after cancer in childhood

Summary

Survival after childhood cancer has improved substantially; therefore, the number of childhood cancer survivors is increasing. This growing population of childhood cancer survivors, however, is at risk of a spectrum of adverse health outcomes. Unfortunately, until now, there was a lack of comprehensive follow-up recommendations. The purpose of this article is to provide information on recently developed harmonized evidence-based guidelines on surveillance investigations to screen for the early detection of breast cancer, cardiomyopathy, male gonadotoxicity, and premature ovarian failure in childhood cancer survivors. We point out the need for a multidisciplinary pediatric and adult specialist team, who together develop multidisciplinary long-term follow-up clinics.

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Pleural effusion in 11:14 translocation q1 multiple myeloma in the setting of proteasome inhibitor presents therapeutic complexity

Summary

Background

Primary malignant pleural effusion has been reported in about 134 cases of multiple myeloma (MM). Associated pleural effusions in cases of MM portend a poor prognosis and identifying them is highly relevant. Reported is the case of a man diagnosed with MM who developed primary myelomatous pleural effusion in the setting of multiple relapses and subsequent mortality within 2 months of the pleural effusion diagnosis.

Presentation

A 61-year-old African American man was diagnosed with MM in 2011. He received induction therapy of lenalidomide and dexamethasone and an autologous stem cell transplant in 2012. Over the next 5 years, the patient went through alternating periods of remission and relapse that were treated with two rounds of thoracic spine radiation therapy and chemotherapeutic agents. In September 2017, the patient presented with worsening dyspnea and was found to have pleural effusion. Fluid analysis showed plasma cell dyscrasia. Fluid drainage was performed, then the patient was discharged after 1 week which was followed by rapid re-accumulation of fluid and rehospitalization about 10 days after discharge. The patient passed away a few weeks after the second admission.

Conclusion

Pleural effusion carries a differential diagnosis which may include malignancy but is commonly thought to be less specific to multiple myeloma but should still remain in the differential diagnosis. To our knowledge, this is the first case of myelomatous pleural effusion (MPE) that was reported after multiple relapses of MM. MPE is a very rare complication of MM, and its presence is a strong indicator of imminent mortality and need for comfort care in case of multiple relapses. End-stage pleural effusion in MM in the setting of proteasome inhibitor adds more therapeutic and diagnostic challenges.

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Practice-changing developments in early use of chemohormonal therapy in metastatic prostate cancer

Summary

The STAMPEDE and CHAARTED trials brought about practice-changing innovation in the management of patients with metastatic, castration-naive prostate cancer (CNPC). These trials reported a clinically meaningful overall survival benefit of chemohormonal therapy consisting of the addition of six cycles of docetaxel to androgen deprivation therapy (ADT) in high-volume metastatic CNPC. Moreover, the STAMPEDE study also transformed our thinking about conducting clinical trials through its adaptive, multigroup, multistage trial design. With the recent results of the LATITUDE trial and publication of another STAMPEDE cohort, the combination of ADT and abiraterone/prednisone became a viable alternative to chemohormonal therapy. Results of these trials have been exhaustively scrutinized and finally incorporated in recent guidelines, although the appropriate selection of patients who will benefit from either therapeutic option remains to be discussed individually. As both combinations lead to an almost identical survival benefit, the decision is often based on patient-related factors and/or personal preferences. This short review provides evidence to support decision-making between chemohormonal therapy and the combination of ADT plus abiraterone/prednisone as well as an outlook on current therapeutic developments in advanced prostate cancer.

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Combined transoral–transhyoid endoscopic approach for hypopharyngeal cancer

Publication date: Available online 3 February 2018
Source:Auris Nasus Larynx
Author(s): Keigo Honda, Makoto Miura, Yasuyuki Hayashi, Toshiya Kimura
Endoscopic transoral surgery for hypopharyngeal cancer is an effective treatment option to avoid invasive open surgery or chemoradiation. Here we describe the case of a 66-year-old patient with cT2N0M0 pyriform sinus cancer whom we treated using a transoral–transhyoid endoscopic approach. Using this approach, a transhyoid route was created in addition to the transoral route and used to extirpate the tumor. En bloc resection of the tumor was completed without difficulty. A combined transoral–transhyoid approach is a useful surgical option for treatment of selected patients with hypopharyngeal cancer. This technique is straightforward to perform and can be used as a backup technique in endoscopic transoral surgery. Also, more complicated lesions can be resected by this approach than by a single-route transoral approach.



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Editorial Board

Publication date: April 2018
Source:Auris Nasus Larynx, Volume 45, Issue 2





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Cribriform plate width is highly variable within and between subjects

Publication date: Available online 13 February 2018
Source:Auris Nasus Larynx
Author(s): Daniel H. Coelho, Taylor S. Pence, Mostafa Abdel-Hamid, Richard M. Costanzo
ObjectiveAll successful endonasal surgery, including functional endoscopic sinus surgery (FESS), depends on knowledge of both anatomy and the specific variations that can occur between and within patients. Familiarity with these structures is a critical component in preventing complications from these procedures, and failure to understand subtle variation can have disastrous results. The aim of this study was to characterize the anatomical variations (if any) of the cribriform plate using a large cadaveric sample set. Better understanding of the disparities within and between patients may have important implications for surgical planning.MethodsWhole human skull specimens (31 specimens, 62 sides) were examined to obtain dimensional measurements of the cribriform plate on the right and left sides.ResultsThe average length of the cribriform plate was 21.28mm (range 15.25–27.73mm, SD 3.30mm). The average width of the cribriform plate (including the crista galli) was 4.53mm (range 1.75–8.03mm, SD 1.20mm). When comparing side differences in individual specimens, there was more variability between widths, relative standard deviation 26.4%, than between lengths, relative standard deviation 15.5%.ConclusionThere is a range of both length and width of the cribriform plate, between and within individuals. This is particularly true for width. In practice, this emphasizes the importance of pre-operative imaging and recognition of anatomic variability for sinus or anterior skull base procedure.



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Treatment of pediatric esthesioneuroblastoma with smell preservation

Publication date: Available online 21 February 2018
Source:Auris Nasus Larynx
Author(s): Giandomenico Maggiore, Maria Silvia Lazio, Oreste Gallo
Olfactory neuroblastoma is a rare malignant tumor of neuroectodermal origin and represents the most common cancer of the nasal cavity in pediatric age. The gold standard of treatment consists of en bloc resection, numerous studies have shown as the endoscopic approaches permit good control of the disease improving the quality of life after the treatment. Herein we describe the case of a 13-year-old patient referred to our outpatient clinic with a polypoid multi-lobed lesion occupying the left nasal cavity and imaging that confirmed a left-sided nasal mass without cribriform plate involvement (Kadish B). We performed an unilateral endoscopic resection with transnasal craniectomy and anterior skull base reconstruction with a flap from the contralateral nasal septum based on the septal branches of the anterior and posterior ethmoidal arteries (Septal Flip Flap, SFF), that provided a faster healing process with reduction of nasal crusting, improvement in the quality of life of patient in the postoperative period and the preservation of the contralateral olfactory bulb that has allowed to save the smell. This treatment strategy of pediatric esthesioneuroblastoma was analyzed in the context of the current literature.



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Usefulness of reconstructed 3D images for cochlear implantation in a case with a facial nerve anomaly

Publication date: Available online 14 February 2018
Source:Auris Nasus Larynx
Author(s): Kenichi Nakamura, Mari Shimada Dias, Toru Sasaki, Hisashi Sugimoto, Miyako Hatano, Makoto Ito
Facial nerve anomalies are a potential problem in patients with cochleovestibular malformations. A case of cochlear implant (CI) surgery in the presence of intra-temporalbone facial nerve bifurcation is presented. During the first surgery, the facial nerve bifurcation obscured the promontory and round window. It was difficult to perform cochleostomy because of the lack of landmarks of the basal turn of the cochlea, and the first surgical attempt at cochleostomy was abandoned. A repeat CT scan was performed after the first surgery with reconstructed 3D images of the temporal bone and the cochlea, and then the cochlea was successfully opened at revision surgery. Reconstructed 3D CT images were very useful to identify the site of cochleostomy in this case with such difficult temporal bone anatomy.



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Topical therapy for refractory rhinosinusitis caused by methicillin-resistant Staphylococcus aureus: First report in a prospective series

Publication date: Available online 6 February 2018
Source:Auris Nasus Larynx
Author(s): Alan H. Shikani, Nadim Khoueir, Mary Ann Jabra-Rizk, Henry J. Shikani, Randall J. Basaraba, Jeff G. Leid
ObjectiveThe incidence of refractory chronic rhinosinusitis (CRS) associated with methicillin-resistant Staphylococcus aureus (MRSA) is rising and remains a therapeutic challenge. The goal of this study is to demonstrate the efficacy of a non-invasive topical therapy against MRSA in these patients.MethodsSeventeen patients with refractory CRS caused by MRSA were treated with a topical therapy protocol. Treatment consisted of weekly endoscopic sinus debridement followed by intra-sinus installation of a hydroxyl-ethylcellulose gel that releases mometasone and a culture-directed antibiotic for a period of 6 weeks, along with daily nasal nebulization of mometasone with the same antibiotic and saline rinses. Clinical outcome was assessed using the Lund–Kennedy (LK) symptom and endoscopic appearance scores. Sinus mucosal tissue was homogenized and cultured, and microbial biofilm burden was assessed based on colony forming units (CFUs) counts.ResultsRhinotopic therapy resulted in clearance of MRSA in 13 of 16 patients (81.2%). Treated patients also demonstrated significant improvement clinically as measured by the LK scores. In addition, a significant decrease in mucosal CFUs was observed post-therapy.ConclusionOur findings demonstrate that topical therapy is an effective method for treating MRSA-associated refractory CRS.



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