Charting the unexplored extracellular matrix in cancer

International Journal of Experimental Pathology, EarlyView.


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Post-chemoradiation volumetric response predicts survival in newly diagnosed glioblastoma treated with radiation, temozolomide and bevacizumab or placebo

Abstract

Background

In the current study we used contrast-enhanced T1 subtraction maps to test whether early changes in enhancing tumor volume are prognostic for overall survival (OS) in newly diagnosed GBM patients treated with chemoradiation with or without bevacizumab (BV).

Methods

798 patients (404 BV and 394 placebo) with newly diagnosed GBM in the AVAglio trial (NCT00943826) had baseline MRI scans available, while 337 BV-treated and 269 placebo-treated patients had >4 MRI scans for response evaluation. The volume of contrast enhancing tumor was quantified and used for subsequent analyses.

Results

A decrease in tumor volume during chemoradiation was associated with a longer OS in the placebo group (HR=1.578,P<0.0001) but not BV-treated group (HR=1.135,P=0.4889). Results showed a higher OS in patients on the placebo arm with a sustained decrease in tumor volume using a post-chemoradiation baseline (HR=1.692,P=0.0005) and a trend toward longer OS was seen in BV-treated patients (HR=1.264,P=0.0724). Multivariable Cox regression confirmed that sustained response or stable disease was prognostic for OS (HR=0.7509, P=0.0127) when accounting for age (P=0.0002), KPS (P=0.1516), post-surgical tumor volume (P<0.0001), MGMT status (P<0.0001), and treatment type (P=0.7637) using the post-chemoradiation baseline.

Conclusions

The post-chemoradiation time point is a better baseline for evaluating efficacy in newly diagnosed GBM. Early progression during the maintenance phase is consequential in predicting OS, supporting the use of progression-free survival rates as a meaningful surrogate for GBM.

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The TNF Receptor Family Member Fn14 is Highly Expressed in Recurrent Glioblastoma (GBM) and in GBM Patient-Derived Xenografts With Acquired Temozolomide Resistance

Abstract

Background

Glioblastoma (GBM) is a difficult-to-treat brain cancer that nearly uniformly recurs, and recurrent tumors are largely therapy-resistant. Our prior work has demonstrated an important role for the TWEAK receptor Fn14 in GBM patho-biology. In this study, we investigated Fn14 expression in recurrent GBM and in the setting of temozolomide (TMZ) resistance.

Methods

Fn14 mRNA expression levels in the non-neoplastic brain, primary (newly diagnosed) GBM, and recurrent GBM (post-chemotherapy and radiation) specimens were obtained from the TCGA data portal. Immunohistochemistry was performed using non-neoplastic brain, patient-matched primary and recurrent GBM, and gliosarcoma (GSM) specimens to examine Fn14 protein levels. Western blot analysis was used to compare Fn14 expression in parental TMZ-sensitive or matched TMZ-resistant patient-derived xenografts (PDXs) established from primary or recurrent tumor samples. The migratory capacity of control and Fn14-depleted TMZ-resistant GBM cells was assessed using the transwell migration assay.

Results

We found that Fn14 is more highly expressed in recurrent GBM tumors than their matched primary GBM counterparts. Fn14 expression is also significantly elevated in GSM tumors. GBM PDX cells with acquired TMZ resistance have higher Fn14 levels and greater migratory capacity than their corresponding parental TMZ-sensitive cells, and the migratory difference is due, at least in part, to Fn14 expression in the TMZ-resistant cells.

Conclusions

This study demonstrates that the Fn14 gene is highly expressed in recurrent GBM, GSM, and TMZ-resistant GBM PDX tumors. These findings suggest that Fn14 may be a valuable therapeutic target or drug delivery portal for treatment of recurrent GBM and GSM patients.

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Meningioma transcription factors link cell lineage with systemic metabolic cues

Abstract

Background

Tumor cells recapitulate cell-lineage transcriptional programs that are characteristic of normal tissues from which they arise. It is unclear why such lineage programs are fatefully maintained in tumors and if they contribute to cell proliferation and viability.

Methods

Here, we used the most common brain tumor, meningioma, which is strongly associated with female gender and high body mass index (BMI), as a model system to address these questions. We screened expression profiling data to identify the transcription factor (TF) genes which are highly enriched in meningioma, and characterized the expression pattern of those TFs and downstream genes in clinical meningioma samples as well as normal brain tissues. Meningioma patient-derived cell lines (PDCLs) were used for further validation and characterization.

Results

We identified eight TFs highly-enriched in meningioma. Expression of these TFs, which included SIX1, readily distinguished meningiomas from other primary brain tumors and was maintained in PDCLs and even in pulmonary meningothelial nodules. In meningioma PDCL, SIX1 and its co-activator EYA2, supported the expression of the leptin receptor (LEPR), the cell-surface receptor for leptin (LEP), the adipose-specific hormone that is high in women and in individuals with high BMI. Notably, these transcriptional regulatory factors, LEPR and LEP all contributed to support meningioma PDCL proliferation and survival, elucidating a survival dependency on both a core transcriptional program and a metabolic cell-surface receptor.

Conclusions

These findings provide one rationale for why lineage TF expression is maintained in meningioma and for the epidemiological association of female gender and obesity with meningioma risk.

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Mapping of genomic EGFRvIII deletions in glioblastoma: insight into rearrangement mechanisms and biomarker development

Abstract

Background

Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM) generated by deletion of exons two to seven of EGFR. The proximal breakpoints occur in variable positions within the 123-kb intron one, presenting significant challenges in terms of PCR-based mapping. Molecular mechanisms underlying these deletions remain unclear.

Methods

We determined the presence of EGFRvIII and its breakpoints for 29 GBM samples using quantitative polymerase chain reaction (qPCR), arrayed PCR mapping, Sanger sequencing, and whole genome sequencing (WGS). Patient-specific breakpoint PCR was performed on tumors, plasma and cerebrospinal fluid (CSF) samples. The breakpoint sequences and single nucleotide polymorphisms (SNPs) were analyzed to elucidate the underlying biogenic mechanism.

Results

PCR mapping and WGS independently unveiled eight EGFRvIII breakpoints in six tumors. Patient-specific primers yielded EGFRvIII PCR amplicons in matched tumors, and in cell-free DNA (cfDNA) from a CSF sample, but not in cfDNA or extracellular-vesicle DNA from plasma. The breakpoint analysis revealed nucleotide insertions in four, an insertion of a region outside of EGFR locus in one, microhomologies in three, as well as a duplication or an inversion accompanied by microhomologies in two, suggestive of distinct DNA repair mechanisms. In the GBM samples that harbored distinct breakpoints, the SNP compositions of EGFRvIII and amplified non-vIII EGFR were identical, suggesting that these rearrangements arose from amplified non-vIII EGFR.

Conclusions

Our approach efficiently "fingerprints" each sample's EGFRvIII breakpoints. Breakpoint sequence analyses suggest that independent breakpoints arose from precursor amplified non-vIII EGFR through different DNA repair mechanisms.

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Seroprevalence of Human Parainfluenza Virus Types 1–4 Among Healthy Children Under 5 Years of Age in Korea

Viral Immunology, Ahead of Print.


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Interleukin-7 Regulates T Follicular Helper Cell Function in Patients with Chronic Hepatitis C

Viral Immunology, Ahead of Print.


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Anti‐epidermal growth factor receptor therapy concurrently with induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma

Cancer Science, EarlyView.


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Association of activities of daily living with the load during step ascent motion in nursing home-residing elderly individuals

Objective This study aimed to examine the association of independence in ADL with the loads during step ascent motion and other motor functions in 32 nursing home-residing elderly individuals. Design Independence in ADL was assessed by using the functional independence measure (FIM). The loads at the upper (i.e., pulling up) and lower (i.e., pushing up) levels during step ascent task was measured on a step ascent platform. Hip extensor, knee extensor, plantar flexor muscle, and quadriceps setting strengths; lower extremity agility using the stepping test; and hip and knee joint pain severities were measured. One-legged stance and functional reach distance for balance, and maximal walking speed, timed up-and-go (TUG) time, five-chair-stand time, and step ascent time were also measured to assess mobility. Results Stepwise regression analysis revealed that the load at pushing up during step ascent motion and TUG time were significant and independent determinants of FIM score. FIM score decreased with decreased the load at pushing up and increased TUG time. Conclusions The study results suggest that depending on task specificity, both one step up task's push up peak load during step ascent motion and TUG, can partially explain ADL's FIM score in the nursing home-residing elderly individuals. Lower extremity muscle strength, agility, pain or balance measures did not add to the prediction. Corressponding author Mitsuhiro Masaki, R.P.T., PhD., Department of Physical Therapy, Niigata University of Health and Welfare, Institute for Human Movement and Medical Sciences, Niigata University of Health and Welfare, 1398 Shimami-cho, Kita-ku, Niigata 950-3198, Japan. E-mail: masaki@nuhw.ac.jp. Office phone: +81-25-257-4312. Office fax: +81-25-257-4312 Author Disclosures No potential conflicts of interest were disclosed for the present study. Kyoritsu Denshi Kogyo Co. Ltd. financed this study. The financial providers did not contribute to the implementation of the study, analysis, interpretation of the data, or preparation of this article. The present study is an expansive analysis of our cross-sectional study that has been published previously as an article titled "Association between physical function and the load pattern during stepping-up motion in community-dwelling elderly women" (2016). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Femoral artery blood flow and microcirculatory perfusion during acute, low-level functional electrical stimulation in spinal cord injury

Objective Functional electrical stimulation (FES) may help to reduce the risk of developing macro- and microvascular complications in people with SCI. Low-intensity FES has significant clinical potential since this can be applied continuously throughout the day. This study examines the acute effects of low intensity FES using wearable clothing garment on vascular blood flow and oxygen consumption in people with SCI. Design Cross-sectional observation study Methods Eight participants with a motor complete SCI received 4x3 minutes of unilateral FES to the gluteal and hamstring muscles. Skin and deep femoral artery blood flow and oxygen consumption were measured at baseline and during each bout of stimulation. Results Femoral artery blood flow increased by 18.1% with the application of FES (P=0.02). Moreover, femoral artery blood flow increased further during each subsequent block of FES (P=0.004). Skin perfusion did not change during an individual block of stimulation (P=0.66). Skin perfusion progressively increased with each subsequent bout (P0.05). Conclusion Low-intensity FES acutely increased blood flow during stimulation, with a progressive increase across subsequent FES bouts. These observations suggest continuous, low-intensity FES may represent a practical and effective strategy to improve perfusion and reduce the risk of vascular complications. Correspondence: Dick Thijssen, Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Byrom Street, L3 3AF, Liverpool, United Kingdom. Email: d.thijssen@ljmu.ac.uk. Tel: +44 (0)151 904 6264 Fax: +44 (0)151 904 6284 Disclosures The authors declare that there is no conflict of interest. This study was supported by funds received from the Stoke Mandeville-Masson research awards. The funding source had no such involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. This research has previously been presented at IFESS conference 2017. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Radio-pharmaceuticals for cancer treatment – are they ready for prime time yet?

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Functional immune characterization of HIV-associated non-small cell lung cancer

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It’s time to rethink weight loss in cancer

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Letter to the editor on “Body mass index and 20-specific cancers - re-analyses of dose-response meta-analyses of observational studies”

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Representation of Obese Participants in Obesity-Related Cancer Randomized Trials

Abstract

Background

Obesity is a risk factor for numerous cancer types, and may influence cancer treatment outcomes. Underrepresentation of obese patients in obesity-related cancer randomized controlled trials (RCTs) may affect generalizability of results. We aimed to assess the reporting of information about eligibility and enrollment of obese participants in obesity-related cancer RCTs.

Methods

We conducted a systematic review of RCTs of 10 obesity-related cancer types (esophagus, colon/rectum, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovary, kidney, and thyroid cancer). We selected RCTs published between 2013 and 2016 in 5 major journals. For each trial, we examined the article, the protocol, and the registration record. We assessed if eligibility criteria limiting the enrollment of obese participants were reported, the proportion of obese participants that were enrolled, and if a subgroup analysis according to obesity status was reported. We systematically contacted corresponding authors and asked for information about eligibility of obese participants and the proportion of obese participants.

Results

We included 76 RCTs. Colon/rectum (n = 20), postmenopausal breast (n = 11), and kidney (n = 11) cancers were the most frequent types. Based on publicly available sources, information on the eligibility of obese participants was available in 5 (7%) trials. The proportion of obese participants could be estimated in 9 (12%) trials only. We found a subgroup analysis in only one RCT. When considering unpublished information, the eligibility of obese participants was explicitly stated in 31 (41%) trials but it was unclear if the remaining 59% trials considered obese participants as eligible and what proportion of obese participants was included. Across 22 trials, the median proportion of obese participants included was 18% [Q1-Q3 11-23].

Conclusion

Information on the eligibility and enrollment of obese participants in cancer RCTs is dramatically underreported. More transparency is needed to understand the applicability of obesity-related cancer RCT results to obese patients with cancer.

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“ARTE and Craft of Bevacizumab in Elderly Patients with Glioblastoma”

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Tailoring treatment of salivary duct carcinoma (SDC) by liquid biopsy:ARv7 expression in circulating tumor cells

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Primary Tumor Sidedness and Benefit from FOLFOXIRI plus Bevacizumab as Initial Therapy for Metastatic Colorectal Cancer

Abstract

Background

Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status.

Patients and methods

Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status.

Results

Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS (23.7 vs 31.0 months, HR = 1.42 [95%CI, 1.09-1.84], P=0.010) and a trend toward shorter PFS (10.2 vs 11.5 months, HR = 1.24 [95%CI:0.98-1.56], P=0.083) than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 vs. 0.89, P-for-interaction=0.099) and OS (HR = 0.56 vs. 0.99, P-for-interaction=0.030) and this advantage was independent of their RAS and BRAF status.

Conclusions

FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.

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Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury

Journal of Neurotrauma, Ahead of Print.


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Mohs Micrographic Surgery Volume and Payment Patterns Among Dermatologists in the Medicare Population, 2013

Objectives: Mohs micrographic surgery (MMS) has expanded markedly in recent years but there is limited information on volume, practice patterns or reimbursement. This study characterizes MMS utilization in the Medicare population. Materials and Methods: We analyzed the Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File Calendar Year 2013 data set for provider service volume and reimbursement for dermatologists who did and did not perform MMS procedures. Results: Total Medicare-funded MMS procedures increased 25% from 2009 (558,447) to 2013 (700,262). Dermatologists who performed MMS had significantly more average services per provider (5419.4 vs. 3627.1, r=0.16, P

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Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma

Objectives: Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients. Materials and Methods: Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated. Results: A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival. Conclusions: Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored. N.L. and K.M. contributed equally. Supported by the Ramathibodi Cancer Center grant. N.N. received funding from the Research University Network (RUN) and Talent Management Program of Mahidol University, and the Ramathibodi Grant for Research Development from Ramathibodi Hospital. An abstract of this work was presented at the 2015 ASCO Annual Meeting, May 29 to June 2, 2015, Chicago, IL. The authors declare no conflicts of interest. Reprints: Nuttapong Ngamphaiboon, MD, Department of Medicine, Division of Medical Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. E-mail: nuttapong.nga@mahidol.ac.th. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas

Objectives: Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). Materials and Methods: The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ2 analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. Results: The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P

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Hatchet Flap With Transposed Nasal Inset for Midfacial Reconstruction

Purpose: The purpose of this study is to report the surgical technique and functional outcomes of the hatchet flap with transposed nasal inset for midfacial defect repairs. Methods: An Institutional Review Board–approved, retrospective review was performed to identify patients treated using the hatchet flap with transposed nasal inset. Patient demographics, disease etiology, defect characteristics, and postoperative complications were collected from preoperative and follow-up visits. Results: The hatchet flap with transposed nasal inset was performed in 5 patients between March 2016 and April 2017. Two patients developed mild transient ischemia of the nasal inset flap tip without necrosis. A suture granuloma was removed in 1 patient. No additional surgical procedures were required after the nasal inset cheek flap. Conclusions: The hatchet flap with transposed nasal inset is an effective procedure to address defects involving the upper cheek, lower eyelid, and medial canthus. Incorporation of the nasal inset helps prevent distortion of the ala and facilitates closure of the flap donor site. This technique may be employed in certain patients as an acceptable alternative to more extensive Mustardé or paramedian forehead flaps. Accepted for publication February 14, 2018. The authors have no financial or conflicts of interest to disclose. Presented at the American Society of Ophthalmic Plastic and Reconstructive Surgery Fall Scientific Symposium on November 10, 2017 in New Orleans, LA; and at the European Society of Ophthalmic Plastic and Reconstructive Surgery on September 16, 2017 in Stockholm, Sweden. Address correspondence and reprint requests to Philip L. Custer, M.D., F.A.C.S., Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8096, St. Louis, MO 63110. E-mail: Custer@wustl.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Transconjunctival Triamcinolone Injection for Upper Lid Retraction in Thyroid Eye Disease—A New Injection Method

Purpose: To evaluate the role of transconjunctival triamcinolone acetonide (TA) injection in the management of upper eyelid retraction in thyroid eye disease. Methods: Retrospective interventional review of all patients who underwent transconjunctival TA injection (40 mg/mL) for thyroid eye disease–related upper eyelid retraction from January 2010 to December 2016 in a single tertiary institution. The present study comprised 2 groups: Patients receiving only TA injection (group 1), and patients receiving both TA injection and other immunosuppressive therapy (group 2). Results: There were a total of 99 patients and 135 eyes. Group 1 comprised of 36 eyes (26.7%), while group 2 comprised 99 (73.3%). Normalization or improvement of margin reflex distance 1 was seen in 77.4% and 97.2% of group 1 patients at early and late review, respectively, and 77.6% and 87.8% of group 2, respectively. Absence or improvement in International Thyroid Eye Disease Society inflammatory index was seen in 83.9% and 86.1% of group 1 at early and late review, respectively, and 71.9% and 76.8% of group 2, respectively. Both active (73.7%) and inactive (79.3%) groups showed good early success for improvement in margin reflex distance 1, with increased late success and no significant difference between the groups. For International Thyroid Eye Disease Society inflammatory index, the active group had better early and late success than the inactive group, with the difference being significant (P = 0.002) for late success. Conclusions: Transconjunctival TA injection is an effective treatment option for thyroid eye disease–related upper eyelid retraction, as a primary and adjunctive treatment, in both active and inactive thyroid eye disease patients. Accepted for publication February 26, 2018. The authors have no financial or conflicts of interest to disclose. The material in this article has been presented as a poster at the American Society of Ophthalmic Plastic and Reconstructive Surgery Annual Meeting, 2017. Address correspondence and reprint requests to Kyung In Woo, M.D., Ph.D., Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. E-mail: eyeminded@hanmail.net © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury

Journal of Neurotrauma, Ahead of Print.


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Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia

Publication date: Available online 19 April 2018
Source:Cancer Cell
Author(s): Michelle L. Churchman, Maoxiang Qian, Geertruy te Kronnie, Ranran Zhang, Wenjian Yang, Hui Zhang, Tobia Lana, Paige Tedrick, Rebekah Baskin, Katherine Verbist, Jennifer L. Peters, Meenakshi Devidas, Eric Larsen, Ian M. Moore, Zhaohui Gu, Chunxu Qu, Hiroki Yoshihara, Shaina N. Porter, Shondra M. Pruett-Miller, Gang Wu, Elizabeth Raetz, Paul L. Martin, W. Paul Bowman, Naomi Winick, Elaine Mardis, Robert Fulton, Martin Stanulla, William E. Evans, Mary V. Relling, Ching-Hon Pui, Stephen P. Hunger, Mignon L. Loh, Rupert Handgretinger, Kim E. Nichols, Jun J. Yang, Charles G. Mullighan
Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Here we report coding germline IKZF1 variation in familial childhood ALL and 0.9% of presumed sporadic B-ALL, identifying 28 unique variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. These results identify IKZF1 as a leukemia predisposition gene, and emphasize the importance of germline genetic variation in the development of both familial and sporadic ALL.

Graphical abstract

Teaser

Churchman et al. identify 28 unique germline IKZF1 coding variants in 45 children with acute lymphoblastic leukemia. Many of these variants are not predicted to be damaging using in silico prediction tools, but functional tests reveal that the majority of them have deleterious effects on IKAROS function.


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A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment

Publication date: Available online 19 April 2018
Source:Cancer Cell
Author(s): Amelie Griveau, Giorgio Seano, Samuel J. Shelton, Robert Kupp, Arman Jahangiri, Kirsten Obernier, Shanmugarajan Krishnan, Olle R. Lindberg, Tracy J. Yuen, An-Chi Tien, Jennifer K. Sabo, Nancy Wang, Ivy Chen, Jonas Kloepper, Louis Larrouquere, Mitrajit Ghosh, Itay Tirosh, Emmanuelle Huillard, Arturo Alvarez-Buylla, Michael C. Oldham, Anders I. Persson, William A. Weiss, Tracy T. Batchelor, Anat Stemmer-Rachamimov, Mario L. Suvà, Joanna J. Phillips, Manish K. Aghi, Shwetal Mehta, Rakesh K. Jain, David H. Rowitch
Gliomas comprise heterogeneous malignant glial and stromal cells. While blood vessel co-option is a potential mechanism to escape anti-angiogenic therapy, the relevance of glial phenotype in this process is unclear. We show that Olig2⁺ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells form dense perivascular collections and promote angiogenesis and BBB breakdown, leading to innate immune cell activation. Experimentally, Olig2 promotes Wnt7b expression, a finding that correlates in human glioma profiling. Targeted Wnt7a/7b deletion or pharmacologic Wnt inhibition blocks Olig2⁺ glioma single-cell vessel co-option and enhances responses to temozolomide. Finally, Olig2 and Wnt7 become upregulated after anti-VEGF treatment in preclinical models and patients. Thus, glial-encoded pathways regulate distinct glioma-vascular microenvironmental interactions.

Teaser

Griveau et al. show that Olig2⁺ glioma cells invade by single-cell vessel co-option, whereas Olig2⁻ glioma cells promote angiogenesis and that anti-VEGF treatment selects for the Olig2⁺/Wnt7⁺ phenotype. Wnt7 is necessary for vessel co-option, and Wnt inhibition enhances the response to temozolomide treatment.


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Oral Health and Dietary Intake in Older Adults

Abstract

Purpose of Review

Previous studies have reported that dietary intake is related to systemic diseases and functions. The oral cavity is the first passage through which food passes for consumption, and decline of oral health is considered to be associated with a lower intake of some foods or nutrients. We focused on the relationship between oral health and dietary intake in older adults.

Recent Findings

Most studies have reported oral health, such as number of teeth, tooth loss, occlusal contacts, masticatory ability, denture use, occlusal force, dysphagia, and hyposalivation are associated with intake of some foods and nutrients adjusting for socioeconomic factors.

Summary

Healthy oral function can lead to enough intake of key nutrients. It is also necessary to clarify the association between oral health and malnutrition, such as weight loss or underweight, and the pathways from oral health to several systemic diseases.

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Generation and characterization of hagfish variable lymphocyte receptor B against glycoprotein of viral hemorrhagic septicemia virus (VHSV)

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Jung Seok Lee, Jaesung Kim, Se Pyeong Im, Si Won Kim, Jassy Mary S. Lazarte, Jae Wook Jung, Tae Won Gong, Young Rim Kim, Jeong Ho Lee, Hyoung Jun Kim, Tae Sung Jung
Variable lymphocyte receptors B (VLRBs) are non-immunoglobulin components of the humoral immune system in jawless vertebrates including hagfish (Eptatretus burgeri) and lamprey (Petromyzon marinus). Hagfish VLRBs consist of leucine rich repeat (LRR) modules with a superhydrophobic C-terminal tail, the latter of which leads to extremely low expression levels in recombinant protein technology. Here, we present an artificially oligomerized VLRB (arVLRB) that conjugates via the C4bp oligomerization domain derived from human C4b-binding protein (hC4bp) rather than the superhydrophobic tail. The resulting arVLRB had a tightly multimerized form with seven monomeric VLRB arms and showed high expression and secretion levels in a mammalian expression system. To isolate antigen-specific arVLRB, we constructed large VLRB libraries from hagfish immunized with the fish pathogen, viral hemorrhagic septicemia virus (VHSV). The selected arVLRBs were found to recognize various types of antigens, including the recombinant target protein, purified viruses, and progeny viruses, with high antigen binding abilities and specificities. We also performed in vitro affinity maturation of the arVLRBs through LRRCT mutagenesis, and found that this enhanced their antigen-binding properties by at least 125-fold. Our epitope mapping analysis revealed that ³⁷DWDTPL⁴², which is located in a region conserved among the glycoproteins of all VHSV isolates, is the recognition epitope of the arVLRBs. Thus, our newly developed arVLRB could prove useful in the development of universal diagnostic tools and/or therapeutic agents for the virus. Together, our novel findings provide valuable insights into hagfish VLRB and its potential use as a novel alternative to conventional antibodies for biotechnological applications.



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Tree nut allergens

Publication date: Available online 19 April 2018
Source:Molecular Immunology
Author(s): Sabine Geiselhart, Karin Hoffmann-Sommergruber, Merima Bublin
Tree nuts are considered as part of a healthy diet due to their high nutritional quality. However, they are also a potent source of allergenic proteins inducing IgE mediated hypersensitivity often causing serious, life-threatening reactions. The reported prevalence of tree nut allergy is up to 4.9% worldwide. The general term "tree nuts" comprises a number of nuts, seeds, and drupes, derived from trees from different botanical families. For hazelnut and walnut several allergens have been identified which are already partly applied in component resolved diagnosis, while for other tree nuts such as macadamia, coconut, and Brazil nut only individual allergens were identified and data on additional allergenic proteins are missing. This review summarizes the current knowledge on tree nut allergens and describes their physicochemical and immunological characterization and clinical relevance.



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Peanut allergens

Publication date: Available online 19 April 2018
Source:Molecular Immunology
Author(s): Chiara Palladino, Heimo Breiteneder
Peanut allergens have the potential to negatively impact on the health and quality of life of millions of consumers worldwide. The seeds of the peanut plant Arachis hypogaea contain an array of allergens that are able to induce the production of specific IgE antibodies in predisposed individuals. A lot of effort has been focused on obtaining the sequences and structures of these allergens due to the high health risk they represent. At present, 16 proteins present in peanuts are officially recognized as allergens. Research has also focused on their in-depth immunological characterization as well as on the design of modified hypoallergenic derivatives for potential use in clinical studies and the formulation of strategies for immunotherapy. Detailed research protocols are available for the purification of natural allergens as well as their recombinant production in bacterial, yeast, insect, and algal cells. Purified allergen molecules are now routinely used in diagnostic multiplex protein arrays for the detection of the presence of allergen-specific IgE. This review gives an overview on the wealth of knowledge that is available on individual peanut allergens.



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Review of surface particulate monitoring of dust events using geostationary satellite remote sensing

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): M. Sowden, U. Mueller, D. Blake
The accurate measurements of natural and anthropogenic aerosol particulate matter (PM) is important in managing both environmental and health risks; however, limited monitoring in regional areas hinders accurate quantification. This article provides an overview of the ability of recently launched geostationary earth orbit (GEO) satellites, such as GOES-R (North America) and HIMAWARI (Asia and Oceania), to provide near real-time ground-level PM concentrations (GLCs). The review examines the literature relating to the spatial and temporal resolution required by air quality studies, the removal of cloud and surface effects, the aerosol inversion problem, and the computation of ground-level concentrations rather than columnar aerosol optical depth (AOD).Determining surface PM concentrations using remote sensing is complicated by differentiating intrinsic aerosol properties (size, shape, composition, and quantity) from extrinsic signal intensities, particularly as the number of unknown intrinsic parameters exceeds the number of known extrinsic measurements. The review confirms that development of GEO satellite products has led to improvements in the use of coupled products such as GEOS-CHEM, aerosol types have consolidated on model species rather than prior descriptive classifications, and forward radiative transfer models have led to a better understanding of predictive spectra interdependencies across different aerosol types, despite fewer wavelength bands. However, it is apparent that the aerosol inversion problem remains challenging because there are limited wavelength bands for characterising localised mineralogy.The review finds that the frequency of GEO satellite data exceeds the temporal resolution required for air quality studies, but the spatial resolution is too coarse for localised air quality studies. Continual monitoring necessitates using the less sensitive thermal infra-red bands, which also reduce surface absorption effects. However, given the challenges of the aerosol inversion problem and difficulties in converting columnar AOD to surface concentrations, the review identifies coupled GEO-neural networks as potentially the most viable option for improving quantification.



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Impacts of heterogeneous reactions to atmospheric peroxides: Observations and budget analysis study

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Mengru Qin, Zhongming Chen, Hengqing Shen, Huan Li, Huihui Wu, Yin Wang
Atmospheric peroxides play important roles in atmospheric chemistry, acting as reactive oxidants and reservoirs of HOX and ROX radicals. Field measurements of atmospheric peroxides were conducted over urban Beijing from 2015 to 2016, including dust storm days, haze days and different seasons. We employed a box model based on RACM2 mechanism to conduct concentration simulation and budget analysis of hydrogen peroxide (H2O2) and peroxyacetic acid (PAA). In this study, heterogeneous reaction is found to be a significant sink for atmospheric H2O2 and PAA in urban Beijing. Here, we recommend a suitable uptake coefficient formula considering the water effect for model research of peroxides. It is found that H2O2 and PAA unexpectedly maintained considerable concentrations on haze days, even higher than that on non-haze days. This phenomenon is mainly ascribed to relatively high levels of volatile organic compounds and ozone on haze days. In addition, high levels of water vapor in pollution episode can promote not only the heterogeneous uptake to aerosol phase but also the production of H2O2. Atmospheric PAA formation is suggested to be sensitive to alkenes and NOX in urban Beijing. In particular, with the help of peroxides, sulfate formation rate from heterogeneous uptake could increase by ∼4 times on haze days, indicating the potential effect of peroxides on enhancement of aerosol oxidative property and secondary sulfate formation.



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Belatacept and auto-immune adverse events

No abstract available

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More Than Just Wait Time? Regional Differences in Liver Transplant Outcomes for Hepatocellular Carcinoma

Background Regional allocation of deceased donor livers has led to variable wait times for HCC patients on the liver transplant list. The purpose of our study was to evaluate how regional differences in wait time affect outcomes for HCC patients. Methods A retrospective, observational study was performed using the OPTN database from 2/27/2002 to 9/25/2015. The cumulative incidences of transplant and waitlist death as well as intention-to-treat and posttransplant survival were evaluated for patients ≥ 18 years of age listed for DDLT with stage II HCC exception points in each UNOS region. A multivariable analysis of predictive factors for posttransplant survival was performed. Results Cumulative incidence of transplant decreased and cumulative incidence of waitlist death increased as regional wait time increased. Intention-to-treat survival decreased with increased regional wait time with long wait time regions 1, 5, and 9 having significantly lower intention-to-treat survival compared to many of the shorter wait time regions (p

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Antigen Presentation Keeps Trending in Immunotherapy Resistance

Through a gain-of-function kinome screen, MEX3B was identified as a mediator of resistance to T cell immunotherapy not previously identified using CRISPR based screens. MEX3B is a post-transcriptional regulator of HLA-A, validating the critical role of tumor-intrinsic antigen presentation in T cell immunotherapy and indicating a new putative molecular target.

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Combined BRAF and HSP90 inhibition in patients with unresectable BRAF V600E mutant melanoma

Purpose: BRAF inhibitors are clinically active in patients with advanced BRAF^V600-mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. Methods: Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAF^V600-mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose. Correlative proteomic studies were performed to confirm HSP inhibitor activity. Results: Objective responses were observed in 15/20 evaluable patients (75%; 95% CI: 51-91%), with 3 complete and 12 partial responses. Median progression-free and overall survival were 9.2 months (95% CI: 3.8-not reached) and 34.6 months (6.2-not reached), respectively. The most common grade 3/4 toxicities were skin toxicities such as rash (n=4, 19%) and cutaneous squamous cell carcinomas (n=3, 14%), along with diarrhea (n=3, 14%). Pharmacodynamic analysis of patients' PBMCs showed increased day 8 HSP70 expression compared to baseline in the three cohorts with XL888 doses ≥45 mg. Diverse effects of vemurafenib-XL888 upon intratumoral HSP-client protein expression were noted, with the expression of multiple proteins (including ERBB3 and BAD) modulated on therapy. Conclusion. XL888 in combination with vemurafenib has clinical activity in patients with advanced BRAF^V600-mutant melanoma, with a tolerable side-effect profile. HSP90 inhibitors warrant further evaluation in combination with current standard-of-care BRAF plus MEK inhibitors in BRAF^V600-mutant melanoma.

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Tamoxifen Resistance Trumped and Oral Selective Estrogen Receptor Degraders Arrive

Predictive tests, to refine the estrogen receptor assay, for the adjuvant treatment of breast cancer with tamoxifen and oral Selective Estrogen Receptor Degraders (SERDs) are required.  A splice variant of the corepressor NCOR2, BQ2313636.1 predicts tamoxifen resistence to adjuvant tamoxifen and AZ9496, the first oral SERD, completes phase one studies

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Blockade of myeloid-derived suppressor cell expansion with all-trans retinoic acid increases the efficacy of anti-angiogenic therapy

Intrinsic and adaptive resistance hamper the success of anti-angiogenic therapies (AAT), especially in breast cancer where this treatment modality has proven largely ineffective. Therefore, novel strategies to improve the efficacy of AAT are warranted. Solid tumors such as breast cancer are characterized by a high infiltration of myeloid-derived suppressor cells (MDSC) which are key drivers of resistance to AAT. Therefore, we hypothesized that all-trans retinoic acid (ATRA), which induces differentiation of MDSC into mature cells, could improve the therapeutic effect of AAT. ATRA increased the efficacy of anti-VEGFR-2 antibodies alone and in combination with chemotherapy in preclinical breast cancer models. ATRA reverted the anti-VEGFR-2-induced accumulation of intratumoral MDSC, alleviated hypoxia, and counteracted the disorganization of tumor microvessels. Mechanistic studies indicate that ATRA treatment blocked the AAT-induced expansion of MDSC secreting high levels of vessel-destabilizing S100A8. Thus, concomitant treatment with ATRA holds the potential to improve AAT in breast cancer and possibly other tumor types.

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Plasminogen Activator Inhibitor-1 polymorphisms as a risk factor for chronic periodontitis in North Indian population

Publication date: Available online 18 April 2018
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Puja Debnath, Jayant Dewangan, Divya Tandon, Vivek Govila, Mona Sharma, Virendra Kumar, Smita Govila, Srikanta Kumar Rath
ObjectivesImpaired plasminogen activator inhibitor-1 (PAI-1), controlling coagulation and the fibrinolytic system is supposed to be involved in the pathogenesis of periodontitis. This study was performed to examine the association of PAI-1 gene polymorphisms with Chronic Periodontitis (CP) and alveolar bone loss severity involved with the disease and for understanding the role of genetic contributions in disease progression.Methods87 volunteers were included in the study. Genomic DNA was isolated from peripheral blood, subsequently, DNA samples were subjected to polymerase chain reaction and endonuclease digestion. Direct gene sequencing were performed for all the samples to identify genotype polymorphisms (rs 11560324) in the 3' untranslated region of PAI-1 gene. For bone loss assessment full mouth IOPA was taken.ResultsStatistical analysis showed that for SNP PAI-I in 3' UTR, genotype CC (homozygous mutant) and allele C (mutant) has a risk associated with CP, although statistically significant association was not found. An increased risk of association of disease severity with CG (heterozygous mutant) and CC (homozygous mutant) genotypes, i.e., an increased carriage rate of genotype CG and CC (homozygous mutant) was evident with the increase in the severity of CP, highlighting an increased susceptibility to CP due to this gene polymorphisms.ConclusionPAI-1 genotype has a risk association with CP and alveolar bone loss severity in North-Indian population.



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Malignant fibrous histiocytoma of the mandible- A case report and review of published case reports

Publication date: Available online 18 April 2018
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Sachin C. Sarode, Gargi S. Sarode, Yashwant Ingale, Manjusha Ingale, A. Thirumal Raj, Shankargouda Patil
The natural history of malignant fibrous histiocytoma (MFH) is still heavily debated. It's anonymous natural history is precisely denoted by its new adapted terminology 'undifferentiated pleomorphic sarcoma (UPS)'. Thus to diagnose a lesion as UPS, it is vital to correlate its histopathological features along with its immunohistochemical (IHC) expressions to confirm the tumor cell lineage. MFH is extremely rare in mandible with the literature search in PubMed database revealing only 13 case reports of MFH involving the mandible. Among these, only 7 case reports provide IHC details of the case. Without IHC data it is not possible to determine the accuracy of the diagnosis in the remaining 6 cases. Here we report an additional 8^th case of MFH involving the ramus and angle of the mandible. Histopathology revealed proliferating malignant spindle cells interspersed with histiocyte-like cells. The tumor cells were strongly positive for vimentin and CD68 and were negative for S-100, epithelial membrane antigen (EMA) and cytokeratin (CK). The diagnosis was made by correlating the histopathological findings with the IHC profile. The report also provides the data (clinical, radiographic, histopathological, immunohistochemical features and treatment details) extracted from the 7 confirmed MFH case reports involving the mandible.



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Emotion intensity modulates perspective taking in men and women: an event-related potential study

When empathizing with another individual, one can imagine the individual's emotional states and how he or she perceives a situation. However, it is not known to what extent imagining the other differs from imagining oneself under different emotional intensity situations in both sexes. The present study investigated the regulatory effect of emotional intensity on perspective taking in men and women by event-related potentials. The participants were shown pictures of individuals in highly negative (HN), moderately negative, and neutral situations, and instructed to imagine the degree of pain perceived from either a self-perspective or an other-perspective. The results showed that there was no N2 differentiation between the self-perspective and other-perspective under all conditions. Nor was there late positive potential differentiation under moderately negative and neutral conditions in either sex. In contrast, late positive potential induced by HN pictures under the self-perspective was significantly larger than that under the other-perspective only in women. These results suggested that women tended to overestimate the pain of HN stimuli from a self-perspective than from an other-perspective. Correspondence to Pinchao Luo, PhD, Department of Applied Psychology, School of Psychology, South China Normal University, Guangzhou 510631, China Tel/fax: +86 208 521 6412; e-mail: luopinchao@m.scnu.edu.cn Received February 23, 2018 Accepted March 20, 2018 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Glutathione-mimetic D609 alleviates memory deficits and reduces amyloid-β deposition in an AβPP/PS1 transgenic mouse model

Excessive extracellular deposition of amyloid-β-peptide (Aβ) in the brain is a pathological hallmark of Alzheimer's disease (AD). Oxidative stress is associated with the onset and progression of AD and contributes to Aβ generation. Tricyclodecan-9-yl-xanthogenate (D609) is a glutathione (GSH)-mimetic compound. Although the antioxidant properties of D609 have been well-studied, its potential therapeutic significance on AD remains unclear. In the present study, we used a mouse model of AD to investigate the effects and the mechanism of action of D609 on AD. We found that D609 treatment significantly improved the spatial learning and alleviated the memory decline in the mice harboring amyloid precursor protein (APP) and presenilin-1 (PS1) double mutations (AβPP/PS1 mice). D609 treatment also increased GSH level, GSH and oxidative glutathione ratio, and superoxide dismutase activity, whereas decreased malondialdehyde and protein carbonyl levels, suggesting that D609 alleviated oxidative stress in AβPP/PS1 mice. In addition, D609 reduced β-secretase 1 level and decreased amyloidogenic processing of AβPP, consequently reducing Aβ deposition in the mice. Thus, our findings suggest that D609 might produce beneficial effects on the prevention and treatment of AD. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. https://ift.tt/1hexVwJ Correspondence to JianZhong Bi, PhD, Department of Neural Medicine, Second Hospital of Shandong University, Jinan, Shandong 250033, China Tel: +86 531 8587 5006, fax: +86 531 8896 2544; e-mail: bjz@sdu.edu.cn Received February 5, 2018 Accepted April 3, 2018 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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The effects of treadmill exercise on autophagy in hippocampus of APP/PS1 transgenic mice

The β-amyloid (Aβ) deposition is one of the major pathological hallmark of Alzheimer's disease. Dysfunction in autophagy has been reported to lead to the Aβ deposition. The current study aimed to investigate the effects of treadmill exercise on autophagy activity and the Aβ deposition and to demonstrate whether exercise-induced reduction in the Aβ deposition was associated with changes in autophagy activity. APP/PS1 transgenic mice were divided into transgenic sedentary (TG-SED, n=12) and transgenic exercise (TG-EXE, n=12) groups. Wild-type mice were also divided into sedentary (WT-SED, n=12) and exercise (WT-EXE, n=12) groups. The WT-EXE and TG-EXE mice were subjected to treadmill exercise for 12 weeks. The levels of Aβ plaques and soluble forms of Aβ, autophagy markers light chain 3 and P62, and lysosomal marker lysosome-associated membrane protein 1 (Lamp1) were measured in the hippocampus. Both Aβ plaques and soluble forms of Aβ (Aβ40 and Aβ42) were significantly increased in TG-SED mice compared with WT-SED mice, whereas exercise reduced Aβ deposition in APP/PS1 transgenic mice. Coincidentally, TG-SED mice displayed a decrease in autophagy activity as evidenced by a significant increase in the levels of light chain 3-II and P62, as well as an accumulation of lysosome as evidenced by a significant over-expression of Lamp1. Interestingly, exercise increased autophagy activity as evidenced by a significant reduction in the levels of P62 and Lamp1 in TG-EXE mice. These findings suggest that treadmill exercise is efficient in decreasing Aβ deposition by enhancing autophagy–lysosomal activity in APP/PS1 transgenic mice, demonstrating a possible approach in Alzheimer's disease prevention and treatment. Correspondence to Bo Xu, PhD, School of Physical Education and Health, East China Normal University, No. 500 Dongchuan Road, Shanghai 200241, China Tel: +86 215 434 5131; fax: +86 215 434 2612; e-mail: bxu@tyxx.ecnu.edu.cn Received March 19, 2018 Accepted April 2, 2018 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Postoperative Monitoring of Free DIEP Flap in Breast Reconstruction with Near-Infrared Spectroscopy: Variables Affecting the Regional Oxygen Saturation

J reconstr Microsurg
DOI: 10.1055/s-0038-1636527

Background The timing of surgical reexploration in microanastomotic thrombosis is directly related to the salvage rate of free flap. Near-infrared spectroscopy (NIRS) is a noninvasive technique, which allows a continuous bedside monitoring of flap oxygenation. The current literature is lacking in the assessment of variables able to modify the NIRS monitoring. The aim of this study is to identify patient and flap-related variables that can affect regional oxygen saturation (rSO2). Methods We retrospectively analyzed the data obtained from 45 consecutive patients undergoing breast reconstruction with deep inferior epigastric perforator (DIEP) flap. The monitoring device used is the Somanetics INVOS 5100C Cerebral/Somatic Oximeter (Covidien). Baseline measures of demographic–anthropometric variables (age, weight, height, body mass index [BMI]) and flap factors (flap size in grams, skin flap area in square centimeters, perforator number, and perforator size in millimeters) were collected from preoperative and intraoperative assessment. We investigated the linear correlation between mean rSO2 and BMI, flap size, skin flap area, perforator number, and perforator size. Results A positive linear correlation between rSO2 values and skin flap area, perforator number, and perforator size was found. A negative linear correlation between rSO2 values and BMI and flap size was found. All correlations are statistically significant. Despite the overall negative linear correlation between rSO2 values and flap size, we observed a bimodal trend: a positive relation up to 800 g, which is inverted above 800 g. Conclusion The NIRS is a reliable additional tool in free flap monitoring. A careful evaluation should be given to patient and surgery factors that can change the oximetry data.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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DIEP Flap Breast Reconstruction Complication Rate in Previously Irradiated Internal Mammary Nodes

J reconstr Microsurg
DOI: 10.1055/s-0038-1625986

Background Postmastectomy radiation therapy (PMRT) is a widely accepted treatment for locally advanced breast cancer. Some patients require additional boost radiation to the internal mammary nodes as the part of regional nodal irradiation (RNI). Delayed breast reconstruction with an autologous free flap using the internal mammary vessels for microvascular flap anastomosis is a common practice for these patients. The aim of our study was to evaluate the effect of RNI on autologous microvascular breast reconstruction. Patients and Methods A retrospective study was performed on 57 patients (69 flaps) undergoing deep inferior epigastric perforator (DIEP) flap for delayed breast reconstruction after radiation therapy. The study group included 37 patients (65%) that received PMRT and RNI to the internal mammary nodes. The control group included 20 patients (35%) that received PMRT alone. Early and delayed surgical complications, including wound complications, fat necrosis, and flap loss, were compared between the groups. Results The patient demographics in both groups were similar. Complication rate showed a higher trend in the study group for flap loss (8.3% versus 0%) and vascular anastomosis failure (5.6% versus 0%), but with no statistical difference (p = 0.54, 0.53, respectively). The control group showed a higher trend in fat necrosis (25% versus 8.3%, p = 0.11). Conclusions DIEP flap breast reconstructions with internal mammary vessels anastomosis should be performed with cautious in patients who had received RNI to internal mammary nodes because of potential added risk for surgical complications.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Free or Perforator-Pedicled Propeller Flaps in Lower Extremity Reconstruction: Defining the Coverage Failure

J reconstr Microsurg
DOI: 10.1055/s-0038-1641725

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Full text

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JAMA Otolaryngology–Head & Neck Surgery Peer Reviewers in 2017

We sincerely thank the 645 peer reviewers who completed manuscript reviews for JAMA Otolaryngology–Head Neck Surgery in 2017.

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Soft-Tissue Augmentation for Tracheoesophageal Puncture Enlargement

This study reports on the use of injectable soft-tissue fillers for the treatment of tracheoesophageal prosthesis enlargement and periprosthetic leakage.

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April 2018 Issue Highlights

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A Painful Submandibular Mass in a Patient With Bruxism

A woman with a history of bruxism and long-term use of a bite guard presented with pain centering on left submandibular area; contrast-enhanced computed tomography demonstrated a mass adjacent to the left submandibular gland. What is your diagnosis?

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Brain-Derived Neurotrophic Factor Therapy and Cochlear Implantation

This Viewpoint cites several examples of how brain-derived neurotrophic factor therapy affects outcomes of cochlear implantation.

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Opsoclonus-Myoclonus Syndrome—Additional Clinical Considerations

To the Editor We read with interest the report by Hsu et al describing a 39-year-old woman with opsoclonus-myoclonus syndrome (OMS). Although an intriguing case, several aspects of the treatment should be addressed for others who may encounter this condition.

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Open Access—Is There a Predator at the Door?

Dear Readers,

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A Pediatric Nasopharyngeal Mass

An otherwise healthy 3-year-old boy presented with symptoms of sleep-disordered breathing, including gasping, apneic episodes at night, and nighttime nasal congestion; intraoperatively he was found to have a nasopharyngeal mass. What is your diagnosis?

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JAMA Otolaryngology–Head & Neck Surgery Year in Review

As I complete my second year as Editor of JAMA Otolaryngology–Head & Neck Surgery, I would like to take this opportunity to thank our authors, reviewers, members of the editorial board, and staff for the many contributions to the journal and to share our accomplishments. This past year, we received 822 submissions and published 94 Original Investigations, 35 Reviews, 34 opinion articles, and 11 Research Letters. In 2017, the acceptance rate for major submissions was 19%. The publication of opinion articles provides context to the original investigations and a forum for active dialogue in our specialty.

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Medical Student Knowledge of Human Papillomavirus–Positive Head and Neck Cancer

This survey examines knowledge of the association of human papillomavirus and head and neck cancer among students at 10 New York State medical schools.

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Onabotulinum Toxin A in Adductor Spasmodic Dysphonia and Laryngeal Tremor

This cohort study examines the outcomes of onabotulinum toxin A treatment in patients with adductor spasmodic dysphonia with or without lateral laryngeal tremor.

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Lymph Node Yield as Quality Metric for Clinically N0 Oral Cancer

To the Editor In their research letter, Tsai et al evaluated lymph node yield in a cohort of patients with clinically N0 oral cavity cancer from the National Cancer Database (NCDB). They found an association of lymph node yield with survival. With a median node count of 23, they used neck dissections with 24 or more nodes as a variable in a multivariable analysis and found 24 or more nodes to be associated with improved survival.

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Postadenotonsillectomy Blood Pressure Changes in Children With Obstructive Sleep Apnea

This case series investigates disparities in blood pressure changes after adenotonsillectomy in hypertensive and nonhypertensive children with obstructive sleep apnea.

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Errors in Questionnaire Scoring Algorithm

In the Original Investigation titled "Development and Initial Validation of a Consumer Questionnaire to Predict the Presence of Ear Disease," published online on August 3, 2017, and in the October 2017 issue of JAMA Otolaryngology–Head & Neck Surgery, there were errors in the analysis code for 3 of the questionnaire items (questions 16, 18, and 19). For these 3 questions, the 4-item rating scales were dichotomized incorrectly. Using the corrected algorithm resulted in changed sensitivity and specificity, odds ratios, and 95% CIs, as detailed herein. The corrections are also explained in a Letter to the Editor. In the abstract Results, descriptions of the sensitivity and specificity have been corrected to 90% (95% CI, 84%-94%) and 72% (95% CI, 59%-82%), respectively, for the training sample and 76% (95% CI, 61%-87%) and 80% (95% CI, 51%-95%) for the test sample, respectively. In the Statistical Analysis paragraph of the Methods section, rating scale items should have been dichotomized as 0 for "never" and "occasionally" and as 1 for "sometimes" and "always" rather than scored on a scale of 0 to 4. In the Results section, the odds ratio and 95% CI for the association between CEDRA score and presence of disease changed. In addition, the probability, sensitivity, and specificity values changed. In the third paragraph of the Discussion, all percentages have changed. Figure 2 has been replaced with a graph incorporating a corrected receiver operating characteristic curve, and the figure caption has been updated. This article was corrected online.

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Association of Metabolic Syndrome With Sudden Sensorineural Hearing Loss

This medical record review evaluates the association of the metabolic syndrome with the rate of recovery among adult patients with sudden sensorineural hearing loss.

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Nonsurgical Treatment for Posttraumatic Complete Facial Nerve Paralysis

This cohort study documents the results of nonsurgical treatment for posttraumatic complete facial paralysis with undisplaced temporal bone fracture and unfavorable electrophysiologic features.

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Hard Swelling on Inner Cheek

A man had a hard swelling of the left inner cheek, with increasing spontaneous pain and swelling; examination revealed an erythematous lesion of the buccal mucosa, adjacent to the maxillary first molar, which produced a small amount of bleeding with palpation. What is your diagnosis?

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Scope of Procedures Performed by Pediatric Otolaryngologists, 2006-2016

This survey study asks directors from 33 US and international pediatric otolaryngology departments to report the percentage of 59 procedures that were performed by their department vs other specialties from 2006 to 2016.

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An Uncommon Cutaneous Lesion

A male smoker in his 60s presented with a right supraclavicular cutaneous mass that had persisted for 2 years; a biopsy of a pulmonary nodule showed a well-differentiated adenocarcinoma with lepidic pattern, and further workup revealed an intestinal tumor as the primary source. What is your diagnosis?

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Association of Reduced Delay in Care With a Dedicated Operating Room in Pediatric Otolaryngology

This study evaluates an otolaryngology-specific operating room time block for unscheduled cases to determine time from initial consultation to surgery and utilization of the dedicated block of time.

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Toward Non-Invasive and Automatic Intravenous Infiltration Detection: Evaluation of Bioimpedance and Skin Strain in a Pig Model

Intravenous (IV) therapy is prevalent in hospital settings, where fluids are typically delivered with an IV into a peripheral vein of the patient. IV infiltration is the inadvertent delivery of fluids into the extravascular space rather than into the vein (and requires urgent treatment to avoid scarring and severe tissue damage), for which medical staff currently needs to check patients periodically. In this paper, the performance of two non-invasive sensing modalities, electrical bioimpedance (EBI), and skin strain sensing, for the automatic detection of IV infiltration was investigated in an animal model. Infiltrations were physically simulated on the hind limb of anesthetized pigs, where the sensors for EBI and skin strain sensing were co-located. The obtained data were used to examine the ability to distinguish between infusion into the vein and an infiltration event using bioresistance and bioreactance (derived from EBI), as well as skin strain. Skin strain and bioresistance sensing could achieve detection rates greater than 0.9 for infiltration fluid volumes of 2 and 10 mL, respectively, for a given false positive, i.e., false alarm rate of 0.05. Furthermore, the fusion of multiple sensing modalities could achieve a detection rate of 0.97 with a false alarm rate of 0.096 for 5mL fluid volume of infiltration. EBI and skin strain sensing can enable non-invasive and real-time IV infiltration detection systems. Fusion of multiple sensing modalities can help to detect expanded range of leaking fluid volumes. The provided performance results and comparisons in this paper are an important step towards clinical translation of sensing technologies for detecting IV infiltration.

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Moving toward uniform and evidence-based practice of radiotherapy for management of cervical cancer in Ontario, Canada

Publication date: Available online 19 April 2018
Source:Brachytherapy
Author(s): Negin Shahid, Timothy Craig, Mary Westerland, Allison Ashworth, Michelle Ang, David D'Souza, Raxa Sankreacha, Anthony Fyles, Michael Milosevic, Iwa Kong
PurposeTo recognize the practice of radiotherapy for management of cervical cancer in Ontario, Canada, and to use the results of the survey to harmonize and standardize practice across the province.Methods and MaterialsAn electronic survey (SurveyMonkey) was sent to all 14 provincial cancer centers by Cancer Care Ontario Gynecology Community of Practice (CoP) in 2013. The survey included 72 questions in four different categories: general/demographic, pretreatment assessment, external beam radiotherapy (EBRT), and brachytherapy (BT).ResultsTen of 14 centers treated cervical cancer patients and had a dedicated BT suite. All 10 centers had a peer review process for quality assurance. EBRT technique was a 4-field box in eight of 10 centers. The dose/fractionation for pelvic EBRT was 45–50 Gy in 1.8–2 Gy/fraction in all but one center. Nine of 10 centers used high-dose-rate BT. Only one center offered interstitial BT. For treatment planning, two centers used CT and MRI, five centers used CT, and three centers used orthogonal x-rays. Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology guidelines were used in four of seven of the centers for target volume delineation and in five of seven centers for organs at risk dose constraints. All but one center prescribed and reported dose to Point A.ConclusionsThe survey identified areas where practice varied across the province. Gynecology CoP used this information to identify priorities for practice change and implemented several strategies to harmonize the care of women with cervical cancer. This highlights the value of interdisciplinary, grass-roots initiatives such as CoPs to standardize practice in a practical manner that directly benefits patients.



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Do You Recommend Prescriptive Diets to Your Patients?

Diets that purport to mitigate health symptoms are gaining popularity.
Medscape Reader Polls

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Metastatic hepatocellular carcinoma masquerading as soft tissue sarcoma: A diagnostic challenge

Diagnostic Cytopathology, EarlyView.


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Liquid‐based cytology in the diagnosis of Langerhans cell sarcoma: A case report

Diagnostic Cytopathology, EarlyView.


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Cytodiagnosis of inflammatory myofibroblastic tumor: A report of three cases in infants

Diagnostic Cytopathology, EarlyView.


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Evaluation of photoshop based image analysis in cytologic diagnosis of pleural fluid in comparison with conventional modalities

Diagnostic Cytopathology, EarlyView.


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Pectoral I Block Does Not Improve Postoperative Analgesia After Breast Cancer Surgery: A Randomized, Double-Blind, Dual-Centered Controlled Trial

Background and Objectives General anesthesia for breast surgery may be supplemented by using a regional anesthetic technique. We evaluated the efficacy of the first pectoral nerve block (Pecs I) in treating postoperative pain after breast cancer surgery. Methods A randomized, double-blind, dual-centered, placebo-controlled trial was performed. One hundred twenty-eight patients scheduled for unilateral breast cancer surgery were recruited. A multimodal analgesic regimen and surgeon-administered local anesthetic infiltration were used for all patients. Ultrasound-guided Pecs I was performed using bupivacaine or saline. The primary outcome was the patient pain score (numerical rating scale [NRS]) in the recovery unit 30 minutes after admission or just before the morphine administration (NRS ≥4/10). The secondary outcomes were postoperative opioid consumption (ie, in the recovery unit and after 24 hours). Results During recovery, no significant difference in NRS was observed between the bupivacaine (n = 62, 3.0 [1.0–4.0]) and placebo (n = 65, 3.0 [1.0–5.0]) groups (P = 0.55). However, the NRS was statistically significantly different, although not clinically significant, for patients undergoing major surgeries (mastectomies or tumorectomies with axillary clearance) (n = 29, 3.0 [0.0–4.0] vs 4.0 [2.0–5.0], P = 0.04). Morphine consumption during recovery did not differ (1.5 mg [0.0–6.0 mg] vs 3.0 mg [0.0–6.0 mg], P = 0.20), except in the major surgery subgroup (1.5 mg [0.0–6.0 mg] vs 6.0 mg [0.0–12.0 mg], P = 0.016). Intraoperative sufentanil and cumulative morphine consumption up to 24 hours did not differ between the 2 groups. Three patients experienced complications related to the Pecs I. Conclusions Pecs I is not better than a saline placebo in the presence of multimodal analgesia for breast cancer surgery. However, its role in extended (major) breast surgery may warrant further investigation. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT01670448. Accepted for publication December 13, 2017. Address correspondence to: Jérôme Cros, MD, MSc, Département d'Anesthésie-Réanimation, Hôpital de la mère et de l'enfant, 8, avenue Dominique Larrey, 87000 Limoges, France (e-mail: jerome.cros@chu-limoges.fr). Funding was provided by Réseau Québécois de Recherche sur la Douleur, Québec, Canada; Fondation d'Anesthésiologie et Réanimation du Québec, Canada; Fonds de Développement du Département d'anesthésiologie de l'Université de Montréal, Québec, Canada; and Fondation de France, Paris, France. This work has been presented in part at Euroanesthesia 2016, London, United Kingdom, May 29, 2016 (presented by J.C., abstract no. 03AP04-3); at the French Society of Anesthesia & Intensive Care Medicine (SFAR) 2016 Annual Meeting, Paris, France, September 24, 2016 (presented by J.C., abstract no. R480 [in French]); and at the World Congress of Pain 2016, Yokohama, Japan, September 27, 2016 (presented by P.B., abstract no. 943). The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Knowledge and Beliefs About Oncofertility and Associations with Quality of Life Among Adolescent and Young Adult Survivors of Pediatric Cancer

Journal of Adolescent and Young Adult Oncology, Ahead of Print.


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Sphingosine‐1‐phosphate selectively activates vagal afferent C‐fiber subtype in guinea pig esophagus

Neurogastroenterology &Motility, EarlyView.


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A GWAS meta‐analysis from 5 population‐based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome

Neurogastroenterology &Motility, EarlyView.


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Systematic review of the mesopancreas: concept and clinical implications

Abstract

Background

In 2007, Gockel et al. coined the term mesopancreas (MP). In the next 10 years, a limited number of publications about MP have been published, but little is known about the oncological benefit of MP resection. We performed a systematic review of the literature on MP.

Methods

An electronic search was performed in PubMed, EMBASE, Cochrane, Latindex, Scielo, and Koreamed databases until 15 June 2017 to identify all published articles dealing with the subject of MP. Some language restriction was done (Chinese and Rumanian).

Results

The search yielded 51 articles; 28 articles were selected as relevant. All were retrospective studies focused more on describing technical variants, feasibility and safety than on the cancer results. The R0 rate in patients with MP resection ranged between 57 and 96.7%. In all the articles with a control group, the R0 rate was higher in the MP excision group. Survival data were explicitly stated only in five series.

Conclusion

MP is a difficult-to-excise retropancreatic area. In theory, it is agreed that MP excision raises the rate of R0 resections, which in turn reflected in an improvement in the oncological results; however, at present there are no randomized studies to prove this. Achieving a worldwide consensus on its concept, landmarks, excision technique and oncological results is essential.

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Systematic review of the mesopancreas: concept and clinical implications

Abstract

Background

In 2007, Gockel et al. coined the term mesopancreas (MP). In the next 10 years, a limited number of publications about MP have been published, but little is known about the oncological benefit of MP resection. We performed a systematic review of the literature on MP.

Methods

An electronic search was performed in PubMed, EMBASE, Cochrane, Latindex, Scielo, and Koreamed databases until 15 June 2017 to identify all published articles dealing with the subject of MP. Some language restriction was done (Chinese and Rumanian).

Results

The search yielded 51 articles; 28 articles were selected as relevant. All were retrospective studies focused more on describing technical variants, feasibility and safety than on the cancer results. The R0 rate in patients with MP resection ranged between 57 and 96.7%. In all the articles with a control group, the R0 rate was higher in the MP excision group. Survival data were explicitly stated only in five series.

Conclusion

MP is a difficult-to-excise retropancreatic area. In theory, it is agreed that MP excision raises the rate of R0 resections, which in turn reflected in an improvement in the oncological results; however, at present there are no randomized studies to prove this. Achieving a worldwide consensus on its concept, landmarks, excision technique and oncological results is essential.

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Sensitization to minor cat allergen components is associated with type‐2 biomarkers in young asthmatics

Clinical &Experimental Allergy, EarlyView.


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Variation in the association of Der p 1 and Der f 1 with asthma and rhinitis in 9‐11‐year‐old schoolchildren: The French six cities study

Clinical &Experimental Allergy, EarlyView.


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Retreatment with pembrolizumab in advanced non-small cell lung cancer patients previously treated with nivolumab: emerging reports of 12 cases

Abstract

Purpose

After approval of anti-programmed cell death (PD)-1 antibodies, treatment for non-small cell lung cancer (NSCLC) has drastically changed. However, even in patients with favorable effects, therapeutic efficacy does not last long. Recently, retreatment with anti-PD-1 antibody has received attention. The aim of this study was to evaluate the efficacy and safety of retreatment with pembrolizumab in NSCLC patients previously treated with nivolumab.

Patients and methods

We retrospectively reviewed NSCLC patients retreated with pembrolizumab who were previously treated with nivolumab. We collected the following data: patient characteristics, number of cycles of nivolumab and pembrolizumab, treatment interval between nivolumab and pembrolizumab, best response, and immune-related adverse events.

Results

Twelve patients were reviewed. The median number of cycles of nivolumab was 12.5 (range 2–32 cycles). Seven patients (58.3%) achieved a partial response (PR) and two patients (16.7%) achieved stable disease (SD). Eight patients (66.7%) received cytotoxic chemotherapy between nivolumab and pembrolizumab. The median number of cycles of chemotherapy treatment was 4 (range 1–9 cycles). The median number of cycles of pembrolizumab was 3.5 (range 1–17 cycles). One patient (8.3%) achieved PR and four patients (33.3%) achieved SD as their best response to pembrolizumab. All patients showing response to pembrolizumab had very high (≥ 80%) tumor PD-Ligand 1 expression.

Conclusions

This study suggested that retreatment with anti-PD-1 antibody is a reasonable option for selected NSCLC patients.

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Association of Behavior With Noise-Induced Hearing Loss Among Attendees of an Outdoor Music Festival

This post hoc secondary analysis of a randomized clinical trial assesses which factors are associated with the occurrence of temporary noise-induced hearing loss among adult attendees of an outdoor music festival.

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Increasing Age of Patients With Oropharyngeal Squamous Cell Carcinoma

This observational study evaluates the changes in age profile over time in patients with oropharyngeal squamous cell carcinoma.

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Proactive Swallowing Rehabilitation and Feeding Tube Placement in Pharyngeal Cancer Patients

This cohort study evaluates the initiation of a proactive speech and language pathology rehabilitation program and its association with rates of feeding tube placement and posttreatment oral intake in patients with head and neck squamous cell carcinoma.

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Beyond “Pharyngocise” for Patients With Head and Neck Cancer

Advances in technology have improved survival rates for patients with head and neck cancer; however, the medical profession continues to pursue opportunities to improve quality of life for survivors. Advances in organ preservation therapies, such as intensity-modulated radiation therapy and proton therapy, are encouraging. However, preservation of swallowing-related quality of life remains challenging. For the past decade, speech-language pathologists (SLPs) have applied neuroplasticity principles to exercise-based swallowing treatment for patients undergoing chemoradiation therapy for head and neck cancer. This intensive daily exercise regimen, termed by some pharyngocise, also includes encouragement to eat and drink throughout radiation treatment. This treatment protocol flipped the traditional swallowing treatment paradigm by using a proactive vs a reactive ("wait and see") approach to treatment. Since approximately 2006, a growing body of research has largely supported better outcomes for patients who either completed the proactive exercises or ate and drank during treatment compared with those who did neither.

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RNA Oncoimmune Phenotyping of HPV-Positive Oropharyngeal Cancer by Nodal Status

This cohort study explores whether a tumor-specific genetic signature exists for node-negative vs node-positive HPV 16–positive/p16-positive oropharyngeal squamous cell carcinomas.

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Baseline Cognition Assessment Among Patients With Oropharyngeal Cancer

This cohort study assesses the baseline cognition of patients with oropharyngeal cancer using the Patient-Reported Outcomes Measurement Information System and National Institutes of Health (NIH) Toolbox Cognitive Battery instrument.

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Gene Expression Profiling in p16-Positive Oropharyngeal Squamous Cell Carcinomas

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with p16 overexpression and a better prognosis than HPV-negative OPSCC. Concurrent treatment with standard-dose radiation therapy (RT) (66-70 Gy) and platinum-based chemotherapy is highly effective for most patients with p16-positive OPSCC, but more than 40% of patients experience severe late toxic effects when treated with concurrent chemoradiation therapy (CRT). The advent of transoral minimally invasive surgical approaches to the oropharynx, such as transoral robotic surgery (TORS) and transoral laser microsurgery (TLM), has provided an opportunity to treat patients with OPSCC while potentially minimizing long term sequelae of CRT. Treatment choice (ie, surgery with or without adjuvant therapy vs primary RT-CRT) and deintensification are areas of current investigation. However, given heterogeneity among patients with p16-positive OPSCC, optimal treatment paradigms remain unclear.

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Patient-Perceived Voice Changes and Quantitative Voice Measures in the Year After Thyroidectomy

This mixed methods study assesses the quality-of-life consequences of postthyroidectomy voice change from the perspective of patients with thyroid cancer and compares patient-perceived voice changes with changes in quantitative vocal variables at 5 time points in the first postoperative year.

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Incidence, pattern and prognosis of brain metastases in patients with metastatic triple negative breast cancer

Abstract

Background

To identify the incidence, recurrence pattern and prognosis of brain metastases (BM) among women with metastatic triple negative breast cancer (mTNBC) treated consecutively at a single institution during a 7-year period.

Methods

Patients with histologically confirmed mTNBC were retrospectively identified. The incidence of BM as first site of recurrence and the cumulative BM incidence were computed. We used the Cox proportional hazards model to identify the univariate and multivariate factors associated with survival.

Results

Four hundred thirty three patients were included with a median overall survival (OS) of 21.6 months after median follow-up for 48.1 months. BM was found in 29% (127/433) of the patients and about a quarter (32/127) of BM was first recurrence. The cumulative incidence of BM at 1 and 2 years was 17 and 25%, respectively. The median time from the diagnosis of extracranial metastases to BM was 10 months. Median OS following a diagnosis of BM was 7.3 months. The longer median OS from time of first recurrent BM was noted compared with those of subsequent recurrent (17.3 vs 6.3 months, p = 0.008). However, patients with first recurrent BM were associated with shorter OS compared with those without BM (17.3 vs 22.1 months, p = 0.006). The independent factors that increased BM death risk were > 3 brain lesions, no BM-directed treatment, subsequent recurrent BM, symptomatic BM and uncontrolled extracranial metastasis.

Conclusions

Patients with mTNBC have a high incidence of early BM with subsequent poor survival. The findings lend support to consideration of screening imaging of the brain for mTNBC patients.

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Dietary patterns, BCMO1 polymorphisms, and primary lung cancer risk in a Han Chinese population: a case-control study in Southeast China

Abstract

Background

We investigated whether BCMO1 variants and dietary patterns are associated with lung cancer risk.

Methods

Case-control study including 1166 lung cancer cases and 1179 frequency matched controls was conducted for three BCMO1 variants (rs6564851, rs12934922, and rs7501331) and four dietary patterns were investigated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results

The rs6564851, rs12934922, and rs7501331 were not found to be associated with lung cancer risk (P > 0.05). In multivariable-adjusted models, compared to the lowest quartile of the score on the "fruits and vegetables" pattern, the highest quintile was associated with a 78.4% decreased risk (OR _{Q4 vs. Q1} = 0.216; 95% CI, 0.164–0.284; P for trend < 0.001). Other patterns were not found the association. The "fruits and vegetables" pattern was associated with a reduced risk of lung cancer with all 3 SNPs irrespective of genotypes (all P for trend< 0.001). The association for the "Frugal" pattern was associated with increased risk of lung cancer among smokers (P for interaction = 0.005). The protective effects of the "cereals/wheat and meat" pattern was more evident for squamous cell carcinoma and other histological type.

Conclusions

We did not observe associations of BCMO1 variants and lung cancer. Diets rich in fruits and vegetables may be protective against lung cancer.

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AB0 blood groups and rhesus factor expression as prognostic parameters in patients with epithelial ovarian cancer – a retrospective multi-centre study

Abstract

Background

AB0 blood groups and Rhesus factor expression have been associated with carcinogenesis, response to treatment and tumor progression in several malignancies. The aim of the present study was to test the hypothesis that AB0 blood groups and Rhesus factor expression are associated with clinical outcome in patients with epithelial ovarian cancer (EOC).

Methods

AB0 blood groups and Rhesus factor expression were evaluated in a retrospective multicenter study including 518 patients with EOC. Their association with patients' survival was assessed using univariate and multivariable analyses.

Results

Neither AB0 blood groups nor Rhesus factor expression were associated with clinico-pathological parameters, recurrence-free, cancer-specific, or overall survival. In a subgroup of patients with high-grade serous adenocarcinoma, however, blood groups B and AB were associated with a better 5-year cancer-specific survival rate compared to blood groups A and 0 (60.3 ± 8.6% vs. 43.8 ± 3.6%, p = 0.04). Yet, this was not significant in multivariable analysis.

Conclusions

AB0 blood groups and Rhesus factor expression are both neither associated with features of biologically aggressive disease nor clinical outcome in patients with EOC. Further investigation of the role of the blood group B antigen on cancer-specific survival in the subgroup of high-grade serous should be considered.

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Optimization of training periods for the estimation model of three-dimensional target positions using an external respiratory surrogate

Abstract

Background

During therapeutic beam irradiation, an unvisualized three-dimensional (3D) target position should be estimated using an external surrogate with an estimation model. Training periods for the developed model with no additional imaging during beam irradiation were optimized using clinical data.

Methods

Dual-source 4D-CBCT projection data for 20 lung cancer patients were used for validation. Each patient underwent one to three scans. The actual target positions of each scan were equally divided into two equal parts: one for the modeling and the other for the validating session. A quadratic target position estimation equation was constructed during the modeling session. Various training periods for the session—i.e., modeling periods (T_M)—were employed: T_M ∈ {5,10,15,25,35} [s]. First, the equation was used to estimate target positions in the validating session of the same scan (intra-scan estimations). Second, the equation was then used to estimate target positions in the validating session of another temporally different scan (inter-scan estimations). The baseline drift of the surrogate and target between scans was corrected. Various training periods for the baseline drift correction—i.e., correction periods (T_Cs)—were employed: T_C ∈ {5,10,15; T_C ≤ T_M} [s]. Evaluations were conducted with and without the correction. The difference between the actual and estimated target positions was evaluated by the root-mean-square error (RMSE).

Results

The range of mean respiratory period and 3D motion amplitude of the target was 2.4–13.0 s and 2.8–34.2 mm, respectively. On intra-scan estimation, the median 3D RMSE was within 1.5–2.1 mm, supported by previous studies. On inter-scan estimation, median elapsed time between scans was 10.1 min. All T_Ms exhibited 75th percentile 3D RMSEs of 5.0–6.4 mm due to baseline drift of the surrogate and the target. After the correction, those for each T_Ms fell by 1.4–2.3 mm. The median 3D RMSE for both the 10-s T_M and the T_C period was 2.4 mm, which plateaued when the two training periods exceeded 10 s.

Conclusions

A widely-applicable estimation model for the 3D target positions during beam irradiation was developed. The optimal T_M and T_C for the model were both 10 s, to allow for more than one respiratory cycle.

Trial registration

UMIN000014825. Registered: 11 August 2014.

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