1.
J Oral Rehabil. 2020 Mar 9. doi: 10.1111/joor.12959. [Epub ahead of print]
International consensus on the most useful assessments used by physical therapists to evaluate patients with temporomandibular disorders: A Delphi study.
von Piekartz H1, Schwiddessen J1, Reineke L1, Armijo-Olivio S2, Bevilaqua-Grossi D3, Biasotto Gonzalez D4, Carvalho GB5,6, Chaput E7,8, Cox E9,10, Fernández-de-Las-Peñas C11,12, Gadotti I13, Gil Martínez A14, Gross A15, Hall T16, Hoffmann M17, Julsvoll E18, Karegeannes M19, La Touche R20,21,22, Mannheimer J23, Pitance L24, Rocabado M25, Strickland M26, Stelzenmüller W27, Speksnijder C28, van der Meer H29, Luedke K30, Ballenberger N31.
Abstract
OBJECTIVE:
To identify assessment tools used to evaluate patients with temporomandibular disorders (TMD) considered to be clinically most useful by a panel of international experts in TMD physical therapy (PT).
METHODS:
A Delphi survey method administered to a panel of international experts in TMD PT was conducted over three rounds from October 2017 to June 2018. The initial contact was made by email. Participation was voluntary. An e-survey, according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) was posted using SurveyMonkey for each round. Percentages of responses were analyzed for each question from each round of the Delphi survey administrations.
RESULTS:
Twenty-three experts (completion rate: 23/25) completed all three rounds of the survey for three clinical test categories: 1) questionnaires, 2) pain screening tools, and 3) physical examination tests. The following was the consensus-based decision regarding the identification of the clinically most useful assessments. 1) 4 of 9 questionnaires were identified: Jaw Functional Limitation (JFL-8), Mandibular Function Impairment Questionnaire (MFIQ), Tampa Scale for Kinesiophobia for Temporomandibular disorders (TSK/TMD), and the Neck Disability Index (NDI). 2) 3 of 8 identified pain screening tests: Visual Analogue Scale (VAS), Numeric Pain Rating Scale (NRS), and pain during mandibular movements. 3) 8 of 18 identified physical examination tests: physiological temporomandibular joint (TMJ) movements, trigger point (TrP) palpation of the masticatory muscles, TrP palpation away from the masticatory system, accessory movements, articular palpation, noise detection during movement, manual screening of the cervical spine, and the Neck Flexor Muscle Endurance Test.
CONCLUSION:
After three rounds in this Delphi survey, the results of the most used assessment tools by TMD PT experts were established. They proved to be founded on test construct, test psychometric properties (reliability/validity), and expert preference for test clusters. A concordance with the screening tools of the diagnostic criteria of TMD consortium was noted. Findings may be used to guide policymaking purposes and future diagnostic research.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Assessments ,TMD; Delphi -study; Physical therapy
2.
Am J Gastroenterol. 2020 Mar 9. doi: 10.14309/ajg.0000000000000588. [Epub ahead of print]
Positive Hepatitis B Core Antibody Is Associated With Cirrhosis and Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.
Chan TT1, Chan WK2, Wong GL1,3, Chan AW4, Nik Mustapha NR5, Chan SL6, Chong CC7, Mahadeva S2, Shu SS1,3, Lai PB7, Chan HL1,3, Wong VW1,3.
Abstract
OBJECTIVES:
Previous exposure to hepatitis B virus (HBV) may increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. We aim to study the impact of previous HBV infection on the severity and outcomes of patients with nonalcoholic fatty liver disease (NAFLD).
METHODS:
This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection.
RESULTS:
In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202-4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity.
DISCUSSION:
Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.
3.
Nicotine Tob Res. 2020 Feb 28. pii: ntaa041. doi: 10.1093/ntr/ntaa041. [Epub ahead of print]
Exploring the Point-of-Sale Among Vape Shops Across the US: Audits Integrating a Mystery Shopper Approach.
Berg CJ1, Barker DC2, Meyers C3, Weber A3, Park AJ3, Patterson A3, Dorvil S3, Fairman RT3, Huang J4, Sussman S5, Livingston MD1, Wagener TL6, Hayes RB7, Pulvers K8, Getachew B3, Schleicher N9, Henriksen L9.
Abstract
INTRODUCTION:
Vape shops represent prominent, unique retailers, subject to Food and Drug Administration (FDA) regulation in the US. This study assessed compliance of US vape shop retail marketing strategies with new regulations (e.g., required age verification, prohibited free samples) and pre-implementation conditions for other regulations (e.g., health warning labels on all nicotine products, required disclosures of e-liquid contents).
METHODS:
In May-July 2018, trained research assistants (ages 23-25) conducted mystery shopper (alone, n=174) and point-of-sale audits (in pairs, n=179) on different occasions in 30 randomly-selected vape shops in each of six US metropolitan areas (Atlanta, Boston, Minneapolis-St. Paul, Oklahoma City, San Diego, and Seattle).
RESULTS:
95.0% of shops displayed minimum-age signage; however, mystery shoppers were asked for age verification at 35.6% upon entry and at 23.4% upon purchase. Although 85.5% of shops had some evidence of implementing FDA health warnings, 29.1% had signage indicating prohibited health claims, 16.3% offered free e-liquid samples, 27.4% had signage with cartoon imagery, and 33.3% were within two blocks of schools. All shops sold open-system devices, 64.8% sold closed-system devices, 68.2% sold their own brand of e-liquids, 42.5% sold e-liquids containing cannabidiol (CBD), 83.2% offered price promotions of some kind, and 89.9% had signage for product and price promotions.
CONCLUSIONS:
Results indicated that most shops complied with some implementation of FDA health warnings and with free sampling bans and minimum-age signage. Other findings indicated concerns related to underage access, health claims, promotional strategies, and CBD product offerings, which call for further FDA and state regulatory/enforcement efforts.
IMPLICATIONS:
Current and impending FDA regulation of vaping products presents a critical period for examining regulatory impact on vape shop marketing and point-of-sale practices. Findings from the current study indicate that vape shops are complying with several regulations (e.g., minimum-age signage, FDA health warnings, free sampling bans). However, results also highlight the utility of mystery shoppers in identifying noncompliance (e.g., age verification, health claims, sampling, CBD product offerings). This study provides baseline data for comparison with future surveillance efforts in order to document the impact of full implementation of the FDA regulations on vape shop practices and marketing.
© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
KEYWORDS:
alternative tobacco products; e-cigarettes; policy; retail marketing; tobacco control
4.
Future Oncol. 2020 Mar 9. doi: 10.2217/fon-2020-0017. [Epub ahead of print]
Clinicopathological study of organ metastasis in endometrial cancer.
Abstract
Aim: Our aim was to analyze the clinicopathological features of lung, liver, bone and brain metastasis in patients with endometrial cancer (EC). Patients & methods: We screened patients diagnosed with EC between 2010 and 2015 from the Surveillance, Epidemiology and End Results database. Results: Among 69,027 eligible EC patients, lung metastasis was the most common. Patients with lung or liver metastasis were at higher risk of bone and brain metastases than those without lung and liver metastasis. Brain metastasis has the lowest survival time (5.0 months) in single organ metastasis. Liver and brain metastasis have the highest death rate in two organ metastasis, and lung, liver and brain metastasis had the lowest survival time (1.0 month) in multi-sites metastasis. Conclusion: Lung metastasis was the most common in EC patients. Assessing distant organ metastasis may help clinicians to determine appropriate follow-up strategy for patients with EC.
KEYWORDS:
SEER; endometrial cancer; metastasis; survival
5.
Pediatr Blood Cancer. 2020 Mar 8:e28152. doi: 10.1002/pbc.28152. [Epub ahead of print]
Impact of Medicaid expansion on access and healthcare among individuals with sickle cell disease.
Kayle M1, Valle J2, Paulukonis S2, Holl JL3, Tanabe P1, French DD4,5,6, Garg R5, Liem RI7,8, Badawy SM7,8, Treadwell MJ9.
Abstract
PURPOSE:
Sickle cell disease (SCD) is associated with high acute healthcare utilization. The purpose of this study was to examine whether Medicaid expansion in California increased Medicaid enrollment, increased hydroxyurea prescriptions filled, and decreased acute healthcare utilization in SCD.
METHODS:
Individuals with SCD (≤65 years and enrolled in Medicaid for ≥6 total calendar months any year between 2011 and 2016) were identified in a multisource database maintained by the California Sickle Cell Data Collection Program. We describe trends and changes in Medicaid enrollment, hydroxyurea prescriptions filled, and emergency department (ED) visits and hospital admissions before (2011-2013) and after (2014-2016) Medicaid expansion in California.
RESULTS:
The cohort included 3635 individuals. Enrollment was highest in 2014 and lowest in 2016 with a 2.8% annual decease postexpansion. Although <20% of the cohort had a hydroxyurea prescription filled, the percentage increased by 5.2% annually after 2014. The ED visit rate was highest in 2014 and decreased slightly in 2016, decreasing by 1.1% annually postexpansion. Hospital admission rates were similar during the pre- and postexpansion periods. Young adults and adults had higher ED and hospital admission rates than children and adolescents.
CONCLUSIONS:
Medicaid expansion does not appear to have improved enrollment or acute healthcare utilization among individuals with SCD in California. Future studies should explore whether individuals with SCD transitioned to other insurance plans or became uninsured postexpansion, the underlying reasons for low hydroxyurea utilization, and the lack of effect on hospital admissions despite a modest effect on ED visits.
© 2020 Wiley Periodicals, Inc.
KEYWORDS:
Medicaid expansion; health disparity; healthcare utilization; hydroxyurea; sickle cell disease
6.
Pediatr Blood Cancer. 2020 Mar 8:e28245. doi: 10.1002/pbc.28245. [Epub ahead of print]
Pediatric hematology and oncology fellow education in sexual and reproductive health: A survey of fellowship program directors in the United States.
Abstract
PURPOSE:
Pediatric oncology clinicians identify a need for increased sexual and reproductive health (SRH) education with adolescent and young adult (AYA) cancer patients. By surveying pediatric oncology fellowship directors, this study clarifies the state of current fellowship education about SRH for the AYA patient.
METHODS:
A survey was sent to all pediatric oncology fellowship program directors (PDs) in the United States consisting of 13 questions pertaining to three primary SRH domains: sexual health, fertility, and safe sex practices. Descriptive statistics and χ2 were used in data analyses.
RESULTS:
Sixty-three PDs responded to the survey (91% response rate). Of these, 88% reported having formal instruction regarding fertility, 41% reported curriculum regarding contraception and 30% reported some education regarding sexual health. The curriculum "being too full" was identified as a barrier to education on fertility (29%), sexual health (40%), and safe sex practices (38%). Not being a required or expected part of the program was more likely to be endorsed as a barrier for sexual health (26%) and safe sex practices (30%) compared with fertility (8%) (P < 0.005). Lack of experts to teach was a more frequently endorsed barrier to education on sexual health (47%) compared with either fertility (23%) or safe sex practices (25%) (P < 0.005).
CONCLUSIONS:
This study identifies important gaps in oncology fellow education about SRH. Future research must explore optimal education strategies that are feasible and acceptable by PDs and fellow learners, and effective in optimizing AYA SRH care.
© 2020 Wiley Periodicals, Inc.
KEYWORDS:
adolescent and young adult; late effects; late effects of cancer treatment; psychosocial; quality of life; reproductive health education; sexual and reproductive health in cancer; sexual health education; sexual health in adolescents and young adults; sexual health in pediatric oncology
7.
Mol Oncol. 2020 Mar 9. doi: 10.1002/1878-0261.12663. [Epub ahead of print]
Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma.
Mitra S1, Lauss M1, Cabrita R1, Choi J2, Zhang T2, Isaksson K3, Olsson H1, Ingvar C3, Carneiro A4, Staaf J1, Ringnér M5, Nielsen K6, Brown KM2, Jönsson G1.
Abstract
The presence of immune cells in the tumor microenvironment has been associated with response to immunotherapies across several cancer types, including melanoma. Despite its therapeutic relevance, characterization of the melanoma immune microenvironments remains insufficiently explored. To distinguish the immune microenvironment in a cohort of 180 metastatic melanoma clinical specimens, we developed a method using promoter CpG methylation of immune cell type-specific genes extracted from genome-wide methylation arrays. Unsupervised clustering identified three immune-methylation clusters with varying levels of immune CpG methylation that are related to patient survival. Matching protein and gene expression data further corroborated the identified epigenetic characterization. Exploration of the possible immune exclusion mechanisms at play revealed likely dependency on MITF protein level and PTEN loss-of-function events for melanomas unresponsive to immunotherapies (immune-low). To understand if melanoma tumors resemble other solid tumors in terms of immune-methylation characteristics, we explored 15 different solid tumor cohorts from TCGA. Low-dimensional projection based on immune cell type-specific methylation revealed grouping of the solid tumors in line with melanoma immune-methylation clusters rather than tumor types. Association of survival outcome with immune cell type-specific methylation differed across tumor and cell types. However, in melanomas immune-cell type-specific methylation was associated with inferior patient survival. Exploration of the immune-methylation patterns in a pan-cancer context suggested that specific immune-microenvironments might occur across the cancer spectrum. Together, our findings underscore the existence of diverse immune microenvironments, which may be informative for future immunotherapeutic applications.
This article is protected by copyright. All rights reserved.
KEYWORDS:
DNA methylation; immune cells; melanoma; pan-cancer; tumor microenvironment
8.
Immunol Rev. 2020 Mar 8. doi: 10.1111/imr.12844. [Epub ahead of print]
Metabolic adaptation orchestrates tissue context-dependent behavior in regulatory T cells.
Abstract
The diverse distribution and functions of regulatory T cells (Tregs) ensure tissue and immune homeostasis; however, it remains unclear which factors can guide distribution, local differentiation, and tissue context-specific behavior in Tregs. Although the emerging concept that Tregs could re-adjust their transcriptome based on their habitations is supported by recent findings, the underlying mechanisms that reprogram transcriptome in Tregs are unknown. In the past decade, metabolic machineries have been revealed as a new regulatory circuit, known as immunometabolic regulation, to orchestrate activation, differentiation, and functions in a variety of immune cells, including Tregs. Given that systemic and local alterations of nutrient availability and metabolite profile associate with perturbation of Treg abundance and functions, it highlights that immunometabolic regulation may be one of the mechanisms that orchestrate tissue context-specific regulation in Tregs. The understanding on how metabolic program instructs Tregs in peripheral tissues not only represents a critical opportunity to delineate a new avenue in Treg biology but also provides a unique window to harness Treg-targeting approaches for treating cancer and autoimmunity with minimizing side effects. This review will highlight the metabolic features on guiding Treg formation and function in a disease-oriented perspective and aim to pave the foundation for future studies.
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
KEYWORDS:
autoimmunity; cancer; immunometabolism; inflammation; metabolic adaptation; regulatory T cell
9.
Res Social Adm Pharm. 2020 Mar 5. pii: S1551-7411(19)30812-5. doi: 10.1016/j.sapharm.2020.02.021. [Epub ahead of print]
Interventions to optimise medication prescribing and adherence in older people with cancer: A systematic scoping review (protocol).
Abstract
BACKGROUND:
Older adults with cancer often require multiple medications including cancer-specific treatments and supportive care medications (e.g. analgesics), as well as medications for pre-existing medical conditions. Increasing numbers of medications pose risks of potentially inappropriate prescribing, drug-drug interactions and drug-disease interactions. The burden of treatment (i.e. the workload of healthcare and its impact on patient functioning and well-being) may also negatively affect the way patients take their medications. Non-adherence to medication in patients with cancer is associated with treatment failure and increased healthcare costs. Therefore, it is crucial that medicines are optimised for older adults with cancer to enhance appropriate prescribing, reduce the complexity of treatment regimens and minimise the risk of non-adherence.
OBJECTIVE:
To provide an overview of evaluations of interventions aimed at optimising medication prescribing and/or adherence in older adults with cancer.
METHODS:
A systematic scoping review will be undertaken. Four databases will be searched from inception: PubMed, EMBASE, CINAHL and PsycINFO. In order to meet inclusion criteria, studies must evaluate an intervention seeking to improve medication prescribing and/or adherence in older adults (aged ≥65 years) with an active cancer diagnosis using a comparative evaluation (e.g. inclusion of a control group). Two reviewers will independently screen titles and abstracts for inclusion and extract data relating to study population, intervention characteristics, outcome assessments and key findings. Extracted data will be collated using tables, figures and accompanying descriptive summaries. The review will be reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines.
PROJECT IMPACT:
The scoping nature of this review will serve to provide an overview of the existing literature on interventions aimed at optimising medication prescribing and adherence in older adults with cancer. The review findings will help to identify research gaps and highlight areas to explore further in future research.
Copyright © 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
Adherence; Cancer; Intervention; Older adults; Oncology; Prescribing
10.
Semin Oncol. 2020 Feb 21. pii: S0093-7754(20)30001-4. doi: 10.1053/j.seminoncol.2020.02.001. [Epub ahead of print]
Locally advanced rectal cancer: The past, present, and future.
Abstract
From a series of clinical trials in the last several decades, current treatment paradigms for locally advanced rectal cancer include: (1) preoperative long-course radiotherapy (RT) combined with radiosensitizing chemotherapy; (2) preoperative short-course RT alone followed by adjuvant postoperative chemotherapy; and (3) total neoadjuvant therapy with induction chemotherapy followed by chemoradiotherapy. Other strategies under active investigation in both institutional and cooperative trials include neoadjuvant chemotherapy alone without RT in select patients, total neoadjuvant therapy, watchful waiting after a clinical complete response as an alternative to surgical resection, and the use of different chemotherapeutic and targeted agents. The focus of this review is on established and novel therapeutic strategies for locally advanced rectal cancer.
Copyright © 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
Chemotherapy; Radiation therapy; Rectal cancer; Treatment
11.
Neurosurg Clin N Am. 2020 Apr;31(2):211-219. doi: 10.1016/j.nec.2019.11.006. Epub 2020 Jan 22.
Percutaneous Hybrid Therapy for Spinal Metastatic Disease: Laser Interstitial Thermal Therapy and Spinal Stereotactic Radiosurgery.
Abstract
Spinal laser interstitial thermotherapy in combination with spinal stereotactic radiosurgery has been developed as a percutaneous minimally invasive approach for the treatment of spinal metastasis. The rational and indications for this hybrid therapy are discussed, along with a brief description of the surgical technique and results. It has been the authors' experience that selected cases of high-grade metastatic epidural spinal cord compression can be effectively treated, achieving durable local control. Lessons learned during the performance of more than 100 cases are reported in addition to future directions for this treatment modality.
Copyright © 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
Image guidance; LITT; Magnetic resonance imaging; Metastatic spine tumors; Minimally invasive spine surgery; Oncology; Separation surgery; Spinal laser interstitial thermotherapy
12.
Oncology. 2020;98(3):131-137. doi: 10.1159/000505099. Epub 2020 Jan 20.
Interleukin-6: A Masterplayer in the Cytokine Network.
Abstract
Interleukin-6 (IL-6) is a member of the pro-inflammatory cytokine family, induces the expression of a variety of proteins responsible for acute inflammation, and plays an important role in the proliferation and differentiation of cells in humans. IL-6 signaling is mediated by building a complex of IL-6, the transmembrane IL-6 receptor (mIL-6R) or with soluble forms of IL-6R (sIL-6R), and the signal-transducing subunit molecule gp130. Therefore, three modes for IL-6 signaling may occur in which IL-6 is binding to mIL-6R (classic), to sIL-6R (trans-signaling), or is joined through IL-6R to gp130 on nearby located cells (trans-presentation). These pathways, and the fact that gp130 is ubiquitously expressed, lead to the pleiotropic functions of IL-6. The control of IL-6 signaling is regulated through the induction of suppressor molecules after activation of the IL-6 pathways as well as through the presence of sIL-6R and gp130 forms in the blood. Vice versa, an overproduction of IL-6 and dysregulation of the IL-6 signaling pathways can result in inflammatory and autoimmune disorders as well as cancer development suggesting that IL-6 plays a significant role in the human cytokine network. Several therapeutic agents have been evaluated for inhibiting the cytokine itself, the signaling via the IL-6 receptor, or target kinases (e.g., JAK/STAT) associated with the signaling pathways. Amongst others, tocilizumab (anti-IL-6R humanized antibody) has been approved for the treatment of rheumatoid arthritis, cytokine release syndrome, and idiopathic multicentric Castleman's disease (iMCD), whereas siltuximab (an IL-6 antagonist) received approval for iMCD only. Although not all IL-6-associated diseases respond to IL-6 blockade, a better understanding of the underlying mechanisms of the IL-6 pathways may, therefore, help to find the best treatment for IL-6-associated diseases in the near future.
© 2020 S. Karger AG, Basel.
KEYWORDS:
JAK/STAT; Molecular signaling ; Interleukin-6 ; IL-6 inhibition
13.
Folia Biol (Praha). 2019;65(3):142-151.
Deregulation of Selected MicroRNAs in Sinonasal Squamous Cell Carcinoma: Searching for Potential Prognostic Biomarkers.
Kovaříková J1, Baranová I1, Laco J2, Rozkošová K2, Vošmíková H2, Vošmík M3, Dundr P4, Němejcová K4, Michálek J5, Palička V1, Chmelařová M1.
Abstract
Sinonasal carcinomas are head and neck tumours arising from the nasal cavity and paranasal sinuses characterized by unfavourable outcome, difficult treatment, diagnosis and prognosis. MicroRNAs are key molecules in the regulation of development and progression of cancer and their expression profiles could be used as prognostic biomarkers, to predict the patients' survival and response to treatment. In this study, we used quantitative real‑time PCR with TaqMan® Advanced miRNA Assays to investigate the relative expression values of selected micro- RNAs in a unique set of formalin-fixed paraffin-embedded tissue samples obtained from 46 patients with sinonasal squamous cell carcinoma. Our results showed statistically significant up-regulation of three mature microRNAs: miR-9-5p (fold change: 6.80), miR-9-3p (fold change: 3.07) and let-7d (fold change: 3.93) in sinonasal carcinoma patients. Kaplan-Meier survival analysis and logrank test identified association between higher expression of miR-9-5p and longer survival of the patients (P = 0.0264). Lower expression of let-7d was detected in the patients with impaired survival, and higher expression of miR-137 was linked to shorter survival of the patients. We also identified several correlations between expression of the studied microRNAs and recorded clinicopathological data. Higher expression of miR-137 and lower expression of let-7d correlated with local recurrence (P = 0.045 and P = 0.025); lower expression of miR-9-5p and higher expression of miR-155-5p correlated with regional recurrence (P = 0.045 and P = 0.036). Higher expression of miR-9-3p correlated with occupational risk (P = 0.031), presence of vascular invasion (P = 0.013) and perineural invasion (P = 0.031). Higher expression of miR-155-5p was present in the samples originating from maxillary sinus (P = 0.011), cN1-3 classified tumours (P = 0.009) and G2-3 classified tumours (P = 0.017). In conclusion, our study supports the hypothesis of future prospect to use expression of miRNAs as prognostic biomarkers of squamous cell sinonasal carcinoma. In particular, miR-9-5p and miR-9-3p seem to be important members of the sinonasal cancer pathogenesis.
14.
PLoS One. 2019 Oct 9;14(10):e0223639. doi: 10.1371/journal.pone.0223639. eCollection 2019.
Illuminating biological pathways for drug targeting in head and neck squamous cell carcinoma.
Choonoo G1,2, Blucher AS1,3, Higgins S2, Boardman M2, Jeng S1,4, Zheng C1,2, Jacobs J1,2,5, Anderson A6, Chamberlin S2, Evans N2, Vigoda M3,6, Cordier B2, Tyner JW1,3,7, Kulesz-Martin M3,6, McWeeney SK1,2,4, Laderas T1,2.
Abstract
Head and neck squamous cell carcinoma (HNSCC) remains a morbid disease with poor prognosis and treatment that typically leaves patients with permanent damage to critical functions such as eating and talking. Currently only three targeted therapies are FDA approved for use in HNSCC, two of which are recently approved immunotherapies. In this work, we identify biological pathways involved with this disease that could potentially be targeted by current FDA approved cancer drugs and thereby expand the pool of potential therapies for use in HNSCC treatment. We analyzed 508 HNSCC patients with sequencing information from the Genomic Data Commons (GDC) database and assessed which biological pathways were significantly enriched for somatic mutations or copy number alterations. We then further classified pathways as either "light" or "dark" to the current reach of FDA-approved cancer drugs using the Cancer Targetome, a compendium of drug-target information. Light pathways are statistically enriched with somatic mutations (or copy number alterations) and contain one or more targets of current FDA-approved cancer drugs, while dark pathways are enriched with somatic mutations (or copy number alterations) but not currently targeted by FDA-approved cancer drugs. Our analyses indicated that approximately 35-38% of disease-specific pathways are in scope for repurposing of current cancer drugs. We further assess light and dark pathways for subgroups of patient tumor samples according to HPV status. The framework of light and dark pathways for HNSCC-enriched biological pathways allows us to better prioritize targeted therapies for further research in HNSCC based on the HNSCC genetic landscape and FDA-approved cancer drug information. We also highlight the importance in the identification of sub-pathways where targeting and cross targeting of other pathways may be most beneficial to predict positive or negative synergy with potential clinical significance. This framework is ideal for precision drug panel development, as well as identification of highly aberrant, untargeted candidates for future drug development.
- PMID:
- 31596908
- PMCID:
- PMC6785123
- DOI:
- 10.1371/journal.pone.0223639
- [Indexed for MEDLINE]
15.
PLoS One. 2019 Sep 4;14(9):e0221941. doi: 10.1371/journal.pone.0221941. eCollection 2019.
Detection of MYD88 L265P mutation by next-generation deep sequencing in peripheral blood mononuclear cells of Waldenström's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance.
Nakamura A1,2,3, Ohwada C1, Takeuchi M1, Takeda Y1, Tsukamoto S1, Mimura N1,4, Nagisa OH1, Sugita Y5, Tanaka H6, Wakita H3, Aotsuka N3, Matsue K7, Yokote K2, Ohara O8,9, Nakaseko C1,10, Sakaida E1,2.
Abstract
We investigated the feasibility of using next-generation sequencing (NGS) technique using molecular barcoding technology to detect MYD88 L265P mutation in unselected peripheral blood mononuclear cells (PBMCs) in 52 patients with Waldenström's macroglobulinemia [1] and 21 patients with IgM-monoclonal gammopathy of undetermined significance (MGUS). The NGS technique successfully detected the MYD88 L265P in unselected PBMCs at a sensitivity of 0.02%, which was ×5 higher than that of AS-PCR. All the results between paired BM and PB samples from 2 IgM MGUS and 4 untreated WM patients matched completely. MYD88 L265P mutation was detected in 14/21 (66.7%), 14/19 (73.7%), and 10/33 (30.3%) with the median mutant allele burden of 0.36% (range, 0.06-2.85%), 0.48% (range, 0.02-32.3%), and 0.16% (range, 0.02-33.8%), in IgM-MGUS, untreated WM, and previously treated WM, respectively. Multiple linear regression analysis identified an absolute peripheral lymphocyte count as the positive predictor of PB mutant allele burden (R2 = 0,72, P<0.0001). Our non-invasive, simple NGS method has the potential to detect MYD88 L265P mutations in PBMCs of IgM MGUS and WM patients, which may especially utilized for monitoring minimal residual tumor burden after treatment.
- PMID:
- 31483817
- PMCID:
- PMC6726192
- DOI:
- 10.1371/journal.pone.0221941
- [Indexed for MEDLINE]
16.
Acta Oncol. 2019 Oct;58(10):1410-1415. doi: 10.1080/0284186X.2019.1654129. Epub 2019 Aug 21.
NTCP model validation method for DAHANCA patient selection of protons versus photons in head and neck cancer radiotherapy.
Hansen CR1,2,3,4, Friborg J3,5, Jensen K3, Samsøe E3,6, Johnsen L1, Zukauskaite R2,7, Grau C3,8, Maare C6, Johansen J7, Primdahl H8, Bratland Å9, Kristensen CA5, Andersen M10, Eriksen JG8,11, Overgaard J11.
Abstract
Introduction: Prediction models using logistic regression may perform poorly in external patient cohorts. However, there is a need to standardize and validate models for clinical use. The purpose of this project was to describe a method for validation of external NTCP models used for patient selection in the randomized trial of protons versus photons in head and neck cancer radiotherapy, DAHANCA 35. Material and methods: Organs at risk of 588 patients treated primarily with IMRT in the randomized controlled DAHANCA19 trial were retrospectively contoured according to recent international recommendations. Dose metrics were extracted using MatLab and all clinical parameters were retrieved from the DAHANCA database. The model proposed by Christianen et al. to predict physician-rated dysphagia was validated through the closed testing, where change of the model intercept, slope and individual beta's were tested for significant prediction improvements. Results: Six months prevalence of dysphagia in the validation cohort was 33%. The closed testing procedure for physician-rated dysphagia showed that the Christianen et al. model needed an intercept refitting for the best match for the Danish patients. The intercept update increased the risk of dysphagia for the validation cohort by 7.9 ± 2.5% point. For the raw model performance, the Brier score (mean squared residual) was 0.467, which improved significantly with a new intercept to 0.415. Conclusions: The previously published Dutch dysphagia model needed an intercept update to match the Danish patient cohort. The implementation of a closed testing procedure on the current validation cohort allows quick and efficient validation of external NTCP models for patient selection in the future.
17.
PLoS One. 2019 Jun 13;14(6):e0218330. doi: 10.1371/journal.pone.0218330. eCollection 2019.
Development of novel monoclonal antibodies with specific binding affinity for denatured human CD26 in formalin-fixed paraffin-embedded and decalcified specimens.
Hatano R1, Yamada T2,3, Madokoro H3, Otsuka H1, Komiya E1, Itoh T1, Narita Y1, Iwata S1, Yamazaki H1, Matsuoka S4, Dang NH5, Ohnuma K1, Morimoto C1.
Abstract
A 110-kDa type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular region, CD26 has a multitude of biological functions and plays an important role in the regulation of inflammatory responses and tumor biology. Our work has focused on CD26 as a novel therapeutic target for various tumors and immune disorders, and we have recently developed a humanized anti-CD26 monoclonal antibody (mAb), YS110, which has promising safety profile and clinical activity in patients with malignant pleural mesothelioma. The development of an anti-human CD26 mAb that can clearly and reliably detect the denatured CD26 molecule in formalin-fixed paraffin-embedded (FFPE) tissues in the clinical setting is therefore of the utmost importance. To develop novel anti-CD26 mAbs capable of binding to denatured CD26, we immunized mice with urea-treated CD26 protein. Hybridoma supernatants were screened for specific reactivity with human CD26 by immunostaining through the use of a set of FFPE human CD26-positive or negative tumor cell lines. This screening method enables us to develop novel anti-human CD26 mAbs suitable for immunohistochemical staining of CD26 in FFPE non-tumor and tumor tissue sections with reliable clarity and intensity. Specifically, these mAbs display strong binding affinity to denatured human CD26 rather than undenatured human CD26, and are capable of detecting denatured human CD26 in decalcified specimens. These novel anti-CD26 mAbs are potentially useful for the analysis of CD26 expression in cancer patients with bony metastasis, and may help decide the appropriateness of YS110 therapy for future cancer patients.
- PMID:
- 31194830
- PMCID:
- PMC6564021
- DOI:
- 10.1371/journal.pone.0218330
- [Indexed for MEDLINE]
18.
J Gynecol Oncol. 2019 Jul;30(4):e57. doi: 10.3802/jgo.2019.30.e57. Epub 2019 Feb 26.
Efficacy and fertility outcomes of levonorgestrel-releasing intra-uterine system treatment for patients with atypical complex hyperplasia or endometrial cancer: a retrospective study.
Leone Roberti Maggiore U1, Martinelli F2, Dondi G2, Bogani G2, Chiappa V2, Evangelista MT2, Liberale V2, Ditto A2, Ferrero S3,4, Raspagliesi F2.
Abstract
OBJECTIVE:
To investigate the efficacy of levonorgestrel-releasing intra-uterine system (LNG-IUS) treatment in patients affected by atypical complex hyperplasia/endometrial cancer (ACH/EC) wishing to preserve their fertility and to present fertility outcomes of those patients who actively tried to conceive.
METHODS:
Data of consecutive women with ACH/EC who underwent fertility-sparing treatment using LNG-IUS were retrospectively evaluated.
RESULTS:
Overall, 48 patients and the mean (±standard deviation) length of follow-up was 82.6±47.2 months. Among patients with ACH, 25/28 (89.3%) had a complete response (CR), 2/28 (7.1%) had a partial response (PR) and 1/28 (3.6%) had a progressive disease (PD). Mean (±standard deviation) time to CR was 6.7±4.0 months. Among patients with G1 EC, 13/16 (81.3%) had a CR, 1/16 (6.3%) had a PR and 2/16 (12.5%) had a PD. Mean (±standard deviation) time to CR was 5.0±2.9 months. Among patients with G2 EC, 3/4 (75.0%) had a CR and 1/4 (25.0%) had a PD. Mean (±standard deviation) time to CR was 4.0±0 months. Only 19 (39.6%) patients who had CR actually attempted to conceive. Eleven (57.9%) women tried to conceive naturally while 8 (42.1%) women underwent an in vitro fertilization (IVF). Fourteen (73.7%) patients wishing to conceive achieved a pregnancy (6 spontaneously and 8 through IVF).
CONCLUSIONS:
Fertility-sparing treatment of patient with ACH/EC with LNG-IUS achieves high regression rates and good fertility outcomes. Future larger multi-institutional studies should be designed to confirm these preliminary findings.
Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.
KEYWORDS:
Endometrial Cancer; Fertility; Hyperplasia; Levonorgestrel; Pregnancy
Comment in
- PMID:
- 31074240
- PMCID:
- PMC6543108
- DOI:
- 10.3802/jgo.2019.30.e57
- [Indexed for MEDLINE]
19.
Expert Opin Drug Deliv. 2019 Apr;16(4):441-451. doi: 10.1080/17425247.2019.1598374. Epub 2019 Apr 18.
Epidermal growth factor receptor (EGFR)-targeted therapies in mesothelioma.
Abstract
INTRODUCTION:
Malignant mesothelioma (MM) is an aggressive malignancy arising from the mesothelial cells lining the pleura and other serosal membranes. It is associated with an extremely poor prognosis and has limited therapeutic options.
AREAS COVERED:
Epidermal growth factor receptor (EGFR) is known to be highly overexpressed in mesothelioma with reported EGFR overexpression between 44 to 97%. Given this, several anti-EGFR agents have been trialed in mesothelioma. In this review, we provide an overview of the current available data on anti-EGFR therapies in MM and future directions of investigation with these targeted agents in MM.
EXPERT OPINION:
While many anti-EGFR therapies have failed to show significant efficacy in the management of MM, the pathway is biologically active and its abrogation preclinically points toward it being a valid target. Toward targeting the pathway, many novel EGFR-based therapies are still being investigated. Current ongoing research of interest in MM include EGFR-targeted nanotechnology approach for drug delivery, antibodies targeting the extracellular EGFR and potentially anti-EGFR antibody drug conjugates.
KEYWORDS:
EGFR overexpression; Epidermal growth factor receptor (EGFR); malignant mesothelioma; targeted therapies
20.
JAMA Ophthalmol. 2019 May 1;137(5):537-542. doi: 10.1001/jamaophthalmol.2019.0238.
Validation Study of the AJCC Cancer Staging Manual, Eighth Edition, Staging System for Eyelid and Periocular Squamous Cell Carcinoma.
Erratum in
- Error in Byline. [JAMA Ophthalmol. 2019]
Abstract
IMPORTANCE:
To our knowledge, there are no validation studies to date of the prognostic value of the AJCC Cancer Staging Manual, eighth edition (AJCC 8), criteria for eyelid and periocular squamous cell carcinoma.
OBJECTIVE:
To determine the association of tumor (T) category in AJCC 8 with local recurrence, nodal metastasis, distant metastasis, and disease-specific survival (DSS) for eyelid and periocular squamous cell carcinoma.
DESIGN, SETTING, AND PARTICIPANTS:
In this retrospective, single-center cohort study, 109 consecutive patients with eyelid and periocular squamous cell carcinoma treated from January 1999 to April 2018 were included. Patients with secondary involvement of the periocular region were excluded.
MAIN OUTCOMES AND MEASURES:
Local recurrence, nodal metastasis, distance metastasis, and DSS.
RESULTS:
Of the 109 included patients, 81 (74.3%) were male, and the median (range) age was 66 (40-91) years. At presentation, 43 patients (39.4%) had recurrent tumor, 4 (3.7%) had nodal metastasis, and 1 (0.9%) had distant metastasis. The median (range) follow-up was 23 (1-161) months. During follow-up, 11 patients (10.1%) developed local recurrence, 7 (6.4%) developed nodal metastasis, 2 (1.8%) developed distant metastasis, and 9 (8.3%) died of disease. The 5-year DSS rate was 87.7% (95% CI, 79.5-96.9). Chronic immunosuppression (hazard ratio, 47.24; 95% CI, 7.33-304.30; P < .001) and presentation with recurrent squamous cell carcinoma (hazard ratio, 5.22; 95% CI, 1.12-24.31; P = .04) were associated with local recurrence during follow-up. Of the 11 patients with local recurrence during follow-up, 7 (64%) had perineural invasion. T category was associated with nodal metastasis; clinical stage of T2c or worse at presentation was associated with higher risk of nodal metastasis and death of disease but not with a higher risk of local recurrence. Distant metastasis was associated with nodal metastasis at presentation (hazard ratio, 32.50; 95% CI, 1.97-536.40; P = .02) and during follow-up. A total of 33 patients (30.3%) had different T categories depending on whether disease was staged according to the seventh or eighth edition of the AJCC Cancer Staging Manual. Compared with AJCC 7, AJCC 8 showed a better predictive value in terms of local recurrence (T3, 17% vs 14%; T4, 11% vs 16%) and DSS.
CONCLUSIONS AND RELEVANCE:
These findings suggest that T category in AJCC 8 is associated with nodal metastasis and DSS. Immunosuppression and presentation with recurrent disease are associated with increased risk of future local recurrence. Patients with tumors of clinical stage T2c or worse at presentation are at increased risk of nodal metastasis and worse DSS and should undergo surveillance for nodal metastasis. Future studies, ideally prospective in design, could provide greater confidence in these findings.
- PMID:
- 30869769
- PMCID:
- PMC6512305
- [Available on 2020-03-14]
- DOI:
- 10.1001/jamaophthalmol.2019.0238
- [Indexed for MEDLINE]
21.
Curr Opin Urol. 2019 May;29(3):210-215. doi: 10.1097/MOU.0000000000000601.
Trimodality therapy for bladder cancer: modern management and future directions.
Abstract
PURPOSE OF REVIEW:
This review examines both trimodality therapy (TMT) in the definitive management of bladder cancer as well as the use of adjuvant radiotherapy for bladder cancer with a specific focus on publications from the last 2 years.
RECENT FINDINGS:
TMT is an effective management strategy for muscle invasive bladder cancer with outcomes similar to radical cystectomy. Effectiveness of this strategy exists in variant histologies and can be personalized with use of biomarkers. There is a role for adjuvant radiotherapy in locally advanced bladder cancer, especially in the age of improved imaging and modern radiotherapy techniques.
SUMMARY:
This review should provide the reader data necessary to support use of TMT and adjuvant radiation therapy in their clinic.
22.
Curr Opin Urol. 2019 May;29(3):203-209. doi: 10.1097/MOU.0000000000000605.
Urinary biomarkers in bladder cancer: where do we stand?
Abstract
PURPOSE OF REVIEW:
To provide a current comprehensive review of the available urinary biomarkers for the detection and surveillance of bladder cancer.
RECENT FINDINGS:
The limitations of urine cytology and invasive nature of cystoscopic evaluation have led to a growing search for an ideal, cost-effective biomarker with acceptable sensitivity and specificity. Current FDA approved biomarkers such as UroVysion fluorescent in situ hybridization, Immunocyt, and nuclear matrix protein 22 do not have the specificity, and thus positive predictive value to warrant their cost as a routine adjunct or replacement for cystoscopy. Several promising commercially available assays such as Cxbladder, Assure MDx, and Xpert BC may perform better than cytology in select populations. Novel genomic, epigenetic, inflammatory, and metabolomic-based assays are being analyzed as potential urinary biomarkers.
SUMMARY:
Urinary biomarkers with high sensitivity and specificity are an unmet need in bladder cancer. Several new assays may meet these criteria and future research may justify use in clinical practice.
23.
J Palliat Med. 2018 Mar;21(S2):S17-S27. doi: 10.1089/jpm.2017.0459. Epub 2017 Nov 1.
Achieving Goal-Concordant Care: A Conceptual Model and Approach to Measuring Serious Illness Communication and Its Impact.
Abstract
BACKGROUND:
High-quality care for seriously ill patients aligns treatment with their goals and values. Failure to achieve "goal-concordant" care is a medical error that can harm patients and families. Because communication between clinicians and patients enables goal concordance and also affects the illness experience in its own right, healthcare systems should endeavor to measure communication and its outcomes as a quality assessment. Yet, little consensus exists on what should be measured and by which methods.
OBJECTIVES:
To propose measurement priorities for serious illness communication and its anticipated outcomes, including goal-concordant care.
METHODS:
We completed a narrative review of the literature to identify links between serious illness communication, goal-concordant care, and other outcomes. We used this review to identify gaps and opportunities for quality measurement in serious illness communication.
RESULTS:
Our conceptual model describes the relationship between communication, goal-concordant care, and other relevant outcomes. Implementation-ready measures to assess the quality of serious illness communication and care include (1) the timing and setting of serious illness communication, (2) patient experience of communication and care, and (3) caregiver bereavement surveys that include assessment of perceived goal concordance of care. Future measurement priorities include direct assessment of communication quality, prospective patient or family assessment of care concordance with goals, and assessment of the bereaved caregiver experience.
CONCLUSION:
Improving serious illness care necessitates ensuring that high-quality communication has occurred and measuring its impact. Measuring patient experience and receipt of goal-concordant care should be our highest priority. We have the tools to measure both.
KEYWORDS:
goal-concordant care; quality measurement; serious illness communication
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