Early detection of pancreatic cancers by novel nanobiosensor-based protease biomarkers using hierarchical decision structure.

e16273 Background: There is a critical need to develop fast, reliable, and cost-effective methods for the detection of pancreatic cancer (PC) at the earliest stage to maximize the impact of treatment. To-date, early detection of PC is close to impossible due to the location of the pancreas and the absence of characteristic symptoms in early cancer stages. Methods: Our team of clinicians and scientists has established a fast and reliable nanobiosensor technology that comprises iron/iron oxide nanoparticles attached to a protease or arginase activatable FRET pair (tetrakis (4- carboxyphenyl) porphyrin (TCPP) /cyanine 5.5). Arginase and seven proteases (MMP1, 3, and 9, cathepsin B, and E, urokinase plasminogen activator, and neutrophil elastase) were identified using the Gene Expression Omnibus (GEO) web tool based on their different expression pattern in pancreatic cancer patients, pancreatitis and healthy control subjects. Protease/arginase activities were measured in serum after 1h of incubation. Based on this data, a novel engineering approach to improved early stage detection of pancreatic cancer is reported here. This study was funded by American Cancer Society Institutional Research Grant (IRG‐16‐194‐07), awarded to the University of Kansas Medical Center. Results: In our study, 159 patients were enrolled at KU Cancer Center from 2000-2019, 47 with metastatic PC, 36 with localized PC, 26 pancreatitis and 50 healthy controls using KUCC Biospecimen Repository. The problem of early stage detection of pancreatic cancer can be modeled as a multi-class classification problem. Conventional classification approaches provide at most 77% accuracy for the dataset under consideration. A new hierarchical decision structure with specific feature engineering at each step is introduced here to improve the performance of the classifier. The fundamental premise of this information fusion-based framework involves tailoring the statistically most significant features with appropriate weights to execute an efficient binary classification task at each hierarchical step. An overall accuracy of 95% was achieved for the detection of patients with early pancreatic cancer (see table). Conclusions: Because of the dire survival statistics of pancreatic cancer, detection at the earliest possible time by means of a liquid biopsy will offer the greatest benefit. Novel nanobiosensor based protease biomarkers achieved high accuracy in early detection of pancreatic cancers by applying hierarchical decision structure. Our results need validation in a larger cohort. Predicted true class considering the following combination of classification methods: Step1 – kNN*, step2 – kNN*, step3 – RFC* (Accuracy = 94.97%).[Table: see text]

Download Full-text

The role of chest computed tomography in the management of COVID-19: A review of results and recommendations

Experimental Biology and Medicine ◽

10.1177/1535370220938315 ◽

2020 ◽

Vol 245 (13) ◽

pp. 1096-1103 ◽

Cited By ~ 1

Author(s):

Molly D Wong ◽

Theresa Thai ◽

Yuhua Li ◽

Hong Liu

Keyword(s):

Computed Tomography ◽

Early Detection ◽

Technology Development ◽

Early Stage ◽

Chest Ct ◽

High Rate ◽

Chest Computed Tomography ◽

Severity Of The Disease ◽

The Impact

The rapid and dramatic increase in confirmed cases of COVID-19 has led to a global pandemic. Early detection and containment are currently the most effective methods for controlling the outbreak. A positive diagnosis is determined by laboratory real-time reverse transcriptase polymerase chain reaction (rRT-PCR) testing, but the use of chest computed tomography (CT) has also been indicated as an important tool for detection and management of the disease. Numerous studies reviewed in this paper largely concur in their findings that the early hallmarks of COVID-19 infection are ground-glass opacities (GGOs), often with a bilateral and peripheral lung distribution. In addition, most studies demonstrated similar CT findings related to the progression of the disease, starting with GGOs in early disease, followed by the development of crazy paving in middle stages and finally increasing consolidation in the later stages of the disease. Studies have reported a low rate of misdiagnosis by chest CT, as well as a high rate of misdiagnosis by the rRT-PCR tests. Specifically, chest CT provides more accurate results in the early stages of COVID-19, when it is critical to begin treatment as well as isolate the patient to avoid the spread of the virus. While rRT-PCR will probably remain the definitive final test for COVID-19, until it is more readily available and can consistently provide higher sensitivity, the use of chest CT for early stage detection has proven valuable in avoiding misdiagnosis as well as monitoring the progression of the disease. With the understanding of the role of chest CT, researchers are beginning to apply deep learning and other algorithms to differentiate between COVID-19 and non-COVID-19 CT scans, determine the severity of the disease to guide the course of treatment, and investigate numerous additional COVID-19 applications. Impact statement The impact of the COVID-19 pandemic has been worldwide, and clinicians and researchers around the world have been working to develop effective and efficient methods for early detection as well as monitoring of the disease progression. This minireview compiles the various agency and expert recommendations, along with results from studies published in numerous countries, in an effort to facilitate the research in imaging technology development to benefit the detection and monitoring of COVID-19. To the best of our knowledge, this is the first review paper on the topic, and it provides a brief, yet comprehensive analysis.

Download Full-text

Circulating Cell-Free Tumour DNA for Early Detection of Pancreatic Cancer

Cancers ◽

10.3390/cancers12123704 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3704

Author(s):

Jedrzej J. Jaworski ◽

Robert D. Morgan ◽

Shivan Sivakumar

Keyword(s):

Pancreatic Cancer ◽

Early Detection ◽

Early Stage ◽

Lower Sensitivity ◽

Detection Rates ◽

Early Stage Disease ◽

Genetic Sequencing ◽

Number Of Factors ◽

Stage Disease ◽

Invasive Method

Pancreatic cancer is a lethal disease, with mortality rates negatively associated with the stage at which the disease is detected. Early detection is therefore critical to improving survival outcomes. A recent focus of research for early detection is the use of circulating cell-free tumour DNA (ctDNA). The detection of ctDNA offers potential as a relatively non-invasive method of diagnosing pancreatic cancer by using genetic sequencing technology to detect tumour-specific mutational signatures in blood samples before symptoms manifest. These technologies are limited by a number of factors that lower sensitivity and specificity, including low levels of detectable ctDNA in early stage disease and contamination with non-cancer circulating cell-free DNA. However, genetic and epigenetic analysis of ctDNA in combination with other standard diagnostic tests may improve early detection rates. In this review, we evaluate the genetic and epigenetic methods under investigation in diagnosing pancreatic cancer and provide a perspective for future developments.

Download Full-text

Program development of a preceptor bootcamp for operational pharmacy preceptors

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxz289 ◽

2020 ◽

Vol 77 (Supplement_1) ◽

pp. S2-S7

Author(s):

Devlin V Smith ◽

Stefani Gautreaux ◽

Alison M Gulbis ◽

Jeffrey J Bruno ◽

Kevin Garey ◽

...

Keyword(s):

Survey Methodology ◽

Medical Center ◽

Academic Medical Center ◽

Cancer Center ◽

University Of Texas ◽

Qualitative Feedback ◽

Md Anderson ◽

The University ◽

Functional Areas ◽

The Impact

Abstract Purpose To describe the development, design, and implementation of a pilot preceptor development bootcamp and feedback related to its feasibility and impact on operational pharmacy preceptors. Summary The University of Texas MD Anderson Cancer Center designed and implemented a pilot preceptor development bootcamp for operational staff pharmacists serving as residency preceptors for longitudinal weekend staffing experiences. A systematic, multipronged approach was taken to identify preceptor development gaps and design a full-day bootcamp curriculum. The resultant curriculum was comprised of content in major functional areas including using the 4 preceptor roles, documenting performance, giving and receiving feedback, and dealing with difficult situations or learners. The impact of the pilot preceptor development bootcamp was assessed using survey methodology and qualitative feedback from debrief discussions. Conclusion Implementation of a pilot preceptor bootcamp program addressing major areas of precepting skill was well received, resulted in positive feedback from operational pharmacy preceptors, and was feasible to implement at a large academic medical center.

Download Full-text

An assessment of the impact of geographic variation on resection rates and survival for early-stage pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15052 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15052-e15052

Author(s):

Bradley D. McDowell ◽

Brian J. Smith ◽

Anna M Button ◽

James R. Howe ◽

Elizabeth A. Chrischilles ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Pancreatic Adenocarcinoma ◽

Early Stage ◽

Stage I ◽

Stage Ii ◽

Survival Times ◽

Resection Rate ◽

Selection Factors ◽

The Impact

e15052 Background: Pancreatic resection is the only known curative option for pancreatic adenocarcinoma. Resection has been previously reported to be underutilized in patients with early stage disease. To develop a better understanding of this issue and control for treatment selection factors, we examined the relationship between geographic area resection rates and survival in patients with stage I/II pancreatic cancer. Methods: We queried Surveillance, Epidemiology, and End Results (SEER) data for patients with stage I/II cancer of the pancreatic head diagnosed from 2004-2009. We excluded patients with less than 3mo survival. Resection rates were calculated within Health Service Areas (HSAs) across all 18 SEER regions. Resection rate was defined as the number of patients who had an operation divided by the total number diagnosed with early stage pancreatic cancer. Multivariate Cox regression was used to estimate the overall survival effect of HSA rates while controlling for age, gender, marital status, poverty level, education, and AJCC stage. Results: 8,323 patients with stage I (n=1,454) and stage II (n=6,869) disease were analyzed. Pancreatectomy was performed in 476 patients (32.7%) with stage I disease and 3,846 (56.0%) with stage II disease. HSA resection rates were arranged into five groups (quintiles) which ranged from 42.7 to 65.7% (Table). Across the quintiles, median overall survival increased from 11 to 14 months, suggesting a positive association with resection rate. Multivariate analysis revealed that for every 10.00% increase in resection rate, the risk of overall death decreased by 5.26% (p<0.001). Conclusions: Patients with early stage pancreatic cancer who live in areas with higher resection rates have longer average survival times. Because geography should not influence treatment response, we conclude that efforts to raise resection rates should increase survival times in patients for whom there is uncertainty about the risk/benefits of resection. [Table: see text]

Download Full-text

Interim results of a screening protocol for early detection of pancreatic cancer in asymptomatic high-risk patients.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.223 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 223-223

Author(s):

Alexandra Gangi ◽

Mokenge Peter Malafa ◽

Jason Klapman

Keyword(s):

Pancreatic Cancer ◽

Clinical Trial ◽

High Risk ◽

Early Detection ◽

Surgical Resection ◽

Early Stage ◽

Needle Aspiration ◽

Screening Protocol ◽

Risk Patients ◽

Asymptomatic Individuals

223 Background: Pancreatic cancer (PC) is the 4th leading cause of cancer deaths in the US but is rarely diagnosed at an early curable stage. Early detection of PC will have measurable improved outcomes in affected patients. This study sets out to evaluate if EUS can detect early stage pre-cancerous or cancerous changes in the pancreas of high risk (HR) patients. Methods: After IRB review, a clinical trial (NCT01662609) to evaluate HR patients was opened to accrual. Study subjects met specified inclusion and exclusion criteria as defined by the protocol. Enrolled subjects underwent EUS followed by screening as defined by study protocol: subjects with normal EUS underwent repeat EUS at 1 year; subjects with abnormal EUS underwent fine needle aspiration (FNA) if a mass or cyst was found and measured ≥ 5mm and did not undergo FNA if the lesion measured < 5mm. Those with indeterminate or benign FNA underwent pancreatic CT scan with repeat EUS/FNA at 3 or 6 months respectively. Those with positive FNA were treated appropriately based on findings. Patients with mass/cyst < 5mm underwent repeat EUS/FNA at 3 months. Targeted follow-up is 5 years. Results: Of the 52 subjects accrued thus far, 41 were available for interim analysis. Twenty-seven (67%) subjects had a normal EUS while 14 (34%) subjects had abnormal findings. Two patients had large cysts with FNA consistent with an intraductal papillary mucinous neoplasms (IPMN). These 2 subjects ultimately underwent surgical resection. The 12 remaining subjects had at least 1 subcentimeter lesion and are being routinely screened per the outlined protocol. Conclusions: EUS screening of asymptomatic individuals who are at high risk for pancreatic cancer as defined by our inclusion criteria frequently detects abnormal lesions in the pancreas. These lesions include high risk IPMNs that warrant surgical resection. Our results validate the results of other high risk screening protocols and support the screening of individuals who are at high risk for development of pancreatic cancer. Clinical trial information: NCT01662609.

Download Full-text

Compliance with National Comprehensive Cancer Network guidelines for antiemesis in cisplatin regimens.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.7_suppl.280 ◽

2016 ◽

Vol 34 (7_suppl) ◽

pp. 280-280

Author(s):

Terri P. Wolf ◽

Dana Ann Little

Keyword(s):

National Comprehensive Cancer Network ◽

Medical Center ◽

Academic Medical Center ◽

Cancer Center ◽

Adherence Rate ◽

Cancer Centers ◽

Nccn Guidelines ◽

Guideline Compliance ◽

Cancer Network ◽

The Impact

280 Background: The members of a network of community cancer centers affiliated with an academic medical center report following National Comprehensive Cancer Network (NCCN) guidelines. To determine guideline compliance, cisplatin regimens were audited. Cisplatin was selected because of its wide use, high emetic potential, and the impact on QOL for patients with unmanaged nausea and vomiting.The community cancer centers affiliated with an academic medical center report following National Comprehensive Cancer Network (NCCN) guidelines for treatment plans. To determine guideline compliance rates, cisplatin regimens were audited. Cisplatin was selected because of its wide use, high emetic potential, and the impact on QOL for patients with unmanaged nausea and vomiting. Methods: Prior to a chart audit, medical oncologists were surveyed on their knowledge of NCCN antiemesis guidelines, frequency of prescribing based on guidelines, and reasons for not using guidelines. Auditors identified patient charts through billing records and reviewed cycle 1 day 1 orders of cisplatin regimens. Secondary data was collected on hydration orders and home medications for antiemesis. Results: Guideline adherence varied from 0% to 76% with overall adherence at 28%. Dexamethasone doses ranged from 2-20 mg (guideline 12 mg) as did serotonin antagonists (5HT3) ordered at higher IV doses of 24-32 mg (guideline 8-16 mg). Conclusions: Although cancer centers report following the guidelines, this study did not find consistent adherence. The cancer center with the highest adherence rate works closely with a pharmacist and has built order sets with the guidelines. One cancer center had wide variances among practitioners. The variances increase the potential for error. The cancer center with lowest adherence rate used 10 mg doses of dexamethasone because the drug is delivered in 10 mg vials. This study identified multiple systems issues impacting guideline compliance. Managing nausea and vomiting is important for patient QOL and to manage costs by decreasing hospitalizations, treatment delays, and nutritional deficits. Understanding prescribing habits relative to guidelines provides an opportunity to change practice and reduce variability.

Download Full-text

Hypoxia induced HIF1a-mediated O-GalNAc glycosylation of cytosolic O-GlcNAcylated proteins to regulate signaling pathways in pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15739 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15739-e15739

Author(s):

Gerrit Wolters-Eisfeld ◽

Baris Mercanoglu ◽

Alina Strohmaier ◽

Cenap Guengoer ◽

Jakob R. Izbicki ◽

...

Keyword(s):

Pancreatic Cancer ◽

Early Stage ◽

Tumor Development ◽

Hek293 Cells ◽

Treatment Resistant ◽

Tn Antigen ◽

Cell Energy ◽

Hif Pathway ◽

The Impact

e15739 Background: Hypoxia induced reprogramming of cell energy metabolism and changes in glycosylation are hallmarks of cancer promoting the induction of an invasive and treatment-resistant phenotype, triggering metastases at an early stage of tumor development. We examined the impact of hypoxia on O-GalNAc glycosylation in human HEK293, PDAC cell lines and clinical specimens. Methods: We profiled the expression of 88 glycosylation related genes by qPCR in HEK293 cells subjected to hypoxia either induced by 1% O2 or 200 mm CoCl2 identifying key O-GalNAc glycosyltransferases downregulated. Functional assays and glycoprotein analysis displayed a pronounced rate of O-GalNAc modified cytosolic proteins derived from hypoxia treated cells and PDAC specimens. Glycosidase assays could validate specificity of detection method used. Aberrant glycotype could be induced by HIF pathway activator ML 228 and inhibited using Echinomycin. PTK and STK analysis of cell lysates displayed correlation between phosphorylation and O-glycosylation in hypoxic samples. Results: Mechanistically we could show, that hypoxia induced decreased levels of C1GALT1C1 results in reduced T-Synthase activity with subsequent expression of truncated O-glycans (Tn antigen). Differential O-GalNAc glycosylation is inducible using HIF pathway activator ML228 under normoxia and the effect is reversed using 5 µM Echinomycin under hypoxia underscoring the role of HIF1a regulated transcription. Interestingly, the pattern of Tn antigen modified proteins derived from hypoxic samples differs significantly from engineered COSMC deficient cells, displaying O-GalNAc moieties in addition to O-GlcNAc in cytosolic protein fractions. Conclusions: Our findings point to a novel crosstalk of O-GalNAc and O-GlcNAcylation under hypoxia extending the knowledge base of differential O-GalNAc glycosylation in pancreatic cancer.

Download Full-text

Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

10.1101/422675 ◽

2018 ◽

Cited By ~ 1

Author(s):

Francois Collin ◽

Yuhong Ning ◽

Tierney Phillips ◽

Erin McCarthy ◽

Aaron Scott ◽

...

Keyword(s):

Pancreatic Cancer ◽

Early Stage ◽

Training Data ◽

Ductal Adenocarcinoma ◽

Data Sets ◽

Cell Free Dna ◽

Non Invasive ◽

Pancreatic Cancers ◽

Free Dna ◽

Circulating Cell Free Dna

AbstractPancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial by enabling surgical resection or earlier application of therapeutic regimens. We investigated the detection of pancreatic ductal adenocarcinoma (PDAC) in a non-invasive manner by interrogating changes in 5-hydroxymethylation cytosine status (5hmC) of circulating cell free DNA in the plasma of a PDAC cohort (n=51) in comparison with a non-cancer cohort (n=41). We found that 5hmC sites are enriched in a disease and stage specific manner in exons, 3’UTRs and transcription termination sites. Our data show that 5hmC density is reduced in promoters and histone H3K4me3-associated sites with progressive disease suggesting increased transcriptional activity. 5hmC density is differentially represented in thousands of genes, and a stringently filtered set of the most significant genes points to biology related to pancreas (GATA4, GATA6, PROX1, ONECUT1) and/or cancer development (YAP1, TEAD1, PROX1, ONECUT1, ONECUT2, IGF1 and IGF2). Regularized regression models were built using 5hmC densities in statistically filtered genes or a comprehensive set of highly variable 5hmC counts in genes and performed with an AUC = 0.94-0.96 on training data. We were able to test the ability to classify PDAC and non-cancer samples with the Elastic net and Lasso models on two external pancreatic cancer 5hmC data sets and found validation performance to be AUC = 0.74-0.97. The findings suggest that 5hmC changes enable classification of PDAC patients with high fidelity and are worthy of further investigation on larger cohorts of patient samples.

Download Full-text

Breast Cancer: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner

Journal of the Advanced Practitioner in Oncology ◽

10.6004/jadpro.2021.12.6.3 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Sheeba Cantanelli, MPAS, PA-C

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Early Stage ◽

Parp Inhibitor ◽

Metastatic Breast ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Vitamin D Levels ◽

The Impact

Sheeba Cantanelli, MPAS, PA-C, of UT Southwestern Medical Center, Simmons Comprehensive Cancer Center, discusses results from studies evaluating adjuvant therapy with a PARP inhibitor in BRCA-mutated HER2-negative metastatic breast cancer; immunotherapy in the treatment of early-stage triple-negative breast cancer; adjuvant capecitabine after neoadjuvant chemotherapy in triple-negative breast cancer; the addition of palbociclib to fulvestrant in HR-positive, HER2-negative advanced breast cancer; and the impact of vitamin D levels on outcomes. Reporting is provided by The ASCO Post.

Download Full-text

Mental health of healthcare professionals during the early stage of the COVID-19 pandemic in Ethiopia

BJPsych Open ◽

10.1192/bjo.2020.130 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Yimenu Yitayih ◽

Seblework Mekonen ◽

Ahmed Zeynudin ◽

Embialle Mengistie ◽

Argaw Ambelu

Keyword(s):

Mental Health ◽

Social Support ◽

Psychological Distress ◽

Healthcare Professionals ◽

Mental Health Problems ◽

Early Stage ◽

Medical Center ◽

Classification Tree ◽

Event Scale ◽

The Impact

Background The coronavirus (COVID-19) pandemic causes healthcare professionals to suffer mental health problems such as psychological distress, anxiety, depression, denial and fear. However, studies are lacking related to Ethiopia and to Africa in general. Aims To study the mental health of healthcare professionals during the COVID-19 pandemic in Ethiopia. Method A hospital-based cross-sectional study was conducted at Jimma University Medical Center among 249 healthcare professionals. The data were collected using self-administered questionnaires between 22 and 28 March 2020. The psychological impact was assessed using the Impact of Event Scale – Revised (IES-R) and symptoms of insomnia were measured using the Insomnia Severity Index (ISI). Social support was evaluated using the three-item Oslo Social Support Scale. Data were analysed using logistic regression to examine mutually adjusted associations, expressed as adjusted odds ratios. The psychosocial status of the healthcare professionals was predicted using a classification tree model supported by the genetic search method. Results The prevalence of psychological distress among healthcare professionals was 78.3%. The mean IES-R score was 34.2 (s.d. = 19.4). The ISI score indicated that the prevalence of insomnia was 50.2%. Higher psychological distress was associated with younger age, having insomnia, not having a daily update on COVID-19, and feeling stigmatised and rejected in the neighbourhood because of hospital work. Conclusions This study indicates that, in Ethiopia, the prevalence of psychological distress among healthcare professionals is high and associated with specific sociodemographic risks.

Download Full-text