Early Detection of Pancreatic Cancer: Role of Biomarkers in Pancreatic Fluid Samples

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths worldwide. Most patients with PDAC present with symptomatic, surgically unresectable disease. Therefore, the establishment of strategies for the early detection is urgently needed. Molecular biomarkers might be useful in various phases of a strategy to identify high-risk individuals in the general population and to detect high-risk lesions during intense surveillance programs combined with imaging modalities. However, the low sensitivity and specificity of biomarkers currently available for PDAC, such as carbohydrate 19-9 (CA19-9), contribute to the late diagnosis of this deadly disease. Although almost all classes of biomarker assays have been studied, most of them are used in the context of symptomatic diseases. Compared to other body fluids, pancreatic juice and duodenal fluid are better sources of DNA, RNA, proteins, and exosomes derived from neoplastic cells and have the potential to increase the sensitivity/specificity of these biomarkers. The number of studies using duodenal fluid with or without secretin stimulation for DNA/protein marker tests have been increasing because of the less-invasiveness in comparison to pancreatic juice collection by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Genomic analyses have been very well-studied, and based on PDAC progression model, mutations detected in pancreatic juice/duodenal fluid seem to indicate the presence of microscopic precursors and high-grade dysplasia/invasive cancer. In addition to known proteins overexpressed both in precursors and PDACs, such as CEA and S100P, comprehensive proteomic analysis of pancreatic juice from patients with PDAC identified many proteins which were not previously described. A novel technique to isolate exosomes from pancreatic juice was recently invented and identification of exosomal microRNA’s 21 and 155 could be biomarkers for diagnosis of PDAC. Since many studies have explored biomarkers in fluid samples containing pancreatic juice and reported excellent diagnostic accuracy, we need to discuss how these biomarker assays can be validated and utilized in the strategy of early detection of PDAC.

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New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial

BMJ Open ◽

10.1136/bmjopen-2020-037267 ◽

2020 ◽

Vol 10 (11) ◽

pp. e037267

Author(s):

Dóra Illés ◽

Emese Ivány ◽

Gábor Holzinger ◽

Klára Kosár ◽

M Gordian Adam ◽

...

Keyword(s):

High Risk ◽

Early Detection ◽

Pancreatic Ductal Adenocarcinoma ◽

Clinical Symptoms ◽

Risk Group ◽

High Risk Group ◽

Ductal Adenocarcinoma ◽

Onset Diabetes ◽

Dismal Prognosis ◽

New Onset

IntroductionPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. The proposed screening programme may allow the detection of PDAC in the early, operable stage. Diagnosing more patients in the curable stage might decrease the morbidity and mortality rates of PDAC and additionally reduce the burden of the healthcare.Methods and analysisThis is a prospective, multicentre observational cohort study. Patients ≥60 years old diagnosed with new-onset (≤6 months) diabetes will be included. Exclusion criteria are (1) Continuous alcohol abuse; (2) Chronic pancreatitis; (3) Previous pancreas operation/pancreatectomy; (4) Pregnancy; (5) Present malignant disease and (6) Type 1 DM. Follow-up visits are scheduled every 6 months for up to 36 months. Data collection is based on questionnaires. Clinical symptoms, body weight and fasting blood will be collected at each, carbohydrate antigen 19–9 and blood to biobank at every second visit. The blood samples will be processed to plasma and analysed with mass spectrometry (MS)-based metabolomics. The metabolomic data will be used for biomarker validation for early detection of PDAC in the high-risk group patients with new-onset diabetes. Patients with worrisome features will undergo MRI or endoscopic ultrasound investigation, and surgical referral depending on the radiological findings. One of the secondary end points is the incidence of PDAC in patients with newly diagnosed DM.Ethics and disseminationThe study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (41085-6/2019). We plan to disseminate the results to several members of the healthcare system includining medical doctors, dietitians, nurses, patients and so on. We plan to publish the results in a peer-reviewed high-quality journal for professionals. In addition, we also plan to publish it for lay readers in order to maximalise the dissemination and benefits of this trial.Trial registration numberClinicalTrials.gov NCT04164602

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Managing Thyroid Nodules in Qatar During the COVID19 Pandemic

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1717 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A841-A842

Author(s):

Zaina Alamer ◽

Gowri Karuppasamy ◽

Arwa Alsaud ◽

Tania Jaber ◽

Hanan Farghaly ◽

...

Keyword(s):

High Risk ◽

Early Detection ◽

Fine Needle Aspiration ◽

Medical Staff ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Morbidity And Mortality ◽

American Thyroid Association ◽

Fine Needle ◽

Thyroid Fine Needle Aspiration

Abstract Background: The Coronavirus disease 2019 (COVID-19) pandemic impacted health care systems in all countries, including Qatar. Hamad Medical Corporation (HMC); In compliance with recommendations, suspended all non-urgent procedures, including thyroid fine needle aspiration biopsies (FNAB). Thyroid nodules are second most common cause of referral to HMC endocrine clinic. FNABs are gold standard to differentiate benign from malignant nodules.1- 2 Methods: Our approach includes a teleconsultation to obtain patient’s history and risk factors. Reviewing neck ultrasound (US), obtaining a calcitonin level if indicated, considering comorbidities associated with a high risk of COVID-19 morbidity and mortality.3 Results: We developed a pathway triaging thyroid (FNAB) to:1-Urgent: patients at higher risk of aggressive thyroid malignancy. Benefits of early detection and treatment outweigh the risk of COVID-19 exposure.4 FNAB should not be delayed.2-Semi-urgent: patients at low risk for COVID-19 and high suspicion thyroid nodules, but no evidence that early detection improves survival2, FNAB may be delayed up to 12 months.3-Non-urgent: patients with asymptomatic nodules that have low or intermediate suspicion US pattern.2 Also, includes nodules with ATA high suspicion US pattern in pregnant women and patients at high risk for COVID-19. The risks outweigh the benefits. FNAB should be delayed until outbreak is controlled.4 When urgent FNAB is indicated, safety of patients and medical staff needs to be addressed.5 We recommend testing patient for COVID-19 before FNAB, utilizing US guidance with rapid on-site adequacy evaluation in all cases. Cervical lymph node FNAB with TG washout should be done if indicated. The patient should wear a mask. All medical staff involved should wear personal protective equipment (PPE). The operator should wear N95 mask and face shield. The patient should be informed about cytopathology results via telemedicine. Conclusion: Triaging thyroid (FNAB) during the COVID-19 pandemic should be based on nodule characteristics and risk of COVID-19 morbidity and mortality. Our group recommends deferring FNAB for asymptomatic patients.4FNAB should not be delayed in selected patients who benefit from early detection and intervention. Table1: Triage of Thyroid fine needle aspiration biopsies (FNAB). ATA: American thyroid association. US: ultrasound.

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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.

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Early Detection and Biomarkers in Pancreatic Cancer

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2007.0086 ◽

2007 ◽

Vol 5 (10) ◽

pp. 1034-1041 ◽

Cited By ~ 36

Author(s):

David E. Misek ◽

Tasneem H. Patwa ◽

David M. Lubman ◽

Diane M. Simeone

Keyword(s):

Pancreatic Cancer ◽

Early Detection ◽

Cancer Control ◽

The United States ◽

Ductal Adenocarcinoma ◽

Protein Biomarkers ◽

Recent Developments ◽

New Biomarkers ◽

Low Sensitivity ◽

Sensitivity Specificity

Major advances in cancer control will be greatly aided by early detection for diagnosing and treating cancer in its preinvasive state before metastasis. Unfortunately, for pancreatic ductal adenocarcinoma (PDAC), which is the fourth leading cause of cancer-related death in the United States, effective early detection and screening are currently not available and tumors are typically diagnosed at a late stage, frequently after metastasis. Partly because of low sensitivity/specificity, existing biomarkers such as CA19-9 are not adequate as early detection markers of pancreatic cancer. Thus, a great need exists for new biomarkers for pancreatic cancer. This article focuses on recent developments in the identification of new serum protein biomarkers that are useful in the early detection of PDAC.

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