scholarly journals Use of Biomarkers and Imaging for Early Detection of Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1965 ◽  
Author(s):  
Shingo Kato ◽  
Kazufumi Honda
Keyword(s):  
Pancreatic Cancer ◽  
General Population ◽  
Early Detection ◽  
Early Stage ◽  
Precancerous Lesions ◽  
Imaging Techniques ◽  
Circulating Tumor Dna ◽  
Proton Density ◽  
Screening Programs ◽  
Pancreatic Steatosis

Pancreatic cancer remains one of the deadliest cancers worldwide, and it is typically diagnosed late, with a poor prognosis. Early detection is the most important underlying factor for improving the prognosis of pancreatic cancer patients. One of the most effective strategies for detecting cancers at an early stage is screening of the general population. However, because of the low incidence of pancreatic cancer in the general population, the stratification of subjects who need to undergo further examinations by invasive and expensive modalities is important. Therefore, minimally invasive modalities involving biomarkers and imaging techniques that would facilitate the early detection of pancreatic cancer are highly needed. Multiple types of new blood biomarkers have recently been developed, including unique post-translational modifications of circulating proteins, circulating exosomes, microRNAs, and circulating tumor DNA. We previously reported that circulating apolipoprotein A2 undergoes unique processing in the bloodstream of patients with pancreatic cancer and its precancerous lesions. Additionally, we recently demonstrated a new method for measuring pancreatic proton density in the fat fraction using a fat–water magnetic resonance imaging technique that reflects pancreatic steatosis. In this review, we describe recent developments in potential biomarkers and imaging modalities for the early detection and risk stratification of pancreatic cancer, and we discuss current strategies for implementing screening programs for pancreatic cancer.

scholarly journals Detection of KRAS Mutations in Circulating Tumor DNA by Digital PCR in Early Stages of Pancreatic Cancer

2016 ◽  
Vol 62 (11) ◽  
pp. 1482-1491 ◽  
Author(s):  
Nora Brychta ◽  
Thomas Krahn ◽  
Oliver von Ahsen
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Surgical Removal ◽  
Plasma Samples ◽  
Kras Mutations ◽  
Detection Rates ◽  
Early Stages ◽  
Tumor Dna

Abstract BACKGROUND Since surgical removal remains the only cure for pancreatic cancer, early detection is of utmost importance. Circulating biomarkers have potential as diagnostic tool for pancreatic cancer, which typically causes clinical symptoms only in advanced stage. Because of their high prevalence in pancreatic cancer, KRAS proto-oncogene, GTPase [KRAS (previous name: Kirsten rat sarcoma viral oncogene homolog)] mutations may be used to identify tumor-derived circulating plasma DNA. Here we tested the diagnostic sensitivity of chip based digital PCR for the detection of KRAS mutations in circulating tumor DNA (ctDNA) in early stage pancreatic cancer. METHODS We analyzed matched plasma (2 mL) and tumor samples from 50 patients with pancreatic cancer. Early stages (I and II) were predominant (41/50) in this cohort. DNA was extracted from tumor and plasma samples and tested for the common codon 12 mutations G12D, G12V, and G12C by chip-based digital PCR. RESULTS We identified KRAS mutations in 72% of the tumors. 44% of the tumors were positive for G12D, 20% for G12V, and 10% for G12C. One tumor was positive for G12D and G12V. Analysis of the mutations in matched plasma samples revealed detection rates of 36% for G12D, 50% for G12V, and 0% for G12C. The detection appeared to be correlated with total number of tumor cells in the primary tumor. No KRAS mutations were detected in 20 samples of healthy control plasma. CONCLUSIONS Our results support further evaluation of tumor specific mutations as early diagnostic biomarkers using plasma samples as liquid biopsy.

scholarly journals The Screening and Early Detection of Pancreatic Cancer: Who, When, and How?

2020 ◽  
Vol 25 (2) ◽  
pp. 65-71
Author(s):  
Jae Hyuck Chang
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
General Population ◽  
Early Detection ◽  
Imaging Modality ◽  
Ductal Adenocarcinoma ◽  
Average Risk ◽  
Cystic Lesions ◽  
Low Prevalence ◽  
New Onset

More than 80% of patients with pancreatic ductal adenocarcinoma (PDA) present with symptomatic, surgically unresectable disease. If a “stage shift” from the current 20% resectable proportion to greater by early detection can be achieved, it will unequivocally lead to improved survival in this otherwise dismal disease. Although the goal of early detection of PDA is laudable, the relatively low prevalence PDA renders general population screening infeasible. To avoid the perils of overdiagnosis and to focus early detection efforts on individuals deemed to be at higher-than-average risk, we need to define those subsets of individuals, such as familial kindred and patients with precursor cystic lesions, chronic pancreatitis, and new-onset diabetes. The next step is to determine when and how often to conduct surveillance in the atrisk individuals and the modalities (biomarkers and imaging) that will be used in the surveillance and diagnostic settings, respectively. Nonetheless, vast challenges still remain in terms of validated blood-based biomarkers, imaging modality, and when and how often the surveillance.

scholarly journals Substantiation of connection between affective disorders and development of malignant neoplasms of pancreas: experience of the center

2021 ◽  
Vol 38 (2) ◽  
pp. 14-22
Author(s):  
V. E. Moiseenko ◽  
Izeta G. Kardanova ◽  
A. V. Pavlovsky ◽  
D. A. Granov ◽  
G. V. Rukavishnikov ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Affective Disorders ◽  
Early Stage ◽  
Depression Scale ◽  
Anxiety And Depression ◽  
Malignant Neoplasms ◽  
European Organization ◽  
Screening Programs ◽  
Russian Version ◽  
The Relationship

Objective. To analyze the relationship between the affective disorders in the form of anxiety and depression and the development of pancreatic cancer and stomach cancer. Today, there is an interest to the relationship between changes in the emotional sphere of patients with malignant neoplasms (MNO) of the pancreas at the early stages of the disease, when there are no other clinically significant symptoms, which allow suspecting the disease at an early stage. Materials and methods. A questionnaire survey was carried out in 63 patients with histologically verified cancer of the pancreas and stomach, who were treated at the FGBU RNTSRKhT named after Acad. A.M. Granov in the period from 2018 to 2020. The survey was conducted using the questionnaire of the European Organization for Research and Treatment of Cancer (EORTC-QLQ-C30 Russian version) and the Hospital Anxiety and Depression Scale (HADS), Russian version. Statistical processing of treatment results was carried out using regression analysis and Mann-Whitney test with the SPSS statistical software package (Statistika 13.0). The probability of error p 0.05 was considered sufficient to conclude that the differences in the data obtained were statistically significant. Results. In a comparative assessment of the indicators of affective disorders in pancreatic cancer patients, there were noted more pronounced affective disorders, such as feeling of depression, feeling of irritation, anxiety and tension, the values of which, according to the results of the analysis of questionnaires, were 1.00 1, 1, 00 1.00 1 and 2.00 1, respectively. In patients with gastric cancer, the values of these affective disorders, according to the survey results, were less pronounced and amounted to 3.00 1.00 1.00, 3.00 1.00, 3.00 1, respectively (p = 0.000). Conclusions. Severe affective disorders, such as anxiety and depression, in patients with pancreatic cancer should be regarded as a factor of the early manifestation of the disease. Further study of this connection can create a theoretical basis for the development of specialized screening programs to identify patients in the risk groups for the development of pancreatic cancer.

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

Cancers ◽  
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.

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

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.

scholarly journals Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancer

2018 ◽  
Author(s):  
Xiaoyu Liu ◽  
Lingxiao Liu ◽  
Yuan Ji ◽  
Changyu Li ◽  
Tao Wei ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Fragment Size ◽  
New Technology ◽  
Mutant Cell ◽  
Circulating Tumor Dna ◽  
Clinical Settings ◽  
Cell Free Dna ◽  
Free Dna ◽  
Target Capture

Analysis of cell-free DNA (cfDNA) is promising for broad applications in clinical settings, but with significant bias towards late-stage cancers. Although recent studies have discussed the diverse and degraded nature of cfDNA molecules, little is known about its impact on the practice of cfDNA analysis. Here we reported a new targeted sequencing by combining single-strand library preparation and target capture (SLHC-seq). By applying the new technology in plasma cfDNA from pancreatic cancer patients, we achieved higher efficiency in analysis of mutations than previously reported using other detection assays. SLHC-seq rescued short or damaged cfDNA fragments along to increase the sensitivity and accuracy of circulating-tumor DNA detection. Most importantly, we found that the small mutant fragments are prevalent in early-stage patients, which provides strong evidence for fragment size-based early detection of pancreatic cancer. Collectively, the new pipeline enhanced our understanding of cfDNA biology and provide new insights for liquid biopsy.

scholarly journals Pathological Changes in Pancreatic Carcinogenesis: A Review

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 686
Author(s):  
Keiko Yamakawa ◽  
Juanjuan Ye ◽  
Yuko Nakano-Narusawa ◽  
Yoko Matsuda
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Precancerous Lesions ◽  
Genetically Engineered ◽  
Diagnostic Methods ◽  
Treatment Modalities ◽  
Pathological Changes ◽  
Local Progression ◽  
Genetically Engineered Mice

Despite advances in diagnostics and therapeutics, the prognosis of pancreatic cancer remains dismal. Because of a lack of early diagnostic methods, aggressive local progression, and high incidence of distant metastasis, most pancreatic cancers are inoperable; therefore, the characteristics of early pancreatic cancer have not been well understood. Autopsy studies revealed the characteristics of prediagnostic pancreatic malignancies, including precancerous lesions, early stage pancreatic cancer, and pancreatic cancer without clinical symptoms (occult cancers). Animal models using hamsters and genetically engineered mice have focused on mechanisms of carcinogenesis, thereby providing insights into risk factors and prevention and serving as a preclinical test for the development of novel diagnostic and treatment modalities. In this review, we have summarized pathological changes in the pancreas of humans and experimental animals during carcinogenesis.

scholarly journals Screening of Pancreatic Cancer for Early Diagnosis

2021 ◽  
Vol 96 (2) ◽  
pp. 110-115
Author(s):  
Jae Hyuck Chang
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
General Population ◽  
Early Detection ◽  
Early Diagnosis ◽  
Average Risk ◽  
Cystic Lesions ◽  
Diagnostic Modalities ◽  
Low Prevalence ◽  
New Onset

Over 80% of patients with pancreatic ductal adenocarcinomas (PDAs) present with symptomatic, surgically unresectable disease. If a “stage shift” from the current 20% proportion of resectability to early detection could be achieved, this would greatly improve the survival of patients with this generally dismal disease. Although the goal of early detection is laudable, the relatively low prevalence of PDA renders general population screening unfeasible. To avoid the perils of overdiagnosis and to focus early detection efforts on individuals deemed to be at higher-than-average risk, we need to define such subsets of individuals, such as kindred of existing patients and those with precursor cystic lesions, chronic pancreatitis, and new-onset diabetes. The next step is to determine when and how often to monitor at-risk individuals and the diagnostic modalities that will be employed in the surveillance. Enormous challenges remain in terms of validated blood-based biomarkers, imaging modalities, and when and how often surveillance.

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