Advancing the Clinical Translation of Cyst Fluid Assays for Early Detection of Pancreatic Cancer

推进囊肿液检测的临床转化以早期检测胰腺癌

基本信息

项目摘要

PROJECT SUMMARY Pancreatic cystic lesions (PCLs) represent an opportunity for early detection of pancreatic adenocarcinoma. The accurate identification of cysts with high grade dysplasia or invasive adenocarcinoma, together referred to as “Advanced Neoplasia” (AN), that warrant surgical intervention represents a critical unmet need in the management of PCLs. Most pancreatic cysts with the potential to develop AN are mucinous; in contrast, non- mucinous PCLs have little or no malignant potential. Biochemical and cytological analysis of aspirated cyst fluid are important tools in the diagnosis and risk stratification of PCLs. However, sensitivity of the only clinical biomarker for mucinous cysts, carcinoembryonic antigen (CEA), is insufficient to allow clinicians to confidently remove patients from surgical consideration. Moreover, the most commonly performed CEA assay requires 500 L of fluid, which is often unavailable. For over 50% of patients that undergo invasive trans-gastric cyst fluid aspiration, inadequate biospecimen is obtained to run the standard of care biochemical tests. In an effort to improve the sensitivity and applicability of cyst fluid analysis, we used our novel multiplex mass spectrometry technology to identify the protease gastricsin which accurately identifies mucinous cysts with an AUC of 0.98 and requires only 5 L fluid. Despite reliance by clinicians on these analyses to guide clinical decision-making, little effort has been directed toward optimization of biospecimen processing for pancreatic cyst fluid. There are no standardized pathways for cyst fluid processing and, unlike other biospecimens such as serum, pancreatic cyst fluid has variable viscosity and contamination with blood and proteinaceous material that could interfere with assay reproducibility. It is unknown if the variability we observe clinically in cyst fluid CEA and cytology reflects true biological differences or inconsistent preanalytical biospecimen processing. The overall objective of this proposal is to improve completeness, reproducibility, and accuracy in pancreatic cyst fluid diagnostic evaluation in order to improve the early diagnosis of pancreatic cancer while avoiding the burdens of overdiagnosis and overtreatment. To achieve our objective, we will systematically evaluate the impact of preanalytical variables on cyst fluid biochemical and cytological analysis (Aim 1) and identify strategies to mitigate the small volumes of available cyst fluid (Aim 2) in order to develop a streamlined, reproducible protocol (Aim 3) that improves the reliable early detection of pancreatic cancer. We will then validate the performance of our streamlined protocol using prospectively - collected clinical samples, and we will evaluate inter-assay variability by implementing the protocols at two independent sites. By improving the reliability of our assays, clinicians will be able to direct surgical intervention appropriately to patients with incipient pancreatic cancer while sparing others unnecessary risks of mortality, substantial morbidity, and health care costs.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Kimberly Saunders Kirkwood其他文献

Neoadjuvant Therapy Decreases Postoperative Pancreatic Fistula, Delayed Gastric Emptying, and Systemic Morbidity in Patients Undergoing Pancreaticoduodenectomy: An American College of Surgeons NSQIP Analysis
  • DOI:
    10.1016/j.jamcollsurg.2020.07.529
  • 发表时间:
    2020-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Alexa Glencer;Jeremy Sharib;Paige Bracci;Tyler J. York;Sophia Hernandez;Kimberly Saunders Kirkwood;Carlos Uriel Corvera
  • 通讯作者:
    Carlos Uriel Corvera
Minimally Invasive Splenectomy Is Associated with Decreased Serious Complications: A 2008-2018 NSQIP Analysis
  • DOI:
    10.1016/j.jamcollsurg.2020.07.195
  • 发表时间:
    2020-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Sophia Hernandez;Tyler J. York;Alexa Glencer;Jeremy Sharib;James Ross;Alexander Sehyun Kim;Paige Bracci;Kimberly Saunders Kirkwood
  • 通讯作者:
    Kimberly Saunders Kirkwood

Kimberly Saunders Kirkwood的其他文献

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{{ truncateString('Kimberly Saunders Kirkwood', 18)}}的其他基金

Neural Regulation of Pancreatic Function
胰腺功能的神经调节
  • 批准号:
    8277330
  • 财政年份:
    1995
  • 资助金额:
    $ 35.93万
  • 项目类别:
NEURAL REGULATION OF PANCREATIC FUNCTION
胰腺功能的神经调节
  • 批准号:
    6380780
  • 财政年份:
    1994
  • 资助金额:
    $ 35.93万
  • 项目类别:
NEURAL REGULATION OF PANCREATIC FUNCTION
胰腺功能的神经调节
  • 批准号:
    6176209
  • 财政年份:
    1994
  • 资助金额:
    $ 35.93万
  • 项目类别:
NEURAL REGULATION OF PANCREATIC FUNCTION
胰腺功能的神经调节
  • 批准号:
    2905536
  • 财政年份:
    1994
  • 资助金额:
    $ 35.93万
  • 项目类别:
NEURAL REGULATION OF PANCREATIC FUNCTION
胰腺功能的神经调节
  • 批准号:
    6524108
  • 财政年份:
    1994
  • 资助金额:
    $ 35.93万
  • 项目类别:
NEURAL REGULATION OF PANCREATIC FUNCTION
胰腺功能的神经调节
  • 批准号:
    2706261
  • 财政年份:
    1994
  • 资助金额:
    $ 35.93万
  • 项目类别:

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