Molecular Detection for Pancreatic Cysts

Overseen By IN-CYST Team

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Pregnant, Incarceration, Pancreatic cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if new tests using blood, stool, pancreas cyst fluid, or pancreas juice can diagnose changes in pancreas cysts that may become cancerous. Participants will join either a group with regular check-ups or a group undergoing immediate pancreatic surgery. Suitable candidates for this trial are individuals with pancreas cysts deemed risky based on specific medical guidelines and who have not previously had pancreatic cancer or surgery.

As an unphased trial, this study provides participants the chance to contribute to groundbreaking research that could enhance early detection methods for pancreatic cancer.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's procedures are likely to be safe?

Research shows that pancreatic surgery, such as the Whipple procedure, can save lives but also carries risks. Studies indicate that this surgery has a low mortality rate of less than 5%. However, complications can still occur afterward. Some patients experience issues like pancreatic leaks or require further medical procedures. Specifically, about 41% of patients reported returning to the hospital, and around 29% needed additional surgeries after recovery. While these numbers might seem high, they highlight that although the surgery is generally safe, it can present challenges. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to detect and manage pancreatic cysts, which can potentially lead to pancreatic cancer. Traditionally, treatment involves monitoring cysts or opting for surgery based on size and appearance. However, this trial introduces a molecular detection method to gather more detailed information from blood, stool, pancreatic juice, and cyst fluid. This approach could lead to more accurate assessments, helping doctors decide who truly needs surgery and who can safely continue clinical follow-up. By focusing on molecular data, this trial aims to personalize treatment plans, potentially reducing unnecessary surgeries and improving patient outcomes.

What evidence suggests that these diagnostic methods are effective for detecting malignant changes in pancreatic cysts?

Research has shown that pancreatic surgery, such as the Whipple procedure, can effectively treat pancreatic issues, including cancer. Studies indicate that this surgery can increase the five-year survival rate to about 25% for those who undergo it successfully. However, this procedure carries significant risks, including complications and leaks from the pancreas. While it can improve long-term survival, the surgery itself is complex and demanding. In this trial, participants will either undergo immediate surgery or join a clinical follow-up group. For pancreatic cysts, treatments using a thin, flexible tube called an endoscope have demonstrated good success rates with fewer serious side effects. ^{1 5 6 7 8}

Who Is on the Research Team?

Shounak Majumder, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with suspected pancreatic cysts who can consent to the study. They must meet specific criteria indicating a higher risk of cancer in their cysts. People are excluded if they've had previous treatments for pancreatic lesions, recent cancer other than skin cancer, past pancreas surgery or necrosis, current pregnancy or nursing, or chemotherapy/radiation within 5 years.

Inclusion Criteria

Patients with pancreatic cystic lesions meeting Fukuoka worrisome or Fukuoka high-risk criteris

Able to provide written informed consent

I might have a cystic tumor in my pancreas.

Exclusion Criteria

I have had chemotherapy or radiation to my abdomen in the past 5 years.

I have had pancreatic cancer or surgery on my pancreas before.

I have had treatment for a pancreatic cyst before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Immediate Surgery

Participants scheduled for surgical resection after their initial clinical evaluation will be assigned to the 'Immediate Surgery' study group. Blood, stool, pancreatic juice, and cyst fluid collection will be done as per protocol.

Until surgical pathology is known

Clinical Follow-up

Participants not undergoing surgery will be assigned to the 'Clinical Follow-up' study group. Blood, stool, pancreatic juice, and cyst fluid collection will be done as per protocol. Participants will be contacted yearly for a telephone interview until they undergo surgery, die, receive a diagnosis that excludes them from the study, or for 5 years.

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Blood Collection
• Endoscopy Exam
• Pancreatic Cyst Fluid Collection
• Pancreatic Juice Collection
• Pancreatic Surgery
• Stool Collection

Trial Overview The study is testing new diagnostic methods using blood, stool, pancreatic juice and cyst fluid to detect malignant or pre-malignant changes in pancreatic cysts. It involves collecting samples from participants and may include an endoscopy exam and possibly surgery.

How Is the Trial Designed?

Group I: Surgical Experimental Treatment 2 Interventions

Participants scheduled for surgical resection after their initial clinical evaluation will be assigned to the "Immediate Surgery" study group. Blood, stool, pancreatic juice and cyst fluid collection will be done as per protocol. Participants in the Immediate Surgery group will be followed until the surgical pathology of their pancreatic cyst is known.

Group II: Clinical Follow-up Experimental Treatment 2 Interventions

Participants not undergoing surgery will be assigned to the "Clinical Follow-up" study group. Blood, stool, pancreatic juice and cyst fluid collection will be done as per protocol. All participants in the Clinical Follow-up group will be contacted yearly for a telephone interview until they undergo surgery, die, receive a diagnosis that excludes them from the study, or for 5 years, and interval medical records will be obtained and reviewed. During follow-up results of clinically indicated follow-up imaging studies will be abstracted

Pancreatic Surgery is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Pancreatic Surgery for:

• Pancreatic cancer
• Pancreatic cysts
• Pancreatitis
• Ampullary cancer
• Bile duct cancer
• Neuroendocrine tumors
• Small intestine cancer

Approved in United States as Pancreatic Surgery for:

• Pancreatic cancer
• Pancreatic cysts
• Pancreatitis
• Ampullary cancer
• Bile duct cancer
• Neuroendocrine tumors
• Small intestine cancer

Approved in Canada as Pancreatic Surgery for:

• Pancreatic cancer
• Pancreatic cysts
• Pancreatitis
• Ampullary cancer
• Bile duct cancer
• Neuroendocrine tumors
• Small intestine cancer

Approved in Japan as Pancreatic Surgery for:

• Pancreatic cancer
• Pancreatic cysts
• Pancreatitis
• Ampullary cancer
• Bile duct cancer
• Neuroendocrine tumors
• Small intestine cancer

Approved in China as Pancreatic Surgery for:

• Pancreatic cancer
• Pancreatic cysts
• Pancreatitis
• Ampullary cancer
• Bile duct cancer
• Neuroendocrine tumors
• Small intestine cancer

Approved in Switzerland as Pancreatic Surgery for:

• Pancreatic cancer
• Pancreatic cysts
• Pancreatitis
• Ampullary cancer
• Bile duct cancer
• Neuroendocrine tumors
• Small intestine cancer

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Molecular analysis of pancreatic cyst fluid, particularly looking for K-ras mutations and loss of heterozygosity, can suggest mucinous cysts and is highly specific for malignancy, but it has low sensitivity, meaning it may miss some cases of cancer.

In a study of 40 patients with intermediate-risk pancreatic cysts, molecular features improved diagnostic yield compared to EUS-FNA alone, but changes in molecular characteristics during surveillance did not correlate with cyst size or other traditional markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of molecular analysis in the diagnosis and surveillance of pancreatic cystic neoplasms. Winner, M., Sethi, A., Poneros, JM., et al.[2018]

In a study of 46 patients undergoing evaluation for pancreatic cysts, the addition of DNA molecular analysis changed clinical management in 28% of cases, indicating its potential impact on treatment decisions.

The most significant changes in management occurred when cyst carcinoembryonic antigen (CEA) levels were intermediate (45-800 ng/mL) or absent, suggesting that DNA analysis can provide valuable insights in these scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular analysis of pancreatic cyst fluid changes clinical management. Arner, DM., Corning, BE., Ahmed, AM., et al.[2022]

In a study of 93 patients undergoing Whipple's surgery for pancreatic adenocarcinoma, extensive resection did not lead to higher rates of postoperative complications or mortality compared to classical resection, with complication rates of 16.67% and mortality rates of 2.38% in the extensive group.

The 1- and 2-year survival rates were slightly higher in the extensive group (63.33% and 23.33%) compared to the classical group (58.82% and 20.59%), but the long-term survival benefits of extensive resection remain uncertain and need further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical comparison on the classical versus extensive Whipple's resection for adenocarcinoma of head of pancreas]. Liu, XB., Yan, LN., Zhai, HJ., et al.[2005]

Pancreaticoduodenectomy, or the Whipple procedure, has seen improved outcomes due to better patient selection and advances in imaging, but it still carries significant risks of morbidity and mortality, especially for pancreatic adenocarcinoma.

Recent studies show that aggressive surgical techniques, including major venous resections, can be performed safely without increasing complications, leading to better outcomes for patients previously deemed unresectable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for the surgical management of pancreatic adenocarcinoma. Ujiki, MB., Talamonti, MS.[2007]

Laparoscopic distal pancreatic resection (LDP) has shown improved survival rates and postoperative safety, with median survival exceeding 2.5 years and a five-year overall survival rate of over 30%, even with suboptimal adjuvant chemotherapy.

While laparoscopic pancreaticoduodenectomy (LPD) is more complex and has a slower adoption due to safety concerns, robotic assistance may enhance surgical safety, making it crucial to monitor long-term outcomes and patient-reported results in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term oncological outcome of laparoscopic techniques in pancreatic cancer. Buanes, T., Edwin, B.[2020]

In a study of 73 patients who underwent Whipple's procedure for periampullary tumors, only 1.4% experienced severe (Grade C) delayed gastric emptying, indicating that this serious complication is rare.

Most patients with milder forms of delayed gastric emptying (Grades A and B) responded well to conservative treatments, suggesting that these milder cases may not significantly impact overall recovery and that the current definitions of complications could be revised.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed Gastric Emptying as a Complication of Whipple's Procedure: Could it be Much Less Frequent than Anticipated? Could the Definition Be Revised? A Single Center Experience. Cakir, M., Akinci, M., Akturk, OM.[2022]

A study of 36 pancreatic cysts showed that detailed molecular analysis, including k-ras mutations and DNA quality, can effectively differentiate malignant cysts from premalignant and benign ones, improving diagnostic accuracy.

The presence of an early k-ras mutation followed by allelic loss was found to be highly predictive of malignancy, with a sensitivity of 91% and specificity of 93%, suggesting that this molecular approach could enhance the conventional evaluation of pancreatic cysts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology. Khalid, A., McGrath, KM., Zahid, M., et al.[2019]

In a study of 327 patients who underwent the Whipple procedure over 20 years, 38.2% experienced complications, with respiratory issues being the most common (9.8%).

Notably, complications like delayed gastric emptying and postoperative pancreatic fistula decreased significantly in the second decade, indicating improvements in surgical outcomes over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications among Patients Undergoing Pancreaticoduodenectomy in Tertiary Care Centers of Nepal: A Descriptive Cross-sectional Study. Neupane, HC., Tamang, TY., Timalsina, S., et al.[2022]

Molecular analysis of pancreatic cyst fluid shows promise as a diagnostic tool, potentially requiring smaller fluid volumes than traditional tests like cytology, and may improve the characterization of cyst subtypes.

Most studies reviewed had moderate sample sizes (16-124 participants) and indicated that molecular analysis could be particularly beneficial for managing smaller cysts, suggesting a need for larger prospective trials to validate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular analysis of cyst fluid aspiration in the diagnosis and risk assessment of cystic lesions of the pancreas. Garud, SS., Willingham, FF.[2021]

Molecular analysis of pancreatic cyst fluid using the PathFinderTG test shows high diagnostic accuracy, with 83% sensitivity and 100% specificity for identifying malignant cysts, and 86% sensitivity and 93% specificity for benign mucinous cysts, based on a study of 35 patients.

The concordance between the molecular diagnosis and clinical consensus diagnosis was high, with an overall agreement rate of 93% for benign nonmucinous cysts, indicating that molecular testing can significantly enhance the accuracy of preoperative diagnoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular analysis of pancreatic cyst fluid: a comparative analysis with current practice of diagnosis. Shen, J., Brugge, WR., Dimaio, CJ., et al.[2022]

In a study of 61 patients undergoing Whipple operations for pancreatoduodenal diseases, the surgical morbidity decreased from 50% to 15% and mortality dropped from 17% to 0% over the years, indicating significant improvements in surgical techniques and postoperative care.

The findings suggest that with specialized surgical teams and advanced technology, the Whipple procedure can be performed with low risk, making it a viable option for patients with both malignant and benign conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pancreatoduodenectomy: myth or reality? Personal experience]. Barboza Besada, E.[2018]

Recent advancements have significantly reduced the operative mortality rates of the Whipple procedure, which was traditionally between 20 to 25 percent, suggesting improved safety for patients undergoing this surgery.

Given that radical pancreaticoduodenectomy (the Whipple procedure) is the only curative treatment for periampullary carcinoma, its role in treatment should be re-evaluated in light of these improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whipple operation revisited. Spain, DA., Greco, RS.[2004]

The Whipple procedure has significantly improved over the past 20 years, with mortality rates dropping from around 20% to near zero in high-volume centers, thanks to advancements in staging and surgical techniques.

Five-year survival rates for pancreatic adenocarcinoma have reached about 20%, and for other periampullary tumors, long-term survival rates are around 40%, indicating better outcomes and the procedure's expanded use in treating both malignant and benign conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution and current status of the Whipple procedure: an update for gastroenterologists. Strasberg, SM., Drebin, JA., Soper, NJ.[2019]

Pancreatic resections, including Whipple procedures and total pancreatectomies, have a high postoperative complication rate of 36%, with a mortality rate of 17.9%, highlighting the risks associated with these surgeries.

Whipple resections resulted in significantly lower mortality (14.7%) compared to total pancreatectomies (23.4%), suggesting that Whipple procedures may be safer and equally effective for certain patients with pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical experience with pancreatic and periampullary cancer. Herter, FP., Cooperman, AM., Ahlborn, TN., et al.[2019]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK560747/

Pancreaticoduodenectomy (Whipple Procedure) - NCBI While it is a life-saving intervention, the surgery is technically challenging and associated with significant risks, including pancreatic leaks, delayed ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1365182X22000739

Quality of life after pancreatic surgery – A systematic review Surgery for patients with pancreatic cancer carries a high risk of major post-operative complications and only marginally improves overall survival.

3. cureus.com cureus.com/articles/350228-whipple-procedure-vs-distal-pancreatectomy-a-study-on-the-efficacy-survival-rates-and-complication-rates-in-patients-with-pancreatic-cancer

Whipple Procedure vs. Distal Pancreatectomy: A Study on ... The Whipple procedure, performed for pancreatic head tumors, offers better long-term survival but carries a higher risk of complications.

4. webmd.com webmd.com/cancer/pancreatic-cancer/whipple-procedure

Whipple Procedure: Will It Cure Pancreatic Cancer? Those who undergo a successful Whipple procedure may boost their 5-year survival rate up to 25%. The Whipple procedure involves removing the ...

5. ghadvances.org ghadvances.org/article/S2772-5723(24)00191-2/fulltext

Short-Term Outcomes of Endoscopic Ultrasound-Guided ... The treatment of pancreatic cysts with endoscopic ultrasound ablation results in acceptable levels of complete resolution, and low incidence of severe adverse ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2023932/

Complications of pancreatic surgery - PMC - PubMed Central Pancreatic surgery has evolved into a safe procedure with mortality rates of <5%. However, postoperative morbidity rates are still substantial.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1365182X20311382

Original article Long-term health after pancreatic surgery 41.3% reported hospitalizations, 17.5% required endoscopies and 28.8% additional operations after full recovery. Need for additional interventions were not ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1091255X23036648

Extended Follow-Up and Outcomes of Patients Undergoing ... This study compares outcomes after pancreaticoduodenectomy for patients with premalignant and malignant pancreatic neoplasms. This retrospective cohort ...