Molecular Detection for Pancreatic Cysts

Overseen by Shounak Majumder, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Mayo Clinic

Disqualifiers: Pregnant, Incarceration, Pancreatic cancer, others

No Placebo Group

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing blood, stool, pancreas cyst fluid, and pancreas juice to find new ways to diagnose dangerous changes in pancreatic cysts. It focuses on patients with high-risk pancreatic cysts. Researchers hope to identify markers in these samples that can help doctors determine if a cyst is likely to become cancerous.

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.

What data supports the effectiveness of this treatment for pancreatic cysts?

The Whipple procedure, a part of the treatment for pancreatic cysts, has shown improved survival rates for pancreatic cancer, with some centers reporting 5-year survival rates of 20% for adenocarcinoma of the pancreas. Additionally, advancements in surgical techniques have significantly reduced mortality rates, making the procedure safer and more effective. ^{1 2 3 4 5}

Is the Whipple procedure generally safe for humans?

The Whipple procedure, a complex surgery for pancreatic conditions, has become safer over time, especially in specialized centers. Mortality rates have dropped significantly, and while complications like delayed gastric emptying can occur, improvements in surgical techniques have reduced risks. ^{2 6 7 8 9}

How is pancreatic surgery different from other treatments for pancreatic cysts?

Pancreatic surgery, such as the Whipple Procedure, is a unique treatment for pancreatic cysts because it involves the physical removal of part or all of the pancreas, which is different from non-surgical methods like molecular analysis that aim to diagnose and manage cysts without surgery. This approach is typically reserved for larger cysts or those suspected to be malignant, whereas molecular analysis can help manage smaller cysts by providing detailed information that might change treatment plans. ^{10 11 12 13 14}

Research Team

Shounak Majumder, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Blood Collection (Diagnostic Test)
• Endoscopy Exam (Procedure)
• Pancreatic Cyst Fluid Collection (Diagnostic Test)
• Pancreatic Juice Collection (Diagnostic Test)
• Pancreatic Surgery (Procedure)
• Stool Collection (Diagnostic Test)

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.

Participant Groups

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 Canada, Japan, China, Switzerland for the following indications:

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+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Surgical experience with pancreatic and periampullary cancer. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Evolution and current status of the Whipple procedure: an update for gastroenterologists. [2019]

3. China pubmed.ncbi.nlm.nih.gov

[Clinical comparison on the classical versus extensive Whipple's resection for adenocarcinoma of head of pancreas]. [2005]

4. United States pubmed.ncbi.nlm.nih.gov

Guidelines for the surgical management of pancreatic adenocarcinoma. [2007]

5. United States pubmed.ncbi.nlm.nih.gov

Whipple operation revisited. [2004]

6. Peru pubmed.ncbi.nlm.nih.gov

[Pancreatoduodenectomy: myth or reality? Personal experience]. [2018]

7. Nepal pubmed.ncbi.nlm.nih.gov

Complications among Patients Undergoing Pancreaticoduodenectomy in Tertiary Care Centers of Nepal: A Descriptive Cross-sectional Study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Long term oncological outcome of laparoscopic techniques in pancreatic cancer. [2020]

9. Turkey 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Molecular analysis of cyst fluid aspiration in the diagnosis and risk assessment of cystic lesions of the pancreas. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Molecular analysis of pancreatic cyst fluid: a comparative analysis with current practice of diagnosis. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology. [2019]

13. Italy pubmed.ncbi.nlm.nih.gov

The role of molecular analysis in the diagnosis and surveillance of pancreatic cystic neoplasms. [2018]

14. China pubmed.ncbi.nlm.nih.gov

Molecular analysis of pancreatic cyst fluid changes clinical management. [2022]