Natural History and Management of Pancreatic Lesions in Von Hippel-Lindau Disease

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Brief Title

Natural History and Management of Pancreatic Lesions in Von Hippel-Lindau Disease

Official Title

Evaluation of the Natural History and Management of Pancreatic Lesions Associated With Von Hippel-Lindau

Brief Summary

      Von Hippel-Lindau disease (VHL) is an inherited cancer syndrome. Patients are at risk for
      developing pancreatic cysts and tumors. These tumors are more aggressive in some people than
      in others. To learn more about this disease, its genetic cause and how best to treat it, this
      study will 1) identify patients with VHL who have pancreatic lesions; 2) examine the
      characteristics of the lesions and how fast they grow; 3) study how well imaging tests can
      reveal lesion characteristics that will help in diagnosis; and 4) perform genetic studies
      using blood and, when possible, tissue samples.

      Patients 12 years of age and older with VHL involving the pancreas may be eligible for this
      study. Participants will undergo some or all of the following tests and procedures:

        -  Interviews with a cancer doctor, cancer nurses, and a surgeon (if surgery is

        -  Computed tomography (CT) scan of the abdomen, chest, or pelvis. This test uses x-rays to
           produce images of body tissues and organs in small sections.

        -  Magnetic resonance imaging (MRI) of the abdomen. This test uses radio waves and a strong
           magnetic field to produce images of body tissues and organs.

        -  Ultrasound of the abdomen. This test uses sound waves to create images body tissues and

        -  Blood tests for routine laboratory chemistries, for tests specific to the pancreas, and
           for genetic studies

        -  24-hour urine studies

      After the tests are completed, the doctor will discuss the results with the patient. Patients
      with a pancreatic tumor that requires surgery will be offered the option of an operation to
      remove as much tumor as possible. Patients with lesions that are not appropriate for surgery
      will be asked to return to National Institutes of Health (NIH) for scans and x-rays every
      year to monitor growth of the lesions. If surgery should become advisable in the future, the
      option will be discussed at that time. Patients with pancreatic cysts will be asked to return
      to NIH every 2 years for scans and x-rays to monitor their condition.

Detailed Description


      Patients with the familial cancer syndrome von Hippel-Lindau (VHL) demonstrate manifestations
      in a variety of organs among them the pancreas. Pancreatic manifestations can range from
      benign cysts and micro cystic adenomas to neuroendocrine tumors of the pancreas which are
      capable of regional and distant spread. These neuroendocrine tumors can result in
      life-threatening complications.

      This protocol is designed to identify VHL patients with pancreatic manifestations and to
      follow these patients with serial imaging studies and germ line and tissue genetic analysis.


      To identify patients with VHL having pancreatic lesions defined by simple cysts, microcystic
      adenomas, neuroendocrine tumors and other solid lesions of the pancreas.

      To follow patients with VHL and pancreatic manifestations by serial examination with
      non-invasive imaging studies.

      For patients with solid lesions of the pancreas, to determine the rate of growth and to
      correlate the growth rate with clinical measures of disease progression.

      To validate non-invasive imaging methods for differentiating benign solid lesions from
      lesions with malignant potential.

      To characterize the time from initial presentation with pancreatic tumors to the time that
      surgery is recommended.


      Patients greater than or equal to 12 years of age who have been diagnosed with VHL.

      Patients/parent must be able to sign an informed consent and be willing to return to National
      Institutes of Health (NIH) for follow-up.


      Demographic data will be collected from the medical record and patient interview for each
      patient participant. Data will be securely stored in a computerized database.

      Patients will be evaluated by the Urologic Oncology Branch personnel as indicated to rule out
      or manage other manifestations of VHL. Imaging studies of regions other than the chest and
      abdomen will be dictated by best clinical practice for the workup and management of VHL
      manifestations as has been previously published.

      All patients enrolled on this study will be offered genetic counseling by a trained genetic

      After their initial on-study evaluation, patients who are not found to have solid lesions of
      the pancreas but rather have only cystic disease of the pancreas, will be re-screened every
      two years with non-invasive imaging studies.

      Surgical resection of solid lesions of the pancreas will be recommended based on previously
      published criteria.

      Based on our analysis of likelihood of tumor growth or risk of metastasis, data will be
      analyzed every two years and appropriate revisions will be made to the surgical management
      guidelines, if indicated by data analysis.

      Projected accrual will be 25 patients per year for a total of 15 years. Thus, we anticipate
      accruing 600 patients on this protocol.

Study Type


Primary Outcome

Number of Patients With Pancreatic Lesions Defined by Simple Cysts, Microcystic Adenomas, Neuroendocrine Tumors & Other Solid Lesions of the Pancreas Who Had Significant Growth in Lesions or Symptoms Related to the Lesions Requiring Surgical Intervention

Secondary Outcome

 Percentage of Participants With Exon 3 Mutation Compared to Participants With Exon 1 or 2 Von Hippel Lindau (VHL) Mutations Who Required an Intervention


Von Hippel-Lindau Disease


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

April 11, 2003

Completion Date

November 29, 2017

Primary Completion Date

November 29, 2017

Eligibility Criteria


        Patients who have been diagnosed with Von Hippel Lindau (VHL) using the following criteria:
        either germ line analysis (12) or clinical criteria and a family history (8, 12) and who
        have at least 1 pancreatic manifestation of VHL as documented on any non-invasive imaging
        study. These manifestations include:

          1. Pancreatic cyst(s).

          2. Solid lesions suspicious for microcystic adenoma(s).

          3. Solid enhancing lesions suspicious for primitive neuroectodermal tumor (PNET)(s).

          4. Any other solid lesion(s) of the pancreas.

        Age greater than or equal to 12 years of age.

        Patients must be willing to return to National Institutes of Health (NIH) for follow-up.

        Patients/parent must be able to sign an informed consent.


        Patients unwilling to undergo serial non-invasive imaging.




12 Years - 80 Years

Accepts Healthy Volunteers



Naris Nilubol, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party

Principal Investigator

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Naris Nilubol, M.D., Principal Investigator, National Cancer Institute (NCI)

Verification Date

October 2018