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Heather Hampel

NCCN has developed new guidelines for the assessment of high-risk familial/genetic colorectal cancer, and has positioned these recommendations within the guidelines for detection, prevention, and risk reduction. The Panel recommends that all patients with colorectal cancer be screened for Lynch syndrome, which occurs in 1 of every 35 patients and is the most common form of hereditary colorectal cancer. Such screening could be universal so that all tumors are genetically tested, or screening could be restricted to patients under the age of 70 and those aged 70 and older who meet clinical criteria.

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Heather Hampel

Either microsatellite instability testing or immunohistochemical staining for the 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) should be performed on all newly diagnosed colorectal cancers. This testing will identify tumors that are microsatellite unstable, which has implications for patient prognosis and possibly treatment. In addition, it will identify patients who are more likely to have Lynch syndrome. Of every 35 colorectal cancer patients, 1 has Lynch syndrome, the most common hereditary cause of colorectal and endometrial cancers. Diagnosis of Lynch syndrome affects the medical management of the patient and their relatives, with potentially life-saving ramifications. Although screening only a subset of patients with colorectal cancer based on age at diagnosis, family history, or histologic criteria will reduce the number of screening tests necessary, it will miss a significant proportion of patients with microsatellite unstable colorectal cancer and many patients with Lynch syndrome. Given that universal screening of all patients with newly diagnosed colorectal cancer using immunohistochemistry as the initial test was recently shown to be cost-effective and comparable with other widely accepted preventive services, it is not necessary to try to reduce costs by restricting screening to a subset of patients, which leads to a reduction in the efficacy of the screening program.

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Dawn Provenzale, Samir Gupta, Dennis J. Ahnen, Travis Bray, Jamie A. Cannon, Gregory Cooper, Donald S. David, Dayna S. Early, Deborah Erwin, James M. Ford, Francis M. Giardiello, William Grady, Amy L. Halverson, Stanley R. Hamilton, Heather Hampel, Mohammad K. Ismail, Jason B. Klapman, David W. Larson, Audrey J. Lazenby, Patrick M. Lynch, Robert J. Mayer, Reid M. Ness, Scott E. Regenbogen, Niloy Jewel Samadder, Moshe Shike, Gideon Steinbach, David Weinberg, Mary Dwyer and Susan Darlow

This is a focused update highlighting the most current NCCN Guidelines for diagnosis and management of Lynch syndrome. Lynch syndrome is the most common cause of hereditary colorectal cancer, usually resulting from a germline mutation in 1 of 4 DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2), or deletions in the EPCAM promoter. Patients with Lynch syndrome are at an increased lifetime risk, compared with the general population, for colorectal cancer, endometrial cancer, and other cancers, including of the stomach and ovary. As of 2016, the panel recommends screening all patients with colorectal cancer for Lynch syndrome and provides recommendations for surveillance for early detection and prevention of Lynch syndrome-associated cancers.

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Randall W. Burt, Jamie A. Cannon, Donald S. David, Dayna S. Early, James M. Ford, Francis M. Giardiello, Amy L. Halverson, Stanley R. Hamilton, Heather Hampel, Mohammad K. Ismail, Kory Jasperson, Jason B. Klapman, Audrey J. Lazenby, Patrick M. Lynch, Robert J. Mayer, Reid M. Ness, Dawn Provenzale, M. Sambasiva Rao, Moshe Shike, Gideon Steinbach, Jonathan P. Terdiman, David Weinberg, Mary Dwyer and Deborah Freedman-Cass

Mortality from colorectal cancer can be reduced by early diagnosis and by cancer prevention through polypectomy. These NCCN Guidelines for Colorectal Cancer Screening describe various colorectal screening modalities and recommended screening schedules for patients at average or increased risk of developing colorectal cancer. In addition, the guidelines provide recommendations for the management of patients with high-risk colorectal cancer syndromes, including Lynch syndrome. Screening approaches for Lynch syndrome are also described.

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Mary B. Daly, Jennifer E. Axilbund, Saundra Buys, Beth Crawford, Carolyn D. Farrell, Susan Friedman, Judy E. Garber, Salil Goorha, Stephen B. Gruber, Heather Hampel, Virginia Kaklamani, Wendy Kohlmann, Allison Kurian, Jennifer Litton, P. Kelly Marcom, Robert Nussbaum, Kenneth Offit, Tuya Pal, Boris Pasche, Robert Pilarski, Gwen Reiser, Kristen Mahoney Shannon, Jeffrey R. Smith, Elizabeth Swisher and Jeffrey N. Weitzel

Overview All cancers develop as a result of mutations in certain genes, such as those involved in the regulation of cell growth and/or DNA repair,1,2 but not all of these mutations are inherited from a parent. For example, sporadic mutations can occur in somatic/tumor cells only, and de novo mutations can occur for the first time in a germ cell (i.e., egg or sperm) or in the fertilized egg itself during early embryogenesis. However, family studies have long documented an increased risk for several forms of cancer among first-degree (i.e., parents, siblings, and children) and second-degree relatives (i.e., grandparents, aunts or uncles, grandchildren, and nieces or nephews) of affected individuals. These individuals may have an increased susceptibility to cancer as the result of 1 or more gene mutations present in parental germline cells; cancers developing in these individuals may be classified as hereditary or familial cancers. Hereditary cancers are often characterized by mutations associated with a high probability of cancer development (i.e., a high penetrance genotype), vertical transmission through either mother or father, and an association with other types of tumors.3,4 They often have an early age of onset and exhibit an autosomal dominant inheritance pattern (i.e., occur when the individual has a mutation in only 1 copy of a gene). Familial cancers share only some features of hereditary cancers. For example, although familial breast cancers occur in a given family more frequently than in the general population, they generally do not exhibit the inheritance patterns or onset age consistent...
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Dawn Provenzale, Kory Jasperson, Dennis J. Ahnen, Harry Aslanian, Travis Bray, Jamie A. Cannon, Donald S. David, Dayna S. Early, Deborah Erwin, James M. Ford, Francis M. Giardiello, Samir Gupta, Amy L. Halverson, Stanley R. Hamilton, Heather Hampel, Mohammad K. Ismail, Jason B. Klapman, David W. Larson, Audrey J. Lazenby, Patrick M. Lynch, Robert J. Mayer, Reid M. Ness, M. Sambasiva Rao, Scott E. Regenbogen, Moshe Shike, Gideon Steinbach, David Weinberg, Mary A. Dwyer, Deborah A. Freedman-Cass and Susan Darlow

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening provide recommendations for selecting individuals for colorectal cancer screening, and for evaluation and follow-up of colon polyps. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Colorectal Cancer Screening panel meeting. Major discussion topics this year were the state of evidence for CT colonography and stool DNA testing, bowel preparation procedures for colonoscopy, and guidelines for patients with a positive family history of colorectal cancer.

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Samir Gupta, Dawn Provenzale, Scott E. Regenbogen, Heather Hampel, Thomas P. Slavin Jr, Michael J. Hall, Xavier Llor, Daniel C. Chung, Dennis J. Ahnen, Travis Bray, Gregory Cooper, Dayna S. Early, James M. Ford, Francis M. Giardiello, William Grady, Amy L. Halverson, Stanley R. Hamilton, Jason B. Klapman, David W. Larson, Audrey J. Lazenby, Patrick M. Lynch, Arnold J. Markowitz, Robert J. Mayer, Reid M. Ness, Niloy Jewel Samadder, Moshe Shike, Shajanpeter Sugandha, Jennifer M. Weiss, Mary A. Dwyer and Ndiya Ogba

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the management of patients with high-risk syndromes associated with an increased risk of colorectal cancer (CRC). The NCCN Panel for Genetic/Familial High-Risk Assessment: Colorectal meets at least annually to assess comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on genes newly associated with CRC risk on multigene panels, the associated evidence, and currently recommended management strategies.

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Dawn Provenzale, Samir Gupta, Dennis J. Ahnen, Arnold J. Markowitz, Daniel C. Chung, Robert J. Mayer, Scott E. Regenbogen, Amie M. Blanco, Travis Bray, Gregory Cooper, Dayna S. Early, James M. Ford, Francis M. Giardiello, William Grady, Michael J. Hall, Amy L. Halverson, Stanley R. Hamilton, Heather Hampel, Jason B. Klapman, David W. Larson, Audrey J. Lazenby, Xavier Llor, Patrick M. Lynch, June Mikkelson, Reid M. Ness, Thomas P. Slavin Jr, Shajanpeter Sugandha, Jennifer M. Weiss, Mary A. Dwyer and Ndiya Ogba

The NCCN Guidelines for Colorectal Cancer (CRC) Screening outline various screening modalities as well as recommended screening strategies for individuals at average or increased-risk of developing sporadic CRC. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize 2018 updates to the NCCN Guidelines, with a primary focus on modalities used to screen individuals at average-risk for CRC.