Steven Libutti, MD
Dr. Libutti is the Director of the Montefiore-Einstein Center for Cancer Care, Associate Director of the Albert Einstein Cancer Center, Professor and Vice-Chairman of the Department of Surgery and Professor in the Department of Genetics at the Albert Einstein College of Medicine and the Montefiore Medical Center.
He received his A.B. from Harvard College and his M.D. from the College of Physicians and Surgeons of Columbia University where he was inducted into the Alpha Omega Alpha medical honor society. He completed his internship, surgical residency and was Chief Resident at the Presbyterian Hospital in New York. Following residency, he completed a fellowship in Surgical Oncology and Endocrine Surgery at the National Cancer Institute (NCI) and was ultimately a tenured Senior Investigator and Chief of the Tumor Angiogenesis Section in the Surgery Branch, NCI.
Dr. Libutti has received numerous honors and awards including the NCI Director’s Gold Star Award, the NCI Director’s Intramural Innovation Award and the NIH Director’s Award. Dr. Libutti has been voted a “Top Doctor in America” and to New York Magazine’s list of the Top Doctors in New York. In 2009, Dr. Libutti was invested as the “Marvin L. Gliedman, M.D., Distinguished Surgeon” at Montefiore Medical Center. He has published over 230 peer reviewed journal articles, 16 book chapters, and has given numerous presentations and lectures. He holds six U.S. patents.
Dr. Libutti’s responsibilities include directing multidisciplinary cancer care, surgical oncology and clinical cancer research. His interests are in endocrine and neuroendocrine tumors involving the thyroid, parathyroid, adrenal glands and pancreas. He is also a leader in regional cancer therapy and tumor targeted gene therapy.
Columbia Univ College of Physicians and Surgeons
New York Presbyterian Hospital
National Institutes of Health
Areas of expertise:
Cancer Surgery, endocrine surgery and cancer research (tumor angiogenesis, antiangiogenic gene therapy, regional perfusion therapy of malignant lesions, and isolation and characterization of unique tumor cytokines).
3400 Bainbridge Avenue
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Endothelial cells are the principle building blocks of blood vessels. Tumors require a blood supply to grow larger than a few millimeters in size. In this way, endothelial cells are important to a tumor because they can form blood vessels that will allow for the delivery of oxygen and nutrients to the tumor. Endothelial cells also provide a gateway for tumor cells to gain entrance to blood vessels in order to travel or metastasize to other locations. In order for tumor cells to cross endothelial cells and gain access to blood vessels, other cells like macrophages have been shown to play an important role.
There are several components of the tumor microenvironment that can influence tumor growth. Among them are endothelial cells or blood vessels, fibroblasts, macrophages and elements of the structural matrix such as collagen and fibronectin. Tumor cells can secrete factors that influence these components and the components themselves can produce factors that influence the tumor. Oxygen and the pH of the surrounding tissues also play a role.
The syndromes we commonly associate with neuroendocrine tumors of the pancreas are MEN1, vHL and neurofibromatosis (NF1). If we also include neuroendocrine tumors in other locations, such as the adrenal glands (pheochromocytoma) you can expand the list to MEN2, SDHB, SDHD, tuberous sclerosis and Carney's Complex.
The von Hippel-Lindau (vHL) syndrome is a familial cancer syndrome resulting from a mutation in the VHL tumor suppressor gene. The syndrome is manifested by tumors in the kidneys, central nervous system and spine, retina, adrenal glands, pancreas and some other sites. The pancreas tumors seen in association with vHL are non-functional pancreatic neuroendocrine tumors and they are seen in between 12% and 15% of patients with vHL. While they often behave in a benign fashion, about 10% of vHL patients with pancreatic neuroendocrine tumors can have a more aggressive biology that can lead to metastases, most often to the liver.
Minimally invasive surgical techniques can be used to resect both primary as well as metastatic sites of neuroendocrine cancers. It depends on the size and location of the tumor as well as the experience and skill of the surgeon.
Generally speaking this has to do with the size and number of tumors in the liver, where they are located, how much normal liver will remain after resection, whether or not important vascular structures are involved and if there is disease outside of the liver. While the particular criteria may vary from one type of tumor to another, these broad factors are considered for most types of metastatic cancer.
A number of factors can determine how aggressive a pancreatic cancer is. Some of these are involvement or invasion of adjacent structures like blood vessels, involvement of lymph nodes or distant organs and characteristics of the tumor cells themselves like proliferative index and the presence of certain mutations.
I think there is a lot of excitement surrounding pancreatic cancer research right now in light of the identification of important pathways involved in the development and progression of both adenocarcinoma and neuroendocrine tumors. Therapies can be targeted against a specific pathway, or targeted directly to the tumor cells themselves to avoid systemic toxicity.
Mutations in genes such as BRCA2 and KRAS, which can lead to pancreatic adenocarcinoma have been identified and open the possibility of understanding these pathways better and developing therapies to block them. Similarly, mutations in genes like MEN1, and DAXX have been shown to be important for the development and progression of pancreatic neuroendocrine tumors.
Currently, new targeted therapies such as EGF receptor inhibitors like erlotinib for pancreatic adenocarcinoma and mTOR inhibitors like everolimus for pancreatic neuroendocrine tumors are showing promise. Clearly, we need more and better agents, but the greater understanding we are developing of how these tumors form and progress will hopefully lead to more effective treatment strategies.