Neuroendocrine cancer is a rare cancer affecting only 125,000 patients in the United States, about five in 100,000 cases are diagnosed in a year. Neuroendocrine cancer is frequently misdiagnosed as common illnesses such as IBS, Chron’s, asthma and even the effects of menopause. It has the unfortunate legacy of originally being known as a benign “cancer-like” disease because it tends to be slow growing. Patients can go months, or even years, before receiving a proper diagnosis, resulting in disease spread. Pancreatic neuroendocrine cancer is the same cancer that Apple executive, Steve Jobs, was first diagnosed with in 2003 and eventually succumbed to in 2011. It is likely he had the disease for decades prior to actual diagnosis. (McDougall, 2011)
Neuroendocrine cancer was first named “karzinoide” (“carcinoma-like”) in 1907 by Siegfried Oberndorfer, a German doctor who was the first to identify the distinct clinical entities of these tumors, and emphasized their benign nature. In 1929, Oberndorfer amended his original classification to describe that these tumors that formed in the small bowel could be malignant and metastasize. (Modlin, Shapiro, 2004)
What makes neuroendocrine cancers unlike other types of cancer is in their very nature. They form in the neuroendocrine system’s glandular endocrine-hormone producing cells that are extensively dispersed throughout the body. The most frequent site of origin for neuroendocrine cancers is in the small intestine, right colon or appendix and are classified as mid-gut. Less frequently they will be found in the foregut, which includes the lung, pancreas, stomach or duodenum. Hindgut involvement is found in the transverse colon, sigmoid colon, or rectum. Very rarely primaries arise from the ovaries, testes, liver, kidneys, bile ducts and other areas throughout the endocrine system. The disease can be genetic in some cases, but there is no known cause for this cancer.
Since these cancers form in endocrine cells, they can secrete various substances, which are frequently used as markers to measure the disease progression. Almost all neuroendocrine tumors secrete serotonin, bradykinin, and chromogranin-A at varying levels. Other substances secreted are substance-P, pancreastatin, neurotensin, pancreatic polypeptide, neurokinin-A, motilin as well as other peptide hormones. Unfortunately, there is no ideal marker for this disease as it varies from patient to patient. (Vinik, Woltering, Warner, Caplin, O’Dorisio, Wiseman, Coppola, Go, 2010)
Functional neuroendocrine tumors are those which secrete a substance that causes a symptom. Serotonin, the most common peptide to be secreted by these tumors, causes symptoms such as flushing, diarrhea, and wheezing. These symptoms are known as carcinoid syndrome. The diarrhea can be chronic, resulting in weight loss, and the excess serotonin can cause a very specific form of heart valve damage. A severe form of carcinoid syndrome is known as a carcinoid crisis and can be life threatening, causing an extreme drop in blood pressure. Carcinoid syndrome (or crisis) can be triggered by what is known as the five “E’s” including 1) epinephrine – from over the counter medications and anesthesia, 2) eating – large meals and certain foods, 3) emotions – stressful situations, 4) exercise – heavy activities, trauma or surgery and 5) ethanol – alcoholic beverages.
Other functional neuroendocrine tumors can secrete insulin, glucagon, vasoactive polypeptide, gastrin, histamines, and somatostatin. Generally speaking these are neuroendocrine tumors that arise from the pancreas, lungs, pituitary and adrenal glands. From dysregulation of blood sugars, excessive stomach acid, skin rashes, explosive diarrhea, foul smelling, greasy stools, and wheezing, the symptoms can be debilitating, if not life threatening. In the case of the pancreatic tumors, they can change and secrete different or various hormones over time. For example, a tumor that began as an insulinoma that secretes insulin can change to glucagonoma and start secreting glucagon.
There are also non-functional neuroendocrine tumors that do not secrete excessive substances, therefore, do not have symptoms. Pancreatic polypeptide and ghrelin are two substances that can be secreted in excess, but neither have a known clinical syndrome, so they are classified as non-functioning.
As with most cancers, the first line of defense, if possible, is surgery. If surgery is not possible or is unsuccessful, there are other treatments available to patients. Somatostatin analogues such as octreotide, which behave like natural somatostatin that the body produces, regulates the edocrine system and can alleviate some of the side effects of the substances secreted by behaving as a universal “off-switch” for the excess secretions. Data suggests that somatostatin analogue medications may make the tumors less active. (Rinke, Müller, Schade-Brittinger, Klose, Barth, Wied, et al., 2009) There are several forms of chemotherapies, either intravenous or oral medications that can be used, depending on the site of origin or aggressiveness. Finally, there are targeted radiotherapy treatments available in Europe that are currently in trials in the United States that are able to bind to the tumors, but can cause collateral damage to kidneys. In most cases the disease is incurable but manageable, but ultimately deadly for many patients.
There is no cure for neuroendocrine cancer but it can be a manageable disease depending on its severity. If a patient is properly diagnosed early in their disease, they can live for many years with intervening treatments. Neuroendocrine cancer patients tend to have many surgeries over the course of their disease as it is the most effective. The largest obstacle to diagnosis is awareness, both in the medical community and in the general population. As a rare disease, many doctors will never even see a patient and there is little funding for research. Patients may bounce from doctor to doctor trying to obtain a diagnosis. There are dedicated specialists throughout the world and patients frequently have to travel for treatment. Despite the lack of research funds, new treatments are being studied, thanks to the specialists and several pharmaceutical companies. The patient community tends to be highly educated in their illness and there are a number of foundations worldwide dedicated to educating and supporting the patient community.
For more extensive information on neuroendocrine cancer, please visit The Carcinoid Cancer Foundation.
Also, visit our Links for more sites dedicated to comprehensive information about carcinoid and neuroendocrine cancers.
- 1 Modlin, I., Shapiro, M., & Kidd, M. (2004, December 1). Siegfried Oberndorfer: origins and perspectives of carcinoid tumors.. . Retrieved July 12, 2014, from http://www.ncbi.nlm.nih.gov/pubmed/15619202
- 2 Warner, R. (2012, January 31). A Review of Carcinoid Cancer. . Retrieved July 12, 2014, from http://www.carcinoid.org/content/review-carcinoid-cancer
- 3 Taub, E. (2012, March 26). Rare Tumor Is Deceptive And Deadly. . Retrieved July 12, 2014, from http://www.nytimes.com/2002/03/26/health/cases-rare-tumor-is-deceptive-and-deadly.html
- 4 Rinke, A., Müller, H., Schade-Brittinger, C., Klose, K., Barth, P., Wied, M., et al. (2009, August 24). Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.. . Retrieved July 12, 2014, from http://www.ncbi.nlm.nih.gov/pubmed/19704057
- 5 Carcinoid Locations and Classification. (2010, May 15). . Retrieved July 12, 2014, from http://www.caringforcarcinoid.org/neuroendocrine-cancer/carcinoid-cancer
- 6 Vinik, A., Woltering, E., Warner, R., Caplin, M., O’Dorisio, T., Wiseman, Go., et al. NANETS Consensus Guidelines for the Diagnosis of Neuroendocrine Tumor. Pancreas, 39, 713-734.
- 6 McDougall, J., MD. (2011, November). McDougall Newsletter: November 2011 – Why Did Steve Jobs Die? Retrieved July 07, 2016, from https://www.drmcdougall.com/misc/2011nl/nov/jobs.htm