Carcinoid Crisis and Other Complications of Carcinoid Syndrome
Our featured experts review the current thinking on carcinoid crisis and its prevention, also noting other potentially serious complications of carcinoid syndrome, such as carcinoid heart disease.
What are your thoughts on carcinoid crisis and some of the other potentially serious complications of carcinoid syndrome?
Associate Professor of Oncology
“Being alert to the possibility of carcinoid crisis is fundamental to its prevention and management.”
Carcinoid crisis can be described as a rare but potentially life-threatening complication of carcinoid syndrome that is thought to result from the sudden release of high levels of serotonin and other active substances from a neuroendocrine tumor, resulting in hemodynamic instability. Being alert to the possibility of carcinoid crisis is fundamental to its prevention and management. It typically occurs during invasive procedures such as surgery or liver embolization, or during the induction of general anesthesia. It rarely happens outside of these types of scenarios.
There is little evidence about the best way to prevent carcinoid crisis. Most would agree on the importance of understanding the risk, recognizing the hemodynamic instability, reacting appropriately with octreotide, and initiating other supportive measures. Preventive care has probably changed somewhat in the last several decades, since many patients are already on long-acting somatostatin analogues (SSAs) at the time of their surgery or procedure. This may reduce the need for the preoperative and postoperative administration of octreotide. At Mayo Clinic, we still administer perioperative SSA therapy as a precaution in individuals who are at risk for carcinoid crisis. We would generally try to have patients on a long-acting SSA at the outset, and we administer perioperative octreotide as well.
Clinicians who are caring for patients with carcinoid syndrome generally already have a good level of awareness about the potential for carcinoid crisis, especially in consideration of procedures such as hepatic artery embolization. It is quite rare for carcinoid crisis to happen in a patient who is not already known to have carcinoid syndrome. Our first indication that the patient has carcinoid syndrome should not be in the operating room; however, occasionally, this does occur (eg, when an undiagnosed patient is undergoing surgery for some other reason). Generally, carcinoid crisis can be very successfully handled with an anesthesia team that is aware of the risk and has the required medication available. For a patient with known carcinoid syndrome who does have an episode of carcinoid crisis, after addressing the episode of carcinoid crisis, the longitudinal treatment plan for that patient’s carcinoid syndrome would not necessarily change.
Some of the other potentially serious complications of carcinoid syndrome include carcinoid heart disease, which can ultimately require valve replacement, and mesenteric fibrosis, which can interfere with blood flow to and from the intestines. Although fibrosis in the heart and in the mesentery may be a local effect of excess serotonin at these sites, the mechanisms involved in cardiac and extracardiac fibrosis are not completely understood.
Professor of Gastrointestinal Oncology
“I think that the standard practices for preventing operative carcinoid crisis have become less definitive in recent years.”
Carcinoid crisis refers to hemodynamic instability that typically occurs during a procedure such as a surgery. However, a problem in interpreting the data is that there has not always been a clear definition of carcinoid crisis. The nature of the hemodynamic instability and the presence of other signs of carcinoid crisis, such as flush, are not always delineated.
In general, carcinoid crisis correlates with carcinoid syndrome, but there are data suggesting that even patients who lack carcinoid syndrome, but undergo surgery for neuroendocrine tumors, may experience similar hemodynamic instability. There are also analyses suggesting that prophylaxis with short-acting octreotide may not be necessary. There is agreement that octreotide should be available to administer (either as a bolus or an infusion) in case there are complications, but not everyone agrees that patients require prophylaxis before surgery. I think that the standard practices for preventing operative carcinoid crisis have become less definitive in recent years. There are no randomized studies, and it is a rare clinical entity, making it challenging to know whether prophylaxis reduces these operative complications. At Moffitt Cancer Center, our surgeons have decided to stop giving prophylactic octreotide before surgery, but it is certainly on hand.
Professor and Chief
Division of Medical Oncology
Department of Medicine
Member, UK Markey Cancer Center
University of Kentucky
“Carcinoid heart disease is another significant complication of carcinoid syndrome, and it is much more common than carcinoid crisis.”
I agree that awareness is key in carcinoid crisis. You cannot prevent something if you do not know that it exists and/or that the patient may be at risk for it. I think that the individuals who are at greater risk for carcinoid crisis may be those whose carcinoid syndrome is not well controlled going into their procedure (eg, patients who are newly diagnosed or are not yet being followed by a medical oncologist).
An established patient who is seeing a medical oncologist will have been stabilized and prepared in anticipation of such a procedure, whether it be a laparotomy to remove the primary tumor or a locoregional treatment. We are fortunate to be able to stabilize patients prior to these procedures, and we do not see carcinoid crisis much anymore because we are prepared for it. As a result, clinicians today are in a much better position to have fewer surprises than in the past.
The type of prophylaxis for carcinoid crisis can vary depending on the circumstances. Self-administration of octreotide 1 hour or so before a dental procedure may be a sufficient precaution for some patients, whereas the team may decide to use an intravenous octreotide drip for patients with high tumor bulk whose tumors are being manipulated in the operating room.
Carcinoid heart disease is another significant complication of carcinoid syndrome, and it is much more common than carcinoid crisis. The historical estimates of the prevalence and incidence of carcinoid heart disease are quite variable. In more recent times, the reported incidence of carcinoid heart disease has decreased as SSA use has increased. Nonetheless, SSAs have not been shown to reverse existing carcinoid heart disease, and it is still important to be vigilant about screening for this complication.
Bardasi C, Benatti S, Luppi G, et al. Carcinoid crisis: a misunderstood and unrecognized oncological emergency. Cancers (Basel). 2022;14(3):662. doi:10.3390/cancers14030662
Clement D, Ramage J, Srirajaskanthan R. Update on pathophysiology, treatment, and complications of carcinoid syndrome. J Oncol. 2020;2020:8341426. doi:10.1155/2020/8341426
Gustafsson BI, Hauso O, Drozdov I, Kidd M, Modlin IM. Carcinoid heart disease. Int J Cardiol. 2008;129(3):318-324. doi:10.1016/j.ijcard. 2008.02.019
Kaltsas G, Caplin M, Davies P, et al; Antibes Consensus Conference Participants. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: pre- and perioperative therapy in patients with neuroendocrine tumors. Neuroendocrinology. 2017;105(3):245-254. doi:10.1159/000461583
Laskaratos F-M, Davar J, Toumpanakis C. Carcinoid heart disease: a review. Curr Oncol Rep. 2021;23(4):48. doi:10.1007/s11912-021-01031-z
Maxwell JE, Naraev B, Halperin DM, Choti MA, Halfdanarson TR. Shifting paradigms in the pathophysiology and treatment of carcinoid crisis. Ann Surg Oncol. 2022 Feb 14. doi:10.1245/s10434-022-11371-0
Pavel M, Öberg K, Falconi M, et al; ESMO Guidelines Committee. Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(7):844-860. doi:10.1016/j.annonc.2020.03.304