Cancer, Intestinal Carcinoid

Article Author:
Mridula Krishnan
Article Editor:
Faiz Tuma
Updated:
11/18/2018 3:02:14 PM
PubMed Link:
Cancer, Intestinal Carcinoid

Introduction

In general, the term carcinoid refers to well-differentiated neuroendocrine tumors (NET) that originate commonly in the gastrointestinal tract (about 55%) and uncommonly in other locations such as the lung, kidneys, or the ovaries. The exception to this includes pancreatic neuroendocrine tumors which are a separate entity called PNET.

The incidence of intestinal carcinoids is on the rise due to increased detection of these tumors on routine imaging for other purposes. Small intestinal carcinoids are mostly located in the ileal region which is 60 cm from the ileocecal valve. Colonic carcinoids are usually detected in elderly patients and are commonly located on the right side, particularly the cecum. Commonly, rectal carcinoids are incidentally discovered on imaging.[1][2][3]

Etiology

Carcinoid tumors are slow-growing neuroendocrine tumors that originate in the cells of the neuroendocrine system. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) are associated with carcinoid syndrome.[4][5]

Epidemiology

Carcinoids are relatively rare tumors. Colorectal carcinoids are more frequent in the Asia/Pacific region than in Europe. In Europe, small intestinal and stomach carcinoids are more prevalent. Intestinal carcinoids have also been found to be more prevalent among African Americans as compared to whites.

Pathophysiology

Many secretory products have been identified in various intestinal carcinoid tumors. The most commonly produced substances include serotonin, histamine, tachykinins, kallikrein, and prostaglandins.

The metabolism of tryptophan is impaired in these patients with intestinal carcinoids. In a healthy individual only 1% of tryptophan is converted into serotonin whereas, in a patient with carcinoid, the majority of tryptophan is metabolized to serotonin. This serotonin is excreted in the urine as 5-hydroxy indole acetic acid (5-HIAA).[6]

History and Physical

In most cases, carcinoids may go unrecognized as patients may be asymptomatic. It may manifest with clinical symptoms only in the presence of liver metastasis. Uncommonly, carcinoid of the ovary or kidneys may clinically manifest even in the absence of metastasis.

Typical history given by patients include gastrointestinal symptoms such as diarrhea and abdominal cramping. Dermatological symptoms commonly manifest as flushing due to histamine release. Occasional signs include the presence of telangiectasias. Other systemic symptoms may also include wheezing as a result of bronchoconstriction due to the release of histamine by the tumor. Also, some tumors may secrete other peptide hormones such as insulin, glucagon, vasoactive intestinal peptide (VIP), secretin or gastrin which may produce other clinical manifestations.

Small bowel neuroendocrine tumors can cause chronic or recurrent abdominal pain and may occasionally lead to small bowel obstruction.

Evaluation

Laboratory testing

A useful initial diagnostic test for carcinoid syndrome is 24 hours urinary excretion of 5-Hydroxy Indole Acetic Acid (5-HIAA). It has 90% sensitivity and specificity for the diagnosis of intestinal carcinoid. This may be falsely positive as a result of ingestion of certain drugs or serotonin rich foods. Other less commonly used tests include chromogranin A concentration and measuring urinary excretion of serotonin.[7]

Imaging

Various modalities have been used to detect intestinal carcinoids including CT, MRI and radiolabelled scans such as octreotide scan, and Gallium 68 DOTATATE scan.

Triple phase contrast-enhanced CT scan is most commonly used as it is widely available. Some of the disadvantages of a CT scan are difficulty in detecting small tumors less than 1 cm in size and difficulty in distinguishing colorectal adenocarcinoma from colorectal carcinoid tumors due to their similarity in appearance.

MRI modality is the most sensitive technique to detect liver metastasis and can be used as an alternative to CT scan.

Octreotide scan has the advantage of detecting metastasis beyond the abdominal region. It is currently in use in conjunction with Positron emission tomography (PET) scanning to increase sensitivity to detect pathologic uptake in the abdominal region. The clinical value of the octreotide scan for surveillance of patients with carcinoid is questionable due to the availability of highly sensitive CT scans.

There is no universal staging system for intestinal carcinoids. The following classification is used:

  • Localized when the disease is limited
  • Regional spread when there is involvement of adjacent organs
  • Distant spread

Treatment / Management

Staging

The current TNM staging system is a combined staging for jejunoileal, duodenal, and ampullary neuroendocrine tumors. In the United States, the newer version is scheduled to go into effect on January 1, 2018, and has separate TNM classifications and prognostications for jejunoileal, and duodenal/ampullary tumors.[8][9][10]

Treatment of Non-metastatic Intestinal Carcinoid:

Surgical Management

  • Carcinoids of the small intestine have a high likelihood of metastasis, irrespective of the size. Therefore, patients without evidence of metastasis should be treated with resection of the involved area of the small bowel including the small bowel mesentery.
  • Colorectal carcinoid tumors are mostly more than 2 cm and are invasive. Patients without metastasis should be treated with partial colectomy and lymphadenectomy.

Treatment of Metastatic Intestinal Carcinoid:

For patients with symptomatic carcinoid syndrome and unresectable disease, initial treatment is advised with a somatostatin analog. However, for patients with metastatic disease that is resectable with curative intent without extrahepatic metastases, resection is preferred over medical therapy.

Medical Management: 

  • Somatostatin analogues: These are first-line agents used for the treatment of symptomatic carcinoid. Right-sided includes octreotide and lanreotide which have been shown to be highly effective in controlling symptoms with intestinal carcinoid. A depot preparation of octreotide is available in the form of monthly intramuscular injections. These are usually well tolerated except for mild symptoms such as nausea or bloating.
  • Interferon: This may be an option for patients with advanced disease who have worsening symptoms while on treatment with somatostatin analogs or who are intolerant of somatostatin analog therapy, but it is less commonly used due to potential adverse effects.
  • Molecular-directed therapy: mTor inhibitors like everolimus are currently approved as second-line therapy for patients who have progressive symptoms despite the use of somatostatin analogues.

Prognosis

For patients with localized disease, the prognosis is good and allows for long-term survival.

In certain patients with isolated liver metastases, survival can be increased with appropriate control of the primary and excision of the metastatic lesion.

Complications

  • Malignant carcinoid syndrome
  • Carcinoid abdominal crises
  • Right-sided valvular heart disease
  • Asthma

Postoperative and Rehabilitation Care

Monitoring for recurrence is as follows:

Appendicular cancers less than 2 cm and localized to the tip do not require any follow-up.

For those who undergo a right hemicolectomy, monitoring is required every 3-6 months with CT or MR scan.

Rectal carcinoids less than 2 cm which have been removed transanally, follow up is required with anoscopy at 6 and 12 months.

Those with intestinal carcinoids need long-term monitoring every 6 months for 3 years.

Pearls and Other Issues

Surveillance

There is limited evidence for recommendations for follow-up after surgical resection. For all resected small intestinal and colonic carcinoid tumors follow long-term surveillance as there is a risk of recurrence even 5 years following resection. For small intestinal carcinoids, the general recommendation for surveillance is with triple phase CT or MRI imaging. Tumors less than 2 cm in size are less likely to metastasize.

Urine 5-HIAA and Chromogranin A are followed every six months for the first couple of days. This is followed by annual surveillance for four years followed by every 2 years up to 10 years after surgery.

Enhancing Healthcare Team Outcomes

The North American Neuroendocrine Tumor Society has released guidelines for surveillance and medical management of midgut neuroendocrine tumors. The guidelines emphasize a multidisciplinary approach for optimal outcomes. While surgery is the ideal treatment for patients with localized lesions, recent studies reveal that cytoreductive surgery with heated intraperitoneal chemotherapy may improve survival in some patients with metastatic peritoneal disease. Because these tumors have an unpredictable behavior, lifelong surveillance is recommended. With expert care, many patients can have a good quality of life or even be cured. [11][12][13] (Level V)

Besides the general surgeon, an oncologist should be involved in the care of this patient. The pharmacist must be aware of the carcinoid syndrome and must have octreotide in the formulary. [14] (Level V)

Prognosis

Prognosis depends primarily on tumor stage, margin status, histologic grade/differentiation, and site of origin. Overall, the prognosis of intestinal carcinoids very good. Even among patients with distant metastasis, 5-year overall survival ranges between 40% to 85%.