OncoLink

Cancer of the Small Bowel

Neha Vapiwala, MD
Updated by Lara Bonner Millar, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 18, 2011

What is the small bowel?

The small bowel, also known as the small intestine, is the portion of the digestive tract that connects the stomach and the large bowel, also called the colon (see colon cancer). There are three distinct parts of the small bowel: 1) the duodenum, 2) the jejunum and 3) the ileum. (Note: Although these three parts can all be grouped under the term "small bowel", there are several notable differences between them, such as blood supply, degree of attachment, surrounding structures, etc.)

In order to fit inside a person's body, the small and large intestines are folded up into a very compact form. However, if you were to unfold the small bowel and measure its full length, it would be about 15 to 20 feet long! In fact, the small bowel makes up about 75% of the entire digestive system.

What does the small bowel do?

The small bowel plays a critical role in the break down and absorption of food, so that important vitamins, minerals and nutrients can be absorbed into the body.

How common is small bowel cancer?

Surprisingly, despite the amazingly long length of the small bowel compared to the rest of the digestive tract, cancer of the small bowel is very rare. This includes either cancers starting in the bowel or cancers spreading there from another body site. Despite comprising 75% of the digestive tract and 90% of the surface of the digestive tract, only 2% of all bowel cancers occur in the small bowel and they represent about 0.5% of all cancers diagnosed in the U.S. This equates to about 5,600 new cases annually and there are approximately 1,100 deaths from small bowel cancer a year. Up to 25% of small bowel tumors present concurrently with tumors in other parts of the body such as the colon or breast.

What are the causes of small bowel cancer?

Unfortunately the cause of most small bowel cancers is unknown. There are, however, some possible risk factors that might increase a person's chance of developing small bowel cancer. Some examples are: Crohn's disease, celiac sprue disease, Peutz-Jegher's syndrome, and intestinal polyposis. Immunodeficiency, (decrease in the body ability to fight disease) such as due to AIDS, appears to increase the risk of small bowel cancers, particularly lymphomas. Small bowel tumors appear to be slightly more common in men.

Also, a study done by researchers at the University of Southern California found that heavy alcohol drinking and high sugar intake were both associated with an increased risk of developing small bowel cancer. Furthermore, the study found that in men, the combination of heavy cigarette smoking and heterocyclic amine ingestion from foods like fried bacon, ham, and barbecued or smoked meat and fish, also increase the risk.

What are the types of small bowel cancer?

There are four main types of small bowel cancer, depending on the appearance under the microscope and the "cell of origin"(cell type in which the cancer starts):

Adenocarcinoma: most common type, typically starts in the lining or inside layer of the bowel, and usually occurs in the duodenum. Like adenocarcinomas of the colon or rectum, these tumors are thought to arise from a benign growth, known as an adenoma, in the small bowel. They are usually more common in males and occur around 50-70 years of age. People with Crohn's disease may present at an earlier age. 75% are advanced staged tumors at presentation.

Sarcoma: typical subtype is "leiomyosarcoma", which starts in the muscle wall of the small bowel and usually occurs in the ileum; one uncommon subtype is gastrointestinal stromal tumor, which can occur in any of the three parts of the small bowel; they make up about 7-15% of cancers of the small bowel.

Carcinoid: starts in the special hormone-making cells of the small bowel and usually occurs in the ileum, sometimes in the appendix (which is the first part of the large bowel). They tend to occur in people between the ages of 50-60 but can occur in the 20's. These tumors are discussed in greater detail in another overview.

Lymphoma: starts in the lymph tissue of the small bowel and usually occurs in the jejunum; typical subtype is non-Hodgkin's lymphoma; primary lymphomas of the small bowel appear to be increasing likely due to AIDS and immunosuppression for transplants. Primary lymphomas of the GI tract in the U.S. usually occur in the stomach with only 10% occurring in the small bowel, interestingly in the Middle East up to 75% of people with GI lymphomas will have small bowel lymphomas.

Every now and then a small bowel cancer may actually be metastatic cancer, meaning that it has spread to the small bowel from a primary cancer located elsewhere in the body.

There are also several benign tumors, which can arise from the small bowel including: adenomas, leiomyomas, fibromas, and lipomas.

What are the signs and symptoms of small bowel cancer?

Given how rare small bowel cancer is compared to many other cancerous and noncancerous diseases, it is already a difficult diagnosis. On top of that, the symptoms of small bowel cancer are usually pretty nonspecific, adding to the difficulty of diagnosis.

Common symptoms include:

  • crampy abdominal pain
  • blood mixed in the stools
  • dark/tarry/black stools (from "digested" blood)
  • weight loss
  • diarrhea
  • jaundice

Again, these symptoms could be caused by a number of medical conditions. If symptoms such as the ones listed above are severe, worsening, or persistent, medical attention should be sought so that a timely and accurate diagnosis can be made. Anytime blood is in the stools or the stools are black, medical attention should be sought.

A far less common presenting symptom is bowel obstruction, in which the tumor blocks the passage of food products through the bowel. The blockage could be complete or partial. Bowel obstruction can cause sharp belly pain, sensation of abdominal bloating, vomiting, and, of course, constipation. In the worst case scenario, the bowel blockage can actually cause the bowel to suddenly rupture, leading to severe pain and shock (dangerous drop in blood pressure). This is a medical emergency requiring surgical repair.

With carcinoid tumors, people can experience watery diarrhea, flushing, wheezing and decreased blood pressure. Specific details on carcinoid tumor are provided in a separate overview.

How is small bowel cancer diagnosed?

A physician will first record your complete medical history and perform a physical examination. Also, the doctor will likely order some basic blood tests, especially if there is a history of blood loss in the stool, diarrhea, etc.

Additional work-up can include:

  • Stool sample to test for blood
  • Endoscopy or colonoscopy to look inside the duodenum and the upper part of the jejunum (from above, through the throat and past the stomach) or the lower part of the ileum (from below). An enteroscopy can investigate more of the small bowel but is more invasive and requires special equipment and training. There is also a pill with a small camera, which can be used to assess the bowel (capsule endoscopy). The pill is swallowed and then takes pictures periodically, which are sent wirelessly to a computer where they can be viewed.
  • Barium x-rays , also known as "small bowel follow-through", in which the patient first drinks barium liquid (which looks white on x-ray) and then gets abdomen x-rays to follow the passage of the barium through the entire small bowel. Enteroclysis, a special kind of barium study, which uses double contrast (both barium and methylcellulose) to get a better picture of the intestine can also be used. This technique can also be used with CT (CAT) scans.
  • CT scans, ultrasound scans and other kinds of x-rays, which sometimes pick up a small bowel tumor, but more importantly look at other parts of the body to see if the cancer may have spread
  • MRI may be ordered if liver involvement is suspected, which can occur with carcinoid tumors.

The above are ways of making a "clinical diagnosis", based on clinical studies (physical exam, radiology studies, etc.). They can identify a small bowel cancer about 50% of the time, the remainder are found through surgery. An actual "pathologic diagnosis" requires biopsy and microscopic evaluation of tissue from the suspected mass. However, it can be quite difficult to clearly visualize - and then access - the tightly folded-up small bowel, biopsies cannot always be done. In these cases, the pathologic diagnosis may have to be made as part of a surgical operation.

How is small bowel cancer staged? What are the important factors for outcome (prognosis)?

Remember that the stage of a cancer is a way to categorize it so that a medical team can recommend the most appropriate treatment and assess the patient's prognosis (likely outcomes). Small bowel staging can be a bit complicated as the staging system is different depending on the type of tumor (for example a lymphoma versus adenocarcinoma). Adenocarcinomas are the most common tumor of the small bowel and their staging is presented below.

Primary Tumor

  • T1a - invades lamina propria
  • T1b - invades submucosa
  • T2 - invades muscularis propria
  • T3 - invades through muscularis propria into the subserosa or into the nonperitonealized perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less
  • T4 - perforates the visceral peritoneum or directly invades other organs or structures (includes other loops of small bowel, mesentery, or retroperitoneum more than 2 cm, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct)

Lymph Nodes

  • N0 - no regional lymph node metastasis
  • N1 - metastasis in 1-3 lymph nodes
  • N2 - metastasis in 4 or more lymph nodes

Metastasis

  • M0 - no
  • M1 - yes

Stage grouping

  • I - T1-T2 N0
  • IIA - T3 N0 M0
  • IIB - T4 N0 M0
  • IIIA - N1
  • IIIB - N2
  • IV - M1

Because the staging system is relatively detailed, a more simplified way of understanding the stage groupings is:

Stage 1: Cancer contained within the small bowel lining or spread into the muscle wall, but not yet involving the lymph nodes or other parts of the body

Stage 2: Cancer spread through the muscle wall, possibly involving other nearby organs (like the pancreas)

Stage 3: Cancer spread to nearby lymph nodes

Stage 4: Cancer spread to other parts of the body (like the lungs)

The 4 stages above apply to initial diagnosis (first time). Small bowel cancer that comes back after initial treatment is called "recurrent cancer."

Prognosis

While the stage is certainly important, perhaps more telling in terms of prognosis and outcome for an individual patient is his/her "group". Small intestine cancer is grouped according to whether or not the tumor can be completely removed by surgery.

It is well recognized that survival for small bowel adenocarcinoma patients is improved if curative surgery is performed. Better disease-specific survival also correlates with younger age, jejunum and ileum location (better than duodenum), and of course lower clinical stage.

For small bowel sarcomas, tumor size, patient age, and disease stage are the most important prognostic factors.

How is small bowel cancer treated?

We will focus on the treatment of adenocarcinomas of the small bowel, as it is most common. Again, treatment varies somewhat based on the tumor type.

Surgery

The main treatment option for small bowel cancer is surgery to remove the tumor (excision) and to reconnect the remaining bowel (anastamosis). Surgery may also be needed for relief of bowel obstruction, (ie, intestinal bypass when the obstructing tumor itself cannot be removed. The success of the surgery as a cure depends on the extent to which the surgeon can remove the entire mass during the operation. This depends on the location of the mass within the bowel as well as the amount of bowel that is involved.

With adequate resection, patients have a 5-year survival rate of 40-60%. The operative mortality rate is generally quoted as less than 5%.

Note: In some cases it could be necessary to remove part of the stomach, colon, the gall bladder or surrounding lymph nodes in order to do a more complete and effective surgery. The type of surgery used is largely dependent on the size of the tumor and its location.

Once disease has spread to the abdominal cavity, it is difficult to manage. At a few select hospitals, as much of the tumor is removed as possible and then heated chemotherapy is placed into the abdominal cavity. However, this technique is not widely used as is still being studied.

Sometimes when a significant part of the bowel has to be removed in order to get the tumor out, there is not always enough bowel left over to reconnect. In these cases, the top end (proximal part) of the bowel is brought up to the wall of the abdomen and connected to a hole in the skin called a stoma. Attached to the stoma is a bag that is worn under one's clothes and collects the stool. This procedure is called an ileostomy, and may be temporary or permanent.

Depending upon the extent of the surgery, special diets, vitamins, supplements, etc. may be needed to help with food digestion and absorption. Any such dietary changes post-surgery would likely be permanent.

Radiation Therapy

This modality of cancer treatment plays a smaller role then surgery in the management of small bowel cancers. In some cases, it can be used post-operatively if there is gross residual tumor or, if there are close surgical margins, to "clean up" any microscopic tumor cells. It may also be used to help palliate symptoms from advanced disease, such as blood loss or pain from the tumor.

Ongoing clinical studies are looking at the use of radiation therapy in combination with radiosensitizing chemotherapy for patients with residual cancer after surgery as well for patients with recurrent small bowel cancer. Some small studies have suggested that neoadjuvant chemoradiation (combined treatment with chemotherapy and radiation prior to surgery) may be of benefit. There are also studies looking at chemoradiation after surgery, where it has shown to be a benefit.

Note: Radiation therapy for bowel cancer can be delivered both as teletherapy (external beam) or, less commonly, brachytherapy (implants, usually at time of surgery).

Chemotherapy

Chemotherapy may be given either in combination with radiation therapy/surgery or by itself as a single treatment in select cases. Unfortunately, there is little evidence that chemotherapy is effective in small bowel cancer, and the search for better drug regimens is ongoing. At present, the little data that is available involves very small numbers of patients (it's a rare cancer, after all) receiving 5-fluorouracil-based treatment. The use of 5-FU in small bowel adenocarcinomas is extrapolated from its efficacy in other gastrointestinal cancer regimens. Other regimens including those containing oxaliplatin and irinotecan have been studied in very small numbers of patients with moderate success.

For small bowel adenocarcinomas, McCrawley et al. showed a 37.5% response rates and a 13-month median survival with infusional 5-FU in advanced stage patients, compared to historical survivals of 4-8 months in these patients without chemotherapy. On the other hand, Fernandez-Trigo and Sugerbaker et al. looked at 7 different randomized prospective studies including patients with bowel sarcomas and found no survival benefit with post-operative chemotherapy.

Chemotherapy may take a primary role in the treatment for the rare primary small bowel cancer that turns out to be a lymphoma.

Biological Therapies

Based on the above, there clearly remains a need for better treatment options. One use of non-standard oncologic therapy for this tumor is interferon:

Interferon is an injectable drug used for some types of small bowel cancers, (usually carcinoid type), that activates the body's immune system to fight the cancer.

Note: For gastrointestinal stromal tumors of the small bowel, there is a large role for targeted therapy drugs. (See Targeted Therapy: Gleevec, Imatinib) There may be a role for antivascular agents such as cetuximab and bevacizumab in the future and trials are ongoing.

References

American Cancer Society. "Small Intestine Cancer" http://www.cancer.org/Cancer/SmallIntestineCancer/DetailedGuide/small-intestine-cancer-diagnosis

Bettini AC, Beretta GD, Sironi P, et al. Chemotherapy in small bowel adenocarcinoma associated with celiac disease: a report of three cases. Tumori. 2003;89(2):193-5.

Crawley C, Ross P, Norman A, et al. The Royal Marsden experience of a small bowel adenocarcinoma treated with protracted venous infusion 5-fluorouracil. Br J Cancer. 1998;78(4):508-10.

Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. Aug 15 2002;347(7):472-80.

Fernandez-Trigo V, Sugarbaker PH. Sarcomas involving the abdominal and pelvic cavity. Tumori. Apr 30 1993;79(2):77-91.

Kelsey CR, Nelson JW, Willett CG, et al. Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2007;69(5):1436-41.

Negri E, Bosetti C, La Vecchia C, et al. Risk factors for adenocarcinoma of the small intestine. Int J Cancer. 1999;82:171–174.

Polyzos A, Kouraklis G, Giannopoulos A, et al. Irinotecan as salvage chemotherapy for advanced small bowel adenocarcinoma: a series of three patients. J Chemother. 2003;15(5):503-6.