Colon Cancer

What is Colon Cancer?

Cancer of the colon and rectum is second only to lung cancer in frequency and in mortality in the United States. However, new advances in treatment, effectiveness of chemotherapy, and ease of detecting early lesions should allow for improved survival in spite of the increasing incidence of this malignancy. Since many colon cancers arise from pre-existing non-malignant lesions, patient education is extremely important in allowing for early detection of these tumors and eradication before they develop into full-blown cancers. As will be discussed later in this article, even full-blown colon cancer is treatable with combination surgery, chemotherapy, and radiation as well as other modalities, such that a diagnosis of colon cancer is not a death sentence and long-term survival is possible.

Like all other cancers, colon cancer starts as a collection of cells that, for reasons that are only first beginning to be understood, begin to divide without control, and form a tumor. These cells are not normal in appearance and grow in a random uncontrolled fashion. Eventually tumor cells can break away from the original tumor and produce metastasis to both local draining lymph nodes, and via the blood stream, to the liver and elsewhere. As we will see in the discussion to follow, prognosis and treatment are dependent on thickness of tumor involvement of the bowel wall, location of the tumor within the colon or rectum, involvement of lymph nodes, and presence of liver metastasis.

Many cancers of the colon arise in, or begin as benign polyps that may be asymptomatic. Thus, means of detecting these polyps before they evolve into cancers is the most effective way of avoiding colon cancer. Before we proceed further with this discussion, the anatomy of the colon and the relationship of its blood supply to the liver need to be discussed.

The Colon begins in the right lower quadrant of the abdomen following entry of the ileum or last part of the small intestine, through the ileo-cecal valve.  This valve serves to slow the passage of liquid small bowel contents into the colon and permit absorption of water contained in the stool. The main function of the colon is the reabsorption of water from the gastrointestinal tract, and the propulsion of stool towards the rectum from where it can be eliminated from the body. The liquid stool passes through the ileo-cecal valve into the cecum, the first part of the colon. The appendix is a small organ that hangs off of the end of the cecum near the ileo-cecal valve.  The stool then travels up the ascending colon to the hepatic flexure, that part of the colon near the liver. The ascending colon is attached to the posterior abdominal wall and does not hang dependently in the abdomen as does the small intestine and other organs. After passing the hepatic flexure, the stool then traverses the transverse colon to the splenic flexure near the spleen. The transverse colon is attached to the posterior abdominal wall by a mesentery,  which is a double layer of connective tissue through which blood vessels travel on their way to supplying blood to the colon. Thus, the transverse colon does hang within the abdomen. After passing the splenic flexure, the stool travels down the descending colon on the left posterior abdomen and enters the sigmoid colon. The descending colon is like the ascending colon in that it too is firmly fixed to the posterior abdominal wall, while the sigmoid colon and transverse colon hang on a mesentery within the abdomen. Finally, the stool enters the rectum where it is stored for defecation. While the stool passes through the colon from the small bowel to the rectum, progressively greater amounts of water are reabsorbed, so that when stool leaves the body, it is essentially a solid containing relatively little water.

The blood supply to the gastro-intestinal tract is different from that which exists to other organs of the body. In every other organ, blood is pumped from the heart through progressively smaller blood vessels to the organ in question down to the tissue level where gas and nutrient exchange occurs. The blood then leaves that organ through progressively larger vessels which lead directly back to the heart. In the case of the GI tract the arterial blood entering the intestine, after gas and nutrient exchange occur, then pours into the portal circulation, which goes to the liver via yet another very specialized vascular bed before being returned the general venous circulation and back to the heart. This is because the liver is responsible for processing all digested nutrients before they can be utilized elsewhere in the body. The topic of liver metabolism is very complex and will not be discussed here. However, understanding of this portal circulation is important because the significance of liver metastasis from GI tract malignancy, particularly colon cancer, is different than other sites of metastasis, or of metastasis to the liver from tumors outside the GI tract.  

Cancer of the colon and rectum does not occur with equal frequency along all areas of the colon. The majority of colon cancers occur within the rectum and sigmoid colon, in fact most can be detected by simple digital rectal exam in the doctor's office. The cecum is affected next most frequently, with the remainder occurring with about equal frequency elsewhere in the colon.

The colon and rectum give rise to several different types of tumors, both benign and malignant, that need to be discussed. Many people present to the gastroenterologist for colonoscopy at which time they are found to have polyps. Polyps occur as two main types, tubular and villous.

Tubular polyps are those that are attached to the bowel wall by a narrow pedicle and hang into the lumen. They are usually small and are most often benign. However, they may develop into a malignancy and their removal is recommended when discovered.

Villous polyps or adenomas are soft, fleshy, broad based masses of varying size that grow from the colonic and rectal mucosal. The larger they are the more likely they are to contain areas of malignant degeneration. Most colonic masses have both tubular and villous properties and are termed tubulo-villous adenomas.

Other types of benign tumors do occur in the rectum and colon including lipomas, fibro-epitheliomas, and hemangiomas to name a few. Unlike tubulo-villous adenomas, these lesions have no malignant potential and simple excision is curative as will be discussed below. All of these lesions can cause bleeding, thus differentiating these lesions from malignant disease is imperative.

Who Gets Colon Cancer?

The incidence of colorectal cancer increases with age but can occur at any age. In some cases there may be a history of colon cancer in the family, however a direct genetic factor has never been established. Though most cases of colon cancer are sporadic and random there are a few conditions that deserve mention.

Ulcerative Colitis is a form of chronic inflammatory bowel disease characterized by inflammation involving the whole colon with diarrhea, often bloody. Long standing Ulcerative Colitis greatly increases the risk of developing cancer in the chronically inflamed colon. Patients with this disease require very close surveillance and often undergo prophylactic colectomy when disease is long standing.

There are several polyposis syndromes in which affected patients may have numerous colonic polyps. Some of these syndromes are hereditary in nature. With increasing numbers of polyps present in the colon, the risk that one of these polyps may become malignant increases progressively. When the number of polyps becomes such that they are impossible to manage by conventional means, prophylactic colectomy may be indicated for these conditions as well.

Should cancer develop in a patient with one of these above described conditions, the management is the same as for cancer arising sporadically. However, colon cancer developing in a patient with Ulcerative Colitis is often more advanced and aggressive than the garden-variety colon cancer. Whether the nature of these cancers is truly more virulent or that this reflects the difficulty of detecting colon cancer in a patient who has a chronic history of bowel complaints and rectal bleeding is a subject of controversy and remains unclear.

What are the Symptoms of Colon Cancer?

The most common presenting symptom that patients themselves seek evaluation for is rectal bleeding. Most often the blood is mixed in the stool, as opposed to on the toilet paper or in the bowl. Those patients who have routine annual physicals may have blood in the stool detected by special tests done during a routine rectal exam. This may detect blood in the stool months before it is visible to the eye and thus if a tumor is present it is usually at an early stage. Blood in the stool may be caused by a variety of conditions both benign and malignant and thus should prompt a thorough exploration, including colonoscopy. Often hemorrhoids may be encountered on digital exam, but this should not be assumed to be the source of bleeding as hemorrhoids are very common and may coexist with a tumor. Thus, the finding of blood in the stool on physical exam, or complaints of blood per rectum should prompt at least a sigmoidoscopy in people under age 40, or a full colonoscopy in people over the age of 40 regardless of the findings of benign rectal conditions such as hemorrhoids, fissures, fistulas or proctitis on digital rectal exam.

More advanced tumors, particularly in elderly patients, may present with anemia, weight loss, abdominal pain or obstructive symptoms as the tumor gets larger and slow blood loss becomes more pronounced. Tumors with metastasis to the liver may present with jaundice, however this is a very late stage and portends a very grim prognosis.

What is the Treatment of Colon Cancer?

As with all conditions in medicine, adequate treatment of colon cancer depends first on adequate diagnosis. Patients presenting to their internist for complaints of rectal bleeding or found on routine physical to have blood in the stool, will generally be sent for evaluation by colonoscopy. Any polyps or masses within the colon will undergo biopsy at that time. Small polyps within the colon may be treated completely adequately at the time of colonoscopy. The caveat to this is that if a small focus of cancer is found in the stalk of a polyp, additional surgery may be necessary to assure adequate margins around the area of cancer. Larger benign tumors of the colon may be treated by colonoscopy with excision as well, though these may require multiple sessions to completely excise the mass. If cancer is encountered in any of the tissue fragments removed, formal colon surgery is indicated. If a diagnosis of colon cancer is made upon colonoscopy with biopsy, patients will generally be referred to a surgeon for treatment.

Before undergoing surgery, the patient is first required to undergo a series of standard diagnostic tests. Many of these are simply the routine preoperative workup common to all major surgery, however, a CT scan of the abdomen and pelvis with contrast, and a CEA blood determination are more specific to the workup for colon cancer.

CT scanning provides additional information about the size of the tumor in question, its involvement with the abdominal or pelvic sidewall, particularly important in cases of rectal cancer, the presence of enlarged lymph nodes, and the presence of nodules in the liver, which may be metastatic. CEA or Carcino-Embryonic Antigen is a protein expressed on the surface of certain malignant tumors. However, it is also elevated in many benign circumstances thus making it useless as a screening test for colon cancer. Nevertheless, a high determination prior to treatment, which subsequently returns to normal following treatment, is useful. If, at a later time this value is again elevated, this is strongly suggestive of recurrence of tumor and will prompt a thorough search.

Patients are generally admitted to the hospital the day before surgery for preparation of the bowel for surgery. Though, this bowel prep varies among different surgeons, generally it is comprised of a combination of enemas, oral laxatives, oral antibiotics, and intravenous fluids to prevent dehydration. This prep is extremely important in cleaning out the colon and reducing the risk of infectious complications that may be associated with surgery on the un-prepped colon.

The greatest concern of most patients undergoing this type of surgery is the need for a colostomy. For the vast majority of elective colon surgery this is unnecessary. Since the colon is prepped as described above and the tumor is located in an area so that adequate surgical margins for colon cancer treatment are obtainable, colostomy is not necessary. Even in the case of emergency surgery on the colon for obstruction, bleeding or perforation, colostomy may be necessary only temporarily to allow the acute inflammation to resolve. The colostomy may then be closed at a second, relatively minor operation several weeks or a few months later, depending on the situation.

For tumors lying low in the rectum, within an inch or two of the anus, a permanent colostomy may be necessary to adequately extirpate the tumor with sufficient margins. This will be discussed further in the discussion of radiation treatment below.

Following surgery, recovery in the hospital takes about a week. The patient is not allowed to eat or drink anything until GI tract function resumes as evidenced by passage of flatus and bowel movement. This does occur naturally in spite of the lack of any oral intake and the vigorous bowel cleansing prior to surgery. The GI tract produces several liters of fluid daily and there is plenty of cellular debris sloughed from the GI tract continuously to form stool in spite of not eating. Generally, it takes 4 to 5 days for GI tract function to resume.

Radiation is often required as an adjuvant to surgery and chemotherapy in the treatment of colon cancer. A large tumor that penetrates the bowel wall and is adherent to or invading the abdominal wall may be a candidate for post-operative radiation if the area of involvement is localized. Additionally, large rectal tumors may be candidates for a short course of high dose radiation, which may shrink the tumor. This may convert an unresectable tumor to one that is resectable or may obviate the need for a permanent colostomy by shrinking it enough that adequate clearance around the tumor near the anus may be obtained allowing for anastamosis.

Chemotherapy for colon cancer is indicated for large tumors that involve the full thickness of the bowel wall or that invades lymph nodes or has metastasis to the liver or other organs. There are several different protocols for chemotherapy for colon cancer all of which are very effective and very well tolerated. Patients do not experience the hair loss and severe illness often associated with chemotherapy for other types of cancers. Many patients do, however, experience varying GI tract complaints such as diarrhea.

Some of the newer agents such as Erbitux and Avastin are more targeted therapies that have shown some extremely good results even in patients with advanced colon cancer.  Because of these treatments, patients are surviving longer and in a better state of health than ever before.  Continued research in theses areas may make colon cancer a distant nightmare of the past.

What is the Prognosis for Colon Cancer?

Colon Cancer staging is based on 3 factors: The level of penetration of the tumor through the bowel wall, involvement of draining lymph nodes, and presence of metastasis to the liver or other organs or involvement of contiguous structures adjacent to the bowel. In many regards liver metastasis from colon cancer is a special circumstance as will be discussed below. There have been several different staging systems employed for colon cancer but the system which is most consistent with the way other cancers are staged is the TNM system which takes into account all of the above factors.

Thus, T status refers only to the level of penetration of the tumor in the bowel wall. A Tumor confined to the bowel wall without full thickness penetration is said to be a T1. A T2 tumor involves full thickness of the bowel wall. T0 is carcinoma in-situ, which means that cancerous changes are present in the lining of the bowel or in a polyp, but there is no invasive cancer present.

N status refers to the presence or absence of lymph node metastasis. M status refers to the presence or absence of metastatic disease. Invasion of an adjacent organ, for the purposes of staging, is equivalent to metastatic spread.

Colon Cancer staging is defined as follows:

Stage 0: T0, N0, M0


Stage I: T1, N0, M0  

 

Stage II: T2, N0, M0 
 

Stage III: any T, N1, M0
Stage IV: any T, any N, M1

Since the liver receives all of the draining circulation from the GI tract before this blood enters the systemic circulation, metastasis to the liver is, to some extent, still contained disease, at least if the number of metastatic lesions in the liver is few. Many attempts have been made in the treatment of liver metastasis from colon cancer with such modalities as cryosurgery, intra-hepatic chemotherapy, hepatic resection, and even liver transplant. A detailed discussion of all of these methods is beyond the scope of this dissertation however; I do wish to make the reader aware of the fact that treatment in this situation is still possible with good results.

Prevention and Early Diagnosis of Colon Cancer?

The best chance of survival from colon cancer is afforded by early diagnosis. Rectal examination with testing of the stool for occult blood should be part of every physical exam. The finding of blood in the stool should warrant an evaluation according to patient age and history. In my own practice, if I find blood in the stool of a patient under the age of 40, without a family history of colon cancer, and no other significant findings, a sigmoidoscopy is warranted. In a patient over the age of 40, or one with other findings, such as weight loss, or change in bowel habits, a full colonoscopy may be indicated. These tests are well tolerated, easy to perform and may be life saving. The finding of hemorrhoids on digital rectal exam should not dissuade one from undergoing these further tests as hemorrhoids are very common, and a tumor may coexist with hemorrhoids and in fact be the actual site of bleeding.

There is much controversy over the role of routine colonoscopy as a screening test for colon cancer. In other countries where routine colonoscopy is performed, colon cancers are detected, on average, at a much earlier stage with better survival rates following treatment. However, colonoscopy does carry a small risk of perforation of the colon, and it is expensive to perform this procedure on every patient every year or so. In this country colonoscopy as a screening test is performed on a much more selective basis. Generally, over the age of 50, most gastroenterologists recommend routine full colonoscopy every 5 years.

Usage of flexible sigmoidoscopy and colonoscopy is tailored to individual patients depending on clinical situation; however, a few special clinical problems warrant discussion.

Patients with ulcerative colitis need more frequent colonoscopy to evaluate the colon for possible malignancy. Those patients who have active ulcerative colitis for more than 10 years have a greatly increased incidence of colon cancer. Prophylactic colectomy is indicated in those patients who have active ulcerative colitis for 20 years, even without any history of malignancy.

As mentioned earlier, several polyposis coli syndromes exist in which the affected patient may have his or her colon blanketed with polyps. Some of these syndromes run in families. These patients may have hundreds, if not thousands of polyps in their colons. Frequent colonoscopy may be necessary to remove these polyps. When colonoscopy can no longer manage these polyps, prophylactic colectomy may be indicated.

I hope that I have answered most of the questions that you may have had, without adding to your confusion. As always, I welcome questions or comments.

Steven P. Shikiar, MD, FACS email