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MALIGNANT MALIGNANT PATHOLOGYPATHOLOGY

Colorectal CancerColorectal Cancer

Cells and Cancer

• Cells are the basic units.

• Chemotherapy drugs work on cells.

• Each cell is specialized in its form and function to perform its own job.

Normal and Cancer Cells

• Normal cells: – divide normally– new ones develop as old ones die– adhere tightly– uniform size and shape– highly differentiated appearance

• Malignant cells:– divide abnormally– new cells constantly develop– are non-adherent and squeeze

surrounding cells– vary in size and shape– highly undifferentiated appearance

Colorectal Cancer Overview

• In the United States, colorectal cancer is the 4th most prevalent cancer and 2nd most frequent cause of cancer death.

• Colorectal cancers have both predisposing factors and risk factors.

• Predisposing factors generally relate to factors that are seen in populations, while risk factors are more specific to individuals.

Risk Factors

• Personal History of Colorectal Cancer

• Personal History of Colorectal Polyps

• Family History of Colorectal Polyps or Colorectal Cancer

• Personal History of Chronic Inflammatory Bowel Disease

• Age

• Excessive Alcohol Consumption

• Long History of Smoking

Prevention

• There are some things individuals can do to try to prevent the development of colorectal cancer:

– High fiber, low fat diet,– Smoking cessation,– Limitation of alcohol intake.

• Screening exams that pick up polyps in their early stage help prevent the polyps from developing into colorectal cancers.

• Aspirin and calcium have not been proven to be beneficial in prevention.

Location of Tumors

• Ascending colon 17%

• Transverse colon 9%

• Descending and

sigmoid colon 35%

• Rectum 39%

Symptoms

• Symptoms are caused by the presence of a tumor.

• By the time symptoms are present, the tumor is often at least a few centimeters in size.

• Screening people without symptoms may be the best way to find very early cancers.

Symptoms of a Cancer in the Ascending Colon

• Gradual or massive blood loss leading to anemia

• Black, hematest-positive stools

• Weight loss

• Fatigue

• Abdominal pain (not common unless rather large)

Symptoms of a Cancer in the Descending Colon

• Cramping

• Abdominal pain

• Nausea and/or vomiting

• Obstructive symptoms w/ distention

• Alternating constipation and diarrhea

• Periodic rectal bleeding (usually bright red or maroon)

Symptoms of a Cancer in the Rectum

• Rectal bleeding (bright red blood) with blood in or on the stool

• Painful spasms

• Change in bowel movements

• Change in diameter of the stools

• Unusual constipation

• Feeling of rectal fullness or that the bowel does not empty completely (tenesmus)

Symptoms of a Cancer in the Rectum

• Painful or ineffectual straining to empty the bowel

• Palpable mass (transabdominal or per rectum)

• Unexplained weight loss

• Constant tiredness

How Cancer Spreads (Metastasis)

• Cancer can spread by several methods:

– By direct extension

– By local “seeding”

– By lymphatic transport

– By vascular transport

• Tumors cells can metastasize from another metastasis in the same way cells from the primary site metastasize.

Local Metastasis

• Direct spread can occur from several mechanisms:– Angiogenesis:

• Cancer cells secrete tumor angiogenesis factor which stimulates new capillaries to develop.

• With its own blood supply, the tumor is better able to invade nearby tissue.

• Tumors that do not have their own blood supply rarely metastasize locally.

• When a tumor grows quickly, the internal pressures vary, causing fingers to project into surrounding tissue - “crab”.

– Serosal Seeding:• Serosal seeding occurs when tumors, which have

invaded a body cavity from surrounding tissue, attach to the surface of organ within the cavity.

Vascular Metastasis

• Tumor cells also spread through the bloodstream.

• Malignant cells do not readily adhere to one another.

• They may break off from the tumor and pass directly into the vessels, metastasizing to distant areas.

• The pattern usually differs from that occurring from lymphatic spread.

Lymphatic Metastasis

• Tumor cells can also spread through lymphatic system.

• This is the rationale for the removing the lymph drainage system during the operation.

• Lymph node evaluation helps to stage tumors.

Prognostic Factors

• Location

• Stage

• Grade

• Tissue type

• Patient factors

Treatment of Colorectal Cancer

• Except for some patients with stage IV cancer, surgery to remove the colorectal cancer is the main treatment.

• The cancer is treated by the stage of the cancer (0 thru 4).

• Adjuvant therapy (additional treatments post-operatively) with chemoradiation therapy may also be used.

• Most adjuvant treatment is given for about 6 months.

• Neoadjuvant chemoradiation therapy (pre-operatively) may also be utilized to downgrade tumor stage.

• Neoadjuvant CRT is usually given for 5-6 weeks, followed by a 5-6 week rest interval, with subsequent colorectal resection.

• Additional adjuvant chemotherapy may then be given post-operatively.

TNM Classification

• T – Tumor– Size– Level of penetration– Grade (well-, moderately-, poorly-differentiated)

• N – Node– Number of nodes– Location (local, regional, distant)

• M – Metastasis– None– Local– Distant

Staging of Colorectal Cancer

• Stage 0:

– The cancer has not grown beyond the inner lining (mucosa) of the intestine.

– Removing or destroying the cancer is all that is needed.– The patient can be treated with polypectomy, local excision,

or full thickness rectal resection.– The patient will need no further treatment other than close

follow-up.

Staging of Colorectal Cancer

• Stage I:

– The cancer has grown through the first layer of the intestine into deeper layers (submucosa or muscularis) but has not spread outside the intestinal wall itself.

– Primary surgery is usually either appropriate colorectal resection or abdominoperineal resection (if the cancer is found too low within the rectum).

– Some small stage I rectal cancers may be treated by removing them through the anus without an abdominal incision, but many surgeons are now recommending radiation and chemotherapy for patients having such surgery.

Staging of Colorectal Cancer

• Stage II:

– The cancer has grown through the wall of the intestine (serosa) into nearby tissue. It has not yet spread to the lymph nodes.

– Stage II rectal cancers are usually treated by appropriate colonic resection or abdominoperineal resection, along with both chemotherapy and radiation therapy. Radiation can be given either before or after the surgery.

– In some cases of stage II rectal cancer, transanal full thickness rectal resection can be done after chemotherapy and radiation therapy. This approach can prevent the need for abdominoperineal resection and colostomy in some cases. A problem with this is there is no way of knowing whether the cancer has spread to the lymph nodes or further into the pelvis. For this reason, this procedure isn’t generally recommended.

Staging of Colorectal Cancer

• Stage III:

– The cancer has spread to nearby lymph nodes, but not to other parts of the body.

– The colorectal tumor is usually removed by appropriate colorectal resection or abdominoperineal resection.

– Radiation therapy will be given before or after surgery, with or without chemotherapy.

– It will also be used for large tumors of the rectum preoperatively to make the surgery more effective as well as to downgrade the stage of the tumor.

– After the surgery, patients receive chemotherapy.

Staging of Colorectal Cancer

• Stage IV:

– The cancer has spread to distant organs and tissues, such as the liver or lungs.

– The goal of surgery (palliative) in this stage is to relieve or prevent blockage of the colon/rectum by the cancer and to prevent local complications such as bleeding.

– Sometimes inserting a tube (stent) through the cancer during colonoscopy can open the blockage.

– The cancer usually cannot be cured by colorectal surgery because it has spread.

– In some cases, it may be possible to remove the colorectal tumor as well as the metastases, if only a few are present, especially with rectal cancer.

Recurrent Colorectal Cancer

• Recurrent colorectal cancer:

– Recurrent cancer means that the cancer has returned after treatment.

– It may come back locally (near the area of the initial colorectal tumor) or in distant organs.

– Surgery to remove local recurrences can extend survival.

– If the recurrent tumor cannot be completely removed initially, combined chemotherapy and radiation therapy may be used, sometimes shrinking the cancer enough that complete surgical removal becomes possible.

Local Recurrence

• In patients with colorectal cancer, 50% undergoing curative resection develop local recurrence.

• Median survival with local recurrence is ~ 16 months.

• Risk factors for local recurrence include: – Site of lesion (colon vs. rectum),– Local extent of tumor,– Perforation, – Nodal involvement.

Local Recurrence

• Risk of local recurrence can be reduced by radiotherapy.

• Preoperative radiotherapy is given as a short course immediately prior to surgery – Reduces local recurrence, – Increases time to recurrence, – Improves 5-year survival.

• Combination pre-operative chemotherapy and radiotherapy (neoadjuvant chemoradiation therapy or CRT) may produce a better outcome.

Recurrent Colorectal Cancer – Distant

• Recurrent colorectal cancer:

• If a cancer comes back in a distant site, it is most likely to first recur in the liver.

• If there are only a few metastases (usually less than 5), these may be treated with local resection followed by chemotherapy.

• Other sites of recurrence are the lung and bones.• Most recurrences develop in the first 2 to 3 years after

surgery.• Recurrent rectal tumors appear able to be more effectively

removed than recurrent colonic tumors.