DEFINITION

Anal cancers are uncommon tumors located in the anus. The anus is the proximal end of the large intestine that connects to the outside of the body. It measures approximately an inch and a half and opens to allow passage of stool from the body.

INCIDENCE

The incidence of anal cancer has increased since the 1980s. This is theorized to be due, in part, to the rise in sexual transmission of the human papilloma virus (HPV). This theory suggests that squamous cell cancer of the anus could be preventable.

In 2007, there will be an estimated 4,650 cases of anal cancer diagnosed in the United States and approximately 690 people will die from this disease. Women are diagnosed with anal cancer slightly more frequently than men. Diagnosis of anal cancer generally occurs in adults over the age of 35 years.

ETIOLOGY AND RISK FACTORS

SIGNS AND SYMPTOMS

DIAGNOSTIC WORKUP

HISTOLOGY

The anus is lined with squamous cells; thus squamous cell carcinoma is the most common form of anal cancer diagnosed in 47% of patients. Cloacogenic or transitional carcinoma, diagnosed in 27% of patients, is a type of squamous cell carcinoma that develops in the cloaca portion of the anus. Fifteen percent of anal cancers are adenocarcinomas that develop in the glands of the anal area. Other histologic diagnoses include basal cell carcinoma identical with that seen in other areas of the skin, Paget’s disease, Bowen’s disease, and melanoma.

CLINICAL STAGING

Clinical staging is essential for determining extent of disease and associated treatment strategies. Staging is done using the American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) system (see table on page 51).

TREATMENT

Treatment decisions are based on several factors, including tumor location and type and stage of disease. The three main modes of treatment are surgery, radiation therapy, and chemotherapy. Historically surgery was the only therapeutic option; however, progress has been made. Combined modality therapy or chemoradiation is the most commonly used approach.

If surgery is an option, several surgical approaches are available depending on the type and location of the tumor:

Radiation therapy can be used as neoadjuvant therapy in combination with chemotherapy or as primary treatment. External beam radiation is the most common method of delivery of high-energy waves. Other forms of radiation include the following:

The chemotherapy agents used to treat anal cancer are as follows:

PROGNOSIS

The most important prognostic factor for anal cancer is the clinical stage. Seventy percent of anal cancers are stage I or II at presentation; most patients at this stage will be cured. Twenty percent of anal cancers have positive lymph nodes on presentation and 30% to 63% have positive nodes at surgery. The local failure rates of T3 and T4 tumors are approximately 50% after combined modality therapy.

Clinical Staging: Anal Cancer

PREVENTION

The causes of many anal cancers remain unknown. Because HPV and HIV infections are known risk factors for the development of anal cancer, reduction in sexual practices that carry a high risk for contracting these infections should be used. Practices to avoid include the following:

A vaccine to protect against HPV types 16 and 18 has recently been approved by the Food and Drug Administration. It is indicated for use in women before they become sexually active to protect against HPV, which is a risk factor for cervical cancer. Studies are continuing to ascertain use in males.

Smoking is also a known risk factor for anal cancer; therefore, smoking cessation can reduce the likelihood of development of anal cancer and other types of cancer.

DEFINITION

Cancer of the biliary tract includes the gallbladder and the extrahepatic biliary ducts from the canals of Hering to the ampulla of Vater. Metastasis most frequently occurs through spreading into local lymph nodes and perineural invasion.

INCIDENCE

It is expected that approximately 9,250 Americans will be diagnosed and 3,250 will die from cancers of the gallbladder and other biliary sites in 2007. The populations at greatest risk are women and Native Americans.

ETIOLOGY AND RISK FACTORS

The exact etiology is unknown for extrahepatic biliary duct cancer, although ulcerative colitis and primary sclerosing cholangitis are predisposing conditions. The etiology of gallbladder cancer is also unknown, although 75% of patients with a diagnosis of gallbladder cancer have a medical history that is positive for gallstones. It is important to note that cancer of the gallbladder will develop in only 1% of patients with gallstones, and therefore gallstones are not considered a risk factor. Risk factors for gallbladder cancer include calcification of the gallbladder (porcelain gallbladder), and there is a sixfold increase in risk among typhoid carriers.

SIGNS AND SYMPTOMS

DIAGNOSTIC WORKUP

HISTOLOGY

Most cancers of the extrahepatic biliary ducts and gallbladder are adenocarcinomas. Other histologic types include carcinoma in situ, papillary carcinoma, mucinous, signet ring, clear cell, oat cell, and squamous cell variants. A differential diagnosis between a primary biliary cancer versus a metastatic adenocarcinoma is determined by the following criteria:

CLINICAL STAGING

Staging is clinically based and is the best possible estimate of the extent of disease before treatment. Staging should be done by the TNM classification published by the American Joint Committee on Cancer. See the tables on pages 52 and 53.

TREATMENT

Extrahepatic Bile Duct

• Classified as being resectable or unresectable

• Surgical procedure varies according to location of tumor and is usually extensive (i.e., Whipple procedure) with a 5% to 10% mortality rate and a cure rate of ≈5%.

• Palliative surgical interventions are similar to those for cancer of the gallbladder.

• External beam radiation may be used in conjunction with surgical intervention.

• Clinical trials

Clinical Staging: Extrahepatic Bile Duct Cancer

Clinical Staging: Gallbladder Cancer

PROGNOSIS

PREVENTION

There is no early detection or screening methods for biliary and gallbladder cancers. Adherence to treatment regimens for managing ulcerative colitis and prevention of gallstones may reduce risk, but no effective prevention strategies have been identified.

DEFINITION

Colon cancer includes cancer of the ascending colon, transverse colon, descending colon, and sigmoid colon. Rectal cancer can develop anywhere between the rectosigmoid junction and the anal canal. Metastasis occurs when tumor invades through the bowel wall and travels to lymph nodes or distant organs, particularly the liver, lungs, and peritoneum.

INCIDENCE

Colorectal (CRC) cancer is the third most common cancer in both men and women. In 2007, an estimated 112,340 cases of colon and 41,420 cases of rectal cancer are expected to occur in the United States. It is expected that 52,180 Americans will die from colon or rectal cancer in 2007.

ETIOLOGY AND RISK FACTORS

SIGNS AND SYMPTOMS

Presenting symptoms may vary depending on the location of the tumor:

DIAGNOSTIC WORKUP

HISTOLOGY

The majority of CRCs are adenocarcinomas. Moderate to well-differentiated tumors are most common. Poorly differentiated or undifferentiated tumors, vascular invasion, or lymphatic spread of tumors are poor prognostic signs.

CLINICAL STAGING

Accurate staging is essential for adjuvant treatment decision making and development of prognosis. Staging is done according to the American Joint Committee on Cancer guidelines by the TNM classification system (see table on page 55). In CRC, staging relates to the depth of tumor invasion through the bowel wall, involvement of regional lymph nodes, and the presence of distant metastasis.

TREATMENT

Colon Cancer

• Surgical removal of the primary tumor and lymph node resection is the initial therapy. If there is presence of synchronous metastasis that is deemed unresectable at any point along the cancer trajectory, a limited colon resection to relieve blockage may be performed.

• Adjuvant chemotherapy depends on the stage of disease and the prognostic risk factors.

˚ Chemotherapy in stage II disease is a topic of controversy and requires informed decision making on the part of the patient.

˚ Adjuvant chemotherapy in stage III is given for a 6-month period.

˚ In stage IV, with evidence of measurable disease, chemotherapy in combination with biological therapy is given indefinitely with the potential for treatment breaks.

• Approved chemotherapy regimens for stage II and stage III disease include the following:

˚ 5-fluorouracil (5-FU)/leucovorin/oxiliplatin (FOLFOX)

˚ 5-FU/leucovorin

˚ Capecitabine

• Approved treatment for stage IV or recurrent disease includes the following:

˚ 5-FU/leucovorin/oxaliplatin (FOLFOX) + bevacizumab

˚ 5-FU/leucovorin/irinotecan (FOLFIRI) + bevacizumab

˚ Capecitabine/oxiliplatin (CAPEOX) + bevacizumab

˚ Single-agent irinotecan

˚ Cetuximab with or without irinotecan

˚ Panitumumab

• Radiation therapy (RT) has a limited role in colon cancer. It may be recommended for patients who have had a bowel perforation in attempt to improve local control. Additionally, it may be used for palliation of painful metastasis.

Clinical Staging: Colon and Rectal Cancers

PROGNOSIS

Five-year overall survival is 93.2%, in stage I, 72% to 85% in stage II, 44% to 83% in stage III, and 8.1% in metastatic or stage IV. The range in overall survival results from the subdivisions of stage II and III disease; there is a decrease in survival as the stage of disease worsens.

PREVENTION

Modifiable lifestyle prevention strategies include the following:

Those who have a family history of colon cancer or a genetic predisposition for colorectal cancer should use routine screening practices as directed by their physicians.