Gastrointestinal Cancers

JoAnn Coleman

I. Gastrointestinal (GI) Cancers—An Overview

A. The GI tract has the highest incidence of malignant tumors.

1. Cancers of the GI tract include parts of the bowel lumen—gastric, colorectal, rectal cancers.

2. Cancers of the GI accessory organs—hepatic, biliary, bile duct, pancreas.

3. Although the esophagus is a part of the GI system, it is viewed and managed as a tumor of the head and neck region.

B. More than 25% of cancer deaths every year in the United States are attributed to cancer of the GI tract.

C. The problems common to all GI cancers stem from the delay in clinical presentation.

1. GI tumors proliferate insidiously and extend locally.

2. Presenting signs and symptoms may be misdiagnosed or self-treated for a long time.

3. As the tumor grows, it can exceed the distensible capacity of the GI lumen and result in obstruction.

D. Most tumors of the GI tract are adenocarcinomas.

E. The metastasis of GI tumors occurs by all three mechanisms of metastasis—local spread, blood vessel invasion, and dissemination through the lymphatic system. This diversity means these tumors metastasize to a large variety of sites outside the GI system.

F. Prognosis of the GI malignancy depends on:

1. Tumor type and site(s) of metastasis

2. Tumor size

3. Degree of cellular differentiation

4. Extent of metastases

5. Availability of effective treatments

6. Person’s general health

G. Diseases have very different prognostic implications and are treated as separate disease processes.

H. Table 12-1 provides an overview of the clinicopathophysiologic features of the GI malignancies (gastric cancer, hepatobiliary cancer, pancreatic cancer, colorectal cancer).

II. Etiology

A. Diseases have variable genetic, environmental, dietary risk factors.

B. Specific risk factors are discussed within Table 12-1.

III. Patient Management

A. Assessment (Specific assessment findings for each type of malignancy are included in Table 12-1.)

1. Patient history

a. Family history may be important in some of these disorders that are associated with familial genetic abnormalities (eg, colorectal cancer, pancreatic cancer).

b. Diet and social history may provide information about carcinogen exposure (eg, esophageal cancer, hepatic cancer) or known dietary risk factors.

c. History of infectious diseases. Viral illnesses or GI infections are known to predispose patients to certain GI malignancies (eg, hepatic cancer, gastric cancer, colorectal cancer).

2. Patient complaints

a. Most patients have subtle changes in eating or bowel habits that are largely ignored or attributed to other medical problems (eg, reflux, change in stool characteristics).

b. Abdominal pain is a common finding in many GI malignancies, although the localization of pain differs with each of the disorders.

(1) Pain localization may be helpful in determining the area of the GI tract that is affected.

(2) Low back pain or epigastric/substernal pain may also represent GI disease.

(3) Pain that is “rebound” or worse with lifting the hand rather than pressing downward signals an acute abdominal crisis and possible surgical candidate.

c. Bleeding from the GI tract is a cardinal symptom of malignancy. Any blood, such as old blood in emesis or stool, or smearing of blood on defecation is important to evaluate for the presence of malignancy.

3. Physical findings

a. All patients with suspected GI malignancy should have a thorough abdominal assessment.

(1) Bowel contours, bulges, pulsations

(2) Bowel sounds for abnormalities

(3) Light and deep palpation for areas of tenderness or masses

b. Signs of abnormal fluid balance, nutrition, and metabolic regulation are common with all GI malignancies.

(1) Dehydration and orthostasis occur due to fluid shifts into the peritoneal space when inflammation is present.

(2) Nutrient absorption is often compromised before a diagnosis of malignancy is made. Symptoms may include dry, flaky skin; taste changes; alopecia; oral tenderness; bruising.

(3) Symptoms may relate to the degree of constipation or diarrhea the patient has experienced.

B. Diagnostic Tests (Unique and specific diagnostic tests for each type of GI malignancy are included in Table 12-1.)

1. Screening guidelines. The only GI cancer for which there are screening guidelines for early detection is colorectal cancer. Colorectal cancer detected in its early stages has an excellent prognosis, and screening tests are adequately sensitive and specific to provide this information. Controversy exists regarding the age at which to start screening (40 versus 50 years of age), best test, and frequency of testing. These guidelines are the recommendations of the Centers for Disease Control (CDC, 2002).

TABLE 12-1 Overview of Gastrointestinal (GI) Malignancies

Key Feature	Gastric Cancer	Pancreatic Cancer	Hepatobiliary Cancer	Colorectal Cancer
Definition/epidemiology	Incidence declining in the United States due to food preparation and preservation Arises from the mucosa or inner lining of the stomach Average age of onset is 50-70 years of age Males have greater incidence than females More prevalent in minority populations in United States Proximal or GE-junction tumors now account for half of all stomach tumors and are associated with a poor prognosis Most present with advanced disease Overall 5-year survival rate is approximately 5% to 15%	Fourth most common cause of cancer-related death in the United States Arises in the lining of the pancreatic ducts Average age of onset is 60-80 years of age Equal incidence among males and females Higher incidence in African Americans Most tumors arise in the head of the pancreas Overall 5-year survival rate is approximately 5%	Hepatobiliary cancers have low incidence in the United States Gallbladder cancer is most common hepatobiliary malignancy, diagnosed in persons between the ages of 70 and 75 with a predilection for females over males Hepatocellular cancer is seventh most common cancer in the world. Average age of onset is 50 to 55 years Increased incidental finding of gallbladder malignancy at the time of elective laparoscopic cholecystectomy Majority of gallbladder and bile duct cancers are adenocarcinomas Five-year survival for stage I tumors after cholecystectomy is greater than 85%; for stage II, III, and IV tumors, 5-year survivals are 25%, 10%, and 2% Cholangiocarcinomas or bile duct cancers can be diagnosed throughout the biliary tree and are classified as intrahepatic or extrahepatic (most common). Bile duct tumors arise from the epithelium of the bile ducts. Intrahepatic tumors tend to present as solitary masses. Extrahepatic tumors encompass hilar carcinomas, in the region of the junction of the right and left hepatic ducts and in the common hepatic and common bile ducts. These tumors occur in conditions where bile is stagnant, infected, or both. Average age of onset of bile duct tumors is between 60 and 70 years of age and equal between males and females	Most common GI malignancy and the second leading cause of cancer death in the United States Colon cancer is more common than rectal cancer Screening and early detection are methods for reducing morbidity and mortality from colorectal cancer Average age of onset is 60 to 70 years Equal incidence in males and females of colon cancer, with rectal cancer more prevalent in men One fourth of colorectal cancers are found in the rectum; remainder are located in some other part of the colon. Most colon cancers are found in the right colon. Overall 5-year survival rate is approximately 50% to 55%.
Risk factors/etiologies	Dietary intake of nitroso-compounds and salts convert nitrates to carcinogenic nitrosamines in the stomach Helicobacter pylori infection Low socioeconomic status Prior gastric resection for peptic ulcer disease Patients with blood group A Pernicious anemia	Cigarette smoking is a major risk factor No clear dietary factors, but fat content and an increased body mass index are associated with increased risk Occupational exposure to chemicals may be a risk factor Relationship among diabetes mellitus and chronic pancreatitis as precursors for pancreatic cancer uncertain at this time Familial pancreatic cancer is rare, but a genetic predisposition may be present in up to 5% of cases.	Cirrhosis associated with hepatitis B or C is a common precursor to hepatocellular malignancy. Exposure to carcinogens such as aflatoxin, found in a number of grains Gallstones associated with chronic cholecystitis is the greatest risk factor for gallbladder cancer, followed by a calcified gallbladder, gallbladder polyps, typhoid carriers, and carcinogens Bile duct cancer risk factors include hepatolithiasis, ulcerative colitis, sclerosing cholangitis, choledochal cysts, chemical carcinogens, and liver fluke infections	Sedentary lifestyle leads to decrease in intestinal tract transit time allowing for potential carcinogens to be in contact longer with colorectal mucosa Diet high in fat Inflammatory bowel disease Obesity Radiation exposure Heavy alcohol consumption Occupational exposure to carcinogens Genetic polyposis syndromes such as familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), hamartomatous polyposis syndromes (Peutz-Jeghers) and Gardener’s syndrome Anal cancer has been associated with infection with the human immunodeficiency virus (HIV)
Signs and symptoms	Complaints similar to peptic ulcer disease or other GI ailments Reflux Indigestion Early satiety Nausea and vomiting Abdominal pain just above the umbilicus Weight loss Loss or decrease in appetite Bloating after meals Advanced disease findings include: Ascites Hepatomegaly Palpable epigastric mass or nodules around the umbilicus	Initial signs and symptomsdepend on the site and extent of tumor Head of pancreas: jaundice; pain, deep and boring and/or radiating around to the back; weight loss; anorexia; steatorrhea or diarrhea; weakness; indigestion Body and tail of the pancreas: pain, dull and vague, localized to epigastrium or back, or episodic and related to meals or constant and severe; weight loss; early satiety; indigestion; vomiting; GI bleed; splenomegaly Palpable gallbladder (Courvoisier’s sign) seen in obstruction of the distal common bile duct Advanced disease presents with ascites, supraclavicular lymph nodes, a periumbilical mass, or a rectal mass Diabetes of recent onset in elderly patients with vague GI symptoms may be from an underlying pancreatic tumor Migratory thrombophlebitis (Trousseau’s sign) may be seen in advanced disease Depression may also be diagnosed in a number of patients before the diagnosis of a pancreatic tumor	Similar for hepatocellular, bile duct and gallbladder tumors Jaundice Dark urine Clay-colored stools Anorexia Weight loss Malaise Abdominal pain Fever or cholangitis	Vary depending on location: Ascending colon presents with anemia; a palpable mass on the right side; vague, dull pain; weakness; weight loss; fatigue; palpitations Transverse colon presents with a change in bowel habits and blood in stool Descending and sigmoid colon may exhibit constipation alternating with diarrhea, abdominal pain, nausea, vomiting, melena or perforation Rectal tumors may present as changes in bowel movement, rectal fullness, urgency, frequency, bleeding, tenesmus, malaise, occult blood, pelvic pain
Diagnostic tests	CT scan is most common study for staging the extent of disease, detecting extragastric extension, lymph node involvement or metastatic disease Barium swallow/upper GI series only shows anatomy of stomach Upper endoscopy (EGD) allows direct visualization of mucosa and mechanism for biopsy of lesions. Accurately detects more than 95% of gastric cancers Endoscopic ultrasound (EUS) can be performed during endoscopy to image and evaluate tumor depth through the layers of the stomach and any lymph node involvement H pylori diagnosis by endoscopy and biopsy, rapid urease test, or carbon-labeled breath test	CT scan is most common study for staging the extent of disease and lymph nodes and metastases Ultrasound may be included in initial examination MRI has not been shown to add any information but may be used if an iodine contrast allergy Cholangiography to define site of biliary obstruction. Use of ERCP visualizes both biliary and GI tracts. Endoscopic ultrasound (EUS) useful in staging tumors for size of tumor, extension into adjacent structures, lymph node involvement and any blood vessel involvement Laparoscopy may be used for staging of the tumor and can identify liver and peritoneal metastases not seen by other studies Percutaneous fine needle aspiration (FNA) biopsy may be performed for unresectable tumors to help direct palliative or neoadjuvant chemoradiation The carbohydrate antigen 19-9 (CA 19-9) is tumor-associated, not tumor-specific, and may be used in conjunction with other studies to help diagnose pancreatic tumor. It is most useful in assessing patients being treated for pancreatic cancer	For hepatocellular tumors, a CT scan or MRI to define extent and number of primary liver lesions, vascular anatomy, blood vessel involvement, involvement with tumor and extrahepatic disease. Alpha-fetoprotein (AFP) levels in the blood are elevated in approximately 60% to 90% of patients Gallbladder and bile duct tumors are best detected by CT scan or MRI. For patients presenting with jaundice further workup should include an ERCP or magnetic resonance cholangio-pancreatography (MRCP). Percutaneous transhepatic cholangiography may also be performed to assess level of biliary obstruction and as a guide for the placement of percutaneous transhepatic biliary stents as needed for palliation of jaundice. Both carcinoembryonic assay (CEA) and CA 19-9 levels may be elevated in gallbladder and bile duct tumors. Percutaneous needle aspiration biopsy, brush or scrape biopsy, or cytological exam of bile may aid in determining diagnosis.	Clinical presentation is useful for identifying potential colorectal cancer in a given patient CT scan MRI used to detect recurrent rectal cancer and tumors too small to be evaluated on CT scan. Colonoscopy Air contrast barium enema Endoscopic ultrasound (EUS) to stage rectal tumors.
General management strategies	Depending on the stage and location of a gastric tumor a partial or total gastrectomy may be performed (see Table 12-2) Chemotherapy is given as adjuvant therapy after surgery and as palliative (primary) therapy for advanced disease (see Table 12-2) Radiation therapy is reserved for palliation of symptoms such as pain, bleeding, or obstruction by tumor (see Table 12-2)	Surgical resection is the best therapeutic option and only opportunity for cure Pancreaticoduodenectomy, the Whipple procedure, is the surgery most often performed for treatment of pancreatic cancer (see Table 12-3) Adjuvant therapy with chemotherapy and radiation therapy is usually administered to prevent recurrence of disease (see Table 12-3) Chemotherapy may be given for palliation (see Table 12-3) Radiation therapy may be given as palliation for pain or bleeding (see Table 12-3) Surgical interventions for palliative relief of biliary and gastric obstruction as well as nerve blocks for pain management have been shown to improve quality of life (see Table 12-3). Nonoperative palliation of obstructive jaundice by either percutaneous or endoscopic stents is effective. Duodenal obstruction may be palliated by a percutaneous gastrostomy tube for stomach decompression or by insertion of a duodenal stent to maintain patency of the lumen	Surgery remains the only curative modality for hepatobiliary tumors (see Table 12-4, Table 12-5, Table 12-6) Alternative therapies for unresectable disease include ablative therapy, chemoembolization, chemotherapy plus radiation for hepatocellular tumors. Palliation includes surgical, endoscopic and interventional radiographic procedures for unresectable gallbladder and bile duct cancers. Chemotherapy and radiation therapy as appropriate therapy remain controversial due to small number of patients and no definitive treatment with proven survival benefit	Surgery is the primary treatment for colon cancer (see Table 12-7 and 12-8). Goals of rectal surgery are cure, local control, restoration of intestinal continuity, preservation of anorectal sphincter function, and preservation of sexual and urinary function. Neoadjuvant, adjuvant, and palliative radiation therapy are used for colorectal cancer (see Table 12-7). Adjuvant chemotherapy is recommended for early rectal cancer and in advanced colon cancer (see Table 12-8). Metastatic disease in the liver or lung should be considered for resection. This can then be followed by adjuvant therapy.

a. For healthy people starting at age 50 years without significant risk factors (see III.B.1.b for description of significant risk factors.)

(1) Fecal occult blood test yearly AND

(2) Flexible sigmoidoscopy or double contrast barium enema once every 5 years

(3) Some advise a colonoscopy every 10 years after age 50 years for a more thorough inspection for polyps or suspicious lesions, but insurance reimbursement for this may be limited.

b. For people at any age with a significant risk factor (immediate family member with colorectal polyps or cancer, or a personal history of inflammatory bowel disease)

(1) Fecal occult blood test and flexible sigmoidoscopy annually OR

(2) Colonoscopy every year

c. For anyone with abnormal basic screening tests, the usual gold standard for follow-up assessment and detection of polyps or GI tumors is the colonoscopy.

2. Laboratory tests. Few laboratory tests are exclusively diagnostic for any GI malignancy, although some tests that may be ordered for diagnosis or monitoring of response to treatment may include tests for:

a. Genetic abnormalities

b. Tumor markers

c. Serum comprehensive chemistry profile, hepatic panel

3. Evaluation for potential GI malignancy often involves radiologic procedures (x-rays, computed tomography [CT] scans) to detect masses.

4. Many patients will also require an endoscopic procedure to visualize and possibly obtain a histopathologic specimen for diagnosis.

C. Treatment is individualized for patients depending on their clinical stage and type of disease. An overview of treatment options is provided in Tables 12-1, 12-2, 12-3, 12-4, 12-5, 12-6, 12-7 and 12-8. Basic concepts of treatment planning for patients with GI malignancies include the following:

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