1. Benign causes. GI bleeding in patients with active cancer is usually caused by acute gastritis, peptic ulcer disease, esophagitis, Mallory-Weiss tears, esophageal varices, ischemic colitis, diverticular disease, or angiodysplasia; only 10% to 15% is caused by direct tumor bleeding.

2. Malignant causes. The most common malignant causes of upper GI bleeding are esophageal cancer, gastric cancer, gastric lymphoma, gastrointestinal stromal tumors (GIST), and metastatic tumors involving the stomach. Lower GI bleeding is usually caused by colorectal cancer or metastatic cancer to the bowel. In order to diagnose bleeding from the small bowel, patients may require enteroscopy or capsule endoscopy; it is most commonly caused by GIST or metastatic cancer (i.e., melanoma).

3. Secondary to cancer treatments. Bleeding is a common complication of radiation therapy (RT), that is, radiation esophagitis, enteritis, or proctitis. Chemotherapy can induce enteric mucositis (cytarabine, fluoropyrimidines, taxanes). In addition, patients may suffer from superimposed infections (Candida or cytomegalovirus [CMV] esophagitis; CMV, Clostridium difficile, or gram-negative bacillus enteritis; typhlitis). Newer antiangiogenic cancer medications (bevacizumab, sunitinib, sorafenib, pazopanib) increase the risk of bleeding and the risk of hemorrhagic complications during surgery.

4. Secondary to supportive therapy in cancer patients. Cancer patients may bleed from erosive esophagitis secondary to oral bisphosphonate or potassium chloride or erosive gastritis secondary to steroids or nonsteroidal anti-inflammatory drugs (NSAIDs).

B. Management. In patients with cancer, the status of their malignancy may influence the aggressiveness of the management. The bleeding is most commonly caused by benign causes, and it is frequently reversible. Therefore, aggressive management should be applied in all patients with good performance status.

Initially, patients are resuscitated with intravenous fluids and blood products and then diagnostic efforts are concentrated on establishing the etiology. Surgical intervention is frequently required in cases of tumor bleeding; patients with persistent GI bleeding from unresectable tumors may be managed with RT. Long-term, successful systemic therapy against cancer is most helpful in the management of bleeding from the tumor.

A. Etiology. Bowel obstruction is defined by the inability of intestinal contents to traverse through the bowel and can be divided into complete and partial, mechanical, or functional. In patients with a history of cancer, it is due to the original tumor or its metastases in 60% to 70% of cases. About 20% to 30% of patients have a benign cause of obstruction, and 10% to 20% have a new, and often resectable, primary lesion. Duodenal obstruction is most commonly caused
by cholangiocarcinoma, pancreatic carcinoma, and gallbladder carcinoma; distal bowel obstruction is secondary mainly to colon and ovarian cancer.

1. Mechanisms of bowel obstruction in malignancy include the following:

a. External pressure on the intestine caused by mesenteric or omental masses

b. Obstructing masses in the bowel lumen

c. Intraluminal masses invading mucosa and impairing peristalsis (pseudo-obstruction)

d. Invasion of the intestine’s neural plexus, causing localized or diffuse ileus clinically indistinguishable from mechanical obstruction

e. Intussusception with certain tumors, notably melanoma

f. Pseudo-obstruction as a paraneoplastic syndrome (see Section IX)

g. Adhesions secondary to previous surgeries

h. Complications of RT or intraperitoneal chemotherapy

i. Use of cholinergic or sympathomimetic drugs (ileus, pseudo-obstruction)

2. Differential diagnosis. Diagnostic considerations in cancer patients include the following:

a. Vinca alkaloid neurotoxicity may produce constipation. Particularly in elderly patients, paralytic ileus or decreased bowel tone may lead to high fecal impaction with bowel obstruction. Impaction is better prevented than treated.

b. Radiation injury of small bowel (see Section VI.C) may be seen on small bowel radiographs or CT scan as mucosal effacement, ulcers, rigidity, narrowing, adhesions, bowel wall thickening, and bowel dilation.

c. Diverticulitis may produce tightly narrowed areas in the distal colon that are often radiologically indistinguishable from constricting carcinoma. In the absence of metastatic disease elsewhere, these lesions must be resected regardless of coexistent tumor.

d. Other nonmalignant causes of ileus and obstruction include adhesions, hernia, inflammatory bowel disease, volvulus, spontaneous intussusception, acute pancreatitis, and bowel infarction.

B. Management of bowel obstruction caused by cancer. The status of a patient’s cancer should be always included in decision making on the aggressive management of gastrointestinal obstruction. Patients with terminal cancer benefit from the aggressive symptom management, but not from surgical intervention, parenteral nutrition, or long-term nasogastric tube placement.

1. Fluid resuscitation. Intraluminal volume sequestration results in fluid depletion. In terminal patients, excessive hydration may worsen patients symptoms since it can increase intraluminal fluid secretion or lead to volume overload.

2. Decompression. Patients with evidence of intestinal obstruction should have decompression by placement of a nasogastric (NG) tube and intermittent suction. Complications of prolonged NG tube use include nasal erosion and sinusitis. The goal is to use decompression with other modalities listed later to minimize time with the NG tube. In refractory cases, venting gastrostomy/percutaneous endoscopic gastrostomy tube decompression is often the only palliative modality available when other measures fail.

3. Stents. Expandable metallic stents have been used to treat obstruction in nearly all portions of the GI tract, including the esophagus, gastric outlet, duodenum, proximal jejunum, terminal ileum, colon, and rectum. Although stent placement requires a trained endoscopist or interventional radiologist, this procedure palliates obstruction in >80% of patients and may obviate the need for surgery in patients who cannot be cured. Complication rates are low but include bleeding, stent migration, and tumor growth into stent. Stents can be used as a “bridge” to improve symptoms while awaiting definitive treatments for obstruction.

a. A history of cancer or even the presence of active tumor is not necessarily a contraindication to surgery. About 75% of patients with a bowel obstruction resume normal bowel function after surgery. Function is maintained until death in 45% of patients. About 25% of these patients do not experience improvement of symptoms with surgery.

b. Surgical intervention should be considered if the obstruction does not improve after 4 to 5 days of decompression and if the following conditions are met:

(1) The patient’s medical condition, including nutritional status, makes the operative risk low.

(2) The patient does not have malignant ascites.

(3) The patient’s life expectancy would be >2 months if the bowel obstruction were relieved.

(4) The patient underwent no more than one surgical intervention for obstruction during the previous year and was significantly palliated by that operation for >4 months.

(5) The most recent operative intervention did not disclose multiple or widespread tumor sites causing obstruction.

a. Chemotherapy may be tried in patients with obstruction caused by carcinomatosis. In some tumors, such as lymphomas treated with chemotherapy or GIST and melanomas treated with targeted therapy, symptomatic improvement is seen within days after starting the therapy.

b. RT to relieve bowel obstruction may be beneficial in patients who have peritoneal carcinomatosis from ovarian carcinoma or extensive abdominal lymphoma that is resistant to chemotherapy. Abdominal irradiation produces severe side effects and is not recommended for other types of malignant bowel obstruction.

(1) NG suction is used to alleviate abdominal pain. Intravenous fluids are given to maintain hydration.

(2) Opioids are given SC or IV for pain control; they are appropriate for continuous abdominal pain but can aggravate colic.

(3) Anticholinergic agents, such as hyoscine butylbromide, 60 to 380 mg/d (Buscopan), or glycopyrrolate (Robinul), may alleviate pain, especially colic, and can also reduce nausea and vomiting. Nausea and vomiting can be treated with various drugs.

(4) Phenotiazines (prochlorperazine, promethazine, chlorpromazine) reduce nausea and vomiting.

(5) Metoclopramide can have its place in patients with functional or partial bowel obstruction; it should not be used with anticholinergics or in patients with colic or complete bowel obstruction.

(6) Haloperidol, 1 to 5 mg SC three times daily, is helpful in patients with nausea and delirium.

(7) Dexamethasone, 6 to 16 mg/d parenterally, can help decrease edema and possibly help decrease obstructive symptoms.

(8) Octreotide, 100 to 300 µg every 8 hours SC, is an effective drug that decreases GI secretions, decreases distention, and in many cases allows the NG tube to be taken out.

(9) Olanzapine (Zyprexa), in doses of 2.5 to 20 mg/d, can reduce vomiting in patients who failed other medications.

1. Liver. The liver is a common site of metastases. Liver metastases account for more than half of the deaths in certain malignancies, such as colorectal cancer.

a. The relative risks of tumor metastasizing to the liver during the course of advanced disease are as follows:

(1) Liver commonly involved: GI tract cancers (including carcinoids, pancreatic adenocarcinoma, and islet cell tumors), lung cancer (especially small cell), breast cancer, choriocarcinoma, melanoma, lymphomas, and leukemias

(2) Liver occasionally involved: carcinoma of the distal esophagus, kidney, prostate, endometrium, adrenal gland, and thyroid; testicular cancers, thymoma; angiosarcoma

(3) Liver rarely involved: carcinoma of the proximal esophagus, ovary, and skin; plasma cell myeloma; most sarcomas

b. Types of metastases

(1) Nodular metastases are the most common type and occur with all tumors capable of metastasizing to the liver, including lymphoma.

(2) Diffuse metastases most frequently occur with lymphomas. Breast cancer, small cell lung cancer, poorly differentiated GI tumors, and, rarely, other types of tumors can also produce diffuse metastases.

2. Extrahepatic biliary obstruction can occur from lymph node metastases in the porta hepatis, particularly from GI cancers and lung cancers (especially the small cell type).

B. Natural history. The clinical course of liver metastases depends on the tumor’s behavior and responsiveness to chemotherapy. In patients with solid tumors, death commonly occurs within 6 months with nodular metastases and more rapidly with diffuse metastases. A liver that appreciably increases in size in <8 weeks is typical in small cell lung cancer and high-grade lymphoma; both of these tumors respond well to treatment. Rapid liver enlargement in patients with other tumor types is less common.

1. Symptoms and signs. Any combination of pain or discomfort in the right upper quadrant, weight loss, fatigue, anorexia, jaundice, or fever should raise the possibility of liver metastases, particularly in patients with a history of cancer. Symptoms are present in 65% of patients and hepatomegaly in 50% when liver metastases are discovered.

a. LFTs should be obtained in all patients suspected of having liver metastases. An elevation of the alkaline phosphatase level that is out of proportion to that of the transaminases suggests either a mass lesion or a biliary obstruction.

b. Liver imaging is obtained in all patients with history, physical findings, or laboratory values suggestive of hepatic metastases. Hepatic CT or MRI scans are the most sensitive techniques. Ultrasonography and^99mTc colloid liver scans have lower diagnostic accuracy. Ultrasound may be useful in determining whether a lesion is solid or fluid. The evaluation of a single focal lesion in the liver is discussed in Chapter 9.

3. Selective hepatic angiography is the most predictive diagnostic test to assess the presence, number, and distribution of hepatic metastases but is usually unnecessary unless an embolization procedure is planned.

4. Liver biopsy should be performed to confirm the presence and type of tumor in the following circumstances:

a. There is no primary history of cancer, and the liver is the only obvious site of disease.

b. There has been a long disease-free interval (>2 years) since the removal of the primary tumor.

c. The liver abnormality is not typical of the natural history of the primary cancer. Suggestive evidence for hepatic metastases in patients with primary tumor type that does not usually metastasize to the liver indicates biopsy if the results are likely to affect therapeutic decisions.

d. Relative contraindications for liver biopsy include the following:

(1) Coagulation protein or platelet abnormalities

(2) Evidence of a vascular tumor (e.g., angiosarcoma)

5. Extrahepatic biliary obstruction. These patients must have special studies to exclude benign causes of obstruction, such as gallstones or bile duct strictures.

a. CT scan or DISIDA (diisopropyl iminodiacetic acid) scan of the liver is performed to look for parenchymal or porta hepatis masses and obstruction of the biliary tree.