Textbook Reading

CHAPTER 160 DIARRHEA AND

CONSTIPATION
Devita, Hellman, Rosenberg. Cancer: Principles and Practice
of Oncology 9th edition. Lippincott Williams & Wilkins
Publishers. 2011
 Introduction
• Constipation and diarrhea are :
– both common problems.
– life-threatening dehydration and electrolyte
abnormalities.
– opioid analgesics  constipation  more
common that diarrhea.
• the strategies to evaluate and manage these
common and distressing symptoms.
 DIARRHEA
• Diarrhea is defined as the frequent passage of loose stools
with urgency.
• Objectively defined, it is the passage of more than three
unformed stools in 24 hours.
• Diarrhea is
– among patients with advanced cancer.
– a major treatment complication (fluoropyrimidines and
irinotecan).
• The causes of diarrhea are diverse  require specific
therapies.
• Severe diarrhea = dehydration, electrolyte imbalance,
malnutrition, declining immune function, and pressure ulcer
formation.
 Chemotherapy-Induced Diarrhea
• The chemotherapy agents commonly causing
diarrhea include :
– 5-fluorouracil,
– capecitabine, and
– irinotecan ( CPT- 1 1 ) .
– The taxane, docetaxel, commonly causes a relatively
mild diarrhea.
• Chemotherapy  acute damage to the intestinal
mucosa  imbalance between absorption and
secretion in the small bowel.
 Neutropenic Colitis
(necrotizing enterocolitis or typhlitis)
• an acute life-threatening complication of chemotherapy
• most commonly observed with high-dose treatments in the
setting of myeloablative therapies.
• also observed with nonmyeloablative therapies, particularly
with taxanes.
• Clinical Presentation:
– neutrophil count falls below 500 mcL.
– fever, abdominal pain, nausea, vomiting, diarrhea, and, not
uncommonly, sepsis.
– Abdominal pain may be diffuse or localized to the right lower
quadrant.
– Sometimes pain is absent, particularly if the patient has
received steroid therapy
 Pathogenesis of neutropenic
enterocolitis
• Multifactorial:
– mucosal injury,
– profound neutropenia, and
– impaired host defense to invasion by microorganisms.
• The microbial infection leads to necrosis of various layers of
the bowel wall.
• The predilection for the cecum is possibly related to its
dispensability and its relatively diminished vascularization.
• Bacteremia or fungemia is also common, usually with enteric
organisms such as pseudomonas or yeasts such as Candida
 Diagnostic Investigations
• The diagnosis is based on signs and symptoms
in the appropriate clinical setting as well as
imaging studies.
– Plain abdominal radiographs
– Computed tomography ( CT) scanning
Targeted Therapy-Associated Diarrhea
• 30 % to 50 % of patients who receive bortezomib,
erlotinib, gefitinib, sorafenib, sunitinib, and
imatinib, and the mammalian target of rapamycin
(mTOR) inhibitors temsirolimus and everolimus.
• The monoclonal therapies targeting epidermal
growth factor receptor (EGFR), cetuximab and
panitumumab, both cause diarrhea in 10 % to 20
% of patients, which may be severe in a small
subset of patients
 Other Causes of Treatment-Related
Diarrhea
• Clostridium Difficile Diarrhea
• Enteral Feeding
• Celiac Plexus Block
Assessment
 General Principles in the
Management of Diarrhea
• Patients must be rehydrated either orally or,
when appropriate, by parenteral infusion.
• In general, milk products should be avoided
• Special attention should be given to patients
who are incontinent of stool due to the risk of
pressure ulcer formation.
• Skin barriers should be used to prevent skin
irritation caused by fecal material.
 Antidiarrhea Medications
• Opioids
• Somatostatin Analogues
• Other Agents (Budesonide)
 Specific Management Guidelines
American Society of Clinical Oncology (ASCO )
guidelines for management of treatment-
induced diarrhea were published in 2004.
– Patients are classified as uncomplicated or
complicated
 Uncomplicated Diarrhea
• Managed conservatively with oral hydration and
loperamide.
• Initial management of mild to moderate diarrhea:
– dietary modifications
– the patient should be instructed to record the number
of stools and report symptoms of life-threatening
sequelae (e.g., fever or dizziness on standing)
– Loperamide: initial dose of 4 mg followed by 2 mg
every 4 hours or after every unformed stool (not to
exceed 16 mg/d) .
 Uncomplicated Diarrhea
• If diarrhea resolves with loperamide, the patients
should be instructed to continue dietary modifications
and to gradually add solid foods to their diet.
• In the case of chemotherapy induced diarrhea, patients
may discontinue loperamide when they have been
diarrhea-free for at least 12 hours .
• The second step, if mild to moderate diarrhea persists
for more than 24 hours, is to increase the dose of
loperamide to 2 mg every 2 hours, and oral antibiotics
may be started as prophylaxis for infection.
 Uncomplicated Diarrhea
• The third step, if mild to moderate
chemotherapy-induced diarrhea has not resolved
after 24 hours on high-dose loperamide (48 hours
total treatment with loperamide) ,  further
evaluation, including complete stool and blood
workup.
– Fluids and electrolytes should be replaced as needed.
– Loperamide should be discontinued, a second-line
antidiarrheal agent such as subcutaneous octreotide (
100 to 150 mcg starting dose, with dose escalation as
needed) or other second-line agents ( e.g., oral
budesonide or tincture of opium ) .
 Complicated Chemotherapy-Induced
Diarrhea
• Patients with mild to moderate diarrhea complicated by
moderate to severe cramping, nausea and vomiting,
diminished performance status, fever, sepsis, neutropenia,
bleeding, or dehydration and patients with severe diarrhea
are classified as complicated and should be evaluated
further, monitored closely, and treated aggressively.
• Aggressive management of complicated cases usually
necessitates admission and involves administering
intravenous fluids, octreotide at a starting dose of 100 to
150 mcg subcutaneous three times a day or intravenous (25
to 50 mcg/h) if the patient is severely dehydrated, with
dose escalation up to 50 mcg subcutaneous three times a
day until diarrhea is controlled, and administration of
antibiotics (e.g., fluoroquinolone) .
 CONSTIPATION
• Constipation is the slow movement of feces through the large
intestine, resulting in infrequent bowel movements and the passage
of dry, hard stools.
• Rome 2 Criteria for chronic constipation is the presence of any two
of the following symptoms for at least 12 weeks ( not necessarily
consecutive) in the previous 12 months:
– straining during bowel movements;
– lumpy or hard stool;
– sensation of incomplete evacuation;
– sensation of anorectal blockage or obstruction;
– less than three bowel movements per week.
• Prevalence : approximately 40 % to 60 % in advanced cancer; the
greatest prevalence occurs in the opioid-treated population.
Treatment-Related Causes
 Differential Diagnosis
1. Low-Fiber Diet
2. Dehydration
3. Lack of Exercise
4. Colonic Pathology
5. Neuromuscular Disorders
6. Metabolic Disorders
7. Psychological Disorders
 Diagnosis
• The medical history can assist in identifying the causes of
constipation.
• An accurate history should elicit the change in bowel
movements: frequency of bowel movements; whether
defecation is associated with blood or mucus (suggestive of
obstruction or hemorrhoids) , pain, or straining; presence
or absence of defecation urge (hard stool or rectal
obstruction in former, colon inertia in latter ) ; manual
maneuvers by patient.
• Questions should also be aimed to determine the cause of
the change in bowel movements, in particular eating and
drinking habits, medication use, and level of physical
activity.
 Diagnosis
• The physical assessment could include a rectal examination to
evaluate sphincter tone and detect tenderness, obstruction, or
blood. Digital rectal examination may reveal:
– hard, impacted feces
– soft stool due to fecal leakage
– complete absence of stool (colonic inertia, high obstruction, or
impacted stools)
– tumor masses
– concomitant disease-hemorrhoids, anal fissure, perianal ulceration,
rectocele or anal stenosis
• If constipation manifests as part of a spinal cord compression
syndrome, full neurological examination is necessary including
assessment of anal sphincter tone (lax with colonic hypotonia) and
rectal sensation.
 Investigation
• Investigations are not routinely necessary,
however, plain abdominal radiography may be
indicated to exclude bowel obstruction and to
distinguish stool from tumor.
• Plain abdominal radiography is also the best way
to assess the degree of constipation.
• More extensive testing can proceed for patients
with severe symptoms, for those with sudden
changes in number and consistency of bowel
movements or blood in the stool, and for older
adults
 General Measures
• General Measures
– Diet
– Fluid Intake
– Physical Activity
• Laxatives: Bulk Laxatives, Osmotic Laxatives,
Magnesium and Sulfate Salts, Stimulant
Laxatives
• Enemas and Suppositories
 Managing Fecal Impaction
• The treatment of a fecal impaction usually
requires the digital fragmentation and extraction
of the stool.
• Lubricating enemas and suppositories may be
helpful.
• Since this is a very uncomfortable procedure,
sedation is generally recommended and
anesthesia may occasionally be needed.
• Once the impaction is relieved, it is crucial that
the patient start a prophylactic daily bowel
regimen.
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