CONSTIPATION: One of the Most Frequently Overlooked Problems in Patients with Cancer

What is constipation

Constipation is defined as “3 or fewer bowel movements per week.” It can result from functional bowel disorders, certain diseases or various medications. This article explains its causes, mechanisms and treatment approaches during cancer and its treatment.

ROME III criteria provide a more comprehensive definition:

Rome III criteria – Classification of chronic (functional) constipation

According to these criteria, at least two of the following symptoms must have been present for 3 months, with complaints beginning at least 6 months earlier.

• Fewer than three bowel movements per week
• Excessive straining during at least one-quarter of bowel movements
• Hard, bulky stools during at least one-quarter of bowel movements
• A sensation of incomplete evacuation during at least one-quarter of bowel movements
• A sensation of blockage or obstruction as stool passes through the anus during at least one-quarter of bowel movements
• Manual assistance during at least one-quarter of bowel movements: digital evacuation or supporting pelvic muscles to pass stool
• Inability to pass soft stool without laxatives
• Absence of irritable bowel syndrome (IBS) symptoms

Is constipation in cancer different from functional constipation?

In cancer-related constipation, rather than the criteria above, quality of life affected by altered bowel habits may be the most important criterion. In constipation caused by diseases such as cancer or medication, reduced bowel movement frequency and amount relative to a person’s normal pattern, with resulting discomfort, affects quality of life and requires treatment. While physicians consider frequency and other criteria according to definitions, patients may describe any change in bowel habits as constipation.

Patients experiencing constipation during cancer may also have:

• Nausea, vomiting,
• Abdominal pain,
• Loss of appetite and 
• Abdominal bloating.

These symptoms may suggest ileus (bowel obstruction), which sometimes requires surgery. Constipation must therefore first be distinguished from ileus in such patients. Certain blood tests and radiological imaging are performed, and close clinical monitoring is required.

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What causes constipation?

Opioids, widely used as painkillers in cancer—narcotic painkillers, including certain drugs prescribed on green and red prescription forms—are the leading cause. However, not every patient taking opioids develops constipation. Individual genetic factors are the most important determinant. Opioids also have receptors in the nerve network affecting stomach and intestinal smooth muscle. Interaction with these receptors causes gastrointestinal effects: nausea, vomiting, early satiety and constipation.

While some chemotherapy drugs mainly cause diarrhea, constipation may be the predominant side effect of others.

Individual differences also occur here. A chemotherapy drug known to cause diarrhea in many patients may, rarely, cause constipation in another patient.

Certain drugs used for nausea and vomiting, epilepsy, depression, hypertension or iron deficiency can cause constipation.

High calcium, low potassium, an underactive thyroid and autonomic neuropathy resulting from diabetes cause constipation outside cancer as well. These causes can also occur in patients with cancer.

After abdominal cancer surgery, adhesions developing during intra-abdominal healing may cause constipation or irregular bowel movements.

Loss of appetite and resulting reductions in food and fluid intake may cause constipation in cancer. Disease-related physical inactivity can also contribute.

Cancer location and type influence constipation. Altered bowel habits, either constipation or diarrhea, or lack of rectal relief after a bowel movement may indicate bowel cancers among abdominal cancers.

Some cancers directly cause constipation. For example, bowel cancer spreading to the peritoneum or other intra-abdominal cancers, particularly gynecological cancers such as ovarian cancer, may cause it. When bowel adenocarcinoma spreads to the peritoneum, increased abdominal pressure and resulting bowel-wall edema reduce bowel function. Disordered bowel movement is also expected when gynecological cancers spread to neighboring abdominal organs or the peritoneum. A cancerous or metastatic mass compressing the spinal cord can also cause constipation. Cancers outside the abdomen may produce tumor-specific proteins (antibodies) affecting the intestinal nerve network or smooth muscle, causing motility disorders. These are called the tumor’s paraneoplastic effects. Tumors reported to cause paraneoplastic constipation include small-cell lung cancer, thymoma, ovarian cancer, breast cancer and neuroblastoma. Constipation alone is a rare consequence of paraneoplastic syndromes, whose symptoms vary widely with or without constipation.

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How Is Constipation Treated in Cancer?

First, patients and relatives should know measures they can implement themselves: dietary changes, increased water intake and physical activity. Drinking at least 2-3 liters of water daily is among the main measures. Treatments for poor appetite should be considered when it reduces food intake. In addition, for cancer-related fatigue as well, clearly recommended physical exercise is a valuable approach to coping with constipation.

Constipation may persist despite these first-line measures. Medications and/or medical methods are then added under physician supervision. Commonly used options are drugs called laxatives, rectal suppositories and enemas.

The first-choice medications for constipation are usually laxatives , which facilitate bowel movements through different mechanisms.

Laxatives can be classified by mechanism:

Bulk-forming agents: These are synthetic polysaccharide (large sugar molecules) or cellulose (natural polysaccharide) derivatives. Their large indigestible sugar molecules retain water and produce bulk. They must be taken with plenty of water; otherwise, they may worsen constipation.

Stool softeners: These are generally not the first choice among laxatives. Evidence for effectiveness alone is insufficient. Adding them is recommended when other laxative treatments are inadequate.

Osmotic laxatives: Most are sugars not absorbed from the bowel. They exert water-attracting (osmotic) effects by drawing water from intestinal cells. Prolonged use may cause electrolyte disorders. Magnesium-containing laxatives act similarly.

Stimulants (bowel stimulants): Their main mechanism is acting on nerves that stimulate bowel movements, increasing motility. Continuous use may cause low potassium and salt accumulation.

Enemas: Usually used when other laxatives fail to produce a bowel movement. However, depending on the need for immediate relief or preventing impaction, they need not always be late-line treatment.

Important points to know when taking laxatives

Laxatives may cause gas and cramps. Long-term use can lead to reduced responsiveness and fluid-electrolyte imbalances. Many are generally not recommended continuously for longer than 2-4 weeks. Bulk-forming agents may also worsen constipation if water intake is insufficient.

Other treatment options

Drugs acting through intestinal serotonin receptors that were approved for constipation were withdrawn because they caused cardiac arrhythmias.

Some antidepressants used for depression and acting mainly on brain serotonin receptors may help constipation.

Several FDA-approved drugs for chronic constipation are not currently available in our country.

Different options exist for constipation caused by opioid painkillers, among its most important causes in cancer.

Many studies show that combining opioids with reduced doses of their antagonists (substances with opposite effects) reduces opioid side effects without changing analgesia.

The role of probiotics (beneficial intestinal bacteria) in constipation treatment

Intestinal microbiota (intestinal bacteria) play an important role in gastrointestinal movement. Many studies show reduced proportions of beneficial bifidobacterium and lactobasilus bacteria in chronic constipation. Chemotherapy is thought to alter microbiota, contributing to chemotherapy-related mucositis, weight loss and constipation. Studies show that microbiota supplements (probiotics) reduce constipation-related findings in chronic constipation. They have also been shown to reduce chemotherapy- and radiotherapy-related mucositis and diarrhea.

Although acupuncture has shown effectiveness for cancer-related pain and fatigue, a recent review stated that its effect on constipation was unclear.

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Constipation caused by cancer and treatment usually resolves when the cause is removed and rarely becomes chronic.

Even fiber supplements, seemingly among the least harmful constipation treatments, may alter blood drug levels; this illustrates why every laxative should be used with the doctor’s knowledge. Regardless of the medication used, drinking 2-3 liters of water daily, diet and exercise should always remain part of treatment. In our next article, we will share appropriate dietary recommendations for constipation in detail.