Constipation often accompanies the course of the malignant process, especially in the terminal - the last 4 stages of cancer. In some situations, it signals extremely unfavorable complications of the disease, but more often it is a natural chronic consequence of the hardships of life for a cancer patient.
Constipation is possible in young and old, all victims are united by one desire - to never experience this condition again, world statistics clarify - symptoms are observed in 12%-19% of adults, but only occasionally.
Chemotherapy and constipation: connection, medications and causes
Patients receiving certain cancer treatments, such as chemotherapy, may experience side effects such as constipation.
Doctors sometimes call this side effect chemotherapy-induced constipation. This is one of the most common reasons why doctors reduce chemotherapy doses or delay or stop treatment. Chemotherapy isn't the only thing that can cause constipation. Other factors associated with cancer treatment may also contribute to hard or difficult stools. This may include changes in diet and fluid intake, as well as decreased physical activity. Some types of cancer, such as a tumor in the abdomen or pelvis, can also directly cause constipation.
This article will explain the connection between chemotherapy and constipation and review treatment options.
Constipation in stomach cancer
Gastric carcinoma disrupts the function of the gastrointestinal tract, but after removal of part or all of the stomach, patients often complain of loose stools. Constipation is promoted by the neurotoxicity of chemotherapy, which includes nerve-damaging platinum derivatives and taxanes. A very severe complication of chemotherapy - intestinal paresis with the absence of peristalsis is clinically manifested by symptoms similar to obstruction, but with the release of gases.
With peritoneal carcinomatosis or intraperitoneal metastases, especially with ascites, symptoms of partial obstruction of the intestinal tube with subcompensated obstruction come to the fore.
Most cancer patients are not helped by taking laxatives and increasing physical activity; treating constipation in a cancer patient is a multidisciplinary task that requires the participation of an oncologist and proctologist, a nutritionist and a clinical pharmacologist. A banal phenomenon in a cancer patient may hide the progression of the disease; Euroonco will help resolve this problem.
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Bibliography
- Achkasov E.E., P.A.V., Alekperov S.F., Shkoda A.S., Belyaev L.B., Volkov V.S., Krutilina O.V., Kalachev O.A. / Classification of obstructive colonic obstruction of tumor origin // Coloproctology; 2009; 3.
- Karlov A.V., Orlova N.V., Parfenov A.I./Dyssynergic defecation is one of the causes of chronic constipation// Ter. Archive; 2015; 87(4).
- Terzi´c, J.; Grivennikov, S.; Karin, E.; Karin, M. /Inflammation and colon cancer// Gastroenterology; 2010; 138.
- De Salvo G.L., Gava C., Lise M. et al. /Curative surgery for obstruction from primary left colorectal carcinoma: Primary or staged resection// The Cochrane Database of Systematic Reviews; 2006; Issue 2.
- Glynne-Jones R., Tan D., Goh V. /Pelvic MRI for guiding treatment decisions in rectal cancer// Oncology; 2014; T. 28; No. 8.
- Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up //Annals of oncology; 2013;T. 24; supple 6.
Chemotherapy and constipation: what is the connection?
Constipation is a decrease in the frequency of bowel movements, as well as hard and dry stools. Researchers estimate that the prevalence of chemotherapy-induced constipation among cancer patients is about 16%. They note that 5% have severe constipation, and 11% have moderate constipation.
The underlying cause of chemotherapy-induced constipation is unclear. Doctors suspect that constipation occurs due to a combination of factors related to chemotherapy. This includes:
- inflammation of the digestive tract
- intestinal secretion disorder
- movement disorders in the digestive tract
- changes in how the digestive tract responds to the nervous system
Specific chemotherapy drugs associated with constipation include:
- gemcitabine (gemzar)
- oxaliplatin (eloxatin)
- Thalidomide (Contergan)
- vinblastine (velban)
- vincristine (oncovin)
general information
Constipation is a condition in which it is impossible to have bowel movements even three times a week. The medical reference defines constipation as “slow, difficult, or systematically insufficient bowel movements.”
It is important to understand that constipation is not a disease, but a symptom. It occurs as a result of a violation of the diet, as a consequence of taking medications. This may be a reaction to pathologies of internal organs, including cancer.
In a number of situations, the symptom indicates the serious development of cancer - metastasis or the final stages of the process.
The “Rome criteria” (this is the name of one of the international protocols) says the following about diagnosing a symptom: it is detected if a person experiences at least two of the following symptoms for six months:
- Defecation – less than 3 times a week;
- Prolonged straining during bowel movements;
- Hard stools or with dense fragments;
- Constant feeling of unsatisfactory bowel movements;
- A feeling of obstruction that is created in the anus;
- Lack of soft stools without taking laxatives;
- Absence of “irritable bowel syndrome”, some others.
Signs of a symptom caused by cancer:
- Nausea and vomiting;
- Pain syndrome in the umbilical area;
- Loss of appetite;
- Bloating.
According to the Rome criteria, to diagnose constipation, symptoms must be observed in every fourth bowel movement and last for more than three months.
Other causes of constipation
Patients receiving chemotherapy may also need to take additional medications to manage side effects, including nausea. Some may need opioids to relieve the pain that cancer may cause. Therefore, it may be difficult for doctors to determine which medication is causing constipation.
Tumors in the intestines or pelvis can also cause constipation. Other factors that may contribute to constipation include:
- lack of physical activity
- bed rest
- diet changes
- low fluid intake
Some also take vitamins and minerals such as iron or calcium during cancer treatment, and this can also cause constipation.
Constipation caused by chemotherapy is treated with laxatives, but overusing these drugs can make your condition worse.
Thyroid problems and cancer-related depression can also cause constipation.
Possible complications
Constipation during a cancer process is usually complicated by a number of clinical manifestations:
- Vomit;
- Bloody discharge;
- Low immunity;
- Loss of strength, feeling of weakness;
- Skin rashes;
- Headache;
- Fever, chills.
A very dangerous manifestation is intestinal obstruction, which becomes a consequence of impaired intestinal activity in terms of motor activity. The cause of this complication is the blocking of the intestine by a tumor. It can be partial, but it can also be complete. Here, urgent surgical intervention is necessary, because there is a threat of necrosis, blood poisoning and, as a result, death is predetermined.
Home remedies for constipation
In addition to medications, there are steps you can take at home to relieve constipation caused by chemotherapy. These include:
- if possible, exercise
- increasing fluid intake to 8–10 glasses throughout the day
- increasing your fiber intake by adding whole grains, brown rice, raw fruits and vegetables, legumes and beans, dried fruit, popcorn, seeds and nuts
A dietitian can help you choose fiber-rich foods to include in your diet. Sometimes a fiber supplement can help.
Patients should also record their bowel movements in a journal, along with details of their diet and fluid intake. With this information, doctors can make recommendations to improve bowel movements.
Some natural laxatives include:
- prunes or plum juice
- rhubarb
- papaya
Hot drinks such as cocoa, tea or hot water with lemon can also help stimulate bowel movements.
Other tips include:
- do not hold bowel movements as soon as you feel the urge to visit the bathroom
- Avoid gas-causing foods such as apples, avocados, beans, peas, cabbage, broccoli, milk, and sodas until constipation goes away.
- avoid chewing gum
- refraining from using straws
- avoid constipating foods such as eggs and cheese
Treatment methods in Medscan
Constipation in cancer requires complex treatment. Taking laxatives and enema procedures only temporarily relieve the unpleasant symptom, without solving the problem at the root. The situation requires a multidisciplinary approach, which is carried out at the Medscan clinic. A group of specialists will make an opinion on your disease, prescribing only the necessary and effective treatment.
Medscan practices a number of treatment methods:
- Surgical intervention. Removing tumor nodes can relieve disturbing discomfort.
- Chemotherapy. Treatment is carried out with the most effective original drugs.
- Radiation therapy. Expert level equipment is used for radiotherapy.
- Immunotherapy helps increase the protective properties of the immune system, thanks to which the body gains the ability to independently identify and destroy atypical cells.
- Targeted therapy is an innovative drug therapy. It is distinguished by targeted damage to malignant cells, without affecting healthy ones.
Other types of oncological care are prescribed at Medscan according to indications.
Treatment Options
Along with general recommendations to increase dietary fiber, fluids, and exercise, doctors may recommend over-the-counter or prescription medications. Emollients, osmotic, stimulant and lubricating laxatives may help.
Volume-forming laxatives
Bulk-forming laxatives work by swelling the inside of the intestines, allowing the intestines to expand slightly and facilitating the passage of stool. The slight dilatation of the intestines stimulates bowel movements and reduces the time it takes for stool to pass. Bulk laxatives include:
- methylcellulose
- psyllium (metamucil)
- polycarbophil
Osmotic laxatives
Osmotic laxatives include:
- lactulose (enulose)
- sorbitol
- polyethylene glycol (MiraLAX)
- Magnesium hydroxide (milk of magnesia)
These laxatives help relieve constipation by drawing fluid into the intestines and keeping it there. Osmotic laxatives promote bowel movements within 24–72 hours).
Emollient laxatives
Softening laxatives are also called stool softeners. These medications work by increasing intestinal fluid and mixing fats and watery substances in the intestines, which softens hard and dry stools and makes them easier to pass.
Emollient laxatives are ineffective if constipation is caused by lack of bowel movement. Doctors often recommend taking emollient laxatives with bulking supplements. Examples of emollient laxatives include:
- docusate calcium
- docusate sodium
- potassium docusate
Stimulant laxatives
These laxatives stimulate neurons in the intestines, causing contractions that push stool. Research shows that these laxatives work better than enemas and bulking agents and are often effective for constipation caused by opioid use. Examples of stimulant laxatives include:
- sodium picosulfate (picodan)
- sennosides (Senokot)
- Castor oil
Lubricating laxatives
Lubricant laxatives work by coating the stool and rectum with a slippery film, making bowel movements easier. The most common laxative lubricant is mineral oil, which can be used orally or rectally.
Rectal laxatives
Doctors recommend these drugs with manual stimulation only for fecal insufficiency or neurogenic bowel dysfunction. The most commonly used rectal laxatives are bisacodyl suppositories and glycerin suppositories.
You should avoid using enemas or suppositories without first consulting your doctor. It is important to always ask a cancer treatment specialist before trying any laxative.
Diagnostic methods
Diagnostic measures begin with examination of the abdomen and peritoneal wall. By examining the rectum by palpation, you can find out the characteristics of the stool, determine formations, scars or its narrowing.
For a more detailed examination, the following are intended:
- Blood and urine tests;
- Radiography;
- Ultrasonography;
- Computed tomography;
- Magnetic resonance imaging;
- Immunohistochemistry.
Liquid mass in the pleural cavity
If the doctor considers it necessary, he may prescribe other research methods.
Chemotherapy: when to see a doctor
Patients taking chemotherapy and experiencing constipation should see a doctor if they have not had a bowel movement for 3 days. However, this duration depends on the type of chemotherapy and protocols at a particular cancer center. Some cancer treatment specialists may indicate a different interval between bowel movements when medical attention is needed.
Patients taking laxatives or stool softeners to relieve constipation should contact their doctor if the medication does not work. If a patient does not have a bowel movement within 1-2 days after taking a laxative or stool softener, they need medical attention.
The following symptoms of constipation also require medical attention:
- blood in or around the anus
- blood in stool
- persistent abdominal cramps or vomiting
- loose or watery stools
The specialist may also indicate additional symptoms of constipation that require medical attention. Patients should follow the instructions given by their doctor.
Common complications from hard, dry stools include:
- rectal rupture
- haemorrhoids
- rectal fissures
Some patients with severe constipation may develop constipation, which is persistent, severe constipation. Constipation can have life-threatening consequences, such as intestinal obstruction.
Completely obstructed stools can increase pressure in the intestines and cause decreased blood flow and tissue death. Sometimes, intestinal rupture may occur.
Constipation in colorectal cancer
One of the most important signs of rectal carcinoma is uneven stool, either constipation or diarrhea, with dissatisfaction with the act due to seemingly incomplete emptying.
The rectum is a well-extensible ampoule, the capacity of the tube is very impressive and reaches 20 cm in the largest diameter. Therefore, obstruction is an infrequent manifestation of the disease, but constipation will be caused by dyssynergism of the muscles involved in the cancerous conglomerate and metastases to the lymph nodes along the neurovascular bundles.
Insufficiency of secretion production by glandular cells with inflammation accompanying the tumor and post-radiation changes add to the chances of stool compaction.
Conclusion
Constipation is common when cancer patients receive certain treatments, such as chemotherapy. Constipation can occur for various reasons. For example, certain chemotherapy drugs or decreased activity or fluid intake can cause constipation.
Exercising, eating fiber, and drinking fluids are ways to naturally stimulate bowel movements. Sometimes medications are needed to relieve constipation. Medication options may include bulking, emollient, stimulant, and osmotic laxatives.
Cancer specialists provide advice to patients on how to manage constipation.
Consequences after chemotherapy in women
Chemical drugs, affecting the ovaries, inhibit the growth and development of follicles, damage the hereditary material of germ cells and cause hormonal disorders.
The most common side effect of chemotherapy drugs is menstrual irregularities and cessation of menstruation. Menopause can be temporary, caused by hormonal imbalances, or permanent, caused by ovarian depletion.
Women have a limited number of eggs. During her entire life, she experiences about four hundred menstrual cycles, which means that four hundred follicles go through the development cycle. Chemotherapy reduces the number of follicles, causing ovarian failure.
Here the consequences depend on age: in girls under twenty years of age, with a sufficient supply of follicles, menstruation is restored in seventy percent of cases. In women over thirty, whose ovaries are already depleted, only in their twenties.
However, pregnancy after chemotherapy is quite possible. By taking care of cryopreservation of eggs, embryos or ovarian tissue in advance, you can avoid infertility. This should be done before starting treatment, since even one course of chemotherapy deteriorates the quality of cells and changes the structure of the hereditary material. But even if the patient begins to think about possible infertility after starting treatment, it is not too late to contact a fertility specialist, although it is necessary to freeze the eggs as early as possible.
You can use the stored eggs at any time. The shelf life of the material is unlimited, and children born using preserved eggs will be no different from those conceived naturally.
It is very important to use contraception or avoid sexual contact during the course of treatment to avoid unwanted pregnancy. A woman should definitely consult her doctor about this, since chemotherapy drugs cause deformities in children.
The side effects of chemotherapy on the developing fetus are so strong that if a woman is diagnosed with cancer during pregnancy, the course of treatment is postponed until after birth.
Introduction
Radiation-induced intestinal damage is one of the most common problems of patients receiving radiation therapy for oncological diseases of the gastrointestinal tract (GIT), gynecological diseases, and urinary tract.
Various terms are used to describe this condition: radiation enteropathy, radiation mucositis, pelvic radiation sickness, but more commonly radiation colitis or enteritis. Radiation proctitis is used to describe lesions of the rectum and sigmoid colon. Manifestations of varying severity, according to various studies, occur in 5–25% of patients [1–3]. Radiation enteritis/colitis can be acute or chronic, while the chronic form can develop from 3 months to 30 years after treatment, which sometimes makes diagnosis difficult. The epithelium of the small intestine is most sensitive, so enteritis is more common and more severe. When the impact is directed to the small pelvis, the rectum and sigmoid colon are exposed to the maximum impact due to their fixed position. In later stages, post-radiation colorectal cancer can occur [4]. Initial changes in the intestine occur within 2–3 hours after exposure to radiation: inhibition of epithelial apoptosis in the crypts, loss of villi. Irradiation of normal tissues results in the formation of reactive ions, which react with intracellular water molecules to form free radicals such as hydroxyl. These radicals lead to DNA destruction and cell death. Secondarily, genes that promote fibrosis are activated by activating the synthesis of collagen and fibronectin. The faster the processes of proliferation in tissues occur, the higher their sensitivity to radiation; therefore, the faster the process of destruction of the cell membrane and cell death. Epithelial cells of the small intestine are more radiosensitive compared to the colon and rectum [3]. Radiation also promotes functional changes in the intestine: hypersensitivity to the stimulating effects of secretogenic components, increased epithelial permeability, changes in motility, impaired sensitivity to gastrointestinal hormones, and disruption of absorption processes.
The development and severity of radiation enteritis/colitis depend on the following factors: radiation dose, duration of irradiation, prior abdominal surgery, body mass index, comorbid conditions such as diabetes mellitus or arterial hypertension, and concurrent chemotherapy [5].
Clinical manifestations of radiation damage to the intestine
The clinic is caused not only by damage to the intestinal mucosa, but also by a slowdown or increase in motility, excessive growth of microbial flora (SIBO - bacterial overgrowth syndrome), decreased absorption of bile acids, increased intestinal permeability, and lactose malabsorption. Acute damage usually occurs in the second week of radiation therapy, peaking in the 4th to 5th week.
The most common symptoms of radiation damage to the intestines include diarrhea, abdominal pain, rectal pain, intestinal bleeding, and malabsorption [5]. More severe manifestations, sometimes requiring surgical intervention, may include intestinal obstruction, intestinal perforation, and fistulas. Patients with diarrhea, abdominal pain, or bloating should be tested for SIBO [3, 5].
Assessing the severity of intestinal damage
Many criteria and indices have been proposed to assess the severity of intestinal damage in patients undergoing radiotherapy, but none have proven their validity [3]. They focus on the clinic and the relationship in time of symptoms with radiation; endoscopy, ultrasound, computed tomography and magnetic resonance imaging are used to diagnose complications.
The most characteristic histological changes when taking a biopsy include the presence of areas of hyalinosis in the lamina propria of the mucous membrane, capillary ectasia with hyalinosis of the walls, the presence of obliterating endarteritis of small arteries and arterioles with accumulation of fibroblasts. Differential diagnosis is carried out with intestinal infections, tumor relapse, SIBO, exocrine pancreatic insufficiency, the onset of inflammatory bowel diseases, and pseudomembranous colitis [3].
Any measures aimed at more precise exposure during irradiation reduce the risk of radiation damage to the intestines. There is an opinion that lying on the stomach using a special board under the stomach during a radiation therapy session reduces the radiation load on the small intestine compared to the position on the back. Evening sessions of radiation therapy lead to a decrease in the frequency and severity of acute damage to the small intestine.
Approaches to the treatment of acute and chronic radiation injuries of the intestine
Unfortunately, there is no reliable evidence that any diet reduces radiation damage to the intestine, according to a review of 22 studies looking at the effectiveness of various foods. Diets with low or modified fat content, diets with low or high fiber content, diets with low lactose content, probiotics and symbiotics were considered. In terms of dietary supplements, antioxidants such as glutamine, arginine, vitamin E and selenium have been shown to have a protective effect on the intestinal mucosa of rats treated with radiotherapy [5, 6].
Research is being conducted to find drugs that reduce intestinal damage during radiation therapy. In vitro studies have confirmed the anti-inflammatory, antifibrotic and antithrombotic potential of statins in irradiated human cells [7]. For example, low doses of lovastatin have a radioprotective effect on human endothelial cells [8]. A retrospective non-randomized cohort study of 308 patients with pelvic radiotherapy assessed the effect of statins and angiotensin-converting enzyme (ACE) inhibitors on the development of gastrointestinal symptoms [9]. Symptoms were recorded prospectively before radiotherapy, weekly during treatment and 1 year later using a questionnaire. The use of a statin or statin+ACE inhibitor during radical pelvic radiotherapy significantly reduced acute symptoms of radiation colitis/enteritis [6]. It is suggested that the combination of pentoxifylline, a xanthine derivative, and vitamin E may reduce radiation-induced fibrosis through antioxidant effects [6, 7, 10].
Probiotics are of some interest. Thus, 5 randomized controlled trials of various probiotics for radiation-induced small intestinal disease have been conducted. We studied the probiotic preparation VSL#3 (a probiotic containing 8 strains of live lactic acid bacteria and bifidobacteria), Lactobacillus acidophilus, Bifidobacterium bifidum. Although some of the studies have shown significant improvements in diarrhea, the study design and patient numbers do not allow probiotics to be fully recommended for prevention at this time [6, 11].
Preliminary studies have shown the protective effect of amifostine, a cytoprotective adjuvant used in cancer chemotherapy, and teduglutide, an analogue of human glucagon-like peptide-2, which showed an increase in the survival of intestinal crypt stem cells during irradiation of mice. The flavonoids hesperidin and quercetin showed decreased levels of tumor necrosis factor α (TNF-α) and caspases in irradiated rats [1, 6].
Approaches to the treatment of acute and chronic radiation injuries of the intestine have some features, but in general they are mainly symptomatic (see table). Manifestations of mild acute radiation enteritis/colitis often resolve on their own within a few weeks. For diarrhea, loperamide, diphenoxylate or bismuth preparations are prescribed, as well as drugs that affect intestinal motility with sufficient fluid intake. For pain, antispasmodics or analgesics are prescribed, and for nausea or vomiting, antiemetics are prescribed [5, 6].
In more severe cases, the synthetic somatostatin analogue octreotide, steroid-containing suppositories, recombinant granulocyte colony-stimulating factor for neutropenia, and epidermal growth factor are used. The following drugs are currently under investigation: Elk-1 inhibitors, P-selectin, anti-IL-6R, cyclooxygenase-2 inhibitors, Rho-kinase inhibitors, small molecule TNF-α inhibitors, recombinant human interleukin-11 (IL-11 ) [12].
The drug rebamipide has a high potential for cytoprotection of the gastrointestinal mucosa from reactive oxygen and activated neutrophils. Rebamipide in studies normalized goblet cell numbers, scavenged hydroxyl radicals, and inhibited neutrophil activation. Rebamipide significantly (dose-dependently) induced mRNA expression in radiation-damaged colon tissue of mice and compensated for the loss of claudins-3 and -4 [13].
Oral antibiotics are prescribed to patients with suspected SIBO, with the most common jejunal isolates being Escherichia coli, Streptococcus, Lactobacillus, Bacteroides, and Enterococcus species. Broad-spectrum antibiotics are used: tetracycline, co-amoxiclav, ciprofloxacin and rifaximin.
For proctitis, enemas with sucralfate, a highly sulfated polyanionic disaccharide, are effective. It stimulates epithelial healing and forms a protective barrier on the damaged surface of the mucous membrane, reduces bleeding, which has been confirmed in randomized studies [3, 6]. But sucralfate is not used in the treatment of radiation-induced small bowel disease.
Glucocorticosteroids and aminosalicylates are used only for severe and moderate forms. Prednisolone and methylprednisolone are widely used as the means of choice at a dose of 0.5–1 mg/kg body weight, followed by a subsequent dose reduction.
If malabsorption is present, a high-calorie, high-protein diet, plenty of fluids, a lactose-free, low-fat diet, a low-fiber diet, medium chain triglycerides (MCFA), enteral and parenteral nutrition are recommended. Hospitalization is required only if parenteral nutrition is required.
If conservative therapy is ineffective, laser therapy is used - argon plasma coagulation, which has proven itself especially well in the correction of radiation proctopathy, or endoscopic cauterization using a heater, BICAP probe [5, 6, 14]. Surgical interventions, sometimes repeated, are required due to the formation of intestinal strictures, fistulas, bleeding and perforations. The surgical approach to the treatment of radiation enteritis has a high risk of postoperative complications (about 30%): intra-abdominal abscess, fistulas, postoperative peritonitis [3, 5, 12].
Conclusion
Management of patients with post-radiation intestinal lesions requires a multidisciplinary approach. Radiation enteritis leads to long-term (or permanent) disability and is considered prognostically unfavorable. The prognosis for radiation damage to the colon is more favorable, but with the development of ulcerative-necrotic changes it is often accompanied by complications requiring surgical treatment (in 20%). The presence of simultaneous damage to all parts of the intestine worsens the prognosis of the disease, but with timely and intensive treatment, 80% of patients can achieve relief and even long-term remission of the disease. Fatal outcomes can result from intestinal perforation, peritonitis, interintestinal fistulas and recurrent massive bleeding, as well as complications in the form of malignant intestinal diseases [15].
