Radiation enteropathy
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Radiation enteropathy is a
syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...
that may develop following abdominal or pelvic
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...
for
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. Many affected people are cancer survivors who had treatment for cervical cancer or prostate cancer; it has also been termed pelvic radiation disease with
radiation proctitis Radiation proctitis or radiation proctopathy is condition characterized by damage to the rectum after exposure to x-rays or other ionizing radiation as a part of radiation therapy. Radiation proctopathy may occur as acute inflammation called "acu ...
being one of the principal features.


Signs and symptoms

People who have been treated with radiotherapy for pelvic and other abdominal cancers frequently develop gastrointestinal symptoms. These include: * rectal bleeding *
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
and steatorrhea * other defecation disorders including fecal urgency and incontinence. *
nutritional deficiencies Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
and
weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...
*
abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...
and
bloating Abdominal bloating (or simply bloating) is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, pres ...
*
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
,
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...
and fatigue Gastrointestinal symptoms are often found together with those in other systems including
genitourinary disorders The genitourinary system, or urogenital system, are the organs of the reproductive system and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathw ...
and
sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction a ...
. The burden of symptoms substantially impairs the patients'
quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
. Nausea, vomiting, fatigue, and diarrhea may happen early during the course of radiotherapy. Radiation enteropathy represents the longer-term, chronic effects that may be found after a latent period most commonly of 6 months to 3 years after the end of treatment. In some cases, it does not become a problem for 20–30 years after successful curative therapy.


Associated conditions

* Small intestinal bacterial overgrowth * Exocrine pancreatic insufficiency *
Bile acid diarrhea Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt di ...
*
Urinary urgency Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
* Sexual dysfunction


Causes

A large number of people receive abdominal and or pelvic radiotherapy as part of their cancer treatment with 60–80% experiencing gastrointestinal symptoms. This is used in standard therapeutic regimens for cervical cancer, prostate cancer,
rectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...
,
anal cancer Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A ...
,
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...
and other abdominal malignancies. Symptoms can be made worse by the effects of surgery, chemotherapy or other drugs given to treat the cancer. Improved methods of radiotherapy have reduced the exposure of non-involved tissues to radiation, concentrating the effects on the cancer. However, as the parts of the intestine such as the
ileum The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine m ...
and the rectum are immediately adjacent to the cancers, it is impossible to avoid some radiation effects. Previous intestinal surgery, obesity, diabetes, tobacco smoking and vascular disorders increase the chances of developing enteropathy.


Pathology


Acute intestinal injury

Early radiation enteropathy is very common during or immediately after the course of radiotherapy. This involves cell death, mucosal
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
and epithelial barrier dysfunction. This injury is termed
mucositis Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer. Mucositis can occur anywhere along the gastrointestina ...
and results in symptoms of nausea, vomiting, fatigue, diarrhea and abdominal pain. It recovers within a few weeks or months.


Long-term effects of radiation

The delayed effects, found 3 months or more after radiation therapy, produce pathology which includes
intestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
mucosal atrophy, vascular sclerosis, and progressive
fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
of the intestinal wall, among other changes in intestinal
neuroendocrine Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...
and immune cells and in the gut microbiota. These changes may produce dysmotility, strictures,
malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety ...
and bleeding. Problems in the terminal ileum and rectum predominate.


Diagnosis

Multiple disorders are found in patients with radiation enteropathy, so guidance including an algorithmic approach to their investigation has been developed. This includes a holistic assessment with investigations including
upper endoscopy Esophagogastroduodenoscopy (EGD) or oesophagogastroduodenoscopy (OGD), also called by various other names, is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract down to the duodenum. It is considered ...
, colonoscopy, breath tests and other nutritional and gastrointestinal tests. Full investigation is important as many cancer survivors of radiation therapy develop other causes for their symptoms such as colonic polyps,
diverticular disease Diverticular disease is when problems occur due to diverticulosis, a condition defined by the presence of pouches in the wall of the large intestine (diverticula). This includes diverticula becoming inflamed (diverticulitis) or bleeding. Colonic p ...
or hemorrhoids.


Prevention

Prevention of radiation injury to the small bowel is a key aim of techniques such as
brachytherapy Brachytherapy is a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment. ''Brachy'' is Greek for short. Brachytherapy is commonly used as an effective treatment for cervical, prost ...
, field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy. Medications including
ACE inhibitors Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volume ...
, statins and
probiotics Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria- host i ...
have also been studied and reviewed.


Treatment

In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others. Medical treatments include the use of
hyperbaric oxygen Hyperbaric medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric oxygen therapy (HBOT), the medical use of oxygen at an ambient pressure ...
which has beneficial effects in
radiation proctitis Radiation proctitis or radiation proctopathy is condition characterized by damage to the rectum after exposure to x-rays or other ionizing radiation as a part of radiation therapy. Radiation proctopathy may occur as acute inflammation called "acu ...
or anal damage. Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and
vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...
or
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
supplements, together with bile acid sequestrants for
bile acid diarrhea Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt di ...
and possibly antibiotics for small intestinal bacterial overgrowth. Probiotics have all been suggested as another therapeutic avenue. Endoscopic therapies including
argon plasma coagulation Argon plasma coagulation (APC) is a medical endoscopic procedure used to control bleeding from certain lesions in the gastrointestinal tract. It is administered during esophagogastroduodenoscopy or colonoscopy. Medical use APC involves the use o ...
have been used for bleeding
telangiectasia Telangiectasias, also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere on ...
in radiation proctitis and at other intestinal sites, although there is a rick of perforation. Surgical treatment may be needed for
intestinal obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Either the small bowel or large bowel may be affected. Signs a ...
,
fistula A fistula (plural: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow or ...
e, or perforation, which can happen in more severe cases. These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common. A systematic review has found there is some promising evidence for non-surgical interventions for late rectal damage, however due to low quality evidence no conclusions could be drawn. Optimal treatment usually produces significant improvements in quality of life.


Prevalence

An increasing number of people are now surviving cancer, with improved treatments producing cure of the malignancy ( cancer survivors). There are now over 14 million such people in the US, and this figure is expected to increase to 18 million by 2022. More than half are survivors of abdominal or pelvic cancers, with about 300,000 people receiving abdominal and pelvic radiation each year. It has been estimated there are 1.6 million people in the US with post-radiation intestinal dysfunction, a greater number than those with inflammatory bowel disease such as Crohn's disease or
ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...
.


Research

New agents have been identified in animal studies that may have effects on intestinal radiation injury. The research approach in humans has been reviewed.


References


External links

{{DEFAULTSORT:Radiation Enteropathy Gastrointestinal tract disorders Diarrhea Diseases of intestines Radiation therapy