Mucositis consists of inflammation or ulceration of the mucous membranes in the oral cavity including the lips, tongue, palate, buccal mucosa, gingiva, or floor of the mouth, while esophagitis involves the mucous membranes of the esophagus (Landers and O’Hanlon-Curry 2008). The prevalence of mucositis and esophagitis among pediatric oncology patients is undetermined because there is no universally recognized definition or assessment tool; however, there is an increased incidence among patients who receive fully ablative chemotherapy, head and neck radiation, or total body irradiation (Hogan 2009). These therapies cause damage or death to the rapidly dividing epithelial mucosal cells and can advance to dysphagia (difficulty swallowing).

Characteristics of mucositis are distinguished according to their etiology. Radiation-induced mucositis typically presents as a whitish discoloration about 2–3 weeks into treatment and develops into deepening erythema with ulcers or inflammation (Hogan 2009). On the other hand, chemotherapy-induced mucositis classically presents 5–8 days after treatment, initially with erythema followed quickly by edema and ulceration (Hogan 2009). Despite the importance of a structured oral assessment, few clinical sites use a formal oral assessment scale (Gibson et al. 2010). Important aspects to consider in assessing the oral cavity include voice, swallow, lips, tongue, saliva, mucous membrane, gingiva, and teeth. A recent systematic review of oral assessment instruments found the Oral Assessment Guide (OAG), as a validated and easy to use scale that was suitable for clinical use (Gibson et al. 2010).

Prevention of mucositis is important because it can cause multiple complications such as pain, infection, malnutrition, dehydration, and decreased quality of life (Hogan 2009). Additionally, severe mucositis may cause a delay and/or reduction of subsequent treatments. Preventative measures include keeping the oral cavity clean with brushing and using nonirritating mouthwashes. Topical and sometimes systemic antifungal, antiviral, and antibiotic medications are used to prevent infections. Research is ongoing to explore methods to decrease saliva production, such as cryotherapy and various medications, to decrease the amount of drug contact with the oral mucous membranes, while additional research is looking at increasing epithelial cell proliferation, such as the use of glutamine, beta-carotene, and prostaglandins (Wohlschlaeger 2004).

Treatment of mucositis and esophagitis primarily focuses on pain control and maintaining nutrition/hydration. Support and close monitoring must be provided for patients with dysphagia, as significant risks are associated with the inability to swallow. In addition to systemic analgesic medication, topical agents such as sucralfate and magnesium hydroxide provide symptomatic relief (Wohlschlaeger 2004). Fluoride rinses and saliva substitutes relieve xerostomia (dry mouth). Fluids and nutrients administered intravenously support the patient’s hydration and nutritional requirements during periods of inadequate oral intake. Agents such as vitamin E and granulocyte-macrophage colony-stimulating factor mouthwash are effective in reducing the duration of mucositis among adults but more research is needed with children (Wohlschlaeger 2004).

Anorexia is a loss of appetite and occurs in 6–60 % of all children treated for cancer (Montgomery et al. 2013). Anorexia can be very distressing to the patient and family as eating has cultural, emotional, and religious significance and is often equated as an action of nurturing and caring (Santucci and Mack 2007). Furthermore, anorexia can cause electrolyte disturbances, weight loss, and malnutrition, which can increase morbidities and delays in treatment. Anorexia can be a result of the disease such as brain tumors, poor prognosis or relapsed leukemia, and advanced cancer (Rogers et al. 2008) (see Chap. 14 on palliative care for more information). Taste changes have been reported by children undergoing cancer treatment as one of the primary causes of eating difficulties (Skolin et al. 2006). Other risk factors include mucositis, dysphagia, xerostomia, constipation, pain, and/or a change in environment resulting in the inability of having foods prepared in a culturally familiar manner and eaten in a relaxing environment (Santucci and Mack 2007).

Anorexia can be mild and temporary or can be severe and prolonged. Severe anorexia can lead to cachexia. Cachexia is a multifactorial metabolic syndrome that causes an increase in the catabolic process associated with reduced food intake (Tuca et al. 2013). Cachexia causes a significant loss in weight, muscle mass, and fat that is often not reversible with increased caloric intake (Tuca et al. 2013).

There are multiple methods to assess eating and nutrition in individuals including nutritional history, anthropometric measurements, and laboratory markers. A patient’s history is one of the most important methods to obtain data during an assessment and should include an assessment of appetite, 24 hour diet recall or food diary, recent diet changes, food preparation methods, use of vitamins and/or supplements, and gastrointestinal symptoms (Huhmann and August 2008). Anthropometric measurements, such as height and weight, are quick and easy measurements commonly used to evaluate nutritional well-being; however, weight can fluctuate in some patients due to fluid shifts and may not accurately represent a patient’s nutritional status. Laboratory measurements are another customary method to assess the nutritional status in patients. Serum protein markers, such as albumin and prealbumin, are traditionally used to evaluate the nutritional status and responses to nutritional interventions. However, conditions such as liver or kidney disease, dehydration, and anemia can affect the accuracy of these tests.

Early intervention of anorexia is important to prevent complications and/or cachexia. Discussions on methods to maintain adequate caloric intake should occur early in treatment and strategies to promote eating are provided in Table 3.2. Food should never be forced on the child and patients report being forced to eat caused them to eat less or not eat at all (Rodgers et al. 2010). Patients who are not interested in eating can benefit from high-calorie oral supplementation but children are often reluctant to drink them because of the taste and consistency. Medications such as progestational drugs, corticosteroids, and cannabinoids can be used to stimulate appetites; however, many of these medications are restricted by the disease and age of the child and can cause unwanted side effects (e.g., hallucinations, irritability, fluid retention) (Santucci and Mack 2007). It is important to educate parents and family caregivers about these potential side effects so they can support the child and make decisions that take into account their child’s psychological and social needs.

Two traditional methods to provide nutritional support include enteral nutrition (EN) and total parenteral nutrition (TPN). EN can be administered through a tube that is passed from the nose to the stomach (nasogastric tube), through a tube inserted directly into the stomach (gastrostomy) by surgery, or through a tube into the small intestine (jejunostomy). TPN is administered through a central venous catheter. EN is beneficial to patients because it preserves the structure and the function of the GI tract; however, it may not be tolerated because the tube placement and feeds can exacerbate symptoms of nausea, vomiting, and diarrhea (Montgomery et al. 2013). TPN may be better tolerated by patients and can provide more caloric, protein, and vitamin supplementation because the nutrition is received intravenously instead of through an already irritated GI tract; however, TPN has been associated with an increased risk of liver complications and infections (Montgomery et al. 2013). Treatment of cachexia includes appetite stimulants and nutritional support but also requires successful treatment of the malignancy to minimize energy expenditure (Santucci and Mack 2007).

Nausea and vomiting are commonly occurring symptoms in pediatric oncology with an incidence as high as 90 % among patients receiving chemotherapy (Phillips et al. 2011) and up to 80 % in patients undergoing radiation therapy (Feyer et al. 2011). These symptoms have very distinct characteristics. Nausea consists of a wavelike sensation of GI distress that may lead to retching or vomiting and is often accompanied by sweating, increased salivation, and weakness, while vomiting is a forcible expulsion of the stomach contents through the mouth that may be accompanied by nausea, rapid breathing, and abdominal cramping (Landers and O’Hanlon-Curry 2008). These symptoms can result from:

The specific emetogenic risk for various radiation sites and chemotherapy agents are listed in Table 3.3. Other factors that may increase the risk of nausea and/or vomiting include prior motion sickness, fatigue, emotional stress such as anxiety or fear, sensitivity to strong odors, and previous bad experiences with nausea or vomiting. Nausea and/or vomiting can occur before the start of treatment, referred to as anticipatory; during administration or within 24 hours after treatment, referred to as acute; or more than 24 hours after completion of treatment, referred to as delayed.

Prompt recognition of these symptoms is crucial as they have significant physical and psychological consequences (Table 3.4). Before treatment begins, an assessment of nausea and vomiting should include type of treatment, prior experience with nausea and vomiting, and effectiveness of previous interventions. Frequent nausea and vomiting assessments should then occur throughout (acute) and after treatment (delayed). Assessments should include current level of nausea and vomiting, effectiveness of pharmacological and non-pharmacological interventions, and level of emotional stress. Anxiety and psychologically conditioned responses may also contribute to anticipatory nausea and vomiting even before chemotherapy infusion and can be addressed with psychological or pharmacologic interventions.

Additional assessments should consist of a thorough evaluation for complications from the nausea or vomiting including anorexia, malnutrition, dehydration, and electrolyte imbalances.

The goal is to prevent nausea or vomiting from occurring. Prevention and treatment strategies consist of various non-pharmacological and pharmacological interventions, which provide individual levels of relief to patients. Therefore, healthcare providers including psychosocial clinicians should encourage a variety of strategies for patients experiencing nausea or vomiting and evaluate the effectiveness of each strategy. Non-pharmacological interventions (Table 3.5) can often be self-initiated by the patient and have little to no side effects. Pharmacological interventions include a variety of antiemetic medications including 5-HT3 receptor antagonists, NK-1 antagonist, dopamine antagonists, benzodiazepines, cannabinoids, and corticosteroids (Phillips et al. 2011). A recent systematic review found 5-hydroxytryptamine-3 (5-HT3) antagonists are more effective than other antiemetic agents even when combined with a corticosteroid (Phillips et al. 2011) and therefore are the drug of choice for prevention and treatment of therapy-related nausea or vomiting. These medications, such as ondansetron, granisetron, and tropisetron, produce little side effects and are generally well-tolerated. The NK-1 antagonist (aprepitant) is also an effective medication but is currently restricted for use only in children 12 years of age and older (Lexicomp 2014). Despite the legalization of marijuana in several states, the medical use of marijuana for nausea and vomiting is controversial due to potential carcinogens and adverse effects on the cardiovascular, respiratory, and central nervous system and the unidentified outcome evidence (Torado 2012). Synthetic oral cannabinoids once commonly prescribed are now recommended for use only in patients with breakthrough nausea and vomiting due to the development of newer antiemetic medications that cause fewer side effects (Torado 2012).

Diarrhea is an increase in quantity, frequency, or fluid content of the stool that is different from usual patterns and can be accompanied by abdominal cramping, flatulence, nausea, vomiting, and fever (Landers and O’Hanlon-Curry 2008). Diarrhea is a result of changes in intestinal absorption and motility caused from a variety of triggers including chemotherapy, radiation therapy, infection, and bowel resection. The incidence of diarrhea varies greatly due to the variety of potential etiologies. Treatment is likely the cause of diarrhea once infection is ruled out with multiple testing of the stool.

Patients with diarrhea require a thorough assessment of their stool output and associated symptoms. Diarrhea is classified according to duration and severity. Duration can be classified as acute (occurring less than 2 weeks), persistent (lasting 2–4 weeks), or chronic, which can continue longer than 4 weeks (Pessi et al. 2014). Severity is categorized as uncomplicated, comprised of diarrhea without associated symptoms, and complicated, consisting of diarrhea with associated symptoms or complicating factors (Shaw and Taylor 2012). Diarrhea can deplete fluids, electrolytes, and nutrition; therefore, information regarding hydration and nutrition status, such as food and fluid consumption, weight loss, and urine output, must be obtained to identify complications (Shaw and Taylor 2012).

Treatment of diarrhea consists of diet modifications and pharmacological management (Table 3.6). Foods that are fatty or spicy or contain dairy or caffeine should be avoided (Shaw and Taylor 2012). Small frequent meals are best tolerated, and oral intake of water, sports drinks, broth, etc., is imperative in maintaining adequate hydration (Shaw and Taylor 2012). Inability to maintain adequate hydration results in the immediate need for the administration of intravenous fluid and likely hospitalization (Shaw and Taylor 2012). Antidiarrheal medication is indicated once infections are excluded. Loperamide is a standard medication administered orally for treatment of diarrhea and can be administered to children 2 years of age or older (Lexicomp 2014). For patients unable to tolerate oral medication or with persistent or complicated diarrhea, octreotide can be administered to infants or children subcutaneously or intravenously (Lexicomp 2014). Use of probiotics is likely to be effective for diarrhea related to cancer therapy; however, more research is needed to determine the optimal probiotic strain, dosage, and timing (Shaw and Taylor 2012).

Constipation involves the infrequent passage of hard, dry stool that can be accompanied with abdominal cramping, abdominal and/or rectal pain, nausea, vomiting, and blood-streaked stools (Landers and O’Hanlon-Curry 2008). Patients may not realize the importance or feel comfortable discussing their bowel movements with others, so healthcare providers should perform a detailed history and provide education. A thorough assessment includes questions of frequency and consistency of stools, associated symptoms, and any personal concerns. Obtaining a past medical history is also important as patients with a previous history of constipation are more prone to developing constipation during their oncology treatment (Pashankar et al. 2011). Constipation is diagnosed when a child with a developmental age of 4 years meets two or more of the following criteria (Pashankar et al. 2011):

The cause of constipation in pediatric oncology patients is multifactorial and includes effects from the disease, treatment, medication(s), or problems with mobility, diet, hydration, or psychological adjustment (Phillips and Gibson 2008). The primary or metastatic disease can obstruct portions of the bowel or compress the spinal cord resulting in an inability to defecate. Several chemotherapy agents, radiation therapy especially to the pelvic area, and commonly used medications such as opioids, antiemetics, antidepressants, and anticonvulsants cause a decrease in bowel motility and secretions that can progress to constipation (Santucci and Mack 2007). In addition, a decrease in activity, inadequate intake of fluids and fiber, and issues of anxiety, lack of privacy, or limited access to a toilet can result in constipation (Landers and O’Hanlon-Curry, 2008). If left untreated, constipation can cause significant pain, lack of appetite, nausea, vomiting, and anal fissures (small tears in the skin around the anus).

Prevention is key for constipation (Table 3.6). Maintaining regular exercise, adequate hydration, and a high-fiber diet are important strategies to prevent constipation. Often medications are used in the prevention and treatment of constipation. Medications include stool softeners such as docusate, osmotic agents such as lactulose, and stimulants such as senna or bisacodyl (Santucci and Mack 2007). Enemas are rarely used in pediatric oncology patients because of the risk for mucosal trauma and subsequent infection.

It is suggested that up to 46 % of pediatric oncology patients experience malnutrition (Bauer et al. 2011). Marked weight loss may be the symptom that first causes families to seek medical attention and prompt the discovery of a cancer diagnosis. Weight loss, greater than 10 % of a child’s bodyweight within 6 months prior to diagnosis, is especially important in Hodgkin and non-Hodgkin lymphoma. This weight loss is considered a “B” symptom, which affects staging and treatment.

Weight loss during therapy is mainly due to the side effects of treatment. Chemotherapy can cause taste changes, dry mouth, nausea, vomiting, anorexia, mucositis, or other conditions which impact appetite and food intake (see Table 3.2 for strategies to promote eating). Depression or mood may also influence eating habits. Radiation that involves the head, neck, or abdominal area also increases the risk for weight loss secondary to esophagitis, mucositis, nausea, vomiting, and diarrhea.

Treatment for weight loss consists of identifying the underlying cause. Side effects of treatment interfering with nutritional intake can often be managed symptomatically. Medications can be administered to decrease nausea and vomiting. Pain medications can also be given to alleviate pain, if that is the underlying cause. If warranted, medications can also be administered to increase appetite.

It is well documented that children treated for childhood acute lymphoblastic leukemia (ALL) often experience weight gain during and after cancer treatment. One study found that obesity rates increased from 14 % at the beginning of therapy to 23 % by the end of therapy in ALL patients (Withycombe et al. 2009). In addition, weight gain appears to continue after therapy with a meta-analysis of 47 studies showing the prevalence of being overweight/obese in ALL survivors ranging from 29–69 % (Zhang et al. 2013). This is significantly higher than the national childhood obesity rate of approximately 17 % (CDC 2014b).

Some brain tumors, in particular craniopharyngiomas, are also associated with an increased risk for obesity. Tumors or treatments (radiation or surgery) that cause hypothalamic-pituitary axis damage are highly problematic. Hypothalamic obesity is a condition that may occur when the normal hypothalamic center functions are disrupted resulting in imbalances in hunger control, satiety, and energy regulation (Lee and Korner 2009). This condition is often described as intractable weight gain and is present in up to 75 % of children with craniopharyngioma (Lustig 2011).

Currently there is no standard treatment to combat excessive weight gain other than recommending that families watch their diet and engage in physical activity. Prevention of obesity is preferred as it is difficult to reverse once it develops. Having a healthy weight is especially critical for childhood cancer survivors as they may already be at risk for cardiovascular issues due to late effects of chemotherapy. Obesity also increases the risk for hypertension, diabetes, metabolic syndrome, depression, decreased quality of life, and secondary cancers (Berenson and Bogalusa Heart Study Group 2012; Kanellopoulos et al. 2013).

When obesity is present, it is important to refer the family for nutritional counseling. Children are often dependent on their parents for food preparation so it is imperative that the whole family be involved in learning healthy eating habits. Likewise, daily family physical activity should be encouraged. In children with hypothalamic obesity, these interventions are often ineffective in significantly reducing weight and may warrant more invasive treatment options such as gastric bypass surgery.

Neuropathy occurs when chemotherapeutic drugs damage the peripheral nerves, which are those outside of the central nervous system such as in the hands and feet (Gilchrist 2012). Neuropathy primarily occurs with drugs that are known to be neurotoxic such as cisplatin, carboplatin, vincristine, and vinblastine. Neuropathy can be sensory in nature and lead to symptoms of burning, tingling, or shooting pain in the hands and feet. Neuropathic jaw pain is also frequently reported in children (McCarthy and Skillings 1992). In addition, neuropathy can impact motor function which can lead to foot drop and problems with balance and coordination. Fine motor skills may also be affected leading to difficulty with grasping objects or performing tasks such as buttoning a shirt. Neuropathy has been reported to occur in up to 18.3 % of children treated for acute lymphoblastic leukemia, brain tumors, and Wilms’ tumor (Purser et al. 2014).

Neuropathy can be a dose-limiting toxicity which means that the severity of symptoms may mandate that a reduced dosage of chemotherapy be administered until the neuropathy resolves. There is no treatment for neuropathy, once it occurs, other than symptom management. This management may include pain medicines or other medications specifically for nerve pain. Physical therapy services may be ordered to address balance issues and muscle weakness. In general, neuropathy tends to resolve once the causing agent is stopped but can linger for months to years in a small percentage of patients.

Neuropathy can limit mobility and decrease a child’s functional status. Participation in sports and other social activities may decline secondary to physical limitations or pain. Neuropathy may increase a child’s reliance on parents as they may be unable to complete tasks such as buttoning a shirt or braiding their hair. For adolescents, this may have greater importance as this is the age at which most begin establishing their independence. Emotional consequences may occur secondary to neuropathy and can range from frustration with the inability to complete tasks independently to anger and/or depression. Emotional changes should be anticipated and mental health professionals should be involved in caring for the child.

Vision changes, such as blurry vision, have been reported in association with multiple chemotherapeutic agents used to treat childhood cancer. These changes are usually short lived and resolve when the chemotherapy is stopped. More severe vision issues, such as decreased vision, have been reported with the use of cisplatin and etoposide (Hilliard et al. 1997). Ocular nerve and optic motor nerve damage have also been reported in those receiving vinblastine and vincristine (Omoti and Omoti 2006). Ophthalmology evaluations are the optimal method for assessing eye and vision changes during treatment.

Alterations in vision can also be secondary to certain cancers and their location. Diseases such as retinoblastoma, optic gliomas, or leukemia that have spread to the central nervous system can physically invade or destroy optic structures. When disease is the cause, vision changes are usually more severe and may include a decrease or total loss of eyesight. In these cases, treatment options to save or spare vision are limited. Depending on the exact location and size of the tumor, surgery or radiation may be considered in the treatment plan. One potential sequelae of surgery is double vision (called diplopia). Treatment for diplopia may consist of occluding the line of vision in one eye, therefore preventing the overlap of visual fields which causes the double vision. This treatment was traditionally done by patching one eye, but more modern methods of treatment include placing an occlusive patch over the inside of one eyeglass lens which directly blocks the line of sight causing the double vision. Children suffering from diplopia may also benefit from completing a vision rehabilitation program. This type of program teaches people to maximize their eye sight through visual training which may include specialized exercises for the eyes.