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A. Arokkh, M.B.A., M.B.B.S., M.H.S.

Vice Chair, A.T. Still University School of Osteopathic Medicine in Arizona

Aneurysmal bone cyst these are relatively rare and benign osteolytic lesions of bone usually occurring in children or young adults. They are not true neoplasms, rather are a hyperplasia filled with blood-filled channels. Because of the availability of alternative therapy and the typically young age of patients, the use of ionizing radiation is a last resort. Radiation therapy is medically necessary only if accompanied by documentation that its use is considered essential by a multi-disciplinary team. The etiology of epithelial tissue in an unusual location is the subject of debate. The use of radiation is reported historically as beneficial, but with little evidence. The 2002 text by Order and Donaldson supplies several references, each with few cases to report, and mainly of mandible or maxillary origin. Angiofibroma of nasopharynx (juvenile nasopharyngeal angiofibroma) While optimum management is controversial, there is general agreement that surgery is preferred if considered safe, as in cases when there is no extension into the orbital apex or base of skull. Since the typical patient is young, regard for the long-term hazard of radiation is important. When radiation is used, the radiation dose is lower than in malignant tumors of the same location. Policy: Radiation therapy is medically necessary in those cases with extension into the orbital apex or base of skull. Angiomatosis retinae (von Hippel Lindau syndrome) Capillary hemangiomas associated with von Hippel Lindau syndrome may be single or multiple, and can severely affect vision. Ankylosing spondylitis the use of radiation therapy in the treatment of ankylosing spondylitis is of historical interest. The risk of radiation-induced cancer and other morbidity contraindicates its use and is often cited as a common example of radiation carcinogenesis in radiobiological studies. Anovulation the use of radiation therapy in the treatment of anovulation is of historical interest only and is occasionally discussed in the treatment of functional pituitary adenomas. Arachnoiditis In the pre-antibiotic era the beneficial use of radiation for the treatment of arachnoiditis was described. Resolution is slow and may take years, during which the risk of hemorrhage is not eliminated. Arthritis (see total lymphoid irradiation for radioimmunosuppression) (see rheumatoid arthritis) (see osteoarthritis) N. Basalioma this synonym for basal cell carcinoma of the skin is sometimes included in lists of "benign" disorders of skin suitable for treatment with radiation therapy. It can be mistaken for other disorders because of the features it shares with psoriasis and eczema. Policy: Cases will require medical review and documentation that no other reasonable alternative exists. Bursitis, synovitis, and tendinitis Randomized studies in 1952, 1970, and 1975 cited in the Order and Donaldson review claimed "no benefit" to the use of radiation therapy for any of these, and the authors of the review recommend against its use. Department of Health, Education, and Welfare survey report of 1977 reporting the results of a survey of American radiation oncologists included these diagnoses as acceptable for treatment, as did the German survey of 2008. There is support in modern era texts, concluding that the use of radiation "may provide an alternative to conventional conservative treatment for patients who are not surgical candidates" (PerezBrady). Typical treatment is with photon beam therapy using, at most, complex treatment planning in five or fewer fractions. The presentation and behavior ranges from truly benign to aggressive with metastatic potential. Surgical resection has historically been the treatment of choice with radiation reserved for technically or medically inoperable cases. Precise histologic classification may help discriminate those truly benign lesions that would not be expected to benefit from radiation therapy from lesions that would be best treated as invasive carcinomas. For those unresectable non-secretory lesions causing symptoms such as pain, radiation may be beneficial. For secreting tumors, radiation therapy is limited to those causing symptoms that are not controllable by medical means. The relationship to subsequent malignant lymphoma is unclear, with malignant lymphoma reported in as many as 30% of cases.

Dysplastic kidneys are usually small because of the reduced number of nephrons, resulting in renal hypodysplasia. Renal dysplasia is often diagnosed during routine antenatal ultrasonography screening or postnatal ultrasonography performed in a dysmorphic infant. Renal dysplasia on ultrasonography is characterized by increased echogenicity, poor corticomedullary differentiation, and parenchymal cysts. Neonates with oligohydramnios and bilateral dysplasia are more likely to be identified earlier. Patients with unilateral renal dysplasia with a normal contralateral kidney showing compensatory growth have excellent outcomes with decreased risk for chronic kidney disease. This contrasts to increased risk for chronic kidney disease in patients with suboptimal compensatory hypertrophy of the contralateral kidney. Chronic kidney disease in such patients may lead to elevated blood pressure, growth retardation (height less than the fifth percentile), and pallor. Blood pressure, urinalysis results, and serum creatinine levels should be initially monitored yearly and subsequently monitored more frequently depending on the stage of chronic kidney disease. Multicystic dysplastic kidney is suspected based on renal abnormalities detected on antenatal ultrasonography or in neonates with an abdominal mass detected by physical examination. Classic findings on renal ultrasonography include multiple noncommunicating cysts with intervening dysplastic renal tissue. The contralateral normal kidney has increased risk for congenital renal anomalies such as vesicoureteral reflux. Posterior urethral valves are identified by antenatal ultrasonography in most cases. Older boys may develop urinary tract infections or voiding dysfunction (urinary frequency, daytime and nocturnal enuresis, and poor urinary stream). This condition would lead to pulmonary hypoplasia because normal amniotic fluid levels between 16 and 28 weeks of gestation are required for normal lung development. Congenital ureteropelvic junction obstruction is most commonly diagnosed upon postnatal evaluation of antenatal hydronephrosis detected on maternal ultrasonography screening. Other less common presentations include urinary tract infection, hematuria, or failure to thrive. Ureteropelvic junction obstruction in older children presents with episodes of flank or abdominal pain (Dietl crisis) accompanied by nausea and vomiting. Children may also rarely exhibit renal injury to the enlarged obstructed kidney after minor trauma, hematuria, renal calculi, or hypertension. It is important to perform ultrasonography during episodes of acute pain because the ultrasonography results may be normal once the pain subsides. The residents ask about the respective heights of girls and boys at the onset of their growth spurts. When compared with girls, boys experience an additional 2 years of growth (at a rate of about 5 cm/year) before growth spurt initiation (Item C233). He has been breastfeeding well, with 4 wet diapers and 2 stools in the past 24 hours. Using the Bhutani nomogram, the pediatric resident labeled his bilirubin risk level as low intermediate with no recommendation for a repeat bilirubin level on discharge. All neonates have physiologic jaundice in the first days after birth because of a relatively high bilirubin load, decreased uptake of bilirubin in the liver, increased enterohepatic circulation, and lower activity of uridine diphosphoglucuronosyl transferase. In addition, immediately after birth, the blood-brain barrier is relatively permeable, allowing passage of bilirubin into the brain where it can damage neurons. The blood-brain barrier strengthens quickly, allowing neonates to tolerate increasingly higher serum bilirubin levels over the first few days after birth. Serum bilirubin level may be accurately predicted with transcutaneous measurement. All neonates should be screened for pathologic jaundice with total bilirubin measurement (serum or transcutaneous) prior to discharge. Premature neonates, born at less than 37 weeks of gestation, are at risk for acute bilirubin encephalopathy at lower bilirubin levels than term neonates. Those at highest risk include those born to Chinese, Japanese, or Filipino parents. Exclusively breastfed neonates who have lost more than 10% of their birthweight within the first 3 days after birth are at higher risk for jaundice, presumably due to increased enterohepatic circulation.

The other 17 studies through 1997 show a reduction in risk similar to that observed in the case-control studies. Higher activity in adult life is generally related to reduced risk of colon cancer, although the cohort results are less consistent than are those from the case-control studies. Inconsistency may, in part, be attributed to studies that focused on college activity and cancer risk many years later, 10,11 or that included both colon and rectal cancer in a single outcome category. Men in the highest activity group for both occupation and recreation had a relative risk that was 0. Leisure-time activity is addressed separately in the Harvard Alumni Study, a cohort of graduates from Harvard College followed since 1960 to study activity and chronic diseases; Lee and colleagues observed a strong inverse association among men who were active both in the 1960s and in 1977 when surveys were administered. Overall, the cohort studies conducted in Denmark, Norway, Sweden, Switzerland, and the United States support a dose-response relation across increasing activity levels: Higher activity levels are related to lower levels of colon cancer risk. Those in the highest activity category have approximately a 40% to 50% reduction in risk of colon cancer compared to the least active category. Studies that examined activity in relation to site of cancer in the colon suggest that the relation between higher activity and lower risk of cancer may be stronger for the left than for the right colon. One large case-control study shows no difference in the strength of association between vigorous activity and proximal or distal colon cancer. Interpretation Despite the variable and often poor measures of activity used, a consistent reduction in risk is observed across different study design and different populations and across occupational and leisure-time activity. A consistent dose-response relation emerges, indicating that those at higher levels of activity are at reduced risk of colon cancer. Across the studies, the evidence suggests that the relation is stronger for the left colon and weaker or absent for rectal cancer. Few studies have addressed the relation between specific activities and cancer risk. Three studies that address physical activity during early adulthood show no relation. Evidence from Lee and colleagues 14 also supports a role later in the pathway to cancer. Men who had increased their level of activity during follow-up of the cohort had a suggestion of lower risk of colon cancer during subsequent follow-up. More data are needed, however, to refine the understanding of the time course between change in physical activity and change in risk of cancer. In general, the studies based on classification of activity by occupation show a stronger dose response than those based on leisure-time activity and support a protective effect across the wide range of activities encompassed by the high-activity occupations. How do we know that physical activity is actually protecting subjects from developing colon cancer In a detailed analysis of the Health Professionals Follow-Up Study, a cohort of some 50,000 men followed to study relations between diet and chronic diseases, Giovannucci et al. In other words, the protectionremained at almost 50% despite controlling for all the other factors known to relate to colon cancer risk. The inverse trend in risk with increasing activity remained statistically significant. Thus, we conclude that activity is not merely a marker of healthier lifestyle, but exerts an independent protective effect. Mechanisms Several biologic mechanisms have been proposed for the protective effect of physical activity, reflecting changes in physiologic measures after physical activity. It is then proposed that the reduced transit time alters the environment within the colon and thereby reduces exposure to carcinogens. Across a gradient of physical activity, insulin sensitivity improves with exercise. Physical activity produces an increase in prostaglandin F 2a, which increases intestinal motility, and a decrease in prostaglandin E 2, which in cell culture can act to stimulate colon cell proliferation. Further support for this possible mechanism comes from laboratory studies on rats and evidence in humans that aspirin and nonsteroidal antiinflammatory drugs, also inhibitors of prostaglandin synthesis, reduce risk of colon cancer. Causal considerations include a consistent decrease in risk with higher levels of physical activity, either measured as occupational activity or leisure-time activity, a dose-response relation with hours of activity per week or level of occupational physical activity, specificity for the relation with colon and not rectum, and a temporal relation such that activity measures precede the onset of colon cancer by years, although relations are stronger for more recent activity rather than distant past activity. The mechanisms by which physical activity reduces exposure to hormones vary by period of life. Young girls participating in strenuous athletic training such as running and ballet dancing have delayed menarche, 28,29 and 30 which is known to reduce the risk of breast cancer, and even moderate-intensity physical activity may also delay menstruation.

If 2 siblings were affected, the recurrence risk would be higher, approaching 10% to 12% (Item C218). Neural tube defects are a major cause of stillbirth, early infantile deaths, and disability in surviving children. The frequency can vary based on socioeconomic factors, seasonality, maternal intake of antiepileptic medications, and the presence or absence of folate deficiency. Neural tube defects during a pregnancy are commonly detected by elevations of the maternal -fetoprotein level or by prenatal ultrasonography. Many diseases "run in families" as demonstrated by recurrence in relatives of an affected individual at a rate higher than in the general population. The inheritance in many cases does not follow a Mendelian pattern, as seen with a well-defined single-gene disorder. Familial clustering of a disorder that does not follow Mendelian inheritance patterns is likely a reflection of complex interactions between genetic and environmental factors known as multifactorial inheritance. These shared interactions could trigger, accelerate, reduce, or protect against a specific disease. Some examples of disorders that display multifactorial inheritance include cleft lip/palate, Alzheimer disease, infantile pyloric stenosis, congenital dislocation of the hip, congenital heart disease, diabetes, and mental health disorders. Twenty-five percent would be correct if the condition was an autosomal recessive disorder, such as sickle cell disease or cystic fibrosis. Fifty percent would be correct if the condition was an autosomal dominant condition, such as Marfan syndrome or neurofibromatosis type 1. Thirty-three percent is a much greater percentage than would be seen in a multifactorial disorder with only 1 affected first-degree relative. Common examples include cleft lip/palate, neural tube defect, Alzheimer disease, congenital hip dysplasia, and diabetes. He has a complex medical history of myocarditis as an infant with subsequent heart transplantation months later. Remarkable findings include: an echocardiogram with normal biventricular function, normal function of all 4 valves, and no pericardial effusion; an electrocardiogram with normal sinus rhythm; and a metabolic panel with a blood urea nitrogen level of 20 mg/dL (7. Immune suppression is an important adjunct to prevent organ rejection in solid organ transplant and to prevent graft-vs-host disease in stem cell (bone marrow) transplant. Calcineurin inhibitors are commonly used after transplant, and an important adverse effect of these medications is renal dysfunction. The rate of posttransplant renal injury in pediatric solid organ transplants ranges from 15% to 30%. These medications cause glomerular vascular constriction, interstitial fibrosis, and arterial hyalinosis. Routine testing to monitor renal function is warranted in all patients who receive calcineurin inhibitors. There are many classes of immunosuppressive agents used in transplant recipients and patients with autoimmune disorders. These agents include calcineurin inhibitors, corticosteroids, mammalian target of rapamycin inhibitors (eg, sirolimus, everolimus), antimetabolites (eg, 6mercaptopurine, azathioprine), and newer biologic agents (eg, infliximab, rituximab, adalimumab). All of these agents can have adverse short- and long-term side effects, and pediatricians caring for children on these medications must be aware of the risks. Calcineurin inhibitors can cause hypertension, associated left ventricular hypertrophy, and metabolic syndrome. Corticosteroids can cause metabolic syndrome, hyperglycemia, and diabetes mellitus. Mammalian target of rapamycin inhibitors can cause hypomagnesemia and abnormal serum lipid levels. The complications of biologic agents depend on the biologic pathways inhibited in addition to immune suppression. Given the effects on the immune system, patients on immunosuppressive agents remain at risk for infection as well as malignancy. In the setting of solid organ or bone marrow transplant, posttransplant lymphoproliferative disorder is a risk of chronic immune suppression. The patient in this vignette is feeling well with normal vital signs and normal cardiac function by echocardiogram, making the renal dysfunction unlikely related to supraventricular tachycardia, antibody-mediated rejection, or poor cardiac function.