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Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e3181eb6a1c
Invited Reviews

Bowel Preparation for Pediatric Colonoscopy Procedures

Hunter, Anna; Mamula, Petar

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Author Information

From Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Received 16 April, 2010

Accepted 25 May, 2010

Address correspondence and reprint requests to Petar Mamula, MD, Children's Hospital of Philadelphia, Division of Gastroenterology, Hepatology and Nutrition, 34th Street and Civic Center Blvd, Philadelphia, PA 19104 (e-mail: mamula@email.chop.edu).

The authors report no conflicts of interest.

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Abstract

Colonoscopy is a routinely performed procedure in children and adolescents. Proper visualization of the intestinal mucosa, completion of the procedure, including examination of the terminal ileum, detection of pathological lesions, and therapeutic maneuvers, all are highly dependent on the quality of the bowel preparation. A significant proportion of patients, in some reports up to one third, are inadequately prepared for the examination, which leads to extended procedure time, incomplete examination, or need for repeat procedure. Aside from efficacy and safety, the most important aspects of colon preparation in pediatrics are ease of administration, palatability, dietary restriction, and minimization of disruption of daily routine. An ideal preparation does not exist and a wide variety of regimens are being used. Several of these have been investigated in pediatric clinical trials. This article reviews the published literature with an emphasis on the most commonly used agents, their mechanism of action, efficacy and ease of use, and safety.

Colonoscopy is a crucial tool in diagnosing a variety of gastrointestinal tract conditions affecting children and adolescents. For example, it is the criterion standard for establishing the diagnosis of 1 of the most common chronic gastrointestinal tract diseases in pediatrics: inflammatory bowel disease. Additionally, colonoscopy provides definitive therapeutic options in patients with colonic polyps or lower gastrointestinal tract bleeding. The success of colonoscopy relies on multiple factors. One of the most important of these factors is appropriate patient preparation, which allows for safe, fast, and complete examination (1). The rates of inadequate preparation vary from study to study; however, 1 trial demonstrated that 37% of the patients required a repeat examination secondary to poor preparation (2). The preparation can pose a significant challenge in the pediatric population. An ideal preparation is one that is low volume and easy to rapidly complete, palatable, inexpensive, and universally successful in complete colon cleanout. Additionally, the ideal preparation would not be associated with adverse events including no significant fluid or electrolyte abnormalities, prolonged dietary adjustments, daily life disruptions, or effects on histology findings.

Historically, cleanouts for colonoscopies in the adult population began with large-volume gut irrigation (3). Some of these contained nonabsorbable carbohydrates, such as mannitol, or incompletely absorbed carbohydrates, such as sorbitol, lactose, or fructose. When these carbohydrates are metabolized by colonic bacteria, combustible gases methane and hydrogen can be produced, resulting in an explosion when exposed to electrocautery in the colon (4). In pediatrics, whole-gut lavage was also used for bowel preparation, with up to 12 L of fluids administered (5–7). Due to the significant potential for fluid and electrolyte shifts, along with prolonged administration, the need for hospitalization, and the risk of hypothermia, these early preparations were abandoned and replaced with various laxatives and polyethylene glycol (PEG) solutions. Table 1 lists colonoscopy preparation agents commonly used in the United States, some of which are approved for treatment of chronic constipation, whereas others are primarily used for colonoscopy cleanout.

Table 1
Table 1
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Uniform preparation protocols are not available, despite the fact that tens of thousands of pediatric colonoscopies are performed yearly in the United States and around the world. Rather, a wide variety of regimens exist (8). It is often the practice of each institution to develop its own protocol, varying the length of preparation, medication and dosages, and dietary changes. This lack of standardization makes it somewhat difficult when trying to compare efficacy and safety of the different regimens. We performed a MEDLINE search of all of the articles available in the English language relating to colonoscopy preparation in children up to March 2010. Several articles have reviewed this topic recently, although primarily in the adult population (3,9–13). Therefore, this review concentrates on published pediatric data, excluding abstracts, and primarily focuses on the mechanism of action, efficacy, ease of use, and safety of available colonoscopy preparations'.

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MECHANISM OF ACTION

Colonoscopy preparation agents can be divided into stimulants and osmotic agents, although some have a combined effect. Laxatives that are considered to be primarily stimulants include senna and bisacodyl. Magnesium citrate, sulfate and phosphate, and sodium phosphate, and sodium picosulfate, which is used outside the United States, exert both stimulant and osmotic effects. Osmotic agents include PEG preparations with electrolytes (PEG-ELS) or PEG-3350 without electrolytes.

Stimulant laxatives induce colonic motility through stimulation of the enteric nervous system and colonic electrolyte and water secretion (14). Laxatives including anthraquinones such as senna, which occurs naturally in plants, are not absorbed (15). After oral administration, sennoside is degraded only in the lower parts of the gastrointestinal tract, releasing its active metabolite rhein anthrone (16), which accelerates colonic transit and produces a bowel movement in 6 to 12 hours (17). Senna is available in a syrup and a tablet formulation. Diphenylmethane derivative bisacodyl is another stimulant available in tablet, enema, and suppository formulations for the treatment of acute and chronic constipation. It induces high-amplitude propagating contractions and shortens colonic transit time (18). It results in a bowel movement within 6 to 8 hours when given orally and 30 to 60 minutes when administered rectally, and has minimal systemic absorption (19).

Laxatives containing magnesium cations or phosphate anions including magnesium sulfate, phosphate, citrate, and sodium phosphate exert combined hyperosmolar and stimulant activity. They stimulate peristalsis indirectly by first increasing the intraluminal osmolarity with resulting water secretion and colonic wall stretching leading to faster transit (20), an effect potentiated by cholecystokinin release (21). Other mechanisms may contribute to their effects as well, including the production of inflammatory mediators. It is estimated that for every additional milliequivalent of Mg2+ in the intestinal lumen, fecal weight increases by about 7 g (22). Phosphate salts are better absorbed than magnesium-based agents and therefore need to be given in larger doses. The sodium phosphate oral solution contains 1.8 g of dibasic sodium phosphate and 4.8 g of monobasic sodium phosphate in 10 mL. A tablet-form preparation contains 1.5 g total sodium phosphate per tablet (23). Sodium phosphate is also frequently used in an enema form and contains 6 g of sodium phosphate and 16 g of sodium biphosphate per 100 mL available in 2 formulations: 67.5 mL for pediatric and 135 mL adult size. Sodium picosulfate is a prodrug hydrolyzed by bacteria in the colon to active metabolite 4,4′-dihydroxydiphenyl-(2-pyridyl)methane. It acts as a stimulant by increasing the frequency and force of peristalsis (24).

Finally, isosmotic PEG-ELS preparations are osmotically balanced, high-volume, nonabsorbable, and nonfermentable electrolyte solutions. These solutions cleanse the bowel with minimal water and electrolyte shifts and provide evacuation primarily by the mechanical effect of large-volume lavage. The conventional total adult dose is 4 L, whereas in children it is prescribed per body weight. Most commonly prescribed doses range from 20 to 40 mL/kg, but not more than 1 L/h, and/or until rectal effluent is clear. PEG-ELS can be given as a split dose with the second half given on the morning of the procedure. However, most children and adolescents undergo colonoscopic procedures in the morning, so sedation restrictions and inconvenience of administration prevent use of this split-dosing regimen. Newer low-volume preparations in combination with bisacodyl or ascorbic acid allow for preparation with only 2 L of solution. Recently, PEG-3350 preparations without electrolytes mixed with various types of fluids have started to be used for colonoscopy preparation in children.

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EFFICACY AND EASE OF USE

The number of published studies investigating the efficacy of various preparation regimens in pediatrics is relatively small, with a combined enrollment of fewer than 1300 subjects. These studies are all single-centered and vary widely in their design, and only a few are prospective and randomized (Table 2) (25–39). The studies used different outcome measures to define the success of a preparation. Some based success on the need for irrigation or suctioning, whereas others described the consistency of remaining stool and cleanliness of the colon, or the extent of colonoscopy. There is no validated pediatric colon cleanliness index. The commonly used and prospectively validated adult index, Ottawa bowel preparation scale, has instead been used in pediatrics (40). The score is calculated by adding 0 to 4 ratings for each of the 3 colon segments and 0 to 2 for fluid quantity rating. The scale ranges from 0 (perfect) to 14 (completely unprepared colon). The Aronchick scale is another validated adult index that has been used or modified for studies in children (41). This index is based on the colon's visual appearance (1 for excellent with >95% of surface seen, 2 for good with liquid stool covering <25% or >90% surface seen, 3 for fair with some semisolid stool that can be suctioned or washed away with >90% surface seen, 4 for poor with semisolid stool that cannot be washed or suctioned and <90% surface seen, and 5 for inadequate/repreparation and repeat procedure required). This scale has also been used in a recent prospective study that validated the pediatric endoscopy patient satisfaction survey (42). Additionally, close monitoring of the preparation process including a checklist was developed in a prospective 2-phase study in 198 pediatric patients (43).

Table 2
Table 2
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Table 2
Table 2
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During the last 3 decades since the introduction of flexible colonoscopy in pediatrics and following the first reports on whole-gut irrigation, there have been more than 1 dozen reports describing the success rates of preparation regimens and their adverse events. Some of the first few concentrated on the PEG-ELS preparations, whereas the more recent studies focused on the use of the same agent without electrolytes. PEG-ELS was first reported for preparation for colonoscopy in adults in 1980 (44) and in pediatrics in 1984 (25). In the latter study, 12 pediatric patients were hospitalized to receive the preparation for colonoscopy. The amount of ingested PEG ranged from 2.5 to 5 L. Eighty-three percent of patients had satisfactory results; however, the same proportion complained of nausea and one quarter vomited during preparation. Twelve additional patients were enrolled, but the results for these patients were not presented. Subsequent to that trial, another study reported that more than half of the enrolled 20 pediatric patients required nasogastric (NG) tube placement for the completion of preparation with sulfate-containing PEG (25). Twenty percent vomited and more than half complained of nausea. The volumes administered to achieve clear rectal output ranged from 16 to 183 mL/kg, or 1.2 to 3.6 L. Since then, sulfate-free PEG-ELS preparations have been developed; however, the large volume and the taste of these preparations continue to be a major obstacle for pediatric patients. In adults, low-volume (2 L) PEG-ELS preparation and bisacodyl was shown to be equally efficacious as the full-volume (4 L) preparation and was better accepted (45). This was also demonstrated in a trial in which ascorbic acid was added to the low-volume PEG preparation (46).

PEG-3350 without electrolytes has been successfully and safely used for the long-term management of constipation and fecal impaction in children of varying ages (27,47–49). Due to its palatability, especially when mixed with sports drinks, this agent has also been increasingly used for bowel preparation for pediatric colonoscopy. A prospective study in which PEG-3350 without electrolytes was mixed with various types of fluids at 1.5 g · kg−1 · d−1 dose given for a 4-day preparation period to 169 patients was published in 2008 (28). In addition to measuring the efficacy of this regimen, the trial examined stool frequency and consistency as predictors of cleanout success. The liquid stool consistency and frequency of 5 or more bowel movements per day during the last 2 days of preparation were excellent predictors of patients who were adequately prepared for colonoscopy, which in this series reached 89%. The cecal and terminal ileal intubation rates were 98% and 86%, respectively. Thirty-six percent of patients experienced adverse events, although these were not described in detail. Similar efficacy results were seen with a similar study design in 46 children, with 91% and 95% adequate preparation rate in the right and left colon, respectively, although more than half received an additional normal saline enema (50). The average dose of PEG-3550 without electrolytes ingested per day was 870 mL or 21 mL · kg−1 · d−1 for 4 days. The cecum was reached in all patients. Similar adverse events profiles including nausea, abdominal pain, and vomiting were recorded as in the previously described study, although these did not prevent completion of the protocol. Excellent compliance and tolerance were reported in 89% and 85% of patients, respectively, and all but 1 stated they would take the same preparation for a future colonoscopy. The length of the regimen in these 2 studies may result in noncompliance outside a trial environment and lead to missed school or workdays. Therefore, a recent retrospective review of 272 children undergoing colonoscopy after 1-day preparation with 1.9 L of PEG-3550 without electrolytes was performed. It demonstrated that a single dose of PEG administered for more than 2 hours on the afternoon before the day of colonoscopy, followed by a clear diet, resulted in an effective bowel cleanout in 93% of patients (29). No standard cleanliness scale was used, however, and the success was measured by reaching the cecum or terminal ileum.

Use of senna preparations has been reported in several pediatric studies. In the first trial, 140 patients were divided in 4 groups depending on the type of laxative (senna vs magnesium citrate), number of sodium phosphate enemas (1 vs 2), and duration of clear liquid diet (1 vs 2 days) (30). Both laxatives demonstrated similar efficacy, although the outcome measures used to determine success were not defined. The study established that only 1 adult-size enema on the day of the procedure, combined with 1 day of a clear liquid diet, was sufficient for preparation. Another prospective randomized trial compared magnesium citrate with senna versus bisacodyl and enema with no dietary restriction versus PEG-ELS (2). The bisacodyl with enema cohort had an unacceptably high rate of poor preparation (37%) requiring repeat examination, leading to premature termination of the enrollment in this group. Excellent cleanout was achieved in 30% of patients in the magnesium citrate/senna group and 48% patients in the PEG group, which increased to 70% and 83%, respectively, when average cleanout results were included. No patients in the magnesium/senna and PEG groups had poor results. Patients' tolerance of the cleanout favored bisacodyl (25% vs 42% vs 10%, respectively) with similar distribution of good compliance rates (80% vs 95% vs 54%, respectively). These results differed with the prior study of bisacodyl with an enema and no dietary restrictions, in which excellent cleanout rates were found in 87%, and good rates in the remaining 13% of patients, with good tolerance of the regimen (31). Another trial demonstrated that bisacodyl with a half day of clear liquid diet and sodium phosphate enema had an excellent cleanout effect (32). In this trial the results were compared with a historic control group of 28 patients who received PEG-ELS. The rate of reaching cecum or terminal ileum was 89% for the PEG and 98% for the bisacodyl group. Overall, 95% of patients had good or excellent results in the bisacodyl group versus 88% in the PEG group. Sixty-nine percent of patients in the PEG group had nausea or vomiting reported, as compared to none in the bisacodyl group.

In comparison, sodium picosulfate was found to be superior to bisacodyl with sodium phosphate enema, with excellent preparation rates of 53% and 33%, respectively, reaching 100% and 71%, respectively, when good preparation rates were included (33). The same proportion of patients had the terminal ileum reached (81%) in both groups. The compliance was excellent in both groups, whereas patients in the bisacodyl group had more abdominal distress compared with the sodium picosulfate group, in which vomiting occurred in 10% of patients. A different retrospective trial found magnesium citrate to be equally effective when compared with a similar preparation with sodium picosulfate (34). Both regimens were equally well tolerated with few reported adverse effects, 11% and 3%, respectively.

The food kit was compared with sodium phosphate in a recent trial (35). The kit consisted of vanilla nutritional shake, lemon drink, chocolate-flavored energy bar, cinnamon applesauce, potato poppers snack, and chicken-flavored noodle soup mix, with the laxative kit containing magnesium citrate and bisacodyl. There was no statistical significance in the difference of cleanout success rates (90% vs 73%, respectively), and both groups were equally compliant with, and tolerant of, the preparation. Adverse effects were commonly reported in both groups, more so for the sodium phosphate group, 83% versus 100%, respectively. Another recent comparison between sodium picosulfate with magnesium oxide and citric acid and PEG-ELS solution demonstrated that the sodium picosulfate preparation cohort tolerated the preparation better and had higher satisfaction rates. This finding was secondary to a significantly higher proportion of patients requiring insertion of NG in the PEG group (2% vs 75%, respectively) (36). The success of preparation and colonoscopy completion rates was similar.

A study comparing oral sodium phosphate and PEG-ELS showed that sodium phosphate resulted in statistically significantly better bowel preparation and was better tolerated than PEG (37). More than half of the patients in the PEG group were unable to drink the prescribed volume, which may have affected efficacy results. Another study comparing oral sodium phosphate to PEG-ELS, administered via nasogastric tube, demonstrated similar efficacy between the 2 preparations (71% vs 73%, respectively) (38). Some advantages regarding tolerance and discomfort were seen in the sodium phosphate group. Finally, in a group of children and adolescents older than 10 years of age and greater than 34 kg weight, a 1-day oral sodium phosphate preparation was more acceptable than a 3-day magnesium citrate with sodium phosphate enema preparation, and both regimens were found to be safe and efficacious (39).

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SAFETY

All colonoscopy preparations are associated with adverse events. The more common ones include electrolyte abnormalities, dehydration, abdominal pain/cramping, nausea, vomiting, bloating, sleep disturbance, and school/work absence. To prevent more serious potential complications, preparations should be avoided in patients with suspected intestinal obstruction or perforation. Adverse events related to tolerance and ability to complete the preparation were reviewed in the previous section. Because there are a limited number of pediatric studies, of which only less than one third reported on laboratory results, some of the relevant adult data are reviewed. Recently, the Food and Drug Administration (FDA) recommended against the use of over-the-counter oral sodium phosphate preparations for colonoscopy preparation.

PEG-ELS are isosmotic preparations that are nonabsorbable and therefore do not cause water or electrolyte shifts. Several pediatric trials reported on electrolyte measurements pre- and postpreparation with PEG-ELS (25,26,36–38). Either there were no statistically significant differences in electrolyte levels noted or the changes were within normal laboratory range. In 1 trial there was more hypokalemia noted in the PEG-ELS group compared with sodium picosulfate group, in which 1 patient was found to have a potassium level of 2.7 mmol/L (36). In addition, 8% of adult patients who prepared with PEG-ELS were noted to have a sodium level of <130 mmol/L after colonoscopy (51). Furthermore, a case of PEG allergy has been reported (52). PEG-ELS preparations do not alter colon histology (53), although 1 trial reported microscopic changes including edema and inflammation (54).

PEG-3350 without electrolytes has been used for bowel cleanout, with reported doses up to 10 times higher than those recommended for standard treatment of constipation. In 1 pediatric trial in which doses of up to 100 g of PEG-3350 per day were used for treatment of fecal disimpaction, there were no electrolyte abnormalities reported (49). Similarly, no electrolyte abnormalities were seen at doses of up to 1.5 g · kg−1 · day−1 for long-term therapy of constipation (49). Only 1 pediatric preparation trial evaluated the electrolyte profile of patients receiving 1.5 g · kg−1 · day−1 of PEG-3550 without electrolytes for 4 days before colonoscopy (50). Small, statistically significant electrolyte level changes were seen, but all of them were within normal laboratory range and were felt to be of no clinical significance. PEG-3350 preparation without electrolytes is commonly used with sports drinks; those drinks, however, contain about 9 times less sodium than PEG-ELS and can lead to a net absorption of “free” water resulting in hyponatremia (55), especially in patients with impaired kidney function. Sports drinks also contain 4 times less potassium and 6 times less chloride when compared with PEG-ELS. Further complications may arise through the addition of different flavorings, which may alter osmolarity. Additionally, added carbohydrates may result in bacterial fermentation and lead to production of combustible gases (56).

Measurement of electrolytes in pediatric studies using senna was not performed, but there were no electrolyte disturbances seen in an adult trial (57). The mean change of serum magnesium level before and after colonoscopy was significant in 1 pediatric trial of magnesium citrate (39). Similarly, mild hypermagnesemia was found in another pediatric trial, although it was deemed clinically insignificant (36).

Metabolic disturbances, including hyperphosphatemia, hypocalcemia, hypernatremia, hyponatremia, hypokalemia, and anion gap metabolic acidosis, have been reported in association with oral sodium phosphate preparations in adults (58) and have been reviewed in detail elsewhere (59). Concerns related to possible adverse events with sodium phosphate colonoscopy preparation in the pediatric population have been previously raised (60). These adverse events can be accompanied by volume depletion and acute kidney injury (AKI) typically attributed to tubular injury (61). The pathophysiology of this process is unknown, but the histopathology suggests that sodium phosphate ingestion leads to obstructive calcium-phosphate crystalluria followed by intratubular nephrocalcinosis (62). The presenting signs and symptoms of AKI can be early or late. Early presentation is of an acute illness that manifests as a change in mental status, tetany, or cardiovascular collapse, usually within hours of bowel preparation. Patients have marked hyperphosphatemia and hypocalcemia and require urgent fluid resuscitation, rapid correction of electrolyte abnormalities, and even hemodialysis. The second pattern of AKI has an insidious onset of renal failure days or months after colonoscopy. At the time of diagnosis, serum phosphorus and calcium levels are normal or near normal unless acute phosphate nephropathy is detected. These patients may never recover their renal function completely and some progress to end-stage renal disease (63). Risk factors include female sex, older age, hypertension, and renal failure, although this may occur with preexisting normal renal function (64). Oral sodium phosphate use in pediatrics was also associated with hyperphosphatemia; however, no clinical signs of hyperphosphatemia were noted (37). In another trial, serum sodium concentration increased with the use of the sodium phosphate oral solution, but remained within normal range, unlike the serum phosphate level, which was above normal in all of the patients (38). Additionally, 3 patients were found to have abnormal serum albumin–corrected calcium levels before colonoscopy, although with no reported symptoms. In contrast, an adolescent who received oral sodium phosphate preparation was found to have limb spasms and an inability to walk and articulate words, associated with hyperphosphatemia and hypocalcemia (65). Sodium phosphate enema use has also been reported in children to cause electrolyte imbalance with hyperphosphatemia, hypocalcemia, resulting in seizures, kidney injury, coma, and even death (66–73). Clear instructions on the proper administration and dosing of enemas need to be given to the families to prevent potential complications. Finally, sodium phosphate has been associated with alteration of micro- and macroscopic appearance of the colon in adults mimicking inflammatory changes (74,75).

Due to accumulating reports of renal injury with the use of oral sodium phosphate for colonoscopy preparation, the FDA recommended against its use for this purpose, prompting the manufacturer to voluntarily withdraw the over-the-counter product from the market. Furthermore, a black box warning was added for the prescription preparations and postmarketing surveillance studies were recommended.

Hypoglycemia has not been reported in any of the pediatric clinical trials; however, it is our personal experience with senna as well as PEG preparation that hypoglycemia infrequently occurs, more so in very young patients. It is our practice to obtain glucose serum levels for all patients undergoing colonoscopy.

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SUMMARY

Since the withdrawal of oral sodium phosphate from the US market, the most commonly used agents for colonoscopy preparation include PEG-3350 solutions, senna, bisacodyl, and magnesium salts. Their efficacy is comparable, although bisacodyl preparation alone was associated with high failure rate in 1 trial. Based on the available data, it is difficult to make precise comparisons. Almost all preparation regimens require some dietary restriction, although the duration of a clear liquid diet may be limited to only 1 day and in some trials, even less time. Currently, PEG-3350 preparation without electrolytes diluted in various types of drinks is 1 of the most frequently used regimens in practice. Its safety profile will need to be investigated further, with a specific focus on hydration and electrolyte status. This and other preparations must be individually tailored according to the patient's age, size, and comorbid conditions.

The ideal preparation regimen for pediatric colonoscopies remains elusive. Available preparations continue to present challenges for children and their families due to taste, volume, and dietary and activity restrictions. These can interfere with compliance and lead to a significant proportion of suboptimal preparations resulting in incomplete examination, pose safety problems during a therapeutic colonoscopy, or require a repeat procedure. The number of scientific studies reported in pediatrics is small, and there is a need for large, prospective, multicenter, and randomized clinical trials. New agents need to be investigated, and the existing agents require further evaluation regarding their safety and dose profiles that provides appropriate preparations with minimal adverse events.

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Cited By:

This article has been cited 1 time(s).

European Journal of Radiology
Intravenous contrast enhanced computed tomography colonoscopy in children with suspected colonic polyps
Bhatia, A; Saxena, AK; Kalra, N; Sodhi, KS; Thapa, BR; Rao, KLN; Khandelwal, N
European Journal of Radiology, 82(6): 905-912.
10.1016/j.ejrad.2012.12.017
CrossRef
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Keywords:

colonoscopy; pediatric; preparation

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