Hirschsprung disease is a developmental disorder of the enteric nervous system resulting in the absence of ganglion cells in the myenteric and submucosal plexus of the large and (rarely) small intestines. This absence of ganglion cells results in a functional obstruction. This condition is primarily diagnosed in the newborn period; however, a significant number of patients will not be diagnosed in the neonatal period and will present later in life with intractable constipation (1). Swenson et al (2) reported that 17% of 501 patients presented after 6 years of age.
Diagnosing Hirschsprung disease can be a difficult task, especially when only a short segment of distal rectum is involved. Excluding the diagnosis is significantly easier because it requires the demonstration of only a single ganglion cell in the distal rectum. However, even this task is complicated by the fact that there is a relative paucity of ganglion cells in this area and they are only found in the submucosa. Surgically obtained full-thickness specimens can confidently provide tissue of adequate depth; however, concerns have been expressed that surgical procedures may result in scarring, making future surgeries more difficult. Less invasive techniques for obtaining adequate specimens have been developed.
The most widely used technique involves a blind suction biopsy. Rectal biopsies have primarily been performed by the suction technique described by Dobbins and Bill (3) in 1965 and Campbell and Noblett in 1969 (4). Complications associated with this technique have included perforation, strictures, perirectal fibrosis, sepsis, rectal bleeding, and a fatality due to pelvic cellulitis. Complication rates have been reported in the range of 1.3% to 2.9% (5–8,12). Failure rates ranged from 8% to 35% (3,6,7,9–11). Increased rates of success have been reported using wall suction rather than manually applied syringe-generated suction. However, this report, with no inadequate specimens, involved only 24 patients (9). It has also been shown that suction rectal biopsies are considerably less successful in more than 3 years of age with failure to obtain submucosa in up to 55% of patients (4,6,12).
Although the suction biopsy is often regarded as a simple and safe bedside technique not requiring anesthesia, the authors' experience was in great contrast to this perception. Our experience involved numerous episodes of device malfunction as well as adverse outcomes including the inability to obtain tissue, excessive bleeding requiring a transfusion, and a suction capsule that would not release from the rectal mucosa. These were the problems that led us to look for an alternative method of obtaining deep rectal biopsies.
There have been numerous other techniques devised to try to avoid these issues. These alternative methods have included the use of the Storz rectal cup biopsy, Gruenwald nasal cutting forceps, Kevorkian-Younge uterine grasp biopsy forceps, laryngeal biopsy forceps, and a rectal punch biopsy (13–15).
Our objective was to determine the capability of a flexible endoscope and jumbo biopsy forceps to obtain adequate specimens in the evaluation of Hirschsprung disease outside the newborn period. We report a retrospective study of rectal biopsies using this technique.
PATIENTS AND METHODS
We retrospectively reviewed 668 rectal biopsies taken during 166 endoscopies on 156 patients being evaluated for Hirschsprung disease from 2001 to 2008 at the Baystate Medical Center Children's Hospital. Patients were chosen for biopsy if they had difficult-to-manage constipation or a history that dated back to the first few days of life.
Four biopsies were taken from each patient approximately 2.5 cm from the anal verge. Biopsies were obtained using a flexible endoscope using jumbo biopsy forceps. Tape was placed on the endoscope at 2.0 cm from the tip, which was advanced just past the anal verge. The forceps was advanced as little as possible from the endoscope. In most patients this resulted in obtaining tissue just past the pectinate line, which could easily be identified. During the first 6 years, the Olympus FB-50U-1 large cup fenestrated biopsy forceps was used. However during the last 2 years the Boston Scientific Radial Jaw 4 Jumbo biopsy forceps was used instead. There were 88 patients who underwent biopsy with the Olympus forceps and 78 patients with the Boston Scientific forceps. Specimens were placed in 10% formalin and stained with hematoxylin and eosin in the usual fashion. Biopsies were considered adequate if at least 1 ganglion cell could be identified in 1 of the 4 biopsies taken from each patient. The biopsies were primarily obtained by 2 of the authors (B.Z.H., A.G.A.). A variety of different endoscopes were used ranging from a colonoscope to an upper endoscope, depending on the size of the patient and what other procedures may have been performed simultaneously. The smallest endoscope was the Olympus GIF-160 gastrointestinal videoscope, which has a 2.8-mm inner channel and an 8.6-mm outer diameter. Although the manufacturer recommends a 3.7-mm channel, we had no problem passing the forceps through a much smaller endoscope. There were 3 patients younger than 6 months of age. The youngest was 7 weeks old and weighed 4.3 kg. In this patient biopsies were obtained using the Olympus GIF-160 gastrointestinal videoscope referred to above. The other 2 were 5 months old with weights of 5.52 kg and 6.8 kg. In both these patients the Olympus GIF-IT 140 therapeutic upper endoscope was used. This endoscope has an outer diameter of 11.3 mm and a 3.7-mm inner channel. Although our experience was limited in small babies, the technique appears to be safe in this age group. Table 1 shows the age distribution of the patients in our study.
At our institution, anesthesia is readily available for endoscopic procedures, so most of the cases were done with an inhalation agent but rarely an intravenous line, unless the patient was undergoing other procedures at the same time. The procedures were so brief and nonstimulating that our anesthesiologists were comfortable not placing an intravenous catheter.
Descriptive statistics are reported for all of the patients combined. Factors in positive biopsy were tested on univariate analysis using the Pearson χ2 for discrete factors and the Student t test for continuous factors. Significant factors on univariate analysis were entered into a multiple logistic regression (16). The present study was approved by the Baystate Medical Center institutional review board.
The overall success rate of this technique was 86%. However, in the last 2 years of the study when the newer biopsy forceps was used, the success rate was 93%. The earlier results were similar to some of the reports with the suction biopsy; however, the 93% success rate demonstrated with the newer forceps surpassed most of the results in the literature. There were no complications reported. The patients ranged in age from 7.5 weeks to 20 years with an average age of 6.8 years. Table 2 shows the proportion of positive biopsies by age and type of forceps and the results of univariate analysis. Patients with adequate biopsies were slightly younger (6.6 years) than patients with inadequate biopsies (8.1 years), but the difference was not statistically significant. We did not find a lower success rate in children (percent positive biopsies) older than 3 years of age as previously described with the suction biopsy. The only factor found to be significantly related to success on univariate analysis was the type of forceps used: the newer type had a significantly higher success rate than the older one (94% vs 78%). Multiple logistic regression was not appropriate because only 1 factor was significant on univariate analysis.
Most patients with Hirschsprung disease present with bowel obstruction and are diagnosed during the first few days or weeks of life. In these patients suction biopsy is the most commonly used technique for making the diagnosis. The jumbo biopsy technique that is reported here offers an alternative to patients who have had difficulty with the suction biopsy. It also offers a number of advantages over the suction biopsy, especially in the older child. It allows direct visualization of the mucosa, potentially increasing its safety profile by making it possible to identify any abnormal vascular structures. It also allows for a more directed biopsy and the avoidance of biopsying the same site twice. Excessive bleeding, although not a problem in the present study, would be rapidly identified and could be treated immediately. Biopsy forceps are a familiar tool to gastroenterologists and do not pose the same problem of equipment malfunction as seen with the Noblett biopsy device with its multiple parts. Although endoscopes are somewhat larger than the Noblett catheter, the technique is probably no more uncomfortable than a suction biopsy, and the anesthesia was used primarily to reduce anxiety and ensure cooperation. The 8.6-mm outer diameter of the upper endoscope we used is certainly small enough to use safely on any full-term infant. Our experience with small infants was limited, and therefore it is difficult to comment on the safety of the technique in this age group.
The shortcomings of this technique would include the small amount of submucosa occasionally obtained. Although many of the biopsies had a moderate amount of submucosa, it was not uncommon to have tissue that only included mucosa. Fortunately, this did not pose a problem for diagnosis because ganglion cells typically adhere to the mucosa as the submucosa is torn away during biopsy (Figs 1 and 2). Despite the superficial nature of many of the biopsies, they were still considered adequate to rule out Hirschsprung disease. The lack of submucosa may make it difficult to assess for more poorly understood disorders such as intestinal neuronal dysplasia. However, many experts feel a surgically obtained full-thickness biopsy is necessary to make this diagnosis. The other shortcoming of the technique would be the cost and number of hospital personnel involved. Our patients were included in our routine endoscopy schedule, which includes full anesthesia support. At other institutions in which pediatric gastroenterologists provide their own sedation, the procedure could clearly be performed with the same amount of sedation routinely used for a flexible sigmoidoscopy. In a cooperative, nonanxious patient it could feasibly be performed with no anesthesia. A suction biopsy done at the bedside of a small baby would clearly require fewer support staff; however, in an anxious older child or an uncooperative toddler, a considerable amount of sedation and support would be required even with the suction device.
One of the surprises of our study was the absence of any patients with Hirschsprung disease. Although uncommon, Hirschsprung disease is well described outside the newborn period. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition position paper on constipation does not give clear guidelines as to the appropriate criteria or frequency for rectal biopsies in older children (17). The criterion we used was constipation with a history dating back to the newborn period, which was unresponsive to aggressive therapy. The absence of Hirschsprung disease in any of our patients would suggest that more stringent criteria should be applied.
There are no data on the use of the jumbo biopsy forceps in children and limited data in adults. Swanson et al (18) demonstrated its use and safety in the assessment of Barrett esophagus. Elmunzer et al (19) demonstrated the safety and superiority of jumbo biopsy forceps in 24 patients with inflammatory bowel disease undergoing surveillance colonoscopy. It should be noted that they used the jumbo biopsy forceps only in the rectosigmoid colon (19). All of our biopsies were taken below the peritoneal reflection, eliminating the possibility of true perforation into the peritoneum. Although we have not used this biopsy forceps in more proximal areas of the bowel, the relatively superficial nature of our biopsies suggest that it would be safe.
The technique reported in the present article is safe, effective, and already familiar to gastroenterologists. The use of a technique that involves visualization of the mucosa to be biopsied would always seem to be the better choice over a “blind biopsy” when the option is available.
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Keywords:Copyright 2011 by ESPGHAN and NASPGHAN
ganglion cells; Hirschsprung disease; jumbo biopsy; suction biopsy