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Suction rectal biopsy yields adequate tissue in children
Journal of Pediatric Surgery xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Suction rectal biopsy yields adequate tissue in children Ann-Christina Brady a, Jacqueline M. Saito a, Karen Lukas a, Tracey Guthrie a, Elizabeth C. Utterson b, Frances V. White c, Patrick A. Dillon a,⁎ a b c
Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States Division of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
a r t i c l e
i n f o
Article history: Received 20 February 2016 Accepted 26 February 2016 Available online xxxx Key words: Hirschsprung disease Ganglion cells
a b s t r a c t Background/purpose: Hirschsprung disease (HD) is diagnosed by rectal biopsy, with suction rectal biopsy (SRB), the preferred technique in neonates. Reported SRB adequacy has varied overall with concern for decreased diagnostic yield in older children. The study aim was to assess SRB adequacy by age in children with the current device used at our institution. Methods: Following IRB approval, a retrospective cohort of children (1 to 18 years) evaluated by SRB for HD was identified through billing records. Data regarding demographics, procedure, results, and complications were collected and analyzed using SPSS. Results: 56 children (median age 3.9 years) underwent SRB with an 80.4% overall success rate. Patients older than 5 years had 90.5% adequacy rate compared to 74.3% in those younger. Univariate analysis revealed weak association of inadequate specimens with younger age and males, and no association with insurance, race/ethnicity, weight–height or BMI percentile, sedation type, or procedure location. SRB under general anesthesia (GA) had 100% adequacy (n = 6). Patients with inadequate initial biopsy achieved diagnosis by SRB with increased sedation (n = 5) or full thickness biopsy under GA (n = 5). Conclusion: With adequacy of 80.4% overall and 90.5% for patients greater than 5 years, SRB is effective in evaluating the older child for HD. © 2016 Elsevier Inc. All rights reserved.
1. HD demographics and diagnosis Occurring in 1 of 5000 live-born infants, Hirschsprung disease (HD) is a motility disorder resulting from the absence of ganglion cells in the Meissner and Auerbach plexuses of the gastrointestinal tract [1]. Full thickness rectal biopsy (FTB) under general anesthesia (GA) was the primary biopsy technique until 1965, when Dobbins and Bill [2] identified ganglion cells on suction rectal biopsy (SRB) and suggested the use of SRB to exclude HD. In 1969, Noblett [3] utilized a device that drew a portion of mucosa and submucosa into a side aperture via manometrically measured suction and excised the tissue using a cylindrical knife. Using this device, Noblett was [3] able to obtain adequate specimens from 116 biopsies in 45 children with no complications. Since that time, SRB has become the procedure of choice for evaluation of very
young children with suspected HD. Despite the overall success of SRB, the complication rate (0–2.9%) [3–12] and specimen adequacy (73%– 100%) [2,3,5–10,12–14] have varied significantly in the literature. Currently, no evidence-based guideline exists for technique selection or sedation use to maximize the diagnostic yield of rectal biopsy in children greater than 1 year. In 2011, Hirsch et al. [15] performed a retrospective review of 668 biopsies performed during 167 endoscopies on 156 patients with the use of a flexible endoscope and jumbo biopsy forceps, usually under an inhalational anesthetic agent to reduce patient anxiety and ensure cooperation, and reported a success rate of rectal biopsy of 94% with no complications. This suggested that increased sedation may lead to improved biopsy adequacy in uncooperative patients.
1.1. Study aim Abbreviations: HD, Hirschsprung disease; SRB, suction rectal biopsy; GA, general anesthesia; PO, oral; IV, intravenous; FTB, full thickness biopsy; BMI, body mass index; IQR, interquartile range. ⁎ Corresponding author at: Division of Pediatric Surgery, Washington University School of Medicine, One Children's Place, Suite 5S60 Street, St. Louis, MO 63110, United States. Tel.: +314 454 6022; fax: +314 454 2442. E-mail address: [email protected] (P.A. Dillon).
We hypothesized that rectal biopsy specimen adequacy is associated with younger age because of the narrower rectal wall thickness compared to older children, and improved with sedation due to enhanced patient cooperation. The aims of this study were to evaluate the SRB results of children aged 1 to 18 years, and to assess the impact of sedation on SRB adequacy in this population.
http://dx.doi.org/10.1016/j.jpedsurg.2016.02.064 0022-3468/© 2016 Elsevier Inc. All rights reserved.
Please cite this article as: Brady A-C, et al, Suction rectal biopsy yields adequate tissue in children, J Pediatr Surg (2016), http://dx.doi.org/10.1016/ j.jpedsurg.2016.02.064
2
A-C. Brady et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
2. Materials and methods 2.1. Human subjects research protection and cohort identification After Washington University Institutional Review Board approval (#201403128), a retrospective cohort of children between ages 1 and 18 years who underwent SRB to evaluate for HD at a single children's hospital was identified through billing records (CPT™ 45100). There were no exclusion criteria. The study period (4/2011 to 2/2015) coincided with the introduction of the rbi2 SRB device (Aus systems Pty Ltd., Allenby Gardens, South Australia) at our institution. 2.2. Rectal biopsy technique and pathologic evaluation The rbi2 SRBs were obtained approximately 2 to 4 cm proximal to the dentate line with negative suction achieved utilizing a syringe and pressure measured by the manometer provided with the device. Two to four specimens from the lateral and posterior rectum were collected at the time of each biopsy session, and specimens were placed in 10% buffered formalin. On analysis by an experienced pediatric pathologist, biopsies were regarded as inadequate due to 1) insufficient depth in which case there was inadequate submucosa for analysis or 2) the presence of squamous and/or transitional epithelium suggestive of a biopsy taken from the normally hypoganglionated anorectal transitional zone. All inadequate biopsies were later reviewed by a single pediatric pathologist with expertise in Hirschsprung disease (F.V.W.) and categorized as either inadequate owing to insufficient submucosa (submucosal thickness less than 25% of mucosal thickness) or to the presence of squamous and/or transitional epithelium. 2.3. Sedation The decision to provide sedation during the SRB was determined by the operating physician. For our study, sedation was recorded when administered, and patients were characterized as receiving no sedation, light-deep sedation (PO or IV midazolam, IV ketamine, inhaled nitrous oxide) or GA. 2.4. Data management and analysis Using REDCAP for data management [16], we recorded the following variables: gender, race, ethnicity, insurance type, age, weight, height, date of biopsy, performing physician, sedation received, dose, and biopsy results. Weight for length (for children b2 years) [17] and body mass index (BMI) (for 2–18 years old) percentile for age and gender [18] were determined. Study outcomes included adequacy of specimen and procedural complications, such as bleeding, blood transfusion and readmission. Descriptive statistics and univariate analysis (chi-square, Fisher's exact, and Mann–Whitney U test) were performed using SPSS Statistics (v.22, IBM, Armonk, NY). 3. Results 3.1. Demographics and outcomes 56 patients were identified in the cohort who underwent SRB during the study period. Cohort demographics, procedural details and outcomes are summarized in Table 1. The median age was 3.9 years with interquartile range (IQR) of 3.83, and weight/length or BMI percentile was 59.2% with IQR of 52.1%. 21 patients underwent SRB without sedation and 35 patients received sedation. In 11 patients (19.6%) an inadequate specimen was obtained with 9 of the 11 occurring in patients aged 1 to 5 years (n = 35). Children older than 5 years (n = 21) had adequate specimens in all but 2 patients, a 90.5% success rate of SRB versus a 74.3% success rate in children 1–5 years. For patients with an inadequate biopsy on initial attempt, sufficient specimens were ultimately
Table 1 Cohort demographics, procedural details and outcomes summary. Variable Age category 1–5 years N5 years Gender Female Race/ethnicity Caucasian African-American Hispanic Other Sedation category None Light-Deep General Provider Gastroenterologist Surgeon SRB sample adequacy Adequate
n (%) 35 (62.5) 21 (37.5) 32 (57.1) 49 (87.5) 3 (5.4) 2 (3.6) 2 (3.6) 21 (37.5) 29 (51.8) 6 (10.7) 53 (94.6) 3 (5.4) 45 (80.4)
obtained either with a second SRB utilizing increased sedation (n = 5) or with FTB under GA (n = 5). One patient with an initial inadequate biopsy was lost to follow-up. On review of all inadequate specimens, nine biopsies were deemed inadequate because of the presence of squamous and/or transitional epithelium and two biopsies were inadequate because of insufficient submucosa. There was 100% concordance between original and reviewed diagnoses. The incidence of HD was 3.6%, and the complication rate was 1.8% (one child readmitted for bleeding without need for transfusion). There were no intestinal perforations or other complications. 3.2. Risk factors for inadequate SRB specimen Although not statistically significant, univariate analysis showed weak associations between inadequate specimens and age b5 years (P = 0.14) and (Fig. 1) male gender (P = 0.12) (Table 2). No significant difference in specimen adequacy in sedated versus nonsedated groups was found. Insurance, race/ethnicity, weight–height or BMI percentile, sedation type (categorized as none, light (oral or IV midazolam), deep (inhaled nitric oxide or IV ketamine) or GA), and procedure location were not associated with biopsy adequacy. All patients who underwent SRB under GA had adequate specimen (n = 6). 4. Discussion Current literature suggests varying biopsy adequacies using SRB devices from 73% to 100% [2,3,5–10,12–14] with controversy regarding SRB effectiveness in the older child. In infants, suction rectal biopsy is documented as having sensitivity of 93% and specificity of 98% for HD [14]. In 1986, Kurer et al. [19] confirmed that SRB was as accurate as FTB for the diagnosis of HD in patients aged from a few weeks to 17 years. Yet, a 1998 retrospective study by Alizai et al. [5] regarding SRB using the Noblett device found inadequate samples in 13% of patients and, despite failing to reach statistical significance, suggested that suction biopsies were less likely to be adequate in children over 6 months of age compared to those younger (82.5% vs. 90.9%). In 2007, Croffie et al. [9] similarly found that SRB was adequate for diagnosis in 73% of patients 1 to 3 years of age, and only 50% of patients older than 3 years in a prospective study of children undergoing SRB. Finally, in 2012 Hayes et al. [12] found that, while not significant, patients younger than 3 years were more likely to have adequate SRB specimens than those older than 3 years (81% vs. 70%). The proposed reasons for these results are multifactorial. First, older children may have increased rectal thickness caused by chronic constipation, which may interfere with
Please cite this article as: Brady A-C, et al, Suction rectal biopsy yields adequate tissue in children, J Pediatr Surg (2016), http://dx.doi.org/10.1016/ j.jpedsurg.2016.02.064
A-C. Brady et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
Fig. 1. Univariate analysis indicates a nonsignificant trend toward inadequate SRB specimen in younger patients.
adequate apposition of the device with the rectal wall [9]. Second, older SRB devices required regular servicing such as blade sharpening which could contribute to worse biopsy yield. Last, the lack of sedation in younger uncooperative patients may have contributed to difficulty in obtaining adequate biopsies. Despite studies to the contrary that document an adequacy rate of 90 to 100% in children older than 1 year [8,14], many physicians adopted a protocol of routine FTB under GA for patients over a particular age. At our facility, children with chronic constipation continued to undergo SRB with or without sedation despite their age. As a result, our retrospective study demonstrates that SRB can be used successfully in the older child to evaluate for the presence of HD. Of the 56 patients aged between 1 and 18 years who underwent SRB, 80.4% had a diagnostic initial biopsy. On subset analysis, 90.5% of children aged 5 to 18 years had successful biopsies, which coincides with the findings of De Lorijn et al. [14] and Pini-Prato et al. [8]. However, the children aged 1 to 5 years tended to have a lower diagnostic yield with SRB of 74.3%. This lower SRB adequacy rate in the younger child is suspected to be caused by decreased cooperation in the toddlers and the need for increased sedation. Our statistical analysis did not identify a difference between sedated and nonsedated groups in regard to biopsy adequacy. We suspect that this finding may be due to selection bias (i.e., cooperative patients were not sedated) and our small population size. Of note, all children who underwent SRB under GA (n = 6), typically in combination with another procedure such as colonoscopy, had adequate specimens. Additionally, all patients who underwent repeat SRB after inadequate initial SRB subsequently were diagnosed with the use of increased sedation. This suggests that sedation level may, in fact, play a role in biopsy adequacy that was not appreciated statistically in this study. Table 2 Biopsy adequacy univariate analysis summary. Predictor Age category 1–5 years N5 years Gender Female Male Provider Gastroenterologist Surgeon Sedation None Light/Deep General
Adequate (%)
P 0.14
26/35 (74.3) 19/21 (90.5) 0.12 28/32 (87.5) 17/24 (70.8) 0.1 44/53 (83.0) 1/3 (33.3) 0.22 18/21 (85.7) 21/29 (72.4) 6/6 (100)
3
Historically, complications with SRB were seen in the neonatal population largely because of dull blades and the use of elevated manometric pressures during biopsy, but these complications are rare using modern devices. In 1983, Rees et al. [4] reviewed 1340 consecutive biopsies using the Noblett instrument and identified a 1.3% complication rate with significant neonatal complications including one fatal complication from pelvic cellulitis, two perforations causing pneumoperitoneum, two inadvertent full thickness biopsies with no clinical manifestations, and three rectal hemorrhages necessitating transfusion. Techniques and devices have been employed in attempts to improve safety especially in the neonatal population and biopsy adequacy, particularly in the older child. These include the use of specific instruments such as laryngeal biopsy forceps [20], cup biopsy forceps [5,15], nasal cutting forceps [7], and uterine biopsy forceps [9], and often employed increased sedation or GA. The rbi-2 device is the SRB instrument used exclusively at our institution. This device has the advantages of precise manometrically measured suction as well as a disposable single use blade for each specimen eliminating the need for blade sharpening and diminishing the risk of patient-to-patient cross infection. In 2009, the Noblett was found to have a statistically significant higher inadequacy rate than the rbi-2 in patients younger than 1 year (20% vs. 7%, P = 0.01) [10]. We have demonstrated that newer devices like the rbi-2 are capable of obtaining sufficient rectal biopsies in older children despite thicker rectal mucosa from prolonged constipation while still maintaining a low complication rate of 1.8%. 5. Conclusions Although previously suspected to yield inadequate biopsies in older children, SRB is an effective means of excluding HD. This study confirms that SRB yields sufficient tissue for HD diagnosis particularly in the older, cooperative child. In children aged 1 to 5 years, increased sedation (deep or GA) may be necessary to obtain a sufficient biopsy. In the event of inadequate initial specimen, SRB under increased sedation should be attempted. This study was limited by its retrospective nature, by potential selection bias in the administration of sedation, and the lack of standardization of sedation provided. A prospective study would be beneficial to determine the most effective means of obtaining adequate SRB specimens in children aged 1 to 5 years. References [1] Langer J. Hirschsprung disease. In: Coran A, editor. Pediatric surgery. Philadelphia: Elsevier Saunders; 2012. p. 1265–78. [2] Dobbins WO, Bill AH. Diagnosis of Hirschsprung's disease excluded by rectal suction biopsy. N Engl J Med 1965;272:990–3. [3] Noblett HR. A rectal suction biopsy tube for use in the diagnosis of Hirschsprung's disease. J Pediatr Surg 1969;4:406–9. [4] Rees BI, Azmy A, Nigam M, et al. Complications of rectal suction biopsy. J Pediatr Surg 1983;18:273–5. [5] Alizai NK, Batcup G, Dixon MF, et al. Rectal biopsy for Hirschsprung's disease: what is the optimum method? Pediatr Surg Int 1998;13:121–4. [6] Pini-Prato A, Martucciello G, Jasonni V. Solo-RBT: a new instrument for rectal suction biopsies in the diagnosis of Hirschsprung's disease. J Pediatr Surg 2001;36:1364–6. [7] Kobayashi H, Li Z, Yamataka A, et al. Rectal biopsy: what is the optimal procedure? Pediatr Surg Int 2002;18:753–6. [8] Pini-Prato A, Martucciello G, Jasonni V. Rectal suction biopsy in the diagnosis of intestinal dysganglionoses: 5-year experience with Solo-RBT in 389 patients. J Pediatr Surg 2006;41:1043–8. [9] Croffie JM, Davis MM, Faught PR, et al. At what age is a suction rectal biopsy less LIkely to provide adequate tissue for identification of ganglion cells? J Pediatr Gastroenterol Nutr 2007;44:198–202. [10] Hall NJ, Kufeji D, Keshtgar A. Out with the old and in with the new: a comparison of rectal suction biopsies with traditional and modern biopsy forceps. J Pediatr Surg 2009;44:395–8. [11] Rahman N, Chouhan J, Gould S, et al. Rectal biopsy for Hirschsprung's disease—are we performing too many? Eur J Pediatr Surg 2010;20:95–7. [12] Hayes CE, Kawatu D, Mangray S, et al. Rectal suction biopsy to exclude the diagnosis of Hirschsprung disease. J Pediatr Gastroenterol Nutr 2012;55:268–71. [13] Athow AC, Filipe MI, Drake DP. Problems and advantages of acetylcholinesterase histochemistry of rectal suction biopsies in the diagnosis of Hirschsprung's disease. J Pediatr Surg 1990;25:520–6.
Please cite this article as: Brady A-C, et al, Suction rectal biopsy yields adequate tissue in children, J Pediatr Surg (2016), http://dx.doi.org/10.1016/ j.jpedsurg.2016.02.064
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[14] De Lorijn F, Reitsma JB, Voskuijl WP, et al. Diagnosis of Hirschsprung's disease: a prospective, comparative accuracy study of common tests. J Pediatr 2005;146:787–92. [15] Hirsch BZ, Angelides AG, Goode SP, et al. Rectal biopsies obtained with jumbo biopsy forceps in the evaluation of Hirschsprung disease. J Pediatr Gastroenterol Nutr 2011;52:429–32. [16] Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81.
[17] http://www.who.int/childgrowth/standards/en/. [accessed on February 13, 2015]. [18] http://www.cdc.gov/healthyweight/assessing/bmi/childrens_bmi/tool_for_schools. html. [accessed on February 6, 2015]. [19] Kurer MHJ, Lawson JON, Pambakian H. Suction biopsy in Hirschsprung's disease. Arch Dis Child 1986;61:83–4. [20] Hirose R, Hirata Y, Yamada T, et al. The simple technique of rectal mucosal biopsy for the diagnosis of Hirschsprung's disease. J Pediatr Surg 1993;28:942–4.
Please cite this article as: Brady A-C, et al, Suction rectal biopsy yields adequate tissue in children, J Pediatr Surg (2016), http://dx.doi.org/10.1016/ j.jpedsurg.2016.02.064
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Suction rectal biopsy yields adequate tissue in children Ann-Christina Brady a, Jacqueline M. Saito a, Karen Lukas a, Tracey Guthrie a, Elizabeth C. Utterson b, Frances V. White c, Patrick A. Dillon a,⁎ a b c
Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States Division of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
a r t i c l e
i n f o
Article history: Received 20 February 2016 Accepted 26 February 2016 Available online xxxx Key words: Hirschsprung disease Ganglion cells
a b s t r a c t Background/purpose: Hirschsprung disease (HD) is diagnosed by rectal biopsy, with suction rectal biopsy (SRB), the preferred technique in neonates. Reported SRB adequacy has varied overall with concern for decreased diagnostic yield in older children. The study aim was to assess SRB adequacy by age in children with the current device used at our institution. Methods: Following IRB approval, a retrospective cohort of children (1 to 18 years) evaluated by SRB for HD was identified through billing records. Data regarding demographics, procedure, results, and complications were collected and analyzed using SPSS. Results: 56 children (median age 3.9 years) underwent SRB with an 80.4% overall success rate. Patients older than 5 years had 90.5% adequacy rate compared to 74.3% in those younger. Univariate analysis revealed weak association of inadequate specimens with younger age and males, and no association with insurance, race/ethnicity, weight–height or BMI percentile, sedation type, or procedure location. SRB under general anesthesia (GA) had 100% adequacy (n = 6). Patients with inadequate initial biopsy achieved diagnosis by SRB with increased sedation (n = 5) or full thickness biopsy under GA (n = 5). Conclusion: With adequacy of 80.4% overall and 90.5% for patients greater than 5 years, SRB is effective in evaluating the older child for HD. © 2016 Elsevier Inc. All rights reserved.
1. HD demographics and diagnosis Occurring in 1 of 5000 live-born infants, Hirschsprung disease (HD) is a motility disorder resulting from the absence of ganglion cells in the Meissner and Auerbach plexuses of the gastrointestinal tract [1]. Full thickness rectal biopsy (FTB) under general anesthesia (GA) was the primary biopsy technique until 1965, when Dobbins and Bill [2] identified ganglion cells on suction rectal biopsy (SRB) and suggested the use of SRB to exclude HD. In 1969, Noblett [3] utilized a device that drew a portion of mucosa and submucosa into a side aperture via manometrically measured suction and excised the tissue using a cylindrical knife. Using this device, Noblett was [3] able to obtain adequate specimens from 116 biopsies in 45 children with no complications. Since that time, SRB has become the procedure of choice for evaluation of very
young children with suspected HD. Despite the overall success of SRB, the complication rate (0–2.9%) [3–12] and specimen adequacy (73%– 100%) [2,3,5–10,12–14] have varied significantly in the literature. Currently, no evidence-based guideline exists for technique selection or sedation use to maximize the diagnostic yield of rectal biopsy in children greater than 1 year. In 2011, Hirsch et al. [15] performed a retrospective review of 668 biopsies performed during 167 endoscopies on 156 patients with the use of a flexible endoscope and jumbo biopsy forceps, usually under an inhalational anesthetic agent to reduce patient anxiety and ensure cooperation, and reported a success rate of rectal biopsy of 94% with no complications. This suggested that increased sedation may lead to improved biopsy adequacy in uncooperative patients.
1.1. Study aim Abbreviations: HD, Hirschsprung disease; SRB, suction rectal biopsy; GA, general anesthesia; PO, oral; IV, intravenous; FTB, full thickness biopsy; BMI, body mass index; IQR, interquartile range. ⁎ Corresponding author at: Division of Pediatric Surgery, Washington University School of Medicine, One Children's Place, Suite 5S60 Street, St. Louis, MO 63110, United States. Tel.: +314 454 6022; fax: +314 454 2442. E-mail address: [email protected] (P.A. Dillon).
We hypothesized that rectal biopsy specimen adequacy is associated with younger age because of the narrower rectal wall thickness compared to older children, and improved with sedation due to enhanced patient cooperation. The aims of this study were to evaluate the SRB results of children aged 1 to 18 years, and to assess the impact of sedation on SRB adequacy in this population.
http://dx.doi.org/10.1016/j.jpedsurg.2016.02.064 0022-3468/© 2016 Elsevier Inc. All rights reserved.
Please cite this article as: Brady A-C, et al, Suction rectal biopsy yields adequate tissue in children, J Pediatr Surg (2016), http://dx.doi.org/10.1016/ j.jpedsurg.2016.02.064
2
A-C. Brady et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
2. Materials and methods 2.1. Human subjects research protection and cohort identification After Washington University Institutional Review Board approval (#201403128), a retrospective cohort of children between ages 1 and 18 years who underwent SRB to evaluate for HD at a single children's hospital was identified through billing records (CPT™ 45100). There were no exclusion criteria. The study period (4/2011 to 2/2015) coincided with the introduction of the rbi2 SRB device (Aus systems Pty Ltd., Allenby Gardens, South Australia) at our institution. 2.2. Rectal biopsy technique and pathologic evaluation The rbi2 SRBs were obtained approximately 2 to 4 cm proximal to the dentate line with negative suction achieved utilizing a syringe and pressure measured by the manometer provided with the device. Two to four specimens from the lateral and posterior rectum were collected at the time of each biopsy session, and specimens were placed in 10% buffered formalin. On analysis by an experienced pediatric pathologist, biopsies were regarded as inadequate due to 1) insufficient depth in which case there was inadequate submucosa for analysis or 2) the presence of squamous and/or transitional epithelium suggestive of a biopsy taken from the normally hypoganglionated anorectal transitional zone. All inadequate biopsies were later reviewed by a single pediatric pathologist with expertise in Hirschsprung disease (F.V.W.) and categorized as either inadequate owing to insufficient submucosa (submucosal thickness less than 25% of mucosal thickness) or to the presence of squamous and/or transitional epithelium. 2.3. Sedation The decision to provide sedation during the SRB was determined by the operating physician. For our study, sedation was recorded when administered, and patients were characterized as receiving no sedation, light-deep sedation (PO or IV midazolam, IV ketamine, inhaled nitrous oxide) or GA. 2.4. Data management and analysis Using REDCAP for data management [16], we recorded the following variables: gender, race, ethnicity, insurance type, age, weight, height, date of biopsy, performing physician, sedation received, dose, and biopsy results. Weight for length (for children b2 years) [17] and body mass index (BMI) (for 2–18 years old) percentile for age and gender [18] were determined. Study outcomes included adequacy of specimen and procedural complications, such as bleeding, blood transfusion and readmission. Descriptive statistics and univariate analysis (chi-square, Fisher's exact, and Mann–Whitney U test) were performed using SPSS Statistics (v.22, IBM, Armonk, NY). 3. Results 3.1. Demographics and outcomes 56 patients were identified in the cohort who underwent SRB during the study period. Cohort demographics, procedural details and outcomes are summarized in Table 1. The median age was 3.9 years with interquartile range (IQR) of 3.83, and weight/length or BMI percentile was 59.2% with IQR of 52.1%. 21 patients underwent SRB without sedation and 35 patients received sedation. In 11 patients (19.6%) an inadequate specimen was obtained with 9 of the 11 occurring in patients aged 1 to 5 years (n = 35). Children older than 5 years (n = 21) had adequate specimens in all but 2 patients, a 90.5% success rate of SRB versus a 74.3% success rate in children 1–5 years. For patients with an inadequate biopsy on initial attempt, sufficient specimens were ultimately
Table 1 Cohort demographics, procedural details and outcomes summary. Variable Age category 1–5 years N5 years Gender Female Race/ethnicity Caucasian African-American Hispanic Other Sedation category None Light-Deep General Provider Gastroenterologist Surgeon SRB sample adequacy Adequate
n (%) 35 (62.5) 21 (37.5) 32 (57.1) 49 (87.5) 3 (5.4) 2 (3.6) 2 (3.6) 21 (37.5) 29 (51.8) 6 (10.7) 53 (94.6) 3 (5.4) 45 (80.4)
obtained either with a second SRB utilizing increased sedation (n = 5) or with FTB under GA (n = 5). One patient with an initial inadequate biopsy was lost to follow-up. On review of all inadequate specimens, nine biopsies were deemed inadequate because of the presence of squamous and/or transitional epithelium and two biopsies were inadequate because of insufficient submucosa. There was 100% concordance between original and reviewed diagnoses. The incidence of HD was 3.6%, and the complication rate was 1.8% (one child readmitted for bleeding without need for transfusion). There were no intestinal perforations or other complications. 3.2. Risk factors for inadequate SRB specimen Although not statistically significant, univariate analysis showed weak associations between inadequate specimens and age b5 years (P = 0.14) and (Fig. 1) male gender (P = 0.12) (Table 2). No significant difference in specimen adequacy in sedated versus nonsedated groups was found. Insurance, race/ethnicity, weight–height or BMI percentile, sedation type (categorized as none, light (oral or IV midazolam), deep (inhaled nitric oxide or IV ketamine) or GA), and procedure location were not associated with biopsy adequacy. All patients who underwent SRB under GA had adequate specimen (n = 6). 4. Discussion Current literature suggests varying biopsy adequacies using SRB devices from 73% to 100% [2,3,5–10,12–14] with controversy regarding SRB effectiveness in the older child. In infants, suction rectal biopsy is documented as having sensitivity of 93% and specificity of 98% for HD [14]. In 1986, Kurer et al. [19] confirmed that SRB was as accurate as FTB for the diagnosis of HD in patients aged from a few weeks to 17 years. Yet, a 1998 retrospective study by Alizai et al. [5] regarding SRB using the Noblett device found inadequate samples in 13% of patients and, despite failing to reach statistical significance, suggested that suction biopsies were less likely to be adequate in children over 6 months of age compared to those younger (82.5% vs. 90.9%). In 2007, Croffie et al. [9] similarly found that SRB was adequate for diagnosis in 73% of patients 1 to 3 years of age, and only 50% of patients older than 3 years in a prospective study of children undergoing SRB. Finally, in 2012 Hayes et al. [12] found that, while not significant, patients younger than 3 years were more likely to have adequate SRB specimens than those older than 3 years (81% vs. 70%). The proposed reasons for these results are multifactorial. First, older children may have increased rectal thickness caused by chronic constipation, which may interfere with
Please cite this article as: Brady A-C, et al, Suction rectal biopsy yields adequate tissue in children, J Pediatr Surg (2016), http://dx.doi.org/10.1016/ j.jpedsurg.2016.02.064
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Fig. 1. Univariate analysis indicates a nonsignificant trend toward inadequate SRB specimen in younger patients.
adequate apposition of the device with the rectal wall [9]. Second, older SRB devices required regular servicing such as blade sharpening which could contribute to worse biopsy yield. Last, the lack of sedation in younger uncooperative patients may have contributed to difficulty in obtaining adequate biopsies. Despite studies to the contrary that document an adequacy rate of 90 to 100% in children older than 1 year [8,14], many physicians adopted a protocol of routine FTB under GA for patients over a particular age. At our facility, children with chronic constipation continued to undergo SRB with or without sedation despite their age. As a result, our retrospective study demonstrates that SRB can be used successfully in the older child to evaluate for the presence of HD. Of the 56 patients aged between 1 and 18 years who underwent SRB, 80.4% had a diagnostic initial biopsy. On subset analysis, 90.5% of children aged 5 to 18 years had successful biopsies, which coincides with the findings of De Lorijn et al. [14] and Pini-Prato et al. [8]. However, the children aged 1 to 5 years tended to have a lower diagnostic yield with SRB of 74.3%. This lower SRB adequacy rate in the younger child is suspected to be caused by decreased cooperation in the toddlers and the need for increased sedation. Our statistical analysis did not identify a difference between sedated and nonsedated groups in regard to biopsy adequacy. We suspect that this finding may be due to selection bias (i.e., cooperative patients were not sedated) and our small population size. Of note, all children who underwent SRB under GA (n = 6), typically in combination with another procedure such as colonoscopy, had adequate specimens. Additionally, all patients who underwent repeat SRB after inadequate initial SRB subsequently were diagnosed with the use of increased sedation. This suggests that sedation level may, in fact, play a role in biopsy adequacy that was not appreciated statistically in this study. Table 2 Biopsy adequacy univariate analysis summary. Predictor Age category 1–5 years N5 years Gender Female Male Provider Gastroenterologist Surgeon Sedation None Light/Deep General
Adequate (%)
P 0.14
26/35 (74.3) 19/21 (90.5) 0.12 28/32 (87.5) 17/24 (70.8) 0.1 44/53 (83.0) 1/3 (33.3) 0.22 18/21 (85.7) 21/29 (72.4) 6/6 (100)
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Historically, complications with SRB were seen in the neonatal population largely because of dull blades and the use of elevated manometric pressures during biopsy, but these complications are rare using modern devices. In 1983, Rees et al. [4] reviewed 1340 consecutive biopsies using the Noblett instrument and identified a 1.3% complication rate with significant neonatal complications including one fatal complication from pelvic cellulitis, two perforations causing pneumoperitoneum, two inadvertent full thickness biopsies with no clinical manifestations, and three rectal hemorrhages necessitating transfusion. Techniques and devices have been employed in attempts to improve safety especially in the neonatal population and biopsy adequacy, particularly in the older child. These include the use of specific instruments such as laryngeal biopsy forceps [20], cup biopsy forceps [5,15], nasal cutting forceps [7], and uterine biopsy forceps [9], and often employed increased sedation or GA. The rbi-2 device is the SRB instrument used exclusively at our institution. This device has the advantages of precise manometrically measured suction as well as a disposable single use blade for each specimen eliminating the need for blade sharpening and diminishing the risk of patient-to-patient cross infection. In 2009, the Noblett was found to have a statistically significant higher inadequacy rate than the rbi-2 in patients younger than 1 year (20% vs. 7%, P = 0.01) [10]. We have demonstrated that newer devices like the rbi-2 are capable of obtaining sufficient rectal biopsies in older children despite thicker rectal mucosa from prolonged constipation while still maintaining a low complication rate of 1.8%. 5. Conclusions Although previously suspected to yield inadequate biopsies in older children, SRB is an effective means of excluding HD. This study confirms that SRB yields sufficient tissue for HD diagnosis particularly in the older, cooperative child. In children aged 1 to 5 years, increased sedation (deep or GA) may be necessary to obtain a sufficient biopsy. In the event of inadequate initial specimen, SRB under increased sedation should be attempted. This study was limited by its retrospective nature, by potential selection bias in the administration of sedation, and the lack of standardization of sedation provided. A prospective study would be beneficial to determine the most effective means of obtaining adequate SRB specimens in children aged 1 to 5 years. References [1] Langer J. Hirschsprung disease. In: Coran A, editor. Pediatric surgery. Philadelphia: Elsevier Saunders; 2012. p. 1265–78. [2] Dobbins WO, Bill AH. Diagnosis of Hirschsprung's disease excluded by rectal suction biopsy. N Engl J Med 1965;272:990–3. [3] Noblett HR. A rectal suction biopsy tube for use in the diagnosis of Hirschsprung's disease. J Pediatr Surg 1969;4:406–9. [4] Rees BI, Azmy A, Nigam M, et al. Complications of rectal suction biopsy. J Pediatr Surg 1983;18:273–5. [5] Alizai NK, Batcup G, Dixon MF, et al. Rectal biopsy for Hirschsprung's disease: what is the optimum method? Pediatr Surg Int 1998;13:121–4. [6] Pini-Prato A, Martucciello G, Jasonni V. Solo-RBT: a new instrument for rectal suction biopsies in the diagnosis of Hirschsprung's disease. J Pediatr Surg 2001;36:1364–6. [7] Kobayashi H, Li Z, Yamataka A, et al. Rectal biopsy: what is the optimal procedure? Pediatr Surg Int 2002;18:753–6. [8] Pini-Prato A, Martucciello G, Jasonni V. Rectal suction biopsy in the diagnosis of intestinal dysganglionoses: 5-year experience with Solo-RBT in 389 patients. J Pediatr Surg 2006;41:1043–8. [9] Croffie JM, Davis MM, Faught PR, et al. At what age is a suction rectal biopsy less LIkely to provide adequate tissue for identification of ganglion cells? J Pediatr Gastroenterol Nutr 2007;44:198–202. [10] Hall NJ, Kufeji D, Keshtgar A. Out with the old and in with the new: a comparison of rectal suction biopsies with traditional and modern biopsy forceps. J Pediatr Surg 2009;44:395–8. [11] Rahman N, Chouhan J, Gould S, et al. Rectal biopsy for Hirschsprung's disease—are we performing too many? Eur J Pediatr Surg 2010;20:95–7. [12] Hayes CE, Kawatu D, Mangray S, et al. Rectal suction biopsy to exclude the diagnosis of Hirschsprung disease. J Pediatr Gastroenterol Nutr 2012;55:268–71. [13] Athow AC, Filipe MI, Drake DP. Problems and advantages of acetylcholinesterase histochemistry of rectal suction biopsies in the diagnosis of Hirschsprung's disease. J Pediatr Surg 1990;25:520–6.
Please cite this article as: Brady A-C, et al, Suction rectal biopsy yields adequate tissue in children, J Pediatr Surg (2016), http://dx.doi.org/10.1016/ j.jpedsurg.2016.02.064
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Please cite this article as: Brady A-C, et al, Suction rectal biopsy yields adequate tissue in children, J Pediatr Surg (2016), http://dx.doi.org/10.1016/ j.jpedsurg.2016.02.064