Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease

Hirschsprung Disease Clinical Trial

— BIOPSY  

Official title:

Prospective Randomised Blinded Study Comparing Full Thickness Biopsy and Rectal Suction Biopsies in the Diagnosis of Mb: Hirschsprung

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05307419
• Other study ID #: S-20190116
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2022
• Est. completion date: February 1, 2024

Study information

• Verified date: May 2022
• Source: University of Southern Denmark
• Contact: Niels mr Bjorn, Dr
• Phone: 23241781
• Email: niels.bjorn[@]rsyd.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this prospective study is to compare the diagnostic accuracy of rectal suction biopsy (RSB) compared to full thickness rectal biopsy (FTB) in the diagnosis of Hirschsprungs Disease (HD) in children. The secondary objective to compare cost-effectiveness of the two procedures

Description:

Diagnostic procedures involving the need of surgically obtaining tissue material, carry the risk of complications and the risk of being inconclusive due to various reasons. Lowering the risk of inconclusive diagnostic tests with highest sensitivity and specificity is of high importance in all diagnostic procedures.

A full thickness rectal biopsy (FTB) includes both the submucosal and the myenteric nerve plexus for histological evaluation for presence of ganglion cells and hypertrophic nerve fibers. FTB is performed in general anesthesia (GA), the biopsy is cut with scissors under direct visualization of the intestine and with suturing of the biopsy defect. The other method is a suction biopsy (RSB) in which the biopsy is more superficial acquiring only the submucosal layers. RSB's are performed with a specially designed rectoscope, and the biopsy is obtained under negative pressure within the scope, without visual guidance. This procedure can be performed without anesthesia in children blow 1 year and does not necessitate suturing of the bowel.

The problem with especially RSB could be that the biopsy is too superficial or too small in size for proper pathological evaluation. As a consequence the child has to undergo a new procedure. There is also the risk of false positive or false negative results, which is a serious clinical issue carrying the risk of performing extensive surgery in an otherwise healthy child.

Inconclusive biopsies differ extensively from series to series. But the two largest studies show a rate of inconclusive biopsies at 10% for RSB and 5% for FTB.(Freidmacher and Bjorn). The biopsy profile is similar with less than 1% severe complications (Above Clavien DindoIII) in both procedures, with bleeding as dominating in RSB and Fever in FTB.

Thus there are different advantages and disadvantages between the two methods of biopsy in children suspicious of HD, and different centers advocate either. A prospective comparison of both methods with the child as its own control is a more precise way to compare the two methods and has never been performed. Thus, this study is expected to give an answer to an important research question that will have potential implication worldwide.

Hypothesis:

Our hypothesis is that FTB has lower rate of inconclusive biopsies compared to RSB in the diagnosis of HD.

Design:

Prospective, biopsy sample randomised study.

Method:

Patients referred for rectal biopsy at Odense University Hospital on the suspicion of HD will undergo both an FTB and RSB performed under GA in the same procedure.

Patients will be randomised to which biopsy will be examined first at the pathology department. If a diagnosis can bed securely made on the first tissue samples the other biopsy materials will be stores for examination by another pathologist 30 days later. If any nerve cell is present the sample is negative for Mb. Hirschsprung. If no nervecells is present the biopsy the patient is positive for mb. Hirschsprung. If the tissue is evaluated as not suitable for diagnosis the sample is inconclusive. If the sample is inconclusive the tissue from the other biopsy method is evaluated immediately to secure a fast diagnosis.

All children between 0-15 years of age undergoing biopsies for diagnosis of the diagnosis of HD in Western Denmark from 1/9 2020 will be offered to participate and parental accept will be acquired.

Cost-effectiveness will be measured upon with data from pathology cost and surgery utensils cost.

These will be compared between the two groups.

Power calculation:

With the assumption of a 5 % inconclusive rate for FTB and 10% for RSB (2,5) a McNemar's test for matched comparison of dichotomous outcome (inconclusive / conclusive) indicates the need for 282 patients to obtain 70% strength and a significance level of 5%. (P-value 0.05).

These calculations are based on the largest numbers of biopsy evaluations in the literature.

In these publications a rate of 5% inconclusive biopsies at FTB and 10% at RSB are found.

Interim analyse will be performed after 25%, 50% and 75%. Above 8% complications on 30-day follow-up will result in the study will be paused and examinations of the complications will be performed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: February 1, 2024
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 15 Years

Eligibility

Inclusion Criteria:

• Patients that are referred for rectal biopsy for suspected HD, age 0-15 years.

• Written informed consent of the parents or guardian.

Exclusion Criteria:

• Lack of consent from parents or guardians.

• Previous surgery on the ano-rectum e.g. crohns disease and/or fistulas

Related Conditions & MeSH terms

• Hirschsprung Disease

Intervention

Procedure:
• Rectal suction biopsy.
Suction biopsy performed
• Full-thickness rectal biopsy.
Full-thickness biopsy performed

Locations

Country	Name	City	State
Denmark	Odense University Hospital	Odense	Fyn

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern Denmark	Odense University Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (10)

Ali AE, Morecroft JA, Bowen JC, Bruce J, Morabito A. Wall or machine suction rectal biopsy for Hirschsprung's disease: a simple modified technique can improve the adequacy of biopsy. Pediatr Surg Int. 2006 Aug;22(8):681-2. Epub 2006 Jul 4. — View Citation

Alizai NK, Batcup G, Dixon MF, Stringer MD. Rectal biopsy for Hirschsprung's disease: what is the optimum method? Pediatr Surg Int. 1998 Mar;13(2-3):121-4. — View Citation

Bjørn N, Rasmussen L, Qvist N, Detlefsen S, Ellebæk MB. Full-thickness rectal biopsy in children suspicious for Hirschsprung's disease is safe and yields a low number of insufficient biopsies. J Pediatr Surg. 2018 Oct;53(10):1942-1944. doi: 10.1016/j.jpedsurg.2018.01.005. Epub 2018 Jan 31. — View Citation

De Lorijn F, Reitsma JB, Voskuijl WP, Aronson DC, Ten Kate FJ, Smets AM, Taminiau JA, Benninga MA. Diagnosis of Hirschsprung's disease: a prospective, comparative accuracy study of common tests. J Pediatr. 2005 Jun;146(6):787-92. — View Citation

Friedmacher F, Puri P. Rectal suction biopsy for the diagnosis of Hirschsprung's disease: a systematic review of diagnostic accuracy and complications. Pediatr Surg Int. 2015 Sep;31(9):821-30. doi: 10.1007/s00383-015-3742-8. Epub 2015 Jul 9. Review. — View Citation

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 Feb;44(2):395-8. doi: 10.1016/j.jpedsurg.2008.10.093. — View Citation

Imaizumi T, Murakami H, Nakamura H, Seo S, Koga H, Miyano G, Okawada M, Doi T, Lane GJ, Okazaki T, Arakawa A, Yao T, Yamataka A. Rectal mucosal/submucosal biopsy under general anesthesia ensures optimum diagnosis of bowel motility disorders. Pediatr Surg Int. 2016 Dec;32(12):1173-1176. Epub 2016 Sep 23. — View Citation

Muise ED, Hardee S, Morotti RA, Cowles RA. A comparison of suction and full-thickness rectal biopsy in children. J Surg Res. 2016 Mar;201(1):149-55. doi: 10.1016/j.jss.2015.10.031. Epub 2015 Oct 28. — View Citation

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 Jun;41(6):1043-8. — View Citation

Stewart CL, Kulungowski AM, Tong S, Langer JC, Soden J, Sømme S. Rectal biopsies for Hirschsprung disease: Patient characteristics by diagnosis and attending specialty. J Pediatr Surg. 2016 Apr;51(4):573-6. doi: 10.1016/j.jpedsurg.2015.10.047. Epub 2015 Oct 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of inconclusive biopsies between FTB and RSB.	Prospective comparison of RSB and FTB when performed on the same patient. Evaluation of diagnostic accuracy.	30 days
Secondary	Surgical and pathology cost.	Cost-effectiveness will be measured from surgical and pathology procedural and utensils costs in euros, between RSB and FTB.	30 days