Subjective Near-infrared Fluorescence Guidance in Perfusion Assessment of Ileal Pouch Formation and Ileal-pouch-anal Anastomosis

The Value of Subjective Near-infrared Fluorescence Guidance in Assessment of Perfusion During Restorative Ileal Pouch Formation and Ileal-pouch-anal Anastomosis

In this prospective, non-randomized cohort study, real-time intraoperative visualization using near-infrared-fluorescence by indocyanine green injection (ICG-NIRF) is performed at three time points during ileal pouch reconstruction. The intraoperative imaging findings are then analysed and correlated with the 30 day postoperative clinical outcome including occurrence of anastomotic leak of the pouch.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Crohn Disease; Ulcerative Colitis; Familial Adenomatous Polyposis; Crohn Colitis; Ileal Pouch
• Intervention / Treatment: Diagnostic test: ICG-NIRF Imaging

Detailed Description

Near-infrared-fluorescence by indocyanine green (ICG-NIRF) utilises the fluorescent property of intravenously injected indocyanine green (ICG) as an intravascular indicator of tissue and bowel perfusion.

The investigators hypothesise that ICG-NIRF is a suitable, reliable and precise method of visualisation of the blood supply and bowel perfusion in the area of ileal pouch formation and the ileal pouch-anal anastomosis.

In this prospective, non-randomized cohort study, restorative proctocolectomy with ileal pouch reconstruction and ileal pouch-anal anastomosis is performed according to standard of care for medically-refractory ulcerative colitis (UC), UC-associated neoplasia, medically-refractory Crohn´s colitis, colorectal carcinoma or familial adenomatous polyposis (FAP) in open or laparoscopic surgery, according to the surgeon's choice.

Written informed consent for participation and ICG-administration is obtained one day before surgery.

Intraoperatively, Indocyanine Green (VerDye, Diagnostic Green GmbH, Aschheim Germany, 25 mg vials) is dissolved in 5 mL sterile water to yield a 5 mg/mL concentration. It will then be administered intravenously at three consecutive time points as a bolus of 2 ml per time point at the most. The overall dose of ICG will amount to no more than 30mg of ICG per patient.

Real-time intraoperative visualization is performed with the SpectrumTM Fluorescence Imaging Platform (Quest Innovations, Middenmeer, The Netherlands) directly after each ICG injection assessing bowel perfusion at three different time points respectively: before and after J-Pouch construction by stapler anastomosis and after ileoanal anastomosis formation.

Clinical data and follow-up Clinical data is be collected from all patients regarding anastomotic leak, bowel ischemia and necrosis as well as 30 day postoperative morbidity, mortality and length and cost of hospital stay.

Subjective data analysis will performed using Microsoft Excel® and IBM SPSS®.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Recruiting
    • Charite Campus Benjamin Franklin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age ≥ 18
• capability of signing the informed consent
• diagnosis of therapy resistent ulcerative colitis, colorectal cancer, Crohn's disease, familial adenomatous polyposis
• restaurative proctocolectomy (RPC) with reconstruction through ileal pouch formation and ileal pouch-anal anastomosis (IPAA) is possible and medically indicated
• ASA score ≤ 3

Exclusion Criteria:

• coexistent malignant tumor of a different ethology
• liver disfunction (MELD score > 10)
• ICG (indocyanine green) specific exclusion criteria as per literature (intolerance to indocyanine green or sodium iodide, iodine allergy, hyperthyroidism, autonomous thyroid adenoma, focal or diffuse autonomies of the thyroid, previously badly tolerated injection of ICG)
• pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ICG-NIRF Imaging; ICG-NIRF imaging is used intraoperatively to visualise precisely the blood supply and bowel perfusion rate in the area of ileal pouch formation and the ileal pouch-anal anastomosis.	Diagnostic test: ICG-NIRF Imaging; intraoperative NIRF Imaging using the fluorescence agent ICG (indocyanine-green) at regions of interest before (T1) + after pouch construction (T2) + after ileoanal anastomosis (T3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
anastomotic leak	occurrence of anastomotic leak within 30 days of surgery	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Operative and post-operative complications	Clavien-Dindo for complication-level classification	30 days
Length of post-operative hospital stay	length in days	100 days

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Publications and helpful links

General Publications

• McDermott FD, Heeney A, Kelly ME, Steele RJ, Carlson GL, Winter DC. Systematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks. Br J Surg. 2015 Apr;102(5):462-79. doi: 10.1002/bjs.9697. Epub 2015 Feb 19.
• Perbeck L, Lindquist K, Proano E, Liljeqvist L. Correlation between fluorescein flowmetry and laser Doppler flowmetry. A study in the intestine (ileoanal pouch) in man. Scand J Gastroenterol. 1990 May;25(5):520-4. doi: 10.3109/00365529009095524.
• Hallbook O, Johansson K, Sjodahl R. Laser Doppler blood flow measurement in rectal resection for carcinoma--comparison between the straight and colonic J pouch reconstruction. Br J Surg. 1996 Mar;83(3):389-92. doi: 10.1002/bjs.1800830330.
• van den Bos J, Jongen ACHM, Melenhorst J, Breukink SO, Lenaerts K, Schols RM, Bouvy ND, Stassen LPS. Near-infrared fluorescence image-guidance in anastomotic colorectal cancer surgery and its relation to serum markers of anastomotic leakage: a clinical pilot study. Surg Endosc. 2019 Nov;33(11):3766-3774. doi: 10.1007/s00464-019-06673-6. Epub 2019 Feb 1.
• van den Bos J, Al-Taher M, Schols RM, van Kuijk S, Bouvy ND, Stassen LPS. Near-Infrared Fluorescence Imaging for Real-Time Intraoperative Guidance in Anastomotic Colorectal Surgery: A Systematic Review of Literature. J Laparoendosc Adv Surg Tech A. 2018 Feb;28(2):157-167. doi: 10.1089/lap.2017.0231. Epub 2017 Nov 6.
• Degett TH, Andersen HS, Gogenur I. Indocyanine green fluorescence angiography for intraoperative assessment of gastrointestinal anastomotic perfusion: a systematic review of clinical trials. Langenbecks Arch Surg. 2016 Sep;401(6):767-75. doi: 10.1007/s00423-016-1400-9. Epub 2016 Mar 11.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: January 4, 2021
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 13, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: anastomotic leak; ulcerative colitis; indocyanine green; pouchitis; restorative proctocolectomy; ileal pouch-anal anastomosis; subjective perfusion rate; near-infrared fluorescence
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; Inflammatory Bowel Diseases; Adenomatous Polyps; Adenoma; Intestinal Polyposis; Ulcer; Crohn Disease; Adenomatous Polyposis Coli; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: EA4/116/19/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: this will be determinable at a later point when more data is available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No