Objective Perfusion Rate Assessment by Near-infrared Fluorescence in Ileal Pouch Formation and Ileal-pouch-anal Anastomosis

The Value of Objective Perfusion Rate Assessment by Near-infrared Fluorescence 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. Postoperatively, a detailed software-based assessment of each pouch recording is performed to determine the objective ICG-NIRF perfusion rate, which is then 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; Ulcerative Colitis Chronic; Ulcerative Colitis in Remission; Ileal Pouch
• Intervention / Treatment: Diagnostic test: ICG-NIRF Imaging plus ingress and egress analysis

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 (ICG, 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.

Postoperative NIRF-perfusion rate assessment Using the Quest Research SoftwareTM, the recordings before and after anastomosis formation will be analysed for their perfusion rate. This analysis will provide objective, quantitative data on the perfusion for a certain time frame which is determined by the length of the video recording. This data will be collected for statistical analysis and correlation with anastomotic leak as well as postoperative outcome.

Clinical data and follow-up Clinical data will 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.

Further data analysis will be 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
• restorative proctocolectomy (RPC) with reconstruction through ileal pouch formation and ileal pouch-anal anastomosis (IPAA) is possible and medically indicated
• ASA (American Society of Anesthesiologists) Physical Status Classification System 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: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: ICG-NIRF Imaging and objective perfusion rate; ICG-NIRF imaging is used to visualise the blood supply and the bowel perfusion rate in the area of the pouch anastomoses. An additional ingress and egress analysis at specific regions of interest is performed. This is to get an objective method of visualisation of the blood inflow and outflow over time and thus bowel perfusion at the anastomotic site.

Diagnostic test: ICG-NIRF Imaging plus ingress and egress analysis; intraoperative NIRF Imaging using the fluorescence agent ICG (indocyanine-green) at regions of interest before (T1) + after pouch construction (T2) + after ileoanal anastomosis (T3) Additional ingress and egress analysis (inflow and outflow analysis) of specificities regions of interest 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	occurence anastomotic leak within 30 days of operation	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

• 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.
• 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, 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 6, 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; near-infrared fluorescence; objective perfusion rate; image guided surgery
• 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: EA4/116/19/2

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