Rectal Cancer Anastomosis 4 Check Study

• Conditions: Rectal Cancer
• Interventions: Combination Product: intraoperative near infrared (NIR) indocyanine green (ICG)-induced fluorescence angiography (FA) and air leak testing to assess the integrity and the perfusion levels of the colorectal anastomosis; Diagnostic Test: Air Leak test; Diagnostic Test: Evaluation of the anastomotic rings

• Registration Number: NCT04637061
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief Summary

Anastomotic failure (AF), including anastomotic leakage (AL), increases morbidity and mortality after colorectal cancer (CRC) resection. An inadequate perfusion of the anastomosis or technical stapling defects may contribute to AF. Several studies evaluated the singular use of intraoperative near infrared (NIR) indocyanine green (ICG)-induced fluorescence angiography (FA) and air leak testing to assess the integrity and the perfusion levels of the colorectal anastomosis. So far, a combined use of these methodologies, although acknowledged has not yet been tested as an indicator of postoperative AF or of intra-operative anastomotic repair in a prospective setting. This study aims to implement the intraoperative anastomotic assessment in a prospective series of patients undergoing rectal resection plus primary anastomosis for rectal cancer with or without ostomy, using a semi-quantitative check of 4 items (4-check). The procedure will include NIR-ICG-induced FA (to assess perfusion), air leak test and evaluation of the anastomotic donuts (to assess for the presence of technical defects). Included patients will be those scheduled for elective rectal resection with total or partial mesorectal excision and primary colo-rectal anastomosis with/or without protective ostomy. Primary outcomes will be the overall incidence of intra-operative anastomotic repair and the rate of post-operative AF. Secondary outcomes will be the overall incidence of adverse events and serious complications, the estimation of costs and resources, the operative time, hospitalization and post-operative measurement of inflammatory markers.

Detailed Description

All consecutive patients undergoing rectal resection (open and mini-invasive procedures) plus primary anastomosis for rectal cancer selected for the study will udergo a surgical intra-operative assessment of the anastomosis based on the check of the following 4 items (4-check):

1. Extra-luminal (serosa) evaluation of the proximal colon and distal rectal stump perfusion based on a semi-quantitative assessment of the near infrared (NIR) indocyanine green (ICG)-induced fluorescence angiography (FA).

2. Endo-luminal (mucosal) evaluation of the proximal colon and distal rectal stump perfusion based on a semi-quantitative assessment of the NIR-ICG-induced FA.

3. Air leak test (extra-luminal and reverse).

4. Assessment of the anastomotic donuts. aiming to test the efficacy of the procedure (overall incidence of intra-operative anastomosis repairs) and the overall incidence of anastomotic failure

Study Timeline

• Status Verified: 2020-11
• Study First Submitted: 2020-11-14
• Study First Submitted QC: 2020-11-14
• Study First Posted: 2020-11-19
• Last Update Submitted: 2020-11-23
• Last Update Posted: 2020-11-25
• Study Start: 2021-01-01
• Primary Completion: 2022-12-31
• Study Completion: 2023-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 287

Inclusion Criteria

• 18 years or older.
• Rectal adenocarcinoma or benign polyp with indication for rectal resection with total or partial mesorectal excision and primary colo-rectal anastomosis with/or without protective ostomy.
• Patients undergoing upfront surgery and patients undergoing neoadjuvant therapy followed by surgery.
• Patients with adequate performance status (Eastern Cooperative Oncology Group Scale score of ≤2).
• Patient must sign the Informed Consent Form (ICF) before any study procedures and agrees to attend all study visits.
• Selection of the patient before inclusion.

Exclusion Criteria

• • Patient pregnant or suspected pregnancy.

  • Patient with a comorbid illness or condition that would preclude the use of surgery.
  • Past medical history of Inflammatory Bowel Disease (IBD).
  • Synchronous cancers requiring extended sub-total or total colectomies.
  • Long lasting therapy with steroids to be continued in the peri-operative period (4 weeks previous and 4 weeks after surgery).
  • Use of antiplatelet drug (anti-aggregant) and/or oral anti-coagulant drug to be continued in the peri-operative period (1 week previous and 4 weeks after surgery).
  • Patients assessed as American Society of Anesthesiologists (ASA) physical status 4.
  • Patients with clinical stage of cT4b tumor after neoadjuvant theapy.
  • Metastatic disease (clinical Stage 4).
  • Patient undergoing emergency procedures.
  • Planned colonic surgery along with major concomitant procedures (i.e. liver resections, other intestinal resections).
  • Previous colon surgery (excluding appendectomy).
  • Non-restorative procedures (i.e. Miles or Hartman resection).
  • Colo-anal manual anastomosis.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
REC4T study patients	Air Leak test	Rectal adenocarcinoma or polyp with indication for resection and primary colo-rectal mechanical anastomosis using a circular stapler with/or without protective ostomy undergoing upfront surgery and patients undergoing neoadjuvant therapy followed by surgery (see Inclusion/Exclusion Criteria)
REC4T study patients	Evaluation of the anastomotic rings	Rectal adenocarcinoma or polyp with indication for resection and primary colo-rectal mechanical anastomosis using a circular stapler with/or without protective ostomy undergoing upfront surgery and patients undergoing neoadjuvant therapy followed by surgery (see Inclusion/Exclusion Criteria)
REC4T study patients	intraoperative near infrared (NIR) indocyanine green (ICG)-induced fluorescence angiography (FA) and air leak testing to assess the integrity and the perfusion levels of the colorectal anastomosis	Rectal adenocarcinoma or polyp with indication for resection and primary colo-rectal mechanical anastomosis using a circular stapler with/or without protective ostomy undergoing upfront surgery and patients undergoing neoadjuvant therapy followed by surgery (see Inclusion/Exclusion Criteria)

Primary Outcome Measures

Name	Time	Method
intra-operative anastomosis repairs	01/01/2021 to 31/12/2022	defined as additional suturing or re-do anastomosis
Rate of 30 day-anastomotic failure (AF)	01/01/2021 to 31/12/2022	defined as anastomotic-related morbidity, including anastomotic leakage, pelvic abscess, anastomotic-related fistula, sinus, and anastomotic stricture

Secondary Outcome Measures

Name	Time	Method
Rate of of adverse events	01/01/2021 to 31/12/2022	any medical or surgical complications
Rate of 30-day major complications	01/01/2021 to 31/12/2022	Clavien-Dindo grade IIIb-IV
C-Reactive Protein (CRP) measurement	01/01/2021 to 31/12/2022	measurement conducted in postoperative days 1, 3 \& 5 (optional) using mg/L
Procalcitonin (PCT) measurement	01/01/2021 to 31/12/2022	measurement conducted in postoperative days 1, 3 \& 5 (optional) using mg/L ng/mL
Measure of costs	01/01/2021 to 31/12/2022	Costs resource utilization for the procedure
Medan length of post-operative stay	01/01/2021 to 31/12/2022	post-operative stay (measured in days)