Short summary

Anastomotic leakage is a common and serious surgical complication to rectal resection. AL can be life threatening and has long-term adverse effects for the patients with reduced quality of life. A prerequisite for optimal anastomotic healing is sufficient blood supply to the tissue. The surgeon evaluates surrogates of bowel perfusion prior to the completion of the anastomosis. Studies suggest that bowel perfusion is easy evaluated using a fluorescent dye. Software to quantify bowel perfusion

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Rationale

Background:

Anastomotic leakage (AL) is a common and serious surgical complication to rectal resection. In Denmark, approximately 800 patients with rectal cancer undergo surgery every year, about 50% of which undergo resection with an anastomosis. According to the Danish Colorectal Cancer registry, DCCG, 10% of patients with an anastomosis developed AL in 2021.

AL can be life threatening and has long-term adverse effects for the patients, with reduced quality of life due to a poor functional result of the neo-rectum known as low anterior rectal syndrome (LARS). Fistulas to the vagina or urinary tract are other severe complications. Furthermore, AL is associated with an increased risk of recurrence. Finally, the AL-associated morbidity is also a significant economic burden to the health care system due to prolonged hospital stay, medicine, and reoperations.

A prerequisite for optimal wound healing, including anastomotic healing, is sufficient blood supply and oxygen delivery to the tissue. The surgeon evaluates so-called surrogates of bowel perfusion (colour, mesenteric pulsation, and arterial bleeding) prior to the completion of the anastomosis. During surgery, the anastomosis is testet by air-insufflation, a so-called "leak-test". Studies suggest that bowel perfusion is easier evaluated using a fluorescent dye. Software to quantify bowel perfusion has been developed, but cut off values for sufficient perfusion remains to be established.

We have conducted a multicentre feasibility study using the Indocyanine green Fluorescent Imaging (ICG-FI) method in sigmoidal and rectal resections in order to standardize the interpretation of the results and we found great inter-observer variability in the interpretation of the results.

We included 55 patients from five colorectal centres in Denmark, and five patients developed clinical AL (9.1%). At the postsurgical analysis, the observer would have done additional resection in six patients based on the ICG-FI, but only one of these patients developed anastomotic leakage. Assessing videos by quantification software, we found a significant difference between patients who developed AL and those who did not. The normalized slope was median 0.08 (0.07;0.10) in leak patients and 0.13 (0.10;0.17) in no-leak patients, (p=0.04)

A Danish research team at Rigshospitalet, Copenhagen, has developed and validated a method of quantifying fluorescence angiography (q-ICG) to assess bowel perfusion. The quantitative perfusion assessment is feasible and easy to perform and has been validated in a series of animal experimental studies.

The methods to quantify the results from ICG-FI needs to be proven in more human studies, especially in rectal and sigmoid resections, to evaluate intraoperative blood flow at the anastomotic site. With the specific aim to define a cut-off value, where blood perfusion to the anastomotic site is sufficient to ensure that poor healing, due to low perfusion, is diminished and thereby is the risk of AL.

Aim:

Primary objective: To establish cut-off values of qICG, where blood flow assumes sufficient for healing, and thereby reduce the risk of leakage.

Secondary objective: To identify which long-term complications grade A, B and C leakages entails on Quality of Life.

Method:

A prospective cohort study.

Pre-operative evaluation

To evaluate which impact disease and treatment has on overall morbidity, patients will be asked to fill questionnaires regarding quality of life and bowel function prior to surgery. The validated EORTC-qlq-cr29 and LARS questionnaires will be used.

These questionnaires will be repeated post-operatively on POD 365.

ICG and anastomotic evaluation

Patient characteristics will be registered. All patients must undergo laparoscopic or robotic rectal resection, possibly combined with trans-anal approach. After the bowel has been resected and the anvil of the circular stapler has been placed in the proximal bowel, the ICG-FI evaluation will take place.

The surgeon will place the camera in a stationary holder or in the robotic arm at the optimal position to view the bowel perfusion. The camera, patient, operating table, or bowel shall not be moved during observation.

The laparoscopic light is switched from white to infra-red and a bolus of 0,2mg/kg ICG, max 25mg, is administered intravenously and flushed with saline. This procedure will be video-documented. When the anastomosis has been established, leakage-test and visual evaluation will be performed. All intra-operative observations will be registered.

Postoperative observation

Patients will be observed daily according to standard post-operative care.

On post-operative day (POD) 5 an abdominal CT scan with rectal enema will be performed to identify all AL, including subclinical. Findings will be registered. If we find a leakage on CT, a flexible endoscopy will be performed. Findings will be addressed according to normal practice in participating centres; surgery, endoscopic lavage, treatment with endosponge and/or antibiotics.

On POD 30 and 90, any complications will be obtained from the electronic patient records.

Pre-operative and on POD 365 the patients will be sent a questionnaire or online survey about their functional symptoms and quality of life, using the validated EORTC-qlq-cr29 questionnaire and the LARS score.

q-ICG:

Videos will postoperatively be analysed using the pixel analysis software q-ICG. We will evaluate the following parameters: Slope, normalized slope, TTP (Time-To-Peak=Tmax), T0 (first fluorescent sign), T1/2max, TR (Time Ratio: T1/2max/Tmax), and Fmax (Maximum fluorescent value).

 

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Description of the cohort

Population:

Patients in the Region of Southern Denmark, older than 18, undergoing laparoscopic or robotic surgery for rectal cancer, were an anastomosis is performed.

Data and biological material

Patient characteristics: height, weight, alcohol and tobacco-consumption, and comorbidity will be obtained from the electronic patient-record. Videos parts of the surgery, endoscopy details and postoperative CT scans will be used to evaluate the anastomosis.

Patients will be asked to fill out internationally validated questionnaires concerning their generel health and bowel funktion.

Collaborating researchers and departments

Department of Surgery A, OUH

• Mark Bremholm Ellebaek

Department of Surgery, Vejle Hospital

• Pernille Oehlenschläger Larsen

Department of surgery, Esbjerg Hospital

• Rasmus Krøjer

Department of Surgery, Aabenraa

• Mindaugas Tiskus

Publications associated with the project

Anastomotic perfusion assessment with indocyanine green in robot-assisted low-anterior resection, a multicenter study of interobserver variation